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Biomedical subjects

K Walker

Publications and source records attributed to K Walker.

At least 163 records · Page 9Linked to original sources
PubMed1985

An LH-RH analogue (Zoladex) in the management of carcinoma of the prostate: a preliminary report comparing daily subcutaneous injections with monthly depot injections.

The luteinizing hormone releasing hormone, Zoladex, has been used in three centres, Pontefract, Antwerp and Mistelbach, to treat carcinoma of the prostate. An initial protocol using a soluble daily injection has been followed by a second study employing a monthly administered depot preparation. After an initial stimulation it has been shown that both daily and monthly injections reduce plasma testosterone to castrate levels. Circulating luteinizing hormone levels are also initially stimulated and then suppressed. Treatment toxicity has been minimal and in these short term studies reduction of acid phosphatase and subjective and objective tumour responses have been similar to those expected from effective hormonal therapy of prostatic cancer.

Buserelin↗
PubMed1985

The effects of abdominal irradiation on intestinal transport in the rat as assessed with isolated epithelial cells.

The time course of the effect of exposure to sublethal irradiation on transport of several substrates by the intestine has been studied using isolated enterocytes. Rats received a single dose of 6 Gy to the abdomen, and isolated intestinal epithelial cells were prepared 3, 7, and 14 days later. The ability of the cells to take up D-glucose, L-leucine, and glycyl-L-leucine was assessed using 2.5-min incubation periods and was compared with the uptake in control cells. It was found that the protein content of the cells increased after irradiation, and although some of this was the result of increased binding of albumin to the cells there was also a nonspecific increase in most cell proteins. Consequently uptake data were expressed per unit number of cells and not per milligram of cell protein. Comparison of uptake expressed in this way showed that D-glucose and glycyl-L-leucine uptake was elevated 3 days after irradiation while that of L-leucine was unaffected. By 14 days after irradiation the glucose and glycyl-L-leucine uptake had returned to normal but the L-leucine transport was depressed. These data indicate that the effects of irradiation upon substrate transport in the intestines are not uniform and that although the cell population is initially reduced the remaining cells can compensate by increasing their transport capacity.

Animals↗
PubMed1985

Intestinal uptake of hexoses and fatty acids in tumor-bearing rats.

An in vitro technique was used to examine the rate of uptake of varying concentrations of glucose, galactose, and a homologous series of saturated fatty acids into the jejunum of control rats and Noble rats bearing prostatic tumor variants of primary human prostatic adenocarcinoma 52. Both groups of animals were healthy, eating and gaining weight normally. The uptake of acetic and butyric acid was reduced in tumor-bearing rats, but the uptake of four medium chain-length fatty acids was unchanged. The similar value of the incremental change in free energy in the control and tumor-bearing animals indicates similar passive permeability properties of the jejunum in the two groups. The uptake of varying concentrations of glucose and galactose was similar in the control and in the tumor-bearing animals. It is concluded that there are only subtle changes in nutrient uptake in tumor-bearing rats that are eating and gaining weight normally. It is suggested that any alteration in nutrient absorption which might occur in the cachectic tumor-bearing animal is probably due to alterations in food intake or body weight, rather than due to a direct effect of the tumor on the intestine.

Adenocarcinoma↗
PubMed1985

Interrelationship between gastric acidity and gastrin concentration in patients with duodenal or gastric ulcer and in healthy subjects.

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.

Adult↗
PubMed1985

Postprandial changes in serum concentrations of gastrin-17, gastrin-34, and total gastrin in patients with duodenal or gastric ulcers and in normal subjects.

