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Biomedical subjects

J C Thalabard

Publications and source records attributed to J C Thalabard.

At least 19 recordsLinked to original sources
PubMed1998

[Hereditary risks of breast cancer. Interaction of genetic factors and hormonal factors].

The association between risk of breast cancer and familial risk is well documented. The first observation was described by Paul Broca around 1850 from his own family. Germinal mutations have been estimated to account for 5 to 10% of breast cancer cases. However, some questions remains unclear in this context of a multifactorial disease. Even if the rise in breast cancer risk associated with BRCAx mutations is well established, the place of a genetic factor among other factors risks of breast cancer remains unclear. The interaction between genetic, environmental and hormonal factors is an important problem. More particularly the effect of oral contraceptives and hormonal replacement therapy in women with or without hereditary susceptibility of breast cancer needs to be addressed.

Breast Neoplasms↗
PubMed1996

Combined curative radiation therapy alone in (T1) T2-3 rectal adenocarcinoma: a pilot study of 29 patients.

AIM: Analysis of a pilot study including 29 consecutive patients with high surgical risk or refusal of colostomy treated with radiation therapy alone with curative intent. PATIENTS: Between 1986 and 1992, 29 patients were treated for infiltrating adenocarcinoma of the rectum. Median age was 72 years. Transrectal ultrasound staging was used in 24 patients (T1, 2; T2, 14; T3, 13; N0, 23; N1, 6). In 20 patients the lower border of the tumor was at 5 cm or less from the anal verge and in 19 patients the diameter exceeded 3 cm. CEA was elevated in seven cases. TREATMENT: Contact X-ray (50 kV) was given first (70 Gy/3 fractions). External beam radiation therapy used a three-field technique in the prone position. Accelerated schedule (39 Gy/13 fractions/17 days) with a concomitant boost "field within the field' (4 Gy/4 fractions). Six weeks later an iridium-192 implant was performed in 21 (20 Gy/22 h). RESULTS: Median follow-up time was 46 months. Overall and specific survival at 5 years was 68% (SE = 0.09) and 76% (SE = 0.08). Local control was obtained in 21/29 patients (72%). There was one grade 2 rectal bleeding and five grade 2 rectal necroses. The overall tolerance was good in these frail patients. DISCUSSION: For T2. T3 or T1 > 3 cm diameter rectal adenocarcinoma, where contact X-ray alone is not recommended, a combined treatment with radiation therapy alone is able to give good local control with acceptable toxicity. This treatment should be restricted to inoperable patients.

Adenocarcinoma↗
PubMed1996

A hidden Markov model approach to neuron firing patterns.

Analysis and characterization of neuronal discharge patterns are of interest to neurophysiologists and neuropharmacologists. In this paper we present a hidden Markov model approach to modeling single neuron electrical activity. Basically the model assumes that each interspike interval corresponds to one of several possible states of the neuron. Fitting the model to experimental series of interspike intervals by maximum likelihood allows estimation of the number of possible underlying neuron states, the probability density functions of interspike intervals corresponding to each state, and the transition probabilities between states. We present an application to the analysis of recordings of a locus coeruleus neuron under three pharmacological conditions. The model distinguishes two states during halothane anesthesia and during recovery from halothane anesthesia, and four states after administration of clonidine. The transition probabilities yield additional insights into the mechanisms of neuron firing.

Action Potentials↗
PubMed1996

Insulin-induced hypoglycemia decreases luteinizing hormone secretion in the castrated male rat: involvement of opiate peptides.

Insulin-induced hypoglycemia (IIH) has been reported to inhibit luteinizing hormone (LH) secretion in ovariectomized ewes as well as in intact or gonadectomized female rhesus monkeys. An infusion of naloxone, a specific opiate receptor antagonist, while able to prevent this inhibitory effect in ewes, was ineffective in monkeys, suggesting a difference in the mechanisms involved in the response to IIH in these two species. The present study was designed to investigate the influence of this stimulus on the dynamics of LH release and the possible activation of an opioidergic pathway in the long-term castrated male rat. Blood samples were collected every 7 min, for several hours, in freely-moving rats bearing a jugular cannula. The intravenous injection of 0.4 IU of insulin triggered an acute hypoglycemia and reduced LH release. In contrast, during a continuous intravenous naloxone infusion (0.5 mg/kg/h), insulin, while still lowering the glycemia, failed to affect the LH secretory pattern. In a control experiment, naloxone infusion alone had no significant effect on mean LH concentration and pulse intervals. These experiments indicate that, in long-term gonadectomized male rats, IIH impairs the LH secretory pattern, and that endogenous opioid peptides are involved in this response.

