Michael Poles, M.D.

Colorectal cancer screening of high-risk populations: A national survey of physicians
White PM; Sahu M; Poles MA; Francois F
2012 Jan 24;5(1):64-64, BMC research notes
ABSTRACT: BACKGROUND: The incidence of colorectal cancer can be decreased by appropriate use of screening modalities. Patients with a family history of colon cancer and of African-American ethnicity are known to be at higher risk of developing colorectal cancer. We aimed to determine if there is a lack of physician knowledge for colorectal cancer screening guidelines based on family history and ethnicity. Between February and April 2009 an anonymous web-based survey was administered to a random sample selected from a national list of 25,000 internists, family physicians and gastroenterologists. A stratified sampling strategy was used to include practitioners from states with high as well as low CRC incidence. All data analyses were performed following data collection in 2009. RESULTS: The average knowledge score was 37 +/- 18% among the 512 respondents. Gastroenterologists averaged higher scores compared to internists, and family physicians, p = 0.001. Only 28% of physicians correctly identified the screening initiation point for African-Americans while only 12% of physicians correctly identified the screening initiation point and interval for a patient with a family history of CRC. The most commonly cited barriers to referring high-risk patients for CRC screening were 'patient refusal' and 'lack of insurance reimbursement.' CONCLUSIONS: There is a lack of knowledge amongst physicians of the screening guidelines for high-risk populations, based on family history and ethnicity. Educational programs to improve physician knowledge and to reduce perceived barriers to CRC screening are warranted to address health disparities in colorectal cancer
— id: 150848, year: 2012, vol: 5, page: 64, stat: Journal Article,

Intrahepatic natural killer T cell populations are increased in human hepatic steatosis
Adler, Michael; Taylor, Sarah; Okebugwu, Kamalu; Yee, Herman; Fielding, Christine; Fielding, George; Poles, Michael
2011 Apr 7;17(13):1725-1731, World journal of gastroenterology : WJG
AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease (NAFLD). METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during surgery. The biopsy was assessed for steatosis and immunocyte infiltration. Intrahepatic lymphocytes (IHLs) were isolated from the remainder of the liver biopsy, and peripheral blood mononuclear cells (PBMCs) were isolated from the blood. Expression of surface proteins on both IHLs and PBMCs were quantified using flow cytometry. RESULTS: Twenty-seven subjects participated in this study. Subjects with moderate or severe steatosis had a higher percentage of intrahepatic CD3+/CD56+ NKT cells (38.6%) than did patients with mild steatosis (24.1%, P = 0.05) or those without steatosis (21.5%, P = 0.03). Patients with moderate to severe steatosis also had a higher percentage of NKT cells in the blood (12.3%) as compared to patients with mild steatosis (2.5% P = 0.02) and those without steatosis (5.1%, P = 0.05). CONCLUSION: NKT cells are significantly increased in the liver and blood of patients with moderate to severe steatosis and support the role of NKT cells in NAFLD
— id: 130915, year: 2011, vol: 17, page: 1725, stat: Journal Article,

Human Microbiome and HIV/AIDS
Saxena D; Li Y; Yang L; Pei Z; Poles M; Abrams WR; Malamud D
2011 Dec 23;:44-51 #, Current HIV/AIDS reports
Understanding of the human microbiome continues to grow rapidly; however, reports on changes in the microbiome after HIV infection are still limited. This review surveys the progress made in methodology associated with microbiome studies and highlights the remaining challenges to this field. Studies have shown that commensal oral, gut, vaginal, and penile bacteria are vital to the health of the human immune system. Our studies on crosstalk among oral and gastrointestinal soluble innate factors, HIV, and microbes indicated that the oral and gut microbiome was altered in the HIV-positive samples compared to the negative controls. The importance of understanding the bacterial component of HIV/AIDS, and likelihood of 'crosstalk' between viral and bacterial pathogens, will help in understanding the role of the microbiome in HIV-infected individuals and facilitate identification of novel antiretroviral factors for use as novel diagnostics, microbicides, or therapeutics against HIV infection
— id: 149845, year: 2011, vol: , page: 44, stat: Journal Article,

Informed consent in the older adult: OSCEs for assessing fellows' ACGME and geriatric gastroenterology competencies
Shah, Brijen; Miler, Roy; Poles, Michael; Zabar, Sondra; Gillespie, Colleen; Weinshel, Elizabeth; Chokhavatia, Sita
2011 Sep;106(9):1575-1579, American journal of gastroenterology
OBJECTIVES: The American Gastroenterological Association fellowship curriculum identifies geriatric components for gastroenterology (GI) training; however, few tools are available for this purpose. Using an objective structured clinical examination (OSCE), we aimed to assess ACGME competencies of communication, professionalism, and geriatric-specific patient care among GI fellows. METHODS: We developed an informed-consent case involving a geriatric patient who needs surveillance colonoscopy. We used a validated faculty skills checklist to rate fellows across three competency domains. Fifteen fellows from four GI training programs participated. RESULTS: Although the fellows excelled at communication and professionalism, only 51% excelled at geriatric-specific patient-care skills. Fellows were least likely to demonstrate collaboration with the patient, to assess patient understanding, and to explain the limits of the test. Communication and geriatric-specific skills were correlated. CONCLUSIONS: OSCEs are a feasible method for assessing geriatric-related ACGME competencies for fellows. The results highlight the need for curriculum development
— id: 149732, year: 2011, vol: 106, page: 1575, stat: Journal Article,

Observing Handoffs and Telephone Management in GI Fellowship Training
Williams, Renee; Miler, Roy; Shah, Brijen; Chokhavatia, Sita; Poles, Michael; Zabar, Sondra; Gillespie, Colleen; Weinshel, Elizabeth
2011 Aug;106(8):1410-1414, American journal of gastroenterology
OBJECTIVES: Gastroenterology (GI) training programs are mandated to teach fellows interpersonal communication and professionalism as basic competencies. We sought to assess important skill sets used by our fellows but not formally observed or measured: handoffs, telephone management, and note writing. We designed an Observed Standardized Clinical Examination (OSCE) form and provided the faculty with checklists to rate fellows' performance on specific criteria. METHODS: We created two new scenarios: a handoff between a tired overnight senior fellow on call and a more junior fellow, and a telephone management case of an ulcerative colitis flare. Fellows wrote a progress notes documenting the encounters. To add educational value, we gave the participants references about handoff communication. Four OSCE stations-handoff communication, telephone management, informed consent, and delivering bad news-were completed by fellows and observed by faculty. RESULTS: Eight faculty members and eight fellows from four GI training programs participated. All the fellows agreed that handoffs can be important learning opportunities and can be improved if they are structured, and that handoff skills can improve with practice. CONCLUSIONS: OSCEs can serve as practicums for assessing complex skill sets such as handoff communication and telephone management
— id: 135568, year: 2011, vol: 106, page: 1410, stat: Journal Article,

Teaching the competencies: using observed structured clinical examinations for faculty development
Alevi, David; Baiocco, Peter J; Chokhavatia, Sita; Kotler, Donald P; Poles, Michael; Zabar, Sondra; Gillespie, Colleen; Ark, Tavinder; Weinshel, Elizabeth
2010 May;105(5):973-977, American journal of gastroenterology
OBJECTIVES: Gastroenterology (GI) training programs must develop the teaching skills of their faculty and provide feedback to their fellows. Many faculty feel uncomfortable offering feedback or identifying specific areas for improvement to the fellows. We developed an Observed Structured Clinical Exam (OSCE) to assess fellows' skills and provided faculty with specific criteria to rate the fellows' performance. We propose that OSCEs can serve as tools for faculty development in delivering effective feedback. METHODS: Faculty completed a Web-based training module and received written guidelines on giving feedback. Four OSCE stations were completed by each fellow with faculty using standardized checklists to assess the fellows' skills. Afterwards, faculty rated each program component and assessed their comfort level with feedback. RESULTS: Eight faculty members and 10 fellows from 5 GI training programs in NYC participated. 100% of the faculty agreed that feedback is an important learning tool, should include the learner's self-assessment, and that feedback skills could improve with practice. Compared to faculty skills prior to the program, 87.5% of the faculty agreed that they focused more on specific behaviors and 75% agreed that giving negative feedback was now easier. CONCLUSIONS: OSCEs can serve as practicums for faculty development in giving constructive feedback
— id: 109575, year: 2010, vol: 105, page: 973, stat: Journal Article,

Lack of CCR5 ligand synthesis by Th17 cells is associated with severe loss of Th17 cells response to HIV infection in vitro
Alvarez, Y.; Poles, M.; Hioe, C.
2010 OCT ;26(10):A113-A114, AIDS research & human retroviruses
— id: 117320, year: 2010, vol: 26, page: A113, stat: Journal Article,

Antiviral and immunological effects of intensification of suppressive art with maraviroc, a CCR5 antagonist
Evering T.; Mehandru S.; Poles M.; Tenner-Racz P.; Parker T.; Markowitz M.
2010 ;3(2):S17-S17, Clinical & Translational Science
OBJECTIVES: GI tract CCR5+CD4+ T cells are selectively infected and depleted during acute HIV-1 infection. Despite ART, GALT T cell depletion and activation persists. We hypothesized that ART intensification (INT) with the CCR5 antagonist maraviroc (MVC) could effect immune reconstitution and decrease immune activation if this was due to ongoing viral replication. METHODS AND POPULATION: We enrolled adults infected with CCR5-tropic HIV-1 and treated with ART during acute/early infection for ~4 yrs prior to entry. Subjects were randomized 2:1 to Arm A: INT with MVC for 24 weeks (n=4); or Arm B: NRTI INT for 12 weeks followed by cross-over to MVC for 12 weeks (n=2). RESULTS: Plasma HIV-1 RNA was <50 copies/ml and GI biopsy RNA was <50 copies of HIV-1 NL43 gag (~1.5x106 copies GAPDH/sample) for all subjects at entry through week 24. Immunohistochemistry revealed 5.36 + 0.86 CD4+ T cells/unit area in the lamina propria (LP) at entry in Arm A. This did not increase significantly after 24 weeks. In Arm A, flow cytometry revealed significant differences (p<0.02) between the PBMC and GALT at entry in the CD4+/CD8+ T cell ratio (1.47+0.14 vs 0.91+0.06) and % activated (CD38+) CD8+ T cells (2.61 +/- 0.41 vs 17.61 +/- 5.02). In Arms A and B, no statistically significant change (p>0.32) was noted in %CD38+ or %proliferating (Ki67+) CD4+ or CD8+ T cells in the GALT between entry, weeks 12 and 24. In both arms, serum endotoxin activity did not significantly change after 24 weeks. SIGNIFICANCE OF STUDY: Thus far, we observe no statistically significant effect of intensification of ART with MVC on a variety of immunologic and virologic parameters in the GALT
— id: 111406, year: 2010, vol: 3, page: S17, stat: Journal Article,

