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Biomedical subjects

D R Fletcher

Publications and source records attributed to D R Fletcher.

At least 73 records · Page 4Linked to original sources
PubMed1983

Elevation of plasma gastrin and pancreatic polypeptide by electrical vagal stimulation in sheep: effects of sequential stimulation.

Gastrin and pancreatic polypeptide (PP) are released into the circulation by vagal stimulation. The individual effects of the anterior and posterior vagal trunks on the release of these peptides are unknown. Four sheep were anaesthetized and studied acutely: both vagi were dissected at the hiatus and the trunks divided. In two sheep, the distal ends of the anterior trunks were stimulated for 5 min with an 8 V, 1 ms impulse at 10 Hz. After 1 h the posterior trunks were stimulated similarly. In the other two sheep, the posterior trunk was stimulated and after 1 h the anterior vagal trunk was stimulated. The anterior and posterior trunk equally stimulated the release of both gastrin and PP in four animals. The second stimulation in these four animals resulted in an 18-fold greater integrated response of gastrin and 20-fold greater response of PP. This potentiation to the second stimulus was observed in further experiments even when the same trunk, posterior or anterior, was stimulated twice. The similarity of influence of the anterior and posterior trunks for the release of PP suggests the existence of mechanisms for vagally stimulated PP release other than branches direct from the vagal trunks.

Animals↗
PubMed1983

The effect of atropine on bombesin and gastrin releasing peptide stimulated gastrin, pancreatic polypeptide and neurotensin release in man.

The effects of 1-h infusions of bombesin and gastrin releasing peptide (GRP) at 50 pmol/kg per h and neurotensin at 100 pmol/kg per h on gastrin, pancreatic polypeptide (PP) and neurotensin release in man were determined following either saline or atropine infusion (20 micrograms/kg). Bombesin produced a rise in plasma neurotensin from 32 +/- 6 to 61 +/- 19 pmol/l and of PP from 26 +/- 8 to 36 +/- 7 pmol/l. There was a further rise of plasma PP to 50 +/- 13 pmol/l after cessation of the infusion. GRP had no significant effect on plasma neurotensin, but compared to bombesin, produced a significantly greater rise in plasma PP from 34 +/- 6 to 66 +/- 19 pmol/l during infusion. There was no post-infusional increase. At this dose, GRP was as effective as bombesin in releasing gastrin, although unlike bombesin its effect was enhanced by atropine. Neurotensin produced a rise in plasma PP from 17 +/- 4 to 38 +/- 8 pmol/l. Atropine blocked the release of PP during GRP and neurotensin infusion. Atropine had no effect on neurotensin or PP release during bombesin infusion, but did block the rise in plasma PP following bombesin infusion. We conclude that, in contrast to meal-stimulated neurotensin release, bombesin-stimulated neurotensin release is cholinergic independent. Despite structural homology, bombesin and GRP at the dose used are dissimilar in man in their actions and sensitivity to cholinergic blockade.

Adolescent↗
PubMed1983

An evaluation of a duodenal perfusion technique in human studies.

A retrospective evaluation was carried out on the standard duodenal perfusion technique in human subjects. Polyethylene glycol (PEG 4000), non-labelled or labelled with 14C, and phenol red were used as duodenal and gastric recovery markers, respectively. The evaluation was limited to the 2-h equilibration period in each study. The studies were carried out on the subjects sitting in an armchair. Multi-perforated wide-bore aspiration tubes accompanied with air ventiles were used for duodenal and gastric aspiration. High perfusion flow rates (less than or equal to 13.5 ml min-1) and a long perfusion segment (15-20 cm) were applied in the duodenum and the collection periods were kept short. An efficient gastric and duodenal aspiration was obtained in most studies with a limited gastro-duodenal and duodeno-gastric flux. On average, the fluctuations in concentration of the duodenal marker (PEG 4000) ('steady state'), expressed as a coefficient of variation (CV), were 13.1 +/- 1.0% (SEM, n = 66). Correlation analysis suggested that the 'steady state' conditions in the duodenum were improved by an efficient gastric and duodenal aspiration and a high perfusion flow rate. This was supported by an inverse correlation found between the magnitude of the gastro-duodenal flux and the marker's fluctuations, the efficiency of the gastric aspiration and the magnitude of the gastro-duodenal flux, and the efficiency of the duodenal aspiration and the magnitude of the duodeno-gastric flux. A high correlation was found between the two duodenal perfusion markers used, PEG 4000 and 14C PEG 4000.

Adult↗
PubMed1983

Organ and plasma metabolism of neurotensin in sheep.

