Gilbert Lau

Fatal retroperitoneal haemorrhage: an unusual complication of percutaneous endoscopic gastrostomy

A 93-year-old lady with dementia, neurological dysphagia and aspiration pneumonia, died from massive retroperitoneal haemorrhage which developed as a rare and, it is believed, hitherto unreported, complication of percutaneous endoscopic gastrostomy (PEG), which was performed for feeding purposes. It is postulated that the initial, unsuccessful attempt at needle puncture of the stomach, under endoscopic guidance, had resulted in iatrogenic perforation and laceration of the splenic and superior mesenteric veins close to their confluence with the portal vein. It would also appear that dense fibrous adhesions between the pyloro-antral region of the stomach and the posterior hepatic surface had altered the immediate anatomical relations of the stomach in such a manner as to have predisposed to these events.

Fatal falls from a height: The use of mathematical models to estimate the height of fall from the injuries sustained

The authors undertook a review of fatal falls from a height, that occurred in 1991-92 in Singapore, with the objective of constructing mathematical models relating the height of fall to the injuries sustained. The 603 cases studied showed a mean age of 41.4 years with a male to female ratio of approximately 2:1. A sub-sample of 416 (69%) of these subjects had fallen from known heights (mean, 26.9 m; range, 3-69.6 m) and were studied in further detail. Bivariate analysis of this group showed that their injury severity score (ISS) was significantly correlated with the height of fall (H) and age (P < 0.01; r = 0.412 and 0.187, respectively). As the ISS is not strictly a continuous variable and varied markedly with H, it was categorised into bands (ISSB) before being subjected to further analysis. Regression modelling to adjust for mutual confounding showed that both height of fall and age were significant independent determinants of the ISSB (P < 0.0001). A model with H as the dependent variable was then constructed to relate the height of fall to ISSB and other statistically significant indicators of the extent and the severity of the injuries sustained. A second model with bands of height (HB) as the dependent variable was similarly constructed to assess the effect of banding both height and ISS. Our findings suggested that the height of fall was significantly associated with age, ISS and the extent of injury (mostly AIS > or = 3), and confirmed the usefulness of these models for investigative purposes. Statistical models could be designed and used to assess any apparent discrepancy between injury severity as determined at autopsy and the suspected/alleged height of fall.

1. A Fatal Case of Hepatic Failure Possibly Induced by Nitrosofenfluramine

A 42-year-old female developed fulminant hepatic failure after having ingested an undetermined quantity of a herbal product over a period of approximately four months prior to the onset of her illness. Clinically, the cause of liver failure was assessed to be drug-induced and she eventually underwent total hepatectomy, with porto-caval shunting, in anticipation of a living-unrelated liver transplant. Unfortunately, her condition deteriorated and she died less than 48 hours postoperatively, approximately three weeks post-admission. An autopsy showed that the subject was deeply jaundiced and severely obese (BMI: 47.1 kgm-2), with evidence of diffuse haemorrhage, including the presence of 1.35 l of blood in the peritoneal cavity. The liver had been removed and was later recovered as a formalin-fixed specimen which was markedly contracted, comprising multiple micronodules interspersed with extensive areas of dense fibrotic tissue. Histologically, there was massive necrosis of the hepatic parenchyma, such that the residual hepatocytes were disposed as nodules displaying variable cellular regeneration and ballooning degeneration, attended by florid ductal proliferation and mixed inflammatory infiltrates. Infective, autoimmune, metabolic, vascular, neoplastic and most other natural causes of massive hepatocellular necrosis were effectively excluded. Analysis of the post-mortem blood samples yielded fluconazole, metronidazole, frusemide, lignocaine and tramadol, (therapeutic agents administered to the patient during her last illness). Subsequent analysis of the residual capsules revealed that they were adulterated by fenfluramine, N-nitrosofenfluramine (1.3-1.6 mg per capsule), nicotinamide (13.3-15.6 mg per capsule) and thyroid extract. None of the herbal ingredients is currently known to be hepatotoxic and much the same applies to fenfluramine, nicotinamide (except when taken in mega-doses) and thyroid extract. However, as nitrosamines are known to be variably hepatotoxic, it would be reasonable to surmise that, in the absence of a more plausible cause of liver damage, N-nitrosofenfluramine was the likely cause of massive hepatocellular necrosis in this instance.

Sudden death arising from a congenital coronary artery fistula

A medico-legal autopsy conducted on a young Chinese man, a victim of sudden unexpected death, with a vague and unconfirmed history of congenital cardiovascular disease, revealed the presence of a congenital right coronary artery (arteriosystemic) fistula communicating with the markedly hypertrophied left ventricle, which showed microscopic evidence of myocardial ischaemia. The pathology of this rare condition is described and briefly reviewed.

