Continuing education programme - Victorian Institute of Forensic Medicine and Department of Forensic Medicine, Monash University.

Given the increasing requirement of the courts for forensic experts to engage in ongoing education, a continuing education programme was developed in forensic medicine at the Victorian Institute of Forensic Medicine to cater for both clinicians and pathologists. The programme consists of a series of cases which are circulatged several times per year. All are actual cases and are reflective of the types of presentations experienced in forensic medicine. Each case includes relevant and appropriate details/findings and may include photographs. A series of questions follow which are answered usually in short-answer format. The answers are returned and correlated by a review panel, and a commentary with the response outcome is distributed to all those involved. The cases presented here are selected from this programme.

A profile of deaths in custody in Victoria, 1991-96.

In Victoria, all deaths in custody are investigated and a coronial inquest is held. The findings are entered into a data base held at the Victorian Institute of Forensic Medicine. Utilizing this data base, all listed cases of deaths in custody during the 6-year period, January 1991-December 1996, were reviewed. The deceased's age, sex, cause and mechanism of death and the custodial service under which they were held at the time of death were correlated. During the 6-year period, there was a total of 96 deaths (90 male, six female) ranging in age from 15-77 years. Of all the cases, 45 occurred whilst in police custody, 30 under corrective services and 21 involved non-custodial corrections. There were 31 accidental deaths, 29 suicides, 17 natural deaths, and 18 police shootings. Excluding police shootings, 42 deaths involved the presence of drugs or alcohol, either as a direct cause of death or as a contributory factor. Drug toxicity alone was implicated in 28 deaths. Deaths from unnatural causes remains the major cause of death of persons in custody. An awareness of these causes must assist in developing mechanisms to further reduce fatalities in this setting.

Fitness for interview: current trends, views and an approach to the assessment procedure.

The medical assessment of a person's fitness to be interviewed by police is undertaken to determine the detainee's competence at interview. A review of this procedure in Victoria was conducted on all cases during the period 1 January 30 June 1997. One hundred and fifty-one cases were assessed. The majority of cases were in the 20-39 years age range with 81.5% of all cases being male. The principal reasons for assessment were concerns about the effects of drugs excluding alcohol (21.9%), and psychiatric issues (25.8%). Following assessment, 47% were considered to be fit for interview but in 14% of these cases an independent third person was recommended. Thirty-five per cent were assessed as being unfit for interview and 58.6% of these were referred for further assessment. Rarely (4.6%) in these cases and those referred for treatment elsewhere were reviews arranged prior to the interview. Despite the significant dependence of the prosecution on confessional evidence, in only 4% of cases was the matter eventually raised in court. The findings indicate that there is a need to ensure that practitioners are appropriately trained in the assessment of drug-affected and psychiatric patients. New guidelines for the assessment are presented which may assist in reducing the degree of subjectivity and opinion variability.

Continuing education programme - Victorian Institute of Forensic Medicine and Department of Forensic Medicine, Monash University.

Given the increasing requirement of the courts for forensic experts to engage in ongoing education, a continuing education programme was developed in forensic medicine at the Victorian Institute of Forensic Medicine to cater for both clinicians and pathologists. The programme consists of a series of cases which are circulated several times per year. All are actual cases and are reflective of the types of presentations experienced in forensic medicine. Each case includes relevant and appropriate details/findings and may include photographs. A series of questions follow which are answered usually in short-answer format. The answers are returned and correlated by a review panel, and a commentary with the response outcome is distributed to all those involved. The cases presented here are selected from this programme.

Continuing education programme - Victorian Institute of Forensic Medicine.

With the increasing requirement of the courts for forensic experts to engage in ongoing education, a continuing education programme (CEP) was developed in the field of clinical forensic medicine at the Victorian Institute of Forensic Medicine in 1996. This programme has been described and was initially established to provide a means of education for the contracted forensic medical officers who provide forensic services to the police via the Institute throughout the State of Victoria. Owing to the sparsity of the population and the considerable distances between forensic practitioners, the CEP was designed to cater for individuals who are working alone: in effect, a distance education programme. Forensic pathologists expressed interest in the programme and it was subsequently modified to include forensic pathology cases. Currently, the programme caters for both clinicians and pathologists, and takes the form of four to five cases with related questions which are circulated several times per year. The cases include a mixture of both challenging and ordinary procedural types that may present to practitioners working in either clinical forensic medicine or forensic pathology, or both. The areas covered include: * injury interpretation * procedural matters in relation to adult and child sexual and physical assault * pharmacology/toxicology interpretation of findings * medico-legal issues (e.g. confidentiality, consent, etc.) * issues relating to alcohol and drugs * traffic medicine * clinical and legal aspects of sudden natural death * suspicious deaths * suicide * interpretation of findings at autopsy * fitness for interview * fitness to plead * psychiatric issues * general clinical medical issues. The presentation of each case includes relevant and appropriate details/findings and may include photographs. A series of questions follow which are answered in either short answer or multiple-choice format. The answers are returned and are correlated by a review panel of forensic physicians and pathologists, and a commentary with the response outcomes is distributed to all those involved. This also includes pertinent references. The cases presented here and in subsequent issues are selected from this programme.

