R. P. Knill-Jones

Hypercalcemia and increased parathyroid-hormone activity in a primary hepatoma. Studies before and after hepatic transplantation.

Abstract A patient with hypercalcemia associated with a carcinoma of the intrahepatic bile ducts showed some decrease in serum calcium after a course of prednisone. Orthotopic liver transplantation...

Use of Sequential Bayesian Model in Diagnosis of Jaundice by Computer

A sequential Bayesian model has been developed for a computer and used to diagnose jaundiced patients admitted to hospital. Up to 102 items of information from the history, physical examination, and special investigations available within 48 hours of admission were collected on 309 patients. The results from these patients were used to calculate the probabilities of 11 possible diseases in 65 new patients and also to place patients into groups for medical or surgical treatment. The overall accuracy of the model in diagnosing patients as having one of 11 diseases was 69%, and where the final probability reached > 0·96, it was 89%. The overall accuracy in making a medical or surgical decision was 89%, and where the final probability reached > 0·96 it was 94%. Improvement in accuracy should result as the number of cases seen with rare conditions increases, and probably a similar model could be developed and used to make most use of those indicants with the highest cost-effectiveness.

Peripheral neuropathy in chronic liver disease: clinical, electrodiagnostic, and nerve biopsy findings

In a prospective study of 70 unselected patients with chronic liver disease, clinical signs of a peripheral neuropathy were observed in 13 patients. Abnormal nerve conduction was demonstrated in nine of these and in one further patient who had no abnormal neurological signs. The occurrence of a neuropathy (in patients with cryptogenic cirrhosis, haemochromatosis, active chronic hepatitis as well as in alcoholic cirrhosis) could not be related to liver function, although it was associated with higher IgA and IgM values. Clinical diabetes was present in six of the 14 patients with neuropathy but there was no relation in the non-diabetic patients between neuropathy and minor impairment of carbohydrate tolerance. Those with neuropathy had a significantly higher incidence of oesophageal varices and there was also a relationship to a history of previous encephalopathy. Sural nerve biopsy was carried out on 14 patients, eight of whom had clinical or electrodiagnostic evidence of neuropathy. Single nerve fibres were examined by teasing and in all nerves histological evidence was found of an indolent process which had damaged whole Schwann cells and which resulted in demyelination and remyelination. Diabetic angiopathy was not seen and axonal degeneration, which was never severe, was found in all disease groups equally.

Liver Transplantation in Man—II, a Report of two Orthotopic Liver Transplants in Adult Recipients

Two patients with primary hepatic malignancy were treated by hepatectomy and orthotopic liver transplantation. In both cases the donor liver was infused with cold solutions and kept chilled without continuous perfusion. There was immediate satisfactory hepatic function in both transplants. The first patient died after 11 weeks from overwhelming bacterial and fungal infections probably secondary to hepatic infarction due to thrombosis of the recipient hepatic artery. The thrombus occurred at the site of the arterial clamp. In an attempt to control the growth before transplantation, the patient had been treated with large doses of chlorambucil, which resulted in extreme marrow depression and septicaemia. The second patient developed cholestatic jaundice during the second and third weeks after transplantation, with histological evidence of mild rejection, which was controlled by increasing the dose of immunosuppressive agents. He is now well, having returned to work six weeks after the operation. Though the first patient showed no evidence of rejection, it is concluded that patients receiving liver allografts should receive immunosuppressive therapy.

Comparative trial of Nutrizym in chronic pancreatic insufficiency.

A cross-over trial of pancreatic replacement therapy was carried out in 12 adults with chronic pancreatic insufficiency. The standard enteric-coated preparation, Pancrex V forte, was compared with Nutrizym, which has an enteric-coated core of pancreatic extract and a shell of bromelains—a mixture of proteolytic enzymes derived from the stem of the pineapple. Nutrizym was significantly more effective than Pancrex V forte in improving fat absorption, and reduced faecal weight. Protein digestion was assessed by measuring the urinary excretion of hydroxyproline after a gelatin meal. Nutrizym produced an earlier and significantly higher peak in hydroxyproline excretion than Pancrex V forte, but the cumulative effect was similar. The value of bromelains was investigated by including a period on the Nutrizym core alone. This was similar to Pancrex V forte in improving fat absorption but had less effect on protein digestion, suggesting that the beneficial effect of Nutrizym compared with Pancrex V forte was due to the added bromelains, and not to differences in enzyme content or enteric coating.

Pitfalls in the diagnosis of jaundice due to carcinoma of the pancreas or biliary tree.

Analysis of 56 patients with obstructive jaundice due to carcinoma of the pancreas or extrahepatic biliary tree showed that unexpected features were present in 25%. Presentation with painless jaundice was uncommon, and the symptoms were more often non-specific, with malaise, anorexia, and vomiting. Abdominal pain was frequent, and the condition was found in young patients. One-fifth presented with serum alkaline phosphatase levels of less than 30 K.A. units. Some had high serum aspartate aminotransferase levels, more characteristic of hepatocellular jaundice. A mathematical model may be helpful in correctly weighting these various criteria.

Clinical and Electroencephalographic Assessment of Diazepam in Liver Disease

The effects of 5 mg of diazepam intravenously were assessed in 23 patients with liver disease, 10 of whom had clinical evidence either in the past or at the time of study of hepatic encephalopathy. Transient drowsiness occurred in all patients, but prolonged deterioration in conscious level was not observed. Serial electroencephalographic recordings showed the development of activity at faster frequencies, similar to that found in normal subjects, a change which is different from that usually observed in cirrhotic patients after administration of chlorpromazine and morphine when slow-wave activity is increased.

Use of Computer-assisted Model in Diagnosis of Drug Hypersensitivity Jaundice

Of 374 patients with jaundice seen in the liver unit over a four-year period 21 were finally thought to be hypersensitive to one of seven different drugs. The clinical, laboratory, and histological features were often difficult to distinguish from those of viral hepatitis, tumour of the extrahepatic biliary tree, or primary biliary cirrhosis. A computer-assisted diagnostic model made use of minor differences, and made a correct diagnosis in all patients. Even when information about drug ingestion was left out it was still correct in 81% of patients. Sixty-four other patients gave a history of ingestion of potentially hepatotoxic drugs of whom 62 were correctly diagnosed by the computer. In the complete series of 374 patients only two were incorrectly computed to have drug jaundice when there was no history of drug ingestion. Two additional patients became jaundiced after exposure to drugs, but were found to have primary biliary cirrhosis.

A controlled trial of a protein-free liver extract in the treatment of chronic liver disease

A double-blind trial of a protein-free liver extract (Ripason) which was administered both orally and intramuscularly is described in 20 patients with stable cirrhosis. Control and treated groups were similar in composition except for age. Both groups showed some symptomatic improvement during the trial. Fewer patients were recorded as worse on Ripason but no significant changes in body weight, haemoglobin, or liver function tests could be detected.