Spironolactone and congestive heart-failure.
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Adolescent↗
Biomedical subjects
B Georges
Publications and source records attributed to B Georges.
[Antibiotic strategies in an intensive care service].
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Anti-Bacterial Agents↗
Increased sodium-calcium exchange current in right ventricular cell hypertrophy induced by simulated high altitude in adult rats.
Ventricular hypertrophy is associated with an increase in action potential (AP) duration which is potentially arrhythmogenic. The implication of the Na-Ca exchange current (I(Na-Ca)) in the lengthening of the AP is controversial. The role of this current in the increased duration of the low plateau of the AP in hypertrophied adult rat ventricular myocytes by simulated chronic high-altitude exposure ( approximately 4500 m) was evaluated. Electrophysiological experiments were carried out on isolated right ventricular myocytes from exposed and control rats with the perforated patch or the conventional whole-cell technique in current or in voltage clamp condition. With the two techniques, a significant increase of the low plateau duration was observed in hypertrophied myocytes as compared to controls. The low plateau in hypertrophied myocytes was depressed when Na was replaced by Li and was no longer recorded when intracellular Ca was buffered with EGTA. Inward tail currents, evoked either on repolarization to -80 mV following a depolarizing pulse to +10 mV or by interrupted AP technique, were greater in hypertrophied than in control myocytes and were abolished when Na was replaced by Li or when intracellular Ca was buffered with EGTA, indicating an increased Na-Ca exchange activity. The Li-sensitive current-voltage curves, obtained by a voltage clamp ramp protocol with an intracellular calcium buffered solution, were not significantly different in both hypertrophied and control myocytes, suggesting no modification in the density of the Na-Ca exchange protein. This was corroborated by the lack of difference in NCX1 mRNA levels between right ventricles from control and exposed rats. We conclude that increased duration of the low plateau of rat ventricular AP in altitude cardiac hypertrophy may be attributed to an increase of the inward I(Na-Ca). This augmented I(Na-Ca)may result from a modification in the intracellular Ca homeostasis.
Action Potentials↗
[Malfunction of an artificial pacemaker secondary to an accidental breaking of the case].
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Aged↗
Cold acclimation or grapeseed oil feeding affects phospholipid composition and mitochondrial function in duckling skeletal muscle.
The phospholipid fatty acid (FA) composition and functional properties of skeletal muscle and liver mitochondria were examined in cold-acclimated (CA, 4 degrees C) ducklings. Phospholipid FA of isolated muscle mitochondria from CA birds were longer and more unsaturated than those from thermoneutral (TN, 25 degrees C) reared ducklings. The rise in long-chain and polyunsaturated FA (PUFA, mainly 20:4n-6) was associated with a higher State 4 respiration rate and a lower respiratory control ratio (RCR). Hepatic mitochondria, by contrast, were much less affected by cold acclimation. The cold-induced changes in phospholipid FA profile and functional properties of muscle mitochondria were reproduced by giving TN ducklings a diet enriched in grapeseed oil (GO, rich in n-6 FA), suggesting a causal relationship between the membrane structure and mitochondrial functional parameters. However, hepatic mitochondria from ducklings fed the GO diet also showed an enrichment in long-chain PUFA but opposite changes in their biochemical characteristics (lower State 4, higher RCR). It is suggested that the differential modulation of mitochondrial functional properties by membrane lipid composition between skeletal muscle and liver may depend on muscle-specific factors possibly interacting with long-chain PUFA and affecting the proton leakiness of mitochondrial membranes.
Animals↗
Sympathetic control of glucagon receptor mRNA levels in brown adipose tissue of cold-exposed rats.
Brown adipose tissue (BAT) is implicated in both cold-induced thermogenesis and regulation of energy expenditure and is mainly controlled by sympathetic innervation. To clarify the permissive and/or complementary roles of glucagon in cold-induced BAT activation, glucagon receptor gene expression and its modulation by sympathetic activity were investigated in rats. One pad of interscapular BAT was surgically denervated while the other pad was sham operated, then rats were either cold-exposed (CE) for 1 week at 4 degrees C or kept near thermoneutrality (25 degrees C, TN). Using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay, it was shown that cold exposure decreased (-44%) the relative abundance of BAT glucagon receptor mRNA, an effect which was prevented by unilateral surgical sympathectomy of BAT. The present results show a negative control by sympathetic nervous activity of glucagon receptor gene expression and/or of glucagon receptor mRNA stability in BAT of cold-exposed rats. The down-regulation of glucagon receptor expression during cold exposure does not support a major role of the peptide in the thermogenic control of BAT.
