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Biomedical subjects

J R Mathias

Publications and source records attributed to J R Mathias.

At least 55 records · Page 3Linked to original sources
PubMed1985

Review: pathophysiology of diarrhea caused by bacterial overgrowth of the small intestine.

The bacterial overgrowth syndrome constitutes an intestinal problem involving alterations in motility and injury to the brush border and mucosa. The overgrowth of bacteria also causes secretion, malabsorption, and maldigestion. These alterations result in a clinical syndrome that manifests itself as weight loss, malabsorption of specific nutrients, and (usually) diarrhea. There are known causes of bacterial overgrowth, such as intestinal diverticuli or surgical procedures involving a vagotomy, but in our experience most cases remain idiopathic. This review evaluates the mechanisms of bacterial overgrowth, as currently understood, and specifically addresses the known causes of diarrhea that results from bacterial contamination of the small intestine.

Animals↗
PubMed1985

Motility of the small intestine: a look ahead.

Motility of the gastrointestinal tract has become an important discipline of gastroenterology. In this paper we review important observations made during the early development of this discipline, note the current level of knowledge, and look ahead to some of the questions we believe will be addressed in the near future. Is the slow wave the action potential equivalent of the longitudinal muscle layer? How does the migrating action potential complex interrelate with the migrating myoelectric complex--are they two separate complexes under different control mechanisms? How do the myenteric plexus neurons relate to these complexes? Does the muscularis mucosa control the contraction and relaxation of the villous tips? Is there a finite area in the small intestine that can function as the pacemaker? How important are substances within the lumen in controlling motility? Finally, we emphasize the importance of structure and function of the plexus neurons in motility studies. We also stress the importance of collaboration and a multidisciplinary approach for future understanding of the mechanisms of the small intestine in health and disease.

Action Potentials↗
PubMed1985

Migrating action potential complex: unmasked by 6-hydroxydopamine.

We have previously described the myoelectric characteristics of a single moving ring contraction, the migrating action potential complex (MAPC), in rabbit ileal loops exposed to certain bacteria or their enterotoxins. The MAPC is thought to act as a defense mechanism of the host, clearing unwanted substances from the lumen. In the present study, 6-hydroxydopamine, a substance that selectively destroys adrenergic varicosities containing the neurotransmitter norepinephrine, unmasked the MAPC from the activity front of the migrating motor complex in an unanesthetized rat model. The animals developed diarrhea and lost weight. The study suggests that the MAPC may also be a physiological complex and under the modulation of the enteric nervous system. The MAPC may not be seen under normal control conditions because the complex migrates with the activity front and is under inhibitory control. Destroying the inhibitory mechanisms unmasked the MAPC from the activity front of the migrating motor complex and allowed neural transmission of the ring contraction.

Action Potentials↗
PubMed1984

Purified Shigella enterotoxin does not alter intestinal motility.

A purified Shigella enterotoxin (pST) and a cell-free lysate with pST removed (CFL-pST) from the whole-cell lysate of Shigella dysenteriae 60 R were used to study their effect on the myoelectric activity and mucosal integrity of rabbit ileal segments. We have previously defined two myoelectric patterns: the migrating action potential complex and repetitive bursts of action potentials that occur in response to certain bacteria and their enterotoxins. The in vivo model consisted of isolated ileal segments in male New Zealand White rabbits. The segments were infused with sterile saline (1 ml/h), pST (2.4-micrograms injection), or CFL-pST (1 ml/h). Myoelectric activity in the segments exposed to pST was similar to that with the saline infusion, but CFL-pST induced significant alterations in myoelectric activity in the form of repetitive bursts of action potentials. The mucosa of the segments exposed to pST showed only mild inflammatory changes. In contrast, CFL-pST caused moderate to severe inflammatory changes with enterocyte necrosis. These studies show that pST, a known enterotoxin, did not alter myoelectric activity and had no significant effect on the integrity of ileal mucosa, as determined by light microscopy. CFL-pST caused both inflammation and tissue necrosis with significant alterations in motor activity. These studies suggest that S. dysenteriae 60 R produces a substance or substances other than pST that cause florid in vivo cytotoxicity and alter myoelectric activity.

