Citations

AbstractBackgroundNausea and vomiting are thought to result from upper gastrointestinal dysfunctions. Our clinical observations led to the hypothesis that colonic motor dysfunction is associated with nausea and vomiting.MethodsWe reviewed electronic medical records (EMR) of 149 patients presenting with complaints of nausea and/or vomiting in a tertiary gastroenterology practice to investigate the association with disorders of colonic motor or evacuation disorders. We extracted demographics, gastric emptying (GEin 149) and colonic transit (CTin 138) of solids, ascending colon emptying half‐time (ACt1/2), rectal evacuation by anorectal manometry (ARM) in 91 and balloon expulsion test (BE) in 55 patients. We estimated the proportions with delayedGEorCT, based on the 5th percentile ofGE(in 319) andCTin 220 healthy volunteers using same method.Key ResultsAmong 11 patients with nausea and/or vomiting with onlyGEmeasured, five had delayed and six normalGE. Among the 149 patients, 77 (52%) patients had evacuation disorders, confirmed by objective tests in 68 patients, and clinical examination in nine patients. In the 138 patients with bothGEandCTmeasured, 106 (76%) had both normalGEandCT, 11 (8%) only delayedGE, 16 (11%) normalGEwith delayedCT, and five (3%) delayedGEandCT. Among 21 patients (15%) with delayedCT, nine had slowACt1/2and 12 evacuation disorder.Conclusions & InferencesIn patients with chronic nausea and/or vomiting in gastroenterology practice, evaluation of colonic motility and rectal evacuation should be considered, since about half the patients have abnormal functions that conceivably contribute to the presenting nausea and/or vomiting.

AbstractProgressive multifocal leukoencephalopathy (PML), a demyelinating disorder caused by brain infection with JC virus, is a neurological complication of immunocompromised states and immunosuppressive therapies. While most commonly seen in the HIV/AIDS population, patients with hematologic malignancies are also at risk following treatment protocols including monoclonal antibodies such as rituximab and after hematopoietic stem cell transplantation. Here, we present the case of PML following allogeneic HCT that highlights potential diagnostic difficulties. We also review the literature regarding PML following HCT and described therapies employed to attempt to treat this disorder.

Abstract Objectives Adults who develop type 2 diabetes (T2D) at later stages are at a higher risk of developing Alzheimer's disease (AD). Pharmacological agents such as dipeptidyl peptidase-4 (DPP-4) inhibitors that increase the levels of glucagon-like peptide-1 (GLP-1) and ameliorate T2D have also become promising candidates as disease-modifying agents in the treatment of AD. The present study investigates the efficacy of vildagliptin, a DPP-4 inhibitor in a streptozotocin (STZ)-induced rat model of AD. Methods Three months following the induction of AD by intracerebral injection of STZ, animals were orally administered with vildagliptin (2.5, 5 and 10 mg/kg) for 30 days. Dose-dependent and time-course effects of vildagliptin on memory retention were investigated during the course of treatment. Following treatment, the animals were sacrificed, and brain tissues were used to evaluate the effects of vildagliptin on hippocampal and cortical GLP-1 levels, amyloid beta (Aβ) burden, tau phosphorylation and inflammatory markers. Key findings The results reveal a time-dependent improvement in memory retention and a dose-dependent attenuation of Aβ, tau phosphorylation and inflammatory markers and increased GLP-1 levels. Conclusions These robust therapeutic effects of vildagliptin demonstrate a unique mechanism for Aβ and tau clearance and reverse the cognitive deficits and pathology observed in AD.

SummaryBackgroundCurrent diagnostic guidelines recommend that eosinophilic oesophagitis (EoE) should be diagnosed only after GERD is excluded by a lack of response to a trial of acid suppression. There is limited information available providing outcome data about the effectiveness of this approach.AimTo examine the impact of double‐dose proton pump inhibitor (PPI) therapy on symptoms, endoscopic and histological features in patients with documented oesophageal eosinophilia consistent with EoE (≥15 eosinophils/high‐power field).MethodsSixty consecutive symptomatic patients with documented oesophageal eosinophilia received open‐label omeprazole 20 mg orally twice daily before meals for 8 weeks. Clinical, endoscopic and histological (resolution: 0–5 eosinophils/HPF, partial improvement: 5–14 eosinophils/HPF), or no improvement: (≥15 eosinophils/HPF) evaluation was repeated at the end of this period. An expert GI pathologist, unaware of the study aims, reviewed all slides.ResultsClinical improvement occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%) obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete clinical and histological remission.ConclusionsMore than 50% of patients with documented oesophageal eosinophilic infiltration in the EoE range improved when treated with a double‐dose PPI trial for 8 weeks. These findings support the published guidelines recommending a PPI trial prior to diagnosing EoE, and confirm the existence of an eosinophilic oesophageal infiltrationPPI‐responsive population.

AbstractDiarrhea is best defined as passage of loose stools often with more frequent bowel movements. For clinical purposes, theBristolStoolFormScale works well to distinguish stool form and to identify loose stools. Laboratory testing of stool consistency has lagged behind. Acute diarrhea is likely to be due to infection and to be self‐limited. As diarrhea becomes chronic, it is less likely to be due to infection; duration of 1 month seems to work well as a cut‐off for chronic diarrhea, but detailed scientific knowledge is missing about the utility of this definition. In addition to duration of diarrhea, classifications by presenting scenario, by pathophysiology, and by stool characteristics (e.g. watery, fatty, or inflammatory) may help the canny clinician refine the differential diagnosis of chronic diarrhea. In this regard, a careful history remains the essential part of the evaluation of a patient with diarrhea. Imaging the intestine with endoscopy and radiographic techniques is useful, and biopsy of the small intestine and colon for histological assessment provides key diagnostic information. Endomicroscopy and molecular pathology are only now being explored for the diagnosis of chronic diarrhea. Interest in the microbiome of the gut is increasing; aside from a handful of well‐described infections because of pathogens, little is known about alterations in the microbiome in chronic diarrhea. Serological tests have well‐defined roles in the diagnosis of celiac disease but have less clearly defined application in autoimmune enteropathies and inflammatory bowel disease. Measurement of peptide hormones is of value in the diagnosis and management of endocrine tumors causing diarrhea, but these are so rare that these tests are of little value in screening because there will be many more false‐positives than true‐positive results. Chemical analysis of stools is of use in classifying chronic diarrhea and may limit the differential diagnosis that must be considered, but interpretation of the results is still evolving. Breath tests for assessment of carbohydrate malabsorption, small bowel bacterial overgrowth, and intestinal transit are fraught with technical limitations that decrease sensitivity and specificity. Likewise, tests of bile acid malabsorption have had limited utility beyond empirical trials of bile acid sequestrants.

AbstractTranslational stories range from straightforward to complex. In this commentary, the story of the rapid and successful translation of rituximab therapy for the treatment of non‐Hodgkin's lymphoma (NHL) is examined. Development of this monoclonal antibody therapy began in the late 1980s. In 1994, rituximab received its first approval for the treatment of NHL by the United States Food and Drug Administration (FDA). Rituximab has since been approved for additional indications and has transformed medical practice. However, the social and political implications of these rapid successes are only beginning to become clear. In this commentary, key events in the rapid translation of rituximab from the bench to bedside are highlighted and placed into this historical framework. To accomplish this, the story of rituximab is divided into the following six topics, which we believe to be widely applicable to case studies of translation: (1) underlying disease, (2) key basic science, (3) key clinical studies in translation, (4) FDA approval process, (5) changes to medical practice, and (6) the social and political influences on translation.

ABSTRACTTwo valuable confirmatory MRI findings of acute spinal cord infarct are highlighted and discussed: concomitant vertebral body infarct and ventral cauda equina nerve root enhancement.

PurposeTo determine normal liver stiffness values evaluated with magnetic resonance elastography (MRE) in healthy normal Asian volunteers and assess its reproducibility.Materials and MethodsLiver stiffness was evaluated with MRE in 41 healthy Asians (23 females, 18 males; mean age, 41.8 years, and mean body mass index [BMI], 23.4 kg/m2) on a 1.5T clinical scanner. The correlations between mean liver stiffness and age, gender, BMI, and fat fraction percentage of the liver were studied. Another 12 volunteers underwent liver MRE exams on two separate days 4–6 weeks apart under similar conditions for reproducibility assessment. Intraclass correlation coefficient (ICC) analysis was performed and within‐subject coefficient of variation (CV) of stiffness was estimated.ResultsThe mean ± standard deviation (SD) of liver stiffness in normal healthy Asian subjects was 2.09 ± 0.22 kPa (95% confidence interval [CI], 2.04–2.15 kPa; range 1.68–2.48 kPa). The mean liver stiffness did not significantly correlate with age, gender, BMI, or fat content of the liver. The ICC for mean liver stiffness was 0.90 (95% CI, 0.78–0.96) and CV ranged from 2.2%–11.4%.ConclusionThe liver stiffness in normal Asians is not affected by age, gender, BMI, or fat content. Liver stiffness with MRE is highly reproducible. J. Magn. Reson. Imaging 2014;39:1–8. © 2013 Wiley Periodicals, Inc.