The Prevalence of Biopsy-Proven Eosinophilic Esophagitis in Hispanics Undergoing Endoscopy Is Infrequent Compared to Caucasians: A Cross-Sectional Study.

INTRODUCTION: The prevalence of eosinophilic esophagitis (EoE), a chronic, immune-mediated, clinicopathologic, inflammatory disorder, has been well described in the pediatric and adult Caucasian population but not as well studied in the Hispanic population. The major aims of this study are to determine the prevalence and gene expression profile of EoE in these populations. METHODS: This is a retrospective cohort study of patients from two institutions predominantly serving a Hispanic population. Patients included at Los Angeles County Hospital (LACH) had an esophagogastroduodenoscopy (EGD) and esophageal biopsies performed for evaluation of dysphagia and/or food impaction, while patients included from the University Hospital Medical Center of El Paso (UHMCEP) had an EGD and esophageal biopsies performed for any appropriate clinical indication. Gene expression analysis which has been shown to accurately diagnose EOE in Caucasians was performed for 9 patients at UHMCEP to determine its accuracy in Hispanics. RESULTS: At LACH, 234 patients were included in the study of whom 155 (66.3%) were Hispanic and 22 (9.4%) were Caucasian. 3.2% of the Hispanic patients and 9.1% of the Caucasian patients were diagnosed with EOE with threefold difference. At UHMCEP 1700 patients were included of whom 1350 (79.4%) were Hispanic and 179 (10.5%) were Caucasian. 0.96% of the Hispanic patients and 7.26% of the Caucasian patients were diagnosed with EOE with a sevenfold difference. Gene expression accurately diagnosed EOE in a small number of both Hispanics and Caucasians who underwent analysis. CONCLUSIONS: Hispanic patients at LAC and UMHCEP had a significantly lower prevalence of EOE as compared to Caucasians at these two institutions and a lower prevalence as compared to Caucasians with EOE previously reported in the literature. Gene expression analysis, which has previously been shown to accurately diagnose EOE in Caucasian patients, accurately diagnosed EOE in a small sample of this Hispanic population. Based on this similar gene expression, other factors such as environmental, ethnic, and cultural causes should be investigated to explain the markedly lower prevalence of EOE in Hispanics.

Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.

The prevalence of recurrent Clostridium difficile infection (RCDI) is increasing; fecal microbiota transplantation (FMT) is an effective therapy. However, there have been no studies of the efficacy of a single session of combined enteral and colonic FMT or characterizations of changes in the microbiota between donors and recipients. We performed a study of 27 patients with RCDI who were given a fixed volume of processed fecal filtrate via enteroscopy and colonoscopy in a single session. Patients were closely monitored, and fecal samples were collected from 2 patient-donor pairs for 16S rRNA analysis. All patients had reduced stool frequency, abdominal pain, white blood cell counts, and elimination of fecal C difficile toxin (P < .05). FMT increased microbial diversity, increasing proportions of Lachnospiraceae (phylum Firmicutes) and reducing proportions of Enterobacteriaceae. FMT was associated with marked changes in the composition of fecal microbiota in 2 patients with RCDI.

Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.

Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) is an alternate treatment option for recurrent C. difficile infection (RCDI) refractory to antibiotic therapy. It has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. To shed light on microbial events associated with RCDI and treatment by FMT, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Post-FMT patient and healthy donor samples collected up to one year after FMT were studied longitudinally, including one post-FMT patient with antibiotic-associated relapse three months after FMT. This analysis allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. Members of the Streptococcaceae, Enterococcaceae, or Enterobacteriaceae were significantly increased and putative butyrate producers, such as Lachnospiraceae and Ruminococcaceae were significantly reduced in samples from RCDI patients before FMT as compared to post-FMT patient and healthy donor samples. RCDI patient samples showed more case-specific variations than post-FMT patient and healthy donor samples. However, none of the bacterial groups were invariably associated with RCDI or successful treatment by FMT. Overall microbiota compositions in post-FMT patients, specifically abundances of the above-mentioned Firmicutes, continued to change for at least 16 weeks after FMT, suggesting that full microbiota recovery from RCDI may take much longer than expected based on the disappearance of diarrheal symptoms immediately after FMT.

