Excess fatigue as a precursor of myocardial infarction

To test the hypothesis that feelings of exhausion are predictiveof future coronary heart disease, a prospective study was doneamong 3877 males, aged 39–65. Feelings of exhaustion wereassessed by the Maastricht Questionnaire. Among those who werefree of coronary heart disease at screening, 59 subjects experienceda fatal or non-fatal myocardial infarction during the 4.2 yearfollow-up period. A multiple logistic regression analysis revealedthat feeling of exhausion were predictive of future myocardialinfarction when controlling simultaneously for blood pressure,smoking, cholesterol, age and the use of antihypertensive drugs.     

TREATMENT OF DIABETES INSIPIDUS IN CHILDREN WITH DDAVP, A SYNTHETIC ANALOGUE OF VASOPRESSIN

The effects of a new, synthetic analogue of vasopressin, DDAVP (l-deamino-8-d-arginine vasopressin), was investigated in 10 children with diabetes insipidus due to deficient secretion of antidiuretic hormone. The lack of pressor activity, and the specific and long-lasting antidiuretic effect of this preparation was confirmed. During an observation period of 8–19 months it was found that intranasal administration of 1.25-10 μg of DDAVP twice daily was sufficient to normalize drinking and urine production in all the patients. No side effects were observed. It is concluded that DDAVP is a valuable alternative in the treatment of vasopressin sensitive diabetes insipidus in children, and that it is well suited for long-term use.     

Azathioprine or mercaptopurine‐induced acute pancreatitis is not a disease‐specific phenomenon

Aliment Pharmacol Ther 31 , 1322–1329

Summary

Background Several reports suggest an increased rate of adverse reactions to azathioprine in patients with Crohn’s disease. Aim To compare the incidence of thiopurine‐induced acute pancreatitis in patients with inflammatory bowel disease (IBD) with that in patients with vasculitis. Methods This retrospective analysis was performed using data collected in three databases by two university hospitals (241 patients with IBD and 108 patients with vasculitis) and one general district hospital (72 patients with IBD). Results The cumulative incidence of thiopurine‐induced acute pancreatitis in Crohn’s disease equalled that of ulcerative colitis (UC) (2.6% vs. 3.7%) and this did not differ from vasculitis patients (2.6% vs.1.9%). In addition, the cumulative incidence of thiopurine‐induced acute pancreatitis in UC patients was not different from that in vasculitis patients. In the IBD group, 100% of thiopurine‐induced acute pancreatitis patients were women, whereas in the vasculitis group the two observed thiopurine‐induced acute pancreatitis cases (n = 2 of 2) concerned were men (P = 0.012). Conclusions In this study, the alleged higher cumulative incidence of thiopurine‐induced acute pancreatitis in Crohn’s disease compared with vasculitis or UC patients was not confirmed. Female gender appears to be a risk factor for developing thiopurine‐induced acute pancreatitis in IBD patients.     

Prevalence of Depressive Symptoms and Depressive Disorder in Primary Care Patients Over 65 Years of Age

The aim of this study was to estimate the prevalence of depressivesymptoms and depressive disorder (ICHPPC-2-defined) in patientsover 65 years of age. A cross-sectional, partly two-phased,study was performed in general practices in The Netherlands.A total of 384 consecutive patients aged 65 and above, 116 menand 265 women were included, both during practice visits andhome visits. Depressive symptoms were recorded with the ZungSelf-rating Depression Scale, the Geriatric Depression Scale,and with physician ratings. Assessments of depressive disorderwere based on an adaptation of interview ratings with the MontgomeryÅsberg Depression Rating Scale. The proportion of patientsconsidered to have depressive symptoms ranged from 11 to 29%of patients, depending on the self-report instrument and thecut-off point. According to interviews a depressive disorderwas estimated to be present in 17%. The high prevalence of depressivesymptoms and depressive disorder suggest a higher index of suspicionof depres sion in elderly general practice patients.     

