Much of our understanding of gut-microbial interactions has come from mouse models. Intestinal im... more Much of our understanding of gut-microbial interactions has come from mouse models. Intestinal immunity is complex and a combination of host genetics and environmental factors play a significant role in regulating intestinal immunity. Due to this complexity, no mouse model to date gives a complete and accurate representation of human intestinal diseases, such as inflammatory bowel diseases. However, intestinal tissue from patients undergoing bowel resection reflects a condition of severe disease that has failed treatment; hence a more dynamic perspective of varying inflammatory states in IBD could be obtained through the analyses of pinch biopsy material. Here we describe our protocol for analyzing mucosal pinch biopsies collected predominantly during colonoscopies. We have optimized flow cytometry panels to analyze up to 8 cytokines produced by CD4+ and CD8+ cells, as well as for characterizing nuclear proteins and transcription factors such as Ki67 and Foxp3. Furthermore, we have ...
World journal of gastroenterology : WJG, Jan 14, 2015
To assess and teach cultural competency skills at the fellowship training level through the use o... more To assess and teach cultural competency skills at the fellowship training level through the use of objective structured clinical examinations (OSCEs). We revised four scenarios to infuse a specific focus on cross-cultural care, and to render them appropriate for gastroenterology fellows. Three are discussed here: (1) Poor Health Literacy; (2) Disclosing/Apologizing for a Complication to a Patient Who Mistrusts the Healthcare System; and (3) Breaking Bad News to a Fatalistic Patient. A fourth case emphasizing shared decision-making will be described elsewhere. Four stations were completed by fellows and observed live by four faculty members, and the fellows' performance was assessed. Eleven fellows from four programs participated in the four OSCE. In the "Poor Health Literacy" case, 18% (2/11) of participants recognized that the standardized patient (SP) had below-basic health literacy. None successfully evaluated the SP's reading skills in a culturally-sensitive ma...
Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an o... more 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 sta...
Gastroenterology (GI) training programs must develop the teaching skills of their faculty and pro... more 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. 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. 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. OSCEs can serve as practicums for faculty development in giving constructive feedback.
The American Gastroenterological Association fellowship curriculum identifies geriatric component... more 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. 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. 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. OSCEs are a feasible method for assessing geriatric-related ACGME competencies for fellows. The results highlight the need for curriculum development.
There is increasing evidence that dysregulation of CD4(+) T cell populations leads to intestinal ... more There is increasing evidence that dysregulation of CD4(+) T cell populations leads to intestinal inflammation, but the regional distribution of these populations throughout the intestinal tract in healthy individuals remains unclear. Here, we show that T(H)17, T(H)22 and T(Reg) cells are enriched in the healthy human cecum compared to the terminal ileum and sigmoid colon, whereas T(H)1 and T(H)2 cells do not significantly vary by location. Transcriptional profiling analysis of paired pinch biopsies from different regions of the intestine identified significant differences in the metabolic state of the terminal ileum, cecum, and sigmoid colon. An increased proportion of T(H)17 cells was positively associated with expression of resistin (RETN) and negatively associated with expression of trefoil factor 1 (TFF1). These results suggest that CD4(+) T helper cells that are important in maintaining mucosal barrier function may be enriched in the cecum as a result of metabolic differences of the surrounding microenvironment.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2004
The purpose of this study was to characterize intestinal mucosal cytokine profiles in subjects wi... more 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.
Gastroenterology (GI) training programs are mandated to teach fellows interpersonal communication... more 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.
Understanding of the human microbiome continues to grow rapidly; however, reports on changes in t... more 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 H...
Liver involvement with opportunistic infections and neoplasms is a well-recognized component of A... more 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.
Diarrhea is a major complication of HIV infection and adversely impacts health care costs, qualit... more 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.
Gastroenterology, Volume 134, Issue 4, Pages A-164, April 2008, Authors:Bani Chander; Robert Kule... more Gastroenterology, Volume 134, Issue 4, Pages A-164, April 2008, Authors:Bani Chander; Robert Kule; Peter J. Baiocco; Sita S. Chokhavatia; Donald P. Kotler; Michael Poles; Sondra Zabar; Elizabeth H. Weinshel. Gastroenterology ...
Gastroenterology, Volume 138, Issue 5, Pages S-126, May 2010, Authors:Roy Miler; Brijen Shah; Mic... more Gastroenterology, Volume 138, Issue 5, Pages S-126, May 2010, Authors:Roy Miler; Brijen Shah; Michael Poles; Sondra Zabar; Colleen C. Gillespie; Elizabeth H. Weinshel; Sita S. Chokhavatia.
Gastroenterology, Volume 138, Issue 5, Pages S-473, May 2010, Authors:Roy Miler; Brijen Shah; Ren... more Gastroenterology, Volume 138, Issue 5, Pages S-473, May 2010, Authors:Roy Miler; Brijen Shah; Renee Williams; Sita S. Chokhavatia; Michael A. Poles; Sondra Zabar; Colleen C. Gillespie; Elizabeth H. Weinshel.
