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Biomedical subjects

D W Powell

Publications and source records attributed to D W Powell.

At least 73 records · Page 4Linked to original sources
PubMed1984

Barrett's esophagus: clinical, endoscopic, histologic, manometric, and electrical potential difference characteristics.

The clinical, endoscopic, histologic, manometric, and esophageal potential difference characteristics of 20 patients with columnar epithelia lining the lower esophagus (Barrett's esophagus) are presented. Endoscopically, two distinct types were identified: a circumferential-type and an island-type Barrett's esophagus. Patients with these types exhibited similarities in mean age, duration of symptoms, mean lower esophageal sphincter pressure, and frequency of gross esophagitis. Only patients with the circumferential lesion, however, had esophageal strictures or esophageal ulcers. Manometric testing revealed a range of lower esophageal sphincter pressures from 3 to 33 mmHg and qualitative motor abnormalities (i.e., aperistalsis, repetitive waves, tertiary waves) in 3 patients. Histologically, the frequency of epithelial types was junctional greater than specialized columnar greater than atrophic fundic epithelium. More importantly, dysplasia was identified in 2 patients with the circumferential lesion and in 1 patient with the island lesion. Potential difference measurements demonstrated that a high potential difference (greater than -25 mV) was highly specific (92%), but only moderately sensitive (70%) for detecting Barrett's esophagus. Based on these findings, we conclude (a) that there are at least two endoscopically distinct types of Barrett's esophagus involving the lower esophagus--a circumferential type and an island type, (b) that both types are associated with chronic gastroesophageal reflux, with the island type being accompanied by less severe epithelial injury than the circumferential type, and (c) that the identification of dysplasia in the two types suggests that both are unstable lesions requiring continued surveillance with endoscopy and biopsy.

Adolescent↗
PubMed1983

Enterotoxigenic diarrhea: mechanisms and prospects for therapy.

Studies over the past decade have led to a rudimentary but working knowledge of intestinal electrolyte transport. Purification of bacterial exotoxins has allowed an understanding of how these agents stimulate cells. Coupled NaCl influx processes and chloride secretory mechanisms have been shown to be affected by exotoxin-stimulated increases in cyclic nucleotides, as well as by increases in intracellular calcium and arachidonic acid metabolites. Catecholamines, somatostatin, phenothiazines, nonsteroidal anti-inflammatory drugs, and opiates appear to be the most promising of the antisecretory drugs. While the mechanism of action of these agents remains to be determined, there is significant hope that effective antisecretory drugs will emerge in the near future.

Animals↗
PubMed1983

Calcium/calmodulin inhibition of coupled NaCl transport in membrane vesicles from rabbit ileal brush border.

The role of Ca2+ and calmodulin in regulating coupled NaCl transport has been investigated in membrane vesicles from rabbit ileal brush border. Uptake of 22Na+ and 36Cl- was determined by a rapid filtration technique in vesicles isolated with a sucrose density gradient ultracentrifugation method. Ca2+ on the inside of the vesicle inhibited Na+ uptake when Cl- was the anion and Cl- uptake when Na+ was the cation by approximately equal to 30%. Ca2+ on the outside had no effect. When gluconate was the anion or when choline was the cation, Na+ or Cl- uptake was reduced by only 9-12%. A similar inhibition of D-[3H]mannitol uptake (10-17%) suggests this was due to a nonspecific decrease in the membrane permeability. Other cations such as Ba2+ and Mg2+ had no effect, but La3+ inhibited Na+ and Cl- uptake to the same degree as Ca2+. Calmodulin (2 microM) in combination with Ca2+ (1 microM, free concentration) significantly inhibited Na+ uptake when Cl- was the anion by 21-32% and Cl- uptake when Na+ was the cation by 20-27%. This effect was completely reversed by 10 microM trifluoperazine. When gluconate was the anion or when choline was the cation, Na+ or Cl- uptake was unaffected by Ca2+/calmodulin and trifluoperazine. The Ki for Ca2+ inhibition of Cl- -coupled Na+ uptake was reduced from 200 microM to 0.2 microM by incubation with 20 microM calmodulin. The Ki for exogenously added calmodulin studied at 1 microM Ca2+ was 0.2 microM. The Ki for trifluoperazine inhibition of the Ca2+/calmodulin response was 3 microM. These results represent compelling evidence for intracellular Ca2+/calmodulin regulation of coupled NaCl transport across the intestinal microvillus membrane. The exact mechanism of this regulation remains to be delineated.

Animals↗
PubMed1983

Coupled sodium-chloride transport by rabbit ileal brush-border membrane vesicles.

