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Biomedical subjects

K A Kelly

Publications and source records attributed to K A Kelly.

At least 199 records · Page 11Linked to original sources

Immunochemical properties of some monoclonal IgE antibodies to 4-hydroxy-3-nitrophenylacetyl (NP).

Several hybridoma cell lines secreting NP-specific, murine IgE antibodies were generated by fusion of P3-X20 (gamma, kappa) tumour cells with spleen cells from (BALB/c X C57B1/6)F1 (CB6F1) mice previously immunized with NP-ovalbumin. Four subclones (designated NP-epsilon-3.57, NP-epsilon-15.88, NP-epsilon-91.58 and NP-epsilon-95.31) were propagated in vivo and milligram quantities of the corresponding IgE antibodies were purified from ascitic fluid by gel filtration, ion exchange chromatography and affinity chromatography. Immunological analyses and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) indicated that NP-epsilon-15.88, NP-epsilon-91.58 and NP-epsilon-95.31 all possessed lambda 1 (or possibly lambda 3) light chains; and that NP-epsilon-3.57 possessed lambda 2 light chains; NP-epsilon-95.31 also expressed the P3-X20 derived, MOPC-21 kappa light chain. Radioallergosorbent test (RAST) titration curves, generated from the interaction of the four monoclonal IgE antibodies with NP-BSA attached to paper discs (NP-BSA-P) were found to be non-overlapping. Measurements of the relative amounts of NP-epsilon-aminocaproic acid (NP-CAP) and 4-hydro-3-iodo-5-nitrophenylacetyl-epsilon-aminocaproic acid (NIP-CAP) that were required to inhibit by 50% the binding of the 4 IgE antibodies to NP-BSA-P indicated that these antibodies were all heteroclitic, since their affinity for NIP appeared to be higher than their affinity for NP. These results, in conjunction with other findings reported in the literature, suggested that the V regions of NP-specific IgE antibodies are similar to the V regions of NP-specific IgM and IgG antibodies, produced by the same mouse strains. Finally, in vitro histamine release measurements demonstrated that two of these monoclonal IgE antibodies could mediate antigen induced histamine release from passively sensitized rat peritoneal mast cells.

Animals↗

Straight ileoanal anastomosis v ileal pouch--anal anastomosis after colectomy and mucosal proctectomy.

The postoperative results of 50 patients who underwent straight ileoanal anastomosis after total colectomy and mucosal proctectomy were compared with those of 74 patients who underwent ileal pouch--anal anastomosis. No deaths occurred. Of the straight ileoanal anastomoses, 32% failed because of sepsis or diarrhea and necessitated abdominal ileostomy; only 1.3% failed in the pouch-anal group (P less than .05). Stool frequency among patients followed up for three months or more (straight ileoanal, n = 30; pouch-anal, n = 33) was less in the pouch-anal group (mean +/- SEM, 7 +/- 1 stools per 24 hours) than in the straight ileoanal group (11 +/- 1/24 hr, P less than .01). Major nocturnal incontinence was also less in the pouch-anal group than in the straight ileoanal group (0% v 20%), and patient satisfaction was better, as measured on a scale of 1 (very poor functional result) to 10 (excellent result) (pouch-anal score, 9; straight ileoanal score, 6; P less than .02). We concluded that ileal pouch-anal anastomosis resulted in less diarrhea, better continence, and an improved quality of life when compared with straight ileoanal anastomosis.

Adult↗

Motilin regulation of canine interdigestive intestinal motility.

The objective was to determine whether motilin regulates cyclical interdigestive motility in the jejunum as well as in the duodenum. In four conscious dogs with an intact innervated duodenum, an autotransplanted (extrinsically denervated) 75-cm loop of proximal jejunum, and an autotransplanted, in situ distal jejunum, interdigestive myoelectrical complexes cycled independently in all three regions of small bowel. Plasma concentration of motilin was greater during phase III of the duodenal cycles (304 +/- 37 pg/ml) than during phase I (235 +/- 37 pg/ml) or phase II (235 +/- 39 pg/ml; P less than 0.05), but the concentration did not vary consistently with the phases of the cycles in the autotransplanted jejunal segments. Intravenous infusions of motilin (0.6 microgram/kg/min for 5 hr), begun 15-30 min after passage of phase III through the duodenum, shortened the interval between phase IIIs in the duodenum from 147 +/- 14 min before infusions to 44 +/- 3 min during the infusions (P less than 0.05), but did not alter consistently the interval between phase IIIs in the autotransplanted jejunal segments. Feeding decreased plasma motilin concentration. The data were consistent with motilin regulation of interdigestive motility in intact, innervated canine duodenum but not in extrinsically denervated jejunum.

Action Potentials↗

A continent ileostomy device.

The feasibility of achieving fecal continence by mechanical occlusion of an end-ileostomy is explored. Accordingly, progressive stomal occlusion with an indwelling occluding device was evaluated in four healthy patients with Brooke ileostomies. Pre-occlusion clinical and physiologic tests were done, including fat balance, intestinal transit time, ileal motility and absorption, ileal compliance, ileal radiography, and ileoscopy. Progressive stomal occlusion was then employed until periods of occlusion of 5 to 8 hours were achieved after 10 to 16 weeks. Pre-occlusion tests were then repeated. Patients mastered use of the occluding device rapidly, and the device achieved reliable stomal continence in each patient. Whereas ileal capacity was small initially, intermittent occlusion resulted in a large, capacious ileal reservoir. Fasting ileal motility was increased slightly by stomal occlusion, although intestinal transit during feeding was not altered. Also, ileal absorption of glucose, electrolytes, vitamin B-12, and fat were not changed, and ileal mucosa at the site of occlusion remained intact endoscopically. The authors concluded that chronic intermittent occlusion of a Brooke ileostomy with an indwelling stomal device achieved enteric continence without impairing intestinal function.

Adult↗

A clinico-physiological comparison of ileal pouch-anal and straight ileoanal anastomoses.

The ileal pouch-anal anastomosis improves clinical results after colectomy and mucosal proctectomy compared to the straight ileoanal anastomosis. The question was what physiologic changes brought about by the pouch led to the improvement. Among 124 patients who had had ileoanal anastomosis, 25 volunteered for a detailed clinicophysiologic evaluation. Fourteen had had the ileal pouch-anal operation a mean of 8 months previously, and 11 had the straight ileoanal operation a mean of 25 months previously. Both groups of patients had satisfactory anal sphincter resting pressures (mean +/- SEM, pouch = 68 +/- 8 cm H2O, straight = 65 +/- 9 cm H2O, p greater than 0.05) and neorectal capacities (pouch = 278 +/- 26 ml, straight = 233 +/- 36 ml, p less than 0.05), and all could evacuate spontaneously. However, the pouch patients had a more distensible neorectum (delta V/delta P pouch = 9.5 +/- 1.3 ml/cm H2O, straight = 4.9 +/- 0.9 ml/cm H2O, p less than 0.05) and smaller amplitude neorectal contractions (pouch = 36 +/- 5 cm H2O, straight = 90 +/- 13 cm H2O; p less than 0.05). We concluded that the pouch-anal anastomosis increased the distensibility of the neorectum and decreased its propulsive drive, and so improved clinical results.

Adult↗

Enhancing the anti-dumping effect of Roux gastrojejunostomy with intestinal pacing.

We wondered whether Roux gastrojejunostomy alone or with intestinal pacing would slow gastric emptying and ameliorate the dumping syndrome after truncal vagotomy and subtotal distal gastrectomy. In five conscious dogs with vagotomy and distal gastrectomy, the Roux loop alone slowed gastric emptying of 100 ml 5% glucose instillates, but not of 100 ml 25% glucose instillates, while pacing the loop backwards slowed emptying of both. Pacing also decreased the postcibal hemoconcentration and hyperglycemia found after the 25% instillates. However, pacing did not alter the postprandial hyper-GIP-emia (gastric inhibitory peptide) and hyperinsulinemia found in Roux gastrectomy dogs, suggesting that pacing worked by slowing emptying of glucose rather than by releasing enteric hormones. Although pacing did not stimulate jejunal action potentials (contractions), the greater the number of action potentials occurring during pacing, the more the slowing (r = .738, p less than .001). We concluded that the combination of Roux gastrojejunostomy and pacing ameliorated postgastrectomy dumping in dogs. The tests provide a basis for treating humans with postgastrectomy dumping.

Animals↗

Dysfunction of the continent ileostomy: clinical features and bacteriology.

