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Biomedical subjects

K D Buchanan

Publications and source records attributed to K D Buchanan.

At least 145 records · Page 8Linked to original sources

Endocrine and exocrine pancreatic function in treated coeliac disease.

Pancreatic function was assessed prospectively in a group of 18 treated adult coeliac patients, most of whom were asymptomatic. The para-aminobenzoic acid (PABA) test indicated exocrine pancreatic insufficiency in three patients, all of whom had persisting gastrointestinal symptoms. Arginine, 5 g intravenously, was used to stimulate pancreatic islet cells; basal and stimulated concentrations of plasma insulin, C-terminal glucagon, N-terminal glucagon, and blood glucose did not differ from asymptomatic nondiabetic control subjects. After gluten withdrawal, coeliac patients who responded clinically had no evidence of significant pancreatic impairment, but consideration of exocrine pancreatic insufficiency is worthwhile in those patients with persisting symptoms.

4-Aminobenzoic Acid↗

Effect of oral verapamil on glibenclamide stimulated insulin secretion.

In order to study the effect of the calcium antagonist, verapamil, on glibenclamide stimulated insulin release, nine healthy fasted male volunteers were given 5 mg oral glibenclamide with either 120 mg oral verapamil or placebo in a double-blind crossover manner 1 week apart. Blood was withdrawn at intervals for drug, hormonal and glucose estimations. Concomitant administration of verapamil resulted in higher levels of glibenclamide at each time point (P less than 0.01) suggesting that verapamil interferes with glibenclamide metabolism. However, levels of plasma glucose, C-peptide, insulin and glucagon did not differ between the verapamil and placebo studies.

Adult↗

Effects of micellar oleic acid on canine jejunal blood flow and neurotensin release.

The purpose of this study was to evaluate the role of neurotensin in the local regulation of the lipid-induced jejunal hyperemia. Total blood flow and the arteriovenous hormone concentration difference were measured in isolated jejunal loops of anesthetized dogs with either saline, bile (10% in normal saline), oleic acid (40 mM in normal saline), or oleic acid and bile in the lumen. The bile-oleic acid mixture produced a sustained increase (+25 +/- 3%) in jejunal blood flow, whereas neurotensin release reached a maximum (1.14 +/- 0.34 pmol X min-1 X 100 g-1) 2 min after initiation of the response and then returned to control. Venous neurotensin concentrations also reached a maximum (51 +/- 17 pmol/l) at 2 min. There were no significant changes in either blood flow or neurotensin release in response to the other test solutions. Intra-arterial infusion of neurotensin did not significantly decrease jejunal vascular resistance (-12 +/- 3%) until venous concentrations of 478 +/- 101 pmol/l were attained. It seems unlikely, then, that neurotensin plays any role in the regulation of the lipid-induced jejunal hyperemia.

Animals↗

Gastric emptying of a solid-liquid meal and gastro-intestinal hormone responses in patients with erosive oesophagitis.

Abnormal gastric motility has been recognised recently in some patients with excessive gastro-oesophageal reflux. The cause of this motility disturbance is unknown. A dual isotope study has been used to assess gastric emptying of solid and liquid components of a test meal in 16 patients with erosive oesophagitis and in 16 control subjects. The release of insulin, gastrin, pancreatic polypeptide, gastric inhibitory polypeptide and neurotensin in response to the test meal was monitored in all subjects. A significant delay in both solid and liquid emptying was observed in patients with erosive oesophagitis. However, they demonstrated no alteration in the pattern of hormone release in response to the test meal.

Adult↗

Meal-stimulated neurotensin immunoreactivity in plasma following gastric surgery: characterisation with two region-specific antisera.

Plasma neurotensin (NT) response to a simple fatty meal, administered via an indwelling naso-gastric tube, has been assessed in two groups of subjects following gastric surgery without resection, and in healthy controls. Two region-specific NT antisera were employed in the radioimmunoassay (RIA) of plasma samples. The first, NT3, recognises only NT 1-13 in plasma extracts, while the second, GNT 21, recognises NT 1-13, NT 1-11 and NT 1-8 equally. In addition, plasma extracts were subjected to reverse-phase high performance liquid chromatography, fractions from which were subjected to each region-specific RIA. There was no significant response to the test meal in the healthy controls. However, both groups of post-gastric surgery subjects, who had undergone either vagotomy and pyloroplasty (V & P) or vagotomy and gastrojejunostomy (V & GJ), displayed significant increases in both intact and N-terminal plasma NT immunoreactivity (IR). The integrated responses of the V & P and V & GJ groups were also significantly higher than the control response but did not differ significantly from one another. The proportion of intact NT to total N-terminal NT-IR in each group was not significantly different.

Adult↗

Circulating gastrointestinal hormones in patients with flatulent dyspepsia, with and without gallbladder disease.

