Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Actuarial survival in the premature infant less than 30 weeks' gestation

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.     

Antisense RNA-mediated reduction of p53 induces malignant phenotype in nontumorigenic rat urothelial cells

p53 mutation is commonly associated with high-grade, high-stage human urothelial carcinomas. Recent studies suggest that p53 mutation in low- grade, low-stage bladder carcinomas may be correlated with the progression of the disease. In the present study, we used antisense RNA methodology in vitro to evaluate the significance of the loss of p53 function at an early stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA in antisense orientation. The transfection resulted in a significant reduction in p53 mRNA expression and protein synthesis, in stimulation of anchorage- dependent growth, and in acquisition of anchorage-independent growth potential. Three such clones, when tested in athymic nude mice, all formed muscle-invasive, high-grade transitional cell carcinomas at s.c. injection sites. When cells were inoculated into an orthotopic site (urinary bladder), one of two antisense transfectants tested formed bulky tumors in the bladder in all seven nude mice and metastases to lungs in three of the seven mice. Analysis of these cells revealed a decrease in the expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene product. Phosphorylation of Rb protein was not inhibited when the cells were starved. No significant difference was observed in the expression of p16 protein. In cell cycle analysis, all antisense transfectants tested escaped from G1 arrest by starvation. Furthermore, secretion of interleukin (IL)-6 into culture medium was increased significantly. Treatment with anti-IL-6 antibody suppressed anchorage-dependent growth. This study directly demonstrates that the loss of p53 function at an early stage of urothelial carcinogenesis may result in acquisition of a malignant phenotype by regulating IL-6 production as well as cell cycle related genes.      

The metabolic syndrome among postmenopausal women in Ecuador.

BACKGROUND: The prevalence of the metabolic syndrome increases with age and after the onset of menopause, and may explain in part the apparent acceleration of cardiovascular disease in postmenopausal women. OBJECTIVE: To determine the prevalence of metabolic syndrome and related risk determinants among postmenopausal women in Ecuador. METHODS: Postmenopausal women >or=40 years of age, non-users of hormone therapy and with an intact uterus, were asked to participate in a metabolic syndrome screening and educational program at the Institute of Biomedicine of the Universidad Católica of Guayaquil, Ecuador. Sociodemographic data, waist circumference and blood pressure measurements were recorded, and a fasting blood sample obtained for serum glucose and lipid profile determinations. Woman were counseled and managed according to the results. Metabolic syndrome was defined in accordance with the criteria of the Third Adult Treatment Panel (ATP III). RESULTS: Three hundred and twenty-five postmenopausal women entered the program. Mean (+/-standard deviation) age was 55.9 +/- 8.1 years, 53.5% of them were aged >or=54 years (median). The prevalence of metabolic syndrome, according to ATP III criteria, was 41.5%. Using the same criteria, 38.8%, 16.6%, 56.9% and 54.2% of the women presented with hypertension, diabetes, hypertriglyceridemia and abdominal obesity, respectively. More than 40% of women determined to have hypertension or diabetes lacked knowing so. Logistic regression analysis determined that age increased the risk of presenting hypertension and diabetes (odds ratio (95% confidence interval): 2.0 (1.2-3.2) and 1.6 (0.9-3.0), respectively, p < 0.05), entities which in turn duplicated the risk of having high triglyceride levels. Sedentary women with <5 years since menopause onset were at higher risk of having abdominal obesity, which was directly related to diabetes and hypertension. CONCLUSIONS: In this postmenopausal Ecuadorian population the prevalence of the metabolic syndrome was high and its determinant factors related to age, time since menopause onset and sedentary habits. Because of the implications for cardiovascular risk, counseling programs directed toward high-risk populations should be encouraged.     

Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups: 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P<00001). A higher percentage of African Americans were treated with PDE-5i vs. those who were not (10.5% vs. 7.1% P<0.0001). The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs. 13.1% P=0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs. 35.1% P=0.0149). Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio: 0.4; 95% confidence intervals: 0.3–0.5; P<0.0001) of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of being diagnosed with prostate cancer. Further research is warranted.     

Residual Infestation and Recolonization during Urban Triatoma infestans Bug Control Campaign,Peru

Chagas disease vector control campaigns are being conducted in Latin America, but little is known about medium-term or long-term effectiveness of these efforts, especially in urban areas. After analyzing entomologic data for 56,491 households during the treatment phase of a Triatoma infestans bug control campaign in Arequipa, Peru, during 2003–2011, we estimated that 97.1% of residual infestations are attributable to untreated households. Multivariate models for the surveillance phase of the campaign obtained during 2009–2012 confirm that nonparticipation in the initial treatment phase is a major risk factor (odds ratio [OR] 21.5, 95% CI 3.35–138). Infestation during surveillance also increased over time (OR 1.55, 95% CI 1.15–2.09 per year). In addition, we observed a negative interaction between nonparticipation and time (OR 0.73, 95% CI 0.53–0.99), suggesting that recolonization by vectors progressively dilutes risk associated with nonparticipation. Although the treatment phase was effective, recolonization in untreated households threatens the long-term success of vector control.