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1.  Association of Increased Upper Trunk and Decreased Leg Fat With 2-h Glucose in Control and HIV-Infected Persons 
Diabetes Care  2011;34(11):2448-2453.
OBJECTIVE
Changes in body fat distribution and abnormal glucose metabolism are common in HIV-infected patients. We hypothesized that HIV-infected participants would have a higher prevalence of impaired glucose tolerance (IGT) compared with control subjects.
RESEARCH DESIGN AND METHODS
A total of 491 HIV-infected and 187 control participants from the second examination of the Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) underwent glucose tolerance testing (GTT). Multivariable regression was used to identify factors associated with GTT parameters.
RESULTS
The prevalence of impaired fasting glucose (IFG) (>110 mg/dL) was similar in HIV-infected and control participants (21 vs. 25%, P = 0.23). In those without IFG, the prevalence of IGT was slightly higher in HIV-infected participants compared with control subjects (13.1 vs. 8.2%, P = 0.14) and in HIV+ participants with lipoatrophy versus without (18.1 vs. 11.5%, P = 0.084). Diabetes detected by GTT was rare (HIV subjects 1.3% and control subjects 0%, P = 0.65). Mean 2-h glucose levels were 7.6 mg/dL higher in the HIV-infected participants (P = 0.012). Increased upper trunk subcutaneous adipose tissue (SAT) and decreased leg SAT were associated with 2-h glucose and IGT in both HIV-infected and control participants. Adjusting for adipose tissue reduced the estimated effects of HIV. Exercise, alcohol use, and current tenofovir use were associated with lower 2-h glucose levels in HIV-infected participants.
CONCLUSIONS
In HIV infection, increased upper trunk SAT and decreased leg SAT are associated with higher 2-h glucose. These body fat characteristics may identify HIV-infected patients with normal fasting glucose but nonetheless at increased risk for diabetes.
doi:10.2337/dc11-0616
PMCID: PMC3198295  PMID: 21926283
2.  The Associations of Regional Adipose Tissue with Lipid and Lipoprotein Levels in HIV-infected Men 
Background
HIV infection and antiretroviral therapy are associated with dyslipidemia, but the association between regional adipose tissue depots and lipid levels is not defined.
Methods
The association of MRI-measured visceral (VAT) and regional subcutaneous adipose tissue (SAT) volume with fasting lipid parameters was analyzed by multivariable linear regression in 737 HIV-infected and 145 control men from the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).
Results
HIV-infected men had higher median triglycerides (TG) (170mg/dl vs. 107mg/dl, p<0.0001), lower high density lipoprotein (HDL-C) (38mg/dl vs. 46mg/dl, p<0.0001) and lower low density lipoprotein (LDL-C) (105mg/dl vs. 125mg/dl, p<0.0001) than controls. After adjustment, greater VAT was associated with higher TG and lower HDL-C in both HIV-infected and control men, while greater leg SAT was associated with lower TG in HIV-infected men with a similar trend in controls. More upper trunk SAT was associated with higher LDL-C and lower HDL-C in controls, while more lower trunk SAT was associated with higher TG in controls. After adjustment, HIV infection remained strongly associated (p<0.0001) with higher TG (+76%, CI: 53, 103), lower LDL-C (−19%, CI: −25,−12), and lower HDL-C (−18%, CI: −22,−12).
Conclusions
HIV-infected men are more likely than controls to have higher TG and lower HDL-C, which promote atherosclerosis, but also lower LDL-C. Less leg SAT and more VAT are important factors associated with high TG and low HDL-C in HIV-infected men. The reduced leg SAT in HIV-infected men with lipoatrophy places them at increased risk for pro-atherogenic dyslipidemia.
doi:10.1097/QAI.0b013e31816d9ba1
PMCID: PMC3156607  PMID: 18360291
3.  Impact of Pneumococcal Vaccination on the Incidence of Pneumonia by HIV Infection Status among Patients Enrolled in the Veterans Aging Cohort 5-Site Study 
Background
Human immunodeficiency virus (HIV)–infected persons have a high incidence of pneumonia and pneumococcal disease. Benefits of vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) among these patients continue to be debated.
Methods
The impact of PPV vaccination on the incidence of pneumonia events (i.e., the composite of pneumococcal pneumonia and pneumonia due to nonspecified organisms) was examined among participants in the Veterans Aging Cohort 5-Site Study, an ongoing prospective study of HIV-infected patients matched to an HIV-uninfected control group. Dates of PPV vaccination and pneumonia were determined by retrospective review of electronic medical records. Time to events was measured for up to 2 years from PPV vaccination or from enrollment for vaccinated and unvaccinated patients, respectively. Kaplan-Meier and Cox proportional hazards regression methods were used to examine the incidence of pneumonia by HIV infection and PPV vaccination status.