Continuing education in forensic medicine: an exercise in distance learning.

Distance education and its application to postgraduate clinical medicine and continuing education in medicine is a recent development. Given the increasing requirement of the courts for forensic experts to engage in ongoing education, a continuing education programme (CEP) was developed in the field of clinical forensic medicine. This programme is the first programme available in clinical forensic medicine. Due to the interest expressed by forensic pathologists, the CEP has been modified to include cases of forensic pathology interest and the programme is now subscribed to by both clinicians and pathologists. The programme is reflective of the types of cases experienced in forensic medicine and is designed for individual practitioners working alone.

Death due to benzhexol toxicity.

A rare case of death due to benzhexol toxicity is reported in a 48-year-old schizophrenic male with a resolving empyema and underlying patchy, mild bronchopneumonia. Toxicological analysis revealed the benzhexol blood and liver concentrations to be 0.12 mg/l and 0.5 mg/kg, respectively. Gastric contents contained 0.4 mg of benzhexol. Other drugs were not detected. It is suggested that for fatalities to occur following benzhexol intoxication, secondary contributory factors, which probably further alter the patient's conscious state, are necessary.

Mice lacking both macrophage- and granulocyte-macrophage colony-stimulating factor have macrophages and coexistent osteopetrosis and severe lung disease.

Mice deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF, CSF-1) were generated by interbreeding GM-CSF-deficient mice generated by gene targeting (genotype GM-/-) with M-CSF-deficient osteopetrotic mice (genotype M-/-, op/op). Mice deficient in both GM-CSF and M-CSF (genotype GM-/-M-/-) are viable and have coexistent features corresponding to mice deficient in either factor alone. Like M-CSF-deficient mice, they have osteopetrosis and are toothless because of failure of incisor eruption. Like GM-CSF-deficient mice, they have a characteristic alveolar-proteinosis-like lung pathology, but it is more severe than that of GM-CSF-deficient mice and is often fatal. In particular, in GM-/-M-/- mice the accumulation of lipo-proteinaceous alveolar material is more marked, and bacterial pneumonic infections are more prevalent and more extensive, particularly involving Gram-negative bacteria. Neutrophilia consistently accompanies pulmonary infections, and some older GM-/-M-/- mice have polycythemia. Survival of GM-/-M-/- mice is significantly reduced compared with mice deficient in either factor alone, and all GM-/-M-/- mice have broncho- or lobar-pneumonia at death. These observations indicate that in vivo, M-CSF is involved in modulating the consequences of GM-CSF deficiency in the lung. Interestingly, GM-/-M-/- mice have circulating monocytes at levels comparable with those in M-CSF-deficient mice and the diseased lungs of all GM-/-M-/- mice contain numerous phagocytically active macrophages, indicating that in addition to GM-CSF and M-CSF, other factors can be used for macrophage production and function in vivo.

Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology.

Mice homozygous for a disrupted granulocyte/macrophage colony-stimulating factor (GM-CSF) gene develop normally and show no major perturbation of hematopoiesis up to 12 weeks of age. While most GM-CSF-deficient mice are superficially healthy and fertile, all develop abnormal lungs. There is extensive peribronchovascular infiltration with lymphocytes, predominantly B cells. Alveoli contain granular eosinophilic material and lamellar bodies, indicative of surfactant accumulation. There are numerous large intraalveolar phagocytic macrophages. Some mice have subclinical lung infections involving bacterial or fungal organisms, occasionally with focal areas of acute purulent inflammation or lobar pneumonia. Some features of this pathology resemble the human disorder alveolar proteinosis. These observations indicate that GM-CSF is not essential for the maintenance of normal levels of the major types of mature hematopoietic cells and their precursors in blood, marrow, and spleen. However, they implicate GM-CSF as essential for normal pulmonary physiology and resistance to local infection.

