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Biomedical subjects

M Duclos

Publications and source records attributed to M Duclos.

At least 55 records · Page 3Linked to original sources

Does functional alteration of the gonadotropic axis occur in endurance trained athletes during and after exercise? A preliminary study.

In men, the hypothalamic-pituitary-testicular axis controls the secretion of testosterone which, in this sex, is a major anabolic hormone. Physical exercise modulates testosterone concentration, affecting the whole axis by poorly understood mechanisms. We have reported in this preliminary study the short and long-term effects of exercise on the function of the gonadotropic axis in trained compared to untrained subjects. Environmental factors known to interfere with pituitary function were minimized. Four marathon and four sedentary men, were studied during 5 days successively using different combinations of two factors: duration and intensity of running tests. Day 0 (D0) was a rest day, and the exercises were: D1 and D2 brief (20 min), light (50% maximal heart rate, HRmax, D1) or intense (80% HRmax, D2), D3 and D4 prolonged (120 min) and light (50% HRmax, D3) or intense (80% HRmax, D4). Testosterone (free and total) and luteinizing hormone (LH) concentrations were measured before, during and after exercise. The baseline concentrations of plasma testosterone were lower in the long distance runners than in the sedentary group [41.8 (SEM 5.5) vs 64.5 (SEM 7.9) pmol.l-1, respectively; P < 0.05]. This phenomenon was centrally mediated as LH concentration was apparently inappropriately low [3.4 (SEM 0.4) vs 4.3 (SEM 1.0) UI.l-1; P > 0.05]. Light to moderate exercise did not modify testosterone and LH concentrations. Conversely, intense and prolonged exercise increased testosterone concentration [73.2 (SEM 9.0) vs 92 (SEM 11.0) pmol.l-1 in the long distance runners and sedentary group, respectively; P < 0.05] and lowered LH concentrations [2.1 (SEM 0.3) vs 3.4 (SEM 0.3) UI.l-1 in the long distance runners and sedentary group, respectively; P < 0.05 compared to D0, at the same time]. In our conditions of exercise, negative feedback of testosterone upon LH persisted, as positive feedback of low testosterone concentrations was apparently lacking (inappropriately low LH concentration with regard to low basal testosterone concentration).

Adult↗

Application of 6-hydroxydopamine into the fatpads surrounding the draining lymph nodes exacerbates adjuvant-induced arthritis.

Adjuvant-induced arthritis (AA) was examined in Lewis rats following local injection of 6-hydroxydopamine (6-OHDA) into the fatpads of the popliteal and inguinal lymph nodes which drain the hindlimbs (DLN). This method of 6-OHDA treatment resulted in noradrenergic (NA) denervation of DLN, spleen, and other organs in the peritoneal cavity, while sparing NA nerve fibers in the hindlimbs. Sympathectomy exacerbated the inflammation and osteopathic destruction of arthritic joints. Significant increases in dorsoplantar width in arthritic rats following denervation were observed by day 27 following immunization compared to nondenervated arthritic animals. Radiographic evaluation on day 27 after immunization confirmed the inflammation of soft tissue and revealed deterioration of bones of the ankle joint in both AA groups compared with the control groups; more extensive joint damage was apparent in arthritic rats following denervation compared to nondenervated arthritic rats. These findings suggest that the NA innervation of DLN and spleen (and possibly other organs of the peritoneal cavity) plays a regulatory role in the expression of AA. These data supports the hypothesis that absence of NA innervation in lymphoid organs during initiation, onset, and progression of the disease results in exacerbation of AA.

Adipose Tissue↗

Comparison of hyperfractionated conformal photon with conformal mixed neutron/photon irradiation in locally advanced prostate cancer.

