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Biomedical subjects

J R Mathias

Publications and source records attributed to J R Mathias.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of Vibrio cholerae recombinant strains on rabbit ileum in vivo. Enterotoxin production and myoelectric activity.

Previous studies have identified the effects of Vibrio cholerae and its enterotoxin, choleragen (CT A+B+), on the myoelectric activity of rabbit ileal loops in vivo. The response was defined as the migrating action potential complex, the single ring contraction that propels luminal contents aborad. In this study the same rabbit model is used to assess whether migrating action potential complex activity or fluid output is induced by recombinant strains of V. cholerae that produce no subunit of cholera toxin (CT A-B-) or only by the inactive binding subunit (CT A-B+). Three live strains were studied: El Tor wild-type N16961 (CT A+B+) and recombinant strains CVD106 (CT A-B+) and JBK70 (CT A-B-). Controls received sterile culture broth. Migrating action potential complex frequency in animals inoculated with CT A+B+ was significantly increased compared with that in all other experimental groups (P less than 0.01). Fluid output was also increased in animals inoculated with CT A+B+ compared with fluid output in all other groups (P less than 0.05). Migrating action potential complex frequency and fluid output in rabbits given CT A-B+ or CT A-B- did not differ from activity in controls. How these recombinant strains induce diarrhea is unknown, but the mechanism may involve bacterial colonization or production of an unknown toxin.

Animals↗
PubMed1991

Leuprolide acetate stimulates smooth muscle of the human reproductive tract.

Leuprolide acetate (10(-4) to 10(-5) M) had a stimulatory effect on spontaneous contractions of human myometrium and fallopian tube in vitro. The uterine and tubal tissues were from patients with dysfunctional uterine bleeding that was treated by hysterectomy. Whether the effect of LA on smooth muscle is a component of the mechanism of therapeutic action or an undesirable side effect remains to be determined.

Digestive System↗
PubMed1991

Intestinal motility changes in rats after enteric serotonergic neuron destruction.

The myenteric plexus consists of several subpopulations of morphologically and chemically distinct neurons known to contain a variety of peptides and amines, one of which is serotonin (5-hydroxytryptamine). These neurons are considered essential for nerve-to-nerve transmission. In the present study, we investigated the effect of 5,6- and 5,7-dihydroxytryptamine (5,6-DHT; 5,7-DHT), indoleamine neurotoxins that selectively and irreversibly injure the serotonergic neurons of the myenteric plexus. Treatment with 5,6-, or 5,7-DHT caused marked disruption of the activity front of the migrating myoelectric complex (MMC), increased its duration, and decreased its propagation velocity. At higher doses, 5,7-DHT also reduced the slow-wave frequency. Immunohistochemical techniques showed that tissue from rats treated with 5,7-DHT was depleted of serotonin-like immunoreactivity within the myenteric plexus neurons. Reserpine also caused motility and immunohistochemical changes similar to those induced by the two neurotoxins. Therefore, destruction of enteric serotonergic neurons disrupts the MMC. These studies support the cellular concepts that serotonergic neurons function as interneurons in the myenteric plexus, modulating and processing the neural stimuli, and that serotonin is an important neurotransmitter in the small intestine.

5,6-Dihydroxytryptamine↗
PubMed1991

Purified choleragenoid does not induce migrating action potential complex activity in rabbit ileum in vivo.

The migrating action potential complex (MAPC), a single ring contraction that propels luminal contents abroad, is elicited by Vibrio cholerae and its enterotoxin, choleragen (A1A2B5), in rabbit ileal loops in vivo. Choleragenoid (B5; the binding subunit) was shown previously to induce MAPCs without activating the adenylate cyclase system and without stimulating fluid output. We restudied purified B5 (extracted by high-performance liquid chromatography) to assess its effects on the myoelectric activity of rabbit ileum: can MAPC activity can be induced without associated fluid production? Four different B5 preparations and two controls, V. cholerae and sterile saline, were used. MAPC activity and ileal fluid output were significantly increased in animals inoculated with A1A2B5 (V. cholerae-El Tor) compared with all other preparations and controls. Importantly, MAPC activity and fluid output in all B5 groups did not differ from those in saline controls, demonstrating that purified B5 does not induce MAPC activity in rabbit ilium in vivo. The previous study showing B5-induced MAPCs may have resulted from A1A2B5 contamination. These results suggest A1A2B5-induced adenylate cyclase activation; myoelectric activity may be interrelated with holotoxin binding that causes a neural response.

