Dual Exposure to Sevoflurane Improves Anesthetic Preconditioning in Intact Hearts

Background: Anesthetic preconditioning (APC) with sevoflurane reduces myocardial ischemia-reperfusion injury. The authors tested whether two brief exposures to sevoflurane would lead to a better preconditioning state than would a single longer exposure and whether dual exposure to a lower (L) concentration of sevoflurane would achieve an outcome similar to that associated with a single exposure to a higher (H) concentration.

Methods: Langendorff-prepared guinea pig hearts were exposed to 0.4 mm sevoflurane once for 15 min (H1-15; n = 8) or 0.4 mm (H2-5; n = 8) or 0.2 mm sevoflurane (L2-5; n = 8) twice for 5 min, with a 5-min washout period interspersed. Sevoflurane was then washed out for 20 min before 30 min of global no-flow ischemia and 120 min of reperfusion. Control hearts (n = 8) were not subjected to APC. Left ventricular pressure was measured isovolumetrically. Ventricular infarct size was determined by tetrazolium staining and cumulative planimetry. Values are expressed as mean +/- SD.

Results: The authors found a better functional return and a lesser percentage of infarction on reperfusion in H2-5 (28 +/- 9%) than in H1-15 (36 +/- 8%; P < 0.05), L2-5 (43 +/- 6%; P < 0.05), or control hearts (52 +/- 7%; P < 0.05).     

Three highly polymorphic microsatellites at the human myelin oligodendrocyte glycoprotein locus, 100 kb telomeric to HLA-F : Characterization and relation to HLA haplotypes

The MOG locus, located on chromosomal bands 6p21.3-p22 and mapped about 100 kb telomeric to HLA-F, was isolated from cosmid ICRFcl09A2434 and shown to contain three microsatellites. These CA-repeat polymorphic markers were characterized in a sample of 173 healthy unrelated individuals and 84 DNAs from the HLA Workshop reference panel, by a method combining fluorescence labeling of PCR products and use of an automated DNA sequencer. For the three markers, frequencies of heterozygotes are well predicted from allele frequencies by the Hardy—Weinberg rule, which suggests that problems of allele nonamplification are unlikely. Typing of cell lines homozygous in the HLA region allowed unambiguous definition of 81 HLA-MOG haplotypes and showed that several HLA ancestral haplotypes extended to the MOG region. The high degree of polymorphism (59%, 51%, and 81% at the three loci, respectively, and 87% at the haplotype level) makes these new markers informative for association or linkage studies with diseases such as hemochromatosis or multiple sclerosis, and for studies aimed at precisely delineating the site of crossover in chromosomes in which recombination occurred in the distal part of the HLA class I region.     

Distribution of the [3H]-label from low doses of radioactive ochratoxin a ingested by rats,and evidence for DNA single-strand breaks caused in liver and kidneys

The distribution of a single low dose of [³H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [³H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased.After a 12-week feeding experiment, with doses of 288.8 g/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.     

Effect of low concentrations of K+ and Cl− on the Na+-dependent neuronal uptake of [3H] dopamine

The specific uptake of [³H] dopamine (DA) was studied using a crude synaptosomal fraction obtained from rat striatum. In a medium containing a 10 mM NaHC03/NaH2PO4 buffer and no added K⁺ ions, addition of NaCl elicited an increase in DA uptake for Na⁺ concentrations from 10 to 60 mM, and then a decrease of uptake for Na⁺ concentrations up to 130 mM. These data confirm that rather low NaCl concentrations produce a maximal DA uptake. This biphasic curve of uptake resulted from significant changes in the V _max of the DA uptake. Except for 10 mM Na⁺, this curve was not significantly modified when 9 mM NaHCO₃/NaH₂PO₄ were replaced by 9 mM NaCl. This result indicates that the Cl^– dependence of the DA uptake is mainly secondary to the Na⁺ dependence. Addition of KCl up to 3 mM did not modify the ascending part of the NaCl-dependent uptake curve. In contrast, the reduction in uptake produced by high Na⁺ concentrations was prevented in a concentration-dependent manner by KCl; this effect resulted from a decrease in the K_m and an increase in the V _max for the uptake.Measurements of membrane potential, with the help of the fluorescent probe 3,3-diethylthiadicarbocyanine iodide [DiSC₂(5)] and purified synaptosomes prepared from rat striatum and cerebral cortex, revealed that addition of 3 mM KCl to a medium containing a high Na⁺ concentration and no K⁺ ions produced a marked and stable decrease in the fluorescence level. This decrease which corresponds to an increase in membrane polarization was blocked by 0.1 mM ouabain. These data suggest that low K⁺ concentrations are likely to prevent the decrease in uptake elicited by high Na⁺ concentrations by restoration, via a Na⁺/K⁺ ATPase-mediated mechanism, of the membrane potential and/or a transmembrane electrochemical Na⁺ gradient more favourable to DA uptake.     

Prevalent diabetes and risk of total,colorectal, prostate and breast cancers in an ageing population: meta-analysis of individual participant data from cohorts of the CHANCES consortium

Background We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I² = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I² = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I² = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I² = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I² = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.Subject terms: Risk factors, Cancer epidemiology     

Caractéristiques des patients admis en médecine interne dans 18 hôpitaux français en aval des urgences et organisation de ces services : enquête transversale de la SNFMI (groupe d’étude SiFMI) en 2015

IntroductionPatients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments.MethodsBetween June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days.ResultsThree hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75–6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine.ConclusionThis study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.