Multiple benign stromal cell tumours of the small bowel.

A rare case of multiple small intestinal stromal cell tumours is described in a 79 year old woman who presented with melaena and anaemia. At surgery, about 40 lesions were noted on the serosal surface of the small intestine, the largest of these tumours being located in the mid-jejunum. This lesion showed central necrosis and haemorrhage with a sinus opening into the jejunal lumen. Histological examination of this jejunal tumour showed epithelioid and spindle shaped cells. A smaller biopsied tumour was a pure spindle cell lesion. Both lesions fitted the criteria for benign stromal cell tumours. Although skenoid fibres were identified, the immunophenotype was characteristically heterogeneous. Multiple benign small intestinal tumours can raise the spectre of metastases when seen at surgery, although their presence in this case does not seem to indicate this.

Origin and involution of hyperplastic bile ductules following total biliary obstruction.

The origin of biliary epithelial cells (BEC) lining hyperplastic bile ductules in the liver in biliary disease is uncertain. Depending on the underlying condition, the hyperplastic BEC may arise by multiplication of existing BEC, transdifferentiation of liver cells to BEC or by both mechanisms. Using histological, autoradiographic and immunohistochemical techniques, the development of these ductules was assessed in rats following total biliary obstruction (TBO) for periods of up to 50 days. Histologically, a biliary cirrhosis developed after 21 days. Apoptosis was observed in both liver cells and BEC at all stages following TBO, and focal involution of hyperplastic ductules by this mode of cell deletion was noted at 50 days. The 3H-thymidine labelling index was approximately 25 times greater (p less than 0.0005) than control values in both liver cells and BEC at all stages following TBO, reaching peak values at 48 h of 6.07 +/- 0.82% for liver cells and 15.99 +/- 1.47% for BEC. In sections stained by the immunoperoxidase technique and using a prekeratin antiserum to identify BEC, an increase in the number of canals of Hering was observed at days 7 and 21. An intermediate-type cell possessing the morphological appearance of a liver cell and expressing prekeratin antigens was seen in an occasional canal of Hering. On the basis of the high cell replication rate of liver cells and BEC and the very occasional intermediate-type cell, it was concluded that hyperplastic BEC are derived essentially from existing BEC by cell division. The contribution to the BEC pool from an intermediate cell type within the canals of Hering was small.

A quantitative analysis of the liver following ligation of the common bile duct.

A quantitative analysis of the liver was performed at intervals of 24, 48, 72 and 96 h and 7, 21 and 50 days following total biliary obstruction (TBO) in the Sprague-Dawley rat. During this period, the liver weight increased from 7.72 +/- 0.51 g (mean +/- SEM) in controls to 24.57 +/- 1.66 g (p less than 0.0005) at 50 days. There was a concomitant reduction in the volume proportion of the liver occupied by liver cells, from 71.37 +/- 1.36% to 21.54 +/- 3.27% (p less than 0.0005), but there were increases in the volume proportions of biliary epithelial cells (BEC) from 0.14 +/- 0.02% to 16.39 +/- 1.12% (p less than 0.0005), of other cell and tissue types from 5.50 +/- 4.89% to 30.73 +/- 2.42% (p less than 0.0005) and of vascular and biliary channel spaces from 22.99 +/- 1.17% to 31.35 +/- 0.87% (p less than 0.0025). In control animals, the liver cell and BEC volume was estimated to be 6240 +/- 360 microns 3 and 100 +/- 10 microns 3, respectively. Following TBO, the liver cell volume was significantly greater than control only from 48-96 h, whereas the BEC increased significantly in volume from 24 to 72 h and then remained approximately 6 times the control value until the end of the period of study. Contrary to the histological appearance and decrease observed in volume proportion, the total liver cell population did not significantly differ from the control value of 8.83 x 10(8) +/- 0.80 x 10(8) cells, other than at 21 days when it increased to 14.90 x 10(8) +/- 1.04 x 10(8) cells (p less than 0.05). When expressed as the number of liver cells/100 g b.wt., an increase from the control value of 4.37 x 10(8) +/- 0.32 x 10(8) cells was observed only at 7 (5.66 x 10(8) +/- 0.42 x 10(8) cells; p less than 0.05) and 21 days (6.94 x 10(8) +/- 0.48 x 10(8) cells; p less than 0.05). This maintenance of liver cell population, following biliary obstruction, at or above the control values matches the clinical observation of preserved liver cell function. The total BEC population in control livers was 1.11 x 10(8) +/- 0.20 x 10(8) cells. A significant increase in this population was observed at 7 days (3.82 x 10(8) +/- 0.62 x 10(8) cells; p less than 0.05) with further increases to 57.90 x 10(8) +/- 6.42 x 10(8) cells (p less than 0.05) at 50 days, 52 times the control value. When expressed as cells/100 g b.wt., similar changes were observed. The results reported here indicate the importance of taking into account the change in the entire organ size and total mass of the cells in question when assessing alterations in their number.

