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Objectives/hypothesis: To determine if sleepiness and sleep study variables (e.g., Apnea-Hypopnea Index [AHI] and lowest oxygen saturation) improve following isolated tonsillectomy for adult obstructive sleep apnea (OSA)., Study Design: Systematic review and meta-analysis., Methods: Nine databases (PubMed/MEDLINE included) were searched through November 24, 2015., Results: Seventeen studies (n = 216 patients, 34.4 ± 10.0 years and body mass index: 29.0 ± 6.1 kg/m(2) ) met criteria. Tonsils sizes were hypertrophied, large, enlarged, extremely enlarged, or grades 2 to 4. Apnea-Hypopnea Index decreased by 65.2% (from 40.5 ± 28.9/hour to 14.1 ± 17.1/hour) (n = 203). The AHI mean difference (MD) was -30.2 per hour (95% confidence interval [CI] -39.3, -21.1) (P value < 0.00001). The AHI SMD was -1.37 (-1.65, -1.09) (large effect). Lowest oxygen saturation improved from 77.7 ± 11.9% to 85.5 ± 8.2% (n = 186). Lowest oxygen saturation MD was 8.5% (95% CI 5.2, 11.8) (P value < 0.00001). The Epworth Sleepiness Scale decreased from 11.6 ± 3.7 to 6.1 ± 3.9 (P value < 0.00001) (n = 125). Individual patient outcomes (n = 54) demonstrated an 85.2% success rate (AHI < 20/hour and ≥ 50% reduction) and a 57.4% cure rate. Individual patient data meta-analysis showed preoperative AHI < 30 per hour to be a significant predictor of surgical success (P value < 0.001) and cure (P value = 0.043); among patients with preoperative AHI < 30 per hour, tonsillectomy success rate was 100% (25 of 25) and cure rate was 84% (21 of 25) with a mean postoperative AHI of 2.4 ± 2.1 per hour; this compares to tonsillectomy success rate of 72.4% (21 of 29), cure rate of 10 of 29 (34.4%), and mean postoperative AHI of 14.3 ± 13.9 per hour for patients with preoperative AHI ≥ 30 per hour., Conclusion: Isolated tonsillectomy can be successful as treatment for adult OSA, especially among patients with large tonsils and mild to moderate OSA (AHI < 30/hour). Laryngoscope, 2016 Laryngoscope, 126:2176-2186, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

A 26-year-old male was presented to a military treatment facility in Afghanistan shortly after taking a weight-lifting supplement called Jack3d with a severe headache and was subsequently found to have suffered a Dejerine-Roussy variant right thalamic hemorrhagic stroke. Jack3d active ingredients include geranamine, schizandrol A, caffeine, beta-alanine, creatine monohydrate, and L-arginine alpha-ketoglutarate. A literature search revealed case reports suggesting some of the constituent ingredients may predispose to stroke and hemorrhage and also revealed a substantial paucity of data existed regarding schizandrol A, a herb used in traditional eastern medicine. The product has no readily apparent disclaimer or warning regarding the risks or lack of data regarding the components. Jack3d is sold as a nutritional supplement and is therefore not subject to same FDA regulation and scrutiny that a pharmaceutical receives. The potential adverse effect was reported to the FDA via MedWatch in accordance with the recently passed Dietary Supplement and Nonprescription Drug Consumer Protection Act.

Frasier syndrome is a relatively rare disorder associated with XY gonadal dysgenesis, gonadoblastoma, and kidney failure. In this report, we identify a classic mutation in the Wilms' tumor 1 gene in one of the original cases of Frasier syndrome reported in this Journal in 1964.

In humans, mutations in the testis-determining gene SRY result in XY sex reversal with pure gonadal dysgenesis (PGD). However, only about 10-15% of the cases of PGD can be explained by mutations within the SRY open reading frame, suggesting the existence of other sex-determining genes. Although SRY is known to bind and bend DNA, its target and mode of action remain elusive. Here, we describe a novel mutation in SRY at codon 127, resulting in a tyrosine (Y) to phenylalanine (F) substitution in the protein. This sequence variant was found not only in the XY female patient but also in her father, who is a phenotypically normal male. However, this Y127F variant was not found in the SRY sequences of 93 other randomly chosen males. This substitution affects a highly conserved tyrosine residue in the HMG box of SRY, in which two de novo mutations have been described previously in XY females with PGD. Furthermore, electromobility shift studies demonstrate that SRY protein harboring the Y127F variant is incapable of binding consensus SRY binding sites in vitro. Taken together, these data suggest that the Y127F variant is a novel mutation with functional consequences and not simply a polymorphism. The allelic variant of SRY transmitted in this family and shared by both a phenotypic female (proband) and a phenotypic male (proband's father) emphasizes the importance of modifier genes in the sex determination pathway.

