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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 73 records · Page 4Linked to original sources
PubMed2001

Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. METHODS: A cohort of 10358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. FINDINGS: Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. INTERPRETATION: Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.

Arteriosclerosis↗
PubMed2001

Hospital inquiries. No quick fix.

The Bristol inquiry highlights the disjunction between ends and means in the NHS. It draws attention to the 'make do and mend' culture in the service. The ethos of 'getting by' is seen as the enemy of excellence. Its most radical theme is the separation of management and regulation.

Cardiac Surgical Procedures↗
PubMed2001

Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex.

Mice that lack all beta1-class integrins in neurons and glia die prematurely after birth with severe brain malformations. Cortical hemispheres and cerebellar folia fuse, and cortical laminae are perturbed. These defects result from disorganization of the cortical marginal zone, where beta1-class integrins regulate glial endfeet anchorage, meningeal basement membrane remodeling, and formation of the Cajal-Retzius cell layer. Surprisingly, beta1-class integrins are not essential for neuron-glia interactions and neuronal migration during corticogenesis. The phenotype of the beta1-deficient mice resembles pathological changes observed in human cortical dysplasias, suggesting that defective integrin-mediated signal transduction contributes to the development of some of these diseases.

Animals↗
PubMed2001

Risk of incident age-related eye diseases in people with an affected sibling : The Beaver Dam Eye Study.

The purpose of this investigation was to determine whether age-related cataract and maculopathy in older siblings predicts development of the same in younger siblings. A population-based study of age-related eye diseases was conducted in 1988--1990 in Beaver Dam, Wisconsin, and a follow-up examination was performed 5 years later. Diagnoses of age-related eye diseases were assigned on the basis of gradings of study photographs. There were 1,088 people from 488 sibships with at least two siblings who could contribute information for these analyses. The authors computed odds ratios and 95% confidence intervals for developing the specific lesion and identifying it 5 years later if an older sibling had it at baseline. The odds ratios were 1.65 (95% confidence interval (CI): 0.91, 2.99) for nuclear cataract, 1.62 (95% CI: 0.92, 2.85) for cortical cataract, 1.95 (95% CI: 0.48, 7.95) for posterior subcapsular cataract, 1.82 (95% CI: 0.91, 3.66) for soft drusen, 8.18 (95% CI: 3.34, 20.08) for retinal pigment epithelium depigmentation, 3.59 (95% CI: 1.71, 7.57) for increased retinal pigment, and 10.32 (95% CI: 0.83, 128.58) for exudative age-related maculopathy. These findings suggest that strong family determinants of lesions of age-related maculopathy are likely, less so for age-related cataract, which confer risk of the same lesion in a younger sibling.

Adult↗
PubMed2001

Temperature development in a modern municipal solid waste incineration (MSWI) bottom ash landfill with regard to sustainable waste management.

Municipal solid waste is treated in incineration plants to reduce the volume, the toxicity and the reactivity of the waste. The final product, municipal solid waste incineration (MSWI) bottom ash, was considered as a material with a low reactivity, which can safely be deposited in a MSWI bottom ash landfill, or which can be used, e.g. in road construction after further treatment. However, temperature measurements in MSWI bottom ash landfills showed temperatures up to 90 degrees C, caused by exothermic reactions within the landfill. Such high temperatures may affect the stability of the flexible polymer membrane liner (FML) and may also lead to an accelerated desiccation of the clay barrier. At the beginning of this study it was uncertain whether those reported results would be applicable to modern landfills, because the treatment techniques in MSWI and landfills have changed, bottom and fly ash are stored separately, and the composition of the incinerated waste has changed significantly since the publication of those results. The aim of this study was to gain detailed knowledge of temperature development under standard disposal conditions in relation to the rate of ash disposal, the variation of layer thickness, and the environmental conditions in a modern landfill. Temperatures were measured at nine levels within the body of a landfill for a period of nearly 3 years. Within 7 months of the start of the disposal, a temperature increase of up to 70 degrees C within the vertical centre of the disposal was observed. In the upper and central part of the landfill this initial temperature increase was succeeded by a decrease in temperature. The maximum temperature at the time of writing (May 2000) is about 55 degrees C in the central part of the landfill. The maximum temperature (45.9 degrees C) at the FML was reached 17 months after the start of the deposition. Since then the temperatures decreased at a rate of 0.6 degrees C per month. Temperature variation within each individual layer corresponds to the temperature of the underlying layer and the overall surface-to-volume ratio of the landfill. The temperatures in the uppermost layer are significantly influenced by the ambient temperatures.

