No abstract

In 100 patients who had taken an acute overdose of paracetamol the liver was biopsied percutaneously on the 4th day or as soon thereafter as recovery of the clotting mechanism allowed. A system for grading the histological changes in the liver is described. The hallmark of severe (grade III) damage is centrizonal necrosis, for which there is probably a dosage threshold. Consequent changes include phagocytosis of cell debris, reticulin collapse, and an inflammatory infiltration; acidophil degeneration of hepatocytes is sometimes prominent; regenerative growth is already evident after 4 days. Mild (grade I) damage is characterized by excess of lipofuscin pigment in centrizonal hepatocytes, sparse focal necrosis of liver cells, and some phagocytosis of lipofuscin. The findings in moderate (grade II) damage are similar but more pronounced. Five patients died in acute hepatic failure, and 22/100 showed severe (grade III) changes but survived. Forty-nine patients representing all three grades of liver damage were rebiopsied after 3 months. Central necrotic zones were found to have been completely reconstituted leaving only minor abnormalities except for one patient who showed mild centrilobular fibrosis and scarring of a nonprogressive nature.

We have studied forty patients who were at risk of hepatic, renal, pancreatic or myocardial injury as a consequence of severe paracetamol overdosage and who were admitted to hospital within 10 h of ingestion. These were sequentially randomized into three treatment groups, comprising intravenous cysteamine therapy (3.6 g over 20 h, n = 14), oral methionine (10 g over 16 h, n = 13) or supportive therapy only (intravenous 10% dextrose with vitamins, n=13). All groups were matched for age, ingestion-treatment interval and severity of poisoning as estimated by stated amount ingested and a logarithmic paracetamol blood level index. One death occurred in the supportive therapy (S) group. Significant differences in peak serum aspartate aminotransferase levels were seen with geometric means in S of 1046 U/l, in cysteamine treatment of 96 U/l and in methionine treatment of 139 Ull (Wilcoxon sum of ranks p < 0.01 in favour of methionine, p < 0.002 in favour of cysteamine). Hepatic necrosis, as shown by ‘blind’ histological assessment, was significantly less frequent in actively treated patients (methionine p < 0.05, cysteamine p < 0.01). These differences in favour of cysteamine and methionine were also reflected in peak serum bilirubin and prothrombin ratio. No significant effects of active treatment were shown for serial plasma creatinine, serum amylase, myocardial enzymes or ECG changes. We conclude that in the context of a prospective controlled trial of active agents: A convincing hepatoprotective effect of early i.v. cysteamine and oral methionine has been demonstrated. No clear difference in efficacy of the two antidotes has been shown. Early methionine administration is associated with few, if any, undesirable side-effects.

In 1995, of 120 doctors who had been suspended and investigated for incompetence by the study group of the Society of Clinical Psychiatrists, five were haematologists and 14 histopathologists. Only 16% of suspensions were proven justified at a tribunal. Two haematologists and three pathologists were reinstated, three haematologists and five pathologists accepted a settlement, four pathologists were dismissed, and two cases were sub judice. Furthermore, this study showed that "women doctors are much less likely to get their jobs back than men whilst, at the same time, more often found not guilty of any professional misdoing".

SUMMARY Marked pancreatic islet cell hyperplasia was found in a patient with laxative-induced diarrhoea. It is suggested that laxative abuse might be an important aetiological factor in patients with pancreatic islet cell hyperplasia and the watery diarrhoea syndrome but in whom no hormonal excess can be demonstrated.The abuse of laxatives is a well-recognised cause of watery diarrhoea and is most frequently seen in middle-aged women (Cummings et al., 1974). The diagnosis of this condition can frequently be difficult because such patients ingest laxatives only intermittently and vegetable laxatives cannot easily be detected in stool and urine. The watery diarrhoea syndrome is an important differential diagnosis and, in the absence of a tumour mass, this is frequently associated with pancreatic islet cell hyperplasia (Verner and Morrison, 1974). In this paper we describe a patient with watery diarrhoea caused by chronic laxative abuse in whom marked pancreatic islet cell hyperplasia was also found. Case historyA thirty-nine year old Caucasian male first presented in 1971 when he required five admissions to hospital for pilonidal sinus surgery. In 1972 he developed a discharging sinus in the right groin and after excision first developed diarrhoea with the passage of bloodstained mucus. Investigations, including barium meal, barium enema, and sigmoidoscopy, were normal. The diarrhoea continued and after losing 19 kg (3 stones) in weight he was admitted for investigation but no abnormality was found apart from a low serum folate. About this time he first complained of cramping lower abdominal pain. In 1973 he was admitted on three occasions for vasectomy, re-excision of a pilonidal sinus, and appendicectomy (appendix histology normal) but during this time the diarrhoea had subsided. In early 1974 he was admitted with chest pain and later that year he developed heartburn, vomiting, and weight loss of 16 kg (2j stones). Investigations were normal Received for publication 30 May 1977 but a laparotomy and cholecystectomy were performed. Neurological and psychiatric assessments at this time were normal.In August 1974 he had a lymph node biopsy and soon after this presented to Medical Outpatients with intractable diarrhoea with a stool volume of 3 1 per day, some lower abdominal pain, and weight loss. At this time laxative abuse was considered but this he denied and tests for phenolphthalein and magnesium in the stool were negative. The watery diarrhoea syndrome was also considered but serum gastrin, enteroglucagon, secretin, vasoactive intestinal polypeptide, and urinary 5 hydroxyindolactic acid concentrations were normal. He never became hypokalaemic. In May 1975 he was admitted for a further laparotomy because of continuing disabling symptoms but the intra-abdominal organs were completely normal. A distal pancreatectomy was performed and a 10 cm segment of the ileum was reversed in an attempt to slow down intestinal transit. Postoperatively there was an immediate cessation of symptoms and his weight returned to nor...