Irritable Bowel Syndrome and HIV: A Cross Sectional Study of the Severity of Gastrointestinal Symptoms and HIV-infected Subjects
Herzog, Keri; Williams, Renee; Cho, Ilseung; Tenner, Craig; Poles, Michael
2010 OCT ;105(6):S479-S479, American journal of gastroenterology
— id: 117311, year: 2010, vol: 105, page: S479, stat: Journal Article,

Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome
Nossa, Carlos W; Oberdorf, William E; Yang, Liying; Aas, Jorn A; Paster, Bruce J; Desantis, Todd Z; Brodie, Eoin L; Malamud, Daniel; Poles, Michael A; Pei, Zhiheng
2010 Sep 7;16(33):4135-4144, World journal of gastroenterology : WJG
AIM: To design and validate broad-range 16S rRNA primers for use in high throughput sequencing to classify bacteria isolated from the human foregut microbiome. METHODS: A foregut microbiome dataset was constructed using 16S rRNA gene sequences obtained from oral, esophageal, and gastric microbiomes produced by Sanger sequencing in previous studies represented by 219 bacterial species. Candidate primers evaluated were from the European rRNA database. To assess the effect of sequence length on accuracy of classification, 16S rRNA genes of various lengths were created by trimming the full length sequences. Sequences spanning various hypervariable regions were selected to simulate the amplicons that would be obtained using possible primer pairs. The sequences were compared with full length 16S rRNA genes for accuracy in taxonomic classification using online software at the Ribosomal Database Project (RDP). The universality of the primer set was evaluated using the RDP 16S rRNA database which is comprised of 433 306 16S rRNA genes, represented by 36 phyla. RESULTS: Truncation to 100 nucleotides (nt) downstream from the position corresponding to base 28 in the Escherichia coli 16S rRNA gene caused misclassification of 87 (39.7%) of the 219 sequences, compared with misclassification of only 29 (13.2%) sequences with truncation to 350 nt. Among 350-nt sequence reads within various regions of the 16S rRNA gene, the reverse read of an amplicon generated using the 343F/798R primers had the least (8.2%) effect on classification. In comparison, truncation to 900 nt mimicking single pass Sanger reads misclassified 5.0% of the 219 sequences. The 343F/798R amplicon accurately assigned 91.8% of the 219 sequences at the species level. Weighted by abundance of the species in the esophageal dataset, the 343F/798R amplicon yielded similar classification accuracy without a significant loss in species coverage (92%). Modification of the 343F/798R primers to 347F/803R increased their universality among foregut species. Assuming that a typical polymerase chain reaction can tolerate 2 mismatches between a primer and a template, the modified 347F and 803R primers should be able to anneal 98% and 99.6% of all 16S rRNA genes in the RDP database. CONCLUSION: 347F/803R is the most suitable pair of primers for classification of foregut 16S rRNA genes but also possess universality suitable for analyses of other complex microbiomes
— id: 112048, year: 2010, vol: 16, page: 4135, stat: Journal Article,

Diversity of 16S rRNA genes within individual prokaryotic genomes
Pei, Anna Y; Oberdorf, William E; Nossa, Carlos W; Agarwal, Ankush; Chokshi, Pooja; Gerz, Erika A; Jin, Zhida; Lee, Peng; Yang, Liying; Poles, Michael; Brown, Stuart M; Sotero, Steven; Desantis, Todd; Brodie, Eoin; Nelson, Karen; Pei, Zhiheng
2010 Jun;76(12):3886-3897, Applied & environmental microbiology
Analysis of intragenomic variation of 16S rRNA genes is a unique approach to examining the concept of ribosomal constraints on rRNA genes; the degree of variation is an important parameter to consider for estimation of the diversity of a complex microbiome in the recently initiated Human Microbiome Project (http://nihroadmap.nih.gov/hmp). The current GenBank database has a collection of 883 prokaryotic genomes representing 568 unique species, of which 425 species contained 2 to 15 copies of 16S rRNA genes per genome (2.22 +/- 0.81). Sequence diversity among the 16S rRNA genes in a genome was found in 235 species (from 0.06% to 20.38%; 0.55% +/- 1.46%). Compared with the 16S rRNA-based threshold for operational definition of species (1 to 1.3% diversity), the diversity was borderline (between 1% and 1.3%) in 10 species and >1.3% in 14 species. The diversified 16S rRNA genes in Haloarcula marismortui (diversity, 5.63%) and Thermoanaerobacter tengcongensis (6.70%) were highly conserved at the 2 degrees structure level, while the diversified gene in B. afzelii (20.38%) appears to be a pseudogene. The diversified genes in the remaining 21 species were also conserved, except for a truncated 16S rRNA gene in 'Candidatus Protochlamydia amoebophila.' Thus, this survey of intragenomic diversity of 16S rRNA genes provides strong evidence supporting the theory of ribosomal constraint. Taxonomic classification using the 16S rRNA-based operational threshold could misclassify a number of species into more than one species, leading to an overestimation of the diversity of a complex microbiome. This phenomenon is especially seen in 7 bacterial species associated with the human microbiome or diseases
— id: 133520, year: 2010, vol: 76, page: 3886, stat: Journal Article,

Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects
Bini, E J; Green, B; Poles, M A
2009 Aug;58(8):1129-1134, Gut: journal of the British Society of Gastroenterology
BACKGROUND: Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. METHODS: We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects >or=50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas >or=10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. RESULTS: The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, p<0.001), and remained highly significant after adjustment for potential confounding variables (odds ratio = 3.00; 95% confidence interval, 1.83 to 4.93). Among patients with colorectal adenocarcinoma, HIV-infected subjects were significantly younger (52.4 (SD 1.3) vs 60.3 (SD 4.0) years, p = 0.002) and were more likely to have advanced cancers (stage III or IV) than control subjects (60.0% vs 16.7%, p = 0.24). Of HIV-infected subjects with advanced neoplasms proximal to the splenic flexure, distal neoplastic lesions were absent in 88.9% of individuals and these would have been missed by flexible sigmoidoscopy. CONCLUSIONS: HIV-infected subjects have a higher prevalence of colonic neoplasms, and adenocarcinomas develop at a younger age and are more advanced than in uninfected subjects. Our findings suggest that screening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study
— id: 100665, year: 2009, vol: 58, page: 1129, stat: Journal Article,

Teaching the Competencies: Using Objective Structured Clinical Encounters for Gastroenterology Fellows
Chander, Bani; Kule, Robert; Baiocco, Peter; Chokhavatia, Sita; Kotler, Don; Poles, Michael; Zabar, Sondra; Gillespie, Colleen; Ark, Tavinder; Weinshel, Elizabeth
2009 May;7(5):509-514, Clinical Gastroenterology & Hepatology
BACKGROUND AIMS: Objective structured clinical encounters (OSCEs) are used widely to educate and assess the competence of medical students and residents; they generally are absent from fellowship training. The Accreditation Council for Graduate Education has cited OSCEs as a best practice for assessing the 6 core competencies. This article reports on the use of an OSCE to assess the competence of second-year gastroenterology fellows in the difficult-to-assess core competencies: interpersonal and communication skills and professionalism. METHODS: We developed a 4-station, faculty-observed OSCE with 4 standardized patients. Information gathering, relationship development, patient education, and counseling skills were assessed. Professionalism skills assessed included obtaining informed consent, delivering bad news, managing difficult situations, and showing interdisciplinary respect. In each station, faculty and standardized patients completed an 18- to 24-item checklist evaluating fellows' performance and provided feedback to the fellows. Nine fellows and 5 faculty from 4 gastroenterology training programs in NYC participated. RESULTS: Fellows and faculty generally highly rated the realism of the OSCE and favorably rated the OSCE for its difficulty and their overall experience. Across all cases, fellows were rated as receiving 'well dones' for 56.4% of the communication items (SD, 18.3%) and for 79.1% of the professionalism items (SD, 16.4%). CONCLUSIONS: Integrating OSCEs into gastroenterology fellowship training may help enhance communication skills and prepare fellows for dealing with difficult clinical situations and provides mechanisms for constructive feedback. OSCEs developed collaboratively can assist in program self-evaluation and reduce costs by sharing resources, in addition to fulfilling Accreditation Council for Graduate Education mandates
— id: 97798, year: 2009, vol: 7, page: 509, stat: Journal Article,

Use of Immobilized HLA-A2:Ig Dimeric Proteins to Determine the Level of Epitope-Specific, HLA-Restricted CD8+ T-Cell Response
Horowitz, A; Li, X; Poles, MA; Tsuji, M
2009 NOV ;70(5):415-422, Scandinavian journal of immunology
A novel assay to assess antigen-specific cytokine release from stimulated CD8+ T cells derived from the mucosal and peripheral blood compartments has been developed and standardized using the influenza A virus matrix protein (MP) peptide, GILGFVFTL. This technology is based on the capacity for the human leucocyte antigen (HLA)-A2:Ig dimeric protein to stimulate CD8+ T cells in a major histocompatibility complex (MHC) class I-restricted fashion without the necessity for antigen presenting cells (APC). This assay has been optimized utilizing a 9-amino acid residue (9mer) peptide, the optimal peptide length for presenting an epitope to CD8+ T cells. Compared to existing assays, this more sensitive and specific methodology requires fewer cells, enabling easier and more accurate monitoring of the CD8+ T-cell response in biological compartments, such as the mucosa during the course of viral infection and may be utilized to assess epitope-specific CD8+ T-cell responses in vaccine trials
— id: 105228, year: 2009, vol: 70, page: 415, stat: Journal Article,

CLINICAL CORRELATIONS: A DAILY DOSE OF MEDICINE
Litvin, CB; Brenner, J; Triola, MM; Poles, MA; Shapiro, N
2009 APR ;24(10):264-265, Journal of general internal medicine
— id: 99174, year: 2009, vol: 24, page: 264, stat: Journal Article,

High frequency of barriers to fecal occult blood testing in HIV-infected patientes in a primary care setting
Fein, D; Aizenberg, D; Soofi, NM; Tenner, CT; Poles, MA; Bini, EJ
2008 MAR ;23(2):314-314, Journal of general internal medicine
— id: 78174, year: 2008, vol: 23, page: 314, stat: Journal Article,

