Motherhood and HIV risk among female sex workers in Andhra Pradesh, India: the need to consider women's life contexts.

This study examines whether the challenges of motherhood among female sex workers (FSW) are linked with vulnerability to sexual risk factors for HIV. FSW at least 18 years of age (n = 850) were recruited through respondent driven sampling for a survey on HIV risk in the Rajahmundry area of Andhra Pradesh, India. Logistic regression models adjusted for demographic characteristics were used to assess the relation between reported caretaking challenges and sexual risk indicators for HIV. In adjusted logistic regression models, FSW who reported three or more children in their household or current child health concerns were significantly less likely to report consistent condom use (adjusted odds ratios (AORs) range: 0.5-0.6) and more likely to take more money for sex without a condom (both AORs: 2.5). Women who reported current child health concerns were also more likely to report an STI symptom in the past 6 months (AOR = 1.6; 95 % confidence interval: 1.1-2.3). Findings suggest that challenging responsibilities related to caretaking of children are associated with heightened vulnerability to HIV risk among FSW. Such findings add to the cumulating evidence urging for the implementation of HIV prevention interventions that consider the multiple challenges across various domains of women's lives.

Migration/mobility and risk factors for HIV among female sex workers in Andhra Pradesh, India: implications for HIV prevention.

We examined the relation between high mobility/migration (sex work in three or more villages/towns within the past year) and HIV risk factors among a sample of female sex workers (FSWs) in Andhra Pradesh, India. We recruited FSWs aged ≥18 years (n = 673) through respondent-driven sampling for a survey on HIV risk. Adjusted logistic and linear regression models assessed high mobility in relation to sexual and physical victimization, sexually transmitted infection (STI) symptoms and treatment, condom use and negotiation, number and/or types of sex trades, number of clients and number of days worked. Twelve percent (n = 82) of FSWs were highly mobile; those with high mobility were more likely to report recent HIV risk factors: sexual violence (adjusted odds ratio [AOR] = 5.2; 95% confidence interval [CI]: 3.0-8.9), physical violence (AOR = 1.7; 95% CI: 1.1-2.7), unprotected sex for more money (AOR = 1.7; 95% CI: 1.1-3.0), at least one STI symptom (AOR = 1.9; 95% CI: 1.1-3.1), a greater number of vaginal sex trades (ß = 3.9, P = 0.003), a greater number of clients (ß = 2.5, P = 0.02) and anal sex with clients (AOR = 2.4; 95% CI: 1.4-4.1). Findings from this study underscore the violence and HIV-related vulnerability faced by mobile/migrant FSWs and highlight the need to inform and tailor related prevention strategies.

Structural interventions: concepts, challenges and opportunities for research.

Structural interventions refer to public health interventions that promote health by altering the structural context within which health is produced and reproduced. They draw on concepts from multiple disciplines, including public health, psychiatry, and psychology, in which attention to interventions is common, and sociology and political economy, where structure is a familiar, if contested, concept. This has meant that even as discussions of structural interventions bring together researchers from various fields, they can get stalled in debates over definitions. In this paper, we seek to move these discussions forward by highlighting a number of critical issues raised by structural interventions, and the subsequent implications of these for research.

The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA.

Calcium transport across a monolayer of Madin-Darby canine kidney (MDCK) cells was measured in response to stimulation of the basal surface with calcium-sensing receptor (CaR) agonists. Stimulation of the CaR resulted in a time- and concentration-dependent inhibition of calcium transport but did not change transepithelial voltage or resistance. Inhibition of transport was not altered by pretreatment of cells with pertussis toxin but was blocked by the phospholipase C (PLC) inhibitor U-73122. To determine a potential mechanism by which the CaR could inhibit calcium transport, we measured activity of the plasma membrane calcium ATPase (PMCA). Stimulation of the CaR on the basal surface resulted in an inhibition of the PMCA in a concentration- and PLC-dependent manner. Thus stimulation of the CaR inhibits both calcium transport and PMCA activity through a PLC-dependent pathway. These studies provide the first direct evidence that calcium can inhibit its own transcellular absorption in a model of the distal tubule. In addition, they provide a potential mechanism for the CaR to inhibit calcium transport, inhibition of PMCA.

