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Biomedical subjects

J R Lindsay

Publications and source records attributed to J R Lindsay.

At least 19 recordsLinked to original sources
PubMed2006

Meal-dependent regulation of circulating glycated insulin in type 2 diabetic subjects.

There is mounting evidence that elevated circulating concentrations of glycated insulin play a role in insulin resistance in type 2 diabetes. This study evaluated the secretion of glycated insulin in response to enteral stimulation in type 2 diabetic subjects. Following a mixed meal (450 kcal; 44 % carbohydrate; 40 % fat; 16 % protein), glycated insulin rose 10-fold to peak (60 min) at 104.5 +/- 25.0 pmol/l (p < 0.001), representing 22 % total circulating insulin. The response paralleled early rises in insulin and C-peptide, which peaked at 90 min and were more protracted. Maximum glucose concentrations were observed at 50 min. These data indicate that type 2 diabetic subjects exhibit a rapid meal-induced release of glycated insulin from readily releasable pancreatic beta-cell stores, which might contribute to impaired glucose homeostasis following enteral nutrition.

Blood Glucose↗
PubMed2005

Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes.

AIMS: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. METHODS: Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1+/-4.2 years, BMI 36.8+/-1.8 kg/m2, glucose 8.9+/-1.2 mmol/l, HbA1c 7.8+/-0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. RESULTS: Following metformin, DPP IV activity was suppressed compared with placebo (AUC0-6 h 3230+/-373 vs. 5764+/-504 nmol ml/l, respectively, P=0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. CONCLUSION: Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.

Administration, Oral↗
PubMed2004

Poor responses to a test dose of subcutaneous octreotide predict the need for adjuvant therapy to achieve 'safe' growth hormone levels.

OBJECTIVE: Somatostatin analogues are an established treatment in acromegaly. This study was designed to evaluate whether the acute serum growth hormone (GH) response to a test dose of octreotide in acromegaly predicts longer-term response to the drug at 3 years. DESIGN AND METHODS: In 23 patients, GH responses across 8 h to a subcutaneous test dose (50 microg) of octreotide were compared with GH levels after 3 years of therapy. The majority had pituitary surgery as primary therapy and at 3 years were receiving at least 600 microg octreotide daily subcutaneously or 20 mg LAR monthly intramuscularly. RESULTS: Seven had a test day GH Nadir of 5 mU/l or less of whom 4 achieved GH < 5 mU/l at 3 years. Sixteen had a test day nadir GH of 10 mU/l or less and of these 8 achieved GH < 5 mU/l at 3 years. Seven of the 23 had a GH Nadir >10 mU/l and of these 3 had achieved GH <5 mU/l at 3 years. However all of these 3 had received external pituitary irradiation within 4 years of the 3 year assessment, as compared with 3 of the <5 mU/l nadir group and 5 of the <10 mU/l nadir group. CONCLUSIONS: In patients on optimal long-term doses of octreotide for acromegaly, absence of a nadir GH <10 mU/l in the 8 h after a test dose was associated with failure to achieve GH levels associated with a normal life expectancy (5 mU/l or less) unless adjunctive external pituitary irradiation was given. As well as testing tolerability a test dose of octreotide may help in determining which patients should be offered early external pituitary irradiation or therapy with a GH receptor antagonist if surgery has failed to achieve 'safe' GH levels.

Acromegaly↗
PubMed2003

Demonstration of increased concentrations of circulating glycated insulin in human Type 2 diabetes using a novel and specific radioimmunoassay.

AIMS/HYPOTHESIS: Glycation of insulin, resulting in impaired bioactivity, has been shown within pancreatic beta cells. We have used a novel and specific radioimmunoassay to detect glycated insulin in plasma of Type 2 diabetic subjects. METHODS: Blood samples were collected from 102 Type 2 diabetic patients in three main categories: those with good glycaemic control with a HbA(1c) less than 7%, moderate glycaemic control (HbA(1c) 7-9%) and poor glycaemic control (HBA(1c) greater than 9%). We used 75 age- and sex-matched non-diabetic subjects as controls. Samples were analysed for HbA(1c), glucose and plasma concentrations of glycated insulin and insulin. RESULTS: Glycated insulin was readily detected in control and Type 2 diabetic subjects. The mean circulating concentration of glycated insulin in control subjects was 12.6+/-0.9 pmol/l ( n=75). Glycated insulin in the good, moderate and poorly controlled diabetic groups was increased 2.4-fold ( p<0.001, n=44), 2.2-fold ( p<0.001, n=41) and 1.1-fold ( n=17) corresponding to 29.8+/-5.4, 27.3+/-5.7 and 13.5+/-2.9 pmol/l, respectively. CONCLUSION/INTERPRETATION: Glycated insulin circulates at noticeably increased concentrations in Type 2 diabetic subjects.

Diabetes Mellitus, Type 2↗
PubMed2003

Effects of nateglinide on the secretion of glycated insulin and glucose tolerance in type 2 diabetes.

AIMS: Glycation of insulin has been demonstrated within pancreatic beta-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes. METHODS: Ten patients (5 M/5 F, age 57.8+/-1.9 years, HbA(1c) 7.6+/-0.5%, fasting plasma glucose 9.4+/-1.2 mmol/l, creatinine 81.6+/-4.5 microM/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min. RESULTS: Plasma glucose and glycated insulin responses were reduced by 9% (P=0.005) and 38% (P=0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% (P=0.005) and 25% (P=0.007) by nateglinide. CONCLUSIONS: Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the antihyperglycaemic action of nateglinide.

Blood Glucose↗
PubMed1980

Profound deafness. Associated sensory and neural degeneration.

