Acid reduction and recurrent enteritis.
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Biomedical subjects
Publications and source records attributed to D L Wingate.
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We have developed a method for prolonged combined anorectal manometry and electromyography (EMG) of the external anal sphincter in ambulant subjects. Fourteen healthy volunteers were studied for a total of 284 hr (mean of 20.3 hr/subject). Anorectal manometry was performed using a probe with twin pressure sensors. EMG was recorded by one indifferent and two differential silver-silver chloride surface electrodes positioned 0.5-0.75 cm from the anus on either side. The sampling reflex occurred frequently and was significantly (P less than 0.001) more common during wakefulness than during sleep and also following meals than during fasting (P less than 0.01). The passage of flatus was associated with transient relaxation of the anal canal in 19% of episodes. In contrast, there was a contractile episode with no preceding relaxation in 75% of episodes. The anal sphincter had significantly (P less than 0.05) more action potentials (APs) during the day (12.8 +/- 3.2 APs/10 min) than at night (1.6 +/- 1.3 APs/10 min). During micturition, anal canal pressure rose (mean 15 mm Hg) in association with powerful external anal sphincter contractions. Our data show that, normally, contractile activity both in the anal canal and external anal sphincter maintains fecal continence during micturition and the passage of flatus. The technique should lead to a better understanding of the normal mechanisms of fecal continence during waking and sleep and of the pathophysiology of disorders of anorectal function.
Continuous 72-h recordings of duodenojejunal contractile activity were obtained from 20 freely ambulant subjects; pressure was detected by two strain-gauge sensors incorporated in a transnasal catheter attached to an encoder and a miniature tape recorder. The subjects were 12 patients with irritable bowel syndrome, 6 of whom were constipation predominant and 6 of whom were diarrhea predominant, and 8 healthy controls. The procedure was well tolerated by all subjects and did not interfere with sleep or normal activity. In all subjects, the diurnal migrating motor complex cycle was characterized by a brief phase 1 and a prolonged phase 2; this was reversed during sleep when phase 2 was virtually absent. All subjects showed a circadian variation in migrating motor complex propagation velocity, and there was no difference in the patterns of motor activity during sleep between any of the groups. During the day, the duration of postprandial motor activity was shorter in irritable bowel syndrome patients than in controls, and diurnal migrating motor complex intervals were shorter in diarrhea-predominant than in constipation-predominant irritable bowel syndrome. In 11 of 12 inflammatory bowel syndrome patients, episodes of clustered contractions recurring at 0.9-min intervals were noted; these episodes had a mean duration of 46 min and were often associated with transient abdominal pain and discomfort. In both groups of irritable bowel syndrome patients, defecation was significantly (p less than 0.01) prolonged with a greater number of voluntary abdominal contractions (p less than 0.01) than in controls. Prolonged ambulant monitoring of proximal bowel motor activity in subjects who are free to move, eat, and sleep as they choose has, for the first time, clearly defined the striking difference in motility between the sleeping and waking state and shown that abnormalities associated with irritable bowel syndrome are confined to the latter.
Subtotal colectomy with ileorectal anastomosis is now frequently offered to patients with slow transit constipation who have severe symptoms and no response to more conventional medical treatment. If this operation is to be successful, the underlying problem should be delay in the progress of contents through the colon but no mechanical or functional obstruction in the small bowel or rectum. We have used a recently described technique of prolonged ambulant manometry and electromyography to investigate anorectal function in these patients. Pressure data were collected using a 2 mm diameter intrarectal probe carrying microtransducers, and external anal sphincter activity was assessed by a pair of silver-silver chloride surface electrodes. Fourteen control subjects and eight patients with colonic inertia were studied. Sampling reflexes, indicative of rectal filling, occurred at mean (SEM) rates of 7.4 (2.0)/hour in controls but were significantly reduced in patients (2.4 (0.3)/hour (p less than 0.01]. Recurrent rectal motor complexes were seen to occur in both groups at intervals of 76 (1.8) minutes in controls and 64.9 (7.2) minutes in patients (p less than 0.1), and with amplitudes of 42.4 (2.1) mmHg and 9.2 (0.7) mmHg (p less than 0.001), respectively. External sphincter electromyographic spike activity did not differ between groups. Our results support the concept of reduced transit of faeces to the rectum from the colon over a 24 hour period in slow transit constipation and suggest that a motor neuropathy may also be present in the rectum.
