Cortisol/glucocorticoid receptor: a critical mediator of the ovulatory process and luteinization in human periovulatory follicles.

STUDY QUESTION: Do cortisol/glucocorticoid receptors play an active role in the human ovary during ovulation and early luteinization? SUMMARY ANSWER: The ovulatory hCG stimulation-induced glucocorticoid receptor signaling plays a crucial role in regulating steroidogenesis and ovulatory cascade in human periovulatory follicles. WHAT IS KNOWN ALREADY: Previous studies reported an increase in cortisol levels in the human follicular fluid after the LH surge or ovulatory hCG administration. However, little is known about the role of cortisol/glucocorticoid receptors in the ovulatory process and luteinization in humans. STUDY DESIGN, SIZE, DURATION: This study was an experimental prospective clinical and laboratory-based study. An in vivo experimental study was accomplished utilizing the dominant ovarian follicles from 38 premenopausal women undergoing laparoscopic sterilization. An in vitro experimental study was completed using the primary human granulosa/lutein cells (hGLC) from 26 premenopausal women undergoing IVF. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted in a private fertility clinic and academic medical centers. Dominant ovarian follicles were collected before the LH surge and at defined times after hCG administration from women undergoing laparoscopic sterilization. Primary hGLC were collected from women undergoing IVF. hGLC were treated without or with hCG in the absence or presence of RU486 (20 µM; dual antagonist for progesterone receptor and glucocorticoid receptor) or CORT125281 (50 µM; selective glucocorticoid receptor antagonist) for 12 or 36 h. The expression of genes involved in glucocorticoid receptor signaling, steroidogenesis, and ovulatory cascade was studied with RT-quantitative PCR and western blotting. The production of cortisol, corticosterone, and progesterone was assessed by hormone assay kits. MAIN RESULTS AND THE ROLE OF CHANCE: hCG administration upregulated the expression of hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1), nuclear receptor subfamily 3 group C member 1 (NR3C1), FKBP prolyl isomerase 5 (FKBP5), and FKBP prolyl isomerase 4 (FKBP4) in human ovulatory follicles and in hGLC (P < 0.05). RU486 and CORT125281 reduced hCG-induced increases in progesterone and cortisol production in hGLC. The expression of genes involved in glucocorticoid receptor signaling, steroidogenesis, and the key ovulatory process was reduced by RU486 and/or CORT125281 in hGLC. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The role of cortisol/glucocorticoid receptors demonstrated using the hGLC model may not fully reflect their physiological roles in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Successful ovulation and luteinization are essential for female fertility. Women with dysregulated cortisol levels often suffer from anovulatory infertility. Deciphering the functional role of glucocorticoid receptor signaling in human periovulatory follicles enhances our knowledge of basic ovarian physiology and may provide therapeutic insights into treating infertility in women. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by P01HD71875 (to M.J., T.E.C., and M.B.) and R01HD096077 (to M.J.) from the Foundation for the National Institutes of Health and the BTPSRF of the University of Kentucky Markey Cancer Center (P30CA177558). The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Effects of substance use screening and brief intervention on health-related quality of life.

PURPOSE: Screening, brief intervention, and referral to treatment interventions have been shown to positively impact alcohol use. These programs utilize motivational interviewing techniques in an effort to reduce risky substance use among those at elevated risk of developing a disorder. However, there is a dearth of research assessing positive impacts above and beyond changes in alcohol use. This study examines potential benefits of brief interventions, utilizing motivation interviewing, on mental and physical quality of life. METHODS: The present quasi-experimental study examined changes in health-related quality of life among individuals presenting at urban emergency departments. The analyses included the use of propensity score matching to minimize potential biases resulting from differences between groups at baseline. RESULTS: The results indicated that the intervention group experienced significant increases in perceptions of mental health over those of the comparison group, regardless of changes in substance use. CONCLUSIONS: These findings have implications for practice, as they suggest that brief substance abuse interventions delivered in the emergency department settings may have effects beyond those targeted by the intervention. Specifically, brief substance abuse interventions may positively impact mental health, thus enhancing the quality of life among targets of the intervention.