The fasting concentrations of total gastrin and gastrin-17 (G-17) were similar in healthy volunteers and in asymptomatic patients with gastric ulcers or duodenal ulcers. However, the fasting serum concentration of gastrin-34 (G-34) was higher in patients with gastric ulcers than in normal subjects, in whom it was higher than in patients with duodenal ulcers. In response to food, the increases in G-17, G-34, and total gastrin were greater in ulcer patients than in healthy subjects. Cimetidine administration was associated with further increases in G-17, G-34, and total gastrin in normal subjects and gastric ulcer patients after meals. The ratio G-17/G-34 was similar in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers. Cimetidine produced an increase in G-17/G-34 in placebo-treated normal subjects and placebo-treated patients with gastric or duodenal ulcers, but the ratio G-17/G-34 was greater in patients with gastric ulcers than in normal subjects. These results indicate that: differences in serum gastrin concentrations between patient groups, treatment regimens, and time of day are better detected by measuring G-17 and G-34 rather than total gastrin; there are differences in fasting and food-stimulated gastrin concentrations between normal subjects and patients with gastric or duodenal ulcers; the fasting concentration of G-34 is higher than G-17 in normal subjects and patients with gastric ulcers but not in patients with duodenal ulcers; food increases G-17 in all subjects but G-34 only in subjects with gastric ulcers; cimetidine increases the fasting concentration of total gastrin in normal subjects and patients with gastric ulcers and increases G-17 and G-34 in normal subjects; cimetidine increases the ratio G-17/G-34 in normal subjects and patients with gastric ulcers, but decreases G-17/G-34 in patients with duodenal ulcers. It is proposed: that measurements of total gastrin concentration should be replaced by measurements of G-17 and G-34 and that such measurements of G-17 and G-34 indicate differences in serum gastrin concentrations between normal subjects and those with peptic ulcers and between those with gastric versus duodenal ulcers. The role of altered gastrin metabolism in the pathogenesis of ulcers needs to be established.

Cimetidine↗
PubMed1984

Effect of external abdominal irradiation on the dimensions and characteristics of the barriers to passive transport in the rat intestine.

Limited information is available on the effect of irradiation on the intestinal absorption of passively transported nutrients. In this study a previously validated in vitro technique was used to measure the uptake of fatty acids (FA), fatty alcohols and cholesterol into the jejunum, ileum and colon of control rats and animals exposed to cesium-137 source irradiation applied to the abdomen. The effective resistance of the intestinal unstirred water layer was measured with lauryl alcohol, and in control rats this resistance was lowest in the ileum, highest in the colon, and of intermediate value in the jejunum. Fourteen days after 600 rads, unstirred layer resistance was reduced by half in the colon when the bulk phase was stirred at 600 rpm, and in the jejunum, ileum and colon when the bulk phase was unstirred (0 rpm). The incremental change in the free energy of transfer (integral of delta Fw----l) was measured with a homologous series of saturated medium-chain length fatty acids; 14 days after 600 and 900 rads the value of integral of delta Fw----l in the jejunum rose significantly, and occurred when light and electron microscopic changes were minimal. Fourteen days after 300 rads, the uptake of FA 6:0-12:0 was reduced, but this decline in uptake appeared to be caused by a fall in the functional surface area of the membrane rather than a change in integral of delta Fw----l. The uptake of cholesterol into the jejunum, ileum and colon was unaffected by irradiation, suggesting that cholesterol and fatty acids may have different diffusion pathways through the membrane. Thus, external abdominal irradiation influences the dimensions and characteristics of the barriers to passive transport in the intestine of the rat, and thereby modifies the uptake of some but not all passively absorbed nutrients. These functional changes are not closely associated with morphological alterations.

Animals↗
PubMed1984

Intestinal uptake of bile acids: effect of external abdominal irradiation.

Abdominal irradiation has recently been shown to influence the uptake of hexoses, amino acids, fatty acids and cholesterol into the jejunum of rats. The present studies were undertaken with a previously validated in vitro technique to determine the effect of abdominal irradiation from a cesium 137 source on the rates of uptake of six bile acids into the jejunum, ileum, and colon. In the ileum of control rats, there were marked differences in the value of the apparent Michaelis constant (Km*), maximal transport rate (Jdm), and apparent passive permeability coefficient (Pd*) between cholic (C), glycocholic (GC), taurocholic (TC), chenodeoxycholic (CDC), and glycochenodeoxycholic (GCDC), and deoxycholic (DC) acid. The Km* for each bile acid except DC was lower three and 14 days after 600 rad, whereas the Jdm for GC fell, but rose for TC, CDC, GCDC and DC and was unchanged for C. The Pd* rose for C, GC, and DC, fell for TC and CDC, but remained unchanged for GCDC 14 days after irradiation. After 600 rad the value of Pd* in the colon was increased at day 3 and 14 for CDC and GCDC, but was unchanged for GC and TC and was decreased for C. The uptake of bile acids was also affected by 300 rad and by 900 rad, but the direction and magnitude of the change was influenced by the intestinal site, the dose of irradiation, and the type of bile acid. The results show that: 1) there likely are multiple ileal carriers for bile acids; 2) abdominal irradiation has a variable effect on these carriers; 3) the passive permeability to bile acids varies with the bile acid and with the site along the intestine; and 4) abdominal irradiation is associated with a rise in the colonic permeability to only some bile acids.

