The hypothalamic-pituitary-adrenocortical (HPA) axis and sympathetic adrenomedullary (SAM) system are the major stress-response pathways. Plasma adrenocorticotropic hormone (ACTH) represents HPA axis activity, while plasma catecholamines are used as markers of the SAM system. Salivary alpha amylase (AA), chromogranin A (CgA), and immunoglobulin A (IgA) are candidate markers of stress activation, although their role has not been established. The Uchida-Kraepelin (U-K) test is a questionnaire that requires intense concentration and effort, and has been used as a tool to induce mental stress. However, it is not clear whether or not the test is effective as a psychological/mental stressor.
In this study, normal young women took the U-K test and serial measurements of plasma ACTH and catecholamines (dopamine, noradrenaline, and adrenaline) (n = 10), as well as salivary AA, CgA, and IgA (n = 16) before, during and after the test.
We found no changes in any of these parameters at any time point during or after the U-K test.
Our findings indicate that the U-K test is not a suitable for measuring the psychological/mental stress of young women because the plasma data showed that it did not affect the HPA axis and SAM system. The U-K test should be employed carefully as a psychological/mental stressor due to insufficient scientific evidence of its effectiveness. In addition, salivary AA, CgA, and IgA should not simply be compared with previous reports, because the mechanism of secretion and normal range of each salivary parameter remain unknown. Salivary AA, CgA, and IgA may not be suitable candidate markers of psychological/mental stress.
In a previous study, chromogranin A (CgA) cell density in the colon of patients with irritable bowel syndrome (IBS) was found to be reduced. It has been suggested that intestinal CgA cell density may be used as a marker for the diagnosis of IBS. The rectum harbours a larger number of large intestinal endocrine cells and is more accessible for biopsies than the colon. The present study aimed at determining the CgA cell density in the rectum of IBS patients. A total of 47 patients with IBS that fulfilled the Rome Criteria III (39 females and 8 males; average age, 38 years) were included. A total of 28 patients had diarrhea (IBS-D) and 19 had constipation (IBS-C) as the predominant symptom. A total of 27 subjects that underwent colonoscopy with rectal biopsies were used as the controls. These subjects underwent colonoscopy due to gastrointestinal bleeding (the source of which was identified as haemorrhoids or angiodysplasia; 19 females and 8 males; average age, 49 years), or health worries. The rectal biopsies were immunostained for CgA and quantified by computer image analysis. The CgA density in the controls was 206.3±22.2 (mean ± SEM), in all IBS patients 190.2±14.3, in IBS-D patients 188.8±14.7 and in IBS-C patients 195.3±34.1. There was no statistically significant difference between the controls, IBS, IBS-D or IBS-C patients (P=0.5, 0.5 and 0.7, respectively). The present study showed that although the rectum comprises the same endocrine cell types as the colon, attention must be paid when drawing conclusions regarding the whole large intestine from studies carried out on the rectum. This particularly applies when endocrine cells are investigated. As CgA cell density represents the total endocrine cell content of the rectum, changes in specific endocrine cells in IBS patients cannot be excluded.
chromogranin A; computer image analysis; immunohistochemistry; irritable bowel syndrome; rectum
Abdominal distension is a common but little understood symptom of the irritable bowel syndrome. The authenticity of the symptom was confirmed by appreciable increases in girth measurement during the day in 20 patients with the irritable bowel syndrome compared with 20 control subjects. Objective corroboration of this finding was shown in the group with the irritable bowel syndrome by a highly significant increase in lateral abdominal 'profile' on computed tomography. Previously postulated mechanisms for distension--namely, retention of gas, depression of the diaphragm, and excess lumbar lordosis--were excluded by the radiological findings. Voluntary protrusion of the abdomen produced a completely different pattern on computed tomography to that observed in the irritable bowel syndrome. These observations suggest that abdominal distension may be related to changes in motility or tone of gastrointestinal smooth muscle.