Drug-susceptible HIV-1 infection despite intermittent fixed-dose combination tenofovir/emtricitabine as prophylaxis is associated with low-level viremia, delayed seroconversion, and an attenuated clinical course
Prada, Nicole; Davis, Brandi; Jean-Pierre, Patrick; La Roche, Matthew; Duh, Fuh-Mei; Carrington, Mary; Poles, Michael; Mehandru, Saurabh; Mohri, Hiroshi; Markowitz, Martin
2008 Oct 1;49(2):117-122, Journal of acquired immune deficiency syndromes. JAIDS
BACKGROUND: Continued high rates of HIV-1 transmission have fueled interest in the use of antiretrovirals to prevent infection. Attenuated infection with failure of tenofovir as prophylaxis has been reported in animal models. Here, we report a case of HIV-1 infection despite intermittent use of fixed-dose combination tenofovir and emtricitabine (FTC). METHODS: The patient was treated with tenofovir DF/FTC for reported repeated high-risk sexual exposures. After seroconversion, he was subjected to routine laboratory testing, CCR5 and HLA genotyping, and biopsy of gastrointestinal (GI) tissue. Resistance testing was performed both as bulk sequencing of plasma and cloning and sequencing of virus derived from plasma, peripheral blood mononuclear cells, and GI tissue. RESULTS: In this patient with no readily identifiable modifying host factors, acute HIV-1 infection with tenofovir DF/FTC-susceptible HIV-1 was associated with an attenuated clinical course, very low postseroconversion HIV-1 RNA levels, slow kinetics of seroconversion, and relative sparing of mucosal CD4+ T cells in the GI tract. CONCLUSIONS: Despite the failure of tenofovir DF/FTC as prophylaxis, selection for drug-resistant transmission did not occur and the blunting of postinfection levels of viremia likely reduced the probability of subsequent forward transmissions during the acute phase. These results support continued investigations of the use of antiretrovirals as a means to reduce HIV-1 transmission
— id: 135294, year: 2008, vol: 49, page: 117, stat: Journal Article,

Mechanisms of gastrointestinal CD4+ T-cell depletion during acute and early human immunodeficiency virus type 1 infection
Mehandru, Saurabh; Poles, Michael A; Tenner-Racz, Klara; Manuelli, Victoria; Jean-Pierre, Patrick; Lopez, Peter; Shet, Anita; Low, Andrea; Mohri, Hiroshi; Boden, Daniel; Racz, Paul; Markowitz, Martin
2007 Jan;81(2):599-612, Journal of virology
During acute and early human immunodeficiency virus type 1 (HIV-1) infection (AEI) more than 50% of CD4+ T cells are preferentially depleted from the gastrointestinal (GI) lamina propria. To better understand the underlying mechanisms, we studied virological and immunological events within the peripheral blood (PB) and GI tract during AEI. A total of 32 AEI subjects and 18 uninfected controls underwent colonic biopsy. HIV-1 viral DNA and RNA levels were quantified in CD4+ T cells derived from the GI tract and PB by using real-time PCR. The phenotype of infected cells was characterized by using combinations of immunohistochemistry and in situ hybridization. Markers of immunological memory, activation, and proliferation were examined by flow cytometry and immunohistochemistry, and the host-derived cytotoxic cellular response was examined by using immunohistochemistry. GI CD4+ T cells harbored, on average, 13-fold higher HIV-1 viral DNA levels and 10-fold higher HIV-1 RNA levels than PB CD4+ T cells during AEI. HIV-1 RNA was detected in both 'activated' and 'nonactivated' mucosal CD4+ T cells. A significantly higher number of activated and proliferating T cells were detected in the GI tract compared to the PB, and a robust cytotoxic response (HIV-1 specificity not determined) was detected in the GI tract as early as 18 days postinfection. Mucosal CD4+ T-cell depletion is multifactorial. Direct viral infection likely accounts for the earliest loss of CD4+ T cells. Subsequently, ongoing infection of susceptible CD4+ T cells, along with activation-induced cellular death and host cytotoxic cellular response, are responsible for the persistence of the lesion
— id: 73131, year: 2007, vol: 81, page: 599, stat: Journal Article,

Prevalence and impact of diarrhea on health-related quality of life in HIV-infected patients in the era of highly active antiretroviral therapy
Siddiqui, Uzma; Bini, Edmund J; Chandarana, Khushbu; Leong, Jennifer; Ramsetty, Sabena; Schiliro, Danise; Poles, Michael
2007 May-Jun;41(5):484-490, Journal of clinical gastroenterology
OBJECTIVES: Before the introduction of highly active antiretroviral therapy (HAART), the majority of HIV-infected patients experienced diarrhea. The aims of this study were to compare the prevalence of diarrhea among HIV-infected and uninfected patients in the HAART era, and to evaluate the impact of diarrhea on health-related quality of life (HRQOL). METHODS: Diarrheal symptoms experienced by 163 consecutive HIV-infected patients and 253 HIV-seronegative control subjects were ascertained using a validated questionnaire. The HRQOL of these patients was assessed using the Medical Outcomes Study (MOS) SF-36 and MOS-HIV Health surveys. RESULTS: Among the 163 HIV-infected patients, the median CD4 cell count was 370 cells/mm and 150 individuals were taking HAART. Significantly, more HIV-infected subjects reported having 3 or more bowel movements daily within the past 7 days than did HIV-seronegative subjects (28.2% vs. 7.1%, P<0.001), even after adjusting for potential confounding variables (odds ratios=6.65; 95% confidence intervals, 3.36-13.17). In addition, diarrhea was significantly more common in HIV-infected patients than in control subjects when assessed by several other criteria. HIV-infected patients reported significantly worse HRQOL across all domains of the MOS SF-36 as compared with control subjects. Among HIV-infected patients, individuals with diarrhea had significantly worse HRQOL in nearly all domains of the MOS-HIV as compared with those without diarrhea. CONCLUSIONS: Diarrhea remains an important clinical problem in HIV-infected patients and is associated with significant impairments in HRQOL. It is important that healthcare providers specifically evaluate their HIV-infected patients for diarrhea so that these symptoms may be optimally managed
— id: 72434, year: 2007, vol: 41, page: 484, stat: Journal Article,

High frequency of barriers to colorectal cancer screening in HIV-Infected patients in a primary care setting
Soofi, NM; Aizenberg, DJ; Tenner, CT; Poles, M; Bini, EJ
2007 APR ;132(4):A471-A472, Gastroenterology
— id: 74587, year: 2007, vol: 132, page: A471, stat: Journal Article,

Function of NKT cells, potential anti-HIV effector cells, are improved by beginning HAART during acute HIV-1 infection
Vasan, Sandhya; Poles, Michael A; Horowitz, Amir; Siladji, Esther E; Markowitz, Martin; Tsuji, Moriya
2007 Aug;19(8):943-951, International immunology
NKT cells are a subset of lymphocytes that share features of T cells and NK cells and bridge the innate and adaptive immune responses. They are able to be infected by HIV, but their function in HIV-infected individuals is not known. NKT cell percentage and function was measured in individuals with acute HIV infection before and 1 year into highly active anti-retroviral therapy (HAART). This study demonstrates that percentages of both CD161+ NKT cells and CD161+, CD4+ NKT cells decline within the first few months after HIV-1 infection, but initiating therapy during the acute infection period can prevent a further decline in these NKT cell subsets during the first year. NKT cell function is also impaired during early HIV infection, but significantly improved by effective treatment with HAART. Finally, preservation of NKT cell function may be important in HIV-infected individuals, as NKT cells display an anti-HIV-1 activity in vitro, mediated by IFN-gamma secretion
— id: 78036, year: 2007, vol: 19, page: 943, stat: Journal Article,

Lack of Mucosal Immune Reconstitution during Prolonged Treatment of Acute and Early HIV-1 Infection
Mehandru, Saurabh; Poles, Michael A; Tenner-Racz, Klara; Jean-Pierre, Patrick; Manuelli, Victoria; Lopez, Peter; Shet, Anita; Low, Andrea; Mohri, Hiroshi; Boden, Daniel; Racz, Paul; Markowitz, Martin
2006 Dec 5;3(12):e484-e484, PLoS medicine
BACKGROUND: During acute and early HIV-1 infection (AEI), up to 60% of CD4(+) T cells in the lamina propria of the lower gastrointestinal (GI) tract are lost as early as 2-4 wk after infection. Reconstitution in the peripheral blood during therapy with highly active antiretroviral therapy (HAART) is well established. However, the extent of immune reconstitution in the GI tract is unknown. METHODS AND FINDINGS: Fifty-four AEI patients and 18 uninfected control participants underwent colonic biopsy. Forty of the 54 AEI patients were followed after initiation of antiretroviral therapy (18 were studied longitudinally with sequential biopsies over a 3-y period after beginning HAART, and 22 were studied cross sectionally after 1-7 y of uninterrupted therapy). Lymphocyte subsets, markers of immune activation and memory in the peripheral blood and GI tract were determined by flow cytometry and immunohistochemistry. In situ hybridization was performed in order to identify persistent HIV-1 RNA expression. Of the patients studied, 70% maintained, on average, a 50%-60% depletion of lamina propria lymphocytes despite 1-7 y of HAART. Lymphocytes expressing CCR5 and both CCR5 and CXCR4 were persistently and preferentially depleted. Levels of immune activation in the memory cell population, CD45RO(+) HLA-DR(+), returned to levels seen in the uninfected control participants in the peripheral blood, but were elevated in the GI tract of patients with persistent CD4(+) T cell depletion despite therapy. Rare HIV-1 RNA-expressing cells were detected by in situ hybridization. CONCLUSIONS: Apparently suppressive treatment with HAART during acute and early infection does not lead to complete immune reconstitution in the GI mucosa in the majority of patients studied, despite immune reconstitution in the peripheral blood. Though the mechanism remains obscure, the data suggest that there is either viral or immune-mediated accelerated T cell destruction or, possibly, alterations in T cell homing to the GI tract. Although clinically silent over the short term, the long-term consequences of the persistence of this lesion may emerge as the HIV-1-infected population survives longer owing to the benefits of HAART
— id: 73132, year: 2006, vol: 3, page: e484, stat: Journal Article,

Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals
Poles, Michael A; Boscardin, W John; Elliott, Julie; Taing, Philip; Fuerst, Marie M P; McGowan, Ian; Brown, Stephen; Anton, Peter A
2006 Sep;43(1):65-68, Journal of acquired immune deficiency syndromes. JAIDS
Although peripheral blood mononuclear cells (PBMCs) and lymph nodes represent a principal reservoir, the contribution of gut-associated lymphoid tissue (GALT) has not been evaluated. In 15 HIV-1-infected subjects with maximal suppression of HIV replication by highly active antiretroviral therapy, we quantified HIV-1 DNA and RNA in mucosal biopsy specimens, PBMCs, and plasma with ultrasensitive assays. We also calculated compartmental burdens of HIV-1 DNA-positive cells and characterized the temporal decay of these reservoirs in a period of 1 year (with projections to >50 years). HIV-1 RNA was detected in 20% of the subjects' mucosal biopsy specimens and in 80% of the PBMC samples. Mucosal HIV-1 DNA was detected in 80% of the subjects and in 100% of the PBMC samples. Calculated numbers of lymphoid cells containing 'potentially replication-competent' HIV-1 DNA showed that the PBMC compartment contained approximately 70,000 such cells, and GALT contained approximately 160,000 cells. Rates of decay slopes for all 15 subjects in both compartments were not statistically significantly different when compared with each other or with zero slope. Our data indicate that GALT is a quantitatively important reservoir of potentially replicative cells containing HIV-1 DNA, harboring at least as many or more of such cells as the PBMC compartment. In well-suppressed patients on highly active antiretroviral therapy, the GALT compartment showed no clear pattern of HIV-1 decay, similar to that in the PBMCs
— id: 92865, year: 2006, vol: 43, page: 65, stat: Journal Article,

