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Biomedical subjects

A Gerard

Publications and source records attributed to A Gerard.

At least 73 records · Page 4Linked to original sources

Pulsatile release of gonadotropin-releasing hormone (GnRH) from the rat hypothalamus in vitro: calcium and glucose dependency and inhibition by superactive GnRH analogs.

We have shown previously that the rat hypothalamus retains in vitro its capacity of generating pulsatile release of GnRH. The present study evaluated if pulsatile release of GnRH in vitro was influenced by metabolic conditions (calcium and glucose availability) and the possible self-regulatory role of GnRH in its pulsatile secretion. In the presence of a calcium-chelating agent (EGTA, 20 mM) or a calcium-channel blocker (D-600, 0.1 mM), the release of GnRH induced by a depolarization (veratridine, 50 microM) was markedly and reversibly decreased. In addition, frequency and amplitude of GnRH secretory pulses were significantly reduced (P less than 0.05). When glucose use was inhibited using 2-deoxyglucose (5.6 mM) the release of GnRH induced by veratridine and the frequency of GnRH pulses were also blunted (P less than 0.05). Superactive agonists of GnRH (Buserelin and D-TRP6-PRO9-N-ET, 10 nM) caused a prompt decrease of GnRH release in basal conditions and in the presence of veratridine. A significant inhibition (P less than 0.05) was observed using buserelin concentrations greater than 0.01 nM, whereas two GnRH analogs without biopotency (Leu8-GnRH, Des-gly10-N picolylamide GnRH, 100 nM) did not affect GnRH release. The two agonists of GnRH reduced by 43% to 66% (P less than 0.05) the occurrence of significant GnRH pulses. We conclude that, in vitro, the hypothalamic neuronal circuitry resulting in GnRH pulsatile secretion is dependent on calcium and glucose availability and is sensitive to an ultrashort-loop inhibitory feedback mechanism.

Animals↗

Purification of androgen-binding protein from rat testis using high-performance liquid chromatography and physicochemical properties of the iodinated molecule.

The androgen-binding protein (ABP) has been purified 87,500-fold from rat testis using 4 steps of HPLC, with a yield of 14%. The molecule was 99% pure with a specific activity estimated to 16,600 pmol/mg protein. The iodinated molecule was eluted in 2 peaks in Sephacryl S300 gel filtration with a molecular mass estimated to be 92,600 +/- 3300 and 50,300 +/- 4000 Da. The column isoelectrofocusing of 125I-ABP demonstrated 3 isoproteins isoelectric at pH 4.7, 4.9 and 5.3 and the sedimentation coefficient was estimated to be 4.7 S in sucrose gradient ultracentrifugation. The 125I-ABP had similar physiochemical properties to the non-labelled ABP of epididymis.

Androgen-Binding Protein↗

In-utero gentamicin-induced nephrotoxicity in rats.

Aminosides lead to a well-known nephrotoxicity. The possibility of the developing kidney being altered in utero after the pregnant mother's administration has been investigated. We gave gentamicin (75 mg/kg/day) to pregnant rats during periods of organogenesis (days 7-11) and the beginning of glomeruli differentiation (days 14-18). A group of nonpregnant females was also treated for the same period and at the same time each day. Gentamicin-treated mothers presented only minor modifications of the blood biology with no acute renal failure when treated nonpregnant females have a hypercreatininemia. The deep cortical area, containing the fully formed nephrons of neonates, presented less glomeruli that were differentiated in the gentamicin group than in the control group. Moreover with both light and electron microscopy, glomeruli and proximal tubules showed evidences of nephrotoxicity in the juxtamedullary cortex. This finding of an in utero aminoside nephrotoxicity demonstrates the possible toxicity of gentamicin on fetus kidneys when given during the pregnancy.

Abnormalities, Drug-Induced↗

Interim analysis of a phase III study on preoperative radiation therapy in resectable rectal carcinoma. Trial of the Gastrointestinal Tract Cancer Cooperative Group of the European Organization for Research on Treatment of Cancer (EORTC).

To improve surgical results of potentially operable rectal cancer (T2, T3, T4, Mo), the European Organization for Research on Treatment of Cancer (EORTC) conducted a two-arm randomized clinical trial to evaluate the effect of administering radiotherapy before radical surgery. Four hundred ten patients were allocated to be treated either by surgery alone or by 34.5 Gy of radiotherapy (in 19 days overall) followed by surgery. The tolerance of the adjuvant radiation therapy was fairly good. The 5-year survival rate was 65% overall and showed no difference between both therapeutic regimens. Similarly, the metastases-free rate was the same in both groups. In contrast, the preoperative radiation therapy showed a marked effect on local control of the disease, the comparison of the time to local recurrence being highly significant between the two treatment groups (P = 0.001). The proportion of patients free of local recurrence at 5 years was 85% in the combined treatment versus 65% in the group of patients treated by surgery alone.

Adult↗

Does the in-utero exposure to furosemide delay the renal maturation?

Two groups of pregnant Wistar rats were constituted, one treated with Furosemide IP and one with saline. The drug was given on days 7-11 and 14-18 of the pregnancy. Litters from the two groups were not different in number of pups, body weight, and/or kidney weight, but exposed in-utero neonates, studied shortly after birth, exhibited a significant lower number of differentiated glomeruli than those of the control group. As well as the difficulty of explaining this phenomenon, this condition raises the problem of a possible compensation by the postnatal nephrogenesis, which is important in the rat, and leads to the question of what will be the total amount of nephrons for the adult life in species with or without complete in utero nephrogenesis.

Animals↗

Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-fluorouracil, followed by radical surgery. Trial of the European Organization on Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.

To improve surgical results of potentially operable rectal cancer, the European Organization on Research and Treatment of Cancer conducted a two-arm randomized clinical trial to compare the efficiency of preoperative administration of radiotherapy, with or without 5-fluorouracil before radical surgery. Two hundred forty-seven eligible patients were admitted from November 1972 through April 1976. The overall survival observed in the group treated with preoperative radiotherapy appears to be better than in the group of patients where preoperative combined modality was administered. Five-year survival is 59% versus 46% with a marginal statistical significance of P = 0.06. Although the combined modality arm had a higher incidence of side effects and postoperative deaths, it had a greater effect than the radiotherapy-alone arm in controlling the disease process, mainly distant metastases to the liver with a result bordering on statistical significance (P = 0.07). The incidence of nonmalignant and intercurrent deaths were higher in the combined modality group, whereas deaths due to malignancy were higher in the radiotherapy-alone group. Observing more stringent selection in disease and patients' criteria, side effects and intercurrent deaths can be effectively reduced with further improvement in adjuvant therapy results.

Adenocarcinoma↗

[Morphologic aspects of intravascular disseminated coagulation. Apropos of 100 cases].

The authors report a morphological study of one hundred cases of disseminated intravascular coagulation (D.I.C.) of various origins. In each case laboratory findings demonstrated an authentic consumption coagulopathy. In all cases organ biopsies were performed either in vitro (rarely), or mainly immediately after death or at autopsy. Optic microscopy was performed for all of them (3 stains were chosen: hemalum eosin saffron, Mallory's phosphotungstic acid hematoxylin stain, P.A.S.). For a smaller number of cases ultrastructural microscopy and immunofluorescence were performed. As far as microscopic findings are concerned, the authors insist particularly upon intravascular microthrombi (fibrinous type and hyalin type). Haemorrhages and particularly necrosis, because of multiple origin, are not detailed. The repartition of these microthrombi is particularly detailed (in connection with the different organs, etiologies, clinical and/or biological findings, treatments). A review of literature is reported.

Adolescent↗