The role of the abdominal muscles in trunk rotation is not comprehensively understood. This study investigated the electromyographic (EMG) activity of anatomically distinct regions of the abdominal muscles during trunk rotation in six subjects with no history of spinal pain. Fine-wire electrodes were inserted into the right abdominal wall; upper region of transversus abdominis (TrA), middle region of TrA, obliquus internus abdominis (OI) and obliquus externus abdominis (OE), and lower region of TrA and OI. Surface electrodes were placed over right rectus abdominis (RA). Subjects performed trunk rotation to the left and right in sitting by rotating their pelvis relative to a fixed thorax. EMG activity was recorded in relaxed supine and sitting, and during an isometric hold at end range. TrA was consistently active during trunk rotation, with the recruitment patterns of the upper fascicles opposite to that of the middle and lower fascicles. During left rotation, there was greater activity of the lower and middle regions of contralateral TrA and the lower region of contralateral OI. The upper region of ipsilateral TrA and OE were predominately active during right rotation. In contrast, there was no difference in activity of RA and middle OI between directions (although middle OI was different between directions for all but one subject). This study indicates that TrA is active during trunk rotation, but this activity varies between muscle regions. These normative data will assist in understanding the role of TrA in lumbopelvic control and movement, and the effect of spinal pain on abdominal muscle recruitment.
Transversus abdominis; Trunk rotation; Regional recruitment; Abdominal muscles; Electromyography
Shoulder dysfunction and injury are common in throwing athletes. Loss of internal rotation has been correlated to shoulder pathologies. The purpose of this study was to assess the effects of a stretching protocol on passive internal rotation. The purpose of this study was assess the effects of a stretching protocol on passive internal rotation motion in the throwing shoulders of collegiate baseball players.
Pre-Post, intervention, using a within subjects comparison of a convenience sample.
Glenohumeral internal rotation and external rotation of the throwing and non-throwing shoulders of NCAA Division I baseball players were measured using a universal goniometer. Determinations were made as to the degree of Glenohumeral Internal Rotation Deficit (GIRD) in the throwing shoulder. A daily (5 days per week), 12-week posterior capsule stretching program was administered. Post-stretching internal rotation and external rotation measures were again obtained. The coaches and athletic trainers of the included team monitored the players for shoulder injuries and innings of training/competition lost due to shoulder injuries during the 12 week intervention.
A significant increase in range of motion was found for dominant arm internal rotation (IR) and total range of motion (TOT) following the stretching program. No statistically significant improvement in range of motion was found for external rotation (ER), non-throwing arm internal rotation (NDIR), non-throwing arm external rotation (NDER), and non-throwing arm total motion (NDTOT).
Implementation of a posterior capsule stretching program may be helpful to facilitate increased passive internal rotation range of motion at the glenohumeral joint. Further research should be performed using a control group not receiving the stretching program in order to more completely establish the impact of stretching on measures of passive glenohumeral range of motion.
Level of Evidence:
GIRD; glenohumeral internal rotation; stretching
OBJECTIVE—To elucidate the character and
distribution of the abnormal muscle tonus in the body axis in
progressive supranuclear palsy. Although neck hypertonus has been well
described in progressive supranuclear palsy, little is known about the
involvement of the truncal muscles.
METHODS—Muscle tonus of the neck and trunk was
separately investigated in 13 patients with progressive supranuclear
palsy by clinical examination and surface EMG during passive rotation.
Muscle hypertonus was graded according to a four point scale, and
subjected to statistical analysis. The results were compared with those
from 13 age matched patients with Parkinson's disease and six healthy volunteers.
RESULTS—In all but one patient with progressive
supranuclear palsy, there was a distinct difference in muscle tonus
between the neck and trunk. A tonic shortening reaction characteristic
of dystonia and an increased tonic stretch reflex (rigidity) were
present in the neck muscles of patients with progressive supranuclear palsy, whereas only normal to moderately increased tonus was noted in
the truncal muscles (neck v trunk, shortening reaction
p=0.0001; stretch reflex p=0.0241). Follow up studies disclosed an
increase in axial muscle tonus with predilection for the neck in three of four patients. In the 13 patients with Parkinson's disease, however, no significant difference was found in muscle rigidity between
the neck and trunk.
