Brachial artery hemodynamic response to acute converting enzyme inhibition by enalaprilat in essential hypertension

To assess the vascular involvement of renin-angiotensin system inhibition in human hypertension, acute effects of intravenous enalaprilat on brachial artery diameter, blood flow, and blood velocity were investigated in hypertensive patients by pulsed Doppler technique and compared with effects of saline vehicle. Compared with saline vehicle, enalaprilat reduced blood pressure (P less than 0.001) and increased brachial arterial diameter (P less than 0.01) and brachial blood flow (P less than 0.01). Enalaprilat effect on arterial pulse pressure was dependent on preinjection pulse pressure (r = -0.76; P less than 0.001), but its effect on mean blood pressure was not dependent on preinjection mean blood pressure. On the other hand, enalaprilat effect on arterial blood flow was negatively correlated with preinjection blood pressure (r = -0.64; P less than 0.02). The findings point to different responses of large and small arteries to intravenous enalaprilat.     

Androgen receptors in colorectal adenomas

Summary To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17–2.7x10^-9 M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P=0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24–3.1x10^-9 M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.     

Cytokines and oncogene activity

Cytokines play a part in the control of cellular growth, differentiation and development. Given such pleiotropic activities, it is not unexpected that the expression of the cytokines is tightly regulated. When cytokine-mediated processes are altered by mutation and/or overexpression of some cytokine or cytokine receptor genes, oncogenic transformation can occur. Oncogenes which derive their transforming potential through this mechanism include sis, which represents the activated form of the platelet-derived growth factor B chain, hst1/K-fgflint-2, which share appreciable homology with the gene family of fibroblast growth factors, fms, which is related to the cell surface receptor for macrophage-colony stimulating factor, and erbB-1, which encodes a truncated form of the epidermal growth factor receptor. Cytokine treatment has resulted in modulation of aberrant oncogene activity in some model systems.     

The clinical relevance of t(14; 18)/BCL-2 rearrangement and DEL 6q in diffuse large cell lymphoma and immunoblastic lymphoma

Background: t(14; 18)/bcl-2 gene rearrangement (R) is claimedto impart a worse rate of complete remission and disease-freesurvival in diffuse large cell lymphoma (DLCL). DEL 6q has alsobeen associated with poor outcome. Design: Retrospective studyof 54 patients with either diffuse large cell or immunoblasticlymphoma who had cytogenetics and/or molecular studies performed.Results: Patient characteristics, complete remission rate, andtime to treatment failure (TTF) were similar at three year follow-upfor groups with and without t(14; 18)/BCL-2R Survival was worsefor the former but the difference was not statistically significant.For DEL 6q, patient characteristics and survival rates weresimilar at three year follow-up for patients with and withoutthe abnormality. TTF was worse for the former but this was notstatistically significant. Conclusion: This study, with equalor greater number of patients with t(14; 18) than previous reports,fails to show a worse prognosis for patients with the t(14;18) chromosomal abnormality. A definite association will awaitfurther accrual of patients and a meaningul multivariate analysis. lymphoma, BCL-2, cytogenetics, DEL 6q     

Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Sterility and efficiency of two methods of cardiac output determination: closed loop and capped syringe methods

A prospective randomized study was done to compare the fluid contamination rates of two methods used to determine cardiac output by thermodilution under in-use conditions. Fifty patients were randomly assigned to have cardiac output measured by the capped syringe or closed loop method, and were followed with quantitative cultures of fluid and catheter. The two treatment groups (n = 25 each) were comparable in terms of age, sex, intensive care unit location, underlying diagnosis, and mean number of cardiac output determinations performed in the first 24 hours after placement of the catheter line. No differences in the rates of fluid contamination were seen at any time between the two groups. The overall fluid contamination rate was 2/124 cultures (1.8% with 95% confidence interval +/- 4.1%) with one colony of Staphylococcus epidermidis from a closed loop sample and one colony of Pseudomonas maltophilia in a capped syringe sample. Although no difference in contamination rates was documented, the closed loop system required less nursing time and effort.     

Tetanus in leprosy patients: report of five cases

It has long been noted that tetanus is rare in leprosy patients. Five cases of tetanus are reported in leprosy patients in Addis Ababa, Ethiopia. Although natural immunity to tetanus occurs and this appears to be higher in leprosy patients than in the general population, it is not completely protective. Further research on the relationship between tetanus and leprosy is indicated. Although firm epidemiologic data are lacking, it is prudent to give leprosy patients at least one dose of tetanus toxoid.