Molecular hybrid positron emission tomography/computed tomography imaging of cardiac angiotensin II type 1 receptors.

Objectives: The goal of this study was to explore the feasibility of targeted imaging of the angiotensin II type 1 receptor (AT1R) in cardiac tissue, using clinical hybrid positron emission tomography/computed tomography (PET/CT).

Background: AT1R is an attractive imaging target due to its key role in various cardiac pathologies, including post-infarct left ventricular remodeling.

Methods: Using the novel AT1R ligand [(11)C]-KR31173, dynamic PET/CT was performed in young farm pigs under healthy conditions (n = 4) and 3 to 4 weeks after experimental myocardial infarction (n = 5).

Retention: building a patient-centered medical home in HIV primary care through PUFF (Patients Unable to Follow-up Found).

Here, we describe our patient-centered medical home (PCMH) quality improvement retention project conducted by a Health Resources and Services Administration (HRSA) Ryan White-funded Primary Care HIV clinic. The single urban academic clinic serving 2,776 active HIV positive patients identified 25.8% (716/2,776) patients who had not been retained in care within the prior six months during two separate six-month interval analyses.

Relative accuracy of cervical and anal cytology for detection of high grade lesions by colposcope guided biopsy: a cut-point meta-analytic comparison.

Background: We recently reported, using a receiver operating characteristic area metric, the first meta-analytic comparison of the relative accuracy of cervical and anal cytology in detecting moderate or severe histopathologic lesions by magnification directed punch biopsy. The aim of the present research was to meta-analytically examine cut-point specific operating characteristics (sensitivity, specificity) of cervical and anal cytology in detecting high grade squamous intraepithelial lesion (HSIL) histopathology by colposcope directed punch biopsy.

Methodology/principal Findings: The primary eligibility requirement was availability of tabulated cytology (normal, atypical cells of unclear significance [ASCUS], low grade squamous intraepithelial lesion, HSIL or atypical squamous cells cannot rule out high grade [ASC-H]) and biopsy ( View Article and Find Full Text PDF

Didanosine Exposure and Noncirrhotic Portal Hypertension in a HIV Clinic in North America: a Follow-up Study.

AIMS: To describe: 1) our cohort of patients diagnosed with NCPH in a HIV academic clinic in North America, and 2) longitudinal follow-up and outcomes of patients following NCPH diagnosis. STUDY DESIGN: Retrospective case series. PLACE AND DURATION OF STUDY: Owen clinic, University of California, San Diego, United States, between October 1990 and December 2010.

Lentivirus transduction of human osteoclast precursor cells and differentiation into functional osteoclasts.

Gene transfer into stem cells has been an ongoing priority as a treatment for genetic disease and cancer for more than two decades. Methods described herein, form the basis for providing the cell source to determine if osteoclast precursor cells (OcP) can be used as therapeutic gene delivery systems in vivo. Osteoclasts and tumor associated macrophages or OcP, support survival, tumor progression and osteolysis in bone cancers.

Comparative accuracy of anal and cervical cytology in screening for moderate to severe dysplasia by magnification guided punch biopsy: a meta-analysis.

Background: The accuracy of screening for anal cancer precursors relative to screening for cervical cancer precursors has not been systematically examined. The aim of the current meta-analysis was to compare the relative accuracy of anal cytology to cervical cytology in discriminating between histopathologic high grade and lesser grades of dysplasia when the reference standard biopsy is obtained using colposcope magnification.

Methods And Findings: The outcome metric of discrimination was the receiver operating characteristic (ROC) curve area.

Reliability and predictive validity of a hepatitis-related symptom inventory in HIV-infected individuals referred for Hepatitis C treatment.

Background: We aimed to determine the reliability and validity of a hepatitis symptom inventory and to identify predictors of hepatitis C (HCV) treatment initiation in a cohort of HIV-infected patients.

Methods: Prospective clinic based study that enrolled patients referred for HCV therapy consideration. A hepatitis symptom inventory and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to HIV/HCV individuals.

Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load.

Human immunodeficiency virus type 1 (HIV-1) genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR) in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL) and CD4+ cell count (CD4) at baseline.

Affinity purification of a chimeric nicotinic acetylcholine receptor in the agonist and antagonist bound states.

Nicotinic acetylcholine receptors (nAChRs) form ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are members of a large family of pentameric ion channels that are of active medical interest. An expression system utilizing a chimerical construct of the N-terminal extracellular ligand binding domain of alpha7 type nAChR and the C-terminal transmembrane portion of 5HT3 type receptor resulted high level of expressions.

A comparison in HIV-associated stigma among healthcare workers in urban and rural Gujarat.

The present study measures levels of stigma within health care settings in urban and rural Gujarat, in an attempt to understand how this may have contributed to the state's increasing HIV incidence. Two sites were studied: a rural hospital in Bardoli and an urban hospital in Surat. HIV-associated stigma among healthcare workers (N=170) was assessed using a Stigma Index.

Molecular imaging of the kidneys.

Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive, and accurate diagnosis. The most recent imaging technology, positron emission tomography, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H(2)(15)O, (82)RbCl, and [(64)Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow.

Radionuclide imaging of angiotensin II type 1 receptor upregulation after myocardial ischemia-reperfusion injury.

Unlabelled: The renin-angiotensin system (RAS) mediates proapoptotic, profibrotic, and proinflammatory processes in maladaptive conditions. Activation after myocardial infarction may initialize and promote cardiac remodeling. Using a novel positron-emitting ligand, we sought to determine the presence and time course of regional myocardial upregulation of the angiotensin II type 1 receptor (AT1R) and the blocking efficacy of various anti-RAS agents.

