Anthony Albanese | U.S. Department of Veterans Affairs (original) (raw)

Papers by Anthony Albanese

Research paper thumbnail of THE UTILIZATION OF d-AMINO ACIDS BY MAN VIII. TRYPTOPHAN AND ACETYLTRYPTOPHAN

Journal of Biological Chemistry, 1948

Research paper thumbnail of Sa1604 Muscle Cramps in Patients With Liver Cirrhosis: Systematic Evaluation of 1224 Cases With Meta-Analysis

Research paper thumbnail of Management of alcohol abuse

Clinics in liver disease, 2012

This article reviews the spectrum of alcohol use disorders. The pharmacologic properties of ethan... more This article reviews the spectrum of alcohol use disorders. The pharmacologic properties of ethanol and its metabolism, and the historical, physical, and laboratory elements that may help diagnose an alcohol use disorder are examined. The concepts of motivational interviewing and stages of change are mentioned, along with the American Society of Addiction Medicine patient placement criteria, to determine the best level of treatment for alcoholism. Various therapeutic management options are reviewed, including psychological, pharmacologic, and complementary/alternative choices. This article provides a basic understanding of available tools to diagnose and treat this cunning and baffling brain and multisystem disease.

Research paper thumbnail of Outcome and Six Month Follow Up of Patients After Ultra Rapid Opiate Detoxification (URODSM)

Journal of Addictive Diseases, 2000

(1) Evaluate the safety and efficacy of Ultra Rapid Opiate Detoxification (UROD); and (2) evaluat... more (1) Evaluate the safety and efficacy of Ultra Rapid Opiate Detoxification (UROD); and (2) evaluate six month outcome data of patients choosing this method. Two center parallel group clinical trial. No grant funding. Two academic medical centers. Ninety-three men and 27 women, aged 18 to 55 years, with opiate dependency self selected to undergo detoxification. UROD followed by naltrexone maintenance and an aftercare program. UROD and aftercare costs were the responsibility of the patients and/or their significant others. (1) Completion of UROD as determined by a non reactive response to a naloxone challenge test under anesthesia and non reactive response to naltrexone administration before discharge. (2) Patient outcome as determined at six month follow up of UROD patients' self reported relapse free status confirmed by urine drug screen, significant other reports, and/or therapist reports. One hundred percent successful detoxification with UROD with low morbidity and no mortality. Relapse data were available for 111/123 procedures performed (90%), with 61/111 patients (55%) with reported relapse free status at the six month follow up interval. For individuals who are addicted to opioids, the Ultra Rapid Opiate Detoxification method appears to be a viable treatment option.

Research paper thumbnail of Safety and efficacy of a new flexible video laparoscope in diagnostic laparoscopy

Gastrointestinal Endoscopy, 1993

Research paper thumbnail of The Regional Distribution of Psychiatric Residency Positions Funded by the Department of Veterans Affairs and Its Relationship to Rural Veteran Populations

Academic Psychiatry, 2021

Objective The authors evaluated the distribution of psychiatry residency positions funded by the ... more Objective The authors evaluated the distribution of psychiatry residency positions funded by the Department of Veterans Affairs between 2014 and 2020 with respect to geographic location and hospital patient population rurality. Methods The authors collected data on psychiatry residency positions from the Veterans Affairs’ Office of Academic Affiliations Support Center and data on hospital-level patient rurality from the Veterans Health Administration Support Service Center. They examined the chronological and geospatial relationships between the number of residency positions deployed and the size of the rural patient populations served. Results Between 2014 and 2020, the Department of Veterans Affairs has substantially increased the number of rural hospitals hosting psychiatry residency programs, as well as the number of residency positions at those hospitals. However, several geographic regions serve high numbers of rural veterans with few or no psychiatry resident positions. Concl...

Research paper thumbnail of A Year 3 Progress Report on Graduate Medical Education Expansion in the Veterans Access, Choice, and Accountability Act

Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 2018

The VA has made progress in implementing mandates to expand medical residency programs to more ru... more The VA has made progress in implementing mandates to expand medical residency programs to more rural and underserved locations and to increase access to family care providers, but some specialties, like geriatrics, remain underrepresented.

