Search PubMed⌕ Search

Biomedical subjects

E A Mayer

Publications and source records attributed to E A Mayer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Correlation of symptom criteria with perception thresholds during rectosigmoid distension in irritable bowel syndrome patients.

OBJECTIVE: Due to a lack of reliable biological markers, the diagnosis of irritable bowel syndrome (IBS) is based on symptom criteria. The possible physiological correlates of these criteria are not known. Our aims were to identify correlations of currently used IBS symptom criteria with distinct alterations in visceral perception. METHODS: Forty-two IBS patients (51% women) with a mean age of 39.5+/-1.4 yr, were included; 64% of patients were recruited from advertisement and 36% were clinic referrals. Patients completed a bowel symptom questionnaire, which included the Rome criteria and symptom severity ratings. Rectal discomfort thresholds were evaluated in all patients and in 19 controls, using a nonbiased tracking protocol consisting of phasic rectal balloon distensions before (PreTh) and after (PostTh) repetitive, high-pressure sigmoid distensions. We assessed the effect of each Rome criteria and symptom severity on PreTh and PostTh. RESULTS: IBS symptom severity was reported as moderate in 38.1% and as severe in 61.9% of patients. Overall, lower thresholds were observed in IBS patients than in controls (PreTh: 28.2+/-1.7 vs. 36.3+/-2.8 mm Hg, p<0.05; PostTh: 25.3+/-1.5 vs. 34.2+/-2.7 mm Hg, p<0.01). When assessing the effect of Rome criteria on rectal thresholds, we found that patients with hard/lumpy stools had lower thresholds than those without them, whereas patients with loose watery stools had higher thresholds than those who lacked them (both p<0.05). The lowering of rectal discomfort thresholds after sigmoid stimulation was observed regardless of the presence or absence of any Rome criteria or symptom severity. CONCLUSION: Although a decrease in rectal discomfort thresholds after sigmoid stimulation is seen in IBS regardless of specific symptoms, baseline and postsigmoid stimulation thresholds are lower in IBS patients with constipation-related symptoms.

Adult↗
PubMed2000

Sleep disturbances in clinic patients with functional bowel disorders.

OBJECTIVE: Sleep deprivation can lower visceral perception thresholds and nonregenerative sleep has been implicated as an etiological factor in chronic hyperalgesia syndromes. The aims of our study were to quantify the self-reported prevalence and type of sleep disturbances in patients with different functional bowel disorders (FBD) and to determine if this prevalence is related to involvement of the upper or lower gastrointestinal (GI) tract, perceived disease severity, or psychological comorbidity. METHODS: We enrolled 505 new FBD patients from an academic referral center specializing in functional GI disorders and 247 community based healthy controls. All patients and controls were prospectively evaluated by validated bowel symptom and sleep questionnaires. A psychological profile was obtained by SCL-90R. RESULTS: We found that 68% of functional dyspepsia (FD), 71.2% of irritable bowel syndrome (IBS)+FD, 50.2% of IBS, and 55.1% of the normal subjects reported having sleep disturbances. Waking up repeatedly during the night and waking up in the morning feeling tired or not rested were the most commonly reported sleep patterns; 57.2% of the patients reported that their abdominal ache awakened them from sleep during the night. Self-reported sleep disturbance was directly related to the perceived intensity of GI symptoms. Self-reported sleep disturbances were equally common in both male (57%) and female (58.4%) FBD patients. There was no significant difference between the mean anxiety and depression scores between patients with and without sleep dysfunction. CONCLUSIONS: FD patients, but not IBS patients, reported sleep disturbances more frequently than healthy control subjects. Abdominal pain or discomfort that awaken FBD patients from sleep during the night were common, and thus a poor discriminating factor between organic and functional disorders.

Abdominal Pain↗
PubMed2000

Perceptual responses in patients with inflammatory and functional bowel disease.