Both the human small intestine and rectum exhibit motor activity in which relatively brief bursts of powerful regular contractions recur with a similar periodicity. We used prolonged ambulant manometry to test the hypothesis that these activities are synchronous. Pressure activity from the duodenojejunum and the rectum was recorded continuously for 24 h in eight freely ambulant healthy adults. A total of 61 migrating motor complexes and 61 rectal motor complexes occurred in the group; the median periodicities of the two rhythms differed significantly (P = 0.025). There was no evidence of synchrony between the two biorhythms. We conclude that they are independent oscillations.
Perfused-tube manometry has hitherto been the standard technique for recording intraluminal intestinal pressure in humans, but it is unsuitable for ambulant use. The aim of our study was to evaluate the ability of resistive strain gauge transducers attached to a fine catheter to detect pressure change. Simultaneous strain gauge and perfused-tube manometry was performed on six fasting subjects; in four, strain gauge activation was continuous and in two, the transducers were activated in a pulsed mode with data encoded as a pulse train with an approximate frequency of 20 Hz. Eight thousand eight hundred eighty-eight pressure waves were recorded by strain gauge, of which 96% were detected by perfused-tube manometry. There was good agreement in both phases II and III of the migrating motor complex. The amplitude of pressure waves recorded by strain gauge was slightly but significantly greater. A proportion (14-17%) of pressure waves recorded by strain gauge were bifid; this was not seen with the perfused tube. These differences are best explained by the greater sensitivity and more rapid rise time of the strain gauges. There was no loss of fidelity in the pulse-interval recording mode. A seventh subject underwent a continuous 72-h recording with the strain gauge catheter attached to a battery-operated encoder and magnetic tape cassette recorder and was freely ambulant during this period. The procedure was well tolerated and motility patterns could be clearly identified. We conclude that intraluminal strain gauge catheters are suitable for prolonged use in ambulant subjects and produce data that are closely comparable to the data acquired from perfused-tube manometry under laboratory conditions.
To address the question of synchrony between two major biorhythms with a similar periodicity, the cortical rapid eye movement (REM)/non-REM sleep cycle and the enteric migrating motor complex (MMC cycle), we recorded upper small bowel motor activity and sleep activity during nocturnal and diurnal sleep in six healthy subjects. Motility was measured continuously using a fine (2.2 mm OD) and relatively comfortable nasojejunal probe with two pressure-sensitive microtransducers positioned under fluoroscopic control on either side of the ligament of Treitz. Sleep stages were recorded while the subjects slept in a sleep laboratory. Each subject was studied twice; once during normal nocturnal sleep and then after acute reversal of sleep by advancing the time of going to bed by 4 h each night for three nights. The total duration of sleep was similar for diurnal and nocturnal sleep. There was a significantly higher number of REM episodes (P less than 0.001) and REM sleep stage shifts (P less than 0.02) during diurnal (reversed) sleep. During sleep (both diurnal and nocturnal) there was a significant reduction in the MMC cycle length (P less than 0.02, P less than 0.03) and the duration of phase II of the MMC (P less than 0.009, P less than 0.02). The distribution of MMCs among sleep stages and REM sleep was consistent with a random distribution. These data show that periodic activity in the gut is modulated by the presence or absence of sleep, but they also are consistent with the hypothesis that the two cycles are independent and that one is not contingent upon the other.
Our study was designed to test the hypothesis that psychoneurosis in irritable bowel syndrome (IBS) may be the secondary effects of the unsatisfactory nature of the medical transactions (diagnosis, explanation, prognosis, and therapy) in IBS rather than a primary cause of the syndrome. We carried out psychometric assessments on three groups of subjects: 10 healthy volunteers, 12 patients diagnosed as suffering from benign gastrointestinal disease, and 18 patients with IBS. We found a significantly raised incidence of psychoneurosis in IBS, but the components of this were predominantly anxiety and obsession; the incidence of depression in all 3 groups was similar. We argue that the data support our hypothesis that the psychoneurotic manifestations are secondary components of IBS; the data do not support the hypothesis that IBS is a manifestation of depression.
We performed esophageal investigations in 20 patients suffering from noncardiac chest pain in order to assess the diagnostic value of short- versus long-term manometric and pH studies. Patients had baseline esophageal manometry with two provocative tests: a Bernstein test and an intravenous injection of edrophonium. On a separate occasion they had a 24-hr ambulatory esophageal pH and motility recording. The Bernstein test provoked chest pain in two patients, while edrophonium injection did not elicit pain in any of the patients. The ambulatory pH study helped to establish the esophagus as the likely source of pain in one patient, and the ambulatory motility one in another. In our experience, ambulatory pH and motility recordings have a low diagnostic yield in the evaluation of patients with noncardiac chest pain.
The motor response of the canine stomach to test meals of varied nutrient content and physical state, administered either orally or intraduodenally, was studied. Oral feeding abolished regular contractions in the proximal stomach. There was a simultaneous fall in the proximal gastric baseline force, which slowly recovered to the preprandial level, at which time regular contractions returned. The magnitude and duration of these events varied with the type of meal, as did the distal gastric response, which was characterized by abolition of the fasting motor pattern and establishment of continuous low-amplitude contractions. Duodenal feeding of a nutrient, but not nonnutrient, meal abolished fasting motor activity in both proximal and distal stomach but did not induce either a fall in proximal gastric baseline force or distal gastric contractions. These results suggest that stimulation of duodenal as well as gastric receptors is required to elicit the normal prandial response of both proximal and distal stomach.
The intestinal EMG obtained from chronically implanted electrodes in canine preparations provides for the evaluation of intestinal motor activity and its control. The basic electrical rhythm (BER) and spike components on the EMG signal provide evidence of control activity and a measure of contraction intensity, respectively. A hardware system is presented in which these two components are separated by filters and the contraction spikes counted in fixed epochs to yield a contraction spike per unit time record against time. The signal is also available in parallel binary form at the end of each epoch, together with a data-ready signal for direct acquisition by computer. Tests of system performance and operating protocols are given. The preprocessor is used as a fast front end to a digital signal processing system specifically built for intestinal EMG analyses.
Based on short recordings, the rectum has been shown to have contractions with a frequency of five to 10 cycles per minute and slow contractions at three cycles per minute. To define anorectal motility over a prolonged period of time, we have studied 12 healthy volunteers using a fine pressure sensitive anorectal probe. A total of 240 hours of recording was obtained. We observed three types of activity in the rectum: (i) runs of powerful phasic contractions with a frequency of two to three per minute, lasting for three to 10 minutes, and recurring to an interval of 92 (1.9) minutes (mean (SEM)) during the day and 56 (1.7) minutes (mean (SEM)) at night, (ii) isolated prolonged contractions lasting for 10-20 seconds and seen mainly during waking, and (iii) clusters of contractions occurring at a frequency of five to six per minute lasting for one to two minutes and seen predominantly during the postprandial period. These clusters of contractions resembled the discrete clustered contractions seen in the ileum, whereas the more powerful and prolonged runs of contractions resembled phase III activity in the small intestine. In contrast, the anal canal showed bursts of contractions which were not temporally related. Our data show that the rectum, like the upper gastrointestinal tract, exhibits periodic motor activity; it remains to be seen whether these two biorhythms are synchronous.
We have measured the effect of the presence of food in the gastrointestinal tract on proximal small bowel motility during sleep. Motility was measured in eight healthy ambulant subjects using two strain-gauge microtransducers incorporated in a fine (2.5 mm OD) nasojejunal tube. The subjects ate a 540-cal evening meal (EM) on the first day. On the following day they ate an equicaloric meal (with similar proportion of carbohydrates, proteins, and fats) at lunch time (MM) and then another equicaloric late meal (LM) 15 min before going to bed. All subjects were asleep within 30 min of completing the LM. Postprandial activity was significantly (P less than 0.001) shortened after LM, but there was no difference in the postprandial motor activity after MM and EM. Migrating motor complex (MMC) cycle lengths were similar after MM, EM, and LM. There was no difference in the duration of phase II of the MMC cycle after MM, EM, and LM even though subjects were asleep during the MMC cycles after LM. The MMC propagation velocity after LM and EM was significantly (P less than 0.01, P less than 0.001, respectively) slower than the diurnal MMC propagation velocity after MM. In health, postprandial activity is diminished during sleep, whereas the consumption of a LM restores the phase II activity usually absent during sleep. A LM also abolishes the expected reduction in nocturnal MMC cycle length but maintains the circadian variation in the propagation velocity of the MMC cycle.
