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Biomedical subjects

G I Sandle

Publications and source records attributed to G I Sandle.

At least 55 records · Page 3Linked to original sources
PubMed1987

Evidence for large intestinal control of potassium homoeostasis in uraemic patients undergoing long-term dialysis.

1. The role of the large intestine in the maintenance of K+ balance in uraemic patients established on long-term dialysis was studied with a rectal dialysis technique in 14 normal subjects, ten normokalaemic patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and seven patients undergoing haemodialysis. Dietary K+ intakes in the normal subjects, CAPD patients and haemodialysis patients were 80-100 mmol/24 h, 70-80 mmol/24 h and 60-70 mmol/24 h, respectively. 2. At an initial intraluminal K+ concentration of 45 mmol/l, rectal K+ secretion in the CAPD patients (2.4 +/- 0.4 mumol h-1 cm-2) was greater than in normal subjects (1.2 +/- 0.2 mumol h-1 cm-2, P less than 0.02). Under similar conditions, rectal K+ secretion was also greater in the haemodialysis patients than in normal subjects, both predialysis (3.7 +/- 0.4 mumol h-1 cm-2, P less than 0.001) and postdialysis (2.4 +/- 0.5 mumol h-1 cm-2, P less than 0.05), even though haemodialysis decreased plasma K+ concentration from 5.3 +/- 0.1 mmol/l to 3.5 +/- 0.2 mmol/l (P less than 0.001). 3. There were no significant differences in rectal Na+ absorption, rectal potential difference, plasma aldosterone concentration, or total body K+ content (measured by whole-body counting of 40K), between the normal subjects and either the CAPD or the haemodialysis patients. 4. These results indicate that K+ homoeostasis is maintained in uraemic patients undergoing long-term dialysis by a combination of K+ losses during dialysis, and enhanced large intestinal K+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Acute effects of dexamethasone on cation transport in colonic epithelium.

Single pharmacological doses of glucocorticoid hormones stimulate net Na+ and water absorption, K+ secretion and electrical potential difference in rat distal colon and human rectum after five hours. To determine the cellular basis of these effects, the Na+ and K+ transport properties of epithelial cell membranes in rat distal colon were studied in vitro five hours after in vivo treatment with dexamethasone 600 micrograms/100 g body weight. Compared with control tissues, dexamethasone increased transepithelial voltage 3.5-fold (p less than 0.001) and short circuit current 4.5-fold (p less than 0.001), and decreased total resistance by 20% (p less than 0.005). Measurements of cell membrane voltages obtained with intracellular microelectrodes indicated that the dexamethasone-induced rise in transepithelial voltage reflected a significant decrease (p less than 0.05) in apical membrane voltage, consistent with the induction of apical Na+ channels and the stimulation of electrogenic Na+ absorption. Apical addition of 10(-4) mol/l amiloride (a Na+ channel blocker) and then 30 mmol/l tetraethylammonium chloride (TEA; a K+ channel blocker) to control tissues had little or no effect on transepithelial electrical parameters, indicating the absence of significant apical Na+ and K+ conductances. In contrast, in dexamethasone treated tissues, amiloride and TEA produced electrical changes that were consistent with the inhibition of glucocorticoid-induced apical Na+ and K+ conductances. Kinetic studies of the basolateral membrane Na+-K+ pump revealed that five hours after administration, dexamethasone had no effect on the maximum capacity of the pump for Na+ transport, but significantly increased the affinity of the pump for Na+, and the number of Na+ ions binding to each pump site. Thus, the acute stimulatory effects of dexamethasone on distal colonic Na+ absorption and K+ secretion reflect increased apical membrane conductance to Na+ and K+, and an increase in the 'efficiency' of the basolateral membrane Na+-K+ pump.

Animals↗
PubMed1986

Enhanced rectal potassium secretion in chronic renal insufficiency: evidence for large intestinal potassium adaptation in man.

