Metabolic and hormonal effects of oral DHEA in premenopausal women with HIV infection: a randomized, prospective, placebo-controlled pilot study.

Women with HIV infection use dehydroepiandrosterone (DHEA) because of its potential effects on mood and energy. We examined the effects of DHEA on the hypothalamic-pituitary-adrenal and gonadal axes and on insulin sensitivity. Fifteen HIV-positive women were randomized to receive placebo (6 subjects) or oral DHEA (9 subjects). ACTH-, CRF-, and GnRH-stimulation tests were performed before and after 8 weeks of treatment. DHEA, DHEA-S, dihydrotestosterone, total testosterone, free testosterone, sex hormone-binding globulin, estrone, estradiol, cortisol, insulin, IGF-1, IGFBP-1, IGFBP-3, and adiponectin in plasma or serum were measured. There was a significant increase in DHEA (p<0.004), DHEA-S (p<0.008), total testosterone (p<0.008), dihydrotestosterone (p<0.004), androstenedione (p<0.04), and estrone (p<0.03) from baseline within the DHEA group but not within the placebo group. There was a significant increase in DHEA (p<0.0006), DHEA-S (p<0.032), total testosterone (p<0.01), and dihydrotestosterone (p<0.005) in the DHEA group compared with the placebo group. Oral DHEA produces significant increases in circulating DHEA, DHEA-S, testosterone, DHT, and, possibly, androstenedione and estrone levels in premenopausal women with HIV infection. In the current pilot study these hormone changes did not affect the pituitary or adrenal axis or insulin/IGF indices. Long-term studies with larger groups of patients are needed to confirm these data and to determine their clinical significance.

Potential advantage of N363S glucocorticoid receptor polymorphism in 21-hydroxylase deficiency.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) shows a range of severity which is explained in part by the different mutations of the CYP21 gene. To better understand the incomplete concordance between genotype and phenotype in CAH the role of the sensitizing N363S polymorphism of the glucocorticoid receptor (GR) was examined in CAH patients. DESIGN: CAH patients were screened for N363S. Laboratory findings and clinical characteristics of carriers and non-carriers were analyzed retrospectively. METHODS: The CYP21 gene of 200 CAH patients was analyzed by allele-specific PCR. The GR gene was tested for N363S by PCR followed by restriction fragment length polymorphism. Antropometric data (height, weight), degree of intrauterine virilization, hormone concentrations (17-OH-progesterone, dehydroepiandrosterone (DHEA), aldosterone, testosterone, plasma renin activity), substitution doses and clinical course were analyzed. RESULTS: The carrier frequency of N363S in CAH patients was equivalent to that of the general Hungarian population (6% vs 7.8%). Interestingly, none of the non-classical CAH (NC-CAH) patients were carriers of the polymorphism. Carrier girls had milder genital virilization than mutation-matched non-carrier controls. There was no significant difference between the carriers and non-carriers in either the substitution doses, the hormonal, or the auxiological parameters. CONCLUSIONS: The association of sensitizing the GR variant with impaired cortisol production in CAH might be compensatory in mild NC-CAH and may prevent severe intrauterine virilization in classical form. Although the exact role of N363S in extrauterine life should be further investigated, the consideration of certain genetic polymorphisms of CAH patients may lead to better, individualized therapeutic regimes.

Screening for mutations of 21-hydroxylase gene in Hungarian patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders, causing impaired secretion of cortisol and aldosterone from the adrenal cortex, with subsequent overproduction of adrenal androgens. The most common enzyme defect causing CAH is steroid 21-hydroxylase deficiency. To determine the mutational spectrum in the Hungarian CAH population, the CYP21 active gene was analyzed using PCR. A total of 297 Hungarian patients with 21-hydroxylase deficiency are registered in the 2nd Department of Pediatrics, Budapest, Hungary, and their clinical status was evaluated. Blood samples for CYP21 genotype determination could be obtained from 167 patients (representing 306 unrelated chromosomes and 56.2% of the total group of patients). Eight of the most common mutations were screened [In2 (intron 2 splice mutation), I172N, Del (Del: apparents large gene conversion), Q318X, R356W, 1761Tins, ClusterE6, V281L] using allele-specific amplification. The most frequent mutation in the Hungarian CAH population was found to be In2. Our results have shown a good genotype/phenotype correlation in case of most mutations; the In2 mutation is associated mostly with the severe form of the disease, whereas I172N was expressed in a wide spectrum of phenotypes. 1999)

Casted titanium for dental applications: an XPS and SEM study.

Casted titanium for dental crowns has been investigated by means of X-ray Photoelectron Spectroscopy (XPS), X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The samples were prepared according to the Ohara process. XRD analysis revealed that the investment consisted essentially of SiO2, Mg2P2O7, SiO2 x H2O and Mg2SiO4. SEM experiments combined with EDX analysis revealed the following atomic concentrations Si (62.6%), Mg (19.7%), P (17.1%), and Ca (0.6%). After casting, the titanium samples exhibit a rough and irregular surface, and XRD analysis indicated that titanium contains essentially the alpha phase and traces of the beta phase. After demoulding titanium samples, the investment side which was in contact with titanium was black colored, proving the reaction between titanium and the investment. XPS analysis performed on this side of the investment indicated that the Si 2p peak presents a shoulder on the low binding energy side and thus suggest that SiO2 has been transformed into metallic Si.

