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Biomedical subjects

E M Kohner

Publications and source records attributed to E M Kohner.

At least 109 records · Page 6Linked to original sources

Tropical pancreatic diabetes in South India: heterogeneity in clinical and biochemical profile.

Clinical and biochemical studies were carried out in 33 patients with diabetes secondary to chronic calcific, non-alcoholic pancreatitis (tropical pancreatic diabetes) and in 35 Type 2 (non-insulin-dependent) diabetic patients and 35 non-diabetic subjects. Despite lower body mass indices, only 25% of patients with tropical pancreatic diabetes had clinical evidence of malnutrition. There was no history of cassava ingestion. Mean serum cholesterol concentration was significantly lower in the tropical pancreatic diabetic patients (p less than 0.01) in comparison with the Type 2 diabetic patients or non-diabetic subjects, due to a significantly decreased concentration of LDL cholesterol (p less than 0.01) and VLDL cholesterol (p less than 0.05). Basal and post-glucose stimulated concentrations of serum C-peptide were highest in those pancreatic diabetic patients (n = 11) who responded to oral hypoglycaemic drugs, intermediate in the majority (n = 17), who were insulin dependent and ketosis resistant and negligible in a small sub-group (n = 5) who were ketosis prone. The occurrence of microangiopathy in pancreatic diabetic patients was common and similar to that in Type 2 diabetic patients. Thus, tropical pancreatic diabetes in South India appears to be heterogeneous with respect to level of nutrition, severity of glucose intolerance, B-cell function, response to therapy and the occurrence of microvascular complications.

C-Peptide↗

Retinal vascular autoregulation in conditions of hyperoxia and hypoxia using the blue field entoptic phenomenon.

Autoregulation of retinal blood flow was studied in seven normal volunteers. The stimuli to autoregulation used were hyperoxia and hypoxia under controlled conditions of isocapnia. Macular blood flow was measured using the blue field entoptic phenomenon, and retinal artery and vein diameters were measured using a computerized digitising system. Results under conditions of isocapnic hypoxia showed a 38% average increase in blood flow and an increase in diameter of 8.2% and 7.4% in retinal arteries and veins, respectively. In hyperoxia, blood flow fell by an average of 36% and retinal artery and vein diameter decreased by 5.6% and 10%, respectively.

Adult↗

Photocoagulation for peripheral neovascularisation in diabetes.

A study of 90 eyes in 72 diabetic patients with peripheral retinal neovascularisation treated by photocoagulation indicated that the subsequent development of further peripheral or disc new vessels is infrequent if panretinal photocoagulation is the initial treatment procedure. Focal or sectorial treatment may be considered only if a small area of neovascularisation is present initially and provided regular follow-up can be guaranteed.

Adult↗

Natural history of peripheral neovascularisation in diabetic retinopathy.

A study of 62 untreated eyes of 54 diabetic patients with peripheral neovascularisation is reported. The study shows that neovascularisation rarely remains confined to one sector of the retina; 18% of eyes had developed disc new vessels within one year, 27% had a vitreous haemorrhage within five years, and 10% developed either macular traction or a retinal detachment.

Adolescent↗

Comparison of stereofundus photographs in patients with insulin-dependent diabetes during conventional insulin treatment or continuous subcutaneous insulin infusion.

Sixty-five patients with mild to moderate nonproliferative diabetic retinopathy who enrolled in a prospective controlled clinical trial had stereofundus photographs assessed for change over an 8-mo period. The entire study group showed a worsening of retinopathy with time (P less than 0.001). The worsening was greater in the pump-treated group (15/32) than in the conventionally treated group (9/33). The significance of this difference ranged from P = 0.67, if changes in mean retinopathy level for each patient were compared, to P = 0.177 if a grading system keyed to the worse eye was compared. The difference in rates of change between treatment groups was found to be related to the baseline mean retinopathy level (P = 0.031), but less significantly so if baseline retinopathy keyed to the worse eye was used as a covariate (P = 0.08). Worsening occurred more frequently in those patients starting with the lower retinopathy levels. Progression was associated with the appearance of retinal infarcts (cotton-wool spots, soft exudates) and/or intraretinal microvascular abnormalities, with the pump patients showing a significant increase in these individual retinal lesions compared with the conventionally treated patients over 8 mo (P less than 0.025).

