Search PubMed⌕ Search

Biomedical subjects

G Schaison

Publications and source records attributed to G Schaison.

At least 199 records · Page 11Linked to original sources

The hormonal control of adenylate cyclase in rabbit myometrium: in vitro inhibition by adenosine and lack of effect of progesterone.

The mechanism by which progesterone modifies uterine smooth muscle cell contraction is still unknown. We investigated the biochemical basis of progesterone effects on myometrium of estradiol-primed rabbits. Progesterone did not affect adenylate cyclase basal activity and displayed no interaction with stimulators of myometrium adenylate cyclase (NaF, guanylyl nucleotides, beta-adrenoreceptor agonists, prostaglandins, forskolin) or with adenosine. On the other hand, adenosine inhibited myometrial adenylate cyclase, which correlates with its contracting properties in vivo; this inhibition is mediated through interaction at 'P sites'. We conclude that whilst adenosine inhibits myometrial adenylate cyclase by acting at 'P sites', progesterone does not interact directly with adenylate cyclase to regulate myometrial contractility.

Adenosine↗

Absence of a direct inhibitory effect of the gonadotropin-releasing hormone (GnRH) agonist D-Ser (TBU)6, des-Gly-NH2(10) GnRH ethylamide (Buserelin) on testicular steroidogenesis in men.

The antigonadal effects of GnRH agonists (GnRH-A) are mediated both through pituitary and testicular inhibitory mechanisms in the rat. To investigate these effects in men, we studied patients having no gonadotropin secretion and compared their testicular response to hCG in the absence or in the presence of GnRH-A. Thirteen patients with acquired pituitary hypogonadotropism had plasma testosterone levels below 1.5 ng/ml and no gonadotropin responses to acute GnRH administration (100 micrograms iv). Testicular responsiveness was evaluated using a single im injection of hCG (5000 IU im). Plasma levels of testosterone, dihydrotestosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), and progesterone were determined before and 4, 12, 24, 48, and 72 h after hCG stimulation. The same protocol was also used in the same patients on day 4 of a 6-day course of treatment with the GnRH-A, D-Ser-(TBU)6, des-Gly NH2 GnRH ethylamide (Buserelin) (3 sc injections of 250 micrograms/day). During the first 4 days of GnRH-A administration, plasma LH, FSH, and testosterone levels were measured daily in order to establish the completeness of the gonadotropin deficiency. Before treatment with hCG, plasma testosterone levels were 0.56 +/- 0.15 and 0.96 +/- 0.22 ng/ml (mean +/- SE) in the absence of GnRH-A and during GnRH-A administration, respectively. The administration of hCG elicited a significant increase in plasma testosterone in both situations; integrated testosterone concentrations were 123.7 +/- 24.9 and 155.5 +/- 27.9 ng/ml . 72 h (P greater than 0.1) in the absence of GnRH-A and during GnRH-A administration, respectively. Likewise the ratios of 17-OHP to progesterone, androstenedione to 17-OHP, and dihydrotestosterone to testosterone after hCG injection were similar in the presence or absence of GnRH-A. Since short term administration of buserelin did not inhibit hCG-induced testosterone secretion in patients with gonadotropin deficiency, we suggest that Buserelin does not grossly modify the function of testicular steroidogenesis enzymes. The antigonadal effects of GnRH-A in man appear to be mediated exclusively through the pituitary.

Buserelin↗

Effects of sodium ipodate and propylthiouracil in athyreotic human subjects, role of triiodothyronine and pituitary thyroxine monodeiodination in thyrotrophin regulation.

