Search PubMed⌕ Search

Biomedical subjects

K A Kelly

Publications and source records attributed to K A Kelly.

At least 73 records · Page 4Linked to original sources

Gastrointestinal peptide hormones during postoperative ileus. Effect of octreotide.

The hypothesis was that postoperative ileus might be caused by a disturbed balance between the motor-stimulating hormones, motilin and substance P, and the motor-inhibitory hormone, vasoactive intestinal polypeptide, and that octreotide might prevent this disturbance and so ameliorate the ileus. In 15 conscious dogs with chronic gastrointestinal electrodes, electrical activity was recorded and blood was drawn for radioimmunoassay of motilin, substance P, and vasoactive intestinal peptide (VIP) during fasting and after a liquid meal. Ileus was then induced by celiotomy and intestinal abrasion. During and after operation, five dogs received 154 mM NaCl only, five dogs octreotide, 0.19 micrograms/kg/hr, and five octreotide, 0.83 micrograms/kg/hr. Plasma levels of motilin, substance P, and VIP were changed little by operation, but cyclical increases in plasma motilin, which occurred preoperatively during phase III of the interdigestive myoelectric complex, were completely abolished postoperatively during ileus, as was the complex itself. Octreotide ameliorated the ileus and restored the cyclic increases in motilin found in health, nor did it alter plasma substance P and VIP. In conclusion, octreotide ameliorates postoperative ileus, but it does not do so by increasing plasma motilin or substance P or decreasing plasma VIP.

Animals↗

New directions in gastrointestinal surgery.

Current trends in national health care are triggering a reassessment of the relationship between gastrointestinal surgery and its parent discipline, general surgery. This paper proposes that general surgery be recognized as a broad-based specialty that provides efficient, cost-effective surgical care across a wide spectrum of diseases, whereas gastrointestinal surgery should be acknowledged as the field emerging from general surgery that deals with advanced surgical care in digestive diseases. The Society for Surgery of the Alimentary Tract, with the strength of its talented membership, should take the lead in developing this new role for gastrointestinal surgery. It should urge public recognition of surgical gastroenterology, broaden its membership in the field, define guidelines for practice, develop research and educational programs, and promote national and international cooperation in gastrointestinal surgery. The net result should be the strengthening of both gastrointestinal surgery and general surgery.

Digestive System Surgical Procedures↗

Prospectively evaluating anal sphincter function after ileal pouch-anal canal anastomosis.

The decreased anal sphincter pressure that occurs after ileal pouch-anal canal anastomosis (IPAA) has usually been attributed to damage of the internal and sphincter. We hypothesized that the operation damages both the internal and the external anal sphincter. Resting pressure in the anal canal (a function of internal and external sphincters), anal squeeze pressure (a function of external sphincter only), and the rectal-anal inhibitory reflex (involving the internal sphincter) were measured manometrically in 10 patients with ulcerative colitis (4 women and 6 men; mean age, 33 years; range: 20 to 49 years). The patients were studied while awake before IPAA, under general anesthesia with striated muscle blockade just before incision, awake 2 months later before ileostomy takedown, and again under anesthesia with blockade just before takedown. The operation decreased maximum resting anal pressure while awake and during anesthesia with blockade. The decrease was detected in the proximal anal canal but not in the distal anal canal. In addition, the operation impaired anal squeeze pressure and abolished the rectal-anal inhibitory reflex. We conclude that IPAA damages both the internal and the external anal sphincter.

Adult↗

Surgical management of Meckel's diverticulum. An epidemiologic, population-based study.

OBJECTIVE: The authors determined whether Meckel's diverticulum, discovered incidentally at operation, should be removed. SUMMARY BACKGROUND DATA: It is not clear from the medical literature whether the risk of an incidental Meckel's diverticulectomy is greater than the risk of leaving the diverticulum in place. METHODS: The authors used the medical experience of Olmsted County, Minnesota residents for the period 1950 to 1992 to answer the question. RESULTS: During the period, 58 residents developed Meckel's complications that required diverticulectomies. The incidence of complications was 87 per 100,000 person-years, and the lifetime risk (to 80 years of age) of developing them was 6.4%. The risks were similar throughout the period and at all ages of life, but were greater among men (124 per 100,000 person-years) than women (50 per 100,000 person-years, p < 0.05). Diverticulectomies for complications carried an operative mortality and morbidity of 2% and 12% and a cumulative risk of long-term postoperative complications of 7%, whereas incidental diverticulectomies done in 87 residents during the period carried corresponding rates of only 1%, 2%, and 2%, respectively. CONCLUSIONS: Meckel's diverticula discovered incidentally at operation should be removed for most patients, regardless of age.

Adolescent↗

Dimethyl sulfoxide modulates NF-kappa B and cytokine activation in lipopolysaccharide-treated murine macrophages.