CONCLUSION—Mild changes in truncal muscle tonus
with prominent neck dystonia and rigidity are characteristic of
progressive supranuclear palsy. It is suggested that separate clinical
evaluation of muscle tonus in the neck and trunk may be helpful for
distinguishing progressive supranuclear palsy from Parkinson's disease.
Passive muscle stretch performed during a period of post-exercise muscle ischemia (PEMI) increases muscle sympathetic nerve activity (MSNA), and this suggests that the muscle metabolites may sensitize mechanoreceptors in healthy humans. However, the responsible substance(s) has not been studied thoroughly in humans. Human and animal studies suggest that cyclooxygenase products sensitize muscle mechanoreceptors. Thus, we hypothesized that local cyclooxygenase inhibition in exercising muscles could attenuate MSNA responses to passive muscle stretch during PEMI. Blood pressure (Finapres), heart rate, and MSNA (microneurography) responses to passive muscle stretch were assessed in 13 young healthy subjects during PEMI before and after cyclooxygenase inhibition, which was accomplished by local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased prostaglandin synthesis to ~34% of the baseline. Before ketorolac Bier block, passive muscle stretch evoked significant increases in MSNA (P < 0.005) and mean arterial blood pressure (P < 0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P = 0.11) or mean arterial blood pressure (P = 0.83). Saline Bier block had no effect on the MSNA or blood pressure response to ischemic stretch. These observations indicate that cyclooxygenase inhibition attenuates MSNA responses seen during PEMI, and suggest that cyclooxygenase products sensitize the muscle mechanoreceptors.
prostaglandins; exercise; nervous system; sympathetic; mechanoreceptor
Irritable bowel syndrome (IBS) and its association with stress, has not been studied among university students in Pakistan. We investigated the prevalence and the pattern of anxiety related IBS symptoms among medical students of Karachi.
An observational case–control study was carried out at three medical colleges of Karachi, Pakistan. Random sampling was done on 360 medical students. Data was collected using validated tools “Rome III Criteria” and “Generalized Anxiety Disorder Questionnaire”. Participants with IBS were diagnosed on the criteria having experienced abdominal discomfort at least 2–3 days/month associated with high level of anxiety. The apparent prevalence of IBS was found to be 28.3%, with a predominance of 87 (85.29%) females (85.29%) over males (14.71%). The psychological symptoms of anxiety were encountered in 57 (55.8%) participants with IBS, among which males were 15.7% and females 84.2% respectively.
Students who more frequently suffer with mental stress and anxiety are more associated with IBS.
Irritable bowel syndrome; Anxiety; Stress; Abdominal discomfort; Medical students
We have recently developed an animal model of fibromyalgia syndrome in the rat. In this model, rats exposed to unpredictable sound stress develop a delayed onset enhancement and prolongation of cytokine-induced mechanical hyperalgesia in muscle and skin. In this study, we tested the hypothesis that our model also manifests symptoms of common co-morbid diagnoses: irritable bowel syndrome, temporomandibular disorder and anxiety. Both visceral sensitivity and cytokine hyperalgesia in masseter muscle were present in the stressed rats. Furthermore, in an established model of irritable bowel syndrome, water avoidance, we observed significant muscle hyperalgesia. Finally, using the elevated plus maze to assess for anxiety level, we observed a significantly higher anxiety level in sound stress exposed rats. Thus, unpredictable sound stress produces a condition in the rat with several features — delayed onset visceral and temporomandibular hyperalgesia and increased anxiety, as well as cutaneous and muscle hyperalgesia — commonly found in patients with fibromyalgia syndrome.
Unpredictable sound stress; visceral hyperalgesia; colorectal distension; anxiety; irritable bowel syndrome; temporomandibular disorder
To determine the changes in salivary chromogranin A (CgA) levels upon awakening in response to of stress by investigating the relationship between salivary CgA levels and the stress response as assessed by GHQ-28 tests.
The study cohort comprised 40 healthy male university students (age range 19–22 years). Salivary CgA levels were measured at 7:00 a.m. (awakening) and at 7:30, 8:00, and 8:30 a.m. (after awakening).
The salivary CgA level was 0.91 ± 0.20 and 0.42 ± 0.1 pmol/ml at 7:00 a.m. in students scoring low (n = 26) and high (n = 14), respectively, on the “severe depression” subscale. This difference in salivary CgA levels at 7:00 between high and low scorers was statistically significant (p < 0.05).
