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Biomedical subjects

R W Summers

Publications and source records attributed to R W Summers.

At least 19 recordsLinked to original sources

CD5+ B cells are decreased in peripheral blood of patients with Crohn's disease.

B cells bearing the CD5 surface marker comprise a substantial minority of the circulating lymphocyte population in healthy individuals. These recently described cells have been implicated in T-independent humoral responses, immunoregulation, and autoimmunity. We undertook to enumerate circulating CD5+ B cells by three-color fluorescence activated flow cytometry in 28 patients with Crohn's disease (CD). None of the CD patients were using immunosuppressive medication. The CD patients were subdivided into "inactive" and "active" groups based upon their Crohn's disease activity index (CDAI). Thirty-two normal subjects served as a control population. The percentage of CD19+ B cells was significantly reduced in both active and inactive CD patients as compared with normal controls (P less than or equal to 0.01). CD5+ B cells were likewise found to be significantly decreased in both inactive and active CD patients (P less than or equal to 0.01) as compared with normal controls. The proportion of CD5+ B cells was significantly lower in the peripheral blood of active as compared with inactive CD patients (P less than or equal to 0.05). The finding that CD5+ B cells are reduced in CD may provide an important clue to immunological dysfunction in inflammatory bowel disease and merits further study.

Adult

Does irradiation produce irreversible changes in canine jejunal myoelectric activity?

We sought to determine whether acute irradiation-induced changes in jejunal myoelectric activity are reversible or chronic and progressive with repeated exposures. Five dogs underwent abdominal irradiation absorbing 938 cGy on four separate occasions, two weeks apart. Recordings of jejunal myoelectric activity were made before and 10-11 days after each irradiation exposure. Ten to 11 days after the first exposure, the animals recovered completely from the acute radiation syndrome, and the myoelectric activity returned to normal. After subsequent exposures, they developed chronic diarrhea, profound weight loss, and progressive changes in myoelectric activity. Slow waves exhibited highly variable configuration, had an irregular rhythm, and were frequently uncoupled. Spike burst activity, duration, and length of migration were reduced in association with abnormal motility patterns even though histologic abnormalities were mild. Such changes are likely to interfere with normal propulsion and contribute to impaired nutrition. The abnormalities suggest that irradiation causes dysfunction of one or more of the cellular elements involved in small bowel motility (muscle, nerve, and interstitial cells) prior to the development of severe histologic abnormalities or mechanical obstruction.

Action Potentials

Intestinal water absorption from select carbohydrate solutions in humans.

Eight men positioned a triple-lumen tube in the duodenojejunum. By use of segmental perfusion, 2, 4, 6, or 8% solutions of glucose (111-444 mM), sucrose (55-233 mM), a maltodextrin [17-67 mM, avg. chain length = 7 glucose units (7G)], or a corn syrup solid [40-160 mM, avg. chain length = 3 glucose units (3G)] were perfused at 15 ml/min for 70 min after a 30-min equilibration period. All solutions were made isotonic with NaCl, except 6 and 8% glucose solutions, which were hypertonic. An isotonic NaCl solution was perfused as control. Water absorption (range: 9-15 ml.h-1.cm-1) did not differ for the 2, 4, and 6% CHO solutions but was greater (P < 0.05) than absorption from control (3.0 +/- 2.2 ml.h-1.cm-1). The 8% glucose and 3G solutions reduced (P < 0.05) net water flux compared with their 2, 4, and 6% solutions, but 8% sucrose and 8% 7G solutions promoted water absorption equivalent to lower CHO concentrations. Water absorption was independent of [Na+] in the original solution. In the test segment, 1) Na+ flux correlated with net water flux (r = 0.72, P < 0.01), K+ (r = 0.78, P < 0.01), and [Na+] (r = 0.68, P < 0.001); 2) Na+ absorption occurred at luminal [Na+] as low as 50 mM; 3) glucose transport increased linearly over the luminal concentration range of 40-180 mM; and 4) net water flux was similar over a range of glucose-to-Na+ concentration ratios of 0.4:1 to 3.5:1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of exercise on intestinal motility and transit in trained athletes.

