Samuel B Ho

VA San Diego Healthcare System, San Diego, California, United States

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Publications (93)541.17 Total impact

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    ABSTRACT: Antiviral therapy for the hepatitis C virus (HCV) reduces all-cause and liver-related morbidity and mortality. Few studies are available from populations with multiple medical and psychiatric comorbidities where the impact of successful antiviral therapy might be limited. The purpose of this study was to determine the effect of sustained virologic response (SVR) on all-cause and liver-related mortality in a cohort of HCV patients treated in an integrated hepatitis/mental health clinic. This was a retrospective review of all patients who initiated antiviral treatment for chronic HCV between January 1, 1997 and December 31, 2009. Cox regression analysis was used to determine factors involved in all-cause mortality, liver-related events and hepatocellular carcinoma. A total of 536 patients were included in the analysis. Median follow-up was 7.5 years. Liver and non-liver-related mortality occurred in 2.7 and 5.0 % of patients with SVR and in 17.8 and 6.4 % of patients without SVR. In a multivariate analysis, SVR was the only factor associated with reduced all-cause mortality (HR 0.47; 95 % CI 0.26-0.85; p = 0.012) and reduced liver-related events (HR 0.23; 95 % CI 0.08-0.66, p = 0.007). Having stage 4 liver fibrosis increased all-cause mortality (HR 2.50; 95 % CI 1.23-5.08; p = 0.011). Thrombocytopenia at baseline (HR 2.66; 95 % CI 1.22-5.79; p = 0.014) and stage 4 liver fibrosis (HR 4.87; 95 % CI 1.62-14.53; p = 0.005) increased liver-related events. Despite significant medical and psychiatric comorbidities, SVR markedly reduced liver-related outcomes without a significant change in non-liver-related mortality after a median follow-up of 7.5 years.
    Digestive Diseases and Sciences 02/2014; · 2.26 Impact Factor
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    ABSTRACT: Methamphetamine (MA) use has increased in the United States in the last 20 years and is a risk factor for hepatitis C virus(HCV) infection. The purpose of this study was to determine the characteristics and HCV infection outcomes of patients with a history of MA use. Subjects consisted of newly entered patients in the Veterans Affairs (VA) HCV registry at a single VA medical center from January 1, 2004, to June 30, 2004, and from January 1, 2007, to June 30, 2007. Univariate and multivariate analyses related to HCV infection antiviral treatment outcomes through 2010 was performed. A total of 198 consecutive eligible HCV registry patients were analyzed, and 40% had a history of MA use. Of patients with MA use history, 46% (36/79) had active use (within 6 months) at initial contact. Active MA users were significantly younger (mean age, 45.5 years), with more concomitant drug use (86%), compared with patients without MA use (mean age, 53.5 years; 42% minority; 29% other drug use). Overall, 71% of the 198 patients reported a history of problematic alcohol use, and 47% of those reported active abuse. Logistic regression analyses indicated that MA use did not significantly adversely affect antiviral treatment initiation, completion, or sustained virological response rates compared with that in patients without MA use. Active alcohol users had lower treatment initiation than patients without alcohol use. MA use is common in recent US veterans with HCV infection and occurs in younger patients with polysubstance use. Prior history or active MA use does not seem to adversely affect HCV infection clinic treatment compared with that in HCV-infected patients without MA use.