Adipose Tissue, Brown↗
Late-onset renal failure in Senior-Loken syndrome.
We report on four patients, from three different families, with Senior-Loken syndrome (SLS). They were unusual in that they reached end-stage renal failure (ESRF) only during the fifth or sixth decade. SLS is an autosomal-recessive disorder defined by the association of nephronophthisis and retinal dystrophy. Affected individuals invariably progress to ESRF, usually before the age of 20 years. The diagnosis was based on typical clinical presentation and characteristic renal histology, that is, a picture of chronic interstitial nephritis with pronounced thickening and multilayering of tubular basement membranes. Deterioration of renal function was slow, leading to ESRF between the ages of 42 and 56 years. Retinal dystrophy, already symptomatic during childhood in two patients, led to severe visual impairment in all. In contrast with four cases of SLS recently reported in very young patients, the NPH1 gene (the main gene responsible for nephronophthisis) was not deleted in our two tested patients. We conclude that SLS should be considered in adults who suffer from both chronic interstitial nephropathy and retinal degeneration. Whether the SLS is a variant of nephronophthisis and whether early- and late-onset renal failure in SLS is accounted for by genetic or allelic heterogeneity remain to be determined.
Adult↗
Influence of time interval and number of blood samples on the error in renal clearance determination using a mono-exponential model: a Monte Carlo simulation.
Mono-compartmental analysis based on 2- and 4-h blood samples (BS) of 51Cr-EDTA (EDTA, ethylenediaminetetraacetic acid) is commonly used for the calculation of the glomerular filtration rate (GFR). The purposes of this study were to estimate the magnitude of error in clearance induced by errors in the time of sampling and activity measurement; to estimate the impact of changing the interval between the BS; and to assess the influence of a higher number of BS in reducing the error. A model of mono-exponential curves based on a finite number of BS was created. Normally distributed random errors were introduced in the time of sampling and activity measurement. In a first step, three different time intervals were used; in a second step, seven different numbers of BS were used, all taken between 120 and 240 min. For each setting, the random errors were successively introduced 200 times and the coefficients of variation (CV) of the calculated clearances were determined. Variable errors in clearance were induced by errors in the time of sampling and activity measurement. In general, the observed errors were higher for high and low clearance, with lower errors for moderately reduced clearances. The errors in indicating the time of sampling played an important role for high clearance, whereas the errors in activity measurements led to important errors for low clearance. Prolonging the interval from 1 to 2 h resulted generally in an important decrease in error, except in the range 60-100 ml x min(-1). Prolonging the interval from 2 to 3 h resulted in only a small additional decrease in error, except for very low clearance. Errors in indicating the time of sampling and in activity measurements induce errors in clearance determination. These errors cannot be significantly reduced by simply increasing the number of BS or by prolonging the interval between the samples. It is probably better, in most cases, to keep using the 2-4-h method and to take extreme care when indicating the time of sampling and when measuring the activity, instead of increasing the number of samples or lengthening the procedure.
Algorithms↗
[Duration of antibiotic treatment in intensive care: current data].
OBJECTIVE: To review the current data on the duration of an antibiotic treatment. METHODS: Analysis of recent and older articles on criteria of discontinuation of an antibiotic treatment in intensive care patients. SYNTHESIS: In intensive care patients the initiation of an antibiotic therapy is more or less codified, in spite of numerous existing problems. The duration of its maintenance, although based on scientific data depends mainly on a multitude of variables. The first step is to assess the therapeutic efficiency in considering the regression of clinical manifestations, the normalization of the acute phase reactants, the sterility of bacteriological samples and the absence of relapse at therapy discontinuation. An assessment after 48 hours is essential, in order to decide the maintenance or the modification of therapy. Finally the indication of bitherapy is considered. The theoretical duration of antibiotic therapy is determined in taking into account the involved microbial agent(s), the centre of infection, the bacterial inoculum, the patient, the presence of foreign material, and the administered antibiotic.
Anti-Bacterial Agents↗
Molecular cloning and characterization of the cDNA encoding the rat liver gamma-butyrobetaine hydroxylase.
Carnitine biosynthesis from lysine and methionine involves five enzymatic reactions. gamma-butyrobetaine hydroxylase (BBH; EC 1.14. 11.1) is the last enzyme of this pathway. It catalyzes the reaction of hydroxylation of gamma-butyrobetaine to carnitine. The cDNA encoding this enzyme has been isolated and characterized. The cDNA contained an open reading frame of 1161 bp encoding a protein of 387 amino acids with a deduced molecular weight of 44.5 kDa. The sequence of the cDNA showed an important homology with the human cDNA recently isolated. Northern analysis showed gamma-butyrobetaine hydroxylase expression in the liver and in some extend in the testis and the epididymis. During this study, it also appeared that BBH mRNA expression was undetectable by Northern analysis during the perinatal period. During the development of the rat, the amount of BBH mRNA appeared after the weaning of the young rat and reached a maximal expression at the adult stage.