Uptake of Na and Cl into brush-border membrane vesicles isolated from rabbit ileal epithelial cells was investigated with a rapid filtration technique using 22Na and 36Cl as tracers. The rank order of anion dependence for Na uptake in the absence of anion gradients was SCN greater than NO3 greater than gluconate. The sequence of cation specificity for Cl uptake was Na congruent to Li greater than K greater than choline. The transport of Na and Cl were both inhibited by harmaline, furosemide, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, and 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid. Carrier mediation of Cl-stimulated Na transport was suggested by the competition for 22Na uptake with increasing concentrations of unlabeled Na in the presence of Cl but not when gluconate was the counterion. Chloride-dependent Na uptake had an apparent Km of 4.5 mM and a Vmax of 20 nmol . mg prot-1 . 15 s-1. Na-H exchange and Cl-OH (or HCO3) exchange were also demonstrated in these vesicles. These findings confirm the presence of an electrically neutral carrier-mediated, Na-Cl-coupled transport process in the apical cell membrane of rabbit ileal epithelial cells. The nature of the coupling of Na to Cl transport, i.e., NaCl symport or a process that combines Na-H antiport with Cl-OH (or HCO3) antiport, remains to be determined.

Animals↗
PubMed1982

Effect of phenolphthalein on monkey intestinal water and electrolyte transport.

To assess Na-K-ATPase inhibiton and prostaglandin synthesis stimulation as the mechanism of the secretory (cathartic) action of phenolphthalein in the primate, we investigated water and electrolyte transport and Na-K-ATPase levels in monkey intestine. Both jejunum and colon were studied with in vivo perfusion and in vitro Ussing chamber techniques. Water, Na, and Cl absorption was inhibited or secretion was induced by phenolphthalein (10(-3) M) in the jejunum and colon when the drug was present in the mucosal bathing (perfusion) solution. Serosal addition of phenolphthalein (10(-4) or 10(-3) M) induced Na and anion absorption in the jejunum but not in the colon. Phenolphthalein inhibited Na-K-ATPase activity in the test tube, but assays of intestine previously perfused or bathed in the drug showed no inhibiton. Indomethacin, in doses sufficient to inhibit prostaglandin synthesis in the intestine, inhibited the secretion induced by phenolphthalein in the jejunum but not in the colon. These inconsistencies cast doubt on the role of Na-K-ATPase inhibition or the role of prostaglandin synthesis stimulation in the mechanism of action of phenolphthalein.

Animals↗
PubMed1982

Esophageal potential difference measurements in esophageal disease.

To determine if esophageal transmural electrical potential difference measurements are of use for evaluating esophageal disease, we recorded potential difference in 129 patients with one or more of the following: heartburn, dysphagia, and chest pain. All potential difference studies were performed at the time of esophageal manometry using a Ringer-perfused catheter technique which yields accurate and reproducible results in healthy subjects. In 103 of the 129 patients, esophageal potential difference measurements could be correlated with findings at manometry, endoscopy, and biopsy. The remaining 26 patients had primary esophageal motor disease and were not biopsied. The results of this investigation showed: (a) that 94% of patients with gross endoscopic lesions have an abnormal esophageal potential difference, (b) that an abnormal esophageal potential difference (found in only 1 of 24 patients with normal mucosa) is highly specific for the presence of esophageal mucosal disease, (c) that the type of potential difference abnormality may suggest the nature of the mucosal abnormality, for example high potential difference with Barrett's esophagus and low potential difference with esophagitis or invasive carcinoma, and (d) that while an abnormal esophageal potential difference is highly sensitive for detecting gross esophagitis (38 of 40 patients), it is less sensitive for diagnosing microscopic esophagitis (8 of 16 patients). Based on these findings we conclude that the measurement of esophageal potential difference at the time of manometry can provide additional valuable information about the state of the esophageal mucosa.

Action Potentials↗
PubMed1981

Pseudomembranous (antibiotic-associated) colitis.

We have come to understand the cause of antibiotic-associated pseudomembranous colitis (PMC) only in the last decade. Clostridium difficile produces the intestinal dysfunction and the characteristic finding of exudative plaques on the mucosa by elaborating a toxin in the colon. This report reviews the development of our knowledge of this disease and the rapid adoption of a rational therapy once the cause was specified. C. difficile or its toxin can be cultured or isolated from the stools of 90% of the patients with PMC. This organism is almost never found in healthy people or in any other conditions except inflammatory bowel disease, where its significance is not yet known. The detection of pseudomembranes by sigmoidoscopy establishes the diagnosis. The laboratory technics that confirm the presence of C. difficile and its toxin are being incorporated into many laboratories around the country. Treatment of diagnosed PMC is relatively simple and usually completely effective. The offending antibiotic is stopped, a proper fluid and electrolyte balance maintained, and oral vancomycin begun, 125 to 500 mg four times a day. Cholestyramine can also be used as an adjunct to this regimen. Relapse can occur in patients treated with oral vancomycin, necessitating a repeat course of therapy.

