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Biomedical subjects

E M Kohner

Publications and source records attributed to E M Kohner.

At least 37 records · Page 2Linked to original sources
PubMed1996

Autoregulation in the human retinal circulation: assessment using isometric exercise, laser Doppler velocimetry, and computer-assisted image analysis.

Autoregulation of blood flow in response to changes in perfusion pressure is known to occur in a number of tissues including the human retina. Defective autoregulation may play a part in the pathophysiology of several retinal diseases. Laser Doppler velocimetry has been used to study retinal blood flow. Technically superior measurements are obtained from veins by this method but arterial measurements might provide additional information. The response of the normal human retina to an acute elevation of systemic blood pressure induced by isometric exercise was investigated in nine normal volunteers using laser Doppler velocimetry and computer-assisted image analysis. Measurements were taken from retinal veins and arteries. Autoregulation was demonstrated by an 8.4% rise in flow in response to a 34% rise in perfusion pressure (P = 0.0007) using data derived from veins and a 4.8% rise in flow in response to a 33% rise in perfusion pressure (P = 0.01) using data derived from arteries. Arteries constricted by 3.4% (P = 0.002) and veins dilated by 1.6% (P = 0.02). Red cell velocity rose in veins by 5.0% (P = 0.008) and in arteries by 12.2% (P = 0.02). The variability in velocity change derived from veins (SD 3.4%) was lower than that from arteries (SD 12.1%). A similar pattern of flow change was found in both sets of data. This makes venous measurements more useful for obtaining statistically reliable results from these techniques.

Adult↗
PubMed1996

Regional retinal blood flow and vascular autoregulation.

The temporal retina is larger than the nasal retina and contains the metabolically active fovea. The variation in the distribution of blood between the temporal and nasal retinal circulations was investigated in 15 healthy volunteers, and the autoregulatory capacity of the temporal and nasal circulations was quantitated using 60% oxygen in the inspired air. Retinal blood flow was determined from red cell velocity using laser Doppler velocimetry and retinal vessel diameter from retinal photographs using a digital image analysis system. Volume flow was lower in the nasal than the temporal circulation by 52.49% (p < 0.001). This is a consequence of both significantly smaller vessels (20.4%, p < 0.001) and slower blood velocity in the nasal circulation (24.64%, p = 0.003) compared with the temporal vessels. After breathing 60% oxygen for 10 minutes, there was significant vasoconstriction (temporal, 10.42 +/- 1.24%, p < 0.001; nasal, 7.66 +/- 1.48%, p < 0.001), slower red cell velocity (temporal, 27.10 +/- 3.92%, p < 0.001; nasal, 27.36 +/- 5.51%, p < 0.001) and a significant reduction in the volumetric flow rate (temporal, 41.16 +/- 3.64%, p < 0.001; nasal, 37.99 +/- 5.07%, p < 0.001). The reduction in the haemodynamic parameters was comparable in the temporal and nasal circulations, indicating similar autoregulatory capacity. Retinal vascular conductance was calculated from volume flow and retinal perfusion pressure. It was 53% larger in the temporal than the nasal circulations. This provides an index of the metabolic needs of the different regions of the retina.

Adult↗
PubMed1996

Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. Subretinal neovascularisation is an important cause of central visual loss, but little is known about the role of this growth factor in its pathogenesis. The aim of this study was to investigate the possible role of VEGF in the development of subretinal neovascularisation. METHODS: Undiluted vitreous samples were obtained from patients undergoing vitrectomy for removal of non-age-related subfoveal neovascular membranes (SFNM). For comparison vitreous from patients undergoing vitrectomy for idiopathic full thickness macular holes (FTMH) and proliferative diabetic retinopathy (PDR) was used. Indirect enzyme linked immunosorbent assay (ELISA), with an antibody directed against the conserved N-terminal region of human VEGF165, was used to determine vitreous levels of VEGF. The growth factor was also localised in the vitreous of patients with SFNM by western blot analysis. RESULTS: The mean (SE) VEGF concentration in the vitreous of patients with SFNM was 27.78 (2.22) ng/ml (n = 8), FTMH was 16.62 (0.9) ng/ml (n = 18), and PDR was 37.77 (3.28) ng/ml (n = 16). The differences between the PDR group and SFNM group versus the FTMH group were both significant (p = 0.0001 and p = 0.0015) as analysed by the Wilcoxon rank sum test). CONCLUSIONS: Vitreous levels of VEGF are significantly elevated in eyes with non-age-related subretinal neovascularisation compared with eyes with FTMH but not as elevated as in PDR. This suggests that VEGF is involved in subretinal angiogenesis.