Structural interventions in public health.

OBJECTIVE: To review structural interventions in public health, identify distinct approaches to structural interventions, and assess their implications for HIV-prevention interventions. METHOD: The MEDLINE, HealthStar, PsychInfo and Sociofile databases were searched on specific health issues, types of public health interventions, and conceptual topics (e.g. empowerment, social structure, and inequality) to compile a list of public health interventions in the United States. We excluded interventions focused on testing and surveillance unless they specifically facilitated prevention, and educational or media campaigns focused on increasing individuals' level of knowledge about a particular health problem. RESULTS: The term 'structural' is used to refer to interventions that work by altering the context within which health is produced or reproduced. Structural interventions locate the source of public-health problems in factors in the social, economic and political environments that shape and constrain individual, community, and societal health outcomes. We identified two dimensions along which structural interventions can vary. They may locate the source of health problems in factors relating to availability, acceptability, or accessibility; and they may be targeted at the individual, organizational, or environmental levels. All together, this framework suggests nine kinds of structural interventions, and it is possible to identify examples of each kind of intervention across a range of public health issues. CONCLUSIONS: The relevance of this framework for developing HIV prevention interventions is considered.

Tyrosine phosphorylation of human platelet plasma membrane Ca(2+)-ATPase in hypertension.

Intracellular Ca(2+) is increased in the platelets of hypertensive individuals. Previously, we demonstrated that platelet plasma membrane Ca(2+)-ATPase (PMCA) activity inversely correlates with diastolic blood pressure and that inhibition of this Ca(2+) pump could explain the elevation of cytosolic Ca(2+) in hypertension. More recently, we discovered that PMCA is phosphorylated on tyrosine residues during thrombin-stimulated platelet aggregation and that this phosphorylation causes inhibition of PMCA activity. In the present work, we tested the hypothesis that tyrosine phosphorylation of PMCA in hypertensive patients could account for the observed inhibition of the Ca(2+) pump. Platelets were obtained from untreated hypertensive and normotensive volunteers. PMCA was immunoprecipitated from solubilized platelets, and tyrosine phosphorylation was quantified by chemiluminescence of immunoblots treated with anti-phosphotyrosine. PMCA content was measured on the same immunoblots by stripping and reprobing with anti-PMCA. Phosphorylation was reported as normalized phosphotyrosine chemiluminescence per nanogram PMCA (mean+/-SE). The average PMCA tyrosine phosphorylation for 15 normotensive subjects was 0.53+/-0. 09, whereas the average for 8 hypertensive individuals was 1.82+/-0. 25 (P<0.0005, Mann-Whitney U test). Age, gender, and systolic blood pressure did not correlate with PMCA phosphorylation. These results suggest that PMCA in platelets of hypertensive individuals is inhibited because of tyrosine phosphorylation, resulting in increased platelet intracellular Ca(2+), hyperactive platelets, and increased risk of heart attack and stroke.

Syringe source, use, and discard among injection-drug users in New Haven, Connecticut.

We examined syringe source, use, and discard practices of injection-drug users (IDUs) in New Haven, Connecticut, a city with both a legal syringe-exchange program (SEP) and non-prescription availability of syringes through pharmacies. The population demographics, syringe use, and discard practices of IDUs who obtained syringes from various sources were compared using structured interview data. Of the 373 IDUs recruited, 268 (72 percent) resided in the city of New Haven. Among the New Haven IDUs, 111 (41 percent) reported pharmacies, 36 (13 percent) reported the New Haven SEP, 90 (34 percent) reported both, and 27 (10 percent) reported neither as their usual source of syringes in the past six months. No significant differences (p value < 0.05) were observed among New Haven IDUs who relied on pharmacies versus the SEP. However, IDUs who relied on the SEP were significantly less likely to report they threw away used syringes, compared with pharmacy users. Both the pharmacies and the New Haven SEP are important sources of sterile syringes for IDUs in New Haven. The lower frequency of syringe discard by IDUs who obtained their syringes primarily through the SEP indicates another public health benefit of programs such as these.