Analysis of hemodynamic changes during beating heart surgical procedures.

BACKGROUND: Coronary artery bypass grafting on the beating heart causes significant hemodynamic compromise during displacement of the heart. The precise mechanisms causing altered hemodynamics have not been clearly understood. The purpose of this study was to define the hemodynamic changes caused by displacing the heart in patients undergoing beating heart surgical procedures. METHODS: Forty-four patients (35 men, 9 women; mean age, 64.5 +/- 9.6 years) underwent off-pump coronary artery bypass grafting. The hemodynamic variables were collected before and after positioning the heart for anastomosis of the left anterior descending, circumflex, and posterior descending coronary arteries. RESULTS: There was a significant increase in right ventricular end-diastolic pressure during positioning for all vessels, and in left ventricular end-diastolic pressure during positioning for the left anterior descending and circumflex coronary arteries. Positioning for the circumflex artery showed the largest increase of left and right ventricular end-diastolic pressure, resulting in the greatest hemodynamic compromise. CONCLUSIONS: In the clinical setting of diseased human hearts, there is a biventricular contribution to altered hemodynamics. The increase of right ventricular end-diastolic pressure in all positions suggests that the major cause of hemodynamic changes is disturbed diastolic filling of the right ventricle, especially by direct ventricular compression.

Right heart circulatory support facilities coronary artery bypass without cardiopulmonary bypass.

BACKGROUND: Revascularization of the posterior wall often causes hemodynamic instability in beating heart coronary artery bypass (CAB). Our previous clinical studies have shown that tilting the heart primarily alters right-heart hemodynamics. The purpose of this study was to evaluate right-heart support in clinical cases. METHODS: Seventeen patients underwent beating heart CAB with right-heart support. The right-heart support system (A-Med Systems, West Sacramento, CA) consisted of a coaxial cannula placed through the right atrium and the tip of the cannula positioned in main pulmonary artery. Blood was removed from the right atrium and returned to the main pulmonary artery. RESULTS: Elective beating heart CAB was accomplished successfully in 17 patients with right-heart support. Anastomoses performed were left anterior descending coronary artery (11), diagonal (3), circumflex (5), obtuse marginal artery (11), and right coronary artery (10). Right-heart support between 1 and 3 L/min improved hemodynamics especially in the circumflex position. No device-related patient incidents occurred, nor were there incidents of infection or air embolism. All 17 patients were discharged to their homes. CONCLUSIONS: The right-heart support system was safe without complications. Exposure of the posterior wall was possible in all cases without hemodynamic compromise.

Health-care facility choice and the phenomenon of bypassing.

Health policy-makers in developing countries are often disturbed and to a degree surprised by the phenomenon of the ill travelling past a free or subsidized local public clinic (or other public facility) to get to an alternative source of care at which they often pay a considerable amount for health care. That a person bypasses a facility is almost certainly indicative either of significant problems with the quality of care at the bypassed facility or of significantly better care at the alternative source of care chosen. When it is a poor person choosing to bypass a free public facility and pay for care further away, such action is especially bothersome to public policy-makers. This paper uses a unique data set, with a health facility survey in which all health facilities are identified, surveyed, and located geographically; and a household survey in which a sample of households from the same health district is also both surveyed and located geographically. The data are analyzed to examine patterns of health care choice related to the characteristics and locations of both the facilities and actual and potential clients. Rather than using the distance travelled or some other general choice of type of care variable as the dependent variable, we are able actually to analyze which specific facilities are bypassed and which chosen. The findings are instructive. That bypassing behaviour is not very different across income groups is certainly noteworthy, as is the fact that the more severely ill tend to bypass and to travel further for care than do the less severely ill. In multivariate analysis almost all characteristics of both providers and facilities are found to have the a priori expected relationships to facility choice. Prices tend to deter use, and improved quality of services to increase the likelihood of a facility being chosen. The answer to the bypassing dilemma seems to be for providers to provide as good quality care relative to the money charged (if any), as other, often further away, providers.