Our findings indicate that depression may influence secretions of salivary CgA via chronic stress-related attenuation of the sympathetic–adrenomedullary system activity.
Chromogranin A; Stress; Awakening; Saliva; Depression
An increase in gastrointestinal (GI) symptoms, including bowel discomfort, abdominal pain/discomfort, bloating, and alterations in bowel patterns, has been reported during premenses and menses menstrual cycle phases and the perimenopause period in women with and without irritable bowel syndrome (IBS).
This article reviews the literature related to one possible physiological mechanism—declining or low ovarian hormone levels—that may underlie the occurrence or exacerbations of abdominal pain/discomfort at times of low ovarian hormones (menses, menopause) in women with or without IBS.
To identify English-only review and data-based articles, PubMed was searched between January 1980 and September 2008 using the following terms: irritable bowel syndrome, functional gastrointestinal disorders, gastrointestinal motility, immune, pain, hyperalgesia, menstrual cycle, menopause, pregnancy, estrogen, estradiol (E2), and progesterone. Studies in animals and in humans were included; drug trials were excluded.
From our review of the literature, 18 papers were identified that were related either to the mechanisms accounting for menstrual cycle fluctuations (n = 12) or to the impact of menopausal status on symptoms of IBS (n = 6). One study reported that visceral pain sensitivity was significantly higher during menses than at other menstrual cycle phases in women with IBS (P < 0.05). Other menstrual cycle phase–linked symptoms, dysmenorrheal symptoms (cramping pain) in particular, were more intense in women with IBS. Animal studies have shed some light on the relationship of ovarian hormones to GI sensorimotor function.
The increase in GI symptoms around the time of menses and early menopause occurs at times of declining or low ovarian hormones, suggesting that estrogen and progesterone withdrawal may contribute either directly or indirectly. This review highlights the need for confirmatory preclinical and clinical studies to unravel the role of ovarian hormones in women with IBS.
irritable bowel syndrome; menstrual cycle; menopause; estrogen; progesterone; gastrointestinal symptoms; pregnancy; immune; pain
The helical shape of the thin filaments causes their passive counterclockwise rotation during muscle stretch that increases tensile stress and torque at first by unwinding and then by winding up the four anchoring Z-filaments. This means storage of energy in the series elastic Z-filaments and a considerable decrease of the liberated energy of heat and work to (h—wap), where h is the heat energy and wap the stretch energy induced from outside by an apparatus. The steep thin filament helix with an inclination angle of 70° promotes the passive rotation during stretch, but impedes the smooth sliding of shortening by increased friction and production of frictional heat. The frictional heat may be produced by the contact with the myosin cross-bridges: (1) when they passively snap on drilling thin filaments from cleft to cleft over a distance 2 × 2.7 nm = 5.4 nm between the globular actin monomers in one groove, causing stepwise motion; or (2) when they passively cycle from one helical groove to the next (distance 36 nm). The latter causes more heat and may take place on rotating thin filaments without an effective forward drilling (“idle rotation”), e.g., when they produce “unexplained heat” at the beginning of an isometric tetanus. In an Appendix to this paper the different states of muscle are defined. The function of its most important components is described and rotation model and power-stroke model of muscular contraction is compared.
active and passive thin filament-rotation; frictional heat
Experimental data on the passive mechanical properties of the ventral interior lateral muscle of the tobacco hornworm caterpillar, Manduca sexta, are reported. The stress–deformation response of the Manduca muscle is shown to be nonlinear pseudo-elastic, capable of large deformations and subject to stress softening during initial loading cycles. The muscle passive mechanical properties also depend on multiple time-dependent processes. In particular, we show new experimental data from cyclic loading tests of an unstimulated muscle with constant maximum stretch and different, constant engineering strain rates. Then, on the basis of these data a constitutive model is derived to reproduce the main characteristics of this behaviour. In formulating the constitutive model, we consider the muscle as a complex macromolecular structure with fibrous components at numerous size scales. The model uses a phenomenological approach to account for different mechanisms by which passive force changes during applied deformation and how the muscle properties recover after unloading.
