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Biomedical subjects

E M Kohner

Publications and source records attributed to E M Kohner.

At least 73 records · Page 4Linked to original sources
PubMed1990

Retinal blood flow during hyperglycemia. A laser Doppler velocimetry study.

The effect of different rates of glucose infusion on the retinal circulation was studied in Gottingen breed minipigs. Seven minipigs were made hyperglycemic rapidly with an intravenous bolus injection of 50% dextrose, after which a slow dextrose infusion maintained hyperglycemia for 60 minutes. Seven minipigs were more gradually made hyperglycemic over 60 minutes with a slow intravenous infusion of 50% dextrose, and a further seven had a control infusion of urea of equal volume and osmolality over 60 minutes. Retinal blood flow (RBF) was determined from the maximum (centerline) velocity of the blood (Vmax) (determined by bidirectional laser doppler velocimetry) and the vessel diameter (D) (determined from monochromatic fundus photographs). Measurements were made in a single temporal retinal vein of each animal at baseline, during, and after each of the infusions. Plasma glucose rose from 6.1 +/- 0.5-25.3 +/- 1.5 mM (mean +/- standard error) during the bolus infusion and from 6.4 +/- 0.7-22.0 +/- 0.7 mM during the slow infusion. The bolus and the slow glucose infusions both produced large increases in RBF (63% and 62%, respectively) which were mainly attributable to increases in Vmax. The urea infusion had no significant effect on RBF, Vmax, or D. The ocular perfusion pressure rose slowly and was significantly elevated after 60 minutes of slow glucose infusion but not after the urea infusion.

Animals↗
PubMed1989

A two-year follow-up study of serum insulinlike growth factor-I in diabetics with retinopathy.

Serum insulinlike growth factor-I (IGF-I) concentration was evaluated prospectively over two years in 35 diabetic patients with severe background or preproliferative retinopathy (group 1) and 24 diabetics with mild background retinopathy matched for age, sex, and glycemic control (group 2). In addition, 12 normal subjects were also studied to assess the variability of individual serum IGF-I levels over two years. Mean serum IGF-I (+/- SD) micrograms/l at entry, one year, and two years was not significantly different in the patient groups (157 +/- 71 v 168 +/- 77; 166 +/- 78 v 159 +/- 87; 143 +/- 58 v 159 +/- 67) or when compared with the normal subjects (181 +/- 47, 188 +/- 30; 221 +/- 56). Eight patients in the preproliferative group and none in the mild background group developed proliferative retinopathy. In this subgroup developing retinal neovascularization, serum IGF-I at the time of the first appearance of retinal new vessels was significantly higher than 3 months (1 to 4 months) before the onset of proliferation (271 +/- 94 v 196 +/- 58; P = .036). Values at the time of proliferation were not, however, significantly different from the mean serum IGF-I value of all patients in group 1 and by 4 months (3 to 6 m) had returned to their previous values. Although a transient elevation of IGF-I occurs at the time of retinal new vessel formation, the rise in serum concentration is not sufficiently great or early enough to be of clinical value as a predictor of retinal neovascularization.

Adult↗
PubMed1989

Long term effectiveness of photocoagulation for diabetic maculopathy.

The long term visual results of photocoagulation for diabetic maculopathy were determined in 128 eyes of 95 patients followed over ten years. The mean age of patients was 55.5 years and mean follow up time was 7 years. Ten year data were available on forty patients (62 eyes) and of the remainder the majority had died. Of those eyes initially with good vision (defined as 6/12 or better), 60% maintained this level of acuity at ten years and of those which deteriorated 50% became blind (defined as 6/60 or worse). A significantly greater proportion of eyes with exudative maculopathy (48%) had good final vision compared to eyes with oedematous and ischaemic maculopathy (26%).

Adult↗
PubMed1989

Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF I) during continuous subcutaneous insulin infusion (CSII).

The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Diabetic retinopathy.

