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Biomedical subjects

L Bourdon

Publications and source records attributed to L Bourdon.

At least 19 recordsLinked to original sources

Beat-by-beat cardiovascular index to predict unexpected intraoperative movement in anesthetized unparalyzed patients: a retrospective analysis.

OBJECTIVE: Unexpected intraoperative movement may be detrimental during delicate surgery. This study tested retrospectively an algorithm based on beat-by-beat circulatory variables (incorporated into a Cardiovascular depth of anesthesia index: CARDEAN in relationship to unexpected movement, and compared its performance to that of the electroencephalogram (EEG)-derived index: BIS-XP 4.0. METHODS: 40 ASA I or II patients presenting for knee surgery had EEG (BIS XP 4.0), beat-by-beat (Finapres) finger non-invasive blood pressure (BP), conventional brachial BP and electrocardiogram (EKG) monitors attached. Anesthesia was induced and maintained with propofol and remifentanil. Before incision, the propofol concentration was set to maintain BIS < 60. From incision to emergence, the anesthesiologist was denied access to BIS or Finapres. Anesthesia adjustment was titrated at the discretion of the anesthesiologist according to conventional signs only: brachial BP, EKG, eyelash reflex, movement. Occurrences of movement and eye signs (divergence of eyeballs, tears, corneal reflex, eyelash reflex) were observed. The CARDEAN algorithm was written retrospectively and tested vs. BIS. RESULTS: 11 movements occurred in 8 patients. CARDEAN > 60 predicted movement in 30% of the cases, 15 to 274 s before movement (sensitivity: 100%, specificity: 95%; relative operating curve ROC = 0.98; prediction probability pk = 0.98). BIS > 60 predicted movement in 19% of cases (sensitivity: 64%; specificity: 94%, ROC: 0.85, pk: 0.85). CONCLUSION: Retrospectively, a cardiovascular index predicted unexpected intraoperative movements. Prospective validation is needed.

Algorithms↗

Substrate utilization during prolonged exercise with ingestion of (13)C-glucose in acute hypobaric hypoxia (4,300 m).

Energy substrate oxidation was measured using indirect respiratory calorimetry combined with tracer technique in five healthy young male subjects, during a 80-min exercise period on ergocycle with ingestion of 140 g of (13)C-labelled glucose, in normoxia and acute hypobaric hypoxia (445 mmHg or 4,300 m), at the same relative [77% V(.-)((O)(2)(max))] and absolute workload (161+/-8 W, corresponding to 77 and 54% V(.-)((O)(2)(max)) in hypoxia and normoxia). The oxidation rate of exogenous glucose was not significantly different in the three experimental situations: 21.4+/-2.9, 20.2+/-1.2 and 17.2+/-0.6 g over the last 40 min of exercise at approximately 77 and approximately 54% V(.-)((O)(2)(max)) in normoxia and in hypoxia, respectively, providing 12.5+/-1.5, 16.8+/-1.1 and 14.9+/-1.1% of the energy yield, although ingestion of glucose during exercise resulted in a higher plasma glucose concentration in hypoxia than normoxia. The contribution of carbohydrate (CHO) oxidation to the energy yield was significantly higher in hypoxia (92.0+/-2.1%) than in normoxia for both a given absolute (75.3+/-5.2%) and relative workload (78.1+/-1.8%). This greater reliance on CHO oxidation in hypoxia was entirely due to the significantly larger contribution of endogenous glucose oxidation to the energy yield: 75.9+/-1.7% versus 66.6+/-3.3 and 55.2+/-3.7% in normoxia at the same relative and absolute workload.

Adult↗

[Fundamentals of chronobiology: nyctohemeral rhythms].

Most biological activities fluctuate throughout the day and contribute to a better adaptation to the organism's daily activity. During the last 30 Years, chronobiology has aimed at studying these biological rhythms, explaining most of the biological mechanisms of i) the endogenous circadian rhythmicity, ii) the neurophysiological mechanisms of the photic system that allows its external resetting, and iii) the neuroendocrine mechanisms of internal rhythm synchronization. Moreover, the description of specific biological rhythm disorders and rhythm problems at the cellular and even the molecular level have prompted the emerging fields of chronopharmacology and chronotherapeutics.