The metabolism of neurotensin (NT) across specific vascular beds of conscious sheep and the stability of NT in plasma have been quantitated. The nature of the metabolites has been characterized with region-specific antiserums and chromatography. NT-(1-13) was infused at 200 pmol X kg-1 X h-1 for 60 min into nine ewes, and blood samples were taken via cannulas in the aorta, pulmonary artery, portal vein, hepatic vein, renal vein, and jugular vein. Two antiserums, one directed towards the N-terminal end of NT (7852) and the other directed to the C-terminal end (C28) were used for radioimmunoassay. Pancreatic polypeptide (PP) was measured also. Using the steady-state concentrations in the aorta, the metabolic clearance rate of NT measured with C28 was 25.8 +/- 3.2 ml X kg-1 X min-1, twice that with 7852. The kidney, brain, and gut were the major organs clearing NT with a greater disappearance of C-terminal than N-terminal immunoreactivity. Gel chromatography of plasma at steady state showed that the NT immunoreactivity consisted of intact NT and N-terminal fragments; no C-terminal fragments were detected. Similarly, incubation of NT in plasma in vitro resulted in the generation of stable N-terminal fragments. The kidney was also the major organ involved in the clearance of PP both in the basal state and after stimulation by NT. Because the C-terminal end of NT is biologically active, these studies suggest that either N-terminal fragments have some unknown biological role or that NT is acting as a local hormone.

Animals↗
PubMed1982

Duodenal perfusion with sodium taurocholate inhibits biliary but not pancreatic secretion in man.

1. A standard duodenal perfusion technique was used to study the effects of luminally perfused sodium taurocholate on basal and stimulated biliary and pancreatic secretion and gastrointestinal hormone release in man. 2. During duodenal perfusion with sodium taurocholate alone, both basal and caerulein/secretin-stimulated bilirubin secretion were suppressed. A successive perfusion with a mixture of the bile salt and essential amino acids in combination overcame the biliary suppression and biliary secretion rose above basal levels. A further increase in bilirubin secretion was not observed in a subsequent perfusion with essential amino acids alone in these studies. 3. No inhibitory effect on basal or caerulein/secretin-stimulated trypsin secretion was observed during the bile salt perfusion; basal trypsin secretion was in fact slightly increased during a prolonged (4 h) perfusion of the bile salt. 4. During bile salt perfusion, basal bicarbonate secretion remained unchanged but caerulein/secretin-stimulated bicarbonate secretion was slightly increased. 5. Plasma levels of pancreatic polypeptide, gastric inhibitory peptide and gastrin did not change significantly during duodenal perfusion with bile salt, but plasma levels of motilin were suppressed. 6. These results support the view that bile salts in the duodenum may regulate biliary and pancreatic secretion in man and affect plasma levels of motilin.

Adult↗
PubMed1982

Effects of duodenal perfusion with sodium taurocholate on biliary and pancreatic secretion in man.

The effects of intraluminal sodium taurocholate (STC) on biliary and pancreatic secretion were studied in man using a duodenal perfusion technique and indocyanine green (ICG) as an exogenous biliary marker. Duodenal perfusion with 15 or 30 mmol/l STC in healthy subjects markedly suppressed caerulein and secretin stimulated biliary indocyanine green (ICG) excretion in a dose responsive manner, i.e. to 40% (17-95%, +/- 2 SD, n = 5) (P less than 0.025) and 32% (26-38%, +/- 2 SD, n = 3) (P less than 0.003) of i.v. ICG infusion, respectively, with a maximum suppression to 26% and 10%, respectively. In cholecystectomized subjects (n = 5), significant changes in ICG excretion were not observed during STC (15 mmol/l) perfusion. There were no suppressive effects on pancreatic enzyme or bicarbonate secretion in any of the subjects. Our observations suggest that the bile salts STC in the duodenum in man activated a mechanism which selectively suppressed biliary excretion. This is probably due to relaxation of the gallbladder and an increase in gallbladder storage of bile.

Adult↗
PubMed1981

Therapeutic arterial embolisation of the spleen: a new cause of free intraperitoneal gas.

Case histories of two patients are presented in whom splenectomy was required for haematological disorders, but because surgery was contraindicated had therapeutic arterial embolisation of the spleen performed as an initial alternative. A significant improvement in the haematological state was achieved in both cases but one of the patients required drainage of a splenic abscess three months later. In both patients the embolisation caused the early appearances of extravascular gas in the spleen and in one patient a pneumoperitoneum also occurred. The possible aetiological factors involved in this phenomenon are discussed, together with the potential role of splenic embolisation. It is concluded that therapeutic embolisation may be a useful alternative to splenectomy in selected poor-risk patients, but carries a significant risk of inducing a splenic abscess. Intrasplenic or intraperitoneal gas may appear as an apparently benign incidental finding in the early post-embolisation period.