In an attempt to improve the probability of complication-free local control for patients with locally advanced prostate cancer, a series of dose-finding studies have been conducted at Wayne State University using conformal neutron and hyperfractionated photon irradiation. In total, 96 patients with locally advanced prostate cancer (T3/T4 N0/N1 M0, and/or Gleason score > or = 8) were treated in two prospective studies. Forty-seven patients received conformal neutron/photon (15 NGy + 18 PhGy) and 49 patients were treated in a dose-escalation study using conformal photons (25 patients/78 Gy and 24 patients/83 Gy minimum dose). The median follow-up for both studies was 20 months (range 6-36 months). There was no significant difference in the rate of chronic gastrointestinal (GI) or gastrourinary (GU) morbidity between the two groups. However, the neutron treated patients had a significantly higher rate of moderate (14%) and severe (12%) hip stiffness. The rates of prostate-specific antigen (PSA) decline and 12-month negative biopsy were comparable. In conclusion, the therapeutic gain of neo-adjuvant hormonal therapy in combination with photon hyperfractionation to 83 Gy appears identical to that seen with the mixed neutron-photon dose of 15 NGy + 18 PhGy. Further efforts at improving the therapeutic ratio of radiotherapy for patients with locally advanced prostate cancer should be undertaken.

Adenocarcinoma↗

Predicting the need for adjuvant systemic therapy in patients receiving postprostatectomy irradiation.

OBJECTIVES: This study was initiated to determine if clinical, pathologic, or biochemical variables available in patients receiving postprostatectomy irradiation could be predictive of treatment outcomes, including the need for subsequent systemic therapy. METHODS: Between January 1992 and January 1995, 50 patients received external beam irradiation for a nonzero or rising postprostatectomy prostate-specific antigen (PSA) level. The median PSA values preoperatively and preradiation were 24 and 2.7 ng/mL, respectively. At the time of treatment, no patient had evidence of disseminated disease. The patients received a combination of axial and noncoplanar irradiation to an average total dose of 65 Gy at 1.8 Gy fractions. Univariate analysis and multivariate logistic regression were performed to identify factors predictive of outcome. RESULTS: Treatment was well tolerated with no grade 3 or higher gastrointestinal or genitourinary complications. A decline in the serum PSA during irradiation occurred in 82% of the patients. During radiation, 13 patients (26%) had a complete response (PSA less than 0.05 ng/mL), 56% had a partial response, and 18% had a rise in their PSA level. With a median follow-up of 16 months, 50% of all patients have an undetectable level of PSA. Twenty-six percent of patients have had evidence of biochemical progression. Seventeen percent of responding patients and 67% of nonresponders have evidence of progression (P= 0.002). On univariate analysis, other significant prognostic factors included clinical stage (P < 0.01), the preradiation PSA level (P < 0.05), and N stage (P < 0.01). On stepwise multivariate logistic analysis, a predictive model was generated from which treatment outcome could be predicted with 80% accuracy (percent correct classification) and an 85% sensitivity. CONCLUSIONS: The outcome of patients with an elevated postprostatectomy PSA level who receive irradiation can be accurately predicted using a combination of clinical stage, preradiation PSA value, Gleason score, and the response to treatment. In this way, patients who do not require additional treatment (that is, hormonal) will avoid the unnecessary cost and toxicity.

Aged↗

Biliopancreatic Diversion with Gastrectomy as Surgical Treatment of Morbid Obesity.

The best procedure for the treatment of morbid obesity has not yet been defined. Biliopancreatic diversion is one of the techniques available, but its results have not been sufficiently documented and the addition of a subtotal gastrectomy to the diversion so as to avoid leaving a blind non-functioning stomach, is still questionable. The purpose of this paper is to report our experience with our first 149 consecutive patients who were treated by biliopancreatic diversion with subtotal gastrectomy for morbid obesity. Operative mortality was 3% and morbidity 12%. The weight loss was marked during the first 6 months and decreased during the following 12 months. The weight stabilized at 2 years and there was subsequently a small increase. In only two out of 48 cases was the weight loss less than 25% of the initial weight at 2 years. The undesirable side-effects were diarrhea in 6%, vomiting in 9% and dyspepsia in 4%. The intervention leads to a malabsorption of carotene, iron, albumin and calcium. Except for carotene the deficiencies were corrected by oral supplement. In two patients, with resistant deficiencies, the diversion was reversed. Eighty-eight percent of the patients are satisfied with this intervention. At 2 years, 70% have reached their weight loss objective without any major side-effects or nutritional deficiencies, but in 14% the outcome of the procedure must be considered unsatisfactory. Biliopancreatic diversion with subtotal gastrectomy is a major operation, but it gives encouraging results so far.

