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Patients who are otherwise unsuitable candidates for coronary bypass surgery or standard coronary angioplasty (PTCA) may be successfully treated with PTCA during ECMO. Five patients (3 men, 2 women), with a mean age of 57 years, are reported on here. They were not considered good candidates for standard therapy because of poor left ventricular function (mean EF, 24; range, 16 to 28%). Patients were supported by percutaneous femoral bypass using a BARD CPS machine, and underwent successful PTCA of either two vessels (three patients) or three vessels (two patients); in addition, one patient had dilatation of a stenotic aortic valve. Patients were supported with ECMO for 26 to 140 (mean 104) minutes, and required transfusion with 0 to 4 (mean 2) units of blood during or after the procedure. Complications included groin hematoma in two patients. All were discharged within 4 days of the procedure. Follow-up of the patients has been completed (4-7 mo) with no further hospitalizations for unstable angina. All patients remain in NYHA Class II or III. These data suggest that ECMO-assisted angioplasty is a safe and effective method of palliation of unstable angina associated with cardiomyopathy.

OBJECTIVES: This study investigated the limitations of probability samples of men who have sex with men (MSM), limited to single cities and to the areas of highest concentrations of MSM ('gay ghettos'). METHODS: A probability sample of 2881 MSM in 4 American cities completed interviews by telephone. RESULTS: MSM who resided in ghettos differed from other MSM, although in different ways in each city. Non-ghetto-dwelling MSM were less involved in the gay and lesbian community. They were also less likely to have only male sexual partners, to identify as gay, and to have been tested for HIV. CONCLUSIONS: These differences between MSM who live in gay ghettos and those who live elsewhere have clear implications for HIV prevention efforts and health care planning. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study characterized the AIDS epidemic among urban men who have sex with men (MSM). METHODS: A probability sample of MSM was obtained in 1997 (n = 2881; 18 years and older) from New York, Los Angeles, Chicago, and San Francisco, and HIV status was determined through self-report and biological measures. RESULTS: HIV prevalence was 17% (95% confidence interval = 15%, 19%) overall, with extremely high levels in African Americans (29%), MSM who used injection drugs (40%), 'ultraheavy' noninjection drug users (32%), and less educated men (< high school, 37%). City-level HIV differences were non-significant once these other factors were controlled for. In comparing the present findings with historical data based on public records and modeling, HIV prevalence appears to have declined as a result of high mortality (69%) and stable, but high, incidence rates (1%-2%). CONCLUSIONS: Although the findings suggest that HIV prevalence has declined significantly from the mid-1980s, current levels among urban MSM in the United States approximate those of sub-Saharan countries (e.g., 14%-25%) and are extremely high in many population subsegments. Despite years of progress, the AIDS epidemic continues unabated among subsegments of the MSM community. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study sought to determine the prevalence and determinants of use of recommended antiretroviral regimens among urban seropositive men who have sex with men (MSM). METHODS: A probability telephone sample of MSM was taken within regions of Chicago, Los Angeles, New York, and San Francisco. Analysis focused on use of antiretroviral therapies. RESULTS: Although the majority of seropositive MSM with CD4 counts below 500 per microliter were using recommended antiretroviral regimens, 26% of seropositive MSM were not receiving such care. Men who were younger, who reported a sexual orientation other than homosexual, who had a more recent interview date, who were at middle levels of affiliation with the gay community, and who reported higher levels of perceived exclusivity on the part of the gay community were less likely to be using recommended antiretroviral regimens. CONCLUSIONS: Although current efforts to make antiretroviral therapies available to HIV-seropositive MSM are reasonably effective, additional efforts are needed for MSM characterized by relative youth and lower social support. [ABSTRACT FROM AUTHOR]

Genomic screening is routinely used to guide the treatment of cancer patients in many countries. However, several multi-layered factors make this effort difficult to deliver within a clinically relevant timeframe. Here we share the learnings from the CRUK-funded Stratified Medicine Programme for advanced NSCLC patients, which could be useful to better plan future studies., (© 2023. The Author(s).)

The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke 1-3 . As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug-biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy-including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug-biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke.

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility. Pneumococcal genetic variation explains a large amount of invasive potential (70%), but has no effect on severity. Serotype alone is insufficient to explain invasiveness, suggesting other pneumococcal factors are involved in progression to invasive disease. We identify pneumococcal genes involved in invasiveness including pspC and zmpD, and perform a human-bacteria interaction analysis. These genes are potential candidates for the development of more broadly-acting pneumococcal vaccines.