Fasting and post-prandial circulating levels of insulin, gastrin, gastric inhibitory polypeptide, pancreatic polypeptide and neurotensin were measured in patients with flatulent dyspepsia, with and without gallbladder disease and post-cholecystectomy. Levels were also measured in non-dyspeptic patients with gallbladder disease and normal controls. There were no consistent significant differences from controls for fasting and post-prandial responses in patients with a history of dyspepsia or those who experienced dyspepsia at the time of the test. In patients with gallbladder disease, with and without dyspepsia, there was a reduced neurotensin response compared to normal controls. It is concluded that circulating levels of these hormones are not related to symptoms of flatulent dyspepsia.

Dyspepsia↗

Natural history of diabetes presenting age 40-69 years: a prospective study of the influence of intensive dietary therapy.

Two hundred and twenty-three newly-diagnosed symptomatic diabetic patients with onset age 40-69 years enrolled in a prospective study of intensive dietary management of diabetes were observed for a period of six years and the data obtained is analysed. The variables studied were weight and fasting levels of plasma glucose and insulin, and of serum total cholesterol and triglyceride. These tests were monitored throughout the study and in addition the oral glucose tolerance test was analysed at entry to the study, after six months intensive dietary management and again after 72 months. Blood pressure, electrocardiogram and the presence of posterior tibial artery pulsation were recorded at entry to the study and at 36 months and 72 months. Approximately 80 per cent of the patients were managed solely by dietary restriction for the entire six years, but 25 patients received oral hypoglycaemic drugs and 26 required insulin treatment. Weight, and fasting glucose and triglyceride values fell in the first few months of intensive dietary management. Analysis of possible risk factors in survivors and patients dead at six years showed no significant differences, apart from a higher mean age at diagnosis in those who died. During the six years of intensive dietary management the mortality from all causes in these diabetic patients was no greater than that for the general population of Northern Ireland.

Adult↗

Gastrointestinal hormones in alcoholic patients with and without liver disease.

To assess the effects of both alcoholism and liver disease on gastroentero-pancreatic hormones, fasting and post-prandial concentrations were analysed in the following four groups: (1) Alcoholic subjects with liver disease; (2) Alcoholic subjects without liver disease; (3) Control subjects with liver disease; (4) Control subjects without liver disease.Liver disease was associated with increased fasting serum glucose, plasma insulin, pancreatic polypeptide, gastrin and vasoactive intestinal polypeptide. Alcoholism in the absence of liver disease did not influence either the fasting or post-prandial concentrations of serum glucose, plasma gastrin, insulin, pancreatic polypeptide, gastric inhibitory polypeptide, N- and C-terminal glucagon or vasoactive intestinal polypeptide. Alcoholism with liver disease depressed plasma gastric inhibitory polypeptide concentrations. The results suggest that the abnormalities in gastroenteropancreatic hormone in alcoholics are likely to be related to liver disease which is often concurrent.

Adult↗

Characterization of immunoreactive forms of pancreatic polypeptide in islet cell tumors using antisera with different regional specificities.

Tumor tissue from a heterogeneous group of patients with clinically and histologically diagnosed islet cell tumors has been assessed for pancreatic polypeptide (PP) content using radioimmunoassay. Immunoreactive forms of PP, obtained by gel filtration of tissue extracts, were detected using antisera with different regional specificities. Normal pancreatic tissue contained one form of PP coeluting with human PP whereas, tumor tissue from patients with insulinoma, Zollinger-Ellison, and WDHA (watery diarrhea hypokalemic achlorhydric) syndromes contained, in addition, higher molecular weight forms of immunoreactive PP. Furthermore, a lower molecular weight form was detected in tumor tissue from a Zollinger-Ellison syndrome patient. The high molecular weight forms of immunoreactive PP were not recognized using a C-terminal-specific antiserum, whereas the smaller form was only detected using this antiserum. The variation in cross-reactivity observed with two antisera in this study emphasizes the limitations of using a single antiserum to detect molecular forms of peptide hormones, particularly those in islet cell tumors.

Adenoma, Islet Cell↗

Trace elements and alcohol.

In our study alcoholic patients with and without cirrhosis have a decreased serum zinc. They also have increased serum copper and iron with an increase in the serum ferritin. There is no evidence of selenium deficiency in either alcoholic group. Alcohol when given with zinc in a single dose to normal volunteers increases the serum zinc and therefore appears to increase the absorption of zinc.

Adult↗

Vincristine-induced abnormalities of gastrointestinal regulatory peptide cells of the rat. An immunocytochemical study.

The microtubule-disrupting drug vincristine is a common component of anti-cancer chemotherapeutic regimes, which produces acute constipation as a side effect. Although generally attributed to damage to the myenteric plexus, the precise mechanism of this disturbance is unknown. In addition, vincristine causes marked aberrations in the secretory response of pancreatic endocrine tissue in both man and rats. No information is available on its possible effect on regulatory peptides of the gastrointestinal tract. In this study we have produced vincristine-induced constipation in rats at a dosage comparable with that employed in the treatment of human subjects. Immunocytochemistry revealed concomitant disturbances in cells exhibiting immunoreactivity for gastrin in the antrum, for gastric inhibitory polypeptide and 5-hydroxytryptamine in the duodenum, for enteroglucagon in the colon, and for somatostatin in all three sites. These widespread effects are transient in nature with normal cell numbers and morphology being reestablished within 6 days. It is suggested that the observed effects are a direct result of microtubule disruption and that gastrointestinal regulatory peptide and amine immunoreactive cells have a rapid regeneration potential.

