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Biomedical subjects

E Fontaine

Publications and source records attributed to E Fontaine.

90 records · Page 5Linked to original sources

Pulmonary histiocytosis X with mediastinal lymph node involvement.

In this report, we describe a patient with the classic histology of pulmonary histiocytosis X, who had bilateral reticulonodular densities and mediastinal lymph node involvement. The diagnosis was confirmed by the use of electron microscopy and immunohistochemical markers (PS100, HLA-DR, and CD1), which allowed us to recognize the lymph node infiltration of X histiocytes. An association of mediastinal lymph node enlargement with pulmonary histiocytosis X has been reported but it has never been histologically documented.

Adult↗

Characterisation of anaerobic curved rods (Mobiluncus spp.) isolated from the urogenital tract.

Thirty-two strains of anaerobic curved rods isolated from vaginal secretions and one isolated from seminal fluid were examined. Growth of all strains on solid media was superior to growth in liquid media, and at 37 degrees C they grew both anaerobically and in O2 5% in N2; they also grew anaerobically at 33 degrees C but not at 42 degrees C. No growth factors were identified, but strains grew more profusely at pH values above 5 X 0. The strains were screened in 80 biochemical tests, and for their susceptibility to 30 different antimicrobial agents. Most of the tests did not differentiate between the strains, but they were divided into four groups on the basis of cell morphology, metronidazole susceptibility, beta-galactosidase activity and arginine and hippurate hydrolysis. Group 1 consisted of 19 strains conforming to the species M. curtisi; group 2 consisted of five strains conforming to the species M. mulieris; group 3 consisted of five strains that resembled M. curtisi morphologically, and group 4 consisted of four strains that resembled M. mulieris morphologically, but the strains in the latter two groups reacted differently in at least one of the three major differential biochemical tests. Of three strains of M. curtisi and three of M. mulieris chosen at random, one of M. mulieris had a SDS-PAGE and fast-protein liquid chromatography protein profile indistinguishable from that of M. curtisi. We conclude that further efforts are required to clarify the taxonomic status of the genus Mobiluncus.

Anti-Bacterial Agents↗

Genotype dependency of the thermic effect of a meal and associated hormonal changes following short-term overfeeding.

The purpose of this experiment was to assess the effects of short-term overfeeding (mixed diet) on the thermic effect of a meal (TEM) and associated hormonal changes and to investigate the role of the genotype in the observed changes. Six pairs of male sedentary monozygotic (MZ) twins consumed an extra 1,000 kcal per day over their individual level of energy expenditure while maintaining a sedentary existence. Resting metabolic rate (RMR) and TEM following a 4.2 MJ meal challenge was measured before and after 22 days of overfeeding. RMR did not change significantly (7% elevation) in response to the positive caloric stimulus, whereas significant increases (P less than 0.01) in TEM were observed. Moreover, postprandial insulin and glucose responses were not modified. Overfeeding did not significantly alter catecholamine levels but induced significant elevations in plasma levels of T3 and T4 (P less than 0.05). Changes in RMR exhibited moderate but nonsignificant within twin pair resemblance in response whereas significant within pair resemblance was noted in the magnitude of TEM changes induced by overfeeding (P less than 0.05). Hormonal responses exhibited a weaker genotype dependency. These results suggest that short-term overfeeding can induce an elevation in TEM with accompanying increases in T3 and T4. Large individual response variation in metabolic and hormonal measures were observed. The similarity of response within twin pairs suggests that sensitivity to change in TEM induced by short-term overfeeding is genetically influenced.

Adult↗

Genotype-controlled changes in body composition and fat morphology following overfeeding in twins.

This study investigated the effects of overfeeding on the body composition and fat morphology characteristics of 6 pairs of male monozygotic twins. Each participant was submitted to a 22-day overfeeding period, supplemented by an additional 1000 kcal/day. Significant changes were observed in body composition and fat morphology as shown by increases in body weight, fat mass, sum of 9 skinfolds, and fat cell diameter. Significant within-pair resemblance for absolute changes was observed for body weight, percent body fat, fat mass, sum of skinfolds, trunk skinfolds, and extremity skinfolds, suggesting a role for the genotype in determining the sensitivity of the response to an energy surplus. Significant within-pair resemblance was noted for the biceps, triceps, and thigh with less resemblance noted in the subscapular, abdomen, suprailiac, calf, axillary, and chest sites, suggesting a variation in genotype dependency for subcutaneous fat. The results suggest that changes in body fat following short-term overfeeding appear to have a genetic basis.

