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Biomedical subjects

R Sutton

Publications and source records attributed to R Sutton.

At least 55 records · Page 3Linked to original sources
PubMed1989

The ATP- and tolbutamide-sensitivity of the ATP-sensitive K-channel from human pancreatic B cells.

The ATP- and sulphonylurea-sensitivity of the ATP-sensitive K-channel was measured in human pancreatic B cells. In inside-out patches, half-maximal inhibition of channel activity was produced by 10 mumol/l ATP (with 2 mM Mg2+) and ATP-inhibition was partially antagonised by ADP. A significantly lower sensitivity to ATP was found in whole-cell recordings. Tolbutamide inhibited whole-cell ATP-sensitive K-currents half-maximally at 18 mumol/l; the sensitivity to tolbutamide was somewhat less in the inside-out patch. Ca-activated K-channels were unaffected by tolbutamide (10 mmol/l). These results resemble those found for rodent B cells and suggest that sulphonylureas exert their therapeutic effects in Type 2 (non-insulin dependent) diabetes by inhibition of the ATP-sensitive K-channel.

Adenosine Triphosphate↗
PubMed1989

Functional assessment of colonic interposition with 99Tcm-labeled milk.

A prospective study was performed to evaluate the use of radionuclide imaging in the assessment of patients who have undergone esophageal reconstruction. Dynamic radionuclide imaging was performed on ten patients aged 11 months to 11 years who had undergone colon interposition via the normal esophageal route for esophageal atresia. Patients were considered clinically unsatisfactory if at the time of imaging feeding was troubled, or if weight gain had fallen to below the third centile before operation and remained below after operation. Each patient underwent erect imaging with a small milk feed labeled with 10 to 20 MBq (250 to 500 muCi) 99Tcm DTPA adjusted according to body surface area; supine studies were subsequently performed on five patients. All five clinically unsatisfactory patients showed conduit emptying delayed beyond 45 minutes and/or spontaneous reflux, significantly different from the clinically satisfactory patients (X2 = 6.4, P less than .02). Conduit complications were subsequently identified in three of the five clinically unsatisfactory patients. Radionuclide imaging with radiolabeled milk was found to be well tolerated, and obtained results that were clinically useful. These results suggest that dynamic radionuclide imaging can be more widely applied in the assessment of esophageal substitutes.

Alanine↗
PubMed1989

Molecular and functional characterization of amylin, a peptide associated with type 2 diabetes mellitus.

The 37-amino acid peptide called amylin is a major component of the islet amyloid deposited in the pancreases of persons with type 2 diabetes mellitus. We report the isolation of a partial cDNA clone and a phage lambda genomic clone of the coding region of the amylin gene. The DNA sequence encodes a protein sequence identical to that of amylin isolated from the amyloid found in the diabetic pancreas and shows that amylin is likely to be synthesized as a precursor peptide, now named proamylin. We have demonstrated that the amylin gene is present on chromosome 12 and that it is probably transcribed in the islets of Langerhans. The sequences of the genes for amylin and the calcitonin gene-related peptides (CGRPs) show strong similarity, especially over their 5' coding regions, where both peptides have a conserved intramolecular disulfide bridge, and also over their 3' coding regions, where the presence of a glycine codon strongly suggests that the carboxyl-terminal residue of amylin, like that of CGRP, is amidated. To examine the functional relevance of these posttranslational modifications, the biological activity of amylin synthesized with or without the disulfide bridge and/or amidation was measured. It was found that both features are necessary for full biological activity, thereby confirming the functional importance of those regions of the molecule whose sequences are conserved at both protein and genetic levels.

Amino Acid Sequence↗
PubMed1989

Pancreatic islet transplantation.

Successful transplantation of the endocrine pancreas in Type I diabetes with complete correction of the glucose metabolic abnormalities may prevent progression or development of the microangiopathic complications of the disease. This could be achieved by transplantation of the whole pancreas as a vascularized graft (the only available clinical approach at present), transplantation of isolated islets or of fetal pancreas. Since transplantation of the pancreas as a vascularized graft is associated with a significant peri-operative morbidity and requires immunosuppression to prevent rejection it is unlikely to be applicable at a relatively early stage of the disease, before microangiopathic complications become irreversible. For this reason transplantation of pancreatic islets or fetal pancreas is the only approach likely to be acceptable. Transplantation of isolated islets in the rodent does correct experimental diabetes, but recurrence of disease is seen in the spontaneous diabetes of the Biobreeding (BB) rat and the non-obese diabetic (NOD) mouse. Furthermore suppression of rejection of allogenic islets has proved difficult. In large mammals, including man, the lack of a technique to prepare isolated islets in a relatively pure form has been a further obstacle to development. Recently this problem has been overcome, allowing separation of islets in relatively large numbers with adequate purity, bringing closer the time when clinical trials might be considered. However, rejection and disease recurrence are likely to remain major obstacles, although experimental work suggests that both can be overcome.