Animals↗

Influence of a transplantable insulinoma on the pancreatic status of insulin and pancreatic polypeptide in the rat.

The effect of endogenous hyperinsulinaemia, produced by syngeneic transplantation of rat insulinoma at an extrapancreatic site, on pancreatic insulin and pancreatic polypeptide has been examined by radioimmunoassay and immunohistochemistry. Twenty days after subcutaneous transplantation, tumour-bearing rats exhibited marked hyperinsulinaemia and hypoglycaemia, with plasma pancreatic polypeptide concentrations similar to controls. Immunoreactive insulin levels in the head and tail of pancreas of tumour-bearing rats were reduced by 90-95% compared with control animals. Immunoreactive pancreatic polypeptide levels in the head of the pancreas were reduced by 70%, but the relatively low levels of peptide in the pancreatic tail were similar in tumour-bearing and control rats. Insulin and pancreatic polypeptide cells were weakly immunofluorescent in tumour-bearing rat pancreas. In conclusion, the presence of an insulinoma at an extrapancreatic site resulted in a severe depletion of endogenous insulin and pancreatic polypeptide, suggesting that there is a functional relationship between the beta and pancreatic polypeptide cell.

Adenoma, Islet Cell↗

Gastrointestinal hormones in anorexia nervosa.

A study was undertaken of fasting and post-prandial blood levels of glucose and a number of gastrointestinal hormones in patients with anorexia nervosa. After an overnight fast their blood levels of glucose, insulin and pancreatic glucagon were significantly lower than those of age-sex matched healthy volunteers. There were no significant differences in the levels of gastrin, total glucagon-like immunoreactivity, vasoactive intestinal polypeptide, pancreatic polypeptide, secretin and gastric inhibitory polypeptide. Serial blood samples were taken for up to two hours after the ingestion of a standard mixed meal (450 kcal) and these showed a significant glucose intolerance, a reduced and delayed insulin response, and a reduced release of gastric inhibitory polypeptide, as compared with the controls. There was an increased release of pancreatic polypeptide but the difference in the post-prandial hormone profile between patients and controls for gastrin did not reach statistical significance.

Adult↗

Cimetidine fails to suppress the rise in plasma secretin during fasting.

The effects of cimetidine on plasma secretin were studied during prolonged fasting in order to determine whether gastric acid output influences secretin release under these circumstances. Twenty healthy volunteers starved for 36 h and were refed with oral glucose. They were given placebo or cimetidine (1.6 g daily) for 24 h before and during the starvation period. After 12 h fasting plasma secretin like immunoreactivity (SLI) was lower (P less than 0.02) in the cimetidine group than in the placebo group. After 36 h plasma SLI was higher (P less than 0.001) in both groups compared to the 12 h value but there was no statistically significant difference between the 2 groups. Refeeding caused prompt suppression of plasma SLI in both groups. Plasma gastrin was lower (P less than 0.001) after 36 h than 12 h in the placebo group only, but there was no significant difference between the groups. Blood glycerol (P less than 0.01) and 3 hydroxybutyrate (P less than 0.02) concentrations were higher after 36 h than after 12 h fasting in both groups. During fasting, sufficient to cause mobilisation of fat and ketosis, cimetidine failed to suppress plasma SLI. This may be due to inadequate suppression of gastric acid output or to some alternative stimulus to secretin release during fasting.

3-Hydroxybutyric Acid↗

Effect of acarbose on biochemical responses and clinical symptoms in dumping syndrome.

A dose of 50 mg of acarbose was administered with a standard breakfast to 13 subjects with dumping syndrome. Significant attenuation of hyperglycaemia (p less than 0.01) was observed, and rises in plasma gastric inhibitory polypeptide, insulin and enteroglycagon were reduced (p less than 0.05). Plasma levels of neurotensin, vasoactive intestinal polypeptide and somatostatin were not affected. Dumping score was reduced, but this did not achieve statistical significance. In a longer-term study, 9 patients took acarbose, 50 mg t.i.d., for 1 month. No significant reduction in the number or severity of dumping attacks was observed, but a majority expressed a preference for the drug and some individuals experienced a marked improvement of symptoms.

Acarbose↗

The effect of chronic treatment with a non-selective beta-adrenoceptor antagonist on the enteroinsular axis and intermediary metabolites.

In a single-blind randomized placebo-controlled cross-over study in hypertensive patients we have examined the effects of treatment with the non-selective beta-adrenoceptor antagonist nadolol on the responses of glucose, intermediary metabolites and the hormones of the enteroinsular axis to the ingestion of a mixed meal. During treatment with nadolol the plasma insulin concentration 30 min after ingesting the meal was significantly lower than on placebo and the plasma glucose rose more slowly. Plasma concentrations of GIP tended to be higher during nadolol than placebo treatment. No significant effects of treatment with nadolol were noted on pancreatic glucagon or intermediary metabolites.

3-Hydroxybutyric Acid↗