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Biomedical subjects

G Schaison

Publications and source records attributed to G Schaison.

At least 19 recordsLinked to original sources

Diagnosis of malignancy in thyroid nodules by factor analysis of spectral and dynamic structures: a simultaneous dual-isotope dynamic study with thallium-201 and iodine-131.

The aim of this study was to identify malignant thyroid nodules using iodine-123 and thallium-201 simultaneous dynamic acquisition. The image sequences acquired were processed by factor analysis of spectral and dynamic structures (FASDS). Some 49 patients were investigated, and their diagnoses were confirmed by histological examination. Data processing enables the estimation of the spectra of the two isotopes and the evaluation of the kinetics and spatial structures related to each tracer. The superimposition of thallium and iodide sum images allowed us to delineate the nodule accurately. Two groups were defined: 21 patients who had 201Tl uptake in the nodule, and 28 who had none. In the first group, 5 nodules were carcinomas, whereas all nodules in the second group were benign. The results of the 201Tl dynamic study improved the diagnosis of carcinoma as the number of false-positive cases decreased. FASDS succeeds in extracting spectral and kinetic information, proving its usefulness in clinical diagnosis.

Adenoma

Cortisol and testosterone: inhibitory agents of the mineralocorticoid pathway. Is there a physiopathological meaning in adrenal tumors?

The authors incubated adrenal mitochondria to study the in vitro action of cortisol and testosterone on the transformation of corticosterone and 18-hydroxycorticosterone into aldosterone. The results show that cortisol at concentrations of 5 x 10(-6) and 10(-4) M inhibit the conversion of corticosterone into aldosterone by 23.6 to 90%; testosterone 5 x 10(-5) and 10(-4) M inhibit the reaction by 78.4 and 87.2%, respectively. The inhibition of the conversion of 18-hydroxycorticosterone into aldosterone is 12.5 to 91% by cortisol with concentrations ranging from 5 x 10(-7) to 5 x 10(-5) M and testosterone 5 x 10(-5) and 10(-4) M inhibits the reaction by 87.3 and 91%, respectively. Aldosterone (10(-8) and 10(-6) M) does not inhibit aldosterone biosynthesis from corticosterone or 18-hydroxycorticosterone. It thus appears that cortisol and testosterone have an effect on the aldosterone biosynthesis pathways in mitochondria. This action may be located at the binding site of the cytochrome P450 11 beta, which catalyzes all hydroxylation steps in the mineralocorticoid biosynthesis pathway. Because cortisol and testosterone may interfere with aldosterone biosynthesis, and since functional zonation is expected in adrenal carcinomas, the presence of these steroids in substantial amounts could explain the very low plasma aldosterone level usually observed, in adrenal carcinomas studied in our laboratory.

Adrenal Gland Neoplasms

The incidence of late-onset congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency among hirsute women.

OBJECTIVE: The present study was designed to determine the incidence of 3 beta-hydroxysteroid dehydrogenase deficiency (3 beta-HSD) in adult women with hyperandrogenism. DESIGN AND PATIENTS: In 78 hirsute patients and 30 normal women in the same age range, an ACTH stimulation test was performed on day 5 of the cycle by administration of a single bolus of 0.25 mg ACTH-(1-24) at 0800 h. MEASUREMENTS: The following steroids were measured before, 30 and 60 minutes after ACTH injection: delta 5-pregnenolone (delta 5-P), 17-hydroxy-delta 5-pregnenolone (17-OH delta 5-P), dehydroepiandrosterone (DHEA), delta 5-androstenediol, progesterone (P), 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T) and cortisol. RESULTS: Maximum ACTH-stimulated values of delta 5-steroids were in excess of the 90% confidence limits of the control group in 19 hirsute women. Ten patients had an isolated increase in delta 5-P, 17-OH delta 5-P, DHEA or delta 5-androstenediol. Nine patients had an increase in two delta 5 steroids and none had increased values of three or four delta 5 steroids. The ratios of 17-OH delta 5-P to 17-OHP, DHEA to A, delta 5-P to P and delta 5-androstenediol to T were increased in 5, 1, 1 and 1 patients respectively. No patient had elevated values of more than one ratio. CONCLUSIONS: Using stringent diagnostic criteria, partial 3 beta-HSD deficiency was excluded in all 78 patients and therefore appears to be a rare disorder.

3-Hydroxysteroid Dehydrogenases

Progesterone stimulates luteinizing hormone secretion by acting directly on the pituitary.