Action Potentials↗
PubMed1989

Debilitating "functional" bowel disease controlled by leuprolide acetate, gonadotropin-releasing hormone (GnRH) analog.

In this informal initial study, four female patients with intractable chronic abdominal pain, daily nausea, intermittent vomiting, and altered stool habits due to "functional" disease were investigated. A gonadotropin-releasing hormone (GnRH) analog agonist, leuprolide acetate (Lupron) [D-leu6, Desgly-NH2(10), Proethylamide9], was administered once daily (0.5 mg subcutaneously) for three months. At the end of the three-month period, three subjects were symptom-free and the fourth experienced only mild and intermittent pain. The leuprolide regimen was continued for an additional three months, and estrogen (0.625 mg orally) and calcium (1000 mg orally) were given daily to prevent osteoporosis. The patients remained symptom-free. A challenge with progesterone then induced recurrence of mild symptoms in each subject. Withdrawing leuprolide induced the baseline symptoms in all patients within three to five days. This regimen has now been continued for up to 15 months, and all four patients have remained generally symptom-free. Progesterone has also been given every three months to induce menses. A fifth patient, with Roux-en-Y syndrome, has also been treated with leuprolide. She is symptom-free after six months and has gained weight. In this initial observation period in patients with severe functional (neuromuscular) bowel disease, the GnRH analog agonist leuprolide controlled pain, nausea, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Migrating myoelectric complex demonstrated in four avian species.

The migrating myoelectric complex (MMC) is demonstrated in four avian species: three gallinaceous birds (Gallus, Phasianus, Coturnix) and an owl (Strix). The complex in birds is strikingly similar to the MMC that is known in mammalian species. It has the same basic pattern of quiescence, followed by a period of irregular spike activity, then a period of intense regular spike activity, and finally a return to quiescence. The frequency and duration of avian MMCs are similar to those of mammals, but the propagation velocity and slow-wave frequency are slower. Granivorous birds (Gallus, Phasianus) and carnivores (Strix) exhibit the same basic motility patterns whether in the fed or fasted states. Interspecific differences occur, however, in the details of frequency, propagation velocity, duration, and slow-wave frequency. The closely related galliforms (chickens, pheasants) are more similar to each other in MMC characteristics than either is to the more distantly related owls.

Action Potentials↗
PubMed1989

Phorbol esters induce retrograde myoelectric activity in rabbit ileum in vivo.

We demonstrated a unique myoelectric response to phorbol esters and a diacylglycerol, 1-oleoyl-2-acetyl-snglycerol, in rabbit ileal loops. This retrograde activity, the orad migrating complex (OMC), was devoid of slow-wave distortion or alterations in slow-wave frequency. The OMC was not inhibited by the cyclooxygenase inhibitor indomethacin or enhanced by addition of the calcium ionophore A23187. The OMC occurred after 4 beta-phorbol 12-myristate 13-acetate, a phorbol ester known to activate protein kinase C, and after 4 alpha-phorbol 12,13-didecanoate, one that does not. Therefore, these studies provide initial evidence that the myoelectric activity induced by phorbol esters and a diacylglycerol is most likely in addition to the activation of protein kinase C.

Animals↗
PubMed1988

Effects of domperidone in patients with chronic unexplained upper gastrointestinal symptoms: a double-blind, placebo-controlled study.

