A tale of two systems. Interview by Emily Friedman.
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Biomedical subjects
Publications and source records attributed to R Klein.
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Unexplained neurological disorders sometimes develop in patients with cancer, even when the primary tumour or its metastases have not invaded the central nervous system. Visual dysfunction in patients with small-cell carcinoma of the lung is one of these paraneoplastic syndromes and is associated with serum auto-antibodies which react with specific subsets of retinal neurons. These sera have now been shown to react with cell lines derived from small-cell carcinoma. The antibodies recognise a small number of antigens shared by retinal and tumour cells, suggesting that an autoimmune response may be triggered by the tumour.
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In a population-based survey of diabetic persons, retinopathy was detected by stereoscopic color fundus photography in 70% of persons under 30 years of age at diagnosis and taking insulin (Group YO), in 62% of persons 30 years of age or older at diagnosis and taking insulin (Group OO-I) and in 36% of persons 30 years of age or older at diagnosis not taking insulin (Group OO-N). The mean duration of known diabetes was 14.6 years in Group YO, 11.0 years in Group OO-I and 6.9 years in Group OO-N. After 20 years of diabetes, proliferative retinopathy was present in about 50% of Group YO, about 25% of Group OO-I and about 5% of Group OO-N. After 15 years of diabetes, macular edema was present in about 18% of Group YO, about 20% of Group OO-I and about 12% of Group OO-N. When present, macular edema tended to be associated with more hard exudate in Group OO-N.
Angiotensin II has a major effect on mineralocorticoid hormone synthesis in patients with idiopathic hyperaldosteronism; it has little or no effect in those with an aldosterone-producing adenoma. To determine if this difference could be of use in clinically separating these two forms of primary aldosteronism, saline infusion tests were performed in 20 patients--14 with surgically proved aldosterone-producing adenoma and six with idiopathic hyperaldosteronism. With the patients receiving a balanced diet containing 120 meq of sodium, 1,250 ml of isotonic saline was infused intravenously between 8 A.M. and 10 A.M. after overnight recumbency. Plasma samples were obtained immediately before and after the infusion. Plasma cortisol level decreased appropriately in both groups, but plasma renin concentration decreased only in those patients with idiopathic hyperaldosteronism (p less than 0.05). Aldosterone and 18-hydroxycorticosterone levels decreased in both groups. To account for the circadian variation in adrenocorticotropin levels during the course of saline infusion, 18-hydroxycorticosterone/cortisol and aldosterone/cortisol ratios were examined. Both ratios increased in every patient with aldosterone-producing adenoma (p less than 0.01 and p less than 0.001, respectively), but these ratios remained unchanged or decreased in the patients with idiopathic hyperaldosteronism. This divergent variation in ratios after saline infusion allows for the differentiation of patients with an aldosterone-producing adenoma from those with idiopathic hyperaldosteronism. In patients with primary aldosteronism, an 18-hydroxycorticosterone/cortisol ratio of less than 3.0 or an aldosterone/cortisol ratio of less than 2.2 after saline infusion is diagnostic of idiopathic hyperaldosteronism.
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Persons with diabetes mellitus have been found to be at increased risk of developing cataracts when compared with nondiabetic persons. This report describes the study of characteristics which may be related to this problem in a population-based sample of diabetic persons. Prevalence of surgical aphakia and cataract increased with increasing age in both younger and older onset diabetic persons. Females had higher rates than males. In multivariate analyses, for younger onset persons, longer duration of diabetes, older age at examination, increased severity of retinopathy, diuretic usage and higher glycosylated hemoglobin levels were significantly associated with greater prevalence of cataract. In older onset persons, age at examination, increased severity of retinopathy, diuretic usage, lower intraocular pressure, smoking and lower diastolic blood pressure were significantly associated with greater prevalence of cataract. Longitudinal data concerning the relationship of some of these characteristics to subsequent development or progression of cataract are necessary before considering the possibility of preventive trials in this condition.
The study was performed to evaluate whether the severity of diabetic retinopathy as assessed by three alternative methods was concordant with the severity of retinopathy as determined from 30 degrees stereoscopic photographs. The three methods were direct ophthalmoscopy through an undilated pupil, nonstereoscopic 45 degrees retinal photography through a pharmacologically undilated pupil and nonstereoscopic 45 degrees photography through a dilated pupil. A single 45 degrees photograph centered between the disc and fovea was taken and direct ophthalmoscopy was performed on 99 persons prior to pharmacological dilation of the pupil. After dilation, another 45 degrees photograph was taken of the same field, as well as 30 degrees stereoscopic color photographs of DRS fields 1, 2 and 4 (modified). Corresponding photographic fields were graded by masked, trained graders for the severity of retinopathy and for the presence of specified diabetic lesions using the Modified Airlie House Classification scheme. For three levels of severity of retinopathy (none, nonproliferative or proliferative) exact agreement between direct ophthalmoscopy and grading of retinopathy from stereoscopic photographs taken with the standard 30 degrees camera was 54.3% (n = 94). For four levels of severity of retinopathy (none, microaneurysms only, all other nonproliferative retinopathy and proliferative retinopathy), exact agreement between gradings of retinopathy of the 45 degrees photographs taken through undilated pupils and 30 degrees photographs taken through dilated pupils was 82.5% (n = 63); and for 45 degrees photographs and 30 degrees photographs taken through dilated pupils it was 86.5% (n = 74). These data suggest that 45 degrees nonstereoscopic fundus photographs, when graded according to a standard classification scheme, provide reasonably reliable photographic representation of the severity of retinopathy when broad overall categories are used.
Diabetic retinopathy was assessed in a population-based study of 2708 diabetic persons in southern Wisconsin. The retinopathy levels as determined by ophthalmoscopy and by the grading of stereoscopic fundus photographs were compared in the eyes of 1949 persons. Ophthalmoscopy was performed by an ophthalmologist and a specially trained optometrist and ophthalmic technician. Consultation among the three examiners was permitted. There was exact agreement between ophthalmoscopy and grading for detecting retinopathy (none, nonproliferative, proliferative) 85.7% of the time. The kappa statistic, which corrects for chance agreement, was 0.749. There were no significant differences among the three ophthalmoscopists. Ophthalmoscopy was more likely to disagree with fundus photography grading in eyes with less severe forms of retinopathy and in patients examined early in the study. Other factors found to influence the degree of agreement were age, visual acuity, and duration of diabetes. It is concluded that with proper training ophthalmoscopy can be an acceptable alternative to fundus photography in certain situations.
In population-based studies and in clinical practice a reliable, objective measure of optic disc cupping is needed. This measure is of special importance when following patients with diagnosed or suspected glaucoma. We have developed a new system using stereoscopic fundus photographs for quantitating optic disc cupping from these photographs. Measurements of the cup are based on cup contour. For this system, measurements of longest and shortest cup and longest and shortest disc diameters by two observers were highly correlated, with correlation coefficients of 0.88, 0.88, 0.77, and 0.82, respectively. Mean cup to disc ratios for long and short disc diameters were within 0.04 (n = 330) between the two observers. The measurements show a high degree of inter- and intra-observer reliability, and are inexpensive in time and materials to perform. This method is well suited to population-based studies.
Blood pressure was measured in a population-based study of diabetic retinopathy in southern Wisconsin. Persons diagnosed prior to 30 years of age and taking insulin (younger onset, n = 996) and those diagnosed at 30 years of age or older (older onset, n = 1,370) were examined. Blood pressures were measured by a standard protocol using a random-zero sphygmomanometer. In both groups of patients, systolic blood pressure increased with increasing age and tended to be higher in older onset than younger onset persons. Hypertension was present in 21.9% of the younger and 58.1% of the older onset group. Older age at examination, presence of proteinuria, larger body mass, gender, and longer duration of diabetes were significantly associated with higher systolic blood pressure.
Diurnal variations in normal hemogram, total serum protein and serum iron are documented in 6 adult owl monkeys, Aotus trivirgatus griseimembra, maintained in an artificial LD 12:12 (35:0.08 lx) with light phase from 03.00 to 15.00 h Central European time. Statistically significant high amplitude rhythms occurred in total leukocyte and in eosinophil numbers with acrophases at 06.35 and 09.53 h, respectively. Erythrocyte numbers and hemoglobin concentration showed statistically significant low amplitude rhythms with almost identical acrophases. Total serum protein exhibited a 10% daily fluctuation. Serum iron concentration showed high amplitude daily variations with a 60% mean range of oscillation.
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A major goal of the study was to assess the methodologies available for the quantification of retinal lesions suitable for application in trials of metabolic management. We describe the methods used for grading stereoscopic color fundus photographs. Overall retinopathy severity level for each eye ranging from normal (level 10) to high-risk category (level 70) was assigned on the basis of gradings of individual lesions. Change in retinopathy severity level over the 8-mo period was detected in 3-62% of patients, depending on the method used and the definition of change. Lesions responsible for change in level were mainly retinal infarcts (soft exudates) and intraretinal microvascular abnormalities.
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