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Biomedical subjects

R Osathanondh

Publications and source records attributed to R Osathanondh.

At least 55 records · Page 3Linked to original sources
PubMed1985

Adrenal steroids in maternal and cord blood after dexamethasone administration at midterm.

We undertook a study designed to evaluate whether it is feasible to suppress fetal adrenal secretion of androgens at mid-pregnancy by giving dexamethasone (DX) to the mother. Levels of DX and adrenal steroids were measured in maternal and cord plasma of 13 DX-treated and 16 untreated mothers undergoing abortion at 18-20 weeks of pregnancy. Maternal adrenal suppression was evidenced by a sharp fall of plasma cortisol (F), cortisone (E), corticosterone (B), and dehydroepiandrosterone sulfate (DHEA-S). However, in cord blood no fall of DHEA-S or corticosterone sulfate (BS) was found up to 20 hours after DX administration, and cord plasma ACTH remained detectable. The failure of DX to suppress the fetal adrenal at mid-pregnancy suggests that this drug would not be effective in the intrauterine treatment of congenital adrenal hyperplasia (C.A.H.).

Adrenal Cortex Hormones↗
PubMed1985

Efficacy of fenoprofen in the treatment of primary dysmenorrhea.

We compared fenoprofen calcium, 200 mg; fenoprofen calcium, 400 mg; aspirin, 650 mg; and a placebo in 85 women for the relief of primary dysmenorrhea in a double-blind, clinical trial. The usefulness of these drugs was judged from data obtained over four consecutive menstrual periods on: restriction of daily activity, pain intensity scores, need for rescue analgesics, withdrawal due to lack of efficacy, and adverse events. Both fenoprofen, 200 mg, and fenoprofen, 400 mg, offered significant (P less than .01) pain relief when compared to placebo and aspirin. Analyses of data on 1, 2 and 3 indicated that aspirin was not significantly different from placebo. The aspirin-treated group reported the greatest number of adverse reactions, but the differences between the four groups were not statistically significant. Our study lends support to the concept of a "plateau analgesic effect" of nonsteroidal antiinflammatory drugs (NSAIDs): fenoprofen, 200 mg, appears to be as effective as fenoprofen, 400 mg. When this type of drug fails to provide relief for a woman suffering from primary dysmenorrhea, switching to another NSAID may be more appropriate than increasing the dosage and the probability of dosage-related side effects.

Adolescent↗
PubMed1985

Midtrimester abortion with Laminaria and vacuum evacuation on a teaching service.

Midtrimester abortion by the dilatation and evacuation (D&E) method has generated controversy among health-care providers; many authorities insist that this procedure should be performed only by a small group of experts. Our institution has been providing abortions for patients who were at 13-16 1/2 menstrual weeks on a teaching service with Laminaria and vacuum evacuation (midtrimester D&E). The procedures were performed under local anesthesia in a separate, specially staffed, in-hospital pregnancy termination unit on an ambulatory basis. Twelve resident physicians at different training levels performed 87% of the procedures under the direct, hands-on supervision of a small but experienced faculty group. Records of 1,392 consecutive patients who underwent midtrimester D&E at Brigham and Women's Hospital between January 1, 1979, and December 31, 1980, were analyzed. There were no maternal deaths or life-threatening complications. Immediate and late morbidity was minimal. There were no major complications that necessitated laparotomy. Despite the use of Laminaria overnight, a "no-touch" rather than full sterile technique and no prophylactic antibiotics, infectious complications were minimal. We conclude that midtrimester D&E can be performed safely and efficiently by resident physicians in an appropriate teaching facility under close supervision. That ultimately can increase accessibility to the D&E procedure by increasing the number of physicians trained in this modality.

Abortion, Induced↗
PubMed1984

Human chorionic gonadotropin and thyroid function in patients with hydatidiform mole.