Clinical Trials as Topic↗

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Assessment of fluorescein angiograms.

Quantitation of the earliest changes in abnormal retinal morphology using fluorescein angiography is potentially superior to retinal photography. However, the critical importance of flawless technique, limitations in the size of the field available for detailed study, and observer variability constitute major disadvantages. A protocol describing standards of photography and of injection was developed. Methodology for counting microaneurysms (Ma) was developed at a central laboratory and applied in suitable photographs obtained at 0 (baseline), 4, and 8 mo in 68 patients. Counts of "definite" or "possible" Ma were made on films projected under standard conditions by two observers known to achieve consistently reproducible results. Semiquantitative assessment of diffusibility of fluorescein reflecting capillary leakage was performed in 61 patients. Leakage was graded according to three degrees of severity permitting study of observer variation, concordance of change in pairs of eyes, and treatment effects. The average number of Ma at baseline was slightly higher in the continuous subcutaneous insulin infusion (CSII) group than in the conventional insulin treatment (CIT) group, but the difference was not statistically significant at the 0.05 level. At both 4 and 8 mo, definite Ma were more prevalent in the CSII group, and the difference was statistically significant at the 0.05 level using both parametric and nonparametric tests. In 27 CSII and 23 CIT patients having complete sets of 0, 4, and 8-mo photographs, Ma counts increased during the 0-4-mo interval. During the 4-8 mo interval, a further increase occurred in the CSII group but contrasted with a decrement observed in the CIT group, which showed no net change from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm↗

Medical conditions in patients with diabetic maculopathy.

Ninety-four patients with untreated diabetic maculopathy in at least one eye had their visual acuity and medical condition assessed and followed for 5 years. The mean patient age was 58 years (range 29 to 73 years) at the diagnosis of maculopathy, and they were predominantly non-insulin-dependent diabetics (NIDD). Thirty-two patients had maculopathy diagnosed at or within 2 years of the diagnosis of diabetes. Visual loss was severe, the mean final vision being 6/36 with 44 eyes blind. In addition to progression of the maculopathy, causes for loss of vision included complications of new vessels (vitreous haemorrhage and macular traction) often leading to complete blindness. Medical abnormalities were commoner than would be expected in a similarly aged normal population. Mean blood pressure was 163/90, 81 patients had degenerative vascular disease, 22 patients had nephropathy, and 35 had raised cholesterol levels. Twenty-six patients died during the study mainly from vascular disease and renal failure. No significant association was found between visual acuity loss and medical conditions, glucose control, type of therapy, age, diabetes duration, and mortality.

Adult↗

Quantitative changes in blood-retinal barrier function in central retinal vein occlusion.

Posterior vitreous fluorescence was measured with a fluorophotometer 60 minutes after intravenous sodium fluorescein (14 mg/kg) in 6 patients (age range 30 to 54 years) with central retinal vein occlusion (CRVO). Plasma free fluorescein was measured at frequent intervals for 60 minutes. A permeability index (PI) was estimated by dividing the area under the vitreous fluorescence scan by the area under the plasma free fluorescein curve. Initially mean PI was 24.3 (range 12.6-31.6) and 2.1 (range 1.3-31.) cm s-1 X 10(-7) in affected and unaffected eyes respectively. After 6 to 12 months, PI in affected eyes approached the values in the unaffected eyes of 5 patients with mild CRVO but remained elevated in one patient who presented with severe (ischaemic) CRVO. In each patient qualitative changes in retinal appearances paralleled quantitative changes in PI. The effect of venous outflow obstruction on the blood-retinal barrier can be quantitated by fluorophotometry.

Adult↗

Measurement of autoregulation of retinal blood flow using the blue field entoptic phenomenon.