Involvement of the retinal microvascular vessels is an almost inevitable consequence of long standing diabetes. In the only large scale epidemiology study of a Caucasian population Klein et al. found some degree of retinopathy in up to 97% of patients with insulin dependent diabetes mellitus (IDDM) after about 15 years diabetes duration and in about 60% of insulin treated patients of older onset, presumably non-insulin dependent diabetic patients (NIDDM). The presence of retinopathy does not indicate impending visual loss in all patients. Thus in IDDM the sight threatening forms of retinopathy is most commonly associated with neovascularization; up to 60% of patients develop this lesion after 20 years diabetes duration, while in the older age group new vessels are far less common. In clinic populations the commonest cause of visual loss in NIDDM is associated with macular oedema but in the population studies of Klein, prevalence of macular oedema was almost as common in IDDM as in NIDDM patients.

Diabetes Mellitus↗
PubMed1989

Long-term follow-up of retinal blood flow in diabetes using the blue light entoptic phenomenon.

The blue light entopic phenomenon was used to measure retinal blood flow in 87 diabetics and 10 normal controls in a longitudinal study. The time interval between the initial and final studies was 21-39 months (mean 31.4). The retinal blood flow velocity did not change in the 10 subjects in the control group nor in those nine patients with no retinopathy, all but one of whom remained free of retinal lesions. In the 24 with background retinopathy the flow velocity fell significantly from 0.71 (SD 0.35) mm/s to 0.48 (0.13) mm/s (p less than 0.01). The velocity also decreased in the preproliferative group of 16 patients from 0.62 (0.39) mm/s to 0.41 (0.14) mm/s (p less than 0.05). The retinopathy status changed in 11 of this group. In those with proliferative retinopathy (now treated) and those treated previously there was no change in flow velocity.

Adult↗
PubMed1989

Does vitreous fluorophotometry reflect severity of early diabetic retinopathy?

To determine the relationship between vitreous fluorophotometry (VF) and severity of diabetic retinopathy (DR) 13 patients with mild to moderate background DR starting continuous subcutaneous insulin infusion were followed up serially for 12 months. They were studied by colour stereo retinal photographs, which were assessed by the Wisconsin Grading System, and by VF, which was assessed by the permeability index of the retina for fluorescein. By four months the severity of DR on colour photographs had deteriorated by at least one level in at least one eye in eight patients. In four patients the DR did not deteriorate. Assessment of anatomical abnormalities by severity of DR on colour photographs correlated well with the functional abnormalities of the blood-retinal barrier(s) assessed by VF, especially for the macular field. Comparison of permeability index data in the patients developing preproliferative or proliferative features of DR (group A) with the same data in patients who did not develop such changes (group B) indicated that group A patients had more severe DR than did group B patients at entry. Grading of colour photographs showed a similar trend but with greater overlap. Considerable overlap in fluorescein permeability remained between those subjects with no visible DR and those with microaneurysms with or without haemorrhages and small hard exudates.

Blood-Retinal Barrier↗
PubMed1989

Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy.

The response to GH releasing hormone (GHRH 1-29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 micrograms by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 micrograms/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU.l-1.h-1; 209 +/- 81 vs 121 +/- 82; P = 0.01). Mean +/- SD IGF-I levels (micrograms/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2-16) pump administration (203 +/- 62 vs 60 +/- 25; P = 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.

Adult↗
PubMed1989

Growth hormone-releasing factor-induced growth hormone secretion from perifused rat anterior pituitary cells: lack of influence of glucose concentration, and normal responses in pituitary cells from diabetic animals.

The mechanism responsible for the suppression of GH secretion in hyperglycaemia and hypoglycaemia in rats has been investigated using perifusion of anterior pituitary cells. When perifused with Krebs-Ringer bicarbonate containing normal (5 mmol/l), high (20 mmol/l) and low (1 mmol/l) concentrations of glucose, the GH responses to GH-releasing factor (GRF) were 85 +/- 5, 85.5 +/- 5.4 and 89 +/- 3.0 (S.E.M.)% respectively compared with the initial response to GRF at 5 mmol/l in each column. The mean GH response to GRF from anterior pituitary cells of normal rats was 6.58 +/- 0.88 micrograms/three pituitaries, which was not statistically different form that of cells from rats with streptozotocin-induced diabetes (5.40 +/- 0.68 micrograms/three pituitaries). It is concluded that GH suppression in diabetic rats and during hypoglycaemia is not mediated by changes in the GH response to GRF.

