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Biomedical subjects

R W Summers

Publications and source records attributed to R W Summers.

At least 37 records · Page 2Linked to original sources
PubMed1995

Colorectal neoplasms. Screening can save lives.

Colorectal cancer is a very important cause of death and disability throughout the world. In the future, it may be possible to reduce the risk of this disease through such measures as dietary modification or use of aspirin or other nonsteroidal anti-inflammatory drugs, but this remains to be proved. It may also be possible to detect persons at high risk or those with early lesions by using noninvasive studies, such as genetic tests or detection of trace markers in the stool, but these approaches either are not yet available or are not proved in clinical trials. However, through careful and systematic clinical history taking and appropriate screening studies, neoplasms can be detected early or in the precancerous stage. Mortality from colon cancer could be reduced dramatically by applying currently available methods as part of a health maintenance program. Fecal occult blood testing and flexible sigmoidoscopy must be integrated into practice routines in the same way that Pap smears and mammography have been accepted by physicians and patients as a way to save lives.

Adenocarcinoma↗
PubMed1995

Impedance planimetry: an integrated approach for assessing sensory, active, and passive biomechanical properties of the human esophagus.

OBJECTIVES: Our objective was to study the biomechanical properties and their relationships to the sensory and motor function of the esophagus, which has seldom been examined in humans. METHODS: We used impedance planimetry, to study these properties. This system measures cross-sectional area (CSA) and intraluminal pressure simultaneously and facilitates calculation of some of the biomechanical properties of the esophageal wall. We performed 15 studies in 12 healthy volunteers. In three subjects, the studies were repeated to test reproducibility. RESULTS: Stepwise increments in balloon pressure from 5 to 40 cm H2O induced an increase in CSA (mean +/- SD), 91 +/- 27 to 469 +/- 63 mm2, the wall tension 27 +/- 4 to 484 +/- 32 mm x cm H2O, and the strain 0.2 +/- 0.1 to 1.3 +/- 0.3. The tension/strain relationship increased exponentially. The compliance did not change. The threshold for first sensation was 30 +/- 11 cm H2O (mean +/- SD). In three subjects, when the balloon was distended > 40 cm H2O, chest pain was induced at a threshold of 62 +/- 3 cm H2O, and the compliance decreased. Balloon distension induced tertiary contractions and secondary peristalsis at thresholds of 15 +/- 4 cm H2O, and 19 +/- 5 cm H2O. Repeat studies showed good correlation (r = 0.9). CONCLUSION: Graded balloon distension increases esophageal CSA, wall tension, and strain. When a threshold is reached, tertiary contractions and secondary peristalsis develop at pressures less than 50% of sensory threshold. At higher pressures, chest pain is induced. Impedance planimetry promises to be a simple, objective, reproducible, and comprehensive technique for evaluating the sensory, motor, and viscoelastic properties of the esophagus.

Adult↗
PubMed1995

Effects of carbohydrate type and concentration and solution osmolality on water absorption.

We studied intestinal absorption of solutions containing either one (glucose, Glu, or maltodextrin, Mal) or two (fructose, Fru, and Glu or sucrose, Suc) transportable carbohydrate (CHO) substrates using segmental perfusion technique in eight healthy male subjects. These CHO were either free or directly transportable monosaccharides (Glu, Fru), bound as the disaccharide (sucrose, Suc), or as oligomers (maltodextrins, Mal). [CHO] was varied from 6% to 8% (120-444 mmol.1(-1)). All solutions contained low [Na+] (15-19 mEq) and [K+] (3-4 mEq). Solutions osmolalities varied from 165 to 477 mOsm.kg(-1). Osmolalities in the test segment ranged from 268 to 314 mOsm.kg(-1). The regression line of osmolality with water absorption differed for single as compared with multiple substrate solutions. The significantly different intercepts of these two regression lines suggest that solutions with multiple substrates produce greater water absorption at a given osmolality than those with one. Comparing all solutions, test segment solute flux (partial r = 0.69) was more important than mean osmolality (partial r = 0.32). In conclusion, solutions with multiple substrates stimulate several different solute absorption mechanisms yielding greater water absorption than solutions with only one substrate.

