Severity of cardiovascular disease in postmenopausal women: associations with common estrogen receptor alpha polymorphic variants

OBJECTIVE: Impaired estrogen action is a risk factor for coronary artery disease (CAD). Associations of CAD with estrogen receptor alpha (ER alpha) polymorphisms, which may influence sensitivity to estrogen, have been reported for men; the data concerning women are not conclusive. We investigated the association of common ER alpha polymorphisms with the severity of CAD and with metabolic and reproductive factors in postmenopausal women undergoing coronary angiography. METHODS: ER alpha polymorphisms at positions c.454-397 T>C (PvuII) and c.454-351 A>G (XbaI) were studied in 157 women (age 45-88 years). The severity of CAD was assessed by the number of arteries with >50% stenosis in the angiography. RESULTS: There was a significant association between the TT, TC, and CC genotypes (PvuII) and the severity of CAD (P=0.008); similar results were obtained for the XbaI polymorphism (P=0.021). These associations were independent of other risk factors for CAD. Women homozygous for the C allele had significantly higher triglyceride and insulin levels; they belonged more frequently to the group with a low number of births (n相似文献   

Evidence for association of sex hormone-binding globulin and androgen receptor genes with semen quality

The roles of androgen receptor AR(CAG)n gene polymorphisms and sex hormone-binding globulin SHBG(TAAAA)n gene polymorphisms on semen quality were studied. One hundred fourteen men were included in the study: 85 with normal sperm count and 29 oligospermic. The genotype analysis, on DNA extracted from spermatozoa, revealed five SHBG(TAAAA)n alleles with 6–10 repeats and 18 AR(CAG)n alleles with 12–32 repeats. The SHBG allelic distribution showed that in men with normal sperm count and motility, those with short SHBG alleles had higher sperm concentration than men with long SHBG alleles ( P  = 0.039). As concerns AR(CAG)n polymorphisms, men with short AR alleles had lower sperm motility compared to those with long AR alleles ( P  < 0.001) in both total study population and normal sperm count men. The synergistic effect analysis of the two polymorphisms revealed an association between sperm motility ( P  = 0.036), because of the effect of AR(CAG)n polymorphism on sperm motility. In conclusion, long AR alleles were found to be associated with higher sperm motility, while short SHBG alleles were associated with higher sperm concentration, supporting the significance of these genes in spermatogenesis and semen quality.     

Short-term Cardiorespiratory Effects of Proportional Assist and Pressure-support Ventilation in Patients with Acute Lung Injury/Acute Respiratory Distress Syndrome

Background: Recent data indicate that assisted modes of mechanical ventilation improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a new mode of support that amplifies the ventilatory output of the patient effort and improves patient-ventilator synchrony. It is not known whether this mode may be used in patients with ALI/ARDS. The aim of this study was to compare the effects of PAV and pressure-support ventilation on breathing pattern, hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS due to sepsis.

Methods: Twelve mechanically ventilated patients with ALI/ARDS (mean ratio of partial pressure of arterial oxygen to fractional concentration of oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure-support ventilation and PAV in random order for 30 min while maintaining mean airway pressure constant. With both modes, the level of applied positive end-expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the end of each study period, cardiorespiratory data were obtained, and dead space to tidal volume ratio was measured.

Results: With both modes, none of the patients exhibited clinical signs of distress. With PAV, breathing frequency and cardiac index were slightly but significantly higher than the corresponding values with pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4 +/- 1.6 vs. 4.1 +/- 1.3 l [middle dot] min-1 [middle dot] m-2, respectively). None of the other parameters differ significantly between modes.     

The role of sex hormone-binding globulin and androgen receptor gene variants in the development of polycystic ovary syndrome

BACKGROUND: Polycystic ovary syndrome (PCOS) may be programmed in utero by androgen excess. Our aim was to examine the role of the sex hormone-binding globulin (SHBG) and androgen receptor (AR) gene polymorphisms, in the phenotypic expression of PCOS. METHODS: A cohort of 180 women with PCOS and 168 healthy women of reproductive age were investigated. BMI was recorded and the hormonal profile was determined on Day 3-5 of menstrual cycle. DNA was extracted from peripheral blood leucocytes and the SHBG(TAAAA)n and AR(CAG)n polymorphisms were genotyped by PCR. RESULTS: Genotype analysis revealed six SHBG(TAAAA)n alleles with 6-11 repeats and 19 AR(CAG)n alleles with 6-32 repeats, present in both PCOS and control women. Long SHBG(TAAAA)n alleles (>8 repeats) were at greater frequency in PCOS than normal women (P = 0.001), whereas short AR(CAG)n alleles (相似文献   

Estimation of inspiratory muscle pressure in critically ill patients

Background  

Recently, a new technology has been introduced aiming to monitor and improve patient ventilator interaction (PVI monitor). With the PVI monitor, a signal representing an estimation of the patient’s total inspiratory muscle pressure (Pmus_PVI) is calculated from the equation of motion, utilizing estimated values of resistance and elastance of the respiratory system.     