Colorectal cancer screening in HIV-infected patients 50 years of age and older: Missed opportunities for prevention - Reply
Reinhold, JP; Tenner, C; Poles, MA; Bini, EJ
2006 APR ;101(4):907-908, American journal of gastroenterology
— id: 63815, year: 2006, vol: 101, page: 907, stat: Journal Article,

High prevalence of colorectal adenomas among asymptomatic HIV-infected patients 50 years of age and older: A prospective screening colonoscopy study
Bini, EJ; Green, B; Poles, MA
2005 ;61(5):AB247-AB247, Gastrointestinal endoscopy
— id: 108212, year: 2005, vol: 61, page: AB247, stat: Journal Article,

Recognition of bacterial glycosphingolipids by natural killer T cells
Kinjo, Y; Wu, D; Kim, G; Xing, GW; Poles, M; Tsuji, M; Kawahara, K; Wong, CH; Kronenberg, M
2005 MAR 4 ;19(4):A405-A405, FASEB journal
— id: 55694, year: 2005, vol: 19, page: A405, stat: Journal Article,

Recognition of bacterial glycosphingolipids by natural killer T cells
Kinjo, Yuki; Wu, Douglass; Kim, Gisen; Xing, Guo-Wen; Poles, Michael A; Ho, David D; Tsuji, Moriya; Kawahara, Kazuyoshi; Wong, Chi-Huey; Kronenberg, Mitchell
2005 Mar 24;434(7032):520-525, Nature
Natural killer T (NKT) cells constitute a highly conserved T lymphocyte subpopulation that has the potential to regulate many types of immune responses through the rapid secretion of cytokines. NKT cells recognize glycolipids presented by CD1d, a class I-like antigen-presenting molecule. They have an invariant T-cell antigen receptor (TCR) alpha-chain, but whether this invariant TCR recognizes microbial antigens is still controversial. Here we show that most mouse and human NKT cells recognize glycosphingolipids from Sphingomonas, Gram-negative bacteria that do not contain lipopolysaccharide. NKT cells are activated in vivo after exposure to these bacterial antigens or bacteria, and mice that lack NKT cells have a marked defect in the clearance of Sphingomonas from the liver. These data suggest that NKT cells are T lymphocytes that provide an innate-type immune response to certain microorganisms through recognition by their antigen receptor, and that they might be useful in providing protection from bacteria that cannot be detected by pattern recognition receptors such as Toll-like receptor 4
— id: 78045, year: 2005, vol: 434, page: 520, stat: Journal Article,

Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report
Markowitz, Martin; Mohri, Hiroshi; Mehandru, Saurabh; Shet, Anita; Berry, Leslie; Kalyanaraman, Roopa; Kim, Alexandria; Chung, Chris; Jean-Pierre, Patrick; Horowitz, Amir; La Mar, Melissa; Wrin, Terri; Parkin, Neil; Poles, Michael; Petropoulos, Christos; Mullen, Michael; Boden, Daniel; Ho, David D
2005 Mar 16;365(9464):1031-1038, Lancet
BACKGROUND: Rapid progression to AIDS after acute HIV-1 infection, though uncommon, has been noted, as has the transmission of multidrug resistant viruses. Here, we describe a patient in whom these two factors arose concomitantly and assess the effects. METHODS: We did a case study of a patient with HIV-1 seroconversion. We genotyped the virus and host genetic markers by PCR and nucleotide sequencing. To ascertain the drug susceptibility of our patient's HIV-1 we did phenotypic studies with the PhenoSense assay. We assessed viral coreceptor use via syncytium formation in vitro and with a modified PhenoSense assay. FINDINGS: Our patient seems to have been recently infected by a viral variant of HIV-1 resistant to multiple classes of antiretroviral drugs. Furthermore, his virus population is dual tropic for cells that express CCR5 or CXCR4 coreceptor. The infection has resulted in progression to symptomatic AIDS in 4-20 months. INTERPRETATION: The intersection of multidrug resistance and rapid development of AIDS in this patient is of concern, especially in view of his case history, which includes high-risk sexual contacts and use of metamfetamine. The public health ramifications of such a case are great
— id: 51102, year: 2005, vol: 365, page: 1031, stat: Journal Article,

Colorectal cancer screening in HIV-infected patients 50 years of age and older: missed opportunities for prevention
Reinhold, Jean-Pierre; Moon, Marianne; Tenner, Craig T; Poles, Michael A; Bini, Edmund J
2005 Aug;100(8):1805-1812, American journal of gastroenterology
OBJECTIVES: Although human immunodeficiency virus (HIV)-infected patients are now living longer, there are no published data on colorectal cancer (CRC) screening in this population. We hypothesized that HIV-infected patients were less likely to be screened for CRC compared to patients without HIV. METHODS: Consecutive HIV-infected patients > or =50 yr old seen in our outpatient clinic from 1/1/01 to 6/30/02 were identified. For each HIV-infected patient, we selected one age- and gender-matched control subject without HIV infection who was seen during the same time period. The electronic medical records were reviewed to determine the proportion of patients that had a fecal occult blood test (FOBT), flexible sigmoidoscopy, air-contrast barium enema (ACBE), or colonoscopy. RESULTS: During the 18-month study period, 538 HIV-infected outpatients were seen and 302 (56.1%) were > or =50 yr old. Despite significantly more visits with their primary care provider, HIV-infected patients were less likely to have ever had at least one CRC screening test (55.6%vs 77.8%, p < 0.001). The proportion of HIV-infected patients who ever had a FOBT (43.0%vs 66.6%, p < 0.001), flexible sigmoidoscopy (5.3%vs 17.5%, p < 0.001), ACBE (2.6%vs 7.9%, p= 0.004), or colonoscopy (17.2%vs 27.5%, p= 0.002) was significantly lower than in control subjects. In addition, HIV-infected patients were significantly less likely to be up-to-date with at least one CRC screening test according to current guidelines (49.3%vs 65.6%, p < 0.001). CONCLUSIONS: A substantial number of HIV-infected patients are > or =50 yr of age and CRC screening is underutilized in this population. Public health strategies to improve CRC screening in HIV-infected patients are needed.
— id: 58182, year: 2005, vol: 100, page: 1805, stat: Journal Article,

Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells
Wu, Douglass; Xing, Guo-Wen; Poles, Michael A; Horowitz, Amir; Kinjo, Yuki; Sullivan, Barbara; Bodmer-Narkevitch, Vera; Plettenburg, Oliver; Kronenberg, Mitchell; Tsuji, Moriya; Ho, David D; Wong, Chi-Huey
2005 Feb 1;102(5):1351-1356, Proceedings of the National Academy of Sciences of the United States of America
The CD1 family of proteins binds self and foreign glycolipids for presentation to CD1-restricted T cells. To identify previously uncharacterized active CD1 ligands, especially those of microbial origin, numerous glycolipids were synthesized and tested for their ability to stimulate mouse and human natural killer T (NKT) cells. They included analogs of the well known NKT cell agonist alpha-galactosyl ceramide (alpha-GalCer), bacterial glycolipids, and variations of the self-glycolipid, sulfatide. Bacterial glycolipids, alpha-galacturonosyl-ceramides from Sphingomonas wittichii, although structurally similar to alpha-GalCer, have significant differences in the sugar head group as well as the ceramide portion. The Sphingomonas glycosphingolipids (GSLs) and sulfatide variants were shown to activate human NKT cells as measured by IL-4 and IFN-gamma secretion. Moreover, CD1d-dimer staining revealed human NKT cell reactivity toward these GSLs and to the sulfatides in a fashion comparable with alpha-GalCer. Because alpha-GalCer is a marine-sponge-derived ligand, our study here shows that bacterium-derived antigens are also able to stimulate mouse and human NKT cells
— id: 78047, year: 2005, vol: 102, page: 1351, stat: Journal Article,

Synthesis and human NKT cell stimulating properties of 3-O-sulfo-alpha/beta-galactosylceramides
Xing, Guo-Wen; Wu, Douglass; Poles, Michael A; Horowitz, Amir; Tsuji, Moriya; Ho, David D; Wong, Chi-Huey
2005 Apr 15;13(8):2907-2916, Bioorganic & medicinal chemistry
Two novel hybrid molecules 3-O-sulfo-alpha/beta-galactosylceramide 3 and 4, which are derived from an immunostimulatory agent alpha-GalCer 1 and self-glycolipid ligand sulfatide 2, were designed and synthesized. Compound 3 was shown to efficiently stimulate human NKT cells to secret IL-4 and IFN-gamma, with activities similar to 1, suggesting that modification of the 3''-OH position of the galactose moiety with sulfate has no significant effect on NKT cell stimulation. As a comparison, the beta-isomer 4 has no affinity to NKT cells, which demonstrates that the alpha-glycosidic bond of galactosylceramide is crucial to the NKT cells activation
— id: 78046, year: 2005, vol: 13, page: 2907, stat: Journal Article,

Increased HIV-1 mucosal replication is associated with generalized mucosal cytokine activation
McGowan, Ian; Elliott, Julie; Fuerst, Marie; Taing, Philip; Boscardin, John; Poles, Michael; Anton, Peter
2004 Oct 1;37(2):1228-1236, Journal of acquired immune deficiency syndromes. JAIDS
The purpose of this study was to characterize intestinal mucosal cytokine profiles in subjects with HIV-1 infection and their relation to mucosal viral load (MVL). Intestinal mucosal cytokine mRNA (interleukin [IL]-2, interferon [IFN]-gamma, IL-12, IL-10, IL-1beta, tumor necrosis factor [TNF]-alpha, IL-6, and regulated upon activation, normal T-cell expressed and secreted [RANTES]) and HIV-1 RNA were quantified using real-time polymerase chain reaction (PCR). On the basis of MVL quantification, the HIV-1-infected subjects were divided into 3 groups: undetectable MVL (<50 copies/microg of tissue total RNA), low MVL (>50 but <5000 copies/microg of tissue total RNA), and high MVL (>5000 copies/microg of tissue total RNA). Compared with the control group, significant reductions in RANTES, IL-2, and IFNgamma expression were seen in the undetectable MVL group (P < 0.005). IL-6 was significantly increased in all the HIV groups (P < 0.005), and RANTES, IL-10, and IFNgamma were increased in the high MVL group (P < 0.005). Subjects with high MVL have generalized immune activation with increases in T helper (Th)1, Th2, and proinflammatory cytokines, whereas subjects with undetectable MVL have reduced expression of multiple cytokines. The pathologic basis for these observations is unclear but may relate to the success or failure of antiretroviral therapy in controlling mucosal viral replication
— id: 135295, year: 2004, vol: 37, page: 1228, stat: Journal Article,

Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract
Mehandru, Saurabh; Poles, Michael A; Tenner-Racz, Klara; Horowitz, Amir; Hurley, Arlene; Hogan, Christine; Boden, Daniel; Racz, Paul; Markowitz, Martin
2004 Oct 20;200(6):761-770, Journal of experimental medicine
Given its population of CCR5-expressing, immunologically activated CD4(+) T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4(+) T cells would be observed in HIV-1-infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4(+) T cells compared with peripheral blood CD4(+) T cells is seen during primary HIV-1 infection. CD4(+) T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4(+) T cell population, a significantly greater CD4(+) T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical
— id: 46100, year: 2004, vol: 200, page: 761, stat: Journal Article,

Colorectal cancer screening in HIV-infected patients 50 years of age and older missed opportunities for prevention
Reinhold, JP; Moon, M; Tenner, CT; Poles, MA; Bini, EJ
2004 APR ;126(4):A13-A13, Gastroenterology
— id: 72432, year: 2004, vol: 126, page: A13, stat: Journal Article,

Hepatitis B virus infection: co-infection with hepatitis C virus, hepatitis D virus, and human immunodeficiency virus
Shukla, Nilesh B; Poles, Michael A
2004 Jun;8(2):445-60, viii, Clinics in liver disease
Hepatitis B virus (HBV) shares routes of transmission, namely exchange of infected body fluids, sharing of contaminated needles, and blood transfusion, with other hepatotropic viruses, such as hepatitis C virus (HCV) and hepatitis D virus (HDV) and with systemic retroviral infections, such as the human immunodeficiency virus (HIV). Thus, many HBV infected patients are co-infected with other viral pathogens. Co-infection appears to increase the risk of progression of liver disease and may have important ramifications on choice of antiviral medication and treatment regimen. This article reviews the current knowledge of co-infection of HBV with HCV, HDV, and HIV
— id: 46083, year: 2004, vol: 8, page: 445, stat: Journal Article,

Gastrointestinal symptoms adversely affect quality of life in patients with HIV
Siddiqui, U; Poles, MA; Leong, J; Schiliro, D; Ramsetty, S; Chandarana, K; Bini, EJ
2004 ;126(4):A379-A380, Gastroenterology
— id: 108230, year: 2004, vol: 126, page: A379, stat: Journal Article,

Natural history and pathogenesis of human immunodeficiency virus infection
Burger, Susanne; Poles, Michael A
2003 May;23(2):115-124, Seminars in liver disease
In this article, we discuss how human immunodeficiency virus (HIV) infection of activated CD4+ cells, expressing the chemokine receptors CCR5 or CXCR4, results in severe immunosuppression while evading the immune response. We describe how infection through mucosal surfaces or via the parenteral route results in rapid spread of the virus throughout the body prior to a vigorous CD8+ cytolytic T cell response, resulting in establishment of a viral set point. Data is examined that suggests the half-life of HIV virions in circulation is less than 6 hours and possibly as short as 30 minutes, whereas that of infected CD4 T cells is on average 1 to 1.5 days. We also explain how the rate of viral replication dictates the rate at which HIV evades the immune response and the rapidity with which resistance to antiviral medications may develop. Lastly, we show how anatomic and cellular reservoirs of latent viral pools have made the long-term goal of complete virus eradication difficult despite enormous advances in our therapeutic armamentarium
— id: 39199, year: 2003, vol: 23, page: 115, stat: Journal Article,

Human immunodeficiency virus type 1 induces persistent changes in mucosal and blood gammadelta T cells despite suppressive therapy
Poles, Michael A; Barsoum, Shady; Yu, Wenjie; Yu, Jian; Sun, Patricia; Daly, Jeanine; He, Tian; Mehandru, Saurabh; Talal, Andrew; Markowitz, Martin; Hurley, Arlene; Ho, David; Zhang, Linqi
2003 Oct;77(19):10456-10467, Journal of virology
Gammadelta T cells are primarily found in the gastrointestinal mucosa and play an important role in the first line of defense against viral, bacterial, and fungal pathogens. We sought to examine the impact of human immunodeficiency virus type 1 (HIV-1) infection on mucosal as well as peripheral blood gammadelta T-cell populations. Our results demonstrate that HIV-1 infection is associated with significant expansion of Vdelta1 and contraction of Vdelta2 cell populations in both the mucosa and peripheral blood. Such changes were observed during acute HIV-1 infection and persisted throughout the chronic phase, without apparent reversion after treatment with highly active antiretroviral therapy (HAART). Despite an increase in the expression of CCR9 and CD103 mucosal homing receptors on peripheral blood gammadelta T cells in infected individuals, mucosal and peripheral blood gammadelta T cells appeared to be distinct populations, as reflected by distinct CDR3 length polymorphisms and sequences in the two compartments. Although the underlying mechanism responsible for triggering the expansion of Vdelta1 gammadelta T cells remains unknown, HIV-1 infection appears to have a dramatic impact on gammadelta T cells, which could have important implications for HIV-1 pathogenesis
— id: 39074, year: 2003, vol: 77, page: 10456, stat: Journal Article,

HIV-associated diarrhea in the era of HAA
Siddiqui, U; Bini, EJ; Chandarana, K; Ramsetty, S; Poles, MA
2003 ;124(4):A147-A147, Gastroenterology
— id: 108244, year: 2003, vol: 124, page: A147, stat: Journal Article,

Primary colonic tuberculosis in HIV
Mehandru, S; Bini, EJ; Poles, MA
2002 SEP ;97(9):S122-S122, American journal of gastroenterology
— id: 55280, year: 2002, vol: 97, page: S122, stat: Journal Article,

The gastrointestinal mucosa as a site of compartmentalized HIV-1 evolution
Poles, MA; Mehandru, S; Elliott, J; Boscardin, J; Anton, P
2002 SEP ;97(9):365-1572, American journal of gastroenterology
— id: 98247, year: 2002, vol: 97, page: 365, stat: Journal Article,

Enterocolonic Mycobacterium avium-intracellulare
Wu, Mark Li-cheng; Poles, Michael A; Thompson, Andrew D; Dry, Sarah M
2002 Mar;126(3):381-381, Archives of pathology & laboratory medicine
— id: 32331, year: 2002, vol: 126, page: 381, stat: Journal Article,

Sensitive and reproducible quantitation of mucosal HIV-1 RNA and DNA viral burden in patients with detectable and undetectable plasma viral HIV-1 RNA using endoscopic biopsies
Anton PA; Poles MA; Elliott J; Mao SH; McGowan I; Lenz HJ; Chen IS
2001 Jun;95(1-2):65-79, Journal of virological methods
Mucosal tissue is the main portal of entry for HIV-1 infection and, in macaques, has been demonstrated to be a significant compartment for viral replication and CD4+ T lymphocyte depletion. Quantitating tissue viral burden in addition to plasma viral load provides insights into HIV-1 pathogenesis and an additional means to gauge antiretroviral response. The aim of this study was to develop reliable, reproducible, and sensitive assays to quantitate tissue viral burden of HIV-1 RNA and DNA using 1-3 endoscopically acquired, rectosigmoid biopsies. Total DNA and RNA were simultaneously extracted following homogenization from the same tissue samples. Quantitative polymerase chain reaction (PCR) assay in the HIV-1 LTR region was used to detect viral DNA and RT-PCR for viral RNA. It was determined that HIV-1 RNA and DNA can be reproducibly quantified from a single rectosigmoid biopsy with minimal intra-assay or intra-patient variability. These results reflect high recovery of extracted nucleic acids with calculated results accurately reflecting in vivo levels. The techniques outlined differ from currently available approaches by incorporating control standards to identify loss or degradation of RNA and DNA from acquisition through the in vitro assay and permit extraction with high yields of RNA and DNA from the same tissue sample
— id: 24381, year: 2001, vol: 95, page: 65, stat: Journal Article,

A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection
Poles MA; Elliott J; Taing P; Anton PA; Chen IS
2001 Sep;75(18):8390-8399, Journal of virology
The gastrointestinal mucosa harbors the majority of the body's CD4(+) cells and appears to be uniquely susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We undertook this study to examine the role of differences in chemokine receptor expression on infection of mucosal mononuclear cells (MMCs) and peripheral blood mononuclear cells (PBMCs) by R5- and X4-tropic HIV-1. We performed in vitro infections of MMCs and PBMCs with R5- and X4-tropic HIV-1, engineered to express murine CD24 on the infected cell's surface, allowing for quantification of HIV-infected cells and their phenotypic characterization. A greater percentage of MMCs than PBMCs are infected by both R5- and X4-tropic HIV-1. Significant differences exist in terms of chemokine receptor expression in the blood and gastrointestinal mucosa; mucosal cells are predominantly CCR5(+) CXCR4(+), while these cells make up less than 20% of the peripheral blood cells. It is this cell population that is most susceptible to infection with both R5- and X4-tropic HIV-1 in both compartments. Regardless of whether viral isolates were derived from the blood or mucosa of HIV-1-infected patients, HIV-1 p24 production was greater in MMCs than in PBMCs. Further, the chemokine receptor tropism of these patient-derived viral isolates did not differ between compartments. We conclude that, based on these findings, the gastrointestinal mucosa represents a favored target for HIV-1, in part due to its large population of CXCR4(+) CCR5(+) target cells and not to differences in the virus that it contains
— id: 24379, year: 2001, vol: 75, page: 8390, stat: Journal Article,