Anti-Bacterial Agents↗
PubMed1981

A current approach to rectal bleeding.

The source of bleeding from the rectum is extremely difficult to specify in many patients with moderate to severe bleeding. Lesions may be located anywhere along the gastrointestinal tract. On the basis of the available literature and reported clinical data, we conclude that moderate to severe rectal bleeding originates from the upper gut in up to 10% of patients, from the small bowel in up to 5%, and from the colon in the remaining 85%. Diverticulosis and vascular dysplasia account for 30-50% of colonic bleeding, and inflammatory bowel disease and ischemic colitis for another 5-15%. No diagnosis is made in 20-30% of patients with moderate to severe rectal bleeding. Patients with rectal bleeding can be classified as those whose bleeding stops spontaneously, those whose bleeding stops and then recurs, and those whose bleeding continues despite conventional treatment. Based on these classifications, we present an approach to the diagnosis and therapy of rectal bleeding.

Colonic Diseases↗
PubMed1981

A current approach to acute upper gastrointestinal bleeding.

The mortality in patients with upper gastrointestinal bleeding has not changed in the past quarter century in spite of the introduction of new modes of therapy and treatment. In this review we address the possible reasons for a lack of change in mortality and the implications raised for the use of new techniques. We review the factors that affect the mortality of acute upper gastrointestinal hemorrhage and the diagnostic accuracy of upper gastrointestinal endoscopy. Based on this information, we present guidelines for the therapy of the major causes of upper gastrointestinal bleeding. These guidelines should be useful until new therapies have been assessed and become generally available.

Age Factors↗
PubMed1981

Barrier function of epithelia.

The ability of an epithelium to prevent permeation of noxious agents has not been well studied except in the gastrointestinal tract where exclusion of H+ has clinical significance. This article reviews the permeation routes across epithelia both as elucidated in the extensive electrophysiological work done in recent years and as demonstrated in morphological studies. We thus place concepts about gastrointestinal barrier function into the framework of transport physiology. Both the permeability and permselectivity of epithelial barriers are reviewed here. The effects of physical agents (pressure and electric current), polyvalent cations, organic compounds with both specific (channel blocking) and nonspecific (detergent) membrane properties, cyclic nucleotides, microfilament-active agents, and particularly H+ on both the barrier function (permeability and permselectivity) and transport function of epithelia are considered. Based on the available data, an important role for active Na+ transport in the maintenance of the epithelial barrier function can be postulated.

Animals↗
PubMed1981

Pathophysiology of acute acid injury in rabbit esophageal epithelium.

To increase our understanding of the pathophysiology of reflux esophagitis, we sought the early sequence of changes in mucosal structure and function in acutely acid-damage rabbit esophagus. Using a perfused catheter technique esophageal potential difference (PD) profiles were obtained in anesthetized rabbits before, during, and after perfusion of the lower one-half of the esophagus with phosphate-buffered saline or 80 mM NaCl. When acid perfusion reduced the lower esophageal PD by 40-50% or 80-100% of the initial values, the esophagus was removed, sectioned, and the mucosa studied with light microscopy, transmission electron microscopy, and Ussing chamber technique for evaluation of sodium and mannitol transport. The earlier stage of acid damage (PD 40-50%) was associated with reduced mucosal resistance fom 2,180 +/- 199 to 673 +/- 157 ohm cm2 and increased passive transport of sodium (0.10 +/- 0.06 to 1.82 +/- 0.48 microeq/h.cm2) and mannitol (0.008 +/- 0.003 to 0.051 +/- 0.012 microM/h.cm2) (p less than 0.05). There was no significant change in shirt circuit current (0.35 +/- 0.05 to 0.35 +/- 0.04) or net sodium transport (0.32 +/- 0.06 to 0.37 +/- 0.12) at this stage, and the only morphologic finding was dilated intercellular spaces on electron microscopy. The later stage of acid damage (PD 80-100%) exhibited a further reduction in resistance to 299 +/- 65 ohm.cm2 (p less than 0.05), a finding now accompanied by a reduction in short circuit current (0.35 +/- 0.05 to 0.21 +/- 0.04 microeq/h.cm2) and complete inhibition of net sodium transport (0.32 +/- 0.06 to 0.01 +/- 0.13) (p less than 0.05). Morphologic studies at this time revealed cellular necrosis, edema, and vesicle formation in the stratum spinosum. Both gross mucosal changes and transmural necrosis were notably absent. When esophageal perfusion was performed with a combination of acid (80 mM HCl-80 mM NaCl) and pepsin (100 microgram/ml), the morphologic and physiologic findings were essentially the same as with acid alone; however, the time of perfusion to reach either the 50 or 100% reduction in PD was shortened. The findings in this model can be explained on an initial increase in cellular and/or paracellular permeability followed by inhibition of active sodium transport. The resulting loss of osmolar regulation leads to cell necrosis in the stratum spinosum.

