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Biomedical subjects

G Fournier

Publications and source records attributed to G Fournier.

At least 19 recordsLinked to original sources

Two variants of transferrable extended-spectrum TEM-beta-lactamase successively isolated from a clinical Escherichia coli isolate.

In a leukaemic patient presenting a septicaemia treated with ceftazidime and amikacin, two clinical Escherichia coli isolates distinguished by their level of resistance to oxyimino-beta-lactams were isolated at an interval of 24 h. The isolates were identified by biotyping and esterase electrophoretic typing and the two host strains were shown to be identical. However, each of these strains exhibited a different transferrable extended-spectrum beta-lactamase. These enzymes had different pI values (5.25 and 5.58), but were both blaTEM-1 mutants. The enzyme with pI 5.25 was identical to TEM-101 (TEM-12) (serine 162 substitution). The enzyme with pI 5.58 showed an additional amino acid substitution (lysine residue instead of an arginine at position 237) and was denominated TEM-23. These data indicate that point-mutations can be successively cumulated in vivo by blaTEM mutants, leading to expression of beta-lactamases with increased hydrolysis rates.

Bacterial Typing Techniques

Brain and adrenal monoamines and neuropeptide Y in codeine tolerant rats.

1. Monoamine turnover and neuropeptide Y (NPY) levels were investigated in the central and peripheral nervous systems in adult male rats chronically treated with codeine. 2. An increase in the dopaminergic turnover was observed in the striatum and cortex. The norepinephrine levels and the serotoninergic turnover were unchanged in all the brain areas. 3. Epinephrine levels were decreased in the adrenal glands. 4. In addition, we observed a significant decrease of NPY levels in the hypothalamus, the striatum and the adrenal glands. These observed changes were not found when assessing NPY level in plasma fluid. 5. The implication of these modifications in the induction of codeine dependence are discussed in view of previous results obtained with morphine.

Adrenal Glands

Lean-body-mass composition and resting energy expenditure before and after long-term overfeeding.

This report deals with the association between the constituents of lean body mass (LBM) and resting metabolic rate (RMR) before and after a 100-d overfeeding period. Computed-tomography (CT) scan of 22 young adult males at nine different body levels were used to estimate adipose tissue mass (ATMCT), LBMCT, skeletal-muscle mass (SMMCT), and non-muscular LBMCT (NM-LBMCT). Before overfeeding, all body constituents, except ATMCT, were significantly correlated with RMR. Only body mass changes were significantly correlated with RMR changes. Comparison of these results with those of several studies in the literature reveals that the relationship between RMR and fat-free mass is highly influenced by the size of the SD for the latter variable. In stepwise-multiple-regression analysis, only SMMCT could be used to predict RMR. It was concluded that SMMCT and ATMCT, but not NM-LBMCT, increased during overfeeding and that the best correlates of RMR remain LBMCT, SMMCT, and body mass.

Adipose Tissue

Overfeeding and energy expenditure in humans.

The effect of overfeeding on energy expenditure was investigated in 23 young men subjected to a 353-MJ energy intake surplus over 100 d. The major part of this excess (222 MJ) was stored as body energy. The increase in energy cost of weight maintenance amounted to 52 MJ and was proportional to body weight gain. When it was added to the obligatory cost of fat and fat-free mass gains, the overall increase in energy expenditure amounted to a mean of 100 MJ. Four months after overfeeding, subjects had lost 82%, 74%, and 100% of the overfeeding gain in body weight, fat mass, and fat-free mass, respectively. We conclude that 1) in response to overfeeding, two-thirds of the excess energy intake is stored as body energy; 2) overfeeding induces an increase in energy cost of weight maintenance proportional to body weight gain, and 3) preoverfeeding energy balance tends to be restored when nonobese individuals return to their normal daily-life habits.

Adipose Tissue

A beta-lactamase-overproducing strain of Alcaligenes denitrificans subsp. xylosoxydans isolated from a case of meningitis.

