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Biomedical subjects

E M Kohner

Publications and source records attributed to E M Kohner.

At least 91 records · Page 5Linked to original sources

Long-term follow-up of patients who underwent yttrium-90 pituitary implantation for treatment of proliferative diabetic retinopathy.

Between 1960 and 1976 117 patients underwent pituitary implantation with yttrium-90 (90Y) for treatment of proliferative retinopathy at the Hammersmith Hospital, London. Mean age at operation was 35 +/- 11 years (mean +/- SD), and mean duration of diabetes 18.6 +/- 10.0 years. Mean insulin dosage prior to implant was 67.2 +/- 24 units, falling to 30.4 +/- 14.9 units post-implant. Thirty-two per cent of patients are still living, 60% are deceased and 8% are lost to follow-up. The 5-year survival rate was 82%. Of the causes of death, 21% died of infection, adrenal insufficiency or hypoglycaemia, 12% of renal failure, and 47% of myocardial or cerebral vascular disease. Ophthalmological follow-up was carried out on the 100 patients operated on between 1965 and 1976. The mean age of this group at implant was 35 +/- 10.5 years, and mean duration of diabetes 17.2 +/- 8.7 years. Visual acuity in the better eye at operation was 6/12 or better in 84% of patients, and this percentage remained similar at the time of the 5 and 10 year follow-up. Blindness (6/60 or worse) in both eyes was present in 12% of patients at the time of 5 and 10 year assessments. By 5 years new vessels on the disc had improved from a mean grading of 2.7 +/- 1.6 to 0.8 +/- 1.2 (p less than 0.001), and by 10 years there was no disc neovascularisation in any eye. There was a similar improvement in the grading of hard exudates, microaneurysms and haemorrhages, but there was an increase in fibrous retinitis proliferans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changes in plasma growth hormone in diabetic and nondiabetic subjects during the glucose clamp.

A group of 22 newly diagnosed noninsulin-dependent diabetic subjects and seven nondiabetic subjects underwent a glucose clamp at plasma glucose 100 mg/dL with insulin infusion rates of 1.0 and 10 mU/kg/min. During both insulin infusion rates, there was a sustained rise in plasma growth hormone (GH) above basal in 18 of the 22 diabetic subjects. Basal GH values were 2.37 +/- 0.67 ng/mL, rising above basal during the lower insulin infusion (6.1 +/- 3.3 ng/mL, P = 0.05) with a further rise at the higher insulin level (8.58 +/- 2.0 ng/mL, P less than 0.001). There was no rise in GH in any of the nondiabetic subjects. In neither group was there any rise above basal in cortisol, prolactin, glucagon, or somatostatin (SRIH). In a group of three nondiabetic subjects, a rise in GH similar to that seen in the diabetic group was induced by elevating the plasma glucose to 200 mg/dL for 60 minutes prior to the euglycemic clamp procedure. However, it is unlikely that changes in plasma glucose account totally for the changes in plasma GH described in the diabetic subjects since a rise in plasma GH was also seen in four diabetic subjects clamped at their fasting plasma glucose. We conclude that in newly diagnosed noninsulin-dependent diabetic subjects there is a rise in plasma GH during the euglycemic clamp procedure, which may be due to both the prior lowering of plasma glucose and the high plasma insulin levels.

Adult↗

Role of fluorescein glucuronide and its metabolism in vitreous fluorophotometry.

Rabbits were given fluorescein or fluorescein glucuronide intravenously. Fluorescein and fluorescein glucuronide concentrations in plasma and vitreous samples were measured by high-performance liquid chromatography. Vitreous fluorophotometry was performed using the Fluorotron Master to compare scans after administration of fluorescein and fluorescein glucuronide, and for comparison of in vivo fluorescence with in vitro high-performance liquid chromatography analysis. Fluorescein glucuronide was shown to enter the vitreous as early as 1 hr after injection. Fluorescein glucuronide was the dominant molecule in both vitreous and plasma of all rabbits at 6 hr. Because fluorescein glucuronide has a lower fluorescence than fluorescein, the fluorophotometer overestimates the vitreous concentration of fluorescein after its administration. Since fluorescein is metabolized rapidly to fluorescein glucuronide in man, entry of fluorescein glucuronide into the eye should be considered in measurements of blood-ocular barrier permeability by vitreous fluorophotometry.

Animals↗

Autoregulation of retinal blood flow in diabetic retinopathy measured by the blue-light entoptic technique.

Autoregulation of retinal blood flow was measured in 23 diabetic patients, 9 with nonproliferative retinopathy, 9 with proliferative retinopathy, and 5 with photocoagulated retinopathy. Three of the proliferative patients were studied on two occasions, at the proliferative stage and after photocoagulation. The stimuli to autoregulation used were isocapnic hyperoxia and hypoxia. Flow velocity of leukocytes in the perifoveal circulation was measured using the blue-field entoptic technique, and retinal artery and vein diameters were measured using a computerized digitizing system. Results under conditions of isocapnic hypoxia showed a mean increase in flow velocity of 41.0 +/- 33.0% (P less than 0.05) in nonproliferative retinopathy, 3.5 +/- 17.0% (not significant) in proliferative retinopathy, and 30.0 +/- 17.0% (P less than 0.05) after photocoagulation. In hyperoxia, flow velocity fell by a mean of 21.0 +/- 21.6% (P less than 0.05) in nonproliferative retinopathy, 33.0 +/- 19.9% (P less than 0.005) in proliferative retinopathy, and 21.0 +/- 26.0% (not significant) in photocoagulated retinopathy. The results are compared with a group of nondiabetic subjects reported previously.