Animals↗
PubMed1981

Morphologic alterations in early acid-induced epithelial injury of the rabbit esophagus.

To arrive at a basic understanding of the pathogenesis of reflux esophagitis, we developed an acute experimental model in the rabbit for studying the early lesion. Acid was perfused in vivo into the lower esophagus while potential difference was monitored intermittently. At varying degrees of potential difference decline, indicating epithelial injury, the esophageal stratified squamous epithelial tissue was removed for morphologic studies and in vitro electrophysiologic and transport studies. At 50 per cent reduction in potential difference, there was dilation of intercellular spaces, which when correlated with physiologic results of increased permeability indicates increased intercellular water. At 100 per cent reduction in potential difference, cells in the midepithelium were observed to be swollen and ruptured, forming vesicular spaces, midepithelial cleavages, and later early ulceration. Results of functional studies at this stage showed inhibition of sodium transport. The midepithelial site of disruption corresponds to the site of active sodium pumping out of cells in other stratified squamous epithelia. Since sodium is transported by esophageal epithelium and this function was inhibited by acid, we propose that this early morphologic lesion may be the result of damage to the sodium-transporting mechanisms of the epithelium.

Animals↗
PubMed1980

Neurohumoral control of esophageal epithelial electrolyte transport.

The neurohumoral control of epithelial esophageal electrolyte transport was investigated by studying the effect of various hormones and neuroeffector agents on the potential difference (PD) in vivo or on the electrical parameters of electrolyte transport in vitro. The rabbit esophagus, which has no submucosal esophageal glands, demonstrated no effect of pentagastrin, cholecystokinin octapeptide, or synthetic secretin in vivo, and no effect of these hormones or of vasopressin, aldosterone, carbachol, epinephrine, or cAMP in vitro. The rabbit esophagus did respond to metabolic substrates (glucose) in vitro by increasing sodium absorption. In contrast, the opossum esophagus, which contains extensive submucosal glands, had a lower electrical resistance, PD, short-circuit current, and sodium absorption with higher chloride secretion. This esophagus responded to carbachol and epinephrine by sodium and chloride secretion. We believe that only the submucosal glands of the esophagus are under significant neurohumoral control while the sodium transporting function of the stratified squamous epithelium of this organ is important in maintaining its barrier function.

Aldosterone↗
PubMed1979

Aspirin-stimulated intestinal electrolyte transport in rabbit ileum in vitro.

Because aspirin and the heavy metal salts of related anions have effects on intestinal ion transport and on diarrheal states, we have studied the effect of aspirin (ASA) on the in vitro rabbit ileum in an attempt to understand its mechanism of action. Ten millimolar of aspirin increased the conductance of rabbit ileum by 10--50% but did not change the permselectivity of the shunt path as determined by measurement of diffusion potentials. In Cl-free and HCO3-free solutions, aspirin reduced both Na absorption and the short-circuit current (Isc), which suggests an effect on electrogenic Na transport. Such an effect was not unexpected, since aspirin interferes with ATP production. However, in Ringer solution, aspirin in concentrations as little as 1 mM in the serosal solution reduced the Isc as before but also stimulated Na and Cl absorption and reduced JRnet (? HCO3 secretion) to zero. Aspirin had no effect on Na transport in the absence of Cl and no effect on Cl transport in the absence of Na, which suggests that aspirin stimulated a coupled transport process. Although these effects of ASA resemble those of alpha-adrenergic agents, ASA's effect was not blocked by alpha-adrenergic blockers such as phentolamine or phenoxybenzamine. The exact mechanism of ASA-stimulated NaCl absorption remains to be determined.

Adrenergic alpha-Antagonists↗