Adipose Tissue↗

The effect of exercise-training on resting metabolic rate in lean and moderately obese individuals.

Two experiments have been performed to establish whether exercise-training has an influence on resting metabolic rate (RMR). In a first study, RMR was measured in a cohort of 59 individuals comprising 20 trained and 39 non-trained subjects. The absolute level of RMR in trained subjects exceeded by 11 percent that observed in the non-trained individuals (P less than 0.01). When comparing regression lines of RMR versus FFM between the two groups, the intercept with the Y axis (RMR values) was also significantly higher in trained subjects (P less than 0.01). The second experiment was conducted to find out whether the trend for an elevated RMR noted in athletes could be reproduced in obese persons engaging in an exercise-training program. Eight moderately obese women were submitted to an 11-week training programme, including 5 hours of aerobic exercise per week performed at a mean intensity of about 50 percent VO2 max. The results showed that exercise-training induced a significant rise in RMR which corresponded to 8 percent of pretraining value in kcal/kg FFM/min (P less than 0.01). Thus, data reported here suggest that aerobic exercise-training is associated with an elevated RMR per unit of fat free mass in both lean and moderately obese individuals.

Adult↗

Contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity of endurance athletes.

The present study was designed to evaluate the contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity characterizing endurance athletes. Plasma glucose and insulin were measured during an oral glucose tolerance test (OGTT) in six endurance athletes. Glucose storage and lipid oxidation during this test were also determined using indirect calorimetry. These measurements were compared to those obtained in five non-trained subjects who were tested before and during the three days following a 90-min cycle ergometer exercise performed at 69% of their VO2max. As expected, preexercise values of non-trained subjects revealed a much higher insulin response to glucose, and a lower glucose storage and lipid oxidation compared to results obtained in endurance trained individuals. Glucose tolerance was comparable in both groups. The morning following the exercise test, i.e. about 16 h after exercise, glucose storage was significantly increased in non-trained subjects to a level similar to that found in trained subjects. Surprisingly, this was accompanied by higher values of glucose during the OGTT without significant changes in insulinaemia. This impairment in glucose homeostasis was transitory since glucose tolerance had returned to control level on day 2 after exercise. At that time, the increase in glucose storage was less pronounced than in day 1. On day 3 after exercise, glucose and insulin responses to glucose were similar to preexercise values. These results indicate that the increase in glucose storage by acute exercise is not systematically associated with an improved glucose homeostasis, suggesting that other adaptive mechanisms also contribute to the improvement of insulin sensitivity in endurance athletes.

Adult↗

Resting metabolic rate in monozygotic and dizygotic twins.

In order to study the influence of heredity on resting metabolic rate (RMR), 20 monozygotic and 19 dizygotic male twins pairs aged 20.6 (SD 2.9) and 21.4 (SD 3.1) years, gave their consent to participate in the experiment. Fat free weight (FFW) was estimated from underwater weighing. RMR was measured by indirect calorimetry using an open circuit system. RMR was expressed as kJ X min-1, kJ/m2 X h-1, kJ/kg X h-1 and kJ/kgFFW X h-1. Significant intraclass coefficients were observed in MZ twins for the different expressions of RMR. The values ranged from r = 0.45 (P less than 0.05) to r = 0.81 (P less than 0.01). However, DZ twins demonstrated lower intraclass coefficients for RMR, with a range from r = 0.21 to r = 0.44. Significant (P less than 0.05) DZ resemblance was revealed only when RMR was expressed as kJ X min-1 and kJ/kg X h-1. Results of the present study suggest that variations in RMR may have a genetic component. Implications for human energy balance and body fat are discussed.

Adipose Tissue↗

Contribution of postexercise increment in glucose storage to variations in glucose-induced thermogenesis in endurance athletes.