Manduca sexta; striated muscles; anisotropy; pseudo-elasticity
OBJECTIVE--To determine the prevalence of symptoms compatible with a clinical diagnosis of irritable bowel syndrome in the general population. DESIGN--Validated postal questionnaire sent to 2280 subjects randomly selected in 10 year age bands from the lists of eight general practitioners. The Manning criteria were used to define irritable bowel syndrome. SETTING--Urban population in Southampton and mixed urban-rural population in Andover, Hampshire. RESULTS--A response of 71% yielded 1620 questionnaires for analysis, of which 412 (25%) reported more than six episodes of abdominal pain in the preceding year, with 350 (22%) reporting symptoms consistent with the diagnosis of irritable bowel syndrome. The male: female ratio was 1:1.38. More subjects with irritable bowel syndrome had constipation and diarrhoea and 35% with the syndrome reported rectal bleeding compared with an overall prevalence of 20%. Other symptoms and conditions including heartburn, dyspepsia, flushing, palpitations, migraine, and urinary symptoms were significantly more common in the group with irritable bowel syndrome. Abdominal pain in childhood was more common in the subjects with irritable bowel syndrome (12%) than without (3%). One third of the group with irritable bowel syndrome had sought medical advice during the study period (male:female ratio 1:1.21); consultation behaviour was influenced by age and the presence of associated symptoms, varied considerably among patients registered with different general practitioners, and was poorly correlated with symptom severity. CONCLUSION--Symptoms consistent with a diagnosis of irritable bowel syndrome are present in almost one quarter of the general population and tend to be associated with a number of other complaints and conditions, some of which may reflect smooth muscle dysfunction.
Forty Parkinsonian patients and 26 normal subjects were instructed not to resist movements of a handle which they maintained in a specified position (1) during tonic activation of muscles against the force produced by a torque motor and (2) while no force was produced by the motor. Electromyographic responses to handle displacements were recorded in biceps muscle (pronating or supinating displacements) or in wrist extensor and flexor muscles (displacements which extended or flexed the wrist). Displacements involving changes of muscle length elicited (1) excitation and inhibition occurring at monosynaptic latency in muscles which were stretched and shortened, respectively; (2) a "silent period" following the initial excitation in the stretched muscle and excitation following the initial inhibition in the shortened muscle (shortening reaction); and (3) (in Parkinsonian patients) sustained oscillations at about 4 to 5 Hz (at rest) or about 6 to 8 Hz (during maintained posture). It was also observed that the initial muscle responses in both the stretched and shortened muscle could be reciprocal and biphasic, with the two peaks of excitation in the agonist occurring during reduced activity of antagonist muscles, and vice versa.
A standardised inventory of stressful life events and a bowel symptom questionnaire were administered at three month intervals for one year to 383 women who were unselected with respect to bowel symptoms. A NEO Personality Inventory was given initially to assess neuroticism. Subjects who satisfied restrictive diagnostic criteria for irritable bowel syndrome were compared with those who complained of abdominal pain plus altered bowel habits but who did not meet restrictive diagnostic criteria (functional bowel disorder) and with controls without bowel dysfunction. The irritable bowel group showed significantly higher levels of stress than the other two groups even when the confounding effects of neuroticism were statistically controlled for. Time lagged correlations showed that stress in one three month interval was significantly correlated with bowel symptoms in the subsequent three month interval for all groups. The slope of the regression line relating stress to bowel symptoms was significantly steeper for the irritable bowel group than for the other two groups at three and six months, suggesting that subjects with irritable bowel syndrome show a greater reactivity to stress. Stress scores were also significantly correlated with the number of disability days and the number of medical clinic visits for bowel symptoms.