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Effective targeted therapy for sepsis requires an understanding of the heterogeneity in the individual host response to infection. We investigated this heterogeneity by defining interindividual variation in the transcriptome of patients with sepsis and related this to outcome and genetic diversity., Methods: We assayed peripheral blood leucocyte global gene expression for a prospective discovery cohort of 265 adult patients admitted to UK intensive care units with sepsis due to community-acquired pneumonia and evidence of organ dysfunction. We then validated our findings in a replication cohort consisting of a further 106 patients. We mapped genomic determinants of variation in gene transcription between patients as expression quantitative trait loci (eQTL)., Findings: We discovered that following admission to intensive care, transcriptomic analysis of peripheral blood leucocytes defines two distinct sepsis response signatures (SRS1 and SRS2). The presence of SRS1 (detected in 108 [41%] patients in discovery cohort) identifies individuals with an immunosuppressed phenotype that included features of endotoxin tolerance, T-cell exhaustion, and downregulation of human leucocyte antigen (HLA) class II. SRS1 was associated with higher 14 day mortality than was SRS2 (discovery cohort hazard ratio (HR) 2·4, 95% CI 1·3-4·5, p=0·005; validation cohort HR 2·8, 95% CI 1·5-5·1, p=0·0007). We found that a predictive set of seven genes enabled the classification of patients as SRS1 or SRS2. We identified cis-acting and trans-acting eQTL for key immune and metabolic response genes and sepsis response networks. Sepsis eQTL were enriched in endotoxin-induced epigenetic marks and modulated the individual host response to sepsis, including effects specific to SRS group. We identified regulatory genetic variants involving key mediators of gene networks implicated in the hypoxic response and the switch to glycolysis that occurs in sepsis, including HIF1α and mTOR, and mediators of endotoxin tolerance, T-cell activation, and viral defence., Interpretation: Our integrated genomics approach advances understanding of heterogeneity in sepsis by defining subgroups of patients with different immune response states and prognoses, as well as revealing the role of underlying genetic variation. Our findings provide new insights into the pathogenesis of sepsis and create opportunities for a precision medicine approach to enable targeted therapeutic intervention to improve sepsis outcomes., Funding: European Commission, Medical Research Council (UK), and the Wellcome Trust., (Copyright © 2016 Davenport et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Black men who have sex with men (MSM) in the United States are disproportionately impacted by HIV. To better understand this public health problem, we reviewed the literature to calculate an estimate of HIV incidence among Black MSM. We used this rate to model HIV prevalence over time within a simulated cohort, which we subsequently compared to prevalence from community-based samples. We searched all databases accessible through PubMed, and Conference on Retroviruses and Opportunistic Infections abstracts for HIV incidence estimates among Black MSM. Summary HIV incidence rates and 95 % confidence intervals (CIs) were calculated using random effects models. Using the average incidence rate, we modeled HIV prevalence within a simulated cohort of Black MSM (who were all HIV-negative at the start) from ages 18 through 40. Based on five incidence rates totaling 2898 Black MSM, the weighted mean incidence was 4.16 % per year (95 % CI 2.76-5.56). Using this annual incidence rate, our model predicted that 39.94 % of Black MSM within the simulated cohort would be HIV-positive by age 30, and 60.73 % by 40. Projections were similar to HIV prevalence found in community-based samples of Black MSM. High HIV prevalence will persist across the life-course among Black MSM, unless effective prevention and treatment efforts are increased to substantially reduce HIV transmission among this underserved and marginalized population.