The role of the large intestine in K+ excretion in chronic renal insufficiency was studied with a rectal dialysis technique in 14 normal subjects and eight normokalaemic, normotensive patients with chronic renal insufficiency. At initial intraluminal K+ concentrations of 10, 20, 30 and 45 mmol/l, net K+ secretion in patients with renal insufficiency was significantly greater than in normal subjects by approximately 1.8 mumol h-1 cm-2. The increase in net K+ secretion was more marked in those patients with creatinine clearances of less than 10 ml/min. In contrast, there were no significant differences in net Na+ and water transport, transmucosal potential difference and plasma aldosterone concentrations between the two groups. With an initial intraluminal K+ concentration of 30 mmol/l, the addition of amiloride (final concentration 1 mmol/l) to the rectal lumen decreased net Na+ absorption and transmucosal potential difference in normal subjects by 69% (P less than 0.005) and 31% (P less than 0.005) respectively, and in patients with renal insufficiency by 75% (P less than 0.05) and 36% (P less than 0.05) respectively, but there was no change in net K+ secretion in either group. These results indicate that the K+ secretory capacity of the rectal mucosa increases in chronic renal insufficiency, and the large intestine may therefore contribute to the maintenance of K+ homoeostasis as renal K+ excretion declines. Increased rectal K+ secretion in renal insufficiency occurs independently of changes in plasma K+ and aldosterone concentrations, net Na+ absorption and transmucosal potential difference, and may reflect stimulation of an active K+ secretory process.

Adult↗
PubMed1986

Effect of glucocorticoids on rectal transport in normal subjects and patients with ulcerative colitis.

The acute effects of single pharmacological doses of glucocorticoid hormones on net electrolyte and water transport and electrical potential difference (pd) in the rectum was studied in control subjects and in patients with either active or inactive ulcerative colitis, using a dialysis technique. Compared with 17 control subjects, nine patients with active ulcerative colitis exhibited marked decreases in net sodium absorption and rectal pd, while these transport parameters were normal in six patients with inactive ulcerative colitis. Intravenous administration of hydrocortisone hemisuccinate (100 mg) resulted five hours later in significant and quantitatively similar increases in net sodium and water absorption and pd in nine control subjects, seven patients with active ulcerative colitis, and six patients with inactive ulcerative colitis. Intravenous administration of methylprednisolone phosphate (40 mg) to eight control subjects produced increases in net sodium and water absorption and pd five hours later, which did not differ significantly from those produced by hydrocortisone; methylprednisolone induced similar changes in two patients with active ulcerative colitis. These results indicate that single pharmacological doses of glucocorticoids stimulate acute increases in rectal sodium and water absorption in control subjects and in patients with acute ulcerative colitis. The ability of systemically administered glucocorticoids to reduce diarrhoea in ulcerative colitis may therefore be related to direct effects on distal colonic sodium and water transport, as well as to their better known anti-inflammatory action.

Acute Disease↗
PubMed1986

Electrophysiology of the human colon: evidence of segmental heterogeneity.

The electrical properties of epithelial cell membranes in human descending and ascending colon were studied using microelectrodes and the Na channel blocker amiloride. Under control (pre-amiloride) conditions, the transepithelial electrical measurements in the two colonic segments were similar. The mucosal addition of 0.1 mM amiloride to descending colon totally abolished the transepithelial voltage (Vt) and short-circuit current (Isc), and significantly increased the total tissue resistance (Rt) by 19% (p less than 0.005). Intracellular recordings in descending colon obtained with microelectrodes revealed that the transepithelial effects of amiloride reflected hyperpolarization of the apical membrane and a significant increase in apical membrane resistance, changes which were consistent with amiloride-blockade of apical Na channels and complete inhibition of electrogenic Na transport. An appreciable amiloride-insensitive conductance was also present in the apical membrane of the descending colon. In contrast, the mucosal addition of 0.1 mM amiloride to ascending colon decreased Vt by only 30% (p less than 0.02) and Isc by 43% (p less than 0.05), but had no significant effect on Rt. These results indicate that electrogenic Na transport accounts totally for Isc in human descending colon in vitro, but only partly for Isc in human ascending colon, suggesting that Na transport in ascending colon is mediated primarily by electroneutral processes, and the apical membrane of human descending colon contains an amiloride-sensitive conductance for Na in parallel with an amiloride-insensitive conductance, which may transport K.

Adult↗
PubMed1986

Dietary potassium modulates active potassium absorption and secretion in rat distal colon.