Animals↗

[Nyctohemeral variations in intraocular pressure].

Intraocular pressure (IOP) varies and depends on many factors. These variations throughout the nycthemeron (the full 24-h period of a night and a day) are the most interesting to study. With the current techniques, it is impossible to measure continuously without waking the subject. Therefore, IOP must be measured hourly over 24 h with a portable tonometer, which provides short measurements in any posture, without requiring the subjects to rise during the night. Intraocular pressure depends on a nyctohemeral rhythm and in healthy subjects is higher at night than during the day, with a nocturnal peak value (acrophase). In the same normal individual, several 24-h measurements are identical. Each individual has his own 24-h IOP pattern. In glaucoma patients, however, the 24-h IOP rhythm was shown to be reversed, with values higher during the day (a midday peak in IOP) than during the night. The time course of the nyctohemeral curve of intraocular pressure is considered to play a role in the prognosis of glaucoma and can serve to classify the type of glaucoma (POAG, NTG). Lowering IOP is still the only option that is available for treating patients with glaucoma. Variations encountered in the individual's nyctohemeral IOP pattern must be taken into consideration to provide the most effective treatment.

Chronotherapy↗

Effect of ambient temperatures ranging from cold to heat on thermoregulation in conscious MK801-treated rats.

The glutamate NMDA receptor has been suggested to be involved in thermoregulation. To further analyse its role, the thermoregulatory responses of rats treated with 0.5 mg.kg-1 of dizocilpine (MK801) were compared with those of control rats treated only with the same volume of saline during a 180-min exposure at one of the six different ambient temperatures, ranging from cold to heat. Colonic temperature (Tco) and tail skin temperature (Ttail) were measured throughout using Cu-Ct thermocouples. In the cold (2.4 and 12.3 degrees C), Tco decreased either sharply (MK801) or progressively (saline), reaching the same final value (2.4 degrees C) or a lower value in the MK801-treated rats (12.3 degrees C). At the same time, Ttail decreased in both groups. In the cool environment (20.7 degrees C), Tco and Ttail decreased in both groups, with lower final values in MK801-treated rats. At thermoneutrality (28.8 degrees C), the MK801-induced hyperthermia remained steady, while Ttail increased in both groups. In the heat (34.6 and 36.2 degrees C), Tco and Ttail increased in both groups, with higher final values in MK801-treated rats. Moreover, at 36.2 degrees C, only MK801-treated rats exhibited heatstroke. It is thus suggested that MK801-induced inhibition of NMDA receptors impairs thermoregulation, especially in the heat.

Animals↗

Clinical follow-up in the rat experimental model of African trypanosomiasis.

Animal models of Human African Trypanosomiasis (HAT) have been developed to understand the pathogenic mechanisms leading to the passage into the neurological phase, most of them referring to histological aspects but not clinical or behavioral data. Our study aimed at defining simple clinical and/or behavioral markers of the passage between the hemolymphatic phase and the meningo-encephalitic stage of the disease. Sprague-Dawley rats (n=24) were infected with Trypanosoma brucei brucei AnTat 1.1E. Food intake and body weight were measured daily from the day of infection until death. Hematocrit was measured twice a week. Behavioral disturbances were evaluated through an Open-field test. A sudden weight loss occurred on the twelfth day after infection, due to a significant drop of food intake starting two days before. The rats developed an anemic state shown by the hematocrit measurements. The Open-field test showed them to be less active and reactive as soon as the second week after infestation. A complementary histological study observed trypanosomes and inflammatory cells in the choroid plexus at the same period. These results are in favor of central nervous system functional disturbances. The observed weight loss is discussed as being a parameter of the entry in the meningo-encephalitic phase. The rat model reproduces neurological symptoms observed in the human disease and may prove to be useful for further neurohistological and therapeutic studies.

Animals↗

[Sleeping sickness: forgotten research?].