Abdomen↗
PubMed1984

Comparative effects of two cimetidine regimens on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer.

The effect of 600 mg of cimetidine given twice daily on 24-hour intragastric hydrogen ion (H+) concentration was compared with that of the standard regimen of 300 mg of cimetidine given four times daily in six patients with asymptomatic duodenal ulcer. According to the double-blind, Latin-square, repeated-measures design, all subjects followed each cimetidine regimen and a placebo regimen for one week. Acid secretion studies and determinations of drug and gastrin levels in the blood were carried out on the last day of each treatment week. Although 600 mg of cimetidine BID suppressed H+ after breakfast and during the night, compared with placebo treatment (P less than 0.01), the 300-mg QID regimen suppressed H+ only after breakfast and supper (P less than 0.05). A higher percentage of pH readings greater than or equal to 3.0 were obtained with 600 mg of cimetidine BID than with 300 mg of cimetidine QID during the night (P less than 0.05); compared with percentages when placebo was taken, the percentages of pH readings greater than or equal to 3.0 were greater both overnight and during a 24-hour period only when 600 mg of cimetidine was given BID (P less than 0.01). The observed difference in intragastric H+ suppression after each regimen could not be explained by variations in serum concentrations of cimetidine or serum concentrations of gastrin. Despite similar peaks of serum cimetidine after evening doses of 300 or 600 mg of cimetidine, nocturnal intragastric acidity was lower in subjects given 600 mg BID. Further, H+ levels after lunch were similar in both cimetidine-treated groups, despite markedly higher serum cimetidine concentrations in patients receiving 600 mg BID. Pharmacokinetic studies showed equivalent elimination half-times and 24-hour areas under the curve of serum cimetidine concentration in patients on the two cimetidine regimens. Postprandial integrated gastrin responses were of similar magnitude in patients on either cimetidine regimen. There was no significant difference in mean serum gastrin concentrations during the night in placebo-treated and cimetidine-treated patients. Only a weak correlation was observed between H+ and serum gastrin concentration. Although a fluctuation of the H+:gastrin ratio occurred after each meal in all groups, the ratio was suppressed by both dosages of cimetidine. The findings suggest that a regimen of 600 mg of cimetidine BID is superior to the standard regimen of 300 mg QID in suppressing intragastric acidity in patients with asymptomatic duodenal ulcer.

Adult↗
PubMed1983

Cimetidine for recurrent ulcer after gastric surgery.

Seven of nine patients with ulcers recurring after a variety of gastric operations enjoyed loss of dyspeptic symptoms within 2 days of taking cimetidine, 1,200 mg/day for 6 weeks, and endoscopic confirmation of healing of the recurrent ulcer was established within 6 weeks of therapy. Once ulcer healing had been achieved in these seven patients, symptomatic remission persisted for over 19 months without maintenance therapy with cimetidine, and no complications suggestive of recurrent ulcerations occurred during this period in these seven patients. The eighth patient with a recurrent ulcer after vagotomy and pyloroplasty had symptoms suggestive of a gastric outlet obstruction in association with a bezoar and an elevated fasting serum gastrin concentration; cimetidine failed to heal the ulcer and a partial gastrectomy with Billroth I anastomosis was undertaken. The ninth patient lost his dyspeptic symptoms while on cimetidine, but 1 month after stopping therapy he succumbed to a massive hemorrhage; autopsy revealed a large pyloric channel ulcer. We suggest that cimetidine is helpful for the control of symptoms and the healing of recurrent ulcers after gastric surgery, but that endoscopy be repeated after an appropriate interval while such patients remain on cimetidine to assure that the disappearance of symptoms is truly associated with a lack of peptic ulceration. If the ulceration persists, we believe that cimetidine should be continued for a longer period.

