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Biomedical subjects

G Sladen

Publications and source records attributed to G Sladen.

7 recordsLinked to original sources
PubMed1999

A trial of a test-and-treat strategy for Helicobacter pylori positive dyspeptic patients in general practice.

Computer models of different strategies for the management of dyspepsia in primary care indicate that a 'test-and-treat' approach is likely to be associated with the lowest costs and acceptable clinical outcomes. We present information on computer modelling studies and report the findings of a randomised trial comparing a Helicobacter pylori test-and-treat strategy with referral to direct access endoscopy in the management of dyspepsia in general practice. We compared costs and clinical outcomes in patients managed for one year in study (test-and-treat) and control (endoscopy) practices in south London. Patients aged less than 45 years presenting with persistent dyspepsia without alarm symptoms (141 study patients, 91 control patients) were studied. In the one-year follow-up period there were 17 endoscopies in the study group: all the control patients underwent initial endoscopy and five further endoscopies were performed. None revealed peptic ulcer or cancer. Forty-three (30%) of the study patients compared with 16 (17%) of the controls were referred to hospital clinics (p < 0.025). The cost of management per patient for one year in the study group was 205.67 Pounds, compared with 404.31 Pounds in the control group (p < 0.0001). Clinical outcomes in both groups at one year were comparable. An H. pylori test-and-treat strategy for dyspeptic patients aged less than 45, employing office-based serology testing, appears to be associated with substantially lower costs than initial endoscopy and with similar clinical outcomes.

Adult↗
PubMed1987

In vivo insulin antagonism but evanescent in vitro tissue effect in rats with growth hormone-secreting tumors.

Rats bearing mammosomatotropic tumors have raised insulin but lowered glucose concentrations. To determine if growth hormone (GH) secreted by these tumors causes insulin antagonism, pancreatic suppression tests utilizing infusions (per kg per min) of glucose (8 mg), insulin (200 ng) and somatostatin (1.4 micrograms) for 130 min were performed. Although the steady state plasma glucose and insulin levels (mean of 90, 100, 110, 120 and 130 min samples) were similar in 8 control and 13 tumor-bearing rats, the decrease from the already depressed basal glucose concentration (mmoles/l +/- SE) in the tumor animals was less than in the controls (0.90 +/- 0.30 vs. 2.56 +/- 0.040, p less than 0.005). Since the interpretation of these results was not entirely clear, glucose and insulin-glucose tolerance tests were performed. The glucose disappearance rates (%/min +/- SE) in the glucose tolerance test were lower in 17 tumor rats (2.00 +/- 0.13) compared to 17 control animals (2.51 +/- 0.22). This difference just missed statistical significance (t = 2.00, value of 2.04 necessary for p = 0.05). The decrease occurred in the presence of increased insulin (nmoles/l X 16 min) levels (4.29 +/- 0.38 vs. 2.58 +/- 0.29, p less than 0.005) suggesting insulin antagonism. The glucose disappearance rates (%/min +/- SE) in the insulin-glucose tolerance test were less in 12 tumor-bearing rats compared to 11 control animals (2.80 +/- 0.29 vs. 4.12 +/- 0.35, p less than 0.02). Thus, these GH-secreting tumors cause insulin antagonism in vivo. Freshly isolated hepatocytes from these tumor-bearing animals manifest decreased insulin binding and action (Diabetologia 25:60, 1983). In the present study, however, insulin binding and action (net glucose-C14 incorporation into glycogen) were normal after the hepatocytes were cultured for two days. This suggests that the changes induced by GH in vivo that lead to insulin antagonism are short-lived.

Animals↗
PubMed1987

Effect of glyburide on glycogen metabolism in cultured rat hepatocytes.

Sulfonylurea agents decrease hepatic glucose production and fasting glucose levels in type II diabetic patients without changing fasting insulin concentrations. This raises the possibility that these drugs may act directly on hepatic carbohydrate metabolism. Cultured rat hepatocytes were used to test this hypothesis. To ascertain whether this in vitro system was suitable to demonstrate an effect of sulfonylurea agents (eg, the well-documented insulin-potentiating action), we initially measured the effect of glyburide (2 micrograms/mL) on insulin-stimulated net glucose-14C incorporation into glycogen. Glyburide increased sensitivity to insulin (ie, shifted the dose-response curve to the left) without affecting either responsiveness or insulin binding. Thus, the ED50 was significantly lowered (8.4 v 15.2 ng/mL), whereas the percent increase (181% v 170%) over the basal level, specific tracer insulin binding (5.3% v 5.1% per mg protein), and the Scatchard plots were similar. Since an effect of sulfonylurea agents could be demonstrated in this system, and the glycogen pathways supply 75% of hepatic glucose production after an overnight fast, we next measured the direct effect of glyburide (2 micrograms/mL) on glycogen storage and breakdown. Glycogenolysis was assessed by measuring the breakdown of prelabeled glycogen (from galactose-14C) and glycogen synthesis by the incorporation of glucose-C14 into glycogen. Glyburide significantly inhibited glycogenolysis and stimulated glycogen synthesis. Furthermore, glyburide significantly stimulated glycogen synthase while glycogen phosphorylase was unaffected. In conclusion, glyburide directly inhibited glycogenolysis, stimulated glycogen synthesis and glycogen synthase, and potentiated the action of insulin on glycogen synthesis at a postbinding site in cultured rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Role of the small intestine in postvagotomy diarrhea.

The response of the small intestine of 6 normal subjects, 6 vagotomy control subjects, and 5 patients with postvagotomy diarrhea to a hyperosmolar liquid meal was investigated using small intestinal intubation. In the patients with postvagotomy diarrhea, the peak jejunal osmolality occurred earlier and was followed by a shorter small bowel transit time than in the vagotomy and normal controls. In the terminal ileum, both fasting and postprandial flow rates were higher in the group with postvagotomy diarrhea, compared with the other groups. This was associated with a high postprandial osmotic load to the colon, due in part to nutrient malabsorption. The postprandial flow of bile acids into the colon was not consistently related to diarrhea. Postvagotomy diarrhea is probably caused by rapid entry of fluid, electrolytes, and malabsorbed nutrients into the colon after meals. The rapid movement of an osmotic load through the upper jejunum, consequent upon the drainage operation, may be the critical trigger factor.

Adult↗
PubMed1978

Autonomic function tests in diabetes mellitus.

Five tests of autonomic function were evaluated in a group of twenty-five diabetics. The Valsalva ratio proved to be the most valuable single indicator of generalised autonomic dysfunction, whilst the blood pressure response to sustained handgrip, the pupillary response to a dilute solution of methacholine and the fall in blood pressure on standing, all proved to be less valuable as indices of autonomic neuropathy either when considered individually or when taken together. The cold pressor test was shown to be of no value in the assessment of patients with autonomic neuropathy. It is suggested that of those examined the Valsalva procedure is the most valuable simple outpatient test for autonomic neuropathy.

Adult↗