Effect of angiotensin converting enzyme inhibition on renal function in the treatment of heart failure

Renal hemodynamics in heart failure and the effects of angiotensin converting enzyme (ACE) inhibition on renal function are reviewed. The incidence of renal dysfunction in patients with congestive heart failure is relatively high; however, the incidence of progression of renal dysfunction during treatment with ACE inhibitors is low. The mild reduction in renal function initially observed represents the physiologic expression of blocking both the systemic and the intrarenal compensatory activities of the renin-angiotensin system. Despite small changes in blood urea nitrogen and serum creatinine noted following initiation of enalapril therapy in the two studies described, there was no further clinically significant increase in blood urea nitrogen and serum creatinine noted during continued treatment in the majority of patients, irrespective of baseline renal function. The use of enalapril as adjunctive therapy with digitalis and diuretics in patients with congestive heart failure, with appropriate adjustment of the dosages of these agents, may benefit many patients.     

Heterologous prime-boost strategy to immunize very young infants against measles: pre-clinical studies in rhesus macaques

Infants in developing countries are at high risk of developing severe clinical measles if they become infected during the "window of vulnerability" (age 4-9 months), when declining maternal antibodies do not protect against wild virus, yet impede successful immunization by attenuated measles vaccine. We developed two Sindbis replicon-based DNA vaccines expressing measles virus hemagglutinin and fusion protein with the goal of priming young infants to respond safely and effectively to subsequent boosting with attenuated measles vaccine. Intradermal prime with DNA vaccines by needle-free injection followed by aerosol or parenteral boost with licensed measles vaccine was well tolerated by juvenile and young infant rhesus macaques, and protected against clinical measles and viremia on wild-type virus challenge. A proteosome-measles vaccine administered alone (three doses) or as a boost following DNA vaccine priming was also safe and protective. These promising results pave the way for clinical trials to assess this prime-boost strategy.     

Characterization of the epitope recognized by a monoclonal antibody highly specific for blood group M antigen

The mouse monoclonal antibody M2A1 of IgG1 class, which is highly specific for blood group M antigen, was obtained and characterized by means of hemagglutination, enzyme-linked immunosorbent assay, immunoblotting, and inhibition assays. The use of modified M glycoprotein preparations for inhibition tests and of variant McN and Henshaw red cell membranes for immunoblotting showed that M2A1 recognized an epitope including the NH2-terminal serine and sialic acid residues of glycophorin A, whereas the fifth glycine residue was not involved. The reactivity of the antibody with M antigen was distinctly dependent on ionic strength and pH; the optimum was at pH 8 to 9. The alpha-amino group of terminal serine residue was not necessary for the reaction with M2A1 antibody, and the results obtained suggested that the positive charge of this group contributed to decreasing antigen-antibody reactions at pH below 8. The reaction of the antibody with blood group N antigen was not detectable in any of the assays used.     

Estimation of Vmax in auxotonic systoles from the rate of relative increase of isovolumic pressure: (dP/dt)kP

High speed oscilloscopic recordings (4000 mm/sec) of left ventricular pressure (micromanometer) and its first derivative were used to calculate contractile element velocity (Vce) during the isovolumic period of auxotonic beats in anesthetized dogs. At 0.5-2.0 msec intervals of isovolumic systole, Vce was derived as (dP/dt)/kP, where k = 24 cm(-1). Plots of Vce and P yielded inverse curves from peak Vce to aortic valve opening pressure which averaged 27 msec in controls, and 11 msec during norepinephrine administration. Extrapolated Vmax, in muscle lengths/second, averaged 3.6 (controls), 3.6 (volume load), and 6.6 (norepinephrine). In each experimental state, Vmax was also determined from force-velocity relations of isovolumic beats (abrupt aortic occlusion) analyzed at 10 msec intervals from conventional pressure recordings. Vmax by both methods correlated well (r = 0.88). While good correlations were also noted between Vmax and maximum dP/dt, (max dP/dt)/integrated isovolumic pressure, (max dP/dt)/peak isovolumic pressure, and (max dP/dt)/kP, only the last two of these successfully distinguished changes between volume load and inotropic stimulation. Thus, assuming an unchanged series elasticity, the contractile state of the auxotonic ventricle may be determined utilizing a single high-fidelity catheter system and high speed recordings of isovolumic pressure.     

Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder.

Vasopressin increases the permeability of the total urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or the the lipophilic solute diphenylhydantoin. In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in to toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyflurane-treated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well. We conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea.     

Flutamide therapy for carcinoma of the prostate.

In our three-year experience with the use of flutamide for the treatment of carcinoma of the prostate, 20 patients with previously untreated stage D carcinoma of the prostate were enrolled in a 12-week double-blind study. Seven patients received 1.5 gm of flutamide daily, seven patients received 0.75 gm of flutamide daily, and six patients received 1.0 mg of diethylstilbestrol daily. Two patients receiving flutamide did not complete the 12-week study. Six patients receiving flutamide and three patients receiving diethylstilbestrol had objective evidence of improvement. Of the patients receiving flutamide, 50% were alive at one year, and 43% were alive at two years. Three of the original 14 patients started on flutamide are alive at 36, 33, and 24 months. In addition, we continued clinical evaluation of flutamide as an open study, enrolling six other patients (four with stage D and two with stage C carcinoma of the prostate). All except one of these patients had received previous hormonal therapy. At present, four are still being followed up at 13, 15, 20 and 24 months, demonstrating that flutamide can give positive results to some patients whose condition is deteriorating despite diethylstilbestrol therapy.     

In-vitro evaluation of cefpirome (HR 810), teicoplanin and four other antimicrobials against enterococci

In-vitro activities of cefpirome (HR 810), a fourth generation cephalosporin, and teicoplanin were compared with those of ampicillin, piperacillin, and vancomycin against 56 clinical isolates of enterococci. Cefpirome had good activity with the MIC90 and MBC90 being 4 and 16 mg/l. Ampicillin and piperacillin had MBC90 of 4 and 16 mg/l. Teicoplanin was extremely active with the MIC90 being 1.6 mg/l while vancomycin had poor cidal activity with the MBC90 being 16 mg/l. A decrease in activity of cefpirome was noted when the inoculum size was increased from 10(3) to 10(7) organisms per ml. Synergy was demonstrated against most Streptococcus faecium isolates with a combination of cefpirome and gentamicin or piperacillin. Against Str. faecalis, with a similar combination, synergy was seen in less than 50% isolates. No antagonism was noted with any of the antibiotic combinations.     

Réalisation d’une transfusion sanguine en néonatologie : état des lieux des pratiques en 2016 en France ; situations aiguës ou chirurgicales exclues

Background

Blood transfusion is common in neonatology, especially in preterm or low birth weight infants. Recommendations were proposed by the French National Authority of Health (HAS) in 2014 and 2015 for red blood cells and platelet transfusion respectively, but an heterogeneity of practical attitudes persist. The objective of this survey is to evaluate transfusion practices in neonatal intensive care units.

Electric muscle stimulation for pressure sore prevention: tissue shape variation

This study measured changes in tissue shape and deformation at the seating interface produced by electric muscle stimulation (EMS) of the gluteus maximus. The purpose of the study was to investigate the application of EMS for pressure sore prevention. Limitations of pressure measurements for analysis of load distribution are discussed and a rationale developed for using tissue shape and deformation to further characterize the seating interface. Ultrasonic imaging of the seating interface is described under three conditions: buttocks suspended, external load applied with no EMS, and external load applied with bilateral EMS of the buttocks. Results show that low level stimulation of the gluteus maximus produces substantial changes in the shape of the loaded buttocks and an external contour more nearly shaped like the suspended buttocks. It is concluded that EMS produces buttock tissue undulation and shape reconfiguration which may assist in preventing pressure sores over the seating surface.