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Biomedical subjects

E A Mayer

Publications and source records attributed to E A Mayer.

At least 19 recordsLinked to original sources
PubMed1996

Symptom duration in patients with irritable bowel syndrome.

OBJECTIVES: The etiology and natural history of irritable bowel syndrome (IBS) is poorly understood. We compared rectal sensory thresholds and compliance, SCL-90 scores, and follow-up questionnaires among normal controls, patients with longstanding ( > 5 y) disease (L-IBS), and patients with recent onset ( > 2 y) disease (R-IBS). The onset of symptoms in R-IBS was related to specific events such as infection (n = 10), surgery (n = 5), and stress (n = 4), but no specific event could be identified in six patients. METHODS: A diagnosis of IBS was made using Manning criteria ( > or = 3) and clinical grounds. Psychological data were obtained by psychometrics (SCL-90) scores. Rectal wall compliance and thresholds for the sensation of stool and discomfort were evaluated using the electronic barostat. RESULTS: The mean thresholds for phasic and ramp distention were similar for R-IBS and L-IBS groups for the perception of stool and discomfort. When compared with normals, the mean stool thresholds for phasic distention were significantly lower for L-IBS and R-IBS groups. SCL-90 scores were significantly increased in L-IBS in the mean phobia score (45 R-IBS vs 61 L-IBS), anxiety score (49 R-IBS vs 63 L-IBS), paranoia score (44 R-IBS vs 60 L-IBS), and hostility score (47 R-IBS vs 61 L-IBS) (all p < 0.05). On follow-up questionnaire, 60% of R-IBS versus 46% of L-IBS patients indicated that their symptoms had improved (p < 0.05). R-IBS patients also experienced fewer episodes of abdominal pain per week at follow-up than L-IBS patients (3.9 +/- 1.0 vs 8.5 +/- 1.7, respectively) (p < 0.05). CONCLUSIONS: Our findings suggest that IBS patients with short symptom duration and fewer psychological symptoms have a better prognosis than patients with a long history of IBS and associated psychological distress, although long term prospective studies are needed.

Adolescent↗
PubMed1995

Altered rectal perception is a biological marker of patients with irritable bowel syndrome.

BACKGROUND & AIMS: Lowered visceral perception thresholds have been suggested as a biological marker of irritable bowel syndrome (IBS). The current study sought to determine the prevalence of altered rectal visceral perception in patients with IBS and the correlation of altered perception thresholds with subjective symptoms. METHODS: Anorectal manometry and rectal perception thresholds to balloon distention were determined in 100 patients with IBS and 15 control subjects. Gastrointestinal and psychological symptoms were assessed by questionnaire. Perception thresholds and symptoms were reassessed after 3 months in 15 patients with IBS. RESULTS: Ninety-four percent of patients showed altered rectal perception in the form of lowered thresholds for aversive sensations (discomfort), increased intensity of sensations, or altered viscerosomatic referral. Hypersensitivity was found only for aversive sensations in response to rapid phasic distention; stool thresholds and thresholds in response to slow ramp distention were normal. Cluster analysis by physiological parameters identified three IBS subgroups with predominant patterns of symptoms. Longitudinal evaluation indicated a correlation between changes in perception thresholds and symptom severity. CONCLUSIONS: Because altered rectal perception is present in almost all patients with IBS and perception thresholds correlate with temporal changes in retrospective symptom severity, altered rectal perception represents a reliable biological marker of IBS.

Adult↗
PubMed1995

The effect of octreotide on human gastric compliance and sensory perception.

Somatostatin or its analogue octreotide (OCT) has previously been shown to modulate gastric emptying, intestinal motor activity and visceral sensation. In the current study we sought to determine the effect of a single dose of OCT (1.25 micrograms kg-1 s.c.), which has previously been shown to have both motor and sensory effects, on proximal gastric compliance and on conscious perception of gastric distention. Gastric distention was performed in 13 healthy male volunteers, by either slow ramp distention (60 ml min-1) or by intermittent pressure steps (phasic distention; 4-20 mmHg) using an electronic distention device. Compliance curves (pressure-volume relationship), and thresholds for innocuous (fullness) and noxious sensations (discomfort, pain) were determined following vehicle or OCT injection. OCT consistently and significantly reduced the rate of the gastric accommodation reflex by 50%, resulting in a reduced compliance at distention pressures greater than 10 mmHg during phasic distention. In contrast, no effect was observed on the compliance curve obtained during ramp distention. OCT selectively increased the threshold for fullness during both ramp and phasic distention. During phasic distention, OCT decreased the volume thresholds for noxious (pain) sensations experienced at volumes greater than 300 ml, without affecting the corresponding pressure threshold. These findings suggest that at low distension volumes, OCT in the dosage used has a direct inhibitory effect on afferents mediating innocuous gastric sensations. The hyperalgesic effect observed during phasic distention may be secondary to OCT's inhibitory effect on the gastric accommodation reflex.

Adult↗
PubMed1994

Reversal of megaduodenum and duodenal dysmotility associated with improvement in nutritional status in primary anorexia nervosa.

Anorexia nervosa is considered one type of eating disorder that may result in severe malnutrition. Patients with this disorder commonly complain of postprandial nausea, abdominal pain, and distension. We describe the radiologic and motility abnormalities associated with anorexia nervosa in a 21-year-old female. Barium gastrointestinal series demonstrated marked dilation of the duodenum, with prolongation of intestinal transit. A 4-hr fasting gastroduodenal motility study showed no propagating migrating motor complexes (MMC). Prolonged, but nonpropagating, bursts of high-amplitude phasic and tonic contractions were seen in the duodenum. In contrast, antral contractions were of low amplitude and esophageal motor function was normal. Metoclopramide and edrophonium caused an increase in gastroduodenal motor activity, but increased contractions were not associated with symptoms. Following a renutrition program that raised the patient's weight from 64 to 80% of her ideal body weight, the radiographic abnormalities and gastrointestinal dysmotility resolved completely. These observations suggest that anorexia-associated gastrointestinal motor dysfunctions are a consequence, not the cause of the generalized protein-calorie malnutrition associated with anorexia nervosa. The facts that motility in different parts of the gut is affected to different degrees and that gastric and duodenal muscle responds normally to exogenous stimulation argue against a generalized myogenic dysfunction and, rather, point to a reversible dysfunction of neural regulation.

Adult↗
PubMed1994

Basic and clinical aspects of visceral hyperalgesia.

Although physiological stimuli in the healthy gastrointestinal tract are generally not associated with conscious perception, chronic abdominal discomfort and pain are the most common symptoms resulting in patient visits with gastroenterologists. Symptoms may be associated with inflammatory conditions of the gut or occur in the form of so-called functional disorders. The majority of patients with functional disorders appear to primarily have inappropriate perception of physiological events and altered reflex responses in different gut regions. Recent breakthroughs in the neurophysiology of somatic and visceral sensation are providing a series of plausible mechanisms to explain the development of chronic hyperalgesia within the human gastrointestinal tract. A central concept to all these mechanisms is the development of hyperexcitability of neurons in the dorsal horn, which can develop either in response to peripheral tissue irritation or in response to descending influences originating in the brainstem. Taking clinical characteristics and the concept of central hyperexcitability into account, a model is proposed by which abdominal pain from chronic inflammatory conditions of the gut and functional bowel disorders such as noncardiac chest pain, nonulcer dyspepsia, and irritable bowel syndrome could develop by multiple mechanisms either alone or in combination.

Animals↗
PubMed1994

Evidence for the hypersensitivity of lumbar splanchnic afferents in irritable bowel syndrome.

BACKGROUND/AIMS: The pathways underlying rectal hypersensitivity to balloon distention in patients with irritable bowel syndrome (IBS) are not known. The aim of this study was to characterize the involvement of sacral and thoracolumbar afferents in the perception of rectal distention. METHODS: Rectal balloon distention was performed in 15 normal control subjects, 6 patients with spinal cord injury, and 50 patients with IBS using a slow-volume ramp (40 mL/min) or rapid phasic step distension. Additional studies were performed in the presence of 2% intrarectal lidocaine. RESULTS: Patients with spinal cord injury with lesions below T7 reported sensations only during phasic distention. Sixty percent of patients with IBS (n = 50) were hypersensitive for discomfort during phasic distention, whereas only 4% were hypersensitive during ramp distention. Less than 15% of patients were hypersensitive for the sensation of stool. In normal patients, lidocaine increased thresholds in response to slow ramp distention by 40%-70% but had no effect on perception in response to other types of distention. Lidocaine had no effect on (1) thresholds in response to either ramp or phasic distention in normosensitive or hypersensitive patients with IBS or (2) the rate of receptive relaxation or rectal compliance in any group. CONCLUSIONS: Rapid phasic distention preferentially stimulates splanchnic afferents. Hypersensitivity of these afferents in patients with IBS is unaffected by mucosally applied lidocaine.

Adult↗
PubMed1994

Sleep and duodenal motor activity in patients with severe non-ulcer dyspepsia.

The prevalence of sleep disturbances was studied in patients with severe non-ulcer dyspepsia. It was also considered if the change in sleep pattern was associated with changes in the rhythmic fasting motor activity of the gastrointestinal tract, and if motor events correlate with the patient's symptoms. Motor activity in the duodenum was monitored over a 24 hour period under freely ambulatory conditions in 10 healthy controls and in 10 patients with severe non-ulcer dyspepsia using a transnasally placed catheter with six solid state pressure transducers connected to a digital data logging device. Symptoms and sleep disturbance were assessed by questionnaire and diary. Based on their symptoms, the patients were separated into two groups: those with dyspepsia symptoms only (non-ulcer dyspepsia; n = 5) and those with dyspepsia and additional functional symptoms thought to arise from the lower gastrointestinal tract (non-ulcer dyspepsia+irritable bowel syndrome; n = 5). When compared with either the control or the non-ulcer dyspepsia+irritable bowel syndrome group, non-ulcer dyspepsia patients had a considerably decreased number of migrating motor complexes during the nocturnal period (0.7 v 4.6), a decreased percentage of nocturnal phase I (5.2% v 78.0%), and an increased percentage of the nocturnal period in phase II (94% v 15.4%). Patients with non-ulcer dyspepsia+irritable bowel syndrome were not different from normal controls. Four of the non-ulcer dyspepsia patients and all of the non-ulcer dyspepsia+irritable bowel syndrome patients reported difficulties with sleep. Clusters of high amplitude tonic and phasic activity, not accompanied by subjective reports of discomfort were noted in several patients in both groups during the study. In eight of 10 patients, abdominal pain was reported during normal motor activity, while in one patient, pain correlated with phase III of the migrating motor complex. In contrast with previous reports in patients with irritable bowel syndrome, our findings suggest an abnormality of diurnal rhythmicity--shown in changed sleep and changed rhythmic duodenal motor activity--in patients with chronic abdominal pain thought to arise from the upper gastrointestinal tract.

Abdominal Pain↗
PubMed1993

VIP modulates intracellular calcium oscillations in human lymphoblasts.