The present study was undertaken to evaluate the contribution of an increment in glucose storage to the reduced glucose-induced thermogenesis (GIT) characterizing endurance-trained individuals. For that purpose, glucose storage and GIT were determined during an oral glucose tolerance test (OGTT) in eight elite endurance athletes exercising between 6 and 16 h/week. Their values were compared with those obtained in five nontrained subjects submitted to two OGTT, i.e., before and 16 h after they had performed a 90-min vigorous exercise. As expected, endurance athletes exhibited a reduced GIT and a greater glucose storage during the OGTT in comparison to the preexercise values of nontrained subjects. Once the latter subjects had performed the 90-min exercise, their glucose storage during the OGTT was similar to the level found in athletes. This adaptation was accompanied by a significant reduction in GIT, which corresponded to 47% of the difference observed between trained and nontrained subjects when both groups maintained their usual life habits. Unlike GIT, resting metabolic rate (RMR) was found to be higher in athletes than in nontrained individuals. When subdividing the athletes into two subgroups on the basis of the duration of their weekly training, it was found that RMR was mainly elevated in those performing the higher amount of exercise. These results demonstrate that the reduced GIT characterizing endurance-trained individuals is partly explained by an increase in glucose storage during an OGTT. As further discussed, this reduced GIT is likely an indirect consequence of modifications of other energy-requiring energy processes rather than a direct result of the postexercise increment in glucose storage.

Adipose Tissue↗

Influence of caffeine on the resting metabolic rate of exercise-trained and inactive subjects.

The effect of caffeine on the resting metabolic rate (RMR) was investigated in endurance exercise-trained (N = 14) and inactive (N = 10) male individuals. Subjects were also classified into regular and non-regular consumers of caffeine. After an overnight fast, RMR was measured using an indirect calorimetry open circuit system. Thereafter, subjects orally consumed 300 mg of caffeine, after which RMR was measured for 90 min. Five of the exercise-trained subjects were also studied after the administration of a placebo. Plasma concentrations of glycerol and free fatty acid and respiratory exchange ratio (R) were measured at each 15-min interval. Before caffeine ingestion, no significant differences were observed in RMR, R, glycerol, free fatty acid and blood pressure levels between exercise-trained and inactive groups. Following caffeine consumption, a three-way analysis of variance revealed that inactive subjects exhibited a greater increase (P less than 0.05) in RMR than did exercise-trained subjects. No significant differences were observed in RMR response between regular or nonregular consumers of caffeine. Moreover, no differences were observed in glycerol, free fatty acid, heart rate, and blood pressure response between exercise-trained and inactive subjects and between regular and non-regular consumers of caffeine. These results suggest that endurance training results in a reduced thermogenic response to a caffeine challenge.

Adult↗

Sensitivity of maximal aerobic power to training is genotype-dependent.

Ten pairs of monozygotic twins of both sexes were submitted to a 20-wk endurance-training program, four and five times per week, 40 min per session, at an average of 80% of the maximal heart rate reserve. Testing and training were performed on cycle ergometers. Maximal aerobic power (MAP in ml O2 X min-1 X kg-1) and ventilatory aerobic (VAT) and anaerobic (VANT) thresholds (ml O2 X min-1 X kg-1) were measured before and after the training program, as well as during the 7th and 14th week to adjust training to changes in maximal heart rate. Considering the 20 individuals as a group, training significantly (P less than or equal to 0.01) increased MAP (from 44 +/- 6 to 50 +/- 6), VAT (25 +/- 3 to 30 +/- 4), and VANT (36 +/- 5 to 42 +/- 6). Thus, MAP improved by 12% of the pre-test value, while mean changes in VAT and VANT reached 20% and 17%, respectively. There were, however, considerable interindividual differences in training gains as exemplified by a range of about 0% to 41% for MAP. Differences in the MAP response to training were not distributed randomly among the twin pairs. Thus, intraclass correlations computed with the amount of improvement in MAP (ml O2 X min-1 X kg-1) reached 0.74 (P less than 0.01) indicating that members of the same twin-pair yielded approximately the same response to training. The same coefficient reached 0.43 and 0.24 for VAT and VANT, respectively (P greater than 0.05). These results suggest that there are considerable individual differences in the adaptive capacity to short-term endurance training. Moreover, sensitivity of maximal aerobic power to such training is largely genotype-dependent.