In view of the controversy regarding the role of human chorionic gonadotropin as the stimulator of thyroid function in patients with trophoblastic tumors, especially hydatidiform mole, we conducted studies to explore whether a correlation between serum human chorionic gonadotropin levels and thyroid function was demonstrable in such patients. Among 47 patients studied, only one was clinically hyperthyroid, although 10 had serum total thyroxine values exceeding those found in normal pregnancy (8 to 17 micrograms/dl). Among 34 patients in whom free thyroxine indices could be calculated, 18 had elevated values for the free thyroxine index (greater than 10.6), and nine had elevated values for both total thyroxine and free thyroxine index. Serum total 3,5,3'-triiodothyronine concentrations were also measured in 17 patients, and only one of them had a value (400 ng/dl) above the normal limit for pregnancy (greater than 350 ng/dl). Among the 13 patients for whom free 3,5,3'-triiodothyronine indices were calculated, three had values above the normal range (greater than 215). A weakly positive correlation (r = 0.35, p less than 0.05, n = 47) between the serum human chorionic gonadotropin levels and serum total thyroxine concentrations was observed in these patients. However, no correlation was found between serum human chorionic gonadotropin levels and free thyroxine index values (r = 0.32, p greater than 0.05, n = 34). Also there was no correlation between serum human chorionic gonadotropin levels and either serum total 3,5,3'-triiodothyronine concentrations (r = 0.32, p greater than 0.1, n = 17) or free 3,5,3'-triiodothyronine index values (r = 0.27, p greater than 0.1, n = 13). chi 2 Analysis revealed no significant relationship between elevations of serum human chorionic gonadotropin concentration and abnormally high values of the free thyroxine index. These studies do not support the premise that human chorionic gonadotropin per se is the thyroid stimulator of molar pregnancy and suggest that a substance or substances, distinct from human chorionic gonadotropin and elaborated by the gestational trophoblastic tissue, are responsible for thyrotoxicosis observed in patients with trophoblastic tumors.

Adolescent↗
PubMed1984

Insulin-stimulated tyrosine protein kinase. Characterization and relation to the insulin receptor.

Utilizing histone phosphorylation as the basis for a quantitative assay, the insulin-stimulated protein kinase in human placenta has been characterized. The kinase copurifies through wheat germ agglutinin-Sepharose and DEAE-cellulose in constant ratio to the insulin binding function. Both activities are bound to the same extent on insulin-Sepharose, and the immobilized kinase, after extensive washing, exhibits activity versus histone, which closely approaches that of the insulin-stimulated, solubilized kinase. In addition, the bound kinase retains the ability to phosphorylate the Mr = 95,000 subunit of the bead-bound receptor. Elution of the beads with sodium dodecyl sulfate yields on electrophoresis two major peptides of Mr = 130,000 and 95,000. Thus, insulin binding and insulin-stimulated histone kinase copurify in a constant stoichiometric ratio in close physical relation and are likely functional expressions of the same molecule. After the DEAE step, the insulin-stimulated kinase phosphorylates histone subfraction 2b exclusively on tyrosine residues. Insulin increases the Vmax for H2b by 3-5-fold and increases the rate of the histone phosphorylation in direct correspondence to the steady state level of specifically bound insulin. ATP is the preferred phosphate donor. The reaction is supported by either Mn2+ or Mg2+. At [ATP] less than 0.5 mM, insulin-stimulated kinase is substantially higher with Mn2+ as the sole divalent cation, as compared to Mg2+. At [ATP] greater than or equal to 0.5 mM, the rates observed with Mn2+ have plateaued, whereas the rates in the presence of Mg2+ show a continued increase such that maximal activity is seen with Mg2+ and 2-3 mM ATP. Under these conditions, the estimated turnover number of the kinase ranges between 30 and 100 pmol of 32P transferred per min/pmol of insulin bound. Thus, the tyrosine kinase activity of the insulin receptor is quantitatively comparable to that estimated for several serine protein kinases and is unlikely to reflect the side reaction of another enzymatic function.

Amino Acids↗
PubMed1983

Ontogeny of human hematopoietic cells: analysis utilizing monoclonal antibodies.

Lymphoid and myeloid cells isolated from second trimester fetal lymphoid organs were characterized by utilizing a panel of monoclonal antibodies that define human lineage-restricted, differentiation, histocompatibility, and activation antigens. At distinct gestational stages, the appearance of morphologically identifiable lymphoid and myeloid cells paralleled the appearance of cells expressing definable lymphoid and myeloid antigens. The proportion of cells in fetal liver, bone marrow, and spleen that expressed histocompatibility, myeloid, and B cell antigens increased with fetal maturation. In contrast, even the earliest fetal thymuses studied were of a phenotype no different than that seen during later stages of ontogeny. Although the cellular lineage of most fetal hematopoietic cells could be identified by this panel of reagents, a considerable number of fetal liver and bone marrow cells did not express any of these antigens, suggesting the possibility that they might represent early hematopoietic progenitor cells. These studies support the notion that the adult cellular phenotype is the result of both an orderly acquisition of differentiation antigens and the migration of these primitive cellular populations to specific fetal organs. Identification of hematopoietic progenitors in fetal tissues may facilitate the identification and isolation of early lymphoid and myeloid progenitor cells in adults.

Antibodies, Monoclonal↗
PubMed1982

Insulin-stimulated tyrosine phosphorylation of the insulin receptor in detergent extracts of human placental membranes. Comparison to epidermal growth factor-stimulated phosphorylation.

