Limitations of extensive TPMT genotyping in the management of azathioprine-induced myelosuppression in IBD patients.

BACKGROUND AND AIMS: TPMT deficiency is associated with azathioprine (AZA)-induced myelosuppression (MS). However, in one previous study, only about » of MS episodes in Crohn's Disease patients under AZA can be attributed to TPMT deficiency. Recently, new TPMT mutations have been described and our aim is to investigate their clinical relevance before and after a first MS episode on thiopurine therapy. METHODS: Clinical data from 61 IBD patients having developed MS during AZA therapy were collected. Sequencing analysis was carried out on TPMT cDNA for the presence of all currently known mutations. RESULTS: Only TPMT *2, *3A and *3C mutations were found in this cohort. TPMT mutations were observed in 15 out of 61 patients (25%). Four out of 15 were homozygous for a TPMT mutation (low methylator, LM genotype) and 11 were heterozygous (intermediate methylator, IM genotype). Median delays of MS onset were 2, 2.75 and 6months in the LM, IM and HM (high methylator, wild type TPMT) groups, respectively. After the first MS episode, 36 patients resumed thiopurine treatment of which 13 experienced a second MS episode. This second episode was also rarely associated with TPMT mutations. CONCLUSIONS: One quarter of MS episodes during AZA were associated with TPMT deficient genotype. After a first leucopenia episode, thiopurine therapy may be resumed in a majority of patients independently of their TPMT genotype.

Issues in managing patients with chronic hepatitis C in public hospitals.

Public hospitals in Belgium are taking care of a disfavoured people such as drug addicts, alcoholics, patients with low income and people referred by refugee centres. Many of these patients are at risk of hepatitis C. The medical and paramedical staff is facing numerous problems in taking care of these patients. Requests of hepatologists from public hospitals are a more effective psychosocial management, an increase of the framing in these hospitals, and a more rapid process of reimbursement of medication for treatment of hepatitis C, allowing to treat the patients according to international standards.

Acute lower gastrointestinal bleeding in Crohn's disease: characteristics of a unique series of 34 patients. Belgian IBD Research Group.

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological characteristics and therapeutic options of hemorrhagic forms of Crohn's disease. METHODS: Thirty-four cases of hemorrhagic forms of Crohn's disease were studied retrospectively. Acute lower gastrointestinal hemorrhage was defined as acute rectal bleeding originating in diseased bowel and requiring a transfusion of at least 2 units of red blood cells within 24 h. Upper gastrointestinal tract hemorrhage or anal lesions and postoperative bleeding were excluded. RESULTS: Mean age at time of hemorrhage was 34.2 +/- 14 yr. Mean duration of disease before the hemorrhage was 5.6 +/- 6 yr. The hemorrhage occurred during a flare up of the disease in 35% of cases. The hemorrhage revealed Crohn's disease in 23.5% of cases. The hemorrhage was more frequent in colonic disease (85%) than in isolated small bowel disease (15%) (p < 0.0001). The origin of bleeding was identified in 65% of cases, by colonoscopy (60%), by angiography (3 patients), or at surgery (1 patient). The bleeding lesion was an ulcer in 95% of cases, most often in the left colon. The treatment was surgical in 20.5% (colectomy in 36%), endoscopical (7 patients, including 5 successes), or medical. Hemorrhage recurred in 12 patients (35%) within a mean time of 3 yr (4 days-8 yr), requiring surgery in 3 cases. No death was observed. CONCLUSIONS: This study performed in a series characterized by a nonsurgical recruitment, the largest to date, shows that hemorrhagic forms of Crohn's disease may reveal disease in 23.5%, occurs in quiescent Crohn's disease in two-thirds of cases. Given the potential efficacy of endoscopical or medical treatment, as well as the absence of mortality, a conservative approach may be suggested as first-line therapy in the majority of patients.

Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis.

BACKGROUND AND AIMS: It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS: Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis. RESULTS: Histological diagnosis was confirmed in 96 patients with collagenous colitis and 80 with lymphocytic colitis. Twenty eight per cent of patients with collagenous colitis and 26% of patients with lymphocytic colitis had overlapping but less pronounced histological features. Both groups were equal in terms of age, use of aspirin and non-steroidal anti-inflammatory drugs, associated autoimmune conditions, arthritis, diarrhoea, and abdominal pain. The male:female ratio was 27:73 for collagenous colitis and 45:55 for lymphocytic colitis (p=0.013). Twenty five per cent of patients with collagenous colitis compared with 14% of patients with lymphocytic colitis were active smokers; only 8.3% of patients with collagenous colitis had stopped smoking compared with 23% of patients with lymphocytic colitis (p=0.013). Drug induced disease was suspected for ticlopidine (two collagenous colitis, four lymphocytic colitis) and flutamide (four lymphocytic colitis). Mean duration of symptoms before diagnosis was two months for lymphocytic colitis and four months for collagenous colitis. Overall prognosis was generally mild; 84% of patients with lymphocytic colitis and 74% of patients with collagenous colitis reported resolution or significant improvement (p=0.033). CONCLUSIONS: Collagenous and lymphocytic colitis are similar but not identical. Patients with lymphocytic colitis present somewhat earlier and are less likely to be active smokers. Symptoms are milder and more likely to disappear in lymphocytic colitis. Ticlopidine and flutamide should be added to the list of drugs inducing colitis.

Benign ulcer in a hiatus hernia complicated with a pericardial fistula.

Penetration of the pericardium by upper gastrointestinal lesions is uncommon. It usually results from trauma, perforation of foreign objects, perforation from gastric or thoracic neoplasm or spontaneous perforation. Unfrequently it is a complication of a benign peptic ulcer of the esophagus or the stomach. Survival from peptic ulcers penetrating to the heart is very rare. From a review of the English literature only 11 survivors have been described. We report the successful outcome of a 76 year old lady with a benign ulcus in a hiatus hernia perforating into the pericardium. Diagnosis of the fistula was established after methylene blue swallow. Treatment consisted of early pericardiotomy and drainage followed by surgical correction of the ulcer and fundoplication of the hiatus hernia.

Biliary phytobezoar: a medical curiosity.

This report describes a case of cholestatic jaundice caused by concretions of vegetable material obstructing the extrahepatic bile ducts. We have named this a biliary phytobezoar, by analogy with its gastric counterpart. The anomaly underlying this curiosity was a surgical cholecystogastrostomy performed 15 yr earlier.

Guanidino compounds in serum and urine of cirrhotic patients.

To investigate the metabolic relationship between urea and guanidinosuccinic acid (GSA), we determined the levels of the guanidino compounds, including GSA, and urea in serum and urine of cirrhotic patients. Linear correlation studies between serum urea and GSA levels were performed. Good positive linear correlation coefficients were found in the Child-Turcotte C subgroup (r = .847, P < .001) and in the total subgroup including B and C patients (r = .848; P < .0001). Serum guanidinoacetic acid levels were significantly increased in the Child-Turcotte C subgroup (P < .0001 for men and P < .001 for women). In contrast, GSA levels were significantly (P < .0001) decreased in the three studied subgroups. Similar results were found for urinary GSA excretion levels. Within each subgroup, serum and urinary GSA levels were significantly lower in patients with alcohol-induced cirrhosis than in nonalcoholic cirrhotic patients. Similar results were obtained for urea. The findings in cirrhotic patients clearly demonstrate a metabolic relationship between urea and GSA. They also show that urea and GSA biosynthesis is significantly lower in cirrhotic patients with an alcoholic origin than in cirrhotic patients with a nonalcoholic origin.

Duodenal diaphragmlike stricture induced by acetylsalicylic acid.

Many reports have mentioned the role of nonsteroidal antiinflammatory drugs in inducing diaphragm-like strictures in the small and large bowel. These lesions are mostly seen in patients with chronic use of nonsteroidal antiinflammatory drugs. We report the case of a 57-year-old man who developed a diaphragmlike stricture in the second part of the duodenum. The patient had been using a preparation containing acetylsalicylic acid during many years. Although a congenital origin of the diaphragm is not completely excluded, we postulate that this stricture probably occurred as a result of acetylsalicylic acid-induced ulcerations, followed by submucosal fibrosis.

Paroxystic neuropsychological symptoms as the early expression of hepatic encephalopathy. A case report.

A 52-year-old patient presented with paroxystic episodes of generalized apraxia, anomia, agraphia and acalculia. The transient character of these attacks was supported by several neuropsychological examinations. Initially a tentative diagnosis of multiple TIA's was made. Treatment consisted of antiplatelet aggregation therapy. Three years later, however, paroxystic neuropsychological symptomatology occurred more frequently with an increase of severity. The patient was again seen and the differential diagnosis included epilepsy or a metabolic disturbance, in casu hepatic encephalopathy. A therapeutic trial with carbamazepine was started but the patient deteriorated further. He developed a flapping tremor and became stuporous. The blood ammonia was high and there were triphasic waves on the EEG. A probable diagnosis of hepatic encephalopathy was made and carbamazepine therapy was withdrawn. There was a good response on low protein diet and lactulose.

Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study.

We conducted a case-control study in five general hospitals in the region of Antwerp, studying 161 patients (102 men, 59 women) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from 'erosive lesions' (peptic oesophagitis, gastric erosions, gastric ulcer(s), or duodenal ulcer(s]. There was a highly significant difference between cases and control subjects in the use of non-steroidal anti-inflammatory drugs (NSAIDs, excluding aspirin) (odds ratio 7.4, p less than 0.001; 95% confidence interval odds ratio 3.7 to 14.7). There also was a significant difference in the use of aspirin (odds ratio 2.2, p = 0.025; 95% CI odds ratio 1.3 to 4.0) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease (odds ratio 5.5, p less than 0.001; 95% CI odds ratio 3.2 to 9.6). There was no significant difference in the use of other drugs, paracetamol and corticosteroids in particular, nor in the use of alcohol or tobacco. The patient group using NSAIDs was older, had more women, and had a higher mortality than the group not using NSAIDs. Among patients with bleeding gastric or duodenal ulcer(s), NSAID users were not more or less likely to have had symptoms of peptic ulcer disease, and had no higher frequency of multiple gastric or duodenal ulcers. The attributable risk for NSAID use was 0.30 (95% CI 0.23 to 0.37) and for aspirin use 0.14 (95% CI 0.08 to 0.20).

The etiology and management of rumination and psychogenic vomiting: a review.

Chronic vomiting, in the absence of discernible physical illness, is a problem sometimes seen in individuals labeled as mentally retarded or mentally ill. This behavior often becomes life-threatening, particularly when it occurs in young children. Over the decades several theoretical analyses have been made of this behavior, and a wide range of treatments have been developed. This paper is a summarization of current and historical literature related to three types of chronic vomiting: (1) rumination in the infant; (2) rumination in the older child and adult; and (3) psychogenic vomiting. Treatment strategies are reviewed in some detail and are evaluated for the practitioner using effectiveness and efficiency as the main evaluative criteria. Several ideas for further research and theoretical analysis are also suggested.

Clinical experience with prolonged combined hemoperfusion-hemodialysis treatment of severe poisoning.

Fifteen patients with severe drug intoxication have been treated by a procedure combining hemoperfusion (HP, cellulose-coated activated charcoal, Adsorba C300, Gambro, Sweden) and hemodialysis (HD). The combined HP-HD treatment resulted in a clearance for amobarbital of 121 +/- 10 ml per min (mean +/-SEM), butobarbital 142 +/- 4 ml per min, carbromal 121 +/- 6 ml per min, hexobarbital 181 +/- 13 ml per min, meprobamate 145 +/- 9 ml per min, methaqualone 137 +/- 5 ml per min, phenobarbital 138 +/- 4 ml per min, and secobarbital 125 +/- 4 ml per min. There was no decrease in drug extraction even after 30 hours of treatment. Duration of treatment (6 to 33 hours) was determined by the clinical state of the patient. Prolonged HP-HD seemed to ben an efficient and sage procedure. Of 15 patients treated, 14 regained consciousness and 12 survived. The platelet count decreased, necessitating cessation of treatment in two cases. There was extraction of oxygen by the charcoal column, without influence on patient Po2. Glucose, urea, creatinine, uric acid, phosphate, and triglycerides were removed by adsorption on charcoal and/or dialysis.