To determine the effect of variations in body stores of potassium on the rate of active potassium transport in the large intestine, unidirectional 42K fluxes were performed under short-circuit conditions across isolated distal colonic mucosa of control, dietary potassium-depleted and dietary potassium-loaded rats. Potassium depletion stimulated net potassium absorption (JK net) (0.87 +/- 0.19 vs. 0.49 +/- 0.04 mu eq X h-1 X cm-2, P less than 0.025) due to a 40% increase in mucosal-to-serosal potassium transport (JK m----s). In sodium-free Ringer solution JK net in the potassium-depleted group was also significantly greater than in controls (1.93 +/- 0.26 vs. 1.01 +/- 0.11 mu eq X h-1 X cm-2, P less than 0.005). In contrast, in chloride-free Ringer solution JK net was identical in the control and potassium-depleted groups (0.39 +/- 0.05 vs. 0.46 +/- 0.07 mu eq X h-1 X cm-2, P = NS). Potassium loading reversed net potassium absorption to net potassium secretion (-0.76 +/- 0.08 mu eq X h-1 X cm-2, P less than 0.001) as the result of a decrease in JK m----s and an increase in serosal-to-mucosal potassium transport (JK s----m). Net potassium secretion was abolished in the absence of either sodium or chloride from the bathing solution but not by mucosal amiloride. In sodium-free Ringer solution JK net was similar in control and potassium-loaded groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1986

Quantitation of tryptic responses to endogenous and exogenous stimulation in chronic pancreatitis.

Using validated double-marker techniques to quantitate tryptic secretion we found that the mean 10-min output of trypsin in duodenal juice after a test meal was very similar to the peak 10-min output of trypsin after pancreozymin (2 Crick-Harper-Raper units/kg, Boots) both in controls as well as in non-diabetic patients with idiopathic chronic pancreatitis. These results show that the disproportionate reduction in mean tryptic activity after endogenous compared with exogenous stimulation in chronic pancreatitis is not due to impaired release of cholecystokinin-pancreozymin from the small intestine, nor to refractoriness of the pancreas to endogenously released hormone: instead, it is due to overdilution of secreted pancreatic enzymes because of accelerated gastric emptying, with or without gastric acid hypersecretion.

Cholecystokinin↗
PubMed1985

The electrical basis for enhanced potassium secretion in rat distal colon during dietary potassium loading.

Previous studies in rat distal colon provide evidence for an active absorptive process for potassium under basal conditions, and for active potassium secretion during chronic dietary potassium loading. The present studies were performed with conventional and potassium-selective microelectrodes to determine the electrical basis for the increase in transcellular (active) potassium secretion observed during potassium loading. Compared to control tissues, potassium loading resulted in a 5-fold increase in transepithelial voltage (VT) and a 52% decrease in total resistance (RT) in the distal colon. The rise in VT was due to a decrease in apical membrane resistance and an increase in basolateral membrane voltage from -45 +/- 2 mV (cell interior negative) in control to -56 +/- 2 mV (p less than 0.001) in potassium loaded tissues. This difference in basolateral membrane voltage reflected in increase in intracellular potassium activity from 86 +/- 4 mM to 153 +/- 12 mM (P less than 0.001). In control tissues, the sequential mucosal addition of the sodium channel blocker amiloride (0.1 mM) and the potassium channel blocker tetraethylammonium chloride (TEA: 30 mM) produced no effect on the electrical measurements. However, in potassium loaded tissues, amiloride and TEA produced transepithelial changes consistent with inhibition of apical membrane conductances for sodium and potassium, respectively, reflected by increases in the resistance ratio, alpha (ratio of apical to basolateral membrane resistances). These data indicate that the decrease in apical membrane resistance during potassium loading was caused by an increase in apical membrane conductance for both potassium and sodium.

Amiloride↗
PubMed1984

Effect of chronic hyperaldosteronism on the electrophysiology of rat distal colon.

Microelectrodes have been used to study the effects of aldosterone on the barriers and forces controlling sodium and potassium transport in rat distal colon. Compared to control tissues, hyperaldosteronism induced by dietary sodium depletion resulted in a 7-fold increase in transepithelial voltage (VT) and a 52% decrease in total resistance (RT). Increased VT reflected both a rise in the basolateral membrane voltage (Vbl) and a fall in the apical membrane voltage (VA). RT was resolved into its separate membrane components using nystatin (585 U X ml-1), and the decrease in RT produced by aldosterone was found to be due entirely to a 66% decrease in the apical membrane resistance (RA). Amiloride had no effect on the control tissues, but restored VT, Vbl and VA in tissues from sodium deprived animals to control values. Amiloride also increased RT in the experimental tissue, but the post-amiloride values remained significantly lower than those in controls. These results indicate, therefore, that hyperaldosteronism results in an increase in VT by hyperpolarizing the basolateral membrane, as well as depolarizing apical membrane in rat distal colon. The fall in RT, however, is due only to a fall in RA since Rbl and junctional resistance (Rj) were unaffected. The data are consistent with the concept that aldosterone acts to stimulate sodium absorption by increasing the rate of cell entry of sodium, through the induction of amiloride-sensitive sodium channels in the apical membrane, and enhances the rate of potassium secretion by increasing the electrical driving force towards the mucosal solution.