Vasoactive intestinal polypeptide (VIP) has been shown to stimulate adenylate cyclase in a human lymphoblast cell line (MOLT 4). In the present study, we monitored fluorescence in cell suspensions and in single fura-2 loaded MOLT 4 lymphoblasts to determine if VIP modulates intracellular calcium concentrations ([Ca2+]i), and if this modulation is mediated by adenylate cyclase. The distribution of [Ca2+]i in resting and stimulated cells was non-homogeneous, with gradients of high [Ca2+]i present in the subplasmalemmal space. In a subset of cells (10-30% of all cells studied), [Ca2+]i showed La(3+)-sensitive, temporal changes in the form of [Ca2+]i oscillations with a baseline [Ca2+]i value of 115 +/- 10 nM, an oscillation amplitude of 150 +/- 18 nM and a mean period of 9.2 +/- 2 s. The remaining non-oscillating cells showed a constant [Ca2+]i level of 75 +/- 5 nM (n = 65 cells from 4 experiments). In the subset of cells with spontaneous [Ca2+]i oscillations, VIP dose-dependently (10(-12) to 10(-8) M) increased the amplitude of oscillations but did not stimulate their frequency. The stimulatory effect of VIP was correlated with baseline [Ca2+]i in these cells, was attenuated in the presence of La3+ (25 microM), but was unaffected by cell depolarization (126 mM KCl). Dibutyryl cyclic AMP (10(-4) to 10(-3) M) and forskolin (10(-4) M) had no effect on [Ca2+]i oscillations, or on [Ca2+]i in cells without oscillations. In cell suspensions, baseline [Ca2+]i was found to be 55.1 +/- 11.2 nM (mean +/- S.E.M., n = 11); VIP, cyclic AMP analogues or forskolin had no significant effect on [Ca2+]i. These findings suggest that: a) VIP modulates the amplitude of [Ca2+]i oscillations generated by a cytosolic [Ca2+] oscillator in a subset of cells at a concentration of 10(-12) M, a thousand-fold below the KD for the VIP receptor; b) baseline [Ca2+] values may be related to both the ability of cells to generate spontaneous [Ca2+] oscillations and of oscillating cells to respond to VIP; c) due to the small number of responding cells, VIP-induced [Ca2+]i changes are not detectable when studied in cell suspensions.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Gastroenterologic causes of chronic pelvic pain.

A large proportion of women with chronic pelvic pain can be found to have gastrointestinal disorders, either pathologic or functional. The location of referred pain from the gastrointestinal tract overlaps that of the reproductive organs. An awareness of the differential diagnosis, a knowledge of the common presentations of gastrointestinal disorders, a thorough history that includes an appropriate discussion of gastrointestinal symptoms, and a relevant examination will ensure that gastrointestinal diagnoses are not overlooked.

Chronic Disease↗
PubMed1992

Spatial and temporal patterns of intracellular calcium in colonic smooth muscle.

Intracellular calcium [Ca2+]i measurements in cell suspension of gastrointestinal myocytes have suggested a single [Ca2+]i transient followed by a steady-state increase as the characteristic [Ca2+]i response of these cells. In the present study, we used digital video imaging techniques in freshly dispersed myocytes from the rabbit colon, to characterize the spatiotemporal pattern of the [Ca2+]i signal in single cells. The distribution of [Ca2+]i in resting and stimulated cells was nonhomogeneous, with gradients of high [Ca2+]i present in the subplasmalemmal space and in one cell pole. [Ca2+]i gradients within these regions were not constant but showed temporal changes in the form of [Ca2+]i oscillations and spatial changes in the form of [Ca2+]i waves. [Ca2+]i oscillations in unstimulated cells (n = 60) were independent of extracellular [Ca2+] and had a mean frequency of 12.6 +/- 1.1 oscillations per min. The baseline [Ca2+]i was 171 +/- 13 nM and the mean oscillation amplitude was 194 +/- 12 nM. Generation of [Ca2+]i waves was also independent of influx of extracellular Ca2+. [Ca2+]i waves originated in one cell pole and were visualized as propagation mostly along the subplasmalemmal space or occasionally throughout the cytoplasm. The mean velocity was 23 +/- 3 microns per sec (n = 6). Increases of [Ca2+]i induced by different agonists were encoded into changes of baseline [Ca2+]i and the amplitude of oscillations, but not into their frequency. The observed spatiotemporal pattern of [Ca2+]i regulation may be the underlying mechanism for slow wave generation and propagation in this tissue. These findings are consistent with a [Ca2+]i regulation whereby cell regulators modulate the spatiotemporal pattern of intracellularly generated [Ca2+]i oscillations.

Animals↗
PubMed1991

Neurokinin receptor-mediated regulation of [Ca]i and Ca-sensitive ion channels in mammalian colonic muscle.

