Hop, W.C.J.

Enzyme replacement therapy and fatigue in adults with Pompe disease (Article)

2013-04-19T00:00:00Z

Background: Pompe disease is a hereditary metabolic myopathy, for which enzyme replacement therapy (ERT) has been available since 2006. We investigated whether ERT reduces fatigue in adult patients with Pompe disease. Methods: In this prospective international observational survey, we used the Fatigue Severity Scale (FSS) to measure fatigue. Repeated measures ANOVA was used to analyze the data over time. In a subgroup of patients, we also evaluated muscle strength using the Medical Research Council Scale, measured pulmonary function as Forced Vital Capacity, and assessed depression using the Hospital Anxiety and Depression Scale. Results: We followed 163 patients for a median period of 4 years before ERT and for 3 years during ERT. Before ERT, the mean FSS score remained stable at around 5.3 score points; during ERT, scores improved significantly by 0.13 score points per year (p < 0.001). Fatigue decreased mainly in women, in older patients and in those with shorter disease duration. Patients' improvements in fatigue were moderately correlated with the effect of ERT on depression (r 0.55; CI 95% 0.07 to 0.70) but not with the effect of ERT on muscle strength or pulmonary function. Conclusions: Fatigue is a common and disabling problem in patients with early and advanced stages of Pompe disease. Our finding that ERT helps to reduce fatigue is therefore important for this patient population, irrespective of the mechanisms underlying this effect.

Laparoscopic versus open surgery for rectal cancer (COLOR II): Short-term outcomes of a randomised, phase 3 trial (Article)

2013-03-01T00:00:00Z

Background: Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe. The aim in the COlorectal cancer Laparoscopic or Open Resection (COLOR II) trial was to compare laparoscopic and open surgery in patients with rectal cancer. Methods: A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries. Patients (aged ≥18 years) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were randomly assigned to either laparoscopic or open surgery in a 2:1 ratio, stratified by centre, location of tumour, and preoperative radiotherapy. The study was not masked. Secondary (short-term) outcomes-including operative findings, complications, mortality, and results at pathological examination-are reported here. Analysis was by modified intention to treat, excluding those patients with post-randomisation exclusion criteria and for whom data were not available. This study is registered with ClinicalTrials.gov, number NCT00297791. Findings: The study was undertaken between Jan 20, 2004, and May 4, 2010. 1103 patients were randomly assigned to the laparoscopic (n=739) and open surgery groups (n=364), and 1044 were eligible for analyses (699 and 345, respectively). Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group (median 200 mL [IQR 100-400] vs 400 mL [200-700], p<0·0001); however, laparoscopic procedures took longer (240 min [184-300] vs 188 min [150-240]; p<0·0001). In the laparoscopic surgery group, bowel function returned sooner (2·0 days [1·0-3·0] vs 3·0 days [2·0-4·0]; p<0·0001) and hospital stay was shorter (8·0 days [6·0-13·0] vs 9·0 days [7·0-14·0]; p=0·036). Macroscopically, completeness of the resection was not different between groups (589 [88%] of 666 vs 303 [92%] of 331; p=0·250). Positive circumferential resection margin (<2 mm) was noted in 56 (10%) of 588 patients in the laparoscopic surgery group and 30 (10%) of 300 in the open surgery group (p=0·850). Median tumour distance to distal resection margin did not differ significantly between the groups (3·0 cm [IQR 2·0-4·8] vs 3·0 cm [1·8-5·0], respectively; p=0·676). In the laparoscopic and open surgery groups, morbidity (278 [40%] of 697 vs 128 [37%] of 345, respectively; p=0·424) and mortality (eight [1%] of 699 vs six [2%] of 345, respectively; p=0·409) within 28 days after surgery were similar. Interpretation: In selected patients with rectal cancer treated by skilled surgeons, laparoscopic surgery resulted in similar safety, resection margins, and completeness of resection to that of open surgery, and recovery was improved after laparoscopic surgery. Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013. Funding: Ethicon Endo-Surgery Europe, Swedish Cancer Foundation, West Gothia Region, Sahlgrenska University Hospital.

The relevance of patient-reported outcomes in a grass pollen immunotherapy trial in children and adolescents with rhinoconjunctivitis (Article)

2013-02-01T00:00:00Z

Background: Patient-reported outcomes (PROs) are the only instruments available to assess the efficacy of an intervention in patients with allergic rhinoconjunctivitis. As allergic rhinoconjunctivitis is a systemic disease, it is now recommended to use not only PROs focusing at classical symptoms, but also health-related quality of life (HRQL) instruments in immunotherapy trials. Methods: A previously published immunotherapy trial in children and adolescents (6-18yr) with hay fever provided us with data to assess the relevance of two of these additional outcome measures, the disease-specific rhinoconjunctivitis quality of life questionnaire (RQLQ) and the generic COOP/WONCA-charts (CWC). A PRO was considered relevant if it was responsive to pollen exposure and at least had a moderate correlation with the classical symptoms of allergic rhinoconjunctivitis. Furthermore, we evaluated a post-season PRO, that is, a global assessment of symptoms (GAS). This assessment is used in clinical trials as a tool for selecting participants with sufficient symptoms and in daily practice to evaluate the patient's complaints during the preceding season. We assessed the correlation of this retrospective score with the actual symptoms during the previous pollen season. Results: Data from 36 children and 63 adolescents were analysed. On the basis of the total scores of the paediatric and adolescent version of the RQLQ, both questionnaires were considered relevant as they were responsive to exposure and showed a moderate to strong correlation with the rhinoconjunctivitis symptoms. However, in both children and adolescents, 40% of the RQLQ items were not relevant according to our definition. The CWC as a whole and the separate charts appear less relevant because of the weak correlations with the daily symptom score from the diary. The correlation between our post-season GAS and the in season daily symptom score was weak. Conclusion: The paediatric and adolescent RQLQ are relevant, but could be shortened as they contain a substantial number of irrelevant items. The CWC are not relevant in the monitoring of children and adolescents with allergic rhinoconjunctivitis caused by grass pollen. The retrospective GAS does not sufficiently reflect the actual symptoms during the preceding season.

Respiratory morbidity and growth after open thoracotomy or thoracoscopic repair of esophageal atresia (Article)

2012-11-01T00:00:00Z

Background: Respiratory morbidity has been described in patients who underwent repair of esophageal atresia as a neonate. We compared the influence of open thoracotomy or thoracoscopy on lung function, respiratory symptoms, and growth. Methods: Functional residual capacity (FRCp), indicative of lung volume, and maximal expiratory flow at functional residual capacity (V′maxFRC), indicative of airway patency, of 37 infants operated for esophageal atresia were measured with Masterscreen Babybody at 6 and 12 months. SD scores were calculated for V′maxFRC. Results: Repair was by thoracotomy in 21 cases (57%) and by thoracoscopy in 16 cases (43%). Lung function parameters did not differ between the types of surgery (FRCp; P =.384 and V′maxFRC; P =.241). FRCpvalues were in the upper normal range and increased from 6 to 12 months (22.5 and 25.4 mL/kg respectively, P =.010). Mean (SD) V′maxFRCwas below the norm without significant change in SD scores from 6 to 12 months (- 1.9 and - 2.3, respectively, P =.248). Neither lung function nor type of repair was associated with clinical evolution up to 2 years. Conclusion: Lung function during the first year was similar in EA infants repaired by thoracotomy or thoracoscopy. Ongoing follow-up including pulmonary function testing is needed to determine whether differences occur at a later age in this cohort.

Lung Function of Infants with Congenital Lung Lesions in the First Year of Life. (Article)

2012-10-23T00:00:00Z

Background: Several studies have evaluated short-term neonatal outcome in infants with congenital lung lesions (CLL) but clinical course and lung function in the longer term have not yet been documented. We hypothesized that clinical course and lung function would be negatively affected by surgical resection. Objective: To evaluate respiratory symptoms and lung function longitudinally in the first year of life in infants with CLL, and to analyse differences herein between infants managed by observation only and infants whose affected lung parts were resected. Methods: We evaluated respiratory symptoms and lung function at 6 and 12 months in 30 patients with CLL. Functional residual capacity (FRCp) and maximal expiratory flow at functional residual capacity (V′maxFRC) were measured with body plethysmography. SD scores were calculated for V′maxFRC. Results: Prevalence of respiratory symptoms did not differ between the groups. Mean FRCp(95% CI) was 25.3 (23.3-27.3) in the group managed by observation versus 27.3 (25.1-29.6) in the group managed by surgery (p = 0.149). Mean (95% CI) SDS V′maxFRC was -1.45 (-1.84 to -1.06) versus -1.41 (-1.90 to -0.91) (p = 0.892). Lung function did not change significantly over the 6-month period. Conclusion: Surgical resection did not seem to have negatively affected the clinical course and lung function. We recommend pulmonary follow-up of all CLL patients into adulthood to further identify any long-term effects of CLL and observation or surgery. Copyright

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: An open-label single-center study (Article)

2012-09-28T00:00:00Z

Abstract. Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods. Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3-6 months and analyzed using repeated-measures ANOVA. Results: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (-1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC. Conclusions: We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.

The influence of Mechanical bowel preparation in elective colorectal surgery for diverticulitis (Article)

2012-08-01T00:00:00Z

Background: Mechanical bowel preparation (MBP) has been shown to have no influence on the incidence of anastomotic leakage in overall colorectal surgery. The role of MBP in elective surgery in combination with an inflammatory component such as diverticulitis is yet unclear. This study evaluates the effects of MBP on anastomotic leakage and other septic complications in 190 patients who underwent elective surgery for colonic diverticulitis. Methods: A subgroup analysis was performed in a prior multicenter (13 hospitals) randomized trial comparing clinical outcome of MBP versus no MBP in elective colorectal surgery. Primary endpoint was the occurrence of anastomotic leakage in patients operated on for diverticulitis, and secondary endpoints were septic complications and mortality. Results: Out of a total of 1,354 patients, 190 underwent elective colorectal surgery (resection with primary anastomosis) for (recurrent or stenotic) diverticulitis. One hundred and three patients underwent MBP prior to surgery and 87 did not. Anastomotic leakage occurred in 7.8 % of patients treated with MBP and in 5.7 % of patients not treated with MBP (p = 0.79). There were no significant differences between the groups in septic complications and mortality. Conclusion: Mechanical bowel preparation has no influence on the incidence of anastomotic leakage, or other septic complications, and may be safely omitted in case of elective colorectal surgery for diverticulitis.

Correlation between radiological assessment of acute ankle fractures and syndesmotic injury on MRI (Article)

2012-07-01T00:00:00Z

Objective: Owing to the shortcomings of clinical examination and radiographs, injury to the syndesmotic ligaments is often misdiagnosed. When there is no indication requiring that the fractured ankle be operated on, the syndesmosis is not tested intra-operatively, and rupture of this ligamentous complex may be missed. Subsequently the patient is not treated properly leading to chronic complaints such as instability, pain, and swelling. We evaluated three fracture classification methods and radiographic measurements with respect to syndesmotic injury. Materials and methods: Prospectively the radiographs of 51 consecutive ankle fractures were classified according to Weber, AO-Müller, and Lauge-Hansen. Both the fracture type and additional measurements of the tibiofibular clear space (TFCS), tibiofibular overlap (TFO), medial clear space (MCS), and superior clear space (SCS) were used to assess syndesmotic injury. MRI, as standard of reference, was performed to evaluate the integrity of the distal tibiofibular syndesmosis. The sensitivity and specificity for detection of syndesmotic injury with radiography were compared to MRI. Results: The Weber and AO-Müller fracture classification system, in combination with additional measurements, detected syndesmotic injury with a sensitivity of 47% and a specificity of 100%, and Lauge-Hansen with both a sensitivity and a specificity of 92%. TFCS and TFO did not correlate with syndesmotic injury, and a widened MCS did not correlate with deltoid ligament injury. Conclusion: Syndesmotic injury as predicted by the Lauge-Hansen fracture classification correlated well with MRI findings. With MRI the extent of syndesmotic injury and therefore fracture stage can be assessed more accurately compared to radiographs.

Exercise capacity, daily activity, and severity of fatigue in term born young adults after neonatal respiratory failure (Article)

2012-06-26T00:00:00Z

Little is known about long-term effects of neonatal intensive care on exercise capacity, physical activity, and fatigue in term borns. We determined these outcomes in 57 young adults, treated for neonatal respiratory failure; 27 of them had congenital diaphragmatic hernia with lung hypoplasia (group 1) and 30 had normal lung development (group 2). Patients in group 2 were age-matched, with similar gestational age and birth weight, and similar neonatal intensive care treatment as patients in group 1. All patients were born before the era of extracorporeal membrane oxygenation, nitric oxide administration, and high frequency ventilation. Exercise capacity was measured by cycle ergometry, daily physical activity with an accelerometry-based activity monitor, and fatigue by the fatigue severity scale. Median (range) VO2peakin mL/kg/min was 35.4 (19.6-55.0) in group 1 and 37.6 (15.7-52.7) in group 2. There was a between-group P-value of 0.65 for exercise capacity. Daily activity and fatigue were also similar in both groups. So, residual lung hypoplasia did not play an important role in this cohort. There were no significant associations between exercise capacity and perinatal characteristics. Future studies need to elucidate whether exercise capacity is impaired in patients with more severe lung hypoplasia who nowadays survive.

Prospective longitudinal evaluation of lung function during the first year of life after repair of congenital diaphragmatic hernia (Article)

2012-05-01T00:00:00Z

OBJECTIVE: To evaluate lung function and respiratory morbidity prospectively during the first year of life in patients with congenital diaphragmatic hernia and to study the effect of extracorporeal membrane oxygenation therapy. DESIGN: Prospective longitudinal cohort study. SETTING: Outpatient clinic of a tertiary-level pediatric hospital. PATIENTS: The cohort of 43 infants included 12 patients treated with extracorporeal membrane oxygenation. Evaluation was at 6 and 12 months; 33 infants were evaluated at both time points. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximal expiratory flow at functional residual capacity and functional residual capacity were measured with Masterscreen Babybody. Z-scores were calculated for maximal expiratory flow at functional residual capacity. Mean maximal expiratory flow at functional residual capacity values at 6 and 12 months were significantly below the expected values (mean z-score -1.4 and -1.5, respectively) without a significant change between both time points. Values did not significantly differ between extracorporeal membrane oxygenation and nonextracorporeal membrane oxygenation-treated patients. Functional residual capacity values were generally high, 47% were above the suggested normal range, and did not change significantly over time. Mean functional residual capacity values in extracorporeal membrane oxygenation-treated patients were significantly higher than in nonextracorporeal membrane oxygenation-treated patients (p = .006). The difference (5.1 mL/kg ± 1.8 SE) did not change significantly between the two time points. Higher mean airway pressure and longer duration of ventilation were associated with higher functional residual capacity. None of the perinatal characteristics was associated with maximal expiratory flow at functional residual capacity. Mean weight z-scores were significantly below zero at both time points (p < .001). Mean weight z-score in extracorporeal membrane oxygenation-treated patients were lower than in nonextracorporeal membrane oxygenation-treated patients (p = .046). CONCLUSIONS: Infants with congenital diaphragmatic hernia have decreased expiratory flows and increased functional residual capacity within the first year of life. Extracorporeal membrane oxygenation-treated patients with congenital diaphragmatic hernia may have more respiratory morbidity and concomitant growth impairment. Close follow-up beyond the neonatal period is therefore required. Copyright

Lung function in young adults with congenital diaphragmatic hernia; A longitudinal evaluation (Article)

2012-03-27T00:00:00Z

Background: Survival rates of patients with congenital diaphragmatic hernia (CDH) have improved to up to 80%. Little is known about long-term consequences of the disease and its treatment. We evaluated lung function and respiratory symptoms longitudinally in a previously studied cohort of CDH patients and age-matched non-CDH patients who underwent similar neonatal intensive care treatment. Study Design: We tested 27 young adults [mean (SD) age: 26.8 years (2.9)] with CDH and 30 non-CDH patients. Dynamic and static lung volumes, midexpiratory flows, and diffusion capacity were expressed as mean (SD) standard deviation scores. Prevalence of respiratory symptoms was evaluated with the European Community Respiratory Health Survey. Results: All data are expressed as mean (SD). FEF25-75in CDH patients had slightly deteriorated since childhood (CDH: -0.7 (1.4) vs. -1.6 (1.5), P<0.001; non-CDH patients: 0.2 (1.4) vs. -0.3 (1.6), P=0.038, ns). Diffusion capacity decreased in both groups (CDH: DLCOc 0.2 (1.1) vs. -1.5 (1.1), P<0.001; non-CDH: DLCOc 0.1 (0.4) vs. -1.1 (1.1), P<0.001). Lung volumes were normal in both groups. The prevalence of asthma was higher than in the normal population (27.6% in patients and 30% in controls, P<0.001). Conclusions: Airflow obstruction and diffusion capacity deteriorated mildly from childhood into adulthood in survivors of CDH. The improved survival of patients with more severe forms of diaphragmatic hernia calls for long-term follow-up of lung function.

Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: Pregnancy complications and neonatal sequelae in untreated and treated pregnancies (Article)

2012-02-01T00:00:00Z

Background: Untreated maternal phenylketonuria or hyperphenylalaninemia may result in nonphenylketonuric offspring with neonatal sequelae, especially intellectual disability, microcephaly, and congenital heart disease (CHD). Dietary treatment to control phenylalanine concentrations can prevent these sequelae. Objective: We aimed to present an overview of reported pregnancy complications and neonatal sequelae of maternal phenylketonuria or hyperphenylalaninemia in untreated and treated pregnancies. Design: A MEDLINE and EMBASE search was conducted for case reports and case series that assessed maternal phenylketonuria or hyperphenylalaninemia during pregnancy. Pregnancy complications (spontaneous abortion, intrauterine-fetal-death, and preterm delivery) and neonatal sequelae [small for gestational age (SGA), microcephaly, CHD, intellectual or developmental disabilities (IDDs), and facial dysmorphism (FD)] were analyzed. Fifteen unpublished pregnancies from our clinic were added. Results: We retrieved 196 pregnancies, of which 126 pregnancies were untreated and 70 pregnancies were treated. The occurrence of pregnancy complications was not significantly different between untreated and treated pregnancies. Except for SGA, all neonatal sequelae were more frequent in untreated pregnancies. Moreover, the occurrence of SGA, microcephaly, and IDDs was significantly related to the mean phenylalanine concentration in each trimester, whereas the occurrence of FD was related only to the first trimester. Conclusions: We present the largest cohort of untreated pregnant women with phenylketonuria or hyperphenylalaninemia since 1980. The results follow the general pattern reported by other researchers. We underline that the treatment of pregnant women with phenylketonuria or hyperphenylalaninemia is of great importance to prevent neonatal sequelae. We strongly recommend starting treatment before conception because we showed the deleterious effect of an increased mean first-trimester phenylalanine concentration on FD.

Reproducibility of echocardiographic measurements of human fetal left ventricular volumes and ejection fractions using four-dimensional ultrasound with the spatio-temporal image correlation modality (Article)

2012-01-01T00:00:00Z

Objectives: To determine the reproducibility, both reliability and agreement, of measurements of fetal left ventricular parameters from volumes obtained by spatio-temporal image correlation (STIC) acquisition applying virtual organ computer-aided analysis (VOCAL) and Simpson's rule (method of discs). Furthermore the success rate of STIC acquisition was determined. Study design: In 84 pregnancies between 20 and 34 weeks of gestation the fetal heart was scanned using the STIC modality. An optimal four-chamber view in end-diastole and end-systole was obtained. Left ventricular end-diastolic volume, left ventricular end-systolic volume, stroke volume and ejection fraction were determined. For calculations based on Simpson's rule only one plane was traced, whereas for VOCAL six planes were traced. To quantify the reliability intraclass correlation coefficients were calculated for both intra- and inter-observer measurements. Agreement of measurements was evaluated by Bland-Altman plots. Results: The STIC volumes of 54 women (64%) were excluded from the study because of poor quality, leaving 30 volumes for further analysis. Intraclass correlation coefficients for intra-observer reliability for VOCAL and Simpson were 0.99 and 0.99 for left ventricular end-diastolic volume, 0.95 and 0.92 for left ventricular end-systolic volume, 0.98 and 0.97 for stroke volume, 0.76 and 0.77 for ejection fraction, respectively. Intraclass correlation coefficients for inter-observer reliability for VOCAL and Simpson were 0.97 and 0.86 for left ventricular end-diastolic volume, 0.97 and 0.86 for left ventricular end-systolic volume, 0.95 and 0.81 for stroke volume, 0.68 and 0.63 for ejection fraction, respectively. According to Bland-Altman plots, the mean percentage difference and 95% limits of intra- and inter-observer agreement for left ventricular stroke volume measurements using VOCAL were -0.2 (-25.1, 24.7)% and 2.8 (-34.2, 39.8)%, respectively. For left ventricular stroke volume measured with Simpson versus VOCAL the mean percentage difference and 95% limits of agreement were -1.8 (-22.1, 18.5)%. Conclusions: 4D STIC enables reproducible measurements of left ventricular volumes. Reliability of the VOCAL mode is not essentially different from the single-plane method used in Simpson's rule. The large percentage of poor quality STIC volumes and the wide limits of inter-observer agreement would create obstacles for the clinical applicability of this technique.

B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency (Article)

2011-12-22T00:00:00Z

Common variable immunodeficiency disorder (CVID) is the most prevalent form of primary idiopathic hypogammaglobulinemia. Identification of genetic defects in CVID is hampered by clinical and immunologic heterogeneity. By flow cytometric immunophenotyping and cell sorting of peripheral B-cell subsets of 37 CVID patients, we studied the B-cell compartment at the B-cell subset level using the κ-deleting recombination excision circle assay to determine the replication history and the Igκ-restriction enzyme hot-spot mutation assay to assess the somatic hypermutation status. Using this approach, 5 B-cell patterns were identified, which delineated groups with unique replication and somatic hypermutation characteristics. Each B-cell pattern reflected an immunologically homogenous patient group for which we proposed a different pathophysiology: (1) a B-cell production defect (n ∇ 8, 18%), (2) an early peripheral B-cell maturation or survival defect (n ∇ 4, 11%), (3) a B-cell activation and proliferation defect (n ∇ 12, 32%), (4) a germinal center defect (n ∇ 7, 19%), and (5) a postgerminal center defect (n ∇ 6, 16%). The results of the present study provide for the first time insight into the underlying pathophysiologic background in 5 immunologically homogenous groups of CVID patients. Moreover, this study forms the basis for larger cohort studies with the defined homogenous patient groups and will facilitate the identification of underlying genetic defects in CVID.

Bowel obstruction after laparoscopic and open colon resection for cancer: Results of 5 years of follow-up in a randomized trial (Article)

2011-12-01T00:00:00Z

Background: Postoperative bowel obstruction caused by intra-abdominal adhesions occurs after all types of abdominal surgery. It has been suggested that the laparoscopic technique should reduce the risk for adhesion formation and thus for postoperative bowel obstruction. This study was designed to compare the incidence of bowel obstruction in a randomized trial where laparoscopic and open resection for colon cancer was compared. Methods: A retrospective analysis was performed, collecting data of episodes of bowel obstruction with or without surgery. Only episodes treated in the hospital where the index surgery took place were included. Data for 786 patients were collected for the 5-year period after cancer surgery. Results: Baseline characteristics for the evaluated laparoscopic (n = 383) and open (n = 403) groups were comparable. The cumulative obstruction percentages at 5 years for the open and laparoscopic groups were 6.5 and 5.1% respectively and did not significantly differ from each other. Tumor stage seemed to influence the risk for bowel obstruction: 2.8% in stage I, 6.6% in stage II, and 7% in stage III, but the differences were not significant. Conclusions: This analysis does not support the hypothesis that laparoscopy leads to fewer episodes of bowel obstruction compared with open surgery.

The VICI-trial: High frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: An international multicentre randomized controlled trial (Article)

2011-11-02T00:00:00Z

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high frequency oscillatory ventilation (HFO) to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to be associated with worse outcome. We therefore aimed to develop a randomized controlled trial to compare initial ventilatory treatment with high-frequency oscillation and conventional ventilation in infants with CDH.Methods/design: This trial is designed as a multicentre trial in which 400 infants (200 in each arm) will be included. Primary outcome measures are BPD, described as oxygen dependency by day 28 according to the definition of Jobe and Bancalari, and/or mortality by day 28. All liveborn infants with CDH born at a gestational age of over 34 weeks and no other severe congenital anomalies are eligible for inclusion. Parental informed consent is asked antenatally and the allocated ventilation mode starts within two hours after birth. Laboratory samples of blood, urine and tracheal aspirate are taken at the first day of life, day 3, day 7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung injury and pulmonary hypertension.Discussion: To date, randomized clinical trials are lacking in the field of CDH. The VICI-trial, as the first randomized clinical trial in the field of CDH, may provide further insight in ventilation strategies in CDH patient. This may hopefully prevent mortality and morbidity.Trial registration: Netherlands Trial Register (NTR): NTR1310.

Gestational sac fluid volume measurements in virtual reality (Article)

2011-11-01T00:00:00Z

Objectives: To evaluate a virtual reality (VR) application for gestational sac fluid volume (GSFV) measurements in first-trimester pregnancies and to study the correlation between different embryonic growth parameters. Methods: This was a prospective cohort study analyzing 180 three-dimensional (3D) ultrasound scans of 42 healthy women, performed between 5 +5 and 12 + 6 weeks' gestational age (GA). The 3D datasets were transferred to the I-Space immersive VR system. The V-Scope application was used to create a 'hologram' of the ultrasound image, allowing depth perception and interaction with the rendered objects. Volumes were measured semi-automatically using a segmentation algorithm. In addition to the GSFV, the total gestational sac volume (GSV) and its diameter (GSD) were measured. The GSV was also calculated using the ellipsoid formula. Previously obtained measurements of embryonic volume and crown-rump length (CRL) were included in the study. The outcomes were analyzed using repeated-measures analysis of variance. Results: The GSFV was measured in 78 scans, and varied from 434 to 81 491 mm3. A positive correlation between GSFV and GA, CRL and GSD was found. Comparison of the GSD formula constructed in our study in relation to GA with a formula that is commonly used clinically showed an increasing difference with increasing GA either side of 8 + 5 weeks. The GSFV/embryonic volume ratio showed a decrease with GA. The GSV calculated using the ellipsoid formula was on average 19.8% larger compared with the GSV measured in VR. Conclusion: New charts for first-trimester GSFV were constructed using VR. These growth charts could be promising tools for studying normal and abnormal embryonic development. Copyright

Validation of a web-based version of the asthma control test and childhood asthma control test (Article)

2011-10-01T00:00:00Z

Rationale Recent guidelines focus on adjusting asthma treatment to the level of asthma control. The availability of a web-based asthma control questionnaire offers the possibility to assess asthma control without the need of outpatient clinic visits. The aim of this study was to evaluate the agreement between web-based and paper-based versions of the Asthma Control Test (ACT) and Childhood Asthma Control Test (C-ACT), short-term reproducibility and satisfaction with both versions. Methods One hundred seventy-three children with stable asthma and a normal lung function were randomized to fill in a web-based or paper-based version of the C-ACT (4-11 years) or ACT (12-18 years). According to a cross-over design, they completed the opposite version after 1 week. Reproducibility was evaluated by repeating the 2nd version (web- or paper-based) 7 days later. Results Eighty-eight children filled in the C-ACT, 68 children filled in the ACT. Intraclass Correlation Coefficient (ICC) for web-based versus paper-based C-ACT was 0.81 (95% confidence interval [95% CI] 0.72-0.87). For ACT this was 0.84 (95% CI 0.76-0.90). For web-based and paper-based C-ACT the reproducibility ICC was 0.82 (95% CI 0.67-0.90) and 0.75 (95% CI 0.59-0.85), respectively. The reproducibility ICC of the ACT for web- and paper-based versions was 0.93 (95% CI 0.87-0.97) and 0.77 (95% CI 0.59-0.88), respectively. Eighty-six percent of patients preferred the web-based version. Conclusion The web-based version of the C-ACT and ACT is reproducible and comparable with the paper-based version in assessing asthma control. Most children and their parents prefer the web-based version. Copyright

Comparing Global Initiative for Asthma (GINA) criteria with the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT) (Article)

2011-09-01T00:00:00Z

Several tools are useful in detecting uncontrolled asthma in children. The aim of this study was to compare Global Initiative for Asthma (GINA) guidelines with the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) in detecting uncontrolled asthma in children. 145 children with asthma filled in a web-based daily diary card for 4 weeks on symptoms, use of rescue medication and limitations of activities, followed by either the C-ACT or ACT. For predicting uncontrolled asthma, score cut-off points of 19 were used for C-ACT and ACT. According to GINA guidelines, asthma was uncontrolled in 71 (51%) children and completely controlled in 19 (14%) children. The area under the curve in the receiver operating characteristic curves for C-ACT and ACT versus GINA guidelines were 0.89 and 0.92, respectively. Cut-off points of 19 for C-ACT and ACT resulted in a sensitivity of 33% and 66% in predicting uncontrolled asthma, respectively. C-ACT and ACT correlate well with GINA criteria in predicting uncontrolled asthma, but commonly used cut-off points for C-ACT and ACT seem to underestimate the proportion of children with uncontrolled asthma as defined by GINA. Copyright

MRI evaluation of urethral diverticula and differential diagnosis in symptomatic women (Article)

2011-09-01T00:00:00Z

OBJECTIVE. The purpose of this study was to evaluate the role of MRI in the diagnosis and differential diagnosis of urethral diverticula in symptomatic women. MATERIALS AND METHODS. Women referred for MRI at a single institution because of suspicion of urethral diverticula were included. All MRI examinations were independently evaluated by two radiologists and compared with patients' follow-up data. Sensitivity and specificity of MRI for urethral diverticula were calculated using surgery and clinical confirmation as the reference standards. Image quality of the urethra and periurethral region performed with the endoluminal coil was compared with the pelvic phased-array coil. RESULTS. From a study group of 60 patients (mean age, 44 years), 20 patients (33%) had urethral diverticula and 28 (47%) had an alternative diagnosis, of which 13 (46%) were visualized with MRI. In the remaining 12 patients (20%) no abnormalities were found. For urethral diverticula, MRI had both sensitivity and specificity of 100%. Twenty patients had a total of 27 diverticula; these were mostly locally round (n = 12) with sharp margins (n = 25) and high (n = 19) homogeneous (n = 16) signal intensity on T2- weighted sequences. The ostium of urethral diverticula was identified in 23 diverticula (85%) by both readers. Agreement was 93% with κ = 0.72. Endoluminal coil placement in the vagina showed the best image quality of the urethra and periurethral region. CONCLUSION. Dedicated MRI is an excellent imaging modality for urethral diverticula; furthermore, MRI will show the alternative diagnosis in almost one half of the remaining patients.

Rate of progression and predictive factors for pulmonary outcome in children and adults with Pompe disease (Article)

2011-09-01T00:00:00Z

Respiratory insufficiency is a serious threat to patients with Pompe disease, a neuromuscular disorder caused by lysosomal acid alpha-glucosidase deficiency. Innovative therapeutic options which may stabilize pulmonary function have recently become available. We therefore determined proportion and severity of pulmonary involvement in patients with Pompe disease, the rate of progression of pulmonary dysfunction, and predictive factors for poor respiratory outcome.In a single-center, prospective, cohort study, we measured vital capacity (VC) in sitting and supine positions, as well as maximum inspiratory (MIP) and expiratory (MEP) mouth pressures, and end expiratory CO2in 17 children and 75 adults with Pompe disease (mean age 42.7years, range 5-76years).Seventy-four percent of all patients, including 53% of the children, had some degree of respiratory dysfunction. Thirty-eight percent had obvious diaphragmatic weakness.Males appeared to have more severe pulmonary involvement than females: at a group level, their mean VC was significantly lower than that of females (p < 0.001), they used mechanical ventilation more often than females (p = 0.042) and the decline over the course of the disease was significantly different between males and females (p = 0.003). Apart from male gender, severe skeletal muscle weakness and long disease duration were the most important predictors of poor respiratory status. During follow-up (average 1.6. years, range 0.5-4.2. years), three patients became ventilator dependent. Annually, there were average decreases in VC in upright position of 0.9% points (p = 0.09), VC in supine position of 1.2% points (p = 0.049), MIP of 3.2% points (p = 0.018) and MEP of 3.8% points (p < 0.01).We conclude that pulmonary dysfunction in Pompe disease is much more common than generally thought. Males, patients with severe muscle weakness, and those with advanced disease duration seem most at risk.

Bronchiectasis and pulmonary exacerbations in children and young adults with cystic fibrosis (Article)

2011-07-01T00:00:00Z

Objective: Respiratory tract exacerbation rate (RTE-R) is a key clinical efficacy end point in cystic fibrosis (CF) trials. Chest CT scanning holds great potential as a surrogate end point. Evidence supporting the ability of CT scan scores to predict RTE-R is an important step in validating CT scanning as a surrogate end point. The objective of this study was to investigate the association between CT scan scores and RTE-R in a cohort of pediatric patients with CF. Methods: A retrospective review of data from pediatric patients with CF included chest CT scans, spirometry, and 2 years follow-up. RTE-R was defined as the number of IV antibiotics courses per year. CT scans were scored with the Brody-II system, assessing bronchiectasis, airway wall thickening, mucus, and opacities. Results: One hundred fifteen patients contributed 170 CT scans. Median age and FEV1at first CT scan were 12 years (range, 5-20 years) and 90% predicted (range, 23% predicted-132% predicted), respectively. Analyzing exacerbation counts using Poisson regression models, bronchiectasis score and FEV1both were found to be strong independent predictors of RTE-R in the subsequent 2 years. For the bronchiectasis score categorized in quartiles, RTE-R increased by factors of 1.8 (95% CI, 0.6-6.1; P =.31), 5.5 (95% CI, 1.9-15.4; P =.001), and 10.6 (95% CI, 3.8-29.4; P <.001), respectively, for each quartile compared with the quartile with the best (ie, lowest) scores. Similarly, time to first respiratory tract exacerbation was significantly associated with quartiles of both bronchiectasis score and FEV1. Conclusions: The CT scan bronchiectasis score is strongly associated with RTE-R in pediatric patients with CF, providing an important piece of evidence in the validation of CT scans as an end point for CF clinical trials.

Transanal endoscopic microsurgery is superior to transanal excision of rectal adenomas (Article)

2011-07-01T00:00:00Z

Aim Comparison of transanal excision (TE) and transanal endoscopic microsurgery (TEM) of rectal adenomas (RA) has rarely been performed. Method From 1990 to 2007, the results of TE (43 RA) and TEM (216 RA) were compared. Rectal adenomas were matched for diameter and distance from the anal verge. Results Operation time was 47.5min for TE and 35min for TEM (P<0.001). Morbidity was 10% after TE and 5.3% after TEM (P<0.001). Negative resection margins were observed in 50% after TE and 88% after TEM (P<0.001). Fragmentation of the excised specimen was observed in 23.8% after TE and 1.4% after TEM (P<0.001). In cases of fragmentation, positive resection margins were observed more frequently. Recurrence was 28.7% after TE and 6.1% after TEM (P<0.001). After TE, RA with a negative resection margin had a local recurrence rate of 0%, compared with 59.6% with a positive margin (P<0.001), and after TEM these rates were 3.2 and 7.7% (P=0.3), respectively. Conclusion Transanal endoscopic microsurgery is superior to transanal excision of RA. © 2011 The Authors. Colorectal Disease

Scoring the proliferative activity of haemangioma of infancy: The Haemangioma Activity Score (HAS) (Article)

2011-06-14T00:00:00Z

Background. Haemangioma of infancy (HOI) is the most frequently occurring benign tumour of infancy. A good, reliable and objective scoring system for haemangioma activity is not yet available. Aim. We have developed a simple system called the Haemangioma Activity Score (HAS) for scoring the (disease) proliferative activity of haemangiomas. The current study was undertaken to validate this system. Methods. We validated the HAS in a comparative study of photographs taken during consultations from 2000 until 2008 (n=78). Agreement between three observers was assessed at two different time points (t0and t1) with a minimum interval of 6months between them, using interclass correlation coefficients (ICC). Results. Agreement between observers was good. The average ICC of the HAS at t0and t1was 0.72 and 0.76, respectively. The average ICC of the HAS for the changes from baseline (HAS at t0minus HAS at t1) was 0.69. Conclusions. We conclude that the HAS is a good system for scoring the proliferative activity of haemangiomas, and believe it to be useful in future investigations. The number of studies comparing different therapies for treating haemangiomas is steadily increasing, and the HAS (before and after treatment) may provide a valuable scoring system for evaluating such therapies. © The Author(s). CED

Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy (Article)

2011-06-03T00:00:00Z

Background: Pompe disease is a rare lysosomal storage disorder characterized by muscle weakness and wasting. The majority of adult patients have slowly progressive disease, which gradually impairs mobility and respiratory function and may lead to wheelchair and ventilator dependency. It is as yet unknown to what extent the disease reduces the life span of these patients. Our objective was to determine the survival of adults with Pompe disease not receiving ERT and to identify prognostic factors associated with survival. Methods. Data of 268 patients were collected in a prospective international observational study conducted between 2002 and 2009. Survival analyses from time of diagnosis and from time of study entry were performed using Kaplan-Meier curves and Cox-proportional-hazards regression. Results: Median age at study entry was 48 years (range 19-79 years). Median survival after diagnosis was 27 years, while median age at diagnosis was 38 years. During follow-up, twenty-three patients died prior to ERT, with a median age at death of 55 (range 23-77 years). Use of wheelchair and/or respiratory support and patients' score on the Rotterdam Handicap Scale (RHS) were identified as prognostic factors for survival. Five-year survival for patients without a wheelchair or respiratory support was 95% compared to 74% in patients who were wheelchair-bound and used respiratory support. In a Dutch subgroup of 99 patients, we compared the observed number of deaths to the expected number of deaths in the age- and sex-matched general population. During a median follow-up of 2.3 years, the number of deaths among the Dutch Pompe patients was higher than the expected number of deaths in the general population. Conclusion: Our study shows for the first time that untreated adults with Pompe disease have a higher mortality than the general population and that their levels of disability and handicap/participation are the most important factors associated with mortality. These results may be of relevance when addressing the effect of ERT or other potential treatment options on survival.

Tibiofibular syndesmosis in acute ankle fractures: additional value of an oblique MR image plane (Article)

2011-05-02T00:00:00Z

Objective: To evaluate the additional value of a 45° oblique MRI scan plane for assessing the anterior and posterior distal tibiofibular syndesmotic ligaments in patients with an acute ankle fracture. Materials and methods: Prospectively, data were collected for 44 consecutive patients with an acute ankle fracture who underwent a radiograph (AP, lateral, and mortise view) as well as an MRI in both the standard three orthogonal planes and in an additional 45° oblique plane. The fractures on the radiographs were classified according to Lauge-Hansen (LH). The anterior (ATIFL) and posterior (PTIFL) distal tibiofibular ligaments, as well as the presence of a bony avulsion in both the axial and oblique planes was evaluated on MRI. MRI findings regarding syndesmotic injury in the axial and oblique planes were compared to syndesmotic injury predicted by LH. Kappa and the agreement score were calculated to determine the interobserver agreement. The Wilcoxon signed rank test and McNemar's test were used to compare the two scan planes. Results: The interobserver agreement (κ) and agreement score [AS (%)] regarding injury of the ATIFL and PTIFL and the presence of a fibular or tibial avulsion fracture were good to excellent in both the axial and oblique image planes (κ 0.61-0.92, AS 84-95%). For both ligaments the oblique image plane indicated significantly less injury than the axial plane (p < 0.001). There was no significant difference in detection of an avulsion fracture in the axial or oblique plane, neither anteriorly (p = 0.50) nor posteriorly (p = 1.00). With syndesmotic injury as predicted by LH as comparison, the specificity in the oblique MR plane increased for both anterior (to 86% from 7%) and posterior (to 86% from 48%) syndesmotic injury when compared to the axial plane. Conclusion: Our results show the additional value of an 45° oblique MR image plane for detection of injury of the anterior and posterior distal tibiofibular syndesmoses in acute ankle fractures. Findings of syndesmotic injury in the oblique MRI plane were closer to the diagnosis as assumed by the Lauge-Hansen classification than in the axial plane. With more accurate information, the surgeon can better decide when to stabilize syndesmotic injury in acute ankle fractures.

Actual outcome in infants with congenital diaphragmatic hernia: The role of a standardized postnatal treatment protocol (Article)

2011-04-01T00:00:00Z

Introduction: The lung-to-head ratio (LHR), measured by ultrasound, and the fetal lung volume (FLV), measured by MRI, are both used to predict survival and need for extra corporeal membrane oxygenation (ECMO) in infants with congenital diaphragmatic hernia (CDH). The aim of this study is to determine whether MRI measurements of the FLV, in addition to standard ultrasound measurements of the LHR, give better prediction of chronic lung disease, mortality by day 28 and need for ECMO. Materials and methods: Patients with unilateral isolated CDH born between January 2002 and December 2008 were eligible for inclusion. LHR and FLV were expressed as observed-to-expected values (O/E LHR and O/E FLV). Univariate and multivariate analyses were performed. Receiver operating characteristic curves were constructed and areas under the curve (AUC) were calculated to determine predictive values. Results: 90 patients were included in the analysis. Combined measurement of the O/E LHR and O/E FLV gave a slightly better prediction of chronic lung disease (AUC = 0.83 and AUC = 0.87) and need for ECMO therapy (AUC = 0.77 and AUC = 0.81) than standard ultrasound measurements of the O/E LHR alone. Combined measurement of the O/E LHR and O/E FLV did not improve prediction of early mortality (AUC = 0.90) compared to measurement of the O/E LHR alone (AUC = 0.89). An intrathoracal position of the liver was independently associated with a higher risk of early mortality (p < 0.001), chronic lung disease (p = 0.007) and need for ECMO therapy (p = 0.001). Discussion: Chronic lung disease and need for ECMO therapy are slightly better predicted by combined measurement of the O/E LHR and the O/E FLV. Early mortality is very well predicted by measurement of the O/E LHR alone. Conclusion: Clinical relevance of additional MRI measurements may be debated.

Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial (Article)

2011-04-01T00:00:00Z

Background Methotrexate and fumarates are effective systemic therapies for moderate to severe psoriasis according to the European S3 guidelines. Objectives We conducted a randomized controlled trial comparing the effectiveness and the adverse events of methotrexate and fumarates. Methods Sixty patients with moderate to severe psoriasis vulgaris were randomly assigned to treatment for 16 weeks with either methotrexate (30 patients; 15 mg per week) or fumarates (30 patients; 30 mg, followed by 120 mg according to a standard progressive dosage regimen) and were followed up for 4 weeks. The primary endpoint with respect to the efficacy was the difference in mean change from baseline in Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment. The study was powered to detect a difference of five points. Analyses were by intention to treat. Results Six patients were excluded because five were not eligible and one withdrew consent. Two patients in the methotrexate group and one in the fumarate group dropped out during the 12 weeks of treatment because of nonappearance at the outpatient clinic. In total, 25 patients in the methotrexate group and 26 in the fumarate group were evaluated in the primary analysis. After 12 weeks of treatment, the mean ± SD PASI decreased from 14·5 ± 3·0 at baseline to 6·7 ± 4·5 in the 25 patients treated with methotrexate, whereas it decreased from 18·1 ± 7·0 to 10·5 ± 6·7 in the 26 patients treated with fumarates. After adjustment for baseline values, the absolute difference (fumarates minus methotrexate) in the mean values at 12 weeks was 1·4 (95% confidence interval −2·0 to 4·7; P = 0·417). Conclusions In this randomized trial methotrexate and fumarates were found to be equally effective in the treatment of patients with moderate to severe psoriasis. No serious or irreversible adverse events were observed in any of the patients.