Adult↗
PubMed1996

The accurate assessment of changes in retinal vessel diameter using multiple frame electrocardiograph synchronised fundus photography.

PURPOSE: Detection and precise quantification of changes in retinal vessel diameter by image analysis techniques is important in a number of fields of research. The retinal vessels have been shown to exhibit pulse related changes in diameter. These may need to be taken into account when studying diameter changes due to other causes. This study examined the effect of using multiple fundus photographs with and without electrocardiographic synchronisation on the size and statistical significance of changes in mean retinal vessel diameter. METHODS: Twelve fundus photographs spaced throughout the cardiac cycle by electrocardiographic synchronisation were taken in 10 normal volunteers: (a) at rest, (b) during isometric exercise, and (c) during oxygen inhalation. Vessel diameters were measured using a computer assisted image analysis system. Subsequently smaller sample sizes, with and without electrocardiograph synchronisation were modeled from the available data. RESULTS: With a group of ten subjects six or more electrocardiograph synchronised photographs enable reliable detection of small diameter changes (1.4%) induced by isometric exercises while other methods either failed to detect change or were unreliable at doing so. With six subjects twelve synchronised photographs were required to reliably detect a change of the same magnitude. Larger diameter changes (5.4%) were detected by any method including a single unsynchronised photograph. CONCLUSIONS: Multiple frame electrocardiograph synchronized fundus photography permits more accurate detection of small changes in retinal vessel diameter.

Adult↗
PubMed1995

Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM complications study.

We present the methodology for 45 degrees retinal photography and detail the development, application and validation of a new system of 45 degrees field grading standards for the assessment of diabetic retinopathy. The systems were developed for the EURODIAB IDDM Complications Study, part of a European Community funded Concerted Action Programme into the epidemiology and prevention of diabetes (EURODIAB). Assessment of diabetic retinopathy was carried out centrally by a trained reader of colour retinal photographs using the newly-developed system. The system proved to be acceptably accurate, repeatable repeatable and relatively simple to apply. It compared well with the recognised 'gold standard' 7-field 30 degrees stereo photography (assessed using a modified Airlie House classification scheme), against which the new system was validated in a series of 48 eyes. Selection was as a stratified random sample based on clinical retinopathy status: 5, no retinopathy; 25, non-proliferative retinopathy; 16, proliferative or photocoagulated; plus 2, eyes with potentially confounding lesions (vein occlusion). Simple presence of retinal lesions was correctly detected by both systems in 43 of the 48 eyes, giving 100% agreement on detection. Both systems correctly identified the two known cases of confounding vein occlusion. In eyes with diabetic retinopathy (n = 41), when severity was expressed in three groups: mild background, moderate/severe background and proliferative/photocoagulated, at least one grader (out of five) using the new system matched the verified results in 38 out of 31 (93%) eyes and three or more graders matched in 31 (76%) eyes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneurysm↗
PubMed1995

The effect of experimental hypertension on retinal vascular autoregulation in humans: a mechanism for the progression of diabetic retinopathy.