To determine if progesterone (P) does affect gonadotropin secretion by acting directly on the pituitary, six women with hypothalamic gonadotropin deficiency were studied. They were treated with 17 beta-estradiol (E2; 2 mg/day, orally) to induce P receptors and maintain constant plasma E2 levels during two 15-day periods separated by 1 month. GnRH was administered iv at a dose of 10 microgram/pulse every 90 min during the last 5 days of E2 treatment. Either P (400 mg/day) or a placebo was administered intravaginally in a cross-over randomized design during the 5 days of pulsatile GnRH therapy. A baseline study of pulsatile LH secretion was performed, with sampling performed every 10 min for 8 h. The sampling was then repeated on day 15 of each study period at the end of pulsatile GnRH administration. Plasma levels of E2 and P were measured every day during the 5 days of either GnRH and P or GnRH and placebo treatment. In the six patients, the observed apulsatile pattern of LH during the baseline study confirmed the diagnosis of complete gonadotropin deficiency. Plasma E2 levels were not significantly different at the time of each pulse analysis (288 +/- 61 vs. 252 +/- 77 pmol/L). The plasma P level achieved with the vaginal pessaries was 22 +/- 5 nmol/L. P treatment resulted in all cases in a significant increase in the mean plasma LH level (5.2 +/- 0.9 vs. 3.6 +/- 0.7 IU/L after GnRH plus placebo; P less than 0.001). Furthermore, LH pulse amplitude was significantly increased by P compared to placebo (3.1 +/- 0.3 vs. 1.4 +/- 0.1 IU/L, respectively; P less than 0.01). Mean plasma FSH levels were significantly increased by GnRH regardless of whether P or placebo was present. In conclusion, these data indicate that a short exposure to physiological levels of P in the range of early luteal phase levels has a stimulatory effect on LH secretion by acting directly at the pituitary level.

Activity Cycles

Differing responses of plasma bioactive and immunoreactive follicle-stimulating hormone and luteinizing hormone to gonadotropin-releasing hormone antagonist and agonist treatments in postmenopausal women.

Plasma bioactive (B) and immunoreactive (I) FSH and LH were measured every 10 min for 8 h in the same postmenopausal women in a three-phase study: 1) during normal pulsatile gonadotropin secretion (basal study; n = 8), 2) 8 h after a single injection of a GnRH antagonist (5 mg Nal-Glu, sc; n = 5), and 3) 21 days after a GnRH agonist injection (D-Trp6, 3.75 mg depot preparation, im; n = 7). I-FSH and I-LH were measured by monoclonal antibody immunoradiometric assays. B-FSH and B-LH were measured in selected samples with the immature rat granulosa cell and mouse interstitial cell assays, respectively. Significant pulsatility of B- and I-FSH and LH was demonstrated in the basal samples, but only the B/I ratio of LH was slightly elevated within the secretion peaks. After GnRH antagonist treatment, I-FSH decreased from a mean pretreatment level of 55.7 +/- 7.8 IU/L by 26% (P less than 0.001), and B-FSH from 313.8 +/- 61.9 IU/L by 44% (P less than 0.01). The B/I ratio decreased from 6.4 +/- 1.7 to 4.5 +/- 1.0 (P less than 0.05). After agonist treatment, the I- and B-FSH levels decreased by 92% and 83% (P less than 0.0001), respectively, but the B/I ratio increased to 17.3 +/- 4.7 (P less than 0.05). The concentrations of I- and B-LH decreased by 75% and 80%, respectively (P less than 0.001), after antagonist treatment. After agonist treatment, I-LH decreased by 92%, and B-LH by 93% (P less than 0.0001). No changes in the B/I ratios of LH were found after either treatment. In conclusion, no changes were found in the quality of circulating LH during the treatments, whereas the antagonist treatment decreased and the agonist treatment increased the B/I ratio of FSH. These findings provide further evidence that the qualitative responses of FSH and LH to treatment with the same GnRH analog are different, and that the suppressive mechanisms of GnRH antagonist and agonist action on gonadotropin secretion are different.

Adult

Nonrandom t(1;22)(p12-p13;q13) in acute megakaryocytic malignant proliferation.

A case of acute megakaryocytic leukemia (M7) and one of acute myeloid hemopathy affecting megakaryocytic and erythrocytic cell lineages in infants are reported. Both patients had t(1;22)(p12-p13;q13). This translocation was previously observed in a congenital M7 leukemia. These studies suggest that t(1;22) translocation can be nonrandom in M7.

Chromosome Banding

Quantitative blood cultures for diagnosis and management of catheter-related sepsis in pediatric hematology and oncology patients.

Paired quantitative blood cultures collected simultaneously via catheter and peripheral vein in Isolator 1.5 ml tubes, were performed in 50 febrile hematology children. Samples were taken to diagnose catheter-related sepsis (CRS) without catheter removal and to monitor the therapeutic efficiency of antimicrobials administered through the infected device by infusion and/or by the antibiotic lock technique (ALT). In 7 children (14%) the colony counts from catheter blood samples were 30-fold higher than the colony counts from peripheral samples, suggesting CRS; in 7 other patients (14%), identical colony counts in both samples suggested sepsis was not catheter-related. One patient (2%) had septicemia caused by E. coli found in the urinary tract; only the peripheral blood cultures were positive. In 6 patients (12%), the Isolator system was not effective for diagnosing bacteremia or CRS; in 29 patients (58%) the febrile episode was not microbiologically documented. All episodes of CRS were cured whatever the treatment was: infusion or ALT.

