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Biomedical subjects

R C Turner

Publications and source records attributed to R C Turner.

At least 127 records · Page 7Linked to original sources
PubMed1990

Comparative effects of quinine and quinidine on glucose metabolism in healthy volunteers.

1. To investigate the relative effects of quinine and quinidine on glucose metabolism, 11 healthy males aged 17-32 years were given three separate 1 h intravenous infusions; normal saline alone, quinine dihydrochloride 10 mg base kg-1 body weight (BW) in normal saline, and quinidine dihydrochloride 10 mg base kg-1 BW in normal saline. A constant infusion of 5 mg glucose kg-1 ideal BW min-1 was given for 1 h before and during each study. 2. Assessment of pancreatic beta cell function and tissue insulin sensitivity from plasma glucose and insulin concentrations at the end of the first hour using the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique confirmed normal glucose tolerance for each subject on each test day. 3. Plasma glucose concentrations at 1 h were similar to those at 2 h. There was no significant difference between the plasma glucose profiles during the three infusion regimes (P greater than 0.05). Plasma insulin rose significantly during the second hour (P less than 0.0001); increments after quinine (geometric mean [-1 s.d- +1 s.d.]; 47.0 [27.8-79.4] mu l-1) were significantly greater than those after quinidine (19.8 [6.1-65.2] mu l-1) and saline (7.5 [0-21.5] mu l-1; P less than 0.05). Plasma quinine concentrations at the end of the infusion (6.5 +/- 4.4 mg l-1) correlated with insulin increments during the second hour (r = 0.662, P = 0.028) and were significantly greater than those of quinidine (3.0 +/- 0.8 mg l-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Glucose metabolism in quinine-treated patients with uncomplicated falciparum malaria.

To investigate host and drug effects on glucose metabolism in acute falciparum malaria, 10 previously untreated, fasting Thai males with uncomplicated infections were given a 2-h intravenous glucose infusion (5 mg/kg ideal body weight min) with an infusion of quinine dihydrochloride (10 mg/kg body weight) during the second hour. Eight patients were restudied in convalescence. Fasting plasma glucose (mean +/- SD) and insulin (geometric mean (-SD to + SD] were higher during acute illness (5.5 +/- 1.0 mmol/l and 6.2 (5.0-7.7) mU/l) than in convalescence (4.2 +/- 0.25 mmol/l and 3.7 (2.1-6.7) mU/l; P less than 0.001 and P = 0.058 respectively). After 1 h, both plasma glucose (9.3 +/- 1.4 vs 7.5 +/- 0.8 mmol/l, P less than 0.001) and insulin (21.2 (13.8-32.5) vs 15.2 (11.2-20.8) mU/l, P = 0.089) remained higher during acute illness; mathematical model (CIGMA) assessment of these values indicated lower tissue insulin sensitivity on admission (97% (71-134] than in convalescence (139% (109-178), P less than 0.025) but normal beta-cell function on both occasions. Two-hour plasma glucose (9.5 +/- 2.0 mmol/l) and insulin (81.8 (51.5-129.9) mU/l) concentrations during acute illness were also significantly higher than in convalescence (7.2 +/- 1.2 mmol/l and 40.1 (23.5-68.4) mU/l, P less than or equal to 0.025) despite similar end-infusion free plasma quinine concentrations (P greater than 0.5). Basal plasma free fatty acid concentrations were increased in acute illness (0.68 +/- 0.24 vs 0.21 +/- 0.12 mmol/l, P less than 0.001) but fell to low levels at 2 h in both studies. These data suggest tissue insulin resistance and augmented quinine-stimulated insulin secretion in acute falciparum malaria, factors which are likely to influence the clinical situation in which malaria-associated hypoglycaemia occurs.

Acute Disease↗
PubMed1990

Chromosome 11 allele loss in sporadic insulinoma.

DNA was extracted from tissue samples of three unrelated cases of insulinoma. Chromosome 11 allele loss was investigated using several chromosome 11 specific probes which detect restriction fragment length polymorphisms. In one case, which proved informative for many of the chromosome 11 markers, allele loss was shown on both 11p and 11q. This finding is of considerable interest as the allele loss closely corresponds to that recently reported in insulinomas occurring in the familial multiple endocrine neoplasia type 1 (MEN-1) syndrome.

Adenoma, Islet Cell↗
PubMed1990

Insulin use in NIDDM. Rationale based on pathophysiology of disease.