Evidence of multimeric forms of HSP70 with phosphorylation on serine and tyrosine residues--implications for roles of HSP70 in detection of GI cancers.

BACKGROUND: Heat-shock protein70 (HSP70) are intracellular protein chaperones, with emerging evidence of their association with various diseases. We have previously reported significantly elevated plasma-HSP70 (pHSP70) in pancreatic cancer. Current methods of pHSP70 isolation are ELISA-based which lack specificity due to cross-reactivity by similarities in the amino-acid sequence in regions of the protein backbone resulting in overestimated HSP70 value. MATERIALS AND METHODS: This study was undertaken to develop a methodology to capture all isoforms of pHSP70, while further defining their tyrosine and serine phosphorylation status. RESULTS: The methodology included gel electrophoresis on centrifuged supernatant obtained from plasma incubated with HSP70 antibody-coupled beads. After blocking non-specific binding sites, blots were immunostained with monoclonal-antibody specific for human-HSP70, phosphoserine and phosphotyrosine. CONCLUSIONS: Our novel immunocapture approach has distinct advantages over the commercially available methods of pHSP70 quantification by allowing isolation of molecular aggregates of HSP70 with additional ability to precisely distinguish phosphorylation state of HSP70 molecules at serine and tyrosine residues.

Serum HSP70: a novel biomarker for early detection of pancreatic cancer.

OBJECTIVES: Heat shock protein 70 (HSP70) is overexpressed in human pancreatic cancer cell lines. To determine if serum HSP70 levels are elevated in patients with pancreatic cancer and can function as a biomarker for early detection of pancreatic cancer. METHODS: Study subjects were divided into 3 groups: histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were determined using a novel immunoelectrophoresis method developed and validated by the authors. Significance of difference between the groups was analyzed with analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with pancreatic cancer from normal controls. RESULTS: The mean ± SE serum HSP70 levels in the PC, CP, and C groups were 1.68 ± 0.083 ng/mL, 0.40 ± 0.057 ng/mL, and 0.04 ng/mL, respectively. Serum HSP70 levels in the PC group were significantly higher compared with either the CP or C groups (P < 0.01). The sensitivity and specificity of elevated serum HSP70 in the PC group was 74% and 90%, respectively. CONCLUSIONS: Serum HSP70 levels are significantly increased in patients with pancreatic cancer and may be useful as an additional biomarker for the detection of pancreatic cancer.

Metastatic methicillin-sensitive Staphylococcus aureus infection.

Staphylococcus aureus bacteremia (SAB) is a common and increasingly recognized hospital- and community-acquired infection. To minimize morbidity and mortality, it is essential to determine which patients are at high risk for metastatic SAB. The risk-scoring system described by Fowler et al and the APACHE II scoring system can be helpful in identifying the clinical predictors of metastatic SAB. Herein we describe a case of metastatic methicillin-sensitive SAB in a previously healthy 19-year-old woman that was complicated by a disseminated pneumonia, an ischemic toe, and an acute intracranial hemorrhage. We also discuss the clinical factors associated with increased risk for complications from SAB and the currently available treatment options.

Variability in the upper limit of normal for serum alanine aminotransferase levels: a statewide study.

UNLABELLED: We conducted a study to characterize the variability in the upper limit of normal (ULN) for alanine aminotransferase (ALT) across different laboratories (labs) in Indiana and to understand factors leading to such variability. A survey was mailed to all eligible labs (n = 108) in Indiana, and the response rate was 62%. The survey queried for ALT ULN, the type of chemical analyzer used, five College of American Pathologists (CAP) sample results, and methods used to establish the reference interval. There was a wide variability in the ALT ULN for both men and women. Eighty-five percent of labs used chemical analyzers belonging to one of the four brands. For all five CAP samples, there was a statistically significant difference in ALT values measured by different analyzers (P < 0.0001), but these differences were not clinically significant. The majority of labs used the manufacturers' recommendations for establishing their ALT ULN rather than in-house healthy volunteer testing (only 17%). When healthy volunteers were tested, the process for testing was haphazard in terms of the number of individuals tested, frequency of testing, and criteria for choosing the reference population. After controlling for chemical analyzer type, there was no significant relationship between ALT ULN values and the method used for its establishment. CONCLUSION: Wide variability in ALT ULN across different labs is more likely due to variable reference intervals of different chemical analyzers. It may be possible to minimize variability in ALT ULN by (1) each lab solely following the manufacturers' recommendations and (2) manufacturers of different analyzers following consistent and rigorous methodology in establishing the reference range. Alternatively, studies should be undertaken to identify outcome-based reference intervals for ALT.