Adolescent↗

On the regulation of cellular energetics in health and disease.

Very recent experimental data, obtained by using the permeabilized cell technique or tissue homogenates for investigation of the mechanisms of regulation of respiration in the cells in vivo, are shortly summarized. In these studies, surprisingly high values of apparent Km for ADP, exceeding that for isolated mitochondria in vitro by more than order of magnitude, were recorded for heart, slow twitch skeletal muscle, hepatocytes, brain tissue homogenates but not for fast twitch skeletal muscle. Mitochondrial swelling in the hypo-osmotic medium resulted in the sharp decrease of the value of Km for ADP in correlation with the degree of rupture of mitochondrial outer membrane, as determined by the cytochrome c test. Very similar effect was observed when trypsin was used for treatment of skinned fibers, permeabilized cells or homogenates. It is concluded that, in many but not all types of cells, the permeability of the mitochondria outer membrane for ADP is controlled by some cytoplasmic protein factor(s). Since colchicine and taxol were not found to change high values of the apparent Km for ADP, the participation of microtubular system seems to be excluded in this kind of control or respiration but studies of the roles of other cytoskeletal structures seem to be of high interest. In acute ischemia we observed rapid increase of the permeability of the mitochondrial outer membrane for ADP due to mitochondrial swelling and concomitant loss of creatine control of respiration as a result of dissociation of creatine kinase from the inner mitochondrial membrane. The extent of these damages was decreased by use of proper procedures of myocardial protection showing that outer mitochondrial membrane permeability and creatine control of respiration are valuable indices of myocardial preservation. In contrast to acute ischemia, chronic hypoxia seems to improve the cardiac cell energetics as seen from better postischemic recovery of phosphocreatine, and phosphocreatine overshoot after inotropic stimulation. In general, adaptational possibilities and pathophysiological changes in the mitochondrial outer membrane system point to the central role such a system may play in regulation of cellular energetics in vivo.

Adenosine Diphosphate↗

Role of substrates in the regulation of mitochondrial function in situ.

Investigations of mitochondrial oxidative phosphorylation have been mainly carried out in isolated mitochondria, where the experimental conditions can be precisely set. However, in intact living systems oxidative phosphorylation takes place in a complex environment, whose experimental dissection is a major challenge. It has long been recognized that the efficiency of oxidative phosphorylation depends on the nature of the respiratory substrates, which feed electrons to the respiratory chain at different levels. Yet, the role of substrates in determining mitochondrial function and their response to energetic stress has been largely overlooked. Here we review recent work showing that the nature of the energetic substrates profoundly affects the mitochondrial responses to manipulations of pathophysiological relevance, such as uncoupling and opening of the permeability transition pore (PTP). Uncoupling of intact hepatocytes caused very different metabolic effects depending on whether carbohydrates or lipids were the energy source. With dihydroxyacetone as the substrate dinitrophenol caused a collapse of the mitochondrial membrane potential and of the ATP/ADP ratio, while the respiratory rate was increased only transiently. With octanoate as the substrate, on the other hand, dinitrophenol caused a dramatic stimulation of the respiratory rate, while the mitochondrial membrane potential and ATP/ADP ratio were affected only marginally. We then review results indicating that the activity of complex I directly regulates the PTP, a finding that emphasizes the importance of the respiratory substrates in PTP regulation.

Adenosine Triphosphate↗

Determination of mitochondrial reactive oxygen species: methodological aspects.

The generation of Reactive Oxygen Species (ROS) as by-products in mitochondria Electron Transport Chain (ETC) has long been admitted as the cost of aerobic energy metabolism with oxidative damages as consequence. The purpose of this methodological review is to present some of the most widespread methods of ROS generation and to underline the limitations as well as some problems, identified with some experiments as examples, in the interpretation of such results. There is now no doubt that besides their pejorative role, ROS are involved in a variety of cellular processes for the continuous adaptation of the cell to its environment. Because ROS metabolism is a complex area (low production, instability of species, efficient antioxidant defense system, several places of production...) bias, variances and limitations in ROS measurements must be recognized in order to avoid artefactual conclusions, and especially to improve our understanding of physiological and pathophysiological mechanisms of such phenomenon.

Analysis of Variance↗

Three-year effectiveness of highly active antiretroviral treatment in the Luxembourg HIV cohort.

UNLABELLED: Clinical trials have shown that highly active antiretroviral treatment (HAART) is able to reduce HIV plasma viral loads to undetectable in 70% to 90% of patients and to increase CD4 cell counts. HAART in community settings (i.e., nonclinical trial situations) is reported to be much less effective. STUDY DESIGN: Observational study. PURPOSE: The aim of our study was to evaluate the effectiveness of protease inhibitor (PI)-based HAART in the Luxembourg HIV cohort after 36 months of treatment in previously treated and untreated patients. The secondary aim was to identify surrogate markers associated with long-term virologic and immunologic outcomes. PATIENTS AND METHOD: Seventy-three PI-naive patients, who started on HAART, combining one PI and two nucleoside reverse transcriptase inhibitors (NRTIs),with a follow-up of 3 years, were evaluated with plasma viral load and CD4 cell counts every 3 months and were analyzed retrospectively. Patients who had been treated previously with NRTI (n = 48) were at a more advanced stage of disease. RESULTS: Overall, there was a mean decrease in viral load compared to baseline of -1.89 log RNA copies/mL (SD = 1.40) that persisted at month 36. Sixty-two percent (62%) of patients reached an undetectable viral load (i.e., below 500 copies/mL): 82% and 53% of NRTI-naive and NRTI-experienced patients, respectively (p =.013). CD4 cell counts increased progressively in both groups with a sustained effect (mean increase of 146 cells/mL +/- 241) at month 36. NRTI-naive patients had a mean increase of 257 cells/mL (SD = 305), in contrast to experienced patients who had an increase of 108 cells/mL (SD = 206) at 3 years. Proportions of patients with a CD4 count under 200 cells/mL fell after 3 years for NRTI-naive (from 66% to 43%) and for experienced patients (from 32% to 13%). Predictors of short duration of viral load response were in decreasing order of importance: clinical AIDS, the use of saquinavir hard gel formulation as initial PI, and the number of NRTIs previously used. Viral load response was the only significant predictor of CD4 changes. CONCLUSION: In a community setting, effectiveness of PI-based HAART at 3 years is still achieved for most patients. NRTI-experienced patients have a good long-term response rate even if it is lower than NRTI-naive patients. A poor treatment response is associated with a more advanced stage of disease before HAART is introduced.

Adult↗

Fast genotypic detection of drug resistance mutations in the HIV-1 reverse transcriptase gene of treatment-naive patients.

OBJECTIVES: This study was performed to assess the frequency of drug resistance mutations in treatment-naive HIV-1-infected patients. STUDY DESIGN/METHODS: Frozen plasma samples from 135 treatment-naive HIV-infected adults were available from the first time the patients were seen for their infection in our center between 1992 and 1997. A rapid genotypic assay based on reverse DNA hybridization (LiPA HIV-1 RT, Murex, London, U.K.) was used to study substitutions at reverse transcriptase (RT) codons 41, 69, 70, 74, 184, and 215. Additionally, a selective polymerase chain reaction (PCR) for the multiple dideoxynucleoside resistance (MddNR) mutation Q151M was performed. RESULTS: 16 patients (12%) harbored virus with one or more drug resistance mutations. The prevalence of patients with drug-resistant virus was 0% in 1992, 17% in 1993, 0% in 1994 (only 6 samples tested), 18% in 1995, 14% in 1996, and 9% in 1997. Mutation K70R (resistance to zidovudine) was found in 8 patients, M41L (resistance to zidovudine) in 5 patients, M184V/I (resistance to ddI/ddC/3TC) in 2 patients, and T215Y/F (resistance to zidovudine) in 4 patients. All samples were wild type at codons 69 (ddC), 74 (ddI), and 151 (MddNR). CONCLUSIONS: Virus strains containing drug resistance mutations are now found in about 1 of 10 treatment-naive HIV-1-seropositive patients in Luxembourg. We believe that testing for drug-resistant virus before starting treatment should be recommended and will help to improve the selection of the most effective antiretroviral treatment. We also suggest the need for an international surveillance program on HIV drug resistance in treatment-naive patients.

Adult↗

[Ultra-rapid detoxification of opiate dependent patients: review of the literature, critiques and proposition for an experimental protocol].

UNLABELLED: Ultra-rapid opioid detoxification (UROD) is an increasingly popular technique for detoxifying patients addicted to opiates. This technique aims at reducing not only the duration but also the intensity of withdrawal by using general anesthesia coupled with a naloxone or naltrexone medication. In this paper the authors attempt to review the history of UROD and the logic of its procedure and results whilst also demonstrating its advantages and limits. METHOD: The MEDLINE database was searched from 1966 to 2000 using the terms "ultra-rapid opioid detoxification, rapid opioid detoxification under anesthesia, naloxone, naltrexone, opioid-related disorders". Additional data sources included bibliographies in textbooks on substance abuse. RESULTS: Nine studies identified in our search were analysed. The technique is based on a three-phases procedure. It consists of a medical and psychiatric selection of patients addicted to opiates, followed by the detoxification itself and finally a medical and psychosocial follow-up. A brief presentation is made of the theoretical aspects based on the use of a specific opioid receptor antagonist (naloxone and naltrexone). Only inpatients were included in the studies. The detoxification and anesthesia protocols varied. In every study all the subjects were completely detoxified. Only three studies included a control group and two used a randomized design. Three studies reported a follow-up beyond 30 days. DISCUSSION: Although this technique constitutes a safe and effective solution for opiate addicted patients, there are criticisms to be made. The absence of an animal model prior to the study of a human model, the lack of comparison with other procedures, the limitation of available literature, the cost and the risks of this technique and the lack of long-term treatment outcomes obtained from rigorous clinical trials, all call for further assessments. A more rigorous protocol based on the main areas of criticism is proposed (presentation of the inclusion and exclusion criterias, description of the three preliminary interviews, presentation of the UROD technique itself and finally a detailled nine month follow-up). CONCLUSION: Ultra-rapid opiate detoxification represents a potentially safe and effective treatment for opiate addicted patients but more rigorous research methods are needed to render this procedure entirely valid.

Anesthesia, General↗

[Relevance of anti-tissue transglutaminase antibodies in coeliac disease diagnosis].

Coeliac disease is precipitated upon exposure to the dietary wheat gluten. Definitive diagnosis relies on intestinal biopsy and regression of clinical and histological disorders with adherence to a gluten-free diet. Coeliac disease is usually associated with a malabsorption syndrome. However, both atypical and silent clinical forms have been recently described and prevalence of the disease may be under-estimated. Serological tests have been developed in order to select candidates for intestinal biopsy, but these biological parameters are not suitable for screening in the general population. Indeed, antigliadin IgG antibodies have a poor specificity. antigliadin IgA antibodies a poor sensitivity. The detection of antiendomysial IgA antibodies (EmA) by immunofluorescence, although considered as the "gold standard" of serological coeliac disease markers, could not be automated, depends on a subjective fluorescence display, and may be limited by the degree of training of the observer. In year 1997, tissue transglutaminase (tTg) has been identified as the main autoantigen recognized by EmA. On this basis, solid-phase enzyme-linked immunosorbent assays (Elisa) have been developed in order to potentially replace the EmA assay. Several commercial kits are now available but their diagnostic performances have not yet been compared. We selected 75 sera, including sera from 26 patients with coeliac disease in order to evaluate five commercial anti-tTG Elisa kits. For all patients, treated or not, detection of anti-tTG antibodies with four of the five tested kits correlates with EmA test. Kits using human tTG have the highest specificity, equivalent to the value of EMA test, and widely better than antigliadin antibodies. Anti-tTG Elisa kits using human tTG may be used as an alternative way to the EmA assay in the next future, and may supplant IgA anti-gliadin antibodies for coeliac disease screening.

Adolescent↗