Adult↗
PubMed1983

Gastrin, gastric emptying, and gastroesophageal reflux after ranitidine.

In a double-blind study comparing ranitidine to placebo in the treatment of symptomatic gastroesophageal reflux disease (GERD), we assessed gastric emptying time, gastroesophageal reflux, and gastrin response to food. Mean half-time for gastric emptying, measured using 99mTc-sulfur colloid, was 109 minutes in GERD and 102 minutes in nine healthy asymptomatic controls. This difference was not significant, but one-third of GERD had emptying times of 2 S.D.s beyond the mean for the normal controls. The patients with GERD refluxed an average of 2.3% (0.1-10%) of the isotope in 120 minutes compared with only 0.2% (0.0-0.5%) in control subjects. Reflux scans and gastric emptying times did not change with healing of esophagitis or with symptomatic improvement from ranitidine and antacids. There was no relationship between the percentage of the test dose refluxed into the esophagus and the rate of gastric emptying. The mean fasting gastrin concentration in GERD, 133 +/- 12 pg/ml, was higher than in healthy controls, 93 +/- 10 pg/ml (p less than 0.01). After stimulation with a standard meal, the integrated gastrin response (IGR) was similar in controls and GERD patients, but IGR was significantly higher after 6 weeks therapy with ranitidine. These results suggest that: 1) gastric emptying time may be prolonged in some patients with GERD, 2) basal but not food-stimulated gastrin concentrations may be abnormal in GERD, 3) reflux scans have limited use in the investigation of GERD, and 4) ranitidine therapy is associated with an increase in food-stimulated gastrin concentrations.

Adult↗
PubMed1983

Clinical algorithms for prehospital cardiac care.

Algorithms for the prehospital management of cardiac arrhythmias were developed and their use by and value to paramedics evaluated. The algorithms, in booklet form, were distributed to half of the Philadelphia paramedic platoons; paramedics in the other platoons followed a narrative protocol that reflected identical contents. An arrhythmia recognition test given 18 months after the algorithm booklets were introduced showed that paramedics who received the booklets scored significantly higher in identifying life-threatening arrhythmias (p = 0.029) than did their counterparts without the booklets. Survival data for 459 patients in ventricular fibrillation treated by paramedics were collected 1 year before and 7 months after the introduction of the algorithm booklets. The paramedics using the algorithms improved their survival rate from 11.25 to 15.1 per cent, while the survival rate for patients treated by paramedics using the narrative protocols decreased from 12.4 to 7.7 per cent. The likelihood of obtaining a ratio of survival odds of this magnitude when there is no true difference is 0.092. Time-to-death was significantly different (p = 0.04) for the two groups of patients. Thus, the use of algorithm booklets as an inexpensive educational aid for paramedics is recommended.

Allied Health Personnel↗
PubMed1983

Effect of abdominal irradiation on the kinetic parameters of intestinal uptake of glucose, galactose, leucine, and gly-leucine in the rat.

A previously validated in vitro technique was used to determine the effect of abdominal irradiation on the intestinal uptake (Jd) of glucose, galactose, leucine, and gly-leucine in the rat. Three days after 600 rads from a cesium-137 source, there was a rise in the jejunal maximal transport rate (Jdm) and the apparent Michaelis constant (Km*) but a decline in the apparent passive permeability coefficient (Pd*) for glucose. Thereafter, there was a progressive decline in Km* and Jdm but a rise in Pd* for glucose uptake. In the ileum, irradiation was associated with an increased Km* and Jdm and a decreased Pd*. Fourteen days after 600 rads, Jd of leucine into the jejunum was unchanged but Jd of leucine into the ileum was increased because of a higher Pd*. The Jd of leucine from gly-leucine was greater than from leucine alone. The Jd of 0.5 to 10 mM gly-leucine into the jejunum was increased after 600 rads, whereas the greater Jd of gly-leucine into the ileum after irradiation was most marked at 40 mM. Fourteen days after 300 rads, the Jd of glucose and galactose was increased into the ileum, whereas the Jd of leucine was decreased and the Jd of these probes into the jejunum and colon was unchanged; 14 days after 900 rads, the Jd of glucose and galactose was unchanged in each site and the Jd of leucine was reduced in the ileum but not the jejunum or colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1982

Use of percollTM in the isolation and purification of rabbit small intestinal brush border membranes.

