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Biomedical subjects

K A Kelly

Publications and source records attributed to K A Kelly.

At least 19 recordsLinked to original sources
PubMed1995

Germinal center T cells exhibit properties of memory helper T cells.

Potential roles of germinal center (GC) T cells in immune memory were investigated by examining T cells in GCs lymph nodes (LNs) following immunization with myelin basic protein (MBP). MBP preferentially stimulates T cells expressing the V beta 8 TCR family in B10.PL mice. By staining lymph nodes with peanut agglutinin, GCs were first identified 8 days after immunization and could still be detected 50 days later. When T cells within GCs were examined at Day 8, the majority (> 90%) were CD45RB-negative and a large percentage (20%) had already proliferated several days before as determined by bromodeoxyuridine (BrdU) incorporation. When BrdU+ V beta 8+ cells were examined in various areas of LNs 3 and 8 weeks after immunization, BrdU+ V beta 8+ cells were approximately fourfold more frequent in GCs than other areas of LNs. When GCs were examined for IL-4 mRNA+ cells using an in situ hybridization method, only 0.01% of GC cells expressed IL-4 mRNA, corresponding to about 1% of GC T cells. Shortly following restimulation with MBP, the frequency of cells expressing IL-4 mRNA increased fivefold. Taken together, these findings indicate that GC T cells possess characteristics associated with memory T cells.

Animals↗
PubMed1995

Early clinical results with the uncut Roux reconstruction after gastrectomy: limitations of the stapling technique.

BACKGROUND: The aim of this study was to review our early clinical experience with the uncut Roux gastrectomy, a modified Billroth II gastrojejunostomy in which four rows of staples occlude the afferent jejunal lumen, while biliary and pancreatic secretions are diverted distally through a jejunojejunostomy. METHODS: Between September 1991 and April 1993, 9 women and 5 men underwent uncut Roux gastrectomy for gastric adenocarcinoma (5), postvagotomy or idiopathic gastroparesis (7), Roux stasis syndrome (1) or anastomotic ulceration with gastric outlet obstruction (1). Subsequently, patients were seen or contacted by phone within the 6 months prior to March 1994. RESULTS: Eight of the 14 patients (57%) had excellent results with stable weight and no nausea, vomiting, heartburn, abdominal pain, or postprandial symptoms. One patient continued to have early satiety and vomiting but maintained stable weight for 19 months postoperatively. Five patients (36%) had poor results with alkaline reflux gastritis or esophagitis. All 5 had documented staple line dehiscence. Four of them were reoperated on and converted to a standard Roux operation with relief of symptoms. CONCLUSIONS: The uncut Roux operation prevents the Roux stasis syndrome, but the current technique has an unacceptably high incidence of dehiscence of the staple lines with subsequent reflux gastritis or esophagitis.

Adult↗
PubMed1995

Epidural analgesia shortens postoperative ileus after ileal pouch-anal canal anastomosis.

PURPOSE: A retrospective study was conducted to determine whether epidural analgesia would speed recovery from postoperative ileus in patients undergoing ileal pouch-anal canal anastomosis. METHODS: Among 85 patients who underwent proctocolectomy with ileal pouch-anal canal anastomosis at the Mayo Medical Center between January 1, 1991 and October 31, 1992, 44 were treated for postoperative pain with continuous infusion of epidural fentanyl citrate supplemented by intravenous morphine on request, while 41 controls were given only systemic morphine sulfate as needed. RESULTS: The patients in the two groups were matched and similar with regard to preoperative and operative risk factors and postoperative morbidity. No operative mortality occurred. Epidural fentanyl analgesia resulted in less need for nasogastric suction and intravenous fluids, more rapid discharge of fecal content, more rapid return to oral intake, and shorter hospitalization. CONCLUSION: Epidural analgesia with fentanyl citrate shortened postoperative ileus after proctocolectomy and ileal pouch-anal canal anastomosis.

Adolescent↗
PubMed1995

Elimination of the Roux stasis syndrome using a new type of "uncut Roux" limb.

BACKGROUND: The Roux stasis syndrome, a syndrome of nausea, vomiting, abdominal pain, and postprandial fullness that follows Roux-en-Y gastrojejunostomy, is thought to result from the jejunal transection performed during the construction of a conventional Roux limb. The purpose of this study was to test a new type of "uncut" Roux limb construction, in which a neuromuscular bridge maintains neuromuscular continuity between the proximal jejunum and the Roux limb, while a jejunojejunostomy provides distal diversion of pancreaticobiliary secretions METHODS: After a distal hemigastrectomy, 5 dogs underwent the uncut Roux operation, while 5 others had a Billroth II reconstruction (controls). Three weeks later, recordings of jejunal myoelectrical activity and assessment of gastric emptying and bile reflux were performed in fully conscious dogs RESULTS: In the dogs with uncut Roux limbs, jejunal pacesetter potentials propagated aborally across the neuromuscular bridge, although their frequency was slightly slower distal to the bridge (proximal 19.5 +/- 0.7 cpm versus distal 18.8 +/- 1.1 cpm; P < 0.05). No frequency change occurred across the comparable area of jejunum of the controls. Both groups had similar rates of gastric emptying. Only small amounts of bile acids were found in gastric aspirates from dogs with uncut Roux limbs. CONCLUSIONS: A new uncut Roux operation eliminated the Roux stasis syndrome by preserving neuromuscular continuity between the proximal jejunum and the Roux limb, and yet provided near-total diversion of bile from the gastric remnant.