Animals↗
PubMed1989

Production of endothelin 1 by cultured bovine retinal endothelial cells and presence of endothelin receptors on associated pericytes.

Endothelinlike immunoreactivity was detected by radioimmunoassay in medium conditioned by cultured endothelial cells obtained from bovine retinal microvessels (9.2 +/- 6.5 pM, n = 4). Sephadex G-25 column chromatography and fast-protein liquid chromatography revealed that most of the endothelinlike immunoreactivity was eluted in an identical position to synthetic endothelin 1. Retinal capillary pericyte-conditioned medium contained 2.9 pM endothelinlike immunoreactivity. In contrast to endothelial cells, retinal pericytes were found to bind endothelin. The dissociation constant and binding capacity were 0.14 nM and 1.5 x 10(5) sites/cell (n = 3), respectively. These findings suggest that endothelin produced by the retinal endothelial cells binds to the pericytes, adding support to the suggestion that pericytes in the retina may have a musclelike function.

Animals↗
PubMed1989

Human diabetic serum does not stimulate bovine retinal endothelial cell growth in culture.

Bovine retinal microvascular endothelial cells were cultured with serum from nondiabetic controls, patients with background, preproliferative, proliferative and inactive (treated) proliferative diabetic retinopathy. Using Coomassie Blue to measure cellular protein, we found no significant increase in retinal endothelial cell growth with serum from patients with preproliferative or proliferative retinopathy.

Animals↗
PubMed1988

Retinal blood velocity in patients with leukocyte disorders.

The blue light entoptic phenomenon was used to measure retinal blood velocity in eight patients with chronic granulocytic leukemia, six patients with leukopenia, and matched control subjects. The retinal leukocyte velocity of the leukemic patients was 0.53 +/- 0.26 (mean +/- SD) mm/s, whereas that of the matched control subjects was 0.46 +/- 0.14 mm/s. There was no significant difference between these two groups (power: 96% for a difference of 0.2 mm/s and 66% for 0.1 mm/s). There was also no significant difference between the leukocyte velocities of the leukopenic patients and control subjects (0.47 +/- 0.19 mm/s and 0.55 +/- 0.14 mm/s, respectively; 89% power for a difference of 0.2 mm/s, 59% for 0.1). There was a correlation between the leukocyte count and the number of leukocytes seen in the entoptoscope. The results suggest that retinal vascular autoregulation can compensate for changes in leukocyte numbers that might have been expected to alter retinal blood flow.

Adult↗
PubMed1988

Evaluation of a non-mydriatic camera in Indian and European diabetic patients.

The value of the Canon CR3-45NM non-mydriatic fundus camera in screening for diabetic retinopathy has been assessed in two ethnic groups, namely, 45 Indian and 40 European diabetic patients. There was 72% agreement between ophthalmoscopy by an ophthalmologist and the photographic assessment, and 100% agreement on clinically important lesions requiring treatment. However, peripheral retinal lesions, seen on ophthalmoscopy but lying outside the photographic field, occurred in 4% of eyes. 6% of photographs were totally unassessable and an additional 12% were only partially assessable. The prevalence and severity of retinopathy was similar in Indian and European patients. The advantages and disadvantages of the non-mydriatic camera in screening for diabetic retinopathy are discussed.

Diabetic Retinopathy↗
PubMed1988

Failure to suppress GH secretion after 2 weeks treatment with atropine or propanthelene in diabetics with proliferative retinopathy.