Since the retinal vessels have no sympathetic innervation, blood flow in response to raised blood pressure is dependent on autoregulation. To determine the effect of hypertension on retinal haemodynamics and the autoregulatory capacity of the retinal circulation under conditions of normoglycaemia and hyperglycaemia, retinal blood flow was measured before and after raising the systemic blood pressure in ten normal control subjects, ten diabetic subjects with blood glucose < 10 mmol l-1 and ten diabetic subjects with blood glucose > 15 mmol l-1. A controlled rise in systemic blood pressure was achieved using an intravenous infusion of tyramine. Retinal volume flow was determined from red cell velocity using laser Doppler velocimetry and from retinal vessel diameter measurements using digital image analysis of fundus photographs. With a 40% increase in mean arterial blood pressure (MAP), there was a significant increase in retinal blood flow of 32.9 +/- 7.1% in non-diabetic controls. In diabetics at the low blood glucose level, the increase in retinal blood flow was significant at 30% increase in MAP (23.6 +/- 8.7%, P = 0.032) and at 40% increase (49.9 +/- 12.03%, P = 0.004). Diabetics with high blood glucose failed to autoregulate at any of the increased levels of MAP (15% increase, 27.0 +/- 11.1%; 30% increase, 66.9 +/- 19.8%; and 40% increase, 101.9 +/- 21.4%; P < 0.022). The coefficients of autoregulation showed that in non-diabetic controls, retinal vascular autoregulation broke down with increases in MAP of between 30 and 40%. In diabetic subjects, it broke down between 15 and 30% in normoglycaemia and at less than 15% in hyperglycaemia. This study demonstrates an impairment in retinal vascular autoregulation in response to raised systemic blood pressure in diabetic subjects, more so at an elevated blood glucose level, thus providing a mechanism for the detrimental effect of hypertension on diabetic retinopathy.

Adult↗
PubMed1995

Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy.

Several mechanisms are implicated in the pathogenesis of diabetic retinopathy. They include biochemical, hemodynamic, and hormonal factors, all of which have an important role in the development of diabetic retinopathy. These factors are not independent of each other, but rather they interact and together are responsible for the well-known lesions of vascular occlusion, microaneurysms, hemorrhages' hard exudates, and eventually new vessel formation.

Animals↗
PubMed1994

The acute effect of smoking on retinal blood flow in subjects with and without diabetes.

PURPOSE: This study investigates the effect of smoking on retinal blood flow and autoregulation in smokers with and without diabetes. METHODS: Eleven patients with diabetes mellitus and ten control subjects were investigated. Laser Doppler velocimetry and retinal photography were used to measure retinal blood flow; vascular autoregulation was assessed with 60% oxygen breathing. These procedures were performed before and after smoking. RESULTS: Both groups demonstrated a significant increase in heart rate and systolic and diastolic blood pressure (P < 0.01). In both groups, smoking caused a significant decrease in retinal blood flow: 9.6% +/- 12% in the control group (P < 0.05) and 16.4% +/- 13.8% in the diabetic group (P < 0.01). The pre-smoking oxygen reactivity was comparable in both groups (P = 0.5); 27.9% +/- 3.3% and 32.0% +/- 5.0% in the control and diabetic groups, respectively. After smoking, oxygen reactivity was reduced significantly in the control group to 9.6% +/- 4.0% (P = 0.002) and eliminated in the patients with diabetes. CONCLUSIONS: This study shows that smoking reduces retinal blood flow and the ability of the retinal vessels to autoregulate to hyperoxia; these effects are likely to be due to the vasoconstrictive effect of nicotine, which is mediated through activation of the sympathetic system. Smoking has been shown previously to increase the level of carboxyhemoglobin, thereby reducing the oxygen-carrying capacity of blood, which, when associated with the reduced blood flow shown in the current study, may reduce retinal oxygen delivery. Hypoxia is a major factor in the progression of diabetic retinopathy; therefore, smoking may exert a detrimental influence, which may be compounded further by the additional effect smoking has on autoregulation.

Adult↗
PubMed1994

Effect of betaxolol on the retinal circulation in eyes with ocular hypertension: a pilot study.

This study investigated the effect of betaxolol, a beta 1 selective blocker, on the retinal circulation in 10 patients with ocular hypertension. In a masked randomised fashion, one eye of each subject received betaxolol and the fellow eye received placebo (hypromellose). Retinal blood flow (RBF) was determined in a major temporal vein of each eye just prior to instillation of drops and 2 h later, using laser Doppler velocimetry and monochromatic fundus photography. There was an increase of 15.0% in RBF (p = 0.03) in the betaxolol-treated eyes. No significant change was observed in the placebo-treated eyes. Intraocular pressure was reduced by 27.7% in the treated eyes, resulting in an increase of 16.9% in perfusion pressure (p = 0.02) compared with an 8.4% increase in placebo-treated eyes (p = 0.15). This study demonstrated that betaxolol increases RBF in eyes with ocular hypertension; this increase is probably related to the increase in perfusion pressure.