This study compared the characteristics of patients with symptoms of irritable bowel syndrome who had either consulted or not consulted a general practitioner in the preceding two years. The subjects were identified by questionnaire in a community survey of irritable bowel syndrome symptoms and samples of 24 consulting and 24 non-consulting patients were interviewed. The groups were well matched for demographic characteristics, although those who consulted for irritable bowel syndrome also consulted more frequently for other problems. The only significant differences in the pattern, frequency and severity of a range of symptoms, which included the Manning criteria, were that more of the consulting patients experienced visible abdominal distension and had a higher mean score for severity of pain than the non-consulters. Mean negative life event scores and anxiety and depression scores were higher in the group who consulted and more of these patients were concerned about the possible serious nature of their symptoms, including fear of cancer, emphasizing the importance of eliciting patients' beliefs and anxieties about the meaning of their symptoms.
The roles of antagonistic activation of abdominal muscles and of intra-abdominal pressurization remain enigmatic, but are thought to be associated with both spinal unloading and spinal stabilization in activities such as lifting. Biomechanical analyses are needed to understand the function of intra-abdominal pressurization because of the anatomical and physiological complexity, but prior analyses have been over-simplified.
To test whether increased intra-abdominal pressure was associated with reduced spinal compression forces for efforts that generated moments about each of the principal axis directions, a previously published biomechanical model of the spine and its musculature was modified by the addition of anatomically realistic three-layers of curved abdominal musculature connected by fascia to the spine. Published values of muscle cross-sectional areas and the active and passive stiffness properties were assigned. The muscle activations were calculated assuming minimized muscle stress and stretch for the model loaded with flexion, extension, lateral bending and axial rotation moments of up to 60 Nm, along with intra-abdominal pressurization of 5 or 10 kPa (37.5 or 75 mmHg) and partial bodyweight (340 N).
The analysis predicted a reduction in spinal compressive force with increase in intra-abdominal pressurization from 5 to 10 kPa. This reduction at 60 Nm external effort was 21% for extension effort, 18% for flexion effort, 29% for lateral bending and 31% for axial rotation.
This analysis predicts that intra-abdominal pressure produces spinal unloading, and shows likely muscle activation patterns that achieve this.
Abdominal muscles; spinal loading; biomechanics
A common characteristic of irritable bowel syndrome (IBS) is that symptoms, including abdominal pain and abnormal bowel habits, are often triggered or exacerbated during periods of stress and anxiety. However, the impact of anxiety and affective disorders on the gastrointestinal (GI) tract is poorly understood and may in part explain the lack of effective therapeutic approaches to treat IBS. The amygdala is an important structure for regulating anxiety with the central nucleus of the amygdala facilitating the activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system in response to stress. Moreover, chronic stress enhances function of the amygdala and promotes neural plasticity throughout the amygdaloid complex. This review outlines the latest findings obtained from human studies and animal models related to the role of the emotional brain in the regulation of enteric function, specifically how increasing the gain of the amygdala to induce anxiety-like behavior using corticosterone or chronic stress increases responsiveness to both visceral and somatic stimuli in rodents. A focus of the review is the relative importance of mineralocorticoid receptor and glucocorticoid receptor-mediated mechanisms within the amygdala in the regulation of anxiety and nociceptive behaviors that are characteristic features of IBS. This review also discusses several outstanding questions important for future research on the role of the amygdala in the generation of abnormal GI function that may lead to potential targets for new therapies to treat functional bowel disorders such as IBS.
irritable bowel syndrome; visceral hypersensitivity; anxiety; amygdala; corticosterone; hypothalamic-pituitary-adrenal axis
To determine whether circulating levels of chromogranin A (CgA) provide prognostic information independently of conventional risk markers in acute coronary syndromes (ACSs).
Methods and results
We measured circulating CgA levels on day 1 in 1268 patients (median age 67 years, 70% male) with ACS admitted to a single coronary care unit of a Scandinavian teaching hospital. The merit of CgA as a biomarker was evaluated after adjusting for conventional cardiovascular risk factors. During a median follow-up of 92 months, 389 patients (31%) died. The baseline CgA concentration was strongly associated with increased long-term mortality [hazard ratio per 1 standard deviation increase in logarithmically transformed CgA level: 1.57 (1.44–1.70), P < 0.001], heart failure hospitalizations [1.54 (1.35–1.76), P < 0.001], and recurrent myocardial infarction (MI) [1.27 (1.10–1.47), P < 0.001], but not stroke. After adjustment for conventional cardiovascular risk markers, the association remained significant for mortality [hazard ratio 1.28 (1.15–1.42), P < 0.001] and heart failure hospitalization [hazard ratio 1.24 (1.04–1.47), P = 0.02], but not recurrent MI.
