Extra-intestinal symptoms in patients with irritable bowel syndrome: related to high total IgE levels and atopic sensitization?

Objective We have previously found that high levels of total IgE, but not atopic sensitization, was a significant predictor for functional gastrointestinal (GI) symptoms. In this study, we aimed to assess the prevalence of extra-intestinal symptoms in IBS patients, and explore their relation to total IgE levels and atopic sensitization. Materials and methods Seventy-one patients with functional GI complaints were included. Severity of GI symptoms, fatigue and musculoskeletal pain was evaluated using the following questionnaires: IBS-Severity Scoring System (IBS-SSS), Fatigue Impact Scale (FIS), FibroFatigue Scale (FFS), and Visual Analog Scales (VAS) for musculoskeletal pain. Levels of total IgE and specific IgE-antibodies were analyzed. Results Fatigue and musculoskeletal pain were demonstrated in 78.9 and 43.7% of the patients, respectively. IBS-SSS scores were significantly correlated with fatigue scores and musculoskeletal pain. Patients with fatigue and musculoskeletal pain had significantly higher IBS-SSS scores than patients without fatigue and musculoskeletal pain. Total IgE levels were significantly higher in IBS patients compared to a healthy control group from a previous study. However, neither total IgE nor atopic sensitization was significantly associated with extra-intestinal symptoms. Conclusions IBS, fatigue, and musculoskeletal pain were significantly associated. Total IgE levels were higher in IBS patients than healthy controls, but not related to intestinal or extra-intestinal symptom severity. Atopy was not associated with any of the co-morbidities. Thus, the clinical significance of high IgE levels in IBS remains unclear and further studies are warranted to explore a common underlying mechanism for the co-morbid triad of IBS, fatigue, and musculoskeletal pain.     

Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome

AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome (IBS).METHODS: Seventy-six patients with IBS were included in the study (62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome III criteria for functional dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29 had constipation as the predominant symptom (IBS-C). Forty-three age and sex-matched healthy volunteers without any gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex (ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software (version 1.7).RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and 126 (0, 262) cells/mm², respectively. There was a significant difference between the tested groups (P < 0.0001). Dunn’s multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489 (130, 966), and in those with IBS only 490 (130, 956). There was no statistical significant difference between these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density (r = 0.65; P < 0.0001) and significantly inversely correlated with that of constipation (r = 90.69; P < 0.0001). The densities of the serotonin cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups (P < 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65 (25, 123). There was no statistically significant difference between these 2 groups of patients (P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups (P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire (r = 0.56; P < 0.0001) and significantly inversely correlated with that of constipation (r = 0.51; P < 0.0001). The densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80), 46 (0, 103) and 206 (194, 314) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically significant difference between the controls and the IBS subgroups (P < 0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls (P < 0.01, P = 0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no statistically significant difference between these 2 groups of patients (P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density (r = 0.38; P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P < 0.0001).CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility.     

Therapist predictors of early patient-rated working alliance: A multilevel approach

Abstract

The present study investigated whether and how various therapists' (N=68) self-reported characteristics relating to their therapeutic work predicted patients' (N = 335) early ratings of the working alliance in a naturalistic psychotherapy study. Results from multilevel modeling demonstrated that certain self-reports accounted well for the therapist effect in the early alliance. The effect of therapists' experiences of difficulties in practice was particularly strong: a negative influence of difficulties termed negative personal reaction (NPR) and a surprising positive influence of another factor, professional self-doubt (PSD), were found. The latter was interpreted as reflecting an attitude of therapist humbleness and sensitivity, which seems to facilitate alliance development. A negative impact of self-reported skills in using one's own and the patients' emotional reactions in the therapeutic relationship (advanced relational skills) was found when controlling for a warm interpersonal style. The negative effect of advanced relational skills depended on the level of NPR difficulties. The findings suggest that therapists should be cautious in using this kind of relational skill unless they experience relating to patients in a warm manner and report low levels of NPR in their practice.     

Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation

Abstract

Objectives. The aim of the study was to investigate if adequate preservation of coronary artery endothelium-dependent relaxation and contractility may be obtained after 8?hours of non-ischemic heart preservation. Design. Porcine hearts were perfused for 8?hours at 8?°C, either in cycles of 15?minutes perfusion and 60?minutes non-perfusion, or by continuous perfusion. The perfusate consisted of a cardioplegic, hyperoncotic nutrition solution with oxygenated red cells, and the perfusion pressure was 20?mmHg. In organ baths, coronary artery segments from the preserved hearts were studied and compared to fresh controls. Results. Endothelium-dependent relaxation and contractility were fully preserved after both intermittent and continuous perfusion, as compared to fresh controls. No myocardial edema was seen; water content of the myocardium was 79.5?±?0.2%, 79.0?±?0.4% and 79.0?±?0.3% (ns) for fresh controls, intermittently perfused, and continuously perfused hearts, respectively. Conclusion. Intact endothelial and contractile function of coronary artery may be obtained after 8?hours of non-ischemic heart preservation.     