1. Accidental Intraventricular Vincristine Administration: An Avoidable Iatrogenic Death

A patient with acute lymphoblastic leukaemia was mistakenly given vincristine intraventricularly, as part of an intensified course of chemotherapy. Despite a CNS washout and supportive treatment, the patient developed progressive ascending paralysis, gradually lapsed into coma and died some 10 days later. Autopsy and post-mortem histological examination showed evidence of brain death caused by florid encephalomyelitis, apparently induced by the intraventricular administration of vincristine.

A fatal case of drug-induced multi-organ damage in a patient with Hansen's disease: dapsone syndrome or rifampicin toxicity?

An elderly patient with borderline tuberculoid Hansens disease (leprosy) developed the diaminodiphenylsulphone syndrome after approximately 8 weeks of multi-drug therapy comprising dapsone and rifampicin. Postmortem histological examination, following autopsy, demonstrated features consistent with drug-induced hepatitis, tubulo-interstitial nephritis and myocarditis. Although these could have been engendered by dapsone toxicity, it was thought that a concommitant adverse reaction to rifampicin, which is known to be hepatotoxic, nephrotoxic and possibly capable of predisposing to the dapsone syndrome, could not be excluded.

Massive hepatocellular [correction of hepatocullular] necrosis: was it caused by Orlistat?

Orlistat (tetrahydrolipostatin) is a lipase inhibitor which is used, in conjunction with appropriate dietary control, for the treatment of obesity. It is generally deemed to be a safe drug, which mainly exerts a topical action on the stomach and small bowel, with negligible systemic absorption and oral bioavailability. Consequently, its adverse effects have largely been limited to relatively mild gastrointestinal disorders. However, there have been recent, published reports of non-fatal acute hepatitis and systemic hypertension associated with its use. The present case concerns a 62-year-old male who died from massive hepatocellular necrosis, consistent with drug-induced, fulminant hepatitis, associated with the use of oral orlistat, presumably administered at the recommended daily dose of 360 mg. It is postulated that this may represent a rare idiosyncratic reaction to the drug.Orlistat (tetrahydrolipostatin) is a lipase inhibitor which is used, in conjunction with appropriate dietary control, for the treatment of obesity. It is generally deemed to be a safe drug, which mainly exerts a topical action on the stomach and small bowel, with negligible systemic absorption and oral bioavailability. Consequently, its adverse effects have largely been limited to relatively mild gastrointestinal disorders. However, there have been recent, published reports of non-fatal acute hepatitis and systemic hypertension associated with its use. The present case concerns a 62-year-old male who died from massive hepatocellular necrosis, consistent with drug-induced, fulminant hepatitis, associated with the use of oral orlistat, presumably administered at the recommended daily dose of 360 mg. It is postulated that this may represent a rare idiosyncratic reaction to the drug.

Bronchioloalveolar carcinoma with metastasis to the pituitary gland: a case report.

An unusual case of metastatic bronchioloalveolar carcinoma of the lung presented as a pituitary tumour in a young adult Chinese female, who subsequently died after having undergone trans-sphenoidal resection. Metastatic cancers of the pituitary are uncommon even in necropsy series and rarely give rise to clinical symptoms. This case draws attention to the fact that, although uncommon, pituitary metastases have been noted with increasing frequency and their distinction from primary pituitary tumours is often difficult. A metastatic pituitary tumour may be the initial presentation of an unknown primary malignancy, wherein the metastatic deposits may also be limited to the pituitary gland. Clinicians and pathologists alike should consider a metastatic lesion in the differential diagnosis of a non-functioning pituitary tumour.

A case of sudden maternal death associated with resuscitative liver injury

A pregnant lady suffered massive pulmonary thromboembolism whilst undergoing pelvic ultrasonography at an obstetric unit. She was vigorously resuscitated for approximately 2 h and later transferred to a cardiovascular surgical department where an emergency pulmonary embolectomy was performed, at which time, some 21 of blood, emanating from lacerations of the right hepatic lobe, were found in the peritoneal cavity. Despite heroic measures, she died intraoperatively, having developed clinical features of disseminated intravascular coagulation. Autopsy demonstrated the presence of multiple liver lacerations which are believed to have been caused by protracted external cardiac massage and would have contributed to her death.

Suicide trends in Singapore: two decades down the road.

In this study, recent trends in the incidence and methods of suicide in Singapore, over the period 1991-2000, were compared with the results of a previous study covering the period 1975-1984 (Tan, 1986). The present study included a total of 3,834 suicidal deaths reported to the coroner and investigated by the Centre for Forensic Medicine of the Health Sciences Authority. The results showed that the crude suicide rate had stabilised over the last decade and that the rate was highest among elderly males. The three most common methods employed were falls from a height (69.3%), hanging (20.7%) and poisoning (5.5%). Comparison of the results of both studies showed that the crude suicide rate had stabilised over the last two decades. However, there was an increase in the suicide rates among males, as compared with the previous study, and a marginal decrease in suicide rates among females over this time. There was also an appreciable change in the methods of suicide employed, in that there was an increase in the proportion of deaths due to falls from a height and corresponding reductions in the proportions of deaths by hanging and poisoning.