A natural history of efavirenz drug-induced liver injury.

BACKGROUND: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, has been a component of first-line antiretroviral therapy (ART) in the South African HIV/AIDS programme since 2004. It is extensively used in ART programmes in other low- and middle-income countries. The natural history of the previously recognised EFV drug-induced liver injury (DILI) is not known. OBJECTIVES: To define and establish a causality assessment for EFV DILI and document its natural history by detailing a patient cohort. All relevant features characterising the patterns of clinical and histological injury, the duration of clinical and biochemical recovery and the associated mortality rate were documented. Factors associated with specific histological patterns of liver injury were analysed. METHODS: Patients were prospectively included after meeting causality and inclusion criteria for EFV DILI. Clinical, demographic and liver histological features (where possible) were documented from the time of presentation and throughout follow-up. Prednisone at 0.25 - 0.5 mg/kg was initiated at the discretion of the treating hepatologist. RESULTS: Fifty patients were prospectively included in the analysis. The median age was 34 (interquartile range (IQR) 29 - 39) years, males being older than females (p=0.014). Most (92%) were female, and 86% were of black African ethnicity. The median duration of ART at presentation was 6 months, with half of the women having initiated ART during pregnancy, at a median gestation of 24 (IQR 11 - 36) weeks. The median CD4 nadir at ART treatment initiation was 517 cells/µL, with no significant difference in CD4 nadir between those who were pregnant and those who were not (p=0.6). The median RUCAM (Roussel Uclaf Causality Assessment Method) score was 7, and among the 75% of patients who had liver biopsies, three histological patterns were identified: submassive necrosis (60%), nonspecific hepatitis (35%), and mixed cholestatic hepatitis (5%). On multivariate analysis, predictors for the development of submassive necrosis included younger age (<30 years; p=0.045), ART initiation in pregnancy (p=0.02), and a baseline CD4 count >350 cells/µL (p=0.018). For the nonspecific hepatitis group, pregnancy was also an associated factor (p=0.04). The mortality rate was 14%, with a median time from admission to death of 15 days. The median (IQR) time to initial hospital discharge was a lengthy 33 (24 - 52) days. Biochemical recovery was prolonged, necessitating a follow-up period of more than a year at an outpatient specialist clinic, with 86% of patients initiating a protease inhibitor-based ART regimen successfully. CONCLUSIONS: EFV DILI is a severe drug complication of ART with appreciable mortality and significant inpatient morbidity, requiring prolonged hospitalisation and follow-up.

Thanatophoric dysplasia: A review.

Thanatophoric dysplasia is a well-known cause of potentially lethal short-limbed dwarfism in the newborn. The diagnosis is usually made by the recognition of characteristic radiological changes and confirmed at autopsy by demonstration of specific morphological and histological changes in the brain. This review is based upon the author's personal experience and archived data of 19 cases and concerns the clinical and radiographic manifestations, autopsy findings, molecular pathogenesis and the approach to antenatal diagnosis.

Atherosclerotic lesions in the thoracic aorta: a South African anatomical and histological mortuary study.

BACKGROUND: Worldwide, the prevalence of cardiovascular diseases such as atherosclerosis is on the increase. Younger people may be especially vulnerable owing to their exposure to risk factors such as drug abuse and HIV. METHODS: The thoracic aortas of 149 South Africans under the age of 50 years were collected at the Salt River Mortuary, Cape Town, and examined macroscopically and microscopically for evidence of anomalies. The sample comprised predominantly males, and included black, coloured and white individuals. RESULTS: A significantly higher level of macroscopic pathology was found in coloured males, although overall prevalence of pathology in this sample was lower than expected. A positive association was also found between body mass index and vascular pathology in the black and coloured population groups. Microscopic anomalies were common and present at high levels, irrespective of age and racial grouping. CONCLUSIONS: The widespread prevalence of microscopic anomalies in all groups suggests that these are normal variations that result from haemodynamic forces. The higher prevalence of atherosclerotic lesions in coloured males, however, probably results from specific genetic conditions such as hypercholesterolaemia or lifestyle factors such as diet or tik abuse. The findings suggest that coloured individuals may be at increased risk of developing cardiovascular disease.

Solid pseudopapillary epithelial neoplasm--a rare but curable pancreatic tumour in young women.