Animals↗
PubMed1989

Physical growth velocity during conservative treatment and following subsequent surgical treatment for primary vesicoureteric reflux.

Physical growth was studied in 6 males and 16 females during 1 year of antimicrobial prophylaxis and during the 2 years following subsequent surgical treatment for severe primary vesicoureteric reflux. Surgery was performed between the ages of 2 and 8 because of either repeated breakthrough infection or persistence of grade III or IV reflux. Height and weight velocities were calculated as yearly rates and then converted into interquartile ratios (IQRs). Neither the mean centile height nor weight attained varied significantly between that at entry, after 1 year of medical treatment and at 2 years after surgery. However, the mean IQR for height velocity (+/- sem) rose significantly from -0.61 (+/- 0.45) during antimicrobial prophylaxis to 0.54 (+/- 0.25) following surgery. Similarly, the mean IQR for weight velocity rose significantly from -0.63 (+/- 0.50) during medical treatment to 0.47 (+/- 0.24) following surgery. These results suggest that surgical treatment is preferable to continued medical treatment in patients with severe primary vesicoureteric reflux who fail to respond to a trial of antimicrobial prophylaxis.

Anti-Infective Agents, Urinary↗
PubMed1989

Atrial natriuretic peptide response to rapid atrial pacing in cardiac-denervated dogs.

The effects of rapid atrial pacing on central hemodynamics, plasma hormones, and renal function were investigated in eight control and nine cardiac-denervated dogs under chloralose anesthesia. Pacing at approximately 250 ppm for 60 min caused similar increases in pulmonary wedge and right atrial pressures, systemic vascular resistance, and plasma atrial natriuretic peptide (ANP) in both groups. In control dogs, pacing produced a fall in both plasma vasopressin (AVP) and plasma renin activity (PRA) and a rise in urine flow rate associated with an increase in free water but not sodium clearance. In contrast, in cardiac-denervated dogs, both plasma AVP and PRA increased during pacing; urine flow rate did not change, and marked sodium retention occurred. This study supports the concept that the increase in urine flow during rapid atrial pacing is mediated by inhibition of renin and AVP secretion through intact cardiac nerves. The secretion of ANP is unaffected by cardiac denervation. The natriuretic and vasodilator actions of high plasma ANP concentrations during rapid atrial pacing can be inhibited either by neurally mediated cardiorenal effects in normal animals or by stimulation of the renin-angiotensin system after cardiac denervation.

Animals↗
PubMed1989

Protease activity in pancreatic islet isolation by enzymatic digestion.

Commercial Collagenase* prepared from Clostridium histolyticum is widely used in isolation of pancreatic islets. It is known that the enzyme is very impure and that there are substantial variations in effectiveness between batches. Our studies suggest that one of the impurities of importance in islet isolation is a protease that has not been very well characterized. Comparison of two batches of enzyme, one of which was known to give good yields of islets and the other poor yields, showed that they had very similar activity against collagen (measured by digestion of insoluble collagen followed by assay of soluble products with ninhydrin) but substantially different activities against azocasein as measured by optical density increase (measured by release of dye). Eighteen batches of Collagenase were examined for efficiency in islet isolation, and the yields obtained correlated with manufacturer's data of activity against casein. The data show that low caseinase activity is associated with performance in islet isolation (r = .5 after adjusting for collagenase activity). The effect of supplementing a batch of collagenase, known to be poor in isolating islets, with proteolytic enzymes was investigated. Trypsin and papain had apparently no effect, but dispase significantly increased yield. Dispase alone failed to digest pancreas. Size-exclusion high-performance liquid chromatography identified a peak associated with high protease activity and efficiency in islet isolation, having an Mr of approximately 30,000, compared to 78,000 for collagenase. The protease, like collagenase, is inhibited by EDTA. Increased Ca2+ and Mg2+ (up to 10 mM) did not affect activity. Both the protease and collagenase are stable under normal use but are inactivated by heating at 56 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Metabolic function of intraportal and intrasplenic islet autografts in cynomolgus monkeys.