To investigate the respective role of triiodothyronine (T3) and thyroxine (T4) in the regulation of TSH secretion, we studied the action of sodium ipodate and propylthiouracil (PTU) in 11 athyreotic patients. The LT4 replacement dose was adjusted to obtain, in each patient, a normal basal TSH level and a normal TSH response to TRH. In the 5 ipodate-treated patients (single 6 g oral dose), the mean serum T3 level fell by 64% below the baseline value and serum rT3 rose 180% above the baseline. The free T4 index (FT4I) did not change whereas the mean serum TSH concentration increased 280% above baseline values. In the 6 PTU-treated patients (250 mg orally every 6 h for 10 days), serum T3 levels fell 33%, serum rT3 increased up to 82% and the FT4I did not change. The mean serum TSH concentration increased 68% above the baseline value. Thus, the mean percentage increase in serum TSH was less in PTU- than in ipodate-treated patients (68% vs 280%). Statistical analysis of the correlation between the serum T3 decrease (delta T3) and the serum TSH (delta TSH) increase demonstrated that for the same T3 diminution, the ipodate-treated group displayed higher increase of TSH than the PTU-treated patients. In the rat, PTU interferes with the 5'-deiodination of T4 in the liver and kidney but not in the pituitary, while ipodate appears to have the same effect in all tissues. If this holds true for human subjects, our data strongly suggest that circulating T4 (through its intrapituitary conversion to T3) shares with serum T3 the capacity to regulate TSH secretion in man.

Adult↗

Effect of carbimazole treatment on specific and non-specific immunological parameters in patients with Graves' disease.

Twenty-two patients with newly diagnosed Graves' disease (GD) were treated with carbimazole (CBZ) for 6 months. Thyroid stimulating immunoglobulins (TSI) and T cell subsets were studied prior to treatment and after 3 and 6 months of therapy. TSI were measured on human thyroid epithelial cell monolayers by the cAMP production after the addition of highly purified GD IgG. Before treatment, serum IgG from 20 out of the 22 patients (91%) stimulated cAMP production significantly compared to normal IgG. The mean index of cAMP production (GD IgG relative to normal IgG) was 2.15. After 3 months of CBZ treatment, a non-significant decrease of the mean cAMP production index was observed, whereas it was significantly decreased at the end of the 6 month course of therapy. Before treatment, total T cells (OKT3+), helper/inducer T cells (OKT4+) and suppressor/cytotoxic T cells (OKT8+) were all significantly decreased compared with controls. After 3 or 6 months of CBZ therapy, both total T cells and helper/inducer T cells returned to a normal level, while cytotoxic/suppressor T cells remained at the same low level. Taken together, these data indicate that treatment with CBZ leads to an early increase of helper/inducer T cells followed 3 months later by a decrease of the TSI level with no change in decreased suppressor/cytotoxic T cells. The disappearance of TSI following the increased helper/inducer T cell level suggests that an anti-idiotypic reaction may have occurred, and the persistent decrease of the suppressor/cytotoxic T subset that CBZ therapy does not act upon the underlying autoimmune disease.

Adult↗

[Acute myelomonocytic leukemias in children with xanthomas. Xantholeukemia].

"Xantholeukemia" is a rare disease which combines a juvenile chronic granulocytic leukemia with skin xanthomas and normal serum cholesterol level. The prognosis is variable, usually lethal, sometimes chronic with possible spontaneous cure. We collected 11 patients aged 3 months to 3 years and half at diagnosis. Nine died, 7 with a terminal "blastic" marrow. Blastic crisis was sometimes present at the onset, sometimes started later, between 9 months and 9 years after the onset. One child is still alive but in blastic crisis. One young girl is hematologically normal 13 years after the onset. At the onset, she had no bad prognostic signs. And she received no treatment. Five children had "café au lait" spots, 4 of them had familial history of neurofibromatosis. This frequent association confirms a genetic predisposition. Eight patients had one or several examinations of bone marrow and blood cytogenetics. Only one had an evident clonal abnormality: monosomy 7 (45 XY, -7) in all bone marrow cells. This monosomy 7 was discovered 21 months after the onset and 3 months before the blastic crisis. No chemotherapy had been used before this karyotype. Chemotherapeutic agents were essentially corticosteroids, 6 mercaptopurine and cytarabine. They gave an imperfect result and did not influence the outcome; therefore an aggressive treatment or a bone marrow transplantation should be discussed.

Acute Disease↗

[Acute promyelocytic leukemia: retrospective study of 119 patients treated with daunorubicin].