Addition of insulin to Triton-solubilized extracts of human placental membranes selectively stimulates the incorporation of 32P from [gamma-32P]ATP into an endogenous 95,000-dalton protein, which is identified as a component of the insulin receptor by immunoprecipitation. The insulin-stimulated increment in 32P is recovered largely in [32P]tyrosine after acid hydrolysis. E Epidermal growth factor (EGF) stimulates the phosphorylation of a 150,000-dalton protein in these detergent extracts. This reaction differs in several respects from the insulin-stimulated phosphorylation of the 95,000-dalton protein. Insulin-stimulated phosphorylation exhibits an absolute requirement for Mn2+ as the sole divalent cation, whereas EGF-stimulated phosphorylation is supported by Mg2+ and Co2+ as well as Mn2+. In the presence of Mn2+, insulin-stimulated phosphorylation is not detected at less than 50 microM ATP, whereas EGF-stimulated phosphorylation is well expressed at 5 microM ATP. Thus, in detergent-solubilized membrane extracts, insulin stimulates the phosphorylation of its own receptor on tyrosine residues. This reaction has enzymatic properties distinct from those of the EGF-stimulated phosphorylation in these same extracts. The role of this insulin-stimulated phosphorylation reaction in the initiation of insulin's many biologic actions merits further study.

Adenosine Triphosphate↗
PubMed1982

A review of possible toxicity of di-2-ethylhexylphthalate (DEHP) in plastic intravenous containers: effects on reproduction.

Many containers for intravenous solutions are made with plasticized polyvinyl chloride, the common form of which is di-2-ethylhexylphthalate (DEHP). Extraction of DEHP into blood and plasma stored in such plastic containers can occur, and harmful effects of DEHP in the human body consequently have been suggested. Reports on toxicity of DEHP in animals during pregnancy and the developmental period are critically reviewed.

Animals↗
PubMed1982

Relaxin in normal and pathogenic pregnancies.

Serum relaxin concentrations were quantitated throughout pregnancy. Relaxin levels were higher in the first than in either succeeding trimester of pregnancy. Relaxin concentrations in third-trimester twin pregnancies were not significantly different from those in singleton pregnancies. Relaxin levels in toxemic pregnancies were similar to those of normal pregnancy. In contrast, relaxin concentrations in pregnancies beyond 43 weeks' gestation and in women with premature labor were significantly lower than levels in normal women in the third trimester of pregnancy.

Female↗
PubMed1981

Presence of immunoreactive luteinizing hormone-releasing factor in hydatidiform mole as compared with normal human trophoblastic tissue.

Concentrations of luteinizing hormone-releasing factor (LRF) and human chorionic gonadotrophin (HCG) were measured by specific radioimmunoassay in homogenates of molar tissue evacuated from four patients at eight to 16 weeks of pregnancy (by menstrual dates), and in normal trophoblastic tissue of equivalent gestational age. In normal trophoblastic tissue HCG concentrations decreased, while LRF concentrations increased, with advancing gestational age. Molar tissue contained high quantities of HCG (2292 +/- 1415 s.e.(mean) iu/g wet weight vs 355 +/- 129 in the placenta) and very low, but consistently measureable, quantities of LRF (23.4 +/- 6.7 pg/g vs 12,808 +/- 2931 in the placenta). The significance of our finding of high HCG concentrations in the presence of low concentrations of LRF in neoplastic trophoblastic tissue is being further investigated.

Chorionic Gonadotropin↗
PubMed1981

Danazol inhibition of steroidogenesis in the human corpus luteum.

In human corpus luteum (CL) microsomes, danazol inhibited 3 beta-hydroxysteroid dehydrogenase, 17,20-lyase, 17 alpha-hydroxylase, and 17 beta-hydroxysteroid dehydrogenase enzymes. Danazol did not inhibit aromatase. The observation that danazol can directly inhibit multiple enzymes of CL steroidogenesis may provide a molecular basis for explaining previous reports that danazol inhibits CL steroidogenesis in the monkey in vivo.

Adult↗
PubMed1981

Cerebrospinal fluid human chorionic gonadotropin levels in normal pregnancy and choriocarcinoma.

We measured human chorionic gonadotropin levels simultaneously in the serum and cerebrospinal fluid of 36 normal pregnant women and of six patients with choriocarcinoma. During normal pregnancy, human chorionic gonadotropin levels in the cerebral spinal fluid correlated well with those in the serum in both the first and third trimesters. A serum-cerebral spinal fluid human chorionic gonadotropin ratio of less than 60 has previously been reported as a sensitive diagnostic test for trophoblastic central nervous system involvement. However, we found this ratio to be less than 60 in one patient undergoing first trimester abortion and in one patient with nonmetastatic choriocarcinoma. Furthermore, two patients with documented trophoblastic cerebral metastases had serum-cerebral spinal fluid human chorionic gonadotropin ratios in excess of 60. Results of our study, thus, indicate that determination of a single serum-cerebral spinal fluid human chorionic gonadotropin ratio may not conclusively prove or exclude trophoblastic central nervous system metastases. Unless it is corroborated by other diagnostic means, a single decreased serum-cerebral spinal fluid human chorionic gonadotropin ratio is insufficient evidence to initiate multimodality treatment for presumptive central nervous system involvement.