Animals↗
PubMed1996

[Importance of ultradian rhythms in endocrinology].

Biological rhythms have been reported for a long time in endocrinology. However, their real study started in the late 60's when the possibility of repeatedly measuring the hormonal signal directly in blood over extended periods of time became available. Although episodic secretory fluctuations have been reported for the majority of hormones, and more specifically peptidic hormones, in mammals, organised secretory episodes on a regular or quasi-regular ultradian basis are less common. Their importance, which is directly connected to the number and the processing of the corresponding receptors on the target cells, is illustrated by the paradigm of the pulsatile release of the gonadotropin hormones. Hormonal ultradian rhythms should be considered both from the nosological and therapeutical point of view.

Activity Cycles↗
PubMed1995

Hypothalamic multiunit activity and pulsatile luteinizing hormone release in the castrated male rat.

Using chronically implanted microelectrodes, multiunit electrical activity (MUA) was recorded from the arcuate nucleus of freely moving gonadectomized male rats. Intermittent increases in MUA activity (MUA volleys) closely associated with luteinizing hormone pulses measured in the peripheral circulation were observed, which confirms that this experimental approach can be used for monitoring the activity of the gonadotropin-releasing hormone-associated hypothalamic pulse generator in the male rat. The mean MUA volley frequency was 22.2 min (range 13-38 min), whereas the mean MUA volley duration was 2.7 +/- 0.8 min (standard deviation). In addition to a large inter-individual variability. MUA volley intervals also showed an important intra-individual variability. This observation suggests that, beside the mean frequency of pulse generator activation, the degree of variability in gonadotropin-releasing hormone-associated pulse generator activity might be an additional relevant parameter in the characterization of the reproductive function in the male rat.

Animals↗
PubMed1995

Adaptive control of therapeutic drug regimens relations between clinical situations: outcomes and simulations using nonlinear dynamic models.

With Bayesian modeling and adaptive control of drug dosage regimens, serum and peripheral drug concentrations can be predicted in clinical situations using linear pharmacokinetic compartmental models (PK). Recently, several pathophysiologic and pharmacodynamic nonlinear models (PD) have been developed. The present report illustrates both their utility and limits for the computation of effects in clinical situations in the setting of actual routine and acute patient care. Patients who received therapy with aminoglycosides or/and vancomycin were selected. For each patient, after estimation of individual pharmacokinetic parameters, the computed outputs of the linear compartmental pharmacokinetic model were used as inputs for 2 different a priori nonlinear dynamic models: 1) the EFFECT modeling program, using a Hill model, and 2) the BACTCIDE program, which is a combination of a simple growth model for the organism and a Hill effect model considering both the microorganism, the antibiotic, and the patient's minimal inhibitory concentration (MIC). The programs (1) and (2) can use as inputs the computed concentrations from any of three compartments: central, peripheral, or a spherical diffusion compartment to compute drug diffusion into endocardial vegetations or abscesses. The EFFECT program can be used alone for the evaluation of drug effects. The BACTCIDE program illustrates differences in activity between concentration-dependent and time-dependent antibiotics. Such nonlinear programs are very sensitive to the MIC values.

Aged↗
PubMed1994

Progestogen use and decreased risk of breast cancer in a cohort study of premenopausal women with benign breast disease.

A cohort study of 1,150 premenopausal French women with benign breast disease diagnosed in two breast clinics between 1976 and 1979 was carried out to analyse the relationship between progestogen use and the risk of breast cancer. The follow-up accumulated 12,462 person-years. The risk of breast cancer was estimated using a Poisson regression analysis on person-time data and the proportional hazards model. In the latter analysis, cumulated progestogen use and age were considered as time-varying covariables and adjustment was performed on the main risk factors for breast cancer. Neither overall progestogen use nor the duration of use was found to be significantly associated with the risk of breast cancer. When progestogens were classified into two categories according to their hormonal potency (19-nortestosterone derivatives vs other progestogens), 19-nortestosterone derivative use was found to be significantly associated with a lower risk of breast cancer. In the adjusted model, the corresponding risk of breast cancer was 0.48 (95% confidence interval 0.25-0.90). In addition, there was a linear trend in the decrease of the relative risk of breast cancer with the duration of use (P = 0.02). These results do not support the hypothesis that progestogens might increase the breast cancer risk. They suggest, instead, that treatment with 19-nortestosterone derivatives might have a beneficial effect on the risk of breast cancer in women with benign breast disease.