Administration, Topical↗
PubMed1994

Vessel diameter changes during the cardiac cycle.

Retinal vessel diameter, which is an important parameter in blood flow measurement, is affected by pulsation during the cardiac cycle and by vasomotion. This project studied these changes by analysing three monochromatic fundus photographs taken in eight arbitrary parts of the cardiac cycle of 10 healthy subjects. It was found that the venous diameter decreased in early systole, increasing thereafter to a maximum level in early diastole and then declined towards end diastole. The maximum change of 4.82% (between early systole and early diastole) (p = 0.03) represents a 9.83% change in volumetric blood flow. The arterial diameter peaked in mid-late systole, increasing by 3.46% (p = 0.01); this represents a blood flow increase of 7.04%. Vasomotion led to changes of 3.71% and 2.61% in arteries and veins respectively. It is concluded that for accurate measurement of retinal blood flow, fundus photographs should be taken synchronised with the electrocardiogram.

Adult↗
PubMed1994

Oxygen reactivity in diabetes mellitus: effect of hypertension and hyperglycaemia.

1. Laser Doppler velocimetry and computerized image analysis of retinal photographs were used to define retinal vascular autoregulation to 60% oxygen breathing. This normally causes vasoconstriction in the retinal circulation. Normotensive and hypertensive diabetic subjects were studied under conditions of relative normoglycaemia (< 10 mmol) and hyperglycaemia (> 15 mmol) together with control subjects. 2. Retinal blood flow was significantly higher in diabetic subjects when hypertensive and hyperglycaemic than in the same diabetic subjects when normotensive. 3. In the normotensive non-diabetic subjects the oxygen reactivity was 41.16 +/- 14.09%. It was significantly reduced in normotensive 'hyperglycaemic' diabetic subjects (21.75 +/- 15.56%), hypertensive diabetic subjects with controlled blood pressure and 'normoglycaemia' (30.49 +/- 14.20%), hypertensive diabetic subjects with controlled blood pressure and 'hyperglycaemia' (18.36 +/- 11.42%), hypertensive diabetic subjects with uncontrolled blood pressure and 'normoglycaemia' (26.91 +/- 13.43%) and hypertensive diabetic subjects with uncontrolled blood pressure and 'hyperglycaemia' (17.17 +/- 13.24%) (mean +/- SD, all P values < 0.05). 4. In conclusion, retinal vascular reactivity is impaired in diabetic subjects both when they are normotensive and when they are hypertensive. Hyperglycaemia, to a degree commonly encountered in clinical practice, impairs retinal vascular auto-regulation even further.

Adult↗
PubMed1994

Accurate vessel width measurement from fundus photographs: a new concept.

Accurate determination of retinal vessel width measurement is important in the study of the haemodynamic changes that accompany various physiological and pathological states. Currently the width at the half height of the transmittance and densitometry profiles are used as a measure of retinal vessel width. A consistent phenomenon of two 'kick points' on the slopes of the transmittance and densitometry profiles near the base, has been observed. In this study, mathematical models have been formulated to describe the characteristic curves of the transmittance and the densitometry profiles. They demonstrate the kick points being coincident with the edges of the blood column. The horizontal distance across the kick points would therefore indicate the actual blood column width. To evaluate this hypothesis, blood was infused through two lengths of plastic tubing of known diameters, and photographed. In comparison with the known diameters, the half height underestimated the blood column width by 7.33% and 6.46%, while the kick point method slightly overestimated it by 1.40% and 0.34%. These techniques were applied to monochromatic fundus photographs. In comparison with the kick point method, the half height underestimated the blood column width in veins by 16.67% and in arteries by 15.86%. The characteristics of the kick points and their practicality have been discussed. The kick point method may provide the most accurate measurement of vessel width possible from these profiles.

Fluorescein Angiography↗
PubMed1994

The effect of aminoguanidine and tolrestat on glucose toxicity in bovine retinal capillary pericytes.