Amiloride↗
PubMed1984

Effect of intraluminal hydrocortisone on solute and water absorption in the human jejunum.

To compare the effects of intravenous and intraluminal hydrocortisone on jejunal transport, the proximal jejunum was perfused with glucose (28 mmol/l) in saline in two groups of normal subjects. In the first group of seven subjects, compared with the control period results there were no changes in sodium, water and glucose absorption during the intravenous administration of hydrocortisone. In contrast, intraluminal hydrocortisone (100 mg/l) increased sodium, water and glucose absorption by 169%, 223% and 81% respectively (P less than 0.001 in each case) above the control values, when peripheral plasma cortisol levels were similar to those achieved with intravenous hydrocortisone. In the second group of three subjects, intraluminal hydrocortisone (10 mg/l and 30 mg/l), followed by an intravenous infusion of hydrocortisone, had no effects on sodium, water and glucose absorption. In a third group of six normal subjects perfused with fructose (28 mmol/l) in saline and bicarbonate (28 mmol/l) in saline intraluminal hydrocortisone (100 mg/l) had no effect on solute and water absorption. These results suggest that intraluminal hydrocortisone stimulates glucose-coupled sodium transport by exerting a topical effect on the apical membrane of the jejunal mucosa.

Adult↗
PubMed1984

Apical membrane properties and amiloride binding kinetics of the human descending colon.

The apical membrane properties of the isolated human descending colon were characterized by use of current fluctuation analysis methods and microelectrode techniques. The Na+ channel blocker amiloride was used to evaluate apical membrane conductance and the transepithelial short-circuit current (Isc). Amiloride significantly reduced Isc and increased the membrane resistance ratio. At submaximal doses of amiloride in the mucosal bathing solution, fluctuation analysis of the Isc revealed a Lorentzian component in the power-density spectra. The dose-response relationship between amiloride and current noise parameters was consistent with a two-state mechanism of blocker interaction with the channel. The on and off rate constants for the blocker-receptor reactions, the single-channel currents, and the Na+ channel density were estimated and were similar to those from Na+ channels from other so-called tight epithelia. In addition, these studies revealed an amiloride-insensitive conductance in the apical membrane in parallel to the amiloride-blockable Na+ channels. This conductance may be due to potassium ions. If so, the apical membrane properties of the human descending colon may closely resemble those of the rabbit descending colon and rat distal colon.

Adult↗
PubMed1983

Constrictive pericarditis and intestinal haemorrhage due to Whipple's disease.

Two months after a pericardectomy for constrictive pericarditis a 37-year-old man presented with diarrhoea, abdominal pain and weight loss. During the course of investigation he developed brisk rectal bleeding and emergency angiography revealed a bleeding site related to an area of abnormal vasculature in the caecum. At laparotomy, the small bowel was found to be inflamed and the mesenteric lymph nodes enlarged. The overall histological appearances, confirmed later on endoscopic duodenal biopsies, were those of Whipple's disease. His symptoms resolved promptly after starting tetracycline therapy. The clinical features of Whipple's disease are protean and often bizarre. We report here a case where the diagnosis was made after the onset of profuse rectal bleeding.

Adult↗
PubMed1983

Monosaccharide absorption and water secretion during disaccharide perfusion of the human jejunum.

During jejunal perfusion of normal subjects with isotonic mannitol-saline containing glucose, maltose or sucrose (112 mmol/l), monosaccharide absorption from disaccharides was greater than expected from the intraluminal concentration of free monosaccharides, and water secretion was greater than with glucose. With equimolar (112 mmol/l) glucose + disaccharide mixtures, intraluminal glucose concentrations were similar to but total glucose absorption less than expected from experiments with the individual sugars. The results favour sequential hydrolysis-absorption whereby high concentrations of monosaccharide accumulate at the brush border and promote sugar uptake by conventional rather than 'disaccharidase-related' transport, and stimulate water secretion by local osmotic effects.

Adolescent↗
PubMed1983

Cyclic adenosine monophosphate stimulates active potassium secretion in the rat colon.