Autoregulation of retinal blood flow was studied in seven normal volunteers. The stimuli to autoregulation used were hyperoxia and hypoxia under controlled conditions of isocapnia. Macular blood flow was measured using the blue field entoptic phenomenon and retinal artery and vein diameters were measured using a computerised digitising system. Results under conditions of isocapnic hypoxia showed a 38 per cent average increase in blood flow and an increase in diameter of 8.2 per cent and 7.4 per cent in retinal arteries and veins respectively. In hyperoxia blood flow fell by an average of 36 per cent and retinal artery and vein diameter decreased by 5.6 per cent and 10 per cent respectively.

Adult↗

Metabolism of fluorescein after intravenous administration.

The measurement of plasma unbound (free) fluorescein is important in the study of blood-ocular barrier kinetics. The authors became concerned about the quantitative significance of the presumed glucuronide metabolite of fluorescein to the measurement of plasma fluorescence in diabetic and normal subjects. Fluorescein was given intravenously (14 mg/kg) to seven normal subjects and eight diabetic subjects. Plasma samples taken during 60 min were subjected to microfiltration, from which aliquots of ultrafiltrate were incubated with beta-glucuronidase. Samples were subjected to high-performance liquid chromatography, and fluorescence activity was measured in the eluent. All subjects showed an additional fluorescence peak to that of fluorescein in plasma and ultrafiltrate 5 min after fluorescein administration and increased thereafter. This additional peak was abolished by incubation of ultrafiltrate with beta-glucuronidase and resulted in a marked increase in fluorescence due to the liberation of fluorescein from its presumed glucuronide. There were no pharmacokinetic differences between normal and diabetic subjects in plasma-free fluorescein and fluorescein glucuronide pharmacokinetics or in their respective binding to plasma proteins. The glucuronide had only 4.5% of the fluorescence of fluorescein, but because more of the glucuronide was unbound (32%) compared with fluorescein (10%) and its concentration increased while that of fluorescein decreased, it constituted an increasing proportion of the fluorescence in the ultrafiltrate. At 60 min, 80% of the fluorescein was present as glucuronide and contributed 20% of the total fluorescence in the ultrafiltrate. Fluorescein-glucuronide is a potential source of variability in studies on blood-ocular barrier kinetics.

Adult↗

Measurement of blood-retinal barrier permeability: a reproducibility study in normal eyes.

Fluorescein penetration into the posterior vitreous depends on plasma-free fluorescein concentration and blood-retinal barrier (BRB) permeability. The reproducibility of two methods of deriving BRB permeability was studied in 19 normal eyes of 14 subjects using vitreous fluorophotometry on two separate occasions. Plasma-free fluorescence was measured at intervals over 1 hr and posterior vitreous fluorescence was measured before (background scan), within 6 min (bolus) and at 60 min (measurement) after intravenous fluorescein (14 mg X kg-1). A computer algorithm subtracted background fluorescence from the measurement scan which was then corrected for signal spread by using a "spread" function derived from the bolus scan. BRB permeability coefficient and vitreous diffusion coefficients were derived by fitting a mathematical model to the plasma and corrected vitreous fluorescence data. A permeability index was also calculated by dividing the area under the vitreous fluorescence by the area under the plasma fluorescence curve. There were no significant differences in the results between right and left eyes. Mean +/- SD values on first and second occasions for all eyes were permeability coefficient: (1.91 +/- 0.94) and (2.08 +/- 0.95) X 10(-7) cm X s-1; diffusion coefficient: (1.33 +/- 0.68) and (1.19 +/- 0.54) X 10(-5) cm2 X s-1; and permeability index: (2.05 +/- 1.03) and (2.11 +/- 1.02) X 10(-7) cm X s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prevention of blindness in diabetic retinopathy.

Diabetic retinopathy, hitherto the most common cause of blindness in those between 30-64 years of age has become treatable. Both diabetic maculopathy and proliferative retinopathy can be treated effectively by photocoagulation. The treatment is most successful if given early, before visual loss becomes irreversible. Recently, vitrectomy with additional microsurgical techniques has been developed and shown to be effective in restoring vision to many patients blind from the complications of proliferative retinopathy.

Adult↗

Computer-aided digitisation of fundus photographs.