Antioxidants are protective against septic shock in animal models. Recently, free radical scavengers have been found to inhibit the activation of the NF-kappa B protein in a number of cell lines. This transcriptional regulatory protein binds to the promoters of the proinflammatory cytokines tumor necrosis factor, interleukin-6, and the macrophage inflammatory proteins. The current work examined lipopolysaccharide-induced NF-kappa B activation in the J774 macrophage-like cell line and primary peritoneal macrophages from lipopolysaccharide-responsive (C3HeB/Fej) and -nonresponsive (C3H/HeJ) murine strains. The DNA-binding activity of the NF-kappa B protein directly correlated with mRNA expression for the genes encoding the proinflammatory cytokines and the free radical scavenging enzyme, superoxide dismutase. Both the p50 and p65 NF-kappa B subunits were detected on gel supershift assays. Minimal NF-kappa B activity was observed following exposure of C3H/HeJ macrophages to lipopolysaccharide. The antioxidant dimethyl sulfoxide decreased the level of NF-kappa B activation in the J774 cells. This correlated with decreased expression of cytokine mRNAs and tumor necrosis factor bioactivity. These results suggest that modulation of NF-kappa B activation may provide a mechanism through which antioxidants protect against endotoxemia in murine models.

Animals↗

Influence of proximal gastric vagotomy on canine gastric motility and emptying.

BACKGROUND: The aim was to determine the effect of proximal gastric vagotomy on proximal gastric tone, distal gastric motility, and gastric emptying in seven conscious dogs. METHODS AND RESULTS: Before vagotomy, insulin (1 unit/kg intravenously) caused a prompt decrease in proximal gastric tone measured with a barostat and a marked increase in distal gastric motility measured with a perfused, pressure-sensitive catheter, both of which were maximal at 30 minutes. Proximal gastric tone then returned to the control level during the ensuing 30 minutes, whereas the increase in distal gastric motility continued. Gastric emptying of an inert marker, polyethylene glycol, was unchanged by insulin. After vagotomy, insulin again caused a prompt decrease in proximal gastric tone, an increase in distal gastric motility, and no change in gastric emptying of marker, but the decrease in proximal gastric tone now persisted for the entire hour after administration of insulin. CONCLUSIONS: Relaxation of the proximal stomach is mediated by pathways not solely dependent on the proximal gastric vagal nerves, but the ability to regain proximal gastric tone is impaired by proximal vagotomy. In contrast, vagal drive to distal gastric motility and gastric antral emptying are preserved after proximal gastric vagotomy.

Animals↗

The future of intestinal pacing.

Pacing the human heart, first done in 1952, is commonly used today. Pacing the canine stomach and small intestine has also been accomplished and has been used to treat a variety of disease models, including dumping, the short bowel syndrome, gastroparesis, the Roux stasis syndrome, and tachygastria. In contrast, pacing the human stomach and small intestine has not progressed as far. Pacing of these organs in man has only been done for short intervals. Moreover, no clear-cut therapeutic applications have as yet emerged. Nonetheless, pacing holds promise as a future therapeutic modality for a variety of disorders of the human stomach and small bowel.

Animals↗

Regulation of T cell production in T cell receptor transgenic mice.

The thymus produces many more cells than it releases into the periphery. According to generally accepted models of T cell development most of this loss occurs in the thymic cortex, among CD4+8+ thymocytes. An interesting situation arises in the case of T cell receptor (TcR) transgenic mice in which all cells can potentially be positively selected, leading to a theoretical increase of about 30-fold in the survival rate of CD4+8+ cells and in their transition to mature CD4+8- or CD4-8+ thymocytes. This in turn should lead to a 30-fold increase in the size of the thymic medulla, in the emigration rate and in the size of the peripheral T cell pool. Increases in medullary or peripheral pool sizes of this magnitude are not seen in TcR transgenic mice. The question was therefore asked whether some form of homeostatic process regulated the size of the mature T cell pool and at what level it might operate. In this report we demonstrate that the increased rate of double-positive to single-positive transition in the TcR transgenic mice is directly reflected in an increased emigration rate, and that the medulla seems to be relatively efficient regardless of the number of cells passing through it. However, the potential increases in emigrant numbers in TcR transgenic mice are offset by the reduced size of the CD4+8+ thymocyte pool. It would appear then that regulation of T cell production, if it occurs, probably does so through regulation of the size of the CD4+8+ thymocyte pool. Mechanisms for regulation of this kind are not yet known.

Animals↗

Integration of canine proximal gastric, antral, pyloric, and proximal duodenal motility during fasting and after a liquid meal.