Background: Sepsis is an increasingly common condition, which continues to be associated with unacceptably high mortality. A large number of association studies have investigated susceptibility to, or mortality from, sepsis for variants in the functionally important immune-related gene MBL2. These studies have largely been underpowered and contradictory., Methods: We genotyped and analyzed 4 important MBL2 single nucleotide polymorphisms (SNPs; rs5030737, rs1800450, rs1800451, and rs7096206) in 1839 European community-acquired pneumonia (CAP) and peritonitis sepsis cases, and 477 controls from the United Kingdom. We analyzed the following predefined subgroups and outcomes: 28-day and 6 month mortality from sepsis due to CAP or peritonitis combined, 28-day mortality from CAP sepsis, peritonitis sepsis, pneumococcal sepsis or sepsis in younger patients, and susceptibility to CAP sepsis or pneumococcal sepsis in the United Kingdom., Results: There were no significant associations (all P-values were greater than .05 after correction for multiple testing) between MBL2 genotypes and any of our predefined analyses., Conclusions: In this large, well-defined cohort of immune competent adult patients, no associations between MBL2 genotype and sepsis susceptibility or outcome were identified., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: Non-typhoidal Salmonella (NTS) causes invasive and frequently fatal disease in African children. Existing strategies to prevent, diagnose, and treat NTS disease are inadequate. An improved understanding of the biology of invasive Salmonella infection will facilitate the development of novel NTS control measures. Despite evidence in mice and man showing a clear role for host genetics in NTS susceptibility, there are no published studies investigating host genetic susceptibility to NTS in African populations., Methods: We conducted a genome-wide association study (SNP Array 6.0, Affymetrix, CA, USA) of NTS bacteraemia in Kenyan children, with replication in Malawian children. We assessed the function of NTS-associated variants in an expression quantitative trait locus (eQTL) dataset of interferon γ (IFNγ) and lipopolysaccharide-stimulated monocytes from 432 healthy European adults. Serum IFNγ (Bio-Plex immunoassay, Bio-Rad Laboratories, CA, USA) in Malawian NTS cases (n=106) during acute disease was correlated with genotype by linear regression., Findings: After whole-genome imputation and quality control, 180 Kenyan cases and 2677 controls were included in an association analysis at 7 951 614 (additive model) and 4 669 537 (genotypic model) loci. After quality control, 143 Malawian cases and 336 controls were included in the replication analysis. An intronic variant in STAT4 was associated (recessive model) with NTS in both Kenyan and Malawian children (Kenya p=5·6 × 10(-9), Malawi p=0·02, combined p=1·4 × 10(-9); odds ratio 7·2, 95% CI 3·8-13·5). The NTS-associated variant was an eQTL for STAT4 expression in IFNγ-stimulated monocytes (p=9·59 × 10(-6)), the NTS risk allele being associated with lower STAT4 expression. In Malawian children with NTS bacteraemia, the same NTS risk allele was associated with lower serum concentrations of IFNγ (p=0·02) at presentation., Interpretation: STAT4 is highly plausible as a susceptibility locus for invasive NTS disease. STAT4 mediates IFNγ release in T cells and natural killer cells in response to interleukin 12 (IL12). Individuals with rare mutations elsewhere in the IL12-IFNγ axis are at risk of disseminated NTS infection. We provide the first evidence, to our knowledge, of a host genetic determinant of NTS disease in African children, and of a STAT4 variant conferring susceptibility to an infectious disease in man., Funding: Wellcome Trust., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM 1,2, and 3) are viral restriction factors that mediate cellular resistance to several viruses. We have genotyped a possible splice-site altering single-nucleotide polymorphism (rs12252) in the IFITM3 gene in 34 patients with H1N1 influenza and severe pneumonia, and >5000 individuals comprising patients with community-acquired mild lower respiratory tract infection and matched controls of Caucasian ancestry. We found evidence of an association between rs12252 rare allele homozygotes and susceptibility to mild influenza (in patients attending primary care) but could not confirm a previously reported association between this single-nucleotide polymorphism and susceptibility to severe H1N1 infection.

Innate immune receptors detect microbial pathogens and subsequently activate adaptive immune responses to combat pathogen invasion. MyD88 is a key adaptor molecule in both Toll-like receptor (TLR) and IL-1 receptor superfamily signaling pathways. This is illustrated by the fact that human individuals carrying rare, naturally occurring MYD88 point mutations suffer from reoccurring life-threatening infections. Here we analyzed the functional properties of six reported non-synonymous single nucleotide polymorphisms of MYD88 in an in vitro cellular system. Two variants found in the MyD88 death domain, S34Y and R98C, showed severely reduced NF-κB activation due to reduced homo-oligomerization and IRAK4 interaction. Structural modeling highlights Ser-34 and Arg-98 as residues important for the assembly of the Myddosome, a death domain (DD) post-receptor complex involving the DD of MyD88, IRAK4, and IRAK2 or IRAK1. Using S34Y and R98C as functional probes, our data show that MyD88 homo-oligomerization and IRAK4 interaction is modulated by the MyD88 TIR and IRAK4 kinase domain, demonstrating the functional importance of non-DD regions not observed in a recent Myddosome crystal structure. The differential interference of S34Y and R98C with some (IL-1 receptor, TLR2, TLR4, TLR5, and TLR7) but not all (TLR9) MyD88-dependent signaling pathways also suggests that receptor specificities exist at the level of the Myddosome. Given their detrimental effect on signaling, it is not surprising that our epidemiological analysis in several case-control studies confirms that S34Y and R98C are rare variants that may drastically contribute to susceptibility to infection in only few individuals.