Results
Among 692 HIV-uninfected and 934 HIV-infected study participants, 59% were vaccinated with PPV. The 2-year incidence of pneumonia was 6% (97 participants developed pneumonia). HIV-infected patients had a higher rate of pneumonia (hazard ratio, 5.81; 95% confidence interval, 3.15–10.71); overall, vaccinated patients showed a trend toward lower risk of pneumonia (hazard ratio, 0.75; 95% confidence interval, 0.50–1.13). Among HIV-infected patients, after controlling for HIV-specific and other variables, vaccination significantly reduced the risk of pneumonia (hazard ratio, 0.65; 95% confidence interval, 0.42–1.00); current smoking, low hemoglobin level, and low CD4 cell count significantly increased such risk. The effect of PPV vaccination among HIV-uninfected patients was not significant.
Conclusions
Among HIV-infected patients, PPV vaccination offered protection against pneumonia. Smoking cessation needs to be pursued as an additional strategy for preventing pneumonia.
doi:10.1086/529201
PMCID: PMC3115628  PMID: 18444830
4.  Veterans Aging Cohort Study (VACS) 
Medical care  2006;44(8 Suppl 2):S13-S24.
Background
The Veterans Aging Cohort Study (VACS) is a study of human immunodeficiency virus (HIV) infected and uninfected patients seen in infectious disease and general medical clinics. VACS includes the earlier 3 and 5 site studies (VACS 3 and VACS 5) as well as the ongoing 8 site study.
Objectives
We sought to provide background and context for analyses based upon VACS data, including study design and rationale as well as its basic protocol and the baseline characteristics of the enrolled sample.
Research Design
We undertook a prospectively consented multisite observational study of veterans in care with and without HIV infection.
Measures
Data were derived from patient and provider self report, telephone interviews, blood and DNA samples, focus groups, and full access to the national VA “paperless” electronic medical record system.
Results
More than 7200 veterans have been enrolled in at least one of the studies. The 8 site study (VACS) has enrolled 2979 HIV-infected and 3019 HIV-uninfected age–race–site matched comparators and has achieved stratified enrollment targets for race/ethnicity and age and 99% of its total target enrollment as of October 30, 2005. Participants in VACS are similar to other veterans receiving care within the VA. VACS participants are older and more predominantly black than those reported by the Centers for Disease Control.
Conclusions
VACS has assembled a rich, in-depth, and representative sample of veterans in care with and without HIV infection to conduct longitudinal analyses of questions concerning the association between alcohol use and related comorbid and AIDS-defining conditions.
doi:10.1097/01.mlr.0000223741.02074.66
PMCID: PMC3049942  PMID: 16849964
HIV/AIDS; alcohol; aging veterans; data management/research design
5.  HIV Infection and the Risk of Diabetes Mellitus 
AIDS (London, England)  2009;23(10):1227-1234.
Background
The influence of HIV infection on the risk of diabetes is unclear. We determined the association and predictors of prevalent DM in HIV infected and uninfected veterans.
Methods
We determined baseline prevalence and risk factors for diabetes among HIV infected and uninfected veterans in the Veterans Aging Cohort Study. Logistic regression was used to determine the odds of diabetes in HIV infected and uninfected persons.
Results
We studied 3,327 HIV-infected and 3,240 HIV-uninfected subjects. HIV infected subjects were younger, more likely to be black race, male, have HCV coinfection and a lower body mass index (BMI). HIV infected subjects had a lower prevalence of diabetes at baseline (14.9% vs. 21.4%, P<0.0001). After adjustment for known risk factors, HIV infected individuals had a lower risk of diabetes (OR 0.84, 95% CI 0.72-0.97). Increasing age, male gender, minority race, and BMI were associated with an increased risk. The odds ratio for diabetes associated with increasing age, minority race and BMI were greater among HIV infected veterans. HCV coinfection and nucleoside and non-nucleoside reverse transcriptase inhibitor therapy were associated with a higher risk of diabetes in HIV infected veterans.
Conclusion
While HIV infection itself is not associated with increased risk of diabetes, increasing age, HCV coinfection and BMI have a more profound effect upon the risk of diabetes among HIV infected persons. Further, long term ARV treatment also increases risk. Future studies will need to determine whether incidence of DM differs by HIV status.
doi:10.1097/QAD.0b013e32832bd7af
PMCID: PMC2752953  PMID: 19444074
HIV; diabetes; HCV; risk; antiretroviral therapy
6.  HIV Testing of At Risk Patients in a Large Integrated Health Care System 
Objective
Early identification of HIV infection is critical for patients to receive life-prolonging treatment and risk-reduction counseling. Understanding HIV screening practices and barriers to HIV testing is an important prelude to designing successful HIV screening programs. Our objective was to evaluate current practice patterns for identification of HIV.
