Liver damage due to perhexiline maleate.

Two middle-aged men, who had received perhexiline in recommended dosage, showed clinical and histological evidence of severe hepatic damage, and one of them died. Histological study of the livers showed a striking resemblance to alcoholic hepatitis.

Liver scintiscanning as a screening test in the detection of alcoholic cirrhosis.

Ninety-nine patients with alcohol related problems underwent a liver scintiscan and biopsy. The scan changes were graded and compared with the histological changes found from percutaneous liver biopsy. The overall correlation between scan and biopsy changes was poor. However, scintiscanning was found to be highly sensitive (90%) in detecting cirrhosis and for this reason is useful as a screening test in selecting alcoholic patients for biopsy.

A case of Mollaret's meningitis associated with a lymphoma.

A patient with recurrent benign meningitis (Mollaret's meningitis) responding to treatment with colchicine by a reduction in frequency of attacks who has subsequently developed a non-Hodgkin's lymphoma is described.

Alcohol liaison in action. The Canterbury experience.

In the changing health service, cooperation between disciplines is essential and innovation important to improve the service for people whose health is at risk or damaged. We describe our response to the challenge of liaison between different disciplines when faced with a multifaceted problem that needs the contribution of medical and psychiatric teams and community workers. Although this method of work has been applied to alcohol misuse, it could also be applied to other clinical problems. Liaison can be successful if these is an identified need and the different groups share a desire to work together. To stimulate the liaison and maintain momentum there need to be driving forces, be they clinical, practical or economic, also a shared philosophy and language, a conceptual base in the care of that group of patients, mutual respect and agreed working arrangements. Psychiatry and medicine operating together can ensure that these patients are treated with fairness and respect. They can tap into resources not easily available to either discipline separately, and so create original and exciting services. They can discover other agencies and individuals in their communities who will cooperate with them in obtaining funds and in pressurising statutory bodies to develop much needed services.

Prevalence of dyspepsia: the epidemiology of overlapping symptoms.

Studies of the epidemiology of dyspepsia have been complicated by the use of different symptom definitions, subject populations and time frames of investigation. Published figures for the prevalence of dyspepsia vary from 20% to 40%, of which perhaps only a quarter can be attributed to peptic ulcer disease. General practitioners see only a fraction of the dyspepsia within the community, the majority of which is either ignored or treated by self-medication. However, dyspepsia still accounts for about 3-4% of all general practice consultations and for about 14% of all patients attending. In about half of all cases, even extensive investigation reveals no underlying organic lesion. There has been much recent interest in the clinical value of grouping dyspeptic symptoms into particular subtypes. These have been called ulcer-like, dysmotility-like and reflux-like. Although these patterns have descriptive value, there is no evidence that they result from discrete pathophysiological processes. Indeed, studies both in general practice and in the community show a large degree of overlap between them.

Serum CA 12-5 concentrations and CA 12-5/CEA ratios in patients with epithelial ovarian cancer.

In attempts to increase the specificity of the CA 12-5 test the ratio of CA 12-5 and CEA concentrations has been determined in 155 cancer patients, all of whom had an increased serum CA 12-5. The patients included 47 with epithelial ovarian cancer, 38 with colorectal cancer, 24 with cervical cancer, 20 with lung cancer, 17 with gastric cancer, and 9 with pancreatic cancer. The CA 12-5/CEA ratio in serum of patients with ovarian cancer ranged from 30 to 920 (mean 251), whereas in other types of cancer the highest ratio was 240 and the mean was 13. All 47 patients with ovarian cancer, but only 7 of the 108 patients with other types of cancer, showed a CA 12-5/CEA ratio greater than 25. About 10% of the patients with gastric or colorectal cancer but none of those with other types of cancer showed an increased ratio. As the predictive value of a CA 12-5/CEA ratio of less than 25 excluding ovarian cancer is 100%, we recommend measuring the CEA concentration in all those with increased CA 12-5 and calculation of the CA 12-5/CEA ratio.

Detection of antibodies to acetaldehyde-albumin conjugates in alcoholic liver disease.

The principal metabolite of ethanol, acetaldehyde, conjugates with various proteins that form antibody-inducing neo-antigens. We have analysed sera from patients with biopsy-proven alcoholic liver disease (hepatitis = 10, cirrhosis = 11, steatosis = 3) and controls = 19 (normal teetotallers and 6 non-alcoholic liver disease). Sera were examined with an enzyme-linked immunoabsorbent assay (ELISA) for antibodies binding preferentially to an acetaldehyde-albumin conjugate. Reactive sera from alcohol misusers were then purified using an amino-hexyl Sepharose affinity column. Antibodies binding to the acetaldehyde-albumin epitopes were significantly raised (P < 0.005) in all groups of alcohol misusers, and were present in greatest titre in those with alcoholic hepatitis. These antibodies were successfully purified using the gel affinity column. We conclude that alcohol misusers have significant titres of antibodies reacting to the acetaldehyde-albumin complex. The role of these antibodies remains nuclear, but may be related to the initiation of an inflammatory response and tissue damage following ethanol consumption.

Rapid onset of blindness due to meningeal carcinomatosis from an oesophageal adenocarcinoma.