Transgene expression in the Nop-tTA driver line is not inherently restricted to the entorhinal cortex

The entorhinal cortex (EC) plays a central role in episodic memory and is among the earliest sites of neurodegeneration and neurofibrillary tangle formation in Alzheimer’s disease. Given its importance in memory and dementia, the ability to selectively modulate gene expression or neuronal function in the EC is of widespread interest. To this end, several recent studies have taken advantage of a transgenic line in which the tetracycline transactivator (tTA) was placed under control of the neuropsin (Nop) promoter to limit transgene expression within the medial EC and pre-/parasubiculum. Although the utility of this driver is contingent on its spatial specificity, no detailed neuroanatomical analysis of its expression has yet been conducted. We therefore undertook a systematic analysis of Nop-tTA expression using a lacZ reporter and have made the complete set of histological sections available through the Rodent Brain Workbench tTA atlas, www.rbwb.org. Our findings confirm that the highest density of tTA expression is found in the EC and pre-/parasubiculum, but also reveal considerable expression in several other cortical areas. Promiscuous transgene expression may account for the appearance of pathological protein aggregates outside of the EC in mouse models of Alzheimer’s disease using this driver, as we find considerable overlap between sites of delayed amyloid deposition and regions with sparse β-galactosidase reporter labeling. While different tet-responsive lines can display individual expression characteristics, our results suggest caution when designing experiments that depend on precise localization of gene products controlled by the Nop-tTA or other spatially restrictive transgenic drivers.     

Estimation of the duration of ventricular fibrillation using ECG single feature analysis

The duration of untreated ventricular fibrillation (VF) is of paramount importance for CPR success. Moreover, therapeutic interventions taking into account the interval between cardiac arrest onset and initiation of CPR improve outcome. This study was performed to investigate whether VF feature analysis could be used to estimate the duration of VF in patients with out-of-hospital cardiac arrest. Demographic data recorded according to the Utstein guidelines and ECG recordings of 376 cardiac arrest patients from three European areas were analysed. Ten features in the time and frequency domain derived from different sub-bands of the initial VF ECG (n=127) were evaluated. The correlation between VF ECG features and cardiac arrest times was investigated using Pearson's correlation coefficient in a subset of 40 patients with reliably estimated downtimes and artefact-free initial VF tracings. No significant correlation (p<.05) between any of the VF ECG features and downtime could be found. The duration of cardiac arrest could not be estimated reliably from human VF ECG single feature analysis.     

Impact of Epigenetic Dietary Compounds on Transgenerational Prevention of Human Diseases

The etiology of most human diseases involves complicated interactions of multiple environmental factors with individual genetic background which is initially generated early in human life, for example, during the processes of embryogenesis and fetal development in utero. Early embryogenesis includes a series of programming processes involving extremely accurate time-controlled gene activation/silencing expressions, and epigenetic control is believed to play a key role in regulating early embryonic development. Certain dietary components with properties in influencing epigenetic processes are believed to have preventive effects on many human diseases such as cancer. Evidence shows that in utero exposure to certain epigenetic diets may lead to reprogramming of primary epigenetic profiles such as DNA methylation and histone modifications on the key coding genes of the fetal genome, leading to different susceptibility to diseases later in life. In this review, we assess the current advances in dietary epigenetic intervention on transgenerational human disease control. Enhanced understanding of the important role of early life epigenetics control may lead to cost-effective translational chemopreventive potential by appropriate administration of prenatal and/or postnatal dietary supplements leading to early disease prevention.     

Insulin-induced hypoglycemia stimulates gastric vagal activity and motor function without increasing cardiac vagal activity

BACKGROUND/AIMS: We investigated whether increasing the efferent vagal activity by insulin-induced hypoglycemia would enhance gastric emptying and volumes in healthy subjects. METHODS: Twenty healthy volunteers (10 males) were examined with and without vagal stimulation by insulin-induced hypoglycemia using a glucose clamp technique. Stomach function was tested by drinking meat soup (0.04 kcal ml(-1)) at a rate of 100 ml min(-1) until maximal capacity. Intragastric volume at maximal drinking capacity was determined by three-dimensional ultrasound. Respiratory sinus arrhythmia (RSA) was used as an index of cardiac vagal activity and plasma pancreatic polypeptide (PP) as a measure of gastric vagal activity, and skin conductance (SC) as a measure of sympathetic tone. RESULTS: Insulin-induced hypoglycaemia increased drinking capacity (p = 0.002), gastric emptying (p = 0.02), PP (p = 0.004) and SC (p = 0.004), while intragastric volume was unchanged (p = 0.7) and RSA decreased (p = 0.03). CONCLUSION: Enhancement of gastric vagal activity by insulin-induced hypoglycemia increased drinking capacity and gastric emptying similarly, resulting in an unchanged intragastric volume. Enhanced efferent vagal activity to the stomach (as measured by PP) was not associated by enhanced cardiac vagal activity (as measured by RSA), possibly a consequence of stress-induced sympathetic activation during the procedure.     

The Prognostic Significance of Heart Rate for Cardiovascular Disease and Hypertension

Five decades ago, hypertension was a debated risk factor for the development of cardiovascular disease. After further studies and the introduction of antihypertensive medications, few, if any, have doubted the important role hypertension plays as a cardiovascular risk factor. Today, a growing body of evidence emphasizes the relationship between heart rate and hypertension, and heart rate and cardiovascular disease, which makes the measurement of heart rate an important component of the cardiovascular risk assessment. Current European guidelines for managing arterial hypertension recommend the measurement of heart rate for risk stratification, but there still are no recommendations for treatment. This review discusses the evidence for a relationship between heart rate and cardiovascular mortality and morbidity and hypertension.