Cities↗
PubMed2001

Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord. These obligatory contralateral connections account for why one side of the brain controls movement on the opposing side of the body. The netrins and slits provide well-known midline signals that regulate axonal crossings at the midline. Herein we report that a member of the ephrin family, ephrin-B3, also plays a key role at the midline to regulate axonal crossing. In particular, we show that ephrin-B3 acts as the midline barrier that prevents corticospinal tract projections from recrossing when they enter the spinal gray matter. We report that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in the spinal gray matter, such that the motor cortex on one side of the brain now provides bilateral input to the spinal cord. This neuroanatomical abnormality in ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding mice that simultaneously move their right and left limbs and thus have a peculiar hopping gait quite unlike the alternate step gait displayed by normal mice. The corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as other ephrins, suggesting that the binding of EphA4-bearing axonal processes to ephrin-B3 at the midline provides the repulsive signal that prevents corticospinal tract projections from recrossing the midline in the developing spinal cord.

Animals↗
PubMed2001

Design and synthesis of inhibitors of adenosine and AMP deaminases.

Nucleosides and nucleotides which are able to undergo covalent hydration in the aglycone ring system are potential inhibitors of the enzymes adenosine deaminase (ADA) and AMP deaminase, respectively. Calculations of the enthalpy of covalent hydration and of enzyme binding energy have been used to design new inhibitors of ADA. The ribosyl triazolotriazine 16, which was synthesized as a result of these calculations, exists predominantly as the covalent hydrate 18 in water and is a potent inhibitor of mammalian ADA (IC(50) 50 nM).

AMP Deaminase↗
PubMed2001

Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the third national health and nutrition examination survey.

Relations of the carotenoids lutein and zeaxanthin in the diet and serum to photographic evidence of early and late age-related maculopathy (ARM) among persons over age 40 years (n = 8,222) were examined. Inverse relations of these carotenoids in the diet or serum to any form of ARM were not observed overall. There was a direct relation of dietary levels to one type of early ARM (soft drusen). However, relations differed by age and race. In the youngest age groups who were at risk for developing early (ages 40-59 years) or late (ages 60-79 years) ARM, higher levels of lutein and zeaxanthin in the diet were related to lower odds for pigmentary abnormalities, one sign of early ARM (odds ratio among persons in high vs. low quintiles = 0.1, 95 percent confidence interval: 0.1, 0.3) and of late ARM (odds ratio = 0.1, 95 percent confidence interval: 0.0, 0.9) after adjustment for age, gender, alcohol use, hypertension, smoking, and body mass index. Relations of these carotenoids to ARM may be influenced by age and race and require further evaluation in separate populations and in prospective studies.

Adult↗
PubMed2001

Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitis.

Sensory nerve-derived neuropeptides such as substance P demonstrate a number of proinflammatory bioactivities, but less is known about their role in inflammatory skin disease. The cell surface metalloprotease neutral endopeptidase (NEP) is the principal proteolytic substance P-degrading enzyme. This study tests the hypothesis that the absence of NEP results in dysregulated inflammatory skin responses. The effector phase of allergic contact dermatitis (ACD) responses was examined in NEP(-/-) knockout and NEP(+/+) wild-type mice and compared with the irritant contact dermatitis response in these animals. NEP was found to be normally immunolocalized in epidermal keratinocytes and dermal blood vessels. The ACD ear swelling response was 2.5-fold higher in animals lacking NEP and was accompanied by a significant increase in plasma extravasation and infiltration of inflammatory leukocytes. The augmented ACD response in NEP(-/-) animals was abrogated by either administration of a neurokinin receptor 1 antagonist or by repeated pretreatment with topical capsaicin. Similar to NEP(-/-) mice, the acute inhibition of NEP in NEP(+/+) animals resulted in an augmented ACD response. In contrast to the ACD responses, little differences were observed in the irritant contact dermatitis response of NEP(-/-) compared with NEP(+/+) animals after epicutaneous application of the skin irritants croton oil or SDS. Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD.

Administration, Cutaneous↗
PubMed2001

The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration.