Has research on sleeping sickness, i.e., human African trypanosomiasis (HAT), been forgotten? To get an idea on funding, we consulted the Medline bibliographic database for the last 14 years. The number of publications on HAT was stagnant over the study period. By comparison there was a steady increase in the number of publications dealing with malaria. These findings suggest that interest in HAT research waned in favor of other endemics even though government or other funding agencies continued to finance research networks. To illustrate this situation, we present the funding and findings of our multidisciplinary working group in a wide range of domains including sleep, endocrine rhythms, identification of biological markers, research on physiopathologic mechanisms of the host-pathogen relationship, and development on new medications. Over the last 14 years, a total of 1 million Euros was spent to produce 68 publications on Medline, i.e., roughly 15000 [symbol: see text] per publication.

Biomedical Research↗

Inhibition of different types of nitric oxide synthase: effect on thermoregulation in the rat exposed to high ambient temperature.

Vascular and immunological mechanisms are both likely to be involved in heatstroke, this condition being preceded by a decrease in cerebral blood flow and an increase in brain cytokine concentrations. As the two mechanisms involve a nitridergic step, we analysed their respective role in heat tolerance by exposing vigil rats to heat after treatment with nitric oxide synthases (NOS) antagonists: non-specific inhibitors N(omega)-nitro-L-arginine (LNA) and N-nitro-L-arginine-methyl-ester (L-NAME); 7-nitroindazol (neuronal NOS inhibitor) and aminoguanidine (AG) (inducible NOS inhibitor). Heat exposure was interrupted when clinical signs occurred or when colonic temperature reached 43 degrees C. LNA and L-NAME dramatically reduced heat tolerance, while AG did not modify it. These results suggest the involvement of constitutive NOS in heat tolerance. Inducible NOS does not seem to be involved in the occurrence of heatstroke.

Animals↗

NMDA receptors are involved in dithiothreitol-induced hypothermia.

Sulfhydryl-reducing agents, such as dithiothreitol, modulate glutamate N-methyl-D-aspartate (NMDA) receptors. Since these receptors are involved in thermoregulatory processes, we studied the effects of their positive modulation, through a dithiothreitol-induced reduction of the receptor redox site, on thermoregulation in rats maintained at an ambient temperature of 20-22 degrees C. Given intraperitoneally at the dose of 25 and 50 mg x kg(-1), dithiothreitol induced dose-dependent hypothermia. The prior administration of 0.5 mg x kg(-1) of (+/-)-dizocilpine maleate (MK801), a non-competitive glutamate NMDA receptor antagonist, blocked most of the dithiothreitol-induced hypothermia. MK801 given alone was followed by slight transient hyperthermia. This confirms the involvement of NMDA receptors in thermoregulation and suggests that they might be under redox modulation.

Animals↗

The duality of sleeping sickness: focusing on sleep.

Sleeping sickness, once under control, is a re-emergent endemic parasitic disease in intertropical Africa. Its originality resides in its duality. Two trypanosome groups (Trypanososma brucei gambiense vs.rhodesiense ) are transmitted to humans by tsetse flies from two geographical areas (Western and Central Africa humid forest vs. Eastern Africa arboreous savannah), provoking a slowly or a rapidly evolutive disease. The two stage (haemolymphatic vs. neurological invasion) pathogenic evolution leads to the duality of the immune response, depending on the host-parasite inter-relation differences in the blood and the brain. In the blood, the immune processes involved are both specific (anti-variant surface glycoprotein (VSG) antibodies) and non-specific (complement-mediated lysis, opsonification-facilitated phagocytosis and antibody dependent cell-mediated cytotoxicity). Although macrophages are activated in the blood and infiltrate the brain, nitric oxide decreases in the blood and increases in the brain, with a breakage in the blood-brain barrier, leading to brain lesions through the production of deleterious molecules. Prophylactic means are affected by the duality of pathogenic processes. This finally leads to a two stage disease (haemolymphatic vs. neurological) with two different therapeutic strategies. The sleep-wake cycle and other biological rhythms are also marked by the disappearance of circadian rhythmicity demasking basic ultradian activities and relationships, such as the interdependence of endocrine profiles and the sleep-wake alternation. 2001 Harcourt Publishers Ltd

Journal Article↗

[Sleeping sickness: major disorders of circadian rhythm].