The pathogenesis and treatment of dysfunction of the continent ileostomy was investigated in 12 patients, five of whom had asymptomatic malabsorption and seven of whom had acute complaints. The number of anaerobic bacteria in jejunal aspirates was increased in patients with pouch malfunction (range 10(3) to 10(8)/g aspirate), but the microbiology of ileal effluent and the morphology of the ileal mucosa could not be correlated with dysfunction. Bile acid breath tests and lactose tolerance tests were not, however, reliable indicators of jejunal bacterial overgrowth. The symptoms, the malabsorption, and the number of jejunal and ileal anaerobic bacteria decreased in patients during treatment with metronidazole, implicating overgrowth of anaerobic bacterial flora in the pathogenesis of the syndrome.

Adolescent↗

Neural control of canine small intestinal interdigestive myoelectric complexes.

Our aim was to determine the role of the extrinsic and intrinsic nerves in the regulation of the small intestinal interdigestive myoelectric complex (IMC). In five dogs, the extrinsic nerves of the jejunoileum were divided, but the bowel was left in situ with its wall intact. After recovery, IMCs were detected in the duodenum (mean IMC period +/- SE = 188 +/- 19 min), from where most migrated distally into and through the jejunum (84%). In addition, extra IMCs appeared in the jejunum. Thus, the mean period of the IMCs in the jejunum (134 +/- 10 min) was shorter than in the duodenum (P less than 0.05). In contrast, after enteric transection and reanastomosis at the ligament of Treitz and at a site 75 cm distal to the ligament, fewer duodenal IMCs migrated into the jejunum (only 61%). However, extra IMCs still arose in the jejunum, so that the mean period of IMCs in the jejunum (111 +/- 5 min) was now similar to that in the duodenum (128 +/- 4 min, P greater than 0.05). Our data were consistent with the hypothesis that extrinsic nerves regulate the frequency of the small intestinal IMCs, while an intact enteric wall aids in their distal propagation.

Action Potentials↗

Postprandial inhibition of canine enteric interdigestive myoelectric complex.

Our aim was to determine whether the passage of postprandial duodenal chyme into the jejunum activates jejunal feedback mechanisms that inhibit the interdigestive myoelectric complex (IMC) of the canine small bowel. In five conscious dogs with 75-cm Vella loops of proximal jejunum and recording electrodes on the duodenum and the loop, intestinal myoelectric activity was recorded for approximately 4 h during fasting. The dogs were then given either a 200-g liver meal orally or they underwent perfusion of the jejunal loop with postprandial duodenal chyme collected from a donor dog given an identical liver meal. Before feeding, IMCs occurred at mean intervals of 126 +/- 16 (SE) min in the duodenum and 88 +/- 10 min in the loop. Feeding by mouth completely inhibited the IMCs in the duodenum but failed to inhibit the IMCs in the loop. However, perfusion of the jejunal loop with duodenal chyme suppressed the IMCs in both the loop and the duodenum. We concluded that postprandial inhibition of duodenal IMCs is mediated in part by neural and/or hormonal factors activated by chyme in the jejunum, whereas local factors inhibit jejunal IMCs. An enteric phase of postprandial IMC inhibition is postulated.

Animals↗

Antral control of canine gastric emptying of solids.

We wondered whether antral mucosal nerves sense the size of particles in gastric chyme and then activate motor mechanisms that allow only small particles to empty. Four conscious dogs with duodenal Thomas cannulas were fed 100 g of bovine liver, half of which was labeled with cyano[57Co]cobalamin. Duodenal chyme was then collected in 15-min periods for 5 h and poured through a stack of sieves of decreasing pore size, and the percentage of radioactivity recovered on each sieve was determined per hour. Five studies were carried out on each dog before and beginning 2 wk after antral mucosal neurolysis, during which the antral mucosal nerves were divided by dissecting the entire antral mucosa circumferentially free from the surrounding antral muscularis. In the control tests, nearly all liver (93%) emptied as particles less than 1.4 mm in diameter, but the percentage emptied as larger particles increased in the 3rd through 5th postprandial h. After antral mucosal neurolysis, the increase in the percentage of larger particles emptied occurred sooner and to a greater extent, but the overall rate of emptying of liver was not changed. We concluded that antral mucosal nerves have a role in regulating the size of gastric particles emptied, but a minor one.

Animals↗

Intestinal pacing for canine postgastrectomy dumping.

Our aim was to determine whether or not postprandial retrograde duodenal pacing would abolish the canine postgastrectomy dumping syndrome. Five dogs underwent truncal vagotomy, distal hemigastrectomy, gastroduodenostomy, and circumferential proximal duodenal myotomy to facilitate pacing. Bipolar stimulating electrodes from an implanted pacing unit were attached to the bowel 35 cm distal to the gastroduodenostomy, and six monopolar recording electrodes were applied at 5-cm intervals proximal to the pacing electrodes. After recovery, gastric emptying was assessed in the fasted conscious dogs using 300-ml gastric instillates of 25% dextrose marked with [14C]polyethylene glycol, while pulse, hematocrit, and defecation were monitored. Each dog underwent five tests with and five tests without retrograde duodenal pacing. Without pacing, the dogs emptied a mean +/- SEM of 237 +/- 14 ml of the instillate by 20 min and developed tachycardia (change in pulse, 45 +/- 4), hemoconcentration (change in hematocrit, 8 +/- 1), and diarrhea in 13 of 25 tests. Retrograde duodenal pacing slowed gastric emptying (157 +/- 20 ml, p less than 0.05) and minimized the adverse cardiovascular sequelae (change in pulse, 25 +/- 5, change in hematocrit, 6 +/- 1; p less than 0.05) and the diarrhea (only 2 of 25 tests, p less than 0.01). We concluded that intestinal pacing ameliorated the postgastrectomy dumping syndrome in dogs. Such an approach may be applicable to humans.

Action Potentials↗

Predicting outcome after endorectal ileoanal anastomosis.

The aim of this study was to determine whether anorectal manometry could predict clinical outcome after closure of a diverting ileostomy made at the time of colectomy, mucosal proctectomy and endorectal ileoanal anastomosis for chronic ulcerative colitis. Twenty-two patients were studied, 6 with ileoanal anastomosis and 16 with ileal pouch-anal anastomosis. Resting anal sphincter pressures and pressure-volume curves (compliance) of the neorectum were assessed before the diverting ileostomy was closed and results were correlated with frequency and leakage of stools 1 month after closure. Before stomal closure, the mean (+/- standard error of the mean) resting sphincteric pressure was 44 +/- 5 cm H2O, while neorectal compliance was 2.3 +/- 0.3 ml/cm H2O. One month later daily stool frequency was 12 +/- 1, while severe leakage occurred in four patients during the day and in eight at night. The greater the sphincteric pressure and the compliance, the fewer were the number of stools per day (p less than 0.01). When pressure and compliance were considered together as an index of anorectal function, the correlation of stool frequency and leakage was even stronger (p less than 0.001). The authors conclude that anorectal manometry can predict early clinical outcome after ileoanal anastomosis.

Adolescent↗

Proximal gastric vagotomy: update.

Experience with proximal gastric vagotomy at the Mayo Clinic from 1973 to Mayo 1980 is reported. Among 298 patients who had proximal gastric vagotomy for chronic duodenal, pyloric channel, or prepyloric ulcers, a recurrent ulcer rate of 7% was present, with a mean follow-up of 49 months. Three recurrences developed in six patients who had proximal gastric vagotomy for gastric ulceration. In 40 patients, proximal gastric vagotomy was combined with gastrojejunostomy, pyloroplasty, or pyloric dilatation for obstructing ulcers. There was a 15% incidence of reoperation in the gastrojejunostomy group. All nine patients who had proximal gastric vagotomy for active or recent bleeding ulcers were dismissed from the hospital without further hemorrhage, and only one developed a recurrent ulcer. It is concluded that proximal gastric vagotomy remains an acceptable operation for chronic duodenal and pyloric ulcers, but its efficacy in gastric ulcers is unproved.

Female↗

Proximal gastric vagotomy and mucosal antrectomy: a possible operative approach to duodenal ulcer.