The innate immune system employs Toll-like receptors (TLRs) for the detection of invading microorganisms based on distinct molecular patterns. For example, TLR9 is activated by microbial DNA and also by short therapeutic CpG-containing oligonucleotides (CpG-ODN). TLR9 activation leads to the production of interferons and the priming of humoral adaptive immune responses. Unfortunately, the principles of ligand recognition by TLR9 are poorly understood, and genetic variants of TLR9, which may affect its function, have not been characterized systematically on the molecular level. We therefore sought to functionally characterize reported single nucleotide polymorphisms of TLR9 in the HEK293 model system. We discovered that two variants, P99L and M400I, are associated with altered receptor function regarding NF-κB activation and cytokine induction. Our investigations show that for the most functionally impaired variant, P99L, the ability to respond to physiological and therapeutic TLR9 ligands is severely compromised. However, CpG-ODN binding is normal. CpG-ODN recognition by TLR9 thus appears to involve two separate events, CpG-ODN binding and sensing. Our studies highlight Pro-99 as a residue important for the latter process. In genotyping studies, we confirmed that both M400I (rs41308230) and P99L (rs5743844) are relatively rare variants of TLR9. Our data add rs41308230 and rs5743844 to the list of functionally important TLR variants and warrant further research into their relevance for infectious disease susceptibility or responsiveness to CpG-ODN-based therapies.

Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8), OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14), OR = 0.43, 95% CI = 0.35-0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.

Background: The interleukin-2-mediated immune response is critical for host defense against infectious pathogens. Cytokine-inducible SRC homology 2 (SH2) domain protein (CISH), a suppressor of cytokine signaling, controls interleukin-2 signaling., Methods: Using a case-control design, we tested for an association between CISH polymorphisms and susceptibility to major infectious diseases (bacteremia, tuberculosis, and severe malaria) in blood samples from 8402 persons in Gambia, Hong Kong, Kenya, Malawi, and Vietnam. We had previously tested 20 other immune-related genes in one or more of these sample collections., Results: We observed associations between variant alleles of multiple CISH polymorphisms and increased susceptibility to each infectious disease in each of the study populations. When all five single-nucleotide polymorphisms (SNPs) (at positions -639, -292, -163, +1320, and +3415 [all relative to CISH]) within the CISH-associated locus were considered together in a multiple-SNP score, we found an association between CISH genetic variants and susceptibility to bacteremia, malaria, and tuberculosis (P=3.8x10(-11) for all comparisons), with -292 accounting for most of the association signal (P=4.58x10(-7)). Peripheral-blood mononuclear cells obtained from adult subjects carrying the -292 variant, as compared with wild-type cells, showed a muted response to the stimulation of interleukin-2 production--that is, 25 to 40% less CISH expression., Conclusions: Variants of CISH are associated with susceptibility to diseases caused by diverse infectious pathogens, suggesting that negative regulators of cytokine signaling have a role in immunity against various infectious diseases. The overall risk of one of these infectious diseases was increased by at least 18% among persons carrying the variant CISH alleles., (2010 Massachusetts Medical Society)

Signals elicited by TLRs following the detection of microbes are integrated and diversified by a group of four cytoplasmic adaptor molecules featuring an evolutionarily conserved Toll/IL-1R signaling domain. Single nucleotide polymorphisms (SNPs) in TLRs and their adaptor molecules have been shown to influence susceptibility to a range of infectious and other diseases. The adaptor MyD88 adaptor-like (Mal)/Toll/IL-1R-containing adaptor protein is involved in TLR2 and 4 signal transduction by recruiting another adaptor molecule, MyD88, to the plasma membrane. In this study, we used naturally occurring variants of Mal as tools to study the molecular biology of Mal in more detail in cellular model systems and to thereby identify functionally interesting variants whose corresponding nonsynonymous SNPs might be of further epidemiological interest. Of seven reported variants for Mal, we found Mal D96N associated with reduced NF-kappaB signaling and cytokine production after overexpression in HEK293 and Huh-7 cells. The D96N mutation prevented Mal from recruiting its signaling partner MyD88 to the plasma membrane and altered posttranslational modification of Mal. These findings led us to investigate the frequency of heterozygosity for the corresponding SNP rs8177400 in a Caucasian case-control study on the etiology of lymphoma, a disease in which TLRs have been implicated. Although rs8177400 did not modify lymphoma risk in general, its frequency of heterozygosity was accurately determined to 0.97%. Our data add rs8177400 (D96N) to the list of functionally important variants of Mal and warrant further research into its immunological, epidemiological, and diagnostic relevance.

Attempts to document changing HIV incidence rates among MSM are compromised by issues of generalizability and statistical power. To address these issues, this paper reports annualized mean HIV incidence rates from the entire published incidence literature on MSM from Europe, North America and Australia for the period 1995-2005. Publications that met the entry criteria were coded for region of the world, sampling method and year of study. From these reports, we calculated a mean incidence rate with confidence intervals for these variables. Although no differences in mean incidence rates were found for MSM from 1995 to 2005, HIV incidence rates are lower in Australia than either North America or Europe. We calculated a mean incidence rate of 2.39% for MSM in the United States, which if sustained within a cohort of MSM, would yield HIV prevalence rate of approximately 40% at age 40. These extrapolations overlap published HIV prevalence rates for MSM younger than age 40 in the United States. HIV incidence rates in the 2-3% range will adversely affect the health of gay male communities for decades to come. This analysis suggests that greater attention should be devoted to the question of how best to design prevention interventions that will lower HIV incidence rates among gay men.

OBJECTIVE: Given the increasing concerns about the levels of obesity being reached throughout the world, this paper analyses the relationship between the most common index of obesity, the BMI, and levels of body fat. RESEARCH METHODS AND PROCEDURES: The statistical relationship, in terms of functional form, between body fat and BMI is analysed using a large data set which can be categorized by race, sex and age. RESULTS: Irrespective of race, body fat and BMI are linearly related for males, with age entering logarithmically and with a positive effect on body fat. Caucasian males have higher body fat irrespective of age, but African American males' body fat increases with age faster than that of Asians and Hispanics. Age is not a significant predictor of body fat for females, where the relationship between body fat and BMI is nonlinear except for Asians. Caucasian females have higher predicted body fat than other races, except at low BMIs, where Asian females are predicted to have the highest body fat. DISCUSSION: Using BMIs to make predictions about body fat should be done with caution, as such predictions will depend upon race, sex and age and can be relatively imprecise. The results are of practical importance for informing the current debate on whether standard BMI cut-off values for overweight and obesity should apply to all sex and racial groups given that these BMI values are shown to correspond to different levels of adiposity in different groups.

Objective: This study estimates the prevalence of depression and describes the correlates and independent associations of distress and depression among U.S. men who have sex with men., Method: A household-based probability sample of men who have sex with men (N=2,881) was interviewed between 1996 and 1998 in four large American cities. With cutoff points of 15 and 22 for the Center for Epidemiological Studies Depression Scale, individual correlates and predictors of distress and depression were examined, and multinomial logistic regression was performed., Results: The 7-day prevalence of depression in men who have sex with men was 17.2%, higher than in adult U.S. men in general. Both distress and depression were associated with lack of a domestic partner; not identifying as gay, queer, or homosexual; experiencing multiple episodes of antigay violence in the previous 5 years; and very high levels of community alienation. Distress was also associated with being of other than Asian/Pacific Islander ethnicity and experiencing early antigay harassment. Depression was also associated with histories of attempted suicide, child abuse, and recent sexual dysfunction. Being HIV positive was correlated with distress and depression but not significantly when demographic characteristics, developmental history, substance use, sexual behavior, and current social context were controlled by logistic regression., Conclusions: Rates of distress and depression are high in men who have sex with men. These high rates have important public health ramifications. The predictors of distress and depression suggest prevention efforts that might be effective when aimed at men who have sex with men.

Objectives: We measured the extent to which a set of psychosocial health problems have an additive effect on increasing HIV risk among men who have sex with men (MSM)., Methods: We conducted a cross-sectional household probability telephone sample of MSM in Chicago, Los Angeles, New York, and San Francisco., Results: Psychosocial health problems are highly intercorrelated among urban MSM. Greater numbers of health problems are significantly and positively associated with high-risk sexual behavior and HIV infection., Conclusions: AIDS prevention among MSM has overwhelmingly focused on sexual risk alone. Other health problems among MSM not only are important in their own right, but also may interact to increase HIV risk. HIV prevention might become more effective by addressing the broader health concerns of MSM while also focusing on sexual risks.