The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of vascular morphogenesis. EphrinB2 may have an active signaling role, resulting in bi-directional signal transduction downstream of both ephrinB2 and Eph receptors. To separate the ligand and receptor-like functions of ephrinB2 in mice, we replaced the endogenous gene by cDNAs encoding either carboxyterminally truncated (ephrinB2(DeltaC)) or, as a control, full-length ligand (ephrinB2(WT)). While homozygous ephrinB2(WT/WT) animals were viable and fertile, loss of the ephrinB2 cytoplasmic domain resulted in midgestation lethality similar to ephrinB2 null mutants (ephrinB2(KO)). The truncated ligand was sufficient to restore guidance of migrating cranial neural crest cells, but ephrinB2(DeltaC/DeltaC) embryos showed defects in vasculogenesis and angiogenesis very similar to those observed in ephrinB2(KO/KO) animals. Our results indicate distinct requirements of functions mediated by the ephrinB carboxyterminus for developmental processes in the vertebrate embryo.

Angiopoietin-1↗
PubMed2001

Aggregation of refractive error and 5-year changes in refractive error among families in the Beaver Dam Eye Study.

OBJECTIVE: To examine aggregation of refraction, myopia, hyperopia, and astigmatism, as well as the 5-year change in each of these measures, among adult family members. DESIGN: Geographically defined, population-based cohort study in Beaver Dam, Wis. Participants were all 43 to 84 years of age in 1988. Family relationships among participants of the study were identified through interviews. The main outcome measures were noncycloplegic refractions. Aggregation was assessed by Pearson correlations and odds ratios (ORs) that both members of a pair were affected. RESULTS: Age-adjusted sibling correlation of refraction was 0.37 and the OR for a sibling to be myopic was 4.18, whereas the OR for being hyperopic was 2.87 (all statistically significant, P<.05). Correlations and ORs for parent-child and cousin relationships were smaller, and those for spousal relationships were not significant. Correlations and ORs for cylinder power and astigmatism were not statistically significant for most relationships considered. There were no statistically significant correlations or ORs for changes in any measure of refractive error. CONCLUSIONS: The strong aggregation of refractive error, including myopia and hyperopia, among siblings along with weaker associations among parent-child and cousin pairs and no associations among spouses suggest a potential genetic influence on refractive error. There is no such suggestion for a genetic influence on the changes in refraction or in cylinder power and astigmatism.

Adult↗
PubMed2001

The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER.

OBJECTIVE: To determine the prevalence of glaucoma in a population-based sample of Hispanic adults older than 40 years. METHODS: Using 1990 census data for Arizona, groups of persons living in sections of the city in Nogales and Tucson were randomly selected with a probability proportional to the Hispanic population older than 40 years. We tried to recruit all eligible adults in homes with 1 self-described Hispanic adult. Detailed ocular examinations at a local clinic included visual acuity testing, applanation tonometry, gonioscopy, an optic disc evaluation, and a threshold visual field test. Open-angle glaucoma (OAG) was defined using a proposed international system for prevalence surveys, including threshold visual field defect and optic disc damage. Angle-closure glaucoma was defined as bilateral appositional angle closure, combined with optic nerve damage (judged by field and disc as for OAG). RESULTS: Examinations were conducted in 72% (4774/6658) of eligible persons, with a 1.97% prevalence (95% confidence interval, 1.58%-2.36%) of OAG (94 persons). The age-specific OAG prevalence increased nonlinearly from 0.50% in those aged 41 to 49 years to 12.63% in those 80 years and older. Angle-closure glaucoma was detected in 5 persons (0.10%). Sex, blood pressure, and cigarette smoking were not significant OAG risk factors. Only 36 (38%) of the 94 persons with OAG were aware of their OAG before the study. Screening results with an intraocular pressure higher than 22 mm Hg (in the eye with a higher pressure) would miss 80% of the OAG cases. CONCLUSIONS: The prevalence of OAG in Hispanic persons was intermediate between reported values for white and black persons. The prevalence increased more quickly with increasing age than in other ethnic groups. Glaucoma was the leading cause of bilateral blindness.

Adult↗
PubMed2001

Relationship of dietary fat to age-related maculopathy in the Third National Health and Nutrition Examination Survey.

