[Assessment of the effect of the COVID-19 health crisis on the aerobic capacities of healthy patients. Analysis of the effort tests of the patients of the sports medicine services of the Angers UHC and the Cholet HC between May 2018 and May 2021]. / Mesure de l'effet de la crise sanitaire COVID-19 sur les capacités aérobies de patients sains. Analyse des épreuves d'effort des patients des services de médecine du sport du CHU d'Angers et du CH de Cholet entre mai 2018 et mai 2021.

Objectives: To measure the impact of the health crisis related to SARS-CoV-2 on the aerobic capacities of healthy patients based on the measurement of VO2max and VO2 at the first ventilatory threshold (AT). To measure the impact of the introduction of the antibacterial filter on the ventilatory parameter measuring device. Materials and methods: Based on a multicentre (Angers and Cholet), observational and retrospective study, we want to analyze the effect of containment measures and the cessation of sports competitions on the measurement of VO2max in healthy patients. For each patient, will be collected: the gross value of the max VO2 and indexed to the weight of the patient, as well as its percentage with respect to the expected theoretical value, the value of the VO2 at the aerobic threshold indexed to the wieght of the patient and the usual cardiorespiratory parameters (HR max, RR max, VE max, RER max). Two samples will be analyzed: patients with only one EFX ("unpaired" sample) and patients with multiple successive EFX over three years ("matched" sample). The impact of the antibacterial filter, used in one of the Sports Medicine departments, will be studied as a secondary issue. Statistical analyses were performed with the IBM SPSS 26 software. For all statistical tests, a p value of 0.05 was used in bilateral testing as the significance criterion. Results: There is a significant difference in the value of VO2max and AT in both the "unpaired" (VO2max: 36.72 vs. 35.08 mL/kg/min, P = 0.014-AT: 21.03 vs. 19.25 mL/kg/min, P < 0.001) and "matched" groups (VO2max: 2.76 vs. 2.64 L/min, P = 0.037-AT: 1.55 vs. 1.38 L/min, P = 0.001), more pronounced in patients over 60 years of age. The impact of the antibacterial filter does not show any particular impact within the "independent" sample. Within the "matched" sample, the significant age difference is not conclusive, but the exclusion of patients over the age of 60 makes the results meaningless.

Lack of ovarian responsiveness to gonadotropic hormones in infantile rats sterilized with busulfan.

Ovarian responsiveness to FSH and LH was examined in infantile rats treated in utero with busulfan (1,4-butanediol dimethanesulfate), a cytotoxic drug which has been shown to cause selective attrition of germ cells in the rat fetus. Pregnant Sprague-Dawley rats were injected ip on day 13 of gestation with busulfan (10 mg/kg BW) suspended in sesame oil or with sesame oil alone (control). Pups were killed on days 6, 8, 10, 12, or 14 postnatally, and trunk blood was collected. The ovaries were removed and either fixed for light microscopy or assessed for responsiveness to FSH and LH by their ability to produce net accumulations of cAMP and gonadal steroids in short term incubations. Ovaries, in which the germ cells were successfully destroyed, consisted of anastomotic cords of the intraovarian rete system surrounded by undifferentiated stromal tissue. A variable number of oocytes usually survived the busulfan treatment and were situated within the cords in irregularly defined follicles. Few treated oocytes proceeded to organize antral follicles by 14 days postnatally, but these follicles showed signs of normal theca and interstitial cell investment. A challenge of FSH or LH in vitro failed to stimulate net accumulations of cAMP, progesterone, androstenedione, or estradiol from treated ovaries whereas these responses were significantly stimulated in controls. Detectable levels of cAMP and steroids were, however, present in incubations of busulfan-treated ovaries on days 12 and 14, and these are likely attributable to the activity of antral follicles that survived the effects of busulfan. From day 8 to 12 plasma gonadotropin levels in treated animals rose significantly above those of controls suggesting that normal ovarian steroidogenesis is also suppressed in treated animals in vivo. Although direct effects of busulfan on somatic cells cannot be dismissed, these results suggest that the presence of germ cells is a prerequisite for the normal development of steroidogenic function in the rat ovary.

Mechanisms of 1S,3R-ACPD-induced neuroprotection in rat hippocampal slices subjected to oxygen and glucose deprivation.

