15-HETE is the main eicosanoid present in mucus of ulcerative protocolitis

Abstract Prostaglandins, leukotrienes and mono-hydroxy acid products of arachidonic acid were measured in mucus of freshly recovered morning stools of a patient with an exacerbation of ulcerative proctocolitis. Eicosanoids in ether extracts were separated by high performance liquid chromatography and amounts determined by radioimmunoassay. Four hydroxy-eicosatetraenoic acids were detected, of which the most important one was identified as 15-hydroxy eicosatetraenoic acid (530 ng/g mucus). Leukotriene B4 was also present (21 ng/g mucus) and small amounts of immunoreactive leukotriene C4 (< 0.8 ng/g mucus). The prostaglandins 6-keto-PGF1α and PGE2 and thromboxane B2 were found in amounts of 3.7, 2.0 and 9.2 ng/g mucus, respectively

Drug-induced chest pain and myocardial infarction. Reports to a national centre and review of the literature

Objectives: To analyse reports of drug-induced myocardial infarction and chest pain sent to a national reporting centre. To review which drugs were suspected of exhibiting these adverse events and what mechanisms were involved. Methods: During the 20-year period 1975 through 1994, a total of 19,141 reports on adverse reactions to drugs were received by the Netherlands Centre for Monitoring of Adverse Reactions to Drugs. Of these 19 141 reports, 220 (1.1%) were concerned with drug-induced chest pain or myocardial infarction. After excluding reports in which the causal relationship was unlikely, poorly documented reports and reports on cases of overdosage, 183 reports (84%) were analysed. Results: There were 130 reports (71%) of drug-induced chest pain and 53 reports (29%) of drug-induced myocardial infarction. A total of 104 reports concerned females (57%). The most frequently reported suspected drugs were the antimigraine drug sumatriptan (33 reports, 4 concerning myocardial inf

Glafenine-associated anaphylaxis as a cause of hospital admission in The Netherlands

Summary. In 1981 generalized anaphylaxis was registered on 166 occasions in Dutch general an

Significance of thromboxane A2 and prostaglandin I2 in acute necrotizing pancreatitis in rats

Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2 levels were not. The significance of these alterations was investigated. Pancreatitis was induced by injecting 5% sodium taurocholate into the pancreatic duct. Iloprost (ZK 36374, a stable analog of prostaglandin I2, 25 ng/kg body weight) decreased the mortality rate from 100% to 50%. When treatment with iloprost was combined with simultaneous administration of either Sibelium (flunarizine R 14 950, 0.2 mg/kg body weight) or dazmegrel (UK 38 485, 50 mg/kg body weight) an additional decrease in the mortality rate was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2 levels. With flunarizine and iloprost the mortality rate was 40% (P<0.05); with dazmegrel and iloprost it was 10% (P<0.01). The results of the present study suggest that thromboxane A2 and prostaglandin I2 play a role in the course of acute necrotizing pancreatitis

Letter to the editor: Diagnosis of erythropoietic protoporphyria with severe liver injury - a case report

Erythropoietic protoporphyria (EPP) is an extremely rare disease which is often unrecognized as diagnosis. In the recent article Lui et al describe a patient with a new diagnosis of EPP with severe liver injury. Approximately 5%-20% of patients with EPP develop liver manifestations. The most severe complication of EPP is an hepatic crisis, which is a medical emergency requiring urgent treatment. Intensive treatment should consist of (exchange) transfusions and preferably in a center that performs liver transplantations

Species differences in the pattern of eicosanoids produced by inflamed and non-inflamed tissue

The synthesis of14C labelled arachidonic acid metabolites was measured in colonic tissues obtained from mice, rats, guinea pigs, rabbits, piglets and in colonic biopsies from humans during colonoscopy. The main eicosanoids formed after stimulation with calcium ionophore A23187 were: in humans, 15-hydroxy-eicosatetraenoic acid (15-HETE); in mice, 12-HETE; in rats, 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandine F1α (6kPGF1α); in guinea pigs, PGD2; in rabbits, 6kPGF1α, PGE2 and 15-HETE; and in pigs PGE2 and 12-HETE. In inflamed 15-HETE production was increased in man, HHT and 12-HETE production in rats and overall eicosanoid production in mice

Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies involving patients with different tumor types including non-small-cell lung cancer (NSCLC), ATP infusion appeared to inhibit loss of weight and deterioration of quality of life (QOL) and performance status. We conducted a randomized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC (stage IIIB or IV). METHODS: Fifty-eight patients were randomly assigned to receive either 10 intravenous 30-hour ATP infusions, with the infusions given at 2- to 4-week intervals, or no ATP. Outcome parameters were assessed every 4 weeks until 28 weeks. Between-group differences were tested for statistical significance by use of repeated-measures analysis, and reported P values are two-sided. RESULTS: Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP. Mean weight changes per 4-week period were -1.0 kg (95% confidence interval [CI] = -1.5 to -0.5) in the control group and 0.2 kg (95% CI = -0.2 to +0.6) in the ATP group (P =.002). Serum albumin concentration declined by -1.2 g/L (95% CI= -2.0 to -0.4) per 4 weeks in the control group but remained stable (0.0 g/L; 95% CI = -0.3 to +0.3) in the ATP group (P =.006). Elbow flexor muscle strength declined by -5.5% (95% CI = -9.6% to -1. 4%) per 4 weeks in the control group but remained stable (0.0%; 95% CI= -1.4% to +1.4%) in the ATP group (P =.01). A similar pattern was observed for knee extensor muscles (P =.02). The effects of ATP on body weight, muscle strength, and albumin concentration were especially marked in cachectic patients (P =.0002, P =.0001, and P =. 0001, respectively, for ATP versus no ATP). QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical scores (-0.2% versus -2.4%; P =. 0002); functional scores (+0.4% versus -5.5%; P =.02); psychologic scores (-0.7% versus -2.4%; P =.11); overall QOL score (+0.1% versus -3.5%; P =.0001). CONCLUSIONS: This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC

Hypertension is frequently present in patients with reflux esophagitis or Barrett's esophagus but not in those with non-ulcer dyspepsia

Background: Elevated mortality due to cardiovascular disease has been reported for patients with Barrett's esophagus (BE). We compared the prevalence of risk factors for cardiovascular disease in patients with BE, reflux esophagitis (RE), and non-ulcer dyspepsia (NUD) with that of the general population. Methods: Patients with upper gastrointestinal complaints and BE, RE, or NUD were compared with a matched cohort from the general population using a questionnaire and blood pressure and cholesterol measurements. Results: Hypertension occurred more frequently in patients with BE (odds ratio 5.1, P<0.0001) and RE (odds ratio 3.8, P<0.001), but not in those with NUD. Serum total cholesterol was higher in BE (P=0.02) and borderline in RE (P=0.06) but not in NUD. Mean HDL cholesterol levels, body mass index, and smoking did not differ. Conclusions: This study suggests that BE and RE found at diagnostic endoscopy are associated with an increased prevalence of hypertension and a higher total cholesterol level than in the general population. If so, this would explain the increased mortality during the follow-up of BE patients, and it should be taken into account when designing or evaluating follow-up studies of BE