Maternal and fetal haemodynamic effects of nifedipine in normotensive pregnant women (Article)

2011-03-01T00:00:00Z

While nifedipine is commonly used for tocolysis, the controversy on its safety remains. So far, the haemodynamic effects on maternal and fetal circulations have not been well documented. Fifteen normotensive women who received 20 mg nifedipine were included in this prospective observational study. The maternal and fetal haemodynamic effects were analysed using maternal echocardiography and fetal Doppler ultrasonography. Nifedipine induced a significant afterload reduction in all women. It triggered a compensatory increase in cardiac output, which maintained blood pressure. These maternal changes had no influence on the uteroplacental and fetal circulations.

Evaluation of interrupter resistance in methacholine challenge testing in children (Article)

2011-03-01T00:00:00Z

Bronchial hyperresponsiveness (BHR) is a key feature of asthma and is assessed using bronchial provocation tests. The primary outcome in such tests (a 20% decrease in forced expiratory volume in 1 sec (FEV1)) is difficult to measure in young patients. This study evaluated the sensitivity and specificity of the interrupter resistance (Rint) technique, which does not require active patient participation, by comparing it to the primary outcome measure. Methacholine challenge tests were performed in children with a history of moderate asthma and BHR. Mean and individual changes in R int and FEV1 were studied. A receiver operating characteristic (ROC) curve was used to describe sensitivity and specificity of Rint. Seventy-three children (median age: 9.2 years; range: 6.3-13.4 years) participated. There was a significant (P<0.01) increase in mean Rint with increasing methacholine doses. However, individual changes of R int showed large fluctuations. There was great overlap in change of Rint between children who did and did not reach the FEV1 endpoint. A ROC curve showed an area under the curve of 0.65. Because of low sensitivity and specificity, the use of Rint to diagnose BHR in individual patients seems limited.

Germline variation in the MTHFR and MTRR genes determines the nadir of bone density in pediatric acute lymphoblastic leukemia: A prospective study (Article)

2011-03-01T00:00:00Z

Background: This study aims to identify folate-metabolism-related genetic risk factors for low bone mineral density (BMD) during/after pediatric acute lymphoblastic leukemia (ALL) treatment. Patients and methods: We investigated the influence of methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) and methionine synthase reductase (MTRR 66A>G) single nucleotide polymorphisms (SNPs) on total body BMD (BMDTB) and lumbar spine BMD (BMDLS) in 83 patients. Homocysteine, folate and vitamin B12 were determined. BMD was measured repeatedly using dual-energy X-ray absorptiometry in patients ≥4years (n=68). Results: Carriers of the MTHFR 677 T-allele showed a lower baseline BMDTBthan non-carriers (-0.38 SDS vs. +0.55 SDS, p=0.01) and BMDTBremained lower during/after treatment. MTHFR 677C>T did not influence treatment-related loss of BMDTB(p=0.39). The MTRR 66 G-allele carriers showed a trend towards a lower BMDTBcompared with non-carriers. Combining these two SNPs, patients carrying ≥2 risk alleles had a significantly lower BMDTB(-1.40 SDS) than patients with one (-0.80 SDS) or no risk alleles (-0.31 SDS). Although carriers of the MTHFR 1298A>C had higher homocysteine levels, this SNP was not related to BMDTB. BMDLSof carriers was similar to non-carriers of the investigated SNPs. Conclusions: The MTHFR 677C>T SNP and the MTRR 66A>G SNP were identified as determinants of impaired BMDTBin childhood ALL patients.

Long-term survival after perforated diverticulitis (Article)

2011-02-01T00:00:00Z

Aim: Short-term survival after emergency surgery for perforated diverticulitis is poor. Less is known about long-term survival. The aims of this study were to evaluate long-term survival after discharge from hospital and to identify factors associated with prognosis. Method: All patients who underwent emergency surgery for perforated diverticulitis in five hospitals in Rotterdam, the Netherlands, between 1990 and 2005, were included. The association between type of surgery (Hartmann's procedure or primary anastomosis) and long-term survival was analysed using multivariate Cox regression analysis, taking into account age American Society of Anesthesiology (ASA) classification, Hinchey score, Mannheim Peritonitis Index (MPI) and surgeon's experience. In addition, survival of the patients was compared with that of the matched general Dutch population. Results Of 340 patients included in the study, 250 were discharged alive from hospital. The overall 5-year survival was 53%. Survival was significantly impaired compared with the expected matched gender-, age- and calendar time-specific survival. Overall survival was significantly related to age and ASA classification. Hinchey score, MPI, number of re-interventions, the surgeon's experience and type of procedure did not influence long-term survival, although a trend was found for Hartmann's procedure to be a risk factor for poorer survival compared with primary anastomosis (hazard ratio for mortality: 1.88; 95% confidence interval, 0.96-3.67; P=0.07). Conclusion Long-term survival of patients after perforated diverticulitis is limited and mainly caused by the poor general condition of the patients, rather than by the severity of the primary disease or calendar-time and type of procedure.

Disturbance of glucose homeostasis after pediatric cardiac surgery (Article)

2011-02-01T00:00:00Z

This study aimed to evaluate the time course of perioperative blood glucose levels of children undergoing cardiac surgery for congenital heart disease in relation to endogenous stress hormones, inflammatory mediators, and exogenous factors such as caloric intake and glucocorticoid use. The study prospectively included 49 children undergoing cardiac surgery. Blood glucose levels, hormonal alterations, and inflammatory responses were investigated before and at the end of surgery, then 12 and 24 h afterward. In general, blood glucose levels were highest at the end of surgery. Hyperglycemia, defined as a glucose level higher than 8.3 mmol/l (>150 mg/dl) was present in 52% of the children at the end of surgery. Spontaneous normalization of blood glucose occurred in 94% of the children within 24 h. During surgery, glucocorticoids were administered to 65% of the children, and this was the main factor associated with hyperglycemia at the end of surgery (determined by univariate analysis of variance). Hyperglycemia disappeared spontaneously without insulin therapy after 12-24 h for the majority of the children. Postoperative morbidity was low in the study group, so the presumed positive effects of glucocorticoids seemed to outweigh the adverse effects of iatrogenic hyperglycemia.

Actual outcome in infants with congenital diaphragmatic hernia: The role of a standardized postnatal treatment protocol (Article)

2011-02-01T00:00:00Z

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly with a high rate of mortality and morbidity. Objective: Our aim was to determine a possible effect of standardized treatment on outcome in infants with CDH. Methods: All prenatally diagnosed patients with unilateral CDH born alive between January 2006 and December 2009 at the Erasmus MC or the University Hospital Mannheim were eligible for inclusion. Patients who underwent a fetal tracheal occlusion were excluded. From November 1, 2007, all CDH patients were treated according to a standardized treatment protocol. Patients were divided into two chronological groups according to their date of birth: without standardized treatment (group 1, Jan 2006-Oct 2007) and with standardized treatment (group 2, Nov 2007-Dec 2009). Outcome measures were mortality by day 28, bronchopulmonary dysplasia (BPD), defined as oxygen dependency at day 28, and need for extracorporeal membrane oxygenation (ECMO) therapy. Uni- and multivariate analyses were performed. Results: 167 patients were included. By day 28, 18% of the infants had died. Of the patients who were alive at day 28, 49% had BPD. An ECMO procedure was performed in 31% of the patients. Overall mortality for all included patients was 22%. In group 1, overall mortality was 33% and in group 2 overall mortality was 12% (p = 0.004). A standardized treatment protocol was independently associated with a reduced risk for mortality by day 28 (OR 0.28, 95% CI 0.11-0.68). Higher observed-to-expected lung-to-head ratios were independently associated with a lower risk for mortality by day 28 (OR 0.97, 95% CI 0.95-0.99), BPD (OR 0.97, 95% CI 0.94-0.98) and need for ECMO (OR 0.98, 95% CI 0.96-0.99). An intrathoracic position of the liver was independently associated with an increased risk for BPD (OR 3.12, 95% CI 1.41-6.90) and need for ECMO therapy (OR 3.25, 95% CI 1.54-6.88). Conclusion: Survival rates in patients with CDH increased significantly after the implementation of a standardized treatment protocol. Copyright

The use of mesh in acute hernia: frequency and outcome in 99 cases (Article)

2011-01-24T00:00:00Z

Background: Incarceration of inguinal, umbilical and cicatricial hernias is a frequent problem. However, little is known about the relationship between the use of mesh and outcome after surgery. The goal of this study was to describe the relationship between the use of mesh in incarcerated hernia and the clinical outcome. Patients and methods: Correspondence, operation reports and patient files between January 1995 and December 2005 of patients presented at one academic and one teaching hospital in Rotterdam were searched for the following keywords: incarceration, strangulation and hernia. The patient characteristics, clinical presentation, pre-operative findings and clinical course were scored and analysed. Results: A total of 203 patients could be identified: 76 inguinal, 52 umbilical, 39 incisional, 14 epigastric, 14 femoral, five trocar and three spigelian hernias. In the statistical analysis, epigastric, femoral, trocar and spigelian hernias were pooled, due to their small group sizes. One patient was excluded from the analysis because the hernia was not corrected during operation. In total, 99 hernias were repaired using mesh versus 103 primary suture repairs. Twenty-five wound infections were registered (12.3%). One mesh was removed during a reintervention for anastomotic leakage, although no signs of wound infection were present. Nine patients died, none of them due to wound-related problems [one cardiovascular, one ruptured aneurysm, two anastomotic leakage, two sepsis e causa incognita (e.c.i.), three pulmonary complications]. Univariate analysis showed that female patients (P = 0.007), adipose patients (P = 0.016), patients with an umbilical hernia (P = 0.01) and patients who underwent a bowel resection (P = 0.015) had a significantly higher rate of wound infections. The type of repair (e.g. primary suture or mesh), use of antibiotic prophylaxis, gender, ASA class and age showed no significant relation with post-operative wound infection. After logistic regression analysis, only bowel resection (P = 0.020) showed a significant relation with post-operative wound infection. Conclusions: Wound infection rates are high after the correction of acute hernia, but clinical consequences are relatively low. Mesh correction of an acute hernia seems to be safe and should be considered in every incarcerated hernia.

Maternal and fetal haemodynamic effects of nifedipine in normotensive pregnant women (Article)

2011-01-01T00:00:00Z

First trimester umbilical cord and vitelline duct measurements using virtual reality (Article)

2011-01-01T00:00:00Z

Background: The umbilical cord and vitelline duct are of vital importance to the fetus, but they are rarely the subject of first trimester two-dimensional (2D) ultrasound evaluation due to the complexity of their shape and morphology. Virtual reality (VR) allows efficient visualisation and measurement of complex structures like the umbilical cord and vitelline duct. Aim: To measure normal first trimester human growth of the umbilical cord length (UCL) and vitelline duct length (VDL) using a VR system; and to correlate both measurements with the gestational age (GA) and crown-rump length (CRL) and the VDL with the yolk sac volume (YSV). Study design: Prospective cohort study. Serial three-dimensional (3D) ultrasound measurements were performed from six to 14 weeks GA, resulting in 125 3D volumes. These volumes were analysed using an I-Space VR system. Subjects: Thirty-two healthy pregnant women with an ongoing, normal pregnancy. Outcome measures: The UCL, VDL, YSV and other related structures were measured. Results: The UCL, measurable in 55% of cases, was positively correlated to advancing GA and CRL (p<0.001). The VDL could be measured in 42% of cases and showed a positive relationship with GA and CRL (p<0.001). There was a significant (p<0.001) relationship between YSV and VDL. Conclusions: The present study, facilitated by a VR system, is the first to provide an in-vivo longitudinal description of normal first trimester growth of the human umbilical cord and vitelline duct. Further studies will reveal whether these parameters can be used in detection of abnormal fetal development.

Well being of obstetric patients on minimal blood transfusions (WOMB trial) (Article)

2010-12-16T00:00:00Z

Background: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands.Methods/Design: The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs.The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%).Discussion: This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs.Trial registration: ClinicalTrials.gov NCT00335023, Nederlands Trial Register NTR335.

Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on Duration of antibiotic Therapy in suspected neonatal early-onset Sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study (Article)

2010-12-08T00:00:00Z

Background: Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis.Methods/Design: The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%.Discussion: Benefit of the study is a possible limitation of unnecessary use of antibiotics. The results of our first study suggest that there is a low risk on discontinuing antibiotic treatment too early, resulting in the development of a neonatal infection with its morbidity and mortality.

Differential expression and prognostic value of HMGA1 in pancreatic head and periampullary cancer (Article)

2010-12-01T00:00:00Z

The high mortality rate and minimal progress made in the treatment of pancreatic cancer over the last few decades, warrant an alternative approach. Treatment protocols should be individualised to the patient guided by prognostic markers. A particularly interesting target would be the architectural transcription factor high mobility group A1 (HMGA1), that is low or undetectable in normal tissue, induced during neoplastic transformation and consequently often exceptionally high in cancer. The aim of the current study was therefore to determine the differential expression of HMGA1 in pancreatic head and periampullary cancer and investigate its relation with outcome. HMGA1 expression was determined by immunohistochemistry on original paraffin embedded tissue from 99 pancreatic head- and 112 periampullary cancers (with R0). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS) and conventional prognostic factors. HMGA1 was expressed in 47% and 26% of pancreatic head- and periampullary cancer, respectively and associated with poor RFS, CSS and OS in periampullary cancer. CSS 5 years following surgery was 25% and 44% for patients with tumours which were positive or negative for HMGA1 protein, respectively. HMGA1 expression was not associated with survival in pancreatic head cancer. In conclusion HMGA1 was identified as an independent prognostic marker predicting poor outcome in periampullary cancer. Although expressed to a higher extent as compared to periampullary cancer, HMGA1 was not associated with survival in pancreatic head cancer.

Randomised controlled trial comparing two different intravenous immunoglobulins in chronic inflammatory demyelinating polyradiculoneuropathy (Article)

2010-12-01T00:00:00Z

Background: Different preparations of intravenous immunoglobulin (IVIg) are considered to have comparable clinical efficacy but this has never been formally investigated. Some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) report that some IVIg brands are more effective than others. A liquid IVIg preparation is more user friendly and potentially can be infused at a faster rate. Objectives: The primary objective was to compare the efficacy of two different IVIg brands in CIDP. The secondary objective was to compare their safety. Methods: This was an investigator-initiated multi-centre randomised controlled double-blind trial. Twenty-seven patients with active but stable CIDP treated with their individual stable IVIg (Gammagard S/D) maintenance dose and interval were randomised to receive four infusions of freeze-dried 5% IVIg (Gammagard S/D) or the new liquid 10% IVIg (Kiovig). The overall disability sum score (ODSS) was used as the primary outcome scale. The equivalence margin was defined as a difference of ≤1 point in mean ΔODSS between treatment groups. Main secondary outcome scales were the MRC sum score and the Vigorimeter. Results: Repeated measurements analysis of variance, adjusted for baseline ODSS, showed a clinically insignificant treatment difference of 0.004 (95% CI -0.4 to 0.4). We also found no significant differences in any of the other outcome measures. Besides a lower occurrence of cold shivers in patients randomised to Kiovig (p=0.03), no significant differences were found in the occurrence of adverse events. Conclusions: This trial demonstrated equal clinical efficacy between a freeze-dried and a liquid IVIg preparation for maintenance treatment of CIDP.

Effect of enzyme therapy in juvenile patients with Pompe disease: A three-year open-label study (Article)

2010-12-01T00:00:00Z

Pompe disease is a rare neuromuscular disorder caused by deficiency of acid α-glucosidase. Treatment with recombinant human α-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response in older children (age 5.9-15.2 years). The five patients that we studied had limb-girdle muscle weakness and three of them also had decreased pulmonary function in upright and supine position. They received 20-mg/kg recombinant human α-glucosidase every two weeks over a 3-year period. No infusion-associated reactions were observed. Pulmonary function remained stable (n= 4) or improved slightly (n= 1). Muscle strength increased. Only one patient approached the normal range. Patients obtained higher scores on the Quick Motor Function Test. None of the patients deteriorated. Follow-up data of two unmatched historical cohorts of adults and children with Pompe disease were used for comparison. They showed an average decline in pulmonary function of 1.6% and 5% per year. Data on muscle strength and function of untreated children were not available. Further studies are required.

Omphalocele: Comparison of outcome following prenatal or postnatal diagnosis (Article)

2010-12-01T00:00:00Z

Objectives To assess the impact of prenatal compared with postnatal diagnosis on outcome for liveborn infants with an isolated or with a non-isolated omphalocele. Methods This was a retrospective analysis of 101 prenatally and 45 postnatally diagnosed cases of omphalocele. Cases were collected from the ultrasound database of the Division of Obstetrics and Prenatal Medicine and the patient database of the Department of Pediatric Surgery. Results Following confirmation at delivery or autopsy, prenatally diagnosed omphaloceles included 21 isolated cases, 44 non-isolated cases with a normal karyotype and 36 non-isolated cases with an abnormal karyotype. Of the prenatally diagnosed apparently isolated cases (n = 31), 12 (39%; 95% CI, 22-58%) revealed associated anomalies after delivery. Liveborn infants with an isolated omphalocele had significantly worse short-term morbidity following prenatal diagnosis (n = 14) compared with diagnosis at birth (n = 29), having a lower gestational age at delivery, lower Apgar scores, longer duration of ventilation and parenteral nutrition, more readmissions and a longer hospital stay. The prenatally diagnosed subset contained more infants with a giant omphalocele (9/14 vs. 3/29, P = 0.001) and liver herniation (8/14 vs. 6/29, P = 0.02). The outcome of liveborn infants with a non-isolated omphalocele diagnosed prenatally (n = 17) was not different from that of those diagnosed at birth (n = 16), except for a greater need for ventilation and parenteral nutrition in the prenatal subset. Conclusion When counseling patients with a prenatal diagnosis of isolated omphalocele, it is important to remember that over one third could turn out to have associated anomalies. Liveborn infants with an isolated omphalocele detected prenatally have worse short-term morbidity than do cases detected at birth. Those with non-isolated omphaloceles detected prenatally have an increased need for ventilation and parenteral nutrition compared with those detected at birth. Copyright

Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma (Article)

2010-11-15T00:00:00Z

Rationale: For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids, evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids. Objective: To evaluate whether salmeterol/fluticasone propionate (SFP), 50/100 μg twice a day, is noninferior regarding symptom control compared with fluticasone propionate (FP), 200 μg twice a day Diskus in children with symptomatic asthma. Methods: A multicenter, randomized, parallel-group, double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function. Measurements and Main Results: A total of 158 children, 6-16 years old, still symptomatic on FP, 100 μg twice a day, during a 4-week runin period, were included. Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups (per protocol analysis: adjusted mean difference [FP minus SFP] 2.6%; 95% confidence interval, -8.1 to 13.4). Both groups showed substantial improvements of about 25 percent points in symptom-free days (both P < 0.001 from baseline). Lung function measurements (FEV1, FVC, PEF rate, and maximal expiratory flow) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week. No differences were found between FP and SFP regarding exacerbation rates, adverse events, or growth. Conclusions: In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid. Clinical trial registered with www.clinicaltrials.gov (NCT 00197106).

Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a biomarker of cardiac filling pressures in pre-eclampsia (Article)

2010-11-01T00:00:00Z

Objective: To evaluate if amino-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels reflect intracardiac filling pressures in pre-eclamptic patients. Study design: In a cross-sectional study we investigated 22 untreated critically ill pre-eclamptic women between 22 and 34 weeks gestation. All patients underwent intra-arterial blood pressure and central hemodynamic measurements and NT-proBNP was determined in stored plasma. Baseline characteristics, plasma NT-proBNP concentrations and relevant laboratory variables were investigated for correlations with hemodynamic values using Spearman's rank correlation test. Results: No significant correlations were demonstrated between NT-proBNP concentrations and variables associated with the severity of the pre-eclampsia. We found significant positive correlations between NT-proBNP and diastolic pulmonary pressure (r = 0.59; p = 0.005) and pulmonary capillary wedge pressure (PCWP) (r = 0.51; p = 0.015). Multiple linear regression analysis showed that the association between NT-proBNP and PCWP was not affected by creatinine level. Conclusion: NT-proBNP is a biomarker of left ventricular cardiac filling pressures in untreated pre-eclamptic patients.

Pain in Guillain-Barré syndrome: A long-term follow-up study (Article)

2010-10-19T00:00:00Z

Background: Pain in Guillain-Barré syndrome (GBS) may be pronounced and is often overlooked. Objectives: To obtain detailed information about pain in GBS and its clinical variants. Methods: This was a prospective cohort study in 156 patients with GBS (including 18 patients with Miller Fisher syndrome [MFS]). We assessed the location, type, and intensity of pain using questionnaires at standard time points during a 1-year follow-up. Pain data were compared to other clinical features and serology. Results: Pain was reported in the 2 weeks preceding weakness in 36% of patients, 66% reported pain in the acute phase (first 3 weeks after inclusion), and 38% reported pain after 1 year. In the majority of patients, the intensity of pain was moderate to severe. Longitudinal analysis showed high mean pain intensity scores during the entire follow-up. Pain occurred in the whole spectrum of GBS. The mean pain intensity was predominantly high in patients with GBS (non-MFS), patients with sensory disturbances, and severely affected patients. Only during later stages of disease, severity of weakness and disability were significantly correlated with intensity of pain. Conclusions: Pain is a common and often severe symptom in the whole spectrum of GBS (including MFS, mildly affected, and pure motor patients). As it frequently occurs as the first symptom, but may even last for at least 1 year, pain in GBS requires full attention. It is likely that sensory nerve fiber involvement results in more severe pain. Copyright

Risk Factors for Chronic Lung Disease and Mortality in Newborns with Congenital Diaphragmatic Hernia (Article)

2010-10-01T00:00:00Z

Background: Congenital diaphragmatic hernia (CDH) is associated with a mortality rate of 10-35% in live-born infants. Moreover, CDH survivors have a substantial risk of developing long-term pulmonary sequelae, such as bronchopulmonary dysplasia (BPD). Objectives: This study aims to evaluate risk factors associated with BPD and mortality in neonates with CDH, with particular focus on the initial ventilation mode. Methods: Eligible for inclusion were live-born infants with CDH born from 2001 through 2006 at the centers participating in the CDH Study Group. BPD (defined as oxygen dependency at day 30) and/or mortality by day 30 served as the primary endpoint. Results: A total of 2,078 neonates were included in the analysis. At day 30, 56% of the patients had either died or met the criteria for BPD. In infants who survived until day 30, the prevalence of BPD was 41%. The overall mortality rate was 31%. High-frequency oscillatory ventilation as initial ventilation mode, a right-sided defect, a prenatal diagnosis, a lower Apgar score at 5 min, a cardiac anomaly, a chromosomal anomaly and a lower gestational age were all associated with BPD and/or mortality by day 30. Conclusions: Despite improvements in neonatal care, the rates of BPD and early mortality in newborns with CDH are still considerable. Several important risk factors for a worse outcome are reported in this nonrandomized prospective observational study.

Reference values for serum creatinine in children younger than 1 year of age (Article)

2010-10-01T00:00:00Z

Reliable reference values of enzymatically assayed serum creatinine categorized in small age intervals are lacking in young children. The aim of this study was to determine reference values for serum creatinine during the first year of life and study the influence of gender, weight and height on these values. Serum creatinine determinations between 2003 and 2008 were retrieved from the hospital database. Strict exclusion criteria ensured the selection of patients without kidney damage. Correlation analysis was performed to evaluate the relation between height, weight and serum creatinine; the Mann-Whitney test was used to evaluate the relation between gender and serum creatinine. A broken stick model was designed to predict normal serum creatinine values. Mean serum creatinine values were found to decrease rapidly from 55 μmol/L on day 1 to 22 μmol/L in the second month of life; they then stabilized at 20 μmol/L until the seventh month, followed by a slight increase. No significant relation was found between serum creatinine and gender, weight and height. We present here reference values of serum creatinine in infants not at risk of decreased renal function. The absence of a relationship with gender, weight and height confirms that height-based equations to estimate glomerular filtration rate are less useful in patients of this age group.

Low bone mass in Pompe disease. Muscular strength as a predictor of bone mineral density (Article)

2010-09-01T00:00:00Z

Pompe disease is an inherited metabolic myopathy caused by deficiency of acid alpha-glucosidase. The introduction of enzyme replacement therapy as treatment for the disease may change prospects for patients and may require that more attention be paid to co-morbidities such as osteoporosis. Methods: Bone mineral status was assessed in children and adults with Pompe disease and compared with reference values by means of dual energy X-ray absorptiometry (DXA) technology (GE Lunar DPX, GE Health Care). Bone mineral density (BMD) of the total body and the lumbar spine (L2-L4) was measured in adults and children; BMD of the femoral neck was measured in adults only. Exclusion criteria were: age < 4 years, severe contractures, and inability to transfer the patient. Results: 46 patients were enrolled in the study; 36 adults and 10 children. The BMD was significantly lower in Pompe patients than in healthy individuals. Sixty-seven percent of patients had a BMD Z-score below -1, 26% were classified as osteoporosis/low bone mass for chronological age (T-score < -2.5 in adults or Z-score < -2 in children), 66% had a BMD Z-score below -1 of the femoral neck, and 34% had a BMD Z-score below -1 for the lumbar spine. Osteoporosis/low bone mass for chronological age was more frequent in patients who were wheelchair-bound, but was also observed in ambulant patients. We found a significant correlation between proximal muscle strength and total body BMD. Of the 10 children, 8 (all four patients with the classic infantile form) had a low BMD. Conclusion: Low BMD is a frequent finding in patients with Pompe disease and may be causally related to decreased proximal muscle strength. BMD should be monitored at regular intervals. Children deserve specific attention.

An innovative virtual reality technique for automated human embryonic volume measurements (Article)

2010-09-01T00:00:00Z

Background: The recent introduction of virtual reality (VR) enables us to use all three dimensions in a three-dimensional (3D) image. The aim of this prospective study was to evaluate an innovative VR technique for automated 3D volume measurements of the human embryo and yolk sac in first trimester pregnancies. Methods: We analysed 180 3D first trimester ultrasound scans of 42 pregnancies. Scans were transferred to an I-Space VR system and visualized as 3D 'holograms' with the V-Scope volume-rendering software. A semi-automatic segmentation algorithm was used to calculate the volumes. The logarithmically transformed outcomes were analysed using repeated measurements ANOVA. Interobserver and intraobserver agreement was established by calculating intraclass correlation coefficients (ICCs). Results:Eighty-eight embryonic volumes (EVs) and 118 yolk sac volumes (YSVs) were selected and measured between 5+5 and 12+6 weeks of gestational age (GA). EV ranged from 14 to 29 877 mm3 and YSV ranged from 33 to 424 mm3. ANOVA calculations showed that when the crown-rump length (CRL) doubles, the mean EV increases 6.5-fold and when the GA doubles, the mean EV increases 500-fold (P < 0.001). Furthermore, it was found that a doubling in GA results in a 3.8-fold increase of the YSV and when the CRL doubles, the YSV increases 1.5-fold (P < 0.001). Interobserver and intraobserver agreement were both excellent with ICCs of 0.99. Conclusion: We measured the human EV and YSV in early pregnancy using a VR system. This innovative technique allows us to obtain unique information about the size of the embryo using all dimensions, which may be used to differentiate between normal and abnormal human development.

Reply: (Article)

2010-09-01T00:00:00Z

Clinical significance of flowcytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG ANLL97/MRC AML12 protocol (Article)

2010-09-01T00:00:00Z

Analysis of minimal residual disease (MRD) in childhood acute myeloid leukemia (AML) may predict for clinical outcome. MRD levels were assessed by flowcytometric immunophenotyping in 94 children with AML enrolled into a single trial (United Kingdom Medical Research Council AML12 and similar Dutch Childhood Oncology Group ANLL97). An aberrant immunophenotype could be detected in 94% of patients. MRD levels after the first course of chemotherapy predicted for clinical outcome: 3-year relapse-free survival was 85%8% (s.e.) for MRD-negative patients (MRD0.1%), 64%10% for MRD-low-positive patients (0.1%MRD0.5%) and only 149% for MRD-high-positive patients (MRD0.5%; P0.001), whereas overall survival was 95%5%, 70%10% and 40%13%, respectively, (P0.001). Multivariate analysis allowing for age, karyotype, FLT3-internal tandem duplications and white blood cell count at diagnosis showed that MRD after the first course of chemotherapy was an independent prognostic factor. Although comparison of paired diagnosis-relapse samples (n23) showed immunophenotypic shifts in 91% of cases, this did not hamper MRD analysis. In conclusion, flowcytometric MRD detection is possible in children with AML. The level of MRD after the first course of chemotherapy provides prognostic information that may be used to guide therapy.

Reversibility of inspiratory lung function parameters after short-term bronchodilators in COPD (Article)

2010-08-01T00:00:00Z

Background: The responsiveness of short-term bronchodilator use on inspiratory lung function parameters (ILPs), including Forced Inspiratory Volume in one second (FIV1), Inspiratory Capacity (IC), Forced Inspiratory Flow at 50% of the vital capacity (FIF50), Peak Inspiratory Flow (PIF) and on the relationship between these values and dyspnea in COPD subjects has been examined only sparsely in past studies. The aim of this study was to assess the effects of inhaled salbutamol 400mcg, ipratropium 80mcg and a placebo on ILP and FEV1 and their relationship to dyspnea, as measured with a Visual Analogue Scale (VAS). Methods: A total of 85 subjects with stable COPD participated in a crossover, randomized, double-blind, placebo-controlled study. Spirometry was performed before and after inhalation of salbutamol, ipratropium or a placebo. The primary analysis was performed using 63 participants with absent reversibility. Results: All ILP and FEV1 values improved significantly after bronchodilator administration except for FIF50 after ipratropium administration. After administration of both bronchodilators, the mean percent changes from initial values did not significantly differ between the various ILPs and FEV1. The mean VAS score showed significant improvements after bronchodilator and placebo inhalation but did not significantly correlate with changes in lung function parameters. For each lung function parameter, patients were further classified as responders if the amount of change was greater than the coefficient of repeatability of the test. Response rates did not differ significantly between the various ILPs. Moreover, no significant differences were found between responders and non-responders with respect to dyspnea after bronchodilator inhalation. This finding applied to all ILP and FEV1 values. Conclusions: In subjects with COPD, all ILP, FEV1 values and VAS scores showed significant improvements after bronchodilator use as well as with placebo. However, ILPs were not more sensitive than FEV1 for detecting responders after bronchodilator use or changes in the VAS score.

Three-dimensional airway changes after le fort III advancement in syndromic craniosynostosis patients (Article)

2010-08-01T00:00:00Z

Background: To investigate the changes of upper airway volume in syndromic craniosynostosis patients following Le Fort III advancement, computed tomographic scans were analyzed and related to the amount of advancement. Methods: In this retrospective study, the preoperative and postoperative computed tomographic scans of 19 patients with syndromic craniosynostosis who underwent Le Fort III advancement were analyzed. In four cases, preoperative polysomnography demonstrated obstructive sleep apnea. The airway was segmented using a semiautomatic region growing method with a fixed Hounsfield threshold value. Airway volumes of hypopharynx and oropharynx (compartment A) and nasopharynx and nasal cavity (compartment B) were analyzed separately, as was the total airway volume. Advancement of the midface was recorded using lateral skull radiographs. Data were analyzed for all patients together and for patients with Crouzon/Pfeiffer and Apert syndromes separately. Results: Airway volume increased significantly in compartment A (20 percent; p = 0.044) and compartment B (48 percent; p < 0.001), as did total airway volume in (37 percent; p < 0.001) in the total study group. No significant differences in volume changes were found comparing Apert with Crouzon/Pfeiffer patients. No distinct relation could be found between advancement of the midface and volume gain either in the total study group or in Apert and Crouzon/Pfeiffer patient groups separately. Postoperative polysomnography showed significant improvement of obstructive sleep apnea in all four patients. Conclusions: A significant improvement of the upper airway after Le Fort III advancement in syndromic craniosynostosis patients is demonstrated. No distinct relation could be observed between advancement and airway volume changes. Copyright

Plasma water as a diagnostic tool in the assessment of dehydration in children with acute gastroenteritis (Article)

2010-07-01T00:00:00Z

Acute gastroenteritis is common in childhood. The estimation of the degree of dehydration is essential for management of acute gastroenteritis. Plasma water was assessed as a diagnostic tool in children with acute gastroenteritis and dehydration admitted to hospital. In a prospective cohort study, 101 patients presenting at the emergency department with dehydration were included. Clinical assessment, routine laboratory tests, and plasma water measurement were performed. Plasma water was measured as a percentage of water content using dry weight method. During admission, patients were rehydrated in 12 h. Weight gain at the end of the rehydration period and 2 weeks thereafter was used to determine the percentage of weight loss as a gold standard for the severity of dehydration. Clinical assessment of dehydration was not significantly associated with the percentage of weight loss. Blood urea nitrogen (r∈=∈0.3, p∈=∈0.03), base excess (r∈=-0.31, p∈=∈0.03), and serum bicarbonate (r∈=∈0.32, p∈=∈0.02) were significantly correlated with the percentage of weight loss. Plasma water did not correlate with the percentage of weight loss. On the basis of the presented data, plasma water should not be used as a diagnostic tool in the assessment of dehydration in children with acute gastroenteritis.

Surviving meningococcal septic shock in childhood: Long-term overall outcome and the effect on health-related quality of life (Article)

2010-06-29T00:00:00Z

Introduction: The purpose of this study was to evaluate associations between long-term physical and psychological outcome variables in patients who survived meningococcal septic shock (MSS) in childhood.Methods: The study population was made up of all MSS patients requiring intensive care treatment between 1988 and 2001.Results: A total of 120 patients visited the follow-up clinic (age at paediatric intensive care unit (PICU) admission 3.1 years; follow-up interval 9.8 years; age at follow-up 14.5 years (all medians)). Four major outcomes were considered: 1) major physical sequelae (defined as major scars and/or orthopaedic sequelae) (29/120), 2) mild neurological impairments (39/120), 3) problem behaviour (defined as a total score above the 90thpercentile of the reference groups on questionnaires to screen for psychopathology) (16/114) and 4) total intelligence quotient < 85 (18/115). No differences were found between patients with major physical sequelae and patients without major physical sequelae as to the presence of problem behaviour or total IQ < 85. Also, no differences were found between patients with mild neurological impairments and patients without as to the presence of problem behaviour or total IQ < 85. Finally, no differences were found between patients with major physical sequelae and patients without as to the presence of mild neurological sequelae. Less favourable scores on behavioural and emotional problems were significantly associated with poorer health-related quality of life (HR-QoL). HR-QoL scores were to a lesser amount predicted by severity of illness at time of PICU admission or by adverse physical outcome.Conclusions: Long-term adverse physical and psychological outcomes in survivors of MSS did not seem to be associated. Poorer HR-QoL was mainly predicted by problem behaviour.

The additional value of an oblique image plane for MRI of the anterior and posterior distal tibiofibular syndesmosis (Article)

2010-06-15T00:00:00Z

Objective: The optimal MRI scan planes of collateral ligaments of the ankle have been described extensively, with the exception of the syndesmotic ligaments. We assessed the optimal scan plane for depicting the distal tibiofibular syndesmosis. Materials and Methods: In order to determine the optimal oblique caudal-cranial and lateral-medial MRI scan plane, two fresh frozen cadaveric ankles were used. The angle of the scan plane that demonstrated the anterior and posterior distal tibiofibular ligament uninterrupted in their full length was determined. In a prospective study this oblique scan plane was then used in addition to the axial and coronal planes, for MRI scans of both ankles in 21 healthy volunteers. Two observers independently evaluated the anterior tibiofibular ligament (ATIFL) and posterior tibiofibular ligament (PTIFL) regarding the continuity of the individual fascicles, thickness and wavy contour of the ligaments in both the axial and the oblique plane. Kappa was calculated to determine the interobserver agreement. McNemar's test was used to statistically quantify the significance of the two scan planes. Results: In the axial plane the ATIFL was in 31% (13/42) partly and in 69% (29/42) completely discontinuous; in the oblique plane the ATIFL was continuous in 88% (37/42) and partly discontinuous in 12% (5/42). Compared with the axial plane, the oblique plane demonstrated significantly less discontinuity (p < 0.001), but not significantly less thickening (p = 1.00) or less wavy contour (p = 0.06) of the ATIFL. In the axial scan plane the PTIFL was continuous in 76% (32/42), partially discontinuous in 19% (8/42) and completely discontinuous in 5% (2/42); in the oblique plane the PTIFL was continuous in 100% (42/42). Compared with the axial plane, the oblique plane demonstrated significantly less discontinuity (p = 0.002), but not significantly less thickening (p = 1.00) or less wavy contour (p = 0.50) of the PTIFL. The interobserver agreement score and kappa (κ) regarding the continuity for the ATIFL in the axial and oblique planes was 91% (κ = 0.79) and 91% (κ = 0.55) respectively; for the PTIFL it was 86% (κ = 0.65) and 100% (κ = not defined). Conclusion: The ATIFL and PTIFL are routinuely scanned in the orthogonal planes. The advantage of MRI scanning in an oblique image plane of about 45 degrees permits a better evaluation of the ligaments compared with the axial plane, particularly a better interpretation of ligament continuity, thickening and wavy contour. This may lead to a reduction in false-positive results, especially regarding partial or complete ligament ruptures. This can be of considerable aid in therapeutic management.

Innovative virtual reality measurements for embryonic growth and development (Article)

2010-06-01T00:00:00Z

Background Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique. Methods In a longitudinal study, three-dimensional (3D) measurements were performed from 6 to 14 weeks gestational age in 32 pregnancies (n = 16 spontaneous conception, n = 16 IVF/ICSI). A total of 125 3D volumes were analysed in the I-Space VR system, which allows binocular depth perception, providing a realistic 3D illusion. Crown-rump length (CRL), biparietal diameter (BPD), occipito-frontal diameter (OFD), head circumference (HC) and abdominal circumference (AC) were measured as well as arm length, shoulder width, elbow width, hip width and knee width. Result SCRL, BPD, OFD and HC could be measured in more than 96 of patients, and AC in 78. Shoulder width, elbow width, hip width and knee width could be measured in more than 95 of cases, and arm length in 82 of cases. Growth curves were constructed for all variables. Ear and foot measurements were only possible beyond 9 weeks gestation. Conclusions This study provides a detailed, longitudinal description of normal human embryonic growth, facilitated by a VR system. Growth curves were created for embryonic biometry of the CRL, BPD, HC and AC early in pregnancy and also of several 'new' biometric measurements. Applying virtual embryoscopy will enable us to diagnose growth and/or developmental delay earlier and more accurately. This is especially important for pregnancies at risk of severe complications, such as recurrent late miscarriage and early growth restriction.

Noninvasive assessment of intra-abdominal pressure by measurement of abdominal wall tension 1 (Article)

2010-05-07T00:00:00Z

Background: Sustained increased intra-abdominal pressure (IAP) has negative effects. Noninvasive IAP measurement could be beneficial to improve monitoring of patients at risk and in whom IAP measurements might be unreliable. We assessed the relation between IAP and abdominal wall tension (AWT) in vitro and in vivo. Materials and methods: The abdomens of 14 corpses were insufflated with air. IAP was measured at intervals up to 20 mm Hg. At each interval, AWT was measured five times at six points. In 42 volunteers, AWT was measured at five points in supine, sitting, and standing positions during various respiratory manoeuvres. Series were repeated in 14 volunteers to measure reproducibility by calculating coefficients of variation (CV). ANOVA was used for analyses. Results: In corpses, all points showed significant correlations between IAP and AWT (P < 0.001 for points 1-4 in the upper abdomen, P = 0.017 for point 5 and P = 0.008 for point 6 in the lower abdomen). Mean slopes were greatest at points across the epigastric region (points 1-3). In vivo measurements showed that AWT was on average 31% higher in men compared to women (P < 0.001), and increased from expiration to inspiration to Valsalva's manoeuvre (all P < 0.001). AWT was highest at points 1 and 2 and in standing position, followed by supine and sitting positions. BMI did not influence AWT. Mean CV of repeated measurements was 14%. Conclusions: AWT reflects IAP. The epigastric region appears most suitable for AWT measurements. Further longitudinal clinical studies are needed to assess usefulness of AWT measurements for monitoring of IAP.

Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia (Article)

2010-05-01T00:00:00Z

Background This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia Design and Methods We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2/GATA), collagen type I alpha 1 (SpI), estrogen receptor 1 (ESR1: PvuII/XbaI), glucocorticoid receptor (BclI)) on body composition, BM(A)D and fracture risk during dexamethasone-based pediatric acute lymphoblastic leukemia treatment. Body composition and BMD were measured repeatedly during and after treatment using dual energy X-ray absorptiometry. Results Non-carriers of VDR 5'-end (Cdx-2/GATA) haplotype 3 revealed a significant larger fat gain than carriers (D%fat: non-carriers: +1.76SDS, carriers: +0.77SDS, P<0.001). At diagnosis and during therapy, lumbar spine BMD was significantly higher in non-carriers of VDR 5'-end (Cdx-2/GATA) haplotype 3 than in carriers. The other SNPs did not influence BMD or fracture risk during/after treatment. The year after treatment completion, lean body mass increased in non-carriers of ESR1 (PvuII/XbaI) haplotype 3 and decreased in carriers (D lean body mass: non-car-riers:+0.28SDS, carriers: -0.55SDS, P<0.01). Conclusions Only VDR 5'-end (Cdx-2/GATA) haplotype 3 was identified as protective factor against excessive fat gain and as a risk factor for lower lumbar spine BMD during treatment. Carrying ESR1 (PvuII/XbaI) haplotype 3 negatively influenced recovery of lean body mass after pediatric acute lymphoblastic leukemia treatment.

PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease (Article)

2010-04-01T00:00:00Z

Screening of blood films for the presence of periodic acid-Schiff (PAS)-positive lymphocyte vacuoles is sometimes used to support the diagnosis of Pompe disease, but the actual diagnostic value is still unknown. We collected peripheral blood films from 65 untreated Pompe patients and 51 controls. Lymphocyte vacuolization was quantified using three methods: percentage vacuolated lymphocytes, percentage PAS-positive lymphocytes, and a PAS score depending on staining intensity. Diagnostic accuracy of the tests was assessed using receiver operating characteristic (ROC) curves. All three methods fully discerned classic infantile patients from controls. The mean values of patients with milder forms of Pompe disease were significantly higher than those of controls, but full separation was not obtained. The area under the ROC curve was 0.98 for the percentage vacuolated lymphocytes (optimal cutoff value 3; sensitivity 91%, specificity 96%) and 0.99 for the percentage PAS-positive lymphocytes and PAS score (optimal cutoff value 9; sensitivity 100%, specificity 98%). Our data indicate that PAS-stained blood films can be used as a reliable screening tool to support a diagnosis of Pompe disease. The percentage of PAS-positive lymphocytes is convenient for use in clinical practice but should always be interpreted in combination with other clinical and laboratory parameters.

Pre- and postnatal diagnosis and outcome of fetuses and neonates with esophageal atresia and tracheoesophageal fistula (Article)

2010-03-01T00:00:00Z

Objectives: Clinical symptoms and ultrasound signs during pregnancy could suggest the presence of esophageal atresia (EA). However, most often EA is diagnosed postnatally. The aim of our study is to evaluate the course and outcome for prenatally and postnatally diagnosed EA. In addition, we studied the outcome of isolated versus nonisolated EA. Methods: In a retrospective data analysis, ultrasound characteristics, maternal and neonatal variables as well as clinical outcome were compared for fetuses/neonates with prenatal (n = 30) or postnatal (n = 49) diagnosis of EA. Clinical outcome in terms of morbidity and mortality of isolated EA was compared with that of EA complicated by chromosomal or structural anomalies. Results: Prenatally diagnosed children were born 2 weeks earlier than postnatally diagnosed children (36.4 weeks vs 38.2 weeks; P = 0.02). The former had higher mortality rates (30 vs 12%; P = 0.05) and more associated anomalies (80 vs 59%; P = 0.04). In both subsets, there was a high morbidity rate in the survivors (not significant). Nonisolated EA was associated with greater occurrence of polyhydramnios (53 vs 27%; P = 0.04) and higher mortality rate (28 vs 0%; P = 0.002). Conclusions: Mortality was significantly higher in prenatally diagnosed infants and in infants with additional congenital anomalies. Isolated EA is associated with good outcome.

Quality of life after adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: A prospective randomized controlled study (Article)

2010-02-15T00:00:00Z

BACKGROUND: Adjuvant therapies for pancreatic and periampullary cancer reportedly achieve only a marginal survival benefit. In this randomized controlled trial, 120 patients with resected pancreatic or periampullary cancer received either adjuvant celiac axis infusion chemotherapy combined with radiotherapy (CAI/RT) or no adjuvant treatment. The objective of the study was to compare the quality of life (QoL) in patients who received CAI/RT after pancreatoduodenectomy with the QoL in patients who did not receive adjuvant treatment. METHODS: During and after CAI/RT, QoL was assessed using the European Organization for Research and Treatment of Cancer QoL Questionnaire C30 every 3 months during the first 24 months after randomization. RESULTS: Eighty-six percent of patients (n=103) completed 1 or more questionnaires. In total, 355 questionnaires were completed. The results indicated that CAI/RT did not impair physical, emotional, or social functioning. During and after CAI/RT, patients had significantly less pain (P=.02) and less nausea and vomiting (P=.01). Overall QoL (global functioning) tended to be better (P=.08) after CAI/RT. CONCLUSIONS: Over a period of 24 months, CAI/RT improved QoL compared with observation alone in patients with resected pancreatic and periampullary cancer. This beneficial effect of CAI/RT was most prominent in the latter half of the follow-up.

National malnutrition screening days in hospitalised children in the Netherlands (Article)

2010-02-01T00:00:00Z

Objective: Nationwide prevalence studies on malnutrition in hospitalised children have not been done. This study aimed to investigate the prevalence of malnutrition of all newly admitted children in The Netherlands during 3 consecutive days. Design: Prospective observational study. Setting: Paediatric wards of 44 hospitals (7 academic and 37 general). Participants: A total of 424 children aged ≥30 days and hospitalised for ≥ 1 day were included, 63% male, 86% non-white. Median age was 3.5 years and median hospital stay was 2 days. Main outcome measures: SD scores < -2 for weight for height and height for age were considered to indicate acute and chronic malnutrition, respectively. Results: Overall 19% of the children had acute and/or chronic malnutrition at admission (academic 22% and general 17%). The proportion of children with chronic malnutrition was significantly higher in academic hospitals (14% vs 6%). Logistic regression analysis allowing for age, underlying disease, ethnicity, surgery and type of centre showed a significant relation between the presence of malnutrition at admission and underlying disease (odds ratio (OR) 2.2). For chronic malnutrition both underlying disease and non-white ethnicity were significantly related to a higher prevalence (OR 3.7 and OR 2.8, respectively). Multiple regression analysis showed that children with acute malnutrition stayed on average 45% longer (95% CI 7% to 95%) in the hospital than children without such malnutrition. Conclusions: This unique nationwide study shows that 19% of children admitted to Dutch hospitals are malnourished at admission. This high prevalence underlines the need for routine screening and treatment of malnutrition in hospitalised children.

Dutch national survey to test the STRONGkids nutritional risk screening tool in hospitalized children (Article)

2010-02-01T00:00:00Z

Background & aims: Children admitted to the hospital are at risk of developing malnutrition. The aim of the present study was to investigate the feasibility and value of a new nutritional risk screening tool, called STRONGkids, in a nationwide study. Methods: A Prospective observational multi-centre study was performed in 44 Dutch hospitals (7 academic and 37 general), over three consecutive days during the month of November 2007.The STRONGkidsscreening tool consisted of 4 items: (1) subjective clinical assessment, (2) high risk disease, (3) nutritional intake, (4) weight loss. Measurements of weight and length were performed. SD-scores <-2 for weight-for-height and height-for-age were considered to indicate acute and chronic malnutrition respectively. Results: A total of 424 children were included. Median age was 3.5 years and median hospital stay was 2 days. Sixty-two percent of the children were classified " at risk" of developing malnutrition by the STRONGkidstool. Children at risk had significantly lower SD-scores for weight-for-height, a higher prevalence of acute malnutrition and a longer hospital stay compared to children with no nutritional risk. Conclusions: The nutritional risk screening tool STRONGkidswas successfully applied to 98% of the children. Using this tool, a significant relationship was found between having a " high risk" score, a negative SD-score in weight-for-height and a prolonged hospital stay.

Ondervoeding bij een vijfde van kinderen opgenomen in Nederlandse ziekenhuizen (Article)

2010-01-01T00:00:00Z

Doel: Het onderzoeken van de prevalentie van ondervoeding bij kinderen opgenomen in Nederlandse ziekenhuizen. Opzet & Methode: Prospectief observationeel onderzoek. Gedurende 3 opeenvolgende dagen werden alle kinderen die werden opgenomen op de kinderafdelingen van 44 Nederlandse ziekenhuizen (7 academisch, 37 algemeen) gescreend op ondervoeding. In totaal werden 424 kinderen geïncludeerd (63% jongens, 86% kaukasisch) met een leeftijd ≥ 30 dagen en een opnameduur van tenminste 1 dag. De mediane leeftijd was 3,5 jaar, de mediane opnameduur 2 dagen. Gewicht en lengte werden gemeten bij opname. Standaarddeviatiescores (SD-scores) < -2 voor gewicht-naar-lengte en lengte-voor-leeftijd werden beschouwd als acute respectievelijk chronische ondervoeding. Resultaten: In totaal was 19% van de kinderen acuut of chronisch ondervoed bij opname (academische ziekenhuizen 22%, algemene ziekenhuizen 17%). Het aandeel kinderen met chronische ondervoeding was significant hoger in de academische ziekenhuizen (14 versus 6%). Logistische regressieanalyse, rekening houdend met leeftijd, onderliggende ziekte, etniciteit, chirurgie en type ziekenhuis, toonde een statistisch significant verband tussen ondervoeding bij opname en onderliggende ziekte (OR: 2,2). Voor chronische ondervoeding waren zowel onderliggende ziekte als niet-kaukasische etniciteit significant gerelateerd aan een hogere prevalentie (OR: 3,7 en 2,8 respectievelijk). Multipele regressieanalyse toonde aan dat kinderen met acute ondervoeding bij opname gemiddeld 45% langer in het ziekenhuis lagen (95%-BI: 7-95) dan kinderen met een normale voedingstoestand. Conclusie: Deze unieke nationale studie laat zien dat 19% van de kinderen bij opname in een ziekenhuis ondervoed zijn. Deze hoge prevalentie laat zien dat screening op en behandeling van ondervoeding noodzakelijk is bij kinderen die in een ziekenhuis worden opgenomen.

Reply to the letter to the editor by Papadimas et al.: "Bone mineral density in adult patients with Pompe disease" (Article)

2010-01-01T00:00:00Z

First trimester umbilical cord and vitelline duct measurements using virtual reality (Article)

2010-01-01T00:00:00Z

Background: The umbilical cord and vitelline duct are of vital importance to the fetus, but they are rarely the subject of first trimester two-dimensional (2D) ultrasound evaluation due to the complexity of their shape and morphology. Virtual reality (VR) allows efficient visualisation and measurement of complex structures like the umbilical cord and vitelline duct. Aim: To measure normal first trimester human growth of the umbilical cord length (UCL) and vitelline duct length (VDL) using a VR system; and to correlate both measurements with the gestational age (GA) and crown-rump length (CRL) and the VDL with the yolk sac volume (YSV). Study design: Prospective cohort study. Serial three-dimensional (3D) ultrasound measurements were performed from six to 14 weeks GA, resulting in 125 3D volumes. These volumes were analysed using an I-Space VR system. Subjects: Thirty-two healthy pregnant women with an ongoing, normal pregnancy. Outcome measures: The UCL, VDL, YSV and other related structures were measured. Results: The UCL, measurable in 55% of cases, was positively correlated to advancing GA and CRL (p < 0.001). The VDL could be measured in 42% of cases and showed a positive relationship with GA and CRL (p < 0.001). There was a significant (p < 0.001) relationship between YSV and VDL. Conclusions: The present study, facilitated by a VR system, is the first to provide an in-vivo longitudinal description of normal first trimester growth of the human umbilical cord and vitelline duct. Further studies will reveal whether these parameters can be used in detection of abnormal fetal development.

Lapatinib: Clinical benefit in patients with HER2-positive advanced breast cancer (Article)

2010-01-01T00:00:00Z

Background: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth factor receptor 2 (HER2), has shown activity in combination with capecitabine in patients with HER 2-positive advanced breast cancer progressive on standard treatment regimens. We present results on preapproval drug access for this combination in such patients occurring in the general oncology practice in the Netherlands. Methods: Patients with HER2-positive advanced breast cancer progressive on schedules containing anthracyclines, taxanes, and trastuzumab were eligible. Brain metastases were allowed if stable. Lapatinib 1250 mg/day was given continuously in combination with capecitabine 1000 mg/m2 twice daily for two weeks in a three week cycle. Efficacy was assessed by use of response evaluation criteria in solid tumours version 1.0. Progression-free survival (PFS) and overall survival (OS) were calculated. Results: Eighty-three patients were enrolled from January 2007 until July 2008. The combination was generally well tolerated and the most common drug-related serious adverse events were nausea and/or vomiting (5%) and diarrhoea (2%). Seventy-eight patients were evaluable for response. Clinical benefit (response or stable disease for at least 12 weeks) was observed in 50 patients (64%) of whom 15 had a partial response and 35 stable disease. The median PFS and OS were 17 weeks (95% CI: 13 to 21) and 39 weeks (95% CI: 24 to 54), respectively. For OS, higher Eastern Cooperative Oncology Group (ECOG) status (p=0.016), brain metastases at study entry (p=0.010) and higher number of metastatic sites (p=0.012) were significantly negative predictive factors. Conclusion: In a patient population with heavily pretreated HER 2-positive advanced breast cancer lapatinib plus capecitabine was well tolerated and offered clinical benefit.

Abdominal wound dehiscence in adults: Development and validation of a risk model (Article)

2010-01-01T00:00:00Z

Background: Several studies have been performed to identify risk factors for abdominal wound dehiscence. No risk model had yet been developed for the general surgical population. The objective of the present study was to identify independent risk factors for abdominal wound dehiscence and to develop a risk model to recognize high-risk patients. Identification of high-risk patients offers opportunities for intervention strategies. Methods: Medical registers from January 1985 to December 2005 were searched. Patients who had primarily undergone appendectomies or nonsurgical (e.g., urological) operations were excluded. Each patient with abdominal wound dehiscence was matched with three controls by systematic random sampling. Putative relevant patient-related, operation-related, and postoperative variables were evaluated in univariate analysis and subsequently entered in multivariate stepwise logistic regression models to delineate major independent predictors of abdominal wound dehiscence. A risk model was developed, which was validated in a population of patients who had undergone operation between January and December 2006. Results: A total of 363 cases and 1,089 controls were analyzed. Major independent risk factors were age, gender, chronic pulmonary disease, ascites, jaundice, anemia, emergency surgery, type of surgery, postoperative coughing, and wound infection. In the validation population, risk scores were significantly higher (P < 0.001) for patients with abdominal wound dehiscence (n = 19) compared to those without (n = 677). Resulting scores ranged from 0 to 8.5, and the risk for abdominal wound dehiscence over this range increased exponentially from 0.02% to 70.1%. Conclusions: The validated risk model shows high predictive value for abdominal wound dehiscence and may help to identify patients at increased risk.

The influence of mechanical bowel preparation in elective lower colorectal surgery (Article)

2010-01-01T00:00:00Z

OBJECTIVE: This study evaluates the effects of mechanical bowel preparation (MBP) on anastomosis below the peritoneal verge and questions the influence of MBP on anastomotic leakage in combination with a diverting ileostomy in lower colorectal surgery. SUMMARY BACKGROUND DATA: In a previous large multicenter randomized controlled trial MBP has shown to have no influence on the incidence of anastomotic leakage in overall colorectal surgery. The role of MBP in lower colorectal surgery with or without a diverting ileostomy remains unclear. METHODS: This study is a subgroup analysis of a prior multicenter (13 hospitals) randomized trial comparing clinical outcome of MBP versus no MBP. Primary end point was the occurrence of anastomotic leakage and secondary endpoints were septic complications and mortality. RESULTS: Total of 449 Patients underwent a low anterior resection with a primary anastomosis below the peritoneal verge. The incidence of anastomotic leakage was 7.6% for patients who received MBP and 6.6% for patients who did not. Significant risk factors for anastomotic leakage were the American Society of Anesthesiologists-classification (P = 0.005) and male gender (P = 0.007). Of total, 48 patients received a diverting ileostomy during initial surgery; 27 patients received MBP and 21 patients did not. There were no significant differences regarding septic complications and mortality between both groups. CONCLUSION: MBP has no influence on the incidence of anastomotic leakage in low colorectal surgery. Furthermore, omitting MBP in combination with a diverting ileostomy has no influence on the incidence of anastomotic leakage, septic complications, and mortality rate. Copyright

Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome (Article)

2009-12-01T00:00:00Z

Objective: Intravenous immunoglobulin (IVIg) is the first choice treatment for Guillain-Barré syndrome (GBS). All patients initially receive the same arbitrary dose of 2g per kg body weight. Not all patients, however, show a good recovery after this standard dose. IVIg clearance may depend on disease severity and vary between individuals, implying that this dose is suboptimal for some patients. In this study, we determined whether the pharmacokinetics of IVIg is related to outcome in GBS. Methods: We included 174 GBS patients who had previously participated in 2 randomized clinical trials. At entry, all patients were unable to walk unaided and received a standard dose of IVIg. Total IgG levels in serum samples obtained immediately before and 2 weeks after the start of IVIg administration were determined by turbidimetry and related to clinical outcome at 6 months. Results: The increase in serum IgG (ΔIgG) 2 weeks after IVIg treatment varied considerably between patients (mean, 7.8g/L; standard deviation, 5.6g/L). Patients with a low ΔIgG recovered significantly more slowly, and fewer reached the ability to walk unaided at 6 months (log-rank p < 0.001). In multivariate analysis adjusted for other known prognostic factors, a low ΔIgG was independently associated with poor outcome ( p = 0.022). Interpretation: After a standard dose of IVIg treatment, GBS patients show a large variation in pharmacokinetics, which is related to clinical outcome. This may indicate that patients with a small increase in serum IgG level may benefit from a higher dosage or second course of IVIg.

Cigarette smoking and risk of MS in multiplex families (Article)

2009-11-27T00:00:00Z

Recent studies suggest that a history of cigarette smoking is a risk factor for multiple sclerosis (MS). We aimed to test the smoking effect in multiplex families, matching for both environmental and genetic factors. In a matched case-control study, 136 MS patients from 106 multiplex MS families were compared with their 204 healthy siblings as controls. Participants completed self-report questionnaires. Conditional logistic regression was used to analyse smoking and MS risk association while controlling for confounding by age and sex. Smoking history was classified in different variables. Within our survey the smoking history of MS patients and the controls did not differ. The odds of MS were comparable for different smoking levels. However, more intense exposure and women showed higher odds ratios, although non-significant. Association studies in families with relatively high genetic loading are unlikely to be confounded by smoking history.

The spectrum of structural abnormalities on CT scans from patients with CF with severe advanced lung disease (Article)

2009-10-01T00:00:00Z

Rationale: In cystic fibrosis (CF), lung disease is the predominant cause of morbidity and mortality. Little is known about the spectrum of structural abnormalities on. CT scans from patients with CF with severe advanced lung disease (SALD). No specific CT scoring system for SALD is available. Objectives: To design a quantitative CT scoring system for SALD, to determine the spectrum of structural abnormalities in patients with SALD and to correlate the SALD system with an existing scoring system for mild CF lung disease and pulmonary function tests (PFTs). Methods: 57 patients with CF contributed one CT made during screening for lung transplantation. For the SALD system, lung tissue was divided into four components: infection/inflammation (including bronchiectasis, airway wall thickening, mucus and consolidations), air trapping/ hypoperfusion, bulla/cysts and normal/hyperperfused tissue. The volume proportion of the components was estimated on a 0-100% scale; mean volumes for the whole lung were computed. Scores were correlated with Brody-II scores and PFTs. Results: The SALD system identified a wide spectrum of structural abnormalities ranging from predominantly infection/inflammation to predominantly air trapping/ hypoperfusion. SALD infection/inflammation scores correlated with Brody-II scores (rs = 0.36-0.64) and SALD normal/hyperperfusion scores correlated with forced expiratory volume in 1 s (FEV1; rs = 0.37). Reproducibility for both systems was good. Conclusions: A CT scoring system was developed to characterise the structural abnormalities in patients with SALD. A wide spectrum was observed in SALD, ranging from predominantly air trapping to predominantly infection/ inflammation-related changes. This spectrum may have clinical implications for patients with SALD.

Recombinant human DNase in children with airway malacia and lower respiratory tract infection (Article)

2009-10-01T00:00:00Z

Background: Children with airway malacia often have protracted courses of airway infections, because dynamic airway collapse during coughing results in impaired mucociliary clearance. The aim of this study was to determine the effect of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) on the recovery of respiratory symptoms in children with airway malacia and lower respiratory tract infection (LRTI). Methods: In a randomized double-blind controlled clinical trial, 40 children with airway malacia andLRTIwere randomlyassigned to receive either 2.5mg nebulized rhDNase or placebo twice daily for 2 weeks. The primary endpoint was the change in the cough diary score (CDS) (scale 0-5) from baseline to the second week of treatment. Secondary endpoints were VAS symptom scores for cough, dyspnea, and difficulty in expectorating sputum, need for an antibiotic course, and lung function data (FVC, FEV1, FEF75, Rinte ). Results: There was no significant difference in the mean change in CDSs from baseline between the rhDNase group and the placebo group (mean difference for daytime 0.19 (95% CI -0.53 to 0.90); for nighttime 0.38 (95% CI -0.30 to 1.05). Proportions of patients requiring antibiotics, and the mean changes in symptom scores and lung function from baseline did not significantly differ between both groups. Conclusion:Treatment with 2weeks of nebulized rhDNase does not enhance recovery or reduce the need for antibiotics in children with airway malacia and LRTI. (Controlled-trials.com number, ISRCTN85366144).

Cystic fibrosis: Are volumetric ultra-low-dose expiratory CT scans sufficient for monitoring related lung disease? (Article)

2009-10-01T00:00:00Z

Purpose: To assess whether chest computed tomography (CT) scores from ultra-low-dose end-expiratory scans alone could suffice for assessment of all cystic fibrosis (CF)-related structural lung abnormalities. Materials and Methods: In this institutional review board-approved study, 20 patients with CF aged 6-20 years (eight males, 12 females) underwent low-dose end-inspiratory CT and ultra-lowdose end-expiratory CT. Informed consent was obtained. Scans were randomized and scored by using the Brody-II CT scoring system to assess bronchiectasis, airway wall thickening, mucus plugging, and opacities. Scoring was performed by two observers who were blinded to patient identity and clinical information. Mean scores were used for all analyses. Statistical analysis included assessment of intra- and interobserver variability, calculation of intraclass correlation coefficients (ICCs), and Bland-Altman plots. Results: Median age was 12.6 years (range, 6.3-20.3 years), median forced expiratory volume in 1 second was 100% (range, 46%-127%) of the predicted value, and median forced vital capacity was 99% (range, 61%-123%) of the predicted value. Very good agreement was observed between end-inspiratory and end-expiratory CT scores for Brody-II total score (ICC = 0.96), bronchiectasis (ICC = 0.98), airway wall thickening (ICC = 0.94), mucus plugging (ICC = 0.96), and opacities (ICC = 0.90). Intra- and interobserver agreement were good to very good (ICC range, 0.70-0.98). Bland-Altman plots showed that differences in scores were independent of score magnitude. Conclusion: In this pilot study, CT scores from end-expiratory and end-inspiratory CT match closely, suggesting that ultralow-dose end-expiratory CT alone may be sufficient for monitoring CF-related lung disease. This would help reduce radiation dose for a single investigation by up to 75%.

Small stitches with small suture distances increase laparotomy closure strength (Article)

2009-09-01T00:00:00Z

Background: There is no conclusive evidence which size of suture stitches and suture distance should be used to prevent burst abdomen and incisional hernia. Methods: Thirty-eight porcine abdominal walls were removed immediately after death and divided into 2 groups: A and B (N = 19 each). Two suturing methods using double-loop polydioxanone were tested in 14-cm midline incisions: group A consisted of large stitches (1 cm) with a large suture distance (1 cm), and group B consisted of small stitches (.5 cm) with a small suture distance (.5 cm). Results: The geometric mean tensile force in group B was significantly higher than in group A (787 N vs 534 N; P = .006). Conclusions: Small stitches with small suture distances achieve higher tensile forces than large stitches with large suture distances. Therefore, small stitches may be useful to prevent the development of a burst abdomen or an incisional hernia after midline incisions.

The sentinel node concept in adenocarcinomas of the distal esophagus and gastroesophageal junction (Article)

2009-09-01T00:00:00Z

Objective: The sentinel node concept is of great value in the treatment of various malignancies. In this study we investigated whether the application of the sentinel node procedure is feasible in esophageal adenocarcinoma and whether it can tailor surgical treatment of the individual patient. Methods: In 40 patients with an adenocarcinoma of the distal esophagus or gastroesophageal junction, blue dye was injected around the tumor intraoperatively. Sentinel nodes (blue-stained) and nonsentinel nodes were identified and dissected during transhiatal esophagectomy. In sentinel nodes negative for tumor cells on routine hematoxylin-eosin examination, multilevel sectioning and immunohistochemical staining were performed to search for micrometastases. Results: The sentinel node procedure was technically successful in 39 of 40 patients (98%). The median number of sentinel nodes identified was 4. Sentinel nodes were present in more than 1 nodal station in 8 patients (21%). In 6 patients in whom the sentinel node was negative for metastasis, nonsentinel nodes were positive for tumor cells (false-negative rate 6/39 = 15%). Micrometastases and isolated tumor cells were detected in 7 of 19 patients (37%) with sentinel nodes, but this finding did not affect the false-negative rate. Conclusion: Detection of sentinel nodes is technically feasible during esophagectomy for cancer. However, given the relatively high false-negative rate of 15% and the high frequency of sentinel nodes in more than 1 nodal station, the clinical relevance of the sentinel node concept (through application of the blue dye technique) in the current treatment of patients with an adenocarcinoma of the distal esophagus or gastroesophageal junction seems limited.

Chlamydia trachomatis respiratory infection in Dutch infants (Article)

2009-09-01T00:00:00Z

Chlamydia trachomatis is the most common bacterial pathogen causing sexually transmitted infections in Dutch adults. As prenatal screening for C trachomatis and treatment of pregnant women is not routine practice in The Netherlands, perinatal transmission of C trachomatis may therefore occur. The presence of C trachomatis in infants less than 6 months of age who presented with respiratory complaints to the Erasmus MC-Sophia hospital was evaluated. Respiratory specimens, primarily nasopharyngeal swabs, were tested for C trachomatis, respiratory viruses and Mycoplasma pneumoniae using PCR, viral isolation in cell cultures and direct immunofluorescence. C trachomatis respiratory tract infection was confirmed to be relatively common with detection in 10 of 148 (7%) infants tested. C trachomatis had not been tested for by the attending physicians, but was the second most frequently detected respiratory pathogen after human Respiratory Syncitial Virus, which was found in 41 (28%) infants.

An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis (Article)

2009-08-01T00:00:00Z

Background: Phaeochromocytomas and paragangliomas are neuro-endocrine tumours that occur sporadically and in several hereditary tumour syndromes, including the phaeochromocytoma-paraganglioma syndrome. This syndrome is caused by germline mutations in succinate dehydrogenase B (SDHB), C (SDHC), or D (SDHD) genes. Clinically, the phaeochromocytoma-paraganglioma syndrome is often unrecognised, although 10-30% of apparently sporadic phaeochromocytomas and paragangliomas harbour germline SDH-gene mutations. Despite these figures, the screening of phaeochromocytomas and paragangliomas for mutations in the SDH genes to detect phaeochromocytoma-paraganglioma syndrome is rarely done because of time and financial constraints. We investigated whether SDHB immunohistochemistry could effectively discriminate between SDH-related and non-SDH-related phaeochromocytomas and paragangliomas in large retrospective and prospective tumour series. Methods: Immunohistochemistry for SDHB was done on 220 tumours. Two retrospective series of 175 phaeochromocytomas and paragangliomas with known germline mutation status for phaeochromocytoma-susceptibility or paraganglioma-susceptibility genes were investigated. Additionally, a prospective series of 45 phaeochromocytomas and paragangliomas was investigated for SDHB immunostaining followed by SDHB, SDHC, and SDHD mutation testing. Findings: SDHB protein expression was absent in all 102 phaeochromocytomas and paragangliomas with an SDHB, SDHC, or SDHD mutation, but was present in all 65 paraganglionic tumours related to multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis type 1. 47 (89%) of the 53 phaeochromocytomas and paragangliomas with no syndromic germline mutation showed SDHB expression. The sensitivity and specificity of the SDHB immunohistochemistry to detect the presence of an SDH mutation in the prospective series were 100% (95% CI 87-100) and 84% (60-97), respectively. Interpretation: Phaeochromocytoma-paraganglioma syndrome can be diagnosed reliably by an immunohistochemical procedure. SDHB, SDHC, and SDHD germline mutation testing is indicated only in patients with SDHB-negative tumours. SDHB immunohistochemistry on phaeochromocytomas and paragangliomas could improve the diagnosis of phaeochromocytoma-paraganglioma syndrome. Funding: The Netherlands Organisation for Scientific Research, Dutch Cancer Society, Vanderes Foundation, Association pour la Recherche contre le Cancer, Institut National de la Santé et de la Recherche Médicale, and a PHRC grant COMETE 3 for the COMETE network.

A randomized trial investigating an exercise program to prevent reduction of bone mineral density and impairment of motor performance during treatment for childhood acute lymphoblastic leukemia (Article)

2009-07-15T00:00:00Z

Background. Reduced bone mineral density (BMD), altered body composition, impaired motor performance and passive ankle dorsiflexion are side effects of acute lymphoblastic leukemia (ALL) treatment. We performed a randomized study investigating whether an exercise program could prevent these side effects. Procedure. At diagnosis we randomized 51 ALL patients (median age: 5.4 years) into a group receiving a 2-year exercise program or a control group receiving standard care. BMD of total body (BMDTB), lumbar spine (BMDLS) and body composition were measured using dual energy X-ray absorptiometry, motor performance with Bayley Scales of Infant Development or Movement-ABC, and passive ankle dorsiflexion with a goniometer. The investigator was blinded to the randomization. Results. Body fat increased equally during treatment in both groups. One year after cessation of therapy more rapid decline of excessive body fat was observed in the intervention group than in the controls (P=0.01). Lean body mass, BMDTBand BMDLSof both groups decreased equally during treatment and increased equally thereafter. Both groups showed a similar decrease in passive ankle dorsiflexion and motor performance during treatment. Adherence to the intervention program varied considerably. Adherence to intervention: 11% of children exercised daily, 37% > once a week, 16% once weekly, 36% < once a week. Conclusions. The exercise program was not more beneficial than standard care in preventing reduction in BMD, motor performance and passive ankle dorsiflexion than standard care, most likely due to unsatisfactory compliance. Increased BMI and body fat in the intervention group normalized faster after cessation of chemotherapy.

Risk factors for abdominal wound dehiscence in children: A case-control study (Article)

2009-07-01T00:00:00Z

Background: In the limited literature concerning abdominal wound dehiscence after laparotomy in children, reported incidences range between 0.2-1.2% with associated mortality rates of 8-45%. The goal of this retrospective case-control study was to identify major risk factors for abdominal wound dehiscence in the pediatric population. Methods: Patients younger than aged 18 years who developed abdominal wound dehiscence in three pediatric surgical centers during the period 1985-2005 were identified. For each patient with abdominal wound dehiscence, four controls were selected by systematic random sampling. Patients with (a history of) open abdomen treatment or abdominal wound dehiscence were excluded as control subjects. Putative relevant patient-related, operation-related, and postoperative variables for both cases and control subjects were evaluated in univariate analyses and subsequently entered in multivariate stepwise logistic regression models to identify major independent predictors of abdominal wound dehiscence. Results: A total number of 63 patients with abdominal wound dehiscence and 252 control subjects were analyzed. Mean presentation of abdominal wound dehiscence was at postoperative day 5 (range, 1-15) and overall mortality was 11%. Hospital stay was significantly longer (p < 0.001) in the case group (median, 42 vs. 10 days). Major independent risk factors for abdominal wound dehiscence were younger than aged 1 year, wound infection, median incision, and emergency surgery. Incisional hernia was reported in 12% of the patients with abdominal wound dehiscence versus 3% in the control group (p = 0.001). Conclusions: Abdominal wound dehiscence is a serious complication with high morbidity and mortality. Median incisions should be avoided whenever possible.

Congenital valvular aortic stenosis: Limited progression during childhood (Article)

2009-07-01T00:00:00Z

Objective: Congenital valvular aortic stenosis is a common congenital heart malformation. The rate of progression in childhood, however, remains to be established. We assessed the progression of peak aortic velocity before intervention as well as the frequency of intervention in paediatric patients with isolated congenital valvular aortic stenosis. Methods: A retrospective cohort study was performed in 245 consecutive patients with aortic stenosis. Both clinical and echocardiographic data were obtained. Results: Over a period of 9.0 (SD 5.2) years (range 0.1-19.4), the mean annual increase in peak systolic velocity was 0.04 m/s/year (95% CI 0.028 to 0.056 m/s/year; p<0.001) as shown by ANOVA. 40 patients underwent a cardiac intervention shortly after their first echocardiogram. Another 33 patients underwent intervention during follow-up. Interventions were performed significantly more often in patients diagnosed at a younger age and/or with a higher peak velocity at diagnosis (p<0.001). Mortality was considerable in those diagnosed in infancy (5-year survival rate of 73% (SD 9%), whereas it was nearly absent in patients diagnosed after infancy. Most patients who died during infancy had progressive left ventricular dysfunction despite adequate relief of left ventricular outflow obstruction. Conclusions: Valvular aortic stenosis in the paediatric age group usually has a good prognosis beyond the neonatal period. Progression over time is usually limited, although a considerable proportion of patients need intervention shortly after initial diagnosis. Mortality, except for the neonatal age group, is nearly absent.

Transanal endoscopic microsurgery is feasible for adenomas throughout the entire rectum: A prospective study (Article)

2009-06-01T00:00:00Z

INTRODUCTION: Transanal endoscopic microsurgery for rectal adenomas is safe and has low recurrence rates. However, the feasibility of the procedure for all rectal adenomas is unclear. This issue was investigated prospectively. METHODS: From 1996 to 2007, 353 consecutive rectal adenomas were evaluated according to a standard protocol. Transanal endoscopic microsurgery was intended in all rectal adenomas. RESULTS: The median diameter was 3 cm and median distance was 8 cm. The peritoneum was opened peroperatively without any adverse effects in 8.7 percent. The conversion rate was 9.6 percent, with an alternative local procedure performed in 4.2 percent and a transabdominal procedure performed in 5.4 percent. Conversion rate correlated with the distance of the tumor (P = 0.007) and the operating surgeon's level of experience (P = 0.004). The median operation time was 45 minutes. Operation time correlated with specimen area, experience, and operating surgeon (all P < 0.001). All rectal adenomas were excised in one piece. Complete margins were observed in 85 percent. Rectal adenomas with incomplete margins were larger (P < 0.001) and were located more proximally (P < 0.001). Morbidity was 7.8 percent and mortality 0.6 percent. The median hospital stay was four days. The median follow-up was 27 months. The recurrence rate at three years was 9.1 percent. The median time from operation to recurrence was 12 (range, 4-54) months. Resection margin status was a predictor of recurrence, with 6.1 percent recurrence in cases of complete margins and 25.2 percent in cases of incomplete margins (P < 0.001). CONCLUSIONS: For nearly all rectal adenomas, transanal endoscopic microsurgery is safe, feasible, and has excellent results.

Long-term patient satisfaction after percutaneous treatment of peripheral vascular malformations (Article)

2009-06-01T00:00:00Z

Purpose: To determine long-term patient satisfaction for percutaneous treatment by using sclerosing agents (sclerotherapy) and/or arterial embolization for peripherally located vascular malformations (VMs). This treatment has been described as successful; however, there is a relative paucity of published long-term results. Materials and Methods: This retrospective study was institutional review board approved; 107 patients treated for symptomatic VM were evaluated. After informed consent was obtained, 66 patients were sent a questionnaire regarding treatment effectiveness and patient satisfaction. Patient files and imaging data were retrieved to obtain information regarding the VMs and VM treatment. Kaplan-Meier survival curves were constructed to analyze clinical success rates over time. Results: The most frequent reasons for patients to seek treatment were pain (89%, n = 59) and swelling (91%, n = 60). The majority of VMs were the low-flow venous type (83%, n = 55). Three months after treatment, clinical success was reported for 58% (n = 38) of patients and clinical failure was reported for 42% (n = 28). At 1-, 2-, 3-, 4-, and 5-year follow-up, clinical success was 49%, 49%, 42%, 42%, and 42%, respectively. Twenty-seven (40%) patients experienced complications, 12 of which required additional treatment. In all, 35 (53%) patients reported being satisfied with their treatment. Patient satisfaction was closely correlated with clinically successful long-term outcome of treatment. Conclusion: Initial partial or complete relief of VM complaints after percutaneous treatment is expected in 58% of patients, irrespective of VM size or classification. These results were durable over a 5-year follow-up period.

Community integration following moderate to severe traumatic brain injury: A longitudinal investigation (Article)

2009-06-01T00:00:00Z

Objective: To evaluate the course and identify determinants of community integration for up to 3 years following moderate to severe traumatic brain injury. Design: Prospective cohort study. Patients: A total of 119 patients with moderate to severe traumatic brain injury aged 16-67 years. Methods: The Community Integration Questionnaire' was completed at 3, 6, 12, 18, 24 and 36 months post-injury. Repeated measures analysis of variance was performed to determine changes over time in the Community Integration Questionnaire and its subscales. Bivariate and multivariate regression analyses were used to identify determinants of community integration 36 months post-injury. Results: Compared with pre-injury, mean home integration, social integration, productivity, and total questionnaire scores decreased 3 months post-injury. Patient scores showed maximal improvement during the first year post-injury. Mean home integration, productivity, and total scores increased to a lesser extent during years 1-3 post-injury. Age, Barthel Index scores, hospital discharge destination, and pre-injury community integration scores were the major determinants of community integration 36 months post-injury (R2=60%). Conclusion: After an initial decline, mean community integration scores gradually improve following moderate to severe traumatic brain injury. Understanding the course and determinants of community integration is necessary in order to determine functional prognosis following traumatic brain injury.

Percutaneous endoscopic gastrostomy (PEG) in children is not a minor procedure: risk factors for major complications (Article)

2009-05-01T00:00:00Z

Percutaneous endoscopic gastrostomy (PEG) provides for enteral nutrition in children with feeding problems. PEG, however, is not without complications. The present study has a twofold aim: (1) comparing our incidence of major complications after PEG with the incidence in other centers, and (2) identifying risk factors for major complications. All patients receiving a PEG or laparoscopic-assisted PEG (lap PEG) in the period 1992-2008 were reviewed. Primary outcome was the occurrence of major complications, defined as the need for surgery, nonprophylactic antibiotics, or blood transfusion, and procedure-related death. Potential risk factors, eg, age under 1 year, mental retardation, scoliosis, constipation, hepatomegaly, upper abdominal surgery, ventriculoperitoneal shunt, peritoneal dialysis, esophageal stenosis, and coagulopathy, were analyzed. Of the 467 patients (448 PEG, 19 lap PEG), 12.6% developed major complications. The complication rate significantly decreased (P = 0.003) over the years. A significantly higher complication rate of 32% (P = 0.02) occurred in children with a ventriculoperitoneal shunt. None of the lap PEG procedures was associated with a major complication, but the difference was not significant, perhaps because of the small numbers in the latter group. The major complication rate after PEG in children is high. Preexisting ventriculoperitoneal shunt is a significant risk factor. Laparoscopically assisted PEG procedures seem to be associated with a lesser major complication rate.

Long-term skin scarring and orthopaedic sequelae in survivors of meningococcal septic shock (Article)

2009-05-01T00:00:00Z

Objective: To assess the incidence of skin scarring and orthopaedic sequelae (amputation, limb-length discrepancy) in patients who survived meningococcal septic shock (MSS) in childhood and to determine the severity and predictors of these sequelae. Methods: 179 consecutive patients (170 of whom were eligible) with septic shock and purpura requiring intensive care between 1988 and 2001 in Rotterdam, the Netherlands were invited to visit a follow-up clinic 4-16 years after paediatric intensive care unit (PICU) discharge. Results: 58 (48%) of 120 follow-up patients (median follow-up interval 10 years; median age at follow-up 14.5 years) had skin scarring due to purpura. This varied from barely visible to extremely disfiguring scars. Ten patients (8%) had undergone amputation(s) of extremities, ranging from one toe to both legs and one arm. Seven patients (6%) had lower limb-length discrepancy, in most cases together with angular deformity, requiring one or more late surgical intervention(s). Patients with scars or orthopaedic sequelae had significantly higher severity of illness scores, determined by the Pediatric Risk of Mortality score, Vasopressor score and Disseminated Intravascular Coagulation score. Gender or Neisseria meningitidis serogroup had no significant influence on the presence of scars or orthopaedic sequelae. Patients with lower limb-length discrepancy were significantly younger at the time of PICU admission. Conclusions: The incidence of long-term skin scarring and orthopaedic sequelae was high (48% and 14%, respectively) in patients who survived MSS in childhood. The severity of these sequelae varied from mild to severe. Patients with scars or orthopaedic sequelae had significantly higher severity of illness scores.

Assessment of biventricular functional reserve and NT-proBNP levels in patients with RV volume overload after repair of tetralogy of Fallot at young age (Article)

2009-04-17T00:00:00Z

Purpose: To assess biventricular functional reserve (FR), NT-proBNP levels and exercise performance, in relation to right ventricular volume in patients with pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) at young age. Methods: In 53 TOF patients (maximum age at repair 2.0 years, interval since repair 15 (5) years) without residual lesions except PR, biventricular FR (derived from magnetic resonance imaging with dobutamine stress), NT-proBNP levels, maximal workload, and peak oxygen uptake were assessed. Results: Mean right ventricular end-diastolic volume was 140(38) ml/m2. Median pulmonary regurgitant fraction was 37% (range 0-57%). Biventricular systolic stress response was normal: mean (SD) ESV decreased (ΔRVESV - 17(8) ml/m2, ΔLVESV - 11(5)), SV increased (ΔRVSV + 12(9) ml/m2, ΔLVSV + 9(6)), FR was positive in all (RV-FR + 11(5)%, LV-FR + 13(6)). No serious adverse effects to dobutamine were encountered. NT-proBNP was increased in 2 patients. Median level was 10 pmol/L (range 2-42). NT-proBNP correlated with PR-percentage but not with right ventricular size. High-risk levels of NT-proBNP indicated a smaller RV-FR and a smaller decrease of biventricular ESV. Mean (SEM) VO2maxwas 96(3)%, mean Workloadmax89(2)% of predicted. Conclusion: At mid to long term follow-up overall NT-proBNP levels are normal and biventricular functional reserve and exercise tolerance are well preserved in TOF repaired at young age, irrespective of RV volume. This questions the validity of isolated PR or RV volume criteria for pulmonary valve replacement in this group. Low-dose dobutamine stress testing is well tolerated and may be a useful additional tool for clinical decision making.

Stability, tipping and relapse of bone-borne versus tooth-borne surgically assisted rapid maxillary expansion; a prospective randomized patient trial (Article)

2009-04-01T00:00:00Z

This study evaluated stability, tipping and relapse after surgically assisted rapid maxillary expansion (SARME), comparing bone-borne and tooth-borne devices, in skeletally matured non-syndromal patients with transverse maxillary hypoplasia. The study is a randomized, open-label, clinical trial. Patients were randomized to bone-borne (n = 25) and tooth-borne (n = 21) groups. The surgical technique for corticotomy was the same in both groups. Expansion was performed using a bone-borne or tooth-borne device. Dental study casts, lateral and postero-anterior cephalograms were taken before treatment, after the distraction phase and at 12-month follow up. Stability, segmental maxillary tipping and relapse were studied. 23 bone-borne and 19 tooth-borne patients were analyzed. There were no significant differences between the two groups. Widening was comparable at canine, premolar and molar level. Relapse was not significant and at follow up the significant increase in distance was sustained. A significant increase in palatal width, at premolar and molar level, occurred in both groups. The maxilla moves slightly downward in SARME. Segmental maxillary tipping occurred in both groups and did not affect relapse. There is no significant difference between the two groups. In SARME, the widening achieved at dental level is stable after 12 months. Over-correction is not necessary. Tipping of the maxillary segments and increases in the retention period are equal in both groups.