BACKGROUND AND AIMS: Enhanced visceral sensitivity following a transient inflammatory process in the gut has been postulated as an aetiological mechanism of irritable bowel syndrome (IBS). In this study we compared perceptual responses to rectosigmoid distension in patients with mild chronic inflammation of the rectum (ulcerative colitis (UC)) and patients without mucosal inflammation (IBS) to determine if chronic low grade mucosal inflammation may be a plausible explanation for rectosigmoid hypersensitivity reported in both IBS and UC patients. METHODS: UC disease activity was quantified using activity index scores. Perception thresholds for discomfort during rectosigmoid distension were compared between 11 UC patients with quiescent or mild disease activity, 18 IBS patients, and 13 healthy controls. RESULTS: Although UC activity index scores negatively correlated with perceptual thresholds for discomfort (r=-0.76, p=0.016), UC patients had higher discomfort thresholds compared with IBS patients and controls before (p=0.02) and after (p<0.001) a noxious sigmoid conditioning stimulus. CONCLUSIONS: Rectal perception was attenuated in UC but enhanced in IBS. In chronic mild inflammation, activation of antinociceptive mechanisms may prevent the development of visceral hyperalgesia. Low grade mucosal inflammation alone is unlikely to be responsible for symptoms in functional gastrointestinal disorders.

Adult↗
PubMed1999

Measurement of symptoms in irritable bowel syndrome clinical trials.

Irritable bowel syndrome (IBS) is a chronic disorder with symptoms that range in intensity from mild and infrequent to severe and continuous. A variety of approaches to symptom assessment are used in IBS, although there is little literature directly comparing or validating them. Determining the presence or absence of specific symptoms is the primary focus of diagnostic evaluation and categorization. In contrast, outcome assessment usually entails assessment of symptom severity. Symptom severity scales can themselves vary on a wide range of factors, including specificity (pain, discomfort, gastrointestinal problem), scaling properties (numerical, analogue, or descriptor), range (usual, highest, lowest), time frame (now, past week), response category (intensity, unpleasantness, change, relief), and use of modifying variables (frequency, impact, location). The measurement properties of similar symptom scales have been investigated more extensively in the context of somatic pain, and these studies will be reviewed in suggesting some guidelines for IBS symptom assessment in clinical trials.

Colonic Diseases, Functional↗
PubMed1999

Emerging disease model for functional gastrointestinal disorders.

In response to perceived or experienced change that is considered threatening to the individual, the central nervous system mounts a stereotypic response that decreases the sensitivity to pain, modulates the autonomic nervous system outflow, and activates the hypothalamic-pituitary-adrenal (HPA) axis. This response of the "emotional motor system" may or may not be associated with the conscious experience of feelings of fear or anxiety. Alterations in these response systems (either up- or downregulation) may produce symptoms, such as viscero-somatic hypersensitivity, altered bowel habits, or increased anxiety.

Colonic Diseases, Functional↗
PubMed1999

Internalization of mu-opioid receptors in rat spinal cord slices.

Cells immunoreactive for the mu-opioid receptor (MOR) in laminae I-II of the spinal cord were identified as small neurons with rostro-caudal dendrites. In spinal cord slices, [D-Ala2,MePhe4-Gly-ol5]enkephalin (DAMGO) or etorphine (1 microM) caused naloxone-sensitive MOR endocytosis in 100% of these neurons, whereas the selective delta- and kappa-opioid agonists [D-Pen2,5]enkephalin (DPDPE) and spiradoline mesylate (U-62,066), respectively, produced negligible internalization at 1 microM. The EC50 for DAMGO was 30 nM, similar to its potency to inhibit cAMP accumulation and to increase [gamma-35S]GTP binding. MOR internalization followed an exponential timecourse with a half-life of 1.7 min. MOR internalization in spinal cord slices was faster and occurred at lower agonist concentrations than in MOR-transfected cells, suggesting that spinal cord neurons have a more effective coupling of MORs to intracellular components mediating endocytosis.

