Treatment of irritable bowel syndrome

Irritable bowel syndrome is characterised by diverse symptoms including abdominal pain, altered bowel function (increased bowel frequency, constipation), bloating, abdominal distension, the sensation of incomplete evacuation, and the increased passage of mucus. No unifying hypothesis explains all these symptoms, and no single agent will alleviate all components of the symptom complex. The currently favoured model to explain the symptoms includes central and end organ components. These may be combined into an integrated hypothesis that incorporates psychological factors (stress, distress, affective disorder) and dysfunction of the gut (disorders of motility, visceral hypersensitivity). Current standard drug treatment generally entails a symptom directed approach with drugs aimed at pain, constipation, and diarrhoea. Development of new drugs has focused mainly on agents that modify the effects of 5-hydroxytryptamine (5-HT) in the gut. Alternatives to this single receptor approach exist, although not all patients respond to educational and psychological interventions, and treatment with drugs will remain an option for non-responders

Susceptibility to intestinal infection and diarrhoea in Zambian adults in relation to HIV status and CD4 count.

BACKGROUND: The HIV epidemic in sub-Saharan Africa has had a major impact on infectious disease, and there is currently great interest in the impact of HIV on intestinal barrier function. A three year longitudinal cohort study in a shanty compound in Lusaka, Zambia, carried out before anti-retroviral therapy was widely available, was used to assess the impact of HIV on susceptibility to intestinal infectious disease. We measured the incidence and seasonality of intestinal infection and diarrhoea, aggregation of disease in susceptible individuals, clustering by co-habitation and genetic relatedness, and the disease-to-infection ratio. METHODS: Adults living in a small section of Misisi, Lusaka, were interviewed every two weeks to ascertain the incidence of diarrhoea. Monthly stool samples were analysed for selected pathogens. HIV status and CD4 count were determined annually. RESULTS: HIV seroprevalence was 31% and the prevalence of immunosuppression (CD4 count 200 cells/microL or less) was 10%. Diarrhoea incidence was 1.1 episodes per year and the Incidence Rate Ratio for HIV infection was 2.4 (95%CI 1.7-3.3; p < 0.001). The disease-to-infection ratio was increased at all stages of HIV infection. Aggregation of diarrhoea in susceptible individuals was observed irrespective of immunosuppression, but there was little evidence of clustering by co-habitation or genetic relatedness. There was no evidence of aggregation of asymptomatic infections. CONCLUSION: HIV has an impact on intestinal infection at all stages, with an increased disease-to-infection ratio. The aggregation of disease in susceptible individuals irrespective of CD4 count suggests that this phenomenon is not a function of cell mediated immunity

A Randomized Controlled Trial of Glucose versus Amylase Resistant Starch Hypo-Osmolar Oral Rehydration Solution for Adult Acute Dehydrating Diarrhea

Background: Reduction of gross diarrhea rate in excess of that seen over time with intravenous therapy and appropriate antibiotics is not usually achieved by oral glucose-electrolyte rehydration therapy for cholera and cholera-like diarrheas. Methodology and Principal Findings: This prospective randomized clinical trial at a tertiary referral hospital in southern India was undertaken to determine whether amylase resistant starch, substituting for glucose in hypo-osmolar oral rehydration solution, would reduce diarrhea duration and weight in adults with acute severe dehydrating diarrhea. 50 adult males with severe watery diarrhea of less than three days' duration and moderate to severe dehydration were randomized to receive hypo-osmolar ORS (HO-ORS) or HO-ORS in which amylase resistant high amylose maize starch 50g/L substituted for glucose (HAMS-ORS). All remaining therapy followed standard protocol. Duration of diarrhea (ORS commencement to first formed stool) in hours was significantly shorter with HAMS-ORS (median 19, IQR 10-28) compared to HO-ORS (median 42, IQR 24-50) (Bonferroni adjusted P, P-adj &lt; 0.001). Survival analysis (Kaplan-Meier) showed faster recovery from diarrhea in the HAMS-ORS group (P &lt; 0.001, log rank test). Total diarrhea fecal weight in grams (median, IQR) was not significantly lower in the HAMS-ORS group (2190, 1160-5635) compared to HO-ORS (5210, 2095-12190) (P-adj = 0.08). However, stool weight at 13-24 hours (280, 0-965 vs. 1360, 405-2985) and 25-48 hours (0, 0-360 vs. 1080, 55-3485) were significantly lower in HAMS-ORS compared to HO-ORS group (Padj = 0.048 and P = 0.012, respectively). ORS intake after first 24 hours was lower in the HAMS-ORS group. Subgroup analysis of patients with culture isolates of Vibrio cholerae indicated similar significant differences between the treatment groups. Conclusions: Compared to HO-ORS, HAMS-ORS reduced diarrhea duration by 55% and significantly reduced fecal weight after the first 12 hours of ORS therapy in adults with cholera-like diarrhea

RSAT™ process development for post-combustion CO2 capture: Scale-up from laboratory and pilot test data to commercial process design