MIDCAB characteristics and results: the CardioThoracic Systems (CTS) registry.

OBJECTIVE: The CardioThoracic Systems (CTS) registry of minimally invasive direct coronary artery bypass (MIDCAB) was established to examine baseline characteristics of patients undergoing this surgical procedure, document details of the procedures including grafting techniques and post-operative complication rates, and assess post-operative graft patency. METHODS: A total of 508 consecutive patients who had MIDCAB using CTS instrumentation between April 1996 and March 1997 at 35 international centers were analyzed. RESULTS: The mean age of patients, 27% of whom were women, was 63 years. Eight percent had previous coronary artery bypass surgery. While nearly all patients had significant stenoses in the left anterior descending artery, 23% had disease in two vessels and 9% in three vessels. Almost all procedures used the left internal mammary artery, with 7% employing multiple or sequential grafts. The entire surgical procedure lasted on average 135 min (median 2 h), with a mean time of 14 min to perform anastomosis. Surgical approaches, including anastomosis technique and method used to maintain bloodless field, varied widely across clinical centers. In-hospital complication rates were relatively low, with 0.6% mortality (0% perioperative), 1.2% conversion to sternotomy with cardiopulmonary bypass, 1.4% conversion to sternotomy without bypass, and 5.5% redo or reintervention. In total, 92% of patients were free from all of these events at hospital discharge; women showed a strong trend toward increased risk for major in-hospital events compared with men. Rib fracture was the most common complication, reported in 12% of patients. Post-operative angiography, performed in 83 patients at an average 2.2 days post-procedure, found full patency in 78 (94%). CONCLUSIONS: The CTS registry data indicates that in the great majority of patients, MIDCAB using CTS instrumentation was performed safely and with acute success. Comparative studies, most importantly clinical trials, are needed to determine the types of patients who benefit most from this procedure, as well as its longer-term outcome.

Price elasticities of demand for curative health care with control for sample selectivity on endogenous illness: an analysis for Sri Lanka.

Estimation of demand for health care with samples of only the ill may bias estimates. Additionally, the lack of exogenous information, especially distance, about the alternative care providers causes omitted variable problems. This paper alleviates both problems through geographic mapping of facility information to individuals, combined with joint estimation of illness (health production) and health care demand. The joint estimation full sample demand results are compared to those from one equation estimation for only the ill sample. The results indicate that the selectivity problem is significant, but that for this sample the magnitude of the bias on the price coefficient is small.

Trends in health services utilization in eight provinces in China, 1989-1993.

Continued pursuit of market-oriented reforms in China seems to have resulted in increasing income disparities. This has raised concerns about possible declines in the use of health services by the poor. Using data from three waves of the China Health and Nutrition Survey (1989, 1991, 1993), we examine whether people age 20-45 in eight provinces became less likely to seek care when ill. We carried out three probit estimations of seeking care when ill; the predictor variables include individual and workplace characteristics, a measure of the severity of illness and community level factors. Health care is broadly defined to include basic level clinics as well as urban hospitals. We find no evidence that health care utilization is decreasing. Rather, for people in a community survey reporting mainly mild or moderate illness, health care continues to be accessible. We consider possible limits of our study and discuss extensively the implications of the use of illness reports from the three cross-sectional surveys as health status indicators.

Safe and effective method of stabilization for coronary artery bypass grafting on the beating heart.

BACKGROUND: There is an emerging interest in performing coronary artery bypass grafting on the beating heart. This study examines the efficacy and safety of two types of coronary artery stabilizers developed to perform coronary artery bypass grafting on the beating heart. METHODS: Four dogs underwent left internal mammary artery to left anterior descending artery anastomosis using a retractor-fixed stabilizer. Measurements of hemodynamic indices and range of motion of the targeted arteriotomy were done before and after application of the stabilizers. Patency of the anastomosis was evaluated by angiography. To clinically validate the safety of this stabilizer, we collected data on 150 patients from centers that had access to the retractor-fixed stabilizer. RESULTS: All animals survived the procedure with no ischemic changes or hemodynamic alterations. A significant reduction in range of motion (mm) of the left anterior descending coronary artery was achieved after application of the stabilizers. Angiographic studies showed good anastomotic patency. Histologic examination showed no myocardial injury. Patient data revealed successful completion of the anastomosis, with conversion to sternotomy or cardiopulmonary bypass in 1 patient each. Intraoperative and postoperative myocardial infarctions occurred in 1 patient each, with one in-hospital death. CONCLUSIONS: Significant stabilization of targeted coronary arteries allowing the performance of safe and reliable anastomosis on a beating heart can be achieved using the stabilizer.

