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Biomedical subjects

G Dupont

Publications and source records attributed to G Dupont.

At least 19 recordsLinked to original sources

[Fatal traffic accidents among the elderly in the county of Ringkøbing].

The cases of all persons aged 70 years or more who were killed in traffic accidents in the County of Ringkøbing during the period 1.1.1983-31.12.1990 were reviewed on the basis of the death certificates and the police reports. A total of 58 deaths were involved and this was significantly greater than in the age group 0-69 years (p < 0.01). Twenty-eight of the accidents (48.3%) were car accidents. The commonest cause of these car accidents was that "give way" signs had not been respected and there were thus no solo accidents. The next most frequent type of accident consisted of knocking down of pedestrians (25.9%), followed by bicycle accidents (15.5%) and moped accidents (8.6%). Out of the total of fatal accidents, only one of the fatally injured persons was under the influence of alcohol (1.7%). If passengers in motor vehicles were excluded, a total of 39 of the fatally injured persons (88.6%) were themselves the cause of the accident concerned. It is concluded that fatal traffic accidents among elderly persons in the County of Ringkøbing constitute a great problem and that the driving abilities of elderly persons should be investigated further.

Accidents, Traffic

[Treatment of injuries in the county of Ringkøbing. 4. Referral and transport of severe traffic accident traumas].

In Denmark, all cases of severe injuries are referred to the nearest hospital regardless of the size of the hospital and the county boundaries. In order to investigate whether this type of referral functions according to plan, the authors investigated referral of all traffic accidents in the County of Ringkøbing during the period 1 January 1983 to 31 December 1990. It was demonstrated that in only one out of 310 traffic accidents with fatal outcome, referral did not function according to plan and that the patient had been transported to a hospital which was not the nearest. It is thus concluded that referral now functions according to plan in its present form. In addition, the authors investigated whether there was any basis for establishing prehospital treatment of injuries in the country. It was found, however, that during a period of eight years (analysed on the basis of post mortem data) a maximum of 20 relevant patients would be involved annually and in whom the mortality might be reduced was concerned. Simultaneously, the average distance for transport to the nearest hospital was found to be only 12.9 km. There is thus no basis for employing massive resources for advanced prehospital service in the County of Ringkøbing. With an ambulance service staffed by doctors from the anaesthetic and intensive care units of the central hospitals it is possible to provide prehospital treatment in 70% of all severe traffic injuries in the County of Ringkøbing.

Accidents, Traffic

Oscillations and waves of cytosolic calcium: insights from theoretical models.

Oscillations in cytosolic Ca2+ occur in a wide variety of cells, either spontaneously or as a result of external stimulation. This process is often accompanied by intracellular Ca2+ waves. A number of theoretical models have been proposed to account for the periodic generation and spatial propagation of Ca2+ signals. These models are reviewed and their predictions compared with experimental observations. Models for Ca2+ oscillations can be distinguished according to whether or not they rely on the concomitant, periodic variation in inositol 1,4,5-trisphosphate. Such a variation, however, is not required in models based on Ca(2+)-induced Ca2+ release. When Ca2+ diffusion is incorporated into these models, propagating waves of cytosolic Ca2+ arise, with profiles and rates comparable to those seen in the experiments.

Animals

General surgery in patients aged 80 years and older.

This study reviews 594 surgical admissions, of patients aged 80 years and older, to departments of general surgery during 1 year. Half of the patients were admitted as emergencies and 60 per cent underwent surgery. The operative mortality rate was 8 per cent and the overall mortality rate for all admissions 9 per cent. The number of complications and the mortality rate after surgery increased in emergency cases and in patients with coexisting disease. Of all admissions, 72 per cent were uncomplicated and in 70 per cent patients could be discharged directly home; such patients do not generally take up beds and are discharged as soon as medical care is no longer indicated. The number of admissions of patients over 80 years of age will increase by about 30 per cent during this decade and, unless additional resources are provided to meet this challenge, new standards must be considered for the distribution of resources and of indications for surgery in both young and old.

Aged

Protein phosphorylation driven by intracellular calcium oscillations: a kinetic analysis.

