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Biomedical subjects

L I Rand

Publications and source records attributed to L I Rand.

28 records · Page 2Linked to original sources

Differential responsiveness to insulin of endothelial and support cells from micro- and macrovessels.

The pathologies of diabetic micro- and macroangiopathy are different, suggesting that diabetes affects these two types of vascular tissue in a dissimilar manner. We have compared insulin receptors and the effects of insulin on cultured endothelium from calf retinal capillaries and aorta, and the vascular supporting cells, retinal pericytes, and aortic smooth muscle cells. 125I-insulin binds to high affinity insulin receptors on all four cell types. Receptor concentrations were similar except for aortic smooth muscle cells, which have 10-fold fewer receptors than the other cell types. Insulin at a concentration of 10 ng/ml stimulated [14C]glucose incorporation into glycogen in retinal endothelial cells and pericytes and aortic smooth muscle cells, but had no effect on aortic endothelium. Insulin over a concentration range of 10 ng/ml-10 microgram/ml, stimulated [3H]thymidine incorporation into the DNA of retinal pericytes, and endothelial cells and aortic smooth muscle cells but had no effect on aortic endothelial cells. These data suggested that a differential response to insulin may exist between endothelium of micro- and macrovasculature, and suggest that retinal capillary endothelium and retinal pericytes are both very insulin-sensitive tissues.

Animals↗

Retinal vascular reactivity to norepinephrine and angiotensin II in normals and diabetics.

Retinal arterial vasoconstriction induced by an infusion of angiotensin II or norepinephrine was investigated in eight normal controls (N), nine diabetics without retinopathy (DNR), and 10 diabetics with retinopathy (DR) by color fundus photographs taken before and after the infusions. Image analysis was done by a semiautomated computerized microdensitometer using a videoscanner. Normal controls and diabetics without retinopathy had a significant reduction in diameter compared with diabetics with retinopathy, who failed to constrict arterioles in response to either vasopressor. The mechanism of this phenomenon is unclear. Semiautomated computerized microdensitometry is reproducible and appears to be a sensitive technique to evaluate the vascular reactivity of the retinal vasculature.

Adult↗

Recent advances in diabetic retinopathy.

Despite the fact that we still do not understand what causes the development of retinopathy in diabetic subjects, major advances in its treatment have taken place. Photocoagulation clearly reduces the retinopathy although how early treatment should be initiated has not been clearly defined. Vitrectomy is capable of restoring vision in many already blind eyes but at some risk. We are inching closer to an understanding of the pathophysiology of retinopathy with development of retinal endothelial and pericyte cell culture techniques, studies of vascular permeability, flow and angiogenesis. Diabetic retinopathy is more common at early durations of diabetes than previously realized. This may allow for prospective intervention studies, using development of retinopathy as an endpoint. Diabetic retinopathy may be a reasonable index of short-term survival.

Angiogenesis Inducing Agents↗

Reproducibility of the densitometric analysis of fluorescein angiograms.

Computer-aided operator-interactive densitometry was applied to assess the reproducibility or retinal-fluorescein angiograms. To achieve this, the fundus camera images of glass tubings of various diameter filled with fluorescein of varying concentrations were subjected to densitometric analysis. These studies were carried out repeatedly at 9-micrometer and 29-micrometer scanning resolutions by three observers and thus the inter- and intra-operator errors could be estimated. The scanned data were analyzed as both optical densities and intensities for some of the measurements. In both analyzing modes good linearity was obtained when the densitometric response was plotted against tubing diameter for various concentrations. To determine the reproducibility of transit time and retinal circulation time analyses, a randomly selected patient's angiogram was repeatedly analyzed by three observers and compared. From these data the inter- and intra-operator errors were also determined for successive frames and the reproducibility of the area under the dye dilution curves for both arteries and veins was computed. The overall densitometric reproducibility was found to be good; however, practical usefulness of the retinal circulation time remains to be established.

Angiography↗

Diabetic retinopathy in Joslin Clinic patients with adult-onset diabetes.

While only a small proportion of adult-onset diabetic patients develop vision threatening retinopathy, this group makes up a major portion of those diabetics seeking ophthalmologic care. Fifty-three percent of patients having fundus photographs at the W.P. Beetham Eye Unit of the Joslin Clinic developed diabetes at the age of 20 or over, and almost 30% at the age of 40 or over. Twenty-two percent of all patients seen with proliferative retinopathy were in this latter group. Ten of 54 patients with proliferative retinopathy in the greater than or equal to 40 onset group were not taking insulin. The older onset patients who developed proliferative retinopathy did so after shorter durations of diabetes and with more visual disability than younger onset patients. Macular edema was more common in adult-onset patients, and its presence in a patient less than 50 years old was usually associated with proliferative or preproliferative retinopathy.