Methods
We used a retrospective cohort analysis of 13,991 at-risk patients seen at 4 large Department of Veterans Affairs (VA) health-care systems. We also reviewed 1,100 medical records of tested patients. We assessed HIV testing rates among at-risk patients, the rationale for HIV testing, and predictors of HIV testing and of HIV infection.
Results
Of the 13,991 patients at risk for HIV, only 36% had been HIV-tested. The prevalence of HIV ranged from 1% to 20% among tested patients at the 4 sites. Approximately 90% of patients who were tested had a documented reason for testing.
Conclusion
One-half to two-thirds of patients at risk for HIV had not been tested within our selected VA sites. Among tested patients, the rationale for HIV testing was well documented. Further testing of at-risk patients could clearly benefit patients who have unidentified HIV infection by providing earlier access to life-prolonging therapy.
doi:10.1007/s11606-006-0028-9
PMCID: PMC1824727  PMID: 17356961
HIV; screening; risk factors
7.  HIV Testing of At Risk Patients in a Large Integrated Health Care System 
Objective
Early identification of HIV infection is critical for patients to receive life-prolonging treatment and risk-reduction counseling. Understanding HIV screening practices and barriers to HIV testing is an important prelude to designing successful HIV screening programs. Our objective was to evaluate current practice patterns for identification of HIV.
Methods
We used a retrospective cohort analysis of 13,991 at-risk patients seen at 4 large Department of Veterans Affairs (VA) health-care systems. We also reviewed 1,100 medical records of tested patients. We assessed HIV testing rates among at-risk patients, the rationale for HIV testing, and predictors of HIV testing and of HIV infection.
Results
Of the 13,991 patients at risk for HIV, only 36% had been HIV-tested. The prevalence of HIV ranged from 1% to 20% among tested patients at the 4 sites. Approximately 90% of patients who were tested had a documented reason for testing.
Conclusion
One-half to two-thirds of patients at risk for HIV had not been tested within our selected VA sites. Among tested patients, the rationale for HIV testing was well documented. Further testing of at-risk patients could clearly benefit patients who have unidentified HIV infection by providing earlier access to life-prolonging therapy.
doi:10.1007/s11606-006-0028-9
PMCID: PMC1824727  PMID: 17356961
HIV; screening; risk factors
8.  Bactericidal and Bacteriostatic Action of Chloramphenicol Against Meningeal Pathogens 
The bacteriostatic and bactericidal effects of chloramphenicol, ampicillin, tetracycline, and sulfisoxazole were compared against several potential meningeal pathogens. Chloramphenicol is bactericidal at clinically achievable concentrations against Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. It is bacteriostatic against gram-negative bacilli of the family Enterobacteriaceae and against Staphylococcus aureus. Chloramphenicol has proven highly efficacious in the treatment of bacterial meningitis caused by those organisms against which it is bactericidal at low concentrations. Because leukocytic phagocytosis in the subarachnoid space is inefficient, we propose that bactericidal activity in cerebrospinal fluid is important for optimal therapy of bacterial meningitis. Chloramphenicol does not provide such activity in meningitis caused by enteric gram-negative bacilli.
PMCID: PMC352780  PMID: 38742
9.  Bactericidal Efficacy of Sch 20569 and Amikacin Against Gentamicin-Sensitive and -Resistant Organisms 
Sch 20569 is a semisynthetic derivative of gentamicin with activity against many gentamicin-resistant gram-negative bacilli. We compared its bactericidal action with that of gentamicin and amikacin against 171 clinical isolates of Enterobacteriaceae, Staphylococcus aureus, and Pseudomonas aeruginosa. Sch 20569 and amikacin showed markedly greater activity than gentamicin against Escherichia coli, Klebsiella, Enterobacter, Citrobacter, and indole-positive Proteus, primarily by virtue of their lethal effect on gentamicin-resistant strains (minimal bactericidal concentration ≥ 12.5 μg/ml). Indole-negative Proteus isolates were uniformly sensitive to Sch 20569, whereas several were resistant to both gentamicin and amikacin. Amikacin was most active against Providencia, as was gentamicin against Serratia. All three agents exhibited similar activity against Pseudomonas. Staphylococcus aureus was more sensitive to gentamicin and Sch 20569 than to amikacin.
