Communication breakdown between physicians and IBS sufferers: what is the conundrum and how to overcome it?

Irritable bowel syndrome is a disorder of gut-brain interaction that leads to a significant healthcare burden worldwide. A good physician-patient relationship is fundamental in managing patients who suffer from this poorly understood chronic disease. We highlight possible reasons for breakdown in communication between physicians and irritable bowel syndrome sufferers and suggest possible ways to overcome such pitfalls.

Assessment of radiological protection systems among diagnostic radiology facilities in North East India.

This study aims to assess the adequacy level of radiological protection systems available in the diagnostic radiology facilities located in three capital cities of North East (NE) India. It further attempts to understand, using a multi-disciplinary approach, how the safety codes/standards in diagnostic radiology framed by the Atomic Energy Regulatory Board (AERB) and the International Atomic Energy Agency (IAEA) to achieve adequate radiological protection in facilities, have been perceived, conceptualized, and applied accordingly in these facilities. About 30 diagnostic radiology facilities were randomly selected from three capitals of states in NE India; namely Imphal (Manipur), Shillong (Meghalaya) and Guwahati (Assam). A semi-structured questionnaire developed based on a multi-disciplinary approach was used for this study. It was observed that radiological practices undertaken in these facilities were not exactly in line with safety codes/standards in diagnostic radiology of the AERB and the IAEA. About 50% of the facilities had registered/licensed x-ray equipment with the AERB. More than 80% of the workers did not use radiation protective devices, although these devices were available in the facilities. About 85% of facilities had no institutional risk management system. About 70% of the facilities did not carry out periodic quality assurance testing of their x-ray equipment or surveys of radiation leakage around the x-ray room, and did not display radiation safety indicators in the x-ray rooms. Workers in these facilities exhibited low risk perception about the risks associated with these practices. The majority of diagnostic radiology facilities in NE India did not comply with the radiological safety codes/standards framed by the AERB and IAEA. The study found inadequate levels of radiological protection systems in the majority of facilities. This study suggests a need to establish firm measures that comply with the radiological safety codes/standards of the AERB and IAEA to protect patients, workers and the public of this region.

Osteochondromatosis and osteochondroma involving bilateral patella and patellar tendon: a case report.

We present a 22-year-old man with osteochondromatosis and osteochondroma involving bilateral patella and patellar tendon with restriction of joint movement and severe arthritis.

Low seroprevalence of systemic cysticercosis among patients with epilepsy in Kerala--South India.

PURPOSE: Neurocysticercosis (NCC) is considered to be rare in Kerala state, India, although it is an important cause of epilepsy in many other parts of India. Our objective was to test this notion by determining the seroprevalence of cysticercosis (CC) in an unselected sample of persons with epilepsy and comparing it to that of persons without epilepsy living in Kerala. METHODS: Individuals with active epilepsy (AE) who had never resided outside Kerala state for more than one month and were attending our center for epilepsy care constituted the cases. Sex-matched persons without epilepsy who had never resided outside Kerala state for more than one month constituted the controls. The demographic details, occupation, and food habits (for the cases and controls), as well as clinical characteristics and imaging (for cases only) were recorded. Sera separated from blood drawn by venipuncture from the cases and controls were assayed for cysticercal antibodies by enzyme-linked immunoelectrotransfer blot (EITB). RESULTS: Of the 80 persons with AE, 12 were seropositive for cysticercus antibodies (15%; 95% CI: 8.8-24.4); among the 68 controls, 7 were seropositive (10.3%; 95% CI: 5.1-19.8). The odds ratio (OR) for seropositivity in the epilepsy group (1.54) was not statistically significant (95% CI: 0.6-4.2). Among the 69 patients who had a brain computed tomography (CT) scan or magnetic resonance imaging (MRI), none had features diagnostic of NCC. Gender, diet (vegetarian vs non-vegetarian, consumption of raw vegetables), drinking water status (clean vs unclean), residence (rural vs urban), exposure to manure, and animal rearing including pigs did not have any association with seropositivity. CONCLUSION: Among the residents of Kerala, most epilepsy is not related to cysticercosis.

