A 51Cr release cytotoxicity assay for use with human intrahepatic biliary epithelial cells.

Human intrahepatic biliary epithelial cells are important immune targets in a variety of hepatobiliary diseases particularly primary biliary cirrhosis and primary sclerosing cholangitis. The ability to isolate and maintain these cells in short term primary tissue culture has permitted us to develop an in vitro cytotoxicity assay for the study of these cells as potential targets to a variety of toxic stimuli. We have therefore established a chromium-51 (51Cr) release cytotoxicity assay for use with primary cultures of human intrahepatic biliary epithelial cells. The method is simple, reproducible and is more sensitive than dye exclusion, light microscopy and release of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase.

Helicobacter pylori eradication in a clinical setting: success rates and the effect on the quality of life in peptic ulcer.

BACKGROUND: Helicobacter pylori eradication for peptic ulcer has been widely taken up. Evidence for the efficacy of different regimens is often derived from small series in clinical trials but there is little reporting of everyday practice with unselected patients. Freedom from ulcer relapse has been demonstrated, but not whether this equates with clinical success. METHODS: We report on a series of 706 patients with H. pylori infection who, between January 1991 and April 1995, received eradication therapy followed by assessment of H. pylori status. Two-hundred and seven of these patients were followed-up by postal questionnaire, validated by parallel questionnaires to their general practitioners, covering clinical outcome measures. RESULTS: The overall eradication rate was 81.7%, and a 1-week course of omeprazole plus two antibiotics was significantly better than a 2-week course of standard triple therapy (85.0% vs. 78.0%, P < 0.05). Amongst 21 first-time failures, a 7-day course of a clarithromycin-containing triple therapy succeeded in 18. The questionnaire replies indicate that, following successful H. pylori eradication, ulcer patients are less likely to consult with ulcer symptoms (P < 0.0005), take medication (P < 0.0005), require further prescription (P < 0.0005), or lose work-time because of their ulcer (P < 0.005). They are more likely to have a subjective sense of ulcer cure (P < 0.0005). CONCLUSIONS: In addition to clear cost savings, social benefits are now demonstrated when H. pylori is eradicated. A well-tolerated 1 week regimen is genuinely effective in everyday practice.

Progression of ulcerative proctosigmoiditis: incidence and factors influencing progression.

OBJECTIVE: To assess the changing distribution of disease within the large bowel in patients presenting with ulcerative proctitis or proctosigmoiditis. To evaluate the influence of clinical exacerbations, smoking, parity and family history in disease extension. DESIGN: Retrospective single-centre study in a university hospital. METHODS: Case records of patients presenting over a 40-year period were examined to evaluate the clinical course and disease distribution from initial presentation to final follow-up. For each patient whose disease extended to the more proximal colon, an age- and sex-matched control patient was identified whose disease remained confined to the original site. Patients completed a questionnaire to provide information on family history, smoking and parity. The differences in clinical exacerbations, family history, smoking and parity were then compared between the two groups. RESULTS: Among 145 patients presenting with proctitis or proctosigmoiditis followed prospectively for a median period of 10.9 years, the disease extended in 53 patients. Using actuarial methods the disease progressed beyond the rectosigmoid area in 16% of patients at 5 years and 31% at 10 years. Among the patients whose disease progressed, progression was preceded in 68% of cases by a clinical exacerbation of the colitis. When patients whose disease progressed were compared with those whose disease remained confined to the original site, no differences were detected in the number of clinical exacerbations, smoking habit, family history or parity. CONCLUSIONS: The factors that are associated with the extension of colitis are probably different from those that predisposed an individual to develop inflammatory bowel disease initially.

High osmolality feedings do not increase the incidence of thrombophlebitis during peripheral i.v. nutrition.