We measured the effect of exercise, at different intensities, on duodenojejunal motor activity in eight trained, ambulant cyclists, using a catheter with two strain gauge transducers connected to a solid-state data logger. Orocecal transit time was measured by H2 breath test. Subjects were studied for two consecutive days and fed twice a day with a similar, 860-kcal meal. Control recordings on the first day were made at rest and a naloxone infusion was given after the evening meal. On the second day, the athletes exercised after meals for 20 min at 80% of peak O2 uptake (VO2max) and naloxone was infused during the second session. On separate days, five subjects exercised for 3 h at 60% VO2max and for 10 min at 90% VO2max. Plasma concentrations of beta-endorphin were determined before and after exercise. The fed pattern was interrupted by an activity front during 2 of 16 sessions of exercise at 80% VO2max, in the presence of naloxone, and 5 of 8 sessions at 90% VO2max, with and without naloxone. It was not affected by exercise at 60% VO2max. Orocecal transit was not affected by intense exercise. The results show that exercise can affect intestinal postprandial motor activity. The effect is intensity related and may not be mediated by opioids.

Adult

Radiation and indomethacin effects on morphology, prostaglandins, and motility in dog jejunum.

Irradiation can have a profound effect on intestinal motor activity. Previous studies have suggested that prostaglandins may play some role in radiation-induced enteritis. The present study investigated the effects of abdominal X-irradiation with or without indomethacin treatment on jejunal myoelectric activity and prostaglandin synthesis by measuring the prostaglandin content of mesenteric arterial and venous plasma and in the intestinal lumen in dogs. After X-irradiation, venous concentrations and arteriovenous concentration differences of prostaglandin (PG)E2, PGF2 alpha, and 6-keto-PGF1 alpha increased markedly. The increased venous concentrations were in part attributable to increased mucosal and/or submucosal synthesis by inference from increased concentrations of these metabolites assayed from the jejunal lumen. Irradiation produced histological damage to the mucosa and submucosa and abnormalities in the migrating motor complex, jejunal slow waves, and a decrease in spike burst activity. Inhibition of prostaglandin synthesis by treating the animals with indomethacin reduced the severity of illness, the histological injury, and changes in myoelectric activity induced by irradiation. Such treatment should be evaluated further to treat patients exposed to large doses of irradiation.

Animals

Effects of cycle exercise on intestinal absorption in humans.

Intestinal absorption was measured in six trained male cyclists during rest, exercise, and recovery periods with the segmental perfusion technique. Each subject passed a multilumen tube into the duodenojejunum. The experiments consisted of 1) a sequence of 1-h bouts of cycling exercise at 30, 50, and 70% maximal O2 uptake (Vo2max) separated by 1-h rest periods or 2) a 90-min bout at 70% VO2max. The cycling was performed on a constant-load Velodyne trainer. Absorption of water and a 6% carbohydrate-electrolyte (2% glucose, 6% sucrose, 20 meq Na+, 2.6 meq K+) solution (both perfused at 15 ml/min) were compared. The effects of perfusing an isotonic electrolyte solution during mild (30% VO2max) exercise were also studied. Fluid was sampled every 10 min from ports 10 and 50 cm distal to the infusion site. Water flux was determined by differences in polyethylene glycol concentration across the 40-cm test segment. Results showed 1) no difference in water or electrolyte absorption rates among rest, exercise, and recovery periods; 2) no difference in absorption rates among the three exercise intensities or different exercise durations; and 3) significantly greater fluid absorption rates from the carbohydrate-electrolyte (CE) solution than from water. Water flux during rest, exercise, and recovery was about sixfold greater from the CE solution than from the isotonic solution without carbohydrate. We conclude that 1) exercise has no effect on water or solute absorption in the duodenojejunum, 2) fluid absorption occurs significantly faster from a CE solution than from water, and 3) fluid absorption is increased sixfold by addition of carbohydrate to an electrolyte solution.

Adult

The prevalence and severity of late effects in normal rat duodenum following intraoperative irradiation.

In humans, a portion of the duodenum is often at risk for radiation-induced complications following intraoperative radiation therapy for pancreatic carcinoma. To determine experimentally the prevalence and severity of late effects in the normal mammalian duodenum, 190 rats received single doses of 0, 15, 20, 25, 30, or 40 Gy orthovoltage X rays to temporarily exteriorized 3 cm circumferential segments of duodenum. The animals were killed 2, 6, 8, or 10 months later. Actuarial survival, change in body weight, and a radiation injury score based on eight histopathologic alterations were used as endpoints. Epithelial atypia, intestinal wall fibrosis, serosal thickening, and vascular sclerosis were the dominant histopathologic alterations at all dose levels throughout the 10-month observation period. The prevalence and severity of histologic radiation injury showed sigmoidal dose-response relationships with the plateaus starting at 20 Gy. Doses of 20 Gy or greater also resulted in a substantial loss of body weight and a high level of early deaths (20-80 days). All endpoints indicate that intraoperative doses of 20 Gy or greater are associated with unacceptable risks of late and irreversible complications.