At the meningoencephalitis stage, human African trypanosomiasis (HAT), sleeping sickness, causes dysregulation of the circadian rhythm of the sleep/wake cycle, rather than hypersomnia. In bedridden patients, total sleep time does not exceed 9 hours. The change in the 24-hour distribution of sleep and wakefulness is proportional to severity of clinical symptoms and laboratory abnormalities. The internal structure of sleep is also altered. All patients present sleep onset rapid eye movement periods (SOREMP), i.e., several sleep episodes beginning with rapid eye movement (REM) sleep. In mild cases, treatment with melarsoprol reverses circadian dysregulation, and SOREMP either decrease in number or disappear. Other circadian disturbances may be observed in HAT. These may include circadian dysrhythmia of hormonal secretions, but the relationship between hormonal pulses and sleep/wake states is preserved. The circadian rhythm of secretion of prolactin, renin, growth hormone and cortisol disappears in severe cases, but persists in mild ones. The amplitude and mean 24-hour value of plasma melatonin are normal with nocturnal peaks and no diurnal secretion. However, peak melatonin secretion occurs 2 hours earlier than in healthy African controls. In conclusion, HAT-induced dysregulation of circadian rhythm is proportional to disease severity. Presence of SOREMP and precocity of peak melatonin secretion support disturbance of the serotoninergic network rather than direct action on the biological clock.

Circadian Rhythm↗

Hydrodynamic model of heat stroke.

This work presents an hydrodynamical model of heat stroke, which is a physiopathological state of stress, due to an exposure of animals to an ambient temperature of approximatively 40 degrees C during two hours. The evolution of body temperature during this stress process is characterised by three phases. A first phase of increase is followed by a plateau which occurs before a second phase of increase which can be lethal. The model is based on the analogy of a boat progressively caught in a whirlpool. The evolution of the degree of freedom lost by the boat is mathematically analysed and this study leads to the same three phases. The theoretical curves calculated during this study are well in agreement with the experimental curves obtained with animals. This analogy is compared to a previous one which has been made during another experiment with animals constrained by chemical intoxications. It seems that stress can be considered as a vital vorticity and that hydrodynamic models are powerful tools in understanding this physiopathological state.

Animal Testing Alternatives↗

Effects of acute hypobaric hypoxia on the appearance of ingested deuterium from a deuterium oxide-labelled carbohydrate beverage in body fluids of humans during prolonged cycling exercise.

To determine whether or not acute hypobaric hypoxia alters the rate of water absorption from a carbohydrate beverage ingested during exercise, six men cycled for 80 min on three randomly assigned different occasions. In one trial, exercise was performed in hypoxia (barometric pressure, P(B) = 594 hPa, altitude 4,400 m) at an exercise intensity selected to elicit 75% of the individual's maximal oxygen uptake (VO2max) previously determined in such conditions. In the two other experiments, the subjects cycled in normoxia (P(B) = 992 hPa) at the same absolute and the same relative intensities as in hypoxia, which corresponded to 55% and 75%, respectively, of their VO2max determined in normoxia. The subjects consumed 400 ml of a 12.5% glucose beverage just prior to exercise, and 250 ml of the same drink at 20, 40 and 60 min from the beginning of exercise. The first drink contained 20 ml of deuterium oxide to serve as a tracer for the entry of water into body fluids. The heart rate (HR) during exercise was higher in hypoxia than in normoxia at the same absolute exercise intensity, whereas it was similar to HR measured in normoxia at the same relative exercise intensity. Both in normoxia and hypoxia, plasma noradrenaline concentrations were related to the relative exercise intensity up to 40 min of exercise. Beyond that duration, when exercise was performed at the highest absolute power in normoxia, the noradrenaline response was higher than in hypoxia at the same relative exercise intensity. No significant differences were observed among experimental conditions, either in temporal profiles of plasma D accumulation or in elimination of water ingested in sweat. Conversely, elimination in urine of the water ingested appeared to be related to the severity of exercise, either high absolute power or the same relative power combined with hypoxia. We concluded that water absorption into blood after drinking a 12.5% glucose beverage is not altered during cycling exercise in acute hypobaric hypoxia. It is suggested that the elimination of water ingested in sweat and urine may be dependent on local circulatory adjustments during exercise.

Absorption↗

Dopamine involvement in thermoregulatory responses to heat in rats.

