Determinants of the effect of estrogen on the progression of subclinical atherosclerosis: Estrogen in the Prevention of Atherosclerosis Trial

OBJECTIVE: To determine the extent to which the estrogen-induced changes in lipids and markers of carbohydrate metabolism explain the beneficial effect of estrogen therapy on the progression of carotid artery intima-media thickness (IMT) in postmenopausal women. DESIGN: A randomized, double-blind, placebo-controlled, single-center trial enrolling 222 postmenopausal women 45 years and older without cardiovascular disease and with low-density lipoprotein (LDL) cholesterol levels of 3.37 mmol/L or greater (> or = 130 mg/dL). Intervention was unopposed micronized 17beta-estradiol versus placebo. Measurements were made using high-resolution B-mode ultrasonography to measure carotid artery IMT at baseline and every 6 months on-trial. RESULTS: Progression of carotid IMT was inversely related to on-trial high-density lipoprotein (HDL) cholesterol (P = 0.04) and was directly related to on-trial LDL-cholesterol (P = 0.005). Compared with placebo, women randomized to estradiol showed a higher mean on-trial HDL-cholesterol level and a lower mean on-trial LDL-cholesterol level. In contrast, fasting glucose, insulin, and hemoglobin A1C were lowered and insulin sensitivity increased with estradiol therapy, but the changes were not related to carotid IMT progression. On-trial HDL-cholesterol and LDL-cholesterol were significant independent determinants of carotid IMT progression, jointly explaining 30% of the treatment effect of unopposed estrogen on the progression of carotid IMT. CONCLUSION: Unopposed 17beta-estradiol reduced carotid IMT progression in postmenopausal women in part by increasing HDL-cholesterol and decreasing LDL-cholesterol. Although women randomized to estradiol showed improvement in all the markers of carbohydrate metabolism, these factors did not play a significant role in carotid IMT progression.     

Longitudinal growth of Bangladeshi infants during the first year of life

The growth in length and weight of 91 poor urban Bangladeshi infants was monitored at monthly intervals from birth to 1 year. At birth 18%, 22% and 8% were below -2.00 standard deviations of the National Center for Health Statistics (NCHS) height-for-age, weight-for-age and weight-for-height, respectively and at 1 year the percentages were 40%, 40% and 7%. Infant weights over the first 6 months associated positively with both mother's BMI and percentage body fat. Higher mean infant weights from 6 to 12 months were associated with both higher educational status of the mother and monthly family income and the latter two variables provided the best model for predicting weight velocity from birth to 12 months. Internal Z-scores, corrected for day of measurement, provided clear evidence of catch-up/catch-down over the first 6 months with heavier and longer babies at birth showing catch-down while lighter and shorter babies demonstrated catch-up. Infants' weights were almost three times more variable than lengths. Monthly incremental variability of both infant weight and length increased sharply from 6 to 12 months with weight showing significantly more variability. The correlations of birth weight and length with subsequent distances and monthly increment revealed that the first 6 months were dominated by catch-up and catch-down but during the latter half of the year the growth phenomena were influenced mainly by earlier intra-uterine or genetic effects.     

A light and electron microscopic study of osteodentin formation in the rat incisor after adriamycin administration

The effect of adriamycin (10 mg/kg body weight) on the rat incisor was investigated in 8-day-old animals at 9 days and 14 days after subcutaneous injection. The drug produced changes that were still present 14 days after administration. During this time osteodentin formation, which appeared to be the principal effect of the drug on the incisors, occurred to such an extent that in some regions of the teeth the pulp chamber was almost completely occluded. The formation of osteodentin began at the periphery of the pulp and gradually advanced towards the central region. Moreover, in some sections of the incisor the dentin layer was greatly reduced to a thin superficial layer, while osteodentin surrounded most of the pulp chamber. Cells that appeared to be differentiated pulp-mesenchymal cells were found within as well as on the surface of the irregular osteodentin matrix. Since this drug has been used in the treatment of childhood osteosarcomas, the possibility of dental abnormalities developing in these children cannot be overlooked.     

Persistence of hepatitis B antigen in Culex quinquefasciatus (Diptera: Culicidae)

Groups of wild-caught Culex quinquefaciatus Say, previously tested for the presence of hepatitis B surface antigen (HBsAg), were tested for the presence of hepatitis B e antigen (HBeAg). This antigen was detected at low levels in blood-fed, half-gravid, and gravid groups. A colony of Cx. quinquefasciatus was established in the laboratory and tested for the persistence of HBsAg and HBeAg. Five days after feeding on blood infected with HBsAg and HBeAg, 9 of 20 (45%) pools of Cx. quinquefasciatus were HBeAg-positive and 5 of 20 (25%) pools were HBeAg-positive; low levels of HBsAg and HBeAg were still detectable 28 d after the infective meal in 2 of 20 (10%) and 1 of 20 (5%) pools, respectively. A crude protease extract was prepared from colony mosquitoes, and the effect of this extract on HBsAg and HBeAg present in human serum was tested in vitro. After 20 h, tests for both antigens were still strongly positive. Low levels of HBsAg were detected in ovaries 7 d after infection. Salivary glands were HBsAg- and HBeAg-negative.     

Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse)

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is a rare disorder of the chemical control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH-1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway because it controls the development of neurons with a definitive or transient noradrenergic phenotype, upstream from the RET receptor tyrosine kinase and tyrosine hydroxylase. We recently showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases. We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients. To analyze the functional consequences of HASH-1 mutations, we developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest, reproducing in vitro the HASH-PHOX-RET pathway. All HASH-1 mutant alleles impaired noradrenergic neuronal development, when overexpressed from adenoviral constructs. Thus, HASH-1 mutations may contribute to the CCHS phenotype in rare cases, consistent with the view that the abnormal chemical control of breathing observed in CCHS patients is due to the impairment of noradrenergic neurons during early steps of brainstem development.     

A locus for autosomal dominant anterior polar cataract on chromosome 17p

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.      

Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study

BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.