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Biomedical subjects

C A Sninsky

Publications and source records attributed to C A Sninsky.

51 records · Page 3Linked to original sources

Normal and abnormal gastrointestinal motility.

The study of GI motility is an area of great current interest and excitement. Our knowledge of normal and abnormal GI motility is expanding exponentially. Perhaps one of the most satisfying consequences of this new knowledge is the ability to reassure patients that their symptoms may not be functional but may be based on a specific physiologic dysfunction. Unfortunately, our ability to treat effectively these newly described disorders has lagged behind our ability to diagnose them, but progress is being made, with promising new therapeutic agents on the horizon. Gastroenterologists remain the best friends of surgeons; most of these patients can and should be managed without surgical intervention. Therapeutic nihilism is not justified, because a carefully considered and properly timed operation may be of tremendous symptomatic benefit to selected patients. As more information and follow-up results are gained, the proper role of surgical intervention in these disorders will be better defined.

Antiemetics↗

Altered tail-skin temperature responsiveness in streptozotocin-induced diabetic rats.

We evaluated the tail-skin temperature response to administration of several doses of isoproterenol in streptozotocin-induced diabetic rats after 48 h and after 4 weeks of diabetes. Blood glucose concentrations were significantly increased over controls 48 hours after administration of streptozotocin (65 mg/kg, i.v.) and remained elevated to a similar degree in the 4-week group. Basal rectal temperature and tail-skin temperature (TST) were not different between controls and the diabetic groups and were not affected by administration of saline. However, administration of isoproterenol (25 micrograms/kg, s.c.) caused a significant rise in TST in the control group, but not in the rats diabetic for 4 weeks. A similar but exaggerated response was observed in the controls after subcutaneous administration of 40 micrograms/kg and 100 micrograms/kg of isoproterenol. The TST response in the 4-week diabetic rats still remained negligible with the two higher doses of isoproterenol. When the data were summarized as area under the TST curve, a dose-dependent increase was observed in the control groups and a significant absence of response was observed in the 4-week group. The rats studied 48 h after streptozotocin injection had a similar TST response to the control group after administration of 40 micrograms/kg of isoproterenol. Colonic temperatures did not significantly change between the two groups in any of the studies, although the colonic temperatures tended to rise in the control groups following administration of isoproterenol. We conclude from this study that the absence of a tail-skin temperature response in rats diabetic for 4 weeks results from either a reduced beta-adrenergic receptor mediated response or an altered neural thermoregulatory reflex response, or both. These changes are probably not due to streptozotocin treatment or increases in blood glucose.

Animals↗

Vincristine alters myoelectric activity and transit of the small intestine in rats.

We investigated the motility of the small intestine in unanesthetized rats receiving vincristine (0.075, 0.50, 0.75 mg/kg i.v.). Motility was determined by two methods: myoelectric activity was monitored with indwelling bipolar electrodes, and intestinal transit was measured by the movement of radiochromium (Na51CrO4). Only the animals injected with the two higher doses had two distinct patterns of altered intestinal myoelectric activity within 2 h of drug administration. The first alteration occurred 44 +/- 6 min after vincristine administration and consisted of a marked increase in action potential activity with disruption of the migrating myoelectric complex. The second alteration consisted of a reappearance of the activity front of the migrating myoelectric complex with a significantly shorter periodicity. A marked reduction in spike activity occurred 3 days after vincristine injection in 3 of 10 animals receiving vincristine. A biphasic response was noted in intestinal transit. Disrupted activity front formation was associated with a significant delay in small bowel transit. In contrast, frequent activity front formation in rats was associated with significantly hastened transit. In summary, vincristine administration induces alterations of myoelectric activity of the small intestine in fasted rats and is associated with changes in intestinal transit.

Action Potentials↗

Myoelectric activity of the small intestine during morphine dependence and withdrawal in rats.

