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D L Wingate

Publications and source records attributed to D L Wingate.

At least 37 records · Page 2Linked to original sources
PubMed1995

Mathematic modelling of the enteric nervous network. 5. Excitation propagation in a planar neural network.

A mathematical model of the enteric nervous system (Auerbach's plexus) as a planar neural network has been developed, based on the actual morphological data of its organization. The network is composed of excitatory (cholinergic) and inhibitory (adrenergic) neurones interconnected by polysynaptic channels, formed of the geometrically non-uniform unmyelinated nerve axons. The synaptic zones are modelled as a three-compartment open pharmacokinetics system, i.e., presynaptic terminal, synaptic cleft and postsynaptic membrane where the pharmacokinetic mechanisms of electrochemical coupling are considered. All the chemical reactions of transformation of acetylcholine and adrenaline within them are described by first order Michaelis-Menten kinetics. The propagation of the electrical impulse along the pathways and in the vicinity of the nerve terminal is described by the modified Hodgkin-Huxley equations. The results of numerical simulation of the propagation of excitation within the neuronal chain, inhibitory feedback circuit, and a planar neuronal network under normal physiological conditions and after treatment with cholinergic/adrenergic agonists and antagonists are presented. The model predicts the dose-dependent influence of pharmacological agents on the neural network function.

Action Potentials↗
PubMed1995

The effect of barium sulphate on small bowel motility in man.

OBJECTIVE: To investigate the effect of barium sulphate on small bowel motor activity. METHODS: Nine healthy male volunteers underwent two separate, ambulatory 24 h manometry studies. Jejunal motor activity was recorded during fasting and after ingestion of 300 ml volumes of barium, water or a glucose solution (1380 kJ). Recordings were analysed visually for recurrence of phase III of the migrating motor complex, and a validated computer program was used to calculate the incidence and amplitude of contractions. RESULTS: Phase III reappeared 71 +/- 10 min after ingestion of barium sulphate. This interval was not significantly different after the intake of water (60 +/- 8 min) or in the fasted state (88 +/- 21 min), but it was significantly shorter than after ingestion of a glucose solution (136 +/- 17 min). The mean incidence of contractions after ingestion of barium was 3.0 +/- 0.5/min. This was significantly higher than that observed after water (1.9 +/- 0.4/min) and also significantly higher than during fasting (1.5 +/- 0.3/min), but not significantly different from the incidence of contractions after ingestion of a glucose solution (2.2 +/- 0.4/min). The mean amplitude of contractions after ingestion of barium was 24.2 +/- 1.4 mmHg. This was significantly higher than the amplitude of contractions during fasting (19.5 +/- 1.0 mmHg), but not significantly different from that after water intake (23.7 +/- 1.3 mmHg) or after ingestion of a glucose solution (21.4 +/- 1.3 mmHg). CONCLUSION: Small bowel motor activity after ingestion of barium sulphate differs distinctly both from the interdigestive and from the postprandial motor pattern. Barium suspensions do not interrupt the migrating motor complex with a typical 'fed' pattern, but contractions are more frequent after ingestion of barium than after the intake of water and are both more frequent and of greater force than the contractions observed during the fasted state.

Adult↗
PubMed1994

Daytime ingestion of alcohol alters nighttime jejunal motility in man.

We studied the effects of acute ingestion of intoxicating doses of alcohol on jejunal motility in six male volunteers ages 24-45 who had two 24-hr ambulatory manometries, one week apart, that each included three standardized meals with either red wine (0.6 g of alcohol/kg) or dealcoholized wine. Breath alcohol was measured at regular intervals for 3 hr following alcohol. The results show that the MMC cycle was significantly (P < 0.01) shorter during the night than during the day in the "nonalcohol" group but not in the "alcohol" group and that the amplitude of contractions was higher during the night than the day in the alcohol group (P < 0.01). All meals interrupted the MMC and induced a fed pattern. After the 300-kcal liquid meal, the duration of the fed pattern was shorter (P < 0.01), with a lower motility index (P < 0.01) and fewer contractions (P < 0.01), than following the two 600-kcal meals. The number of clustered contractions occurring in the postprandial period was lower in the alcohol group than in the nonalcohol group. After the three alcohol doses, a breath alcohol peak was reached in 20-60 min, and in all subjects, breath alcohol fell below 22 micrograms/100 ml after the third hour. This study showed that alcohol had only minor effects on postprandial contractile activity but abolished the circadian variation of the MMC normally seen in healthy subjects. The fact that breath alcohol was low by the time of onset of sleep, suggests that the effects on the MMC may be mediated through central rather than local mechanisms.

Adult↗
PubMed1994

Small bowel motility following major intra-abdominal surgery: the effects of opiates and rectal cisapride.

