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Biomedical subjects

E A Mayer

Publications and source records attributed to E A Mayer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Characteristics of patients with irritable bowel syndrome recruited from three sources: implications for clinical trials.

BACKGROUND: Variation in the characteristics of irritable bowel syndrome patients recruited for clinical trials from different sources could affect their response and the generalizability of trial results. AIM: To describe and compare the characteristics of three different groups of irritable bowel syndrome patients recruited into a 'mock clinical trial.' METHODS: We enrolled 245 irritable bowel syndrome patients from three sources: (i) 121 from British primary practitioners; (ii) 72 from California newspaper advertisements; and (iii) 52 from a California gastroenterologist's practice. We obtained demographic, clinical, and Hospital Anxiety and Depression (HAD) Scale data. RESULTS: Most patients were young to middle-aged women; the majority reported symptoms for > 5 years in all three groups. Subject characteristics varied among the groups. Typically, primary care patients were anxious, smokers and daily alcohol drinkers who had sought care recently for irritable bowel syndrome and tried antispasmodic drugs. Their symptoms were intermediate in severity between those of the other two groups. Advertisement subjects were the oldest, most highly educated, most often depressed, and were least likely to have sought care recently for symptoms, which were almost uniformly only moderate in severity. Gastroenterologist patients tended to be anxious and had nearly all sought care recently for symptoms, which were the most severe and most likely to include all three pain-related Rome I criteria. CONCLUSION: Recruitment methodology affects important characteristics of an irritable bowel syndrome study group.

Adolescent↗
PubMed2001

Involvement of spinal calcitonin gene-related peptide in the development of acute visceral hyperalgesia in the rat.

This study aimed to characterize the role of the neuropeptide calcitonin gene-related peptide (CGRP) in the development of mechanically induced visceral hyperalgesia. Tonic colorectal distension (CRD) was performed in fasted, conscious male Sprague-Dawley rats. The visceromotor reflex associated with noxious CRD was determined as the number of contractions during each of two consecutive tonic distensions (10 min at 60 mmHg), which were separated by a series of phasic distensions (repeated 15-s distensions to 80 mmHg at 30-s intervals). The effect of the CGRP receptor antagonist h-CGRP8-37 given intrathecally (i.t.) (0.03-3 nmol rat-1) or intravenously (i.v.) (20 microg kg-1 bodyweight [bw]) on the visceromotor response was evaluated. The dose for i.v. administration was chosen based on previous results from similar studies. In addition, the effect of a CGRP monoclonal antibody (6 mg kg-1 bw) given intravenously was evaluated. Compared to the baseline response, a significant increase in the number of abdominal contractions was observed during the second tonic distension. The i.t. application of h-CGRP8-37 dose-dependently reduced the numbers of abdominal contractions both during the first and the second tonic distension period, with a maximum effect observed at a peptide concentration of 3 nmol. Intravenous administration of h-CGRP8-37 or of the CGRP antiserum produced a small reduction of the visceromotor response induced by the second tonic distension and had no effect on colonic compliance. The development of mechanically induced colorectal hyperalgesia by repeated tonic distension involves the spinal release of CGRP, while peripheral release of CGRP plays only a minor role.

Acute Disease↗
PubMed2001

Role of peripheral N-methyl-D-aspartate (NMDA) receptors in visceral nociception in rats.

BACKGROUND & AIMS: N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that have an important role in long-term potentiation and memory processing in the central nervous system. The aims in this study were to determine whether NMDA receptors are expressed in the peripheral nervous system and identify their role in mediating behavioral pain responses to colonic distention in the normal gut. METHODS AND RESULTS: Immunohistochemical localization of the NR1 subunit showed that NMDA receptors are expressed on the cell bodies and peripheral terminals of primary afferent nerves innervating the colon. Dorsal root ganglia neurons retrogradely labeled from the colon in short-term culture responded to addition of NMDA with increased intracellular [Ca2+]. Activation of peripheral NMDA receptors in colonic tissue sections caused Ca2+-dependent release of the proinflammatory neuropeptides, calcitonin gene-related peptide and substance P. Behavioral pain responses to noxious mechanical stimulation were inhibited in a reversible, dose-dependent manner by intravenous administration of memantine, a noncompetitive antagonist of the NMDA receptor. Single fiber recordings of decentralized pelvic nerves showed that colorectal distention responsive afferent nerve activity was inhibited by memantine. CONCLUSIONS: Peripheral NMDA receptors are important in normal visceral pain transmission, and may provide a novel mechanism for development of peripheral sensitization and visceral hyperalgesia.