Array comparative genomic hybridization, expression array, and protein analysis of critical regions on chromosome arms 1q, 7q, and 8p in adenocarcinomas of the gastroesophageal junction (Article)

2009-02-01T00:00:00Z

Survival rates of adenocarcinomas of the gastroesophageal junction (GEJ) are low, because these tumors are generally in an advanced stage by the time they are detected. Chromosomal regions 1q32, 7q21, and 8p22 display critical alterations in GEJ cancers; however, the genes underlying alterations in these genomic areas are largely unknown. To delineate overexpressed genes, we performed array comparative genomic hybridization (aCGH) and mRNA expression analysis of 15 GEJ adenocarcinoma samples using a fine-tiling cDNA array covering chromosome segments 1q31.3∼q41 (193.9-215.8 Mb: 21.9 Mb), 7q11.23∼q22.1 (72.3-103.0 Mb: 30.7 Mb), and 8p23.1∼p21.3 (11.1-20.7 Mb: 9.6 Mb). Based on a mRNA overexpression criterion, 11 genes were selected: ELF3 and SLC45A3 on 1q; CLDN12, CDK6, SMURF1, ARPC1B, ZKSCAN1, MCM7, and COPS6 on 7q; and FDFT1 and CTSB on 8p. The protein expression levels were subsequently determined by immunohistochemical analysis of the cancer samples. There was a significant correlation between genomic amplification, mRNA, and protein expression or overexpression for CDK6, a cell cycle regulator on 7q21.2 (92.1 Mb; P < 0.01); other genes showed less stringent associations. In conclusion, using a straightforward approach we constructed a targeted gene profile for GEJ adenocarcinomas.

A randomized trial of cryo stripping versus conventional stripping of the great saphenous vein (Article)

2009-02-01T00:00:00Z

Objective: This multicenter randomized clinical trial compared cryo stripping of the great saphenous vein (GSV) with conventional stripping. Methods: The study randomized 494 patients with symptomatic (CEAP) clinical severity class 2 to 4 to cryo stripping (n = 249) or conventional stripping (n = 245). The primary outcome was residual GSV 6 months after surgery measured by venous duplex ultrasound imaging. Secondary outcomes were quality of life, operation time, and postoperative neural damage. Duration of follow-up was 6 months. Quality of life was measured at 6 and 26 weeks postoperatively with the Aberdeen Varicose Vein Questionnaire (AVVQ) and Medical Outcomes Study Short-Form 36 (SF-36) Health Survey. Results: The two groups were well matched at baseline. The percentage of patients with residual GSV at 6 months (primary outcome) was 44% (102 of 230) in the cryo group and 15% (33 of 215) in the conventional group (difference 29%; 95% confidence interval [CI], 21%-37%, P < .001). Median operation time was significantly shorter in the cryo group (30 minutes) compared with the conventional group (39 minutes). Neural damage was 12% in both groups, and thus not significantly different. Scores on the subdomains of the SF-36 showed no significant change between the groups. The AVVQ after conventional stripping was 8.0, which was a better result than the 11.7 result after cryo stripping (difference 2.6 points; 95% CI, 1.0-4.2; P = .001, repeated measurements analysis of variance with adjustment for baseline scores). Conclusions: Cryo stripping accounts for numerous procedural failures and hence residual GSV in patients. The AVVQ showed small but significantly better results for patients after a conventional stripping. Cryo stripping has no benefits over conventional stripping.

Lung morphology assessment using MRI: A robust ultra-short TR/TE 2D steady state free precession sequence used in cystic fibrosis patients (Article)

2009-02-01T00:00:00Z

To evaluate feasibility and diagnostic quality of ultra-short TR/TE two-dimensional (2D) steady state free precession (SSFP) MRI for cystic fibrosis (CF) patients. We performed lung MRI at 1.5 Tesla in 20 CF-patients (6-17 years, 12 males). Axial, coronal, and sagittal sections were acquired in inspiration and expiration with maximum breath-hold time 10 s. MR and CT images were scored using a modified Brody scoring system to assess bronchiectasis, mucous plugging, atelectasis/consoli-dations, and air trapping. All images were scored by two experienced observers. A complete MR investigation took maximally 15 min. Maximal breath-holds were only 10 s and well tolerated. MRI identified major bronchiectasis, mucous plugging and at-electasis. End-expiratory scans showed patches of parenchyma with reduced signal intensity that may corresponded to areas of trapped air on expiratory CT scans. This MRI protocol based on ultra-short TR/TE 2D SSFP is quick and well tolerated and provides highly relevant imaging features as seen on CT in CF patients. Most importantly, the SNR of the expiratory scans enables to visualize air trapping. The preliminary results of this study suggest MRI as a noteworthy additional imaging tool for routine monitoring of CF patients.

Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease (Article)

2009-02-01T00:00:00Z

To determine the rate of disease progression in patients with late-onset Pompe disease, we collected longitudinal data on pulmonary function and skeletal muscle strength in 16 patients whose symptoms had started in childhood or adulthood. The mean duration of follow-up was 16 years (range 4-29 years). During the follow-up period, eight patients (50%) became wheelchair bound and three (19%) became ventilator dependent. At a group level, pulmonary function deteriorated by 1.6% per year, and proximal muscle weakness progressed gradually. At the individual level, however, the rate and extent of progression varied highly between patients. In two thirds of patients, pulmonary function and muscle strength declined simultaneously and to the same extent. The remaining one third of patients showed a variable, sometimes rapidly progressive course, leading to early respirator or wheelchair dependency. These individual differences, especially in pulmonary dysfunction, indicate the need for regular monitoring every 6-12 months depending on the rate of disease progression.

Daily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthma (Article)

2009-01-15T00:00:00Z

Rationale: Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FE NO0.05), a marker of eosinophilic airway inflammation, can be measured at home. Objectives: We assessed daily FENO0.05 telemonitoring in the management of childhood asthma. Methods: Children with atopic asthma (n = 151) were randomly assigned to two groups: FE NO0.05 plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FENO0.05 and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks. Measurements and Main Results: Telemonitoring was feasible with reliable FENO0.05 data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV1 and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weekswas0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FE NO0.05 group. Conclusions: Thirty weeks of daily FENO0.05 and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FENO0.05 monitoring compared with daily symptom monitoring only.

Cutoff values for FENO-guided asthma management (Article)

2009-01-01T00:00:00Z

Early pregnancy volume measurements: Validation of ultrasound techniques and new perspectives (Article)

2009-01-01T00:00:00Z

Objective: To investigate accuracy and reliability of four different ultrasound-related volume-measuring methods. Design: Observational study. Setting: Both in vitro and in vivo. Population or Sample: Ten phantoms for in vitro measurements and 28 pregnancies with gestational ages ranging from 6 to 11 weeks for in vivo measurements were included. Methods: Three-dimensional (3D) ultrasound images of phantoms (with known variable contents) and yolk sacs were used to calculate volumes using four different methods: Virtual Organ Computed-Aided AnaLysis (VOCAL), inversion mode, Sono Automatic Volume Calculation (SonoAVC) and V-Scope. V-Scope is a newly developed 3D volume visualisation application using a Barco I-Space virtual reality system. Intra- and interobserver agreement was established by calculating intraclass correlation coefficients (ICC). Main outcome measure: Evaluation of accuracy and reliability by comparing the different techniques with true volumes (in vitro) and with each other (in vitro and in vivo). Results: In the in vitro study, volume measurements by VOCAL, inversion mode and V-Scope proved to be accurate. SonoAVC measurements resulted in a substantial systematic underestimation. Correlation coefficients of measured versus true volumes were excellent in all four techniques. For all techniques, an intra- and interobserver agreement of at least 0.91 was found. Yolk sac measurements by the different techniques proved to be highly correlated (ICCs > 0.91). Conclusions: We demonstrated that VOCAL, inversion mode and V-Scope can all be used to measure volumes of hypoechoic structures. The newly introduced V-Scope application proved to be accurate and reliable.

Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer a prospective randomized controlled trial (Article)

2008-12-01T00:00:00Z

Background: Success of surgical treatment for pancreatic and periampullary cancer is often limited due to locoregional recurrence and/or the development of distant metastases. Objective: The survival benefit of celiac axis infusion (CAI) and radiotherapy (RT) versus observation after resection of pancreatic or periampullary cancer was investigated. Methods: In a randomized controlled trial, 120 consecutive patients with histopathologically proven pancreatic or periampullary cancer received either adjuvant treatment consisting of intra-arterial mitoxantrone, 5-FU, leucovorin, and cisplatinum in combination with 30 × 1.8 Gy radiotherapy (group A) or no adjuvant treatment (group B). Groups were stratified for tumor type (pancreatic vs. periampullary tumors). Results: After surgery, 120 patients were randomized (59 patients in the treatment group, 61 in the observation group). The median follow-up was 17 months. No significant overall survival benefit was seen (median, 19 vs. 18 months resp.). Progressive disease was seen in 86 patients: in 37 patients in the CAI/RT group, and in 49 patients in the observation group (log-rank P < 0.02). Subgroup analysis showed significantly less liver metastases after adjuvant treatment in periampullary tumors (log-rank P < 0.03) without effect on local recurrence. Nonetheless, there was no significant effect on overall survival in these patients (log-rank P < 0.15). In patients with pancreatic cancer, CAI/RT had no significant effect on local recurrence (log-rank P < 0.12) neither on the development of liver metastases (log-rank P < 0.76) and consequently, no effect on overall survival. Conclusion: This adjuvant treatment schedule results in a prolonged time to progression. For periampullary tumors, CAI/RT induced a significant reduction in the development of liver metastases, with a possible effect on overall survival. Especially in these tumors, CAI/RT might prove beneficial in larger groups and further research is warranted. Copyright

Reliability of three-dimensional sonographic measurements in early pregnancy using virtual reality (Article)

2008-12-01T00:00:00Z

Objective: To establish the reliability of three-dimensional (3D) ultrasound measurements in early pregnancy using a virtual reality system (the Barco I-Space). Methods: The study included 28 pregnancies with gestational ages ranging from 6 to 14 (median, 10) weeks. 3D volumes were acquired and offline measurements were made, where possible, of the yolk sac diameter, crown-rump length, biparietal diameter, head circumference and abdominal circumference, using specialized 3D imaging software (4DView). The datasets were then transferred to the Barco I-Space, a virtual reality system that allows the observer to perceive depth and interact with volume-rendered (ultrasound) data. The 3D rendered volumes were measured using a virtual pointer, controlled by a wireless joystick. For intraobserver variability, 3D and virtual reality volumes were measured twice by one operator. For interobserver variability, another operator performed the same measurements once. All measurements were repeated three times and their mean values were used for comparisons. Results: All intraclass correlation coefficients (ICCs) comparing 4DView measurements with I-Space measurements were >0.97. Intra- and interobserver ICCs for the 4DView measurements were >0.96 and for the I-Space ones were >0.98, representing good agreement. Conclusions: The application of virtual reality is a novel method of visualizing 3D ultrasound data and perception of the depth in the I-Space offers possibilities for measuring non-planar structures. We have demonstrated that early pregnancy measurements in the I-Space are reliable. New areas of embryonic and fetal biometry can now be explored using this technique, which we tentatively name 'virtual embryoscopy'. Copyright

Airway dimensions in bronchopulmonary dysplasia: Implications for airflow obstruction (Article)

2008-12-01T00:00:00Z

The cause of lung function abnormalities in bronchopulmonary dysplasia (BPD) is incompletely understood, even in the "new era" of this disease. Altered airwaywall dimensions are important in the pathogenesis of airflow obstruction in diseases such as asthma and chronic obstructive pulmonary disease. Whether airway wall dimensions contribute to lung function abnormalities in BPD is unknown. The purpose of this study was to investigate airway wall dimensions in relation to airway size in BPD. Lung tissue of patients with BPD was obtained at autopsy, and lung tissue from children who died from sudden infant death syndrome (SIDS) served as control. Airway wall dimensions and epithelial loss were measured in 75 airways from 5 BPD patients and 176 airways from 11 SIDS patients. Repeated measures analysis of variance was used to assess the relationships between airway wall dimensions and airway size for BPD and SIDS patients. Little epithelial loss was present in the BPD patients while extensive loss was observed in some of the SIDS patients. The inner wall area, outer wall area, epithelium area and smooth muscle area were all substantially larger (all P < 0.001) in BPD than in SIDS patients. It is likely that the increased thickness of the airway wall components contributes to airflow obstruction in BPD patients.

Recovery of graft function in pediatric kidney transplantation is not affected by delayed introduction of cyclosporine (Article)

2008-11-15T00:00:00Z

BACKGROUND.: Delayed graft function and acute rejections adversely affect the long-term survival of kidney transplantation. To decrease the incidences of these phenomena, we changed the initial immunosuppressive protocol in pediatric kidney transplantation in the Netherlands. METHODS.: We compared a cohort (n=123) treated with basiliximab and delayed onset cyclosporine (CsA) with the preceding cohort (n=110) in which CsA was started already preoperatively. Both cohorts were treated with mycophenolate mofetil and corticosteroids as well. All consecutive transplantations were included. RESULTS.: The incidence of delayed graft function did not significantly differ between the cohorts (10% and 13%, in basiliximab and control group). Significantly fewer patients in the basiliximab group had acute rejection episodes (20% vs. 36% in control group, P=0.007). The mean estimated glomerular filtration rate at 1 year and graft survival at 2 years posttransplant did not differ between groups (62 vs. 64 mL/min 1.73 m, and 89% vs. 92%, respectively). CONCLUSION.: Postponed onset of CsA in triple immunosuppressive therapy (corticosteroids, CsA, and mycophenolate mofetil) with addition of basiliximab did not reduce the incidence of delayed graft function in pediatric kidney transplantation. Yet, fewer acute rejections were noted. Long-term favorable effects could not be detected in this study.

High-normal thyroid function and risk of atrial fibrillation: The Rotterdam study (Article)

2008-11-10T00:00:00Z

Background: Overt and subclinical hyperthyroidism are both well-known independent risk factors for atrial fibrillation. We aimed to investigate the association of high-normal thyroid function with the development of atrial fibrillation in a prospective population-based study in the elderly. Methods: The association between thyroid-stimulating hormone (TSH) levels and atrial fibrillation was examined in 1426 subjects with TSH levels in the normal range (0.4-4.0 mU/L) and without atrial fibrillation at baseline. In 1177 of the 1426 persons in this group, we also examined the association between free thyroxine levels within the normal range (0.86-1.94 ng/dL [to convert to picomoles per liter, multiply by 12.871]) and atrial fibrillation. During a median follow-up of 8 years, 105 new cases of atrial fibrillation were identified. Hazard ratios (HRs) were calculated with 95% confidence intervals (CIs) using Cox proportional hazards models after adjustment for age, sex, current smoking, former smoking, body mass index, systolic blood pressure, hypertension, history of myocardial infarction, presence of heart failure, left ventricular hypertrophy on the electrocardiogram, diabetes mellitus, total cholesterol level, and time of the drawing of blood samples. Results: The risk of atrial fibrillation was associated with the TSH level. The multivariate adjusted HR was 1.94 (95% CI, 1.13-3.34, lowest vs highest quartile; P for trend, .02). The multivariate adjusted level of free thyroxine showed a graded association with risk of atrial fibrillation (HR, 1.62; 95% CI, 0.84-3.14, highest vs lowest quartile; P for trend, .06). Conclusion: Within the normal range of thyroid parameters, persons with high-normal thyroid function are at an increased risk of atrial fibrillation.

Long-term health status in childhood survivors of meningococcal septic shock (Article)

2008-11-01T00:00:00Z

Objective: To assess long-term health status in patients who survived meningococcal septic shock in childhood. Design: Medical and psychological follow-up of a cross-sectional cohort. Setting: Pediatric intensive care unit (PICU) of a tertiary care university hospital. Participants: All consecutive patients with septic shock and purpura who required intensive care between 1988 and 2001. Intervention: Patients and their parents were invited to our follow-up clinic 4 to 16 years after PICU discharge. Outcome Measures: Health status was assessed with a standard medical interview, physical examination, renal function test, and the Health Utilities Index Mark 2 (HUI2) and 3 (HUI3). Results: One hundred twenty patients (response rate 71%) participated in the follow-up (median age at PICU admission, 3.1 years; median follow-up interval, 9.8 years; median age at follow-up, 14.5 years). Thirty-five percent of patients had 1 or more of the following neurological impairments: severe mental retardation with epilepsy (3%), hearing loss (2%), chronic headache (28%), and focal neurological signs (6%), like paresis of 1 arm. One of the 16 patients with septic shock-associated acute renal failure at PICU admission showed signs of mild chronic renal failure (glomerular filtration rate, 62 mL/min/1.73m2; proteinuria; and hypertension). Scores were significantly lower on nearly all HUI2 and HUI3 attributes compared with Dutch population data, indicating poorer health in these patients. Conclusions: In patients who survived meningococcal septic shock in childhood, one-third showed long-term neurological impairments, ranging from mild to severe and irreversible. Patients reported poorer general health as measured by HUI2 and HUI3.

Immunohistochemical evaluation of a panel of tumor cell markers during malignant progression in Barrett esophagus (Article)

2008-11-01T00:00:00Z

Histopathologic grading of dysplasia in Barrett esophagus (BE) shows substantial interobserver and intraobserver variation. We used immunohistochemical analysis with a set of tumor cell markers, ie, epidermal growth factor receptor (EGFR), ERBB2 (HER2/neu), MYC, CDKN2A (p16), SMAD4, MET, CCND1 (cyclin D1), CTNNB1 (β-catenin), and TP53 (p53), in histologic sections of endoscopic biopsies of 86 patients with BE in various stages of neoplastic progression. The markers, except SMAD4, were scored as 0 (<1% of cells stained), 1 (1%-25%), 2 (26%-50%), or 3 (>50%). All markers, except EGFR, showed a significant trend for immunohistochemical protein overexpression during malignant progression in BE (P < .01). When the successive stages along the metaplasia-low-grade dysplasia (LGD)-high-grade dysplasia (HGD)-adenocarcinoma axis were compared, protein overexpression of β-catenin separated LGD from metaplasia, whereas protein overexpression of cyclin D1 and p53 discriminated HGD from LGD (all P < .001). β-Catenin can be helpful for a diagnosis of LGD in BE, although it stains positively in a subset only, whereas p53 remains an appropriate marker to define HGD. In case of doubt, cyclin D1 can be added to separate LGD from HGD in BE.

Mycophenolate mofetil versus cyclosporine for remission maintenance in nephrotic syndrome (Article)

2008-11-01T00:00:00Z

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m2per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period. Of the 12 patients in the MMF group, two discontinued the study medication. Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period (p = 0.03). Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period. Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08). None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic acid were performed in seven patients. The patient with the lowest area under the curve had three relapses within 6 months. In children with frequently relapsing minimal change nephrotic syndrome, MMF has a favourable side effect profile compared to CsA; however, there is a tendency towards a higher relapse risk in patients treated with MMF.

Isolated or non-isolated duodenal obstruction: Perinatal outcome following prenatal or postnatal diagnosis (Article)

2008-11-01T00:00:00Z

Objectives To determine whether the pre- or postnatal diagnosis of either isolated or non-isolated duodenal obstruction (DO) is associated with different outcomes. Methods A single-center retrospective analysis was carried out of 91 cases diagnosed with a DO between January 1991 and June 2003. Data on the diagnosis, treatment and outcomes of the cases were gathered, and differences between the groups were analyzed. Results Twenty-eight cases of DO were diagnosed before and 63 after birth. Of 15 presumed isolated cases in the prenatally diagnosed group, four revealed associated or chromosomal anomalies after birth. The types of obstruction present were significantly different between the prenatally (n = 11) and postnatally (n = 27) detected subsets of isolated DO. The prenatally detected subset displayed a lower median gestational age at delivery, lower median birth weight and a higher prematurity rate (8/11 vs. 8/27). The diagnosis of DO occurred significantly later in the postnatally detected subset than the postnatal confirmation of the diagnosis in the prenatally detected cases. In the non-isolated cases of DO, no difference was found in the type of chromosomal or associated anomaly or the type of obstruction between the prenatally detected (n = 17) and postnatally detected subsets (n = 36). Trisomy 21 was present in 7/17 (41%) vs. 22/36 (61%) cases, respectively. Two terminations and three intrauterine deaths occurred in the prenatal non-isolated subset. The liveborn infants from the prenatally detected non-isolated subset (n = 12) showed a significantly higher prematurity rate (9/12 vs.14/36), lower median birth weight and earlier confirmation of diagnosis after delivery. After surgery, outcome was similar between both subsets of isolated and non-isolated DO. All the infants with an isolated DO survived. Neonatal death occurred in three prenatally and five postnatally diagnosed cases with non-isolated DO. Conclusions The outcome of prenatally and postnatally diagnosed DO is not essentially different despite more prematurity and a lower birth weight in the former. Of the prenatally detected cases of DO assumed to be isolated, 25% revealed additional chromosomal or associated anomalies after delivery, which influenced outcome. Copyright

Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy (Article)

2008-10-01T00:00:00Z

Background: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. Results: A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 μg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. Conclusion: The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright

Radiotherapy for Peyronie's Disease: A European survey (Article)

2008-09-11T00:00:00Z

Background and purpose. Peyronie's Disease (PD) is a benign condition characterized by penile nodules, pain and curvature. Radiotherapy has been used for many years with positive outcomes, however all studies published were non-randomized or non-controlled. The purpose of this survey was to understand which treatment policy is followed in Europe before setting up a randomized trial. Materials and methods. A questionnaire was sent out to 908 European radiotherapy institutions, 402 questionnaires were sent back and filled out correctly (44.5%). The questionnaire consisted of different items, regarding number of patients referred, fraction dose, total dose and technique used, and eventually treatment outcome of clinical trials. Results. Seventy-three institutions irradiate PD (19%), 304 do not (81%). Reasons for not treating were insufficient referrals from urologists or no interest in treating benign diseases. The most common fraction dose is 2 (range 0.5-8) Gy and the total radiation dose 20 (range 3-30) Gy. Most of the institutions use electrons (n = 44) or orthovoltage (n = 32). Decreased pain is reported in about 80% of the cases, and side effects by eight institutions. Conclusions. So far, a large variation of treatment schedules for radiotherapy of PD has been detected in European countries. Although the results are good and side effects minimal, there is still a need to set up a European randomized trial to prospectively evaluate the efficacy of radiotherapy for PD.

Left ventricular isovolumic relaxation and renin-angiotensin system in the growth restricted fetus (Article)

2008-09-01T00:00:00Z

Objective: To determine left ventricular isovolumic relaxation time (LV IRT) in normally developing and growth restricted fetuses (FGR) as an indicator of fetal cardiac afterload and neonatal systolic blood pressure. Study design: A prospective longitudinal study in 124 normally developing and 47 growth restricted fetuses (FGR). LV IRT, fetal heart rate (FHR) and umbilical artery pulsatility index (PI) were determined at 2-3 week intervals starting at 22-26 weeks of gestation until delivery. Renin and angiotensin I levels were measured by radioimmunoassay in umbilical venous blood after delivery. Systolic blood pressure was measured at day 1 and day 5 of postnatal life. To evaluate the association between LV IRT, gestational age and FHR, bivariate regression analyses were performed. Results: Mean LV IRT (62 ± 8 ms) was 29 percent longer in FGR as compared to the normal subset (47 ± 6 ms) at all gestational ages (p < 0.001). Mean postnatal active plasma renin level (7.78 ± S.D. 1.03 ng/ml) and postnatal angiotensin I level (4.21 ± 0.70 ng/ml) in the FGR subset were significantly higher (p < 0.001) than in the normal subset (4.81 ± 1.04 ng/ml, renin and 2.69 ± 0.44 ng/ml, angiotensin I). There was a significant difference (p < 0.01) in systolic blood pressure between the two subsets on postnatal day 1 (FGR 52 ± 6 mmHg vs. normal 46 ± 4 mmHg) and day 5 (FGR 76 ± 5 mmHg vs. normal 60 ± 6 mmHg). Conclusion: Left ventricular isovolumic relaxation time may act as a sensitive index of increased arterial afterload in the growth retarded fetus and may herald raised systolic blood pressure in the early neonatal period.

L-Asparaginase and the effect of age on coagulation and fibrinolysis in childhood acute lymphoblastic leukemia (Article)

2008-08-01T00:00:00Z

Alterations in haemostasis are frequently observed in children with acute lymphoblastic leukemia (ALL). It was the objective of this study to analyse age-related disturbances in coagulation and fibrinolysis parameters during the induction phase of the antileukemic treatment. Sixty-four children were classified by age into three groups (1-5, 6-10, 11-16 years), and studied during induction treatment of ALL including four weeks of dexamethasone, followed by two weeks tapering of dexamethasone during which 6,000 IU/m2native L-Asparaginase (total 4 doses) was administered intravenously twice weekly. Blood samples were collected immediately before each L-Asparaginase infusion to analyze procoagulant (fibrinogen, factor [F] II, FV, FVII, F IX, F X) and anticoagulant factors (antithrombin [AT], protein C, protein S), parameters of thrombin generation (F1+2,TAT) and fibrinolysis (α2-antiplasmin, plasminogen, PAP, D-dimer). Children were in a hypercoagulable state after four weeks of dexamethasone due to upregulation of coagulation parameters. Upregulation was highest in the two youngest age groups. During L-Asparaginase treatment the 11- to 16-year-olds showed lower values in procoagulant and, even more, in anticoagulant factor levels compared to the younger children.Activation markers of thrombin generation and fibrinolysis did not change over time during the study period. Decreased synthesis of α2-antiplasmin and plasminogen during L-Asparaginase treatment resulted in less potential of clot lysis by plasmin in children older than 11 years of age. In conclusion, a more severe decline of anticoagulant and fibrinolytic parameters in children between 11 and 16 years of age underline that these children are at higher risk of thrombosis during ALL induction treatment.

Non-invasive measurement of intra-abdominal pressure: A preliminary study (Article)

2008-08-01T00:00:00Z

The importance of measuring intra-abdominal pressure (IAP) has increased since the negative effects of sustained increased IAP, also known as intra-abdominal hypertension (IAH), have become known. The relation between IAP and abdominal wall tension has been included in several reports. We have developed a device to measure abdominal wall tension by measuring force and distance. This device enables us to investigate the correlation between the abdominal wall tension and IAP. The abdomens of two corpses (one female, one male) were insufflated with air. IAP was increased and measured at intervals by means of a laparoscopic set-up. Abdominal tension was measured at seven points on the abdominal wall at each interval. Pearson's correlation coefficients were used to determine the relationship between IAP and tension for each point measured. ANOVA was used to assess relations between measured tensions versus applied pressure, locations and subjects. In both corpses, all points showed significant (p < 0.001) correlations between IAP and abdominal wall tension. The points along the mid transverse plane appear to be more similar compared to more cranial and caudal points. We have assessed the feasibility of a device that non-invasively can track changes in IAP. Measurements performed with the device are preliminary results, and further investigation is needed.

A 10-year follow-up study on endoscopic total extraperitoneal repair of primary and recurrent inguinal hernia (Article)

2008-08-01T00:00:00Z

Background: To determine whether endoscopic repair is favorable in the long term, follow-up recurrence rates afrter 10 years need to be assessed. Methods: Between January 1995 and January 1996, 306 consecutive patients underwent total extraperitoneal (TEP) inguinal hernia repair. Long-term follow-up assessment occurred from January 2006 to May 2006. Results: After a 10-year follow-up period, six (4%) recurrences were found in the primary inguinal hernia group and three recurrences (11%) in the recurrent inguinal hernia group. Age, experience, hospital stay, and operating time were not significantly correlated with recurrences. Conclusion: The long-term results of TEP primary inguinal hernia repair demonstrate it to be an effective and safe procedure with an acceptable recurrence rate. Recurrence rates may be underestimated because the findings show that recurrences continue to occur for as long as 10 years.

The anatomical limits of the posterior vaginal vault toward its use as route for intra-abdominal procedures (Article)

2008-08-01T00:00:00Z

Background: The use of natural openings for abdominal surgery started at the beginning of the 21th century. A trans-Douglas endoscopic device has been designed to perform most of the intra-abdominal operations in women through the pouch of Douglas. The posterior vaginal vault is limited in size and could be damaged by an oversized instrument. This study investigates the optimal dimensions of the instrument by measuring the limiting factor in the passage. Methods: In ten female embalmed bodies the transversal and sagittal diameter of the fornix posterior vaginalis was measured by two observers. The pouch of Douglas was filled to its maximal capacity with mouldable latex through an open abdomen. By internal vaginal examination the connective tissue borders of the fornix posterior were palpated and the impression in the cast was measured. The mean value of these two diameters was evaluated in this study. The level of agreement between the observers was calculated. Results: The mean fornix posterior diameter was 2.6 cm (standard deviation, SD 0.5 cm) with a range of 2.0-3.4 cm. The mean difference between the two observers of all measurements was 0.08 cm (not significant). Both observers had an acceptable intraobserver variation. The interobserver agreement was excellent. Conclusion: Instruments with dimensions within the measured limits can be used safely for intra-abdominal operations via the natural orifice of the vagina.

Fractional exhaled nitric oxide in infants during cow's milk food challenge (Article)

2008-08-01T00:00:00Z

Cow's milk allergy (CMA) is the most common food allergy in early childhood. The golden standard for the diagnosis of CMA is a food challenge after a period of elimination. Increased levels of fractional exhaled nitric oxide (FENO) have been shown after bronchial allergen provocation. We evaluated whether FENOmay also be a predictor of a positive reaction during cow's milk challenge in infants. Forty-four infants [mean age (range): 4.2 (3.7-4.6) months] suspected of CMA underwent an open food challenge with cow's milk formula administered in ascending quantities, starting with 2 ml and then 6, 20, 60 and 200 ml until a clinical reaction occurred. Off-line FENOsamples were obtained during tidal breathing by means of a facemask covering infants' nose and mouth. FENOwas measured twice before the challenge (baseline), immediately before each new dose of milk and after a positive reaction or after the last dose of milk. Eleven children showed immediate positive clinical responses to cow's milk, whereas 13 infants presented only a late-type reaction. FENOvalues before or after a positive reaction (either immediate or late) were not different from FENOvalues at baseline. Baseline FENOin infants with a positive reaction did not differ from FENOin infants without a reaction at any time point. We conclude that FENOvalues are not predictive and not related to the occurrence of a positive reaction during a cow's milk challenge in infants, suggesting that a positive reaction may not result from eosinophilic activation.

Whole-body protein turnover in peritoneal dialysis patients: A comparison of the [15N]glycine end product and the [13C]leucine precursor methods (Article)

2008-08-01T00:00:00Z

Background. Two well-described methods for measuring whole-body protein turnover (WBPT) are the precursor method using a primed continuous infusion of [1-13C]leucine and the end-product method with a single oral dose of [15N]glycine. We previously measured the effects of amino acid (AA)-containing dialysate on protein anabolism in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using the [1-13C]leucine technique. Here, we examine whether the less invasive [15N]glycine method could also be appropriate for studying nutritional interventions. Methods. We compared the results of WBPT measurements using a single oral dose of [15N]glycine with those obtained with the primed continuous infusion of [1-13C]leucine during AA and glucose (G) dialysis and G-only dialysis in 12 CAPD patients in the fed state. Results. The end-product method showed a wide variation for protein synthesis and breakdown measurements. It did not detect a small but significant increase in protein synthesis with AA-containing dialysate as shown by the precursor method. However, a significant relation was found between both methods for net protein synthesis (i.e. protein synthesis minus breakdown) during AA and G (r = 0.75, P = 0.005) or during G-only dialysis (r = 0.86, P < 0.001). The agreement between the two methods for the net protein balance was good [intra-class correlation coefficient (ICC) = 0.88] with G-only dialysate and moderate (ICC = 0.70) with AA and G dialysate. Conclusion. While the precursor method shows less variation, the more convenient end-product method may be useful in larger groups of selected patients including those on PD.

Molecular dissection of the chromosome band 7q21 amplicon in gastroesophageal junction adenocarcinomas identifies cyclin-dependent kinase 6 at both genomic and protein expression levels (Article)

2008-08-01T00:00:00Z

Amplification of chromosome band 7q21 has been frequently detected in various types of cancer including gastroesophageal junction (GEJ) adenocarcinomas. At present, no gene has been disclosed that can explain this frequent amplification of 7q21 in GEJ carcinomas. Therefore, a detailed genomic analysis of the 7q21 region was performed on a selected series of GEJ adenocarcinomas, i.e., 14 primary adenocarcinomas and 10 cell lines, by array comparative genomic hybridization (aCGH) with a 7q11.22-q31.2 contig array. A distinct peak of amplification was identified at 92.1 Mb in 7q21.2, precisely comprising cyclin-dependent kinase 6 (CDK6), a gene involved in cell cycle regulation. A smaller peak was seen at 116.2 Mb in 7q31.2, the locus of the MET proto-oncogene. No distinct peak was detected for the hepatocyte growth factor (HGF) at 81.3 Mb in 7q21.11. An immunoprofile of HGF, CDK6 and MET revealed a strong correlation between aCGH and immunohistochemical protein expression for CDK6 (P = 0.002). Furthermore, immunohistochemistry did not show expression of CDK6 in Barrett's dysplasia and carcinoma in situ, correlating expression of CDK6 with a malignant phenotype. We conclude that high-resolution genomic analysis and immunoprofiling identify CDK6 as the main candidate target for the recurrent amplification of 7q21 in GEJ adenocarcinomas.

Cardiac status after childhood growth hormone treatment of Turner syndrome (Article)

2008-07-01T00:00:00Z

Context: In Turner syndrome (TS), GH treatment is well established. Data on cardiac status after discontinuation of treatment are scarce. This study aimed to assess biventricular size and function in TS at least 6 months after discontinuation of GH treatment. Methods: TS patients and healthy women prospectively underwent cardiac magnetic resonance imaging. Ventricular two-dimensional tomographic cine data were acquired to obtain biventricular volume, mass, and ejection fraction. Atrioventricular valve flow measurements were performed using a two-dimensional flow-sensitized sequence. Flow velocity curves were calculated and indices of biventricular diastolic filling were derived. Results: Thirty-one patients [mean (SD) age 20 (2) yr, body surface area 1.75 (0.15)m2, 5 (2) yr after GH discontinuation] and 23 normal control women [age 21 (2) yr, body surface area 1.80 (0.13)m2] were included. Compared with controls, patients had smaller mean end-diastolic volumes [right ventricle (RV), 84 (11) ml/m2vs. 79 (10), P = 0.02; left ventricle (LV), 81 (10) vs. 72 (9), P < 0.001], end-systolic volumes [RV 38 (7) ml/m2vs. 36 (6), P = 0.04; LV 34 (5) vs. 29 (4), P < 0.001], and stroke volumes [RV 46 (6) ml/m2vs. 43 (6), P = 0.03; LV, 47 (7) vs. 44 (4), P = 0.02]. Patients had a higher meanheart rate [79 (13) beats/min vs. 71 (10), P < 0.05]. Biventricular ejection fraction, mass, cardiac output, and diastolic filling pattern were comparable. Conclusion: After discontinuation of GH treatment TS patients showed no myocardial hypertrophy and well-preserved biventricular function. Ventricular volumes were smaller in Turner patients, compared with controls, whereas mean heart rate was higher. These last observations may be part of the natural development in TS and not linked to GH treatment, which at this point we consider safe. Copyright

The outcome of gastroschisis after a prenatal diagnosis or a diagnosis only at birth. Recommendations for prenatal surveillance (Article)

2008-07-01T00:00:00Z

Objectives: To establish in infants with gastroschisis whether outcome is different when comparing a prenatal diagnosis with a diagnosis only at birth with the intention to develop a prenatal surveillance protocol. Intestinal atresia established after birth and preterm versus term delivery were studied as risk factors. Study design: All 24 fetuses and 9 infants diagnosed with gastroschisis and referred to our tertiary center between January 1991 and June 2003 were studied retrospectively. Results: The infants of the prenatal subset delivered at our tertiary center and 18 survived. There were two pregnancy terminations, three intrauterine deaths at 19, 33 and 36 weeks respectively and one neonatal death. All nine infants in the postnatal subset survived. Eight were out born and one was delivered at our tertiary center. Prenatal bowel dilatation did not correlate with outcome. Between the prenatal and postnatal subset no significant difference in outcome of live-born infants was established. For four infants with intestinal atresia a significant difference was demonstrated for induction of preterm labour (P < 0.05), duration of parenteral nutrition (P < 0.01), number of additional surgical procedures (P < 0.001) and length of hospital stay (P < 0.01). The fifteen infants born prior to 37 weeks of gestation spent a significantly longer period in hospital compared to those delivered at term. When the cases with bowel atresia were excluded this difference was no longer present. Five of the 33 cases were diagnosed with associated anomalies which mainly involved the urinary tract. Conclusion: Neonatal outcome of live born infants following a prenatal diagnosis of gastroschisis is not different from a diagnosis at birth. The presence of intestinal atresia is the most important prognostic factor for morbidity. The supplemental value of prenatal diagnosis to the outcome of infants with gastroschisis may be in the prevention of unnecessary intrauterine death and detection of intestinal complications. A proposed surveillance protocol for fetuses with gastroschisis focused on intrauterine signs of pending distress such as a dilated stomach, intra abdominal bowel dilatation with peristalsis, notches in the umbilical artery Doppler signal, development of polyhydramnios and an abnormal CTG registration may improve outcome.

The role of topical negative pressure in wound repair: Expression of biochemical markers in wound fluid during wound healing (Article)

2008-07-01T00:00:00Z

The clinical effects of topical negative pressure therapy (TNP) on wound healing are well described in numerous articles. While the mechanism(s) of action are not completely understood, it is postulated that reduction of local and interstitial tissue edema, increased perfusion of the (peri-) wound area, changed bacterial composition, and mechanical stimulation of the woundbed contribute to the clinical success. Our hypothesis is that with the removal of excessive fluid, proteolytic enzymes negatively influencing the healing process are removed. Our aim was to assess whether the concentrations of albumin, matrixmetalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) were different between wounds treated with TNP and conventional gauze therapy. We analyzed wound fluid samples of 33 wounds treated with either TNP therapy (n=15) or conventional therapy (n=18) on albumin, pro- and activated MMP-9, TIMP-1, and the ratio of total MMP-9/TIMP-1. Albumin levels were found to increase significantly in acute wounds compared with chronic wounds; however, no difference could be found on comparing TNP with conventional therapy. We did find significantly lower levels of pro-MMP-9 and lower total MMP-9/TIMP-1 ratio in TNP-treated wounds during the follow-up of 10 days. These data strongly suggest that TNP therapy influences the microenvironment of the wound.

The acquisition of tolerance toward cow's milk through probiotic supplementation: A randomized, controlled trial (Article)

2008-06-01T00:00:00Z

Background: Cow's milk allergy (CMA) is the most frequently diagnosed food allergy in infancy. In general, patients have a good prognosis because the majority acquire tolerance within the first years. Interventions have been proposed to accelerate tolerance and reduce morbidity. Probiotic supplementation could be effective through modulation of the immune system. Objective: We sought to determine whether supplementation with a combination of probiotics (Lactobacillus casei CRL431 and Bifidobacterium lactis Bb-12) accelerates tolerance to cow's milk (CM) in infants with CMA. Methods: We performed a double-blind, randomized, placebo-controlled trial in 119 infants with CMA. Infants received CRL431 and Bb-12 supplemented to their standard treatment of extensively hydrolyzed formula for 12 months. Primary outcome was clinical tolerance to CM at 6 and 12 months of treatment. Furthermore, we analyzed T- and B-lymphocyte subsets (CD3+, CD3+CD4+, CD3+CD8+, and CD20+) in peripheral blood at randomization and at 12 months with flow cytometry and examined the presence of viable probiotic strains in fecal samples. Results: The cumulative percentage of tolerance to CM at 6 and 12 months was similar in both groups: 56 (77%) in the probiotics group versus 54 (81%) in the placebo group. Infants in the placebo group had higher percentages of CD3+and CD3+CD4+lymphocytes compared with those seen in probiotic-treated infants. Probiotic intake was confirmed because probiotics were isolated from feces more often in treated infants than in the placebo group. Conclusion: Supplementation of CRL431 and Bb-12 to extensively hydrolyzed formula does not accelerate CM tolerance in infants with CMA.

Polymorphisms in genes related to folate and cobalamin metabolism and the associations with complex birth defects (Article)

2008-06-01T00:00:00Z

Objective: To investigate the associations between biomarkers and genetic variants involved in homocysteine metabolism and the risk of complex birth defects. Methods: Total homocysteine (tHcy), folate, cobalamin, apo-transcobalamin (apo-TC) and apo-haptocorrin (apo-HC) were measured in the amniotic fluid of 82 women who were pregnant with a child having a complex birth defect, such as neural tube defect, cleft lip and/or palate, heart defect or omphalocele, and in 110 women pregnant with a non-malformed child. The determined genotypes of the child comprised of 5, 10-methylenetetrahydrofolate reductase (MTHFR 677C>T, 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G) and transcobalamin (TCN2 776C>G). Univariate and multivariate logistic regression analyses were performed. Results: Significantly lower cobalamin and higher apo-TC, apo-HC, tHcy and folate concentrations were determined in amniotic fluids of cases compared with controls (p ≤ 0.001). Logistic regression analysis revealed that after adjustment for maternal age, children carrying the MTHFR 677T allele showed a four-fold increased risk of having a complex birth defect, OR (95% CI) = 4.0 (1.1-15.4). Other genotypes did not show significant associations. Conclusion: The MTHFR 677C>T polymorphism in conjunction with reduced folate- and/or cobalamin status may increase the risk of complex birth defects. Copyright

Eight years experience with enzyme replacement therapy in two children and one adult with Pompe disease (Article)

2008-06-01T00:00:00Z

Pompe disease (type 2 glycogenosis, acid maltase deficiency) is a disorder affecting skeletal and cardiac muscle, caused by deficiency of acid α-glucosidase. In 2006 enzyme therapy with recombinant human α-glucosidase received marketing approval based on studies in infants. Results in older children and adults are awaited. Earlier we reported on the 3-year follow-up data of enzyme therapy in two adolescents and one adult. In the present study these patients were followed for another 5 years. Two severely affected patients, wheelchair and ventilator dependent, who had shown stabilization of pulmonary and muscle function in the first 3 years, maintained this stabilization over the 5-year extension period. In addition patients became more independent in daily life activities and quality of life improved. The third moderately affected patient had shown a remarkable improvement in muscle strength and regained the ability to walk over the first period. He showed further improvement of strength and reached normal values for age during the extension phase. The results indicate that both long-term follow-up and timing of treatment are important topics for future studies.

Indications for incisional hernia repair: An international questionnaire among hernia surgeons (Article)

2008-06-01T00:00:00Z

Background: Incisional hernia repair can be a significant challenge for both surgeon and patient. Despite the growing amount of literature describing various methods of surgical techniques, little has been published regarding the natural course of incisional hernia and the opinions about indications for incisional hernia repair. Methods: A questionnaire was sent to a group of surgeons internationally renowned in incisional hernia surgery and research. Results: Pain and limitations of daily activities were considered the most important indications for repair. Cosmetic complaints were seen as least important. About 23% of patients were asymptomatic. More than 20% did not receive surgical treatment. Conclusions: A large proportion of patients with incisional hernia is not operated. Despite this large group of patients, valid data describing the natural course are absent. A prospective trial monitoring incisional untreated hernias as well as comparing conservative treatment with repair should be performed.

Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: A randomized, placebo-controlled trial (Article)

2008-05-01T00:00:00Z

Background. Invasive pulmonary aspergillosis (IPA) is a significant problem in patients with chemotherapyinduced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. Methods. We performed a randomized, placebo-controlled trial of patients with hematologic disease with expected neutropenia for ≥10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to >300 cells/mm3. In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer-Mycoses Study Group definitions. Kaplan-Meier curves were compared with log-rank tests for intent-to-treat and on-treatment populations. Results. A total of 271 patients were studied during 407 neutropenic episodes. According to the intent-totreat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P = .005). According to the on-treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA (odds ratio, 0.14; 95% confidence interval, 0.02-0.66; P = .007). Some adverse effects, but none serious, in the liposomal amphotericin B group were reported, most frequently coughing (16 patients vs. 1 patient; P = .002). Conclusion. In high-risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.

Association between apolipoprotein-ε4 and long-term outcome after traumatic brain injury (Article)

2008-04-01T00:00:00Z

Objectives: To investigate the effect of carrying the apolipoprotein epsilon 4 (APOE-ε4) allele on global functional outcome, on activity limitations and participation restrictions, and on community integration at 3, 6, 12, 18, 24 and 36 months after traumatic brain injury. Method: The Glasgow Outcome Scale (GOS), the Sickness Impact Profile-68 (SIP-68) and the Community Integration Questionnaire (CIQ) were assessed in 79 moderate and severe traumatic brain injury patients at 3, 6, 12, 18, 24 and 36 months post injury. Repeated measures analyses of variance were performed with APOE-ε4 status and time of measurement as independent variables and the GOS, SIP-68 and CIQ as dependent variables. Analyses were adjusted for baseline age, gender and Glasgow Coma Scale. Results: Patients with the APOE-ε4 allele had a significantly better global functional outcome on the GOS than patients without the APOE-ε4 allele. No significant associations were found between APOE-ε4 status and the SIP-68 and CIQ. Discussion: In contrast to other studies, we found that carrying the APOE-ε4 allele had a protective influence on outcome. Multiple mechanisms, and in some cases competitive mechanisms, may explain the variable relation between the APOE-ε4 allele and outcome after traumatic brain injury.

Changes during exercise of ECG intervals related to increased risk for ventricular arrhythmia in repaired tetralogy of Fallot and their relationship to right ventricular size and function (Article)

2008-03-14T00:00:00Z

Purpose: Our study aimed to assess pro-arrhythmogenic electrocardiographic changes during maximal physical exercise in patients operated for Tetralogy of Fallot (TOF). Methods: TOF patients prospectively underwent: 1) bicycle ergometry, 2) cardiac MRI, and 3) 24-hour Holter. ECG data was analyzed at rest, at 60% of peak exercise and at peak exercise. R-R duration, QRS-, QT- and JT-duration and dispersions were assessed. Changes of ECG parameters during exercise were calculated and correlated to RV volume, RVEF, RV wall-mass, PR-percentage and VO2max. Exercise ECG data from healthy controls were used as reference. Results: Thirty-one patients (mean age at repair (SD) 0.8 (0.5) years, age at study 16 (5) years) and 25 controls (age 12 (2) years) were included. With exercise mean QTc and JTc dispersions increased in patients (p < 0.001), but not in controls. At peak exercise JTc dispersion was larger in patients (p < 0.01). QTc did not change with exercise in patients (p = 0.14) and decreased in controls (p < 0.05). At all levels of exercise mean QTc, QRS and QRS dispersion were larger in patients (all p < 0.001). Significant associations were found for; 1) a larger increase of JTc dispersion with a higher PR-percentage, a larger RV volume, a larger RV wall-mass, 2) a larger QTc increase with a larger RV volume and worse RVEF. Conclusion: During physical exercise inhomogeneity of repolarisation, known to predispose for re-entry ventricular arrhythmia, increases in repaired TOF. Larger inhomogeneity is found with more severe PR.

Environmental factors in the etiology of esophageal atresia and congenital diaphragmatic hernia: Results of a case-control study (Article)

2008-03-01T00:00:00Z

BACKGROUND: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and congenital diaphragmatic hernia (CDH) are severe congenital anomalies. Their etiologies are mostly unknown and are thought to be multifactorial. No specific environmental factors have consistently been described as risk factors. METHODS: In a study conducted during the years 2000 to 2004 in a pediatric surgical referral center in the Netherlands, parents of children with EA/TEF or with CDH of the Bochdalek type and parents of a group of children without major birth defects filled out a questionnaire about possible exposure to environmental risk factors during the period from 1 month before conception to the end of the first trimester of pregnancy. Children with chromosomal anomalies were excluded. RESULTS: Questionnaires were returned for 47 out of 64 cases (73%) with EA/TEF, for 63 out of 77 cases (82%) with CDH, and for 202 out of 243 controls (83%). In EA/TEF, maternal age was borderline significantly higher than in controls (32.2 vs. 30.6 years, p = .05). Contact with herbicides or insecticides was associated with EA/TEF in univariate analysis (OR 2.0; 95% CI: 1.0-4.1) and in multivariate analysis, although of borderline significance. In univariate analysis, CDH was significantly associated with maternal use of alcohol (OR 2.9; 95% CI: 1.6-5.2). CONCLUSIONS: We found a significant association between maternal alcohol use around the time of conception and CDH. A possible explanation might be the effect of alcohol on the retinoic acid pathway. An association was found between contact with herbicides or insecticides and EA/TEF.

Surviving meningococcal septic shock: Health consequences and quality of life in children and their parents up to 2 years after pediatric intensive care unit discharge (Article)

2008-02-01T00:00:00Z

OBJECTIVE: To assess health consequences and health-related quality of life (HR-QoL) in children with meningococcal septic shock up to 2 yrs after discharge from the pediatric intensive care unit and to assess their parents. To determine major predictors of that outcome. PATIENTS AND METHODS: A prospective cohort study. Follow-up of all consecutive children with septic shock and purpura requiring intensive care treatment between 2001 and 2005, and their parents. HR-QoL was assessed with the Child Health Questionnaire (children) and Medical Outcomes Study 36-item Short-Form Health Survey (parents). RESULTS: Of 53 eligible families, 47 participated (28 boys/19 girls; median age at the time of pediatric intensive care unit admission, 3.7 yrs; median Pediatric Risk of Mortality score, 21). A total of 26 children (55%) had scars as a result of skin necrosis; two (4%) had amputation of a digit or digits. In 21 children (45%), chronic complaints were reported. Children with and without chronic complaints did not differ significantly with regard to severity of illness and age at the time of pediatric intensive care unit admission. Significantly lower scores were found on HR-QoL scales concerning mainly physical functioning and health perception in comparison with normative data. There was a significant negative association between severity of illness and the HR-QoL scale concerning physical functioning. Children with chronic complaints had significantly lower scores on the HR-QoL scale concerning pain. Eight of 47 mothers (17%) at the time of the study had anxiety or depression requiring professional help. Mothers with and without these problems differed significantly with regard to age of their child at the time of pediatric intensive care unit admission. Parents showed significantly higher scores on HR-QoL scales concerning physical functioning and bodily pain in comparison with normative data. There was a significantly negative association between the presence of emotional problems and HR-QoL scores in mothers. CONCLUSIONS: Up to 2 yrs after discharge from the pediatric intensive care unit, there is still a considerable effect on health and HR-QoL in children, especially on the physical scales. Severity of illness and chronic complaints negatively affected HR-QoL scales in children. Quite a few mothers suffered from emotional problems.

Increased systemic inflammation is a risk factor for COPD exacerbations (Article)

2008-02-01T00:00:00Z

Background: COPD is characterized by episodic increases in respiratory symptoms, so-called exacerbations. COPD exacerbations are associated with an increase in local and systemic inflammation. Data of a previously published study in a well-characterized COPD cohort were analyzed to define predictive factors of acute exacerbations, particularly focusing on systemic inflammation. Objective: To determine if an elevated systemic inflammatory status measured at baseline is related to the occurrence of acute exacerbations in patients with COPD. Methods: The occurrence of moderate (requiring oral prednisolone) and severe exacerbations (requiring hospitalization) was prospectively recorded over 1 year. At the beginning of the study, lung function values (FEV1, FVC, functional residual capacity, and diffusion capacity of the lung for carbon monoxide [DLCO]) and serum levels of C-reactive protein, fibrinogen, lipopolysaccharide binding protein, tumor necrosis factor (TNF)-α, and its soluble receptors (soluble TNF receptors 55 and 75) as markers of systemic inflammation were determined. Results: Two hundred seventy-seven person-years of follow-up were analyzed in the total group of 314 patients: 186 patients were responsible for 411 exacerbations (374 moderate and 37 severe). Multivariate analyses showed that a higher initial fibrinogen level and a lower FEV1predicted a higher rate of both moderate and severe exacerbations. Additional independent predictors of a severe exacerbation were a higher number of prestudy severe exacerbations and lower DLCO. A higher number of prestudy moderate exacerbations was the only additional independent risk factor for the rate of moderate exacerbations. Conclusion: This study demonstrates that besides lung function impairment systemic inflammation manifested by elevated fibrinogen levels is an independent risk factor for exacerbations of COPD. Attenuation of systemic inflammation may offer new perspectives in the management of COPD patients to reduce the burden of exacerbations.

Vibration therapy reduces CPAP need in a prospective randomised controlled trial (Article)

2008-01-01T00:00:00Z

Background: Increased mucus production is a common phenomena following ventilatory support, which might increase morbidity. In order to reduce airway obstruction we tested the effect of vibration therapy on the duration of ventilatory support. Methodology: We conducted a randomised control study in a level IIIC NICU (28 beds) of a university hospital. Compared were nonactive techniques to vibration therapy in preterm infants with a gestational age of 26 - 33 weeks. All infants were ventilated or receive respiratory support by nasal CPAP. Results: 104 infants were enrolled, 49 in the vibration group and 55 in the control group. Demographic characters were in the vibration group compared to control group mean birth weight 1274 (± 335) gram vs. 1240 (± 351) gram and mean gestational age 29.8 (± 1.3) weeks vs. 29.9 (± 1.4) weeks. Vibration therapy did not reduce ventilation time (100 vs. 80 hours, p = 0.88) however duration of CPAP decreases significant (57 vs 157 hours, p < 0.018). Conclusion: Vibration therapy reduced Mean Airway Pressure, oxygen requirements and CPAP need in preterm infants, but did not reduce the duration of mechanical ventilation.

A Single-Lumen Central Venous Catheter for Continuous and Direct Intra-abdominal Pressure Measurement (Article)

2008-01-01T00:00:00Z

Background: Abdominal compartment syndrome (ACS) is associated with high morbidity and mortality rates. Therefore, the need for a good diagnostic tool to predict intra-abdominal hypertension (IAH) and progression to ACS is paramount. Bladder pressure (BP) has been used for several years for intra-abdominal pressure (IAP) measurement but has the disadvantage that it is not a continuous measurement. In this study, a single-lumen central venous catheter (CVC) is placed through the abdominal wall into the abdominal cavity to continuously and directly monitor the intra-abdominal pressure (CDIAP). The aim of this study was to evaluate the use of CDIAP to measure BP as a representative of the true IAP. Methods: Both BP and CDIAP were prospectively recorded on a variety of surgical patients admitted to the intensive care unit (ICU) from March 2003 up to December 2004. At the end of the surgical procedure, the CVC was placed through the abdominal wall and connected to a pressure transducer. In addition, the BP was measured through the urine drainage port after clamping the catheter and filling the bladder with 50 ml of 0.9% saline. At least three paired measurements (BP and CDIAP) were performed for at least one day on the ICU in a standardized manner at preset time intervals on each patient. The paired measurements were compared using the Bland-Altman (B-A) method. Data are presented as mean ± standard deviation. Results: Over a period of 22 months (March 2003 until December 2004), 125 paired measurements of both BP and CDIAP were recorded on 25 patients. The mean age was 72.4 ± 6.6 years. Eighteen patients underwent central vascular surgery, and seven patients with peritonitis received laparotomy. The mean CDIAP was 11.4 ± 4.8 (range 2-30) mmHg, and the BP was 12.9 ± 5.3 (range 3-37) mmHg. The mean difference between CDIAP and BP was 1.6 ± 2.7 mmHg. There was an acceptable level of agreement (intraclass correlation 0.82) between IAP measured by BP and IAP measured via CDIAP. Conclusion: Continuous direct intra-abdominal pressure measurement proved that the BP measurement approach of Kron is representative of the IAP. CDIAP measurement is accurate and makes it easier for the nursing staff to be informed of the IAP.

One single dose of etomidate negatively influences adrenocortical performance for at least 24 h in children with meningococcal sepsis (Article)

2008-01-01T00:00:00Z

Objective: To investigate the effect of one single bolus of etomidate used for intubation on adrenal function in children with meningococcal sepsis. Design: Retrospective study conducted between 1997 and 2004. Setting: University-affiliated paediatric intensive care unit (PICU). Patients and participants: Sixty children admitted to the PICU with meningococcal sepsis, not treated with steroids. Interventions: Adrenal hormone concentrations were determined as soon as possible after PICU admission, and after 12 h and 24 h. To assess disease severity, PRISM score and selected laboratory parameters were determined. Measurements and main results: On admission, before blood was drawn, 23 children had been intubated with etomidate, 8 without etomidate and 29 were not intubated. Children who were intubated had significantly higher disease severity parameters than those not intubated, whereas none of these parameters significantly differed between children intubated with or without etomidate. Children who received etomidate had significantly lower cortisol, higher ACTH and higher 11-deoxycortisol levels than those who did not receive etomidate. Arterial glucose levels were significantly lower in children who were intubated with etomidate than in non-intubated children. When children were intubated with etomidate, cortisol levels were 3.2 times lower for comparable 11-deoxycortisol levels. Eight children died, seven of whom had received etomidate. Within 24 h cortisol/ACTH and cortisol/11-deoxycortisol ratios increased significantly in children who received etomidate, but not in children who did not, resulting in comparable cortisol/ACTH ratios with still significantly lowered cortisol/11-deoxycortisol ratios 24 h after admission. Conclusions: Our data imply that even one single bolus of etomidate negatively influences adrenal function for at least 24 h. It might therefore increase risk of death.

The role of endorectal ultrasound in therapeutic decision-making for local vs. transabdominal resection of rectal tumors (Article)

2008-01-01T00:00:00Z

INTRODUCTION: In rectal tumors, preoperative biopsies frequently fail to diagnose an invasive carcinoma. Endorectal ultrasound is considered a useful adjunct in preoperative staging of rectal tumors. However, feasibility of endorectal ultrasound and its role in therapeutic decision-making in presumed rectal adenomas is sparsely studied. METHODS: Endorectal ultrasound was performed in 268 tumors referred for local excision because biopsies showed tubulovillous adenoma. Feasibility of endorectal ultrasound was studied and ultrasound staging was compared with definite histopathologic findings. RESULTS: In 231 tumors, endorectal ultrasound was technically feasible (86 percent). Median distance from the dentate line was 11 cm in nonassessable tumors and 7 cm in assessable tumors (P < 0.001). In 21 tumors, endorectal ultrasound was not conclusive, mainly in tumors being recurrent or after recent endoscopic manipulation (P < 0.001). With endorectal ultrasound the rate of preoperative missed carcinomas could be reduced from 21 to 3 percent (P < 0.01). In diagnosing tubulovillous adenomas, sensitivity and specificity of endorectal ultrasound was 89 and 86 percent, respectively. CONCLUSIONS: Endorectal ultrasound is technically feasible in almost all presumed rectal adenomas, referred for local excision. Proper endorectal ultrasound interpretation is possible in 78 percent of all presumed rectal adenomas. Endorectal ultrasound is very reliable in diagnosing tubulovillous adenomas, and therapeutic decision-making regarding local excision vs. radical surgery based on endorectal ultrasound is valid.

Mechanical bowel preparation for elective colorectal surgery: a multicentre randomised trial (Article)

2007-12-22T00:00:00Z

Background: Mechanical bowel preparation is a common practice before elective colorectal surgery. We aimed to compare the rate of anastomotic leakage after elective colorectal resections and primary anastomoses between patients who did or did not have mechanical bowel preparation. Methods: We did a multicentre randomised non-inferiority study at 13 hospitals. We randomly assigned 1431 patients who were going to have elective colorectal surgery to either receive mechanical bowel preparation or not. Patients who did not have mechanical bowel preparation had a normal meal on the day before the operation. Those who did were given a fluid diet, and mechanical bowel preparation with either polyethylene glycol or sodium phosphate. The primary endpoint was anastomotic leakage, and the study was designed to test the hypothesis that patients who are given mechanical bowel preparation before colorectal surgery do not have a lower risk of anastomotic leakage than those who are not. The median follow-up was 24 days (IQR 17-34). We analysed patients who were treated as per protocol. This study is registered with ClinicalTrials.gov, number NCT00288496. Findings: 77 patients were excluded: 46 who did not have a bowel resection; 21 because of missing outcome data; and 10 who withdrew, cancelled, or were excluded for other reasons. The rate of anastomotic leakage did not differ between both groups: 32/670 (4·8%) patients who had mechanical bowel preparation and 37/684 (5·4%) in those who did not (difference 0·6%, 95% CI -1·7% to 2·9%, p=0·69). Patients who had mechanical bowel preparation had fewer abscesses after anastomotic leakage than those who did not (2/670 [0·3%] vs 17/684 [2·5%], p=0·001). Other septic complications, fascia dehiscence, and mortality did not differ between groups. Interpretation: We advise that mechanical bowel preparation before elective colorectal surgery can safely be abandoned.

BRCA1 mutation and young age predict fast breast cancer growth in the Dutch, United Kingdom, and Canadian magnetic resonance imaging screening trials (Article)

2007-12-15T00:00:00Z

Purpose: Magnetic resonance imaging (MRI) screening enables early detection of breast cancers in women with an inherited predisposition. Interval cancers occurred in women with a BRCA1 mutation, possibly due to fast tumor growth. We investigated the effect of a BRCA1 or BRCA2 mutation and age on the growth rate of breast cancers, as this may influence the optimal screening frequency. Experimental Design: We reviewed the invasive cancers from the United Kingdom, Dutch, and Canadian MRI screening trials for women at hereditary risk, measuring tumor size at diagnosis and on preceding MRI and/or mammography. We could assess tumor volume doubling time (DT) in 100 cancers. Results: Tumor DT was estimated for 43 women with a BRCA1 mutation, 16 women with a BRCA2 mutation, and 41 women at high risk without an identified mutation. Growth rate slowed continuously with increasing age (P = 0.004). Growth was twice as fast in BRCA1 (P = 0.003) or BRCA2 (P = 0.03) patients as in high-risk patients of the same age. The mean DT for women with BRCA1/2 mutations diagnosed at ages ≤40, 41 to 50, and >50 years was 28, 68, and 81 days, respectively, and 83, 121, and 173 days, respectively, in the high-risk group. Pathologic tumor size decreased with increasing age (P = 0.001). Median size was 15 mm for patients ages ≤40 years compared with 9 mm in older patients (P = 0.003); tumors were largest in young women with BRCA1 mutations. Conclusion: Tumors grow quickly in women with BRCA1 mutations and in young women. Age and risk group should be taken into account in screening protocols.

Tadalafil (Cialis) and Erectile Dysfunction After Radiotherapy for Prostate Cancer: An Open-Label Extension of a Blinded Trial (Article)

2007-12-01T00:00:00Z

Objectives: To determine the efficacy of tadalafil (Cialis) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer in an extended open-label phase of the blinded trial. Methods: Sixty patients entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received tadalafil 20 mg or placebo for 6 weeks and then crossed over to the alternate medication. Of these 60 patients, 51 (85%) entered a 6-week open-label extension phase. The data were collected using the International Index of Erectile Function (IIEF) questionnaire. Side effects were also recorded. Results: All patients completed the double-blind cross-over study. The 9 patients who did not wish to enter the open-label phase had had significantly worse scores statistically on the erectile function domain of the IIEF with tadalafil in the blinded trial (P = 0.03). For all IIEF domains, except for sexual desire, tadalafil was equally effective in the double-blind phase as in the open-label phase. For nearly all the IIEF questions, tadalafil caused a significant increase in the mean scores from baseline in the run-in period of the blinded trial. The side effects were mild or moderate and had significantly decreased compared with tadalafil in the blinded trial. Conclusions: Tadalafil is effective in many patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy for prostate cancer. In the open-label extension of the trial, tadalafil showed the same efficacy as in the blinded phase.

Intratumoral distribution of 1p loss in oligodendroglial tumors (Article)

2007-12-01T00:00:00Z

The favorable response of oligodendrogliomas correlates well with characteristic chromosomal losses, of which loss of the short arm of chromosome 1 is most predictive. Oligodendrogliomas are histopathologically heterogeneous tumors and, in addition to the classic honeycomb histology, fields of nonclassic histology are often encountered. Information about the distribution of 1p loss in various regions of oligodendroglioma is, therefore, important to interpret findings in tumor biopsies. In this study we investigated the distribution of 1p loss in multiple fields in 24 biopsy specimens of oligodendroglioma consisting of classic and nonclassic histology by fluorescent in situ hybridization and loss of heterozygosity analysis. By fluorescent in situ hybridization analysis, loss of 1p was found in all fields examined in 37% of the tumor samples, and no loss was detected in 46%. In fields of classic oligodendroglial and polar spongioblastoma-like histology, significantly more loss for 1p was found (p < 0.001 and p < 0.01, respectively). Although fluorescent in situ hybridization analysis indicated heterogeneity for 1p loss in the other 17% of tumors, loss of heterozygosity analysis of these samples pointed to homogeneity of 1p status in all fields. The 1p status of the fields with classic histology significantly correlated with the status of the other fields in the same tumors (Spearman's rho 0.918, p < 0.001). These results point to genotypic homogeneity for 1p in oligodendroglial tumors.

Long-term health-related quality of life in survivors of meningococcal septic shock in childhood and their parents (Article)

2007-12-01T00:00:00Z

Objective: To assess long-term health-related quality of life (HR-QoL) in patients who survived meningococcal septic shock in childhood, and their parents. Patients and methods: All consecutive patients with meningococcal septic shock requiring intensive care treatment between 1988 and 2001, and their parents. HR-QoL was assessed by the Child Health Questionnaire and the SF-36. Scores were compared with reference data of Dutch general population samples. Lower scores indicated poorer HR-QoL, higher scores more favourable HR-QoL. Results: One hundred and forty-five patients (response rate 82%) agreed to participate (age PICU admission 3.5 years; follow-up interval 10 years; age follow-up 14.6 years (all medians)). In patients, regardless of age and of patient- versus parent-report, significantly lower scores were found mainly on physical (physical functioning, general health perception) domains and/or physical summary score. In patients <18 years, according to parent-reports, significantly lower scores were also found on psychosocial HR-QoL domains, whereas in patients <12 years, according to patients themselves, significantly higher scores were found on psychosocial domains. As to parents themselves, we found significantly higher scores on the majority of HR-QoL scales (both physical and psychosocial). Conclusions: In patients who survived meningococcal septic shock in childhood significantly lower HR-QoL scores were found on the physical domains. This could indicate that the patient's disease episode and present health status had a negative impact on their present physical HR-QoL. Overall long-term HR-QoL in parents was significantly higher.

Authors' reply [4] (Article)

2007-12-01T00:00:00Z

MR imaging of hepatocellular carcinoma: Relationship between lesion size and imaging findings, including signal intensity and dynamic enhancement patterns (Article)

2007-12-01T00:00:00Z

Purpose: To assess the relationship between lesion size and MR imaging findings of pathologically-proven hepatocellular carcinoma (HCC). Materials and Methods: In a retrospective, single-center study, 37 consecutive patients were identified between 1999 and 2005 that underwent preoperative MRI and surgical resection of HCC. A total of 47 lesions (mean size = 6.85 cm, range = 1-25 cm) were assessed for signal intensity (SI), enhancement patterns, and secondary morphologic features. Interobserver rating, percentage enhancement, and contrast-to-noise-ratio (CNR) were determined. Lesions were assessed for combinations of typical MRI features. Regression analysis was used to assess relations between MRI findings and tumor size. Results: On fat-suppressed T2-weighted (T2w) fast-spinecho, smaller lesions had lower SI compared to larger lesions (P < 0.05). In the arterial phase, smaller lesions showed significantly higher percentage enhancement compared to larger lesions (P < 0.05). In the delayed phase, smaller lesions showed less pronounced washout (P < 0.05). Heterogeneity of the lesions, including fatty infiltration, internal nodules, or mosaic pattern, was observed significantly more frequently in larger lesions (P < 0.001). The classic combination of high T2w signal, strong arterial enhancement, and delayed phase washout was present in 23 of 44 lesions (52%). Conclusion: Smaller HCC often showed lower SI on T2w, more intense arterial enhancement, and less pronounced delayed washout compared to larger HCC.

Imbalances in circulating lymphocyte subsets in Hu antibody associated paraneoplastic neurological syndromes (Article)

2007-12-01T00:00:00Z

In paraneoplastic neurological syndromes (PNS) associated with small cell lung cancer (SCLC) and Hu antibodies, neuron-specific Hu antigens expressed by the tumour hypothetically trigger an immune response that cross-reacts with Hu antigens in the nervous system, resulting in tumour suppression and neuronal damage. To gain more insight into the hypothesized cell-mediated immune pathogenesis of these syndromes, we analysed the circulating lymphocyte subsets in untreated patients with SCLC, PNS and Hu antibodies (n = 18), SCLC without PNS (n = 19) and controls (n = 29) using flow cytometry. SCLC patients with PNS had a variety of imbalances within their circulating lymphocyte subsets as compared with SCLC patients without PNS and healthy controls: (i) a lymphopenia of the major subsets (i.e. B, CD4+and CD8+T lymphocytes); (ii) increased proportions of activated CD4+and CD8+T cells; (iii) reduced numbers of terminally differentiated effector CD8+T cells and cells with a cytotoxic T-cell phenotype (CD56+and CD57+). Although indirect, our data provide further support for the involvement of T cells in the pathogenesis of Hu antibody associated PNS.

Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation: Long-term results of EORTC trial 40891 (Article)

2007-11-01T00:00:00Z

BACKGROUND: The role of adjuvant chemoradiation in pancreatic cancer remains unclear. This report presents the long-term follow-up results of EORTC trial 40891, which assessed the role of chemoradiation in resectable pancreatic cancer. METHODS: Two hundred eighteen patients were randomized after resection of the primary tumor. Eligible patients had T1-2 N0-N1a M0 pancreatic cancer or T1-3 N0-N1a M0 periampullary cancers, all histologic proven. Patients in the treatment group (n = 110) underwent postoperative chemoradiation (40 Gy plus 5-FU). Patients in the control group (n = 108) had no further adjuvant treatment. FINDINGS: After a median follow-up of 11.7 years, 173 deaths (79%) have been reported. The overall survival did not differ between the 2 treatment groups (Chemoradiation treatment vs. Controls: death rate ratio 0.91, 95% CI: 0.68-1.23, P value 0.54). The 10-year overall survival was 18% in the whole population of patients (8% in the pancreatic head cancer group and 29% in the periampullary cancer group). INTERPRETATION: These results confirm the previous short-term analysis, indicating no benefit of adjuvant chemoradiation over observation in patients with resected pancreatic cancer or periampullary cancer. Patients with pancreatic cancer may survive more than 10 years. Only 1 of 31 cases recurred after year 7.

Randomized clinical trial of mesh versus non-mesh primary inguinal hernia repair: Long-term chronic pain at 10 years (Article)

2007-11-01T00:00:00Z

Background: Open mesh or non-mesh inguinal hernia repair may influence the incidence of chronic postoperative pain differently. Methods: A total of 300 patients scheduled for repair of a primary unilateral inguinal hernia were randomized to non-mesh or mesh repair. The primary outcome measure was clinical outcome including persistent pain and discomfort interfering with daily activity. Long-term results at 3 years of follow-up have been published. Included here are 10-year follow-up results with respect to pain. Results: Of the 300 patients, 87 patients (30%) died and 49 patients (17%) were lost to follow-up. A total of 153 were physically examined in the outpatient clinic after a median long-term follow-up of 129 months (range, 109 to 148 months). None of the patients in the non-mesh or mesh group suffered from persistent pain and discomfort interfering with daily activity. Conclusions: Our 10-year follow-up study provides evidence that mesh repair of inguinal hernia is equal to non-mesh repair with respect to long-term persistent pain and discomfort interfering with daily activity. An important new finding from the patient's perspective is that chronic postoperative pain seems to dissipate over time.

The effect of neo-rectal wall properties on functional outcome after colonic J-pouch-anal anastomosis (Article)

2007-11-01T00:00:00Z

Background/aims: It has been suggested that normal function of both anal sphincters is essential for a good functional outcome after colonic J-pouch-anal anastomosis (CPAA). However, CPAA patients may have impaired continence despite adequate sphincter function. The present study was designed to identify those factors, which contribute to the functional outcome after a handsewn CPAA. Materials and methods: Forty patients were studied before and 1 year after pouch surgery. Faecal continence was evaluated using the Rockwood faecal incontinence severity index (RFISI). At both occasions, maximum anal resting pressure (MARP) and maximum anal squeeze pressure (MASP) were recorded. In addition, sensory perception threshold-volumes (SPT-V) and compliance were assessed using an 'infinitely' compliant polyethylene bag connected to an electronic barostat assembly. Results: The median RFISI score 1 year after surgery was higher than the median RFISI score before surgery (13 vs 7 (p<0.01). The median MARP dropped significantly (p<0.01) whereas the median MASP remained unaffected. The mean compliance, calculated at three different sensation levels, and the pouch sensory perception threshold-volumes (PSPT-V) were lower than those of the original rectum (p<0.05). The reduction of MARP showed no correlation with the post-operative change in RFISI scores. Low PC and low PSPT-V were associated with higher RFISI scores. Conclusion: Low pouch compliance and low SPT-V adversely affect functional outcome after a handsewn colonic J-pouch-anal anastomosis.

Complex congenital malformations and the impact of the plasminogen activator system and β-hCG in amniotic fluid (Article)

2007-11-01T00:00:00Z

Objective: The plasminogen activator system and β-hCG may affect neural crest cells and angiogenesis, and thereby embryogenesis. Therefore, we investigated these parameters in amniotic fluids of pregnancies with a complex congenital malformation. Study design: In a case-control study amniotic fluid samples were collected from 62 pregnancies with a complex congenital malformation and from 110 healthy control pregnancies at an obstetric department of a large university hospital in the Netherlands. We determined concentrations of tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitors (PAI-1, PAI-2), tPA∼PAI-1 and uPA∼PAI-1 complexes, and β-hCG with enzyme-linked immunosorbent assays. Mann-Whitney U-tests and analysis of covariance, adjusting for gestational and maternal age, were performed for data comparisons. Results: Compared with controls, cases demonstrated significantly lower adjusted geometric mean levels of uPA (24%), tPA (≥19%) and tPA∼PAI-1 (35%). Cases showed significantly higher adjusted mean levels of β-hCG (≥48%) and PAI-2 (10 ng/mL) than controls. Mean PAI-1 and uPA∼PAI-1 levels were comparable between both groups. Conclusions: Disturbances in the plasminogen activator system and β-hCG levels are suggested to be involved in the pathogenesis of complex congenital malformations by affecting neural crest cell migration and angiogenesis.

High-resolution array comparative genomic hybridization of chromosome 8q: Evaluation of putative progression markers for gastroesophageal junction adenocarcinomas (Article)

2007-11-01T00:00:00Z

Amplification of 8q is frequently found in gastroesophageal junction (GEJ) cancer. It is usually detected in high-grade, high-stage GEJ adenocarcinomas. Moreover, it has been implicated in tumor progression in other cancer types. In this study, a detailed genomic analysis of 8q was performed on a series of GEJ adenocarcinomas, including 22 primary adenocarcinomas, 13 cell lines and two xenografts, by array comparative genomic hybridization (aCGH) with a whole chromosome 8q contig array. Of the 37 specimens, 21 originated from the esophagus and 16 were derived from the gastric cardia. Commonly overrepresented regions were identified at distal 8q, i.e. 124-125 Mb (8q24.13), at 127-128 Mb (8q24.21), and at 141-142 Mb (8q24.3). From these regions six genes were selected with putative relevance to cancer: ANXA13, MTSS1, FAM84B (alias NSE2), MYC, C8orf17 (alias MOST-1) and PTK2 (alias FAK). In addition, the gene EXT1 was selected since it was found in a specific amplification in cell line SK-GT-5. Quantitative RT-PCR analysis of these seven genes was subsequently performed on a panel of 24 gastroesophageal samples, including 13 cell lines, two xenografts and nine normal stomach controls. Significant overexpression was found for MYC and EXT1 in GEJ adenocarcinoma cell lines and xenografts compared to normal controls. Expression of the genes MTSS1, FAM84B and C8orf17 was found to be significantly decreased in this set of cell lines and xenografts. We conclude that, firstly, there are other genes than MYC involved in the 8q amplification in GEJ cancer. Secondly, the differential expression of these genes contributes to unravel the biology of GEJ adenocarcinomas. Copyright

Outcome after emergency surgery for acute perforated diverticulitis in 200 cases (Article)

2007-10-01T00:00:00Z

Background: Mortality and morbidity rates of acute perforated diverticulitis remain high. The ideal treatment is still controversial. The object of this study was to compare patients with perforated diverticulitis treated either by resection with primary anastomosis (PA) or Hartmann's procedure (HP). Methods: A multicenter study was carried out on 200 consecutive patients with acute perforated diverticulitis who were presented in the surgical units of four affiliated teaching hospitals in Rotterdam, The Netherlands, between 1995 and 2005. Mortality and morbidity were compared in relation to type of surgery, ASA classification, age, gender, Mannheim Peritonitis Index (MPI), Hinchey score, surgeon's experience, and the time of operation. Results: There was a tendency for more severely affected patients (Hinchey, MPI, ASA and age) to undergo HP. Multivariate logistic regression analysis showed no significant difference in mortality between HP and PA. After HP, more patients needed one or more reinterventions to treat postoperative complications compared to PA. Besides, HP resulted in a longer total hospital and intensive care unit stay. Specialist colorectal surgeons performed significantly more frequently a PA instead of a HP and had fewer postoperative complications than general surgeons. The time of operation did not influence the choice of surgical procedure. Conclusion: Selected patients with perforated diverticulitis can be managed well by PA, as it does not seem to be inferior to HP in terms of severe postoperative complications that need surgical or radiological reintervention and mortality. This decision should be made while taking into account the patient's concomitant diseases, response on preoperative resuscitation and the availability of a surgeon experienced in colorectal surgery. Copyright

Influence of coping styles on quality of life in men with new and increasing lower urinary tract symptoms: The Krimpen study in community-dwelling men (Article)

2007-10-01T00:00:00Z

Objective: The present study aims to determine the influence of coping on quality of life (QOL) in elderly men developing lower urinary tract symptoms (LUTS). Materials and Methods: Longitudinal population-based study with a follow-up period of 6.5 years on 1,688 men aged 50-78 years. Data were collected through self-administered questionnaires, including the Sickness Impact Profile (SIP, three domains), Inventory of Subjective Health (ISH), International Prostate Symptom Score (IPSS), and the Utrecht Coping List (UCL). Various physical and urological measurements were completed. Multiple linear regressions were used to determine the change in QOL in men with incident LUTS in relation to coping behavior. Results: Overall no significant association is found between changes in LUTS with a change in QOL. However, a positive change in QOL is significantly associated with a change in LUTS when men use the coping style active problem solving and a negative relation exists with coping style reassuring thoughts. Conclusion: Different coping styles have a different impact on the relation between a change in LUTS and a change in generic QOL in community-dwelling elderly men. This makes a future exploration of the clinical treatment possibilities warranted. Copyright

Long-term asthma treatment guided by airway hyperresponsiveness in children: A randomised controlled trial (Article)

2007-09-01T00:00:00Z

Management plans for childhood asthma show limited success in optimising asthma control. The aim of the present study was to assess whether a treatment strategy guided by airway hyperresponsiveness (AHR) increased the number of symptom-free days and improved lung function in asthmatic children, compared with a symptom-driven reference strategy. In a multicentre, double-blind, parallel-group, randomised, 2-yr intervention trial, 210 children (aged 6-16 yrs) with moderate atopic asthma, selected on the basis of symptom scores and/or the presence of AHR, were studied. At 3-monthly visits, symptom scores, forced expiratory volume in one second (FEV1) and methacholine challenge results were obtained, and medication (five levels of fluticasone with or without salmeterol) adjusted according to algorithms based on symptom score (reference strategy, n=104) or AHR and symptom score (AHR strategy, n=102). After 2 yrs, no difference was found in the percentage of symptom-free days between treatment strategies. Pre-bronchodilator FEV1was higher in the AHR strategy (2.3% predicted). This was entirely explained by a gradual worsening of FEV1in a subgroup of 91 hyperresponsive children enrolled with low symptom scores (final difference between study arms was 6%). Asthma treatment guided by airway hyperresponsiveness showed no benefits in terms of number of symptom-free days, but produced a better outcome in terms of pre-bronchodilator forced expiratory volume in one second in allergic asthmatic children, especially those characterised by low symptom scores despite airway hyperresponsiveness. Copyright

Desktop simulator: Key to universal training? (Article)

2007-09-01T00:00:00Z

Background: Training of skills in simulators is preferred over learning on patients so as to avoid undue injury to patients and to allow more efficient use of resources. Most simulators are costly and require a dedicated space. The aim of this study was to evaluate a simple desktop simulator, the Mirror Trainer. Methods: Thirty medical students were randomly assigned to three groups. One group was taught laparoscopic suturing in the Mirror Trainer, the second group used a pelvic training box, while the third group served as a control group and did not receive any training. All suture attempts during training were recorded on video. A blinded, independent investigator analyzed the videos. At the completion of training, the suturing skills of each participant were evaluated in an animal model. Results: Training with the Mirror Trainer required less time than with the pelvic trainer (p < 0.001). Compared with the control group, the Mirror Trainer group and the pelvic trainer group were significantly faster at creating three knots in the pig (p = 0.001 and p = 0.004, respectively). Both training groups performed equally well on the animal model (p = 0.99). Conclusion: The Mirror Trainer and the pelvic trainer are equally effective in teaching laparoscopic suturing skills but training with the Mirror Trainer requires less time, can be done on any desktop, and is less costly.

Wnt pathway-related gene expression during malignant progression in ulcerative colitis (Article)

2007-08-01T00:00:00Z

Long-standing ulcerative colitis (UC) has been associated with a high risk of developing colonic adenocarcinoma. Importantly, both low- and high-grade dysplasia are strongly related to the presence or development of malignancy. The canonical Wnt/β-catenin signaling pathway is of crucial importance in cancer development and progression, but its role in UC-related carcinogenesis remains to be determined. We evaluated the immunolabeling patterns of β-catenin, as well as the products of Wnt-associated cancer genes E-cadherin, cyclin D1 and c-myc, along the dysplasia-carcinoma pathway in UC. For this purpose, immunohistochemistry (IHC) was performed on 18 adenocarcinomas and 17 dysplasias, derived from 21 patients. We found that intracellular β-catenin accumulation, the hallmark of Wnt signaling activation, is observed in dysplasia, together with enhanced labeling of nuclear protein cyclin D1 and reduction of membranous labeling of E-cadherin. c-myc displayed moderate immunolabeling in the (pre)malignant lesions. Thus, the Wnt pathway is activated in early stages of malignant progression in UC. Furthermore, upregulation of the oncogene cyclin D1 and downregulation of tumor suppressor E-cadherin also occurs in the (pre)neoplastic state. This may contribute to the high potential for malignant degeneration of dysplasia in UC-related colitis.

Albumin and whole-body protein synthesis respond differently to intraperitoneal and oral amino acids (Article)

2007-08-01T00:00:00Z

Patients with peritoneal dialysis are at risk for malnutrition and hypoalbuminemia, which are indicators of poor outcome. Recently, it was shown that dialysis solutions containing amino acids (AAs) and glucose improve protein anabolism in peritoneal dialysis patients. We determined if the same solutions could increase the fractional synthesis rate of albumin along with whole-body protein synthesis. Changes in the fractional albumin synthetic rate reflect acute change in hepatic albumin synthesis. A random-order cross-over study compared the effects of Nutrineal® (AA source) plus Physioneal® (glucose) dialysate with Physioneal® alone dialysate. Eight patients in the overnight fasting state were compared to 12 patients in the daytime-fed state. Fractional albumin synthetic rate and whole-body protein synthesis were determined simultaneously using a primed-continuous infusion of L-[1-13C]-leucine. Fractional albumin synthesis on AAs plus glucose dialysis did not differ significantly from that on glucose alone in the fasting or the fed state. Protein intake by itself (fed versus fasting) failed to induce a significant increase in the fractional synthetic rate of albumin. Conversely, the oral protein brought about a significant stimulation of whole-body protein synthesis. Our findings show that the supply of AAs has different effects on whole-body protein synthesis and the fractional synthetic rate of albumin.

Complications and relapse in alveolar distraction osteogenesis in partially dentulous patients (Article)

2007-08-01T00:00:00Z

Vertical distraction of the alveolar process is an efficient method for augmentation prior to inserting dental implants. In this study, complications of this procedure and relapse of the transport segment were evaluated in partially dentulous patients. Twenty patients underwent distraction by means of extraosseous distractors. The location of the defects was the anterior mandible (4), posterior mandible (4), anterior maxilla (10) and posterior maxilla (2). Bone height was measured on panoramic radiographs preoperatively, after distraction and after implant placement at the mesial and distal point of the implant(s). Mean alveolar distraction was 6.5 mm at the mesial point (P < 0.001) and 6.1 mm at the distal point (P < 0.001). The mean relapse at the mesial point was 20% and at the distal point 17% (P < 0.05). The intraoperative and postoperative problems encountered were fracture (1) and lingual (4) and palatal (6) displacement of the transport segment. Overall complication rate was 55%. Of all implants placed (n = 63) one was lost. Implant success rate was 98%. Distraction seems to be a suitable treatment for vertically deficient alveolar bone, but a relatively high although manageable complication rate must be confronted, including considerable relapse.

