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1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model. 2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization. 3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model. 4. It is concluded that, in health, liver blood flow may be calculated accurately and non-invasively after a single intravenous injection of ICG.

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal. 2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions. 3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min--1 m--2, range 376--672 increased to 704, 528--1968; P less than 0.01) and indocyanine green (359, 227--473 increased to 435, 358--985; P less than 0.01). 4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed. 5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.

1. The hepatic extraction ratios of chenodeoxycholic acid and ursodeoxycholic acid have been measured in 12 patients without, and 20 patients with, liver disease. 2. Ten of the patients without liver disease were studied during cardiac catheterization, with a continuous infusion technique. Two of the patients without liver disease and all those with liver disease received an intravenous bolus of [14C]chenodeoxycholic acid or [14C]ursodeoxycholic acid, during transvenous liver biopsy. 3. The extraction ratio of chenodeoxycholic acid was 0.63 +/- 0.03 (mean +/- mean +/- SEM) and of ursodeoxycholic acid 0.53 +/- 0.01, in the patients without liver disease. In those with mild liver disease, extraction was slightly impaired (chenodeoxycholic acid; 0.49 +/0 0.03; ursodeoxycholic acid: 0.43 +/- 0.05), whereas in those with more severe liver disease it was greatly reduced (chenodeoxycholic acid: 0.16 +/- 0.08; ursodeoxycholic acid: 0.07 +/- 0.01). 4. The results suggest that (a) direct measurements confirm the accuracy of indirect estimates of hepatic extraction of chenodeoxycholic acid, (b) hepatic extraction of chenodeoxycholic acid is lower than that of cholic acid and glycocholic acid, but higher than that of ursodeoxycholic acid, (c) progressive impairment of the extraction ratios of these two bile acids occurs as the severity of liver disease increases, and (d) the ratios are correlated with indocyanine green extraction ratios.

It has been established practice for 60 years to prepare thyrotoxic patients undergoing thyroidectomy with Lugol's iodine. However, evidence in support of its claimed benefits, namely a reduction in the vascularity and friability of the toxic thyroid gland, is scanty. We have therefore determined the effect of Lugol's iodine on thyroid blood flow, as measured by thyroid uptake of thallium-201, in nine patients with Graves' disease and one euthyroid patient. Thallium-201 uptake, as well as serum thyroxine and triiodothyronine, fell significantly after treatment with iodine. Although not correlated with thyroid function tests, thallium-201 uptake was significantly correlated with thyroid weight. These results support the contention that thyroid blood flow is reduced in thyrotoxic patients treated with Lugol's iodine.

The clearance, half-life time, fractional elimination rate and distribution volume of indocyanine green (10 mg . m-2) were measured in 20 control subjects and 63 patients with histologically confirmed liver disease. Mean clearance was significantly impaired only in the patients with alcoholic and primary biliary cirrhosis; in those with active chronic hepatitis, with or without cirrhosis, or with acute hepatitis, clearance was normal. However, half-life time and fractional elimination rate were impaired in all but one group of patients. This discrepancy arose because of a significantly increased distribution volume in all groups with chronic liver diseases except primary biliary cirrhosis. Thus, in chronic liver disease, half-life times and fractional elimination rates do not necessarily reflect hepatic uptake; measurement of clearance is therefore to be preferred.

A three generation family study was carried out after inappropriate treatment with radioactive iodine of a 50 year old woman with a raised serum total thyroxine concentration and free thyroxine index. Subsequent investigations showed that she and five members of her family had raised thyroxine binding globulin concentrations. Free thyroxine and free triiodothyronine concentrations were normal. Problems encountered in the recognition of this thyroxine binding protein disorder are discussed. Clinicians and clinical biochemists should be aware of these pitfalls and thus avoid further incorrect treatment on the basis of biochemical findings, even though free hormone estimations are now becoming readily available.

A patient who presented with dysphagia was found to have a cholangiocarcinoma, with metastases in the para-oesophageal lymph nodes. Although dysphagia has been described as a presenting feature of some metastatic carcinomas, to the authors' knowledge, there have been no reports of it as a presenting symptom of a cholangiocarcinoma.

In a survey of the prevalence of chronic hepatitis B in a male homosexual population, liver biopsies were done in 28 asymptomatic patients who had persistently raised aminotransferases. Four patients had active cirrhosis (AC), 13 had chronic active hepatitis (CAH) of various degrees of severity and 11 had either chronic persistent hepatitis (CPH) or minor changes of the type seen in hepatitis B virus carriers. Core associated antigens and surface antigen, were demonstrated by the PAP immunoperoxidase method in 20 cases. Core and surface antigens tended to be present in the same areas of the biopsy and quantitation showed higher core to surface antigen ratios in CAH than in CPH, the difference being statistically significant. In seven cases no core-associated antigens were demonstrated in the presence of surface antigen: most of these patients had either inactive disease or active cirrhosis. In one carrier neither antigen was demonstrated. Ten patients had two or more biopsies. Four of these had no treatment and the amounts of core and surface positive cells in the liver did not increase. Six were treated with immunosuppressants. This did not alter the degree of either inflammation or fibrosis. but the number of surface and core antigen positive cells in the liver was higher after treatment in almost every case.

A double-blind controlled trial of 12 months' treatment with (+)-cyanidanol-3 was carried out in 26 patients with chronic hepatitis B liver disease. Treatment did not improve liver blood tests nor histological appearances of the liver, but there was a trend towards reduction of serum titres of hepatitis B surface antigen.

Lymphocytes from 39 patients with HBsAg positive chronic liver disease were incubated with their own hepatocytes to investigate mechanisms of lymphocyte-mediated liver damage. Cytotoxicity was significantly increased in 46% overall, and in 73% of those with chronic active hepatitis. Unlike HBsAg negative chronic active hepatitis where only non-T cells were cytotoxic, HBsAg positive patients had both cytotoxic T and non-T cells. A purified liver membrane complex (LSP) and aggregated IgG both blocked non-T cytotoxicity without affecting T cell cytotoxicity; this suggests that the former is probably an antibody-dependent cell-mediated reaction against normal membrane components. This was confirmed in preliminary studies which demonstrated that preincubation of hepatocytes with the F(ab)2' fragment of an anti-human IgG reduced non-T lymphocyte cytotoxicity. T-cell cytotoxicity was restricted to HBeAg-positive patients, suggesting a relationship between T-cell cytotoxicity and viral replication. Purified HBsAg, however, blocked cytotoxicity in only three of 11 cases. Non-T lymphocytes reacting with normal membrane components may contribute to liver damage in both 'autoimmune' and virus-associated chronic liver disease, whereas cytotoxic T-cells, probably reacting with viral determinants, are exclusive to those with viral replication.

The results of 193 transjugular liver biopsies performed with a modified needle are described. An adequate specimen was obtained in 97%, and complications were rare, although puncture of the liver capsule does occur and caused bleeding in two patients. Fever after the procedure was reduced by ultrasonic cleaning of the needle. Although not easy, this technique is safe and preferable in the management of selected patients, but in most patients percutaneous biopsy is to be preferred.

We report the clinical details of a 77 year old man with classical tetralogy of Fallot. The patient had clubbing and cyanosis at birth, and exertional squatting in childhood. He was asymptomatic as an adult until the seventh decade, when he developed biventricular failure and had an episode of bacterial endocarditis. He finally died of cerebral infarction and bronchopneumonia following abdominal surgery. In spite of investigations, the diagnosis was not made in life, but only discovered at post-mortem. A persistent ductus arteriosus was also found. Increased pulmonary blood flow via the ductus is believed to have facilitated this patient's unusual longevity.