Despite high concordance, distinct mutational and phenotypic drug resistance profiles in human immunodeficiency virus type 1 RNA are observed in gastrointestinal mucosal biopsy specimens and peripheral blood mononuclear cells compared with plasma
Poles MA; Elliott J; Vingerhoets J; Michiels L; Scholliers A; Bloor S; Larder B; Hertogs K; Anton PA
2001 Jan 1;183(1):143-148, Journal of infectious diseases
The gastrointestinal mucosa is a major lymphoid tissue reservoir for human immunodeficiency virus (HIV) replication. Genotypic and phenotypic resistance patterns of HIV type 1 (HIV-1) RNA isolated from colonic mucosa were compared with those from the plasma and peripheral blood mononuclear cells (PBMC) of 7 patients. Genotyping was performed using full-sequence analysis, and phenotyping was performed using a recombinant virus assay. Mutations in the reverse-transcriptase (kappa=.84) and protease (kappa=.73) genes were highly concordant among compartments. Similarly, phenotypic resistance patterns were highly concordant among compartments (intraclass correlation coefficient,.91). In 5 instances among 3 patients, a different genotypic result was observed between plasma and the other tissue compartments. Mixtures of wild-type and mutated HIV-1 RNA were present in the mucosa and PBMC but not in the plasma. Despite significant concordance among compartments, mucosal- and PBMC-derived viral RNA showed instances of discordance with plasma-derived virus that may suggest compartmentalization of virus
— id: 24382, year: 2001, vol: 183, page: 143, stat: Journal Article,

HIV-related diarrhea is multifactorial and fat malabsorption is commonly present, independent of HAART
Poles MA; Fuerst M; McGowan I; Elliott J; Rezaei A; Mark D; Taing P; Anton PA
2001 Jun;96(6):1831-1837, American journal of gastroenterology
OBJECTIVE: Highly active antiretroviral therapy (HAART) has significantly decreased the incidence of infectious diarrhea affecting HIV-infected patients. Still, diarrhea remains a common symptom in HIV. We sought to determine the incidence of fat malabsorption as a cause of diarrhea in HIV patients receiving non-HAART (nucleoside analog only) and HAART (protease inhibitor-containing) antiretroviral regimens. METHODS: From June, 1995, to April, 1999, 88 HlV-infected patients underwent evaluation for diarrhea, which included endoscopy. We examined the incidence of fat malabsorption with a 24-h stool collection for fecal fat in a cohort of these patients (N = 33). Patients were divided into two groups, those receiving protease inhibitor-containing HAART and those receiving less intensive, nucleoside analog-only, non-HAART regimens. RESULTS: Thirty of 33 patients (90.9%) had fat malabsorption. Twenty of 21 patients not receiving HAART (95.2%) had fat malabsorption with a mean of 34 +/- 38 g of stool fat and a mean stool weight of 797 +/- 454 g. Ten of 12 patients receiving HAART (83.3%) had fat malabsorption with a mean of 46 +/- 86 g of stool fat and a mean stool weight of 800 +/- 647 g. Stool weight correlated with the degree of fat malabsorption (R = 0.77). CONCLUSION: Fat malabsorption represents a commonly undiagnosed entity in HIV-infected patients with diarrhea, whether or not they are receiving HAART therapy. Fecal fat determination should be considered a routine part of the diagnostic workup of HIV-infected patients experiencing diarrhea
— id: 24380, year: 2001, vol: 96, page: 1831, stat: Journal Article,

Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue
Anton PA; Elliott J; Poles MA; McGowan IM; Matud J; Hultin LE; Grovit-Ferbas K; Mackay CR; Chen ISY; Giorgi JV
2000 Aug 18;14(12):1761-1765, AIDS
OBJECTIVE: To examine compartmental differences in co-receptor expression on CD4 lymphocytes between blood and gut using endoscopic biopsies. DESIGN: Mucosal and peripheral CD4 T cells from healthy controls were compared for co-receptor expression and vulnerability to infection by HIV-1. METHODS: Expression of CCR5 and CXCR4 was quantified by flow cytometry on isolated mucosal CD4 lymphocytes obtained from endoscopic biopsies and blood from healthy controls. Vulnerability to in vitro infection by both R5 and X4 strains was assessed by measuring p24. RESULTS: Biopsies yielded sufficient lymphocytes for flow cytometric characterization and infectivity studies. The percentage of mucosal CD4 T lymphocytes that expressed CCR5 and the per cell expression of CCR5 were both significantly increased compared with that in peripheral blood CD4 T lymphocytes. CXCR4 was expressed on the majority of CD4 lymphocytes in both compartments. In vitro infection of mucosal mononuclear cells supported greater viral replication of both R5 and X4 strains than peripheral blood mononuclear cells. CONCLUSIONS: Enhanced expression of CXCR4 and CCR5 on CD4 lymphocytes in normal intestinal mucosa predicts increased vulnerability to infection by both R5 and X4 HIV-1. Endoscopic biopsies provide a useful mucosal tissue sampling technique to identify compartmental immunologic differences that may be exploited by HIV-1 in establishing initial mucosal infection
— id: 24383, year: 2000, vol: 14, page: 1761, stat: Journal Article,

Hepatitis C Virus/Human immunodeficiency virus coinfection: clinical management issues [In Process Citation]
Poles MA; Dieterich DT
2000 Jul;31(1):154-161, Clinical infectious diseases
The use of highly active antiretroviral therapy (HAART) has extended the healthy lifespan of patients infected with human immunodeficiency virus (HIV); deaths among people with AIDS declined for the first time in 1996, after the institution of this therapeutic approach. As the life expectancy of HIV-infected patients increases, greater attention will need to be focused on the recognition and management of potentially severe concurrent illnesses that may increase their mid- to long-range morbidity and mortality. The incidence of infection by hepatitis C virus (HCV) is increased among patients with HIV disease, reflecting shared epidemiological risks. HCV not only may have an impact on the health status of HIV-infected patients but also may decrease their quality of life and increase their health care costs. Although clinicians have been reluctant to treat viral hepatitis C in the HIV-infected population, this therapeutic nihilism is unwarranted. The majority of studies have concluded that treatment of hepatitis C in HIV-infected patients results in an initial efficacy and long-term response similar to those in the HIV-seronegative population. Furthermore, treatment of HCV infection in HCV/HIV-coinfected patients may improve tolerance for antiretroviral medications. Physicians caring for patients with HIV infection require up-to-date information to make rational decisions regarding HCV coinfection to ensure that morbidity and mortality are minimized and that quality of life and medical care costs are optimized
— id: 14719, year: 2000, vol: 31, page: 154, stat: Journal Article,

HIV and Hepatitis Virus Infection
Poles MA; Dieterich DT
2000 Apr;2(2):177-184, Current infectious disease reports
As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIV-infected patients results in an initial efficacy and a long-term response similar to those seen in the HIV-seronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective
— id: 14717, year: 2000, vol: 2, page: 177, stat: Journal Article,

Infections of the liver in HIV-infected patients [In Process Citation]
Poles MA; Dieterich DT
2000 Sep;14(3):741-759, Infectious disease clinics of North America
The liver is a common site of pathology in HIV-infected patients. In patients with controlled HIV and minimal immunosuppression, infection with hepatitis viruses is common owing to the risk factors of sexual transmission or parenteral drug use. In patients with AIDS, the liver is a common site of lymphohematogenous dissemination of several infectious pathogens. A thorough diagnostic approach leads to a diagnosis of most hepatobiliary processes. The therapeutic nihilism that has surrounded hepatic disease, including viral hepatitis, is unwarranted, because treatment of the underlying HIV and the hepatic process may improve the quality of life and longevity of these patients
— id: 14718, year: 2000, vol: 14, page: 741, stat: Journal Article,

Routine endoscopy in liver transplant candidates: is it indicated?
Poles MA; Martin P
1999 Apr;94(4):871-872, American journal of gastroenterology
— id: 24384, year: 1999, vol: 94, page: 871, stat: Journal Article,

HIV-Related hepatic disease: when and why to biopsy
Poles MA
1998 Oct;8(4):939-962, Gastrointestinal endoscopy clinics of North America
Patients infected with HIV are susceptible to a variety of hepatic processes that are related to immunosuppression or are associated with the risk factors of homosexuality and parenteral drug use. These processes present in a myriad of ways including fever, right upper quadrant pain, and hepatomegaly, or simply as asymptomatic elevations of liver tests. Care of these patients demands systematic evaluation and treatment to ensure that morbidity and mortality are minimized and quality of life and medical care costs are optimized
— id: 24386, year: 1998, vol: 8, page: 939, stat: Journal Article,

Isolation of human intestinal defensins from ileal neobladder urine
Porter EM; Poles MA; Lee JS; Naitoh J; Bevins CL; Ganz T
1998 Sep 4;434(3):272-276, FEBS letters
We describe the isolation of naturally occurring human intestinal defensins HD-5 and HD-6 from ileal neobladder urine and ileal mucosa. Using an antibody-based detection assay, we found multiple N-terminally processed forms of HD-5. The predominant HD-5 forms in tissue were longer than those in neobladder urine (amino acid (aa) 23-94 and 29-94 versus aa 36-94, 56-94 and 63-94) suggesting that Paneth cells store prodefensin that is processed to mature defensin during or after degranulation. Search for mature HD-6 yielded aa 69-100 as the predominant form in both sources. The ileal neobladder is a promising model to study human Paneth cell secretion
— id: 24385, year: 1998, vol: 434, page: 272, stat: Journal Article,

Adenovirus colitis in human immunodeficiency virus infection: an underdiagnosed entity
Yan Z; Nguyen S; Poles M; Melamed J; Scholes JV
1998 Sep;22(9):1101-1106, American journal of surgical pathology
Adenovirus infection of the gastrointestinal tract in human immunodeficiency virus (HIV)-infected patients is rarely reported, probably because of a lack of familiarity of most pathologists with diagnostic criteria during routine light microscopy and possible misidentification as cytomegalovirus infection. We studied colonoscopic biopsy specimens from 135 HIV-infected patients with clinically suspected cytomegalovirus colitis during a 4.5-year period to morphologically identify the presence of adenovirus infection. Immunohistochemical staining for adenovirus was performed for confirmation on all suspected cases. Adenovirus infected cells showed characteristic amphophilic or eosinophilic nuclear inclusions, predominantly affecting the surface epithelium and characteristically involving goblet cells. Sixteen cases showed morphologic features of adenovirus infection, all confirmed by immunohistochemistry. Twelve cases also showed cytomegalovirus infection, whereas 4 showed adenovirus alone. In 10 cases, adenovirus colitis was not recognized during initial routine histopathologic diagnostic evaluation. Adenovirus inclusions also were discovered in the stomach, the duodenum, and the liver in single cases. Conclusions are as follows: (1) Adenovirus colitis has been underdiagnosed at our institution and, we suspect, in general. (2) The morphologic features and nuclear inclusions of adenovirus colitis are characteristic and can be identified reliably by routine light microscopy. (3) Adenovirus infection also may be diagnosed morphologically in extracolonic sites, such as the stomach, the small intestine, and the liver. (4) Coinfection of adenovirus with cytomegalovirus and other agents is seen frequently, but, less frequently, adenovirus may be identified as a sole pathogen
— id: 7949, year: 1998, vol: 22, page: 1101, stat: Journal Article,