Evaluation of an innovative program to address the health and social service needs of drug-using women with or at risk for HIV infection.

Drug-using women with or at risk for HIV infection have many competing unmet needs, especially for social services, drug treatment, and medical care. High-risk drug-using women were recruited through street outreach, at needle exchange sites, a prison, and local community based organizations in New Haven, Connecticut for a study of the service needs of out-of-treatment drug users and the ability of an interactive case management intervention (ICM) to address those needs. These women were administered baseline and follow-up interviews to identify their health and social service needs and the degree to which these needs were resolved. The women who chose to enroll in the interactive case management intervention (n = 38) did not differ demographically nor in their HIV risk behaviors from those not receiving case management (n = 73). Provision of ICM was most successful in meeting needs for supportive mental health counseling, basic services, and long term housing. The impact of interactive case management was less evident for the acquisition of medical and dental services, which were accessed comparably by women not receiving the intervention. Overall, the women who enrolled in the ICM intervention showed a significant decrease in the number of unmet service needs as compared to those who did not enroll. Multiple contacts were required by the case manager to establish trust and to resolve the unmet service needs of these high-risk women. Women with or at risk for HIV infection can be effectively engaged in an ICM intervention in order to meet their multiple unmet service needs, although such interventions are time-and-labor intensive.

A sequence in the 5' flanking region confers progestin responsiveness on the human c-myc gene.

Previous reports have shown that progestins stimulate the proliferation of the human breast cancer cell line T47D in culture. Under different conditions other reports have shown progestin stimulation, inhibition or no effect on growth. It has also been shown that c-myc expression is stimulated at early times by progestins. We are currently testing the hypothesis that the mechanism of growth enhancement by progestins involves the stimulation of expression of c-myc. This hypothesis predicts a progesterone regulatory region in or near the c-myc gene. We have identified a region, from -2327 to -1833, which serves this function. This region includes a 15 bp sequence with homology to the PRE (progesterone response element) consensus sequence. Human progesterone receptor (PR) binds to this sequence in a specific, ligand-enhanced manner in electrophoretic mobility shift assays (EMSA). A 3507 bp HindIII-XbaI fragment of the 5' flanking region of the c-myc gene, -2327 to +1180, containing the progestin regulatory region and the c-myc promoter, confers progestin responsiveness to the CAT (chloramphenicol acetyl transferase) reporter gene in progesterone receptor (PR)-rich T47D human breast cancer cells, but not in PR-negative MDA-MB-231 cells. Removal of the progestin regulatory region abrogates progestin responsiveness. These data demonstrate that the sequence from -2327 to -1833 of the human c-myc gene includes a positive progestin regulatory region.

Investigation of the validity and reliability of four objective techniques for measuring forward shoulder posture.

Clinicians often rely on visual inspection and descriptive terms to documents a patient's forward shoulder posture. The purpose of this study was to assess the validity and intrarater reliability of four objective techniques to measure forward shoulder posture. Subjects were 25 males and 24 females. Subjects had a lateral cervical spine radiograph taken, from which the horizontal distance from the C7 spinous process to the anterior tip of the left anterior acromion process was measured. Subjects then proceeded twice through a random order of four measurements: the Baylor square, the double square, the Sahrmann technique, and scapular position. These results were then used to determine the intrarater reliability of each technique. Multiple regression analyses were performed on each measure's mean scores to determine both the correlation with and the predictive value for the radiographic measurement. The intraclass correlation coefficients for intrarater reliability ranged from .89 to .91. The correlation coefficients ranged from -.33 to .77, and the coefficients of determination ranged from .10 to .59 (N = 49). The researchers demonstrated clinical reliability for each technique; however, validity compared with the radiographic measurement could not be established. These techniques may have clinical value in objectively measuring change in a patient's shoulder posture as a result of a treatment program. Before any of these measures could be universally recommended in clinical practice, future research is necessary to establish interrater reliability and assess each technique's ability to detect postural changes over time.