Adult↗
PubMed1994

Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women.

The effect of aging on the number of non-growing follicles (NGF) and early-growing follicles (EGF) was studied in humans through use of a database obtained by pooling two subsets of ovarian pairs (2 x 43 pairs) collected in two distinct populations. A previously suggested model of exponential regression of NGF counts in relation to the subject's age was tested but did not adequately fit the observed data points. This lack of fit is attributable mainly to the existence of a significant relation between a woman's age and the corresponding NGF count decay rate. Consequently, various regression models were tested. Two different periods of decay rate were observed for each population of small follicles. The first corresponds to younger ages with a decay rate that is slow for both types of follicles, although faster for NGF than for EGF. The second period corresponds to older ages with an accelerated decay rate that appears similar for NGF and EGF. The changing points were found at 38.0 +/- 2.4 and 39.0 +/- 1.9 yr (mean +/- SD) for NGF and EGF, respectively. Extrapolation of the fitted model suggested the presence of approximately 402,000 healthy NGF per ovary at birth and a total exhaustion of the follicular stock at around 74 yr of age. These results support the view that depletion of the NGF pool is caused mainly by atresia in younger women but mainly by entrance of NGF into the growing pool in older women. The mechanisms triggering accelerated entrance into the growth phase of NGF are discussed in relation to the previously reported increase in FSH plasma levels that starts in the late thirties, approximately, and precedes the menopausal period by several years.

Adolescent↗
PubMed1994

Stochastic modeling of the hypothalamic pulse generator activity.

Luteinizing hormone (LH) is released by the pituitary in discrete pulses. In the monkey, the appearance of LH pulses in the plasma is invariably associated with sharp increases (i.e, volleys) in the frequency of the hypothalamic pulse generator electrical activity, so that continuous monitoring of this activity by telemetry provides a unique means to study the temporal structure of the mechanism generating the pulses. To assess whether the times of occurrence and durations of previous volleys exert significant influence on the timing of the next volley, we used a class of periodic counting process models that specify the stochastic intensity of the process as the product of two factors: 1) a periodic baseline intensity and 2) a stochastic regression function with covariates representing the influence of the past. This approach allows the characterization of circadian modulation and memory range of the process underlying hypothalamic pulse generator activity, as illustrated by fitting the model to experimental data from two ovariectomized rhesus monkeys.

Animals↗
PubMed1993

[Socioeconomic stakes of menopause: evaluation of the cost-effectiveness studies].

The extension of hormonal replacement therapy to all women after their menopause as a preventive action is becoming a major public health issue. Cost-effectiveness analysis represents an appropriate tool to address the economical aspects of this issue. Out of the 3 studies reported in the past recent years on this topic, the Oxford Hormone Therapy Group study is the only one to take into account all possible outcomes of the hormonal replacement therapy. Its conclusions, however, cannot be extended directly to other countries, as the hormonal replacement therapy may differ in many aspects, like: 1) the chemical nature, metabolism and mode of administration of the hormones used, both as regard the oestrogen component and the progestative one; 2) the acceptability of the therapy in relation to its side effects; 3) the age-specific morbi-mortality data in relation to hip fractures, breast cancer and cardiovascular diseases.

Cost-Benefit Analysis↗
PubMed1993

Effects of naloxone on estrogen-induced changes in hypothalamic gonadotropin-releasing hormone pulse generator activity in the rhesus monkey.