Animals

Human intestinal water absorption: direct vs. indirect measurements.

Distilled water, a carbohydrate-electrolyte (CE; 4% sucrose, 2% glucose, 17.2 meq/l NaCl, and 2.8 meq/l KCl) solution, or a 10% glucose solution, all containing the nonabsorbed indicator polyethylene glycol (PEG) and deuterium oxide (D2O, 30 ppm), were infused (15 ml/min) into the duodenojejunum of seven men by using the triple lumen technique. Net water absorption was determined directly from the change in PEG concentration and was calculated from plasma D2O derived from D2O in the perfusion solutions. The protocol included a 45-min equilibration period followed by a 90-min test period. Intestinal samples were drawn at 10-min intervals from 15 to 45 min and at 15-min intervals thereafter. Blood was drawn at 45, 50, 55, 60, 75, 90, 105, 120, and 135 min. Intestinal samples were analyzed for D2O, Na+, K+, osmolality, PEG, and glucose; blood was analyzed for D2O. Results (+/- SE; positive values secretion, negative values absorption) showed net fluid absorption from distilled water (-9.40 +/- 1.28 ml.h-1.cm-1) and the CE (-13.30 +/- 1.22 ml.h-1.cm-1) solution, but net secretion (4.40 +/- 1.25 ml.h-1.cm-1) from the 10% glucose solution. All values were significantly (P less than 0.05) different from each other. Perfusing the CE solution caused net Na+ and K+ absorption, whereas perfusing the 10% dextrose solution caused net electrolyte secretion. Rates of D2O accumulation in the plasma were independent of the solutions perfused.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose

Early results of combined electrohydraulic shock-wave lithotripsy and oral litholytic therapy of gallbladder stones at the University of Iowa.

One hundred thirty-three patients were entered into a randomized, double-blind, placebo-controlled trial of extracorporeal shock-wave lithotripsy for symptomatic gallstones versus extracorporeal shock-wave lithotripsy plus adjuvant litholytic therapy with ursodeoxycholic acid (UDCA). Six months after lithotripsy, patients receiving placebo were crossed over to UDCA therapy without unblinding the study. One hundred sixteen patients have completed 6 months of follow-up. Five patients were dropped from the study. Nine percent have required cholecystectomy (11 patients with biliary colic and 1 with acute cholecystitis). Ninety-one patients had a solitary stone (64 patients had stones less than or equal to 20 mm and 27 patients had stones greater than 20 mm in diameter), and 25 patients had two to three stones. Fifty percent were retreated. Cumulative stone-free rates at 6, 12, and 18 months were 26%, 39%, and 41%, respectively. At 6 months there was a significant advantage for patients treated with UDCA versus placebo (36% vs 17% were stone free) that had disappeared by 12 months (placebo-treated patients had received 6 months of UDCA). Patients with solitary stones equal to or less than 20 mm in diameter treated with UDCA had stone-free rates at 6, 12, and 18 months of 58%, 58%, and 62%, respectively, versus 27%, 56%, and 50%. The difference was significant only at the 6- month follow-up. Stone-free rates for patients with large solitary stones and multiple stones were very low. Extracorporeal shock-wave lithotripsy is both safe and effective therapy for treatment of symptomatic gallstones in patients with a solitary stone equal to or less than 20 mm in diameter. UDCA markedly improves the efficiency of the procedure and results in a stone-free gallbladder sooner.

Administration, Oral

Irradiation increases superoxide dismutase in rat intestinal smooth muscle.

We investigated whether X-irradiation could induce the enzyme superoxide dismutase (SOD) in intestinal muscle. Groups of rats received abdominal irradiation and the time course and dose response for SOD activity determined. Jejunal smooth muscle homogenates were analyzed for the activities of copper/zinc (CuZn) and manganese (Mn) SOD activity and for a mitochondrial marker enzyme, citrate synthase. A progressive rise in Mn SOD activity occurred at 20, 46, and 72 h after 1500 R. No significant changes in Cu-Zn SOD activity occurred at any time after 1500 R. At 20 h after 250 R of X-irradiation, Mn SOD activity increased but no further increase occurred at higher irradiation exposures. At the same time, CuZn SOD activity at 20 h after irradiation was greater than controls only at an exposure of 1000 R (p less than 0.05). Using Western blotting, we were able to clearly demonstrate an increase in immunoreactive Mn SOD protein in muscle samples 20 h after 1500 R. The rise in Mn SOD is not simply due to increase in mitochondrial numbers or increase in all mitochondrial enzyme activities because activity of the mitochondrial marker enzyme citrate synthase was decreased after X-irradiation. Transmission electron microscopic studies demonstrated damage to mitochondria after a dose of 3000 R. The data yield evidence that free radicals play a role in irradiation-induced intestinal smooth muscle injury.