Given the ubiquitous nature of signal-induced Ca2+ oscillations, the question arises as to how cellular responses are affected by repetitive Ca2+ spikes. Among these responses, we focus on those involving protein phosphorylation. We examine, by numerical simulations of a theoretical model, the situation where a protein is phosphorylated by a Ca(2+)-activated kinase and dephosphorylated by a phosphatase. This reversible phosphorylation system is coupled to a mechanism generating cytosolic Ca2+ oscillations; for definiteness, this oscillatory mechanism is based on the process of Ca(2+)-induced Ca2+ release. The analysis shows that the average fraction of phosphorylated protein increases with the frequency of repetitive Ca2+ spikes; the latter frequency generally rises with the extent of external stimulation. Protein phosphorylation therefore provides a mechanism for the encoding of the external stimulation in terms of the frequency of signal-induced Ca2+ oscillations. Such a frequency encoding requires precise kinetic conditions on the Michaelis-Menten constants of the kinase and phosphatase, their maximal rates, and the degree of cooperativity in kinase activation by Ca2+. In particular, the most efficient encoding of Ca2+ oscillations based on protein phosphorylation occurs in conditions of zero-order ultrasensitivity, when the kinase and phosphatase are saturated by their protein substrate. The kinetic analysis uncovers a wide variety of temporal patterns of phosphorylation that could be driven by signal-induced Ca2+ oscillations.

Calcium

Allosteric regulation, cooperativity, and biochemical oscillations.

Allosteric regulation is associated with a number of periodic phenomena in biochemical systems. The cooperative nature of such regulatory interactions provides a source of nonlinearity that favors oscillatory behavior. We assess the role of cooperativity in the onset of biochemical oscillations by analyzing two specific examples. First, we consider a model for a product-activated allosteric enzyme which has previously been proposed to account for glycolytic oscillations. While enzyme cooperativity plays an important role in the occurrence of oscillations, we show that these may nevertheless occur in the absence of cooperativity when the reaction product is removed in a Michaelian rather than linear manner. The second model considered was recently proposed to account for signal-induced oscillations of intracellular calcium. This phenomenon originates from a nonlinear process of calcium-induced calcium release. Here also, the cooperative nature of that positive feedback favors the occurrence of oscillations but is not absolutely required for periodic behavior. Besides underlining the importance of cooperativity, the results highlight the role of diffuse nonlinearities distributed over several steps within a regulated system: even in the absence of cooperativity, such mild nonlinearities (e.g., of the Michaelian type) may combine to raise the overall degree of nonlinearity up to the level required for oscillations.

Allosteric Regulation

Comparison of creatinine and inulin clearances in multiple trauma.

Creatinine clearance (Ccr) is a good predictor of renal dysfunction. However, numerous analytical interferences have been observed with the classical measurement of creatinine by Jaffé's procedure. This prospective study was conducted to compare 4 methods for determining creatinine; and also endogenous creatinine clearance with inulin clearance (Cin) to estimate the glomerular filtration rate. The 4 different techniques for measuring creatinine were: 1) 2 techniques using Jaffé's colorimetric reaction: one with rapid and the other with slow kinetics: 2) 2 more selective methods: enzymatic procedure and high performance liquid chromatography (HPLC). Measurements were performed in 13 multiple trauma patients after stabilization and in 5 comatose patients (control group) over a 3-day period, with strict 24-h urine collection. On the second day, inulin clearance and para-aminohippuric acid clearance (Cpah) were measured. Measurement of creatinine by Jaffé's procedure yields significantly higher levels than those obtained by the other methods. Higher levels of both plasma and urinary creatinine were observed in the multiple trauma patients with all the methods used. There were no significant differences in Ccr, Cin, Cpah between the multiple trauma patients and the control patients. The best correlations between inulin clearance and creatinine clearance were observed for Jaffé's rapid kinetics (r = 0.90) in the control group and for the enzymatic procedure in the multiple trauma group (r = 0.55). Plasma creatinine is not a useful indicator in multiple trauma. The correlation between creatinine clearance and inulin clearance is not very strong in multiple trauma, indicating that the relative evolution (not the absolute values) of creatinine clearance is of interest.