Anti-Bacterial Agents

Steroid control of gonadotropin secretion.

Current knowledge about the mechanism and site of action of estradiol (E2) and progesterone (P) during the menstrual cycle and the physiological role of androgens is reviewed. In normal women, the positive feedback effect of E2 at the pituitary level is the principal event of the follicular phase inducing the LH surge. P, by its negative feedback at the hypothalamic level and by its positive feedback at the pituitary level regulates GnRH and LH secretion during the luteal phase. Androgens do not directly play a role in gonadotropin regulation.

Androgens

Effects of gonadotrophin releasing hormone antagonist and agonist on the pulsatile release of gonadotrophins and alpha-subunit in postmenopausal women.

OBJECTIVE: The present study was designed to further assess the mechanism of action of GnRH and GnRH analogues. DESIGN AND PATIENTS: Both the Nal-Glu GnRH antagonist and the D-Trp6 GnRH agonist were administered sequentially to nine normal, post-menopausal women. MEASUREMENTS: A baseline study of pulsatile LH, FSH and free alpha-subunit secretion was performed, with sampling every 10 min for 8 h, and then repeated 8 h after a single subcutaneous injection of Nal-Glu GnRH antagonist (5 mg). Sampling was repeated 21 days after the intramuscular injection of a depot preparation of D-Trp6 GnRH (3.75 mg) in the same women. RESULTS: The baseline sampling period showed synchronous pulses of LH and free alpha-subunit. The antagonist Nal-Glu decreased plasma LH (71%) and free alpha-subunit (43%). However, with the single dose of 5 mg, pulsatile LH and free alpha-subunit release were not completely suppressed and remained temporally correlated. The GnRH agonist had a potent inhibitory action on plasma immunoreactive LH (IRMA) (93%). In contrast, it increased the mean plasma levels of free alpha-subunit from 1.66 +/- 0.01 to 5.06 +/- 0.02 micrograms/l (205%). The pulsatile secretory patterns of both LH and free alpha-subunit were abolished by the agonist. Immunoreactive FSH levels were decreased by the antagonist (24%) and suppressed by the agonist (93%). CONCLUSIONS: The pulsatile study confirms the different mechanism of action of GnRH analogues. Following antagonist administration, low amplitude free alpha-subunit pulses persist and are synchronous with residual LH pulses. In contrast, LH and free alpha-subunit are not maintained under agonist treatment. These data provide evidence for the differential regulation of LH and free alpha-subunit by GnRH.

Female

Testicular tumors in congenital adrenal hyperplasia: steroid measurements from adrenal and spermatic veins.

The present study reports the case of a 25-yr-old man with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in whom bilateral testicular tumors did not regress after suppressive treatment with dexamethasone. Catheterization of left testicular and adrenal veins confirmed the enzyme deficiency in the gonadal lesions. The presence of specific 11 beta-hydroxylated steroids (11 beta-hydroxyandrostenedione, 21-deoxycortisol, and 21-deoxycorticosterone) in the gonadal vein demonstrated the adrenal nature of the testicular tumor. In addition, catheterization allowed further study of the secretion of mineralocorticoids and androgens in the adrenal venous effluent. Plasma levels of deoxycorticosterone were increased in the peripheral vein and decreased in the adrenal vein, confirming the conversion of progesterone by peripheral 21-hydroxylase activity. Plasma levels of delta 5-3 beta-hydroxysteroids, particularly dehydroepiandrosterone and its sulfate, were very low, suggesting a sustained stimulation of 3 beta-hydroxysteroid dehydrogenase activity. This study documents that in patients with congenital adrenal hyperplasia and bilateral testicular tumors, catheterization of a gonadal vein measuring specific 11 beta-hydroxylated steroids confirms the adrenal nature of the gonadal lesions.

Adrenal Cortex Hormones

Thiamine responsive anemia: report of a new case associated with a thiamine pyrophosphokinase deficiency.

We report a new case of thiamine responsive anemia in a three years old boy with the characteristic association of anemia, diabetes mellitus and deafness. Thiamine therapy corrected anemia as described. A thiamine pyrophosphokinase deficiency (TPK) was found which was not influenced by treatment. However normal levels of thiamine pyrophosphate (TPP) were obtained without correction of all symptoms particularly dyserythropoïesis. Thus, etiology of the syndrome is not only a thiamine pyrophosphokinase deficiency as previously suggested.