Effect of provider characteristics on choice of contraceptive provider: a two-equation full-information maximum-likelihood estimation.

We use surveys of households and health-care facilities conducted in the same area at the same time to determine which characteristics of providers attract users of contraceptives. By using the full-information maximum-likelihood technique to jointly estimate choice of contraceptive method and choice of provider, we avoid self-selection bias. Results support the need for modeling quality and for jointly estimating the choice of contraceptive method and the choice of provider to avoid biased estimates of coefficients. The results suggest that for the Cebu, Philippines region, small local clinics that focus on family planning tend to be most favored by clients.

Effect of porous coating and loading conditions on total hip femoral stem stability.

An examination of femoral bone-prosthesis interface behavior under different load types is undertaken using finite-element analysis. Three-dimensional finite-element models are made of two designs of hip prostheses after implantation in a femur. Femoral geometry was determined by computed tomography scans. The models were loaded in one-legged stance and stairclimbing configurations. The implants were modeled as both smooth surfaced and porous coated. The amount of contact and the relative motion between bone and implant were calculated. It is shown that torsional loads such as occur during stairclimbing contribute to larger amounts of implant micromotion than does stance loading. Contact at the bone-prosthesis interface is more dependent on load type than on implant geometry or surface coating type.

Distribution of medical insurance in China.

This paper investigates factors related to the distribution of medical insurance coverage in China, using information from an eight-province household survey of almost 16,000 individuals, conducted in 1989. Results of bivariate analyses show that medical insurance coverage, defined very broadly, varies considerably by individual and regional characteristics. Age, gender, education, occupation, employment sector, urbanization, level of industrial and commercial development, and province are all related to being insured or not. In addition, we find that the type of insurance program available to people varies by these same factors, and that the benefits provided by the seemingly uniform public and worker programs also vary, especially by province and degree of urban development. When the individual and regional variables are considered together in logistic regression analyses, the factors most strongly statistically related to the likelihood of being insured are where one works and where one lives. The distribution of insurance benefits in China appears to result in a pattern in which the rural and the poor, who are often at great risk of illness, are less likely to have medical insurance.

Quality of services and demand for health care in Nigeria: a multinomial probit estimation.

This study attempts to empirically answer three important policy questions for a population sample from Ogun State, Nigeria: 1. Would price (fee) increases for health care lead to large reductions of care usage or to shifts across types of care used? 2. Would price increases lead to net increases in revenues for the health system? 3. Would the price increases have larger impacts (in the form of reductions in health care usage) on lower income members of the population? Household data are combined with data on prices and quality of care, collected directly from facilities, to estimate the demand for outpatient health care. Many of the statistical problems of demand estimation with micro level data are avoided by an innovation--the first use of the multinomial probit estimation method for health demand. A separate but related problem, that the price data used in such studies are usually endogenous (in fact usually are expenditures, which are to a great degree determined by the actual care choice) is avoided by the collection of a specific exogenous price variable directly from the health providers. Because the health care 'good'--outpatient health care--can vary to such a degree across providers, quality of care must be controlled in order that the coefficients on prices and other variables will not be biased. A strong circumstantial case can be made that past estimation efforts probably underestimated the impact of prices of care on provider choices, because those providers charging higher prices also tend to provide higher quality care and those charging lower prices to provide care of lower quality. Because of this fear of bias on the extremely important price coefficient, effective control of the quality of the care available at the alternative accessible care providers is almost certainly at this time the most important marginal innovation to demand estimation. Most past researchers simply have not had available to them exogenous quality of care information collected via a facility (provider) survey. This study tried several health care provider quality variables and finally used three distinct variables which were statistically significant: (a) expenditure per person in population served; (b) percentage of times drugs are available; and (c) interviewers evaluation of the physical condition of the facility. Price of a visit to the facility is also included, and also is an exogenous variable collected directly from the alternative available providers. For the variables of most interest for this study, price and quality of care, the results are quite reasonable and much as expected.(ABSTRACT TRUNCATED AT 250 WORDS)

Equity and the utilization of health services: report of an eight-province survey in China.