Effect of immediate hemoglobin A1c results on treatment decisions in office practice.

OBJECTIVE: To assess the effect of an immediately available hemoglobin A1c (HbA1c) result on glycemic control and physician decisions about pharmacologic therapy in an office practice. METHODS: In a 1-year retrospective review of medical records, HbA1c results were analyzed in 115 patients beyond the age of 65 years, who had type 2 diabetes and were referred for the first time to a private endocrinology practice between April 1, 1997, and March 31, 1998. These patients were classified into two groups: group A (N = 93, insured by standard Medicare) had immediate HbA1c results (during the patient encounter) and group B (N = 22, insured by Medicare health maintenance organization [HMO]) had commercial laboratory HbA1c results available within 2 to 3 days. We reviewed the changes in the HbA1c level during the 12-month period and the presence or absence of a change in therapy at each visit. HbA1c levels were measured by ion-exchange low-pressure liquid chromatography in group A and by one of three capitated commercial laboratories (depending on HMO contracts) in group B. RESULTS: At the end of the 12 months, the mean HbA1c decrease was 1.03 +/- 0.33% in group A and 0.33 +/- 0.83% in group B. During the first visit, 52% of the patients in group A had pharmacologic treatment interventions, whereas only 27% in group B had such interventions. CONCLUSION: Rapid availability of the HbA1c results during the clinical encounter improves the ability of the physician to make appropriate therapeutic decisions and results in improved glycemic control.

[Clinical application of analysis of microsatellite markers in the prenatal diagnosis of cystic fibrosis]. / Mikroszatellita elemzés klinikai alkalmazása a cisztikus fibrózis praenatalis diagnosztikájában.

Cystic Fibrosis (CF) is an autosomal recessive hereditary disease, caused by the defect of a membrane transport protein. The defect is due to the mutation of the gene coding this protein. To date, these mutations have been analysed by direct mutational analyses in prenatal diagnosis. During gene sequencing, intragenic polymorphic markers (microsatellites) were identified, enabling the indirect analysis of the mutant allele. The markers characterize the given allele, so that the inheritance according to the Mendelian rules could be followed. We introduced a DNA-diagnostic method based on the amplification of three intragenic microsatellites. This new and efficient prenatal diagnostic tool would provide more reliable test results for previously screened CF families, in which direct mutation analysis was not informative.

Sequential pituitary MR imaging in Sheehan syndrome: report of 2 cases.

We present the evolution of pituitary changes in the cases of 2 patients with Sheehan syndrome as assessed by MR imaging. Both patients had severe postpartum hemorrhage, symptoms of pituitary gland apoplexy, and hypopituitarism. Sequential MR imaging demonstrated evidence of ischemic infarct in the pituitary gland with enlargement followed by gradual shrinkage during several months, to pituitary atrophy.

Obesity and cortisol status.

The fact, that obesity is a prominent feature of hypercortisolism (Cushing's syndrome) has stimulated investigation on the possible existence of the reverse relationship, namely that hypercortisolism is a feature of obesity. We have reviewed half a century of literature on this question, and have found out the following: (1) Hypercortisolism can exist in two forms: systemic hypercortisolism, in which there is an overall bodily excess of cortisol, and tissue, or intracellular, hypercortisolism, in which there is increased intracellular concentration of cortisol without an overall bodily excess. (2) There are two parameters of systemic hypercortisolism: CPR and plasma cortisol concentration. Proper evaluation of the first parameter requires correction for the active metabolic mass, which is best performed by expressing CPR per gram of urinary creatinine. The second parameter can be confounded by the marked moment-to-moment fluctuations in plasma cortisol concentrations due to cortisol's episodic secretion. Proper evaluation requires measuring the 24-hour mean concentration. Of these two parameters of systemic cortisol status, the plasma concentration is the more critical and accurate. (3) Corrected CPR is normal in obese individuals, and 24-hour mean plasma cortisol concentrations are slightly but definitely subnormal. This combination of findings indicates diminished stimulability of the hypothalamic-pituitary-adrenal (HPA) axis, which normally regulates bodily cortisol status. This deduction is supported by empirical studies on HPA reactivity. (4) Tissue hypercortisolism, due to increased intracellular activity of 11beta-HSD-1, which catalyzes reduction of cortisone to cortisol, has been reported in obese mice and humans. The findings of various studies are not consistent, and whether the enzymatic overactivity is a cause or a result of obesity is still unclear.

[Rutherford back-scattering spectrometry and photoelectron spectroscopy of the calcium/titanium interface]. / Etude par spectrométrie de rétrodiffusion de Rutherford (RBS) et par spectroscopie de photoélectrons (XPS) des interfaces calcium/titane.

Evaporation of calcium on commercially pure titanium was performed. Heatings under vacuum or oxygen flow improved calcium diffusion in the titanium substrate. X-Ray Photoelectron Spectroscopy did not revealed any superficial segregation of titanium but revealed the formation of CaCO3. The film formed on titanium was characterized using X-ray photoelectron spectroscopy with argon-ion sputtering. The results indicated that: the surface layer consisted of CaCO3; the interface contained CaCP3, CaO et TiO2; only CaO was present in the bulk titanium.