In the ovariectomized rhesus monkey, estradiol (E2) markedly reduces the frequency of the GnRH pulse generator as monitored by LH pulse frequency and the concurrent changes in hypothalamic electrical activity, an action mimicked by morphine. In addition, the duration of the increments in multiunit electrical activity (MUA volleys) that precede each LH pulse is decreased by estrogen administration, an action also shared by morphine. The role of endogenous opioids in these actions of E2 was investigated in 8 ovariectomized animals restrained in primate chairs. They were fitted with indwelling cardiac catheters and with bilateral arrays of recording electrodes chronically implanted in the mediobasal hypothalamus. Physiological serum E2 levels achieved by subcutaneous implantation of E2-containing Silastic capsules increased MUA volley interval from 50.8 +/- (SEM) 1.6 min in the control period to 81.1 +/- 6.2 min following E2. Mean MUA volley duration decreased from 21.9 +/- 1.0 to 13.0 +/- 0.7 min. The placement of empty Silastic capsules had no effect on MUA volley duration or interval. Naloxone administration (2.5 mg bolus followed by a 1 mg/h infusion lasting 4-8 h) completely (n = 4) or partially (n = 2) blocked the effects of E2 on MUA volley interval in 6 of the 8 monkeys, and was without effect in the remainder. In contrast, however, naloxone had little or no effect on the action of E2 on MUA volley duration, (13.0 +/- 0.7 vs. 14.0 +/- 0.9 min). These findings suggest that the inhibitory action of E2 on GnRH pulse generator frequency, like that of all other gonadal steroids studied to date, may be mediated by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Ovarian control of gonadotropin hormone-releasing hormone pulse generator activity in the rhesus monkey: duration of the associated hypothalamic signal.

The activity of the GnRH pulse generator in the rhesus monkey is associated with abrupt increases in multiunit electrical activity (MUA) volleys recorded from the mediobasal hypothalamus that precede each pulse of LH in the peripheral circulation. In long-term ovariectomized animals the duration of these MUA volleys is 10-25 min and consists of a brief initial 'overshoot' followed by a plateau phase that ends in a rapid decline to baseline activity. In intact monkeys, however, the MUA volley lasts only 1-3 min, a duration equivalent to the overshoot in ovariectomized animals. In addition, the maximal frequency of neuronal activity during each MUA volley is reduced in normal animals when compared to castrates. As shown in earlier studies, estradiol given to ovariectomized monkeys causes a reduction in the duration of MUA volleys to that characteristic of intact animals within 3-5 h. In contrast to this acute effect of estradiol, the increase in MUA volley duration following ovariectomy is a gradual phenomenon, 4-6 weeks being required to achieve the MUA volley duration observed in long-term ovariectomized monkeys. A similar slow time course was observed for the increase in maximal neuronal frequency during each MUA volley. This protracted effect of ovariectomy on MUA volley duration and firing rate may be the consequence of hypothalamic remodelling but this consideration must be tempered by the observation that estradiol reverses these phenomena within hours.

Animals↗
PubMed1993

Ambient light modifies gonadotropin-releasing hormone pulse generator frequency in the rhesus monkey.

In the course of previous studies using continuous monitoring of the electrophysiological correlates of GnRH pulse generator activity, characterized by episodic increases in hypothalamic multiunit electrical activity (MUA volley), it was noticed that the nocturnal slowing of pulse generator frequency was an acute phenomenon observable in the first MUA volleys after the lights were turned off, as was the increase in frequency when the lights were turned on in the morning. This suggested that the reduction in pulse generator frequency at night may not be the consequence of an intrinsic diurnal rhythm, but an effect of light per se. Indeed, as reported herein, such an effect was observed when the lights were turned on or off at times other than the normal illumination period (normal light schedule, lights on from 0700-1900 h). That this was not simply a response to arousal was shown by awakening the animals with loud recorded noises in total darkness at the same unaccustomed times without a resulting change in frequency. This suggests that the effect of light is specific, perhaps mediated by the retino-hypothalamic tract. This direct action of light, however, is superimposed upon a diurnal rhythm, as shown by a reduction in pulse generator frequency during the subjective night when the monkeys were kept in constant light or constant darkness.

Animals↗
PubMed1992

Identification of pulses in hormone time series using outlier detection methods.

The identification of discrete hormonal secretory pulses is of critical importance in clinical endocrinology. Pulses are defined as sudden increases in hormone concentration followed by exponential decay. We propose a model-based iterative procedure for pulse detection in pulsatile hormone time series. Our model is seen to be analogous to the model for innovation outliers in autoregressive series, and outlier detection techniques for pulse identification are adapted to the endocrine context. An original feature of the procedure is that it distinguishes between true pulses and gross observation outliers in the series. Simulation experiments are used to investigate the behaviour of the method under physiologically or clinically relevant circumstances. Five experimental endocrine series from rhesus monkeys, where the times of the pulses are known from the concomitant recording of the electrical activity of the hypothalamus, are analysed.

Animals↗