BACKGROUND: Peripheral i.v. nutrition has been advocated for patients who require short-term i.v. nutrition support to avoid the complications and expense of central venous catheterization. Feeding formulas for peripheral administration have usually been modified by increasing the proportion of lipid, because increasing osmolality is reported to cause thrombophlebitis. The aim of this study was to determine whether standard feeding formulas can be given via the peripheral route and also to establish whether increasing osmolality does increase the incidence of thrombophlebitis under these conditions. METHODS: Thirty-six patients requiring parenteral nutrition were randomized to receive either a "high" (1700 mOsmol/L) or "standard" (1200 mOsmol/L) osmolality feeding containing 2000 kcal and 12 g nitrogen via a peripheral line. RESULTS: Twenty patients (mean age 55.6 years, range 16 to 78) received standard osmolality feedings using 20 peripheral feeding lines for a mean duration of 6.8 days (range 2 to 16) with 10 line failures (8 thrombophlebitis, 2 occlusion). Nineteen patients (mean age 56.1 years, range 27 to 83) received high osmolality feedings via 20 lines for a mean of 6.3 days (range 0 to 18) with five line failures (4 thrombophlebitis, 1 occlusion), one failed insertion, one line removed at the patient's request, and four lines that fell out. Forty lines were inserted overall of which 19 (47.5%) were removed electively, 12 (30%) developed thrombophlebitis, 3 (7.5%) occluded, 4 (10%) fell out, 1 (2.5%) was a failed insertion, and 1 (2.5%) was removed for nonmedical reasons. CONCLUSIONS: Increasing osmolality of total parenteral nutrition did not increase episodes of thrombophlebitis in this trial and did not affect the success rate of the lines. We conclude that standard total parenteral nutrition formulas of higher osmolality than previously thought can be safely given via the peripheral route for short-term feeding and do not increase the risk of thrombophlebitis.

Chickenpox in the elderly.

Chickenpox (varicella) is primarily a childhood disease. Few escape infection until adulthood. We report three cases of chickenpox infection in elderly patients. They all developed the illness in December 1985.

Intercellular adhesion molecule-1 and MHC antigens on human intrahepatic bile duct cells: effect of pro-inflammatory cytokines.

Human intrahepatic biliary epithelial cells were isolated from the livers of patients with primary biliary cirrhosis and from normal livers and established in primary culture. The in vitro expression of intercellular adhesion molecule-1, HLA class I, and HLA class II on biliary epithelial cells was studied in response to tumour necrosis factor-alpha (0-500 U/ml), interferon-gamma (0-500 U/ml), and interleukin-1 (0-5 U/ml) by immunohistochemical staining and a semiquantitative scoring system validated by spectrophotometry and previously validated by laser confocal microscopy. The non-stimulated expression of intercellular adhesion molecule-1 and HLA class II was higher on cells derived from the primary biliary cirrhosis liver than on cells from normal liver, a difference not seen with HLA class I expression. A statistically significant increase in intercellular adhesion molecule-1 expression was seen with all three cytokines in cells derived from both primary biliary cirrhosis and normal liver. Increase in HLA class I expression was seen only with interleukin-1 5 U/ml for cells derived from both normal and diseased liver. Increase in HLA class II expression was seen only with interferon-gamma 500 U/ml for cells derived from diseased liver and with interleukin-1 5 U/ml for cells derived from both diseased and normal liver. These data show that pro-inflammatory cytokines increase expression of intercellular adhesion molecule-1, HLA class I, and HLA class II on human intrahepatic biliary epithelial cells in vitro and are consistent with the hypothesis that these locally acting factors may play a part in the pathogenesis of immune mediated disorders such as primary biliary cirrhosis in which immune mediated bile duct damage occurs.

Stress and oesophageal motility in normal subjects and patients with irritable bowel syndrome.