A resistant (R) clinical isolate of Alcaligenes denitrificans subsp. xylosoxydans was recovered from CSF during treatment including piperacillin. This variant selected in vivo, and a second variant obtained in vitro from the initially susceptible (S) strain, both exhibited resistance to penicillins (ticarcillin, piperacillin) and cephalosporins, but remained susceptible to latamoxef and imipenem. Clavulanate (2 mg/L) restored the susceptibility of the two R-variants to penicillins. A beta-lactamase of pI 9.5 was detected in both S and R strains, but overproduction was observed only in the in-vivo and in-vitro R-variants. This inducible beta-lactamase hydrolysed benzylpenicillin, cephalothin and cephaloridine efficiently, but amoxycillin, ticarcillin and cefoperazone were only moderate substrates. The enzyme was inhibited by clavulanate, cloxacillin and imipenem (IC50 between 3 and 9 mM), but not by aztreonam and chloride ions (1 mM). Resistance to beta-lactams was not transferable by conjugation to Escherichia coli or Pseudomonas aeruginosa, and DNA agarose gel electrophoresis indicated that no plasmid was present in the isolates. Restriction patterns of chromosomal DNA isolated from the S and R isolates were similar after digestion by NotI and HindIII.

Adult

Adipose tissue lipolysis after long-term overfeeding in identical twins.

Ten pairs of young male sedentary, non-obese, monozygotic (MZ) twins, aged 21 +/- 2 years (mean +/- s.d.), were overfed for a period of 100 days during which they ingested 4.2 MJ (1000 kcal) per day above their individual energy needs, 6 days per week. There was a mean 8.4 kg increase in body weight and the average gain in body fat reaches 5.6 kg (P less than 0.0001). A biopsy of subcutaneous abdominal fat was performed, before and after the treatment, to determine fat cell weight as well as basal and catecholamine stimulated lipolyses from collagenase isolated adipocytes. Although analysis of variance revealed an increase in abdominal fat cell weight, no significant changes were noted in basal and catecholamine-stimulated lipolyses, due to large variation among individuals, results being expressed either per cell number or corrected for cell surface area. However, significant intrapair resemblance was observed in the changes of basal and epinephrine stimulated lipolyses (ri of about 0.60 in both cases), suggesting a concordant within-pair response, despite large between-pair variation. These results support the notion that the genotype may play an important role in regulating the response of abdominal adipose cells lipolytic activity to caloric excess.

Abdomen

The effects of chronic administration of morphine on the levels of brain and adrenal catecholamines and neuropeptide Y in rats.

1. Monoamine turnover and neuropeptide Y (NPY) levels were investigated in the central and peripheral nervous systems in adult male rats chronically treated with morphine. 2. The well-recognized biochemical alterations (serotoninergic turnover increased in the hypothalamus, hippocampus and striatum; dopaminergic turnover increased in the striatum and cortex; adrenaline levels decreased in the adrenal glands) were observed. 3. In addition, we observed a significant decrease of the NPY levels in the hypothalamus, the striatum and the adrenal glands. The observed changes were not reflected in plasma. 4. Our results contribute to the evidence that brain and adrenal monoamines and NPY could be involved in the mechanism of morphine tolerance and/or dependence.

Adrenal Glands

Human resting energy expenditure in relation to dietary potassium.

This study investigates the putative effect of potassium on energy expenditure. Eight young adult men were submitted to two different normocaloric mixed diets in a randomized order, containing either 163 +/- 9 or 69 +/- 2 mmol potassium/d. On the fifth day of each diet, after an overnight fast, resting metabolic rate (RMR) was measured over a 1-h period. After these measurements, either a potassium load (50 mmol) or a placebo were given to subjects submitted to the low- or the high-potassium diet, respectively. RMR was then measured again for 3 h and the last hour was kept for further analysis. Results showed that acute and chronic variations in potassium intake do not induce significant changes in RMR, and chronic but not acute changes in serum potassium concentration were significantly correlated with changes in energy expenditure (r = 0.74, P less than 0.05) by mechanisms that remain to be elucidated.

Adult

Comparison of production of volatile hydrocarbons by phenylhydrazine-induced peroxidation in rats chronically treated with lead.

We have studied the effect of a chronic pretreatment by lead on the peroxidation processes by measuring the production of the four main volatile hydrocarbons: ethane and pentane as index of lipid peroxidation; propane as marker of protein peroxidation and ethylene as index of both lipid and protein peroxidations. Our results have shown that: 1) lead alone did not increase the physiological formation of alkanes indicating that lead is not able per se to initiate the peroxidative processes; 2) after phenylhydrazine injection, lipid peroxidation makers were not modified, except pentane in male lead-treated rats. Conversely, ethylene and propane exhalation were increased 45 min after phenylhydrazine injection in lead-treated rats indicating a potentialisation of the oxidative effect of phenylhydrazine, mainly on proteins, by lead.

Animals

The response to long-term overfeeding in identical twins.