A retrospective study of 119 patients with acute promyelocytic leukemia (APL) treated with similar DNR containing regimens in reported. Antecedent of radiation exposure or cancer was found in 10 patients. At presentation hyperleucocytosis was rare (13/119 greater than 30 000/microliter); variant form was identified in 5 cases. Organomegaly was uncommon and severe metabolic abnormality was never noted at presentation. DIC was observed in 75% of pts; t (15;17) was confirmed in 25/30 pts. Complete remission (CR) rates have increased from 43% to 76% on account of improvement of supportive therapy with adequate DIC management. Addition of ARA C did not improve CR rates (72%). Surprisingly duration of CR seems related to maintenance therapy as 11/26 pts receiving 6 MP-MTX maintenance regimen were long-term survivors as compared to 1/34 comparable pts receiving cyclic monthly courses of chemotherapy.

Adolescent↗

[Thrombocythemia with Philadelphia chromosome. Secondary appearance of chronic myeloid leukemia].

The finding of a Philadelphia chromosome in a case of apparently primary thrombocythaemia should change the diagnosis for that of chronic myeloid leukaemia. This theoretical view is supported by the case reported here, where a Philadelphia-chromosome was detected in the bone marrow cells of a patient with severe thrombocythaemia; a typical myeloid leukaemia developed 21 months after the onset of the disease; survival was of short duration.

Adult↗

Philadelphia chromosome-positive chronic myelocytic leukemia in children. Survival and prognostic factors.

The survival and the prognostic significance of the diagnostic characteristics of 39 children with Philadelphia chromosome-positive chronic myelocytic leukemia (Ph1-positive CML), seen between 1963-1976 at the Hôpital Saint-Louis of Paris, have been analyzed. The disease predominated in children older than age 4 years (95%), with girls being more affected than boys (24 versus 15). The clinical and hematological picture at presentation was similar to that observed in adults with Ph1-positive CML. Most children of this series were treated with busulfan which, as in adults, led to reduction of leucocytosis and organomegaly but did not prevent the occurrence of blastic crisis. Well-documented blastic crisis was observed in 78% of cases. Of 39 children, 12 were still alive, all in the chronic phase. Twenty-seven have died, 21 of them after blastic crisis, 4-156 months after diagnosis (median survival, 53 months). The effect of each diagnostic characteristic on survival was evaluated using the log-rank test. Of the 14 characteristics studied, only the degree of blood and marrow blastosis was associated with a shorter survival. Age, sex, bleeding, lymphadenopathy, hepatomegaly, degree of splenomegaly, hemoglobin level, total leucocyte, immature granulocyte (promyelocytes + myelocytes + metamyelocytes), eosinophil, basophil, and platelet counts in the peripheral blood were of no prognostic significance. The failure to attain a level of statistical significance for some characteristics found to be of prognostic value for adults, could be due to the small sample size and/or to the disease homogeneity. The results of this study, however, stress the importance of the initial blastic infiltration in determining the duration of survival, which is ultimately determined by the occurrence of terminal acute leukemia. In conclusion, this study shows that the Ph1-positive CML of childhood exhibits the same course, incidence of blastic crisis, and survival as the disease of adults. It also indicates that treatment with moderate chemotherapy, such as busulfan, has no effect on the duration of survival. Therefore, new therapeutic approaches are urgently needed for the treatment of this disorder in children.

Adolescent↗

Leydig-cell function in children after direct testicular irradiation for acute lymphoblastic leukemia.

To assess the effect of testicular irradiation on testicular endocrine function, we studied 12 boys with acute lymphoblastic leukemia who had been treated with direct testicular irradiation 10 months to 8 1/2 years earlier. Insufficient Leydig-cell function, manifested by a low response of plasma testosterone to chorionic gonadotropin or an increased basal level of plasma luteinizing hormone (or both), was observed in 10 patients, 7 of whom were pubertal. Two of these patients had a compensated testicular endocrine insufficiency with only high plasma concentrations of luteinizing hormone. Testosterone secretion was severely impaired in three pubertal boys studied more than four years after testicular irradiation. A diminished testicular volume indicating tubular atrophy was found in all pubertal patients, including three who had not received cyclophosphamide or cytarabine. These data indicate that testosterone insufficiency is a frequent complication of testicular irradiation, although some patients continue to have Leydig-cell activity for several years after therapy.