    Journal of Addiction Medicine 12/2013; · 1.73 Impact Factor
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    Digestive Diseases and Sciences 05/2013; · 2.26 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: The Veterans Health Administration (VHA) is the largest single provider of care for hepatitis C virus (HCV) infection in the US. We analyzed the cost-effectiveness of treatment with the HCV protease inhibitors boceprevir and telaprevir in a defined managed care population of 102,851 patients with untreated chronic genotype 1 infection. METHODS: We used a decision-analytic Markov model to examine 4 strategies: standard dual-therapy with pegylated interferon-alfa and ribavirin (PR), the combination of boceprevir and PR triple therapy, the combination of telaprevir and PR, or no antiviral treatment; sensitivity analysis was performed. Sources of data included published rates of disease progression, the census bureau, and VHA pharmacy and hospitalization cost databases. RESULTS: The estimated costs for treating each patient were $8000 for PR, $31,300 for boceprevier and PR, and $41,700 for telaprevir and PR. Assuming VHA treatment rates of 22% and optimal rates of sustained viral response, PR, boceprevir and PR, and telaprevir and PR would reduce relative liver-related deaths by 5.2%, 10.9%, and 11.5%, respectively. Increasing treatment rates to 50% would reduce liver-related deaths by 12%, 24.7%, and 26.1%, respectively. The incremental cost-effectiveness ratios were $29,184/quality of adjusted-life years (QALY) for boceprevir and PR and $44,247/QALY for telaprevir and PR vs only PR. With the current 22% treatment rate, total system-wide costs to adopt boceprevir and PR or telaprevir and PR would range from $708 million to $943 million. CONCLUSIONS: Despite substantial upfront costs of treating HCV-infected patients in the VHA with PR, or telaprevir and PR, each regimen improves quality of life and extends life expectancy, by reducing liver-related morbidity and mortality, and should be cost effective. Further efforts to expand access to direct-acting antiviral therapy are warranted.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2013; · 5.64 Impact Factor
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    ABSTRACT: Most individuals infected with the hepatitis C have not received antiviral treatment, with mental health and substance abuse problems being the primary barrier. Interventions have been developed to address these barriers among HCV patients considered "high-risk" for antiviral treatment. We present the design and methods of a prospective, randomized controlled multisite trial being conducted in the Veterans Affairs Healthcare System. The study employed a parallel design and the three study sites randomized a total of 364 VA patients with HCV to either Integrated Care (IC) or Usual Care (UC). The IC intervention consisted of a mental health provider (MHP) performing a) brief interventions to address risk factors; b) collaborative consultation with the HCV treatment clinicians; and c) case management prior to and during antiviral treatment. Clinical outcomes were abstracted from patient medical records and self-report questionnaires were completed at baseline, 4-months, 16-months, and 22-months after enrollment. The primary outcome of the study was sustained viral response (SVR). Secondary clinical outcomes were HCV treatment initiation and completion rates. Other secondary outcomes included substance use, depression, PTSD symptoms, quality of life, healthcare satisfaction, and healthcare utilization. The Integrated Care intervention has the potential to transform HCV antiviral treatment by increasing the number of HCV-infected individuals that can be successfully treated.
    Contemporary clinical trials 05/2013; · 1.51 Impact Factor
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    ABSTRACT: Objective. Chronic hepatitis C infection afflicts millions of people worldwide. Although antiviral treatments are increasingly effective, many hepatitis C virus (HCV) patients avoid treatment, do not complete or respond to treatment, or have contraindications. Self-management interventions are one option for promoting behavioral changes leading to liver wellness and improved quality of life. Our objective was to evaluate whether the effects of the HCV self-management program were sustained at the 12-month follow-up assessment. Methods. Veteran Affairs patients with hepatitis C (N = 134; mean age = 54.6 years, 95% male, 41% ethnic minority, 48% homeless in last 5 years) were randomized to either a 6-week self-management workshop or an information-only intervention. The weekly 2-hour self-management sessions were based on a cognitive-behavioral program with hepatitis C-specific modules. Outcomes including hepatitis C knowledge, depression, energy, and health-related quality of life were measured at baseline, 6 weeks, 6 months, and 12 months later. Data were analyzed using repeated measures ANOVA. Results. Compared with the information-only group, participants attending the self-management workshop improved more on HCV knowledge (p < .005), SF-36 energy/vitality (p = .016), and the Quality of Well-Being Scale (p = .036). Similar trends were found for SF-36 physical functioning and Center for Epidemiologic Studies Short Depression Scale. Conclusion. Better outcomes were sustained among self-management participants at the 12-month assessment despite the intervention only lasting 6 weeks. HCV health care providers should consider adding self-management interventions for patients with chronic HCV.
    Health Education &amp Behavior 02/2013; · 1.54 Impact Factor
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    ABSTRACT: To determine the pattern of secreted mucin expression in Helicobacter pylori (H. pylori)-related, nonsteroidal anti-inflammatory drug (NSAID)-related and idiopathic gastric ulcers. We randomly selected 92 patients with H. pylori-associated (n = 30), NSAID-associated (n = 18), combined H. pylori and NSAID-associated gastric ulcers (n = 24), and patients with idiopathic gastric ulcers (n = 20). Immunohistochemistry for T-cell CD4/CD8, and for mucin 5AC (MUC5AC) and mucin 6 (MUC6), was performed on sections of the mucosa from the ulcer margin. Inflammation score was assessed according to the Sydney system. MUC5AC was expressed on the surface epithelium (98.9%) and neck glands (98.9%) with minimal expression in the deep glands (6.5%). MUC6 was strongly expressed in the deep glands (97.8%), variable in the neck glands (19.6%) and absent in the surface epithelium (0%). The pattern of mucin expression in idiopathic ulcer margins was not different from the expression in ulcers associated with H. pylori, NSAIDs, or combined H. pylori and NSAIDs. CD4/CD8 ratio was higher in H. pylori-positive patients (P = 0.009). Idiopathic ulcers are associated with hospitalized patients and have higher bleeding and mortality rates. Idiopathic ulcers have a unique clinical profile. Gastric mucin expression in idiopathic gastric ulcers is unchanged compared with H. pylori and/or NSAID-associated ulcers.
    World Journal of Gastroenterology 09/2012; 18(33):4597-603. · 2.55 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: Iron deficiency anemia (IDA) is a common problem among the elderly, and often no cause is identified after routine upper endoscopy and colonoscopy exams. The purpose of this study was to determine the long-term outcomes and predictors of gastrointestinal pathology and death in patients with endoscopy-negative IDA. METHODS: This was a retrospective review of consecutive endoscopy negative-IDA patients during 2002-2004 at the VA San Diego Healthcare System. RESULTS: Mean age was 69.3 years (range 42-93), and included 105 men and nine women. Mean length of follow-up was 65.1 months. IDA resolved in 56 patients. None of these patients developed evidence of any clinically significant gastrointestinal pathology. The remaining 58 patients had persistent anemia (n = 47) or recurrent anemia (n = 11). Only 2/47 patients with persistent anemia were found to have clinically significant but benign gastrointestinal pathology during follow-up. In contrast, 6/11 patients with recurrent anemia were subsequently found to have gastrointestinal pathology. Deaths during follow-up occurred in 7 (12.5 %) patients with resolved anemia, compared with 20 (34.5 %) patients with recurrent or persistent anemia (p = 0.006). Significant independent predictors of death included persistent or recurrent anemia, anti-platelet or anticoagulant use, and congestive heart failure. CONCLUSIONS: Patients with iron deficiency anemia and negative upper endoscopy and colonoscopy often have a favorable outcome, especially if the anemia resolves with treatment. In patients with recurrent anemia a malignancy within reach of standard endoscopy and colonoscopy are possible, and repeating these procedures is warranted before consideration of further investigations.
    Digestive Diseases and Sciences 09/2012; · 2.26 Impact Factor
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    ABSTRACT: The ratio of Helicobacter pylori/NSAID-negative gastric ulcers is increasing. Idiopathic gastric ulcers have unique clinical and endoscopic features, and are associated with more bleeding complications and a higher mortality. Alterations in gastric mucin expression and sialylation pattern may be important in ulcer pathogenesis. The purpose of this study was to determine the expression pattern of membrane-bound mucins and side chain sugars in H. pylori associated-, NSAID-, and idiopathic-gastric ulcers. We randomly selected 92 patients with H. pylori (group 1, n = 30), NSAID (group 2, n = 18), combined H. pylori and NSAID associated gastric ulcers (group 3, n = 24), and patients with idiopathic gastric ulcers (group 4, n = 20). Immunohistochemistry for T-cell CD4/CD8, MUC1, MUC4, MUC17, and ECA and SNA lectins staining was performed on sections from the ulcer margins. Inflammation score was assessed according to the Sydney system. Bleeding and mortality rates were significantly higher in group 4. CD4 positive T cell count was higher in H. pylori positive patients (P = 0.009). Staining intensity of MUC17 was higher in group 1 than in group 4, foveola and glands alike, with 11.50 ± 3.47 versus 6.80 ± 4.02, and 9.61 ± 4.26 versus 7.59 ± 3.26, respectively (P < 0.0001). This was a mirror image with MUC1. SNA lectin staining was increased in group 4, in parallel to MUC1 expression, indicating more abundant α2-6 sialylation in that group. Cytoplasmic MUC17 staining was significantly decreased in the cases with idiopathic ulcer. The opposite was demonstrated for MUC1. This observation might be important, since different mucins with altered sialylation patterns likely differ in their protection efficiency against acid and pepsin.
    Digestive Diseases and Sciences 05/2012; 57(10):2535-44. · 2.26 Impact Factor
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    ABSTRACT: Liver biopsy remains the standard, recommended method for assessing liver damage associated with chronic hepatitis C (HCV) infection. However, there is considerable debate about how liver biopsy should best be used, especially with the advent of more efficacious antiviral therapies. To identify the factors that influence the use of liver biopsy for HCV patients, we describe variations in liver biopsy use at the delivery system and patient level in a national VA sample. We analyzed VA HCV registry data for 171,893 VA patients with confirmed chronic HCV. Delivery system characteristics included geographic region and specialist time. Patient characteristics included antiviral treatment indicators, contraindications, volume of healthcare visits, and demographic variables. Logistic regression was used to explore correlates of biopsy use. Liver biopsy use in the VA system increased from 1997 to 2003 but began declining in 2004. Rates of liver biopsy from 2004 to 2006 varied by VA region, ranging from 5% to 18%. Treatment contraindications and laboratory tests were significantly associated with more biopsies. Demographic variables (higher age, lower BMI, race/ethnicity, and less% service connected disability) were associated with fewer biopsies. Regional variability remained significant independent of volume of care and specialist time. Liver biopsy rates in the VA system have variability that seems unrelated to clinical need. New antiviral therapies and non-invasive assessment techniques may create additional uncertainty for the role of liver biopsy, perhaps explaining its decline in recent years. The availability of more effective antiviral therapies may also affect biopsy rates in the future.
    Journal of Hepatology 04/2012; 57(2):252-9. · 9.86 Impact Factor
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    ABSTRACT: Currently colonoscopy quality indicators emphasize our ability to improve polyp detection (e.g., preparation quality, withdrawal times of ≥6 min). The completeness of a polyp resection may also be an important determinant of quality and efficient colonoscopy. The primary aim of this study was to determine the incidence of an incomplete polyp resection despite a perceived complete polypectomy. This was a retrospective quality assurance project conducted at the San Diego Veterans Affair Medical Center and University of California San Diego Medical Center from July 2007 to April 2008. The patients recruited to this study were undergoing surveillance and screening colonoscopy. The resection quality was evaluated in 65 polyps of 47 patients. Twenty-two polyps were removed with standard biopsy forceps, jumbo forceps (18), hot snare (18), and cold snare (7). Biopsies were taken from the post-polypectomy site base and perimeter for histologic examination in order to confirm histologic absence of all polypoid appearing mucosa. The post-polypectomy sites of ten polyps (15%) were found to have residual polypoid tissue. Six were removed by standard biopsy forceps, jumbo forceps (2), hot snare (1), and cold snare (1). When compared to other polypectomy devices, standard biopsy forceps were more likely to result in an incomplete resection (27 vs. 9%; P = 0.076). The endoscopist may not be visually accurate in determining when a polyp is completely resected, and alternative devices and techniques for polyp resection should be considered.
    Digestive Diseases and Sciences 03/2012; 57(7):1786-91. · 2.26 Impact Factor
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    ABSTRACT: Adequate colon cleansing is an important factor in performing quality colonoscopy. Split dose Polyethylene Glycol (PEG) solutions have been shown to improve colon cleansing, but the effectiveness in a large clinical practice of elderly co-morbid patients has not been demonstrated. The aim of this study was to assess the efficacy of a simplified split PEG bowel prep in Veterans Health Administration (VHA) patients. Prospective pre-post study design of VHA patients undergoing routine colonoscopy. Bowel prep quality was assessed using a standardized semi-quantitative 5-point scale. "Standard" 4L PEG prep was consumed once the evening before the procedure. "Split" prep was consumed half in the early evening and half in the late evening or early morning depending on procedure time. Right colon preps were Excellent/Good in 81.4% of split preps (n=199) vs. 63% of standard preps (n=447, p<0.001). Left colon preps were Excellent/Good in 85.9% of split preps vs. 71.6% of standard preps (p<0.001). Diabetics (n=133) had significantly more right colon preps rated fair or worse compared to non-diabetics irrespective of prep (39.9% vs. 29.0%, p=0.02). Split prep in diabetics resulted in fewer right colon preps rated fair or worse compared to diabetics using standard prep (28.3% vs. 45.9%, p=0.049). Average adenomas detected per colonoscopy were 1.04 for split prep vs. 0.85 for standard prep (p=NS). Patient satisfaction was higher for split preps. System-wide implementation of a split PEG prep resulted in significantly improved bowel cleansing in VHA patients, particularly in the right colon. Improved bowel cleansing with split preps was associated with higher patient satisfaction.
    Journal of interventional gastroenterology. 01/2012; 2(4):177-182.
  • Article: Response.
    Gastrointestinal endoscopy 01/2012; 75(1):230. · 6.71 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) screening rates are low in many areas and cost-effective interventions to promote CRC screening are needed. Recently in a randomized controlled trial, a mailed educational reminder increased CRC screening rates by 16.2% among U.S. Veterans. The aim of our study was to assess the costs and cost-effectiveness of a mailed educational reminder on fecal occult blood test (FOBT) adherence. In a blinded, randomized, controlled trial, 769 patients were randomly assigned to the usual care group (FOBT alone, n = 382) or the intervention group (FOBT plus a mailed reminder, n = 387). Ten days after picking up the FOBT cards, a 1-page reminder with information related to CRC screening was mailed to the intervention group. Primary outcome was number of returned FOBT cards after 6 months. The costs and incremental cost-effectiveness ratio (ICER) of the intervention were assessed and calculated respectively. Sensitivity analyses were based on varying costs of labor and supplies. At 6 months after card distribution, 64.6% patients in the intervention group returned FOBT cards compared with 48.4% in the control group (P < 0.001). The total cost of the intervention was $962 or $2.49 per patient, and the ICER was $15 per additional person screened for CRC. Sensitivity analysis based on a 10% cost variation was $13.50 to $16.50 per additional patient screened for CRC. A simple mailed educational reminder increases FOBT card return rate at a cost many health care systems can afford. Compared to other patient-directed interventions (telephone, letters from physicians, mailed reminders) for CRC screening, our intervention was more effective and cost-effective.
