If direct contracting ever flowers, doctors could face thorny risks.
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Biomedical subjects
Publications and source records attributed to F Diamond.
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We discuss the relationship among certain generalizations of results of Hida, Ribet, and Wiles on congruences between modular forms. Hida's result accounts for congruences in terms of the value of an L-function, and Ribet's result is related to the behavior of the period that appears there. Wiles' theory leads to a class number formula relating the value of the L-function to the size of a Galois cohomology group. The behavior of the period is used to deduce that a formula at "nonminimal level" is obtained from one at "minimal level" by dropping Euler factors from the L-function.
Shwachman-Diamond syndrome is a rare congenital disorder of unknown etiology. Characteristic abnormalities of this disease include pancreatic insufficiency, skeletal anomalies, growth retardation, recurrent infections, and hematologic abnormalities. Significant morbidity and mortality in these patients result from respiratory infections, which are not well explained on the basis of neutrophil defects. We have had the opportunity to perform an in-depth clinical immunologic and endocrinologic evaluation of a patient with this syndrome with recurrent respiratory tract infections. She was found to have profound humoral immunologic defects, and serum thymulin was absent. In addition, endocrinologic evaluation for growth retardation revealed growth hormone deficiency. The patient responded to treatment with supplemental growth hormone and intravenous gammaglobulin with accelerated growth and cessation of infections. This case is unique in that it links growth hormone deficiency and hypogammaglobulinemia in a non-X-linked manner and may provide the basis for treatment of other patients with this rare syndrome.
Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 micrograms/kg s.c. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1-7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I.
The availability of unlimited but costly supplies of biosynthetic growth hormone has led to pressure for pharmacologic use (as opposed to replacement therapy in proven deficiency states). Commercial and altruistic motives have converged to promote community height screening among individuals who have been perceived by themselves or parents as short. This does not meet accepted criteria for health screening. Height screening of large populations of children yields few unrecognized medical conditions. If the goal of community screening is to identify abnormally short individuals (less than 3%) who might benefit from growth hormone treatment and if the unproven assumption is correct that stature correlates with success and happiness, then those less likely to appear for screening need to be recruited to avoid elitist domination. The annual cost of such growth promotion would be greater than $10 billion, with no evidence for substantial health benefits. Growth monitoring of all children through improved height measurement in schools and in physicians offices, as part of health supervision, is a more sound community approach than height screening.
To assess the effects of drug and alcohol abuse (DAA) on the physical changes and hormones of puberty in adolescents, 26 males (13 5/12-22 years) enrolled in a drug rehabilitation program were examined. In 22 subjects four timed blood samples were obtained sequentially at 15 minute intervals for measurement of serum concentrations of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and dehydroepiandrosterone sulfate (DHAS). The mean duration of DAA was 3.7 years, with marijuana and alcohol being the most frequently abused substances. The study subjects were compared to a matched control group of non-substance-abusing teenagers. All heights and weights of the DAA subjects fell within two standard deviations of the mean on the Tanner Growth Charts and no statically significant differences in the Tanner stages of sexual maturation were found between the DAA and control groups. The mean (+/- SD) testosterone level of the DAA group (221 +/- 109 ng/dl) was less than half that of the control group (477 +/- 193 ng/dl, p less than 0.001). Mean LH concentration in the DAA group (3.9 +/- 3.0 mIU/ml) was significantly less than that of the control group (10 +/- 4.9 mIU/ml, p less than 0.01). In both the DAA and control populations there was a significant (p less than 0.01) correlation between serum concentrations of LH and testosterone. The mean FSH level of the DAA group (3.3 +/- 1.1 mIU/ml) was significantly less (p less than 0.02) than that of the control group (4.7 +/- 1.9 mIU/ml). To assess the effects of treatment, six boys underwent repeat blood sampling 7-12 months after drug and alcohol withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.
The authors' experience with stillbirth within one week of a reactive nonstress test was reviewed to determine the reliability of this test in postdates patients and general high-risk patients. The corrected stillbirth rates were the same in both groups. Thirty-three percent of stillbirths in postdates patients occurred as early as 41.5 weeks' gestation. The cause of stillbirth in postdates patients was not clear even after careful autopsy. In the general high-risk group, 60% of stillbirths were due to an acute event with the remainder due to chronic fetal compromise that was not predicted by the nonstress test. Induction at 41.5 weeks' gestation or more comprehensive fetal surveillance than weekly nonstress testing are possible approaches to the management of postdates pregnancy, which need to be further studied.
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The records of 117 patients who had serial nonstress tests (N = 285) and oxytocin challenge tests (N = 268) were analyzed to determine whether baseline uterine contractility and/or oxytocin sensitivity changed with increasing gestational age. The results obtained in patients who were delivered before, at, and after term were compared. Uterine contractility and oxytocin sensitivity increased in all groups as gestational age progressed. No significant differences in uterine contractility were noted among groups; however, oxytocin sensitivity was significantly increased in the preterm group (p less than 0.001) and decreased in the postterm group (p less than 0.001). Our results suggest that the response of the uterus to oxytocin early in pregnancy may help to identify patients who will be delivered before or after term.
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