Social support and prognosis in patients at increased psychosocial risk recovering from myocardial infarction.

Objective: To compare the impact of network support and different types of perceived functional support on all-cause mortality or nonfatal reinfarction for patients with a recent acute myocardial infarction (AMI). Design: Participants were recruited from the Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial; 2,481 AMI patients with depression or low social support were randomized to a cognitive-behavioral intervention or to a usual care control group. Data collection for certain measures of social support was limited: 2,466 participants completed the ENRICHD Social Support Inventory; 2,457 completed the Perceived Social Support Scale; 1,296 completed the Social Network Questionnaire; and 707 completed the Interpersonal Support and Evaluation List, Tangible Support subscale. Patients also completed the Beck Depression Inventory and were followed for up to 4.5 years. Main Outcome Measure: Time to death or nonfatal reinfarction. Results: Over the follow-up period, 599 patients (24%) died or had a nonfatal AMI. Survival models controlling age, sex, race, socioeconomic status, smoking, antidepressant use, and a composite measure of increased risk revealed that higher levels of perceived social support were associated with improved outcome for patients without elevated depression but not for patients with high levels of depression. Neither perceived tangible support nor network support were associated with more frequent adverse events. Conclusion: AMI patients should be assessed for multiple dimensions of perceived functional support and depression to identify those at increased psychosocial risk who may benefit from treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Risk factors for Kaposi's sarcoma in HIV-positive subjects in Uganda

BACKGROUND: Kaposi's sarcoma (KS) is associated epidemiologically with HIV infection and with human herpesvirus 8 (HHV-8 or KSHV). Both KS and HIV infection are common in Uganda. We conducted a case-control study of 458 HIV-seropositive. Ugandan adults with KS and 568 HIV-seropositive subjects without KS to examine risk factors for HIV-associated KS. METHODS: We recruited newly diagnosed adult KS cases from five hospitals in Kampala, Uganda and controls from a large referral clinic for HIV infection at Mulago Hospital. All cases and controls were counselled and tested for HIV and answered an interviewer-administered questionnaire about their home, socio-economic conditions, lifestyle and sexual behaviour before they became ill. Only HIV-seropositive subjects were included in the analysis. RESULTS: There were 295 males and 163 females with KS and 227 male and 341 female controls. Age distribution was similar but there was a higher proportion of cases (45%) than controls (29%) residing in rural regions of Uganda. KS cases were more likely than controls to have a higher level of education (X2 for trend, 4.8; P = 0.03), to have occupations associated with affluence [chi 2 for heterogeneity, 17.3 on 5 degrees of freedom (df); P = 0.004] and to come from larger settlements [adjusted odds ratio (OR) for settlements of > 1000 versus 10-99 houses, 1.8; 95% confidence interval (CI), 1.1-3.0]. Cases were more likely than controls to have high household income (chi 2 for trend, 32.6; P < 0.001) and other markers of urban or rural wealth such as owning several cows (chi 2 for trend, 9.5; P = 0.002). Cases were more likely to travel away from home (adjusted OR, 1.6; 95% CI, 1.1-2.3) and more likely to have spent increasing time in contact with water (chi 2 for trend, 12.3; P < 0.001). Few indices of sexual behaviour were related to risk of KS, including reported number of sexual partners. Cases were more likely than controls to be married to one rather than several spouses (adjusted OR, 1.6; 95% CI, 1.2-2.2) and to have reported a history of sexually transmitted diseases (STD) (adjusted OR, 1.6; 95% CI, 1.2-2.3). CONCLUSIONS: Among HIV-infected subjects, KS cases are characterized by better education and greater affluence, compared with controls. Urban address, travel away from home, exposure to water, monogamous marriage and self-reported STD were also more frequent among KS cases than controls. The higher socio-economic status of persons with HIV and KS may be a marker for enhanced exposure to a possibly sexually transmitted agent, or for a delayed exposure to a childhood infection. The risk posed by exposure to water among KS cases requires further study.     