Cultured bovine retinal capillary pericytes (BRP) were used to investigate the effect of an aldose reductase inhibitor, tolrestat, and an inhibitor of advanced glycation end products (AGE) formation, aminoguanidine, on glucose toxicity. Glucose at high concentration reduced the replicative activity of pericytes in a dose-dependent manner. Tolrestat completely inhibited the production of sorbitol in cells exposed to a high concentration of glucose but failed to protect the cells from glucose toxicity. These results suggest that sorbitol accumulation in cells is probably not the major mechanism for glucose toxicity. In contrast, the addition of aminoguanidine at 10 mM concentration to the culture media protected pericytes from glucose toxicity. The degree of protected pericytes from glucose toxicity. The degree of protection was dose-dependent and evident at aminoguanidine concentration as low as 1 mM. The drug was only slightly toxic to BRP but induced morphological changes in pericytes with the loss of cellular processes and decreased cell spreading. This may suggest some action of aminoguanidine on the pericyte cytoskeleton. High concentration of glucose significantly increased the level of early glycation but not fluorescent AGE formation on BRP proteins. This was inhibited by the addition of aminoguanidine suggesting that glycation of cellular/membrane proteins and other mechanisms may play an important role in the toxic action of high glucose levels in cultured pericytes.

Aldehyde Reductase↗
PubMed1994

Retinal blood flow changes during pregnancy in women with diabetes.

PURPOSE: To study retinal blood flow (RBF) during pregnancy in subjects with and without diabetes and to relate the changes to progression in diabetic retinopathy. METHODS: RBF in a major temporal retinal vein was measured, where possible, during all three trimesters (T1 to T3) and the postpartum period (PP) using laser Doppler velocimetry (measuring velocity [V]) and monochromatic fundus photographs (measuring diameter [D]). RESULTS: In the subjects without diabetes (n = 19), no significant change in RBF was demonstrated. V was significantly greater in T3 than in PP (P = 0.01). D was significantly smaller in T1 to T3 than in PP (P < or = 0.01). RBF in the subjects with diabetes was significantly higher in T2 and T3 than in PP (P < 0.05). V increased from T1 to T2 (P = 0.04) and decreased from T2 to PP (P = 0.001) and from T3 to PP (P = 0.002). The only significant change in D was a smaller value in T1 than in PP (P = 0.003). However, it was only those subjects whose DR progressed (n = 11) who had a significant increase in RBF during pregnancy (P = 0.0001). CONCLUSIONS: These data suggest that the hyperdynamic circulation present in pregnancy led to compensatory retinal vessel constriction (autoregulation) in the group without diabetes; this was largely absent in the patients with diabetes, with resultant increase in retinal blood flow associated with worsening retinopathy. This finding lends further support to the hypothesis that increased retinal blood flow is a pathogenic mechanism for diabetic retinopathy.

Adult↗
PubMed1993

Raised serum apolipoprotein (a) in active diabetic retinopathy.

Progressive capillary occlusion often leads to severe retinopathy within 15-20 years of the onset of Type 1 (insulin-dependent) diabetes mellitus. Lipoprotein(a), a complex formed by apolipoprotein(a), apo B-100 and lipids, is considered an independent, genetically determined, predictor of cardiovascular disease. It may have antifibrinolytic properties in view of its similarity to plasminogen. To test the hypothesis that circulating lipoprotein(a) is associated with the process that leads to clinically active diabetic retinopathy, we measured the circulating levels of apolipoprotein(a) (which are strictly correlated with those of lipoprotein(a)) in two groups of patients with Type 1 diabetes of at least 15 years duration: 25 with active retinopathy and 27 without clinically detectable retinal lesions. Thirty-eight healthy subjects of the same age and sex served as controls. Serum apolipoprotein(a) was higher in the patients with active retinopathy (36(2-193) U/dl, geometric mean and range) than in those without clinically detectable retinal lesion (17(1-160)) and the control subjects (14(0-115)), p < 0.01 in both cases. The distribution of apolipoprotein(a) levels was skewed to the left, as expected, in the patients without clinically evident retinal lesions and the control groups, but there was a bimodal trend of distribution among those with active retinopathy. The levels of glycated haemoglobin were similar in the two groups of diabetic patients, and no significant differences were found for total and HDL cholesterol, triglycerides or apolipoproteins A1 and B between them and the control subjects. These preliminary results suggest that serum apolipoprotein(a) is elevated in patients with active retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