Complete suppression of GH secretion may halt the development of retinal new vessels in patients with diabetic proliferative retinopathy. We have investigated the effectiveness of two cholinergic antagonists, atropine and propanthelene given orally for 2 weeks, in suppressing 24-h GH and IGF-I levels. Seven insulin-dependent diabetics (3 males, 4 females; aged 22-34 years) with active proliferative retinopathy and 6 matched non-diabetic normal subjects were studied in random order with at least 2 weeks between treatments. Suppression of GHRH-induced GH release was demonstrated in both groups of subjects. Twenty-four hour GH secretion was not, however, suppressed in either the patient group (mean area under the GH curve mU.l-1.h-1 +/- SD; baseline: 251 +/- 108.7; after atropine: 174 +/- 106.9; after propanthelene: 180 +/- 72.4; P greater than 0.05) or in the control group (baseline: 103 +/- 53.1; after atropine: 73 +/- 83.6; after propanthelene: 122 +/- 71.6; P greater than 0.05). GH release at times of hypoglycemia was not suppressed. Mean IGF-I concentration was not significantly reduced. Two subjects (one patient and one control) could not tolerate atropine for more than one week. We conclude that repeated doses of atropine and propanthelene do not achieve complete 24-h GH suppression and are associated with a high incidence of unpleasant adverse reactions.

Adult↗
PubMed1988

Quantitative magnetic resonance imaging in assessment of the blood-retinal barrier.

Application of magnetic resonance imaging (MRI) in two-dimensional quantitative assessment of blood-retinal barrier dysfunction was investigated in rabbits using a 0.1 T (4.25 MHz) resistive system. Reliable and consistent measurements of vitreous T1 were obtained repeatedly, in slices of width 5 mm and X-Y resolution of 1.2 mm. Calibration of reduction of T1 in eyes after injection of gadolinium-DTPA (Gd-DTPA) was performed, resulting in a dose-related response of relaxation rate (1/T1) to the dose of Gd-DTPA injected. Follow-up scans of injected eyes demonstrated a gradual spread of the T1 "hot-spot" as the contrast agent diffused through the vitreous. T1 rose gradually to basal levels by 72 hr. No local effect of Gd-DTPA was found by ophthalmoscopy. Xenon arc photocoagulation of rabbit retina reduced T1 from 1638 +/- 54 (n = 6, mean +/- SD) ms to 1408 +/- 118 (n = 4) msec (P less than 0.01) throughout the vitreous 5-7 hr after treatment. In treated rabbits receiving 1.0 mmol/l Gd-DTPA intravenously, T1 adjacent to lesions 90-120 min after injection was further reduced in a 63 microliter voxel to 670 +/- 50 ms (mean +/- SD, n = 5) with a minimum pixel value of 285 +/- 52 ms. It was estimated that this represented leakage into vitreous of 8.3 nmol Gd-DTPA. Plasma Gd-DTPA concentrations declined rapidly, with half-life of 20-40 min. The findings indicate that MRI is a technique with the potential for repeated quantitative three-dimensional assessment of blood-retinal barrier dysfunction.

Animals↗
PubMed1987

Reliability of a single beta-thromboglobulin measurement in a diabetic population: importance of PGE1 in anticoagulant mixture. Damad Study Group.

During the collection of samples for plasma beta-thromboglobulin (beta-TG) determination, it is well established that artificially high values can be observed due to in-vitro release. To estimate the reliability of a single beta-TG measurement, blood samples were collected simultaneously from both arms on two separate occasions in 56 diabetic patients selected for a clinical trial. From each arm, blood was taken into two tubes containing an anticoagulant mixture with (tube A) and without (tube B) PGE1. The overall mean value of B-TG in tube B was 1.14 times higher than in tube A (p less than 0.01). The markedly large between-arms variation accounted for the most part of within-subject variation in both tubes and was significantly greater in tube B than in tube A. Based on the difference between B-TG values from both arms, the number of subjects with artificially high B-TG values was significantly higher in tube B than in tube A on each occasion (overall rate: 28% and 14% respectively). Estimate of between-occasions variation showed that B-TG levels were relatively stable for each subject between two occasions in each tube. It is concluded that the use of PGE1 decreases falsely high B-TG levels, but a single measurement of B-TG does not provide a reliable estimate of the true B-TG value in vivo.

Adult↗