Qualitative and quantitative analysis of granules in atrial appendage cardiocytes in different physiological states.

Atrial appendage cardiocytes of mammals, including man, contain multiple cytoplasmic granules that vary in number in different physiological states. Using morphologic and comprehensive morphometric techniques, these granules were assessed in Sprague-Dawley rats following dehydration for 5 days, volume-loading by substituting 1% NaCl as drinking water for 7 days, unilateral nephrectomy plus volume-loading for 7 days, and in late term pregnant animals (18-20 days; term approximately 21 days). Although principally located in the paranuclear region, granules were observed throughout the sarcoplasm. Cytological features indicative of synthetic activity and granule formation were readily apparent in all groups with the exception of pregnant rats where they were infrequently observed. Granule contents were released by exocytosis and observed in the right appendage of control, dehydrated and nephrectomy/volume-loaded groups and left appendage of volume-loaded animals. Exocytosis was not observed in pregnant animals. By point counting, the proportional volume of cardiocytes occupied by granules (Vv) in controls was significantly greater for right than for left appendage (2.12 +/- 0.22% vs 1.29 +/- 0.16%; mean +/- SEM; p less than 0.05). A significantly similar difference was found for nephrectomy/volume-loaded animals. There was no significant difference in Vv for right appendage between the control and experimental groups; for left appendage there was a significant increase in Vv to 2.42 +/- 0.09% (p less than 0.05) for volume-loaded animals only. Estimation of the maximum diameter of granule profiles in control animals was 238 +/- 9 nm and 230 +/- 6 nm for right and left appendages, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of intrahepatic bile ducts in rat foetal liver explants in vitro.

The origin of intrahepatic bile ducts was investigated in organ cultures of 13, 16 and 19-day foetal rat livers embedded for up to 10 days in a semi-solid agar gel on a filter-raft assembly. Following 10 days in culture, 13-day foetal explants consisted of liver cell trabeculae lined by endothelial cells. Although maturation of the liver cells and bile canaliculi was observed, duct development was found in less than 10% of the explants. Supplementation of the media with putative inducers of bile duct development or culture of explants adjacent to other tissues did not induce regular duct development. By contrast, explants from the porta hepatis of 19-day foetuses cultured for 4 days, but not 10 days, regularly contained duct-like structures. The formation of the few ducts in cultures of 13-day foetal liver explants indicates that these cells can arise by transformation of hepatoblasts but that specific inducers of development are required for predictable and continuous differentiation of biliary epithelial cells.

Morphological and immunohistochemical assessment of intrahepatic bile duct development in the rat.

The hypotheses that intrahepatic bile ducts are derived either by a transformation of periportal liver cells or by dichotomous branching of the extrahepatic bile ducts were investigated in fetal and postnatal rat livers by histological and immunohistochemical methods using an antiserum to prekeratin which, in the liver, binds to biliary epithelial cells (BEC). In conventionally stained sections, bile duct development was observed to begin in the 19 day fetus around the larger branches of the portal vein, with the formation of lumina surrounded by cuboidal or elongated hepatoblast-like cells on the portal aspect and readily distinguished hepatoblasts on the lobular aspect. At 21 days, these structures had developed into canals of Hering lined jointly by recognizable liver cells and BEC. The number of canals of Hering per portal tract peaked at 22 days' gestation and diminished in number at birth and over the ensuing 56 h, with a concomitant increase in fully formed ducts. Bile ducts lined completely by BEC were first found at 20 days. Immunohistochemically, prekeratin antigens were first detected at 20 days in duct-like structures not only in phenotypic BEC but also in adjacent cells with an hepatoblast phenotype. Such intermediate cells were present until birth. These findings support the view that intrahepatic bile ducts develop by a reorganization and modulation of the periportal hepatoblasts to BEC.