To determine whether cyclic adenosine monophosphate influences active potassium transport in the rat colon, we studied the effect of dibutyryl cyclic adenosine monophosphate and theophylline on unidirectional transmural 42K fluxes across proximal colonic mucosa under short-circuited conditions. Active potassium secretion (-0.19 +/- 0.02 microEq/h X cm2) was present in animals maintained on a normal potassium diet. Both 0.5 mM dibutyryl cyclic adenosine monophosphate and 5 mM theophylline significantly increased net potassium secretion by 0.49 +/- 0.04 and 0.33 +/- 0.03 microEq/h X cm2, p less than 0.001, respectively; the stimulation of net potassium secretion was secondary to an increase in serosal-to-mucosal potassium transport without change in mucosal-to-serosal potassium movement. A similar increase in active potassium secretion (from -0.15 +/- 0.03 to -0.32 +/- 0.03 microEq/h X cm2, p less than 0.005) was produced by bethanechol, a cholinergic muscarinic agonist that alters sodium and chloride transport by a noncyclic adenosine monophosphate, calcium-dependent process. In animals maintained on a high potassium diet, active potassium secretion was significantly increased to -0.79 +/- 0.17 microEq/h X cm2 (p less than 0.001). In these potassium-loaded animals, theophylline produced a greater increase in active potassium secretion (0.91 +/- 0.10 vs. 0.33 +/- 0.03 microEq/h X cm2, p less than 0.001) than in animals fed a normal potassium diet. These studies demonstrate that cyclic adenosine monophosphate and noncyclic adenosine monophosphate mediated secretogogues stimulate active potassium secretion. We speculate that the mechanism by which cyclic adenosine monophosphate increases active potassium secretion is related to an increase in luminal potassium conductance.

Animals↗
PubMed1982

Inter-relationships between the absorptions of hydrocortisone, sodium, water and actively transported organic solutes in the human jejunum.

The effect of intraluminal hydrocortisone (100 mg/l) on sodium and water transport in the small intestine was investigated by jejunal perfusion (flow rate 15 ml/min) of healthy subjects with normal saline and saline containing 56 mmol/l galactose or alanine. Minimal absorption of sodium and water occurred with normal saline and did not change significantly in the presence of hydrocortisone. Galactose and alanine enhanced sodium and water absorption and further significant increases occurred in the presence of hydrocortisone. Glucocorticoid induced increases in absorption were detected within 20-30 min, while plasma cortisol concentrations were in the normal range. 43% of the perfused dose of hydrocortisone was absorbed with normal saline (p less than 0.01). There was a significant positive correlation (p less than 0.0025) between hydrocortisone and water absorption. Thus, in the presence of actively absorbed organic solutes, hydrocortisone rapidly increased sodium absorption and the concurrent increase in water absorption appears to have facilitated passive absorption of hydrocortisone.

Adult↗
PubMed1982

Propranolol absorption in untreated coeliac disease.

1. To compare the bioavailability and the elimination of propranolol in seven untreated coeliac patients and six normal subjects, plasma concentrations were measured after oral and intravenous propranolol. The bioavailability and clearance of propranolol were similar in both groups. 2. With the use of a perfusion technique, propranolol absorption in the proximal jejunum was found to be decreased by 71% in five untreated coeliac patients, compared with the absorption in four normal subjects. 3. There results indicate that propranolol absorption is decreased in the proximal jejunum in untreated coeliac disease but overall absorption in the small bowel is not impaired.

Absorption↗
PubMed1981

Flexible sigmoidoscopy in outpatients with suspected colonic disease.

One hundred and fifteen patients attending a gastroenterology clinic were investigated by flexible sigmoidoscopy as outpatients. There were asked to fast before the examination and give a high-volume enema and sedated before the examination. A standard long colonoscope was used rather than the 60-cm sigmoidoscope, which limits the distance that can be examined and forces the operator to work very close to the patient. Preparation was considered good in 95 patients and 49 were examined as far as the hepatic flexure or beyond. Sixty-one patients were found to have lesions of the colon, 25 of them ulcerative colitis, 16 a poly, and nine carcinoma. Despite the fact that these patients were selected (some of them had already had ulcerative colitis diagnosed), flexible sigmoidoscopy proved to be a valuable initial outpatient investigation. The proximal colon was well visualised in 46 patients and a subsequent barium enema was considered unnecessary. There were no complications and the procedure seemed to be well tolerated.

Ambulatory Care↗