Economic implications of three strategies for the control of taeniasis.

OBJECTIVE: To evaluate the cost-effectiveness of three strategies for the control of taeniasis in a community, in terms of cost per case treated. METHODS: A study was conducted in South India to determine the prevalence of taeniasis by screening stool samples from 653 randomly chosen subjects, for coproantigens. The costs incurred in the project were used to estimate the cost per case screened and treated. A one-way sensitivity analysis was carried out for varying rates of taeniasis, different screening strategies and mass therapy. Further sensitivity analysis was carried out with different manpower and test costs. RESULTS: The rate of taeniasis as detected by ELISA for coproantigen was 3 per 1000 (2 of 653 samples). Our study showed that mass therapy without screening for taeniasis would be the most economical strategy in terms of cost per case treated if field workers are employed exclusively for either mass therapy or screening. For each strategy, costs per case treated are higher at low prevalence of taeniasis, with a sharp rise below 15%. CONCLUSIONS: In places that are endemic for taeniasis and neurocysticercosis, mass therapy or screening for taeniasis should be considered. Screening by stool microscopy is not cost-effective in terms of cost per case of taeniasis treated owing to its low sensitivity. Although the cost per case of taeniasis treated is high at low prevalence of taeniasis for all options, incorporating mass therapy into existing mass drug distribution programmes might prove to be the most cost-effective control strategy.

Relative seroprevalence of cysticercus antigens and antibodies and antibodies to Taenia ova in a population sample in south India suggests immunity against neurocysticercosis.

We evaluated the exposure of a community in Vellore district of south India to Taenia solium infection and its relationship to the prevalence of neurocysticercosis (NCC) causing active epilepsy. Seroprevalence of Taenia cysticercus antigens and antibodies were determined in 1064 randomly chosen asymptomatic individuals, antibodies to T. solium ova in 197 selected sera, and prevalence of taeniasis by a coproantigen test in 729 stool samples. The prevalence of NCC causing active epilepsy in Vellore district was determined in a population of 50 617. Coproantigens were detected in 0.8% (6 samples), Taenia cysticercus antigens in 4.5% (48 sera) and cysticercus IgG antibodies in 15.9% (169 sera) of the population. Cysticercus antibodies were directed against relatively low molecular weight cyst glycoprotein antigens in 14.9% (158 sera) of the population. IgG antibodies to Taenia ova were found in 81 (41.1%) of the selected samples. Prevalence of NCC causing active epilepsy was 1.3 per 1000 population. These results show high exposure of the population to the parasite and a relatively high prevalence of active infections (4.5% antigen positives) but a low prevalence of NCC causing active epilepsy (0.13%). These findings may indicate that the population is protected against developing neurocysticercosis. IgG antibodies directed against Taenia ova and low molecular weight cyst antigens may contribute to protection.

Detecting spatial clusters of Taenia solium infections in a rural block in South India.

Neurocysticercosis (NCC) is a major cause of seizures/epilepsy in countries endemic for the disease. The objectives of this study were to spatially map the burden of active epilepsy (AE), NCC, taeniasis, seroprevalence for cysticercal antibodies and positivity to circulating cysticercal antigens in Kaniyambadi block (approximately 100 villages comprising 100 000 population) of Vellore district and to detect spatial clusters of AE, NCC, taeniasis and seroprevalence. Using geographic information system (GIS) techniques, all 21 study villages with over 8000 houses (population of 38 105) were mapped. Clustering of different indices of Taenia solium infection was determined using a spatial scan statistic (SaTScan). There was a primary spatial cluster of AE with a log likelihood ratio (LLR) of 10.8 and relative risk (RR) of 22.4; however, no significant clustering for NCC was detected. Five significant spatial clusters of seropositivity for cysticercal antibodies, two clusters of seropositivity for cysticercal antigens and one for taeniasis were detected (LLR of 8.35 and RR of 36.67). Our study has demonstrated the use of GIS methods in mapping and identifying 'hot spots' of various indices of T. solium infection in humans. This spatial analysis has identified pockets with high transmission rates so that preventive measures could be focused on an intensive scale.