A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.

Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23.

Manic depressive illness, or bipolar disorder (BP), is characterized by episodes of elevated mood (mania) and depression. We designed a multistage study in the genetically isolated population of the Central Valley of Costa Rica to identify genes that promote susceptibility to severe BP (termed BPI), and screened the genome ot two Costa Rican BPI pedigrees (McInnes et al., submitted). We considered only individuals who fulfilled very stringent diagnostic criteria for BPI to be affected. The strongest evidence for a BPI locus was observed in 18q22-q23. We tested 16 additional markers in this region and seven yielded peak lod scores over 1.0. These suggestive lod scores were obtained over a far greater chromosomal length (about 40 cM) than in any other genome region. This localization is supported by marker haplotypes shared by 23 of 26 BPI affected individuals studied. Additionally, marker allele frequencies over portions of this region are significantly different in the patient sample from those of the general Costa Rican population. Finally, we performed an analysis which made use of both the evidence for linkage and for association in 18q23, and we observed significant lod scores for two markers in this region.

Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis.

It is now feasible to map disease genes by screening the genome for linkage disequilibrium between the disease and marker alleles. This report presents the first application of this approach for a previously unmapped locus. A gene for benign recurrent intrahepatic cholestasis (BRIC) was mapped to chromosome 18 by searching for chromosome segments shared by only three distantly related patients. The screening results were confirmed by identifying an extended haplotype conserved between the patients. Probability calculations indicate that such segment sharing is unlikely to arise by chance. Searching the genome for segments shared by patients is a powerful empirical method for mapping disease genes. Computer simulations suggest that, in appropriate populations, the approach may be used to localize genes for common diseases.

Activity of a maize ubiquitin promoter in transgenic rice.

We have used the maize ubiquitin 1 promoter, first exon and first intron (UBI) for rice (Oryza sativa L. cv. Taipei 309) transformation experiments and studied its expression in transgenic calli and plants. UBI directed significantly higher levels of transient gene expression than other promoter/intron combinations used for rice transformation. We exploited these high levels of expression to identify stable transformants obtained from callus-derived protoplasts co-transfected with two chimeric genes. The genes consisted of UBI fused to the coding regions of the uidA and bar marker genes (UBI:GUS and UBI:BAR). UBI:GUS expression increased in response to thermal stress in both transfected protoplasts and transgenic rice calli. Histochemical localization of GUS activity revealed that UBI was most active in rapidly dividing cells. This promoter is expressed in many, but not all, rice tissues and undergoes important changes in activity during the development of transgenic rice plants.

Functional capacity in heart failure. Comparison of methods for assessment and their relation to other indexes of heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Left ventricular (LV) dysfunction plays a primary role in the pathogenesis of congestive heart failure and correlates with prognosis, but a strong quantitative relation between exercise performance and indexes of LV function has not been demonstrated. We examined the relation between LV ejection fraction at rest, oxygen consumption at peak exercise (VO2), patient and physician assessments of clinical severity, and other clinical attributes in 804 patients with moderate heart failure. METHODS AND RESULTS: Ejection fraction correlated weakly with VO2, and mean ejection fraction was related to severity of symptoms. There was a statistical association between the patient's self-assessed quality of life questionnaire score and the physician-assigned New York Heart Association (NYHA) functional class; NYHA class was statistically associated with exercise performance. To identify other factors that might influence exercise capacity, comparisons of clinical attributes were made between patients grouped by VO2 within each stratum of LV function. Exercise performance was inversely related to plasma norepinephrine levels within the ejection fraction < 25% stratum. The percentage of patients reaching their anaerobic threshold was not different between groups, yet the peak heart rate increased with VO2 within all strata. Elevated venous pressure and cardiomegaly were inversely related to exercise performance. CONCLUSIONS: Clinical scales based on physician and patient assessment of symptoms were statistically associated with exercise capacity but do not accurately predict individual exercise performance. The strong association of heart rate response to exercise performance suggests that the variability of the chronotropic response to exercise contributes to differences in exercise capacity among patients with a similar degree of LV dysfunction.

