Hyperhomocysteinemia, malnutrition, and inflammation in ESRD patients

Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general population, but in end-stage renal disease patients some studies show a reverse association, i.e. higher levels of homocysteine are associated with better clinical outcome. In this brief review, we review the evidence that malnutrition, hypoalbuminemia, inflammation and diabetes mellitus may lower circulating levels of homocysteine. As these factors are strong predictors of clinical outcome, this may explain why lower homocysteine levels in end-stage renal disease patients are associated with worse clinical outcome. We conclude that these factors need to be taken into account in multivariate models evaluating the impact of hyperhomocysteinemia as a risk factor in end-stage renal disease patients.     

Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution.

PURPOSE: Human invasive breast cancers (IBC) show enormous histologic and biological diversity. This study comprehensively evaluated diversity in ductal carcinoma in situ (DCIS), the immediate precursors of IBCs. EXPERIMENTAL DESIGN: The extent of diversity for conventional histologic grade and standard prognostic biomarkers assessed by immunohistochemistry was evaluated in a series of pure DCIS (n = 200) compared with a contemporaneous series of IBCs (n = 200). A subset of the DCIS (n = 25) was evaluated by DNA microarrays for the presence of luminal, basal, and erbB2 intrinsic subtypes. The extent of diversity within individual cases of DCIS (n = 120) was determined by assessing multiple regions independently for histologic (nuclear) grade and several biomarkers by immunohistochemistry, which approximate microarrays in determining intrinsic subtypes. RESULTS: DCIS showed a broad distribution of conventional histologic grades and standard biomarkers ranging from well to poorly differentiated, nearly identical to IBCs. Microarrays showed the same intrinsic subtypes in DCIS as in IBCs. However, higher resolution analysis showed that multiple histologic grades, biomarker phenotypes, and intrinsic subtypes often coexist within the same DCIS, and these diverse regions probably compete for dominance. Diversity within cases of DCIS was highly correlated with mutated p53 (P = 0.0007). CONCLUSIONS: These results support the hypothesis that poorly differentiated DCIS gradually evolve from well-differentiated DCIS by randomly acquiring genetic defects resulting in increasingly abnormal cellular features. This diversity is amplified by defects resulting in genetic instability (e.g., p53 mutation), and the alterations are propagated to IBC in a manner independent of progression to invasion.     

Repair of paracolostomy hernias with Marlex mesh

The author's limited experience with the use of Marlex mesh to repair large paracolostomy hernias on five patients supports the experiences of others who have used this method of repair. The use of synthetic material in the repair of these often troublesome hernias is by no means conclusive since it was used only in a small number of patients. However, it is encouraging enough to warrant further use.     

Career preferences and perceptions of the medical labor market among Mexican interns

This paper examines the relationship between choice of career and perception of the medical labor market, as well as the effects of social origin, type of medical school, and place of internship. The data are derived from a survey of interns which was conducted in Mexico during 1978, when a substantial proportion of physicians was unemployed or underemployed.Career preferences were operationalized in terms of type of activity (general practice or specialty), site (ambulatory or hospital) and institution (public assistance, social security or private). Perceptions of the medical labor market were measured as an ‘objective’ feasibility perception and a ‘subjective’ opportunity assessment. Additionally, composite indices of career preferences and perceptions were constructed in order to take account of two integrated career patterns: dominant (or majority preference) vs alternative (or minority preference).Analysis of the data consistently revealed that perception of the medical labor market had a much stronger impact on preference for alternative than for dominant career patterns. Whereas social origin had no effect on career preference, type of medical school and place of internship exhibited a statistical ineraction with career preference, suggesting that certain structural conditions of the medical school and the teaching hospitals lead to preference for alternative rather than dominant careers.The implications of the findings are discussed with regard to health manpower policy, to conceptions of rational career choice and to the professional status of medicine in Mexico.     

Are leukocytosis and lipid peroxidation involved in ischemic or reperfusion injury in cardiac surgery?

We have studied the hypothesis that free-radical generation during cardiac surgery could explain partly the pathophysiology of ischemic or reperfusion injury during cardiopulmonary bypass (CPB). Ten patients undergoing cardiac surgery using CPB were prospectively studied. Malondialdehyde (MDA) was measured as a marker of free-radical-induced lipid peroxidation (LPO) using the thiobarbituric acid method, and leukocytes were counted during ischemia and reperfusion. Both MDA and leukocytes increased significantly, especially after starting reperfusion. There was significant correlation between LPO and leukocytosis (r = 0.8, p less than 0.005). It is concluded that free radicals generated during ischemia and reperfusion lead to an increase of LPO, which is shown for the first time to be associated with leukocytosis in cardiac surgical patients. The implication of this observation is of importance for the treatment strategy using free-radical scavengers in reducing the harmful effects of ischemia and reperfusion in cardiac surgery.     

The Use of in vitro Lymphocyte Responsiveness to Specific Mitogenic Agents in the Immunological Monitoring of Human Renal Allograft Recipients

In the course of immunologically monitoring the clinical progress of 16 renal allograft recipients, blood was drawn at serial intervals and patient in vitro lymphocyte reactivity to streptolysin-O and streptokinase-streptodornase studied. In vitro lymphocyte responsiveness to these specific mitogens provided no consistent guide to the adequacy of immunosuppression for maintenance of stable renal function. Variations in responsiveness gave no indication of either impending or actual rejection crises. Short-term culture (4 h) assessment of phyto-hemagglutinin responsiveness using the ³H-uridine method also failed to provide clinically useful information for these purposes. We conclude that conventional specific and non-specific mitogenic assays of lymphocyte functional integrity cannot be used to evaluate either the effectiveness of immunosuppressive medication or the development of rejection episodes.