Urinary eosinophil protein X in children with atopic asthma (Article)

2007-07-02T00:00:00Z

The aim of this study was to investigate the relationship between urinary eosinophil protein X (uEPX) and asthma symptoms, lung function, and other markers of eosinophilic airway inflammation in asthmatic school children. Methods. A cross-sectional study was performed in 180 steroid dependent atopic children with stable moderately severe asthma, who were stable on 200 or 500μg of fluticasone per day. uEPX was measured in a single sample of urine and was normalized for creatinine concentration (uEPX/c). Symptom scores were kept on a diary card. FEV1and PD20methacholine were measured. Sputum induction was performed in 49 and FENOlevels measured in 24 children. Results. We found an inverse correlation between uEPX/c and FEV1(r=-.20, P=.01) and a borderline significant correlation between uEPX/c and PD20methacholine (r=-.15, P=.06). Symptom score, %eosinophils and ECP in induced sputum and FENOlevels did not correlate with uEPX/c. Conclusion. uEPX/c levels did not correlate with established markers of asthma severity and eosinophilic airway inflammation in atopic asthmatic children. Copyright

Increased levels of circulating endothelial progenitor cells and circulating endothelial nitric oxide synthase in patients with gliomas (Article)

2007-07-01T00:00:00Z

Objective: Gliomas are among the highest vascularized tumors. We hypothesized that patients with gliomas have increased levels of circulating endothelial progenitor cells (EPCs) and circulating endothelial nitric oxide synthase (eNOS). Methods: The fraction of EPCs was quantified by fluorescence-activated cell sorter analysis using anti-CD34, -CD133 and -KDR (kinase insert domain receptor) monoclonal antibodies in unselected peripheral blood samples of 32 patients with gliomas. Control groups included 47 patients with other central nervous system tumors or diseases, 10 patients with recent ischemic strokes, and 19 healthy blood donors. The circulating eNOS concentration of plasma was measured by a colorimetric assay in the same samples. In addition, CD34+CD105+KDR+and CD34+CD146+KDR-cell fractions were measured. Results: The percentage of CD34+CD133+KDR+EPCs in the blood of glioma patients is significantly greater than that in the blood of patients with other central nervous system tumors or diseases (p = 0.003), stroke patients (p = 0.005), or healthy donors (p = 0.013). The plasma eNOS concentration is also significantly greater in glioma patients compared with each of the control groups (p < 0.001 for all groupwise comparisons). No significant differences in the levels of the EPCs or eNOS between any of the control groups were demonstrated. In the glioma patients, the level of eNOS correlated with the fraction of CD34+CD105+KDR+cells (r = 0.748; p = 0.008). Interpretation: The data are suggestive of increased mobilization of EPCs contributing to neoplastic vasculogenesis in glioma. The increased levels of EPCs and eNOS in the peripheral blood of glioma patients trigger further investigations as to their value as independent parameters for use in clinical practice.

Impact of late-onset Pompe disease on participation in daily life activities: Evaluation of the Rotterdam Handicap Scale (Article)

2007-07-01T00:00:00Z

With the recent approval of enzyme replacement therapy for Pompe disease, insight into the social consequences of this disorder becomes even more relevant. The aim of this study was to measure the impact of late-onset Pompe disease on participation in daily life activities and to evaluate the applicability of the Rotterdam Handicap Scale (RHS) for use in Pompe disease. Two hundred fifty-seven adult patients from different countries participated in the study. The mean RHS score was 25.9 ± 6.5 on a scale of 9-36. Individual item scores were lowest for 'domestic tasks indoors', 'domestic tasks outdoors', and 'work/study'. The mean RHS score differed significantly between patients with and without respiratory support (22.9 vs. 28.5, p < 0.001) and patients with and without a wheelchair (20.9 vs. 29.5, p < 0.001). No differences in RHS score were found between countries. The RHS showed good internal consistency and excellent Test-retest reliability. A ceiling effect of 8% was present. We conclude that the RHS seems suitable for this patient population and that Pompe disease has a large impact on the participation in daily life activities, in particular on the ability of patients to fulfil their work or study.

RhDNase before airway clearance therapy improves airway patency in children with CF (Article)

2007-07-01T00:00:00Z

Introduction: Little is known about the optimal timing of rhDNase nebulization in relation to airway clearance therapy (ACT). Objective: To compare the effects of rhDNase before ACT versus rhDNase after ACT in children with CF. Methods: Design: randomized, double blind, double dummy, cross over study. Inclusion criteria: CF, stable clinical condition, rhDNase maintenance therapy. Children in Group I inhaled rhDNase 30 minutes before ACT, and placebo directly after ACT in week 1-3. The protocol was reversed during week 4-6. Group II performed the reversed sequence. Patients continued their daily routine ACT. Primary endpoint: MEF25%pred. Pulmonary functions tests were performed on days 0, 14, 21, 35 and 42. In weeks 3 and 6 children scored cough and sputum production on daily diary cards. Results: 24 patients completed the study. Mean age = 12 years (range 7-19). Mean MEF25%pred was 5.8% higher after 3 weeks of rhDNase before ACT, compared to rhDNase after ACT (58.3% vs 52.5%, p = 0.01). There were no significant differences for any of the other variables. Conclusion: Inhalation of rhDNase before ACT improves peripheral airway patency in children with cystic fibrosis. Since all children were already on maintenance rhDNase therapy before the study, this effect is additional to any existing effect of regular rhDNase.

New insights into fatigue and health-related quality of life after delivery (Article)

2007-05-07T00:00:00Z

Background. A delivery has a major impact on the health-related quality of life (HRQoL) of the new mother, especially on fatigue. A common complication during delivery that might have a relationship with maternal morbidity is blood loss. The objectives were to investigate fatigue and HRQoL in women after vaginal delivery (VD), elective caesarean section (CS) and emergency CS, and its relationship with postpartum hemoglobin (Hb) levels during the first 6 weeks postpartum. Methods. Some 141 patients (71 after VD, 36 after elective CS and 34 after emergency CS) completed the HRQoL questionnaires MFI and EQ-5D between 12 and 24 h after VD and 24-48 h after CS (t=0). At 1, 3 and 6 weeks postpartum these questionnaires were repeated, together with the SF36. Results. Patients after VD had higher mean physical HRQoL scores than after CS. The average period to reach full physical recovery was 3 weeks after VD, 6 weeks after elective CS, and >6 weeks after emergency CS. Mean mental HRQoL scores of the study groups were similar or even better compared to reference values. The significant correlation between Hb level and mean physical HRQoL scores found at t=0 had disappeared at 1 week postpartum. Conclusions. Results of this study provided insights into the natural course of fatigue and HRQoL postpartum. Important differences in fatigue and HRQoL scores were observed between the 3 modes of delivery. These HRQoL measures can be used in future clinical trials to assess the effects of interventions postpartum.

Randomized clinical trial of the impact of early enteral feeding on postoperative ileus and recovery (Article)

2007-05-01T00:00:00Z

Background: Postoperative convalescence is mainly determined by the extent and duration of postoperative ileus. This randomized clinical trial evaluated the effects of early oral feeding on functional gastrointestinal recovery and quality of life. Methods: One hundred and twenty-eight patients undergoing elective open colorectal or abdominal vascular surgery participated in the trial. Of these, 67 were randomized to a conventional return to diet, and 61 to a regimen allowing resumption of an oral diet as soon as tolerated (free diet group). Results: Reinsertion of a nasogastric tube was necessary in 20 per cent of the free diet group and 10 per cent of the conventional group (P = 0.213). The complication rate was similar for both groups, as was return of gastrointestinal function. A normal diet was tolerated after a median of 2 days in the free diet group compared with 5 days in the conventional group (P < 0.001). Quality of life scores were similar in both groups. Conclusion: Early resumption of oral intake does not diminish the duration of postoperative ileus or lead to a significandy increased rate of nasogastric tube reinsertion. Tolerance of oral diet is not influenced by gastrointestinal functional recovery. As there is no reason to withhold oral intake following open colorectal or abdominal vascular surgery, postoperative management should include early resumption of diet. Copyright

Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care (Article)

2007-04-01T00:00:00Z

Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers. Objective: To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting. Methods: Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year. Results: Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: -0.08, 95%CI, -0.66-0.50; P = .78). No differences were found for rescue medication-free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P = .001). Conclusion: Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents. Clinical implications: Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy.

Long-term follow-up of a randomized clinical trial of non-mesh versus mesh repair of primary inguinal hernia (Article)

2007-04-01T00:00:00Z

Background: Prospective studies and meta-analyses have indicated that non-mesh repair is inferior to mesh repair based on recurrence rates in inguinal hernia. The only reliable way to evaluate recurrence rates after hernia surgery is by long-term follow-up. Methods: Between September 1993 and January 1996, a multicentre clinical trial was performed, in which 300 patients with unilateral primary inguinal hernia were randomized to non-mesh or mesh repair. Long-term follow-up was carried out from June 2005 to January 2006. Results: Median follow-up was 128 months for non-mesh and 129 months for mesh repair. The 10-year cumulative hernia recurrence rates were 17 and 1 per cent respectively (P = 0-005). Half of the recurrences developed after 3 years' follow-up. There was no significant correlation between hernia recurrence and age, level of expertise of the surgeon, contralateral hernia, obesity, history of pulmonary disease, constipation or prostate disease. Conclusion: After 10 years mesh repair is still superior to non-mesh hernia repair. Recurrence rates may be underestimated as recurrences continue to develop for up to 10 years after surgery. Copyright

Long-term survival after radical resection for pancreatic head and ampullary cancer: A potential role for the EGF-R (Article)

2007-04-01T00:00:00Z

Background/Aim: Pancreatic cancer has a dismal prognosis. Ampullary cancer (defined as cancer of the ampulla of Vater or the distal common bile duct) has a better prognosis and is thought to be a biologically different tumor. The aim of this study was to find factors that could predict survival after radical (R-0) resection for pancreatic head and ampullary cancers. Methods: We analyzed clinical and pathological data from 93 patients who underwent a true R-0 resection for pancreatic head or ampullary cancer. Furthermore, we performed a tissue microarray protein expression analysis for several growth factor receptors and oncogenes: HER-2, EGF-R, ER, PR, C-myc, p53, p16, RB-1, and chromogranin A as a neuroendocrine differentiation marker. Results: Median survival (14 vs. 42 months) and time to recurrence (16 vs. 42 months)were significantly longer for ampullary than for pancreatic head cancers. Preoperative pain, perineural invasion, lymph node metastasis, and tumor differentiation grade are indicators of a poor survival. No differences in protein expression were found between groups, except for EGF-R which was expressed more in pancreatic head cancers (p = 0.026). Conclusions: Outcomes for ampullary cancers are better than for pancreatic head cancers. This different biological behavior can possibly be explained by differences in EGF-R expression. Copyright

Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement (Article)

2007-04-01T00:00:00Z

The aim of this study was to identify immunobiological subgroups in 133 infant acute lymphoblastic leukemia (ALL) cases as assessed by their immunophenotype, immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement pattern, and the presence of mixed lineage leukemia (MLL) rearrangements. About 70% of cases showed the pro-B-ALL immunophenotype, whereas the remaining cases were common ALL and pre-B-ALL. MLL translocations were found in 79% of infants, involving MLL-AF4 (41%), MLL-ENL (18%), MLL-AF9 (11%) or another MLL partner gene (10%). Detailed analysis of Ig/TCR rearrangement patterns revealed IGH, IGK and IGL rearrangements in 91, 21 and 13% of infants, respectively. Cross-lineage TCRD, TCRG and TCRB rearrangements were found in 46, 17 and 10% of cases, respectively. As compared to childhood precursor-B-ALL, Ig/TCR rearrangements in infant ALL were less frequent and more oligoclonal. MLL-AF4 and MLL-ENL-positive infants demonstrated immature rearrangements, whereas in MLL-AF9-positive leukemias more mature rearrangements predominated. The immature Ig/TCR pattern in infant ALL correlated with young age at diagnosis, CD10 negativity and predominantly with the presence and the type of MLL translocation. The high frequency of immature and oligoclonal Ig/TCR rearrangements is probably caused by early (prenatal) oncogenic transformation in immature B-lineage progenitor cells with germline Ig/TCR genes combined with a short latency period.

Three-dimensional sonography of prenatal skull base development (Article)

2007-04-01T00:00:00Z

Objective: To explore longitudinally the development of the fetal skull base using three-dimensional (3D) sonography. Methods: Serial 3D sonographic measurements of anterior skull base length, posterior cranial fossa length and skull base angle were made in 126 normal singleton pregnancies at 18-34 weeks of gestation. In a sub-study of 22 pregnancies, intraobserver variability was determined. Regression analysis for repeated measurements was performed by means of the random coefficients model. Results from an earlier publication on brain volume were extended to the total patient cohort. Results: Measurements were technically successful in 69-94% of cases. The coefficient of variation for differences between repeated tests within women was 3.5-7.6% and between repeated analyses of the same recorded volume it was 3.0-5.1%. A statistically significant gestational age-related increase was established for both the anterior skull base length and the posterior cranial fossa length and the skull base angle showed a small but significant flexion of about 6°. A higher increment in posterior cranial fossa length relative to anterior skull base angle was established. A significant quadratic relationship could be established for both anterior skull base length (P < 0.0001) and posterior cranial fossa length (P < 0.0001) but not for skull base angle, relative to brain volume. Conclusion: The reproducibility was acceptable for all fetal skull base measurements. The more pronounced growth in posterior cranial fossa length relative to anterior skull base length is influenced by brain growth. The small flexion of the skull base angle, however, may be caused by other factors. Copyright

Dialysis Fistulae Patency and Preoperative Diameter Ultrasound Measurements (Article)

2007-04-01T00:00:00Z

Background: This study was designed to investigate the possibility of defining a vascular diameter with a practical cut-off point, which predicts a successful patency for radiocephalic arteriovenous fistulae in dialysis patients. Methods: This is a retrospective analysis of prospectively gathered data. Consecutive patients (n = 148) with chronic renal failure, needing vascular access for haemodialysis, were included if they underwent duplex ultrasound examination to evaluate preoperatively the vascular status and diameters for radiocephalic arteriovenous fistulae (RCAVF) construction. The associations between the diameter of the radial artery and cephalic vein and primary failure at six weeks, primary and secondary patency at one year were investigated. Results: There was no significant association between either radial artery diameter or dilated cephalic vein diameter and primary failure. There was an association between radial artery diameter and primary patency (Overall P = 0.042). Males had a significantly larger mean radial artery diameter than females (P = 0.005). Gender did not influence primary patency. Conclusion: We recommend using radial artery diameters of ≥2.1 mm and ≤2.5 mm for RCAVF construction, this diameter category having the highest patency at 1 year. A single cut-off guideline cannot be recommended.

Surgical techniques preventing chronic pain after Lichtenstein hernia repair: State-of-the-art vs daily practice in the Netherlands (Article)

2007-04-01T00:00:00Z

Background: Morbidity associated with open inguinal hernia repair (IH repair) mainly consists of chronic pain. The aim of this study was to identify possible disparities between state-of-the-art Lichtenstein repair, and its application in general practice. Methods: A questionnaire was mailed to all surgeons and surgical residents (n = 1,374) in the Netherlands in February 2005. The objective was to determine the state of general practice with respect to technical steps during the Lichtenstein repair that are suggested to be involved in the development of chronic pain, as recently updated by Lichtenstein's successor, Amid. Results: More than half of the respondents do not act according to the Lichtenstein guidelines with respect to surgical steps that are suggested to be involved with the origin of chronic pain of somatic origin. Compliance with Amid's guidelines with respect to the handling of the nerves is variable. Surgeons conducting high numbers of IH repair are more likely to operate according to the key principles of the state-of-the-art Lichtenstein repair. Conclusion: There is a substantial disparity between the state-of-the-art Lichtenstein repair and its application in general practice with respect to steps that are suggested to play a role in the origin of chronic groin pain.

Laparoscopically assisted vs open colectomy for colon cancer: A meta-analysis (Article)

2007-03-01T00:00:00Z

Objective: To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colectomy for cancer is oncologically safe. Data Sources: The databases of the Barcelona, Clinical Outcomes of Surgical Therapy (COST), Colon Cancer Laparoscopic or Open Resection (COLOR), and Conventional vs Laparoscopic-Assisted Surgery in Patients With Colorectal Cancer (CLASICC) trials were the data sources for the study. Study Selection: Patients who had at least 3 years of complete follow-up data were selected. Data Extraction: Patients who had undergone curative surgery before March 1, 2000, were studied. Three-year disease-free survival and overall survival were the primary outcomes of this analysis. Data Synthesis: Of 1765 patients, 229 were excluded, leaving 796 patients in the laparoscopically assisted arm and 740 patients in the open arm for analysis. Three-year disease-free survival rates in the laparoscopically assisted and open arms were 75.8% and 75.3%, respectively (95% confidence interval [CI] of the difference, -5% to 4%). The associated common hazard ratio (laparoscopically assisted vs open surgery with adjustment for sex, age, and stage) was 0.99 (95% CI, 0.80-1.22; P=.92). The 3-year overall survival rate after laparoscopic surgery was 82.2% and after open surgery was 83.5% (95% CI of the difference, -3% to 5%). The associated hazard ratio was 1.07 (95% CI, 0.83-1.37; P = .61). Disease-free and overall survival rates for stages I, II, and III evaluated separately did not differ between the 2 treatments. Conclusion: Laparoscopically assisted colectomy for cancer is oncologically safe.

Recombinant human deoxyribonuclease in infants with respiratory syncytial virus bronchiolitis (Article)

2007-03-01T00:00:00Z

Background: Treatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase). Methods: In a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions. Results: There were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95% confidence interval, 0.96 to 1.33); for the duration of supplemental oxygen, the ratio was 1.28 (95% confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions. Conclusions: Administration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis.

Late development of pancreas necrosis during acute pancreatitis: An underestimated phenomenon associated with high morbidity and mortality (Article)

2007-03-01T00:00:00Z

OBJECTIVE: The purpose of this study is to assess the prognostic significance of late parenchymal pancreas necrosis as observed on serial contrast-enhanced computed tomographic (CT) scan. METHODS: Eighty-four patients with acute necrotizing pancreatitis were included. All initial CT scans were examined on complete contrast enhancement of the pancreas parenchyma (viable pancreas) or incomplete enhancement indicating parenchymal necrosis of the pancreas (PN).Secondly, all serial CT scans were evaluated to investigate whether late PN occurred in the group with a viable pancreas on initial CT scan. Characteristics of this group were evaluated. RESULTS: Thirteen patients showed signs of PN on initial CT scan. Late necrosis occurred in 5 patients. The average hospital stay in this subgroup was 46.7 days; complication rate, 100%; and mortality, 40%.A significant difference in hospital stay (average of 45.1 days vs 24.3 days; P = 0.003), complication rate (72% vs 33%; P = 0.006), and mortality (28% vs 6%; P = 0.019) was found when the group with eventual PN was compared with the group with no signs of PN (on initial and serial CT). CONCLUSIONS: This study shows a significant increase in hospital stay, complication rate, and mortality when eventual PN is shown on CT scan. Patients with late PN especially have a poor prognosis.

Craniofacial variability index determined by three-dimensional ultrasound in isolated vs. syndromal fetal cleft lip/palate (Article)

2007-03-01T00:00:00Z

Objective: This study was undertaken to employ craniofacial pattern profile analysis in fetal facial clefts and to evaluate the craniofacial variability index (CVI) in distinguishing between isolated and syndromal clefts. Methods: Three-dimensional (3D) sonographic assessment of 16 different fetal craniofacial measurements was performed in each of eight pregnancies complicated by an isolated facial cleft and seven pregnancies with a syndromal cleft. The measurements covered various aspects of facial width, depth and height. Measured values were compared to gestational age-specific normal values for calculation of Z-scores and the CVI. The number of abnormal Z-scores, i.e. < -2 or > +2, found among the measured values and the CVI in the group of isolated facial clefts were compared to those in the group with syndromal clefts. Results: The CVI could be calculated in 14 of 15 fetuses (93%). More abnormal Z-scores and a higher mean CVI were found in the group with more severe (bilateral) facial clefts. Most abnormal values were found in the facial width measurements. Syndromal cleft lip/palate was associated with significantly more abnormal Z-scores and a higher mean CVI than isolated cleft lip/palate (P < 0.05). Conclusion: Craniofacial variability index may be a valuable tool for distinguishing between isolated and syndromal fetal cleft lip/palate. Copyright

Craniofacial variability index in utero: A three-dimensional ultrasound study (Article)

2007-03-01T00:00:00Z

Objective: This study was undertaken to develop a craniofacial pattern profile analysis by three-dimensional (3D) ultrasound and to introduce a craniofacial variability index (CVI) which can assist in the evaluation of fetal facial anatomy. Methods: Serial 3D sonographic measurements of 16 different fetal craniofacial parameters were performed at 18-34 weeks of gestation in 126 normal singleton pregnancies. In another six pregnancies complicated by fetal abnormality, a single 3D recording was obtained. The 16 measurements cover various aspects of the facial anatomy, such as width, depth and height. For each parameter, regression analysis was performed to calculate gestational age-specific Z-scores and normal limits for the CVI (the latter quantifies the variability between the 16 Z-scores). Results: The 95th percentile of normal CVI data increased from 1.08 at 18 weeks to 1.27 at 34 weeks of gestation. The CVI was situated above the 95th percentile in three out of six fetuses with abnormalities. In abnormal subjects, 2-8 of 16 parameters showed abnormal values. Conclusions: Craniofacial pattern profile analysis and the CVI may aid in the evaluation of fetal facial anatomy. They could be a valuable tool in syndrome delineation and for distinguishing between normal and abnormal craniofacial development. Copyright

Impact on Quality of Life of a Telemedicine System Supporting Head and Neck Cancer Patients: A Controlled Trial During the Postoperative Period at Home (Article)

2007-03-01T00:00:00Z

Objectives: Telemedicine applications carry the potential to enhance the quality of life of patients, but studies evaluating telemedicine applications are still scarce. The evidence regarding the effectiveness of telemedicine is limited and not yet conclusive. This study investigated whether telemedicine could be beneficial to the quality of life of cancer patients. Design and Measurements: Between 1999 and 2002, we conducted a prospective controlled trial evaluating the effects of a telemedicine application on the quality of life of patients with cancer involving the head and neck, using quality of life questionnaires that covered 22 quality of life parameters. All patients had undergone surgery for head and neck cancer at the Erasmus MC, a tertiary university hospital in The Netherlands. Patients in the intervention group were given access to an electronic health information support system for a period of six weeks, starting at discharge from the hospital. Results: In total, we included 145 patients in the control group and 39 in the intervention group. At 6 weeks, the end of the intervention, the intervention group had significantly improved QoL in 5 of the 22 studied parameters. Only one of these five quality of life parameters remained significantly different at 12 weeks. Conclusions: This study adds to the sparse evidence that telemedicine may be beneficial for the quality of life of cancer patients.

Clinical condition at mid-to-late follow-up after transatrial-transpulmonary repair of tetralogy of Fallot (Article)

2007-02-01T00:00:00Z

Objectives: To assess the clinical condition at mid-to-late follow-up in tetralogy of Fallot corrected by a transatrial-transpulmonary approach at a young age and to identify risk factors associated with right ventricular dilation/dysfunction and with decreased exercise tolerance. Methods: Patients with tetralogy of Fallot underwent cardiac magnetic resonance imaging, maximal bicycle ergometry, electrocardiography, Holter monitoring, and spirometry. Multivariate linear regression analyses were used to determine independent predictors for selected clinical parameters. Results: Fifty-nine patients (mean ± SD), age at repair 0.9 ± 0.5 years, interval since repair 14 ± 5 years, were included. The median pulmonary regurgitant fraction was 32% (0%-57%). Compared with published data on healthy controls, Fallot patients had significantly larger right ventricular end-diastolic and end-systolic volumes and smaller right ventricular and left ventricular ejection fractions. Maximum oxygen consumption was 97% ± 17% and maximum workload 89% ± 13% of predicted. Median QRS duration was 110 ms (82-161 ms). No important ventricular arrhythmias were found. Compared with patients without a transannular patch, patients with a patch had more pulmonary regurgitation, a larger right ventricle, worse right ventricular and left ventricular ejection fractions, but comparable exercise capacity. Multivariate regression analysis identified the following independent determinants for larger right ventricular volumes: longer interval since repair, longer QRS duration, and higher pulmonary regurgitation percentage. The following were independent determinants for smaller right ventricular ejection fraction: abnormal right ventricular outflow tract wall motion, longer interval since repair, and longer QRS duration. For smaller maximum oxygen consumption, the independent determinants were smaller right ventricular ejection fraction and longer QRS duration. Conclusions: At mid-to-late follow-up, clinical condition in tetralogy of Fallot corrected according to contemporary surgical approaches appears well preserved. However, even these patients show right ventricular dilation and dysfunction associated with impaired functional capacity. Abnormalities relate to right ventricular outflow tract motion abnormalities, longer interval since repair, longer QRS duration, and more severe pulmonary regurgitation.

Clinical correlates of the biological variation of sperm DNA fragmentation in infertile men attending an andrology outpatient clinic (Article)

2007-02-01T00:00:00Z

Determination of sperm DNA fragmentation, as assessed by the sperm chromatin structure assay (SCSA), has become an important tool for the evaluation of semen quality. The aim of the present study was to describe the biological variation of sperm DNA fragmentation in men attending an andrology clinic and to identify clinical correlates of the biological variation of sperm DNA fragmentation. For this study, two consecutive semen samples from 100 patients attending our andrology outpatient clinic were subjected to semen analysis, performed in parallel according to WHO guidelines and by SCSA. A good agreement between pairs of samples was found for SCSA-derived variables, as indicated by a significantly lower median coefficient of variation (CV) of the DNA Fragmentation Index (DFI) and the high DNA stainability (HDS) compared with WHO semen parameters. In half of the men attending our andrology clinic, however, the individual biological variation of DFI and HDS, expressed as CV of two samples, exceeded 10%. Dysregulation of spermatogenesis, as seen as testicular insufficiency or varicocele, was not associated with increased variability of DFI or HDS. A backward multiple linear regression analysis, however, indicated that the biological variation of DFI may be more profound in men with characteristics of normal spermatogenesis. In conclusion, we confirm previous reports that sperm DNA fragmentation has a lower biological variability than classical semen parameters. We hypothesize that the sperm chromatin structure may be more influenced in patients with normal spermatogenesis, whereas in men with disturbed spermatogenesis, the chromatin structure may be already so impaired that the effect of unidentified factors leading to variability of sperm DNA fragmentation in time may not be as profound.

Randomized clinical trial comparing feeding jejunostomy with nasoduodenal tube placement in patients undergoing oesophagectomy (Article)

2007-01-01T00:00:00Z

Background: Feeding jejunostomy is frequently performed in patients undergoing oesophageal surgery, but can lead to serious complications. This prospective randomized trial compared the efficacy and complications of feeding jejunostomy with those of nasoduodenal tube feeding in oesophageal surgery. Methods: Over an 18-month period, 150 consecutive patients undergoing oesophageal resection were randomized to participate in the trial. Enteral access was by jejunostomy in 79 patients and by nasoduodenal tube in 71. Enteral feeding was started on the first day after surgery. Results: Full enteral feeding took 3 days to be established in both groups. Minor catheter-related complications occurred in 28 patients (35 per cent) in the jejunostomy group, and in 21 (30 per cent) in the nasoduodenal group (P = 0.488). One patient had jejunostomy leakage that required reoperation. Enteral nutrition was given for a median of 11 days in the jejunostomy group and for 10 days in the nasoduodenal group. Nine patients who had a jejunostomy and five with a nasoduodenal tube did not tolerate full enteral feeding (P = 0.411). Conclusion: Nasoduodenal tube feeding is safe and efficient after oesophageal resection. Copyright

An IGF-I gene polymorphism modifies the risk of developing persistent microalbuminuria in type 1 diabetes (Article)

2007-01-01T00:00:00Z

Objective: Derangements of the GH-IGF-I axis have been associated with microalbuminuria (MA) in type 1 diabetes. The aim of this study was to investigate whether an IGF-I gene promoter polymorphism influenced the development of persistent MA in type 1 diabetes. Design: A prospective follow-up study of a cohort of 277 patients with newly diagnosed type I diabetes consecutively enrolled between September 1979 and August 1984. Methods: Urinary albumin excretion rate over 24 h was measured in each patient at least once a year. Persistent MA was defined as a urinary albumin excretion rate between 30 and 300 mg/24 h. Results: During a median follow-up of 18.0 years (range 1.0-21.5), 79 of 277 patients developed persistent MA. IGF-I gene genotype was available for 216 subjects; in 73% of the subjects, the wild-type genotype of this IGF-I gene polymorphism was present, while 27% had the variant type. At baseline, there were no differences in IGF-I levels and HbA1c, values between subjects with the wild type and subjects with variant type. By Kaplan-Meier analysis, subjects with the variant type of this polymorphism had during follow-up a higher risk of development of MA compared subjects with the wild type (P=0.03). Conclusions: Subjects with the variant type of an IGF-I gene polymorphism had a significantly increased risk of developing MA. This risk was not mediated through changes in circulating IGF-I levels. Our study suggests that in type I diabetes, this IGF-I gene polymorphisin is a risk factor of MA.

Peritoneal dialysis with solutions containing amino acids plus glucose promotes protein synthesis during oral feeding (Article)

2007-01-01T00:00:00Z

Inadequate food intake plays an important role in the development of malnutrition. Recently, an increased rate of protein anabolism was shown in fasting state in patients who were on automated peritoneal dialysis with combined amino acids (AA) and glucose (G) dialysate serving as a source of both proteins and calories. This study investigated the effects of such a dialysis procedure in the daytime in the fed state in patients who were on continuous ambulatory peritoneal dialysis (CAPD). A crossover study was performed in 12 CAPD patients to compare, at 7-d intervals, a mixture of AA (Nutrineal 1.1%) plus G (Physioneal 1.36 to 3.86%) versus G only as control dialysate. Whole-body protein turnover was studied by primed constant intravenous infusion of13C-leucine during the 9-h dialysis. For meeting steady-state conditions during whole-body protein turnover, frequent exchanges with a mixture of AA plus G were done using an automated cycler. Fed-state conditions were created by identical liquid hourly meals. Using AA plus G dialysate, as compared with the control, rates of protein synthesis increased significantly (2.02 ± 0.08 versus 1.94 ± 0.07 μmol leucine/kg per min [mean ± SEM]; P = 0.039). Rates of protein breakdown and net protein balance did not differ significantly between AA plus G and G. In conclusion, dialysate that contains AA plus G also improves protein synthesis in fed CAPD patients. The use of such a mixture may contribute to long-term improvement of the nutritional status in malnourished CAPD patients with deficient food intake. Copyright

Aerosol therapy by pressured metered-dose inhaler-spacer in sleeping young children: To do or not to do? (Article)

2006-08-01T00:00:00Z

One third of young children are distressed during inhalation therapy. It has been suggested that administration during sleep could be a good alternative for these children. A laboratory study in our department using an infant upper airway model showed significantly higher lung doses from a pressured metered-dose inhaler (pMDI)-spacer for sleep-breathing patterns compared with wake-breathing patterns. Objective: We set up a daily life study to investigate the feasibility of aerosol administration by means of pMDI-spacer in sleeping young children. Design: Over a period of 3 weeks, 30 children (age range, 6 to 23 months) with recurrent wheeze daily inhaled 1 puff of budesonide aerosol (200 μg) while awake and 1 puff during sleep. Filters positioned between the chamber and the facemask trapped the budesonide aerosol. Parents scored the child's asthma symptoms, degree of cooperation, and feasibility of administration on diary cards. Results: In 69% of the sleep administrations, the children woke up, and in 75% of these cases the children were distressed. The mean filter dose (expressed as the percentage of the nominal dose) while awake was 47%, and during sleep it was 16% (p = 0.007). The median within-subject dose variability while awake was 50%, and during sleep it was 110% (p = 0.007). Conclusion: Aerosol administration by means of pMDI-spacer during sleep offers no advantage and is not a feasible treatment option in most young children.

Multiplex bead array assay for detection of 25 soluble cytokines in blister fluid of patients with complex regional pain syndrome type 1. (Article)

2006-03-31T00:00:00Z

Inflammatory processes are known to be involved at least in the early phase of complex regional pain syndrome type 1 (CRPS1). Blister fluid obtained from the involved extremities displayed increased amounts of proinflammatory cytokines IL-6 and TNFalpha compared with the noninvolved extremities. The aim of this paper is to investigate the involvement of mediators by measurement of several other cytokines using new detection techniques that enable multiple cytokine measurement in small samples. The use of a multiplex-25 bead array cytokine assay and Luminex technology enabled simultaneous measurement of representative (1) proinflammatory cytokines such as GM-CSF, IL-1beta, IL-1RA, IL-6, IL-8, and TNF-alpha; (2) Th1/Th2 distinguishing cytokines IFN-gamma, IL-2, IL-2R, IL-4, IL-5, and IL-10; (3) nonspecific acting cytokines IFN-alpha, IL-7, IL-12p40/p70, IL-13, IL-15, and IL-17; and (4) chemokines eotaxin, IP-10, MCP-1, MIP-1alpha, MIP-1beta, MIG, and RANTES. Although minimal detection levels are significantly higher in the bead array system than those in common ELISA assays, in blister fluid, IL-1RA, IL-6, IL-8, TNF-alpha, IL-12p40/p70, MCP-1, and MIP-1beta were detectable and increased in CRPS1 affected extremities. Levels of IL-6 and TNF-alpha simultaneously measured by ELISA (Sanquin Compact kit) and by multiplex-25 bead array assay (Biosource) were highly correlated (r = 0.85, P < .001 for IL-6 and r = 0.88, P < .001 for TNF-alpha). Furthermore, IP-10 and eotaxin were detectable but diminished in CRPS1, whereas detectable amounts of IL-10 were similar in involved and noninvolved extremities. Multiplex bead array assays are useful systems to establish the involvement of cytokines in inflammatory processes by measurements in blister fluids of CRPS1. Ten representative cytokines were detectable. However, detection levels and amounts measured are at least 3 times higher in the multiplex-25 array assay than in the ELISA assays used simultaneously for the measurement of cytokines.

Comparison of laparoscopic and mini incision open donor nephrectomy: single blind, randomised controlled clinical trial (Article)

2006-01-01T00:00:00Z

OBJECTIVES: To determine the best approach for live donor nephrectomy to minimise discomfort to the donor and to provide good graft function. DESIGN: Single blind, randomised controlled trial. SETTING: Two university medical centres, the Netherlands. PARTICIPANTS: 100 living kidney donors. INTERVENTIONS: Participants were randomly assigned to either laparoscopic donor nephrectomy or to mini incision muscle splitting open donor nephrectomy. MAIN OUTCOME MEASURES: The primary outcome was physical fatigue using the multidimensional fatigue inventory 20 (MFI-20). Secondary outcomes were physical function using the SF-36, hospital stay after surgery, pain, operating times, recipient graft function, and graft survival. RESULTS: Conversions did not occur. Compared with mini incision open donor nephrectomy, laparoscopic donor nephrectomy resulted in longer skin to skin time (median 221 v 164 minutes, P < 0.001), longer warm ischaemia time (6 v 3 minutes, P < 0.001), less blood loss (100 v 240 ml, P < 0.001), and a similar number of complications (intraoperatively 12% v 6%, P = 0.49, postoperatively both 6%). After laparoscopic nephrectomy, donors required less morphine (16 v 25 mg, P = 0.005) and shorter hospital stay (3 v 4 days, P = 0.003). During one year's follow-up mean physical fatigue was less (difference - 1.3, 95% confidence interval - 2.4 to - 0.1) and physical function was better (difference 6.2, 2.0 to 10.3) after laparoscopic nephrectomy. Function of the graft and graft survival rate of the recipient at one year censored for death did not differ (100% after laparoscopic nephrectomy and 98% after open nephrectomy). CONCLUSIONS: Laparoscopic donor nephrectomy results in a better quality of life compared with mini incision open donor nephrectomy but equal safety and graft function.

Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial. (Article)

2005-10-01T00:00:00Z

RATIONALE: Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma. OBJECTIVE: We evaluated whether titrating steroids on FENO improved asthma management in children. METHODS: Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a FENO group (n=39) in which treatment decisions were made on both FENO and symptoms, or to a symptom group (n=46) treated on symptoms only. Children were seen every 3 months over a 1-year period. MEASUREMENTS: Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyperresponsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose. RESULTS: Changes in steroid dose from baseline did not differ between groups. In the FENO group, hyperresponsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p=0.04). FEV1 in the FENO group improved, and the change in FEV1 was not significantly different between groups. The FENO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. FENO increased in the symptom group; the change in FENO from baseline differed between groups (p=0.02). CONCLUSION: In children with asthma, 1 year of steroid titration on FENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation.

Euthyroid sick syndrome in meningococcal sepsis: the impact of peripheral thyroid hormone metabolism and binding proteins. (Article)

2005-10-01T00:00:00Z

CONTEXT AND OBJECTIVES: The objective of this study was to elucidate the influence of disease severity, deiodination, sulfation, thyroid hormone binding, and dopamine use on thyroid function in euthyroid sick syndrome. SETTING: The study was performed at a university-affiliated pediatric intensive care unit (PICU). DESIGN: This was an observational cohort study. PATIENTS: Sixty-nine children with meningococcal sepsis were studied. MAIN OUTCOME MEASURES: Differences in thyroid function among nonsurvivors, shock survivors, and sepsis survivors on PICU admission were the main outcome measures. RESULTS: The main study group consisted of 45 non-dopamine-treated children. All children had decreased total T3 (TT3)/rT3 ratios without elevated TSH. T4 sulfate levels were decreased in 88%. Nonsurvivors had paradoxically higher TT3/rT3 ratios than shock survivors (0.71 vs. 0.30); this ratio also correlated with shorter duration of disease (r = -0.43). TT4 and T4-binding globulin (TBG) levels declined with increasing disease severity. TBG levels correlated inversely with elastase levels (r = -0.46). Only TSH levels were significantly lower in 24 dopamine-treated children compared with non-dopamine-treated children (0.65 vs. 0.84), whereas other thyroid hormones did not significantly differ. Both higher TT3/rT3 ratios and lower TT4 levels were predictive for mortality, but this disappeared when IL-6 was entered into the regression model. CONCLUSIONS: All children with meningococcal sepsis showed signs of euthyroid sick syndrome. Alterations in peripheral thyroid hormone metabolism related inversely to the duration of disease and seemed to be enacted by profound induction of type 3 deiodinase rather than by down-regulation of type 1. Lower TT4 levels were related to increased turnover of TBG by elastase. Dopamine was found to suppress only TSH secretion, not other thyroid hormone levels, on PICU admission. Both the TT3/rT3 ratio and TT4 levels were predictive for mortality, but were not superior to IL-6.

A randomized, placebo-controlled GH trial in very preterm infants who were at risk for bronchopulmonary dysplasia and were treated with dexamethasone. (Article)

2005-10-01T00:00:00Z

Very preterm infants who develop bronchopulmonary dysplasia are often treated with dexamethasone (DEXA) to wean them from the ventilator. As DEXA has growth-suppressive and catabolic effects, which might have long-term consequences on growth and organ development, we investigated whether high-dose GH treatment could overcome these effects. In a randomized, double-blind, placebo-controlled trial, 30 ventilated very low birth weight infants were assigned to receive either GH or placebo treatment after start of DEXA. DEXA was given for 24 d (starting dose 0.5 mg . kg(-1) . d(-1), tapering off every third day). Simultaneously, high-dose GH (0.3 mg . kg(-1) . d(-1)) or placebo was administered during 6 wk. During high-dose DEXA treatment (dose 0.5-0.3 mg . kg(-1) . d(-1)), no gain in head circumference, weight, crown-heel length, and knee-heel length occurred in the GH and placebo groups. Growth during the 6-wk study period was not different between the GH and the placebo groups. Two patients in the placebo group died, but the number and the severity of adverse effects was not statistically different between the GH and placebo groups. In conclusion, high-dose GH treatment did not improve growth in DEXA-treated very preterm infants and thus cannot be recommended to prevent growth failure in these infants. During high-dose DEXA, a complete growth arrest occurred, including stunting of head growth. Growth in head circumference and weight with lower dose DEXA was comparable to growth after discontinuation of DEXA.

Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality. (Article)

2005-09-01T00:00:00Z

CONTEXT: Adequate adrenal function is pivotal to survive meningococcal sepsis. OBJECTIVES: The objective of the study was to evaluate adrenocortical function in meningococcal disease. DESIGN: This was an observational cohort study. SETTING: The study was conducted at a university-affiliated pediatric intensive care unit. PATIENTS: Sixty children with meningococcal sepsis or septic shock participated in the study. MAIN OUTCOME MEASURES: The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured. RESULTS: Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ. CONCLUSIONS: Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.

Changes in airway dimensions on computed tomography scans of children with cystic fibrosis. (Article)

2005-07-15T00:00:00Z

RATIONALE: In cystic fibrosis (CF), chronic bacterial infection and inflammation lead to progressive airway wall thickening and lumen dilatation. Objectives: To quantify airway wall thickening and lumen dilatation in children with CF over a 2-year interval. METHODS: Children with CF (n = 23) who had two computed tomography (CT) scans (CT(cf1) and CT(cf2)) combined with pulmonary function tests (PFTs), with a 2-year interval between measurements, were compared with control subjects (n = 21) who had one CT (CT(controls)). On cross-sectional cut airway-artery pairs, airway wall area (WA), airway lumen area (LA) and perimeter, and arterial area (AA) were quantified. LA/AA (= marker of bronchiectasis), airway wall thickness (AWT), and WA/AA (= markers of wall thickness) were calculated. CT scans were scored using four different scoring systems. PFTs were expressed as percent predicted. RESULTS: Airway WA-to-AA ratio was 1.45 (p < 0.001) and airway LA-to-AA ratio was 1.92 times higher (p < 0.001) in children with CF compared with age-matched control subjects. LA/AA and WA/AA remained unchanged from CT(cf1) to CT(cf2) and did not increase with age. AWT as a function of airway size increased from CT(cf1) to CT(cf2) by 2% (0.03 mm; p = 0.02). The change in AWT was inversely related to the change in forced expiratory flow between 25 and 75% of expiratory VC (p = 0.002). CONCLUSIONS: In CF, quantitative measurements of airways on CT scans show an increased ratio between airway LA and AA and progressive airway wall thickening. Scoring systems show progression of bronchiectasis but unchanged AWT. PFTs remained stable.

Low-molecular weight caldesmon as a potential serum marker for glioma. (Article)

2005-06-15T00:00:00Z

PURPOSE: Testing the feasibility of using the serum low-molecular weight caldesmon (l-CaD) level as a serum marker for the presence of glioma. EXPERIMENTAL DESIGN: Within a total of 230 serum samples, the l-CaD level was measured in healthy volunteers (30), patients with gliomas (57), nonglial intracranial tumors (107), and nontumor neurologic diseases (36) by ELISA. The specificity of the assay was monitored by combination of immunoprecipitation and immunoblotting. RESULTS: The serum level of l-CaD is significantly higher in the group of glioma patients as compared with any of the other groups (P < 0.001). The cutoff value of 45 yields optimal sensitivity and specificity of the assay (91% and 84%, respectively; area under the curve score = 0.91). The specificity of ELISA was confirmed by the immunoprecipitation/immunoblotting control experiments. There were no significant differences in serum l-CaD levels between patients with low- or high-grade gliomas. CONCLUSIONS: The serum l-CaD level as determined by ELISA is a good discriminator between glioma patients versus patients with other intracranial tumors, other neurologic diseases, and healthy people. Prospective studies are required to test the contribution of the assay in making the diagnosis of glioma, or its feasibility for monitoring the tumor during treatment.