Adult↗
PubMed1981

Reoperations for hyperparathyroidism.

During a 20 year period, 27 patients have undergone reoperations for primary hyperparathyroidism. Hypercalcemia has been successfully controlled in 21 of the 27 patients after a total of 64 operations. Reasons for failure at initial exploration included surgical error in 12, multiple gland disease in five, unusual parathyroid gland location in five, carcinoma of the parathyroid gland in two and unknown in three. A variety of techniques were used to localize missing parathyroid glands prior to reoperation. Selective venous sampling was the most helpful but gave correct localizing information in only nine of 18 patients. Postoperatively, hypoparathyroidism was temporary in two patients and permanent in four. Recurrent laryngeal nerve injury was temporary in one patient, permanent and unilateral in two and bilateral in one patient. Reoperations for hyperparathyroidism are associated with increased morbidity and decreased success. Most importantly, failure at the initial operation is preventable in most patients.

Adolescent↗
PubMed1980

Effect of neurotensin on gastric function in man.

Neurotensin is a peptide recently discovered in the human ileum and it is released into plasma after ingestion of food. Neurotensin was infused intravenously into 12 healthy volunteers at a mean dose of 2.4 pmol/kg/min, the mean rise in plasma levels being 89 +/- 8 pmol/l. An inhibition of both gastric acid and pepsin output, and also a delay in gastric emptying of oral glucose, were observed. Neurotensin may therefore have a physiological role in modulating gastric function in man.

Adult↗
PubMed1980

Monooxygenase activity of human liver in microsomal fractions of needle biopsy specimens.

1 Methods are described for the determination of mixed function oxidase activity in microsomal fractions from percutaneous needle biopsies of human liver. 2 Activities of needle biopsy samples were comparable with those of wedge biopsy sample obtained at laparotomy from different subjects. 3 Although cytochrome P-450 content of liver from rat and man was similar, human AHH activity was only 10% of that in the rat. 4 In biopsies with preserved hepatic architecture, AHH activity and cytochrome P-450 content showed a significant positive correlation. 5 Cigarette smoking significantly increased both AHH activity and turnover number, but not cytochrome P-450 content, of biopsies with normal architecture. 6 The presence of liver disease caused a significant decrease in AHH activity and cytochrome P-450 content.

Animals↗
PubMed1980

Neurotensin infusion in man: pharmacokinetics and effect on gastrointestinal and pituitary hormones.

Synthetic neurotensin was infused into five healthy subjects at a mean dose of 2.3 pmol/kg . min for 30 min, producing a rise in plasma neurotensin concentrations, measured by RIA of 104 +/- 10 (mean +/- SEM) pmol/liter. The mean disappearance half-time on stopping the infusion was 3.8 +/- 0.2 min. The MCR was 16 +/- 1 ml/kg . min, and the apparent space of distribution was 88 +/- 6 ml/kg. During the neurotensin infusions, plasma pancreatic polypeptide rose by 145 +/- 54 pmol/liter. In contrast to results in experimental animals, there was no significant change in the pulse or blood pressure of the subjects or any significant change in blood glucose or plasma concentrations of insulin, glucagon, gastric inhibitory peptide, gastrin, motilin, or vasoactive intestinal peptide. Similarly, there was no change in plasma concentrations of TSH, GH, PRL, LH, and FSH.

Adult↗
PubMedDate not supplied

Laparoscopic cholecystectomy for complicated gallstone disease.

After performing selectively 25 laparoscopic cholecystectomies (LC) to determine the place of LC in the management of complicated gallstones, all patients presenting with gallstones were evaluated by the authors for LC. Eighty-six consecutive patients were evaluated and 84 were studied. Follow-up in every case exceeded 6 months. In three of 10 patients with acute cholecystitis, LC was not possible; each had a history longer than 48 h and all had gangrene of the gallbladder. In four patients with empyema, LC was successful, but operative cholangiography failed. Operative cholangiography was successful in 76 of the remaining 77. Of eight patients suspected of having stones in the CBD, cholangiography excluded stones in six and confirmed them in two. Cholangiography identified three other patients with totally unsuspected CBD stones. Of the five patients with CBD stones, four had them flushed to the duodenum at LC following transcystic balloon dilatation of the papilla and one had a post-op. ERCP. Of four patients with acute pancreatitis, three had LC in the same admission. LC was possible in all three patients with morbid obesity. We conclude that with experience, LC is possible for complicated gallstones. In acute cholecystitis, the probability of success is higher with earlier operative intervention. Operative cholangiography is essential. It not only identifies unsuspected CBD stones but also allows LC without ERCP in those with suspected CBD stones and with modification it allows treatment of those stones.

Acute Disease↗