Action Potentials↗
PubMed1984

Alterations in motor function of the small intestine from intravenous and intraluminal cholecystokinin.

Cholecystokinin has been found within the lumen of the gastrointestinal tract; however, its effect on intestinal motility has not been studied. We examined the effect of intraluminal and intravenous infusion of the octapeptide of cholecystokinin (CCK-OP) on myoelectric activity in the intestine of rabbits. CCK-OP was infused intraluminally at 1,000 ng X kg-1 X h-1, and portal venous blood samples were obtained hourly for plasma immunoreactive CCK. CCK-OP was also infused intravenously at a similar rate, and hourly peripheral venous blood samples were obtained for plasma immunoreactive CCK. Myoelectric activity was monitored in a 12-cm ligated ileal segment and the proximal adjacent small intestine after the infusion of intraluminal or intravenous CCK-OP. Intraluminal infusion of CCK-OP caused a significant increase (P less than 0.01) in both migrating action potential complexes (MAPC) and repetitive bursts of action potentials (RBAP) (3.1 +/- 0.8 MAPC/h and 4.6 +/- 1.3 RBAP/h). In contrast, intravenous CCK-OP induced only repetitive bursts of action potentials (8.3 +/- 1.7 RBAP/h, P less than 0.01). In summary, alterations in intestinal motility may vary according to the route of administration of the individual peptide. Furthermore, results from these studies suggest that intraluminal release of regulatory peptides may be important in the modulation of intestinal motility.

Action Potentials↗
PubMed1983

99mTc-labeled solid-phase meal: a quantitative clinical measurement of human gastric emptying.

A solid-phase meal labeled with 99mTc-sulfur colloid provides an improved clinical test for the quantitative evaluation of human gastric emptying. We studied 12 healthy male controls and five male patients with known gastric stasis secondary to a vagotomy and drainage procedure. All subjects were fasted for 8 hours before the study, and each consumed an unbuttered biscuit and a poached egg white containing 1 mCi of 99mTc-sulfur colloid. For 2 hours, 60-second counts were measured every 10 minutes by a Pho Gamma III scintillation camera. The t1/2 for control subjects was 60 minutes, at which time patients with gastric stasis had retained 98% of the test meal. At 120 minutes, control subjects and patients with gastric stasis had 4.7% and 89%, respectively, of the meal remaining in the stomach. The solid-phase test meal labeled with 99mTc-sulfur colloid is easy to perform and can be used clinically to quantitatively measure gastric emptying in humans. This test can discriminate between control subjects and patients with known gastric stasis.

Bread↗
PubMed1983

Myoelectric effects of vasoactive intestinal peptide on rabbit small intestine.

Myoelectric recording techniques were used to study the motility of rabbit ileum during infusions of vasoactive intestinal peptide (VIP). VIP was infused intravenously at a rate of 300 pmol X kg-1 X h-1, and peripheral venous blood samples were obtained hourly for VIP assay. VIP was also infused intraluminally at a similar rate, and hourly portal vein blood samples were obtained for VIP assay. Alterations in motility were observed after both intravenous and intraluminal infusions of VIP. These alterations in motility consisted of the migrating action potential complex and repetitive bursts of action potentials. The VIP infusion rate used and the mean peripheral plasma VIP level of 267 +/- 29 pg/ml attained during intravenous VIP infusion were similar to those that induced intestinal secretion in other animal species. Portal venous VIP levels (93 +/- 21 pg/ml) were unchanged during the intraluminal infusion of VIP. These studies show that intravenous infusion of VIP causes alterations in motility of rabbit ileum. These alterations in motility with concomitant secretion of water and electrolytes may contribute to the diarrhea induced by VIP infusion. In addition, intraluminal infusion of VIP also induced alterations in myoelectric activity, which suggested that this peptide has a luminal effect as well as a hormonal effect.

Action Potentials↗
PubMed1983

Migrating action-potential complexes in vitro in cholera-exposed rabbit ileum.