This paper investigates equity with respect to one component of welfare in China--the provision and use of health services. Based upon a large-scale survey of almost 16,000 individuals in eight provinces in China, we examine a sub-sample of working-age adults who have identified themselves as injured or ill during the four weeks prior to being interviewed. We found that, beyond the level of severity of the reported condition, very few individual-level factors are related to the use of services when ill or injured. Only gender (female) and employment in state-run enterprises are associated with higher patterns of use. These results suggest that China has achieved a very wide distribution of clinics and other services at the local level, and that they are widely used by those who identify need for them. It is rare to be over half an hour away by bike from some form of care and the majority of care appears to be reasonably inexpensive. This broad availability of services contrasts with recent reports from China stressing declining accessibility, and paints a picture of relatively equal access to health care.

Nutrition, lactation, and birth spacing in Filipino women.

The Cebu Longitudinal Health and Nutrition Survey is used to examine the roles of women's nutrition and infant feeding in determining time from birth to menses and time from menses to conception. The analysis sample includes 2,648 Filipino women followed for 24 months postpartum. Recently devised statistical estimation techniques to control for unobserved heterogeneity and endogeneity are employed in estimating a two-state hazard model. Low body mass index and lower dietary fat intake are associated with increased duration of postpartum amenorrhea. Contraceptive use, high dietary fat consumption, higher parity, and absence of spouse predict a longer waiting time to conception once menses have returned. Simulation of the hazard model is used to examine the effects of the key nutrition and lactation factors.

The effects of baseline ovarian cysts on cycle fecundity in controlled ovarian hyperstimulation.

Patients undergoing COH were prospectively studied in 174 cycles for the presence of baseline ovarian cysts. In 37.4% of all cycles, a baseline cyst > 10 mm mean diameter was found, but a cyst was more common in subsequent cycles than on the first (41.5% versus 15.8%). Cycle fecundity as determined by life table analysis was significantly higher if no baseline cyst were present (0.25 versus 0.06, P > 0.01). These findings suggest that baseline ovarian cysts may adversely affect the chances for pregnancy in COH not associated with IVF or GIFT.

The use of clomiphene citrate in the treatment of azoospermia secondary to incomplete androgen resistance.

An infertile male with a deletion within the AR gene is discussed. The patient presented with azoospermia and, after daily CC treatment, was found to have sperm within his ejaculate. However, the ultimate goal of pregnancy was not achieved, nor were there enough sperm present to warrant an IVF attempt.

Growth dynamics during the first two years of life: a prospective study in the Philippines.

This study examines determinants of growth from birth to 24 months in a sample of approximately 3000 urban and rural Filipino children. Individual, household, and community data were collected bimonthly during the Cebu Longitudinal Health and Nutrition Survey. Separate longitudinal, multivariate models were used to identify determinants of weight in children from birth to 6 months and 6-24 months of age. Previous weight, male gender, mother's height, and season of the year showed significant positive associations with weight in all models. Full and mixed breast-feeding significantly increased weight, but the effects of breast-feeding declined as children got older. Breast-feeding had a direct growth-enhancing effect in addition to its indirect effect through the prevention of diarrheal morbidity. Detrimental effects of recent diarrheal morbidity were particularly important in the older age group, but these effects were mitigated by breast-feeding. Since infant feeding variables are included in the models, the results strongly suggest an effect of diarrheal morbidity on growth independent of its known effects on infant feeding and dietary intake. Febrile respiratory infections had important detrimental effects on weight in both age groups.