CgA is an independent predictor of long-term mortality and heart failure hospitalizations across the spectrum of ACSs and provides incremental prognostic information to conventional cardiovascular risk markers.
Acute coronary syndromes; Chromogranin A; Troponin T; Echocardiography; Prognosis
Irritable bowel syndrome (IBS) is reported by one in ten of the population accounting for up to 40% of new referrals to gastroenterology outpatients. Patients characteristically have abdominal discomfort and disturbed bowel habit. Diarrhoea-predominant IBS is characterised by frequent loose stools with associated urgency and abdominal cramps. Current symptomatic treatments can reduce bowel frequency but often fail to reduce discomfort.
Mesalazine is an anti-inflammatory drug used to treat patients with inflammatory bowel disease. There is one pilot study suggesting it may be beneficial to patients who have diarrhoea-predominant IBS but these findings need to be confirmed in a larger trial. The current study aims to test the effectiveness of mesalazine to reduce symptoms in diarrhoea-predominant IBS patients. The study will also investigate the mode of action of the drug, especially its impact on mast cell activation.
This is a multicentre randomised, double-blind, placebo-controlled trial using a parallel group design. At least 108 participants with diarrhoea-predominant IBS will be recruited through at least six hospitals. The intervention is a 12-week course of 2g mesalazine granules taken up to twice a day. The comparator is a blinded placebo granule formulation.
Outcome measures include stool diaries, symptom questionnaires, stool and blood samples together with rectal mucosal biopsies. The daily stool diary will record stool frequency and form, urgency, bloating, abdominal pain and a global satisfaction with control of IBS scored each week. The questionnaires will assess bowel symptoms, while the samples and biopsies will be used to analyse underlying mechanisms of any response.
Primary outcome will be the average stool frequency during weeks 11 and 12 of the treatment period and will be compared between treatment arms using an analysis of covariance in the form of a general linear model incorporating baseline characteristics that are thought a priori to strongly predict outcome. The primary efficacy parameter will be the difference in mean frequency between treatment arms.
This report describes a randomised controlled trial that will provide evidence of any benefit of treating diarrhoea-predominant IBS patients with mesalazine. The results will be available toward the end of 2013.
Irritable bowel syndrome; Diarrhoea-predominant; Mesalazine
Fick hypothesized in 1911 that the erector spinae muscles are not active when the trunk is in the fully flexed position. This effect was later called the flexion-relaxation phenomenon (FRP) and is believed to be the result of the ligaments and other passive elements of the spine taking over the load of the muscles. This study examined the effect of loading on the EMG activity of five males and five females during postures of standing at 45 degrees, 90 degrees, and full flexion. The results showed major differences in the relationship between the electromyographic signal (EMG) of the erector spinae and loading for the four postures. The erector spinae muscles did not activate in positions of full flexion (or even 90 degrees for some subjects) for loading as high as 50% of their maximum voluntary contraction, suggesting that alternative muscles are being activated and that the passive tissues may be put under higher loads than originally thought in these positions. The results suggested that the FRP could be used as a biofeedback tool to illustrate to workers that their muscles are not turning on in the fully flexed positions, and therefore, these positions should be avoided.
Disturbances in biological rhythms could lead to unfavorable health impact. This study aimed to evaluate the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS) in rotating shift workers, and to determine the factors that have significant association with the prevalence of FD and IBS. The research had been carried out among nurses and nursing assistants working at Ewha Womans University Mokdong Hospital between December 2010 and February 2011. The subjects completed self-reported questionnaires, including the quality of the sleep and the level of stress. The prevalence of FD and IBS defined by ROME III criteria, and factors associated the disorders in rotating shift workers were compared with those of day workers. A total of 207 subjects were included in the study with 147 rotating shift workers (71.0%), and 60 (29.0%) day workers. The prevalence of IBS in rotating shift workers was higher than that in day workers (32.7% vs 16.7%, P = 0.026). However, no significant difference in the prevalence of FD was observed between the two groups (19.7% vs 20.0%, P = 0.964). In the multivariate analysis, the risk factors for IBS were rotating shift work (OR, 2.36; 95% CI, 1.01-5.47) and poor sleep quality (OR, 4.13; 95% CI, 1.82-9.40), and the risk factors for FD were poor sleep quality (OR, 2.31; 95% CI, 1.01-5.28), and severe stress (OR, 2.19; 95% CI, 1.06-4.76). A higher prevalence of IBS among rotating shift workers could be directly associated with the circadian rhythm disturbance. The circadian rhythm disturbance may be related with the pathogenesis of IBS.