The role of dopamine in thermoregulatory challenges was studied in rats exposed to thermoneutrality then to heat with pretreatment by SCH23390 (i.p., D1/D5 receptor antagonist), sulpiride (i.p., D2 receptor antagonist) or piribedil (i.p., D2/D3 receptor agonist). Heat exposure leads to a rise in rectal temperature followed by a steady plateau ending with a terminal increase. The duration of both heat exposure and the plateau increased largely after SCH23390 and rose slightly after sulpiride. Piribedil was ineffective on these parameters but lowered rectal temperature at thermoneutrality. It is suggested that the thermoregulatory failure observed in heat-exposed rats may implicate dopamine through D1/D5 and in a lesser extent through D2 receptors. The inefficacy of piribedil suggests that dysregulations in synaptic transmission may exist.

Analysis of Variance↗

Voltametric assessment of brain nitric oxide during heatstroke in rats.

Anesthetized rats exposed to a high ambient temperature develop heatstroke with brain ischemia. Since nitric oxide (NO) plays an important role during normothermic ischemia, its cortical and cerebellar production were continuously assessed in pentobarbital anesthetized rats exposed to heat by using differential pulsed voltammetry. After 60 min at thermoneutrality, the rats were submitted to an ambient temperature of 40 degrees C until death. After 60 min in the heat, the rats were injected intraperitoneally with saline, MK801 (1 mg.kg(-1)), an antagonist of N-methyl-D-aspartate (NMDA) receptors, or L-arginine p-nitroanilide (L-ANA; 100 mg.kg(-1)), an inhibitor of NO synthase. Just before death, a 70% increase in NO production was observed in both the cerebellum and the cortex of saline-treated rats. The cortical increase in NO was not modified by MK801 while the NO signal was suppressed by L-ANA.

Animals↗

Plasma myosin and creatine kinase time-course after a concentric-eccentric field exercise.

The effect of a concentric (uphill run)-eccentric (downhill run) field exercise of 22.3 km long was examined in five healthy male volunteers to compare the time course of changes in plasma creatine kinase (CK) activity and beta myosin heavy chain (beta MHC) concentration observed during the recovery. CK and beta MHC were examined in blood sampled before exercise, immediately and 5 hours after exercise ceased. Screenings were conducted 1, 2, 3, 4, 5 and 7 days later. For every subject, the peak of plasma CK was transient and observed within the first 24 hours of recovery. In contrast to CK changes, plasma beta-MHC elevation was delayed and the peak, also transient, was observed the second or the third day after the exercise. The highly significant relationship between individual values of CK and beta MHC (P < 0.001) demonstrates that beta MHC could be used as a marker of skeletal muscle damage after acute exercise.

Adult↗

Twenty-four-hour profiles and sleep-related variations of cortisol, thyrotropin and plasma renin activity in healthy African melanoids.

The 24-h hormone profiles have been well documented in caucasians living in a temperate climate, but they have never been examined in melanoid subjects under equatorial conditions, with a 12-h light-dark cycle in a hot climate. To establish normal data for this population, blood samples were taken at 10-min intervals over 24 h in five healthy young melanoids living in Abidjan (Ivory Coast). Cortisol and thyroid stimulating hormone (TSH) concentrations and plasma renin activity (PRA) were determined by radio-immunoassay and sleep was registered using polysomnography. Data were compared with results obtained in Strasbourg (France) from six healthy aged-matched caucasians. The 24-h profile of cortisol concentration was similar in both groups, with a 2-h phase advance in the melanoids. Nocturnal fluctuations of PRA, strongly linked to the rapid eye movement-non rapid eye movement (REM-NREM) sleep cycles, occurred in both groups, with higher levels in the caucasians in the last 2 h of sleep along with greater amounts of NREM sleep. After an evening increase in TSH, the sleep onset-related decrease seen in the caucasians was not observed in the melanoids. In both groups, increasing concentrations of TSH and cortisol occurred with awakening, decreasing concentrations being observed during slow-wave sleep. As in the caucasians studied in the temperate climates, the melanoid subjects living at the equator showed the same temporal organization of hormone rhythms within the 24-h period and the same relationships between the pulses and specific sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