Anastomosis, Roux-en-Y↗
PubMed1995

Effect of electrical stimulation on gastric electrical activity, motility and emptying.

The aim was to measure the effect of gastric electrical stimulation on the frequency of canine antral pacesetter potentials (PPs), the strength of antral contractions, and the rate of gastric emptying while fasting, after feeding and with pentagastrin stimulation. Four conscious dogs with a stimulating electrode placed 10 cm proximal to the pylorus and recording electrodes and strain gauges placed 7, 5 and 3 cm proximal to the pylorus underwent myoelectric and strain gauge recordings while fasting, after feeding (250 ml 5% dextrose labelled with polyethylene glycol), and during pentagastrin infusion (0.5 micrograms kg-1 min-1) on four separate days. On each day, electrical stimulation was done using one of four stimulation frequencies (0, 6, 30 and 1200 stimuli per minute [s.p.m.]). Stimulation at 6 and 30 s.p.m. increased the fasting and fed PP frequency, whereas 1200 s.p.m. stimulation did not. Feeding decreased the maximum driven frequency, and pentagastrin increased it. Neither the motility index nor the gastric emptying rate were consistently changed by stimulation at any frequency. In conclusion, canine proximal antral stimulation at 6 and 30 s.p.m. sped PP frequency during fasting and after feeding, but stimulation over a wide range of frequencies had little effect on gastric contractions and emptying.

Animals↗
PubMed1995

Ectopic jejunal pacemakers after jejunal transection and their relationship to transit.

The hypothesis was that orally moving pacesetter potentials distal to a site of jejunal transection and anastomosis would slow transit through jejunum containing them and that reoperation with excision of bowel containing these pacesetter potentials would restore transit to the control. In six conscious dogs with jejunal serosal electrodes for recording myoelectric activity and a jejunal perfusion/aspiration catheter for measuring transit, jejunal pacesetter potential frequency decreased distal to a midjejunal transection and anastomosis from 18.7 +/- 0.3 (SE) cycles/min (cpm) proximal to the site to 14.4 +/- 0.6 cpm distal to the site (P < 0.05). In addition, orally propagating pacesetter potentials occurred > 25% of the time in a 37 +/- 7 cm length of bowel distal to the site during fasting and after feeding. Transit through the segment with the orally moving pacesetter potentials was slowed during feeding (half time before and after transection, 7.7 +/- 1.1 and 13 +/- 2.0 min, respectively, P < 0.05). Resection of the segment with the abnormal pacesetter potentials shortened the length of bowel containing them to 24 +/- 2 cm (P > 0.05) and restored transit to the control. In conclusion, orally moving pacesetter potentials distal to a canine jejunal transection and anastomosis slowed transit through the segment of bowel containing them. Resection of the segment restored transit to the control.

Analysis of Variance↗
PubMed1995

Increased stem cell factor release by hemangioma-derived endothelial cells.

BACKGROUND: Capillary hemangiomas, the most common tumors in young children, consist of proliferating capillary vessels and endothelial cells. These tumors also contain large numbers of mast cells, compared with the normal surrounding skin or tissue. We have recently shown that stem cell factor (SCF), the gene product of the murine steel locus, can act as a chemoattractant for mast cells. In this study, we investigated whether SCF might be involved in the recruitment and maintenance of mast cells in hemangiomas. EXPERIMENTAL DESIGN: Cultured endothelial cells derived from a murine hemangioma were compared with normal vascular endothelial cells for the ability to produce and release SCF, a mitogen for mast cells. RESULTS: Conditioned medium from hemangioma-derived endothelial cells stimulated the proliferation of cultured mast cells. This proliferative activity was potentiated by interleukin-3. The same conditioned medium was unable to stimulate proliferation of mast cells expressing a defective receptor for SCF. The medium was also unable to stimulate proliferation when it was preincubated with neutralizing antibodies specific for SCF. Immunoprecipitation and Western blot analysis of the conditioned media from hemangioma cells and normal endothelial cells demonstrated the 31,000 molecular weight SCF in hemangioma-conditioned medium only. In addition, proliferative activity for mast cells could not be demonstrated in the conditioned medium of the normal endothelial cells, although Northern blot analysis indicated that both normal and hemangioma-derived endothelial cells express SCF mRNA. Reverse transcriptase-polymerase chain reaction techniques were used to amplify the DNA sequence coding for the proteolytic cleavage site used for release of SCF. Results indicated that both normal and hemangioma-derived endothelial cells express the same transcript for SCF. CONCLUSIONS: Our data suggest that increased release of SCF is a property of hemangioma-derived endothelial cells that may account for the high numbers of mast cells observed in hemangioma tissue. This increased release of SCF is not due to alternate splicing of SCF transcripts by hemangioma cells.

Animals↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