Impact of Essentiale L on ethanol-induced changes in rat brain and erythrocytes.

INTRODUCTION: The present study was designed to investigate the effect of Essentiale L, a mixture of polyenylphospholipids from soybeans, on oxidative stress in various brain regions, on erythrocytes (RBC) and on RBC membrane composition in ethanol-administered rats. METHODS: Adult male albino rats of body weight 150-170 g were divided into four groups and administered either isocaloric glucose (5 g/kg body weight/day) or ethanol (6 g/kg body weight/day) through oral gavage. Essentiale L was administered to a set of ethanol-fed rats and the control rats at a dosage of 300 mg/kg body weight/day through oral gavage. The treatment protocol was carried out for 45 days. At the end of the experimental period, the animals were sacrificed, and the biochemical parameters related to the lipid profile, oxidative stress and thiol status were assayed in the brain regions, RBC and RBC membrane. RESULTS: Ethanol administration resulted in increased levels of lipid peroxidation products in RBC and different brain regions, such as the cortex, cerebellum, striatum, hippocampus and hypothalamus, and depletion of enzymatic and nonenzymatic antioxidants and alterations in oxidised glutathione/glutathione (GSSG/GSH) ratio and thiol groups (protein-bound and total), signifying oxidative stress. Ethanol-treated rats also showed significant alterations in protein content and lipid composition in RBC membranes. Significant differences in the relative proportions of hexose, hexosamine and sialic acid of the membranes were observed. Administration of Essentiale L prevented all the alterations induced by ethanol and returned their levels to near-normal. CONCLUSION: These findings suggest that Essentiale L, a therapeutic adjunct for liver diseases, also has bioprotective effects on nonhepatic tissues and cells.

Isolation of lactobacilli with probiotic properties from the human stomach.

AIMS: Recent evidence suggests that the human gastric microbiota is much more diverse than previously thought. The aim of this study was to assess the potential for isolating lactobacilli from the human stomach. METHODS AND RESULTS: Lactobacilli were selectively cultured from gastric biopsies from 12 patients undergoing routine endoscopy. Lactobacilli were present in four of 12 biopsies. We isolated, in total 10 different strains representing five species (Lactobacillus gasseri, L. fermentum, L. vaginalis, L. reuteri and L. salivarius). The 10 isolates varied greatly in their ability to inhibit the growth of two Gram-positive bacteria and two Gram-negative bacteria. Furthermore, the acid and bile resistance profiles of the 10 isolates spanned a wide range. CONCLUSIONS: Five different Lactobacillus species were cultured from human gastric biopsies for the first time. SIGNIFICANCE AND IMPACT OF THE STUDY: Diverse Lactobacillus species are more prevalent in the human stomach than previously recognized, representing an untapped source of bacteria with beneficial probiotic and/or biotechnological properties.

Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat.

INTRODUCTION: The present study was designed to investigate whether cinnamon bark extract (CBEt) mitigates the adverse effects of fructose loading on glucose metabolism and lipid profile in rats. METHODS: Adult male albino rats of body weight 150-170 g were divided into five groups and fed with either control or high fructose diet (HFD). CBEt was administered to HFD-fed rats orally at two doses (a low and a high dose) while the control diet-fed rats were treated with a high dose of CBEt. The treatment protocol was carried out for 60 days after which the oral glucose tolerance test was carried out. Biochemical parameters related to glucose metabolism and lipid profile were assayed. RESULTS: The levels of glucose, insulin and protein-bound sugars were higher and activities of enzymes of glucose metabolism were altered in HFD-fed rats, as compared to control animals. The levels were brought back to near-normal when administered with CBEt at high dose. CBEt also prevented the hyperlipidaemia observed in fructose-fed rats and improved glucose tolerance. CBEt did not show any significant effect in fructose-fed rats when administered at low dose. CONCLUSION: These findings indicate the improvement of glucose metabolism in-vivo by CBEt in fructose-fed rats.

PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts.