OBJECTIVE: To evaluate the associations between dietary fat and age-related maculopathy (ARM) in persons 40 years or older who participated in the Third National Health and Nutrition Examination Survey. METHODS: We used a single, nonmydriatic, fundus photograph of 1 eye to ascertain ARM status in 7883 of 11 448 survey participants. Intake of fat was estimated from 24-hour recall, and specific sources of dietary fat were estimated from responses to food frequency questionnaires. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) that accounted for complex survey design, nonresponse, and potential risk factors for ARM (age, smoking, race, sex, body mass index, history of cardiovascular disease or hypertension, eye color, and sedentary lifestyle). Persons aged 40 to 79 years (n = 7405) were included in analyses for early ARM (n = 644); those 60 years or older (n = 4294) were included in analyses for late ARM (n = 53). RESULTS: After adjustment for age, race, eye color, and sedentary lifestyle, OR for early ARM was 1.4 (95% CI, 0.9-2.2; P for trend,.10) among persons in high vs low quintiles of total fat intake (percentage of total energy). Associations for specific types of fatty acids (as percentages of caloric intake) were in the same direction and unrelated to ARM. The OR for late ARM was 0.7 (95% CI, 0.2-2.6; P for trend,.60) in persons 60 years or older. Further adjustments for other potential confounders did not significantly affect the ORs. CONCLUSION: Age-related maculopathy was not significantly associated with dietary fat in this large cross-sectional survey.

Adult↗
PubMed2001

Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts.

OBJECTIVE: To investigate whether a computer vision system is comparable with humans in detecting early retinal lesions of diabetic retinopathy using color fundus photographs. METHODS: A computer system has been developed using image processing and pattern recognition techniques to detect early lesions of diabetic retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool spots). Color fundus photographs obtained from American Indians in Oklahoma were used in developing and testing the system. A set of 369 color fundus slides were used to train the computer system using 3 diagnostic categories: lesions present, questionable, or absent (Y/Q/N). A different set of 428 slides were used to test and evaluate the system, and its diagnostic results were compared with those of 2 human experts-the grader at the University of Wisconsin Fundus Photograph Reading Center (Madison) and a general ophthalmologist. The experiments included comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases excluded in the latter). RESULTS: In the training phase, the agreement rates, sensitivity, and specificity in detecting the 3 lesions between the retinal specialist and the computer system were all above 90%. The kappa statistics were high (0.75-0.97), indicating excellent agreement between the specialist and the computer system. In the testing phase, the results obtained between the computer system and human experts were consistent with those of the training phase, and they were comparable with those between the human experts. CONCLUSIONS: The performance of the computer vision system in diagnosing early retinal lesions was comparable with that of human experts. Therefore, this mobile, electronically easily accessible, and noninvasive computer system, could become a mass screening tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

Aged↗
PubMed2001

How many steps of progression of diabetic retinopathy are meaningful? The Wisconsin epidemiologic study of diabetic retinopathy.

OBJECTIVE: To determine whether a 1-step or more or 2-step or more progression on the Early Treatment Diabetic Retinopathy Study retinopathy severity scale over a 4-year period is meaningful in predicting the subsequent incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) over the following 6 years. DESIGN: Population-based study of diabetic persons with 10 years of follow-up. SETTING AND PATIENTS: Eleven-county area in southern Wisconsin. There were 1025 persons with diabetes who had fundus photographs at baseline and at 4- and 10-year follow-up examinations. MAIN OUTCOME MEASURES: Incidence of PDR or CSME between the 4- and 10-year follow-up examinations as determined by masked grading of color stereoscopic fundus photographs of 7 standard fields. RESULTS: In a univariate analysis, those with 1 or more steps of progression (n = 551) over the first 4 years of the study were significantly (P<.0001) more likely to develop PDR over the next 6 years than those with no progression (n = 474) (26% vs 4%) (relative risk, 5.85; 95% confidence interval, 4.05-8.47). Similarly, those with 2 or more (n = 364) (33%) or 3 or more (n = 231) (41%) steps of progression over the first 4 years of the study were significantly (P<.0001) more likely to develop PDR over the next 6 years than those with lesser progression (n = 661 [7%] and n = 794 [9%], respectively) (relative risk, 5.10; 95% confidence interval, 3.83-6.80; and relative risk, 4.61; 95% confidence interval, 3.57-5.99, respectively). Similar associations were apparent at every level of retinopathy, duration of diabetes, and glycosylated hemoglobin, and by type of diabetes at baseline. There were also associations between retinopathy progression and incidence of CSME. CONCLUSIONS: It seems that 1 or more or 2 or more steps of progression of retinopathy over a 4-year period strongly predict the development of PDR over the next 6 years. Therefore, using these end points of progression would result in the need for fewer subjects or shorter follow-up in some clinical trials.

Adult↗