Our aim was to develop proximal gastric vagotomy with mucosal antrectomy as an operative approach to duodenal ulcer. We performed mucosal antrectomy in four dogs by excising the antral mucosa via a circular corporal myotomy, removing a circumferential band of corporal seromuscularis, anastomosing the corporal and pyloric mucosas endoantrally, and reapproximating the corporal and antral seromuscularis. Gastric emptying and serum gastrin were assessed before and 4 weeks after operation. A second operation, proximal gastric vagotomy, was then done, and the tests were repeated 4 weeks later. The concentration of gastrin in the serum during fasting was lower after mucosal antrectomy than before operation, as was the postprandial concentration; the values remained low after proximal gastric vagotomy. Gastric emptying of liquids and indigestible solids was unaltered by mucosal antrectomy or mucosal antrectomy plus proximal gastric vagotomy. The emptying of digestible solids was slowed somewhat by mucosal antrectomy to 75% of the control rate, but no further change was found after proximal gastric vagotomy. We concluded that mucosal antrectomy eliminated the gastrin-producing antral mucosa and, in combination with proximal gastric vagotomy, did not greatly alter gastric emptying of liquids or solids. The combined operation might have a role in the surgical treatment of duodenal ulcer.

Animals↗

Achieving ileostomy continence with a prestomal ileal pouch and a stomal occlusive device.

To determine whether an artificial, indwelling, stomal occluding device could provide reliable continence for persons with an ileostomy and a prestomal ileal pouch, the device was tested first in four dogs and then in humans. After initial assessment of pouch volume and pressure-volume relationships in the dogs, the animals underwent progressively longer periods of stomal occlusion with the artificial device, such that 4 weeks later, they were tolerating occlusion for periods of 8 hours. The device achieved complete continence for gas and stool without discomfort in every dog. The pouch capacity rapidly increased, so that infusion of 500 ml of water at 4 weeks elicited less than a 10 cm H2O increase in intrapouch pressure. These encouraging canine results prompted use of this approach in a 55-year-old obese man undergoing proctocolectomy for chronic ulcerative colitis. The device achieved continence in the patient for 4- to 6-hour periods by 2 months after operation without discomfort or adverse sequelae. We concluded that the artificial device rapidly increased pouch capacity and effectively maintained leakproof fecal continence in dogs and humans with an ileostomy and a prestomal ileal pouch.

Animals↗

Physiologic aspects of continence after colectomy, mucosal proctectomy, and endorectal ileo-anal anastomosis.

We examined the physiology of continence in 12 patients at least four months after colectomy, mucosal proctectomy, and endorectal ileo-anal anastomosis for ulcerative colitis and familial polyposis. The mean fecal output (+/-SEM) was 598 +/- 60 gm, passed as 12 +/- 4 movements/24 hr, of which 4 +/- 1 were passed at night. The patients were generally continent during the day and could distinguish gas from stool, but 11 of 12 leaked stools at night. Anal sphincter resting pressures (71 +/- 8 cm H2O) and squeeze pressures (171 +/- 15 cm H2O) of patients were similar to those of ten healthy controls (P greater than 0.05), although the rectal inhibitory reflex was absent in the patients. After operation, the distal bowel had a pressure-volume curve of greater slope (0.15 +/- 0.05 ml/cm H2O) than it had in controls (0.07 +/- 0.01 ml/cm H2O, P less than 0.05) and a lesser maximum capacity (patients, 248 +/- 31 ml; controls, 406 +/- 26 ml; P less than 0.05). The greater the capacity of the neorectum, the fewer was the number of bowel movements/day (r = 0.91, P less than 0.001). We concluded that the operation preserved the anal sphincter, although it decreased the capacity and compliance of the distal bowel and impaired continence.

Adult↗

Suppression of IgE antibody production in sensitized mice and rats by tolerogenic conjugates of synthetic hydrophilic polymers with antigen or hapten: effect on antigen-induced histamine release from peritoneal mast cells.

IgE antibodies were produced in mice and rats by immunization with ragweed pollen extract (RAG) or dinitrophenylated ovalbumin (DNP3-OA). Treatment of these animals with tolerogenic conjugates of (i) the antigen (RAG or OA) with monomethoxypolyethylene glycol (mPEG), or (ii) DNP with polyvinyl alcohol (DNP-PVA) resulted, within 7-14 days, in a fall in circulating IgE antibodies and in mast cell sensitivity, as assessed by the radioallergosorbent test (RAST) and in the in vitro antigen-induced histamine release (HR) test, respectively. The reduction in responsiveness was more marked in mice than rats; 10 days after a booster immunization, the IgE antibody titres in the RAG-mPEG-treated group of mice were approximately 10-fold lower than in the saline-treated group, with a 100-fold difference in cell sensitivity. DNP-PVA treatment of mice produced a more than 10-fold reduction in IgE anti-DNP titres with a substantial reduction in histamine release.

Animals↗