Intraportal islet autografting can restore near-normal glucose homeostasis in large diabetic animals, but the long-term failure rate of such grafts remains high. To assess the effect of the site of transplantation, we compared the hormonal responses to glucose (500 mg/kg i.v.) of intraportal (IP) and intrasplenic (IS) islet autografts in the cynomolgus monkey previously rendered diabetic by total pancreatectomy. Intravenous glucose tolerance tests (IVGTTs) 6 wk after IP grafting (n = 10) demonstrated nearly normal plasma glucose changes, with qualitatively normal but quantitatively reduced insulin and glucagon responses; only two animals have maintained these responses for greater than 2 yr. IVGTTs 6 wk after IS grafting (n = 4) demonstrated more abnormal plasma glucose changes, with qualitatively normal but weak insulin responses and glucagon levels that did not fall in response to hyperglycemia; only one animal has maintained fasting normoglycemia for greater than 9 mo. These results suggest that IS transplantation confers no benefit over IP transplantation in this model.

Animals↗
PubMed1988

Pacemaker policy.

Explore the source record for details and available documents.

Bradycardia↗
PubMed1988

Rebound increase in plasma renin and vasopressin following graded infusions of atrial natriuretic peptide in man.

The effects of graded infusions of atrial natriuretic peptide (ANP) on hemodynamics, renal function, plasma renin activity (PRA) and plasma arginine vasopressin (AVP) were investigated in a two part study in 6 volunteers. Three 30-min iv infusions of either saline control or ANP at graded rates of 4, 10 and 40 pmol kg-1 min-1 were given. ANP infusions were associated with a significant increase in sodium clearance from 1.08 +/- 0.21 to 2.83 +/- 0.50 ml/min, an increase in hematocrit and a net fluid loss. Plasma AVP remained constant during ANP infusions but increased significantly afterwards when plasma ANP concentrations were falling rapidly, and this was accompanied by marked antidiuresis. PRA fell by 23% during the saline control infusions and by 50% during ANP infusions. Following cessation of ANP infusions there was a significant rebound increase in PRA. No changes were observed in blood pressure, heart rate, glomerular filtration rate or renal plasma flow. These results suggest an interaction in man between ANP and the hormones renin and AVP.

Adult↗
PubMed1988

Exocrine contamination impairs implantation of pancreatic islets transplanted beneath the kidney capsule.

The effect of exocrine contamination on islets implanted under the kidney capsule has been studied by histological examination of pure or exocrine-contamination human, monkey, or rat islets transplanted to the kidney capsule of the nude rat, monkey, or rat, respectively. Exocrine contamination resulted in an appearance suggestive of impaired islet implantation, due to tissue necrosis and subsequent fibrosis. The effect of exocrine contamination was examined quantitatively in a rat islet isograft model in which handpicked DA rat islets were transplanted under the kidney capsule of normal DA rats. The islets were either pure or deliberately recontaminated with exocrine tissue (50 or 90% contamination). Four hundred pure islets were placed under one kidney capsule and 400 islets (of similar size and from the same islet preparation) were contaminated and then placed under the contralateral kidney capsule. After 2 weeks the kidneys were removed and extracted for insulin content. The insulin content of kidneys bearing islets contaminated by either 50 or 90% exocrine tissue was significantly reduced when compared to the contralateral kidney bearing pure islets. These findings support the view that exocrine contamination of islets resulted in impaired islet implantation when transplanted to a confined site such as the kidney subcapsule.

Animals↗
PubMed1988

Decline of atrial natriuretic peptide release in dogs during sustained rapid cardiac pacing.

1. To assess the ability of the atria to maintain elevated plasma concentrations of atrial natriuretic peptide (ANP), the temporal changes in plasma ANP concentrations were studied in seven chloralose-anaesthetized dogs during 4 h of sustained rapid cardiac pacing. 2. Heart rate increased from 124 +/- 26 (mean +/- SEM) to 278 +/- 28 beats/min for the 4 h duration of rapid cardiac pacing. Mean pulmonary wedge pressure increased from 3.6 +/- 1.8 to 17.4 +/- 7.1 mmHg at 30 min (P less than 0.01) and mean right atrial pressure rose from -1.7 +/- 1.9 to 2.0 +/- 2.8 mmHg at 30 min (P less than 0.01). Both remained constant at these elevated pressures for the entire 240 min of rapid pacing. 3. Arterial ANP concentrations increased in all dogs from 87 +/- 11 to a maximum of 1263 +/- 592 pmol/l at 30 min (P less than 0.01), falling to 411 +/- 42 pmol/l after 60 min and to 146 +/- 70 pmol/l after 240 min of rapid continuous pacing (P less than 0.01 compared with 30 min). Coronary sinus ANP concentrations showed a similar pattern, rising from 241 +/- 79 to a maximum of 1837 +/- 203 pmol/l after 30 min (P less than 0.01). These peak values likewise were not sustained, falling to 962 +/- 198 pmol/l after 60 min and 297 +/- 41 pmol/l after 240 min of rapid pacing (P less than 0.01 compared with 30 min). 4. It is concluded that atria are unable to maintain the peak concentrations of ANP reached after 30 min of rapid pacing despite persistently elevated atrial pressures.