The effects of domperidone, a peripherally acting dopamine antagonist, were compared with those of placebo in a double-blind randomized study in 16 patients with idiopathic gastric stasis, chronic symptoms of "nonulcer dyspepsia" (including nausea, vomiting, and abdominal pain), and altered gastroduodenal motility. Patients received either domperidone or placebo orally (20 mg before meals and at bedtime) for six weeks. Symptoms were assessed by daily diaries kept by the patients for two weeks while receiving no medication for their gastrointestinal complaints (baseline), and throughout the six-week treatment phase. Studies of gastric emptying of a radiolabeled solid-phase meal were performed at baseline and six weeks after treatment. All patients had delayed gastric emptying at baseline, defined as a half-emptying time of more than mean + 1 SD (from studies of normal controls). An 18- to 24-hr recording of gastroduodenal motor function during fasting was also performed at baseline and after six weeks of either domperidone or placebo treatment. After six weeks of treatment, the symptom scores significantly improved in the domperidone group (P less than 0.05), but not in the placebo group. Gastroduodenal motor activity was unchanged from baseline recordings after six weeks. Solid-phase gastric emptying also showed no improvement in either the domperidone or placebo group of patients. Although domperidone therapy had no significant effect on motility, it appears to be an effective drug for the treatment of the symptoms of nonulcer dyspepsia.

Adult↗
PubMed1988

Gastric emptying in infants with gastroesophageal reflux. Measurement with a technetium-99m-labeled semisolid meal.

It is well established that liquid emptying occurs in the absence of motor activity of the stomach. In contrast, solid-phase emptying is controlled in part by antral peristalsis and is, therefore, a more precise indicator of gastric motility. We developed a semisolid, radionuclide gastric emptying test using rice cereal and technetium-99m-sulfur colloid to assess antral physiology in infants with vomiting. Computer-programmed mathematical models were used to determine the shape of a line that best fit our emptying data points. Linear, simple exponential [f = 2-(t/t1/2)], and power exponential [f = 2(t/t1/2)beta] patterns of emptying were calculated, where f is the fraction of the meal remaining in the stomach at time t, and t1/2 is the time when 50% of the meal has emptied and is a determinant of the shape of the curve. In infants with simple regurgitation (chalasia) and those with vomiting and failure to gain weight, we made statistical comparisons between gastric emptying patterns after analysis of the mean percentage of retained radionuclide at 120 min, calculated t1/2, and area under the curve. The coefficient of determination, R2, was calculated as an index of whether a curve provided goodness of fit to the data. Differences between groups of patients were statistically significant for all parameters of each mathematical model. However, higher coefficients of determination were noted in the power exponential model. The data suggest that the power exponential mathematical model provides the best analysis of the gastric emptying patterns for infants with chalasia and those with vomiting and failure to gain weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1988

Abnormal gastroduodenal motility in children and adolescents with recurrent functional abdominal pain.

To determine whether motor activity of the stomach and proximal small intestine is a factor in recurrent abdominal pain in adolescents, we prospectively investigated eight patients with recurrent abdominal pain and compared them with seven normal adolescents. All patients underwent a detailed examination to exclude other known organic causes of the pain. The gastroduodenal motor activity during fasting was studied with a semiconductor recording probe. The recordings were analyzed for periodicity, duration, and propagation velocity of the activity front of the migrating motor complex. The amplitude of the antral and duodenal contractions was also determined. The patients with recurrent abdominal pain had more frequent migrating motor complexes, but these were shorter in duration and moved more slowly down the intestine (slower propagation velocities). The patients also had high-pressure duodenal contractions that were associated with abdominal pain during the study period. These studies suggest that altered intestinal motility may be the underlying mechanism of recurrent abdominal pain in some children.

Abdomen↗
PubMed1988

Dopamine and norepinephrine in the gastrointestinal tract of mice and the effects of neurotoxins.

Evidence is lacking for neurons containing dopamine and acting as a neurotransmitter in the gastrointestinal tract. The relative percentage of dopamine to norepinephrine in noradrenergically innervated tissues (e.g., spleen) is known to be relatively constant within a species, and an increased percentage in any given tissue supports the premise that dopaminergic cells are present. We measured levels of norepinephrine, dopamine and the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) from segments of the gastrointestinal tract of mice after injection of: 1) saline (control); 2) 6-hydroxydopamine (6-OHDA); or 3) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In control tissues the ratio of dopamine/norepinephrine was higher (P less than .001) than in the spleen; DOPAC was present and the DOPAC/dopamine ratios were similar to those in the central nervous system (where dopaminergic neurons are present). Dopamine and norepinephrine were decreased by 6-OHDA in most myenteric plexus/smooth muscle tissues compared with controls and DOPAC was unmeasurable in most samples after 6-OHDA. In contrast, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine decreased norepinephrine but not dopamine in the smooth muscle/myenteric plexus. High dopamine/norepinephrine percentages, 6-OHDA depletion of dopamine and presence of DOPAC together suggest the presence of dopamine-containing neurons in the myenteric plexus of the gastrointestinal tract of mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

WHR 1049, a potent metabolite of lidamidine, has antidiarrheal and antimotility effects on the small intestine in rats.

Lidamidine HCl has been suggested to be effective in treating certain motor disorders of the gastrointestinal tract. Lidamidine has alpha-2 agonist as well as local anesthetic properties. We studied the antimotility and antidiarrheal activity of WHR 1049, a hepatic metabolite of lidamidine known to have some activity and to persist longer in the serum than does lidamidine. We recorded the intestinal myoelectric activity of fasted unanesthetized rats with bipolar electrodes implanted on their proximal jejunum. We found that lidamidine HCl, given by gavage, inhibited fasting myoelectric activity in a dose-dependent manner (using 0.5-4.0 mg/kg). Neither saline nor tetracaine inhibited myoelectric activity. WHR 1049 given by gavage also inhibited myoelectric activity and was 30 times as potent as lidamidine (milligram per milligram, using 0.0625- to 0.25-mg/kg doses). Pretreatment with yohimbine (5 mg/kg s.c.), before administration of WHR 1049, decreased the myoelectric activity inhibition by two-thirds (but did not completely block it). Castor oil (1 ml/200 g b.wt.) was given to induce diarrhea and did so when given alone or with saline (vehicle) pretreatment. When these animals were pretreated with 0.25 mg/kg of WHR 1049, the same dose of castrol oil did not induce diarrhea for a 6-hr observation period. We conclude that WHR 1049 is a potent metabolite of lidamidine that inhibits myoelectric activity, has significant alpha-2 agonist activity and blocks induced diarrhea. Because tetracaine does not inhibit myoelectric activity we suggest that the local anesthetic properties of lidamidine do not account for any of the myoelectric activity inhibition. WHR 1049 may account for much of the antimotility and antidiarrheal activity of lidamidine.

Action Potentials↗
PubMed1987

Chronic alterations in jejunal myoelectric activity in rats due to MPTP.

Parkinsonian patients may have symptoms consistent with intestinal pseudo-obstruction, but a primary intestinal abnormality has not been shown. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after conversion to a toxic metabolite via the monoamine oxidase system, can induce Parkinson's disease by destroying dopaminergic neurons in the substantia nigra in humans and primates. Rodents have some catecholamine depletion but much less so than primates. Using chronic bipolar electrodes on the proximal jejunum of Wistar rats, we show significant, chronic migrating myoelectric complex disruption (P less than 0.001) and prolongation of irregular spike activity (P less than 0.001). Pargyline (a monoamine oxidase inhibitor) pretreatment significantly blocked these myoelectric changes. Sinemet (L-dopa and carbidopa), given after MPTP to replete dopamine, decreased the MPTP-induced migrating myoelectric complex disruption. Jejunal myenteric plexus dopamine levels were significantly decreased (to 61% of control) after MPTP but after much higher doses than were required to disrupt migrating myoelectric complex activity (180 mg/kg total vs. 30 mg/kg). Dopamine in the central nervous system was not depleted. We conclude that MPTP causes intestinal myoelectric disruption (which can be blocked by pargyline and decreased by Sinemet) possibly through enteric, but not central, nervous system effects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Effect of lidamidine hydrochloride and loperamide on gastric emptying and transit of the small intestine. A double-blind study.

We performed a double-blind randomized study in 24 healthy volunteers, to evaluate the effects of two doses of lidamidine hydrochloride, loperamide, and placebo on transit of the small intestine and gastric emptying. Transit time of the small intestine was determined by measuring the rise in breath hydrogen excretion after ingestion of lactulose. Although there was a trend for prolonged intestinal transit time in both lidamidine groups, this difference was not significant compared with that in the placebo group. Loperamide significantly slowed transit when compared with placebo or lidamidine (p less than 0.001). Gastric emptying was assessed by using a solid-phase radiolabeled meal. Three parameters of gastric emptying were analyzed: half-emptying time, area under the gastric emptying curve, and beta. Although there was a trend for a longer half-emptying time in the group that received 12 mg of lidamidine, this difference approached, but did not reach, statistical significance (p = 0.06) compared with placebo. The area under the gastric emptying curve, a potentially more sensitive parameter for measuring gastric emptying, was significantly increased in the group receiving 12 and 18 mg of lidamidine (p less than 0.05) compared with the group receiving loperamide or placebo. In summary, lidamidine significantly delayed gastric emptying but had no significant effect on small bowel transit. These data suggest that the antidiarrheal properties of lidamidine are the result of enhanced absorption or inhibition of secretion of fluid and electrolytes.

Adolescent↗
PubMed1985

Development of an improved multi-pressure-sensor probe for recording muscle contraction in human intestine.

We have developed an improved semiconductor recording probe for monitoring motility of the upper small intestine in humans. The probe consists of six ultraminiature silicon pressure sensors spaced 10 cm apart and encased in a flexible polyurethane sheath. The probe is small [2.67 mm (8F) diameter], is easily passed transnasally, and is tolerated by patients for prolonged recording periods (24-36 hr) with a minimum of discomfort. The initial semiconductor and catheter material were those designed for use in the cardiovascular system, but they proved to be easily damaged by gastric acid and enzymes. After improvement of this probe, we now have recordings from more than 100 patients for an approximate total of 6000 hr of recording time. The improved probe is a durable recording device that facilitates the investigation of motility of the small intestine in humans in health and disease.

Humans↗
PubMed1985

Alterations of myoelectric activity associated with Campylobacter jejuni and its cell-free filtrate in the small intestine of rabbits.

We evaluated the effects of a culture of Campylobacter jejuni and its cell-free filtrate on myoelectric activity of isolated ileal segments in New Zealand White rabbits. Hematoxylin and eosin staining and scanning electron microscopy were used to assess the association between histologic changes and alterations in intestinal myoelectric activity. A culture of C. jejuni was shown to cause a significant increase in repetitive bursts of action potentials (RBAPs) (6.9 +/- 1.2 RBAP/h; p less than 0.001) compared with controls (0.3 +/- 0.1). Cell-free filtrates of C. jejuni cultures were also observed to induce RBAPs (5.0 +/- 0.9 RBAP/h; p less than 0.001). The fraction within the filtrate that induces alterations in motility was not destroyed by heating to 100 degrees C for 15 min (6.3 +/- 1.2 RBAP/h). Although no gross histologic changes were noted by hematoxylin and eosin staining of intestine exposed to a culture of C. jejuni for 8 h, blunting of villi with a cellular infiltrate was noted in rabbits exposed for 24 h. Scanning electron microscopy disclosed patchy villous tip damage in 3 of 5 animals exposed to cell-free filtrates for 8 h. These studies suggest C. jejuni is pathogenic and produces a heat-stable substance that alters intestinal myoelectric activity in rabbits.

Action Potentials↗
PubMed1985

Nausea, vomiting, and abdominal pain after Roux-en-Y anastomosis: motility of the jejunal limb.

The Roux-en-Y anastomosis is a surgical procedure performed to divert the pancreaticobiliary juices from the gastric pouch in patients who have alkaline reflux gastritis or esophagitis, or both, that develop after vagotomy and Billroth I or II operations. After the Roux-en-Y procedure the inflammation subsides but is often replaced by a characteristic group of symptoms--chronic abdominal pain, nausea, and vomiting worsened by eating. Using a semiconductor recording probe, we investigated the Roux limb in 7 subjects who were fasted and then fed (liquid and solid meals). In the fasted state the migrating motor complex was either completely absent or grossly disrupted. Only 1 subject converted to a fed-state motility pattern in the Roux limb after a liquid meal (Osmolite), and all 7 subjects failed to convert to a fed state after a solid meal. These studies suggest that the Roux-en-Y syndrome of pain, nausea, and vomiting is secondary to a defect in motor function and that the Roux limb is acting as an area of functional obstruction.

Adult↗