The objective of this study was to determine whether cholera-exposed rabbit ileum exhibits altered myoelectric activity in vitro, without central nervous system connections. Whole-cell lysate of Vibrio cholerae, 100 mg in 1 ml saline, was injected into the jejunum of New Zealand White rabbits. Segments of ileum were removed at 12 and 24 h after inoculation and studied in vitro using myoelectric recording techniques. Propagating ring contractions were visualized and corresponded to intense action-potential activity that propagated over consecutive electrode sites. This altered myoelectric activity was similar to the previously described migrating action-potential complex (MAPC) in vivo after infection of rabbit ileum with live V. cholerae, its wholecell lysate, or the purified enterotoxin choleragen, with one exception. All MAPC activity propagated aborally in the in vivo-infected loops; in contrast 26% of the MAPCs propagated retrograde in the in vitro loops. Control segments were injected with saline, and no in vitro MAPCs were observed. Thus, the MAPC stimulated by cholera toxin may be maintained by the enteric nervous system of the gut wall. Although a role for extrinsic nerves is not excluded, our observations suggest that the small intestine may work autonomously, independent of the central nervous system.

Action Potentials↗
PubMed1983

Altered myoelectric activity in the experimental blind loop syndrome.

Nutrient malabsorption and diarrhea are characteristic of the blind loop syndrome. Alterations in motility have been implicated as a cause of bacterial overgrowth, but the possibility that altered motility may result from alterations in the flora has not been explored. The purpose of this study was to characterize the myoelectric activity of the small intestine in the blind loop rat model. Eight groups of rats were studied: rats with self-filling blind loops, which develop bacterial overgrowth; rats with self-emptying blind loops, which are surgical controls that do not develop overgrowth; unoperated litter mates; rats with self-filling blind loops and unoperated controls treated with chloramphenicol, 200 mg/d i.p.; rats with surgically removed self-filling blind loops; operated control rats; and gnotobiotic rats with self-filling blind loops. In the untreated rats with self-filling blind loops, there was altered myoelectric activity characterized by an increased percentage of slow waves occupied by action potentials and by organized activity similar to the migrating action potential complex. Migrating action potential complex activity and percentage of slow waves occupied by action potentials were significantly decreased with chloramphenicol therapy; that decrease correlated with a decrease in aerobes and anaerobes. Migrating action potential complex activity was abolished in rats with surgically removed self-filling blind loops; they also showed a significant decrease in percentage of slow waves occupied by action potentials. Gnotobiotic rats with self-filling blind loops showed no alteration in myoelectric activity. These data indicate: (a) bacterial overgrowth is associated with a significant increase in percentage of slow waves occupied by action potentials and migrating action potential complex activity; (b) chloramphenicol significantly reduced both percentage of slow waves occupied by action potentials and migrating action potential complex activity; and (c) surgical removal of the loop reduced the alterations in motor function. This study suggests that the altered myoelectric activity in this model of bacterial overgrowth was due, in part, to the abnormal bacterial flora and supports the concept that alterations in motility may contribute to the diarrhea that is characteristic of the blind loop syndrome.

Action Potentials↗
PubMed1982

Ergonovine-induced esophageal spasm in patients with chest pain resembling angina pectoris.

We studied the effect of ergonovine maleate (EM) on esophageal motor activity in 18 consecutive patients with angina-like chest pain. Significant coronary artery disease was excluded in each patient by cardiac catheterization studies. Baseline esophageal motility was abnormal in 12 patients (66%). After injection of EM, ten patients developed their typical chest pain at the onset of repetitive contractions. Thus, chest pain and esophageal dysfunction were clearly linked. Compared with saline injection, only the repetitive contractions were significantly increased after AM in these patients (P less than 0.01). Amplitude and duration of contractions were increased after EM, but not significantly. Due to potentially serious adverse effects, however, EM cannot be recommended for routine use as a provocative agent.

Adult↗
PubMed1982

Escherichia coli heat-stable toxin: its effect on motility of the small intestine.