Adult

Minimal model for signal-induced Ca2+ oscillations and for their frequency encoding through protein phosphorylation.

In a variety of cells, hormonal or neurotransmitter signals elicit a train of intracellular Ca2+ spikes. The analysis of a minimal model based on Ca2(+)-induced Ca2+ release from intracellular stores shows how sustained oscillations of cytosolic Ca2+ may develop as a result of a rise in inositol 1,4,5-trisphosphate (InsP3) triggered by external stimulation. This rise elicits the release of a certain amount of Ca2+ from an InsP3-sensitive intracellular store. The subsequent rise in cytosolic Ca2+ in turn triggers the release of Ca2+ from a second store insensitive to InsP3. In contrast to the model proposed by Meyer and Stryer [Meyer, T. & Stryer, L. (1988) Proc. Natl. Acad. Sci. USA 85, 5051-5055], the present model, which contains only two variables, predicts the occurrence of periodic Ca2+ spikes in the absence of InsP3 oscillations. Such results indicate that repetitive Ca2+ spikes evoked by external stimuli do not necessarily require the concomitant, periodic variation of InsP3. The model is closely related to that proposed by Kuba and Takeshita [Kuba, K. & Takeshita, S. (1981) J. Theor. Biol. 93, 1009-1031] for Ca2+ oscillations in sympathetic neurones, based on Ca2(+)-induced Ca2+ release. We extend their results by showing the minimal conditions in which the latter process gives rise to periodic behavior and take into account the role of the rise in InsP3 caused by external stimulation. The analysis further shows how signal-induced Ca2+ oscillations might be effectively encoded in terms of their frequency through the phosphorylation of a cellular substrate by a protein kinase activated by cytosolic Ca2+.

Animals

Latency correlates with period in a model for signal-induced Ca2+ oscillations based on Ca2(+)-induced Ca2+ release.

Oscillations in cytosolic Ca2+ develop in a variety of cells after an induction phase, called latency, the duration of which depends on the magnitude of external stimulation. Experiments in hepatocytes indicate that the period and latency of Ca2+ oscillations both decrease as the level of the stimulus increases. We analyze the correlation between period and latency in a model recently proposed for signal-induced Ca2+ oscillations. We show that the linear relationship between period and latency observed in the experiments arises naturally in this model as a result of the mechanism of Ca2(+)-induced Ca2+ release on which it is based.

Animals

Oscillatory dynamics in intercellular communication.

The role of biological rhythms in the control of intercellular communication is briefly reviewed. In particular, pulsatile cAMP signaling in the slime mold, Dictyostelium discoideum, the pulsatile release of the hormone GnRH in higher animals, and cytosolic calcium oscillations are discussed, with special reference to underlying molecular mechanisms. It is pointed out that there exists an optimal pattern of periodic stimulation by hormones and that frequency encoding has some advantages in comparison with amplitude encoding, especially concerning the accuracy of control.

Biological Clocks

[Update on prolactin].

Normal serum prolactin levels range from 5 to 20 ng/ml (circadian rhythm, effect of stress, relation with estrogen secretion). Neuroleptics increase serum prolactin levels. Normal concentrations are restored within 24 to 48 hours of discontinuation of the drug. When neuroleptics are given for a long period of time, serum prolactin concentrations fall gradually to low levels. There is no conclusive evidence that prolactin plays a role in breast tumors in women. Epidemiologic studies have shown that neuroleptics are not responsible for increased incidences of these tumors.

Animals

[Comparison of 2 semi-quantitative methods for evaluating blood glucose in newborn infants].

Blood glucose levels were assessed in 49 neonates, using 2 blood glucose test strips. Results were compared to blood glucose levels. Correlations between values from the test strips and values from the laboratory were better using the Haemo-Glukotest (r = 0.91) than using the Dextrostix (r = 0.82). As compared to values from the laboratory, however, both glucose test strips gave higher values and did not properly identify all cases of hypoglycemia.

Blood Glucose