Abnormalities, Multiple

Study of tolerance and effectiveness of a varicella vaccine in leukemic children.

Chickenpox could be a severe disease in immunocompromised patients. Live attenuated vaccine is now available. We conducted a trial in 37 leukemic children with OKA varicella vaccine. Full immunization was observed in all 20 seronegative patients. Few side effects and no generalized vaccinal infection were observed. Further studies are warranted to assess the benefit of vaccination in leukemic patients considering the effectiveness of Varicella Zoster Immuno-Globulins and Aciclovir.

Adolescent

[Short-term effect of delayed-action injectable bromocriptine in macroprolactinoma. French multicenter study].

In this prospective multicenter trial, 61 patients presenting with a macroprolactinoma were studied over a 1 month-period following a single 50 mg intragluteal injection of the long-acting repeatable (L.A.R.) form of bromocriptine. The effects of the drug were evaluated mainly by repetitive plasma prolactin measurements on days 1, 3, 7, 14 and 28 after injection, and by repeated visual-field and computed tomography scanning examinations. Normalization of PRL levels was obtained in 23% of patients during the first month following injection. In 6 patients (9.8%), PRL values remained within normal range on day 28 after injection. In these latter patients, PRL levels were significantly lower than in the patients whose PRL values were not normal on day 28 (312 +/- 111 vs 2454 +/- 484 ng/ml [m +/- SEM]). The mean lowest PRL levels were achieved on day 3. The mean percent maximal decrease in PRL levels ranged between 70 and 72% from days 3 to 14 but constantly remained below 50% in 6 patients. An improvement in visual field was observed by day 7 in 45% of patients presenting initially with visual field defects. In particular, in half of the patients with bilateral quadranopsia or hemianopsia, such visual impairments had disappeared after 1 month of treatment. Computed tomography scanning examinations showed in 11% of the patients a more than 20% reduction in tumor mass by day 7 following injection. On day 28, the percent reduction in tumor size was 20-40% in 28% and above 40% in 10% of the patients. Most adverse effects (digestive symptoms, dizziness, postural hypotension) were observed during the first 24 hours of treatment. Local and systemic tolerability was in general good. In macroprolactinoma patients, a single 50 mg injection of bromocriptine LAR was thus able to achieve in the short-term a clear cut reduction in tumor size in 2/5 patients and normalization of PRL levels in 1/10 of patients. A study of the effects of monthly administration of bromocriptine LAR is currently under progress to assess the long-term efficacy of this drug.

Adult

Stimulatory effect of thyroid hormone on RA-induced granulocytic differentiation in leukemic cells.

Retinoic acid, vitamin D3, and dexamethasone are known inducers of myeloid leukemic cell differentiation. Recent evidence indicates that these drugs mediate their biological effects through binding to a nuclear receptor which belongs to the steroid/thyroid hormone receptor superfamily. This paper shows that the ligands of the other receptors of this family, estrogens, progesterone, androgens and thyroid hormone, do not induce leukemic cell differentiation. However, thyroid hormone potentiates, by one order of magnitude, the dose-response effect of retinoic acid in HL-60 cells.

Cell Differentiation

Anterior and posterior hypopituitarism with pituitary stalk abnormalities.

Hypopituitarism and diabetes insipidus are often idiopathic conditions. A retrospective study of 6 cases of diabetes insipidus and 8 cases of partial or global idiopathic anterior hypopituitarism has shown that MRI is of considerable value to detect abnormalities of the pituitary stalk or hypothalamo-pituitary "relay". On the basis of MRI findings, some cases of idiopathic hypopituitarism can now be grouped together in a new entity which may be called hypopituitarism due to neonatal transection of the pituitary stalk.

Adolescent

Late luteal administration of the antiprogesterone RU486 in normal women: effects on the menstrual cycle events and fertility control in a long-term study.

Twelve regularly cycling women, with contraindications to other methods of contraception, received RU486 (Roussel UCLAF, Romainville, France), once a month as a method of fertility control. The study was designed for 18 consecutive cycles. Each patient recorded basal body temperature, detected urinary luteinizing hormone peak, and collected saliva samples during each luteal phase for progesterone (P) determinations. A single dose of RU486, 600 mg, was given on the day before the expected date of the menses and 8 days later in case of continuing pregnancy after the first dose. Blood samples were collected for estradiol, P, and beta-human chorionic gonadotropin analyses on these two occasions. The compliance was poor and the results of only 137 cycles were obtained. The menstrual cyclicity was not significantly modified during this long-term study. Of the 137 cycles, 22 pregnancies occurred (16%), and 4 (18.2%) were not interrupted by the second dose of RU486. Thus, because of the high failure rate, use of RU486 at the time of the natural P withdrawal cannot be advocated as a "once-a-month" contragestive agent.

Adult