Amino Acid Sequence↗
PubMed2001

Gender-related differences in IBS symptoms.

OBJECTIVE: Women are more likely than men to report irritable bowel syndrome (IBS) symptoms as well as chronic visceral and musculoskeletal pain. The study tests the general hypothesis that female IBS patients differ from their male counterparts in symptoms related to the viscera and musculoskeletal system, and that these differences are related to the menstrual cycle. METHODS: Seven hundred fourteen Rome positive IBS patients were evaluated for GI and extracolonic symptoms, psychological symptoms (SCL-90R), and quality of life (QOL) (SF-36). In addition, 54 postmenopausal women were compared with 61 premenopausal women and 54 age-matched males, all with IBS. RESULTS: Male and female subjects reported similar GI levels of symptom severity and psychological problems. Abdominal distension associated with a sensation of bloating was more commonly reported by female patients, as were symptoms of constipation. Female patients more often reported nausea, alterations of taste and smell, and unpleasant sensations on the tongue, muscle stiffness in the morning, greater food sensitivity, and side effects from medications. Forty percent of female patients reported menstrual cycle-related worsening of symptoms, but few symptom differences were found between pre- and postmenopausal women, making it unlikely that most of the gender differences observed are directly tied to the menstrual cycle. CONCLUSIONS: Female patients report higher levels of a variety of intestinal and nonintestinal sensory symptoms despite similar levels of IBS severity, abdominal pain, psychological symptoms, and illness impact. The apparent differences in sensitivity to nonpainful visceral sensations, medications, and food may represent altered sensory processes, autonomic responses, and/or cognitive hypervigilance.

Abdominal Pain↗
PubMed2001

Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome.

OBJECTIVES: Abdominal bloating and distension are common symptoms of irritable bowel syndrome (IBS). The postulated pathophysiological mechanisms underlying these symptoms include increased production, retention, or perception of gas or luminal contents. The aims of this study were to prospectively compare the prevalence of, and clinical factors related to, bloating and distension in an IBS patient population. METHODS: A total of 714 consecutive patients who met Rome I criteria for IBS were prospectively surveyed, and were classified as having bloating alone (B) or bloating and distension (B+D) based on a comprehensive bowel symptom questionnaire. GI, extraintestinal, and psychological symptoms, as well as health-related quality of life measures were also assessed using validated survey instruments. RESULTS: A total of 542 IBS patients (76%) who reported abdominal bloating were studied. Of these, 132 patients fulfilled criteria for the B group, whereas 410 patients fulfilled criteria for the B+D group. There was a significantly different gender distribution in the B and B+D groups (female:male ratios, 1.4:1 and 2.8:1, respectively p < 0.02). There was also a significantly different bowel habit subgroup distribution, with a greater predominance of constipation in B+D group and of diarrhea in the B group (p < 0.03). Both groups were similar in other clinical parameters, including progressive worsening of symptoms during the day, and relief by passing stool or gas. Both bloating and distension worsened when other abdominal symptoms worsened. Abdominal distension was associated with greater symptom severity and less diurnal variation in symptoms, and was less often perceived as associated with food intake. CONCLUSIONS: Bloating and visible abdominal distension may arise from two distinct but interrelated physiological processes. Although the sensation of bloating may be related to enhanced sensitivity to visceral afferent stimulation, abdominal distension in more severely affected patients may be related to triggering of a visceromotor reflex affecting the tone of abdominal wall muscles.

Abdomen↗
PubMed2001

Duodenal fat intensifies the perception of heartburn.

BACKGROUND: Patients with gastro-oesophageal reflux disease (GORD) frequently report that meals high in fat worsen heartburn. Nevertheless, studies to determine whether high fat meals promote gastro-oesophageal reflux have produced conflicting and equivocal conclusions. PATIENTS AND METHODS: To determine, alternatively, whether fat in the small intestinal lumen intensifies the perception of heartburn, we studied 11 patients with typical heartburn from GORD. After being placed on omeprazole to suppress endogenous acid, these fasting subjects underwent oesophageal perfusions with graded doses of HCl at pH values of 1.0, 1.5, 2.0, and 2.5. Oesophageal perfusions were conducted while the duodenum was perfused with saline (control) and again with fat at 8 g/h. RESULTS: Time to onset, intensity, and severity of heartburn varied with dose of oesophageal acid (p<0.01). Time to onset was significantly (p<0.01) shorter, and intensity and severity of heartburn significantly (p<0.05) greater, during duodenal perfusion with fat. CONCLUSION: We conclude that duodenal fat intensifies the perception of heartburn.