Association of estrogen receptor-alpha gene polymorphisms with stroke risk in patients with metabolic syndrome

Objective –  The vascular protective effects of estrogens are mediated by their binding to the two known estrogen receptors. In this study, we examine the association of stroke with two common polymorphisms of the ESR1 gene in patients with metabolic syndrome.
Materials and methods –  DNA from 130 patients hospitalized for ischemic stroke and 240 healthy controls were genotyped for ESR1 Pvu II and Xba I polymorphisms.
Results –  Comparing female and male patients, it was found that CCGG diplotype is more frequent in male patients ( P  = 0.03). In addition, the AA genotype is associated with the onset of stroke at a younger age in the male patient group ( P  < 0.05).
Conclusions –  These findings suggest that Pvu II and Xba I polymorphisms may affect the age at onset of the first stroke and the probability of developing cerebrovascular disease.     

Is proportional-assist ventilation with load-adjustable gain factors a user-friendly mode?

Objectives  The aim of this study was to compare the number of interventions (ventilator settings and sedatives, analgesics and vasoactive medication dose manipulations) between critically ill patients on proportional-assist ventilation with load-adjustable gain factors (PAV+) and those on pressure support (PS). Design  Retrospective analysis of data from a previous randomized clinical trial. Methods  A total of 208 patients who were mechanically ventilated on controlled modes and met criteria for assisted breathing were randomized to receive either PS (n = 100) or PAV+ (n = 108). Changes in ventilator settings and in the dose of sedatives, analgesics, and vasoactive medications were identified during the period in which the patients were ventilated either with PS (30.4 ± 17.4 h) or PAV+ (30.0 ± 18.1 h) and classified as changes to facilitate weaning (CFW) or changes to respond to deterioration (CD). Results  The mean number of changes in ventilator settings was significantly higher with PS than that with PAV+ (10.7 ± 5.7 vs. 8.9 ± 4.6). With PS the proportion of these changes classified as CFW was significantly lower than that with PAV+ (59.8% vs. 69.2%). Dyssynchrony as a cause of CD was more likely to occur with PS than with PAV+ (42 vs. 3%). The mean number of changes in the dose of sedatives, analgesics, and vasoactive medications was higher with PS than with PAV+, the difference being significant only for sedatives (4.06 ± 3.8 vs. 2.82 ± 3.4). Conclusions  Compared to PS, PAV+ is associated with fewer intervention in terms of ventilator settings and sedative dose changes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Association of SHBG gene polymorphism with menarche

The age of menarche may be subject to hereditary influencesbut the specific determinants are unknown. Our aim was to investigatethe possible association of a functional (TAAAA)_n polymorphismin the promoter of the sex hormone-binding globulin (SHBG) genewith the timing of menarche. This polymorphism has been associatedwith polycystic ovary syndrome (PCOS) and is considered to contributeto SHBG levels. We studied 130 healthy normal-weight adolescentfemales from a closed community in North–Western Greece.Information on menarche was obtained through interviews. TheBMI was recorded. Genomic DNA was isolated from peripheral bloodleukocytes for genotyping the TAAAA repeat region. We subdividedour subjects into two groups based on median age of menarche:those with menarche <13 years and those with menarche 13years. Genotype analysis revealed six (TAAAA)_n alleles containing5–10 TAAAA repeats. The distribution of alleles was differentin the two groups. Girls with late menarche had more frequentlylonger TAAAA alleles (>8 repeats), while girls with early menarchehad shorter alleles at a greater frequency (P=0.048). The majorcontribution to early menarche was by the 6 TAAAA repeat allele.Furthermore, carriers of the longer allele genotypes had latermenarche (13.24±1.15 years) than those with shorter allelegenotypes (12.67±1.15, P=0.018). These findings provideevidence for a genetic contribution of SHBG gene to the ageof menarche.