In conclusion, these findings suggest the following: (1) NK receptor activation results in [Ca2+]i oscillations; (2) the receptor-mediated [Ca2+]i increase is partially due to influx of Ca2+ through L-type Ca2+ channels and partially to release from intracellular stores; (3) the receptor-mediated depolarization results from activation of a Cl- channel at the cell resting potential; (4) NK receptor-mediated release of [Ca2+]i may play a role in Cl- channel activation; (5) there is no evidence for multiple NK receptor types involved in cell activation.

Animals↗
PubMed1991

Can regulatory peptides be regarded as words of a biological language.

Despite the complexities of individual systems, neurocrine, endocrine, and growth factor-mediated signaling systems show striking similarities in the molecules they use for communication and in their signal-transduction mechanisms. In contrast to the traditional view in cell biology, which has focused on the regulatory aspects of neurocrine and endocrine messengers and growth factors, an analysis of various aspects of peptidergic cell-to-cell communication on the basis of information theory is suggested. According to theorems for efficient and error-free encoding, the differences in rate and distance of information transfer and in noise interference between neurocrine, endocrine, and growth factor-mediated messages require different encoding strategies. These differences are reflected in the use of plurichemical transmission (to increase information content) or in the number and sequence of amino acids within peptide molecules (to protect against noise interference). In contrast to the quantitative information content, the qualitative information of the messages is not transmitted but is retrieved when the message interacts with transduction networks at the receiver cell. The semantic information is contained within the rules specifying the conditional co-occurrences of signals. The suggested analysis provides a framework for the understanding of various aspects of cell-to-cell communication, such as structure-function relationship of regulatory peptides, multiple receptor subtypes, plurichemical transmission, and transduction networks. The data discussed are consistent with the role of regulatory peptides as signals in a universal structured code for biological communication.

Animals↗
PubMed1990

Role of visceral afferent mechanisms in functional bowel disorders.

This report analyzes the clinical and physiological evidence supporting a role for altered visceral afferent mechanisms in the pathogenesis of two functional bowel syndromes: noncardiac chest pain and the irritable bowel syndrome. Considerable recent evidence indicates that increased contractility is present only in a minority of patients and that hypercontractile episodes are not temporally related to abdominal pain. In contrast, altered sensation and motor reflexes in response to physiological stimuli, such as mechanical distention or acid, is common when appropriately investigated. The vagal and spinal afferent innervation mediates visceral sensation and is involved in multiple reflex loops regulating gastrointestinal effector function, such as motility and secretion. Sensory input can be modulated peripherally at the afferent nerve terminal, at the level of prevertebral ganglia, the spinal cord, and the brainstem. An up-regulation of afferent mechanisms would result both in altered conscious perception of physiological stimuli and in altered motor reflexes. Current evidence is consistent with an alteration in the peripheral functioning of visceral afferents and/or in the central processing of afferent information in the etiology of altered somatovisceral sensation and motor function observed in patients with functional bowel disease.

Afferent Pathways↗
PubMed1990

The activation of calcium and calcium-activated potassium channels in mammalian colonic smooth muscle by substance P.