Shiftwork; Sleep Disturbance; Irritable Bowel Syndrome; Functional Dyspepsia
Previous research suggests proprioceptive neuromuscular facilitation (PNF) stretching techniques produce greater increases in range of motion than passive, ballistic, or static stretching methods. The purpose of our study was to measure the duration of maintained hamstring flexibility after a 1-time, modified hold-relax stretching protocol.
Design and Setting:
The study had a 1 × 1 mixed-model, repeated-measures design. The independent variables were group (control and experimental) and time (0, 2, 4, 6, 8, 16, and 32 minutes). The dependent variable was hamstring flexibility as measured in degrees of active knee extension with the hip flexed to 90°. Measurements were taken in a preparatory military academy athletic training room.
Thirty male subjects (age, 18.8 ± 0.63 years; height, 185.2 ± 14.2 cm; weight, 106.8 ± 15.7 kg) with limited hamstring flexibility in the right lower extremity were randomly assigned to a control (no-stretch) group or an experimental (stretch) group.
All subjects performed 6 warm-up active knee extensions, with the last repetition serving as the prestretch measurement. The experimental group received 5 modified (no-rotation) hold-relax stretches, whereas the control group rested quietly supine on a table for 5 minutes. Posttest measurements were recorded for both groups at 0, 2, 4, 6, 8, 16, and 32 minutes.
The repeated-measures analysis of variance revealed a significant group-by-time interaction, a significant main effect for group, and a significant main effect for time. Dunnett post hoc analysis revealed a significant improvement in knee-extension range of motion in the experimental group that lasted 6 minutes after the stretching protocol ended.
Our findings suggest that a sequence of 5 modified hold-relax stretches produced significantly increased hamstring flexibility that lasted 6 minutes after the stretching protocol ended.
active knee-extension test; knee joint range of motion
Alterations in corticotropin-releasing factor (CRF) signaling pathways have been implicated in irritable bowel syndrome (IBS) pathophysiology. We aimed to: 1) determine the effect of the selective CRF receptor 1 antagonist (CRF1), GW876008, relative to placebo, on regional activation and effective connectivity of a stress-related emotional-arousal circuit during expectation of abdominal pain using functional magnetic resonance imaging (fMRI) in human subjects with a diagnosis of IBS and healthy controls (HCs), and 2) examine GW876008 effects on state-trait anxiety and hypothalamic-pituitary-adrenal (HPA) axis response. While there were no drug-related effects on peripheral HPA activity, significant central effects were observed in brain regions associated with the stress response. Effective connectivity analysis showed drug-induced normalizations between key regions of the emotional-arousal circuit in patients. During pain expectation, orally administered GW876008 relative to placebo produced significant blood oxygen level-dependent (BOLD) signal reductions in the amygdala, hippocampus, insula, anterior cingulate and orbitomedial prefrontal cortices across groups. Patients showed significantly greater BOLD responses in the left locus coeruleus and hypothalamus following placebo compared to HCs, and BOLD signal decreases in the left hypothalamus following drug. The inhibitory effects of GW876008 in the hypothalamus in patients were moderated by anxiety; patients having average and high levels of state anxiety showed drug-related BOLD decreases. GW876008 represents a novel tool for elucidating the neuronal mechanisms and circuitry underlying hyperactivation of CRF/CRF1 signaling and its role in IBS pathophysiology. The unique state anxiety effects observed suggest a potential pathway for therapeutic benefit of CRF1 receptor antagonism for patients with stress-sensitive disorders.