A method is described for the analysis of standard retinal colour photographs with the facility to compare accurately photographs taken serially, thus yielding information on the change in the retinal disease over a period of several years. The reproducibility of placement of a microaneurysm on the same photograph by the same observer is equivalent to +/- 6.6 microns at the retina and inter-observer variation is equivalent to +/- 7.2 micron at the retina. Overall accuracy of placement of a point is 10 micron at the retina.

Aneurysm↗

The effect of plasma glucose on the growth hormone response to human pancreatic growth hormone releasing factor in normal subjects.

Pituitary responsiveness to 44 amino acid human pancreatic growth hormone releasing factor was tested under conditions of euglycaemia and hyperglycaemia in six normal subjects. A 100 micrograms dose of growth hormone releasing factor was given at a fasting blood glucose of 5.1 +/- 0.4 mmols/l (mean +/- S.D.), and at a blood glucose level of 10.9 +/- 1.5. Under conditions of hyperglycaemia, the GH response to releasing factor was significantly depressed when compared to results obtained at fasting blood glucose (n = 6, t = 3.902, P = 0.0114). This is in keeping with the hypothesis that hyperglycaemia, mediated by the hypothalamus, causes decreased pituitary sensitivity to natural growth hormone releasing hormone.

Adult↗

Growth hormone response to hyperinsulinaemia in insulin-dependent diabetics. Comparison of patients with and without retinopathy.

Growth hormone levels were measured in glucose clamp studies on 13 insulin-dependent diabetic patients with retinopathy and 9 age, sex, and weight matched patients without retinopathy. Four non-diabetic subjects were used as controls. The glucose was kept constant at 12 +/- 0.85 mmol/l (mean +/- S.D.) in the diabetic groups, and at 6 mmol/l in the non-diabetic controls. Insulin was infused at sequential rates of 0.3, 1.0, and 10 mU/kg/min. Basal levels of growth hormone were not significantly different in those with and without retinopathy (5.7 +/- 4.9, 9.4 +/- 10.6 mU/l p = 0.21). Growth hormone levels were compared in each group during a 60 minute steady state period for each insulin infusion rate. At all 3 infusion rates, the diabetics with retinopathy produced a rise in growth hormone, while the non-diabetics did not (1.24 +/- 0.6 mU/l). The patients with retinopathy produced more growth hormone than those without at each infusion rate (12.2 +/- 11.5 vs. 2.8 +/- 5.1, p = 0.03; 10.6 +/- 11.1 vs. 1.6 +/- 1.7, p = 0.02; 19.7 +/- 20.6 vs. 4.2 +/- 4.8, p = 0.03). These data confirm that insulin alone can stimulate growth hormone secretion in insulin-dependent diabetics with retinopathy. Evidence is provided indicating that patients with retinopathy produce more growth hormone than those without.

Adult↗

Evidence for a central abnormality in the regulation of growth hormone secretion in insulin-dependent diabetes.

To assess pituitary and hypothalamic function in diabetes, 100 micrograms growth hormone releasing factor 1-44 was administered to 10 normal subjects at fasting plasma glucose (5.2 +/- 0.1 mmol/l, mean +/- S.E.M.), 10 insulin-dependent diabetics while euglycaemic (6.4 +/- 0.3 mmol/l), and 10 while hyperglycaemic (13.1 +/- 1.3 mmol/l). Six of the diabetics participated in both parts of the study. The normal subjects and euglycaemic diabetics produced similar peaks in growth hormone (118.2 +/- 37.6 vs 105.2 +/- 23.9 mU/l, p = 0.69). The peak growth hormone level was reached between 30 and 45 minutes in all the normal subjects, but varied between 15 and 75 minutes in the diabetics. While all normal subjects suppress their growth hormone response to releasing factor when hyperglycaemic, not all the diabetics did so, and the suppression did not reach statistical significance on comparison of euglycaemic and hyperglycaemic diabetics (105.2 +/- 23.9 vs 64.7 +/- 19.4 mU/l, p = 0.2). Comparison of results from those diabetics studied at both euglycaemia and hyperglycaemia again showed no significant difference (140.8 +/- 30.9 vs 90.2 +/- 27.7 mU/l, p = 0.22). These results suggest a central, possibly hypothalamic, abnormality to account for the disruption of growth hormone regulation in diabetes.

Adult↗