Amino Acid Sequence↗
White adipose tissue fatty acids of Alpine marmots during their yearly cycle.
Alpine marmots (Marmota marmota) were maintained on a laboratory diet, and the fatty acid composition of gonadal and subcutaneous white adipose tissues (WAT) was studied during a yearly cycle. Fatty acids (FA) released from isolated adipocytes were also identified after stimulation of in vitro lipolysis. Analysis of the FA composition of WAT depots showed that marmot WAT mainly contained monounsaturated FA (65%, mostly oleic acid, 18:1n-9) although laboratory food contained 45% of linoleic acid (18:2n-6) and only 21% of 18:1n-9. During stimulated lipolysis, saturated FA were preferentially released from isolated adipocytes whereas unsaturated FAs were retained. Despite this selective release of FA from isolated WAT cells in vitro, and despite the FA composition of the food, marmots maintained a constant FA composition in both WAT depots throughout the year. Six months of hibernation and fasting as well as an intense feeding period did not affect this composition. The potential adaptive benefit of such regulation of WAT composition, based on a high level of monounsaturated FA, might be to maintain fat with appropriate physical properties allowing animals to accommodate to and survive the wide range of body temperatures experienced during hibernation.
Adipose Tissue↗
Convergent peptide libraries, or mixotopes, to elicit or to identify specific immune responses.
Many recent studies have demonstrated the flexibility of epitope recognition by the immune system. This can be explored using a particular type of combinatorial peptide library, termed as 'convergent', consisting essentially of closely related molecular species; from this a fuzzy set can be constructed, which comprises several variants of a peptide that would act in synchrony to represent a model antigen and its recognition by the immune system.
Amino Acid Sequence↗
The predictive value of cardiac troponin T measurements in subjects on regular haemodialysis.
BACKGROUND: Cardiac troponin T (cTnT) is a subunit of the cardiac actin-myosin complex, which leaks into the circulation when myocardial necrosis is present. Detection of cTnT is associated with a poor outcome in patients with unstable angina, and is a useful tool for risk stratification. The value of cTnT determination in patients with renal failure has been questioned, and the specificity of cTnT in this particular group has not been established. METHODS: In the present study, 94 patients at a single centre were followed prospectively after three determinations of cTNT, at 1-month intervals. The outcome after 12 months was chosen as the end-point. cTnT was measured using both a quantitative chemiluminiscence immunoassay and a qualitative rapid bedside immunoassay on a test strip. The maximum of three measurements was used and was correlated with different parameters and outcome. The following statistical tests were performed: Kaplan-Meier analysis, Cox's proportional regression analysis for measuring survival and logistic regression for analysing factors influencing cTnT. RESULTS: Forty seven of the 94 patients had a positive cTnT by test strip defined as >0.10 ng/ml. Twenty four patients died in the follow-up period (14 from cardiovascular causes). Twenty of the 24 non-survivors had an increased cTnT by test strip and 23 had increased cTnT by laboratory immunoassay. The outcome analysed by a Cox's proportional regression analysis showed that the factors which influenced survival significantly were cTnT, the presence of ischaemic heart disease, C-reactive protein (CRP) and prealbumin. A logistic multivariate analysis revealed that age and CRP significantly influenced cTnT. A good correlation was found between cTnT determined by test strip and in the laboratory. CONCLUSION: cTnT is elevated in a large number of patients on regular haemodialysis and is a significant independent predictor of outcome. Increased cTnT is significantly predicted by age and CRP.
Aging↗
Adaptation of BTI-TN5B1-4 (high five) insect cells for large-scale production in a stirred bioreactor.
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Animals↗
[Continuous versus intermittent cefepime infusion in critical care. Preliminary results].