Amino Acids↗
PubMed1994

Analysis of T-lymphocyte subpopulations in inflammatory bowel diseases by three-color flow cytometry.

In order to better define changes in the relative proportion of peripheral blood T-lymphocyte subpopulations in patients with inflammatory diseases of the bowel, we performed simultaneous three-color fluorescence-activated cytometric (FACS) analysis using fluorophore-conjugated monoclonal antibodies with specificity for CD4, CD8, Leu 8, and CD45RA on 22 normal control subjects, 28 patients with Crohn's disease (CD), 15 patients with ulcerative colitis (UC), and 11 patients with intestinal inflammation secondary to etiologies other than inflammatory bowel disease (NIBD). This staining combination allowed enumeration of distinct T-cell subpopulations as follows: virgin CD4+, recall antigen helper T cells, nonspecific B-cell helper T cell, virgin CD8+, cytotoxic effector and suppressor effector and recall antigen cytotoxic T cells based on a synthesis of published functional analyses. No differences in the proportion of CD4+ or CD8+ cells or in the CD4+/CD8+ ratios were evident when UC and NIBD patients were compared to normal subjects. A significant reduction in the proportion of CD4+ cells and an increase in CD8+ cells was observed, however, in the CD group. When two-color analysis was performed, several significant differences in the proportions of circulating lymphocytes were seen. Specifically, these included significant increases in the number of CD4+, Leu 8- (P < 0.01) cells in all disease groups and an increase in CD4+, CD45RA+ cells in the NIBD group. Conversely, significant decreases in the proportions of CD8+, Leu 8+ (P < 0.01) cells were evident in the Crohn's disease group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Morphology and pathology of radiation-induced esophagitis. Double-blind study of naproxen vs placebo for prevention of radiation injury.

Radiation-induced esophagitis can cause substantial morbidity. Experiments in lab animals have shown that pretreatment with indomethacin protects the esophagus from radiation damage. We conducted a prospective, double-blind, randomized trial of naproxen vs placebo in patients undergoing thoracic radiation therapy for lung cancer. Twenty-eight patients were enrolled, of which 26 completed the study. Sixteen patients were given a short course of radiation (30 Gy/10 fractions/2 weeks), and 10 patients were given a longer course and a larger dose (40-50 Gy/25 fractions/5 weeks). Half of the irradiated patients were treated with naproxen, 375 mg, taken orally twice a day, and half were given an identical placebo. All patients were given ranitidine 300 mg, taken orally once a day. Study drugs were taken throughout the course of radiation. Endoscopy with esophageal biopsies and brushings was performed before and on the last day of treatment. Patients kept a daily diary for symptom scoring. Symptoms such as chest pain, dysphagia, odynophagia, and/or heartburn were reported in 15 patients from both subgroups, resulting in diet restriction to liquids only in eight patients and requiring temporary discontinuation of radiation therapy in one of them. Approximately half the patients in each subgroup developed esophagitis, usually mild and usually limited to the proximal esophagus. Severity of symptoms was not proportional to the severity of esophagitis. Candidiasis was documented in eight patients, but only four had symptoms that were severe in one. We conclude that acute radiation injury to the esophagus is observed in approximately half the patients receiving radiation therapy and can result in substantial morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1994

Effects of solution osmolality on absorption of select fluid replacement solutions in human duodenojejunum.

