Sigmoidoscopy service in a district general hospital: open-access versus hospital-referred.

In a retrospective analysis of open-access versus hospital-referred flexible sigmoidoscopies, the two groups are compared with reference to the demographic data, presenting symptoms, sigmoidoscopy findings and diagnostic yield. Overall, 1090 patients underwent sigmoidoscopy during 12 months, 544 in the open-access and 546 in the hospital-referred group. There was a preponderance of females in both groups, but patients in the hospital-referred group were older. Diarrhoea was the most common presenting symptom, followed by rectal bleeding. Significantly more patients presented with rectal bleeding with or without diarrhoea and abdominal pain in the open-access group, while there were more patients with iron deficiency in the hospital-referred group. The number of patients with colonic carcinoma was similar in the two groups, but significantly more early carcinomas were found in the open-access group. There were significantly more patients with haemorrhoids in the open-access group. The positivity rate was similar in the two groups (52% in the open-access vs 46% in the hospital-referred group). Of the 24% of patients 40 years or under, none had carcinomas. In this age range the positivity rate was no different in the two groups (32% in the open-access vs 23% in the hospital-referred group). The diagnostic yield of open-access flexible sigmoidoscopy is thus comparable to hospital-referred sigmoidoscopy, suggesting that it should be freely available to GPs.

A prospective randomised controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma.

In a prospective controlled clinical trial, 108 patients with pancreatic adenocarcinoma were randomly allocated to receive tamoxifen 20 mg b.d., cyproteron acetate 100 mg t.d.s. or no active treatment. The median survival of those receiving tamoxifen was longer than either of the other two groups (5.25 compared to 4.25 and 3 months, respectively) but this difference did not achieve statistical significance. Cox regression analysis of 12 clinical and biochemical features showed that, for the entire group of patients, survival was significantly longer in younger patients, those undergoing surgical bypass and those with better initial performance status. However, even when adjustment was made to allow for the distribution of these prognostic variables within the three groups, the difference in survival still did not achieve statistical significance. No side-effects attributable to treatment was observed.

Mechanisms responsible for antibody-dependent, cell-mediated cytotoxicity to isolated hepatocytes in chronic active hepatitis.

Lymphocytes from patients with chronic active hepatitis have been found to be cytotoxic for isolated rabbit hepatocytes. Although this reaction has been shown to be of the antibody-dependent type, no autologous serum was added to the assay system and in the present experiments the source of the antibody has been sought. The failure of puromycin to block the reaction argued against a role for antibody synthesised during the culture period, and the demonstration that normal mononuclear cells could become cytotoxic when preincubated in chronic active hepatitis sera was more in favour of the passive acquisition of an antibody from the circulation. Evidence for the existence of free antibody in the sera reacting with hepatocyte surface antigens came from an additional series of experiments in which it was shown that preincubation of hepatocytes in chronic active hepatitis sera rendered them susceptible to damage by normal mononuclear cells. This effect was almost completely abolished by adding a membrane lipoportein fraction of human liver (LSP) to the sera during the preincubation step, suggesting that the LSP contained those antigens on the hepatocyte surface against which the majority of the antibodies were directed.

Lymphocyte cytotoxicity in chronic active hepatitis: effect of therapy and correlations with clinical and histological changes.

A study of lymphocyte cytotoxicity for rabbit hepatocyte cultures in 15 patients with untreated chronic active hepatitis showed positive results in all cases, both HBsAg positive and negative. After immunosuppressive therapy cytotoxicity became negative and remained negative, in four of nine patients followed serially. In 51 patients established on therapy for periods from three months to 12 years, cytotoxicity was negative in 19 and all patients are currently alive. However, in the remaining 32 patients in whom cytotoxicity was positive there has been a 34% mortality. Cytotoxicity remained persistently positive in 12 of 15 patients followed serially, and persistently negative in seven of nine. Cytotoxicity showed a significant association with histological disease activity, especially the extent of piecemeal necrosis, but not with biochemical tests of liver function, immunoglobulins, or autoantibodies. The basis of this cytotoxicity test is an antibody dependent cell-mediated autoimmune reaction directed against a liver specific protein, and the results suggest that in some cases immunosuppressive therapy is followed by control of this reaction. It may be possible to stop therapy in these patients, but in those in whom the reaction continues, as shown by continuing cytotoxicity, the prognosis is not as good and the use of other drug schedules would seem worthy of trial.