Escherichia coli heat-stable enterotoxin is a low-molecular-weight substance that has been shown to induce the active secretion of fluid and electrolytes in the small intestine. In this study, we have characterized the effects of purified E. coli heat-stable toxin (ST, strain 18D, serotype 042:K86:H37) on the motility of rabbit small intestine by using myoelectric recording techniques. Substances, such as cholera toxin, that activate the adenylate cyclase-cAMP system induced predominantly migrating action-potential complex activity. E. coli ST, a toxin that activates the guanylate cyclase-cGMP system, was infused into isolated in vivo ileal loops of New Zealand White rabbits. Inactivated toxin was also studied by exposing the ST to 1 mM dithiothreitol for 90 min. Active E. coli ST induced only repetitive bursts of action potentials. When the toxin was inactivated with dithiothreitol, no alteration in myoelectric activity was observed. We speculate that repetitive bursts of action-potential activity may represent a virulent factor of the bacterium, altering motor activity to slow transit and allowing for bacterial proliferation and invasion.

Action Potentials↗
PubMed1982

Myoelectric effects of Clostridium difficile: motility-altering factors distinct from its cytotoxin and enterotoxin in rabbits.

Clostridium difficile is a bacterium that causes antibiotic-associated pseudomembraneous enterocolitis. This bacterium produces a cytotoxin that induces tissue culture assay positivity and an enterotoxin that causes in vivo mucosal injury. In previous studies we have described two altered myoelectric patterns in response to certain diarrheagenic organisms in an in vivo rabbit model. The first pattern was called the migrating action potential complex and is associated with noninvasive agents; the second pattern was called repetitive bursts of action potentials and is characteristic of invasive or cytolytic agents. In this study, we evaluated the effects of purified cytotoxin (2.5-3.75 micrograms) and enterotoxin (140 micrograms) from C. difficile on the myoelectric activity in isolated ileal loops in New Zealand White rabbits. These observations in myoelectric activity were correlated with the results of similar studies by using the crude culture filtrates from C. difficile, or the products of Amicon XM50 filtration of its culture supernatant resulting in a high molecular weight product (0.3 mg protein/ml) and a low molecular weight product (0.57 mg protein/ml). Monopolar silver-silver chloride electrodes were used to record all myoelectric activity for an 8-h period. The animals were then killed, and tissue obtained from the ileal loops was histologically evaluated. Crude culture filtrates of C. difficile induced 7.0 migrating action potential complexes/hour and 6.8 repetitive bursts of action potentials/hour. Saline controls induced no migrating action potential complexes and 0.1 repetitive bursts of action potentials/hour. The high molecular weight filtration product obtained from the culture supernatant of C. difficile induced significantly more repetitive bursts of action potentials (41.1/h) than all agents studied. The purified cytotoxin or enterotoxin induced no migrating action potential complex activity and minimal repetitive bursts of action potential activity (0.9/h and 0.6/h, respectively). These values were not different from the saline controls; however, only the enterotoxin and the high molecular weight filtration product caused mucosal damage. These studies suggest that C. difficile produces a heat-labile substance or substances that alter the motility of the small intestine independent of the proteins responsible for in vivo tissue damage and cytotoxin assay positivity.

Action Potentials↗
PubMed1980

Alteration of myoelectric activity of small intestine by invasive Escherichia coli.

Invasive strains of Escherichia coli (4608-58 and TD 213 CL) altered myoelectric activity of the small intestine in New Zealand White rabbits. The altered myoelectric activity had two distinct complex patterns. The first was defined as repetitive bursts of action potentials (RBAPs) that occurred predominantly in infected ligated ileal loops. The RBAP activity is characterized by action potential discharge activity greater than 1.5 s in duration and occurring on three or more successive slow waves on the same electrode recording site. These bursts of action potentials often migrated to adjacent electrode sites. The second complex pattern, defined as the migrating action potential complex (MAPC), occurred predominantly in the uninfected small intestine orad to the ligated ileal loop. The MAPC consists of action potential discharge activity of 2.5 s or longer that propagates aborally over at least two consecutive electrode sites. These studies demonstrated an altered myoelectric pattern, the RBAP, characteristic of invasion within the infected ligated loop. The MAPC, characteristic of noninvasion, was noted in the uninfected proximal small intestine.

Action Potentials↗
PubMed1980

Shigella dysenteriae I enterotoxin: proposed role in pathogenesis of shigellosis.