We report a 49 year old man who presented with left leg weakness, frontal headache, impaired concentration and dysphagia. He was thought to have a benign oesophageal stricture on barium swallow and oesophagoscopy though this was not initially biopsied. During admission his vision deteriorated so that he could only recognize bright light. Repeat oesophagoscopy demonstrated an oesophageal adenocarcinoma. The diagnosis of meningeal carcinomatosis was confirmed at post-mortem. Sudden bilateral blindness is a common feature of meningeal carcinomatosis but, as this is rare, it is not commonly considered in the differential diagnosis of visual loss. The visual loss can be explained by vascular insufficiency in association with tumour cuffing of the subarachnoid space of the optic nerve sheath, by neuronal toxins, or other, as yet unknown, mechanisms.

Experimental hepatic necrosis: studies on coagulation abnormalities, plasma clearance, and organ distribution of 125I-labelled fibrinogen.

Studies in the rat with hepatic necrosis induced by carbon tetrachloride showed that the abnormalities in one-stage coagulation tests and the increased catabolism of fibrinogen were similar to those found in man with acute viral or drug-induced hepatic necrosis. Determination of the distribution of the radioactive label shows that excessive deposition was maximal in the liver but also occurred in the spleen. The appearance is delayed by heparin but accelerated by tranexamic acid.

Malignant carcinoid tumour with gangrene of the small intestine.

Four patients with a malignant carcinoid tumour of the small bowel (three had the carcinoid syndrome) developed gangrene of the small intestine. Attention is drawn to this seldom recognized complication, as early surgery may be life saving.

Liver transplantation in man--IV, Haemorrhage and thrombosis.

Blood coagulation and fibrinolytic factors have been measured in 13 patients treated by liver transplantation. During operation intravascular coagulation and fibrinolysis were increased, but seldom to a degree which would cause abnormal bleeding. Measurement of the catabolism of radioactive fibrinogen showed that increased intravascular coagulation continued for long periods after the operation. Despite secondarily increased fibrinolysis, there was a high incidence of thrombosis. Treatment with anticoagulants or with fibrinolysis inhibitors may be valuable in these patients.

Controlled trial of phetharbital, a non-hypnotic barbiturate, in unconugated hyperbilirubinaemia.

Eleven patients with mild unconjugated hyperbilirubinaemia (Gilbert's syndrome) took part in a double-blind cross-over trial of phenobarbitone and phetharbital, a non-hypnotic barbiturate. Significant reductions in plasma bilirubin were observed with both drugs, but six patients complained of sleepiness on phenobarbitone, and phetharbital was preferred by most patients. Phetharbital was also effective in the rare severe unconjugated hyperbilirubinaemia of the Crigler-Najjar syndrome (Type 2). Symptoms attributed to Gilbert's syndrome, including nausea and abdominal pain, were less consistently relieved.

75se-selenomethionine in the scintiscan diignosis of primary hepatocellular carcinoma.

Forty-eight patients with ;cold areas' on (99m)Tc sulphur colloid liver scintiscans were scanned again using (75)Se-selenomethionine. In 11 patients with primary hepatocellular carcinoma considerable uptake of (75)Se-selenomethionine could be demonstrated in the area of the tumour and uptake of (75)Se-selenomethionine was also observed over extrahepatic metastases in two of these cases. In contrast uptake was low in cholangiocellular carcinoma, Kupffer cell sarcoma, and secondary hepatic deposits (excepting melanoma metastases). No cause for the ;cold area' on the (99m)Tc scan could be discovered in 16 of 25 patients with cirrhosis and in these patients the uptake of the two isotopes in the area of the ;false positive' filling defect was almost equal. Positive identification of primary hepatocellular tumours using this dual scanning technique can be of value in determining and assessing treatment by surgery or cytotoxic therapy.

Ligation of the hepatic artery in the treatment of heart failure due to hepatic haemangiomatosis.

An infant presenting with high-output cardiac failure and a single large diffuse haemangioma of the liver is described. Corticosteroid therapy failed to produce any improvement, but hepatic artery ligation was followed by dramatic disappearance of the signs of cardiac failure and a decrease in the size of the liver without any evidence of lasting liver damage.

Early and intensive therapy of intravascular coagulation in acute liver failure.

Four consecutive patients, three with fulminant hepatic failure and one with a severe relapse of serum hepatitis, who showed evidence of intravascular coagulation, were treated intensively with heparin and fresh frozen plasma. Rapid correction of the coagulation disturbance was achieved, and all four patients recovered completely. The necessity for starting such treatment early in the course of the disease and before the onset of major gastrointestinal bleeding is stressed, and it is suggested that intravascular coagulation may act as an intermediary in the pathogenesis of the hepatic necrosis.

Chemotherapy in advanced gastric cancer: a controlled, prospective, randomised multi-centre study.

Seventy-six patients with advanced gastric adenocarcinoma were studied in a prospecitive, randmoised, controlled trial using vincristine, methotrexate, cyclophosphamide, and 5-fluorouracil in an initiation course and mitomycin-C with 5-fluorouracil as maintenance therapy. Thirty-seven patients were inoperable and 39 had the primary tumour resected with histological evidence of residual disease. Survival in the inoperable group was short and showed no significant difference between treated and control patients. The median survival times for treated and control groups were 9.5 and 9.0 weeks respectively. In the resected patients there was no difference in ultimate overall survival between the groups but up to 20 weeks there was a suggestion that the probability of survival in treated patients was higher (P = 0.06). The patients were well-matched and it is concluded that chemotherapy has had an early effect but that a further trial with more detailed stratification, particularly of staging and histological grade, is needed. No patient received treatment for longer than two years and unacceptable toxicity occurred in only two patients. Nausea occurred more frequently in the treated group but was short-lived and clinically manageable.