BACKGROUND: Solid pseudopapillary epithelial neoplasms (SPENs) of the pancreas are rare but curable tumours that have a low-grade malignant potential and occur almost exclusively in young women, with an excellent prognosis after complete resection. This study examines the clinicopathological characteristics of these tumours and evaluates the role of surgery in relation to their size and location. STUDY DESIGN: We reviewed the pre-, intra- and postoperative data on 21 patients with SPENs who underwent resection during a 30-year period. Data including demographic information, presenting symptoms and signs, extent of operation, histology, tumour markers and postoperative complications were evaluated to establish the optimal surgical management. RESULTS: All 21 tumours occurred in women (mean age 24.6 years, range 13-51 years). Sixteen patients presented with nonspecific abdominal complaints and a palpable abdominal mass, in 1 patient the tumour was found during emergency laparotomy for a complicated ovarian cyst, 1 patient presented with severe abdominal pain and shock due to a ruptured tumour, and in 3 patients the tumour was detected incidentally during imaging. The correct pre-operative diagnosis of SPEN was made in 10 patients. Incorrect preoperative diagnoses included hydatid cyst (3 patients), mesenteric cyst (2), pancreatic cystadenoma (2), ovarian cysts (1), islet cell tumour of the pancreas (1), and cavernous haemangioma of the liver (1). The mean diameter of the tumours was 12.5 cm (range 8 - 20 cm), and they occurred in the head (8), neck (5), body (2), and tail (6) of the pancreas. All SPENs were resected. Five patients had a pylorus-preserving pancreaticoduodenectomy, 4 a central pancreatectomy with distal pancreaticogastrostomy, 8 a distal pancreatectomy, 3 a local resection and one a total pancreatectomy and portal vein graft. In 1 patient, 2 liver metastases were resected in addition to the pancreatic primary tumour. The patient who presented in shock with tumour rupture and bleeding into the lesser sac later died of multiple organ failure after successful resection. Postoperative complications included a stricture at the hepaticojejunostomy after pancreaticoduodenectomy, which resolved after stenting, and a pancreatic duct fistula after local tumour resection, which required a distal pancreatectomy. Other complications were bleeding (2 patients) requiring re-operation and intraabdominal fluid collections requiring percutaneous drainage (3) or operation (1). Mean postoperative hospital stay was 16 days (range 6 - 40 days). Twenty patients are alive and well without recurrence, including the patient with metastases, with a mean follow-up of 6.6 years (range 6 months-15 years). CONCLUSIONS: This study demonstrated that SPENs of the pancreas are uncommon, but should be considered in the differential diagnosis of a cystic mass of the pancreas in a young woman. Despite the indolent biological behaviour of SPENs, most patients required major pancreatic resection. Surgery is curative regardless of the size or location of the tumour. Metastases are rare, as is recurrence after complete surgical resection.

Warfarin-induced skin necrosis in HIV-1-infected patients with tuberculosis and venous thrombosis.

BACKGROUND: At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB). METHODS: We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa. RESULTS: Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/microl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 6.2 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin grafting at a specialist centre. CONCLUSION: This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The occurrence of 6 WISN cases in a 40-month period may be attributed to (i) hypercoagulability, secondary to HIV-1 and TB: (ii) short concurrent heparin and warfarin therapy; and (iii) high loading doses of warfarin. Active prevention and appropriate management of WISN are likely to improve the dire morbidity and mortality of this unusual condition.

Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.

BACKGROUND: The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear. METHODS: Antigen-specific interferon gamma (IFNgamma) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB. RESULTS: Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis, respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (> or = 20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative alveolar lymphocyte IFNgamma responses had poor performance outcomes. CONCLUSION: Provided evaluable results are obtained, the RD-1, but not the heparin-binding haemagglutinin or purified protein derivative, alveolar lymphocyte IFNgamma ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.

Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis.

The clinical utility of antigen-specific interferon (IFN)-gamma release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.

Four decades of conjoined twins at Red Cross Children's Hospital--lessons learned.

Conjoined twins represent a rare but fascinating congenital condition, the aetiology of which remains obscure. Over the past four decades, the paediatric surgeons at Red Cross Children's Hospital have been involved in the management of 46 pairs of conjoined twins, of which 33 have been symmetrical and 12 asymmetrical. Seventeen symmetrical twins have undergone separation with 22 children (65%) surviving; all of the live asymmetrical twins survived separation. We describe the important features of this unique cohort, outline our approach to management and present the results of this approach. We consider some of the ethical and moral dilemmas we have confronted, and discuss the prenatal diagnosis, obstetric implications and postnatal care of these children, including the relevant investigations and anaesthetic and surgical management. Specific aspects related to the cardiovascular system, hepatobiliary and gastrointestinal tracts, urogenital tract, central nervous system and musculoskeletal system are highlighted.