The ryanodine receptor (RyR)/calcium release channel on the sarcoplasmic reticulum (SR) is the major source of calcium (Ca2+) required for cardiac muscle excitation-contraction (EC) coupling. The channel is a tetramer comprised of four type 2 RyR polypeptides (RyR2) and four FK506 binding proteins (FKBP12.6). We show that protein kinase A (PKA) phosphorylation of RyR2 dissociates FKBP12.6 and regulates the channel open probability (Po). Using cosedimentation and coimmunoprecipitation we have defined a macromolecular complex comprised of RyR2, FKBP12.6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein, mAKAP. In failing human hearts, RyR2 is PKA hyperphosphorylated, resulting in defective channel function due to increased sensitivity to Ca2+-induced activation.

Calcineurin is downstream of the inositol 1,4,5-trisphosphate receptor in the apoptotic and cell growth pathways.

The inositol 1,4,5-trisphosphate receptor (IP(3)R) is a calcium (Ca(2+)) release channel found on the endoplasmic reticulum of virtually all types of cells. Human T lymphocytes (Jurkat) that are made deficient in IP(3)R do not generate Ca(2+) signals in response to T cell receptor stimulation, fail to translocate the nuclear factor for activated T cells to the nucleus, and are remarkably resistant to induction of apoptosis with CD95 (Fas), dexamethasone, gamma irradiation, and T cell receptor stimulation using anti-CD3 antibody. Expression of constitutively active calcineurin A in IP(3)R-deficient T cells restored nuclear factor for activated T cells translocation to the nucleus and dephosphorylation of Bad and rendered the cells sensitive to apoptotic inducers. Induction of apoptosis required both active calcineurin A (DeltaCnA) and activation-dependent colocalization of CnA with its substrate. Thus, the Ca(2+)-dependent phosphatase calcineurin (CnA) is downstream of the IP(3)R in both the cell growth and apoptotic signaling pathways.

Fiscal and monetary policies in the South Pacific Island countries: an evaluation.

PIP: This paper evaluates the fiscal and monetary policies of South Pacific Island Countries (SPICs) in terms of its efficacy on economic growth. To this effect, the backgrounds on the existing fiscal and monetary policies are discussed with emphasis on their inefficiencies and limitations. In addition, the findings of an empirical study conducted in the countries of Fiji, Tonga, Vanatau, and Samoa regarding the efficacy of the policies are presented. The results, which were subjected to various tests of statistical significance, indicate that both policies were ineffective in all four SPICs. However, monetary policy had a positive impact on growth in Fiji, Tonga, and Vanatau. In view of such, several policy implications are cited, including 1) that delays and inefficiencies involved in the execution of public projects should be minimized; 2) quality and components of public expenditures is of critical significance; and 3) financial sectors should be improved.^ieng

Inhibition of intimal thickening after balloon angioplasty in porcine coronary arteries by targeting regulators of the cell cycle.

BACKGROUND: Although percutaneous transluminal coronary angioplasty (PTCA) is a highly effective procedure to reduce the severity of stenotic coronary atherosclerotic disease, its long-term success is significantly limited by the high rate of restenosis. Several cellular and molecular mechanisms have been implicated in the development of restenosis post-PTCA, including vascular smooth muscle cell (VSMC) activation, migration, and proliferation. Recently, our group demonstrated that rapamycin, an immunosuppressant agent with antiproliferative properties, inhibits both rat and human VSMC proliferation and migration in vitro. In the present study, we investigated (1) whether rapamycin administration could reduce neointimal thickening in a porcine model of restenosis post-PTCA and (2) the mechanism by which rapamycin inhibits VSMCs in vivo. METHODS AND RESULTS: PTCA was performed on a porcine model at a balloon/vessel ratio of 1.7+/-0.2. Coronary arteries were analyzed for neointimal formation 4 weeks after PTCA. Intramuscular administration of rapamycin started 3 days before PTCA at a dose of 0.5 mg/kg and continued for 14 days at a dose of 0.25 mg/kg. Cyclin-dependent kinase inhibitor (CDKI) p27(kip1) protein levels and pRb phosphorylation within the vessel wall were determined by immunoblot analysis. PTCA in the control group was associated with the development of significant luminal stenosis 4 weeks after the coronary intervention. Luminal narrowing was a consequence of significant neointimal formation in the injured areas. Rapamycin administration was associated with a significant inhibition in coronary stenosis (63+/-3.4% versus 36+/-4.5%; P<0.001), resulting in a concomitant increase in luminal area (1.74+/-0.1 mm2 versus 3. 3+/-0.4 mm2; P<0.001) after PTCA. Inhibition of proliferation was associated with markedly increased concentrations of the p27(kip1) levels and inhibition of pRb phosphorylation within the vessel wall. CONCLUSIONS: Rapamycin administration significantly reduced the arterial proliferative response after PTCA in the pig by increasing the level of the CDKI p27(kip1) and inhibition of the pRb phosphorylation within the vessel wall. Therefore, pharmacological interventions that elevate CDKI in the vessel wall and target cyclin-dependent kinase activity may have a therapeutic role in the treatment of restenosis after angioplasty in humans.