We undertook this study to determine whether there are differences in the responses of different persons to long-term overfeeding and to assess the possibility that genotypes are involved in such differences. After a two-week base-line period, 12 pairs of young adult male monozygotic twins were overfed by 4.2 MJ (1000 kcal) per day, 6 days a week, for a total of 84 days during a 100-day period. The total excess amount each man consumed was 353 MJ (84,000 kcal). During overfeeding, individual changes in body composition and topography of fat deposition varied considerably. The mean weight gain was 8.1 kg, but the range was 4.3 to 13.3 kg. The similarity within each pair in the response to overfeeding was significant (P less than 0.05) with respect to body weight, percentage of fat, fat mass, and estimated subcutaneous fat, with about three times more variance among pairs than within pairs (r approximately 0.5). After adjustment for the gains in fat mass, the within-pair similarity was particularly evident with respect to the changes in regional fat distribution and amount of abdominal visceral fat (P less than 0.01), with about six times as much variance among pairs as within pairs (r approximately 0.7). We conclude that the most likely explanation for the intrapair similarity in the adaptation to long-term overfeeding and for the variations in weight gain and fat distribution among the pairs of twins is that genetic factors are involved. These may govern the tendency to store energy as either fat or lean tissue and the various determinants of the resting expenditure of energy.

Adult

Two novel transferable extended-spectrum beta-lactamases from Klebsiella pneumoniae in Tunisia.

Two novel beta-lactamases conferring multiresistance to antibiotics including oxyimino beta-lactams have been identified in two nosocomial K. pneumoniae strains isolated in Tunis in 1986 and 1988. Both enzymes were encoded by ca. 150-kilobase plasmids. Donor and transconjugant strains producing these enzymes exhibited highly similar pattern of resistance (CTX phenotype) to beta-lactams including penicillins and oxyimino beta-lactams e.g. cefotaxime, ceftriaxone, ceftazidime, and aztreonam. High and variable synergy (16 to 1066-fold) was obtained when combined to 0.1 microgram/ml of clavulanate (beta-lactamase inhibitor). The isoelectric points of these two enzymes were 5.4 and 6.4. These beta-lactamases differed from TEM types by hydrolysis for cefotaxime or ceftriaxone but were inhibited by clavulanate and cloxacillin. DNA hybridization studies suggested that that the genes of these enzymes may be derived from genes encoding TEM-type enzymes.

DNA, Bacterial

Captopril induces correction of postrenal transplant erythremia.

Kidney transplant patients may develop post-transplant erythremia (PTE), and in order to avoid thromboembolism venesection, anticoagulation and native kidney removal have been suggested. We propose captopril as an alternative therapy for PTE. Seven hypertensive PTE patients, aged 42 +/- 10 years with stable renal function, were investigated to exclude primary or secondary polycythemia. All patients manifested true erythrocytosis [red blood cells (RBC) mass greater than 20% of predicted level] with concomitant increases in hematocrit and hemoglobin levels. Captopril was introduced in gradually increasing doses up to 75 mg/day under careful monitoring of blood pressure and renal function. Weekly follow-up was arranged to evaluate drug efficacy. After captopril, a significant reduction with normalization of the RBC mass (42 +/- 4 vs 31 +/- 5 ml/kg: P less than 0.005) was observed. The RBC counts and hematocrit and hemoglobin levels also decreased. One patient had recurrent erythrocytosis after captopril withdrawal. Captopril may be a simple, effective, and non aggressive treatment for postrenal transplant erythremia.

Adult

Outbreak of nosocomial infections due to Klebsiella pneumoniae producing SHV-4 beta-lactamase.

One hundred and fifty-four clinical isolates of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins, aztreonam and amikacin were responsible for an outbreak of nosocomial infections lasting eight months in a university hospital in Paris. This outbreak occurred in the intensive care unit (39 patients), haematology units (8 patients) and surgical and medical units (11 patients). Antibiotic resistant strains were isolated from the urinary tract (48%), wound and drainage fluids (21%), respiratory tract (14%), blood (12%) and stools (5%). High resistance to oxyimino-beta-lactams was mediated by a plasmid-encoded beta-lactamase with an isoelectric point of 7.8 (SHV-4). This CAZ-type enzyme conferred a higher level of resistance to ceftazidime and aztreonam (geometric mean MIC 135 mg/l) than to cefotaxime (geometric mean MIC 14 mg/l). All isolates were of the same biotype (weakly urease positive and no sucrose fermentation). Eight Klebsiella pneumoniae strains isolated in different units and at different times of the outbreak were of the same serotype, had common plasmid patterns and harboured a large self-transferable plasmid of about 180 kilobases encoding resistance to penicillins, oxyimino-beta-lactams, aminoglycosides, tetracycline and trimethoprim. These eight large plasmids had indistinguishable EcoRI restriction patterns. These results suggest that a single strain of Klebsiella pneumoniae was responsible for this outbreak.