Substantial narrowing of the Niemann-Pick C candidate interval by yeast artificial chromosome complementation

Niemann-Pick disease type C (NP-C) is an autosomal recessive lipidosis linked to chromosome 18q11-12, characterized by lysosomal accumulation of unesterified cholesterol and delayed induction of cholesterol-mediated homeostatic responses. This cellular phenotype is identifiable cytologically by filipin staining and biochemically by measurement of low-density lipoprotein-derived cholesterol esterification. The mutant Chinese hamster ovary cell line (CT60), which displays the NP-C cellular phenotype, was used as the recipient for a complementation assay after somatic cell fusions with normal and NP-C murine cells suggested that this Chinese hamster ovary cell line carries an alteration(s) in the hamster homolog(s) of NP-C. To narrow rapidly the candidate interval for NP-C, three overlapping yeast artificial chromosomes (YACs) spanning the 1 centimorgan human NP-C interval were introduced stably into CT60 cells and analyzed for correction of the cellular phenotype. Only YAC 911D5 complemented the NP-C phenotype, as evidenced by cytological and biochemical analyses, whereas no complementation was obtained from the other two YACs within the interval or from a YAC derived from chromosome 7. Fluorescent in situ hybridization indicated that YAC 911D5 was integrated at a single site per CT60 genome. These data substantially narrow the NP-C critical interval and should greatly simplify the identification of the gene responsible in mouse and man. This is the first demonstration of YAC complementation as a valuable adjunct strategy for positional cloning of a human gene.     

Isolation and identification of a compound from soybean cyst nematode,Heterodera glycines,with sex pheromone activity

A single compound with sex pheromone activity was isolated from the female soybean cyst nematode,Heterodera glycines, by a sequence of four high-performance liquid chromatographic steps and identified as vanillic acid by a combination of ultraviolet spectroscopy and chromatography. The structure was confirmed by gas chromatography-mass spectrometry. Both attractancy and coiling behavior in male soybean cyst nematode were elicited by authentic vanillic acid.     

Major depression and medication adherence in elderly patients with coronary artery disease.

Little is known about the effects of depression on adherence to medical treatment regimens in older patients with chronic medical illnesses. Poor adherence may explain the increased risk of medical morbidity and mortality found in depressed medical patients. Ten of 55 patients over the age of 64 with coronary artery disease met the criteria for major depression from the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev., American Psychiatric Association, 1987). All patients were prescribed a twice-per-day regimen of low dose aspirin to reduce their risk for myocardial infarction. Medication adherence was assessed for 3 weeks by an unobtrusive electronic monitoring device. Depressed patients adhered to the regimen on 45% of days, but nondepressed patients, on 69% (p?     

Relationship between surface and free tropospheric ozone in the Western U.S

Ozone is an important air pollutant that affects lung function. In the U.S., the EPA has reduced the allowable O(3) concentrations several times over the last few decades. This puts greater emphasis on understanding the interannual variability and the contributions to surface O(3) from all sources. We have examined O(3) data from 11 rural CASTNET sites in the western US for the period 1995-2009. The 11 surface sites show a similar seasonal cycle and generally a good correlation in the deseasonalized monthly means, indicating that there are large scale influences on O(3) that operate across the entire western US. These sites also show a good correlation between site elevation and annual mean O(3), indicating a significant contribution from the free troposphere. We examined the number of exceedance days for each site, defined as a day when the Maximum Daily 8-h Average (MDA8) exceeds a threshold value. Over this time period, more than half of these sites exceeded an MDA8 threshold of 70 ppbv at least 4 times per year, and all sites exceeded a threshold value of 65 ppbv at least 4 times per year. The transition to lower threshold values increases substantially the number of exceedance days, especially during spring, reflecting the fact that background O(3) peaks during spring. We next examined the correlation between surface O(3) and free tropospheric O(3) in the same region, as measured by routine balloon launches from Boulder, CO. Using ozone measured by the balloon sensor in the range of 3-6 km above sea level we find statistically significant correlations between surface and free tropospheric O(3) in spring and summer months using both monthly means, daily MDA8 values, and the number of surface exceedance days. We suggest that during spring this correlation reflects variations in the flux of O(3) transport from the free troposphere to the surface. In summer, free tropospheric and surface concentrations of O(3) and the number of exceedance days are all significantly correlated with emissions from biomass burning in the western US. This indicates that wildfires significantly increase the number of exceedance days across the western U.S.     

Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study

PURPOSE: To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors. PATIENTS AND METHODS: A total of 304 men with advanced disseminated germ cell tumors were randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response. Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed. RESULTS: Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments. Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP. CONCLUSION: BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.     

2-Amino-4-methylpyridine as a potent inhibitor of inducible NO synthase activity in vitro and in vivo

1. The ability of 2-amino-4-methylpyridine to inhibit the catalytic activity of the inducible NO synthase (NOS II) enzyme was characterized in vitro and in vivo. 2. In vitro, 2-amino-4-methylpyridine inhibited NOS II activity derived from mouse RAW 264.7 cells with an IC50 of 6 nM. Enzyme kinetic studies indicated that inhibition is competitive with respect to arginine. 2-Amino-4-methylpyridine was less potent on human recombinant NOS II (IC50 = 40 nM) and was still less potent on human recombinant NOS I and NOS III (IC50 = 100 nM). NG-monomethyl-L-arginine (L-NMMA), N6-iminoethyl-L-lysine (L-NIL) and aminoguanidine were much weaker inhibitors of murine NOS II than 2-amino-4-methylpyridine but, unlike 2-amino-4-methylpyridine, retained similar activity on human recombinant NOS II. L-NMMA inhibited all three NOS isoforms with similar potency (IC50S 3-7 microM). In contrast, compared to activity on human recombinant NOS III, L-NIL displayed 10 x selectivity for murine NOS II and 11 x selectivity for human recombinant NOS II while aminoguanidine displayed 7.3 x selectivity for murine NOS II and 3.7 x selectivity for human recombinant NOS II. 3. Mouse RAW 264.7 macrophages produced high levels of nitrite when cultured overnight in the presence of lipopolysaccharide (LPS) and interferon-gamma. Addition of 2-amino-4-methylpyridine at the same time as the LPS and IFN-gamma, dose-dependently reduced the levels of nitrite (IC50 = 1.5 microM) without affecting the induction of NOS II protein. Increasing the extracellular concentration of arginine decreased the potency of 2-amino-4-methylpyridine but at concentrations up to 10 microM, 2-amino-4-methylpyridine did not inhibit the uptake of [3H]-arginine into the cell. Addition of 2-amino-4-methylpyridine after the enzyme was induced also dose-dependently inhibited nitrite production. Together, these data suggest that 2-amino-4-methylpyridine reduces cellular production of NO by competitive inhibition of the catalytic activity of NOS II, in agreement with results obtained from in vitro enzyme kinetic studies. 4. When infused i.v. in conscious unrestrained rats, 2-amino-4-methylpyridine inhibited the rise in plasma nitrate produced in response to intraperitoneal injection of LPS (ID50 = 0.009 mg kg-1 min-1). Larger doses of 2-amino-4-methylpyridine were required to raise mean arterial pressure in untreated conscious rats (ED50 = 0.060 mg kg-1 min-1) indicating 6.9 x selectivity for NOS II over NOS III in vivo. Under the same conditions, L-NMMA was nonselective while L-NIL and aminoguanidine displayed 5.2 x and 8.6 x selectivity respectively. All of these compounds caused significant increases in mean arterial pressure at doses above the ID50 for inhibition of NOS II activity in vivo. 5. 2-Amino-4-methylpyridine also inhibited LPS-induced elevation in plasma nitrate after either subcutaneous (ID50 = 0.3 mg kg-1) or oral (ID50 = 20.8 mg kg-1) administration. 6. These data indicate that 2-amino-4-methylpyridine is a potent inhibitor of NOS II activity in vitro and in vivo with a similar degree of isozyme selectivity to that of L-NIL and aminoguanidine in rodents.