Adult↗

Insulin resistance in maturity onset diabetes of the young.

Insulin resistance was assessed by euglycaemic clamp studies in matched groups of MODY, classical NIDDM patients and non-diabetic control subjects. The MODY patients metabolised less glucose (4.8 +/- 0.3 mg/Kg/min) than the classical NIDDM patients (7.0 +/- 0.5 mg/Kg/min) at an insulin infusion rate of 1.0 mU/Kg/min (p less than 0.05). At an insulin infusion rate 10 mU/Kg/min the differences between the MODY and the classical NIDDM patients were not significant. At both infusion rates the two diabetic groups metabolised less glucose than the control subjects. The results indicate that despite their younger age, the patients with MODY are more insulin resistant than the patients with classical NIDDM.

Adult↗

The effect of acute hyperglycemia on flow velocity in the macular capillaries.

The effect of acute hyperglycemia on retinal blood flow was measured in 12 diabetic patients (mean blood glucose, 276 mg%) on continuous subcutaneous insulin infusion and six nondiabetic controls (mean blood glucose, 198 mg%). Flow velocity measurements in macular capillaries were made using the blue field entoptic method. Retinal artery and vein diameters were measured using red-free fundus photographs. No significant change in flow velocity or retinal vessel diameter was noted in either group.

Acute Disease↗

Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiography.

Fluorescein angiography was used to study retinal microvascular perfusion in 20 patients undergoing coronary artery surgery. Colour retinal photographs and fluorescein angiograms were obtained preoperatively and at 5-14 days postoperatively. In 10 patients retinal fluorescein angiograms were also obtained intraoperatively during cardiopulmonary bypass, and all were found to have retinal microvascular occlusions after 40-160 min of extracorporeal circulation. 3 patients had in addition focal leakage of fluorescein, and 6 had foci of abnormal drainage of dye. These changes are consistent with retinal microembolism, and appeared to have resolved by the time of the postoperative study. No new pathological features appeared in the retina after surgery. Intraoperative fluorescein angiography of the retina may prove valuable for investigation of cerebrovascular microembolism in the territory of the internal carotid artery during cardiopulmonary bypass in man.

Aged↗

Measurement of blood-retinal barrier function in central retinal vein occlusion.

Vitreous fluorophotometry was used to measure blood-retinal barrier permeability to fluorescein in eight patients (mean age, 42.9 years; range, 30 to 55 years) with central retinal vein occlusion (CRVO). Permeability coefficient was derived by fitting a mathematical model to the posterior vitreous fluorescence scan and plasma-free fluorescein concentration curve at 60 minutes after intravenous fluorescein sodium (14 mg X kg-1). A permeability index (PI) was estimated by dividing the area under the vitreous fluorescence scan by the area under the plasma-free fluorescein curve. The permeability coefficient and PI were comparable and highly correlated. Initial mean permeability coefficient was 28.78 X 10(-7) cm X s-1 (range, 14.42 X 10(-7) to 41.10 X 10(-7) and 1.89 X 10(-7) cm X s-2 (range, 0.96 X 10(-7) to 2.76 X 10(-7) in eight affected and seven unaffected eyes, respectively. The permeability coefficient and PI in unaffected eyes did not differ significantly from 18 eyes of ten normal subjects. After three to 12 months, permeability coefficient and PI in affected eyes approached the values in the contralateral eyes of four patients with mild and one patient with moderate CRVO but remained elevated in the remaining patients. The permeability coefficient and PI correlated well with changes in severity of retinal appearances on color photographs and fluorescein angiograms. Vitreous fluorophotometry quantitated changes in blood-retinal barrier permeability in CRVO.

Adult↗

Serum immunoreactive insulin responses to a glucose load in Asian Indian and European type 2 (non-insulin-dependent) diabetic patients and control subjects.

The serum immunoreactive insulin response to an oral glucose load was estimated in 15 Asian Indian and 29 European non-diabetic subjects, and in 45 Asian Indian and 72 European Type 2 (non-insulin-dependent) diabetic patients. In the non-diabetic group, basal insulin values were higher in the Asian Indians than the Europeans (16.7 +/- 3.0 vs. 6.9 +/- 0.7 mU/l, p less than 0.001), and remained higher throughout the glucose tolerance test. Total insulin response was also higher in the Asian Indians (p less than 0.001), and linear regression analysis revealed basal insulin, body mass index and race to be important predictors of insulin response. Amongst the diabetic patients, basal insulin values were again higher in the Asian Indians compared with the Europeans (18.0 +/- 5.0 vs. 11.5 +/- 0.9 mU/l, p less than 0.05). Total insulin response was also greater (p less than 0.01). Linear regression analysis revealed the basal insulin value to be the only significant predictor of insulin response. The results demonstrate higher insulin levels in Asian Indians than Europeans in both normal subjects and Type 2 diabetic subjects. The insulin response to a glucose load is also greater in the Asian Indians. In the control subjects, ethnic differences contribute to this response, whereas in the diabetic patients this is a function of the elevated basal insulin values of the Asian Indians.

Adult↗

Does microaneurysm count reflect severity of early diabetic retinopathy?

In a group of 55 insulin-dependent diabetic patients with early diabetic retinopathy, microaneurysm counts from fluorescein angiograms were related to the level and severity of retinopathy derived by grading eight standard stereo color photographs as used in the Early Treatment of Retinopathy Study (ETDRS). All patients were studied at 0, 8, and 24 months. Significant correlations were present between both "definite" and "possible" microaneurysm count and retinopathy level of the eye studied and the mean retinopathy level of the two eyes, at all three time intervals, (P less than 0.05-less than 0.001). Similarly, there were significant correlations between microaneurysm counts and severity of the following lesions: microaneurysms and haemorrhages, cotton-wool spots (P less than 0.05-less than 0.001); to a lesser degree, severity of hard exudates (P less than 0.1-less than 0.001) and intraretinal microvascular abnormalities (P not significant-less than 0.001). There was no correlation between microaneurysm count and venous abnormalities (as at no time were there more than 11 eyes with any venous abnormality). We conclude that microaneurysm counts from fluorescein angiograms accurately reflect the severity of important signs in early diabetic retinopathy.

Adolescent↗

Regional cerebral glucose transport in insulin-dependent diabetic patients studied using [11C]3-O-methyl-D-glucose and positron emission tomography.

Regional cerebral [11C]3-O-methyl-D-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 mM), and four were studied at hyperglycaemic plasma glucose levels (mean 13 mM). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 mM had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and D-glucose for the passive facilitated transport carrier system for hexoses across the blood-brain barrier (BBB). It is concluded that the number and affinity of D-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of D-glucose across the BBB.

3-O-Methylglucose↗

Measurement of retinal blood flow in diabetes by the blue-light entoptic phenomenon.

Retinal blood flow velocity was measured in 24 normal volunteers and compared with the results obtained in 101 diabetics at different stages of retinopathy. The blue-light entoptic phenomenon was used to measure retinal flow velocity. Results showed that there was a significantly higher capillary flow velocity in those patients with background retinopathy (0.74 +/- 0.32 mms/s) over the group of normals (0.54 +/- 0.19 mm/s) and those diabetics with no retinopathy (0.51 +/- 0.24 mm/s). Retinal flow velocity was reduced at the preproliferative stage of retinopathy to 0.37 +/- 0.2 mm/s. Proliferative retinopathy showed a slightly greater flow velocity (0.56 +/- 0.27 mm/s), which was reduced following photocoagulation (0.42 +/- 0.14 mm/s).

Adult↗

Retinal revascularisation in diabetic retinopathy.

The case history of a 33-year-old diabetic patient who has had diabetes for 24 years is presented. When first seen in 1975 he had bilateral proliferative retinopathy with new vessels in the retinal periphery. He had large areas of capillary non-perfusion lateral to the macula in the right eye associated with the new vessels. Nine years later, after extensive repeated photocoagulation, revascularisation of large areas previously not perfused were seen. The vessels are in the plane of the retina and do not have the appearance of new vessels.

Adult↗

Severe retinopathy and mild carbohydrate intolerance: possible role of insulin deficiency and elevated circulating growth hormone.

8 patients with severe progressive diabetic retinopathy despite continued mild carbohydrate intolerance on diet therapy alone were studied; each patient had presented initially with visual deterioration and none had experienced hyperglycaemic symptoms. By comparison with 8 carefully matched diet-treated diabetics without retinopathy, the retinopathy patients had increased circulating growth hormone levels and relative insulin deficiency. Several other factors of possible importance in the aetiology of microangiopathy, including circulating intermediary metabolites, platelet aggregation, blood viscosity, and lipids were similar in the two groups. It is possible that hypoinsulinaemia together with growth hormone excess may contribute to the development of eye disease in these patients with otherwise mild diabetes.

Adult↗

Retinopathy in tropical pancreatic diabetes.

In a study of the retinopathy profile of 40 patients with tropical pancreatic diabetes, a form of secondary diabetes seen in tropical countries, diabetic retinopathy was detected in 13 patients. Ten patients had background retinopathy and three patients had proliferative retinopathy requiring laser photocoagulation. In two patients, fibrous retinitis proliferans was present. Three patients had evidence of diabetic maculopathy. To our knowledge, this is the first report of severe and sight-threatening retinopathy occurring with secondary diabetes. Retinopathy in these forms of diabetes has hitherto been considered to be rare or, if present, only of a mild background type.

Adult↗