Adult↗
PubMed2001

V. Stress and irritable bowel syndrome.

Different types of stress play important roles in the onset and modulation of irritable bowel syndrome (IBS) symptoms. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional, and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility and secretion and in alterations in the perception of visceral events. Functional brain imaging techniques are beginning to identify brain circuits involved in the perceptual alterations. Animal models have recently been proposed that mimic key features of the human syndrome.

Animals↗
PubMed2001

Basic pathophysiologic mechanisms in irritable bowel syndrome.

Converging evidence supports the concept that the irritable bowel syndrome (IBS) symptom complex results from altered regulation of gastrointestinal motility and epithelial function, as well as an altered perception of visceral events. Despite similar symptoms, there is likely heterogeneity of underlying dysfunction and pathogenesis in different subgroups of IBS patients: the syndrome may be produced by primary alterations in the central nervous system (CNS; top down model), or by primary alterations in the periphery (bottom up model), or by a combination of both. One plausible mechanism by which alterations in the CNS result in symptoms, is the enhanced responsiveness of central stress/emotion circuits. The physiological effects of psychological and physical stressors on gut function and brain-gut interactions are mediated by outputs of the emotional motor system in terms of autonomic, neuroendocrine, attentional and pain modulatory responses. IBS patients show an enhanced responsiveness of this system manifesting in altered modulation of gastrointestinal motility, secretion, immune function and in alterations in the perceptual and emotional response to visceral events.

Animals↗
PubMed2001

Depression, anxiety, and the gastrointestinal system.

Functional disorders of the digestive system, such as irritable bowel syndrome, are often associated with affective disorders, such as depression, anxiety, panic, and posttraumatic stress disorder (PTSD). Some of these associations are observed not only in clinical populations, but also in population-based samples, suggesting a relationship with pathophysiologic mechanisms underlying both gastrointestinal (GI) dysfunction and certain affective disorders. Sustained and acute life-threatening stressors play an important role in the onset and modulation of GI symptoms as well as in the development of affective disorders and PTSD. A neurobiological model is proposed that attempts to explain the development of visceral hypersensitivity, the neuroendocrine and autonomic dysfunction characteristic of functional GI disorders, as well as the overlap with affective disorders.

Anxiety Disorders↗
PubMed2000

Mechanical activation of dorsal root ganglion cells in vitro: comparison with capsaicin and modulation by kappa-opioids.

The aim of this study was to characterize plasma membrane pathways involved in the intracellular calcium ([Ca(2+)](i)) response of small DRG neurons to mechanical stimulation and the modulation of these pathways by kappa-opioids. [Ca(2+)](i) responses were measured by fluorescence video microscopy of Fura-2 labeled lumbosacral DRG neurons obtained from adult rats in short-term primary culture. Transient focal mechanical stimulation of the soma, or brief superfusion with 300 nM capsaicin, resulted to [Ca(2+)](i) increases which were abolished in Ca(2+)-free solution, but unaffected by lanthanum (25 microM) or tetrodotoxin (10(-6) M). 156 out of 465 neurons tested (34%) showed mechanosensitivity while 55 out of 118 neurons (47%) were capsaicin-sensitive. Ninty percent of capsaicin-sensitive neurons were mechanosensitive. Gadolinium (Gd(3+); 250 microM) and amiloride (100 microM) abolished the [Ca(2+)](i) transient in response to mechanical stimulation, but had no effect on capsaicin-induced [Ca(2+)](i) transients. The kappa-opioid agonists U50,488 and fedotozine showed a dose-dependent inhibition of mechanically stimulated [Ca(2+)](i) transients but had little effect on capsaicin-induced [Ca(2+)](i) transients. The inhibitory effect of U50,488 was abolished by the kappa-opioid antagonist nor-Binaltorphimine dihydrochloride (nor-BNI; 100 nM), and by high concentrations of naloxone (30-100 nM), but not by low concentrations of naloxone (3 nM). We conclude that mechanically induced [Ca(2+)](i) transients in small diameter DRG somas are mediated by influx of Ca(2+) through a Gd(3+)- and amiloride-sensitive plasma membrane pathway that is co-expressed with capsaicin-sensitive channels. Mechanical-, but not capsaicin-mediated, Ca(2+) transients are sensitive to kappa-opioid agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

The evolving neurobiology of gut feelings.