Research paper thumbnail of Delayed GALT reconstitution in duodenum compared to rectum in hiv-infected patients initiating antiretroviral therapy

AIDS, 2019

HIV-CONTROLS HIV+ subjects P value Month 0 Month 9 HIV-vs. HIV+ Month 0 HIV-vs. HIV+ Month 9 Mont... more HIV-CONTROLS HIV+ subjects P value Month 0 Month 9 HIV-vs. HIV+ Month 0 HIV-vs. HIV+ Month 9 Month 0 vs. 9 in HIV+ CD4+ T cells/mm 3 blood-436 (283-572) 693 (452-848)-<0.001 CD4+ T cells/mm 2 rectum 395 (340-478) 51 (29-88) 135 (54-167) <0.001 <0.001 0,013 CD4+ T cells/mm 2 duodenum 566 (509-688) 48 (31-184) 158 (116-254) <0.001 <0.001 0,011 %CD4+ T cells blood 58.2 (52.7-69.8) 28.3 (21.5-35.5) 40.5 (35.4-36.1) <0.001 <0.001 <0.001 %CD4+ T cells rectum 63.1 (51.7-67.1) 18.9 (13.4-24.1) 38.7 (34.8-41.3) <0.001 <0.001 <0.001 %CD4+ T cells duodenum 44.4 (38.4-55.3) 6.3 (4.0-11.6) 17.3 (11.6-27.8) <0.001 <0.001 <0.001 CD8+ T cells/mm3 blood CD8+ T cells/mm 2 rectum 188 (133, 258) 698 (518, 792) 403 (328, 635) <0.001 <0.001 0,0019 CD8+ T cells/mm 2 duodenum 543 (360-713) 1345 (1084-1776) 843 (686-955) <0.001 0,003 <0.001 %CD8+ T cells blood 36.7 (26.6-42.6) 63.4 (56.8-69.1) 52.6 (45.6-58.5) <0.001 <0.001 <0.001 %CD8+ T cells rectum 30.9 (22.5-32.9) 72.2 (66.0-81.0) 51.4 (44.9-57.4) <0.001 <0.001 <0.001 %CD8+ T cells duodenum 44.2 (38-54.6) 88.7 (79.6-92.0) 73.0 (66.2-82.4) <0.001 <0.001 <0.001 CD4/CD8 ratio blood 1.

Research paper thumbnail of The VA MISSION Act of 2018: A Potential Game Changer for Rural GME Expansion and Veteran Health Care

The Journal of Rural Health, 2019

Research paper thumbnail of Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial

PLOS Pathogens, 2016

Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrat... more Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV-controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/ emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by highperformance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8 + T-cell density decline, greater normalization of mucosal CCR5 + CD4 + T-cells and increase of the naïve/memory CD8 + T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the

Research paper thumbnail of Role of intestinal myofibroblasts in HIV-associated intestinal collagen deposition and immune reconstitution following combination antiretroviral therapy

AIDS (London, England), Jan 11, 2015

To investigate the potential role of mucosal intestinal myofibroblasts (IMFs) in HIV and associat... more To investigate the potential role of mucosal intestinal myofibroblasts (IMFs) in HIV and associated fibrosis in gut-associated lymphoid tissue. Profibrotic changes within the secondary lymphoid organs and mucosa have been implicated in failed immune reconstitution following effective combination antiretroviral therapy (cART). Microbial translocation is believed to be sustaining these systemic inflammatory pathways. IMFs are nonprofessional antigen-presenting cells with both immunoregulatory and mesenchymal functions that are ideally positioned to respond to translocating microbial antigen. Duodenal biopsies were obtained from patients naïve to cART, who underwent trichrome staining and were examined for tissue growth factor-beta (TGF-β) expression. Combined immunostaining and second harmonic generation analysis were used to determine IMF activation and collagen deposition. Confocal microscopy was performed to examine IMF activation and Toll-like receptor (TLR)4 expression. Finally, ...

Research paper thumbnail of Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: A randomized cross-over trial

Pharmacology Biochemistry and Behavior, 2009

Background-Abuse liability is thought to possibly be lower in long-than in short-acting opioids b... more Background-Abuse liability is thought to possibly be lower in long-than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects. Methods-We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Center Inventory, and underwent cue reactivity testing. To perform the latter, subjects watched a video intended to produce a positive or a negative affect, after which a vial of medication was or was not presented (the cue) and then indicated their craving for drugs on 5 different VASs (the reactivity). Results-Differences in Addiction Research Inventory scores were statistically significant but clinically unimportant. Neuropsychological test results were mixed and unrelated to the medications studied. Cue reactivity did not differ among conditions but was uniformly high. Conclusions-Using several markers of abuse liability, long-acting opioids do not have lower abuse potential than do short-acting opioids or placebo. Although cue reactivity did not differ among the conditions, uniformly high results in these patients suggest that it may have some value as a component of abuse liability testing.