Poikiloderma, tendon contracture and pulmonary fibrosis: a new autosomal dominant syndrome?

Members of two generations of a South African family have a unique syndrome comprising poikiloderma, tendon contractures and progressive pulmonary fibrosis. The condition is clinically important as the skin changes, which involve the face, have considerable cosmetic impact, while lung involvement is potentially lethal in adulthood. Skin manifestations which facilitate diagnosis include facial telangiectasia, mottled hypo- and hyperpigmentation, papules and epidermal atrophy. The scalp, facial and body hair are fine and scanty. The tendon contractures lead to progressive digital flexion deformities and abnormalities of the ankles and feet, with disturbance of gait. Pulmonary involvement manifests as progressive dyspnoea. Pedigree data are compatible with an autosomal dominant mode of transmission. Poikiloderma of Weary is characterized by linear sclerotic and fibrous bands and not tendon contractures and is not associated with potentially lethal pulmonary fibrosis. Rather than name this disorder a variant of Weary syndrome, it might be prudent to use as an umbrella title one composed by Weary himself: 'hereditary sclerosing poikiloderma' (HSP), under which variants such as HSP Weary type, HSP with cardiac involvement (aortic stenosis described as inconsistently associated with Weary syndrome) and HSP with tendon/pulmonary involvement (current family) may be classified. The manifestations in this family differ from other poikilodermata and, to the best of our knowledge, have not been previously documented.

My approach to performing a perinatal or neonatal autopsy.

An opportunity to determine the cause of death, factors that may have a role in it, and the extent and cause of malformations is provided by perinatal autopsy. The family may be assisted in finding closure after the death of their infant by the information obtained. Insight into classifying infants appearing normal into one of three groups, small, appropriate and large for gestational age, has been provided, as each group tends to have specific causes of death. In infants with congenital anomalies, patterns of malformation may lead us to the diagnosis. An accurate diagnosis is required to provide counselling for a subsequent pregnancy.

Preterm prelabour rupture of the membranes before 28 weeks: better than feared outcome of expectant management in Africa.

OBJECTIVE: To document the prognosis after conservative management of patients with membrane rupture at gestations less than 28 weeks. STUDY DESIGN: Prospective observational study of 78 women with confirmed membrane rupture at less than 28 weeks gestation, managed conservatively. Antibiotics were given from the time of membrane rupture till delivery. Patients were delivered if clinical infection supervened, there was fetal compromise, spontaneous labour ensued or if the pregnancy continued to 34 completed weeks gestation. RESULTS: The mean gestational age at membrane rupture was 23.3+/-3.17 weeks (16.5-27.8) and the median 24 weeks. Mean latency period was 24.1+/-29.1 days (1.5-154) with a median of 12.5 days. Eight women (10%) delivered between 24 and 48 h, 25 (32%) within 7 days and 55 (70%) within 1 month. Of note is that 23 patients (30%) had latency periods of greater than 1 month. The mean gestational age at delivery was 26.7+/-3.92 weeks. Overall of the 78 women there were 81 fetuses delivered, of which 35 (43%) survived. Survival was related to latency period, birth weight and gestational age at delivery. Sixteen women (20%) developed chorioamnionitis. There was no increase in the incidence of clinical infection with increasing latency period. Compression limb abnormalities occurred in 17% of neonates and lung hypoplasia in 18%. CONCLUSION: Conservative management of patients with very preterm prelabour membrane rupture offers a survival rate of at least 40% with no serious complications in a study of 78 women.

Association of angiomyolipoma and oncocytoma of the kidney: a case report and review of the literature.