Much of our understanding of gut-microbial interactions has come from mouse models. Intestinal im... more Much of our understanding of gut-microbial interactions has come from mouse models. Intestinal immunity is complex and a combination of host genetics and environmental factors play a significant role in regulating intestinal immunity. Due to this complexity, no mouse model to date gives a complete and accurate representation of human intestinal diseases, such as inflammatory bowel diseases. However, intestinal tissue from patients undergoing bowel resection reflects a condition of severe disease that has failed treatment; hence a more dynamic perspective of varying inflammatory states in IBD could be obtained through the analyses of pinch biopsy material. Here we describe our protocol for analyzing mucosal pinch biopsies collected predominantly during colonoscopies. We have optimized flow cytometry panels to analyze up to 8 cytokines produced by CD4+ and CD8+ cells, as well as for characterizing nuclear proteins and transcription factors such as Ki67 and Foxp3. Furthermore, we have ...
World journal of gastroenterology : WJG, Jan 14, 2015
To assess and teach cultural competency skills at the fellowship training level through the use o... more To assess and teach cultural competency skills at the fellowship training level through the use of objective structured clinical examinations (OSCEs). We revised four scenarios to infuse a specific focus on cross-cultural care, and to render them appropriate for gastroenterology fellows. Three are discussed here: (1) Poor Health Literacy; (2) Disclosing/Apologizing for a Complication to a Patient Who Mistrusts the Healthcare System; and (3) Breaking Bad News to a Fatalistic Patient. A fourth case emphasizing shared decision-making will be described elsewhere. Four stations were completed by fellows and observed live by four faculty members, and the fellows' performance was assessed. Eleven fellows from four programs participated in the four OSCE. In the "Poor Health Literacy" case, 18% (2/11) of participants recognized that the standardized patient (SP) had below-basic health literacy. None successfully evaluated the SP's reading skills in a culturally-sensitive ma...
Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an o... more 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 sta...
Gastroenterology (GI) training programs must develop the teaching skills of their faculty and pro... more 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. 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. 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. OSCEs can serve as practicums for faculty development in giving constructive feedback.
The American Gastroenterological Association fellowship curriculum identifies geriatric component... more 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. 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. 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. OSCEs are a feasible method for assessing geriatric-related ACGME competencies for fellows. The results highlight the need for curriculum development.
There is increasing evidence that dysregulation of CD4(+) T cell populations leads to intestinal ... more There is increasing evidence that dysregulation of CD4(+) T cell populations leads to intestinal inflammation, but the regional distribution of these populations throughout the intestinal tract in healthy individuals remains unclear. Here, we show that T(H)17, T(H)22 and T(Reg) cells are enriched in the healthy human cecum compared to the terminal ileum and sigmoid colon, whereas T(H)1 and T(H)2 cells do not significantly vary by location. Transcriptional profiling analysis of paired pinch biopsies from different regions of the intestine identified significant differences in the metabolic state of the terminal ileum, cecum, and sigmoid colon. An increased proportion of T(H)17 cells was positively associated with expression of resistin (RETN) and negatively associated with expression of trefoil factor 1 (TFF1). These results suggest that CD4(+) T helper cells that are important in maintaining mucosal barrier function may be enriched in the cecum as a result of metabolic differences of the surrounding microenvironment.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2004
The purpose of this study was to characterize intestinal mucosal cytokine profiles in subjects wi... more 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.
Gastroenterology (GI) training programs are mandated to teach fellows interpersonal communication... more 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.
Understanding of the human microbiome continues to grow rapidly; however, reports on changes in t... more 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 H...
Liver involvement with opportunistic infections and neoplasms is a well-recognized component of A... more 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.
Diarrhea is a major complication of HIV infection and adversely impacts health care costs, qualit... more 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.
Gastroenterology, Volume 134, Issue 4, Pages A-164, April 2008, Authors:Bani Chander; Robert Kule... more Gastroenterology, Volume 134, Issue 4, Pages A-164, April 2008, Authors:Bani Chander; Robert Kule; Peter J. Baiocco; Sita S. Chokhavatia; Donald P. Kotler; Michael Poles; Sondra Zabar; Elizabeth H. Weinshel. Gastroenterology ...
Gastroenterology, Volume 138, Issue 5, Pages S-126, May 2010, Authors:Roy Miler; Brijen Shah; Mic... more Gastroenterology, Volume 138, Issue 5, Pages S-126, May 2010, Authors:Roy Miler; Brijen Shah; Michael Poles; Sondra Zabar; Colleen C. Gillespie; Elizabeth H. Weinshel; Sita S. Chokhavatia.
Gastroenterology, Volume 138, Issue 5, Pages S-473, May 2010, Authors:Roy Miler; Brijen Shah; Ren... more Gastroenterology, Volume 138, Issue 5, Pages S-473, May 2010, Authors:Roy Miler; Brijen Shah; Renee Williams; Sita S. Chokhavatia; Michael A. Poles; Sondra Zabar; Colleen C. Gillespie; Elizabeth H. Weinshel.
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