David Y. Graham

Baylor College of Medicine, Houston, Texas, United States

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Publications (642)4870.95 Total impact

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    ABSTRACT: Background & aims: Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer. Methods: We searched PubMed, Cochrane Library, and ClinicalTrials.gov, reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow up. Results: After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio, 0.53; 95% confidence interval (CI), 0.44-0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication (P=.037 for interaction); the incidence rate ratio of gastric cancer decreased in a non-linear fashion with increasing baseline incidence of gastric cancer (P=.018, in comparison with the linear model). The benefit also modestly increased with age (P=.023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI, 0.49-0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI, 0.35-0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period. Conclusions: In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk.
    Full-text · Article · Feb 2016 · Gastroenterology
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    ABSTRACT: Although the age-adjusted incidence of gastric cancer is declining, the absolute number of new cases of gastric cancer is increasing due to population growth and aging. An effective strategy is needed to prevent this deadly cancer. Among the available strategies, screen-and-treat for Helicobacter pylori infection appears to be the best approach to decrease cancer risk; however, implementation of this strategy on the population level requires a systematic approach. The program also must be integrated into national healthcare priorities to allow the limited resources to be most effectively allocated. Implementation will require adoption of an appropriate screening strategy, an efficient delivery system with a timely referral for a positive test, and standardized treatment regimens based on clinical efficacy, side effects, simplicity, duration, and cost. Within the population, there are subpopulations that vary in risk such that a "one size fits all" approach is unlikely to be ideal. Sensitivity analyses will be required to identify whether the programs can be utilized by heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations. (Gut Liver 2016;10:12-26)
    Full-text · Article · Jan 2016 · Gut and liver
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    ABSTRACT: Excessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn’s disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD pathogenesis. The role of microRNAs (miRNAs), noncoding RNAs involved in regulating numerous biological processes, to IBD pathology, in terms of initiation and progression, remains ill-defined. In the present study, we evaluated the relationship between colon, peripheral blood, and saliva whole miRNome expression in IBD patients and non-inflammatory bowel disease (non-IBD) controls to identify miRNAs that could discriminate CD from UC. Quantitative real-time PCR (qRT-PCR) was used to validate and assess miRNA expression. Microarray analysis demonstrated that upwards of twenty six miRNAs were changed in CD and UC colon biopsies relative to the non-IBD controls. CD was associated with the differential expression of 10 miRNAs while UC was associated with 6 miRNAs in matched colon tissues. CD was associated with altered expression of 6 miRNAs while UC was associated with 9 miRNAs in whole blood. Expression of miR-101 in CD patients and miR-21, miR-31, miR-142-3p, and miR-142-5p in UC patients were altered in saliva. Our results suggest that there is specific miRNA expression patterns associated with UC versus CD in three separate tissue/body fluids (colon, blood, and saliva). Further, the aberrant miRNA expression profiles indicate that miRNAs may be contributory to IBD pathogenesis, or at least reflect the underlying inflammation. Scrutinizing miRNA expression in saliva and blood samples may be beneficial in monitoring or diagnosing disease in IBD patients. A panel of miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375) may be used as markers to identify and discriminate between CD and UC.
    Full-text · Article · Dec 2015 · BMC Immunology
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    ABSTRACT: Aim: Gastric cancer is etiologically related to interactions between Helicobacter pylori infection, environmental, and host factors. Gastric carcinoma is associated with a cascade of increasing atrophic gastric mucosal damage. Prostate stem cell antigen polymorphisms have been associated with an increased risk of gastric cancer. Here, we examined the interaction between prostate stem cell antigen polymorphisms and H. pylori in the progression of H. pylori gastritis. Methods: Prostate stem cell antigen polymorphisms (TT, TC and CC) among H. pylori infected and uninfected Bhutanese were compared with the severity of H. pylori gastritis (neutrophils, monocytes, atrophy scores, H. pylori density, and the presence and extent of intestinal metaplasia) using the updated Sydney system. Results: Biopsies from 339 patients were included. The proportion of biopsies with intestinal metaplasia was also significantly (P<0.05) greater among those with the TT genotype than with either the CT or CC genotype. Despite no significant differences in inflammation or H. pylori density scores, the scores for the premalignant condition, intestinal metaplasia in both the gastric corpus and antrum, among H. pylori infected with the TT genotype was significantly (P <0.05) greater than C allele carriers. Conclusions: Prostate stem cell antigen TT genotype was associated with more than a 3-fold increase in the prevalence and extent of gastric mucosal intestinal metaplasia compared to C allele carriers among H. pylori infected Bhutanese. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Journal of Digestive Diseases
  • David Y Graham
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    ABSTRACT: There have been hundreds of H. pylori eradication trials and yet doubt remains regarding the best regimen for any situation. With most regimens, treatment failure is the result of resistance to one component (e.g., clarithromycin). Thus, if one knows the treatment success with two groups (all with susceptible and with all with resistant infections), one can construct a normogram that provides a reliable estimate of the outcome at any prevalence of resistance. The same data can be used to estimate the prevalence of resistance in any clinical trial, the effects duration of therapy, and effects of any procedures to improve outcome (e.g., increasing the proton-pump inhibitor dose, the duration of therapy, etc.). Because the Hp-normo-graham can reliably predict the outcome of clinical trials, it can also obviate the need for many clinical trials in populations where resistance is common. Here, we illustrate the construction of Hp-normo-graham and its use to describe the effects of resistance, duration of therapy, attempts to improve results, and the prevalence of resistance and to obviate the need for many clinical trials.
    No preview · Article · Nov 2015 · Helicobacter
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    ABSTRACT: Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne's disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50-100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis.
    No preview · Article · Oct 2015 · Expert review of gastroenterology & hepatology
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    ABSTRACT: Importance: Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology, pathophysiology and the epithelial response, including host restriction to gastrointestinal infections such as HRV infection. HRVs remain a major worldwide cause of diarrhea-associated morbidity and mortality in children ≤ age five. Current in vitro models of rotavirus infection rely primarily on the use of animal rotaviruses because HRV growth is limited in most transformed cell lines and animal models. We demonstrate that HIEs are novel, diverse cellular and physiologically relevant epithelial cultures, which recapitulate in vivo properties of HRV infection. HIEs will allow the study of HRV biology, including human host-pathogen and live, attenuated vaccine interactions, host and cell-type restriction, viral-induced fluid secretion, cell-cell communication within the epithelium, and the epithelial response to infection in cultures from genetically diverse individuals. Finally, drug therapies to prevent/treat diarrheal disease can be tested in these physiologically active cultures.
    No preview · Article · Oct 2015 · Journal of Virology
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    Wei Zhang · Qi Chen · Xiao Liang · Wenzhong Liu · Shudong Xiao · David Y Graham · Hong Lu
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    ABSTRACT: Objective To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. Design Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. Results Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (eg, susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. Conclusions These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. Trial registration number NCT02175901.
    Full-text · Article · Sep 2015 · Gut
  • Akiko Shiotani · David Y Graham

    No preview · Article · Sep 2015 · Gastroenterology clinics of North America
  • Akiko Shiotani · David Y. Graham

    No preview · Article · Sep 2015

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Full-text · Article · Jul 2015 · Gut
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    ABSTRACT: To investigated the performance of the tissue resonance interaction method (TRIM) for the non-invasive detection of colon lesions. We performed a prospective single-center blinded pilot study of consecutive adults undergoing colonoscopy at the University Hospital in Sassari, Italy. Before patients underwent colonoscopy, they were examined by the TRIMprobe which detects differences in electromagnetic properties between pathological and normal tissues. All patients had completed the polyethylene glycol-containing bowel prep for the colonoscopy procedure before being screened. During the procedure the subjects remained fully dressed. A hand-held probe was moved over the abdomen and variations in electromagnetic signals were recorded for 3 spectral lines (462-465 MHz, 930 MHz, and 1395 MHz). A single investigator, blind to any clinical information, performed the test using the TRIMprob system. Abnormal signals were identified and recorded as malignant or benign (adenoma or hyperplastic polyps). Findings were compared with those from colonoscopy with histologic confirmation. Statistical analysis was performed by χ(2) test. A total of 305 consecutive patients fulfilling the inclusion criteria were enrolled over a period of 12 months. The most frequent indication for colonoscopy was abdominal pain (33%). The TRIMprob was well accepted by all patients; none spontaneously complained about the procedure, and no adverse effects were observed. TRIM proved inaccurate for polyp detection in patients with inflammatory bowel disease (IBD) and they were excluded leaving 281 subjects (mean age 59 ± 13 years; 107 males). The TRIM detected and accurately characterized all 12 adenocarcinomas and 135/137 polyps (98.5%) including 64 adenomatous (100%) found. The method identified cancers and polyps with 98.7% sensitivity, 96.2% specificity, and 97.5% diagnostic accuracy, compared to colonoscopy and histology analyses. The positive predictive value was 96.7% and the negative predictive value 98.4%. Among the 281 non-IBD subjects, there were 7 cases with discordant results (2.5%) between TRIMprob and the reference standard including 5 false positive results (1.8%) and 2 false negative (0.7%) results. The main limitation of the TRIMprob system is the need for trained operators. The study confirmed that TRIM provides rapid, accurate, convenient and noninvasive means to identify individuals most likely to benefit from colonoscopy.
    Full-text · Article · Jul 2015 · World Journal of Gastroenterology
  • David Y Graham
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    ABSTRACT: As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. © 2015 John Wiley & Sons Ltd.
    No preview · Article · Jun 2015 · Helicobacter
  • David Y. Graham · Sun-Young Lee
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    ABSTRACT: Bismuth triple therapy was the first effective Helicobacter pylori eradication therapy. The addition of a proton pump inhibitor helped overcome metronidazole resistance. Its primary indication is penicillin allergy or when clarithromycin and metronidazole resistance are both common. Resistance to the primary first-line therapy have centered on complexity and difficulties with compliance. Understanding regional differences in effectiveness remains unexplained because of the lack of studies including susceptibility testing and adherence data. We discuss regimen variations including substitutions of doxycycline, amoxicillin, and twice a day therapy and provide suggestions regarding what is needed to rationally and effectively use bismuth quadruple therapy. Published by Elsevier Inc.
    No preview · Article · Jun 2015 · Gastroenterology clinics of North America
