Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitis.

BACKGROUND: In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies. METHODS: We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events. RESULTS: Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred. CONCLUSION: In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC.

Interaction of rat prostate androgen receptors with polynucleotides, RNA, DNA and cloned DNA fragments.

Androgen receptors were partially purified from prostates of mature (non-castrated) rats by chromatography on 2',5'-ADP-Sepharose and labelled by exchange with 5 alpha-[3H]dihydrotestosterone. The partially purified receptor preparation was free of DNAase activity and sedimented at approx. 3 S. The specificity of the interaction of this androgen receptor with nucleotides was investigated in a competitive binding assay using inhibition of binding of the steroid receptor complex to ADP-Sepharose. Certain polyribonucleotides were strongly bound (e.g., poly(UG), poly(AU), poly(G) and poly(U] and competed more effectively for the receptor binding sites than prostate RNA. Restriction fragments of genomic clones from the genes which code for prostatic binding protein showed only moderate affinity for the 3 S receptor form. These data suggest that the 3 S form of the androgen receptor lacks the specific domain or conformation necessary for specific interaction with DNA, but retains a high affinity for certain forms of RNA. Some potent inhibitors of proteolysis (diisopropylfluorophosphate, leupeptin) did not have any effect on the form of the receptor isolated from mature intact animals. A possible function of the 3 S form in post-transcriptional processing is discussed.

Successful recovery of a patient with thallium poisoning.

We describe a patient suffering from protracted and life-threatening thallium poisoning. She was treated with Prussian blue and forced diuresis, and made a good recovery. Cisapride may be effective in improving gastric emptying and relieving constipation resulting from the thallium and the treatment. Haematological abnormalities occurred in the early phase of the poisoning, with a prolonged fall in the CD4/8 lymphocyte ratio during recovery.

Low molecular weight heparin treatment in steroid refractory ulcerative colitis: clinical outcome and influence on mucosal capillary thrombi.

BACKGROUND: In ulcerative colitis, a state of hypercoagulation has frequently been observed. Unfractionated heparin has shown beneficial effects as an adjuvant treatment of steroid refractory ulcerative colitis in open trials and in one placebo-controlled trial. Low molecular weight heparin (LMWH) offers advantages in the method of administration, but it has not been evaluated in severe ulcerative colitis. We therefore assessed the tolerability, safety and potential therapeutical effects of LMWH in hospitalized patients with steroid refractory ulcerative colitis. METHODS: Twenty-five patients with severely active ulcerative colitis were included in an open-labelled trial. All patients had a flare-up of disease under glucocorticosteroid treatment. Nadroparine calcium 5.700 IE anti-Xa/0.6 mL s.c. was self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events, and changes in clinical symptoms and in laboratory, endoscopical and histological results were analysed. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. In 20 of 25 patients, a good clinical and laboratory response was observed. Also, the endoscopic and histological signs of inflammation were found to be significantly improved. However, this was not accompanied by a significant reduction in the number of mucosal microvascular thrombi after 8 weeks of LMWH treatment. CONCLUSION: LMWH may be a safe adjuvant therapy for patients with active, glucocorticosteroid refractory ulcerative colitis.

DNA and ribonucleotide binding characteristics of two forms of the androgen receptor from rat prostates.

Androgen receptors (sedimentation value approximately 4S and Stokes radius 2.8 nm) present in the cytoplasmic fraction obtained from prostates of castrated rats bind to DNA-Sepharose and double stranded DNA. A receptor fragment (sedimentation value approximately 3S and Stokes radius 2.3 nm) obtained from rat prostates in the course of a purification procedure showed greatly diminished binding affinity for both DNA-Sepharose and soluble DNA. In contrast, both the 4S cytosol receptor and the 3S receptor form interacted with equal affinity with prostate RNA or poly(UG). These observations provide evidence that for DNA binding a different or additional part of the receptor molecule is required than for RNA and polyribonucleotide binding.

Endoscopic pancreatic drainage in chronic pancreatitis.

A nasopancreatic drain, pancreatic duct endoprostheses, and pancreatic stone extraction were used to treat 32 patients with chronic pancreatitis. Thirty patients were treated endoscopically. Endoscopic treatment via the minor papilla in 2 patients with pancreas divisum was not performed. Three patients had subsequent surgery because of complications; one of them died. Seventeen patients with chronic relapsing pancreatitis improved, with 15 patients asymptomatic during a follow-up of 2 to 69 months (median, 11). Seven of 10 patients with chronic pain improved, with 6 patients pain-free during a follow-up of 10 to 34 months (median, 11). In 7 patients, pancreatic pseudocysts could be drained endoscopically by positioning an endoprosthesis into the cyst or by performing a cystoduodenostomy. Six patients had concomitant placement of a biliary endoprosthesis to treat common bile duct strictures within the pancreatic head. One of 32 treated patients died as a result of a complication. We consider endoscopic therapy a viable alternative to surgery in select patients with chronic pancreatitis.