The study of human colonic motility under physiological conditions has proved to be an elusive goal. We have used a two-stage pernasal technique to position sensors in the human colon for the prolonged monitoring of motility in freely ambulant subjects. Nine healthy volunteers were studied for a total recording time of 263 h, each study lasting between 13 and 48 (mean 29) h. Motor activity in all regions of the large bowel was characterized by scant and irregular contractions with infrequent bursts that did not conform to any pattern. No motor coordination was apparent between different regions of the large bowel. Contractile activity throughout the large bowel was reduced to a minimum during sleep and was enhanced on waking. Meals were an inconsistent stimulus to motor activity. The technique obviates the need for colonic preparation and allows complete freedom of the subjects throughout the study. In demonstrating the practical feasibility of this mode of studying the colon, these preliminary data highlight a requirement for the availability of appropriate equipment but raise questions about the design and use of such equipment and methods of data analysis.
Capsaicin is a neurotoxin that destroys small sensory neurons with unmyelinated axons, including a subpopulation of vagal sensory neurons. Capsaicin treatment attenuates suppression of food intake induced by systemic administration of cholecystokinin (CCK) but not by gastric distension. However, both gastric distension and intravascular CCK alter the discharge of dorsal hindbrain neurons by a vagal mechanism. Therefore, it is plausible that some hindbrain neurons receive convergent input from capsaicin-sensitive vagal neurons that are responsive to CCK and also from capsaicin-insensitive neurons that are responsive to gastric distension. To investigate this possibility we made extracellular recordings from gastric distension-responsive hindbrain neurons during intra-arterial cholecystokinin octapeptide (CCK-8) administration in anesthetized intact and capsaicin-pretreated rats. We found that capsaicin-pretreated rats exhibit attenuated neuronal discharge responses to CCK-8 but not to gastric distension. These results are consistent with the existence of convergent CCK-sensitive and gastric distension-sensitive afferent inputs to hindbrain neurons and suggest that various gastrointestinal sensory modalities may be communicated to the brain by populations of neurons that can be distinguished by their sensitivity to neurotoxins.
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Intracellular recordings were made in vitro from neurons in the myenteric plexus of freshly dissected preparations of the duodenum of the rat. Nearly one-quarter of neurons (18 out of 77) had long after-hyperpolarizations following their action potentials. Over 60% of neurons (20 out of 32) which were tested exhaustively by focal stimulation at seven points around the recording site were seen to receive fast excitatory synaptic inputs. These were of very short duration (10-30 ms) and were reversibly blocked by the nicotinic antagonist hexamethonium. Only four out of 18 after-hyperpolarization cells (22%) had visible fast synaptic inputs. Seven out of 32 neurons tested received slow excitatory synaptic inputs lasting up to 60 s that were associated with a decrease in conductance and an increase in excitability. No evidence for muscarinic synaptic potentials was seen; only four cells out of 30 with fast excitatory postsynaptic potentials had slow excitatory synaptic potentials visible after a single-shot stimulus; in none of these were the slow excitatory postsynaptic potentials blocked by atropine (up to 1 x 10(-5) M). No inhibitory postsynaptic potentials were recorded in any of the 77 neurons recorded in this study. The effects of five neurotransmitter candidates (acetylcholine, GABA noradrenaline, 5-hydroxytryptamine and substance P) applied by pressure microejection were studied. It is concluded that most of the neurophysiological features reported in the extensively studied guinea-pig small bowel myenteric plexus are present in the rat duodenum. However, the apparent lack of muscarinic synaptic potentials and inhibitory synaptic potentials suggests that there may be some differences between the two species. Our recordings also differ slightly from recently reported studies of rat myenteric neurons grown in cell culture.