The efficacy and mechanisms of 1-amino-cyclopentyl-1S,3R-dicarboxylate (1S,3R-ACPD)-induced neuroprotection were investigated in rat hippocampal slices subjected to 10 min of oxygen and glucose deprivation. Neuronal viability was assessed by measuring both the amplitude of evoked population spike in the CA1 pyramidale and by imaging CA1 neurons using a live/dead fluorescence assay with confocal microscopy. CA1 pyramidal neurons in oxygen-glucose deprived slices remained viable for up to 120 min following the insult but were dead by 240 min. Pretreatment with 1S,3R-ACPD significantly protected the oxygen-glucose deprived slices in a concentration-dependent fashion. Oxygen-glucose deprived slices pretreated for the same period with the protein kinase C (PKC) activation phorbol 12-myristate 13-acetate (PMA; 1 microM) were significantly protected whereas oxygen-glucose deprived slices treated with the adenylyl cyclase activator, forskolin (30 microM) were not. Oxygen-glucose deprivation induced a rapid and persistent decrease (approximately 50%) in PKC activity and a > 6 fold increase in cyclic adenosine monophosphate (cAMP) levels in whole hippocampal slices. While 1S,3R-ACPD did not stimulate PKC activity and had no effect on basal cAMP in whole slices, it significantly enhanced the rate of return of cAMP to basal levels following reperfusion. Consistent with this observation, the 1S,3R-ACPD-induced neuroprotection was inhibited by forskolin (30 microM). These results suggest that in vitro neuroprotection of CA1 neurons by 1S,3R-ACPD involves metabotropic glutamate receptors negatively linked to cAMP and possibly those which increase PKC activity.

Localization of epidermal growth factor (EGF) receptor in the rat corpus luteum, and EGF and transforming growth factor-alpha stimulation of luteal cell steroidogenesis in vitro.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) have potent mitogenic effects on granulosa and theca cells. However, their effects on steroidogenesis by these cells is controversial, and there is limited information regarding their effects on luteal cell steroidogenesis. The present study investigated the cellular distribution of the EGF receptor (EGF-R) in the rat corpus luteum (CL) by immunocytochemical staining, and the effects of EGF and TGF-alpha on progesterone and 20 alpha-dihydroprogesterone (20 alpha-OH-P) production in cultures of luteal cells. Using a primary antibody directed against the human EGF-R peptide, specific EGF-R staining was obtained in the CL. Both small and large luteal cells had EGF-R staining. In initial cell culture experiments, treatment of freshly isolated luteal cells with EGF or TGF-alpha (0.5-50 ng/ml) for 24 h had no effect on progesterone and 20 alpha-OH-P accumulation. Addition of LH (250 ng/ml) alone caused a 3.5-fold increase in both progestins, but co-treatment with EGF or TGF-alpha produced no further enhancement of progestin accumulation. However, when cells were seeded overnight and the attached cells were washed prior to growth factor treatment for 3 days with media change every 24 h, both EGF and TGF-alpha caused dose-dependent increases in progesterone accumulation/24 h period (up to 2-fold at 50 ng/ml growth factor) on days 1 and 2 but not day 3 of treatment. 20 alpha-OH-P accumulation was similarly stimulated (up to 2.5-fold) by EGF and TGF-alpha under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma levels of tumor necrosis factor during a longitudinal survey in an endemic area of malaria.

The plasma levels of tumor necrosis factor were measured during a longitudinal survey of 84 subjects living in an endemic area of malaria. In most cases, the plasma tumor necrosis factor was found at its highest level during the malaria transmission peak and became normal again during the dry season. Children having suffered from malarial attack keep low tumor necrosis factor levels compared to adults and asymptomatic children. These results suggest that tumor necrosis factor could be associated with the development of resistance against malaria.

Radioimmunoassays for androsterone, 5alpha-androstane-3alpha, 17beta-diol and 5alpha-androstane-3beta, 17beta-diol.

Androsterone (3alpha-hydroxy-5alpha-androstan-17-one), 5alpha-androstane-3alpha, 17beta-diol and 5alpha-androstane-3beta, 17beta-diol were conjugated at C-16 through sulfur to bovine and human serum albumin. Rabbits injected with these conjugates produced antibodies suitable for radioimmunoassays of these hormone metabolites. Samples were purified on Sephadex LH-20 columns. Levels of these steroids were measured in a rat blood serum pool and in ovarian tissue extract pools.

[Influence of surgical biliary pathology on the diffusion of ceftriaxone in the biliary tract]. / Influence de la pathologie biliaire chirurgicale sur la diffusion de la ceftriaxone dans l'arbre biliaire.