Journal Article↗

Comparison of insulin-like growth factor 1 and insulin effects on prolactin-induced lactogenesis in the rabbit mammary gland in vitro.

In organ culture of pregnant rabbit mammary gland, a low casein synthesis occurs with prolactin (PRL) alone. Insulin markedly potentiates the effect of PRL. Only pharmacological concentrations of insulin (5 micrograms/ml) exert the maximal enhancement, suggesting a possible interaction with the insulin-like growth factor 1 (IGF1) receptor. The presence of IGF1 and insulin binding sites was analyzed and the biological effects of both peptides were compared. Binding of iodinated human IGF1 or porcine insulin to mammary microsomes prepared from mid-pregnant rabbits revealed distinct high affinity binding sites for both peptides (Kd approximately 2 nM). In rabbit mammary explants, we confirmed that only non-physiological concentrations of insulin (greater than or equal to 100 ng/ml) exerted a significant stimulation of the PRL effect. Surprisingly, IGF1 was not found to be more potent than insulin on a molar basis, which did not provide evidence for the exclusive involvement of the IGF1 receptor. Near-physiological concentrations of IGF1 (approximately 100 ng/ml), however, exerted a significant enhancement which suggested a possible action for IGF1 on PRL-induced lactogenesis in vivo.

Animals↗

Characteristics of growth hormone response to the administration of growth hormone-releasing hormone (GRF) in the lamb.

Human growth hormone releasing hormone (GRF 1-44 or GRF 1-29) was administered to lambs at two different physiological stages (suckling: 5-6 week-old and weaned: 14-15 week-old) when growth hormone (GH) secretory patterns were different: suckling lambs exhibited flat basal GH profiles (5-10 ng/ml) while the weaned lambs had frequent spontaneous episodes of GH release (15-65 ng/ml). The iv injection of GRF evoked an immediate release of GH. In each case, plasma GH levels reached a maximum 1-4 min after the injection. The secretory spike was multiphasic and lasted 30-60 min. Administration of GRF (0.1 microgram/kg) in weaned lambs induced GH pulses with an amplitude comparable to that of endogenous peaks. The induction of a GH peak occurred even when a spontaneous peak immediately preceded the GRF injection. Also, spontaneous peaks were observed during the hour following a GRF-induced GH peak. In suckling lambs, GRF injected intravenously as a single bolus in a range of 0.01 to 0.5 microgram/kg (2 to 100 pmoles/kg) stimulated GH release in a dose-dependent manner. Chronic administration of GRF (0.75 nmole GRF 1-44 or GRF 1-29 per kg twice daily for 21 days) in newborn lambs increased significantly (p less than 0.001) the acute response to GRF during the course of the treatment. GH response to GRF 1-44 and GRF 1-29 was the same. These data show that lambs are highly responsive to GRF action during both suckling and weaning and suggest that there is no in vivo desensitization of the pituitary gland after acute or chronic GRF administration.

Animals↗

Secretory profiles and production rate of growth hormone in ruminant lambs.

Secretory profiles and production rates of growth hormone (GH) were determined in 6 ruminant lambs during winter. The mean GH concentrations (3.78 +/- 2.17 ng/ml) calculated were based upon blood sampling obtained every 3 min using a withdrawal pump. Body clearance (0.162 +/- 0.031 1/h/kg) was calculated from bolus intravenous oGH administration. The data were analysed by non-linear regression analysis; a bicompartmental model was selected to describe the data. production rate was 14.6 +/- 7.98 micrograms/kg/24 h. It has been emphasized that the experimental design used gave an accurate estimate of GH production rate.

Animals↗

Characterisation of blood and synovial fluid lymphocytes from patients with rheumatoid arthritis and other joint diseases by monoclonal antibodies (OKT series) and acid alpha-naphthyl esterase staining.