Tuberculosis due to Mycobacterium bovis in patients coinfected with human immunodeficiency virus.

We reviewed 86 cases of human immunodeficiency virus and tuberculosis coinfection; 34.9% were caused by Mycobacterium bovis. Patients with M.

Estimating the accuracy of anal cytology in the presence of an imperfect reference standard.

Background: The study aim is to estimate sensitivity and specificity of anal cytology for histologic HSIL in analyses adjusted for the imperfect biopsy reference standard.

Methods And Principal Findings: Retrospective cohort study of an anal dysplasia screening program for HIV infected adults. We estimated the prevalence of histologic HSIL by concurrent cytology category and the associated cytology ROC area.

Utility of clinical assessment, imaging, and cryptococcal antigen titer to predict AIDS-related complicated forms of cryptococcal meningitis.

Background: This study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. The outcome was complicated cryptococcal meningitis: prolonged (>/= 14 days) altered mental status, persistent (>/= 14 days) focal neurologic findings, cerebrospinal fluid (CSF) shunt placement or death. Predictor variable operating characteristics were estimated using receiver operating characteristic curve (ROC) analysis.

Desert dust exposure is associated with increased risk of asthma hospitalization in children.

Rationale: Desert dust particles, including quartz, which causes inflammatory responses in the airway in animal studies, are transported to widespread regions around the globe. Epidemiologically, areas impacted by desert dust storms, such as communities in the Middle East and the Caribbean, seem to have higher incidences of asthma than might be expected.

Objectives: We investigated the magnitude of association between airborne mineral dust concentration and hospitalization of children for asthma exacerbation by using Light Detection And Ranging (LIDAR) with a polarization analyzer for an exposure measurement, which can distinguish mineral dust particles from other particles.

An immunoaffinity liquid chromatography-tandem mass spectrometry assay for detection of endogenous aggrecan fragments in biological fluids: Use as a biomarker for aggrecanase activity and cartilage degradation.

The degradation of articular cartilage by aggrecanases (ADAMTS-4 and ADAMTS-5) plays a significant role in the pathology of osteoarthritis (OA). To monitor aggrecanase activity in OA, we have developed a sensitive, accurate, and versatile assay for detection of two specific cleavage sites on aggrecan. The assay uses an immunoaffinity-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect cleavage at the (374)ARGS site and the (1820)AGEG site.

Radioligands for the angiotensin II subtype 1 (AT1) receptor.

Over the last years, ligands for angiotensin II subtype 1 receptor (AT1R) have been developed as an alternative to the use of angiotensin-converting enzyme (ACE) inhibitors for controlling high blood pressure. Radiolabeled versions of these ligands have proven vital to the development of more potent and specific drugs for the treatment of hypertension. Imaging studies using radiolabeled AT1R ligands have also elucidated the role these receptors play in angiogenesis as well as in various disease states beyond hypertension.

Denial of risk behavior does not exclude asymptomatic anorectal sexually transmitted infection in HIV-infected men.

Background: The Centers for Disease Control recommend screening for asymptomatic sexually transmitted infection (STI) among HIV-infected men when there is self-report of unprotected anal-receptive exposure. The study goals were: (1) to estimate the validity and usefulness for screening policies of self-reported unprotected anal-receptive exposure as a risk indicator for asymptomatic anorectal infection with Neisseria gonorrhoeae (GC) and/or Chlamydia trachomatis (CT). (2) to estimate the number of infections that would be missed if anal diagnostic assays were not performed among patients who denied unprotected anorectal exposure in the preceding month.

Treatment of HIV-related inflammatory cerebral cryptococcoma with adalimumab.

Cryptococcomas have been described in AIDS patients in the setting of immune reconstitution inflammatory syndrome. We report the first case of human immunodeficiency virus-related inflammatory cerebral cryptococcoma to be treated with a recombinant human monoclonal tumor necrosis factor antagonist.

Structures of care in the clinics of the HIV Research Network.

As the HIV epidemic has evolved to become a chronic, treatable condition the focus of HIV care has shifted from the inpatient to the outpatient arena. The optimal structure of HIV care in the outpatient setting is unknown. Using the HIV Research Network (HIVRN), a federally sponsored consortium of 21 sites that provide care to HIV-infected individuals, this study attempted to: (1) document key features of the organization of care in HIVRN adult clinics and (2) estimate variability among clinics in these parameters.

Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration.

Background: Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration.

Design: Cross-sectional analysis.

Predictive validity of a brief antiretroviral adherence index: retrospective cohort analysis under conditions of repetitive administration.

Background: Newer antiretroviral (ARV) agents have improved pharmacokinetics, potency, and tolerability and have enabled the design of regimens with improved virologic outcomes. Successful antiretroviral therapy is dependent on patient adherence. In previous research, we validated a subset of items from the ACTG adherence battery as prognostic of virologic suppression at 6 months and correlated with adherence estimates from the Medication Event Monitoring System (MEMS).

Synthesis and in vivo evaluation of novel PET radioligands for imaging the endothelin-A receptor.

Unlabelled: The endothelin subtype-A (ETA) receptor is a member of a family of G-protein-coupled receptors that plays a central role in vasoconstriction, cell proliferation, and hormone production. The aim of this study was to synthesize and evaluate in vivo (11)C- and (18)F-labeled analogs of the potent and selective ETA antagonist N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940).

Methods: Protected precursors and authentic nonradioactive standards were synthesized by reductive amination and subsequent alkylation of protected aldehyde 1.

Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (+/-)3,4-methylenedioxymethamphetamine ("ecstasy") users: relationship to cognitive performance.

Background: (+/-)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related.