The aim was to investigate the integration of proximal gastric, antral, pyloric, and duodenal motility during fasting and after feeding. Using a proximal gastric barostat and a manometric assembly with an array of side holes astride the gastroduodenal junction, the gastrointestinal interdigestive migrating motor complex was detected in five of seven conscious fasting dogs. During phase III of the complex, which lasted a mean +/- SEM of 13 +/- 0.5 min, 9.6 +/- 0.9 volume waves were present in the proximal stomach. The volume waves were coordinated with clusters of antral waves 64 +/- 11% of the time and with inhibition of duodenal waves 91 +/- 3% of the time. A 300-ml calorie-dense liquid meal abolished the complex and promptly increased proximal gastric volume in five of six dogs. Volume waves were nearly completely suppressed, while antral waves decreased from 24 +/- 3.0 waves/10 min to 10 +/- 2.8 waves/10 min (P < 0.05) and isolated pyloric pressure waves increased from 7.2 +/- 2.8 waves/10 min to 22 +/- 3.3 waves/10 min (P < 0.005). In summary, proximal gastric motility was integrated with antral, pyloric, and duodenal motility under both fasting and fed conditions. The integrated patterns likely account for the efficient clearance of indigestible solids during fasting and the controlled emptying of nutrients with feeding.

Animals↗

Effects of bright light on mood in normal elderly women.

Reduced light appears to be a key factor in seasonal affective disorder (SAD). This study asks whether the reduced levels of light experienced by elderly persons might result in depression and other SAD symptoms, and how normal elderly persons might respond to bright light interventions similar to those used to treat SAD. In interviews with 140 senior citizens, we found virtually no seasonal variation in mood and behavior and very little depressed affect. Seventeen of these seniors who had good mental and physical health, with no major eye problems, participated in a crossover study of the effects of bright light on both positive and negative affect and sleep. Although sleep did not appear to be affected, the bright light intervention tended to make these normal elderly persons feel worse--more irritable, anxious, and agitated. These findings confirm earlier reports that bright light is not beneficial for normal individuals who are unaffected by seasonal changes.

Affect↗

Treatment of acute postoperative ileus with octreotide.

Our hypothesis was that postoperative ileus is caused by the release of neurotransmitters in the gut wall that inhibit motility. We reasoned that blocking the release with octreotide would prevent ileus. We placed serosal electrodes on the small intestine and stomachs of 15 dogs and inserted a duodenal cannula. After the animals recovered, electrical activity was recorded, and small bowel transit, colonic transit, and gastric emptying were studied radiographically and scintigraphically. Ileus was induced by celiotomy and intestinal abrasion. Dogs were randomized to receive on postoperative days 0 through 3 either a placebo (n = 5), octreotide, 1.5 micrograms/kg/8 hr subcutaneously (n = 5), or octreotide 0.83 micrograms/kg/hr intravenously (n = 5). Both doses of octreotide resulted in a faster return to preoperative values of small bowel interdigestive myoelectric activity and transit and colonic transit than did the placebo. The larger dose of octreotide, however, slowed gastric emptying. In conclusion, octreotide shortened the duration of postoperative ileus in the small bowel and colon of dogs.

Animals↗

Gastric motor physiology and pathophysiology.

The stomach has two distinct physiologic motor areas: the proximal stomach and the distal stomach. The proximal stomach, with its slow, sustained contractions, has a key role in regulating intragastric pressure and gastric emptying of liquids, while the distal stomach, with its peristaltic contractions, has a major role in mixing, trituration, and emptying of solids. Diseases and operations that disturb the motility of these two areas can result in unique adverse motor sequelae. For example, operations that impair proximal gastric motility, such as proximal gastric resection, may cause rapid gastric emptying of liquids and subsequent dumping and diarrhea. In contrast, operations that impair distal gastric contractions, such as truncal vagotomy, may cause slow gastric emptying of solids and chronic gastric atony. Knowledge of the physiology of the stomach in health and of the pathophysiology with disease and after operation provides a basis for the successful treatment and prevention of these disorders.

Animals↗

Spectrum of extraintestinal disease due to Aeromonas species in tropical Queensland, Australia.

During a 12-month period, the clinical spectrum of extraintestinal disease due to Aeromonas species was determined for 56 patients in tropical Queensland (Australia). Forty-six patients acquired their infection in the community, six patients were infected in the hospital, and four patients were colonized. Demographic risk factors included male gender (67%) and Aboriginal ethnic background (35%). The disease ranged from deep-seated infection (four cases) to soft-tissue infection of varying intensity (48 cases). Among patients whose infections were community acquired, 22 required hospitalization and 27 suffered trauma-associated infection. Seventeen patients (63%) in the latter group had lacerations to the hands and feet that were contaminated with surface water or soil. The appearance of the wounds was not pathognomonic, and diagnosis was made by laboratory evaluation. Aeromonas was the sole pathogen in nine patients. Polymicrobial infections were due to Aeromonas and mainly Staphylococcus aureus and/or mixed enteric bacteria. Aeromonas hydrophila was the most common species isolated (71%), followed by Aeromonas sobria (25%). In nine cases, the empirical antibiotic regimen prescribed did not adequately cover infection due to Aeromonas. Infection was seen regularly throughout the year, but a cluster of cases also occurred during the tropical Australian wet season.