Animals↗
PubMed1988

Atrial natriuretic peptide released by rapid ventricular pacing in dogs does not cause a natriuresis.

1. The relationships between the haemodynamic, renal and endocrine changes induced by rapid ventricular pacing were studied in ten chloralose-anaesthetized dogs paced from the right ventricular apex for 60 min at 250 beats/min. 2. Pacing increased mean right atrial and mean pulmonary wedge pressure (P less than 0.05), and decreased cardiac output and mean arterial pressure (P less than 0.05). 3. Coronary sinus atrial natriuretic peptide (ANP) concentrations were approximately fourfold greater than arterial concentrations; both increased markedly during pacing (P less than 0.01). Plasma concentrations of arginine vasopressin and plasma renin activity did not change significantly. 4. Urine flow and free water clearance increased during the latter 30 min of pacing (P less than 0.05). There was no significant change in sodium clearance despite high sustained concentrations of ANP. 5. Without the availability of specific inhibitors of ANP release or action, we are unable to exclude the possibility that ANP may have prevented sodium clearance from otherwise decreasing during rapid ventricular pacing. Nevertheless, the dissociation between elevated ANP concentrations and natriuresis in this study indicates that a rise in ANP concentrations per se is not sufficient to produce a natriuresis.

Animals↗
PubMed1988

Benefits of dual chamber pacing in sick sinus syndrome.

The effects of DDD (fully automatic) and VVI (ventricular demand) pacing modes on exercise tolerance, symptom diary cards, and Holter monitoring were investigated in a randomised double blind crossover study of 16 patients who had had DDD pacemakers implanted because of frequent syncope. Eight patients presented with sick sinus syndrome and, with one exception, retrograde atrioventricular conduction and eight age and sex matched patients presented with 2:1 or complete atrioventricular block. Maximal symptom limited exercise in those with atrioventricular block was significantly higher after one month of DDD pacing than after VVI pacing. In those with sick sinus syndrome, however, maximal effort tolerance was not significantly different for the two pacing modes. In all but one patient with sick sinus syndrome sinus rhythm developed during exercise in VVI pacing. For both VVI and DDD modes maximal atrial rates were significantly lower in those with sick sinus syndrome. Palpitation and general wellbeing were significantly improved during DDD pacing in the eight patients with sick sinus syndrome. Shortness of breath was improved by DDD pacing in the eight patients with atrioventricular block but not in those with sick sinus syndrome. Holter monitoring showed that sick sinus syndrome patients remained in paced rhythm, either DDD or VVI, for most of the 24 hour period. DDD pacing was better than VVI pacing in sick sinus syndrome with retrograde atrioventricular conduction. Despite their ability to show sinus rhythm and inhibit their pacemakers on exercise patients with sick sinus syndrome are just as likely to have symptomatic benefit from DDD pacing as patients with atrioventricular block.

Adult↗
PubMed1988

Bilateral inguinal hernias: simultaneous or sequential repair?

Two hundred and forty four patients underwent either simultaneous bilateral inguinal hernia repair (n = 122) or unilateral inguinal hernia (n = 122) repair at a general hospital between January 1971 and December 1981. The two groups of patients were matched for age and sex. Both groups had a similar overall incidence of post-operative complications and in both groups the duration of post-operative stay and duration of operating time were similar. Chest infections developed in 12 patients after bilateral repair and in 3 patients after unilateral repair (P less than 0.02). All patients were assessed prospectively from 4 to 15 years after operation, when no significant difference in the number of recurrent hernias was found. Our results suggest that simultaneous bilateral inguinal herniorrhaphy is economical in terms of both operating time and duration of hospital stay, and that this economy is not bought at a cost of increased short term morbidity or long-term recurrence rate.

Adult↗