Patterns of oesophageal motility were recorded in 17 healthy volunteers and 12 patients with the irritable bowel syndrome. Recordings were taken at rest and under stress by hyperventilation, a dichotic hearing challenge and a cold pressor test. In healthy volunteers the dichotic hearing challenge was associated with a significant increase in the mean amplitude of oesophageal peristalsis from 69.9 mmHg to 82.4 mmHg (p less than 0.01) and in the percentage of simultaneous waves from 9.7% to 24.5% (p less than 0.01). The cold pressor test increased the peristaltic amplitude from 69.9 mmHg to 87.1 mmHg (p less than 0.001) and the percentage of simultaneous waves from 9.7% to 34.4% (p less than 0.01). Both manoeuvres were associated with increases in pulse and blood pressure. In patients with irritable bowel syndrome, the resting mean oesophageal peristaltic amplitude was higher than that seen in normal volunteers (95.9 mmHg v 69.9 mmHg p less than 0.05). Changes in oesophageal motility during stress were similar in these patients to those seen in normal subjects although the changes were not significant. This study refutes the hypothesis that symptoms of irritable bowel syndrome and their association with stress are attributable to increased sensitivity of oesophageal motility to disruption by stressful stimuli.

A simple clinical colitis activity index.

BACKGROUND: The appropriate medical treatment of patients with ulcerative colitis is determined largely by the severity of symptoms. Hospital assessment of the severity of disease activity includes investigation of laboratory indices and sigmoidoscopic assessment of mucosal inflammation. AIMS: To develop a simplified clinical colitis activity index to aid in the initial evaluation of exacerbations of colitis. METHODS: The information for development of the simple index was initially evaluated in 63 assessments of disease activity in patients with ulcerative colitis where disease activity was evaluated using the Powell-Tuck Index (which includes symptoms, physical signs, and sigmoidoscopic appearance). The new index was then further evaluated in 113 assessments in a different group of patients, by comparison with a complex index utilising clinical and laboratory data, as well as five haematological and biochemical markers of disease severity. RESULTS: The newly devised Simple Clinical Colitis Activity Index, consisting of scores for five clinical criteria, showed a highly significant correlation with the Powell-Tuck Index (r = 0.959, p < 0.0001) as well as the complex index (r = 0.924, p < 0.0001) and all laboratory markers (p = 0.0003 to p < 0.0001). CONCLUSIONS: This new Simple Colitis Activity Index shows good correlation with existing more complex scoring systems and therefore could be useful in the initial assessment of patients with ulcerative colitis.

New monoclonal antibodies reacting with bile ducts: further insights into the pathogenesis of bile ductular proliferation in biliary diseases.

We have produced a range of monoclonal antibodies which stain human intrahepatic bile ducts of different sizes. Amongst 26 monoclonal antibodies produced, five clones reacted specifically with bile ducts of different sizes, of which three have been maintained in culture and their viability following freezing and thawing confirmed. Staining patterns varied between normal adult liver tissue, normal fetal liver tissue and a variety of hepatobiliary diseases. The antibodies provide further evidence of the immunological heterogeneity of the human intrahepatic biliary tree and support the hypothesis that proliferating bile ductules are derived from periseptal hepatocytes. The preparation of the antibodies, their staining reactions in normal adult, normal fetal and a variety of liver diseases are described.

Spontaneous regression of hepatocellular carcinoma.

A 63 year old white woman presented with abdominal discomfort, anorexia, and weight loss. Investigations showed hepatocellular carcinoma with pulmonary metastases. The primary and secondary tumours resolved without specific treatment.

Serious paracetamol poisoning and the results of liver transplantation.

Paracetamol poisoning is the most common cause of fulminant liver failure in the United Kingdom. An accurate assessment of prognosis at the time of referral will allow the appropriate application of liver transplantation in this setting. The outcome of 92 patients consecutively admitted to a specialist liver unit with severe poisoning has been examined. In patients who did not have a transplant, a fatal outcome was seen for 26/82 (32%), and was associated with late presentation, coma grade, prothrombin time prolongation, metabolic acidosis, and renal dysfunction. Cerebral oedema, and sepsis were responsible for most deaths. Prognostic criteria defined at King's College Hospital seemed to predict the outcome of patients who did not have a transplant managed on the Birmingham liver unit. Seventeen patients were listed for transplantation, 10 had liver transplantation, and seven of 10 survived. Seven were listed but not transplanted, and one of seven survived. Psychological rehabilitation of patients who had a transplant has not proved difficult. These results suggest a role for liver transplantation in the management of selected patients with paracetamol poisoning.