Anti-Bacterial Agents

Long-term exercise training with constant energy intake. 1: Effect on body composition and selected metabolic variables.

The effects of long-term negative energy balance generated by exercise while maintaining a constant energy intake were studied in five healthy young males (25 +/- 3 years; mean +/- s.d.). After 2 weeks of monitoring to determine habitual energy intake, they were subjected to a 100-day experimental period during which they exercised on a cycle ergometer, 6 days a week, twice a day at 55 per cent of VO2 max. The daily energy deficit was 4.2 MJ for a total of 353 MJ for the duration of the treatment. Body weight decreased from 86.7 to 78.7 kg (P less than 0.001). More than 80 per cent of the weight loss was accounted for by the reductions in fat mass. Fat-free mass did not change significantly. The data suggest that subcutaneous fat was lost about evenly from the trunk and from the limbs as estimated from skinfolds. Cardiorespiratory and metabolic responses to submaximal work loads indicate that the low intensity exercise regimen was capable of inducing some of the known adaptations of exercise training such as a decrease in plasma insulin and norepinephrine concentrations during exercise, reductions in heart rate, pulmonary ventilation and blood lactate concentration at a given exercise intensity, and an increase in skeletal muscle oxidative capacity. The energy cost of sitting and standing was not decreased in spite of the loss in body mass. However, the energy cost of submaximal cycling and walking exercises was reduced considerably. These results clearly demonstrate that it is quite possible to lose fat while preserving fat-free mass through regular prolonged exercise of moderate intensity if energy intake is kept constant at baseline level. They also emphasize the importance of the individual differences in response to negative energy balance.

Adult

[Enzymatic resistance to cefotaxime in 56 strains of Klebsiella spp., Escherichia coli and Salmonella spp. at a Tunisian hospital (1984-1988)].

The enzymatic and plasmid-encoded resistance towards oxyimino-beta-lactams has been recently reported as related to the production of an extended-spectrum beta-lactamase (e.g. SHV-2, CTX-1 or TEM-3), in particular in our hospital since 1984. The prevalence of that resistance has been examined from January 1984 to December 1988 in function of specimen, unit and type of enzyme among 8,421 isolates of Klebsiella spp., E. coli, Salmonella spp. Each isolate showing a diameter of inhibition zone size inferior or equal to 25 mm for cefotaxime, the double disk synergy test was performed between a disk of amoxicillin and a clavulanic acid disk of cefotaxime, ceftriaxone, ceftazidime and aztreonam. In case of synergy, sonicated extracts have been prepared and examined by isoelectrofocusing with the detection of beta-lactamase activity by ceftriaxone and nitrocefin. 56 isolates (K. pneumoniae, K. oxytoca, E. coli, S. wien, S. typhimurium scored positive including 27 in pediatrics, 18 in surgery, and 8 in medicine. 41% of isolates have been obtained from blood cultures and 26.8% from urines. A majority of isolates (49/56) produced the SHV-2 type, but other types mediating the resistance phenotype CTX have been individualized initially by their isoelectric points e.g. 5.4 (TEM-20 in K. pneumoniae in July 1986), 6.4 (TEM-21 in E. coli, 1 K. pneumoniae in July 1988). The prevalence of resistance to cefotaxime from 1984 to 1988 has increased (from 0.3 to 1.4%), the highest rate being observed in pediatrics (5.6% in 1984 and 22.1% in 1988).

Cefotaxime

[Cardiogenic shock caused by 5-fluorouracil].

The authors report the observation of one patient in whom the first administration of chemotherapy with fluoro-5 uracil has induced a severe but reversible cardiogenic shock. The latter was preceded by a prolonged, constrictive thoracic pain without myocardial infarction constitution. The cardiac toxicity of fluoro-5 uracil has been well described in the form of anginal pains receding with the discontinuation of the treatment. However, the possible occurrence of arrhythmias, of collapse and even sudden deaths leads the authors to suggest the daily clinical and electrical observation of the patients treated with fluoro-5 uractil.

Fluorouracil