Because basal hyperglycemia is a major feature in non-insulin-dependent diabetes mellitus, diabetes control can be monitored by the fasting blood glucose concentration. A hierarchical sequence of therapies is proposed in which the major aim is to maintain near-normal fasting blood glucose concentrations, in the expectation that this will help prevent development of long-term complications. When diet and tablet therapy are no longer effective in keeping the fasting blood glucose level less than 6 mM, a basal insulin supplement from a long-acting insulin such as ultralente can be added. When monitored by fasting blood glucose concentration, there is little risk of hypoglycemia, and the patient can continue a normal life-style without restrictions concerning exercise or the size of individual meals. A basal insulin supplement does not induce marked weight gain. The dose of insulin required can be predicted from the level of the fasting blood glucose and the degree of obesity, which provides an index of the accompanying insulin resistance. Based on current evidence, insulin therapy is equally appropriate in patients with insulin deficiency and insulin resistance, because the benefit from maintaining near-normal glucose concentrations probably outweighs a putative risk of hyperinsulinemia. In more severely affected patients, additional regular insulin to cover meals is needed. Lowering fasting blood glucose to normal with a basal insulin supplement reduces endogenous insulin production, and this may be advantageous if accompanying production of islet amyloid polypeptide and islet amyloid formation are also reduced.

Diabetes Mellitus, Type 2↗
PubMed1990

Dose-dependent increase in in vitro platelet sensitivity to adenosine-5'-diphosphate in young complication-free diabetic males.

In vitro platelet aggregation in response to a wide range of final adenosine-5'-diphosphate (ADP) concentrations was assessed in 11 young, diabetic males without detectable vascular complications and in 11 closely-matched controls. First phase aggregation was assessed using a particle collision theory model and the "sigmoid Emax" dose-response equation. Platelets from the diabetics required a significantly lower ADP concentration to attain a sticking probability of 0.2 (EC20; median [95% confidence limits]; 0.38 mumol/l ADP [0.25-0.52]) than those from the controls (0.55 mumol/l [0.28-0.67]; p = 0.016). At higher concentrations (EC50, EC80), there were no significant differences between the two groups (p greater than 0.05). Second phase aggregation, assessed from threshold for initiation of the release reaction, occurred at lower ADP concentrations in the diabetic group (2.0 mumol/l [1.2-4.4] vs 3.2 mumol/l [1.6-7.0]; p = 0.009). Consistent with the multistep nature of ADP-induced aggregation, these results indicate dose-dependent platelet function abnormalities in diabetics without vasculopathy. Enhanced reversible microaggregate formation (associated with platelet shape change) at low ADP concentrations may precede other first phase changes in early diabetes and would explain apparent inconsistencies in the results of previous studies involving similar subject groups.

Adenosine Diphosphate↗
PubMed1990

Rapid restoration of normoglycaemia using intravenous insulin boluses.

The reduction of elevated fasting plasma glucose levels to near normal by repeated intravenous bolus insulin doses, given according to a simple algorithm, has been studied in 17 Type I and 23 Type II, healthy diabetic patients. Using a formula based on the patient's plasma glucose, height and bodyweight with insulin boluses given every 30 min if the plasma glucose remained above 6 mmol/1, plasma glucose levels were reduced to less than 7.5 mmol/1 in 28 (70%) patients by 60 min at which time the mean (+/- 1 SD) plasma glucose level in the Type I diabetic patients had reduced from 18.2 +/- 4.9 to 8.9 +/- 3.5 mmol/1 and in the Type II diabetic patients from 12.3 +/- 3.1 to 5.9 +/- 1.4 mmol/1. None of the patients had symptomatic hypoglycaemia although in one Type I patient the plasma glucose level fell to 2.2 mmol/1. The rate of fall of glucose in the less insulin sensitive patients was not increased by giving more insulin. The regimen allows a reproducible and prompt glycaemic reduction in fasting diabetic patients.

Adult↗
PubMed1990

Plasma proinsulin in first-degree relatives of type 2 diabetic subjects.

Glucose intolerant relatives of Type 2 diabetic subjects have impaired insulin secretory responses to glucose but their proinsulin secretion has not been assessed. Plasma intact proinsulin was measured in 101 normoglycaemic and glucose intolerant first-degree relatives of Type 2 diabetic subjects both fasting and one hour after an infusion of glucose of 5 mg glucose.kg ideal weight.min-1. Geometric mean (+/- SD) plasma proinsulin increased from 2.4 (+2.5-1.2) and increased to 4.5 (+4.2-2.1) pmol/l at 1 hour (p less than 0.001). Linear regression revealed no relationship of fasting or achieved proinsulin with sex or obesity and a non-significant trend towards increasing fasting and achieved proinsulin with age and fasting plasma glucose. Proinsulin was assessed as a ratio to the simultaneous plasma C-peptide to estimate the relative amounts of insulin and proinsulin secreted by the beta-cells. Analysis of partial correlation coefficients, controlling for age and obesity, showed that the Achieved Proinsulin/Achieved C-peptide ratio was related to both fasting (r = 0.27, p = 0.004) and achieved plasma glucose (r = 0.25, p = 0.008). Glucose intolerant relatives (n = 37) had a small but significant increase in relative proinsulin secretion compared with normoglycaemic relatives (n = 64) (Achieved Proinsulin/Achieved C-peptide 0.07 +/- 0.05 vs 0.04 +/- 0.02 p less than 0.01). This is in accord with abnormal beta cell function being an early feature of Type 2 diabetes but does not distinguish between a primary beta-cell abnormality and a secondary effect of mild hyperglycaemia.

Adult↗
PubMed1990

Application of structural model of glucose-insulin relations to assess beta-cell function and insulin sensitivity.

A structural mathematical model of glucose-insulin relationships based on known quantitative responses of the major organs involved with glucose metabolism has been computed. Different degrees of beta-cell function and insulin sensitivity can be included, and the effect of their interaction assessed (i) in a steady state, basal homeostasis after an overnight fast and (ii) in response to a glucose infusion. By comparing a patient's basal plasma glucose and insulin (or C-peptide) concentrations with the predictions of a basal homeostatic model, the degree of impairment of beta-cell function and insulin sensitivity can be assessed. Similarly, the plasma glucose and insulin (or C-peptide) concentrations after a continuous glucose infusion can also be compared with predictions from the model to estimate beta-cell function and insulin sensitivity. These assessments of pathophysiology can be applied to data from individual patients or to patient populations.

Blood Glucose↗
PubMed1990

The effect of patient-carried reminder cards on the performance of health maintenance measures.

We designed a card that patients carried and showed to their physicians at scheduled appointments to remind them to perform six health maintenance procedures: influenza vaccination, pneumococcal vaccination, rectal examination and hemoccult test, Papanicolaou's smear, physician breast examination, and mammography. Prompt sheets were also attached to all charts to remind physicians to perform these same procedures. One hundred seventy-five patients received the card and the physician prompt sheets on their charts. Two hundred forty-eight patients received only physician's prompt sheet. The card group had significant increases in the performance of influenza vaccinations (47% vs 29%), rectal examination and hemoccult tests (59% vs 46%), Papanicolaou's smears, (30% vs 20%), and physician breast examinations (52% vs 29%). There was not a significant increase in the performance of pneumococcal vaccines (22% vs 24%) or mammography (18% vs 19%). We conclude that patient-carried health maintenance reminder cards are useful in increasing the physician performance of influenza vaccinations, rectal examinations and hemoccult tests, Papanicolaou's smears, and breast examinations.

Adult↗
PubMed1989

Bronchoalveolar lavage in the diagnosis of lipoid pneumonia.

Lipoid pneumonia (LP) is an uncommon entity with the characteristic radiographic features and histologic findings of alveoli filled with vacuolated, lipid-laden histiocytes. We questioned whether bronchoalveolar lavage (BAL) could be useful in the confirmation of LP. We examined lipid stains (oil-red O) in BAL specimens from 18 cases, representing a variety of pulmonary disease states, and compared them with an index case of confirmed LP. The index case of LP had a history of chronic intranasal use of mentholated petrolatum with subsequent x-ray findings of progressive air bronchograms. Positive histochemical confirmation (oil-red O) performed on frozen sections of transbronchial lung biopsy was obtained. Eleven of the non-LP cases had no intracellular staining of BAL macrophages with oil-red O stain, whereas the index case of LP exhibited markedly positive intracytoplasmic staining of macrophages for lipid. The remaining seven cases showed minimal to mild lipid staining with only one other case having moderate staining. This study demonstrates that BAL macrophages from patients with a variety of pulmonary states and without suspected LP do not demonstrate significant staining for intracellular lipids, in contrast with the expected strong positivity of LP. Lipid staining of BAL specimens, although not entirely specific, may be a preferred method for confirming the diagnosis of LP, thereby avoiding more invasive procedures.

Adult↗
PubMed1989

Localisation of islet amyloid peptide in lipofuscin bodies and secretory granules of human B-cells and in islets of type-2 diabetic subjects.

Islet amyloid peptide (or diabetes-associated peptide), the major component of pancreatic islet amyloid found in type-2 diabetes, has been identified by electron-microscopic immunocytochemistry in pancreatic B-cells from five non-diabetic human subjects, and in islets from five type-2 diabetic patients. The greatest density of immunoreactivity for islet amyloid peptide was found in electron-dense regions of some lysosomal or lipofuscin bodies. The peptide was also localised by quantification of immunogold in the secretory granules of B-cells, and was present in cytoplasmic lamellar bodies. Acid phosphatase activity was also demonstrated in these organelles. Immunoreactivity for insulin was found in some lysosomes. These results suggest that islet amyloid peptide is a constituent of normal pancreatic B-cells, and accumulates in lipofuscin bodies where it is presumably partially degraded. In islets from type-2 diabetic subjects, amyloid fibrils and lipofuscin bodies in B-cells showed immunoreactivity for the amyloid peptide. Abnormal processing of the peptide within B-cells could lead to the formation of islet amyloid in type-2 diabetes.

