Werf, M.J. van der

A common polymorphism in the CYP3A7 gene is associated with a nearly 50% reduction in serum dehydroepiandrosterone sulfate levels. (Article)

2005-09-01T00:00:00Z

CONTEXT: CYP3A7, expressed in the human fetal liver and normally silenced after birth, plays a major role in the 16alpha-hydroxylation of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and estrone. Due to a replacement of part of the CYP3A7 promoter with a sequence identical with the same region in the CYP3A4 promoter (referred to as CYP3A7*1C), some individuals still express a variant of the CYP3A7 gene later in life. OBJECTIVE: The objective of this study was to examine the effect of the CYP3A7*1C polymorphism on serum steroid hormone levels. DESIGN, SETTING, PARTICIPANTS: Two population-based cohort studies were performed. Study group 1 consisted of 208 subjects randomly selected from the Rotterdam Study, and study group 2 consisted of 345 elderly independently living men. MAIN OUTCOME MEASURES: Serum DHEA(S), androstenedione, estradiol, estrone, and testosterone levels were the main outcome measures. RESULTS: In study groups 1 and 2, heterozygous CYP3A7*1C carriers had almost 50% lower DHEAS levels compared with homozygous carriers of the reference allele [study group 1, 1.74 +/- 0.25 vs. 3.33 +/- 0.15 micromol/liter (P = 0.02); study group 2, 2.09 +/- 0.08 vs. 1.08 +/- 0.12 micromol/liter (P < 0.001)]. No differences in circulating DHEA, androstenedione, estradiol, or testosterone levels were found. However, in study group 2, serum estrone levels were lower in heterozygous CYP3A7*1C carriers compared with homozygous carriers of the reference allele (0.11 +/- 0.002 vs. 0.08 +/- 0.006 nmol/liter; P < 0.001). CONCLUSION: The CYP3A7*1C polymorphism causes the persistence of enzymatic activity of CYP3A7 during adult life, resulting in lower circulating DHEAS and estrone levels.

Diagnosis of urinary schistosomiasis: a novel approach to compare bladder pathology measured by ultrasound and three methods for hematuria detection (Article)

2004-01-01T00:00:00Z

We aggregated published data from field studies documenting prevalence of Schistosoma haematobium infection and bladder pathology determined by ultrasonography or hematuria detected by reagent strip, questionnaire, or visual examination. A mathematical expression was used to describe the associations between prevalence of pathology/morbidity and infection. This allows for indirect comparison of these methods, which are rarely used simultaneously. All four methods showed a similar, marked association with infection. Surprisingly, ultrasound revealed higher prevalences of pathology in schools than in communities with the same prevalence of infection, implying a need for age-related cut-off values. Reagent strip testing yielded a higher prevalence than questionnaire, which in turn was higher than by visual examination. After correction for morbidity due to other causes, a consistent ratio in prevalence of hematuria of 3:2:1 resulted for the three respective methods. The simple questionnaire approach is not markedly inferior to the other techniques, making it the best option for field use.

Sequencing: not always the "gold standard". (Article)

2004-01-01T00:00:00Z

No effect of recall period length on prevalence of self-reported haematuria in Schistosoma haematobium-endemic areas (Article)

2003-07-01T00:00:00Z

Assessing prevalence of haematuria by interview is commonly used as a rapid method to identify communities for mass treatment of Schistosoma haematobium infection. We analysed, using 21 published studies, to what extent the prevalence estimates of haematuria were affected by the length of the recall period for which respondents were requested to report symptoms. There was a strong positive association between prevalence of haematuria and infection, but no effect of recall period length. This suggests that the choice of recall period is of minor importance in control programmes or studies based on reported haematuria.

Schistosomiasis Morbidity and Management of Cases in Africa (Doctoral Thesis)

2003-05-21T00:00:00Z

Schistosomiasis is one of the most prevalent parasitic infections and an important public health problem in many developing countries. The main early symptom if Schistosoma haematobium infection is hematuria, and S. mansoni infection causes bloody diarrhea. Current estimates of the number of individuals with symptoms and the burden of disease due to schistosoma infection lack detail and precision and are considered to be too low. Therefore we aimed at determining more accurate estimates using data from published field studies. We developed a method to associate prevalence of schistosoma infection with prevalence of morbidity in a population. In the second part of this thesis we explored the quality of schistosomiasis case management and determined the probability that patients with symptoms from S. haematobium or S. mansoni infection that report at the health system receive adequate treatment. The pre-requisits for schistosomiasis case management turned out to be less favourable in Ghana than in Mali and Senegal.