Platelet factor 4 and beta-thromboglobulin in inflammatory bowel disease and giant cell arteritis.

BACKGROUND: As platelet factors are important in the inflammatory response, we examined the course of platelet factor 4 and beta-thromboglobulin in relation to disease activity in inflammatory bowel disease and in giant cell arteritis. PATIENTS AND METHODS: In a prospective study, the platelet count, platelet factor 4 and beta-thromboglobulin were measured in 20 patients with Crohn's disease, 18 with ulcerative colitis and 19 with giant cell arteritis, during active and inactive disease, as well as in 51 controls without inflammation. RESULTS: Platelet counts were significantly higher in active vs. inactive Crohn's disease, ulcerative colitis and giant cell arteritis. Levels of platelet factor 4 and beta-thromboglobulin were significantly higher in active inflammatory bowel disease and giant cell arteritis, as well as in inactive inflammatory bowel disease and giant cell arteritis, than in the non-inflammatory controls. A positive correlation was found between the Crohn's disease activity index and the platelet count, platelet factor 4 and beta-thromboglobulin. Also, a positive correlation was found between the ulcerative colitis activity index and beta-thromboglobulin. However, even after 12 months of follow-up, in Crohn's disease and ulcerative colitis the mean levels of platelet factor 4 and beta-thromboglobulin were significantly higher than the levels of the controls. CONCLUSION: Platelet factors were correlated with inflammatory bowel disease activity. Levels of platelet factor 4 and beta-thromboglobulin, however, were markedly raised for a long time in clinically inactive inflammatory bowel disease, which might point to a pre-thrombotic state of disease.

Small cell lung cancer with paraneoplastic nephrotic syndrome.

We present a case of nephrotic syndrome, associated with small cell lung carcinoma. Renal biopsy revealed membranous glomerulonephritis, probably due to immune complex deposition with tumour antigen. Complete remission of the small cell lung carcinoma after chemotherapy was followed by regression of the nephrotic syndrome. This regression persisted even when brain metastases developed, without simultaneous relapse of tumour outside the central nervous system.

Differential behavior of coagulation factor XIII in patients with inflammatory bowel disease and in patients with giant cell arteritis.

The aim of this prospective study was to examine the role of coagulation factor XIII (FXIII) in relation to disease activity in inflammatory bowel disease (IBD) and in giant cell arteritis. Plasma FXIII activity was studied during active and inactive disease in newly diagnosed patients with Crohn's disease (CD; n = 20), ulcerative colitis (UC; n = 18) and giant cell arteritis (GCA; n = 19), in 3-month intervals (median follow-up 12 months). FXIII was also measured in two noninflammatory control groups, age and sex matched for IBD (n = 25) and GCA (n = 26). FXIII activity was significantly lower in active CD or UC than in active GCA or the noninflammatory controls. Both in CD and UC, FXIII activity correlated inversely with indices of clinical disease activity, the erythrocyte sedimentation rate, fibrinogen and C-reactive protein levels. Low FXIII activity is a characteristic feature of active IBD, and serial measurements may be useful to assess IBD activity.

14C-urea breath test in C pylori gastritis.

14C-urea breath test was used to detect Campylobacter pylori colonisation in 129 consecutive non-ulcer dyspepsia patients. Fasting patients were given 3 microCi (110 kBq) of 14C-labelled urea after a test meal. Breath samples were collected at 10 minute intervals for 90 minutes and the C-14 activity was counted on a liquid scintillation analyser. Urea derived 14CO2 appears in the exhaled breath of Campylobacter pylori culture positive individuals within 20-30 minutes. Likelihood analysis revealed a most favourable cut off level of [0.07% dose 14C-urea/mmol CO2] multiplied by body weight at t = 40 minutes, to separate culture positive from culture negative subjects. Using this upper limit of normal, a positive likelihood ratio of 50 and a negative likelihood ratio of 0.05 was calculated. Sensitivity of the test was 95% and specificity 98%. The 14C-urea breath test is a simple, sensitive and non-invasive test, that detects viable C pylori microorganism and semiquantitatively assesses the bacterial load of C pylori colonisation. Administration of a single dose of colloidal bismuth subcitrate resulted in a rapid decrease in 14CO2 excretion, so this test can be used to confirm eradication of the bacterium in therapeutic trials without endoscopy, or need for culture.