Buprenorphine and hepatic pruritus.

Pruritus in cholestatic liver disease can be difficult to treat. It may be related to impaired excretion of large opioid peptides. Buprenorphine, a drug with partial opiate antagonist properties, was used in a double-blind trial of five patients with uncontrollable itching. One patient improved clinically, one patient had good relief from pruritus and three had intolerable side-effects. Buprenorphine may be of limited use in intractable pruritus.

Effect of oral cyclosporin on renal function in Crohn's disease.

Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0, 6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m2; at six weeks: 100.9 ml/min/1.73 m2; mean ERPF at baseline: 497.3 ml/min/1.73 m2; at six weeks: 398.5 ml/min/1.73 m2). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m2), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m2). Serum creatinine rose significantly (median pretreatment 72 mumol/liter; median at four weeks 86 mumol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction.

Plasma viscosity in inflammatory bowel disease.

AIMS: To assess the relation of plasma viscosity to disease activity in patients with inflammatory bowel disease. METHODS: Crohn's disease (n = 60) and ulcerative colitis (n = 71) were diagnosed on the basis of typical histological or radiological features. Active Crohn's disease was defined as a Crohn's disease activity index of 150 or over. Active ulcerative colitis was defined as a liquid stool passed three times a day or more with blood. Blood samples were assessed for haemoglobin concentration, total white cell count, platelets, plasma viscosity, erythrocyte sedimentation rate, serum albumin, and C-reactive protein. RESULTS: Plasma viscosity was higher in those with active Crohn's disease compared with those with inactive Crohn's disease or active ulcerative colitis. Plasma viscosity correlated significantly with erythrocyte sedimentation rate, C-reactive protein, and platelet count in patients with Crohn's disease. In ulcerative colitis plasma viscosity correlated only with serum C-reactive protein. Plasma viscosity showed a low sensitivity for detecting active Crohn's disease, with 48% of those with active disease having a plasma viscosity within the laboratory reference range. CONCLUSIONS: Plasma viscosity is related to disease activity in Crohn's disease, but is insufficiently sensitive for it to replace erythrocyte sedimentation rate as a measure of the acute phase response in Crohn's disease.

Long-term treatment of Crohn's disease with cyclosporine: the effect of a very low dose on maintenance of remission.

Low-dose oral cyclosporine was used to maintain remission in patients with Crohn's disease. In seven patients, cyclosporine was used as a steroid-sparing agent; in 14 it was given for refractory active disease as an adjunct to conventional treatment, and then continued as maintenance treatment. Cyclosporine was given at an initial dose of 5 mg/kg reduced by 1 mg/kg at 2-month intervals until a maintenance dose of 2 mg/kg was reached. Of the seven patients in whom cyclosporine was used as a steroid-sparing agent, six had a relapse. Remission was achieved in seven of the refractory active group, but cyclosporine was withdrawn because of side effects in six of the patients in this group. Of the seven patients who had achieved remission, six subsequently had a relapse. Therefore, 12 of 14 patients (86%) in remission had a relapse despite cyclosporine maintenance. Ten of these (83%) had a relapse at a cyclosporine dose of 2 or 3 mg/kg. Cyclosporine levels at relapse (median, 74 ng/ml) were lower than the mean levels over the first 6 weeks of treatment (median, 130 ng/ml; p = 0.02). Our data do not support the use of cyclosporine to maintain remission in Crohn's disease.

Prognostic indicators and clinical course in proctosigmoiditis.

The progress and outcome of proctosigmoiditis (PS) varies from a benign self limited illness to severe or continuous disease which may require major surgery. This study identifies certain clinical features in the presenting attack which appear to influence the subsequent course of the disease. Ninety-nine patients with PS were referred to a colitis clinic between 1975 and 1985. Sixty have been followed for at least five years or have required surgery. They have been classified as follows. Group A-asymptomatic after presenting attack (n = 14), group B-symptoms after presenting attack for less than 10% of follow-up (n = 25), group C symptoms for greater than 10% of follow-up (n = 11), group D - patients requiring surgical intervention (n = 10). Data obtained during the initial attack, including sex, age, length of history, disease extent, length of first attack and therapy, were analysed. There was no significant difference in the length of history or extent of disease between groups. The mean ages in groups A-D were 40, 45, 30 and 24 years respectively. The ages of groups A and B were not significantly different, but differed from group C (p less than 0.05) and from group D (p less than 0.005). The length of the first attack was significantly shorter (p less than 0.01) in groups A and B (median 1.0 and 3.0 months respectively) than in groups C and D (median 5.0 and 6.0 months respectively).

Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity.

Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease.

Serum interleukin-2-receptor in coeliac disease: response to treatment and gluten challenge.