These experiments examined relationships between initial osmolality and carbohydrate (CHO) composition of an infused solution and osmolality and water and CHO absorption in a test segment. A triple-lumen tube with a 10-cm mixing segment and a 40-cm test segment was passed into the duodenojejunum. The infusion port was approximately 10 cm beyond the pyloric sphincter. Perfusion solutions were hypotonic (186 mosmol/kg; solution A), isotonic (283 mosmol/kg; solution B), and hypertonic (403 mosmol/kg; solution C). All solutions contained 18 meq Na+ and 3 meq K+. In the mixing segment, osmolality increased 83 mosmol/kg and decreased 90 mosmol/kg for solutions A and C, respectively. Corresponding changes in the test segment were an increase of 60 mosmol/kg and a decrease of 34 mosmol/kg. The osmolality of solution B did not change. In the test segment, mean osmolality and water and total solute fluxes were not significantly different among solutions, but solution C produced 27% greater fluid absorption than did solution A. When net fluid movement from mixing and test segments was determined, solution A produced 17% greater fluid absorption than did solution C. The mean increases in plasma and urine volumes over the 80-min test period were not significantly different. In the test segment, water flux correlated with CHO and Na+ fluxes but not with osmolality. In conclusion, 1) significant differences in solution osmolality were eliminated within the proximal duodenum and 2) perfusing 6% CHO solutions with osmolalities ranging from 186 to 403 mosmol/kg did not produce significant differences in fluid homeostasis (plasma volume) at the end of an 80-min test period.

Body Water↗
PubMed1993

Excitatory amino acid regulation of the enkephalin phenotype in mouse embryonic spinal cord cultures.

Expression of the preproenkephalin gene in developing spinal cord-dorsal root ganglia (SC-DRG) cultures was determined by Northern analysis following treatments with different agonists and antagonists of the glutamate receptor. Cultures (10-12 days old) were treated with various concentrations (10(-7)-10(-3) M) of N-methyl-D-aspartate (NMDA), quisqualate, kainic acid (KA), 2-amino-5-phosphonovaleric acid (APV) and 5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine maleate (MK801) either with or without blocking spontaneous electrical activity with 1 microM tetrodotoxin (TTX). In electrically active cultures, treatments with NMDA and KA increased preproenkephalin transcripts (mRNAppENK), showing maximum effects at 1 microM (4-fold and 2-fold, respectively), while treatments with quisqualate and MK801 caused concentration-dependent down-regulation in mRNAppENK. The most effective concentrations of NMDA (1 microM) and quisqualate (10 microM) altered mRNAppENK levels within 4 h of treatment and peaked after 24 h for NMDA and 48 h for quisqualate treatment. Co-treatment with APV completely blocked the NMDA-induced rise of mRNAppENK. During electrical blockade, none of the concentrations of NMDA tested showed any effect on enkephalin expression, neither could NMDA pre-treatment prevent the TTX-induced down-regulation of mRNAppENK. Our results indicate that the activity-dependent establishment of the enkephalin phenotype is modulated through the selective activation of the NMDA-glutamate receptor.

Amino Acids↗
PubMed1993

Changes in colonic motility following abdominal irradiation in dogs.

The purpose of the study was to compare colonic motor patterns before and after a single abdominal dose of X-rays in dogs. Recordings were made from five serosally implanted strain gauges at equidistant intervals along the colon in seven dogs (2 dogs also had 2 jejunal electrodes and 1 had ileal electrodes). Control recordings were made for 3 h in the fasted state and daily for 2 wk after an absorbed X-ray dose of 938 cGy was delivered to the abdomen. The duration of migrating colonic motor complexes decreased from 7.2 +/- 0.5 to 3.9 +/- 0.4 min while the mean amplitude fell from 10.3 +/- 0.6 to 1.8 +/- 0.2 g (P < 0.05). The rate of nonmigrating colonic motor complex occurrence increased from 0.6 +/- 0.1 to 1.2 +/- 0.2 per hour (P < 0.05). Colonic giant migrating contractions were rarely observed during control recordings (2 in 80 h of recording). In contrast, repetitive clusters of giant contractions were observed 5-8 days after exposure in five of seven dogs (1.5/h) and were associated with restlessness, whining, and passage of diarrheal stools (sometimes bloody) with nearly every occurrence. The basic colonic motility patterns were less disrupted than were jejunal myoelectric patterns at the same irradiation dosage. However, the study demonstrates the important role of colonic giant migrating contractions in pathological diarrheal states such as irradiation injury.

Abdomen↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