Vitamin E and its role in the prevention of atherosclerosis and carcinogenesis: a review.

Epidemiological and experimental studies suggest that antioxidants like vitamin E (alpha-tocopherol) may play an important role in prevention of chronic disease. Several observational surveys have linked populations with a large intake of vitamin E with reduced incidence of heart disease. These observations have been strengthened by the demonstration of strong antioxidant activity by vitamin E in cellular, molecular and animal experiments. These results have highlighted a potential role for vitamin E supplementation in the prevention of chronic disease in humans. Interestingly however, large-scale clinical trials of vitamin E and other antioxidants in preventing specific disease processes (e.g., coronary artery disease) have generated conflicting and mixed outcomes. In this review, the role of vitamin E in the prevention of atherosclerosis and carcinogenesis has been carefully examined with particular emphasis on salient human studies (clinical trials) and their limitations. In addition, pertinent biochemical, physiological and metabolic features of vitamin E have also been incorporated. A list of common natural food sources of vitamin E has been provided. Important in vitro and animal studies related to the antiatherosclerotic and anticarcinogenic actions of vitamin E have been discussed in detail. Finally, the direction of future investigations in primary and secondary prevention of chronic diseases by vitamin E supplementation has been outlined.

Vitamin C as an antioxidant: evaluation of its role in disease prevention.

Vitamin C in humans must be ingested for survival. Vitamin C is an electron donor, and this property accounts for all its known functions. As an electron donor, vitamin C is a potent water-soluble antioxidant in humans. Antioxidant effects of vitamin C have been demonstrated in many experiments in vitro. Human diseases such as atherosclerosis and cancer might occur in part from oxidant damage to tissues. Oxidation of lipids, proteins and DNA results in specific oxidation products that can be measured in the laboratory. While these biomarkers of oxidation have been measured in humans, such assays have not yet been validated or standardized, and the relationship of oxidant markers to human disease conditions is not clear. Epidemiological studies show that diets high in fruits and vegetables are associated with lower risk of cardiovascular disease, stroke and cancer, and with increased longevity. Whether these protective effects are directly attributable to vitamin C is not known. Intervention studies with vitamin C have shown no change in markers of oxidation or clinical benefit. Dose concentration studies of vitamin C in healthy people showed a sigmoidal relationship between oral dose and plasma and tissue vitamin C concentrations. Hence, optimal dosing is critical to intervention studies using vitamin C. Ideally, future studies of antioxidant actions of vitamin C should target selected patient groups. These groups should be known to have increased oxidative damage as assessed by a reliable biomarker or should have high morbidity and mortality due to diseases thought to be caused or exacerbated by oxidant damage.

The pharmaceutical industry and research in 2002 and beyond.

The success of the pharmaceutical industry will continue to depend on its ability to satisfy the clinical needs of established market economies. The number and quality of new drugs emerging from development pipelines seems likely to rise due to increased research and development budgets of the merged pharmaceutical companies, efficiencies across all facets of the development process, increasing use of new technologies and availability of new targets from the ongoing work on the role of human genes in disease pathways. In addition to the traditional small-molecule drugs, the market for protein products, including monoclonal antibodies and therapeutic vaccines, is likely to expand as advances in recombinant and formulation technologies are made. Current work on relatively newer fields of pharmaceutical research, such as novel G-protein-coupled receptors, chemokines/cytokines, integrins and control of cell cycle regulation and signal transduction pathways (kinases, phosphatases and transcription factors) will lead to new drugs over the next decade. It is tempting to argue that a progressive fall in the number of new drugs in the last decade of the 20th century reflects the end of an era as companies struggle to identify any remaining quality products using old-style drug hunting practices.