Concentrations of the soluble interleukin-2 receptor (sIL-2R) in the serum of 33 patients with coeliac disease were measured by ELISA. The levels of sIL-2R were significantly raised in 15 patients with untreated coeliac disease compared with treated patients and age- and sex-matched symptomatic and non-symptomatic control groups. Longitudinal studies in individual coeliac patients showed that serum sIL-2R fell following commencement of a gluten-free diet. Gluten challenge of 16 treated coeliac patients for 1 week resulted in a significant increase in serum sIL-2R, which returned to prechallenge levels within 4 weeks of recommencement of a gluten-free diet. We suggest that serum sIL-2R levels in patients with coeliac disease reflect specific immunological activation in response to gluten ingestion. Measurement of serum sIL-2R may therefore be useful in the assessment of response to treatment in patients with coeliac disease.

Cellobiose/mannitol sugar test--a sensitive tubeless test for coeliac disease: results on 1010 unselected patients.

The cellobiose/mannitol (Ce/Ma) test is a non-invasive technique for investigating intestinal permeability. In coeliac disease there is a decreased absorption of small molecules and paradoxically increased absorption of large molecules. The simultaneous administration of cellobiose and mannitol as two probe molecules allows the permeability of the small bowel mucosa to be studied, eliminating extraneous factors such as gastric emptying, and incomplete urine collection. One thousand and ten patients presenting to a gastroenterology clinic with symptoms, signs, or biochemical indices compatible with coeliac disease had a Ce/Ma test. Eight hundred and seventeen had a normal test and of these 197 had a jejunal biopsy showing 148 normal mucosa, two coeliac disease, 43 non-specific abnormalities, four giardiasis. One hundred and ninety three had an abnormal test; of these 132 had a jejunal biopsy showing 62 normal mucosa, 48 coeliac disease, and 22 other abnormalities. Considering those who had jejunal biopsies, the sensitivity of the test for coeliac disease is 96%, specificity 70%, the predictive value of the positive 36%, and predictive value of the negative 99%. Eleven per cent of the patients with a 'false positive' test had abnormalities in the jejunal biopsy or a diagnosis which could explain the abnormal permeability.

Lactulose/mannitol test: an ideal screen for celiac disease.

A lactulose/mannitol (La/Ma) test was compared with a standard cellobiose/mannitol test (Ce/Ma) in 17 patients with newly diagnosed celiac disease and 12 healthy controls. The mean La/Ma test was 0.163 (SEM 0.076) in celiacs and 0.016 (SEM 0.002) in controls. The mean Ce/Ma test was 0.132 (SEM 0.024) in celiacs and 0.014 (SEM 0.002) in controls (p less than 0.001). There is no significant difference between the new La/Ma test and the Ce/Ma test. Eighty-two patients referred to a general gastroenterology clinic with symptoms or signs of celiac disease performed a La/Ma test. A jejunal biopsy was indicated in 44 of these. In this selected group the sensitivity was 89%, specificity 54%, and negative predictive value of 95%. The La/Ma test fulfills the criteria of a screening test; it is sensitive, of low cost, and simple to perform, and it has the advantage of a simple enzyme assay and does not cause diarrhea in patients with hypolactasia. It can, therefore, be used in screening large patient populations.

Abnormal intestinal permeability and jejunal morphometry.

The cellobiose and mannitol differential sugar test is a non-invasive investigation of small bowel permeability, in which urinary recoveries of cellobiose and mannitol after a hyperosmolar oral load are expressed as a ratio to give a permeability index. Changes in the cellobiose:mannitol ratio often occur in coeliac disease, but some patients with abnormal permeability have normal jejunums by routine microscopy. Using computed morphometry the perimeter:lamina propria area index of jejunal biopsy samples was measured and compared with the cellobiose:mannitol ratio in three groups of patients: (i) those with coeliac disease with villous atrophy; (ii) those with normal jejunums and sugar test results: and (iii) those with normal jejunums but abnormal sugar test results. In addition to the expected difference in perimeter:lamina propria area index between patients with coeliac disease and those with normal findings (p less than 0.001), the index was also abnormal in patients with normal jejunums but abnormal sugar test results: (p less than 0.001 compared with group 1) and (0.01 greater than p greater than 0.001 compared with group 2). There was a significant overall correlation between the perimeter:lamina propria area index and cellobiose:mannitol ratio (p = 0.001). This study shows that computed jejunal morphometry can identify patients with subtle morphological changes that are related to abnormal intestinal permeability.

Somatostatin analogue SMS 201-995 long term therapy for vipoma.

The definitive treatment of a pancreatic tumour secreting vasoactive intestinal polypeptide is surgical removal of the tumour, but when curative resection is not possible symptomatic treatment of the endocrine hyperfunction is important. Streptozotocin, although effective for palliation, can involve unpleasant side effects. We report the long term use of subcutaneous somatostatin analogue SMS 201-995 in an elderly man presenting with severe watery diarrhoea and anaemia due to a pancreatic vipoma. Good symptomatic improvement has been achieved with no side effects over a period of 24 months. We suggest there is a use for subcutaneous SMS 201-995 in elderly patients with inoperable pancreatic gut hormone producing tumours with metastases and in those where surgery would carry a high operative risk.