    BMC Gastroenterology 08/2011; 11:93. · 2.11 Impact Factor
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    ABSTRACT: Mucus is a protective gel that lines respiratory tract surfaces. To identify potential roles for secreted gel--forming mucins in lung development, we isolated murine lungs on embryonic days (E) 12.5-18.5, and postnatal days (PN) days 5, 14, and 28. We measured the mucin gene expression by quantitative RT-PCR, and localization by histochemical and immunohistochemical labeling. Alcian blue/periodic acid--Schiff--positive cells are present from E15.5 through PN28. Muc5b transcripts were abundant at all time points from E14.5 to PN28. By contrast, transcript levels of Muc5ac and Muc2 were approximately 300 and 85,000 times lower, respectively. These data are supported by immunohistochemical studies demonstrating the production and localization of Muc5ac and Muc5b protein. This study indicates that mucin production is prominent in developing murine lungs and that Muc5b is an early, abundant, and persistent marker of bronchial airway secretory cells, thereby implicating it as an intrinsic component of homeostatic mucosal defense in the lungs.
    American Journal of Respiratory Cell and Molecular Biology 06/2011; 44(6):755-60. · 4.15 Impact Factor
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    ABSTRACT: Chronic hepatitis C infection (HCV) is a major health problem that disproportionately affects people with limited resources. Many people with HCV are ineligible or refuse antiviral treatment, but less curative treatment options exist. These options include adhering to follow-up health visits, lifestyle changes, and avoiding hepatotoxins like alcohol. Herein, we describe a recently developed self-management program designed to assist HCV-infected patients with adherence and improve their health-related quality of life (HRQOL). The development of the Hepatitis C Self-Management Program (HCV-SMP) was informed by scientific literature, qualitative interviews with HCV-infected patients, self-management training, and feedback from HCV clinical experts. The Hepatitis C Self-Management Program (HCV-SMP) is a multi-faceted program that employs cognitive-behavioral principles and is designed to provide HCV-infected people with knowledge and skills for improving their HRQOL. The program consists of six 2-h workshop sessions which are held weekly. The sessions consist of a variety of group activities, including disease-specific information dissemination, action planning, and problem-solving. The intervention teaches skills for adhering to challenging treatment recommendations using a validated theoretical model. A randomized trial will test the efficacy of this novel HCV self-management program for improving HRQOL in a difficult to reach population.
    Patient Education and Counseling 05/2011; 83(2):252-5. · 2.37 Impact Factor
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    ABSTRACT: Studies suggest that endoscopist-related factors such as colonoscopy withdrawal time are important in determining the adenoma detection rate (ADR). To determine the importance of withdrawal technique in differentiating among endoscopists with varying ADRs. Prospective, multicenter study. Five academic tertiary-care medical centers. This study involved 11 gastroenterology faculty endoscopists. A retrospective review of screening colonoscopies was performed to categorize endoscopists into low, moderate, and high ADR groups. Video recordings were randomly obtained for each endoscopist on 20 (10 real, 10 sham) withdrawals during colonoscopies performed for average-risk colorectal cancer screening. Three blinded reviewers assigned withdrawal technique scores (total of 75 points) on 110 video recordings. A separate reviewer recorded withdrawal times. Withdrawal technique scores and withdrawal times. Mean (± standard deviation [SD]) withdrawal technique scores were higher in the moderate (62 ± 2.5) and high (59.5 ± 3) ADR groups compared with the low (40.8±3) ADR group (P = .002). Mean (± SD) withdrawal times were 6.3 ± 1.8 minutes (low ADR), 10.2 ± 1.5 minutes (moderate ADR), and 8.2 ± 1.8 minutes (high ADR) (P = .29). A comparison of the withdrawal times and technique scores of the two individual endoscopists with the lowest and highest ADRs did not find a significant difference in withdrawal times (6.6 ± 1.7 vs 7.4 ± 1.7 minutes) (P = .36) but did find a nearly 2-fold difference in technique scores (36.2 ± 9 vs 62.8 ± 9.9) (P = .0001). Not adequately powered to detect small differences in withdrawal times. Withdrawal technique is an important indicator that differentiates between endoscopists with varying ADRs. It is possible that withdrawal technique is equal to, if not more important than, withdrawal time in determining ADRs.
    Gastrointestinal endoscopy 04/2011; 74(1):128-34. · 6.71 Impact Factor
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    ABSTRACT: The membrane-bound mucin MUC17 (mouse homolog Muc3) is highly expressed on the apical surface of intestinal epithelia and is thought to play a role in epithelial restitution and protection. Therefore, we hypothesized that MUC17 has a role in protection of the intestinal mucosa against luminal pathogens. Human intestinal cell lines were transfected by electroporation (Caco-2 and HT 29/19A) and by retroviral expression vector (LS174T, a cell line with high levels of MUC17 expression) using MUC17 siRNA. Transepithelial electrical resistance, permeability, tight-junction protein expression, adhesion, and invasion in response to enteroinvasive Escherichia coli (EIEC) were measured in all cell lines. In some experiments, the effect of the addition of exogenous purified crude mucin or recombinant Muc3 cysteine-rich domain protein (Muc3 CRD1-L-CRD2) as preventative or protective treatment was tested. Reduction of endogenous MUC17 is associated with increased permeability, inducible nitric oxide synthase and cyclooxygenase 2 induction, and enhanced bacterial invasion in response to EIEC exposure. Bacterial adhesion is not affected. Exogenous mucin (Muc3) and recombinant Muc3CRD treatment had a small but significant effect in attenuating the effects of EIEC infection. In conclusion, these data suggest that both native and exogenous MUC17 play a role in attachment and invasion of EIEC in colonic cell lines and in maintaining epithelial barrier function.
    AJP Gastrointestinal and Liver Physiology 03/2011; 300(6):G1144-55. · 3.65 Impact Factor
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    ABSTRACT: Mucus is a protective gel that lines respiratory tract surfaces. To identify potential roles for secreted gel-forming mucins in lung development, we isolated mouse lungs at embryonic (E) days 12.5-18.5, and post-natal (PN) days 5, 14, and 28. We measured mucin expression by quantitative RT-PCR (qRT-PCR) and localization by histochemical and immunohistochemical labeling. AB-PAS positive cells are present from E15.5 through PN28. Muc5b mRNA expression is abundant at all timepoints from E14.5 to PN28. By contrast, Muc5ac and Muc2 transcript levels are approximately 300 and 85,000 times lower, respectively. These data are supported by immunohistochemical studies demonstrating Muc5ac and Muc5b protein production and localization. These studies show that mucin production is prominent in developing mouse lungs and that Muc5b is an early, abundant, and persistent marker of bronchial airway secretory cells, thereby implicating it as an intrinsic component of homeostatic mucosal defense in the lungs.
    American Journal of Respiratory Cell and Molecular Biology 03/2011; · 4.15 Impact Factor
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    ABSTRACT: Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection. Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3-4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B, n = 31). Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8-12 weeks, and late virologic response from 16-24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients. Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.
    Digestive Diseases and Sciences 03/2011; 56(3):880-8. · 2.26 Impact Factor

Publication Stats

1k Citations
541.17 Total Impact Points

Institutions

  • 2008–2014
    • VA San Diego Healthcare System
      San Diego, California, United States
    • Overton Brooks VA Medical Center
      Shreveport, Louisiana, United States
  • 2013
    • Boston University
      Boston, Massachusetts, United States
  • 2012–2013
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 2008–2013
    • University of California, San Diego
      • Department of Medicine
      San Diego, California, United States
  • 2007–2012
    • University of California, Irvine
      Irvine, California, United States
  • 2010
    • University of California, San Francisco
      San Francisco, California, United States
  • 2009
    • CSU Mentor
      Long Beach, California, United States
  • 1999–2008
    • University of Minnesota Twin Cities
      • • Department of Medicine
      • • Department of Otolaryngology
      • • Department of Laboratory Medicine and Pathology
      Minneapolis, MN, United States
  • 2006
    • University of Michigan
      • Department of Pathology
      Ann Arbor, MI, United States
  • 2001–2006
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
  • 2004–2005
    • Vanderbilt University
      • Department of Medicine
      Nashville, MI, United States
  • 2003
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States