Ceftriaxone is a third generation cephalosporin remarkable for its wide distribution in the biliary tract. The purpose of this study was to determine whether biliary tract pathology, as observed during surgery, had an influence on this distribution. 52 patients about to be operated upon and presenting with a high risk of bile infection received a single 1 or 2 g dose of ceftriaxone administered intravenously over 20 min during the hour that preceded surgery. Samples of blood and of bile from the gallbladder (GB) and the common bile duct (CBD), as well as specimens of the GB wall were taken during the operation. In patients whose GB was normal at laparotomy (apart from stones) ceftriaxone concentrations in bile and GB wall were 10-25 and 2 times respectively higher than in plasma. In patients with a grossly distended but not infected GB (hydrocholecystis) ceftriaxone levels were high in CBD bile but null in GB bile and only one-quarter to one-half of plasma levels in GB wall. In patients with stones in the CBD or inflamed GB wall ceftriaxone levels were high in bile (although lower than in cases with normal GB) and similar to plasma levels in GB wall. When malignant pancreatic lesions were present ceftriaxone concentrations could not be measured in both GB and CBD bile but reached 50% of plasma concentrations in GB wall.(ABSTRACT TRUNCATED AT 250 WORDS)

[Tumor necrosis factor during the course of neuromalaria: new therapeutic perspectives]. / Tumor necrosis factor au cours du neuropaludisme: nouvelles perspectives thérapeutiques.

Malaria remains one of the major public health problem in tropical and subtropical world. Malaria pathogeny depends partly on parasite multiplication and partly on some elements of the immunological response. It has recently become evident that one of these elements, Tumor Necrosis Factor (TNF), is directly implicated in the pathogenesis of cerebral malaria. TNF increase cytoadherence of infected erythrocytes to the brain microvascular endothelium. In a study involving african children with cerebral malaria high levels of TNF were positively correlated with a fatal outcome. We have previously demonstrated that in vitro Plasmodium falciparum products can directly stimulate the production of TNF from human macrophages. The aim of this work was to identify this soluble parasitic substance. Our results demonstrated that this substance could be a repetitive amino-acid sequence of the Ring-infected Erythrocyte Surface Antigen (RESA). The immunization against this kind of well-known peptides may be used as anti-disease vaccine. The elimination of mortality would be an essential target instead of parasitic clearance.

[Clinical, pharmacokinetic and therapeutic study of amikacin with single daily dose and in combination in neutropenic children with fever]. / Etude clinique, pharmacocinétique et thérapeutique de l'amikacine en dose unique journalière et en association chez l'enfant neutropénique fébrile.

BACKGROUND: The efficacy of single daily dose of amikacin has been recently demonstrated in neutropenic children with fever. POPULATION AND METHODS: Eighteen children aged 1 to 15 years were included in the study. All patients were febrile and granulocytopenic and had indwelling intravenous catheter. Amikacin was administered as a 30-minute intravenous infusion once daily (20 mg/kg on day 1, then 15 mg/kg) for 3 to 30 days; the patients received amikacin in combination with piperacillin and vancomycin. Serum levels of amikacin were measured on days 1, 3, 6 and 10, and 30 min, 60 min and 180 min after the end of the infusion. RESULTS: All patients responded favourably to the antibiotic therapy. Sixty-two kinetics were performed: peak amikacin concentrations measured (30 min after 30-min infusion) on day 1 averaged 43.7 micrograms/mL (+/- 13.8). A significant increase in peak serum concentrations was observed during the treatment (day 3 vs day 10) without change in the trough serum concentrations. The volumes of distribution were considerably important in these granulocytopenic children and there was a large inter and intra-patient variability; the elimination half-life of the amikacin was short (1.45 h). There was no significant nephrotoxicity in any patient. CONCLUSION: The use of single daily dose amikacin in combination with a broad spectrum beta-lactam antibiotic and vancomycin was efficient and safe in febrile granulocytopenic children. The simulation of the amikacin behaviour in the deep compartment should be evaluated; in fact, it might reflect better accumulation of the drug than serum concentrations.

Low incidence of sepsis due to viridans streptococci in a ten-year retrospective study of pediatric acute myeloid leukemia.

BACKGROUND: Infections remain an important cause of morbidity and mortality in children with acute myeloid leukemia (AML), and particularly viridans group streptococci (VGS) sepsis. The present study, conducted between 1993 and 2003 in children with AML, sought to assess the frequency and characteristics of infectious complications (ICs), the incidence of VGS sepsis, the interest of preventive decontamination, and a possible cytarabine dose-effect on the occurrence of ICs. METHODS: Medical charts of 78 children treated according to the EORTC 58921 clinical trial were analyzed retrospectively. Patients were isolated in laminar air flow rooms, received non-absorbable gut decontamination, gum decontamination with vancomycin mouthwash, and trimethoprim-sulfamethoxasole. ICs were categorized as microbiologically documented infections (MDI), clinically documented infections (CDI), or fever of unknown origin (FUO). RESULTS: Overall, 268 ICs occurred: 57.5% FUO, 8.5% CDI, and 34% MDI. Bloodstream infections occurred in 58 febrile episodes: Gram-positive bacteria represented 83% of the pathogens including 66.1% Staphylococcus species and 8.5% Streptococcus species (6.8% VGS), Gram-negative bacteria represented 13.5% of the pathogens and yeasts 3.5%. Five patients died of infection (6.4%). None died from bacterial infection and no case of VGS sepsis required intensive care. Invasive fungal infection was proven in four patients. Number of ICs was significantly different according to gum and gut decontamination status, and according to the cytarabine dose during the first intensification. No resistant strains were detected in spite of the use of local antibiotics. CONCLUSION: The low rate of VGS and enterobacteriaceae sepsis was probably due to the effective decontamination. Our supportive care strategy could potentially help enhance overall survival in children with AML.