In an open-label study, 69 children with organic or idiopathic growth hormone deficiency (GHD) were treated with recombinant human growth hormone (Saizen) for an average of 64.4 mo, with treatment periods as long as 140.9 mo. Auxologic measurements, including height velocity, height standard deviation score, and bone age, were made on a regular basis. The data suggest that long-term treatment with Saizen in children with GHD results in a positive catch-up growth response and proportionate changes in bone age vs height age during treatment. In addition, long-term Saizen therapy was well tolerated, with the majority of adverse events related to common childhood disorders or existing baseline medical conditions and not to study treatment. There were no significant changes in laboratory safety data or vital signs, and no positive antibody tests for Saizen.

Before 1985 the use of growth hormone (GH) was governed by a philosophy of scarcity and conservation of resources. Between 1956 and 1959 human pituitary GH was shown to be effective. The competition for gland collection and extraction that followed benefited only certain patients with motivated parents and only a few investigators. To maximize gland collection, the distribution of GH for clinical investigation, and the number of patients who could be treated, the National Institutes of Health and the College of American Pathologists formed the National Pituitary Agency (NPA). In Canada a similar program was developed by the Canadian Medical Research Council. For more than 20 years the NPA supervised most of the GH treatment in the United States. Commercial pituitary GH entered the U.S. market in 1976, and competition soon appeared. Patients treated through the NPA were subjects in clinical studies for part of the first year of treatment, after which the limited availability of GH dictated treatment for only part of the year and caps on final heights. By 1984 treatment was year round and the height caps largely unenforced. In the last year of its distribution NPA GH was used in 2450 patients in the United States and commercial pituitary GH was used in 600 to 800; slightly more than 300 patients were being treated in Canada. And then, in 1985, came Creutzfeldt-Jacob disease. While the not-so-good old days are gone and need not be lamented, there remains virtue in a conservative therapeutic philosophy. If anything can be learned from the use of pituitary GH in children, it is a healthy respect for the law of unintended consequences.

We have previously demonstrated that the tissue-specific regulation of human aromatase cytochrome P450 (P450arom) gene expression is, in part, the consequence of the use of tissue-specific promoters. Promoter I.1 (PI.1) and PI.2-specific transcripts are expressed in the placenta, whereas promoter II (PII) appears to be the only active promoter in the corpus luteum. Testicular and ovarian sex cord tumors with annular tubules (SCTATs) associated with gynecomastia in prepubertal boys and isosexual precocity in girls with Peutz-Jeghers syndrome (P-JS) have been previously reported. In the present study, we investigated the regulatory elements directing P450arom gene transcription in samples of SCTAT from three prepubertal boys and a girl with P-JS and an ovarian granulosa cell tumor from an adult woman, as well as in healthy fetal and adult testicular and ovarian tissues. Placental tissue was used as a control. Using polymerase chain reaction linked to reverse transcription and northern blotting, we determined the tissue-specific use of various P450arom promoters by analyzing specific 5'-termini from messenger RNA templates. Results indicate a universal gonadal promoter (PII) directs P450arom gene expression in healthy fetal and adult ovaries and testes, as well as in SCTAT of the P-JS and an adult ovarian granulosa cell tumor. These results are interpreted to mean that use of PII in human ovary and testis is preserved from the fetal period into adult life as well as in transformed neoplastic Sertoli and granulosa cells. On the other hand, transcripts from placenta are specific for PI.1 (and to a much lesser extent, PI.2). In SCTAT, immunoreactive P450arom is detected only in the cytoplasm of neoplastic cells, whereas the normal-appearing sex cords do not contain any immunoreactive P450arom. These results further suggest that the markedly increased aromatase expression of these transformed neoplastic cells is not a consequence of using different tissue-specific promoters. Rather it appears to involve activation (or failure of inhibition) of the upstream regulatory elements of the same promoter, which is normally functional in all gonadal tissues, namely the proximal PII.