Animals

The pathophysiology, evaluation and management of motility disorders of the biliary tract.

Significant advances in the understanding of biliary tract physiology have occurred during the past 20 years. Through careful studies in animals, the fluid mechanics and normal regulatory mechanisms involved in sphincter of Oddi function have been partially elucidated. Many of the basic concepts have been validated in human studies by newly developed testing methods. Endoscopic retrograde cholangiopancreatography is crucial in demonstrating both normal anatomy and mechanical or structural abnormalities of the duct system. Fat-meal--or CCK-stimulated ultrasonography and quantitative hepatobiliary scintigraphy offer reliable and noninvasive screening methods to evaluate patients with suspected sphincter of Oddi dysfunction. Biliary manometry is key in defining normal and abnormal motility patterns of the sphincter of Oddi region. The existence of the problem is being solidly established, but the optimal therapy is still somewhat unclear. The use of endoscopic balloon dilatation is not encouraging; drug therapy holds promise, but must be subjected to careful clinical trials. Sphincter surgery is fading from use and is being replaced by endoscopic sphincterotomy. Unfortunately the long-term results of sphincterotomy and the overall safety of the procedure are not known. Biliary motility problems do exist, but both diagnostic studies and therapeutic maneuvers require judgement and skill in their application. Use of potentially harmful treatments must be employed only after careful and thorough testing.

Biliary Tract

Intraoperative irradiation in a rat model: histopathological changes in irradiated segments of duodenum.

During intraoperative radiation therapy for carcinoma of the head of the pancreas in humans, a portion of duodenum is often at risk for radiation-induced complications because of its fixed anatomical position within the treatment field. This study was undertaken to determine the feasibility of using the rat as a model to determine the radiotolerance of normal mammalian duodenum. The procedures used to exteriorize and irradiate a selected segment of duodenum are described. Histopathologic changes in 5-cm segments of midduodenum were studied 14 and 28 days after 0, 30, 40, or 50 Gy X-radiation. Complete denudation of the epithelium and thickening of the muscularis and serosal layers occurred in all irradiated segments by day 14. By day 28, even though crypt and villus architectures were atypical, large areas of epithelial regeneration were seen in rats receiving 30 Gy. In contrast, complete denudation of the epithelium were still evident along most of the length of the irradiated segments in rats receiving 40 or 50 Gy. Serosal fibrosis was prominent in all irradiated animals, regardless of dose. These results indicate that radiation doses above 30 Gy carry high risks of complications. The rat is considered a suitable animal model.

Animals

Changes in jejunal myoelectrical activity during exercise in fed untrained dogs.

Seven female dogs (15-20 kg) were instrumented with seven bipolar electrodes sutured at 3-cm intervals to the serosal surface of the proximal jejunum and were exercised at different intensities and durations on a motor-driven treadmill. Slow-wave frequency increased (P less than 0.05) from preexercise control during prolonged (90 min) exercise and during recovery after short-term exercise (30 min) at 70% heart rate reserve (HRR). These changes were associated with an increase in core temperature. Spike-burst frequency (SBF) increased (P less than 0.05) with moderate exercise (50% HRR), but the magnitude was small. When exercise was extended beyond 30 min and during all recovery periods, SBF decreased significantly. Exercise produced migrating myoelectrical complexes in three experiments and less dramatic pattern changes characterized as "clustered contractions" (regular spike bursts preceded and followed by the absence of spike bursts) in at least nine other experiments. We conclude that exercise does alter jejunal myoelectrical activity, but myoelectrical patterns may be more important in explaining exercise-induced gastrointestinal symptoms than changes in spike-burst frequency or duration.

Animals

A comparative study of the effects of four motor-stimulating agents on canine jejunal spike bursts. The use of a computer program to analyze spike burst spread.

The intestinal myoelectric effects of four motor-stimulating drugs were compared in conscious dogs. Dogs were fed a standardized 400-kcal meal, and the myoelectric activity was monitored before and after drug administration. Graded doses of metoclopramide, cisapride, bethanechol, and cholecystokinin (CCK) were compared by means of a computer program to identify spike bursts and determine their frequency, duration, and length of migration. Bethanechol and CCK produced the greatest increase in myoelectric activity in terms of spike burst frequency and duration but the least in terms of length of spike burst spread. Metoclopramide had minimal measurable myoelectric effects. Cisapride had the greatest effect on the length of spike burst migration but little effect on spike burst frequency and duration. The results suggest that cisapride is a more efficient prokinetic agent than bethanechol, CCK, or metoclopramide. The greater length of spike burst spread caused by cisapride was associated with a more rapid rate of transit along the monitored segment of bowel when compared with control. This confirms the correlation between length of spike burst spread and propulsive efficiency.