Adenovirus colitis in human immunodeficiency virus infection: an underdiagnosed entity
Yan Z; Nguyen S; Poles M; Melamed J; Scholes JV
1998 Sep;22(9):1101-1106, American journal of surgical pathology
Adenovirus infection of the gastrointestinal tract in human immunodeficiency virus (HIV)-infected patients is rarely reported, probably because of a lack of familiarity of most pathologists with diagnostic criteria during routine light microscopy and possible misidentification as cytomegalovirus infection. We studied colonoscopic biopsy specimens from 135 HIV-infected patients with clinically suspected cytomegalovirus colitis during a 4.5-year period to morphologically identify the presence of adenovirus infection. Immunohistochemical staining for adenovirus was performed for confirmation on all suspected cases. Adenovirus infected cells showed characteristic amphophilic or eosinophilic nuclear inclusions, predominantly affecting the surface epithelium and characteristically involving goblet cells. Sixteen cases showed morphologic features of adenovirus infection, all confirmed by immunohistochemistry. Twelve cases also showed cytomegalovirus infection, whereas 4 showed adenovirus alone. In 10 cases, adenovirus colitis was not recognized during initial routine histopathologic diagnostic evaluation. Adenovirus inclusions also were discovered in the stomach, the duodenum, and the liver in single cases. Conclusions are as follows: (1) Adenovirus colitis has been underdiagnosed at our institution and, we suspect, in general. (2) The morphologic features and nuclear inclusions of adenovirus colitis are characteristic and can be identified reliably by routine light microscopy. (3) Adenovirus infection also may be diagnosed morphologically in extracolonic sites, such as the stomach, the small intestine, and the liver. (4) Coinfection of adenovirus with cytomegalovirus and other agents is seen frequently, but, less frequently, adenovirus may be identified as a sole pathogen
— id: 154271, year: 1998, vol: 22, page: 1101, stat: Journal Article,

Treatment of gastrointestinal cytomegalovirus infection with twice-daily foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients with AIDS
Dieterich DT; Poles MA; Lew EA; Martin-Munley S; Johnson J; Nix D; Faust MJ
1997 Jun;41(6):1226-1230, Antimicrobial agents & chemotherapy
Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients
— id: 7140, year: 1997, vol: 41, page: 1226, stat: Journal Article,

Diarrheal diseases associated with HIV infection
Lew EA; Poles MA; Dieterich DT
1997 Jun;26(2):259-290, Gastroenterology clinics of North America
Diarrhea is a major complication of HIV infection and adversely impacts health care costs, quality of life, and even survival of patients. There is a wide variety of potential causes of diarrhea in HIV-infected patients, and the number of pathogens found continues to increase with time. In addition, there is some controversy concerning the role of some organisms in the pathogenesis of diarrhea and the appropriate diagnostic evaluation of affected patients. This article reviews our current understanding of these pathogens and some of the diagnostic and therapeutic approaches for diarrhea associated with HIV infection
— id: 14723, year: 1997, vol: 26, page: 259, stat: Journal Article,

Diagnosis and treatment of hepatic disease in patients with HIV
Poles MA; Lew EA; Dieterich DT
1997 Jun;26(2):291-321, Gastroenterology clinics of North America
Liver involvement with opportunistic infections and neoplasms is a well-recognized component of AIDS, affecting most patients. The cause of hepatic disease in these patients may be divided into hepatitis, granulomatous disease, mass lesions, vascular lesions, hepatotoxic drugs, and nonspecific findings. With a rational approach, most patients with AIDS and liver disease can be diagnosed and treated in a cost-effective manner with low morbidity
— id: 12313, year: 1997, vol: 26, page: 291, stat: Journal Article,

Oxandrolone as a treatment for AIDS-related weight loss and wasting
Poles MA; Meller JA; Lin A; Weiss WR; Gocke M; Dieterich DT
1997 Jan 22-26;4:193-193, Conference on Retroviruses & Opportunistic Infections
Wasting decreases immune function, and is associated with decreased quality of life and increased mortality in patients with AIDS. Many modalities have been used in the treatment of this problem, but few promote positive nitrogen balance and increase body cell mass. We studied 21 patients with AIDS-related weight loss, defined as loss of greater than 5% usual body weight, or a baseline of less than 100% ideal body weight (IBW). Patients were treated with oxandrolone, 10 mg orally, twice daily. All subjects were men who acquired HIV through unprotected homosexual sex, with the exception of one woman who acquired the disease through unprotected heterosexual contact. The mean age of patients was 38 years, and mean CD4 count was 55. All patients were evaluated with bioelectrical impedance analysis (BIA). BIA mean values for weight, body cell mass (BCM), fat, intracellular water (ICW) and extracellular water (ECW) were calculated for patients at baseline, and then for those patients who took the medication for 30 days, 60 days, 90 days, and 120 days, respectively. Mean changes from baseline in weight, BCM, fat and ICW were significant (p is less than 0.05) at all points in time (except at 120 days, due to the small sample size at this time). At 30 days, weight increased by a mean of 6.5 pounds, BCM increased by a mean of 3.4 pounds, fat increased by a mean of 1.6 pounds, and ICW increased by a mean of 1.4 liters. At 60 days, weight increased by a mean of 12.9 pounds, BCM increased by a mean of 6.9 pounds, fat increased by a mean of 3.0 pounds, and ICW increased by a mean of 2.9 liters. At 90 days, weight increased by a mean of 11.3 pounds, BCM increased by a mean of 4.2 pounds, fat increased by a mean of 5.2 pounds, and ICW increased by a mean of 1.8 liters. At 120 days, weight increased by a mean of 16.0 pounds, BCM increased by a mean of 6.6 pounds, fat increased by a mean of 6.8 pounds, and ICW increased by a mean of 2.7 liters. Change in ECW was significant (p is less than 0.05) only at 90 days. At that time, ECW was decreased by a mean of 1.1 liters from baseline. Of note, values for mean body composition, including % ideal body weight, % BCM, and % fat were also recorded at baseline, and at 30-day intervals thereafter, and were noted to rise steadily throughout the study period. Percent IBW increased from 92.2% at baseline to 101.3% at 90 days and to 106.7% at 120 days. Treatment with oxandrolone resulted in a significant (p is less than 0.05) increase in weight gain, and importantly, in BCM at 90 days. A significant (p is less than 0.05) increase in ICW and a significant (p is less than 0.05) decrease in ECW were also found to occur at 90 days. Final analysis for the 120-day follow-up has not been completed at this time. Thus, the common nutritional abnormalities that occur in AIDS-related weight loss and wasting were reversed
— id: 6006, year: 1997, vol: 4, page: 193, stat: Journal Article,

Liver biopsy findings in 501 patients infected with human immunodeficiency virus (HIV)
Poles MA; Dieterich DT; Schwarz ED; Weinshel EH; Lew EA; Lew R; Scholes JV
1996 Feb 1;11(2):170-177, Journal of acquired immune deficiency syndromes & human retrovirology
Patients infected with human immunodeficiency virus (HIV) are at risk for a variety of liver diseases. We undertook a retrospective study of 501 HIV-seropositive patients to assess the yield of percutaneous liver biopsy. The most common indications for liver biopsy were liver test abnormalities (89.5%), fever for 2 weeks (71.9%), and hepatomegaly (52.0%). The most common biopsy-derived diagnosis was Mycobacterium avium complex (MAC), seen in 87 (17.4%) biopsies. Mycobacterium tuberculosis was found in 13 biopsies (2.6%). In 28 biopsies (5.6%) mycobacteria was seen, but speciation of the organism was not possible. Chronic active viral hepatitis was seen in 60 biopsies (12.0%). Opportunistic hepatic infection from other organisms was found in 14 biopsies (2.8%). The most common neoplasm was lymphoma, which was seen in 12 biopsies (2.4%). MAC infection of the liver was associated with elevated alkaline phosphatase (p = 0.01). Among patients with fever for 2 weeks after an extensive negative workup including bone marrow biopsy, 58.2% had a diagnosis by liver biopsy. Overall, 64.3% of liver biopsies yielded a histopathological diagnosis, 45.7% of which were potentially treatable. We could not evaluate whether liver biopsy had a positive effect on patient outcome and survival, nor did we attempt to prove that liver biopsy resulted in a change in treatment or a change in preprocedure clinical diagnosis. Thus, questions about the efficacy of liver biopsy cannot be answered. Liver biopsy may be a helpful diagnostic tool in HIV-positive patients with fever, liver test abnormalities or hepatomegaly
— id: 6947, year: 1996, vol: 11, page: 170, stat: Journal Article,

Oxandrolone as a treatment for wasting in HIV
Poles, MA; Lin, A; Weiss, WR; Gocke, M; Dieterich, DT
1996 OCT ;23(4):133-133, Clinical infectious diseases
— id: 52756, year: 1996, vol: 23, page: 133, stat: Journal Article,

Immunohistochemical detection of hepatitis C virus in liver biopsy specimens from patients with AIDS
Scholes, J; Eng, S; Melamed, J; Poles, M; Theise, ND
1996 ;74(Suppl 1):795-795, Laboratory investigation
— id: 53084, year: 1996, vol: 74, page: 795, stat: Journal Article,

Adenovirus colitis in HIV infection: An underdiagnosed entity
Yan, Z; Son, N; Singh, M; Poles, M; Melamed, J; Scholes, J
1996 ;74(Suppl 1):388-388, Laboratory investigation
— id: 53078, year: 1996, vol: 74, page: 388, stat: Journal Article,

TREATMENT OF MICROSPORIDIA WITH ALBENDAZOLE IN 42 PATIENTS WITH AIDS
DIETERICH, DT; GREANEY, EJ; DELATORRE, C; POLES, MA; LEW, EA
1995 APR ;108(4):A810-A810, Gastroenterology
— id: 86750, year: 1995, vol: 108, page: A810, stat: Journal Article,

Gastrointestinal emergencies in the patient with AIDS
Lew E; Dieterich D; Poles M; Scholes J
1995 Apr;11(2):531-560, Critical care clinics
The clinical importance of gastrointestinal disorders among patients with acquired immunodeficiency syndrome (AIDS) is enormous. Estimates of gastrointestinal complaints among AIDS patients range from 30% to 90%. Many of these patients may be chronically ill and have multiple simultaneous opportunistic pathogens and neoplasms. The diagnosis and management of serious gastrointestinal complications that often occur in the setting of chronic illness represent major challenges in the care of patients with AIDS
— id: 12787, year: 1995, vol: 11, page: 531, stat: Journal Article,

Gastrointestinal emergencies in the patient with AIDS
Lew E; Dieterich D; Poles M; Scholes J
1995 Apr;11(2):531-560, Critical care clinics
The clinical importance of gastrointestinal disorders among patients with acquired immunodeficiency syndrome (AIDS) is enormous. Estimates of gastrointestinal complaints among AIDS patients range from 30% to 90%. Many of these patients may be chronically ill and have multiple simultaneous opportunistic pathogens and neoplasms. The diagnosis and management of serious gastrointestinal complications that often occur in the setting of chronic illness represent major challenges in the care of patients with AIDS
— id: 154272, year: 1995, vol: 11, page: 531, stat: Journal Article,

The endoscopic brush cytology specimen in the diagnosis of intestinal microsporidiosis
Orenstein JM; Lew E; Poles MA; Dieterich D
1995 Oct;9(10):1199-1201, AIDS
— id: 24387, year: 1995, vol: 9, page: 1199, stat: Journal Article,

Treatment with albendazole for intestinal disease due to Enterocytozoon bieneusi in patients with AIDS
Dieterich DT; Lew EA; Kotler DP; Poles MA; Orenstein JM
1994 Jan;169(1):178-183, Journal of infectious diseases
To determine the efficacy and safety of albendazole for treatment of intestinal microsporidosis due to Enterocytozoon bieneusi, 29 patients with AIDS were studied. All had chronic diarrhea, weight loss, and evidence of malabsorption. After 1 month of treatment with albendazole (400 mg orally twice a day), the mean number of bowel movements decreased from 7.0 to 3.8 stools/day (P < .0001) and the mean weight gain was 0.56 kg (P = .259). Albendazole at this dose did not clear E. bieneusi on follow-up small-bowel biopsies, but ultrastructural studies revealed an apparent decrease in parasite burden in 2 patients and an increased proportion of dividing plasmodia in 5 patients. There were no significant adverse events associated with this dose of albendazole. A formal double-blind placebo-controlled study using higher doses has recently been approved and will soon be underway (AIDS Clinical Trial Group protocol 207)
— id: 6359, year: 1994, vol: 169, page: 178, stat: Journal Article,

USE OF RIBAVIRIN FOR RECURRENT HEPATITIS-C VIRUS (HCV) IN LIVER-TRANSPLANT PATIENTS AFTER FAILURE OF INTERFERON
DIETERICH, DT; DIFLO, T; POLES, MA; LEW, EA; TEPERMAN, L
1994 APR ;106(4):A884-A884, Gastroenterology
— id: 52457, year: 1994, vol: 106, page: A884, stat: Journal Article,

Predisposition to cytomegalovirus infection of the gastrointestinal tract
Poles MA; Lew EA; Dieterich DT
1994 May 1;120(9):810-810, Annals of internal medicine
— id: 14724, year: 1994, vol: 120, page: 810, stat: Journal Article,

Actinomyces infection of a cytomegalovirus esophageal ulcer in two patients with acquired immunodeficiency syndrome
Poles MA; McMeeking AA; Scholes JV; Dieterich DT
1994 Sep;89(9):1569-1572, American journal of gastroenterology
Esophageal disease is a significant cause of morbidity among patients with the acquired immunodeficiency syndrome (AIDS). Many organisms have been implicated in the pathogenesis of dysphagia and odynophagia. We describe a unique presentation of actinomyces esophageal infection in two homosexual male patients with AIDS and biopsy proven CMV esophagitis. After failure of esophagitis to resolve with ganciclovir or foscarnet therapy, the patients underwent repeat endoscopy and were subsequently found to have a secondary infection of the ulcers by Actinomyces. Treatment with intravenous penicillin G resulted in symptomatic and histopathological resolution of esophageal disease. This appears to be the first report of Actinomyces infection of esophageal ulcers in AIDS patients, possibly a commonly overlooked diagnosis
— id: 12895, year: 1994, vol: 89, page: 1569, stat: Journal Article,

Treatment of gastrointestinal cytomegalovirus infection using twice daily administration of foscarnet in AIDS patients
Dieterich D; Lew E; Poles M; Johnson J; Munley SM
1993 Dec 12-16;1:146-146, National Conference on Human Retroviruses & Related Infections
To determine the pharmacokinetics (pk) as well as evaluate the safety and efficacy of foscarnet (FOS) treatment at a dose of 90 mg/kg IV q12h in upper and lower gastrointestinal (GI) cytomegalovirus (CMV) infection 10 patients with the Acquired Immunodeficiency Syndrome (AIDS) were studied. Plasma FOS concentrations were measured by ion-pair reversed-phase liquid chromatography on days 1 and 20. Safety was evaluated by monitoring clinical/laboratory variables and adverse events. Efficacy was measured by histopathological examination of biopsies and endoscopic grading which were performed at baseline, week 3 and week 6. If resolution occurred at week 3, FOS was discontinued. Five patients with upper GI CMV disease and 5 with lower GI CMV disease were enrolled into study. Median age was 43.5 years and median CD4 count was 26.5 cells/mm3. On day 1, mean peak and trough plasma FOS levels were 621 +/- 130 and 37 +/- 20 micromolar, while on day 20, levels were 687 +/- 141 and 48 +/- 14 micromolar, respectively. FOS was discontinued in 1 patient after he developed hypokalemia and an increased serum creatinine. Another patient's 24 hour creatinine clearance decreased below 50 mg/ml after three weeks, but he completed therapy. Mild edema was noted in 2/10 patients (20%), but resolved. Eight of 10 patients (80%) required 6 weeks for full resolution. Nine of 10 patients (90%) responded histopathologically (P=.0067) and 9/10 (90%) responded endoscopically (P=.0004). In conclusion, the peak concentrations of twice daily administration of FOS were higher than those necessary to inhibit CMV. There was no difference in the pk between days 1 and 20. This regimen appears to be safe and effective in the treatment of gastrointestinal CMV disease in AIDS patients
— id: 5985, year: 1993, vol: 1, page: 146, stat: Journal Article,

Foscarnet treatment of cytomegalovirus gastrointestinal infections in acquired immunodeficiency syndrome patients who have failed ganciclovir induction
Dieterich DT; Poles MA; Dicker M; Tepper R; Lew E
1993 Apr;88(4):542-548, American journal of gastroenterology
This compassionate-use study examined the efficacy of foscarnet in patients with AIDS and cytomegalovirus (CMV) gastrointestinal disease who had failed ganciclovir induction. Nineteen male homosexuals with AIDS and biopsy-proven CMV gastrointestinal disease who had twice failed standard ganciclovir induction (defined as progression of clinical CMV disease) were studied. Foscarnet 60 mg/kg every 8 h was administered intravenously for 14 days, then maintenance was utilized at 90 or 120 mg/kg every day with 1 L normal saline daily. Endpoints included endoscopic appearance, blinded histopathologic analysis of biopsies for CMV inclusions, and changes in symptoms by 50% from baseline. Patients were evaluated before and 2-3 wk after foscarnet. Histopathologic improvement was seen in 67%, whereas 74% improved clinically after a median duration of 7.5 days (1-12). Among the nine with esophageal disease, six patients (68%) had a clinical response and six of eight (75%) had a pathologic response. Among the 10 with colonic disease, eight patients (80%) had a clinical response and six (60%) had a pathologic response. Reversible elevations in creatinine were seen in two of 17 (12%). Three patients with esophageal disease developed strictures late in therapy requiring dilation. Median survival after foscarnet induction was 5.0 months. Foscarnet appears to induce remission of CMV gastrointestinal disease in 67% of patients when ganciclovir induction has failed. Reversible nephrotoxicity occurred in 12%. Strictures may be a late complication of CMV esophagitis
— id: 13210, year: 1993, vol: 88, page: 542, stat: Journal Article,

Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients
Dieterich DT; Poles MA; Lew EA; Mendez PE; Murphy R; Addessi A; Holbrook JT; Naughton K; Friedberg DN
1993 May;167(5):1184-1188, Journal of infectious diseases
Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied
— id: 8401, year: 1993, vol: 167, page: 1184, stat: Journal Article,

Two patients with CMV colitis and over 500 CD4+ cells
Poles MA; Lew EA; Dieterich T
1993 Dec 12-16;1:146-146, National Conference on Human Retroviruses & Related Infections
Cytomegalovirus (CMV) is a common cause of diarrhea in patients infected with the human immunodeficiency virus (HIV). Infection with this entity is typically regarded as an effect of severe immunosuppression, only seen in AIDS patients when their CD4+ count is below 100 cells/mm3, and usually below 50 cells/mm3. We report two cases of HIV seropositive patients without a history of prior opportunistic infections, both with CD4+ counts over 500 cells/mm3 (510, and 664) documented on two separate occasions. Each patient presented with diarrhea and fever. One also had cramping abdominal pain, and the other hematochezia. Examination of stool samples for enteric bacterial pathogens, ova and parasites, acid fast bacilli, fungi, and assay for Clostridium difficile toxin failed to reveal an etiology. On sigmoidoscopy, the colonic mucosa of each appeared erythematous and inflamed. Biopsies of mucosa showed characteristic CMV inclusions and inflammation, diagnostic for CMV colitis. Both patients underwent induction with ganciclovir, which resulted in clinical endoscopic improvement. Post treatment biopsies showed no evidence of CMV. These patients illustrate the remarkable variability of CMV infection in patients infected with HIV. In patients with CD4+ counts above 500 who present with diarrhea of unknown etiology, CMV must remain a consideration
— id: 5995, year: 1993, vol: 1, page: 146, stat: Journal Article,

PILOT-STUDY OF INTERFERON-ALPHA-2B TREATMENT OF CHRONIC ACTIVE HEPATITIS-C IN PATIENTS CO-INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS [HIV-1]
SCHWARZ, ED; HASSLET, P; BRODE, R; LEE, M; JAGIRDAR, J; POLES, MA; REDDY, R; DIETERICH, DT
1993 OCT ;18(4):A254-A254, Hepatology
— id: 52216, year: 1993, vol: 18, page: A254, stat: Journal Article,

COMPLICATIONS OF LIVER BIOPSIES IN PATIENTS SEROPOSITIVE FOR HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)
SCHWARZ, ED; LEW, RJ; DICKER, MA; POLES, MA; LEW, EA; DIETERICH, DT
1993 APR ;104(4):A777-A777, Gastroenterology
— id: 54198, year: 1993, vol: 104, page: A777, stat: Journal Article,

RESULTS OF 452 LIVER BIOPSIES IN PATIENTS SEROPOSITIVE FOR HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)
DIETERICH, D; POLES, M; LEW, E; SCHWARTZ, E; WEINSHEL, E; LEE, M; SCHOLES, J
1992 OCT ;16(4):A69-A69, Hepatology
— id: 51856, year: 1992, vol: 16, page: A69, stat: Journal Article,