BACKGROUND/AIMS: Human small bowel motility is altered after laparotomy. Opiate analgesia is a possible cause of these alterations, and cisapride is a potential therapy. METHODS: Continuous proximal small bowel manometry was performed for up to 92 hours in 23 patients after major intra-abdominal surgery. They were treated with rectal cisapride (30 mg three times daily) or placebo until the clinical resolution of ileus. Small bowel manometry was performed for 30 hours in 5 volunteers receiving 1 mg/kg meperidine over 3 hours. RESULTS: Phase III activity was present within 3 hours of the end of surgery in all patients. Initially, the migrating motor complex (MMC) period was markedly reduced (mean, 22 minutes) but gradually increased. Phase II activity was absent until a median of 40 hours had elapsed. Phase III contractile amplitude was markedly attenuated in the jejunum, in contrast to that in the duodenum, presumably as a result of dilatation and/or altered tone, increasing to normal by 72 hours. In the volunteer group, although the MMC period was reduced by meperidine, it remained significantly greater than that of the placebo patient group for approximately 48 hours and phase II was reduced but not eliminated. Cisapride induced some changes in motor activity but did not accelerate the recovery of normal motility. Clinical outcome, assessed by the return of bowel sounds and passage of flatus, was accelerated by cisapride, but the trend was not significant (P = 0.11). CONCLUSIONS: This is the first published study using prolonged manometry to show the gradual evolution of small bowel motor activity after major intra-abdominal surgery. The findings suggest that surgery decreases the MMC period to the equivalent of the absolute refractory period, thereby eliminating phase II, which returns as the MMC period lengthens. Cisapride, at the dosage given, confers only modest benefit.

Abdomen↗
PubMed1994

Biomechanics of small bowel motility.

A biomechanical model and results of numerical simulation of the propagation of electromechanical waves of deformation along the small bowel are presented. The organ is modelled as a soft orthotropic cylindrical biological shell reinforced by orthogonally interwoven smooth muscle elements, embedded in a connective tissue network. The dynamic reaction starts as a response to the propagation of a depolarization wave along the smooth muscle layers. The muscle layers contract independently but in a coordinated way with the generation of active forces. The mechanical properties of the wall are assumed to be nonlinear. Deformations of the bioshell are finite. The governing system of equations is obtained and solved numerically. The finite-difference method of the second order accuracy over the time and space variables was used. The dynamics of strain distribution in the biological shell and shape changes are analysed.

Biomechanical Phenomena↗
PubMed1994

Mathematical modelling of the enteric nervous network. 1: Cholinergic neuron.

A mathematical model is proposed to describe the coupled electrochemical mechanisms of nerve-pulse transmission via cholinergic synapse. Based on pharmacological and morphophysiological data, the model describes the dynamics of the propagation of the electric signal along the unmyelinated geometrically non-uniform axon of the neuron and the chemical mechanisms of the transformation of the electrical signal in the synaptic zone into the postsynaptic output. The combined nonlinear system of partial and ordinary differential equations has been obtained and solved numerically. The results of numerical simulation of the function of the cholinergic neuron quantitatively and qualitatively describe the dynamics of Ca2+ ions influx into the terminal, acetylcholine release from the vesicles, accumulation of its free fraction, diffusion into the synaptic cleft, and binding with the receptors on the postsynaptic structures with the generation of the fast excitatory postsynaptic potential. They are in good agreement with the observed experimental findings.

Acetylcholine↗
PubMed1994

Modelling of the enteric nervous network: 3. Adrenergic neuron.

A mathematical model is developed to investigate the coupled electrochemical processes of nerve-pulse transmission via adrenergic synapse. Based on pharmacological and morphophysiological data, the model describes the dynamics of the propagation of the electric signal along the unmyelinated geometrically non-uniform axon of the neuron and the chemical mechanisms of the transformation of the electrical signal in the synaptic zone into the post-synaptic output. The combined nonlinear system of partial and ordinary differential equations has been obtained and solved numerically. The results of computer simulation of the function of the idealized adrenergic neuron quantitatively and qualitatively describe the dynamics of Ca2+ ion influx into the terminal, noradrenaline release from the free 'releasable' store, its diffusion into the synaptic cleft, binding with the adrenoceptors on the pre- and post-synaptic structures with the generation of the inhibitory post-synaptic potential, and utilization of noradrenaline by neuronal and non-neuronal capture mechanisms.

Adrenergic Fibers↗
PubMed1993

Mathematical modelling of the enteric nervous network. II: Facilitation and inhibition of the cholinergic transmission.

The pharmacokinetic responses of the cholinergic enteric neurone to treatment with acetylcholinesterases, tetrodotoxin, some chloride salts of divalent cations, botulinum toxin, beta-bungarotoxin and changes in the concentration of calcium ions in the external medium and repetitive stimulation are presented. The numerical results obtained reproduce quantitatively the effects of toxins and salts of divalent cations acting at different levels of acetylcholine release from the nerve-terminal. The addition of cholinergic agonists potentiates the action of acetylcholine and increases the amplitude of the generated excitatory postsynaptic potential. A decrease in the concentration of extracellular Ca2+ ions reduces the amplitude of the excitatory postsynaptic potential and significantly increases synaptic transmission time. The effect of tetrodotoxin is the blockade propagation of the action potential along the nerve axon and, as a consequence, acetylcholine release from the vesicular store. All these effects have been shown to be dose-dependent. The repetitive stimulation of the neurone reproduces the effects of accumulation and potentiation. The possible applications of the model for the analysis of the enteric nervous system function are discussed.