The bi-directional communication between limbic regions and the viscera play a central role in the generation and expression of emotional responses and associated emotional feelings. The response of different viscera to distinct, emotion-specific patterns of autonomic output is fed back to the brain, in particular to the cingulofrontal convergence region. Even though this process unfolds largely without conscious awareness, it plays an important role in emotional function and may influence rational decision making in the healthy individual. Alterations in this bi-directional process such as peripheral pathologies within the gut or alterations at the brain level may explain the close association between certain affective disorders and functional visceral syndromes.

Animals↗
PubMed2000

Differences in somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia.

BACKGROUND: Irritable bowel syndrome (IBS) and fibromyalgia (FM) are considered chronic syndromes of altered visceral and somatic perception, respectively. Because there is a significant overlap of IBS and FM, shared pathophysiological mechanisms have been suggested. Although visceral perception has been well studied in IBS, somatic perception has not. AIMS: To compare hypervigilance and altered sensory perception in response to somatic stimuli in patients with IBS, IBS+FM, and healthy controls. METHODS: Eleven IBS females (mean age 40), 11 IBS+FM females (mean age 46), and ten healthy female controls (mean age 39) rated pain perception in response to pressure stimuli administered to active somatic tender points, non-tender control points and the T-12 dermatome, delivered in a predictable ascending series, and delivered in an unpredictable randomized fashion (fixed stimulus). RESULTS: Although IBS patients had similar pain thresholds during the ascending series compared with controls, they were found to have somatic hypoalgesia with higher pain thresholds and lower pain frequency and severity during fixed stimulus series compared with IBS+FM patients and controls (P<0.05). Patients with IBS+FM were more bothered by the somatic stimuli and had somatic hyperalgesia with lower pain thresholds and higher pain frequency and severity. CONCLUSIONS: Both hypervigilance and somatic hypoalgesia contribute to the altered somatic perception in IBS patients. Co-morbidity with FM results in somatic hyperalgesia in IBS patients.

Adult↗
PubMed2000

Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism.

Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 and, by unknown mechanisms, induce widespread inflammation. We found that a large proportion of primary spinal afferent neurons, which express proteinase-activated receptor 2, also contain the proinflammatory neuropeptides calcitonin gene-related peptide and substance P. Trypsin and tryptase directly signal to neurons to stimulate release of these neuropeptides, which mediate inflammatory edema induced by agonists of proteinase-activated receptor 2. This new mechanism of protease-induced neurogenic inflammation may contribute to the proinflammatory effects of mast cells in human disease. Thus, tryptase inhibitors and antagonists of proteinase-activated receptor 2 may be useful anti-inflammatory agents.

Animals↗
PubMed2000

Gender differences in regional brain response to visceral pressure in IBS patients.

In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed.

Adult↗
PubMed2000

The impact of irritable bowel syndrome on health-related quality of life.

BACKGROUND & AIMS: Few data are available to evaluate health-related quality of life (HRQOL) of people with irritable bowel syndrome (IBS). We evaluated and compared the impact of IBS on HRQOL using previously reported HRQOL data for the U.S. general population and for people with selected chronic diseases. METHODS: Using the SF-36 Health Survey, we compared the HRQOL of IBS patients (n = 877) with previously reported SF-36 data for the general U.S. population and for patients with gastroesophageal reflux disease (GERD), diabetes mellitus, depression, and dialysis-dependent end-stage renal disease (ESRD). RESULTS: On all 8 SF-36 scales, IBS patients had significantly worse HRQOL than the U.S. general population (P < 0. 001). Compared with GERD patients, IBS patients scored significantly lower on all SF-36 scales (P < 0.001) except physical functioning. Similarly, IBS patients had significantly worse HRQOL on selected SF-36 scales than patients with diabetes mellitus and ESRD. IBS patients had significantly better mental health SF-36 scale scores than patients with depression (P < 0.001). CONCLUSIONS: IBS patients experience significant impairment in HRQOL. Decrements in HRQOL are most pronounced in energy/fatigue, role limitations caused by physical health problems, bodily pain, and general health perceptions. These data offer further insight into the impact of IBS on patient functional status and well-being.

Adult↗