Mononuclear cell preparations from peripheral blood (PBL) and synovial fluid (SFL) of 27 Patients with rheumatoid diseases (15 patients with definite rheumatoid arthritis (RA), 10 with other inflammatory joint diseases (OJD), 1 with sarcoid arthritis (SA) and 1 with traumatic arthritis (TA) were examined for lymphocyte subpopulations determined by monoclonal antibodies of the OKT series and by the dot-like, acid alpha-naphthyl esterase staining (ANAE) activity. In patients with classic, active RA, blood T cells carrying the OKT8+ (suppressor/killer) phenotype were significantly reduced leading to an elevated OKT4/OKT8 ratio of 4.1 +/- 0.4 compared with 2.1 +/- 0.1 in healthy controls. In 10 patients with OJD this diminution of OKT8+ cells in peripheral blood was less pronounced or absent. As regards SFL subpopulations, patients with RA and OJD exhibited a similar distribution pattern with an elevation of OKT8+, Ia+ and ANAE negative cells and a similar OKT4/OKT8 ratio of 1.5 +/- 0.3 and 1.6 +/- 0.4, respectively. Similar results were also obtained in the only patient with TA, whereas the patient with SA and one RA patient with relapse after surgical synovectomy exhibited high OKT4/OKT8 ratios, both in synovial fluid and peripheral blood. Neither the OKT markers nor the dot-like ANAE staining pattern were significantly correlated to parameters of systemic or local disease activity as estimated by erythrocyte sedimentation rate and a local disease activity index.

Adolescent↗

[Functional respiratory disorders in children with left-to-right shunt].

The respiratory function of 19 children aged from 2 months to 9 years old with a cardiac lesion giving a left-to-right shunt was studied and analysed with respect to the hemodynamic disturbance. Respiratory function tests (RFTs) included measurement of functional residual capacity (FRC), the partial pressure in oxygen (Pa 02) on arterialised blood taken from the ear lobe, dynamic pulmonary compliance (CI dyn.) and total pulmonary resistance (RI). FRC and RI were not significantly modified. On the other hand, CI. dyn. was low (-31.2 +/- 22.9%, p less than 0,001) as were the CI. dyn. CFR ratio (-25.5 +/- 20.9%, p less than 0.001) and the Pa 02 (-7.6 +/- 12.7% p less than 0.02). There was a significant correlation between the reduction of CI. dyn. and mean pulmonary arterial pressure (PAP) and the increase in the pulmonary blood flow. In addition, a significant correlation was also found between the reduction in Pa 02 and the PAP and increase in pulmonary blood flow. These results show that cardiac lesions with left-to-right shunts give rise to diffuse changes in respiratory function and are discussed in the light of the abnormalities in pulmonary development previously described in pulmonary biopsy of patients with left-to-right shunts. The value of RFTs in the surveillance of patients with left-to-right shunts is underlined.

Airway Resistance↗

Erythropoietin receptor expression in biopsy specimens from patients with uterine cervix squamous cell carcinoma.

Hypoxia, an important mechanism of radioresistance, is a strong stimulus for erythropoietin (EPO) production. The stimulatory effects of EPO are mediated through the activation of its receptors, EPO receptors (EPORs). The objective of this study is to determine whether EPORs are expressed in biopsy specimens of patients with squamous cell carcinoma of the cervix. Eighteen biopsy specimens were studied after obtaining Institutional Review Board-approved consent. Standard immunohistochemistry techniques were utilized. Expression of EPORs was present in 16 out of 18 (88.9%) specimens. The intensity (qualitative) and the frequency (semiquantitative) of EPORs expression showed a statistically significant correlation (P= 0.00379). Statistical analysis was performed to determine whether EPORs expression is related to other parameters such as age, FIGO stage, histologic grade, and hemoglobin levels. Only age showed a statistically significant correlation with EPORs frequency of expression (P= 0.00878). Currently, work is in progress in our laboratory to study the radiobiologic effects of EPO on the radiation response of cultured cancer cell lines in vitro.

Adult↗