The significance of stimulation in the leucocyte migration test as an indicator of cellular hypersensitivity--studies using Tamm-Horsfall glycoprotein as antigen.

To determine whether stimulation of leucocyte migration in the presence of an antigen is a reliable indicator of sensitization, the results of leucocyte migration using a kidney antigen (Tamm-Horsfall glycoprotein) were compared with those of lymphocyte transformation using the same antigen and with the lymphocyte cytotoxicity for cells known to synthesize this antigen. There was a close correlation between the results of all three tests and these findings strongly suggest that the stimulation of leucocyte migration as an immunological phenomenon was as valid as inhibition in demonstrating sensitization.

Lymphocyte cytotoxicity for isolated hepatocytes in alcoholic liver disease.

To determine whether an autoimmune reaction to liver-specific proteins occurs in alcoholic liver disease, the cytotoxic effect of lymphocytes on isolated hepatocytes was determined in 27 alcoholic patients. Cytotoxicity was demonstrated in 15 of 17 patients with a histological diagnosis of alcoholic hepatitis, but in none of 10 with other forms of alcoholic liver disease. The ability of a liver-specific membrane lipoprotein to block the reaction suggests that sensitization to this antigen is responsible for the cytotoxicity. The demonstration of cytotoxicity using T cell-depleted, but not B and K cell-depleted, lymphocytes suggests an antibody-dependent cell-mediated reaction. There was a close correlation between cytotoxicity and the presence of alcoholic hyalin, liver cell necrosis, and piecemeal necrosis, but not with other histological features, immunoglobulines, autoantibodies, or standard liver function tests. The persistence of this autoimmune response, induced in some way by alcohol or one of its metabolites, may be important in the progression of acute alcoholic hepatitis to chronic liver disease.

Studies on plasma cytotoxicity and liver regeneration in fulminant hepatic failure.

The possibility that the blood of patients with fulminant hepatic failure might contain substances which prevent or delay liver regeneration was investigated using a microcytotoxicity assay system based on the culture of isolated rabbit hepatocytes in vitro. Results showed significant cytotoxicity of the plasma as compared to controls, an effect which was reduced by charcoal haemoperfusion. The effect was also reduced in vitro by heating and dialysis. The bile acids chenodeoxycholic and lithocholic acid were cytotoxic when added to control human plasma. Evidence was also obtained from a completely different in vivo assay system that high blood levels of ammonia may inhibit hepatic regeneration.

Autoimmune reaction to a liver specific membrane antigen during acute viral hepatitis.

Lymphocyte cytotoxicity for isolated hepatocytes has been demonstrated in 93% of cases of acute viral hepatitis tested within two weeks of the onset of symptoms. The frequency of cytotoxicity during this time was similar for HBsAg positive and negative cases. However, after this time it was significantly higher in HBsAg positive than negative cases, 90% and 25% respectively (P less than 0-01). Cytotoxicity was found in B-cell, but not T-cell, enriched fractions of lymphocytes, compatible with an antibody-dependent K-cell mediated reaction. In two cases the assay remained positive on retesting six months later, and follow-up liver biopsies showed the features of chronic aggressive hepatitis. These findings suggest that, in addition to the known immunological reactions against viral antigens that occur during the acute phase of viral hepatitis, an autoimmune reaction directed against a liver specific protein is also initiated; and if this reaction persists then chronic hepatitis may develop.

Analysis of time intervals involved in admission to a coronary care unit.