1. The regulation of Ca2(+)-activated K+ channels by the agonist substance P in freshly dissociated smooth muscle cells from the rabbit longitudinal colonic muscle was characterized using the patch clamp technique. 2. In the cell-attached recording mode, when pipette and bath solutions contained equal [K+] (126 mM), the Ca2(+)-activated K+ channels showed a linear current-voltage relationship (between -50 mV and 50 mV) with a slope conductance of 210 +/- 35 pS (n = 12). Reversal potential measurements indicated that the channel was highly selective for K+ over Na+ (PK/PNa = 110). 3. Channels were activated by depolarizing membrane voltages and cytosolic Ca2+, and in inside-out patches channel activation depended sigmoidally on voltage and [Ca2+]. The potential for half-activation at a cytosolic [Ca2+] of 5 x 10(-6) M was 0 mV. A tenfold increase in cytosolic Ca2+ resulted in a 60 mV shift of the sigmoidal voltage activation curve to more negative potentials. 4. Threshold concentrations of substance P (10(-12) M), which did not result in cell contraction, caused a prolonged activation of K+ channels. The K+ channels were observed to open in clusters: simultaneous opening of multiple channels was interrupted by complete, prolonged channel closure. 5. Lowering bath [Ca2+] to submicromolar concentrations abolished the effect of substance P. The activation of K+ channels by substance P (10(-12) M) was also inhibited by the dihydropyridine nifedipine (10(-6) M), a blocker of L-type Ca2+ channels. 6. In the whole-cell recording mode, with the pipette solution containing 126 mM-KCl, 0.77 mM-EGTA and 1 mM-ATP, depolarization from a holding potential of -70 mV elicited outward currents which increased to steady-state values. These were K+ currents as they were blocked by TEA (tetraethylammonium, 30 mM) and Ba2+ (1 mM) and were abolished when pipette K+ was replaced by Cs+. 7. The depolarization-activated outward current was not affected by lowering extracellular [Ca2+] or by the Ca2+ channel antagonists Cd2+ (200 microM), nifedipine (10(-6)-10(-5) M) or verapamil (10(-6) M). The current was greatly reduced when the EGTA concentration in the pipette solution was increased from 0.77 to 10 mM. 8. When the pipette solution contained CsCl, membrane depolarization activated inward currents. The peak inward current was identified as current through L-type Ca2+ channels based on its voltage- and time-dependent kinetics, and its modulation by dihydropyridines.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Neurokinin inhibition of cholinergic myenteric neurons in canine antrum.

Neurokinins regulate gastrointestinal motility by interacting with receptors on both muscle layers and on myenteric plexus neurons. To determine if specific neurokinin (NK) receptor agonists can mediate inhibitory effects on myenteric neurons, we studied the effect of the NK-1 agonist substance P methylester (SPME) and the putative endogenous NK-2 receptor ligand neurokinin A (NKA) on [3H]acetylcholine [( 3H]ACh) release induced by electrical field stimulation from muscle strips cut from the canine gastric antrum. SPME but not NKA caused a dose-dependent inhibition of stimulated [3H]ACh release in tissues containing the myenteric plexus. The inhibition was not seen in longitudinal muscle without myenteric plexus. Pretreatment of tissues with indomethacin or antiserum to vasoactive intestinal polypeptide (VIP) but not naloxone or adrenergic or cholingergic blockade abolished the SPME-induced inhibition. Exogenous VIP stimulated the release of prostaglandin E2 (PGE2) from full thickness strips, and both VIP and PGE2 inhibited [3H]ACh release induced by electrical depolarization. These findings suggest that NK-1 receptor agonists can selectively inhibit stimulated [3H]ACh release and that this inhibition may involve the release of VIP and PGE2 from neurons within the myenteric plexus.

Acetylcholine↗
PubMed1990

Substance P and CGRP mediate motor response of rabbit colon to capsaicin.

Primary afferent nerve terminals located in the mammalian gut wall may play a role in region-specific modulation of gastrointestinal motility. In the present study, we sought to characterize the effect of neuropeptides released from these afferents by capsaicin (CAP) on contractile activity of smooth muscle from the distal rabbit colon. CAP caused a release of acetylcholine and immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) from the muscle coat. CAP caused a dose-dependent transient stimulation of longitudinal muscle contractions, followed by prolonged inhibition of spontaneous but not stimulated contractile activity. The initial stimulation was abolished by the SP antagonist spantide and by atropine. The inhibitory effect was reduced by repeated exposure of muscle to CGRP. The effect of CGRP on spontaneous contractions differed between longitudinal and circular muscle. In longitudinal muscle, a stimulation was preceded by a transient inhibition, whereas in circular muscle, only inhibition was seen. Both effects were resistant to tetrodotoxin. Repeated exposure of circular but not longitudinal muscle to CGRP resulted in a disappearance of the peptide's inhibitory effect. Exogenously applied CGRP was only a weak antagonist of contractions stimulated by SP and bethanechol. These findings suggest that in the rabbit colon at least the following two neuropeptides are released from CAP-sensitive nerve fibers: a neurokinin peptide from nerve terminals located within the myenteric plexus and CGRP from terminals probably located within the circular muscle layer.

Acetylcholine↗