Research paper thumbnail of Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation

Journal of acquired immune deficiency syndromes (1999), Jan 15, 2011

The relationship between gut microbial community composition at the higher-taxonomic order level ... more The relationship between gut microbial community composition at the higher-taxonomic order level and local and systemic immunologic abnormalities in HIV disease may provide insight into how bacterial translocation impacts HIV disease.

Research paper thumbnail of W1830 CD4+ T-Cell Depletion in Gut-Associated Lymphoid Tissue and CD8+ T-Cell Hyperactivation in Peripheral Blood are Linked to Greater Gut-Proportion of Enterobacteriales and Bacteroidales in HIV Therapy Pre-Clinical Trial Analysis

Gastroenterology, 2010

No abstract is available. To read the body of this article, please view the PDF online. ... © 201... more No abstract is available. To read the body of this article, please view the PDF online. ... © 2010 AGA. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution. ... Advertisements on this site do not constitute a guarantee or endorsement by the journal, Association, or publisher of the quality or value of such product or of the claims made for it by its manufacturer.

Research paper thumbnail of Antituberculosis Drug–induced Hepatotoxicity

American Journal of Respiratory and Critical Care Medicine, 1998

Until recently it was thought that age greater than 35 yr was the main risk factor for the develo... more Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p Ͻ 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p Ͻ 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs. Ungo JR, Jones D, Ashkin D, Hollender ES, Bernstein D, Albanese AP, Pitchenik AE. Antituberculosis drug-induced hepatotoxicity: the role of hepatitis C virus and the human immunodeficiency virus.

Research paper thumbnail of S-adenosyl-L-methionine Treatment for Alcoholic Liver Disease: A Double-Blinded, Randomized, Placebo-Controlled Trial

Alcoholism: Clinical and Experimental Research, 2011

BackgroundS -adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and re... more BackgroundS -adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione (GSH), the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALD). The aim of this study was to determine the efficacy of SAM in treatment of ALD in a 24 week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoint was changes in serum levels of methionine metabolites. Methods-We randomized 37 patients with ALD to receive 1.2 grams of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects and a post-treatment liver biopsy was performed in 14 subjects. Results-Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra-or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies. Conclusions-Whereas abstinence improved liver function, twenty-four weeks of therapy with SAM was no more effective than placebo in the treatment of ALD.

Research paper thumbnail of Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens

AIDS, 2012

Objectives: To examine immune restoration in duodenal tissue and correlates of reduction of immun... more Objectives: To examine immune restoration in duodenal tissue and correlates of reduction of immune activation in chronic HIV-infected patients randomized to different treatment regimens. Design: Randomized clinical trial (RCT) comparing raltegravir to a non-nucleoside reverse transcriptase inhibitor-based regimen, both with fixed-dose tenofovir difumerate/emtricitabine. Methods: Antiretroviral therapy (ART)-naive volunteers underwent upper endoscopy for duodenal biopsies before and after 9 months of therapy. Tissue was paraffinembedded for immunohistochemistry or digested into single-cell suspensions for flow cytometry of lymphocyte subsets and activation phenotype. Plasma-soluble CD14 levels were measured as a surrogate for bacterial translocation. Results: Sixteen HIV-positive and seven control individuals completed study procedures. Small increases in duodenal lamina propria CD4 þ T-cell numbers were observed, especially when viewed relative to populations in control volunteers, with no differences between treatment arms. The increase in CD4 þ T-cell percentage was due largely to declines in CD8 þ T-cell numbers, which were disproportionately increased compared to peripheral blood and controls. Patients randomized to the raltegravir arm had consistent declines in both sCD14 levels and CD8 þ T-cell numbers in the duodenal tissue lamina propria. Conclusions: This first RCT of lymphocyte population restoration in duodenal tissue demonstrates more modest increases in CD4 þ T-cell numbers during the first 9 months of therapy than when considering CD3/CD4 percentages only. Although reduced after 9 months of ART, disproportional increased CD8 populations persist in duodenal gastrointestinal-associated lymphoid tissue (GALT). Local rather than systemic antigenic stimulation appears to be driving expanded CD8 þ T lymphocytes in GALT. Factors other than viral-induced CD8 expansion may be contributing to this local immunologic response.