Time intervals between the onset of the presenting symptom (chest pain) and arrival in a coronary care unit were studied for 221 admissions arranged by conventional means. The median figure for "patient delay" was 60 minutes, for "general-practitioner delay" 20 minutes, for "ambulance delay" 30 minutes, and for "transit delay" 30 minutes. The median "total delay" was three hours 30 minutes.Only 4.5 per cent of the patients were under intensive coronary care within one hour, the time of the highest mortality risk. A mobile coronary service should be capable of increasing the proportion of patients brought under special care within the first hour, but the time taken by the patient to realise the nature of the emergency and summon aid is likely to remain the most critical factor.

Lymphocyte cytotoxicity for kidney cells in renal tubular acidosis of autoimmune liver disease.

Sensitisation to a renal tubular antigen, Tamm-Horsfall glycoprotein, has been shown to be common in patients with renal tubular acidosis complicating autoimmune liver disease, and it has been suggested that this immune reaction, by damaging renal tubular cells, might be responsible for the acidification defect. The lymphocytes from 10 out of 13 patients with chronic active hepatitis or primary biliary cirrhosis and an associated renal tubular acidosis were shown to be cytotoxic for a kidney cell line known to secrete Tamm-Horsfall glycoprotein. The cytotoxic reaction was blocked by this antigen, but not by two other proteins, indicating that sensitisation to the renal glycoprotein was the likely cause of the target cell damage. Significant reduction in cytotoxicity after the addition of aggregated IgG suggested that the reaction was of the antibody-dependent cell-mediated type. These results, together with the finding of antigenic material in the surface membrane of liver cells that cross reacts immunologically with Tamm-Horsfall glycoprotein, provide an explanation for the association between chronic liver disease and renal tubular dysfunction.

The cytotoxicity of plasma from patients with acute hepatic failure to isolated rabbit hepatocytes.

The cytotoxicity of plasma from patients with various types of liver disease to rabbit hepatocytes maintained in vitro has been investigated using a microcytotoxicity assay system. Plasma from patients with fulminant hepatic failure and uncomplicated viral hepatitis showed significant cytotoxicity compared to controls. The cytotoxic effect of plasma from patients with fulminant hepatic failure was reduced by charcoal haemoperfusion, or heating and dialysis. The bile acids chenodeoxycholic acid and lithocholic acid were cytotoxic when added to control human plasma. Such toxic factors may be responsible for the delay in liver regeneration often seen in patients with fulminant hepatic failure.

Antibody-dependent cell-mediated (K cell) cytotoxicity against isolated hepatocytes in chronic active hepatitis.

Lymphocytes from 12 of 17 patients with chronic active hepatitis were cytotoxic towards isolated hepatocytes in a microcytotoxicity assay. Enriched fractions of B cells, prepared by removal of E-rosetted cells, were cytotoxic in all 12 cases, whereas T-cell fractions, prepared by removal of erythrocyte-antibody-complement-rosetted cells, were cytotoxic in only 1 case (P less than 0-0005). HBsAg positive and negative cases reacted similarly. In 6 patients the addition of 5 mug aggregated IgG significantly reduced cytotoxicity from 54% +/- 15 to 13% +/- 15 (mean +/- 1S.D.) suggesting that K cells may be the effector cell in an antibody-dependent, cell-mediated reaction directed against a liver-specific membrane lipoprotein.

Changes in plasma urate concentration immediately after acute myocardial infarction.

The plasma urate concentration of 70 patients with acute myocardial infarction increased progressively up to the seventh day and was significantly higher than in a group of 23 patients with ischaemic changes only. Diuretic treatment might have accounted for an early rise in urate levels but the persistent increase seen at seven days could not be so explained.

Effects of long-term practolol therapy on plasma-lipids after acute myocardial infarction.

In a double-blind controlled trial lasting 12 months, long-term practolol therapy had no significant effect on plasma-lipid concentrations in twenty patients who had had acute myocardial infarction.