Aims: To measure the prevalence and independent associations of heavy and problematic use of alcohol and recreational drugs among a household-based sample of urban MSM (men who have sex with men)., Design: Cross-sectional survey., Participants: Men who identified as being gay or bisexual or who reported sex with another man in the prior 5 years were included in this analysis (n = 2172)., Setting: A probability telephone sample of MSM was taken within Zip Codes of four large American cities (Chicago, Los Angeles, New York and San Francisco) estimated to have total concentrations of at least 4% of all households with one resident MSM., Measurements: Standard measures of alcohol use, problems associated with alcohol use, and recreational drug use were administered by trained telephone interviewers., Findings: Both recreational drug (52%) and alcohol use (85%) were highly prevalent among urban MSM, while current levels of multiple drug use (18%), three or more alcohol-related problems (12%), frequent drug use (19%) and heavy-frequent alcohol use (8%) were not uncommon. The associations of heavy and/or problematic substance use are complex, with independent multivariate associations found at the levels of demographics, adverse early life circumstances, current mental health status, social and sexual practices and connection to gay male culture., Conclusions: The complex pattern of associations with heavy and/or problematic substance use among urban MSM suggests that heavy and/or problematic substance use is grounded in multiple levels: the individual, the interpersonal and the socio-cultural.

For some time now researchers have argued the efficacy of pulsatile versus nonpulsatile hemodynamic support. Pulsatile systems, while providing a more physiological pumping source, are burdened with a multiparametric output function that can greatly affect the utility of such ventricular assist device (VAD) support. A simplified approach to the optimization of the pulsatile VADs' output function has been developed. This approach yields device outputs of approximately 5.5 L/min at physiologic pressures while demonstrating clinically acceptable blood chemistry. Obtaining this optimal operating point involves the determination of the VAD system output function for a range of fill-enhancing vacuum settings. A quantitative method for evaluating synchronous versus asynchronous pumping modes as related to coronary perfusion is also demonstrated.

Approximately 1.0% of open heart surgery patients become unweanable from cardiac bypass during the surgical procedure. In addition, nearly 20% of patients accepted for cardiac transplantation die while waiting for a donor heart. Pulsatile pneumatic ventricular assist devices (VADs) provide a realistic solution to these dilemmas. Currently, there are five manufacturers who are competing for the major market share in the clinical use of these devices. Novacor, Thermetics, Thoratec, Symbion, and Abiomed all have competitive VAD systems. Because no one system is optimal for all patients, the limitations, similarities, and strengths of each system should be known to enhance the patient's outcome when using these devices. Successful use of VAD systems, either as a bridge to transplantation or to ventricular recovery, is best approached by adherence to strict patient selection. Once instituted, VAD management centers on detailed attention to anticoagulation and prompt diagnosis and treatment of various complications.

Theoretical analysis predicts that performing magnetic resonance (MR) imaging with partial (less than 90 degrees) flip angles can reduce imaging times two- to fourfold when lesions with elevated T1 values are being examined. This time savings occurs because repetition time (TR) is reduced when imaging is performed with partial flips. Partial flip MR imaging can also improve signal-to-noise ratio (S/N) in fast body imaging. For this study, analytical tools were used to predict image contrast and S/N for short TR, partial flip sequences. Experimental implementation of the short TR, partial flip sequences that analytical work had predicted would be optimal supported the analytical predictions and demonstrated their validity. Partial flip MR imaging is applicable to reducing imaging time only when the ratio of signal differences to noise exceeds threshold values in conventional MR images. Partial flip sequences can be used to advantage in MR imaging of both the head and the body, and the observed effects are predictable through theoretical analysis.

Two fast magnetic resonance (MR) imaging techniques, advanced Fourier and partial-flip imaging, were used at 0.35 T to examine 21 patients with suspected intracranial lesions; the results were quantitatively compared with a conventional spin-echo study. Both of the fast MR techniques yielded a fourfold reduction in imaging time per section. The advanced Fourier sequence showed contrast that was identical to the conventional spin-echo study with signal-to-noise ratios of 58% and 57% for the first and second echoes, respectively. The partial-flip sequence showed a contrast of 109% and 57% for lesions versus substantia alba, and 107% and 78% for substantia grisea versus substantia alba relative to the first and second echoes of the conventional spin-echo study. The partial-flip sequence was particularly sensitive to magnetic susceptibility; this produced artifacts that may undermine the usefulness of partial flip for routine screening in certain parts of the brain. However, this susceptibility significantly improved the detection of intracranial hemorrhage when compared with the spin-echo sequence, particularly when combined with phase mapping of the partial-flip study.