Efficacy of fluticasone propionate on lung function and symptoms in wheezy infants. (Article)

2005-02-15T00:00:00Z

The role of inhaled corticosteroids in the treatment of recurrent or persistent wheeze in infancy remains unclear. We evaluated the effect of 3 months of treatment with inhaled fluticasone propionate, 200 microg daily (FP200), on lung function and symptom scores in wheezy infants. Moreover, we evaluated whether infants with atopy and/or eczema respond better to FP200 as compared with non-atopic infants. Forced expiratory flow (Vmax(FRC)) was measured at baseline and after treatment. Sixty-five infants were randomized to receive FP200 or placebo, and 62 infants (mean age, 11.3 months) completed the study. Mean Vmax(FRC), expressed as a Z score, was significantly below normal at baseline and after treatment in both groups. The change from baseline of Vmax(FRC) was not different between the two treatment arms. After 6 weeks of treatment, and not after 13 weeks, the FP200 group had a significantly higher percentage of symptom-free days and a significant reduction in mean daily cough score compared with placebo. Separate analysis of treatment effect in infants with atopy or eczema showed no effect modification. We conclude that in wheezy infants, after 3 months of treatment with fluticasone, there was no improvement in lung function and no reduction in respiratory symptoms compared with placebo.

Reduced nasal IL-10 and enhanced TNFa responses during rhinovirus and RSV-induced upper respiratory tract infection in atopic and non-atopic infants (Article)

2005-02-01T00:00:00Z

Rhinovirus and respiratory syncytial virus (RSV) are the most prevalent inducers of upper respiratory tract infections (URTI) in infants and may stimulate immune maturation. To estimate the amount of immune stimulation, nasal immune responses were examined during rhinovirus and RSV-induced URTI in infants. Nasal brush samples were taken from infants (2-26 months; 57% atopic family) with rhinovirus-induced URTI (N=20), with RSV-induced URTI (N=7), and with rhinovirus-induced rhinitis (N=11), from children with asymptomatic rhinovirus infection (N=7) and from eight non-infected children. Numbers of nasal brush cells positive for Th1-, Th2-, regulatory and proinflammatory cytokines were measured by immunohistochemistry or by measuring protein levels using a cytometric bead array analysis. During rhinovirus and RSV-induced URTI, fewer regulatory cytokine IL-10 positive cells were found compared to non-infected children. This fall was accompanied by an increase in levels of the Th1 cytokine TNFalpha. IL-10 responses were inversely related to TNFalpha responses. No enhanced responses were observed for IFNgamma, IL-12 and IL-18. Cytokine responses were comparable in children with rhinovirus-induced URTI and in children with rhinitis, while responses in asymptomatic rhinovirus-infected children were located between those for symptomatic and asymptomatic rhinovirus-infected children. Cytokine responses did not depend on the age of the child or atopy in the family. In conclusion, reduced nasal IL-10 responses during URTI in infants could facilitate the induction of a TNFalpha response. TNFalpha in turn could replace the immature production of IL-12, IL-18 and IFNgamma during URTI to induce an effective clearance of the viral infection and which could stimulate the maturation of Th1 cytokine production in infancy.

Efficacy of fluticasone on cough: a randomised controlled trial. (Article)

2005-01-01T00:00:00Z

Cough may be the consequence of bronchial hyperresponsiveness (BHR) and inflammation. This study was designed to investigate the short-term effects of an inhaled steroid (fluticasone propionate (FP)) on cough, and to determine the effects of smoking, BHR, allergy and forced expiratory volume in one second (FEV1) on the efficacy of FP. In a community-based primary healthcare centre, 135 previously healthy adults suffering from cough for > or =2 weeks were enrolled in a randomised, double-blind, placebo-controlled trial of inhaled FP 500 microg b.i.d. for 2 weeks. Participants completed daily diary cards of lower respiratory tract symptoms. The primary outcome measure was the decrease in mean total daily cough score (0-6) during the second week of treatment. In the FP group, the cough score decreased from 3.8 at baseline to mean+/-SEM 1.4+/-0.2 during the second week. In the placebo group, this decrease was from 3.8 to 1.9+/-0.1 and was statistically significantly less. A favourable effect of FP was only detectable in nonsmokers, in whom the score was 0.9 points lower compared with placebo. The clinical relevance of this finding has to be established further. Allergy, FEV1 and BHR at baseline did not affect the efficacy of FP. In conclusion, anti-inflammatory treatment with the inhaled steroid fluticasone propionate reduces cough in otherwise healthy adults who do not smoke.

Epstein-Barr virus and disease activity in multiple sclerosis (Article)

2005-01-01T00:00:00Z

OBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study with 73 RR MS patients followed for an average of 1.7 years with frequent neurological examination and blood sampling. Antibodies to various EBV proteins were measured by ELISA and plasma EBV DNA was measured by PCR. RESULTS: All MS patients had IgG antibodies to EBV (viral capsid antigen (VCA) and/or EBV nuclear antigen (EBNA)), irrespective whether samples were taken at stable disease or exacerbation. A significantly elevated percentage of the patients (48%) had antibodies against EBV antigens (early antigen, EA) that indicate active viral replication, compared with the age matched healthy controls (25%). Antibodies against a control herpesvirus, cytomegalovirus, were similar between the two groups. The percentage of EA positive individuals and EA titres did not differ between stable disease or exacerbation. Anti-VCA IgM was positive in three cases, unrelated to disease activity. Using a highly sensitive PCR on 51 samples taken at exacerbation visits, only three patients were found to have one timepoint with viraemia, and this viraemia was unrelated to disease activity. Of special note was the fact that anti-EA seropositive patients remained seropositive during follow up, with stable titres over time. We hypothesised that these patients may constitute a subgroup with higher disease activity, due to the triggering effect of a chronic attempt of the virus to reactivate. The EA positive group did not differ from the EA negative with respect to clinical disease activity or other characteristics. However, in the EA positive group, analysis with gadolinium enhanced MRI indicated more MRI disease activity. CONCLUSIONS: There was no evidence for increased clinical disease activity in the subgroup of MS patients with serological signs of EBV reactivation. However, the observation that chronic EBV reactivation may be associated with increased inflammatory activity as assessed by gadolinium enhanced MRI lesions should be reproduced in a larger and independent dataset.

Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission (Article)

2005-01-01T00:00:00Z

BACKGROUND: Nitric oxide in exhaled air (FE(NO)) is a marker of eosinophilic airway inflammation. A study was undertaken to determine whether FE(NO) predicts asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids are discontinued. METHODS: Forty children (21 boys) of mean age 12.2 years on a median dose of 400 mug budesonide or equivalent (range 100-400) were included. FE(NO) was measured before and 2, 4, 12, and 24 weeks after withdrawal of steroids. A relapse was defined as more than one exacerbation per month, or need for beta agonist treatment on 4 days per week for at least 2 weeks, or diurnal peak flow variability of >20%. FE(NO) measurements were performed online with an expiratory flow of 50 ml/s. RESULTS: Nine patients relapsed. Two and 4 weeks after withdrawal of steroids geometric mean FE(NO) in children who were about to relapse was higher than in those who did not relapse: 35.3 ppb v 15.7 ppb at 2 weeks (ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb v 15.9 ppb at 4 weeks (ratio 2.6; 95% CI 1.3 to 5.1). An FE(NO) value of 49 ppb at 4 weeks after discontinuation of steroids had the best combination of sensitivity (71%) and specificity (93%) for asthma relapse. CONCLUSION: FE(NO) 2 and 4 weeks after discontinuation of steroids in asymptomatic asthmatic children may be an objective predictor of asthma relapse.

The open lung concept: effects on right ventricular afterload after cardiac surgery. (Article)

2004-09-01T00:00:00Z

BACKGROUND: The open lung concept (OLC) is a method of ventilation intended to maintain end-expiratory lung volume by increased airway pressure. Since this could increase right ventricular afterload, we studied the effect of this method on right ventricular afterload in patients after cardiac surgery. METHODS: We studied 24 stable patients after coronary artery surgery and/or valve surgery with cardiopulmonary bypass. Patients were randomly assigned to OLC or conventional mechanical ventilation (CMV). In the OLC group, recruitment manoeuvres were applied until Pa(o(2))/FI(O(2)) was greater than 50 kPa (reflecting an open lung). This value was maintained by sufficient positive airway pressure. In the CMV group, volume-controlled ventilation was used with a PEEP of 5 cm H(2)O. Cardiac index, right ventricular preload, contractility and afterload were measured with a pulmonary artery thermodilution catheter during the 3-h observation period. Blood gases were monitored continuously. RESULTS: To achieve Pa(O(2))/Fl(O(2)) > 50 kPa, 5.3 (3) (mean, SD) recruitment attempts were performed with a peak pressure of 45.5 (2) cm H(2)O. To keep the lung open, PEEP of 17.0 (3) cm H(2)O was required. Compared with baseline, pulmonary vascular resistance and right ventricular ejection fraction did not change significantly during the observation period in either group. CONCLUSION: No evidence was found that ventilation according to the OLC affects right ventricular afterload.

Transjugular intrahepatic portosystemic shunts: long-term patency and clinical results in a patient cohort observed for 3-9 years. (Article)

2004-05-01T00:00:00Z

PURPOSE: To retrospectively assess the outcome of transjugular intrahepatic portosystemic shunt (TIPS) placement in a nonselected group of consecutive patients. MATERIALS AND METHODS: TIPS placement was attempted in 82 patients. Patients were followed up for at least 3 years according to a standard protocol that included repeated shunt evaluations. Fifty-four patients underwent TIPS placement for variceal bleeding, 24 for refractory ascites, and four for other indications. Recurrent bleeding, effect on ascites, long-term patency, development of encephalopathy, and survival and complication rates were evaluated with Kaplan-Meier survival analysis and Cox multivariate analysis. RESULTS: TIPS placement was successful in 75 patients (91%). Mean follow-up lasted 29.4 months. Primary patency was 22% and 12%, primary-assisted patency was 67% and 46%, and secondary patency was 91% and 91% at 1- and 5-year follow-up, respectively. Nonalcoholic liver disease (P =.007) and increasing platelet counts (P =.006) independently predicted development of shunt insufficiency. The 1- and 5-year rates of recurrent variceal bleeding were 21% and 27%, respectively. In the majority of patients with refractory ascites, a beneficial effect of TIPS placement was observed. The risk for encephalopathy was 25% at 1-month follow-up and 52% at 3-year follow-up. The risk for chronic or severe intermittent encephalopathy was 15% at 1-year follow-up and 20% at 3-year follow-up. Serum creatinine levels (P =.001) and age (P =.02) were independent risk factors. Overall survival rate was 61%, 49%, and 42% at 1-, 3-, and 5-year follow-up, respectively. Age (P =.03), serum albumin level (P =.02), and serum creatinine level (P <.001) were independently related to mortality. CONCLUSION: The risk for definitive loss of shunt function was 17% at 5-year follow-up, indicating that surveillance with shunt revision-when indicated-results in excellent long-term TIPS patency. TIPS placement effectively protects against recurrent bleeding.

Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements. (Article)

2004-05-01T00:00:00Z

PURPOSE: To retrospectively compare thin-section computed tomographic (CT) scores obtained with five scoring systems for assessment of pulmonary disease in children with cystic fibrosis and to determine additional value of bronchial and arterial dimension measurements. MATERIALS AND METHODS: Scores obtained with five thin-section CT scoring systems were compared. A score of 0 indicated the absence of abnormalities; a higher score meant that more structural abnormalities were seen. Three observers assigned scores and then reassigned scores after intervals varying from 1-2 weeks to 1-2 months at review of thin-section CT scans obtained in 25 children with cystic fibrosis. Interobserver and intraobserver reliability was calculated with intraclass correlation coefficients. Quantitative measurements of bronchial and arterial dimensions were obtained. Thin-section CT scores were correlated (Spearman correlation) with bronchial and arterial dimensions and with results of pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV(1)). RESULTS: Scores with all five scoring systems were reproducible, with intraclass correlation coefficients of 0.74 and higher (P <.05), and showed significant correlations with FEV(1) (R = -0.73 to -0.69, P <.01). Ratio of bronchial diameter to accompanying pulmonary arterial diameter was correlated with thin-section CT scores but not with FEV(1). Ratio of bronchial wall thickness to accompanying pulmonary arterial diameter was not correlated with thin-section CT scores or PFT results. CONCLUSION: Thin-section CT scores were reproducible and were correlated with PFT results. Measurements of bronchial dimensions were not significantly related to scores or PFT results.

Anovaginal fistulas: evaluation with endoanal MR imaging. (Article)

2004-04-01T00:00:00Z

PURPOSE: To evaluate endoanal magnetic resonance (MR) imaging in the assessment of anovaginal fistulas and associated findings. MATERIALS AND METHODS: In a retrospective descriptive study, two radiologists systematically reviewed MR findings in 20 patients with a clinically proved anovaginal fistula and looked for the main fistula tract, the internal opening in the anal canal and/or vagina, secondary fistula tracts, abscesses within the rectovaginal septum, and sphincter damage. Interobserver variability was calculated, and clinical records were searched for possible underlying causes that could explain the complexity of anovaginal fistulas. The kappa value was calculated. Patients with or without a complex anovaginal fistula were compared in regard to the presence of any underlying disease or condition. Statistical significance was calculated with the Fisher exact test. RESULTS: In all 20 patients, anovaginal fistulas were identified on T2-weighted MR images as predominantly high-signal-intensity linear abnormalities extending between the anal canal and the vagina. In all patients, the fistulas were typically located in the sagittal plane, and the mean distance from the anal verge to the fistula was 25.0 mm (range, 13-32 mm). The internal opening in the anal canal was detected in all patients. The internal opening in the vagina was detected in 19 (95%) patients. In seven (35%) patients, an anovaginal fistula with an additional abnormality was found and included an abscess within the rectovaginal septum (n = 1), a perianal fistula (n = 3), and a perianal fistula in combination with an abscess (n = 3). Defects of the external anal sphincter were present in three (15%) patients. There was complete agreement between observers for all items on endoanal MR images, except for the presence of secondary fistula extensions (agreement, 90%; kappa, 0.74). History of obstetric trauma, pelvic floor surgery, or Crohn disease was present in 10 (50%) patients. Of these patients, six (60%) had a complex anovaginal fistula and four (40%) had a simple anovaginal fistula. In the remaining 10 patients without relevant medical history, one (10%) had a complex anovaginal fistula. This difference tended toward statistical significance (P =.057). CONCLUSION: Endoanal MR imaging allows evaluation of anovaginal fistulas and additional abnormalities, such as abscesses within the rectovaginal septum, secondary perianal fistula tracts, and sphincter damage.

Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk (Article)

2004-01-01T00:00:00Z

OBJECTIVE: Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be obtained at relatively low costs, even in small animals such as rabbits. We tested the long-term safety and efficacy of recombinant human -glucosidase (rhAGLU) from rabbit milk for the treatment of the lysosomal storage disorder Pompe disease. The disease occurs with an estimated frequency of 1 in 40,000 and is designated as orphan disease. The classic infantile form leads to death at a median age of 6 to 8 months and is diagnosed by absence of alpha-glucosidase activity and presence of fully deleterious mutations in the alpha-glucosidase gene. Cardiac hypertrophy is characteristically present. Loss of muscle strength prevents infants from achieving developmental milestones such as sitting, standing, and walking. Milder forms of the disease are associated with less severe mutations and partial deficiency of alpha-glucosidase. METHODS: In the beginning of 1999, 4 critically ill patients with infantile Pompe disease (2.5-8 months of age) were enrolled in a single-center open-label study and treated intravenously with rhAGLU in a dose of 15 to 40 mg/kg/week. RESULTS: Genotypes of patients were consistent with the most severe form of Pompe disease. Additional molecular analysis failed to detect processed forms of alpha-glucosidase (95, 76, and 70 kDa) in 3 of the 4 patients and revealed only a trace amount of the 95-kDa biosynthetic intermediate form in the fourth (patient 1). With the more sensitive detection method, 35S-methionine incorporation, we could detect low-level synthesis of -glucosidase in 3 of the 4 patients (patients 1, 2, and 4) with some posttranslation modification from 110 kDa to 95 kDa in 1 of them (patient 1). One patient (patient 3) remained totally deficient with both detection methods (negative for cross-reactive immunologic material [CRIM negative]). The alpha-glucosidase activity in skeletal muscle and fibroblasts of all 4 patients was below the lower limit of detection (<2% of normal). The rhAGLU was tolerated well by the patients during >3 years of treatment. Anti-rhAGLU immunoglobulin G titers initially increased during the first 20 to 48 weeks of therapy but declined thereafter. There was no consistent difference in antibody formation comparing CRIM-negative with CRIM-positive patients. Muscle alpha-glucosidase activity increased from <2% to 10% to 20% of normal in all patients during the first 12 weeks of treatment with 15 to 20 mg/kg/week. For optimizing the effect, the dose was increased to 40 mg/kg/week. This resulted, 12 weeks later, in normal alpha-glucosidase activity levels, which were maintained until the last measurement in week 72. Importantly, all 4 patients, including the patient without any endogenous alpha-glucosidase (CRIM negative), revealed mature 76- and 70-kDa forms of -glucosidase on Western blot. Conversion of the 110-kDa precursor from milk to mature 76/70-kDa alpha-glucosidase provides evidence that the enzyme is targeted to lysosomes, where this proteolytic processing occurs. At baseline, patients had severe glycogen storage in the quadriceps muscle as revealed by strong periodic acid-Schiff--positive staining and lacework patterns in hematoxylin and eosin--stained tissue sections. The muscle pathology correlated at each time point with severity of signs. Periodic acid-Schiff intensity diminished and number of vacuoles increased during the first 12 weeks of treatment. Twelve weeks after dose elevation, we observed signs of muscle regeneration in 3 of the 4 patients. Obvious improvement of muscular architecture was seen only in the patient who learned to walk. Clinical effects were significant. All patients survived beyond the age of 4 years, whereas untreated patients succumb at a median age of 6 to 8 months. The characteristic cardiac hypertrophy present at start of treatment diminished significantly. The left ventricular mass index decreased from 171 to 599 g/m2 (upper limit of normal 86.6 g/m2 for infants from 0 to 1 year) to 70 to 160 g/m2 during 84 weeks of treatment. In addition, we found a significant change of slope for the diastolic thickness of the left ventricular posterior wall against time at t = 0 for each separate patient. Remarkably, the younger patients (patients 1 and 3) showed no significant respiratory problems during the first 2 years of life. One of the younger patients recovered from a life-threatening bronchiolitis at the age of 1 year without sequelae, despite borderline oxygen saturations at inclusion. At the age of 2, however, she became ventilator dependent after surgical removal of an infected Port-A-Cath. She died at the age of 4 years and 3 months suddenly after a short period of intractable fever of >42 degrees C, unstable blood pressure, and coma. The respiratory course of patient 1 remained uneventful. The 2 older patients, who both were hypercapnic (partial pressure of carbon dioxide: 10.6 and 9.8 kPa; normal range: 4.5-6.8 kPa) at start of treatment, became ventilator dependent before the first infusion (patient 2) and after 10 weeks of therapy (patient 4). Patient 4 was gradually weaned from the ventilator after 1 year of high-dose treatment and was eventually completely ventilator-free for 5 days, but this situation could not be maintained. Currently, both patients are completely ventilator dependent. The most remarkable progress in motor function was seen in the younger patients (patients 1 and 3). They achieved motor milestones that are unmet in infantile Pompe disease. Patient 1 learned to crawl (12 months), walk (16 months), squat (18 months), and climb stairs (22 months), and patient 3 learned to sit unsupported. The Alberta Infant Motor Scale score for patients 2, 3, and 4 remained far below p5. Patient 1 followed the p5 of normal. CONCLUSION: Our study shows that a safe and effective medicine can be produced in the milk of mammals and encourages additional development of enzyme replacement therapy for the several forms of Pompe disease. Restoration of skeletal muscle function and prevention of pulmonary insufficiency require dosing in the range of 20 to 40 mg/kg/week. The effect depends on residual muscle function at the start of treatment. Early start of treatment is required.

Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia (Article)

2004-01-01T00:00:00Z

OBJECTIVE: The objective of this study was to determine the best treatment of incisional hernia, taking into account recurrence, complications, discomfort, cosmetic result, and patient satisfaction. BACKGROUND: Long-term results of incisional hernia repair are lacking. Retrospective studies and the midterm results of this study indicate that mesh repair is superior to suture repair. However, many surgeons are still performing suture repair. METHODS: Between 1992 and 1998, a multicenter trial was performed, in which 181 eligible patients with a primary or first-time recurrent midline incisional hernia were randomly assigned to suture or mesh repair. In 2003, follow-up was updated. RESULTS: Median follow-up was 75 months for suture repair and 81 months for mesh repair patients. The 10-year cumulative rate of recurrence was 63% for suture repair and 32% for mesh repair (P < 0.001). Abdominal aneurysm (P = 0.01) and wound infection (P = 0.02) were identified as independent risk factors for recurrence. In patients with small incisional hernias, the recurrence rates were 67% after suture repair and 17% after mesh repair (P = 0.003). One hundred twenty-six patients completed long-term follow-up (median follow-up 98 months). In the mesh repair group, 17% suffered a complication, compared with 8% in the suture repair group (P = 0.17). Abdominal pain was more frequent in suture repair patients (P = 0.01), but there was no difference in scar pain, cosmetic result, and patient satisfaction. CONCLUSIONS: Mesh repair results in a lower recurrence rate and less abdominal pain and does not result in more complications than suture repair. Suture repair of incisional hernia should be abandoned.

Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors (Article)

2004-01-01T00:00:00Z

OBJECTIVE: A prospective randomized multicenter study was performed to assess whether the results of pylorus-preserving pancreaticoduodenectomy (PPPD) equal those of the standard Whipple (SW) operation, especially with respect to duration of surgery, blood loss, hospital stay, delayed gastric emptying (DGE), and survival. SUMMARY BACKGROUND DATA: PPPD has been associated with a higher incidence of delayed gastric emptying, resulting in a prolonged period of postoperative nasogastric suctioning. Another criticism of the pylorus-preserving pancreaticoduodenectomy for patients with a malignancy is the radicalness of the resection. On the other hand, PPPD might be associated with a shorter operation time and less blood loss. METHODS: A prospective randomized multicenter study was performed in a nonselected series of 170 consecutive patients. All patients with suspicion of pancreatic or periampullary tumor were included and randomized for a SW or a PPPD resection. Data concerning patients' demographics, intraoperative and histologic findings, as well as postoperative mortality, morbidity, and follow-up up to 115 months after discharge, were analyzed. RESULTS: There were no significant differences noted in age, sex distribution, tumor localization, and staging. There were no differences in median blood loss and duration of operation between the 2 techniques. DGE was observed equally in the 2 groups. There was only a marginal difference in postoperative weight loss in favor of the standard Whipple procedure. Overall operative mortality was 5.3%. Tumor positive resection margins were found for 12 patients of the SW group and 19 patients of the PPPD group (P < 0.23). Long-term follow-up showed no significant statistical differences in survival between the 2 groups (P < 0.90). CONCLUSIONS: The SW and PPPD operations were associated with comparable operation time, blood loss, hospital stay, mortality, morbidity, and incidence of DGE. The overall long-term and disease-free survival was comparable in both groups. Both surgical procedures are equally effective for the treatment of pancreatic and periampullary carcinoma.

A randomised study on the efficacy and safety of an automated Tru-Cut needle for percutaneous liver biopsy (Article)

2004-01-01T00:00:00Z

BACKGROUND: We studied whether the theoretical advantages of a spring-loaded liver biopsy needle exist in clinical practice and if so if they are dependent upon the experience of the physician performing the biopsy. METHODS: In a stratified randomised study we enrolled 215 consecutive patients to compare the safety and efficacy of a new automatic biopsy gun (Acecut) with that of a standard Tru-Cut needle. RESULTS: A total of 464 biopsies were performed. The endpoints of the study were number of needle passes needed per patient, tissue yield of each needle pass and post-biopsy complications. The performance of the automatic needle was superior and more consistent with respect to tissue yield compared with the Tru-Cut needle (median yield 100% and 80%, respectively; p < 0.001). The difference was most marked for inexperienced physicians. There was no difference between the two needles in the number of passes needed. More post-biopsy pain and post-biopsy use of analgesics were observed in the automatic needle group (p = 0.04). CONCLUSION: The automatic Tru-Cut needle offers an advantage, particularly for physicians with no or limited experience in liver biopsies. However more post-biopsy pain and post-biopsy use of analgesics were observed in the automatic needle group.

Effect of dexamethasone treatment on serum GH, IGF-I, and the binding proteins IGFBP-1 and -3 in ventilated very preterm infants. (Article)

2003-07-01T00:00:00Z

Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator. The aim of this study was to evaluate the short-term effect of dexamethasone (DEXA) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia. We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [median (range) gestational age 27.5 wk (25.9-32.0 wk), median (range) birth weight 970 g (610-2150 g)] immediately before and 2 d after the start of DEXA treatment. On both days of study, serum GH profiles were obtained, and serum IGF-I and IGF binding protein (IGFBP) -1 and -3 levels were measured. The ventilation score and the nutritional intake were calculated. Before the start of DEXA treatment, the median serum mean GH level was 12.0 microg/L (6-28.4 microg/L), whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 microg/L (1.7-11.9 microg/L). During DEXA treatment, mean, baseline, and maximal GH levels (Pulsar analysis) were significantly lower compared with pretreatment levels (p < 0.01, p < 0.01, and p < 0.05, respectively). Serum IGF-I and IGFBP-3 levels did not decline during DEXA. Serum IGFBP-1 levels were significantly lower compared with pretreatment levels (p < 0.01). Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered. Ventilation score and nutritional intake did not significantly correlate with serum GH, IGF-I, or IGFBP-1 or -3 levels, either before or after the start of DEXA. Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels, without an acute decline in serum IGF-I levels. A concomitant decrease in serum IGFBP-1 levels was found.

Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants (Article)

2003-01-01T00:00:00Z

BACKGROUND: To investigate clinical variables such as gestational age, sex, weight, the therapeutic regimens used and mechanical ventilation that might affect morphine requirements and plasma concentrations of morphine and its metabolites. METHODS: In a double-blind study, neonates and infants stratified for age [group I 0-4 weeks (neonates), group II > or =4-26 weeks, group III > or =26-52 weeks, group IV > or =1-3 yr] admitted to the paediatric intensive care unit after abdominal or thoracic surgery received morphine 100 micro g kg(-1) after surgery, and were randomly assigned to either continuous morphine 10 micro g kg(-1) h(-1) or intermittent morphine boluses 30 micro g kg(-1) every 3 h. Pain was measured using the COMFORT behavioural scale and a visual analogue scale. Additional morphine was administered on guidance of the pain scores. Morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) plasma concentrations were measured before, directly after, and at 6, 12 and 24 h after surgery. RESULTS: Multiple regression analysis of different variables revealed that age was the most important factor affecting morphine requirements and plasma morphine concentrations. Significantly fewer neonates required additional morphine doses compared with all other age groups (P<0.001). Method of morphine administration (intermittent vs continuous) had no significant influence on morphine requirements. Neonates had significantly higher plasma concentrations of morphine, M3G and M6G (all P<0.001), and significantly lower M6G/morphine ratio (P<0.03) than the older children. The M6G/M3G ratio was similar in all age groups. CONCLUSIONS: Neonates have a narrower therapeutic window for postoperative morphine analgesia than older age groups, with no difference in the safety or effectiveness of intermittent doses compared with continuous infusions in any of these age groups. In infants >1 month of age, analgesia is achieved after morphine infusions ranging from 10.9 to 12.3 micro g kg(-1) h(-1) at plasma concentrations of <15 ng ml(-1).

Extra-fine particles improve lung delivery of inhaled steroids in infants: a study in an upper airway model (Article)

2003-01-01T00:00:00Z

BACKGROUND: The particles of a new hydrofluoroalkane-134a (HFA)-beclomethasone dipropionate (BDP) metered-dose inhaler (Qvar; 3M Pharmaceuticals; St. Paul, MN) are considerably smaller than those of chlorofluorocarbon (CFC)-BDP. This may improve lung deposition in infants who inhale nasally and have irregular breathing patterns and small airways. Aim: To compare the dose delivered to the lungs of HFA-BDP and CFC-BDP at different breathing patterns using an upper airway model of an infant. METHODS: An anatomically correct upper airway model of a 9-month-old child with an open nasal airway was connected to an impactor and breathing simulator. HFA-BDP, 100 microg, and CFC-BDP, 100 micro g, were delivered to the model through a detergent-coated, small-volume spacer. The total dose leaving the model (lung dose), its particle size distribution, and median mass aerodynamic diameter (MMAD) were assessed during simulated tidal breathing with tidal volumes (VTs) of 50 mL, 100 mL, and 200 mL, and 30 breaths/min. Dose was expressed as percentage of nominal dose. RESULTS: Lung doses for HFA-BDP were 25.4%, 26.5%, and 30.7% compared with 6.8%, 4.8%, and 2.1% for CFC-BDP at VTs of 50 mL, 100 mL, and 200 mL, respectively. The dose of particles < 2.1 microm to the lung for HFA-BDP was 23 to 28% compared with 0.6 to 0.8% for CFC-BDP. The lung dose of CFC-BDP mainly consisted of particles between 2.1 microm and 4.7 microm. MMAD for HFA-BDP was 1.2 microm, and 2.6 to 3.3 microm for CFC-BDP depending on VT. The lung dose for CFC-BDP decreased significantly with increasing VT. HFA-BDP lung dose did not alter significantly with VT. CONCLUSIONS: In this infant model study, the use of HFA-BDP with a high dose of particles < 2.1 microm improves the dose delivered to the lungs substantially. Furthermore, the large proportion of extra-fine particles in HFA-BDP results in lung doses less dependent on breathing pattern compared with CFC-BDP.

The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature (Article)

2003-01-01T00:00:00Z

OBJECTIVE: Infantile Pompe's disease is a lethal cardiac and muscular disorder. Current developments toward enzyme replacement therapy are promising. The aim of our study is to delineate the natural course of the disease to verify endpoints of clinical studies. METHODS: A total of 20 infantile patients diagnosed by the collaborative Dutch centers and 133 cases reported in literature were included in the study. Information on clinical history, physical examination, and diagnostic parameters was collected. RESULTS: The course of Pompe's disease is essentially the same in the Dutch and the general patient population. Symptoms start at a median age of 1.6 months in both groups. The median age of death is 7.7 and 6 months, respectively. Five percent of the Dutch patients and 8% of all reported patients survive beyond 1 year of age. Only 2 patients from literature became older than 18 months. A progressive cardiac hypertrophy is characteristic for infantile Pompe's disease. The diastolic thickness of the left ventricular posterior wall and cardiac weight at autopsy increase significantly with age. Motor development is severely delayed and major developmental milestones are generally not achieved. For the Dutch patient group, growth deviates significantly from normal despite start of nasogastric tube feeding. Levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, or creatine kinase-myocardial band isoenzyme are typically elevated, although aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase increase significantly with age. The patients have fully deleterious mutations. Acid alpha-glucosidase activity is severely deficient. CONCLUSIONS: Survival, decrease of the diastolic thickness of the left ventricular posterior wall, and achievement of major milestones are valid endpoints for therapeutic studies of infantile Pompe's disease. Mutation analysis and measurement of the alpha-glucosidase activity should be part of the enrollment program.

Self reported stressful life events and exacerbations in multiple sclerosis: prospective study (Article)

2003-01-01T00:00:00Z

OBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of department of neurology in the Netherlands. PARTICIPANTS: Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded. MAIN OUTCOME MEASURE: The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events. RESULTS: Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress. CONCLUSION: Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis.

Acutely altered hemodynamics following venous obstruction in the early chick embryo (Article)

2003-01-01T00:00:00Z

In the venous clip model specific cardiac malformations are induced in the chick embryo by obstructing the right lateral vitelline vein with a microclip. Clipping alters venous return and intracardiac laminar blood flow patterns, with secondary effects on the mechanical load of the embryonic myocardium. We investigated the instantaneous effects of clipping the right lateral vitelline vein on hemodynamics in the stage-17 chick embryo. 32 chick embryos HH 17 were subdivided into venous clipped (N=16) and matched control embryos (N=16). Dorsal aortic blood flow velocity was measured with a 20 MHz pulsed Doppler meter. A time series of eight successive measurements per embryo was made starting just before clipping and ending 5h after clipping. Heart rate, peak systolic velocity, time-averaged velocity, peak blood flow, mean blood flow, peak acceleration and stroke volume were determined. All hemodynamic parameters decreased acutely after venous clipping and only three out of seven parameters (heart rate, time-averaged velocity and mean blood flow) showed a recovery to baseline values during the 5h study period. We conclude that the experimental alteration of venous return has major acute effects on hemodynamics in the chick embryo. These effects may be responsible for the observed cardiac malformations after clipping.

Worsening of V'maxFRC in infants with chronic lung disease in the first year of life: a more favorable outcome after high-frequency oscillation ventilation. (Article)

2002-12-15T00:00:00Z

Little is known about the development of maximal flow at functional residual capacity, a measure of airway patency, in infants with chronic lung disease (CLD). In a follow-up study, we evaluated V'maxFRC in very low birth weight infants with CLD, treated with high-frequency oscillation ventilation (HFOV) or conventional mechanical ventilation. In 36 infants with CLD, V'maxFRC was evaluated at 6 and/or 12 months corrected age, and the relationship between perinatal factors and lung function was studied. Mean (SD) birth weight and gestational age were 837 (152) g and 26.8 (1.7) weeks, respectively. At 6 and 12 months, mean V'maxFRC was significantly below normal. Between 6 and 12 months, there was a mean (95% confidence interval) reduction in V'maxFRC (Z score) of 0.5 (0.2-0.7) (p < 0.001). At 12 months, the mean V'maxFRC (Z score) was higher for children initially treated with HFOV (n = 15), as compared with children treated with conventional mechanical ventilation (n = 16): mean (95% confidence interval) difference was 0.6 (0.2-1.0) (p = 0.008). We conclude that very low birth weight infants with CLD have decreased V'maxFRC that worsen during the first year of life. Initial treatment with HFOV was associated with a more favorable outcome of V'maxFRC at 12 months corrected age.

Migration of the femoral stem after impaction bone grafting (Article)

2002-08-01T00:00:00Z

We report the initial results of an ongoing randomised, prospective study on migration of the Exeter and Elite Plus femoral stems after impaction allografting, as measured by radiostereometry. Clinically, the impaction technique gave good results for both stems. The mean subsidence in the first year was 1.30 mm and 0.20 mm for the Exeter and the Elite Plus stems, respectively. In the second year, the Exeter stem continued to subside further by a mean of 0.42 mm, while the Elite Plus stem did not do so. Subsidence of the Exeter stem correlated with deficiency of bone stock as graded on the Gustilo and Pasternak scale. This correlation was not found for the Elite Plus stem. None of the other parameters which were studied predisposed to subsidence. There was no significant association between the amount of subsidence and the radiological appearance of the graft for either stem. Our findings do not support the theory that radial compression, due to subsidence of the Exeter stem, is the essential stimulus for remodelling in impaction allografting.

Occlusion of the pancreatic duct versus pancreaticojejunostomy: a prospective randomized trial. (Article)

2002-01-01T00:00:00Z

OBJECTIVE: Using a prospective randomized study to assess postoperative morbidity and pancreatic function after pancreaticoduodenectomy with pancreaticojejunostomy and duct occlusion without pancreaticojejunostomy. SUMMARY BACKGROUND DATA: Postoperative complications after pancreaticoduodenectomy are largely due to leakage of the pancreaticoenterostomy. Pancreatic duct occlusion without anastomosis of the pancreatic remnant may prevent these complications. METHODS: A prospective randomized study was performed in a nonselected series of 169 patients with suspected pancreatic and periampullary cancer. In 86 patients the pancreatic duct was occluded without anastomosis to pancreatic remnant, and in 83 patients a pancreaticojejunostomy was performed after pancreaticoduodenectomy. Postoperative complications were the endpoint of the study. All relevant data concerning patient demographics and postoperative morbidity and mortality as well as endocrine and exocrine function were analyzed. At 3 and 12 months after surgery, evaluation of weight loss, stools, and the use of antidiabetics and pancreatic enzyme was repeated. RESULTS: Patient characteristics were comparable in both groups. There were no differences in median blood loss, duration of operation, and hospital stay. No significant difference was noted in postoperative complications, mortality, and exocrine insufficiency. The incidence of diabetes mellitus was significantly higher in patients with duct occlusion. CONCLUSIONS: Duct occlusion without pancreaticojejunostomy does not reduce postoperative complications but significantly increases the risk of endocrine pancreatic insufficiency after duct occlusion.

Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL (Article)

2002-01-01T00:00:00Z

We performed sensitive polymerase chain reaction-based minimal residual disease (MRD) analyses on bone marrow samples at 9 follow-up time points in 71 children with T-lineage acute lymphoblastic leukemia (T-ALL) and compared the results with the precursor B-lineage ALL (B-ALL) results (n = 210) of our previous study. At the first 5 follow-up time points, the frequency of MRD-positive patients and the MRD levels were higher in T-ALL than in precursor-B-ALL, reflecting the more frequent occurrence of resistant disease in T-ALL. Subsequently, patients were classified according to their MRD level at time point 1 (TP1), taken at the end of induction treatment (5 weeks), and at TP2 just before the start of consolidation treatment (3 months). Patients were considered at low risk if TP1 and TP2 were MRD negative and at high risk if MRD levels at TP1 and TP2 were 10(-3) or higher; remaining patients were considered at intermediate risk. The relative distribution of patients with T-ALL (n = 43) over the MRD-based risk groups differed significantly from that of precursor B-ALL (n = 109). Twenty-three percent of patients with T-ALL and 46% of patients with precursor B-ALL were classified in the low-risk group (P =.01) and had a 5-year relapse-free survival (RFS) rate of 98% or greater. In contrast, 28% of patients with T-ALL were classified in the MRD-based high-risk group compared to only 11% of patients with precursor B-ALL (P =.02), and the RFS rates were 0% and 25%, respectively (P =.03). Not only was the distribution of patients with T-ALL different over the MRD-based risk groups, the prognostic value of MRD levels at TP1 and TP2 was higher in T-ALL (larger RFS gradient), and consistently higher RFS rates were found for MRD-negative T-ALL patients at the first 5 follow-up time points.

Fewer intraperitoneal adhesions with use of hyaluronic acid-carboxymethylcellulose membrane: a randomized clinical trial (Article)

2002-01-01T00:00:00Z

OBJECTIVE: To assess the effectiveness of bioresorbable Seprafilm membrane in preventing abdominal adhesions in a prospective clinical randomized multicenter trial. SUMMARY BACKGROUND DATA: Adhesions occur frequently after abdominal operations and are a common cause of bowel obstruction, chronic abdominal pain, and infertility. To reduce the formation of adhesions, a mechanical barrier composed of hyaluronic acid and carboxymethylcellulose was developed, preventing adherence of tissues after abdominal surgery. METHODS: Between April 1996 and September 1998, all patients requiring a Hartmann procedure for sigmoid diverticulitis or obstructed rectosigmoid were randomized to either intraperitoneal placement of the antiadhesions membrane under the midline during laparotomy and in the pelvis, or as a control. Direct visual evaluation of the incidence and severity of adhesions was performed laparoscopically at second-stage surgery for restoration of the continuity of the colon. RESULTS: A total of 71 patients were randomized; of these, 42 could be evaluated. The incidence of adhesions did not differ significantly between the two groups, but the severity of adhesions was significantly reduced in the Seprafilm group both for the midline incision and for the pelvic area. Complications occurred in similar numbers in both groups. CONCLUSIONS: Seprafilm antiadhesions membrane appears effective in reducing the severity of postoperative adhesions after major abdominal surgery, although the incidence of adhesions was not diminished. The authors recommend using Seprafilm when relaparotomy or second-look intervention is planned. Long-term studies are needed to assess the cost-effectiveness and value of Seprafilm in preventing bowel obstruction, chronic abdominal pain, and infertility.

Prospective study on the relationship between infections and multiple sclerosis exacerbations (Article)

2002-01-01T00:00:00Z

One of the characteristics of multiple sclerosis is the unpredictable occurrence of exacerbations and remissions. These fluctuations in disease activity are related to alterations in (auto-)immune activity. Exacerbations lead to short-term morbidity, but may also influence long-term disability. This longitudinal study in 73 patients with relapsing-remitting multiple sclerosis assessed the contribution of systemic infections to the natural course of exacerbations. In addition, we analysed whether infections lead to an increase in the number of gadolinium-enhancing lesions. A total of 167 infections and 145 exacerbations were observed during 6466 patient weeks. During a predefined at-risk period (ARP) of 2 weeks before until 5 weeks after the onset of a clinical infection (predominantly upper airway infections), there was an increased risk of exacerbations (rate ratio 2.1), which is in accordance with previous studies. Exacerbations with onset during the ARP led more frequently to sustained deficit [increase of > or =1 Expanded Disability Status Scale (EDSS) point or > or =0.5 above EDSS 5.5 for >3 months] than exacerbations with onset outside the ARP, with a rate ratio of 3.8. Minor and major exacerbations were equally distributed between the ARP and non-ARP onset groups. ARP exacerbations were associated with significantly higher plasma levels of the inflammatory marker soluble intracellular adhesion molecule 1 than non-ARP exacerbations, indicating relatively enhanced immune activation during ARP relapses. Three serial MRI scans were performed after the onset of an infection over a 6-week period. There was no difference in the number of gadolinium-enhancing lesions between the three time points. In conclusion, exacerbations in the context of a systemic infection lead to more sustained damage than other exacerbations. There is no indication that this effect occurs through enhanced opening of the blood-brain barrier.

Enhanced antifungal efficacy in experimental invasive pulmonary aspergillosis by combination of AmBisome with Fungizone as assessed by several parameters of antifungal response (Article)

2002-01-01T00:00:00Z

In common with a proportion of patients with invasive pulmonary aspergillosis (IPA), the efficacy of AmBisome treatment regimens in our rat model remains suboptimal. To investigate whether this might be the result of initially low antifungal activity of amphotericin B at the site of infection when administered in the liposomal form, Fungizone was added to AmBisome at the start of treatment. Groups of granulocytopenic rats with left-sided IPA received 10 day treatment regimens with either AmBisome 10 mg/kg/day (n = 25) or AmBisome 10 mg/kg/day combined with a single dose of Fungizone 1 mg/kg at day 1 (n = 27). Parameters of treatment response included survival, serum galactomannan (GM), size and quality of pulmonary macroscopic lesions, lung weight, viable fungal counts (cfu) and chitin content of the infected lung, and extra-pulmonary disseminated fungal infection. In a separate experiment the significance of early start of treatment to obtain therapeutic efficacy was investigated. Compared with untreated controls, both treatment regimens showed a significant increase in survival and change in parameters of fungal infection except left lung cfu. The combination treatment showed a significant increase in survival compared with AmBisome monotherapy (P = 0.02) and a significant decrease in left lung chitin content (P = 0.03). Differences in circulating GM concentrations between the two treatment regimes approached significance (P = 0.06). Delay in the start of treatment from 16 to 24 h after fungal inoculation resulted in a significant decrease in therapeutic efficacy (P = 0.02). It is concluded that the efficacy of AmBisome therapy can be enhanced by the addition of Fungizone at the start of treatment. This is probably a result of active amphotericin B being immediately available in the lung at the start of treatment.

Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors (Article)

2002-01-01T00:00:00Z

Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. The median age was 22 months (range, 4-185 months). Eight patients died. Nonsurvivors had extremely high GH levels that were significant different compared with mean GH levels in survivors during a 6-h GH profile (131 vs. 7 mU/liter; P < 0.01). Significant differences were found between nonsurvivors and survivors for the levels of total IGF-I (2.6 vs. 5.6 nmol/liter), free IGF-I (0.003 vs. 0.012 nmol/liter), IGFBP-1 (44.3 vs. 8.9 nmol/liter), IGFBP-3 protease activity (61 vs. 32%), IL-6 (1200 vs. 50 ng/ml), and TNFalpha (34 vs. 5.3 pg/ml; P < 0.01). The pediatric risk of mortality score correlated significantly with levels of IGFBP-1, IGFBP-3 protease activity, IL-6, and TNFalpha (r = +0.45 to +0.69) and with levels of total IGF-I and free IGF-I (r = -0.44 and -0.55, respectively). Follow-up after 48 h in survivors showed an increased number of GH peaks, increased free IGF-I and IGFBP-3 levels, and lower IGFBP-1 levels compared with admission values. GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the cytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.

Pulmonary arterial wall distensibility assessed by intravascular ultrasound in children with congenital heart disease: an indicator for pulmonary vascular disease? (Article)

2002-01-01T00:00:00Z

BACKGROUND: Both pulmonary hypertension and pulmonary overflow are associated with functional and structural changes of the pulmonary arterial wall. Current techniques to evaluate the pulmonary vasculature neglect the pulsatile nature of pulmonary flow. STUDY OBJECTIVES: To determine whether the dynamic properties of the pulmonary arterial wall are altered in patients with abnormal pulmonary hemodynamics due to congenital heart defects, and whether these changes are associated with the progression of pulmonary vascular disease (PVD). PATIENTS AND METHODS: In 43 children with PVD due to congenital heart defects and 12 control subjects, pulmonary arterial pulsatility (the relative increase in vessel area during the cardiac cycle) and distensibility (the inverse of the stress/strain elastic modulus) were determined with intravascular ultrasound. Results were correlated with clinical and hemodynamic parameters. RESULTS: Pulsatility correlated with pulmonary pulse pressure (p < 0.001), pulmonary-to-systemic vascular resistance ratio (PVR/SVR) [p = 0.001], and hemoglobin concentration (p = 0.01). However, when corrected for these variables, pulsatility did not differ between patients and control subjects. In contrast, arterial wall distensibility decreased with the severity of PVD and correlated independently with pulmonary-to-systemic arterial pressure ratio (p < 0.001) and PVR/SVR (p = 0.03), and with hemoglobin concentration (p < 0.01). Adjusted for hemodynamic variables, distensibility was still decreased in patients with PVD compared to control subjects. CONCLUSIONS: These results demonstrate that pulmonary arterial wall distensibility is progressively decreased in PVD; moreover, this decreased distensibility is, in part, related to increased distending pressure as a result of pulmonary hypertension but also, in part, to stiffening of the arterial wall during the disease process. Arterial wall distensibility may be of additional value in the evaluation of pulmonary vasculature and ventricular workload.

Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies : early cancers may contain aggressive genetic features (Article)

2001-01-01T00:00:00Z

No objective parameters have been found so far that can predict the biological behavior of early stages of prostatic cancer, which are encountered frequently nowadays due to surveillance and screening programs. We have applied comparative genomic hybridization to routinely processed, paraffin-embedded radical prostatectomy specimens derived from patients who participated in the European Randomized Study of Screening for Prostate Cancer. We defined a panel consisting of 36 early cancer specimens: 13 small (total tumor volume (Tv) < 0.5 ml) carcinomas and 23 intermediate (Tv between 0.5-1.0 ml) tumors. These samples were compared with a set of 16 locally advanced, large (Tv > 2.0 ml) tumor samples, not derived from the European Randomized Study of Screening for Prostate Cancer. Chromosome arms that frequently (ie, > or = 15%) showed loss in the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas frequent (ie, > or = 15%) gain was seen of 20q (15%). In the intermediate cancers, loss was detected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q, and 18q (both 17%). No consistent gains were found in this group. In the large tumors, loss was seen of 13q (69%), 8p (50%), 5q, 6q (both 31%), and Y (15%). Gains were observed of 8q (37%), 3q (25%), 7p, 7q, 9q, and Xq (all 19%). Comparison of these early, localized tumors with large adenocarcinomas showed a significant increase in the number of aberrant chromosomes per case (Rs = 0.36, P = 0.009). The same was true for the number of lost or gained chromosomes per case (Rs = 0.27, P: = 0.05; Rs = 0.48, respectively; P < 0.001). Interestingly, chromosomal alterations that were found in previous studies to be potential biomarkers for tumor aggressiveness, ie, gain of 7pq and/or 8q, were already distinguished in the small and intermediate cancers. In conclusion, our data show that chromosomal losses, more specifically of 6q and 13q, are early events in prostatic tumorigenesis, whereas chromosomal gains, especially of 8q, appear to be late events in prostatic tumor development. Finally, early localized tumors, as detected by screening programs, harbor cancers with aggressive genetic characteristics.

Controlled low flow off line sampling of exhaled nitric oxide in children (Article)

2001-01-01T00:00:00Z

BACKGROUND: The aim of this study was to validate exhaled nitric oxide (eNO) values obtained with an alternative off line, single breath, low flow balloon sampling method against on line sampling according to ERS and ATS guidelines in children who could perform both methods. METHODS: One hundred and twenty seven white children of median age 14.1 years, all pupils of a secondary school, participated in the study. They performed the two different sampling techniques at three different flows of 50, 100, 150 ml/s. Additional measurements were done in random subgroups to determine the influence of the dead space air on eNO values obtained off line by excluding the first 220 ml of exhaled air. All children completed a questionnaire on respiratory and allergic disorders and underwent spirometric tests. RESULTS: The off line eNO values were significantly higher than the on line values at all flows. At 50 ml/s the geometric mean (SE) off line eNO was 18.7 (1.1) ppb and the on line eNO was 15.1 (1.1) ppb (p<0.0001). However, when dead space air was discarded, off line and on line values were similar: at 50 ml/s off line eNO was 17.7 (1.0) ppb and on line eNO 16.0 (1.2) ppb. There was a good agreement between off line eNO values without dead space air and on line eNO: for 50 ml/s the mean on/off line ratio was 0.95 (95% agreement limits 0.63 to 1.27). The off line eNO level at 50 ml/s in 80 children with negative questionnaires for asthma, rhinitis, and eczema was 13.6 (1.0) ppb compared with 33.3 (1.1) ppb in the remaining children with positive questionnaires on asthma and allergy and/or recent symptoms of cold (p<0.0001). CONCLUSIONS: In children, off line assessment of eNO using constant low flow sampling and excluding dead space air is feasible and produces similar results as on line assessment with the same exhalation flow rate. Both sampling methods are sufficiently sensitive to differentiate between groups of otherwise healthy school children with and without self-reported asthma, allergy, and/or colds. We propose that, for off line sampling, similar low flow rates should be used as are recommended for on line measurements.

Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections (Article)

2001-01-01T00:00:00Z

To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy.

Genomic alterations in malignant transformation of Barrett's esophagus (Article)

2001-01-01T00:00:00Z

The incidence of adenocarcinoma in Barrett's esophagus has been increasing rapidly over the past decades. Neoplastic progression is characterized by three well-defined premalignant stages: metaplasia, low-grade dysplasia, and high-grade dysplasia. A genome-wide overview, based on comparative genomic hybridization, was performed, evaluating 30 Barrett's adenocarcinomas and 25 adjacent precursors, i.e., 6 metaplasias, 9 low-grade dysplasias, and 10 high-grade dysplasias. The frequency of losses and gains significantly increased in the subsequent stages of malignant transformation. Losses of 5q21-q23, 9p21, 17p12-13.1, 18q21, and Y were revealed in low-grade dysplasias. This was followed by loss of 7q33-q35 and gains of 7p12-p15, 7q21-q22, and 17q21 in high-grade dysplasias along with high-level amplification (HLA) of 7q21 and 17q21. In the invasive cancers, additional losses of 3p14-p21, 4p, 4q, 8p21, 13q14-q31, 14q24.3-q31, 16q21-q22, and 22q as well as gains of 3q25-q27, 8q23-24.1, 12p11.2-12, 15q22-q24, and 20q11.2-q13.1 were distinguished along with HLAs of 8p12-p22 and 20q11.2-q13.1. Approximately one-third of the alterations in the dysplasias were also found in the adjacent adenocarcinomas, illustrating that multiple clonal lineages can be present in Barrett's esophagus. Novel findings include loss on 7q, gain on 12p, and the observation of several HLAs in high-grade dysplasias. Furthermore, loss of 7q33-q35 was found to represent a significant distinction between low-grade and high-grade dysplasia (P = 0.01), whereas loss of 16q21-q22 and gain of 20q11.2-q13.1 were disclosed to significantly discriminate between high-grade dysplasia and adenocarcinoma (P = 0.02 and P = 0.03, respectively). This inventory of genetic aberrations increases our understanding of malignant transformation in Barrett's esophagus and might provide useful biomarkers for disease progression.

Interrupter resistance in preschool children: measurement characteristics and reference values (Article)

2001-01-01T00:00:00Z

There is a need for quick, reliable, and noninvasive lung function tests to assess airway obstruction in preschool children both for pediatric pulmonary care as well as for research purposes. We studied feasibility, reproducibility, and validity of measurements of the respiratory system using the interrupter technique (interrupter resistance [Rint]) and obtained reference values in children from a general population, 2 to 7 yr of age. Accuracy was studied by comparisons of Rint with plethysmographic airway resistance (Raw) in 20 patients (7 to 14 yr) with mild to severe chronic airways obstruction and was satisfactory in patients with FEV(1) > 60% predicted. The technique proved sensitive enough to detect changes in airway caliber within a small group of 12 children who developed mild respiratory tract infections. Among children from a general population, subgroups with mild respiratory symptoms or mild respiratory disease had higher mean Rint values. Airway obstruction was better detected using expiratory rather than inspiratory interruptions, both programmed at peak tidal ventilatory flow. Reproducibility within subjects was satisfactory (intraclass correlation 0.82 and 0.79). The same applied to interobserver agreement (intraclass correlation 0.98). The interrupter technique proves to be a reliable and practical test of airway function, suitable for clinical and epidemiologic studies in preschool children.

Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant (Article)

2001-01-01T00:00:00Z

The clinical and pathological findings of four females with primary biliary cirrhosis (PBC) with an unusual and hitherto not well recognised course are reported. Patients suffered severe pruritus and weight loss with progressive icteric cholestasis which did not respond to such treatments as ursodeoxycholic acid and immunosuppressives. In all cases liver histology revealed marked bile duct loss without however significant fibrosis or cirrhosis. Further diagnostic studies and repeat biopsies confirmed the absence of liver cirrhosis as well as other potential causes of hyperbilirubinaemia. Comparison of the fibrosis-ductopenia relationship for our cases with that for a group of 101 non-cirrhotic PBC patients indicated that in the former the severity of bile duct loss relative to the amount of fibrosis was significantly higher. The proportion of portal triads containing an interlobular bile duct was 3%, 4%, 6%, and 10% compared with 45% (median; range 8.3--100%) for controls (p<0.001). Three patients received a liver transplant 6--7 years after the first manifestation of PBC because of progressive cholestasis, refractory pruritus, and weight loss, while the fourth patient is considering this option. In one case cirrhosis had developed at the time of transplantation while the others still had non-cirrhotic disease. These cases suggest that cholestatic jaundice in non-cirrhotic PBC may be secondary to extensive "premature" or accelerated intrahepatic bile duct loss. Although the extent of fibrosis may be limited initially, progression to cirrhosis appears to be inevitable in the long run. Despite intact protein synthesis and absence of cirrhotic complications, liver transplantation in the pre-cirrhotic stage for preventing malnutrition and to improve quality of life should be considered for these patients.

Off-line sampling of exhaled air for nitric oxide measurement in children: methodological aspects (Article)

2001-01-01T00:00:00Z

Measurement of nitric oxide in exhaled air is a noninvasive method to assess airway inflammation in asthma. This study was undertaken to establish the reference range of exhaled NO in healthy school-aged children and to determine the influence of ambient NO, noseclip and breath-holding on exhaled NO, using an off-line balloon sampling method. All children attending a primary school (age range 8-13 yrs) underwent NO measurements on two occasions with high and low ambient NO. Each time, the children performed four expiratory manoeuvres into NO-impermeable balloons, with and without 10 s of breath-holding and with and without wearing a noseclip. Exhalation flow and pressure were not controlled. NO was measured within 4 h after collection, by means of chemiluminescence. All children completed a questionnaire on respiratory and allergic disorders, and performed flow/volume spirometry. With low ambient NO, the mean exhaled NO value of 72 healthy children with negative questionnaires and normal lung function was 5.1 +/- 0.2 parts per billion (ppb) versus a mean of 6.8 +/- 0.3 ppb in the remaining 49 children with positive questionnaires for asthma and allergy, and/or recent symptoms of cold (p=0.001). Exhaled and ambient NO were significantly related, especially with ambient NO > 10 ppb (r = 0.86, p=0.0001 versus r=0.34, p=0.004 for ambient values <10 ppb). The use of a noseclip, with low ambient NO and without breath-holding, caused a small decrease in exhaled NO values (p=0.001). The effect of breath-holding on exhaled NO depended on ambient NO. With ambient NO > 10 ppb, exhaled NO decreased, whereas with ambient NO < 10 ppb, exhaled NO increased after 10 s breath-hold. It is concluded that off-line sampling in balloons is a simple and, hence, attractive method for exhaled nitric oxide measurements in children which differentiates between groups with and without self-reported asthma, allergy and colds, when ambient nitric oxide is < 10 parts per billion. Wearing a noseclip and breath-holding affected measured values and should, therefore be standardized or, preferably, avoided.

Hormonal and metabolic stress responses after major surgery in children aged 0-3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphine (Article)

2001-01-01T00:00:00Z

Children aged 0-3 yr were stratified for age and randomized to receive either continuous morphine (CM, 10 microg x kg(-1) x h(-1)) with three-hourly placebo boluses or intermittent morphine (IM, 30 microg x kg(-1) every 3 h) with a placebo infusion for postoperative analgesia. Plasma concentrations of epinephrine, norepinephrine, insulin, glucose and lactate were measured before and at the end of surgery and 6, 12 and 24 h after surgery. Pain was assessed with validated pain scales [the COMFORT scale and a visual analogue scale (VAS)] with the availability of additional morphine doses. Minor differences occurred between the randomized treatment groups, the oldest IM group (aged 1-3 yr) having a higher blood glucose concentration (P=0.003), mean arterial pressure (P=0.02) and COMFORT score (P=0.02) than the CM group. In the neonates, preoperative plasma concentrations of norepinephrine (P=0.01) and lactate (P<0.001) were significantly higher, while the postoperative plasma concentrations of epinephrine were significantly lower (P<0.001) and plasma concentrations of insulin significantly higher (P<0.005) than in the older age groups. Postoperative pain scores (P<0.003) and morphine consumption (P<0.001) were significantly lower in the neonates than in the older age groups. Our results show that continuous infusion of morphine does not provide any major advantages over intermittent morphine boluses for postoperative analgesia in neonates and infants.

Longitudinal survey of lymphocyte subpopulations in the first year of life (Article)

2000-01-01T00:00:00Z

Age-matched reference values for lymphocyte subpopulations are generally obtained via cross-sectional studies, whereas patients are followed longitudinally. We performed a detailed longitudinal analysis of the changes in lymphocyte subpopulations in a group of 11 healthy infants followed from birth up to 1 y of age, with special attention for early developmental markers, markers of maturation, and markers of activation. We found that T and B lymphocytes increased at 1 and 6 wk of age, respectively. In contrast, NK cells showed a sharp decline directly after birth, suggesting that they are more important during pregnancy than thereafter. CD45RA+--mainly CD4+--naive T lymphocytes were high at birth, and increased further during the first year of life; they form a large expanding pool of cells, ready for participation in primary immune responses. The absolute counts of CD45RO+ memory T lymphocytes were similar in infants and adults, albeit with a lower level of expression of CD45RO on infant T lymphocytes. Almost all infant T lymphocytes expressed CD38 throughout the first year of life. The abundant expression of CD38 on an infant's T lymphocytes might be related to a greater metabolic need of the large population of naive untriggered cells that are continually involved in primary immune responses during the first year of life. The high B lymphocyte counts in infants mainly concerned CD38+ B lymphocytes throughout the first year of life. Also, the relative frequencies of CD1c+ and CD5+ B lymphocytes were higher throughout the first year of life than in adults. Therefore, CD1c, CD5, and CD38 could be markers of untriggered B lymphocytes. In conclusion, our longitudinal survey of T and B lymphocytes, NK cells, and their subpopulations during the first year of life helps to complete the picture of lymphocyte development in infants. This information contributes to the correct interpretation of data from infants with possible immune disorders.

Cartilaginous airway wall dimensions and airway resistance in cystic fibrosis lungs (Article)

2000-01-01T00:00:00Z

It is not clear how airway pathology relates to the severity of airflow obstruction and increased bronchial responsiveness in cystic fibrosis (CF) patients. The aim of this study was to measure the airway dimensions of CF patients and to estimate the importance of these dimensions to airway resistance using a computational model. Airway dimensions were measured in lungs obtained from CF patients who had undergone lung transplantation (n=12), lobectomy (n=1), or autopsy (n=4). These dimensions were compared to those of airways from lobectomy specimens from 72 patients with various degrees of chronic obstructive pulmonary disease (COPD). The airway dimensions of the CF and COPD patients were introduced into a computational model to study their effect on airway resistance. The inner wall and smooth muscle areas of peripheral CF airways were increased 3.3- and 4.3-fold respectively compared to those of COPD airways. The epithelium was 53% greater in height in peripheral CF airways. The sensitivity and maximal plateau resistance of the computed dose/response curves were substantially increased in the CF patients compared to COPD patients. The changes in airway dimensions of cystic fibrosis patients probably contribute to the severe airflow obstruction, and to increased bronchial responsiveness, in these patients.

The effect in premature infants of prenatal corticosteroids on endogenous surfactant synthesis as measured with stable isotopes (Article)

2000-01-01T00:00:00Z

Most in vitro studies show that prenatal administration of corticosteroids stimulates the synthesis of surfactant phosphatidylcholine (PC), but studies in animals are controversial. Whether prenatal corticosteroids stimulate surfactant PC synthesis in humans has not been studied. We studied endogenous surfactant PC synthesis in relation to prenatal corticosteroid treatment in 27 preterm infants with respiratory distress syndrome. Infants received a 24-h infusion of the stable isotope [U-(13)C]glucose, starting approximately 5 h after birth. We measured (13)C-incorporation into palmitic acid in surfactant PC from serial tracheal aspirates and in plasma triglycerides and phospholipids by isotope-ratio mass spectrometry. Premature infants had received either zero (n = 11), one (n = 4), or two doses (n = 12) of prenatal betamethasone (12 mg intramuscularly). The fractional synthesis rate (FSR) of surfactant PC from glucose was 1.7 +/- 0.3%/d without corticosteroid treatment, 2.9 +/- 1.4%/d with one dose of prenatal corticosteroid, and 5.8 +/- 1.3%/d after two doses of prenatal corticosteroid. Using multiple regression analysis, we found that the FSR of surfactant PC increased by 40% (confidence interval: 7 to 82%/d, p < 0.02) per dose of corticosteroid and doubled after two doses of corticosteroid. The (13)C-enrichment of plasma triglycerides and phospholipids was not increased by corticosteroid. These data show for the first time that prenatal corticosteroid treatment stimulates surfactant synthesis in the preterm infant.

Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors (Article)

2000-01-01T00:00:00Z

To get insight in the endocrine and metabolic responses in children with meningococcal sepsis 26 children were studied the first 48 h after admission. On admission there was a significant difference in cortisol/ACTH levels between nonsurvivors (n = 8) and survivors (n = 18). Nonsurvivors showed an inadequate cortisol stress response in combination to very high ACTH levels, whereas survivors showed a normal stress response with significantly higher cortisol levels (0.62 vs. 0.89 micromol/L) in combination with moderately increased ACTH levels (1234 vs. 231 ng/L). Furthermore, there was a significant difference between nonsurvivors and survivors regarding pediatric risk of mortality score (31 vs. 17), TSH (0.97 vs. 0.29 mE/L), T3 (0.53 vs. 0.38 nmol/L), reverse T3 (rT3) (0.75 vs. 1.44 nmol/L), C-reactive protein (34 vs. 78 mg/L), nonesterified fatty acids (0.32 vs. 0.95 mmol/L), and lactate (7.3 vs. 3.2 mmol/L). In those who survived, the most important changes within 48 h were seen in a normalization of cortisol and ACTH levels, but without a circadian rhythm; a decrease of rT3 and an increase in the T3/rT3 ratio; and a decrease in the levels of the nonesterified free fatty acids and an unaltered high urinary nitrogen excretion. At this moment, it is yet unknown whether the hormonal abnormalities are determining factors in the outcome of acute meningococcal sepsis or merely represent secondary effects. Understanding the metabolic and endocrine alterations is required to design possible therapeutic approaches. The striking difference between nonsurvivors and survivors calls for reconsideration of corticosteroid treatment in children with meningococcal sepsis.

Aerosol delivery from spacers in wheezy infants: a daily life study (Article)

2000-01-01T00:00:00Z

The aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized crossover study in 25 wheezy infants aged 5-26 months, a metal spacer (Nebuchamber), a detergent coated (DC) and a non-detergent coated (nonDC) plastic spacer (Babyhaler) were tested at home for 7 days each. Budesonide (200 microg b.i.d) was administered via a Nebuchamber or fluticasone (125 microg b.i.d) via a Babyhaler. Aerosol was trapped in filters, positioned between the spacer and face mask. Cooperation was scored on diary cards. Electrostatic charge (ESC) of the spacers was measured. Evaluations of the administration technique were made from video recordings. Median (range) dose delivery of the filters expressed as per cent (%) of nominal dose, was 34% (3-59), 23% (1-49), and 41% (12-55) for the Nebuchamber, nonDC-Babyhaler, and DC-Babyhaler respectively. Considerable dose variability was found, median (range) within-subject dose variability, expressed as coefficient of variation, for the Nebuchamber (49% (15-249)) was significantly higher when compared with both nonDC- (36% (12-325)) and DC-Babyhalers (27% (10-122)), for which dose variabilities were similar. Detergent coating was effective to reduce electrostatic charge, and to increase dose delivery, but had no effect on dose variability. Bad cooperation was an important cause for high dose variability for all spacers (r=0.5-0.6, p<0.02). Many mistakes were made during the administration procedure.

Clinical and virologic response to combination treatment with indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 infection: A multicenter study in The Netherlands. (Article)

2000-01-01T00:00:00Z

Abstract OBJECTIVE: To evaluate the clinical, immunologic, and virologic response to indinavir, zidovudine, and lamivudine in children with human immunodeficiency virus-1 (HIV-1) infection. STUDY DESIGN: Twenty-eight HIV-1-infected children (3 months to 16 years of age) with or without prior treatment with reverse-transcriptase inhibitors and a HIV-1 RNA >5000 copies/mL and/or a CD4 cell count less than the lower limit of the age-specific reference value were treated with indinavir, zidovudine, and lamivudine. Pharmacokinetics of indinavir were determined in each child. RESULTS: The combination treatment was well tolerated in the majority of patients. Clinical improvement was seen in all patients. After 6 months of therapy, 70% of the patients had an HIV-1 RNA load below 500 copies/mL, whereas 48% of the children had a viral load below 40 copies/mL. Relative CD4 cell counts in relation to the lower limit of the age-specific reference value increased significantly from a median value of 79% at baseline to 106% after 6 months of therapy. The doses of indinavir necessary to achieve area under the curve values comparable to adult values varied from 1250 mg/m(2)/d to 2450 mg/m(2)/d. CONCLUSIONS: Highly active antiretroviral therapy consisting of indinavir, zidovudine, and lamivudine in children reduced HIV-1 RNA to less than 500 copies/mL in 70% of the children within 6 months. Improved CD4 cell counts were observed in most patients, as was a better clinical condition (no invasive or opportunistic infections, increased weight gain). Side effects of the triple therapy were mild. Highly active antiretroviral therapy can be used as successfully in children as in adults.

Anesthesia for endobronchial laser surgery: a modified technique (Article)

1999-01-01T00:00:00Z

We describe a technique for endobronchial surgery with the neodynium:yttium-aluminum-garnet laser, in which an insufflation catheter with side holes placed into the contralateral mainstem bronchus is used for high-frequency positive pressure ventilation. Thirty-five patients (45 procedures) were treated during general anesthesia using a rigid bronchoscope in combination with a fiberoptic bronchoscope. Perioperatively, oxygen saturation (SaO2), mean arterial pressure, and heart rate were recorded. SaO2 during the recovery period was comparable to that during the intraoperative period but was significantly (P < 0.05) higher than that before the induction of anesthesia. There was a considerable (> or = 5%) increase in SaO2 at the end of the treatment in six patients, which indicates that the recanalization of the treated airway was successful. Our data support the assumption that, during endobronchial resection, selective ventilation of the nonaffected lung was adequate; in addition, subcarinal placement of the insufflation catheter with side holes was advantageous. We conclude that this technique contributes to the prevention of lung complications during endobronchial laser surgery. Implications: We describe a technique in which an insufflation catheter with side holes placed into the contralateral mainstem bronchus largely prevented inhalation of laser smoke and aspiration of blood and debris.

Variability of aerosol delivery via spacer devices in young asthmatic children in daily life (Article)

1999-01-01T00:00:00Z

Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1-4 (group I, n=17) and 5-8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler in group I and Volumatic in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 microg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean+/-SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV). Mean filter dose in group I was 41.7+/-10.1% for Nebuchamber and 26.0+/-4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2+/-9.2% for Nebuchamber and 19.4+/-7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003). There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5-8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age.

Compliance, hysteresis, and collapsibility of human small airways (Article)

1999-01-01T00:00:00Z

We tested the hypothesis that airway wall dimensions are important determinants for the mechanical properties of airways. Lung tissue was obtained from 31 smokers with different degrees of chronic obstructive pulmonary disease (COPD) who were operated on for a solitary lung lesion. Segments of small airways (n = 35) were mounted on cannulas in an organ bath and inflated and deflated cyclically between +15 and -15 cm H(2)O. For each airway this was done at baseline, after methacholine, and after isoprenaline. Specific compliance (sCdyn), specific hysteresis (seta), and pressure at which the airways collapsed (Pcol) were calculated from each recording. Airway wall dimensions were measured morphometrically. Lung function parameters of airflow obstruction were correlated to sCdyn, seta, and Pcol. At baseline, after methacholine, and after isoprenaline sCdyn was 0.059, 0.052, and 0. 085 cm H(2)O(-)(1), seta was 13.5, 12.9, and 7.1%, and Pcol was -3.4, -3.5, and -1.9 cm H(2)O, respectively. Differences between sCdyn, seta, and Pcol after methacholine and after isoprenaline were highly significant (p < 0.001). Of all dimensions studied, smooth muscle area, but not total wall area, was the most important determinant for sCdyn and for seta after methacholine. Specific hysteresis at baseline correlated to residual volume as a fraction of total lung capacity (RV/TLC) (r = 0.5, p = 0.05) and, in the presence of methacholine, to FEV(1)/FVC (r = -0.68, p = 0.02) and RV/TLC (r = 0. 5, p = 0.05). We conclude that, in this study, smooth muscle area and smooth muscle tone, but not total wall area, are determinants for compliance, hysteresis, and collapsibility of isolated airways obtained from smokers.

Flow-dependency of exhaled nitric oxide in children with asthma and cystic fibrosis (Article)

1999-01-01T00:00:00Z

The concentration of nitric oxide in exhaled air, a marker of airway inflammation, depends critically on the flow of exhalation. Therefore, the aim of this study was to determine the effect of varying the flow on end-expiratory NO concentration and NO output in children with asthma or cystic fibrosis (CF) and in healthy children. Nineteen children with stable asthma, 10 with CF, and 20 healthy children exhaled from TLC while controlling expiratory flow by means of a biofeedback signal at approximately 2, 5, 10 and 20% of their vital capacity per second. NO was measured in exhaled air with a chemiluminescence analyser. Comparisons between the three groups were made by analysing the NO concentration at the endexpiratory plateau and by calculating NO output at different flows. Exhaled NO decreased with increasing flow in all children. Children with asthma had significantly higher NO concentrations than healthy children, but only at the lowest flows. Asthmatics using inhaled steroids (n=13) tended to have lower median exhaled NO than those without steroids. The slope of linearized (log-log transformed) NO/flow plots was significantly steeper in asthmatics than in healthy controls. CF patients had a significantly lower NO concentration and output over the entire flow range studied, compared to asthmatic and control subjects, with a similar NO/flow slope as control subjects. In conclusion, the nitric oxide concentration in exhaled air is highly flow-dependent, and the nitric oxide-flow relationship differs between asthmatics versus cystic fibrosis patients and control subjects. Assessment of the nitric oxide/flow relationship may help in separating asthmatics from normal children.

The follicle-stimulating hormone (FSH) threshold/window concept examined by different interventions with exogenous FSH during the follicular phase of the normal menstrual cycle: duration, rather than magnitude, of FSH increase affects follicle development (Article)

1998-01-01T00:00:00Z

According to the threshold concept, FSH concentrations need to surpass a distinct level to stimulate ovarian follicle growth. The window concept stresses the significance of a limited duration of elevated FSH levels above the threshold for single dominant follicle selection. The aim of this study was to investigate effects on follicle growth of increased FSH levels, differing in duration and magnitude of elevation, during the follicular phase. Twenty-three normo-ovulatory (cycle length, 26-31 days), young (age, 20-31 yr) women volunteered for this study. In all subjects a series of daily transvaginal sonography scans of the ovaries and blood sampling [for FSH and estradiol (E2) determinations] were performed during two consecutive cycles. The first study cycle (control cycle) started 10 days after urinary assessment of the LH surge in the preceding cycle (DayLH) and was concluded on the day of ovulation assessed by transvaginal sonography scans. The second series of daily monitoring (intervention cycle) started 10 days after DayLH in the control cycle. After randomization, subjects received either 375 IU urinary FSH, s.c., as a single injection on Day(LH+14) (group A; n = 11) or 75 IU daily from Day(LH+19) until Day(LH+23) (group B; n = 12). In group A, FSH levels increased on the day after injection to a median concentration of 10.1 IU/L, which was 1.9 times higher (P < 0.01) than levels on matching days during the control cycle. Concentrations returned to basal levels 3 days after injection. In group B, a moderate elevation of FSH concentrations (15% increase; P < 0.05) was observed compared to levels during the control cycle. In group A, E2 concentrations increased (P = 0.03) 1 day after FSH injection and returned to baseline levels within 2 days. In group B, E2 levels started to increase after the first injection of FSH and remained significantly higher (P < 0.01) during the following 5 days compared to those on matching days in the control cycle. Compared to matching days in the control cycle an increased number of follicles 8-10 mm in size was found in group A (P < 0.01) during the period from Day(LH+14) until Day(LH+19), without an increase in follicles 10 mm or larger thereafter. In contrast, in group B, the numbers of both 8- to 10-mm and 10-mm or larger follicles were higher during the period from Day(LH+19) until Day(LH+24) in group B (P = 0.02 and P < 0.01, respectively). Results from the present study suggest that a brief, but distinct, elevation of FSH levels above the threshold in the early follicular phase does not affect dominant follicle development, although the number of small antral follicles did increase. In contrast, a moderate, but continued, elevation of FSH levels during the mid to late follicular phase (effectively preventing decremental FSH concentrations) does interfere with single dominant follicle selection and induces ongoing growth of multiple follicles. These findings substantiate the FSH window concept and support the idea of enhanced sensitivity of more mature follicles for stimulation by FSH. These results may provide the basis for further investigation regarding ovulation induction treatment regimens with reduced complication rates due to overstimulation.

Effects of flutter and PEP mask physiotherapy on symptoms and lung function in children with cystic fibrosis (Article)

1998-01-01T00:00:00Z

Recently, the flutter was introduced as a new device to improve sputum expectoration. Preliminary data suggested a significant improvement in expectoration and lung function during flutter treatment in patients with cystic fibrosis (CF). The aim of the present study was to compare the effects of the flutter and the positive expiratory pressure (PEP) mask on symptoms and lung function in children with CF. In a crossover randomized study 22 patients with CF (mean age 12 yrs, range 7-17 yrs) performed physiotherapy using either the flutter or the PEP mask twice a day during two treatment periods of 2 weeks, separated by a one week wash-out period, in a random sequence. Lung function parameters (peak expiratory flow, forced vital capacity (FVC), forced expiratory volume in one second, maximal midexpiratory flow, maximal expiratory flow at 25% of FVC, thoracic gas volume, total lung capacity, residual volume/total lung capacity, airway resistance and specific airway conductance) and changes in transcutaneous oxygen haemoglobin saturation were assessed before and after the first supervised session and at the end of each treatment period. Throughout the study peak flow was measured and symptoms were scored daily. No significant changes in any lung function parameter occurred after a single session or after 2 weeks of physiotherapy with either method. There was no difference in acceptability and subjective efficacy. In conclusion, any superiority of the flutter over the positive expiratory pressure mask technique for expectoration could not be confirmed during 2 weeks of daily treatment in children with cystic fibrosis. Both methods are well accepted by children and do not change lung function. Long-term comparison of both methods, including expectoration measurements, seems to be required for further evaluation of the potential success of physiotherapy in cystic fibrosis.

Hydrogen peroxide in exhaled air of healthy children: reference values (Article)

1998-01-01T00:00:00Z

An increased content of hydrogen peroxide (H2O2), a marker of inflammation, has been described in the condensate of exhaled air from adults and children with inflammatory lung disorders, including asthma. However, the normal range of [H2O2] in the exhaled air condensate from healthy children has not been established. Therefore, the aim of this study was to determine the reference range of exhaled [H2O2] in healthy school-aged children. Ninety-three healthy nonsmoking children (48 female and 45 male, mean age 10 yrs, range 8-13 yrs), with a negative history for allergy, eczema or respiratory disease and with a normal lung function, participated. Exhaled air condensate was examined fluorimetrically for the presence of H2O2. In addition, the reproducibility of [H2O2] within subjects and between days and the stability of [H2O2] during storage at -20 degrees C were assessed. The median [H2O2] in the exhaled air condensate of all children was 0.13 microM, with a 2.5-97.5% reference range of <0.01-0.48 microM. No significant difference existed between males and females. There was no correlation between exhaled [H2O2] and age or lung function. Repeated [H2O2] measurements on 2 consecutive days showed satisfactory within-subject reproducibility and [H2O2] in stored samples remained stable for at least 1 month at -20 degrees C. In conclusion, this study provides reference data for exhaled hydrogen peroxide in a large group of healthy children. The observed levels were lower than those reported previously for healthy adults and were independent of age, sex and lung function.

Complement activation in relation to capillary leakage in children with septic shock and purpura (Article)

1998-01-01T00:00:00Z

To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.

Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis (Article)

1997-01-01T00:00:00Z

To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis.

Assessment of Prognostic Factors in Clinical Medicine (Doctoral Thesis)

1996-09-25T00:00:00Z

Patients suffering from a certain disease generally differ greatly regarding the course of their disease. The identification of factors from which much of this variability between patients can be explained may be of great importance. The study of such prognostic factors in clinical medicine is usually done for a variety of reasons which to some extent may overlap each other. One of the reasons may be to better understand how the disease is likely to behave. It is hardly ever possible nowadays to study the pure natural history of a disease because usually some form of treatment will have been undertaken. The treatment often will be curative in intent, but may also be directed towards the relief of symptoms or avoiding or delaying these in case no curative treatment is available. It is known from their natural history that certain illnesses do not require treatment at all because they are self-limited processes. Knowledge about prognostic factors in such cases will make it possible to provide information to the patient about the probable duration and course of the disease. Knowledge of factors which are related to the outcome of disease may be helpful to physicians in understanding the mechanism of the disease. Such better understanding may assist in modifying treatment protocols, searching for new treatments or fonnulating strategies for the optimal use of expensive medical tests. Sometimes knowledge of prognostic factors may be of use to alter the course of disease by remedial action. This will particularly be so if these factors are elements of lifestyle such as diet, exercise or habits. For instance, patients with alcoholic liver cirrhosis who stop taking alcohol appear to have a better prognosis regarding survival as compared to those who continue drinking alcohol [Borowsky et ai, 1981]. Such scientifically based facts may be helpful in encouraging patients to change their drinking habits. Knowledge of prognostic factors often will be of importance in planning therapeutic trials. It may be desirable to evaluate certain therapies only in patients who belong to certain prognostic categories. Also the number of patients required in a randomized clinical trial depends on the distribution of prognostic factors among patients to be included in the study.

Clinical features and mortality in patients with early-onset Alzheimer's disease. (Article)

1996-01-01T00:00:00Z

In a population-based study of 198 patients with probable early-onset Alzheimer's disease (AD), we studied the occurrence of extrapyramidal signs (tremors and rigidity), myoclonus, psychosis and seizures, as well as their predictive value for mortality. The presence of tremors was significantly associated with the presence of rigidity. The occurrence of myoclonus was significantly associated with the occurrence of seizures. Psychosis and seizures in AD patients were not associated with mortality. The occurrence of extrapyramidal signs and myoclonus at any point in time during the course of AD increased the risk of mortality significantly. When evaluating their relative importance, extrapyramidal signs appeared to be the most important predictor of mortality.

Foreign material in postoperative adhesions (Article)

1996-01-01T00:00:00Z

OBJECTIVE: The authors determined the prevalence of foreign body granulomas in intra-abdominal adhesions in patients with a history of abdominal surgery. PATIENTS AND METHODS: In a cross-sectional, multicenter, multinational study, adult patients with a history of one or more previous abdominal operations and scheduled for laparotomy between 1991 and 1993 were examined during surgery. Patients in whom adhesions were present were selected for study. Quantity, distribution, and quality of adhesions were scored, and adhesion samples were taken for histologic examination. RESULTS: In 448 studied patients, the adhesions were most frequently attached to the omentum (68%) and the small bowel (67%). The amount of adhesions was significantly smaller in patients with a history of only one minor operation or one major operation, compared with those with multiple laparotomies (p < 0.001). Significantly more adhesions were found in patients with a history of adhesions at previous laparotomy (p < 0.001), with presence of abdominal abscess, hematoma, and intestinal leakage as complications after former surgery (p = 0.01, p = 0.002, and p < 0.001, respectively), and with a history of an unoperated inflammatory process (p = 0.04). Granulomas were found in 26% of all patients. Suture granulomas were found in 25% of the patients. Starch granulomas were present in 5% of the operated patients whose surgeons wore starch-containing gloves. When suture granulomas were present, the median interval between the present and the most recent previous laparotomy was 13 months. When suture granulomas were absent, this interval was significantly longer--i.e., 30 months (p = 0.002). The percentage of patients with suture granulomas decreased gradually from 37% if the previous laparotomy had occurred up to 6 months before the present operation, to 18% if the previous laparotomy had occurred more than 2 years ago (p < 0.001). CONCLUSIONS: The number of adhesions found at laparotomy was significantly larger in patients with a history of multiple laparotomies, unoperated intra-abdominal inflammatory disease, and previous postoperative intra-abdominal complications, and when adhesions were already present at previous laparotomy. In recent adhesions, suture granulomas occurred in a large percentage. This suggests that the intra-abdominal presence of foreign material is an important cause of adhesion formation. Therefore intra-abdominal contamination with foreign material should be minimized.

Physiological and morphological determinants of maximal expiratory flow in chronic obstructive lung disease (Article)

1996-01-01T00:00:00Z

Maximal expiratory flow in chronic obstructive pulmonary disease (COPD) could be reduced by three different mechanisms; loss of lung elastic recoil, decreased airway conductance upstream of flow-limiting segments; and increased collapsibility of airways. We hypothesized that decreased upstream conductance would be related to inflammation and thickening of the airway walls, increased collapsibility would be related to decreased airway cartilage volume, and decreased collapsibility to inflammation and thickening of the airway walls. Lung tissue was obtained from 72 patients with different degrees of COPD, who were operated upon for a solitary peripheral lung lesion. Maximal flow-static recoil (MFSR) plots to estimate upstream resistance and airway collapsibility were derived in 59 patients from preoperatively measured maximal expiratory flow-volume and pressure-volume curves. In 341 transversely cut airway sections, airway size, airway wall dimensions and inflammatory changes were measured. Airflow obstruction correlated with lung elastic recoil and the MFSR estimate of airway conductance but not to airway collapsibility or to the amount of airway cartilage. The upstream conductance decreased as the inner wall became thicker. Airway collapsibility did not correlate with the amount of airway cartilage, inflammation, or airway wall thickness. We conclude that the maximal flow-static recoil model does not adequately reflect the collapsibility of the flow-limiting segment.

Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis (Article)

1995-01-01T00:00:00Z

OBJECTIVE: A randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. SUMMARY BACKGROUND DATA: Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available. METHODS: Between April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score > or = 3) and/or computed tomography criteria (Balthazar grade D or E). Patients were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups. RESULTS: Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria. CONCLUSION: Reduction of gram-negative colonization of the digestive tract, preventing subsequent pancreatic infection by means of selective decontamination, significantly reduces morbidity and mortality in patients with severe acute necrotizing pancreatitis.

Blood transfusions and local tumor recurrence in colorectal cancer. Evidence of a noncausal relationship (Article)

1994-01-01T00:00:00Z

OBJECTIVE. The authors analyzed the effect of blood transfusions on the pattern of colorectal cancer recurrence. BACKGROUND. Retrospective studies suggest that blood transfusions are associated with a poor prognosis in patients who undergo operations for colorectal malignancies. In a previously published, randomized trial, it was investigated whether autologous blood transfusions could overcome this putative detrimental effect. However, this did not appear to be the case. METHODS. In the current study, the authors analyzed the patterns of recurrence in 420 patients who underwent curative operations for colorectal cancer. RESULTS. Patients who did not require transfusions (N = 143) had significantly better disease-free survival than those who did need transfusions (N = 277); percentages at 4 years were 73% and 59%, respectively (p = 0.001). No difference was found between both groups in comparing cumulative percentages of patients having metastases; percentages at 4 years were 25% in the group that did not undergo transfusion and 27% in the transfused group. The percentage of cases having local recurrence, however, was significantly increased (p = 0.0006) in the transfused group as compared with the group that did not undergo transfusion; percentages at 4 years were 20% and 3%, respectively. The groups of patients receiving only allogeneic, only autologous, or both types of transfusions all had a significantly higher incidence of local recurrence than the patients who did not receive transfusions, but no differences were found between these three groups. CONCLUSIONS. These findings suggest that the association between blood transfusions and prognosis in colorectal cancer is a result of the circumstances that necessitate transfusions, leading to the development of local recurrences, but not of distant metastases.