Adult↗

Psychologic stress and glycemic control: a comparison of patients with and without proliferative diabetic retinopathy.

Using a case/control design, patients with (cases) and without (controls) proliferative diabetic retinopathy were compared using three psychosocial measures: life events, psychiatric symptomatology, and ego development. Cases reported significantly more symptoms. They also demonstrated a modest and significant correlation of negative life events with HgbA1c that was not shown in the controls. When the relationship of life events with glycemic control was explored in cases of varying durations of proliferative retinopathy, we found that the association between negative life events and HgbA1c was accounted for by the cases with a recent onset of retinopathy. Patients in this recent group showed a trend towards more negative life events that decreased with longer duration of proliferative retinopathy. This study suggests that the onset of proliferative retinopathy portends a life crisis during which metabolic control is sensitive to additional life stress and that this association is not found among patients whose illness is more stable.

Adult↗

Psychosocial correlates of mild visual loss.

Studies of the psychosocial aspects of visual impairment have emphasized the effects of blindness, giving relatively little attention to the effects of mild or partial visual impairment. Consequently, we know little about when in the course of visual loss significant psychosocial dysfunction develops. To address this question, we assessed psychosocial functioning at three times over eight months in 31 adults with proliferative diabetic retinopathy and mild to moderate visual impairment in at least one eye. Examination of the correlations between visual and psychosocial measures revealed strong and significant correlations between visual acuity and adjustment (range of r = -0.45 to -0.68), between visual acuity and psychological symptoms (range of r = -0.39 to -0.50), and between visual acuity and emotion-focused coping (range of r = -0.38 to -0.53). The strength of these correlations and their occurrence in three independent measures of psychosocial functioning suggest a clinically meaningful relationship between visual and psychosocial functioning in the range of mild to moderate visual impairment. Psychosocial dysfunction related to visual impairment develops long before blindness. Further prospective research on the psychosocial aspects of partial visual impairment will clarify this relationship and may help justify early intervention with rehabilitation in the visually impaired who do not qualify for services for the blind.

Adaptation, Psychological↗

Psychosocial aspects of diabetic retinopathy.

Diabetic retinopathy, particularly in the more advanced stages, poses many difficult psychosocial problems and demands major adjustments by the patient. Our review of this literature has identified specific problems relevant to patient care, future research, and public policy. For example, proliferative retinopathy often leads to at least partial visual impairment, psychiatric symptoms, and difficulties with glycemic control. Partial visual impairment appears to cause as much psychosocial disruption as severe blindness. This suggests that most rehabilitation programs that serve the legally blind may come too late in the course of this illness. This review emphasizes the paucity of past research on psychosocial aspects of diabetic retinopathy and raises some questions for future research.

Activities of Daily Living↗

Risk of proliferative diabetic retinopathy in juvenile-onset type I diabetes: a 40-yr follow-up study.

The development of proliferative diabetic retinopathy was studied in three cohorts consisting of 292 patients with recent juvenile-onset, type I (insulin-dependent) diabetes who were followed 20-40 yr beginning in 1939, 1949, and 1959. The risk of this severe eye complication was almost nonexistent during the first 10 yr of diabetes, rose abruptly to its maximum level (approximately 30/100 person-years), and remained at that level for the next 25 yr. This pattern did not vary with sex, age at onset of diabetes, or level of glycemic control during the first 5 yr of diabetes. However, the risk of proliferative retinopathy was strongly related to the level of glycemic control during the several years preceding onset of this complication. This was a dose-dependent relationship, with patients in the highest quartile of the distribution of the index of frequency of hyperglycemia having a 10-fold higher risk than individuals in the lowest quartile. A virtually identical pattern was observed in patients who developed diabetes in 1959 as was observed in those who developed diabetes in 1949 or 1939. In contrast, diabetic nephropathy as evidenced by persistent proteinuria showed a lower incidence in the 1959 than in the 1939 cohort. In conclusion, these incidence data do not support the notion that the risk of proliferative retinopathy is mainly a function of duration of diabetes. Instead, the pattern of occurrence of this severe eye complication in type I diabetes suggests that the process leading to the development of proliferative retinopathy consists of two or more stages and that progression through each stage may be governed by different factors.

Adolescent↗