Colonoscopy‐controlled intra‐individual comparisons to screen relevant neoplasia: faecal immunochemical test vs. guaiac‐based faecal occult blood test

Aliment Pharmacol Ther 31 , 432–439

Summary

Background Guaiac‐based faecal occult blood tests (g‐FOBTs) are most commonly used in colorectal cancer (CRC) screening programmes. Faecal immunochemical tests (FITs) are thought to be superior. Aim To compare performance of a g‐FOBT and a quantitative FIT for detection of CRCs and advanced adenomas in a colonoscopy‐controlled population. Methods We assessed sensitivity and specificity of both FIT (OC‐sensor) and g‐FOBT (Hemoccult‐II) prior to patients’ scheduled colonoscopies. Results Of the 62 invasive cancers detected in 1821 individuals, g‐FOBT was positive in 46 and FIT in 54 (74.2% vs. 87.1%, P = 0.02). Among 194 patients with advanced adenomas, g‐FOBT was positive in 35 and FIT in 69 (18.0% vs. 35.6%, P < 0.001). Sensitivity for screen relevant tumours (197 advanced adenomas and 28 stage I or II cancers) was 23.0% for g‐FOBT and 40.5% for FIT (P < 0.001). Specificity of g‐FOBT compared to FIT for the detection of cancer was 95.7% vs. 91.0%, P < 0.001) and for advanced adenomas (97.4% vs. 94.2%, P < 0.001). Conclusions Faecal immunochemical test is more sensitive for CRC and advanced adenomas. Sensitivity of FIT for screen relevant tumours, early‐stage cancers and advanced adenomas, is significantly higher. Specificity of g‐FOBT is higher compared with FIT.     

Carbohydrate Recognition on MUC1-Expressing Targets Enhances Cytotoxicity of a T Cell Subpopulation

The influence of the epithelial mucin MUC1 on T cell-mediated lysis was analysed using lymph node lymphocytes (LNL) from patients with colorectal carcinoma. LNL were stimulated with allogeneic, MUC1-transfected B cells and the bulk cultures were cloned. Alloreactive cytotoxic T cell clones were obtained which preferentially lysed MUC1-expressing targets. The majority was CD4⁺ and MHC-class II-restricted, and a minor group was CD8⁺ and MHC-class I-restricted. All the clones expressed CD3 and TCRαβ, and were CD56⁻. The capacity to preferentially kill MUC1-expressing targets was stable in several clones for up to 6 months in culture. The enhancing effect of MUC1 on the lysis was investigated in more detail. It was only seen after inhibition of O-linked glycosylation in the targets. Furthermore, this effect was completely abrogated by the monoclonal antibody 3C9, directed against the Thomsen–Friedenreich antigen (T-antigen, Galβ1–3GalNAc bound α1–3 to Ser/Thr) as well as by the soluble disaccharide Galβ1–3GalNAc, but not by other similar disaccharides. The authors conclude that in their system the preferential killing of MUC1-expressing targets is due to the recognition of an internal carbohydrate epitope accessible on underglycosylated MUC1, possibly T-antigen, by an auxiliary receptor molecule on T cells.     

Information Selection and Signal Probability in Multisource Monitoring Under the Influence of Centrally Active Drugs: Phentermine Versus Pentobarbital

The present study is concerned with the relationship between drug-induced arousal shifts and sampling [(monitoring)] behaviour in a three-source task with ana priori signal occurrence probability of 0·6, 0·3, and 0·1. The multisource monitoring task and procedure was adopted from Hockey (1973) who reported that an arousing treatment, loud noise, produced increased sampling of the course associated with the high signal probability while sleep loss, presumed to decrease arousal level, resulted in a reduction of sampling on this source. Consistent with these findings it was expected that phentermine 20 mg (a stimulant, with a chemical structure related to that of amphetamines) and pentobarbital 100 mg (a barbiturate) would show the same pattern of results, given their opposite effects on brain arousal. Twenty-four male subjects participated in the study and received the drugs according to a placebo-controlled double-blind, three-way crossover design. In contrast to the results from Hockey's study, neither phentermine nor pentobarbital significantly affected average sampling behaviour on the high probability source. Differential drug effects appeared primarily on the low probability source, in that phentermine significantly reduced sampling on this source and pentobarbital produced the highest number of sampling responses to detect signals on this source. The possible reasons for the discrepancy between Hockey's and the present results are discussed.