AIM: The association between renal carcinoma and angiomyolipoma is rare. Only 14 cases have been reported in the literature. The purpose of this paper is to present an additional case and review the literature on this association. PATIENT AND METHODS: A healthy 42 year old woman was found to have a left flank mass incidentally when she presented for a Papanicolaou smear. The computerised tomography scan revealed a left lower pole renal mass consistent with a renal cell carcinoma. A nephrectomy was performed and the patient recovered uneventfully. The nephrectomy specimen was processed routinely. In addition to haematoxylin and eosin staining, immunohistochemistry for CAM 5.2, vimentin, CD34, antismooth muscle actin, and HMB45 was carried out. Transmission electron microscopy was also performed. RESULTS: Macroscopically, the lower pole of the kidney contained a well circumscribed, non-encapsulated, tan coloured tumour with a large area of central haemorrhage measuring 10.5 cm. In addition, there was a 0.4 cm poorly circumscribed unencapsulated yellow nodule adjacent to the tumour. Microscopically, the larger tumour showed characteristic features of an oncocytoma. Numerous mitochondria were seen on electron microscopy. The smaller yellow nodule was an angiomyolipoma. CONCLUSIONS: This paper presents an additional case of oncocytoma associated with angiomyolipoma. Of the 15 cases described in the literature, three were associated with the tuberous sclerosis complex, all from a single study. In tuberous sclerosis, angiomyolipomas are more commonly associated with renal cell carcinoma. If angiomyolipomas are found incidentally in nephrectomy specimens together with other tumours, it is important to exclude tuberous sclerosis retrospectively.

Absence of the ductus venosus with direct connection between the umbilical vein and right atrium.

Abnormalities of the ductus venosus are rare. We present the case of a dichorionic, diamniotic twin pregnancy in which complete absence of the ductus venosus, with direct communication between the umbilical vein and right atrium, was detected in one infant on antenatal ultrasonography. Autopsy confirmed the aberrant course of the umbilical vein, which also had an abnormal histological structure. Associated congenital anomalies included an ostium secundum type atrial septal defect, absent inferior vena cava, single left pulmonary vein, stenosed right pulmonary artery, proliferation of the hepatic arterioles with reduction of portal venules, and a duplex ureter. The literature is reviewed and pathogenesis relevant to this case is discussed.

Evaluation of alternative methods of cervical cancer screening for resource-poor settings.

BACKGROUND: Noncytologic methods of screening for cervical carcinoma and its precursor lesions are needed for resource-poor settings in which cervical carcinoma continues to be an important cause of morbidity and mortality. METHODS: Two thousand nine hundred forty-four women ages 35-65 years were recruited from Cape Town, South Africa and screened using a combination of a Papanicolaou (Pap) smear, human papillomavirus (HPV) DNA testing, direct visual inspection after the application of a 5% acetic acid solution (DVI), and cervicography. Cervicography was considered primarily as a method with which to quality control the DVI examinations. Women with squamous intraepithelial lesions (SIL) or carcinoma on Pap smear, positive DVI examination (acetowhite lesion or cervical ulcer/growth), high levels of high risk HPV DNA (relative light units [RLU] > 10x positive control), or positive Cervigramtrade mark were referred for colposcopy and cervical biopsy. RESULTS: Pap smears were positive in 8.1% of all women screened and identified 65 (78%) of all cases of biopsy confirmed high grade disease (high grade SIL or invasive carcinoma). DVI and cervicography were classified as positive in 18.1% and 10.5%, respectively, of women screened and identified 58 (67%) and 46 (58%) of all cases of high grade disease, respectively. The results of HPV DNA testing varied depending on the cutoff value used to define a positive result. At the standard cutoff level (RLU > 1x positive control), 16.2% of women screened were classified as high risk HPV DNA positive, as were 63 women with high grade disease (73%). CONCLUSIONS: DVI and HPV DNA testing identified similar numbers of high grade SIL (cervical intraepithelial neoplasia Grade 2,3) and invasive carcinoma cases as Pap smears. However, both classify considerably more women without cervical disease as being test positive.

Widespread axonal injury in gunshot wounds to the head using amyloid precursor protein as a marker.

In order to determine whether axonal injury (AI) is a factor in cases of penetrating head injury, the brains of 14 patients who died shortly after sustaining a fatal gunshot wound (GSW) to the head were examined, and the presence of AI determined using immunohistochemical staining for amyloid precursor protein (APP). The distribution of AI was mapped throughout the cerebral hemispheres and brain stem. AI was present in all cases in a diffuse distribution distant to the missle track with severe involvement of the brain stem in all cases. There was no axonal APP immunoreactivity in the direct region of the missle track at the point of primary axotomy. The APP-positive AI in these cases is likely to be a mixture of primary and secondary AI as APP immunostaining is unable to distinguish primary AI due to mechanical deformation from AI secondary to hypoxic-ischemic damage.

Axonal injury in falls.