Adolescent↗

[Fanconi's anemia. Incidence of its development into leukemia].

Fanconi's anaemia (FA) is a hereditary disease transmitted in a recessive manner, characterized by congenital malformations and bone marrow aplasia. A high rate of chromosome breakage is observed in mitoses of cultured blood cells, but the caryotypes are normal. Forty-four patients (27 boys and 17 girls) were followed in the same department between 1962 and 1976. Most were treated with androgens, sometimes combined with corticosteroids. Nine patients died of acute granuloblastic leukaemia, with more than 25% bone marrow blasts; in three of these, cytogenetic examination showed clonal anomalies. Five patients were in preleukaemic state with non-blastic bone marrow; 4 showed clonal anomalies and 2 of these died of aplasia; the 5th patient had gross liver and spleen enlargement and died of haemorrhage. Among the 30 remaining patients 12 are still alive and 18 died of cerebral haemorrhage (7), hepatic failure (3), cardiac failure (1), pancreatitis (1), septicaemia (2) or graft-versus-host reaction after bone marrow transplantation. One patient transplanted 4 years ago has complete chimerism and is still alive without treatment. The incidence of leukaemic or preleukaemic state in this series was 30%, while no case of leukaemia was observed in 200 patients with acquired aplastic anaemia. Neither parents norsibship had leukaemia. Androgen treatment apparently did not increase the risk of leukaemia which developed within 1 to 13 years (mean = 5 years) of the diagnosis, was preceded by a 2 1/2 year long preleukaemic state with clonal chromosomal anamolies and invariably was of the granulocytic type. None of the patients developed cancer. The median survival in this series was 4 1/2 years.

Acute Disease↗

[Monitoring anticancerous and antileukemic chemotherapy in children].

Chemotherapy is essential for the treatment of malignant diseases in childhood. Monitoring a child on chemotherapy includes: 1) looking for evidences of relapse or metastases; 2) if necessary, adjusting doses according to blood counts; 3) preventing and treating intercurrent infections, which are mostly viral, once the initial regimen is completed; 4) diagnosing and, if possible, treating, harmful side-effects, which cannot always be precluded; 5) helping both patient and family to live a normal life; in this respect, normal school attendance is of particular significance.

Antineoplastic Agents↗

Treatment of hyperandrogenic states in women.

Hyperandrogenic states have to be treated according to their etiology. But, idiopathic hirsutism represents the majority of observed cases. Its pathophysiology is still under discussion. The ovary and/or adrenal origin has led to various treatments with corticoids or combined estrogen-progestogen preparations. However, practical problems are different. After ruling out a tumoral process or mild congenital adrenal hyperplasia, a rational and efficient treatment must be proposed. It has now become possible with the use of both antiandrogen and antigonadotropin drugs. Cyproterone acetate is the best therapeutic agent because of its antiandrogen, antigonadotropin and progestogen properties. Because of its antiestrogen effects, cyproterone acetate must be used in combination with estrogens as a substitutive therapy to permit regular bleeding.

Androgens↗

[Cranio-facial and dental manifestations of erythrocyte abnormalities].

Various types of erythrocyte lesions are observed: hemoglobin anomalies, enzyme disorders, membrane anomalies. This leads to a reduction in the duration of life of the erythrocytes or to abnormal erythropoiesis with, in both cases, reactive development of hematopoietic tissue. This extension of the medullary field in bones results in alterations that are initially visible on radiography, and then, in the severe forms, in the development of mainly craniofacial and dental dysmorphia with, in some cases, additional secondary enamel and dentine anomalies of the hemolytic origin. These anomalies were present to varying degrees in a series of patients in whom cranial radiographies were performed. In two cases there was a fortuitous association of dental anomalies of the melanodontia and opalescent dentine types. These patients may raise particular problems during dental care and treatment: risk of infection, respect of drug contraindications, latent cardiac insufficiency.

Adult↗