Adolescent↗

Emigration of selected subsets of gamma delta + T cells from the adult murine thymus.

Cells bearing the gamma delta form of the TCR make up only 1-3% of T cells in the adult murine thymus and peripheral lymphoid organs. Evidence from studies of nude mice suggests that the development of at least some gamma delta T cells is thymus dependent; however, until now it has not been directly demonstrated that gamma delta cells are exported from the thymus. In this paper we have used the technique of labelling thymocytes in vivo with FITC, followed by flow cytometric analysis to trace cells emigrating from the thymus to the spleen. Using this approach we have been able to demonstrate for the first time that gamma delta T cells are exported from the adult murine thymus to the spleen. We also demonstrate that the cells emigrating to the spleen are a selected subset of gamma delta thymocytes being heat stable antigen positive, Thy-1+, and expressing low levels of CD44 (Pgp-1). In addition, investigation of TCR V gamma gene usage among adult gamma delta + thymocytes, recent emigrants, and spleen cells, indicated a selective emigration of gamma delta cells expressing certain V gamma genes.

Animals↗

A randomized trial of laser vaporization in the management of cervical intraepithelial neoplasia associated with human papilloma virus infection.

A randomized controlled trial was carried out at colposcopy clinics in the Birmingham and Midland Hospital for Women, to determine the efficacy of laser vaporization in the management of cervical Human Papilloma Virus (HPV) infection occurring alone or in association with cervical intraepithelial neoplasia (CIN), and to study the natural history of these lesions. The subjects were 365 women referred for investigation of cytological abnormality who were found to have histological evidence of HPV infection alone or in association with CIN1 or CIN2 and were considered suitable for local destructive treatment. The intervention consisted of immediate treatment using a carbon dioxide laser or no treatment. Women in both groups were followed by cytological and colposcopic examinations at intervals of four months. Twelve months after randomization, 25 per cent of women in the non-treatment group had progressed to a more severe degree of histological abnormality compared with 4 per cent in the treatment group (95 per cent confidence interval (CI) for difference in proportion 14-28 per cent). Spontaneous regression of cytological abnormality occurred in 26 per cent (95 per cent CI 19-33 per cent) of untreated women. It is concluded that the short-term efficacy of laser vaporization in the treatment of these lesions has been established. The substantial rate of spontaneous regression suggests, however, that intervention is frequently unnecessary.

Actuarial Analysis↗

Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity.

OBJECTIVE: This study sought to determine the basal and peak-stimulated acid secretion from the proximal gastric pouch and its relationship to absorption of free and food-bound vitamin B12 after gastric bypass for morbid obesity. SUMMARY BACKGROUND DATA: Gastric bypass can be performed safely and provides acceptable weight loss, but concerns remain about possible long-term complications such as vitamin B12 malabsorption. The authors hypothesized that by constructing a small pouch of gastric cardia, acid secretion into the pouch would be low, leading to maldigestion of food-bound vitamin B12 with subsequent malabsorption. METHODS: Basal and pentagastrin-stimulated peak acid outputs from the proximal gastric pouch were measured in ten patients after vertical Roux-en-Y gastric bypass using a perfused orogastric tube technique. Absorption of free and food-bound 57Co-vitamin B12 was evaluated separately using 24-hour urinary excretion. RESULTS: Basal (mEq/hr, mean +/- standard error of the mean [SEM]) and peak-stimulated (mEq/30 min) acid secretions from the proximal gastric pouch were markedly decreased compared to those for age- and sex-matched hospital control subjects (0.01 +/- 0.01 vs. 4.97 +/- 0.66 and 0.08 +/- 0.04 vs. 12.11 +/- 1.34, respectively; p < 0.001 for each). While absorption of free vitamin B12 was not statistically different from that of control subjects (11 +/- 2 vs. 15 +/- 2%; p > 0.05), absorption of food-bound vitamin B12 was decreased (0.8 +/- 0.2 vs. 3.7 +/- 0.5%; p < 0.01). CONCLUSIONS: After vertical Roux-en-Y gastric bypass for morbid obesity, acid secretion is virtually absent and food-bound vitamin B12 is maldigested and subsequently malabsorbed. The results of this study suggest that postoperative vitamin B12 supplementation is important and can be achieved with either monthly parenteral vitamin B12 or daily oral crystalline preparations.

Adult↗