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    ABSTRACT: Noroviruses are the leading cause of acute gastroenteritis worldwide, and norovirus vaccine prevention strategies are under evaluation. The immunogenicity of two doses of bivalent GI.1/GII.4 (50μg VLP of each strain adjuvanted with aluminum hydroxide and MPL) norovirus vaccine administered to healthy adults in a phase 1-2 double-blind, placebo-controlled trial was determined using virus-specific, serum total antibody ELISA, IgG, IgA and histoblood group antigen (HBGA) blocking assays. Trial participants subsequently received an oral live virus challenge with a GII.4 strain and vaccine efficacy results have been reported previously (D.I. Bernstein et al. J Infect Dis 211:870-878, 2015, doi:10.1093/infdis/jiu497). This report assesses the impact of pre-challenge serum antibody levels on infection and illness outcomes. Serum antibody responses were observed in vaccine recipients by all antibody assays, with first dose seroresponse frequencies ranging from 88-100% for the GI.1 antigen and from 69-84% for the GII.4 antigen. There was little increase in antibody level after the second vaccine dose. Among placebo subjects, higher pre-challenge serum anti-GII.4 HBGA-blocking and IgA antibody levels, but not IgG or total antibody levels, were associated with a lower frequency of virus infection and associated illness. Notably, some placebo subjects without measurable serum antibody pre-challenge did not become infected after norovirus challenge. In vaccinees, anti-GII.4 HBGA-blocking antibody levels >1:500 were associated with a lower frequency of moderate-to-severe vomiting or diarrheal illness. In this study, pre-challenge serum HBGA antibody titers correlated with protection in placebo subjects; however, other factors may impact the likelihood of infection and illness after virus exposure. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Jun 2015 · Clinical and vaccine Immunology: CVI
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    ABSTRACT: Background: Both cold-only snare and hot polypectomy snare are used for the removal of small colorectal polyps. Objective: To compare the outcome of cold snare polypectomy of small colorectal polyps with a snare exclusively designed as a cold snare versus cold snare polypectomy by using a traditional polypectomy snare. Design: Prospective, randomized, controlled study. Setting: Municipal hospital in Japan. Interventions: Patients with colorectal polyps 10 mm or smaller in diameter were randomized to dedicated cold snare (dedicated cold snare group) or traditional cold snare (traditional cold snare group). The primary outcome measure was complete resection rates by cold snaring based on pathological examination. Secondary outcomes included bleeding within 2 weeks after polypectomy and identification of submucosal arteries and injured arteries in the resected specimens. Results: Seventy-six patients having 210 eligible polyps were randomized: dedicated cold snare group, N = 37 (98 polyps) and traditional cold snare group, N = 39 (112 polyps). Patient demographic characteristics including the number, size, and shape of the polyps removed were similar in the 2 groups. The complete resection rate was significantly greater with the dedicated cold than with the traditional cold snare (91% [89/98] vs 79% [88/112], P = .015), with a marked difference with 8- to 10-mm polyps, both flat and pedunculated. Immediate bleeding and hematochezia rates were similar (19% vs 21%, P = .86; 5.4% vs 7.7%, P =.69). No delayed bleeding occurred. Histology demonstrated a similar prevalence of arteries and injured arteries in the submucosa (33% [32/96] vs 30% [31/104], P =.59; 3.1% [3/96] vs 6.7% [7/104], P =.24). Limitations: Small sample size, single-center study. Conclusion: Polypectomy by using a dedicated cold snare resulted in complete polyp removal more often than did cold snaring with a traditional snare, especially polyps 8 to 10 mm in diameter, whether flat or pedunculated.
    Full-text · Article · Apr 2015 · Gastrointestinal endoscopy

