Low-FODMAP vs regular rye bread in irritable bowel syndrome:Randomized SmartPill~ study

AIM To compare the effects of regular vs low-FODMAP rye bread on irritable bowel syndrome(IBS) symptoms and to study gastrointestinal conditions with Smart Pill?.METHODS Our aim was to evaluate if rye bread low in FODMAPs would cause reduced hydrogen excretion,lower intraluminal pressure,higher colonic p H,different transit times,and fewer IBS symptoms than regular rye bread.The study was a randomized,double-blind,controlled cross-over meal study.Female IBS patients(n = 7) ate study breads at three consecutive meals during one day.The diet was similar for both study periods except for the FODMAP content of the bread consumed during the study day.Intraluminal p H,transit time,and pressure were measured by Smart Pill,an indigestible motility capsule.RESULTS Hydrogen excretion(a marker of colonic fermentation) expressed as area under the curve(AUC)(0-630 min) was [median(range)] 6300(1785-10800) ppm?min for low-FODMAP rye bread and 10 635(4215-13080) ppm?min for regular bread(P = 0.028).Mean scores of gastrointestinal symptoms showed no statistically significant differences but suggested less flatulence after low-FODMAP bread consumption(P = 0.063).Intraluminal pressure correlated significantly with total symptom score after regular rye bread(ρ = 0.786,P = 0.036) and nearly significantly after lowFODMAP bread consumption(ρ = 0.75,P = 0.052).We found no differences in p H,pressure,or transit times between the breads.Gastric residence of Smart Pill was slower than expected.Smart Pill left the stomach in less than 5 h only during one measurement(out of 14 measurements in total) and therefore did not follow on par with the rye bread bolus.CONCLUSION Low-FODMAP rye bread reduced colonic fermentation vs regular rye bread.No difference was found in median values of intraluminal conditions of the gastrointestinal tract.     

Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response

Recent studies have shown that a single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene plays a major role in predicting therapeutic response in hepatitis C virus (HCV)-infected patients treated with pegylated interferon (PEG-IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics, IFN pharmacokinetics, IFN pharmacodynamics, and gene expression profiles. Two prospective cohorts (human immunodeficiency virus [HIV]/HCV-coinfected and HCV-monoinfected) completing treatment with IFN/ribavirin were enrolled. Patients were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort, frequent serum sampling was completed for HCV RNA and IFN levels. DNA microarray of peripheral blood mononuclear cells and individual expression of IFN-stimulated genes (ISGs) were quantified on IFN therapy. The IL28B-favorable (CC) genotype was associated with improved therapeutic response compared with unfavorable (CT or TT) genotypes. Patients with a favorable genotype had greater first- and second-phase viral kinetics (P = 0.004 and P = 0.036, respectively), IFN maximum antiviral efficiency (P = 0.007) and infected cell death loss (P = 0.009) compared with unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of natural killer cells, from patients with unfavorable genotypes (P <0.004). Induction of innate immunity genes was also lower in unfavorable genotypes. ISG expression at baseline and induction with IFN was independent of IL28B genotype. CONCLUSION: Carriers of the IL28B-favorable genotype were more likely to have superior innate immune response to IFN therapy compared with unfavorable genotypes, suggesting that the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated with more rapid viral kinetics and improved treatment response outcomes independent of ISG expression.     

Early diagnosis of dengue in travelers: Comparison of a novel real-time RT-PCR,NS1 antigen detection and serology

BackgroundThe increased traveling to dengue endemic regions and the numerous epidemics have led to a rise in imported dengue. The laboratory diagnosis of acute dengue requires several types of tests and often paired samples are needed for obtaining reliable results. Although several diagnostic methods are available, proper comparative data on their performance are lacking.ObjectivesTo compare the performance of novel methods including a novel pan-DENV real-time RT-PCR and a commercially available NS1 capture-EIA in regard to IgM detection for optimizing the early diagnosis of DENV in travelers.Study designA panel of 99 selected early phase serum samples of dengue patients was studied by real-time RT-PCR, NS1 antigen ELISA, IgM-EIA, IgG-IFA and cell culture virus isolation.ResultsThe novel real-time RT-PCR was shown specific and sensitive for detection of DENV-1-4 RNA and suitable for diagnostic use. The diagnostic rate using combination of RNA and IgM detection was 99% and using NS1 and IgM detection 95.9%. The results of RNA and NS1 antigen detection disagreed in 15.5% of samples that had only RNA or NS1 antigen detected.ConclusionsThe diagnostic rates of early samples are higher when either RNA or NS1 antigen detection is combined with IgM detection. Besides the differences in the RNA and NS1 detection assays, the observed discrepancy of results could suggest individual variation or differences in timing of these markers in patient serum.     

Audio Vestibular Status in CML Patients on Imatinib Mesylate with Review of Literature

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm occasionally presenting with features of leukostasis as primary symptoms. Hearing loss is occasionally reported in CML patients. Further whether Imatinib mesylate has any effect on vestibular functions is not known. We conducted a preliminary study to assess hearing pattern in patients with CML on long term TKI therapy. This is a single center, cross sectional study from northern-India. Patients of CML who were on regular Tyrosine kinase inhibitors (TKI) therapy for at least 6 months underwent audiovestibular evaluation. A total of 44 CML patients on TKI therapy were assessed over a period of 6 months. The median age of the patients was 41 years, the mean duration of TKI therapy was 36 months. Four patients were found to have otological disorder clinically. On pure tone audiometry of 88 ears normal hearing pattern were found with at low and mid frequencies. There was a down sloping type of curve at higher frequencies in PTA in most of the patients. Cold caloric tests in 42 patients were found as equal response in both ears. We conclude from this preliminary study that there are no audio vestibular dysfunctions amongst patients of CML on TKI. It’s a negative study wherein we have ruled out any auditory deficits secondary to Imatinib therapy. Further studies are required to evaluate the audiometric profile in CML patients before Imatinib therapy and to be compared with the patients already on Imatinib in a large cohort.     

Specificities and Opsonophagocytic Activities of Antibodies to Pneumococcal Capsular Polysaccharides in Sera of Unimmunized Young Children

An enzyme immunoassay (EIA) for antibodies to pneumococcal capsular polysaccharides (Pnc PSs) detects in some cases antibodies that are cross-reactive within different Pnc PSs. Recently, it has been suggested that for detection of only serotype-specific antibodies, EIA can be modified by removing cross-reactive antibodies by absorption with an irrelevant PS, e.g., the type 22F PS. The opsonophagocytosis assay measures the functional activities of antibodies in vitro, and the results of that assay correlate with in vivo protection better than measurement of the antibody concentration by EIA. We compared these different methods for measuring antibodies to type 1, 6B, 11A, 14, 19F, and 23F Pnc PSs in the sera of unimmunized young children who had been monitored for pneumococcal carriage, acute otitis media, and acquisition of antibodies to Pnc PSs from 2 to 24 months of age. Serum samples with antibody increases after contact with a pneumococcus of a homologous serotype contained specific antibodies and often had opsonophagocytic activity (OPA) (20 of 46). In samples with antibody increases from children who had not had contact with a pneumococcus of a homologous serotype, the antibodies found to be type specific by conventional EIA were usually cross-reactive and infrequently had OPA (10 of 68). When type 22F PS absorption was used in the EIA, most of the false antibody increases were eliminated, but most of the true antibody increases were still detected and the association between the antibody concentration detected by EIA and OPA was improved. However, there were serotype-dependent differences in the frequency of OPA. Use of absorption with a heterologous PS in EIA should be encouraged, and both the specificity of EIA and the sensitivity of opsonophagocytic assays should be further evaluated and improved.