The cases of deafness presented here have been selected primarily to illustrate the degree to which the acoustic ganglion has degenerated in profound or total deafness. Examples of seven types of acquired diseases of the inner ear and one type of probable congenital degeneration of uncertain cause are given. The number of surviving ganglion cells in each 5-mm section of the cochlea has been expressed as a percentage of the normal average count corresponding to that section of the organ of Corti. The state of the acoustic ganglion has been correlated with that of the organ of Corti and the peripheral axons. Attention is directed to factors other than the presence of ganglion cells, such as disease of the labyrinthine capsule and/or labyrinthitis ossificans, that may influence the possibility of successful insertion of a cochlear implant.

Adolescent↗
PubMed1977

Inner ear degeneration in Reye's syndrome.

A 9-year-old girl developed Reye's syndrome. On admission to the hospital on the fourth day of illness, responses for verbal stimuli had been absent, but were present for painful stimuli. Coma developed on the fourth day and was present until death ten days later. The fundus of both internal meatus showed vascular congestion of nerves with evidence of repeated hemorrhages. All structures within the endolymphatic system showed advanced degeneration, with exception of the tectorial membrane and cupulae. One ear showed vascular congestion, formation of thrombi, and free hemorrhage within the modiolus and spiral ganglion. In the other ear, congested vessels in nerves in the meatus were obstructed by swelling at the cribriform area. The degenerative changes corresponded closely to those produced experimentally in guinea pigs by interruption of arterial circulation to the inner ear.

Child↗
PubMed1976

Sensorineural deafness due to osteitis fibrosa.

A 91-year-old woman with deafness died from renal failure. Autopsy revealed osteitis fibrosa cystica generalisata, chronic myeloid leukemia, renal atrophy, and hyperplastic parathyroid glands. The temporal bones showed senile osteoporosis, osteitis fibrosa, and chronic myeloid leukemia. The inner ears showed extensive degeneration of cochlear sensorineural elements. The perilymph showed a general increased staining reaction with hematoxylin-eosin that was most evident in localized areas, where marrow spaces of osteitis fibrosa communicated directly with perilymph. It appears that the active diseased marrow exerted a toxic effect on the sensorineural elements of the cochlea by diffusion through the perilymph.

Aged↗
PubMed1976

Histopathologic features of the inner ear associated with Kearns-Sayre syndrome.

We describe the histopathologic features of the inner ear in a 19-year-old girl with bilateral total deafness associated with Kearns-Sayre syndrome. The inner ear shows advanced degree of cochleo-saccular degeneration, with almost complete absence of the organ of Corti in all turns. The spiral ganglion shows a reduction of about 60% to 70% of cells, with almost complete degeneration of nerve fibers in the bony spiral lamina. PAS-positive material was found accumulated in globules between the collapsed Reissner membrane and remains of marginal cells of the stria and in the degenerated sensory cell area of the saccular macula.

Adult↗
PubMed1976

Transfer of sulphur to the digestive tract of sheep.

The transfer of sulphate from plasma to digestive tract and from digestive tract to plasma in crossbred sheep was estimated by the use of isotope dilution techniques with Na235SO4. The passage of 35S along the digestive tract was simultaneously measured by reference to two inert radioactive markers infused intraruminally. In the first experiment, three sheep given a roughage-based diet containing 174 +/- 7 mg S/day received an intravenous infusion of Na235SO4 for 7 days before collections were made of plasma and of digesta from the rumen, abomasum and terminal ileum. Similar collections were made in the second experiment in which four sheep received intraruminal infusions of Na235SO4. From estimates of infusion rate of 35S, specific radioactivity of 35S in plasma and digesta and rate of flow of sulphur in the digestive tract the following calculations were made: The transfer of sulphate from the plasma to the rumen was calculated as 29 mg S/day. Of this only 12 mg S/day passed as organic sulphur in digesta from the stomach. As the net gain of sulphur in the stomach in this experiment was 153 mg/day, sulphate transferred from the plasma contributed only a small amount of sulphur derived from endogenous sources in the stomach. In contrast, the substantial passage of 35S into the intestinal lumen during intravenous infusion of 35SO4 suggested that 38 and 41 mg S/day of the 236 and 145 mg organic S/day flowing from the small and large intestine respectively was derived from plasma sulphate, corresponding to about 26% of the dose.

Animals↗
PubMed1976

Recurrent meningitis and labyrinthine gusher, related to congenital defects of the labyrinthine capsule and stapes footplate.

A congenital defect in the bony footplate of the stapes is now known to be a point of lowered resistance to extension of bacterial middle ear suppuration to the vestibule and thence to the meninges. Tomographic demonstration of the congenital pathologic condition of the ear permits the surgeon preoperatively to chart his surgical course. Despite antibiotic and chemotherapy, recurrent meningitis remains a serious disease as manifested by the death of two of the patients reported. The capacity for surgical correction of the congenital defect is manifested by one of our patients who has been free of meningitis for more than two years after surgery. If a congenital defect is considered in each case of recurrent meningitis, it is believed the mortality of this serious disease can be reversed.

Adult↗
PubMed1976

Paget's disease and sensori-neural deafness: temporal bone histopathology of Paget's disease.

Four cases with Paget's disease of the temporal bone are presented to illustrate the pathogenesis of the associated deafness. One case illustrates the combination of severe deafness due to bilateral otosclerosis with probably asymptomatic bilateral Paget's disease. One case with advanced Paget's disease presents features to explain early stages of sensori-neural deafness before actual cellular invasion of the inner ear. One case of profound deafness due to Paget's disease presents a different stage of cellular invasion of the inner ear by the disease on each side. One case illustrates invasion of the internal auditory meatus by Paget's disease with infiltration of the acoustic division of the nerve and profound deafness.

Adult↗