Amyloid precursor protein (APP) immunocytochemistry was used as a marker for axonal injury (AI) in a series of 16 cases of head trauma associated with fatal falls. Nine cases were falls from not more than the person's own height (falls from < or = own height) and seven cases were falls from a distance greater than the person's own height (falls from > own height). AI was recorded on a series of line diagrams of standard brain sections divided into 116 sectors. AI around focal lesions (infarcts, hemorrhages, contusions) was distinguished from nonfocal axonal injury that was distant from any focal area of damage. The percentage of sectors showing focal AI provided the Focal Axonal Injury Score (FAIS) and the percentage showing nonfocal AI the Non-Focal Axonal Injury Score (NFAIS). The FAIS is a measure of secondary AI and the NFAIS of diffuse axonal injury (DAI). The percentage of sectors involved with AI (focal and nonfocal) provided the cumulative Axonal Injury Score (AIS). A semiquantitative grading system was also used to assess the severity of axonal injury in each sector and the sum of the grades from all sectors was expressed as a percentage to provide the Axonal Injury Severity Score (AISS). Widespread AI was present in all cases irrespective of the height of the fall. AI was present in the midbrain (94%), pons (94%), corpus callosum (100%), central grey matter (100%), and cerebral hemispheric white matter (94%). AIS ranged from 10 to 94 in falls from < or = own height (mean 73) and from 38 to 92 in falls from > own height (mean 82). AISS ranged from 6 to 95 in falls from < or = own height (mean 65) and 28 to 95 in falls from > own height (mean 72). There was no statistically significant difference in AIS or AISS between the two groups. The extent and severity of AI cannot be predicted from biomechanical data, such as the height of the fall, as the total AI in a given case is a variable mixture of Nonfocal AI (DAI) and Focal AI arising by secondary mechanisms, and APP immunostaining is unable to distinguish primary from secondary AI. However, the combination of the Hypoxic-Ischemic Score (HIS) defined as the percentage of sectors showing any hypoxic-ischemic damage ranging from neuronal "red cell change" to infarction in conjunction with the FAIS and NFAIS provided a measure of the relative contribution of primary and secondary AI in a given brain.

Progress in the moral reasoning of baccalaureate nursing students between program entry and exit.

Changes in moral reasoning between entry into and exit from a baccalaureate nursing program and the relationship between student characteristics and moral reasoning at entry and exit were explored in this descriptive study. The moral reasoning of four cohorts of students was measured using the Defining Issues Test (DIT). Admission grade point average, prior college credits, and gender accounted for 10% of the variance in DIT P% scores at entry and 14% of the variance at exit from the program. Female students had significantly higher moral reasoning scores than men. Age did not contribute significantly to explaining DIT score variance. DIT P% scores at entry for all four cohorts were within the range of reported norms for college students. Exit scores for all four cohorts were between the normative means for undergraduate students and graduate students. DIT P% score gains between entry and exit were significant for all four cohorts. Students whose entry scores were in the lowest categories had the greatest mean gains.

Intramuscular haemangioma of the chest wall. A case report.

Intramuscular haemangiomas of thoracic skeletal muscle are uncommon tumours. They are locally invasive and tend to recur if not completely and widely excised. This report illustrates the diagnosis and management of a 25-year-old man with an intramuscular haemangioma of the chest wall. A literature report on the aetiology and management of these tumours is also given.

Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury.

Axonal injury (AI), as defined by amyloid precursor protein (APP) positive axonal swellings, was recorded on a series of line diagrams of standard brain sections divided into 116 sectors to provide an Axonal Injury Sector Score (AISS) ranging from 0 to 116. This sector scoring method of recording axonal damage and providing a topographic overview of AI was applied to a series of 6 mild head injury cases [Glasgow Coma Scale (GCS) 13-15] and six severe head injury cases (GCS 3-8). The AISS ranged from 4 to 107 overall and varied from 4 to 88 in the mildly injured group and 76 to 107 in the severe head injury group, supporting the concept that there is a spectrum of AI in traumatic head injury and that the AISS is a measure of the extent of AI. APP immunostaining demonstrated positive axonal swellings 1.75 h after head injury and analysis of the pattern of AI in the mild and severe head injury groups showed that axons were more vulnerable than blood vessels and that the axons in the corpus callosum and fornices were the most vulnerable of all.

Lipoma of corpus callosum associated with dysraphic lesions and trisomy 13.

We report on a further case of corpus callosal lipoma and frontal cranial defects. Most cases in the literature of corpus callosal lipoma in association with "dysraphic" lesions have been frontal in location. Malformation of the corpus callosum is said to be associated with 50% of these lipomas. Trisomy 13 was confirmed by the 13q14 cosmid probe on paraffin-embedded liver tissue.