Cholinergic amacrine cells in the rabbit retina accumulate muscimol.

The cholinergic amacrine cells of the rabbit retina form two mosaics placed symmetrically on either side of the inner plexiform layer. Recently, these cells have been reported to contain immunocytochemical markers for GABA. In this paper, we labeled the cholinergic cells with DAPI, then incubated the retina in [3H]-muscimol, a neuronal marker for GABA. Subsequently, we converted the DAPI fluorescence of the displaced cholinergic matrix to an opaque product by photooxidation in the presence of DAB. Autoradiography showed that all of the displaced cholinergic amacrine cells were labeled with [3H]-muscimol, thus confirming the immunocytochemical results. The cholinergic cells account for approximately 80% of the cells in the ganglion cell layer which take up [3H]-muscimol.

Efficacy of oral sucralfate suspension in prevention and treatment of chemotherapy-induced mucositis.

The efficacy of orally administered sucralfate suspension in preventing and treating chemotherapy-induced mucositis was evaluated in a double-blind trial. Forty-eight children and adolescents with newly diagnosed acute nonlymphocytic leukemia were randomized to receive suspensions of either sucralfate or placebo orally every 6 hours during the first 10 weeks of intensive remission-induction chemotherapy. Patients given sucralfate suspension were less likely than subjects receiving placebo to acquire colonization with potentially pathogenic microorganisms: 14 (58%) of 24 versus 22 (92%) of 24, respectively (p = 0.008). However, no effect on preexisting colonization was noted. Subjective reporting of discomfort, objective scoring of the severity of mucositis, and the maximal percent of body weight lost during therapy were similar; 58% of patients receiving sucralfate reported no oral pain compared with 25% receiving placebo (p = 0.06). Ten episodes of gastrointestinal bleeding, 25 documented infections, and 886 days with fever were also equally distributed between sucralfate and placebo groups. We conclude that sucralfate suspension is of limited, if any efficacy, in the prevention and treatment of chemotherapy-induced mucositis. Sucralfate administration can, however, reduce acquisition of alimentary colonization with potential pathogens, perhaps by interfering with adherence to mucosal membranes.

Vancomycin, ticarcillin, and amikacin compared with ticarcillin-clavulanate and amikacin in the empirical treatment of febrile, neutropenic children with cancer.

We assessed two antibiotic regimens--vancomycin, ticarcillin, and amikacin, as compared with a vancomycin placebo, ticarcillin-clavulanate, and amikacin--as initial empirical therapy for febrile, neutropenic children with cancer. In a randomized, double-blind clinical trial, the planned 10-day treatment was unsuccessful in 15 percent of the vancomycin, ticarcillin, and amikacin group (n = 53), as compared with 38 percent of the group receiving ticarcillin-clavulanate and amikacin (n = 48) (P = 0.010). Of 10 episodes of breakthrough bacteremia, 9 (1 fatal) occurred in patients treated with ticarcillin-clavulanate and amikacin (P = 0.006). Each of the 10 microbial isolates was a gram-positive bacterium with similar susceptibilities to vancomycin and ticarcillin-clavulanate in vitro. Both regimens were well tolerated. None of the patients had detectable renal dysfunction, but those receiving vancomycin, ticarcillin, and amikacin were more likely to have twofold increases in serum hepatic-enzyme activity. Rashes consistent with the "red-man" syndrome occurred in three patients upon the infusion of vancomycin and in three others who received a placebo. We conclude that the combination of vancomycin, ticarcillin, and amikacin is more effective than ticarcillin-clavulanate and amikacin as empirical antibiotic therapy in clinical settings in which gram-positive bacteremias are a serious problem.