Adolescent↗
PubMed1989

Analysis of the HepG2/erythrocyte glucose transporter locus in a family with type 2 (non-insulin-dependent) diabetes and obesity.

A recent report has shown an association between a specific Xba1 restriction fragment of the human HepG2-Erythrocyte glucose transporter gene and Type 2 (non-insulin dependent) diabetes. To further examine the significance of this finding we have studied Type 2 diabetic pedigrees for linkage between the Xba1 alleles of this glucose transporter gene and diabetes. One large pedigree, in which the diabetic phenotype was associated with obesity and insulin resistance, was informative. In this family the disease did not co-segregate with the glucose transporter locus. Formal linkage analysis was performed assuming autosomal dominant inheritance with age-dependent penetrance. At putative gene frequencies of 0.01 and 0.001 the logarithm of the odds for linkage versus non-linkage at a recombination fraction of 0.001 was -1.84 and -3.32 respectively (a value of less than -2 indicates definite non-linkage). Genetic variations in the HepG2-Erythrocyte glucose transporter gene are unlikely to be responsible for the development of diabetes in this pedigree.

Adult↗
PubMed1989

Similar reduction of first- and second-phase B-cell responses at three different glucose levels in type II diabetes and the effect of gliclazide therapy.

To characterize the abnormal B-cell response to glucose in type II diabetes, five diet-treated diabetic and six weight-matched non-diabetic subjects were studied using the hyperglycemic clamp technique on three separate days at glycemic levels of 7.5, 10 and 15 mmol/L for 150 minutes with assessment of plasma insulin and C-peptide responses. To reduce possible secondary effects of hyperglycemia, diabetic subjects on a weight-maintaining diet were chosen who had only a slight elevation of the fasting plasma glucose, mean 6.0 mmol/L. They had a normal time-course of both first- and second-phase responses, but both were impaired at each glucose clamp concentration. The first-phase and second-phase C-peptide responses of the diabetic subjects were similarly reduced to mean 49% and 59% of normal, respectively, and the first- and second-phase insulin responses were also reduced to mean 39% and 44% of normal, respectively. The ratio of second- to first-phase plasma C-peptide responses were similar in the diabetic and normal subjects, median 1.6 and 1.5, respectively, as were the same ratios for the insulin responses, 1.4 and 1.1, respectively. The previously described selective reduction of the first-phase response in type II diabetes may be partly a function of the bolus intravenous glucose tests used, in which impaired glucose tolerance in the diabetics gave a greater glycemic stimulus to the second phase than in normal subjects, and partly secondary to long-term hyperglycemia. The diabetic subjects were re-studied after treatment with a sulphonylurea, gliclazide, with a normal fasting plasma glucose, mean 5.1 mmol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Hepatic glucose output in humans measured with labeled glucose to reduce negative errors.

Steele and others have suggested that minimizing changes in glucose specific activity when estimating hepatic glucose output (HGO) during glucose infusions could reduce non-steady-state errors. This approach was assessed in nondiabetic and type II diabetic subjects during constant low dose [27 mumol.kg ideal body wt (IBW)-1.min-1] glucose infusion followed by a 12 mmol/l hyperglycemic clamp. Eight subjects had paired tests with and without labeled infusions. Labeled infusion was used to compare HGO in 11 nondiabetic and 15 diabetic subjects. Whereas unlabeled infusions produced negative values for endogenous glucose output, labeled infusions largely eliminated this error and reduced the dependence of the Steele model on the pool fraction in the paired tests. By use of labeled infusions, 11 nondiabetic subjects suppressed HGO from 10.2 +/- 0.6 (SE) fasting to 0.8 +/- 0.9 mumol.kg IBW-1.min-1 after 90 min of glucose infusion and to -1.9 +/- 0.5 mumol.kg IBW-1.min-1 after 90 min of a 12 mmol/l glucose clamp, but 15 diabetic subjects suppressed only partially from 13.0 +/- 0.9 fasting to 5.7 +/- 1.2 at the end of the glucose infusion and 5.6 +/- 1.0 mumol.kg IBW-1.min-1 in the clamp (P = 0.02, 0.002, and less than 0.001, respectively).

Diabetes Mellitus↗
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↗