Animals

Electrohydraulic shock wave lithotripsy (ESWL) fragmentation of retained common duct stones.

Retained or recurrent stones in the common bile duct remain a clinical problem in 2% to 5% of patients undergoing cholecystectomy. Nonoperative extraction via the T tube tract or endoscopic sphincterotomy is successful in 85% to 95% of patients; however, the remainder require reoperation. This study evaluates the efficacy of electrohydraulic shock wave lithotripsy therapy of common duct stones too large to be extracted endoscopically or by T tube. Six patients were entered into the study. Ages ranged from 62 to 93 years. All patients either had severe preexisting systemic disorders or were of an advanced age. Stones ranged in size from 10 to 41 mm, with a mean largest dimension of 22 mm. In all patients either extraction by traditional nonoperative means failed or there was a stone that was considered to be too large to be extracted successfully. Patients were treated with 1200 to 2400 shocks at 16 to 20 kV. Five of six patients were treated with local anesthesia and sedation. Stones were successfully fragmented in all but one patient. Five patients required extraction of the remaining fragments either through the T tube tract (one patient) or via endoscopic sphincterotomy. All patients were free of stones at discharge, with the exception of one patient with severe cirrhosis who had an intrahepatic stone behind a right hepatic duct stricture. This stone had been successfully fragmented but an endoscopic retrograde cholangio-pancreatogram revealed some residual fragments despite normal alkaline phosphatase and bilirubin values. There were no hospital deaths, although the patient with the intrahepatic stone died of bleeding varices several months later. Electrohydraulic shock wave lithotripsy seems to be an effective adjuvant treatment in clearing the bile duct of stones that would otherwise require reoperation.

Aged

Effect of irradiation on morphology and motility of canine small intestine.

In addition to severe damage to the intestinal mucosa, there is evidence based on altered transit that irradiation affects intestinal motor function. A single dose of 938 cGy to the intestine of dogs consistently produced an acute intestinal radiation syndrome consisting of vomiting and diarrhea but was not lethal. In the fasting state, the migrating myoelectric complex was uniformly interrupted. After a meal, jejunal myoelectric activity analyzed by a computer program showed a progressive decline in the number, duration, and length of migration of spike bursts. There were occasionally bizarre motility patterns consisting of clusters of migrating spike bursts. Slow waves demonstrated irregular rhythm and nonuniform morphology. They occasionally migrated in an orad direction and at times were totally uncoupled. At 24 hr and four days after irradiation, the muscle and the neural plexus were nearly normal by light microscopy, but the mucosa exhibited severe necrosis. Therefore, irradiation produces profound functional abnormalities in intestinal muscle even though the morphology is minimally altered.

Animals

Mechanisms of motility changes during acute intestinal obstruction in the dog.

We investigated the effects of autonomic drugs and the role of intestinal contents on the motility changes that occur during acute obstruction. Myoelectric activity was recorded from seven electrodes spaced at 3-cm intervals along the midjejunum of nine conscious dogs. Another animal had electrodes evenly placed throughout the small bowel. Obstruction was created by inflation of an intraluminal balloon. Systemic arterial blood pressure and pulse rate were monitored. Initially, motor activity of the small intestine increased proximal to an acute intestinal obstruction and decreased distally. Recordings from the entire small intestine revealed that these effects occurred almost immediately in the region of the obstruction but not at more distant sites. Within 2-3 h, however, proximal hypermotility had extended to the duodenum and distal inhibition had progressed to the terminal ileum. Diversion of intestinal contents without obstruction reduced myoelectric activity distal to the site of drainage. However, reinfusion of chyme distal to the site of obstruction failed to restore inhibited motor activity to control levels. Atropine sulfate (50 micrograms/kg) decreased and neostigmine (5 micrograms X kg-1 X min-1) potentiated the hyperactivity proximal to the obstruction, but neither agent significantly affected the distal inhibition. Phentolamine (1 mg/kg) and propranolol (1 mg/kg) had no effect on proximal or distal motor activity during obstruction; these were doses that blocked cardiovascular responses to adrenergic agonists. These results suggest that changes in luminal contents and in nervous activity both contribute to the intestinal motility changes that accompany obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals