Oral and Maxillofacial Surgery

Nasal reconstruction after malignant tumor resection: An algorithm for treatment (Article)

Moolenburgh, S.E. — 2011-03-01T00:00:00Z

On the Le Fort III Osteotomy (Doctoral Thesis)

Nout, E. — 2010-11-19T00:00:00Z

Patienten met een sterk verminderde ontwikkeling van het middengezicht kunnen al vroeg na de geboorte ernstige problemen met de ademhaling en een bedreigde visus ontwikkelen. Op kinderleeftijd worden grote operaties uitgevoerd om deze ernstige functionele symptomen te corrigeren. In dit proefschrift wordt een aantal fundamentele en klinische studies beschreven die handelen over de gevolgen van het chirurgisch naar voren verplaatsen van het middengezicht. Bij deze operatie wordt de neus, bovenkaak en jukbeenderen inclusief oogkassen naar voren geplaatst, de zogenaamde Le Fort III osteotomie (LF III). Het doel van dit proefschrift was om meer inzicht te verwerven in het effect van de LF III op de anatomie en te bepalen in hoeverre deze ingrepen het obstructief slaap apneu syndroom (OSAS) kan verbeteren. Ten slotte werd er gekeken naar de lange termijn uitkomsten van deze ingrepen en geassocieerde complicaties. Analyses van CT-scans wezen uit dat na een LF III een duidelijke voorwaartse verplaatsing van de onderste randen van de oogkas plaatsvindt samen met een significante volume toename van de oogkassen. De oogbol positie blijft nagenoeg onveranderd. Na LF III treedt verder bij het merendeel van de patienten een volume toename van de bovenste luchtweg op; een verbetering van OSAS treedt niet bij alle patienten op. Er werd geconcludeerd dat behalve de onderontwikkeling van het middengezicht, ook het samenvallen van de wand van de bovenste luchtweg en mogelijk luchtweg obstructies op niveau van de onderkaak een rol spelen. Als er sprake is van een duidelijke volumetoename van de bovenste luchtweg na LF III en de slaapstudie weinig winst laat zien, is endoscopie van de bovenste luchtweg geindiceerd om het niveau van de obstructie vast te stellen. Met betrekking tot de lange termijn resultaten kan gesteld worden dat de LF III een adequate behandeling is voor de onderontwikkeling van het middengezicht. Echter, een verkeerde stand van tanden en kiezen lijkt na de operatie frequent aanwezig te zijn. Hoewel een flink aantal patienten wel een indicatie heeft om deze verkeerde stand van tanden en kiezen later chirurgisch te laten corrigeren, vindt bij deze patientengroep slechts weinig additionele chirurgie plaats. Hoogstwaarschijnlijk zijn patientfactoren hier debet aan. Ten aanzien van de in deze studie geregistreerde milde en ernstige complicaties kan de conclusie worden getrokken dat die zowel verband houden met de ingreep zelf als met het apparaat dat na de operatie aan de schedel gefixeerd wordt om het aangezicht langzaam naar voren te laten bewegen. Door specifieke voorzorgsmaatregelen te nemen, het nauwkeurig bestuderen van de voorgeschiedenis en de medewerking van de patient vooraf door een psycholoog te laten evalueren, kunnen deze complicaties worden voorkomen en kan een optimaal behandelresultaat worden bereikt.

Long-term functional outcome in 167 patients with syndromic craniosynostosis; Defining a syndrome-specific risk profile (Article)

Jong, A.A.W. de — 2010-10-01T00:00:00Z

Objective: Little is known about the long-term prevalence of elevated intracranial pressure (ICP), obstructive sleep apnoea (OSA), level of education, language and motor skills, impaired sight and hearing in craniosynostosis syndromes. The objective of this study was to define the prevalence per syndrome of elevated ICP, OSA, impaired sight and impaired hearing. Methods: A retrospective study was undertaken on 167 consecutive patients diagnosed with Apert, Crouzon, Pfeiffer, Muenke or Saethre-Chotzen syndrome, aged 1-25 years and treated between 1983 and 2008. The mean age at time of referral and review was 1 years and 2 months and 10 years and 3 months, respectively. Results: Patients with Apert and Crouzon/Pfeiffer syndromes had the highest prevalence of elevated ICP (33% and 53%, respectively) and OSA (31% and 27%, respectively), while Saethre-Chotzen syndrome was also associated with a fair risk for elevated ICP (21%). The prevalence of impaired sight (61%) and hearing (56%) was high in all syndromes. Conclusion: Based on these data, a syndrome-specific risk profile with suggestions for screening and treatment is presented.

Hyperbaric oxygen therapy in the management of radiation-induced injury in the head and neck region: A review of the literature (Article)

Spiegelberg, L. — 2010-08-01T00:00:00Z

Purpose: Radiotherapy is generally used in the treatment of malignant tumors in the head and neck region. It causes a hypoxic, hypocellular, and hypovascular environment that leads to injury to surrounding normal tissue, both acute and chronic, ranging from xerostomia to osteoradionecrosis. These side effects are debilitating and greatly influence quality of life in these patients. Hyperbaric oxygen (HBO) therapy is clinically used to prevent or treat these side effects by enhancing oxygen pressure and thereby regeneration. Although this therapy is widely applied, its mechanism of action is still poorly understood, and controversy exists in the literature about its clinical use. This review therefore aims to analyze the existing experimental and clinical research on this topic. Materials and Methods: A systematic search was performed in PubMed for experimental and clinical studies conducted regarding the use of HBO therapy in previously irradiated tissue, in the period from January 1990 to June 2009. Results: Experimental research is scarce, and clinical studies are especially lacking in terms of randomized controlled studies. Although discussions on the subject are ongoing, most studies suggest a beneficial role for HBO in previously irradiated tissue. Conclusion: Further research, both experimental and clinical, is necessary to unravel the working mechanism of HBO therapy and validate its clinical use.

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

Nout, E. — 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

Internal carotid dissection after Le Fort III distraction in Apert syndrome: A case report (Article)

Nout, E. — 2010-03-18T00:00:00Z

A 10-year-old girl with Apert syndrome underwent a Le Fort III osteotomy with the positioning of internal and external distraction devices. The operation was straightforward with no intraoperative complications. Very soon after completion of surgery an anisocoria (unilateral dilation of a pupil) was noticed. This was followed by intracranial oedema which was fatal. The aetiology was dissection of the right internal carotid artery is reported. The complications of Le Fort osteotomies are discussed regarding patients with complex syndromal craniosynostosis and midface hypoplasia, such as Apert syndrome.

Obstructive sleep apnea in children with syndromic craniosynostosis: long-term respiratory outcome of midface advancement (Article)

Bannink, N. — 2010-02-01T00:00:00Z

Almost 50% of patients with Apert, Crouzon or Pfeiffer syndrome develop obstructive sleep apnea (OSA), mainly due to midface hypoplasia. Midface advancement is often the treatment of choice, but the few papers on long-term outcome report mixed results. This paper aimed to assess the long-term respiratory outcome of midface advancement in syndromic craniosynostosis with OSA and to determine factors contributing to its efficacy. A retrospective study was performed on 11 patients with moderate or severe OSA, requiring oxygen, continuous positive airway pressure (CPAP), or tracheostomy. Clinical symptoms, results of polysomnography, endoscopy and digital volume measurement of the upper airways on CT scan before and after midface advancement were reviewed. Midface advancement had a good respiratory outcome in the short term in 6 patients and was ineffective in 5. In all patients without respiratory effect or with relapse, endoscopy showed obstruction of the rhino- or hypopharynx. The volume measurements supported the clinical and endoscopic outcome. Despite midface advancement, long-term dependence on, or indication for, CPAP or tracheostomy was maintained in 5 of 11 patients. Pharyngeal collapse appeared to play a role in OSA. Endoscopy before midface advancement is recommended to identify airway obstruction that may interfere with respiratory improvement after midface advancement.

Early Hyperbaric Oxygen Therapy for Reducing Radiotherapy Side Effects: Early Results of a Randomized Trial in Oropharyngeal and Nasopharyngeal Cancer (Article)

Teguh, D.N. — 2009-11-01T00:00:00Z

Purpose: Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT). Methods and Materials: From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up. Results: On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001). Conclusions: Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth.

Long-term follow-up of craniofacial alterations in juvenile idiopathic arthritis (Article)

Twilt, M. — 2009-11-01T00:00:00Z

Objective: To investigate changes in the craniofacial skeleton in relation to the changes in condylaralterations that occur during long-term follow-up in patients with juvenile idiopathic arthritis. Materials and Methods: Temporomandibular joint (TMJ) involvement is defined as a condylaralteration that is observed on the orthopantomogram. Lateral cephalograms were used to determine linear and angular measurements. Results: Seventy of 97 patients from the initial study cohort were included, with a mean follow up of 68 months. The overall prevalence of condylar alterations and posterior rotation of them andible decreased; however, the prevalence of retrognathia remained the same. Patients showed improvement in the degree of retrognathia and posterior rotation (40% ANB, 51% OPSN,and 44% GO-GN-SN). Improvement in the degree of retrognathia was seen more often inpatients with improved condylar alterations than in patients with persistent alterations and in those without alterations (50%, 33%, and 28%, respectively). The degree of posterior rotation improved almost equally in patients without TMJ involvement and in patients with improved condylar alterations(57% and 50% by OP-SN, and 67% and 38% GO-GN-SN, respectively) and did not improve in patients with stable persistent alterations. Conclusion: Both condylar and craniofacial alterations can improve in patients with juvenile idiopathicarthritis. (Angle Orthod. 2009;79:1057-1062.)

Histomorphometric comparison between continuous and discontinuous distraction osteogenesis (Article)

Djasim, U.M. — 2009-10-01T00:00:00Z

Introduction: Experimental research on optimising the distraction protocol has been performed extensively in the past. However, relatively little research has been done on the rhythm of distraction. Findings in the orthopaedic literature showed that the outcome of distraction osteogenesis (DO) is positively influenced by increasing the rhythm of distraction. The aim of this study is to quantitatively compare continuous with discontinuous rhythms of distraction in rabbits. Materials and methods: Tissue blocks of regenerated bone were harvested from thirty-eight young adult female New-Zealand White rabbits. After a latency period of three days, rabbits were subjected for eleven days to either single daily activation of the distractor at a rate of 0.9 mm/d, or triple daily activation at a rate of 0.9 mm/d, or continuous activation at a rate of 0.9 mm/d. After three weeks of consolidation, bone regenerates were analysed using histomorphometry. Results: The continuous DO group showed significantly (p < .01) more regenerate bone volume in the central part of the regenerate than the discontinuous DO groups. Higher osteoblastic activity was seen, as well as more blood vessels (p < .05). Bone volume and the number of blood vessels correlated significantly in the central part of the regenerate (p < .05). Also, the early mineral apposition rate (MAR) was higher than the late MAR (p < .05). Conclusions: Continuous DO significantly accelerates bone formation when compared with discontinuous DO.

Osteoradionecrosis of tympanic bone: Reconstruction of outer ear canal with pedicled skin flap, combined with hyperbaric oxygen therapy, in five patients (Article)

Dumans, A.G. — 2009-10-01T00:00:00Z

Objective: To evaluate the results of one-stage surgical repair of the meatal skin defect in patients with long-lasting osteoradionecrosis of the outer ear canal, using a postauricular, inferiorly pedicled skin flap. All patients were also treated with hyperbaric oxygen both pre- and post-operatively.Methods: A prospective study evaluating the results of a one-stage surgical procedure to repair the meatal skin defect in five patients with osteoradionecrosis of the outer ear canal. All patients were treated with hyperbaric oxygen both pre- and post-operatively.Results: In four of the five patients, intact canal skin was achieved after surgery and hyperbaric oxygen therapy. One patient needed a second operation to cover a small remaining area of bare bone. In one patient, wound healing was unsatisfactory and an area of bare bone remained.Conclusion: In cases of osteoradionecrosis of the outer ear canal, the skin defect can be repaired with an inferiorly pedicled skin flap. Although not yet scientifically proven, the peri-operative application of hyperbaric oxygen may be of additional value to improve wound healing in areas of compromised tissue.

Primary epithelial tumors of the lacrimal gland; a retrospective analysis of 22 patients (Article)

Snaathorst, J. — 2009-07-01T00:00:00Z

This study analyzed the clinical and histopathological aspects, treatment and prognosis of 22 patients with primary epithelial tumors of the lacrimal gland treated in a single institution over 25 years. 191 lacrimal gland lesions retrieved from the archives of the Department of Pathology, Erasmus University Medical Center, were retrospectively reviewed. The clinical and surgical pathology files of 22 primary epithelial neoplasms (16 benign; 6 malignant tumors) were studied. All benign tumors were pleomorphic adenomas; 50% of the malignant neoplasms were adenoid cystic carcinomas. The mean time from complaint to diagnosis was 3 years for benign tumors and 6 months for malignancies. Most benign tumors were treated by local excision; no recurrences occurred. Treatment of malignant tumors varied but generally involved extensive surgery with postoperative radiotherapy. 50% of these patients showed regional and/or distant metastasis. 33% of patients with malignancy died of their disease. Most primary epithelial tumors of the lacrimal gland are pleomorphic adenomas. They have a long duration of symptoms before diagnosis, are treated by limited surgery and recur infrequently. Malignant tumors have a short duration of symptoms, are sometimes mistaken for inflammatory disease, and are, even in case of aggressive surgery, characterized by a high rate of local recurrence and metastasis.

Distraction assisted treatment of a unilateral complex facial cleft (Article)

Versnel, S.L. — 2009-07-01T00:00:00Z

Unilateral maxillary hypoplasia is a characteristic feature of an oblique facial cleft. This three-dimensional shortage of osseous structures and soft tissue becomes more prominent over the years and is difficult to correct. The authors describe a 17-year-old boy born with a unilateral nasomaxillary dysplasia and nasal dysplasia (Tessier type 1, 2, 3) who underwent a hemi-Le Fort III distraction with a rigid external distraction (RED) system. This distraction, in combination with initial peroperative advancement and retained with elastic traction with a facial mask, achieved a substantial horizontal improvement of the hemi-midface; this resulted in a better projection of the left cheek, infra-orbital rim, nasal ala, and improved occlusion. Owing to the underdevelopment of the maxilla and zygoma in all three dimensions, contour deformities remain. Creating several bone segments for multidirectional distraction would jeopardize vascularization of the bone. Good long-term planning is essential in these complicated cases, and more long-term results need to be assessed. The major reconstructive challenge for this complex pathology continues.

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

Koudstaal, M.J. — 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.

Continuous Versus Discontinuous Distraction: Evaluation of Bone Regenerate Following Various Rhythms of Distraction (Article)

Djasim, U.M. — 2009-04-01T00:00:00Z

Purpose: To investigate continuous distraction osteogenesis (DO) of the nasal bones in a rabbit model, and to compare data from this continuous DO study with data from a previously conducted discontinuous DO study. In addition, radiographic and ultrasonographic bone-fill scores were determined to investigate whether these scores provided reliable predictive value for the amount of new bone formation in the distraction area. Materials and Methods: Skeletally mature female New Zealand White rabbits were subjected to distraction of the nasal bones. A custom-made continuous distractor was used to perform automatic non-stop distraction. Bone data were obtained from radiography, ultrasonography, and microcomputed tomography. Data from this experiment were compared with data from a previous study on discontinuous distraction rhythms. Results: Ultrasonographic bone-fill scores correlated significantly to actual bone volume in contrast to radiographic bone-fill scores. Bone volume was significantly higher in the continuous DO group compared with the discontinuous DO groups. Conclusion: Continuous distraction resulted in accelerated osteogenesis compared with discontinuous distraction. Furthermore, bone-fill scores based on ultrasonography showed a significant correlation with actual bone volumes.

Congenital epulis of the jaw: A series of five cases and review of literature (Article)

Küpers, A.M. — 2009-02-01T00:00:00Z

This article describes five cases of congenital epulis, a rare and benign swelling in the mouth of a newborn, which is not widely known. We present five cases: four cases presented as single pedunculated nodules of the gingiva and in one case two nodules were present. Of all, 50% were located at the maxilla. Excision was performed in four of the five cases and in one case, spontaneous regression was awaited. No recurrence was reported. The characteristic features of congenital epulis are a pedunculated, flesh-pink coloured tumour with a predominant occurrence on the anterior maxillary alveolar ridge in a female newborn. Although the aetiology is unknown, most authors suggest a mesenchymal, rather than an odontogenic, origin. Endogenous hormonal factors might influence growth prenatally. Histological findings include granular cells with eosinophilic cytoplasm and small, eccentric nuclei. Despite the fact that the lesion can be a striking sight, spontaneous regression is possible and can be awaited. Indications for non-radical excision under local anaesthesia are severe upper airway obstruction and interference with feeding technique. In conclusion, we provide clinical and histological information about congenital epulis, so that this entity will be more easily recognised and relevant information given to parents.

Sensory Testing of Inferior Alveolar Nerve Injuries: A Review of Methods Used in Prospective Studies (Article)

Poort, L.J. — 2009-02-01T00:00:00Z

Purpose: The inferior alveolar nerve (IAN) can be injured during trauma or surgery. So far there is no consensus for evaluating IAN injury. This study aimed to identify a testing method suitable for daily clinical practice which allows us to identify nerve injury, grade its severity, and monitor its recovery. Materials and Methods: Covering a 20-year period, prospective studies on sensory changes after mandibular procedures were reviewed regarding sensory testing methods; 75 studies on third molar removal, osteotomy, fracture, and implants were included. Results: These studies reported varying incidences. In third molar removal and implant studies, a limited number of sensory tests were used, whereas in osteotomy and fracture studies more detailed testing was performed, using reproducible tests like light touch test with Semmes-Weinstein monofilaments and 2-point discrimination. Conclusions: Sensory function was not uniformly tested and presented, making a comparison of data impossible and highlighting the need for uniform testing methodology. Based on the results of this review, the light touch test with Semmes-Weinstein monofilaments for grading is recommended, using a grid and control site describing unilateral or bilateral nerve injury. Additionally, a visual analog scale-based questionnaire should be used to evaluate subjective sensibility. Using this method to test IAN injuries will allow comparison of future studies and provide valuable insight in the severity and prognosis of IAN injuries.

A baby with a white lesion in the upper jaw [Een zuigeling met een molaar.] (Article)

Bouw, F.P. — 2009-01-01T00:00:00Z

A 6-month-old girl had a floating molar due to Langerhans cell histiocytosis.

Relapse and Stability of Surgically Assisted Rapid Maxillary Expansion: An Anatomic Biomechanical Study (Article)

Koudstaal, M.J. — 2009-01-01T00:00:00Z

Purpose: This anatomic biomechanical study was undertaken to gain insight into the underlining mechanism of tipping of the maxillary segments during transverse expansion using tooth-borne and bone-borne distraction devices. Materials and Methods: An anatomic biomechanical study was performed on 10 dentate human cadaver heads using tooth-borne and bone-borne distraction devices. Results: The amount of tipping of the maxillary halves was greater in the tooth-borne group, but the difference was not significant. Four of the specimens demonstrated an asymmetrical widening of the maxilla. Conclusions: Segmental tipping was seen in both study groups. In this anatomic model, tooth-borne distraction led to greater segmental tipping compared with bone-borne distraction. Keep in mind, however, that this anatomic model by no means depicts a patient situation, and any extrapolation from it must be done with great care. The fact that the tooth-borne group demonstrated greater tipping might reflect the general opinion that bone-borne distraction causes less segmental angulation than tooth-borne distraction. Some tipping was seen in the bone-borne group, suggesting that overcorrection to counteract relapse will be necessary with this treatment modality.

Rabbits as a model for research into craniofacial distraction osteogenesis (Article)

Djasim, U.M. — 2008-12-01T00:00:00Z

Various factors affect the choice of the appropriate animal for craniofacial research. We have evaluated the rabbit as a suitable animal for research on craniofacial distraction osteogenesis. We describe our experience with housing and handling them, surgical and experimental protocols, and compare them with other animals. We introduce, and describe the use of, a continuous hydraulic distractor on the nasal bones of the rabbit. Fifty-two skeletally mature New Zealand White rabbits were used. Forty-two of the 52 operations were uneventful. Ten of the fifty-two developed complications, of which two were animal-related, and the other eight distractor-related. During the experiments the animals stayed healthy, and the distraction procedures were well tolerated. Rabbits are excellent for use in biological research on craniofacial distraction osteogenesis. Specifically, their nasal bones are easily accessible, the size and shape of the nasal bones allow various commercially available as well as custom-made distractors to be attached to the bones easily, their care and housing are relatively simple and inexpensive, and harvesting of tissue for further analyses is no problem because their skulls are of a manageable size and shape compared with other laboratory animals.