We have previously demonstrated that the tissue-specific regulation of human aromatase cytochrome P450 (P450arom) gene expression is, in part, the consequence of the use of tissue-specific promoters. Promoter I.1 (PI.1) and PI.2-specific transcripts are expressed in the placenta, whereas promoter II (PII) appears to be the only active promoter in the corpus luteum. Testicular and ovarian sex cord tumors with annular tubules (SCTATs) associated with gynecomastia in prepubertal boys and isosexual precocity in girls with Peutz-Jeghers syndrome (P-JS) have been previously reported. In the present study, we investigated the regulatory elements directing P450arom gene transcription in samples of SCTAT from three prepubertal boys and a girl with P-JS and an ovarian granulosa cell tumor from an adult woman, as well as in healthy fetal and adult testicular and ovarian tissues. Placental tissue was used as a control. Using polymerase chain reaction linked to reverse transcription and northern blotting, we determined the tissue-specific use of various P450arom promoters by analyzing specific 5'-termini from messenger RNA templates. Results indicate a universal gonadal promoter (PII) directs P450arom gene expression in healthy fetal and adult ovaries and testes, as well as in SCTAT of the P-JS and an adult ovarian granulosa cell tumor. These results are interpreted to mean that use of PII in human ovary and testis is preserved from the fetal period into adult life as well as in transformed neoplastic Sertoli and granulosa cells. On the other hand, transcripts from placenta are specific for PI.1 (and to a much lesser extent, PI.2). In SCTAT, immunoreactive P450arom is detected only in the cytoplasm of neoplastic cells, whereas the normal-appearing sex cords do not contain any immunoreactive P450arom. These results further suggest that the markedly increased aromatase expression of these transformed neoplastic cells is not a consequence of using different tissue-specific promoters. Rather it appears to involve activation (or failure of inhibition) of the upstream regulatory elements of the same promoter, which is normally functional in all gonadal tissues, namely the proximal PII.

Sixty-nine growth hormone-deficient patients were treated for 1 year with somatotropin (recombinant DNA-derived human growth hormone) produced in mouse cells. The growth velocity of the 50 patients (72%) in whom the effectiveness of this growth hormone could be evaluated increased from a mean (+/- SD) of 3.5 +/- 1.1 to 8.7 +/- 1.6. cm/y. An enhanced rate of weight gain was also observed. Bone age was not unduly accelerated. One of 66 patients developed antibodies to recombinant growth hormone, which did not affect the response to therapy. No patient developed antibodies to host cell proteins. An increased insulin response to a standard glucose load, without any change in glucose tolerance, was observed after 1 year of treatment. This authentic sequence human growth hormone preparation produced in mammalian cells is both effective and safe in the treatment of children with growth hormone deficiency.

In five clinical studies performed in Austria, France, the FRG, Italy, Switzerland, the UK and the USA, 304 growth hormone (GH)-deficient children were treated with recombinant human GH (rhGH) of mammalian cell origin. Two hundred and twenty-five patients were previously untreated (naive patients), and 79 were transferred from pituitary hGH after interruption of therapy for at least 6 months (transfer patients). Two treatment protocols, differing in both dose and frequency of injections, were used: (1) a dose of 0.6 IU/kg body weight per week was administered in 3 s.c. injections to 203 patients (178 naive, 25 transfer; group 1); and (2) a dose of 0.45 IU/kg body weight per week was administered in 7 s.c. injections to 101 patients (47 naive, 54 transfer; group 2). After 1 and 2 years of treatment, 143 and 109 naive, and 51 and 46 transfer patients, respectively, were still prepubertal, and their data were analyzed for efficacy. During the 1st year of treatment, both naive and transfer patients on daily injections (group 2) demonstrated better growth than those on 3 injections per week (group 1), with height velocities (HVs) of 10.6 +/- 2.7 cm/year (group 2) versus 8.6 +/- 2.0 cm/year (group 1) for naive patients (p < 0.001), and 9.9 +/- 1.9 cm/year (group 2) versus 7.2 +/- 2.7 cm/year (group 1) for transfer patients (p < 0.001). The corresponding changes in height standard deviation score (delta H SDS) for chronological age (CA) were +1.3 +/- 0.6 (group 2) versus +0.8 +/- 0.5 (group 1) for naive patients (p < 0.01), and +1.1 +/- 0.3 (group 2) versus +0.6 +/- 0.4 (group 1) for transfer patients (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Testosterone (T) and estradiol (E2) concentrations were determined and correlated with beta human chorionic gonadotropin (beta-HCG) concentrations in 43 paired maternal and cord sera (22 female and 21 male infants). Mean (+/- SD) maternal E2 concentrations were significantly (P less than .005) higher when the sex of the fetus was male than when the sex of the fetus was female (20.6 +/- 3.9 vs 13.5 +/- 3.2 ng/ml). Maternal T concentrations were not significantly different when related to the sex of the fetus (males, 114.8 +/- 60.7 vs females, 113.8 +/- 54.5 ng/100 ml, P greater than .1). Regression analysis did not show a significant correlation between maternal T or E2 concentrations and maternal beta-HCG concentrations. Mean cord serum T and E2 concentrations of male infants were significantly greater than that of female infants (T, 38.8 +/- 8.5 vs 25.8 +/- 7.1 ng/100 ml, P less than .005; E2, 9.1 +/- 3.3 vs 6.6 +/- 2.0 ng/ml, P less than .005). Regression analysis showed a significant (P less than .005) correlation between cord beta-HCG concentrations and E2 concentrations for male infants (r = .7) and female infants (r = .6). A significant correlation between cord beta-HCG concentrations and T concentrations was found for male infants (r = .5; P less than .01) but not for female infants (r = .3; P greater than .05). There was no correlation between maternal and infant E2 concentrations (males, r = .3, P greater than .05; females, r = .3, P greater than .2) or T concentrations (males, r = .02, P greater than 0.4; females, r = .06, P greater than .3). These data (1) confirm the sex difference in cord serum T and E2 concentrations, (2) indicate that the lower beta-HCG concentrations in mothers of male infants are associated with E2 concentrations which are greater than those in mothers of female infants, and (3) are consistent with an influence of beta-HCG on fetal T and E2 secretion.