PMCID: PMC429584  PMID: 817661
10.  Synergy Between Cephalosporin and Aminoglycoside Antibiotics Against Providencia and Proteus 
Clinical isolates of Providencia and Proteus with relative aminoglycoside resistance were tested for susceptibility to combinations of gentamicin or tobramycin with cephalothin or cefazolin. The minimal bactericidal concentration of aminoglycoside for one-third of the strains was reduced by fourfold or more in the presence of one-fourth of the minimal bactericidal concentration of either cephalosporin. This effect was achieved by clinically attainable concentrations of cephalothin or cefazolin.
PMCID: PMC429016  PMID: 15825407
11.  In Vitro Bactericidal Effectiveness of Four Aminoglycoside Antibiotics 
The antibacterial activity of four aminoglycoside antibiotics (gentamicin, Sch 13706, tobramycin, and sisomicin) was tested against eight gram-negative and three gram-positive species. A total of 323 strains were studied by the broth dilution technique. Tobramycin and sisomicin had greater bacteriostatic and bactericidal activity against Pseudomonas strains than did gentamicin and Sch 13706. Of the four antibiotics, sisomicin was most active against Klebsiella, Enterobacter, Escherichia coli, indole-negative and -positive Proteus, and Streptococcus pyogenes. Gentamicin was most effective against Serratia. A fourfold or greater difference existed frequently between the minimal inhibitory and bactericidal concentrations of all antibiotics against Enterobacter and Serratia. This difference was greatest with tobramycin. Staphylococcus aureus was highly susceptible, Providencia relatively resistant, and enterococcus uniformly resistant to the antibiotics studied. Agar diffusion susceptibility testing with gentamicin and tobramycin showed that organisms susceptible to less than 6.2 μg/ml usually yielded zones 17 to 26 mm in diameters. Zones of 15 to 16 mm represented intermediate susceptibility which varied with the organism and antibiotic. Several Serratia strains required 6.2 to 12.5 μg of gentamicin/ml or 25 to 50 μg of tobramycin/ml for bactericidal activity despite minimal inhibitory concentrations of 0.09 to 3.1 μg/ml and zone sizes greater than 13 and 17 mm, respectively. Studies with Enterobacter and tobramycin yielded similar results.
PMCID: PMC444365  PMID: 4790579
12.  THE INTERACTION IN VITRO BETWEEN POLYMORPHONUCLEAR LEUKOCYTES AND MYCOPLASMA 
The Journal of Experimental Medicine  1971;134(6):1417-1430.
The interaction, between mycoplasma (PPLO) and human or rabbit leukocytes was examined in vitro. Upon incubation of M. hominis or M. arthritidis for 2 hr with rabbit peritoneal exudate granulocytes or leukocytes from human peripheral blood, no killing of mycoplasma was observed either in the presence or absence of type-specific antiserum. However, 14CO2 production from glucose-1-14C was stimulated up to 10-fold in the presence of live or heat-killed PPLO. The extent of stimulation depended upon the number of organisms and the presence of type-specific antiserum. The stimulation of 14CO2 production seems not because of tight adherence of PPLO to the leukocytes, since PPLO were quantitatively recovered in the medium after sedimenting the granulocytes. The enhanced conversion of medium lysolecithin to cellular lecithin that accompanies phagocytosis of polystyrene particles was significantly reduced when PPLO were also present. Mycoplasma alone elicited no stimulation of lecithin formation. Killing of E. coli, a microorganism readily engulfed and killed by leukocytes in vitro, was diminished when the leukocytes were preincubated with mycoplasma. These findings indicate that M. hominis and M. arthritidis are not ingested by granulocytes to any detectable extent, but that these organisms affect the leukocytes' metabolism and also impair phagocytosis of E. coli.
PMCID: PMC2139108  PMID: 4942406
13.  STUDIES OF PPLO INFECTION  
The Journal of Experimental Medicine  1969;129(6):1163-1181.
Extracts of five arginine-utilizing mycoplasmas inhibit PHA-induced lymphocyte mitosis, while extracts of five glucose-utilizing mycoplasmas do not. Evidence is presented supporting the view that the inhibitory factor is the enzyme arginine deiminase. This enzyme inhibits the reactions of human lymphocytes to antigens as well as PHA, and the secondary production of antibody by rabbit lymph node fragments in vitro. Addition of enzyme to the cells several days after the initial mitotic or antigenic stimulus reduces, but does not abolish, further cellular activity. The production of serum proteins by hepatoma cells is totally unaffected by the mycoplasmal extract. It is concluded that arginine is an essential amino acid for the small lymphocyte, but not for the transformed cell nor for a number of other cell types. Suggestive evidence has been obtained that other enzymes similarly affect lymphocyte reactions.
PMCID: PMC2138654  PMID: 4306341

Results 1-13 (13)