Brain Neoplasms↗
PubMed1980

Danazol inhibits human adrenal 21-and 11 beta-hydroxylation in vitro.

The effects of danazol on steroidogenesis in vitro in the 16-20 week old human fetal adrenal were examined by studying: 1) danazol binding to adrenal microsomal and mitochondrial cytochrome P-450, and 2) enzyme kinetics of danazol inhibition of the adrenal microsomal 21-hydroxylase and the mitochondrial 11 beta-hydroxylase. The addition of danazol to preparations of adrenal microsomes or mitochondria elicited a type I cytochrome P-450 binding spectrum. Danazol bound to microsomal cytochrome P-450 binding spectrum. Danazol bound to microsomal cytochrome P-450 with a high affinity apparent spectral dissociation constant (KS) of 1 microM and with a lower affinity K's of 10 microM. Danazol bound to mitochondrial cytochrome P-450 with a KS of 5 microM. In addition, danazol competitively inhibited the microsomal 21-hydroxylase (apparent enzymatic inhibition constant KI = 0.8 microM) and the mitochondrial 11 beta-hydroxylase (KI = 3 microM). These findings demonstrate that low concentrations of danazol directly inhibit steroidogenesis in the human fetal adrenal in vitro.

Abortion, Legal↗
PubMed1980

Effects of luteinizing hormone on steroidogenesis by thecal tissue from human ovarian follicles in vitro.

The steroidogenic responsiveness of human thecal tissue to different doses of LH was investigated in vitro in relation to the health of the follicle and to the responsiveness of stromal tissue. The results show that small incremental increases in LH, over a low range of concentrations (1 to 10 ng/ml), markedly increased the thecal output of androstenedione from healthy and/or atretic follicles. Theca from healthy follicles were also stimulated to increase their output of progesterone and estradiol in response to small increases in LH whereas theca from atretic follicles produced more variable amounts of progesterone and were unable to generate estradiol. In contrast, relatively high concentrations of LH (50 ng/ml) reduced the total steroid output from the theca of both healthy and atretic follicles while 'switching on' a low level of steroidogenesis in stromal tissue. These data suggest that the steroidogenic response of thecal tissue is related to the mass of tissue (i.e., the size of the follicle), the health of the follicle and the amount of LH to which it is exposed.

Adult↗
PubMed1980

Steroidogenesis by the human oocyte-cumulus cell complex in vitro.

The ability of the human oocyte-cumulus cell complex to synthesize progesterone, androgens and estrogens and to modify its endocrine environment in vitro was investigated. Germinal-vesicle stage oocytes with adhering layers of cumulus cells were recovered from human ovaries and maintained for 40--50 h in vitro in a culture medium with or without antral fluid. The results show that oocyte-cumulus (O-C) cell complexes were capable of synthesizing progesterone, androgens and estrogens. Oocytes with the capacity of resuming meiosis in vitro were part of an O-C complex producing significantly more progesterone than those O-C complexes containing oocytes incapable of resuming meiosis. Irrespective of the stage of oocyte maturation at the end of culture, testosterone and estrone were respectively the major androgen and estrogen produced. It is concluded that the oocyte-cumulus compartment of the antral follicle is a steroidogenically competent unit and that it has the capacity to modify the endocrine microenvironment of the follicle.

Adult↗
PubMed1980

The intraovarian sites of androgen and estrogen formation in women with normal and hyperandrogenic ovaries as judged by in vitro experiments.

The status of oocytes, the follicular fluid concentrations of steroids, and the in vitro steroidogenic capacities of stromal tissue, thecal tissue, and granulosa cells from a 15-yr-old girl with primary amenorrhea, ovarian hyperandrogenism, insulin-resistant diabetes mellitus, and acanthosis nigricans were compared to those from normal adult human ovaries. Most oocytes (95%) in the antral follicles recovered from the hyperandrogenic ovaries were degenerative, and the antral fluid levels of testosterone were 30- to 200-fold higher than those in normal ovaries. Granulosa cells from the hyperandrogenic ovaries produced mainly estradiol as did those from normal healthy follicles. The thecal tissues produced 2- to 6-fold more androgen than similar tissues from normal ovaries. However, the stroma from the hyperandrogenic ovaries produced 49- to 250-fold more testosterone than that generated by normal tissues. These data suggest that the removal of stromal tissue as well as follicular tissue from patients with certain types of hyperandrogenism may sometimes contribute to a reduction in androgen secretion.

Adolescent↗