Research paper thumbnail of Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy

AIDS, 2013

Objectives: To examine the impact of serum-derived bovine immunoglobulin, an oral medical food kn... more Objectives: To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. Design: Open-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study. Methods: HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms. Results: All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P ¼ 0.008) and improvements in stool consistency (P ¼ 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 þ lymphocyte densities increased by a median of 139.5 cells/mm 2 from 213 to 322 cells/mm 2 (P ¼ 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P ¼ 0.039), and then fell below baseline in four of five who continued receiving SBI (P ¼ 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 þ lymphocyte densities (r ¼ À0.74, P ¼ 0.046). Conclusion: SBI significantly increases intestinal mucosal CD4 þ lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.

Research paper thumbnail of Management of Alcohol Use Disorder

Journal of Addiction and Therapies, 2017

This monograph is a review article on the spectrum of alcohol use disorders.We discuss the pharma... more This monograph is a review article on the spectrum of alcohol use disorders.We discuss the pharmacological properties of ethanol along with its metabolism. The historical, physical and laboratory elements that may assist in diagnosis of an alcohol use disorder are examined. The concepts of motivational interviewing and stages of change are mentioned, along with the ASAM patient placement criteria to determine the best level of treatment when the subject is ready to take action. Various therapeutic management options are reviewed including psychologic, pharmacologic, and complementary/alternative choices. The purpose of this article is to give the clinician a basic understanding of the tools available to diagnose and treat this "Cunning and baffling" brain and multisystem disease.

Research paper thumbnail of S-adenosyl-L-methionine Treatment for Alcoholic Liver Disease: A Double-Blinded, Randomized, Placebo-Controlled Trial

Alcoholism: Clinical and Experimental Research, 2011

Background-S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and re... more Background-S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione (GSH), the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALD). The aim of this study was to determine the efficacy of SAM in treatment of ALD in a 24 week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoint was changes in serum levels of methionine metabolites.

Research paper thumbnail of THE UTILIZATION OF d-AMINO ACIDS BY MAN VIII. TRYPTOPHAN AND ACETYLTRYPTOPHAN

Journal of Biological Chemistry, 1948

Research paper thumbnail of Sa1604 Muscle Cramps in Patients With Liver Cirrhosis: Systematic Evaluation of 1224 Cases With Meta-Analysis

Research paper thumbnail of Management of alcohol abuse

Clinics in liver disease, 2012

This article reviews the spectrum of alcohol use disorders. The pharmacologic properties of ethan... more This article reviews the spectrum of alcohol use disorders. The pharmacologic properties of ethanol and its metabolism, and the historical, physical, and laboratory elements that may help diagnose an alcohol use disorder are examined. The concepts of motivational interviewing and stages of change are mentioned, along with the American Society of Addiction Medicine patient placement criteria, to determine the best level of treatment for alcoholism. Various therapeutic management options are reviewed, including psychological, pharmacologic, and complementary/alternative choices. This article provides a basic understanding of available tools to diagnose and treat this cunning and baffling brain and multisystem disease.

Research paper thumbnail of Outcome and Six Month Follow Up of Patients After Ultra Rapid Opiate Detoxification (URODSM)

Journal of Addictive Diseases, 2000

(1) Evaluate the safety and efficacy of Ultra Rapid Opiate Detoxification (UROD); and (2) evaluat... more (1) Evaluate the safety and efficacy of Ultra Rapid Opiate Detoxification (UROD); and (2) evaluate six month outcome data of patients choosing this method. Two center parallel group clinical trial. No grant funding. Two academic medical centers. Ninety-three men and 27 women, aged 18 to 55 years, with opiate dependency self selected to undergo detoxification. UROD followed by naltrexone maintenance and an aftercare program. UROD and aftercare costs were the responsibility of the patients and/or their significant others. (1) Completion of UROD as determined by a non reactive response to a naloxone challenge test under anesthesia and non reactive response to naltrexone administration before discharge. (2) Patient outcome as determined at six month follow up of UROD patients&amp;amp;#39; self reported relapse free status confirmed by urine drug screen, significant other reports, and/or therapist reports. One hundred percent successful detoxification with UROD with low morbidity and no mortality. Relapse data were available for 111/123 procedures performed (90%), with 61/111 patients (55%) with reported relapse free status at the six month follow up interval. For individuals who are addicted to opioids, the Ultra Rapid Opiate Detoxification method appears to be a viable treatment option.

Research paper thumbnail of Safety and efficacy of a new flexible video laparoscope in diagnostic laparoscopy

Gastrointestinal Endoscopy, 1993

Research paper thumbnail of The Regional Distribution of Psychiatric Residency Positions Funded by the Department of Veterans Affairs and Its Relationship to Rural Veteran Populations

Academic Psychiatry, 2021

Objective The authors evaluated the distribution of psychiatry residency positions funded by the ... more Objective The authors evaluated the distribution of psychiatry residency positions funded by the Department of Veterans Affairs between 2014 and 2020 with respect to geographic location and hospital patient population rurality. Methods The authors collected data on psychiatry residency positions from the Veterans Affairs’ Office of Academic Affiliations Support Center and data on hospital-level patient rurality from the Veterans Health Administration Support Service Center. They examined the chronological and geospatial relationships between the number of residency positions deployed and the size of the rural patient populations served. Results Between 2014 and 2020, the Department of Veterans Affairs has substantially increased the number of rural hospitals hosting psychiatry residency programs, as well as the number of residency positions at those hospitals. However, several geographic regions serve high numbers of rural veterans with few or no psychiatry resident positions. Concl...

Research paper thumbnail of A Year 3 Progress Report on Graduate Medical Education Expansion in the Veterans Access, Choice, and Accountability Act

Federal practitioner : for the health care professionals of the VA, DoD, and PHS, 2018

The VA has made progress in implementing mandates to expand medical residency programs to more ru... more The VA has made progress in implementing mandates to expand medical residency programs to more rural and underserved locations and to increase access to family care providers, but some specialties, like geriatrics, remain underrepresented.

Research paper thumbnail of Delayed GALT reconstitution in duodenum compared to rectum in hiv-infected patients initiating antiretroviral therapy

AIDS, 2019

HIV-CONTROLS HIV+ subjects P value Month 0 Month 9 HIV-vs. HIV+ Month 0 HIV-vs. HIV+ Month 9 Mont... more HIV-CONTROLS HIV+ subjects P value Month 0 Month 9 HIV-vs. HIV+ Month 0 HIV-vs. HIV+ Month 9 Month 0 vs. 9 in HIV+ CD4+ T cells/mm 3 blood-436 (283-572) 693 (452-848)-<0.001 CD4+ T cells/mm 2 rectum 395 (340-478) 51 (29-88) 135 (54-167) <0.001 <0.001 0,013 CD4+ T cells/mm 2 duodenum 566 (509-688) 48 (31-184) 158 (116-254) <0.001 <0.001 0,011 %CD4+ T cells blood 58.2 (52.7-69.8) 28.3 (21.5-35.5) 40.5 (35.4-36.1) <0.001 <0.001 <0.001 %CD4+ T cells rectum 63.1 (51.7-67.1) 18.9 (13.4-24.1) 38.7 (34.8-41.3) <0.001 <0.001 <0.001 %CD4+ T cells duodenum 44.4 (38.4-55.3) 6.3 (4.0-11.6) 17.3 (11.6-27.8) <0.001 <0.001 <0.001 CD8+ T cells/mm3 blood CD8+ T cells/mm 2 rectum 188 (133, 258) 698 (518, 792) 403 (328, 635) <0.001 <0.001 0,0019 CD8+ T cells/mm 2 duodenum 543 (360-713) 1345 (1084-1776) 843 (686-955) <0.001 0,003 <0.001 %CD8+ T cells blood 36.7 (26.6-42.6) 63.4 (56.8-69.1) 52.6 (45.6-58.5) <0.001 <0.001 <0.001 %CD8+ T cells rectum 30.9 (22.5-32.9) 72.2 (66.0-81.0) 51.4 (44.9-57.4) <0.001 <0.001 <0.001 %CD8+ T cells duodenum 44.2 (38-54.6) 88.7 (79.6-92.0) 73.0 (66.2-82.4) <0.001 <0.001 <0.001 CD4/CD8 ratio blood 1.

Research paper thumbnail of The VA MISSION Act of 2018: A Potential Game Changer for Rural GME Expansion and Veteran Health Care

The Journal of Rural Health, 2019

Research paper thumbnail of Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial

PLOS Pathogens, 2016

Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrat... more Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV-controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/ emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by highperformance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8 + T-cell density decline, greater normalization of mucosal CCR5 + CD4 + T-cells and increase of the naïve/memory CD8 + T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the

Research paper thumbnail of Role of intestinal myofibroblasts in HIV-associated intestinal collagen deposition and immune reconstitution following combination antiretroviral therapy

AIDS (London, England), Jan 11, 2015

To investigate the potential role of mucosal intestinal myofibroblasts (IMFs) in HIV and associat... more To investigate the potential role of mucosal intestinal myofibroblasts (IMFs) in HIV and associated fibrosis in gut-associated lymphoid tissue. Profibrotic changes within the secondary lymphoid organs and mucosa have been implicated in failed immune reconstitution following effective combination antiretroviral therapy (cART). Microbial translocation is believed to be sustaining these systemic inflammatory pathways. IMFs are nonprofessional antigen-presenting cells with both immunoregulatory and mesenchymal functions that are ideally positioned to respond to translocating microbial antigen. Duodenal biopsies were obtained from patients naïve to cART, who underwent trichrome staining and were examined for tissue growth factor-beta (TGF-β) expression. Combined immunostaining and second harmonic generation analysis were used to determine IMF activation and collagen deposition. Confocal microscopy was performed to examine IMF activation and Toll-like receptor (TLR)4 expression. Finally, ...

Research paper thumbnail of Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: A randomized cross-over trial

Pharmacology Biochemistry and Behavior, 2009

Background-Abuse liability is thought to possibly be lower in long-than in short-acting opioids b... more Background-Abuse liability is thought to possibly be lower in long-than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects. Methods-We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Center Inventory, and underwent cue reactivity testing. To perform the latter, subjects watched a video intended to produce a positive or a negative affect, after which a vial of medication was or was not presented (the cue) and then indicated their craving for drugs on 5 different VASs (the reactivity). Results-Differences in Addiction Research Inventory scores were statistically significant but clinically unimportant. Neuropsychological test results were mixed and unrelated to the medications studied. Cue reactivity did not differ among conditions but was uniformly high. Conclusions-Using several markers of abuse liability, long-acting opioids do not have lower abuse potential than do short-acting opioids or placebo. Although cue reactivity did not differ among the conditions, uniformly high results in these patients suggest that it may have some value as a component of abuse liability testing.

Research paper thumbnail of Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation

Journal of acquired immune deficiency syndromes (1999), Jan 15, 2011

The relationship between gut microbial community composition at the higher-taxonomic order level ... more The relationship between gut microbial community composition at the higher-taxonomic order level and local and systemic immunologic abnormalities in HIV disease may provide insight into how bacterial translocation impacts HIV disease.

Research paper thumbnail of W1830 CD4+ T-Cell Depletion in Gut-Associated Lymphoid Tissue and CD8+ T-Cell Hyperactivation in Peripheral Blood are Linked to Greater Gut-Proportion of Enterobacteriales and Bacteroidales in HIV Therapy Pre-Clinical Trial Analysis

Gastroenterology, 2010

No abstract is available. To read the body of this article, please view the PDF online. ... © 201... more No abstract is available. To read the body of this article, please view the PDF online. ... © 2010 AGA. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution. ... Advertisements on this site do not constitute a guarantee or endorsement by the journal, Association, or publisher of the quality or value of such product or of the claims made for it by its manufacturer.

Research paper thumbnail of Antituberculosis Drug–induced Hepatotoxicity

American Journal of Respiratory and Critical Care Medicine, 1998

Until recently it was thought that age greater than 35 yr was the main risk factor for the develo... more Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p Ͻ 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p Ͻ 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs. Ungo JR, Jones D, Ashkin D, Hollender ES, Bernstein D, Albanese AP, Pitchenik AE. Antituberculosis drug-induced hepatotoxicity: the role of hepatitis C virus and the human immunodeficiency virus.

Research paper thumbnail of S-adenosyl-L-methionine Treatment for Alcoholic Liver Disease: A Double-Blinded, Randomized, Placebo-Controlled Trial

Alcoholism: Clinical and Experimental Research, 2011

BackgroundS -adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and re... more BackgroundS -adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione (GSH), the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALD). The aim of this study was to determine the efficacy of SAM in treatment of ALD in a 24 week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoint was changes in serum levels of methionine metabolites. Methods-We randomized 37 patients with ALD to receive 1.2 grams of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects and a post-treatment liver biopsy was performed in 14 subjects. Results-Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra-or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies. Conclusions-Whereas abstinence improved liver function, twenty-four weeks of therapy with SAM was no more effective than placebo in the treatment of ALD.

Research paper thumbnail of Gastrointestinal-associated lymphoid tissue immune reconstitution in a randomized clinical trial of raltegravir versus non-nucleoside reverse transcriptase inhibitor-based regimens

AIDS, 2012

Objectives: To examine immune restoration in duodenal tissue and correlates of reduction of immun... more Objectives: To examine immune restoration in duodenal tissue and correlates of reduction of immune activation in chronic HIV-infected patients randomized to different treatment regimens. Design: Randomized clinical trial (RCT) comparing raltegravir to a non-nucleoside reverse transcriptase inhibitor-based regimen, both with fixed-dose tenofovir difumerate/emtricitabine. Methods: Antiretroviral therapy (ART)-naive volunteers underwent upper endoscopy for duodenal biopsies before and after 9 months of therapy. Tissue was paraffinembedded for immunohistochemistry or digested into single-cell suspensions for flow cytometry of lymphocyte subsets and activation phenotype. Plasma-soluble CD14 levels were measured as a surrogate for bacterial translocation. Results: Sixteen HIV-positive and seven control individuals completed study procedures. Small increases in duodenal lamina propria CD4 þ T-cell numbers were observed, especially when viewed relative to populations in control volunteers, with no differences between treatment arms. The increase in CD4 þ T-cell percentage was due largely to declines in CD8 þ T-cell numbers, which were disproportionately increased compared to peripheral blood and controls. Patients randomized to the raltegravir arm had consistent declines in both sCD14 levels and CD8 þ T-cell numbers in the duodenal tissue lamina propria. Conclusions: This first RCT of lymphocyte population restoration in duodenal tissue demonstrates more modest increases in CD4 þ T-cell numbers during the first 9 months of therapy than when considering CD3/CD4 percentages only. Although reduced after 9 months of ART, disproportional increased CD8 populations persist in duodenal gastrointestinal-associated lymphoid tissue (GALT). Local rather than systemic antigenic stimulation appears to be driving expanded CD8 þ T lymphocytes in GALT. Factors other than viral-induced CD8 expansion may be contributing to this local immunologic response.

Research paper thumbnail of Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy

AIDS, 2013

Objectives: To examine the impact of serum-derived bovine immunoglobulin, an oral medical food kn... more Objectives: To examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy. Design: Open-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study. Methods: HIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms. Results: All eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P ¼ 0.008) and improvements in stool consistency (P ¼ 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 þ lymphocyte densities increased by a median of 139.5 cells/mm 2 from 213 to 322 cells/mm 2 (P ¼ 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P ¼ 0.039), and then fell below baseline in four of five who continued receiving SBI (P ¼ 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 þ lymphocyte densities (r ¼ À0.74, P ¼ 0.046). Conclusion: SBI significantly increases intestinal mucosal CD4 þ lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.

Research paper thumbnail of Management of Alcohol Use Disorder

Journal of Addiction and Therapies, 2017

This monograph is a review article on the spectrum of alcohol use disorders.We discuss the pharma... more This monograph is a review article on the spectrum of alcohol use disorders.We discuss the pharmacological properties of ethanol along with its metabolism. The historical, physical and laboratory elements that may assist in diagnosis of an alcohol use disorder are examined. The concepts of motivational interviewing and stages of change are mentioned, along with the ASAM patient placement criteria to determine the best level of treatment when the subject is ready to take action. Various therapeutic management options are reviewed including psychologic, pharmacologic, and complementary/alternative choices. The purpose of this article is to give the clinician a basic understanding of the tools available to diagnose and treat this "Cunning and baffling" brain and multisystem disease.

Research paper thumbnail of S-adenosyl-L-methionine Treatment for Alcoholic Liver Disease: A Double-Blinded, Randomized, Placebo-Controlled Trial

Alcoholism: Clinical and Experimental Research, 2011

Background-S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and re... more Background-S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione (GSH), the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALD). The aim of this study was to determine the efficacy of SAM in treatment of ALD in a 24 week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoint was changes in serum levels of methionine metabolites.