  • No preview · Article · Apr 2015 · Gastroenterology
  • Ping-I Hsu · David Y. Graham

    No preview · Article · Apr 2015 · Gastroenterology

  • No preview · Article · Apr 2015 · Gastroenterology

Publication Stats

22k Citations
4,870.95 Total Impact Points


  • 1975-2016
    • Baylor College of Medicine
      • • Section of Gastroenterology and Hepatology
      • • Department of Medicine
      • • Veterans Affairs Medical Center
      Houston, Texas, United States
  • 2005-2015
    • Michael E. DeBakey VA Medical Center
      • Center for Innovations in Quality, Effectiveness and Safety
      Houston, Texas, United States
    • University of Toronto
      Toronto, Ontario, Canada
  • 2000-2015
    • Università degli Studi di Sassari
      • Dipartimento di Scienze Biomediche
      Sassari, Sardinia, Italy
    • National University of Colombia
      Μπογκοτά, Bogota D.C., Colombia
    • Houston Methodist Hospital
      Houston, Texas, United States
    • Prince of Wales Hospital, Hong Kong
      Chiu-lung, Kowloon City, Hong Kong
  • 2014
    • Kurume University
      • Research Center for Innovative Cancer Therapy
      Куруме, Fukuoka, Japan
  • 2013
    • University of Padova
      Padua, Veneto, Italy
  • 1988-2012
    • Houston medical Center
      Ворнер Робинс, Georgia, United States
  • 2011
    • Oita University
      • Faculty of Medicine
      Ōita, Ōita, Japan
  • 2009
    • Marshall University
      Huntington, West Virginia, United States
  • 1990-2008
    • Spokane VA Medical Center
      Spokane, Washington, United States
  • 2006
    • Wakayama University
      Wakayama, Wakayama, Japan
  • 2001-2005
    • Shinshu University
      • Department of Clinical Laboratory Sciences
      Shonai, Nagano, Japan
    • American University Washington D.C.
      Washington, Washington, D.C., United States
  • 2004
    • Showa General Hospital
      Edo, Tōkyō, Japan
  • 2003
    • Kangbuk Samsung Hospital
      Sŏul, Seoul, South Korea
  • 1996-2003
    • United States Department of Veterans Affairs
      Бедфорд, Massachusetts, United States
    • University of Texas Health Science Center at Houston
      Houston, Texas, United States
  • 1994-2003
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
  • 2002
    • Duke University
      Durham, North Carolina, United States
  • 2001-2002
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 1997
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
  • 1983-1994
    • Texas Medical Center
      Houston, Texas, United States
  • 1988-1989
    • Houston Zoo
      Houston, Texas, United States