The bactericidal activity of beta-lactams is time-dependent, and the time spent above the MIC (T > MIC) is the best predictor of efficacy. A prospective, randomized, open-label study was conducted in intensive care unit (ICU) patients with gram-negative rod infections to compare the efficacy of cefepime given as a continuous versus an intermittent infusion. Of the 18 patients included to date, 14 had severe pneumonia and four bacteremia. All patients received amikacin, 15 mg/kg/d, and cefepime, 4 g/d. Patients were randomized to cefepime administration as a continuous infusion (Group 1, n = 9) or as an intermittent infusion (Group 2, n = 9, 2 g every 12 h). No significant differences were found between the two groups for age, sex, initial infection, IGS II score (46 vs 48, NS) or the MIC of the gram-negative organism. Mechanical ventilation and hospital stay durations, recovery rates, and pharmacokinetic parameters (24-h AUIC, 12-h AUIC, T > MIC, and T > 5 x MIC) were compared in the two groups using the chi-square and Mann-Whitney tests. P values < 0.05 were considered statistically significant. There were no significant differences for mechanical ventilation duration, recovery rate, hospital stay duration (34 vs 36 days, NS), 24-h AUIC (624 vs 473, NS), or the 12-h AUIC (235 vs 238, NS). There were two interesting findings: T > MIC was significantly (P < 0.05) higher in Group 1 (23.84 +/- 0.2) than in Group 2 (20.7 +/- 3), and T > 5 x MIC was also significantly (P < 0.01) higher in Group 1 (23.61 +/- 0.6) than in Group 2 (16.6 +/- 6). Although clinical outcomes were similar in the two groups, it is reasonable to assume that the longer time spent with a cefepime level above the MIC in the continuous infusion group was associated with a more stable bactericidal effect.
Bacteremia↗
Tissue-specific modulation of rat glucagon receptor mRNA by thyroid status.
The influence of thyroid status on glucagon receptor mRNA levels was investigated in rats using a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Glucagon receptor mRNA was detected in liver, brown and white adipose tissues (BAT and WAT) and brain. In BAT and WAT, pharmacologically-induced moderate hypothyroidism resulted in a marked reduction in the relative abundance of glucagon receptor mRNA. Short-term treatment of hypothyroid rats with exogenous 3,3',5'-triiodo-L-thyronine (T3), resulting in a marked hyperthyroidism, reversed the phenomenon in BAT while the reversal was only partial in WAT. In the liver, there was no significant effect of mild hypothyroidism while there was a positive effect of hyperthyroidism. In brain, the relative tissue abundance of glucagon receptor mRNA was not affected by the large changes in plasma T3. The present results therefore indicate that thyroid status may modulate the relative abundance of glucagon receptor mRNA in a tissue-specific manner.
Adipose Tissue↗
[Severe methicillin-resistant Staphylococcus aureus infections. Emergence of resistance to fusidic acid or fosfomycin during treatment with continuous infusion of vancomycin].
OBJECTIVES: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and to assess the relationship with serum levels of vancomycin METHODS: A retrospective study was performed in patients hospitalized in our intensive care unit during a 3-year period (1993-1995) who were treated for severe MRSA infection with continuous infusion vacomycin and fosfomycin or fucidic acid. We analyzed the development of resistance and serum levels of vancomycin. RESULTS: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomycin developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 micrograms/ml vs. 22.64 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 +/- 1.07 micrograms/ml vs. 21.85 +/- 0.78 microgram/ml, p < 0.01). CONCLUSIONS: Our findings confirm that in spite of continuous vancomycin infusion at an initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfomycin or fucidic acid an develop during ongoing treatment. Vancomycin levels of at least 20 micrograms/ml should be obtained as rapidly as possible.
Anti-Bacterial Agents↗
Characterization of human lactoferrin produced in the baculovirus expression system.
Lactoferrin, an iron-binding 80-kDa glycoprotein, is a major component of human milk whose structure is now well defined. The binding site of lactoferrin to the membrane receptor of lymphocyte has been located in the region 4-52, but the amino acids directly involved in the interaction have not been identified yet. To gain further insights into the structure-function relationships of the lactoferrin binding site, we first expressed the cDNA encoding human lactoferrin in the lepidoptera Spodoptera frugiperda cells (Sf9) using a recombinant baculovirus. The selected transformant secreted and N-glycosylated protein of 78 kDa which was immunoprecipitated by specific anti-lactoferrin antibodies. To confirm the structure and the function of the recombinant lactoferrin, the protein was purified by ion-exchange chromatography and its physical, biochemical, and biological properties were compared with those of the native protein. In particular, the N-terminal amino acid sequence and the iron-binding stability as a function of pH, of both proteins, were identical. The main difference concerns the glycosylation which leads to glycans of lower molecular masses as detected by the electrophoretic mobility of lactoferrin after N-glycosidase F treatment and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. Despite the different glycosylation features, the recombinant lactoferrin retained the binding property to the Jurkat human lymphoblastic T-cell line of the native lactoferrin. On the basis of these analyses, production of protein mutants generated by site-directed mutagenesis is now in process.
Animals↗