HLA-A, - B, and -C antigens were studied in 67 Mexican-American and 38 black-American diabetic patients who had the onset of their disease before age 31 yr. Control populations consisted of 322 Mexican-American and 367 black-American subjects for HLA-A, -B, and -C antigens. In addition, HLA-DRw antigens were studied in 60 Mexican-American and 34 black-American diabetic patients. Control populations for HLA-DRw antigens consisted of 189 Mexican-American and 145 black-American subjects. We found that juvenile-onset--diabetic patients of Mexican-American origin who had the onset of their disease before age 19 demonstrated a significant increase in HLA-DRw4. HLA-DRw4 was also significantly increased in black-American patients with juvenile-onset diabetes mellitus. HLA-DRw2 was not detected in any patient with juvenile-onset diabetes in either ethnic group. A significant association was found between HLA-B18 and HLA-DRw3 in Mexican-American juvenile-diabetic patients. These findings, which are comparable to those in similar Caucasian patients, provide additional information to support the hypothesis that HLA-DRw antigens play a major role in determining the susceptibility to juvenile-onset diabetes mellitus.

The in vivo conversion of progesterone to deoxycorticosterone (DOC) by peripheral 21 hydroxylation was studied in normal men and women. The technique used was to infuse labeled progesterone under steady state conditions and isolate the precursor and product from blood by multiple chromatography steps. DOC was chromatographed as both the steroid and its acetylated derivative. The conversion rate was found to be 1.3 +/- 0.1% in men and women despite differences in the concentration of progesterone during the cycle. Since progesterone was very low in men and women in the follicular phase of the cycle, we conclude that DOC is derived from direct secretion. However, progesterone rises to 1073 +/- 101 ng per dl in the luteal phase and the calculations indicate that DOC increases from 8.3 +/- 0.4 (SE) to 15.6 +/- 1.3 ng per dl. 3/4 of luteal phase DOC is from conversion of progesterone. Acute ACTH increases both progesterone and DOC, and almost all of the DOC in plasma is from direct secretion. However, chronic ACTH excess and adrenal 21 hydroxylase deficiency is associated with a fraction (1/4-1/5) of DOC from progesterone indicating that the peripheral conversion rate is unrelated to the adrenal enzyme defect.

Human chorionic gonadotropin (HCG) concentrations were determined in paired maternal and cord sera using an essay specific for the beta subunit of HCG. The sera of 46 mothers and 46 infants, 24 female and 22 male, were studied. Results were compared to those obtained using a radioimmunoassay for luteinizing-hormone (LH) which cross-reacted with HCG. With either assay system, mean maternal HCG concentrations were lower when the sex of the fetus was male than when the sex of the fetus was female. Mean cord HCG concentrations of male (0.09 +/- 0.02 IU/ml) and female (0.09 +/- 0.04 IU/ml) infants were not different as determined by the beta HCG assay. In contrast, the mean cord serum concentration of HCG was significantly greater (P less than .005) in male infants (0.29 +/- 0.05 IU/ml) than in female infants (0.23 +/- 0.09 IU/ml) as determined by the cross-reacting assay. HCG concentrations were lower in both maternal and cord sera when assayed in the specific HCG system than when assayed in the cross-reacting system. There was a significant correlation (r=.9; P less than .005) between the results obtained with the two assays in both maternal and cord blood. Regardless of the assay system employed, the cord serum concentration of HCG was markedly less than the corresponding maternal serum concentration. There was no correlation between maternal and cord serum HCG concentrations with either assay. These data are in agreement with the results of previous studies employing less specific methodology which indicated that maternal serum HCG concentrations were less when the fetus was male than when it was female. They are also consistent with a placental barrier effect with regard to HCG transfer to the fetus. The difference in results obtained in cord blood with the two assay systems suggests that the newborn male infant secretes more LH and/or alpha LH subunits than the newborn female infant.