Animals↗
PubMed1999

Involvement of stretch-sensitive calcium flux in mechanical transduction in visceral afferents.

The spinal and vagal visceral innervation to the gastrointestinal tract contains mechanosensitive afferents that are activated by contraction, distension of smooth muscle or movement in the receptive field. The mechanism by which free nerve endings detect changes in smooth muscle tension is not clear. The present study investigated the effects of mechanical stimulation on dorsal root ganglion neurons in vitro. Neurons were cultured using standard techniques and used in experiments after 24-72 h. Intracellular calcium [Ca2+]i was visualized using a video microscopic technique (Attoflour) in Fura-2 loaded neurons. DRG neurons innervating the stomach or colon were identified by the presence of a retrograde tracer, dextran-conjugated Texas Red, injected into the visceral wall 14-28 days previously. Increases in [Ca2+]i were measured in response to transient (0.5 s) mechanical stimulation of the cell soma using a flame polished probe. Approximately 25% of the whole population of DRG neurons (n = 199) were mechanosensitive, showing a transient rise in [Ca2+]i. In labeled afferents (n = 12), approximately 40% of neurons were mechanosensitive. The increase in [Ca2+]i in response to mechanical stimulation was reduced (100 microM) or abolished (250 microM) by superfusion with gadolinium or by removal of extracellular calcium. Cell somata of visceral spinal afferents show a stretch-sensitive calcium flux that may be involved in sensory transduction of mechanical stimuli that lead to autonomic and sensory reflexes.

Animals↗
PubMed1999

Differential effects of chemical and mechanical colonic irritation on behavioral pain response to intraperitoneal acetic acid in mice.

Abdominal contractions are a viscerosomatic reflex response to noxious colorectal irritation in rats. In this study we characterize the modulating effect of chemical and mechanical colonic irritation on this reflex response to peritoneal irritation induced by diluted acetic acid (HAc) in conscious C57BL/6N mice. Pain responses were scored by counting the number of abdominal contractions during the 30-min period after intraperitoneal (i.p.) injection of either vehicle or HAc. Abdominal contractions were induced by 0.6% but not by 0.3% HAc. Chemical irritation of the colon by intraluminal 25% turpentine did not produce abdominal contractions by itself, but significantly increased the effect of both 0.3 and 0.6% i.p. HAc, administered 60 min after the luminal stimulus. Mechanical stimulation of the anorectum and colon by insertion of a balloon did not modify the effect of 0.6% HAc, while the insertion plus the inflation to 0.1 and 0.2 ml (30 s on/30 s off for 10 min) reduced the response to i.p. HAc by 35 and 88%, respectively. This inhibitory effect was reversed by naloxone (5 mg/kg, s.c.) pretreatment, while naloxone alone did not modify the effect of 0.6% HAc. These results demonstrate that chemical irritation of visceral afferents in the colonic mucosa and peritoneum of mice interact to enhance viscerosomatic pain responses, while the activation of colonic mechanoreceptors inhibits peritoneal irritation-induced pain responses and induces a freezing behavior by a naloxone-sensitive mechanism.

Abdominal Muscles↗
PubMed1999

Common functional gastrointestinal disorders: nonulcer dyspepsia and irritable bowel syndrome.

Up to 35% of the world population suffer from functional gastrointestinal disorders (FGD), accounting for about 40% of gastroenterologic and 12% of primary care practice. Society incurs high costs from FGD morbidity in terms of medical workups and absenteeism from work. FGD are characterized by chronic and recurrent symptoms of the gastrointestinal (GI) tract without detectable structural or biochemical abnormalities. In the absence of universal biologic markers, the diagnosis is based on consensus symptom criteria (1). This chapter reviews current knowledge of the pathophysiology and provides a practical approach to patients with functional dyspepsia and irritable bowel syndrome, 2 of the most common functional GI syndromes.

Algorithms↗
PubMed1999

Review article: gender-related differences in functional gastrointestinal disorders.

Many functional gastrointestinal disorders and other chronic visceral pain disorders such as interstitial cystitis and chronic pelvic pain are more common in women than in men. In irritable bowel syndrome (IBS) there is a 2:1 female to male ratio in prevalence of symptoms in community samples. Female irritable bowel syndrome patients are more likely to be constipated, complain of abdominal distension and of certain extracolonic symptoms. While animal studies have clearly demonstrated gender-related differences in pain perception and antinociceptive mechanisms, unequivocal evidence for gender-related differences in human pain perception or modulation has only been provided recently. Gender-related differences may be related to constant differences in the physiology of pain perception, such as structural or functional differences in the visceral afferent pathways involved in pain transmission or modulation, and/or they may be related to fluctuations in female sex hormones. Preliminary evidence suggests that female irritable bowel syndrome patients show specific perceptual alterations in regards to rectosigmoid balloon distension and that they show differences in regional brain activation measured by positron emission tomography. This preliminary evidence suggests that gender-related differences in symptoms and in the perceptual responses to visceral stimuli exist in IBS patients and can be detected using specific stimulation paradigms and neuroimaging techniques.

Animals↗
PubMed1999

Improvement in pain and bowel function in female irritable bowel patients with alosetron, a 5-HT3 receptor antagonist.

BACKGROUND: No currently available treatment provides consistent relief of irritable bowel syndrome. Colonic sensory and motor function are modulated partly through 5HT3-receptors. AIM: To evaluate effects of the 5HT3-receptor antagonist, alosetron, in irritable bowel syndrome. METHODS: Randomized, double-blind, placebo-controlled, dose-ranging (1, 2, 4, 8 mg b.d. alosetron), 12-week trial in 370 patients with diarrhoea-predominant or alternating constipation and diarrhoea irritable bowel syndrome. Weekly measurement of adequate relief was the key end-point; other irritable bowel syndrome symptoms were collected daily using an electronic phone system. RESULTS: Alosetron (1 mg or 2 mg b.d.) significantly (P < 0.05 vs. placebo) increased the proportion of females, but not males, reporting adequate relief. Stool consistency, frequency and percentage days with urgency improved over placebo (P < 0.05) within the first month with all doses of alosetron, and persisted throughout the trial with all doses in female patients. With 1 mg b.d. alosetron, females had improved stool consistency and urgency within the first week, and adequate relief and improved stool frequency within the first 2 weeks. There was no consistent improvement in bowel function among male patients. CONCLUSION: In female irritable bowel syndrome patients with predominant diarrhoea or alternating constipation and diarrhoea, alosetron is effective in treatment of abdominal pain and discomfort and bowel-related symptoms.

Abdominal Pain↗
PubMed1999

Impact of advertisement and clinic populations in symptoms and perception of irritable bowel syndrome.

BACKGROUND: This study assessed the impact of recruitment on irritable bowel syndrome clinical trials, by determining whether irritable bowel syndrome patients recruited from advertisement or a specialty clinic differ in clinical and physiologic measures. METHODS: We prospectively surveyed 657 irritable bowel syndrome patients who either: (i) were referred from a functional bowel disease clinic (52%); or (ii) responded to advertisement for clinical trials (48%), using questionnaires about bowel and psychological symptoms, and quality of life. In a subset of 42 irritable bowel syndrome patients (29 advertisement and 15 clinic patients), rectal discomfort thresholds were measured before and after repetitive sigmoid stimulation. RESULTS: While the advertisement population more commonly consulted primary care physicians, the clinic population more commonly consulted gastroenterologists. The clinic population reported more prevalent and severe abdominal pain, and higher psychological symptom scores, while the advertisement population had greater quality of life. In the visceral perception studies, both subgroups were hypersensitive to rectal distension. CONCLUSION: Compared to the clinic population, the advertisement population had less severe abdominal pain and psychological symptoms, better quality of life but similar visceral perception. The differences in clinical self-reports may have consequences for enrolment of these different patient populations into clinical trials.

Adult↗