Acetylcholine↗
PubMed1993

The computer as referee in the analysis of human small bowel motility.

The aim of this study was to determine whether visual analysis of graphic records of small bowel motility is a reliable method of discriminating pressure events caused by bowel wall contraction from those of extraenteric origin and to compare this method with computerized analysis. Each of six independent observers was supplied with the same pair of records of 1 h of fasting diurnal duodenojejunal motility, acquired with a 3-channel ambulant data-logging system; one record included many artifacts due to body movement while the other did not. The observers were asked to identify and classify pressure events and to measure the duration and amplitude of "true" contractions. A computer program for on-line analysis is described; the algorithm was designed to overcome the problems of a variable baseline and sudden changes in pressure due to body movements that are unavoidable in prolonged recording from the small bowel of ambulant subjects. For regular contractions (phase III of migrating motor complex) there was good agreement between observers but not for irregular contractions, particularly when movement artifacts were abundant. When the observers were asked to repeat the analysis 6 mo later, there was poor agreement with their original identification of irregular contractions and artifacts. There was, however, good agreement between the computer analysis, which was totally reproducible, and the median decisions of the observer group; this agreement supports the validity of our computer algorithm. We conclude that computer analysis is not merely a valuable ergonomic aid for analysis of large quantity of data acquired in prolonged ambulatory monitoring, but also that, even for brief recordings, it provides a standard of reproducibility unmatched by "expert" inspection. Visual analysis is unreliable and thus susceptible to subjective bias; this may, in part, account for conflicting reports of small bowel motility under similar conditions reported by different workers in our own and other laboratories.

Algorithms↗
PubMed1992

A soluble recombinant fusion protein of the transmembrane envelope protein of equine infectious anaemia virus for ELISA.

The use of the bacterial expression vector, pGex, to produce an abundant, soluble fusion protein of gp45 from equine infectious anaemia virus is described. Purification of the recombinant protein was achieved by one step affinity chromatography on immobilized glutathione using competitive elution so no harsh conditions were required. This provides a readily available antigen that is defined, plentiful and cheap. Yields of 3.5 mg of purified soluble protein/litre of bacterial culture were obtained. This antigen was found to be suitable for ELISA. Background reactivity to either the glutathione-S-transferase (GST) fusion partner by immune sera or the EIA-GST fusion protein by normal sera were negligible.

Amino Acid Sequence↗
PubMed1992

Assessment by prolonged ambulatory manometry of the effect of oral cisapride on proximal small bowel inter-digestive motility.

The effects of cisapride, given orally at standard therapeutic dosage (10 mg tds), on proximal small bowel interdigestive motility in ten healthy volunteers was assessed by prolonged ambulatory manometry. Cisapride did not alter the duration of the MMC cycle, duration of phase II or the propagation rate of phase III in either the daytime or nighttime periods. However, when compared to studies, in which subjects received no drug, both nighttime and daytime phase II mean contractile amplitude, but not contractile incidence, were significantly increased (P < or = 0.001) by cisapride. Cisapride significantly increased the incidence of distally propagated clustered activity. We conclude that the major effects of cisapride on healthy small bowel motor function is to increase the mean contractile amplitude and incidence of distally propagated clustered activity.

Administration, Oral↗
PubMed1992

Abnormal REM sleep in the irritable bowel syndrome.

Motor abnormalities of the small bowel that occur only during the waking state have been reported in the irritable bowel syndrome (IBS), suggesting that central nervous system arousal is a necessary condition for expression of the disorder and that it may reflect inappropriate brain-gut interaction. This possible relationship was explored further by synchronous polysomnography and recording of upper small bowel motility in six healthy subjects and six patients with IBS. During sleep, there was no difference in the patterns of intestinal motility between the two groups. There was no difference between the rapid eye movement (REM) latency or number of REM episodes, but the proportion of REM sleep was markedly increased (36.5% +/- 5.7% vs. 18.2% +/- 5.7%; P less than 0.01) in the IBS group, although the duration of sleep was similar (468 +/- 13 minutes in IBS vs. 444 +/- 10 minutes in controls; P greater than 0.1). Sleep apnea was detected in three of six patients with IBS but was not seen in controls. The data are consistent with the model of IBS as a disorder of brain-gut interaction.

Adult↗
PubMed1991

The irritable bowel syndrome.

The irritable bowel syndrome (IBS) is a familiar problem in the clinic, but as a disease entity it remains ill defined. Much confusion has arisen in the past, because of the inappropriate inclusion within the category of IBS of almost any patient with unexplained abdominal discomfort. Recent work has established that IBS patients can be positively identified by a cluster of specific symptoms. With the use of these criteria, it seems likely that IBS patients suffer from a diffuse motor abnormality of the gut associated with visceral hypersensitivity; although there is no associated psychopathology, a central nervous system component to the disorder is possible. Better insight into IBS promises more effective management.

Colonic Diseases, Functional↗