We investigated the effect of morphine dependence on the migrating myoelectric complex (MMC) of the small intestine, whether bacterial overgrowth developed in morphine-dependent rats, and the effect of naloxone, 0.5 mg/kg sc, and methylbromide naltrexone, 1.0 mg/kg sc, a peripheral opioid antagonist, on the MMC in morphine-naive and morphine-dependent rats. We also evaluated intestinal motility during naloxone-induced withdrawal in animals pretreated with clonidine, 100 micrograms/kg sc. Intestinal myoelectric activity was monitored by four indwelling electrodes in unanesthetized, fasted rats. D-[14C]xylose breath tests were performed before and after morphine-pellet implantation to evaluate the presence of bacterial overgrowth of the small intestine. Naloxone had no effect on myoelectric activity of the small intestine in morphine-naive rats. Cycling activity fronts were present in morphine-dependent animals, but there was a significant prolongation of activity front periodicity and slowing of the propagation velocity. No significant increase in 14CO2 excretion was noted in the morphine-dependent rats. After injection of naloxone, the morphine-dependent rats had a marked increase in spike activity with no identifiable activity fronts for 89 +/- 8 min. Similarly, methylbromide naltrexone disrupted activity fronts, but for a significantly shorter period. Clonidine prevented the marked increase in spike activity that occurred during naloxone-induced withdrawal. We conclude from our studies that myoelectric activity of the small intestine develops incomplete tolerance to morphine; bacterial overgrowth is not a feature of morphine dependence in the rat; alterations of intestinal myoelectric activity are a component of the opiate withdrawal syndrome, and they appear at least partially mediated by a peripheral mechanism that can be suppressed by an alpha 2-adrenergic agonist.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Long-term response to subtotal colectomy in colonic inertia.

The purpose of this study was to determine the long-term outcome of patients who had previously undergone subtotal colectomy for severe idiopathic constipation at the University of Florida between 1983 and 1987. In addition, we aimed to determine whether preoperative motility abnormalities of the upper gastrointestinal tract are more common among those patients who have significant postoperative complications after subtotal colectomy. We evaluated 13 patients who underwent subtotal colectomy for refractory constipation between 1983 and 1987 at the University of Florida. Preoperatively, all patients exhibited a pattern consistent with colonic inertia as demonstrated by means of radiopaque markers. Each patient was asked to quantitate the pain intensity and frequency of their bowel movements before and after surgery. In seven patients an ileosigmoid anastomosis was performed, whereas in six patients an ileorectal anastomosis was used. Abdominal pain decreased after subtotal colectomy. Patients with abnormal upper gastrointestinal motility preoperatively experienced greater postoperative pain than those with normal motility regardless of the type of anastomosis. In addition, the number of postoperative surgeries was similar in those patients with abnormal upper motility compared to those with normal motility. Overall, the total number of bowel movements per week increased from 0.5 +/- 0.03 preoperatively to 15 +/- 4.5 (P < 0.007) postoperatively. The results of our study suggest that patients with isolated colonic inertia have a better long-term outcome from subtotal colectomy than patients with additional upper gastrointestinal motility abnormalities associated with their colonic inertia.

Adolescent↗

Chronic intestinal pseudo-obstruction.

Chronic intestinal pseudo-obstruction denotes the clinical picture that results due to the failure of intestinal peristalsis to overcome the normal resistance to flow and is characterized by recurrent episodes of signs and symptoms of intestinal obstruction in the absence of any mechanical compromise of the intestinal lumen. The region(s) of the gut affected may be isolated or diffuse. It is not uncommon to find evidence of autonomic neuropathy and smooth muscle dysfunction with extraintestinal manifestations such as urinary symptoms from abnormal ureter or bladder function. Intestinal pseudo-obstruction can be caused by a variety of diseases, and for simplicity, certain authors have divided it into myopathic and neuropathic categories. Intestinal pseudo-obstruction may present at any age with a variable amount of abdominal pain, distension, nausea, diarrhea, or constipation and with laboratory abnormalities usually reflecting the degree of malabsorption and malnutrition present. The radiologic findings are varied but commonly include paralytic ileus or signs of apparent clinical obstruction with dilated loops of bowel. The number of pseudo-obstruction cases is dependent on how one defines the condition. It appears prudent to require radiographic abnormalities consistent with obstruction on a plain film of the abdomen for the diagnosis. More recently, studies have focused on the gastrointestinal manometric abnormalities of the stomach and small intestine in chronic intestinal pseudo-obstruction during fasting and fed states; however, sensitivity and specificity of these abnormalities are not well defined. Treatment is aimed at limiting symptoms and maintaining adequate nutrition. Prokinetic agents should be tried in an attempt to restore normal intestinal propulsion. However, their overall efficacy appears to be variable. It is still too premature to consider intestinal pacing or small bowel transplantation in this condition. Surgical approaches to chronic intestinal pseudo-obstruction should be limited to patients refractory to medical therapy, and even then, an approach focused on the patient's primary presenting symptoms should be considered.

Chronic Disease↗