[Quantitative study of aerobic and anaerobic fecal flora in necrotizing enterocolitis of the newborn infant]. / Etude quantitative de la flore fécale aérobie et anaérobie dans l'entérocolite nécrosante du nouveau-né.

A quantitative study of the fecal flora was carried out in 21 neonates with necrotizing enterocolitis (NEC), (4 infants being born at term) and 57 control infants (30 born at term and 27 born before term). In the population as a whole Klebsiella was detected more frequently in NEC than in the controls. This was especially true in premature infants where Klebsiella was found in 65% of the affected infants versus 33% of the controls (p less than 0,05), while no Klebsiella was detected in the 4 term infants with NEC and in 87% of the term controls. These data suggest that Klebsiella could play a role in the pathogenesis of NEC, especially in the premature infant. Therefore, it seems required to avoid the artificial selection of Klebsiella in the neonate.

Factors influencing resumption of meiotic maturation and cumulus expansion of porcine oocyte-cumulus cell complexes in vitro.

The present study was undertaken to examine effects of various combinations of epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-beta 1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), androstenedione (A4), and estradiol-17 beta (E2) on meiotic maturation and cumulus expansion in the pig using an in vitro model system. Oocyte-cumulus cell complexes (OCC) were cultured in the media containing the above-mentioned agents for 24 hr and were observed for germinal vesicle breakdown (GVBD), indicative of initiation of meiotic maturation, and for expansion of their cumulus cells. Treatment with EGF significantly increased (P < 0.05) incidence of GVBD, with maximal stimulation occurring at 1 ng/ml (55% vs. 12% in the control). Concentrations of EGF as low as 100 pg/ml significantly stimulated GVBD over control (37% vs. 12%). Addition of EGF (1 ng/ml) and FSH (1.5 micrograms/ml) together and LH (2 micrograms/ml) and FSH (1.5 micrograms/ml) together resulted in significantly higher (P < 0.01) GVBD levels than were observed in response to EGF, FSH, or LH alone. Addition of E2 (1 microgram/ml) had no effect by itself but significantly decreased the incidence of GVBD in the presence of FSH and of LH + FSH. Addition of A4 (1 microgram/ml) significantly reduced the percentage of oocytes undergoing GVBD when added alone or with FSH. Although both EGF and LH stimulated cumulus expansion, FSH was more effective in stimulating cumulus expansion than EGF or LH. TGF-beta 1 had no effect on GVBD or cumulus expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostanoid content of human milk: relationships to milk fatty acid content.

Analysis of human milk was conducted to determine if transitions in milk lipid composition and thus the changes in fatty acid synthesis that occur during lactogenesis are related to levels of specific prostanoids present in milk lactated. Serial samples representative of a complete expression and reflecting varying concentrations of milk fatty acids were collected over the first 37 days of lactation. Milk from mothers delivering infants at term and mothers delivering premature infants of 28-33 weeks gestational age was compared to examine potential relationships between prostanoid concentration and gestational age effects on milk lipid content. Milk levels of prostaglandin E, prostaglandin F and the metabolite of prostacyclin--6-keto-prostaglandin F1 alpha were determined by radioimmunoassays. Transitions in fatty acid content for all milk lipid classes were determined by quantitative analysis of fatty acids by glass capillary gas liquid chromatography. During lactation the levels of prostaglandin E correlated with milk content of 6-keto prostaglandin F1 alpha. For term mothers, milk content of prostaglandin E, 6-keto prostaglandin F1 alpha, total fatty acids and medium chain fatty acids increased from early lactation when compared with subsequent days sampled. Levels of these milk constituents observed for early milk of preterm mothers were significantly different when compared with term mothers and in addition did not follow the same longitudinal pattern during subsequent days of lactation. Physiologically significant levels of prostaglandins in milk may reflect the balance between hormonal and subcellular controls over lactogenesis. It is also conceivable that the presence of these prostanoids in milk may influence gastrointestinal physiology and nutrient absorption in the neonate.