AbstractIt is believed that a RSAT™ (Regenerable Solvent Absorption Technology) process is the most viable nearterm technology for post-combustion CO2 capture from power plant flue gas. The Babcock & Wilcox Power Generation Group, Inc. (B&W) has deployed a suite of research tools to evaluate and develop the CO2 scrubbing technology, including laboratory, pilot-scale, and simulation modeling capabilities. Since the construction and operation of test facilities require significant resources, it is essential to effectively utilize these research tools by choosing a scale-up approach which provides robust design data for a commercial process while minimizing the amount of experimentation required.The scale-up protocol used for RSAT CO2 scrubbing processes was rigorously developed using rate-based modeling concurrent with acquiring fundamental laboratory and pilot plant data for process validation. These development activities were not conducted in series but rather overlapped to yield an optimized commercial CO2 scrubbing process in a reasonable time frame with a high degree of design confidence [1,2].This paper presents the scale-up protocol used in evaluating the RSAT process which encompasses both laboratory and pilot-scale testing as well as rate-based modeling to achieve a commercial-scale RSAT process design. This document demonstrates the qualification of test data from a packed tower scale-up point of view. Solvent screening research activities recently conducted within B&W successfully demonstrate the scale-up protocol used for RSAT process development. The time and cost of process development can be significantly reduced through rigorous rate-based modeling in conjunction with laboratory experiments and pilot plant validation

Giardiasis: Impact on child growth

Artículo científico -- Universidad de Costa Rica. Instituto de Investigaciones en Salud, 1986Chronic disorders of the gastrointestinal tract may impair physical growth during infancy and childhood. Growth retardation has been particularly well documented in children with Crohn's disease and coeliac disease in which growth retardation may occur in the absence of gastrointestinal symptoms. Recurrent and persistent infection in infancy and childhood is also associated with growth retardation, the major offenders being infections of the respiratory and gastrointestinal tracts. The pathogenic mechanisms of growth disturbance in chronic disease are poorly understood. Possible candidates include reduced dietary intake as a result of anorexia, food withholding following cultural practice or physician's advice and increased energy expenditure associated with fever and infection. Nutritional deprivation due to intestinal malabsorption is probably a less important factor in inflammatory bowel disease but may be more relevant in coeliac disease and infective disorders of the intestine. Although Giardia is now an established intestinal pathogen its relationship to child growth and development has not been clearly defined. However, giardiasis (1) frequently affects infants and children; (2) is known to cause morphological damage of the small intestine and malabsorption of a variety of nutrients 15 ; (3) is not always a self-limiting infection and may persist for many weeks or months; (4) has been shown to impair physical growth in some individuals with Giardia infection. There is, however, very little population-based data on the effect of Giardia infection on physical growth during infancy and childhood and thus the impact of this parasite at a community level is largely unknown. The parasite may be excreted by apparently asymptomatic individuals and thus before widespread strategies for the control of this infection are introduced the extent of its clinical impact must be established.Universidad de Costa Rica. Instituto de Investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Age-Specific Effects of Mirror-Muscle Activity on Cross-Limb Adaptations Under Mirror and Non-Mirror Visual Feedback Conditions

Cross-limb transfer (CLT) describes the observation of bilateral performance gains due to unilateral motor practice. Previous research has suggested that CLT may be reduced, or absent, in older adults, possibly due to age-related structural and functional brain changes. Based on research showing increases in CLT due to the provision of mirror visual feedback (MVF) during task execution in young adults, our study aimed to investigate whether MVF can facilitate CLT in older adults, who are known to be more reliant on visual feedback for accurate motor performance. Participants (N = 53) engaged in a short-term training regime (300 movements) involving a ballistic finger task using their dominant hand, while being provided with either visual feedback of their active limb, or a mirror reflection of their active limb (superimposed over the quiescent limb). Performance in both limbs was examined before, during and following the unilateral training. Furthermore, we measured corticospinal excitability (using TMS) at these time points, and assessed muscle activity bilaterally during the task via EMG; these parameters were used to investigate the mechanisms mediating and predicting CLT. Training resulted in significant bilateral performance gains that did not differ as a result of age or visual feedback (both p > 0.1). Training also elicited bilateral increases in corticospinal excitability (p < 0.05). For younger adults, CLT was significantly predicted by performance gains in the trained hand (β = 0.47), whereas for older adults it was significantly predicted by mirror activity in the untrained hand during training (β = 0.60). The present study suggests that older adults are capable of exhibiting CLT to a similar degree to younger adults. The prominent role of mirror activity in the untrained hand for CLT in older adults indicates that bilateral cortical activity during unilateral motor tasks is a compensatory mechanism. In this particular task, MVF did not facilitate the extent of CLT

DAS181 treatment of severe lower respiratory tract parainfluenza virus infection in immunocompromised patients: A phase 2 randomized, placebo-controlled study

BACKGROUND: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. METHODS: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. RESULTS: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). CONCLUSIONS: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877

An integrated portable system for single chip simultaneous measurement of multiple disease associated metabolites

Metabolites, the small molecules that underpin life, can act as indicators of the physiological state of the body when their abundance varies, offering routes to diagnosis of many diseases. The ability to assay for multiple metabolites simultaneously will underpin a new generation of precision diagnostic tools. Here, we report the development of a handheld device based on complementary metal oxide semiconductor (CMOS) technology with multiple isolated micro-well reaction zones and integrated optical sensing allowing simultaneous enzyme-based assays of multiple metabolites (choline, xanthine, sarcosine and cholesterol) associated with multiple diseases. These metabolites were measured in clinically relevant concentration range with minimum concentrations measured: 25 μM for choline, 100 μM for xanthine, 1.25 μM for sarcosine and 50 μM for cholesterol. Linking the device to an Android-based user interface allows for quantification of metabolites in serum and urine within 2 min of applying samples to the device. The quantitative performance of the device was validated by comparison to accredited tests for cholesterol and glucose