Bacterial strains of Shigella dysenteriae I (3818-T and 3818-O) and Shigella enterotoxin altered myoelectric activity of the small intestine in New Zealand White rabbits. These agents were compared with activity caused by sterile culture broth or sterile saline. The altered myoelectric activity was characterized by two distinct complexes: repetitive bursts of action potentials (RBAP), characteristic of invasive strains of bacteria, and the migrating action potential complex (MAPC), characteristic of noninvasive bacteria. RBAP activity was the predominant myoelectric complex observed with S. dysenteriae strain 3818-T, an invader and toxin producer; S. dysenteriae strain 3818-O, a noninvader and toxin producer; and by Shigella enterotoxin. MAPC activity was present but was significantly less in all cases. These studies of the small intestine demonstrate an alteration in myoelectric activity characterized principally by RBAP activity indicative of invasion.

Action Potentials↗
PubMed1979

Strain differentiation of Neisseria gonorrhoeae by reverse passive hemagglutination.

A reverse passive hemagglutination test that utilizes human erythrocytes coated with antibody to gonococci was developed to distinguish differences among 11 strains of Neisseria gonorrhoeae. Different rabbits were immunized with each strain of gonococcus. Antibody was purified by passing antiserum over an immunoadsorbent column containing homologous cell walls trapped in a cross-linked polyacrylamide gel. Antibody, after absorption with N. meningitidis, was used for coating 11 individual suspensions of erythrocytes, each with antibody to one gonococcal strain. The panel of coated erythrocytes was added to microtiter trays containing dilutions of homologous bacterial lysate and lysates from 10 heterologous strains. Agglutination titers were highest with homologous lysates, although cross-reactions occurred among some heterologous lysates. Lysates of nongonococcal Neisseria species and of other genera did not agglutinate coated erythrocytes. The reverse passive hemagglutination test can be a useful procedure to distinguish differences among strains of N. gonorrhoeae.

Antibodies, Bacterial↗
PubMed1978

Effect of toxigenic Escherichia coli on myoelectric activity of small intestine.

When exposed to cholera toxin (CT), distal ileal loops of the rabbit small intestine showed an alteration in myoelectric activity. This alteration was defined as the migrating action potential complex (MAPC). The purpose of this study was to determine, using myoelectric recording techniques, the effects of live toxigenic Escherichia coli (TEC) on motility. Live TEC, live nontoxigenic E. coli (NTEC), and culture filtrates of these organisms were studied. Live TEC and its filtrate induced MAPC activity similar to that of CT. Live TEC induced a mean of 3.8 MAPCs/h, significantly greater than induced by live NTEC. TEC filtrate induced a mean of 14.2 MAPCs/h, significantly greater than NTEC filtrate. Heating the TEC filtrate to 100 degrees C before use resulted in a significant decrease of MAPC activity. This experiment demonstrated that live TEC and its culture filtrate altered ileal myoelectric activity. The effect may have been mediated by a heat-labile enterotoxin. This study suggests that alterations in small intestinal motility may be important in the pathogenesis of TEC diarrhea.

Action Potentials↗
PubMed1978

Ricinoleic acid effect on the electrical activity of the small intestine in rabbits.

Using myoelectric recording techniques, we examined the myoelectric effects of castor oil; ricinoleic acid (cis isomer), the active ingredient of castor oil; and ricinelaidic acid (trans isomer) in the small intestine of New Zealand white rabbits. Ricinoleic acid, 2 microgram/kg per min (6mM), was perfused into a distal 12-cm ileal loop. An abnormal myoelectric pattern developed that was similar to the alteration in the electrical activity that has previously been reported for cholera enterotoxin. Castor oil, 0.85 ml/kg, had a similar effect. Ricinelaidic acid, 2 microgram/kg per min, induced no activity. A second preparation consisted of an intraluminal perfusion of ricinoleic acid, 2 microgram/kg per min, into the first section of the duodenum. The abnormal myoelectric pattern was observed in the jejunum and the ileum but not the duodenum. The mean onset time for the development of this altered myoelectric state for all experiments was 3.5 h. These studies suggest that an active motility component in addition to the secretory state exists throughout the small intestine that is exposed to castor oil or ricinoleic acid.

Action Potentials↗