Blood transfusion practices in military medicine

Background: This observational study was conducted in a small, 45 bed border static hospital, located in a field area, where no blood bank facilities were available. The present study was conducted to elucidate the blood transfusion practices of this hospital.     

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFNγ, IL-1α, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1α, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.     

Relation of habitual cocoa consumption to aortic stiffness and wave reflections, and to central hemodynamics in healthy individuals

The effect of habitual cocoa consumption on arterial stiffness and wave reflection indexes, as well as on peripheral and central blood pressure, was assessed in 198 healthy subjects. In conclusion, higher cocoa intake was an independent determinant of low arterial stiffness and wave reflection indexes and was also independently associated with significantly lower central (aortic) pulse pressure.     

Anterior cingulate dysfunction in geriatric depression

BACKGROUND: Although several brain abnormalities have been identified in geriatric depression, their relationship to the pathophysiological mechanisms leading to the development and perpetuation of this syndrome remain unclear. METHODS: This paper reviews findings on the anterior cingulate cortex (ACC) function and on the relationship of ACC abnormalities to the clinical presentation and the course of geriatric depression in order to elucidate the pathophysiological role of ACC in this disorder. RESULTS: The ACC is responsible for conflict detection and emotional evaluation of error and is connected to brain structures that regulate mood, emotional valence of thought and autonomic and visceral responses, which are functions disturbed in depression. Geriatric depression often is accompanied by abnormalities in some executive functions and has a clinical presentation consistent with ACC abnormalities. Indices of ACC dysfunction are associated with adverse outcomes of geriatric depression. CONCLUSIONS: Converging findings suggest that at least some ACC functions are abnormal in depression and these abnormalities are pathophysiologically meaningful. Indices of ACC dysfunction may be used to identify subgroups of depressed elderly patients with distinct illness course and treatment needs and serve as the theoretical background for novel treatment development.     

Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist.