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Biomedical subjects

L Bourdon

Publications and source records attributed to L Bourdon.

28 records · Page 2Linked to original sources

On the nature of the link between malignant hyperthermia and exertional heatstroke.

Malignant hyperthermia (MH) is a rare myopathy inducing severe accident when carriers are exposed to triggering agents. MH susceptibility (MHS) is assessed by pharmacological tests performed on muscle strips. Exertional heat stroke (EHS) is a severe accident occurring during long and strenuous exercise. It has been observed that numerous EHS patients are susceptible to MH according to pharmacological tests. Because most of those EHS-MHS subjects were soldiers, we hypothesize that military duty could select subjects with infraclinical myopathy and therefore would increase the MHS:EHS subject ratio.

Animals↗

Twenty-four-hour plasma cortisol and prolactin in human African trypanosomiasis patients and healthy African controls.

We have previously demonstrated that human African trypanosomiasis (sleeping sickness) at the stage of meningoencephalitis results in a major disruption of the circadian rhythmicity of sleep and wakefulness that is proportional to the severity of the disease. This paper examines the corresponding 24-hourly secretion in cortisol and prolactin and compares it with the hourly distribution of sleep composition in infected patients and healthy African subjects. The secretion of cortisol in humans follows a circadian rhythm relatively independent of the sleep-wake cycle, whereas that of prolactin exhibits fluctuations over the 24-hr day that are strongly related to the sleep-wake cycle. After the clinical classification of the patients according to the severity of the disease, hourly blood samples were taken over 24 hr via an indwelling catheter. Plasma cortisol and prolactin were analyzed by radioimmunoassay, and the variations in the hourly concentrations were analyzed for the presence of a potential 24-hr rhythm (circadian). All of the healthy African subjects showed significant circadian rhythms in both cortisol and prolactin secretion, similar to data on humans from temperate regions, and a sleep-related anamnestic afternoon peak of prolactin. Major disruptions in the circadian rhythms of plasma cortisol and prolactin were found in the three patients with the most severe illness, in contrast to the four who were less severely ill and the healthy controls. Thus, it appears that as the disease progresses in severity, major disruptions begin to occur in body circadian rhythms, not only in the sleep-wake cycle as reported elsewhere, but also in cortisol and prolactin secretion, suggesting that sleeping sickness affects the circadian timing system.

Adolescent↗

Use of a spreadsheet program for circadian analysis of biological/physiological data.

Biological/physiological data sampled over a period of 24 h can be subjected to a mathematical analysis to determine the presence of circadian rhythmicity. Several procedures have been proposed, most being complex. To render such an analysis simpler and easy to use by non-mathematicians, we developed and tested the cosinor technique using a commonly available commercial spreadsheet (Excel). It can be used to analyze equally or unequally time-spaced data over 24 h with missing data, as well as to calculate the significance and the main limit of the resultant circadian rhythm (mesor, amplitude, acrophase and their confidence limits). Examples of its application to hourly samples of plasma cortisol and minute-by-minute rectal temperatures are shown.

Body Temperature↗

Effect of triazolam on responses to a cold-water immersion in humans.

Managing alertness of soldiers during sustained operations is a source of serious concern for military unit commanders. A frequently employed strategy is to induce sleep before an operation, especially operations requiring prolonged travel. Sleep-inducing drugs could have an action on thermoregulation through their effect on alertness and a possible direct effect on the brain. The goal of this study was therefore to evaluate the effect of a commonly prescribed triazolam (Halcion) on thermoregulatory responses to cold-water immersion. Eight subjects were immersed twice in 18 degrees C water for up to 90 min in the morning; once after ingesting 0.25 mg triazolam (TRZ) the prior evening, and again after placebo (PLB) treatment. There were no significant differences between trials for mean duration of the immersion, the change in rectal temperature and mean skin temperature. Total metabolic heat production was similar for both conditions: 767 +/- 107 vs. 781 +/- 105 kj.m-2 for TRZ and PLB, respectively. The results should be considered in light of a large variation among the subjects in sensitivity to TRZ, which was unrelated to biometrical characteristics such as surface area-to-mass ratio, lean body mass, % body fat, and physical fitness. Although not statistically significant, there was a trend for a smaller increase in plasma free fatty acid and glycerol concentrations after water immersion with TRZ. The results suggest that the ingestion of a single dose of triazolam 11 h prior to a cold-water immersion is not likely to accelerate the rate of onset of hypothermia. Individual sensitivity, however, may predispose some sensitive subjects to negative effects in this regard.

Adipose Tissue↗

Effect of modafinil on heat production and regulation of body temperatures in cold-exposed humans.

Military personnel often undergo sustained operations that affect vigilance and alertness. Pharmacological agents may be used to enhance vigilance. Most such agents also have thermogenic properties. Whether a new promising stimulant, modafinil (Lyons and French, Aviat. Space Environ. Med. 1991; 62:432-435), has a beneficial effect on cold tolerance in the military context, is not known. The goal of this study was, therefore, to evaluate the effect of this new drug on thermal balance and the regulation of body temperatures in neutral conditions and when challenged by a cold exposure. Nine subjects underwent three trials each: two in the cold (3 h at rest, 10 degrees C) 0.5 h after the ingestion of either placebo or modafinil (200 mg), and one in thermal neutrality with modafinil (same conditions except Tdb = 29.3 degrees C). As expected, cold produced a drop in Tre and Tsk and an increase in Vo2. Although non-significant, there was a tendency for a slightly greater drop in Tre with modafinil (0.65 degrees C vs. 0.57 degrees C with placebo). A similar tendency was found for the heat debt (S) which was greater with modafinil than with placebo (16.1 +/- 0.7 vs. 14.7 +/- 0.6 kJ.kg-1, respectively, +9.5%, p = 0.11). This tendency appears to be the combined result of a slightly lower mean heat production during the test and a slightly greater mean dry heat loss. When tested at thermal neutrality, the drug had no effect on any thermal or metabolic parameters. The results demonstrate that the ingestion of a single dose of modafinil has no significant acute effect on thermal balance in neutral conditions and on thermoregulation in normal subjects exposed to cold. However, a tendency for slightly greater cooling was noted with modafinil. It is not known whether the use of modafinil in conjunction with sleep deprivation (a likely scenario) could magnify this effect.

Adult↗

Improved noninvasive diagnostic testing for malignant hyperthermia susceptibility from a combination of metabolites determined in vivo with 31P-magnetic resonance spectroscopy.

BACKGROUND: Phosphorus magnetic resonance spectroscopy (31P-MRS) in vivo has been suggested recently as a possible noninvasive diagnostic test in malignant hyperthermia (MH) susceptibility. However, differences between protocols and also within subjects may have led to inconsistent MRS abnormalities reported during and after exercise. The aim of the current study was to detect discriminant abnormalities in the leg muscles using in vivo 31P-MRS during the rest period. METHODS: Fourteen patients shown to be MH-susceptible and 22 patients MH-negative on the basis of in vitro caffeine/halothane contracture tests according to the European MH group protocol were compared to 36 control subjects using in vivo 31P-MRS during the rest period. A score of MRS combined abnormalities was calculated from a stepwise discriminant function analysis. RESULTS: The MH-susceptible group had a significantly (P < 0.01) higher inorganic phosphate (Pi) to phosphocreatine (PCr) (Pi/PCr) value (0.134 +/- 0.022) than either the MH-negative (0.097 +/- 0.016) or the control (0.101 +/- 0.017) group. The MH-susceptible group also exhibited a significantly (P < 0.01) higher phosphodiesters (PDE) to PCr (PDE/PCr) value (0.093 +/- 0.056) than either the MH-negative (0.034 +/- 0.021) or the control (0.029 +/- 0.019) group. Combining both MRS parameters, 13 of the 14 MH-susceptible patients demonstrated abnormal MRS test results (score value < 1.65). Conversely, 21 of the 22 MH-negative patients had normal MRS results (score value > or = 1.65). The sensitivity and specificity of this threshold value were 93 and 95%, respectively. CONCLUSIONS: This study confirms that 31P-MRS could be useful for distinguishing noninvasively between MH-susceptible and MH-negative patients if several MRS parameter are combined. Moreover, the present MRS approach appears to be more reliable and easier than that used during exercise.

Adolescent↗

Exertional heatstroke and muscle metabolism: an in vivo 31P-MRS study.

An impairment of muscle energy metabolism has been suggested as a predisposing factor for, as well as a consequence of exertional heatstroke (EHS). Thirteen young men were investigated 6 months after a well-documented EHS using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined at rest, during a graded standardized exercise protocol (360 active plantar flexions) and during recovery. Also the leg tissue blood flow was determined by venous occlusion plethysmography during the MRS procedure. Sixteen age-matched healthy male volunteers served as control group. In resting muscle, there were no significant differences between the groups as regards pHi, Pi/PCr, and ATP/PCr+Pi+PME ratios. During steady state exercise conditions, effective power outputs were similar for both groups at each level of exercise: 20, 35, and 50% of maximal voluntary contraction (MVC) of the calf muscle. No significant differences were shown between the two groups in Pi/PCr, pHi, or changes of leg blood flow at each level of exercise. At 50% MVC, Pi/PCr was 0.48 +/- 0.08 vs 0.47 +/- 0.05 (P = 0.96), pHi was 6.94 +/- 0.03 vs 6.99 +/- 0.02, respectively (P = 0.13). Finally, the rate of PCr resynthesis during recovery was not significantly different between the two groups: t1/2 PCr = 0.58 +/- 0.07 vs 0.50 +/- 0.05 min, respectively (P = 0.35). Therefore, no evidence of an impairment of muscle energy metabolism was shown in the EHS group during a standardized submaximal exercise using 31P-MRS performed 6 months after an EHS.

Adenosine Triphosphate↗