T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to apoptosis.

The type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) calcium release channel is present on the endoplasmic reticulum of most cell types. T lymphocytes which have been made deficient in IP3R1 lack detectable IP3-induced intracellular calcium release and exhibit defective signaling via the T-cell receptor (TCR) (T. Jayaraman, E. Ondriasova, K. Ondrias, D. Harnick, and A. R. Marks, Proc. Natl. Acad. Sci. USA 92:6007-6011, 1995). We now show that IP3R1-deficient T cells are resistant to apoptosis induced by dexamethasone, TCR stimulation, ionizing radiation, and Fas. Resistance to TCR-mediated apoptosis in IP3R1-deficient cells is reversed by pharmacologically raising cytoplasmic calcium levels. TCR-mediated apoptosis can be induced in calcium-free media, indicating that extracellular calcium influx is not required. These findings suggest that intracellular calcium release via the IP3R1 is a critical mediator of apoptosis.

Regulation of the inositol 1,4,5-trisphosphate receptor by tyrosine phosphorylation.

Tyrosine kinases indirectly raise intracellular calcium concentration ([Ca2+]i) by activating phospholipases that generate inositol 1,4,5-trisphosphate (IP3). IP3 activates the IP3 receptor (IP3R), an intracellular calcium release channel on the endoplasmic reticulum. T cell receptor stimulation triggered a physical association between the nonreceptor protein tyrosine kinase Fyn and the IP3R, which induced tyrosine phosphorylation of the IP3R. Fyn activated an IP3-gated calcium channel in vitro, and tyrosine phosphorylation of the IP3R during T cell activation was reduced in thymocytes from fyn-/- mice. Thus, activation of the IP3R by tyrosine phosphorylation may play a role in regulating [Ca2+]i.

Inositol 1,4,5-trisphosphate receptor in skeletal muscle: differential expression in myofibres.

The role of inositol 1,4,5-trisphosphate as a second messenger in signal transduction has been well established in many cell types. However, conflicting reports have led to a controversy regarding the role, if any, of inositol 1,4,5-trisphosphate signalling in skeletal muscle. Indeed, expression of the inositol 1,4,5-trisphosphate receptor has not previously been demonstrated in skeletal muscle. In the present study we used in situ hybridization, immunohistochemistry, and [3H]-inositol 1,4,5-trisphosphate binding to demonstrate that rat skeletal muscle fibres contain inositol 1,4,5-trisphosphate receptors. RNAse protection and partial sequencing suggested that the inositol 1,4,5-trisphosphate receptors expressed in skeletal muscle was most similar to the non-neuronal form of the type 1 inositol 1,4,5-trisphosphate receptor. While in situ hybridization showed inositol 1,4,5-trisphosphate receptor mRNA in all types of skeletal myofibres, immunodetectable inositol 1,4,5-trisphosphate receptor protein and specific [3H]-inositol 1,4,5-trisphosphate binding sites were preferentially expressed in slow oxidative (type I) and fast oxidative-glycolytic (type IIA) fibres, but not in fast glycolytic (type IIB) fibres. These findings indicate that an inositol 1,4,5-trisphosphate receptor is preferentially expressed in oxidative fibres of skeletal muscle.