(1) Intestinal absorption is altered under a variety of circumstances in health and disease and to determine a possible relationship between intestinal absorptive function and intestinal brush border membrane composition, we undertook the isolation and purification of rabbit jejunal and ileal brush borders, to allow further studies of their lipid composition under varied experimental conditions. (2) A modification of an established method (Schmitz, J., Preiser, H., Maestracci, D., Ghosh, B.K., Cerda, J.J. and Crane, R.K. (1973) Biochim. Biophys. Acta 323, 98-112) utilized CaCl2 aggregation and sequential centrifugation followed by purification of the brush border pellet (P2) at 27,000 X g on a PercollTM (Pharmacia) self-forming gradient. The PercollTM was removed by ultracentrifugation for 30 min at 100 000 X g, utilizing a batch rotor in the Beckman airfugeTM. (3) Pure brush border membrane vesicles were obtained and characterized by specific marker analysis and electron microscopy. Comparative marker analyses performed on P2 and final PercollTM preparations from animals showed that the purification achieved was 8-11-fold greater when compared to the original homogenates. Verification of purity was also demonstrated by the absence of DNA and very low levels of Beta-gluconridase and (Na+ + K+)-ATPase in the PercollTM preparations. (4) Comparative lipid analyses of P2 and final PercollTM preparations showed that levels of total phospholipid and free fatty acids were several-fold higher in the PercollTM preparations on a per mg protein basis. (5) A comparison of the activity of enzyme markers and the levels of total free fatty acids in P2 pellets obtained after Cacl2 and MgCl2 aggregation showed that CaCl2 aggregation gave the more consistently reproducible results. (6) Although standard procedures of membrane preparations not involving density gradient separation provide membranes of reasonable purity for the estimation of lipid components, we consider the final purification step of density gradient separation using PercollTM is essential for determining small quantitative changes which might occur in the membrane lipid composition under experimental conditions were intestinal absorptive function is altered.

Alkaline Phosphatase↗
PubMed1982

Pathophysiologic and ultrastructural basis for intestinal symptoms in Fabry's disease.

Fabry's disease is a rare, sex-linked disorder of glycolipid metabolism. We describe a patient with watery diarrhea, early satiety, and asymptomatic cholelithiasis. The jejunal aspirate demonstrated bacterial overgrowth; sigmoidoscopy showed rectal angiokeratoma corpora diffusum. The gastric emptying rate measured with 99mTc-sulfur colloid was markedly prolonged and the fasting gastrin was elevated at 276 pg/ml. The (14C)glycocholate breath test demonstrated a markedly elevated peak at 4 h, associated with an increased fecal bile acid loss of 0.82 g/day. Oral cholecystogram showed a solitary radiolucent stone in a functioning gallbladder. The bile acid pool size and lithogenic index were normal. Light microscopy of small bowel and rectal biopsy specimens revealed normal surface epithelium, but enlarged and vacuolated ganglion cells in Meissner's plexus. Electron microscopy showed laminated and amorphous osmiophilic deposits within ganglion cells of the submucosal plexus, within smooth muscle cells of the muscularis mucosae, and within endothelial cells lining arterioles, venules, and capillaries, but not in autonomic nerve fibers or enterocytes. The diarrhea and early satiety responded promptly to metoclopramide and to tetracycline. The early satiety was likely on the basis of delayed gastric emptying due to deposition of sphingolipid within ganglion cells of the autonomic nervous system; the diarrhea was likely on the basis of intestinal stasis with bacterial overgrowth and bile salt wastage.

Adult↗