Health authorities. Its all in the balance.
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Budgets↗
Biomedical subjects
R Klein
Publications and source records attributed to R Klein.
Is obesity related to microvascular and macrovascular complications in diabetes? The Wisconsin Epidemiologic Study of Diabetic Retinopathy.
BACKGROUND: There are few epidemiological data describing the relationship of obesity to the incidence of microvascular and macrovascular complications in patients with diabetes. METHODS: In a population-based study performed in southern Wisconsin, 1370 persons diagnosed as having diabetes when they were 30 years of age or older (mean[+/- SD] age, 66.6 +/- 11.3 years) participated in a baseline examination, 987 in a 4-year follow-up examination, and 533 in a 10-year follow-up examination. Height and weight were measured using standard protocols. Individuals were characterized as underweight, normal weight, overweight, and obese by body mass index (expressed as weight in kilograms divided by the square of the height in meters) status. Outcomes included incidence and progression of retinopathy, incidence of gross proteinuria, incidence of lower-extremity amputation, and death due to ischemic heart disease, death due to stroke, and all-cause mortality. RESULTS: The prevalence of being obese was 25.2%. After other risk factors were controlled for, being underweight was associated with higher incidence of diabetic retinopathy, death from stroke, and all-cause mortality. Body mass was not associated with progression of retinopathy, incidence of gross proteinuria, amputation of a lower extremity, or death due to ischemic heart disease. CONCLUSIONS: These data suggest that obesity in persons with older-onset diabetes is not related to the long-term incidence of microvascular and macrovascular complications.
Adult↗
Tyrosine phosphorylation of transmembrane ligands for Eph receptors.
Axonal pathfinding in the nervous system is mediated in part by cell-to-cell signaling events involving members of the Eph receptor tyrosine kinase (RTK) family and their membrane-bound ligands. Genetic evidence suggests that transmembrane ligands may transduce signals in the developing embryo. The cytoplasmic domain of the transmembrane ligand Lerk2 became phosphorylated on tyrosine residues after contact with the Nuk/Cek5 receptor ectodomain, which suggests that Lerk2 has receptorlike intrinsic signaling potential. Moreover, Lerk2 is an in vivo substrate for the platelet-derived growth factor receptor, which suggests crosstalk between Lerk2 signaling and signaling cascades activated by tyrosine kinases. It is proposed that transmembrane ligands of Eph receptors act not only as conventional RTK ligands but also as receptorlike signaling molecules.
3T3 Cells↗
The rationing debate. Defining a package in healthcare services the NHS is responsible for. The case against.
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Decision Making↗
Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice.
TrkA high-affinity receptors are essential for the normal development of sympathetic paravertebral neurons and subpopulations of sensory neurons. Paravertebral sympathetic neurons and chromaffin cells of the adrenal medulla share an ontogenetic origin, responsiveness to NGF, and expression of TrkA. Which aspects of development of the adrenal medulla might be regulated via TrkA are unknown. In the present study we demonstrate that mice deficient for TrkA, but not the neurotrophin receptor TrkB, show an early postnatal progressive reduction of acetylcholinesterase (AChE) enzymatic activity in the adrenal medulla and in preganglionic sympathetic neurons within the thoracic spinal cord, which are also significantly reduced in number. Quantitative determinations of specific AChE activity revealed a massive decrease (-62%) in the adrenal gland and a lesser, but still pronounced, reduction in the thoracic spinal cord (-40%). Other markers of the adrenal medulla and its innervation, including various neuropeptides, chromogranin B, secretogranin II, amine transporters, the catecholamine-synthesizing enzymes tyrosine hydroxylase and PNMT, synaptophysin, and L1, essentially were unchanged. Interestingly, AChE immunoreactivity appeared unaltered, too. Preganglionic sympathetic neurons, in contrast to adrenal medullary cells, do not express TrkA. They must, therefore, be affected indirectly by the TrkA knock-out, possibly via a retrograde signal from chromaffin cells. Our results suggest that signaling via TrkA, but not TrkB, may be involved in the postnatal regulation of AChE activity in the adrenal medulla and its preganglionic nerves.
Acetylcholinesterase↗
The prevalence of age-related maculopathy by geographic region and ethnicity. The Colorado-Wisconsin Study of Age-Related Maculopathy.
OBJECTIVES: To determine the prevalence of age-related maculopathy (ARM) in a biethnic population and to determine if there are ethnic and/or geographic differences in the prevalence of ARM. DESIGN: Prevalence data from 2 population-based studies, the San Luis Valley Diabetes Study (n = 1541, ages 21-74 years) and the Beaver Dam Eye Study (n = 3999, ages 43-74 years), were compared. SETTING: Southern Colorado and central Wisconsin. MAIN OUTCOME MEASURE: Color stereoscopic fundus photographs were graded for ARM using the Wisconsin Age-related Maculopathy Grading System. Similar questionnaire, laboratory, and clinical data on potential risk factors were available from both studies. RESULTS: Late-stage ARM was significantly less frequent among Hispanics than non-Hispanic whites (NHW) in Beaver Dam (odds ratio [OR] = 0.07; 95% confidence interval [CI] = 0.01-0.49; Hispanics vs Beaver Dam NHW). The prevalence of any ARM was significantly lower among San Luis Valley NHW (10.4%) than Beaver Dam NHW (14.3%) (OR = 0.67; 95% CI = 0.50-0.91). This prevalence difference was not explained by any of the risk factors examined (smoking, cardiovascular disease, diabetes, alcohol consumption, etc). The 2 NHW groups reported different European heritages. CONCLUSIONS: Late-stage ARM appeared to be rare among Hispanics but there was no ethnic difference in prevalence of any ARM. The 33% difference in risk among NHW by geographic location was not reduced when controlling for possible risk factors or confounders, suggesting that genetic heritage may be an important determinant of risk for ARM.
Adult↗
Incidence of retinopathy and associated risk factors from time of diagnosis of insulin-dependent diabetes.
OBJECTIVE: To describe the prevalence at baseline and 4-year incidence of retinopathy and its relation to glycemic control from the time of diagnosis of insulin-dependent diabetes. DESIGN: Geographically defined population-based study. SETTING: Twenty-eight-county area in Wisconsin. STUDY POPULATION: Incipient cohort of children, teenagers, and young adults (n = 354) up to 30 years of age with newly diagnosed insulin-dependent diabetes. MAIN OUTCOME MEASURE: Diabetic retinopathy as determined by gradings from 30 degrees color stereoscopic photographs of the Diabetic Retinopathy Study 7 standard fields. RESULTS: The prevalence of retinopathy at diagnosis was 1.3%. Four years after diagnosis of diabetes, retinopathy was first identified in 5.1% of our cohort and in 9.7% of those 15 years of age or older. After controlling for age, subjects with a mean glycosylated hemoglobin level of 12% or greater were 3.2 times as likely (95% confidence interval, 1.1-9.9) to have retinopathy present at follow-up as were subjects with a mean glycosylated hemoglobin level of less than 12%. CONCLUSION: Population-based data on the frequency and incidence of retinopathy from the time of diagnosis of insulin-dependent diabetes mellitus provided by this study suggest a possible reduction in risk of developing retinopathy in those in whom glycemic control is achieved from the time of diagnosis.
Adolescent↗
Barriers to prevention of vision loss caused by diabetic retinopathy.
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Blindness↗
Diabetic retinopathy assessed by fundus photography in Pima Indians with impaired glucose tolerance and NIDDM.
In a population-based epidemiological study, 991 Pima Indians with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 288 without diabetes aged > or =15 years were examined for retinopathy by fundus photography with a 45 degrees fundus camera after mydriasis. The photographs were graded using a modified Airlie-House classification scheme. The associations of several factors with retinopathy were studied by logistic regression. Non-proliferative retinopathy was present in 11.2 % (19/169) subjects at the time of diagnosis of diabetes and in 8.3% (4/48) in newly diagnosed subjects who had a documented non-diabetic oral glucose tolerance test within 4 years prior to diagnosis of diabetes. The prevalence of retinopathy in subjects with impaired glucose tolerance was 12% (8/68). Retinopathy at the time of diagnosis of diabetes was significantly associated with lower body mass index and higher systolic blood pressure but not glycaemia. Retinopathy was present in 375 (37.8 %) diabetic subjects and 14 (5.2 %) non-diabetic subjects. Among all subjects with diabetes (duration 0-37 years), stepwise multivariate analysis showed non-proliferative retinopathy to be associated with duration of diabetes, mean blood pressure, fasting plasma glucose, treatment with insulin and albuminuria. Proliferative retinopathy was seen in 34 (2.7%) of diabetic and none of the non-diabetic subjects, and was associated with 2 h post-load glucose concentrations, as well as albuminuria, insulin treatment, younger age, and diastolic blood pressure. These data confirm the need for fundus examination at the time of diagnosis of diabetes and during long-term follow-up. Albuminuria and blood pressure are potentially modifiable risk factors and the impact of treating these on incidence and progression of diabetic retinopathy need to be assessed.
Adolescent↗
Influence of high impact loading on ultrasound bone measurements in children: a cross-sectional report.
Evidence suggests that weight-bearing exercise during the growing years may enhance peak bone mass. The purpose of this study was to compare ultrasound bone measurements, serum alkaline phosphatase (S-ALP), serum osteocalcin (S-OC), and dietary calcium in highly active and normal healthy male children. Subjects were 33 elite and subelite male gymnasts and 40 normoactive controls matched for age (9.4 +/- 1.1 years), height (133.9 +/- 5.9 cm), and weight (30.1 +/- 3.8 kg). Measurements of broadband ultrasound attenuation (dB/MHz) through the calcaneus (CBUA) and ultrasound velocity (m/s) through the calcaneus (CVOS), distal radius (RVOS), and proximal phalanx of the index finger (PVOS) were performed using a Contact Ultrasonic Bone Analyzer (CUBA Research). Gymnasts had significantly greater CVOS (P < 0.001), RVOS (P < 0.0001), and PVOS (P < 0.05). There were no differences in CBUA, S-ALP, or S-OC between groups. RVOS correlated significantly with dietary calcium intake in all subjects (P < 0.05) and training time in the gymnasts (P < 0.05). Though gymnasts had significantly greater calcium intakes than controls (P < 0.05), whose mean value was below the RDA, after controlling for calcium intake in the gymnasts alone, RVOS was still significantly correlated with training time (P < 0.05). These preliminary results suggest that the heavy musculoskeletal loading inherent in gymnastics training produces positive adaptive responses in the growing skeleton. Furthermore, ultrasound appears to provide a safe, noninvasive means of comparing the skeletal status of exercising and normal healthy children, whereas single samples of biochemical markers did not discriminate between the groups.
Bone Density↗
[Autoantibody pattern in scleritis and episcleritis].
BACKGROUND: Episcleritis and scleritis can be caused by various systemic disorders, which can be triggered by infectious diseases. We studied the autoantibody pattern against various organ-specific and non-organ-specific antigens in episcleritis and scleritis patients. MATERIAL AND METHODS: Sera from 46 patients (episcleritis n = 28, scleritis n = 18) were studied for antibodies against nuclei, smooth muscle cells, mitochondria, endothelial cells, sarcolemma, liver cells, heart muscle fibrils, parietal cells and thyroid cells by immunofluorescence testing. Titers of antibodies against thyroglobulin, laminin, keratin and microsomes were evaluated by ELISA. RESULTS: In patients with episcleritis the pattern of autoantibodies found was different from that in scleritis patients. Thus, in episcleritis the levels of antibodies against sarcolemma (32%), parietal cells (25%), laminin (38%), keratin (58%) and microsomes (28%) were elevated, while scleritis patients, besides keratin antibodies (50%), demonstrated anti-nuclear antibodies (ANA) in 28% of cases. These differences were not significant. Approximately 5% of normal control patients show these antibodies. CONCLUSIONS: Previous studies have shown that episcleritis rarely develops into scleritis. Our results suggest that this may be due to different underlying diseases. While 28% of scleritis patients had ANA, which may suggest an autoimmune disposition related to collagenosis, episcleritis patients had a different autoantibody pattern such as has been found in various infectious diseases and diseases for which triggering by infectious organisms seems possible, such as anterior uveitis, ankylosing spondylitis and Behçet disease. Investigations in larger groups of patients are needed to check the statistical significance of these differences.
Adult↗
Axonal growth and pathfinding: from phenomena to molecules.
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Animals↗
Incorporating fat-modified foods into a food frequency questionnaire improves classification of fat intake.
OBJECTIVE: To determine the extent to which incorporating fat-modified foods into a food frequency questionnaire influences the agreement of energy and nutrient estimates with estimates obtained from food records. DESIGN: Subjects completed four 2-day food records at 3-month intervals. At the end of the recording period, a food frequency questionnaire was administered to assess usual daily intake during the preceding year. SUBJECTS/SETTING: One hundred and three subjects selected from a population-based sample of adults participating in the Beaver Dam Eye Study. STATISTICAL ANALYSES PERFORMED: Subjects were categorized into three groups on the basis of their frequency of consumption of fat-modified foods. For each group, correlations were calculated between food record estimates and estimates obtained from the original food frequency questionnaire, the original with a low-fat option, and the fat-modified questionnaire. RESULTS: For persons categorized as high consumers of fat-modified foods, incorporating questions regarding the consumption of these products resulted in higher correlations with food record estimates (original vs fat-modified version) for percentage of energy from total fat (.32 vs .47), saturated fat (.20 vs .41), oleic acid (.32 vs .50), and linoleic acid (.40 vs .46). High consumers differed in several characteristics that could be associated with disease risk (eg, higher ratios of serum total cholesterol to high-density lipoprotein cholesterol). CONCLUSIONS: Failure to account for the consumption of fat-modified foods in epidemiologic studies may result in misclassification of fat exposures. Because patterns of misclassification could be different for those at risk for disease, results of epidemiologic studies could be biased if these foods are excluded. Thus, incorporating fat-modified foods into food frequency questionnaires will improve the ability of researchers to correctly classify fat exposures and to evaluate potentially important relationships between fat intake and disease risk.
Aged↗
Cardiovascular disease, selected cardiovascular disease risk factors, and age-related cataracts: the Beaver Dam Eye Study.
PURPOSE: To examine the associations of cardiovascular disease and selected cardiovascular disease risk factors with the prevalence of age-related cataract. METHODS: We conducted a population-based prevalence study of adults aged 43 to 86 years (n = 4,926) in Beaver Dam, Wisconsin. An ocular examination including lens photographs, medical history, height and weight measurement, blood testing, and photograph grading was performed according to standard protocols. RESULTS: Age and sex influenced most of the relationships between risk variables and cataract. Many relationships apparent in univariate analyses were not significant when controlling for confounders. In multivariate models, higher glycated hemoglobin was significantly and consistently associated with increased risk of nuclear cataract in women. For cortical cataract, higher serum high density lipoprotein cholesterol was associated with decreased risk in women. For posterior subcapsular cataract, men with higher ratios of total to high-density lipoprotein cholesterol were at increased risk. History of cardiovascular disease was not associated with cataracts in persons with or without diabetes after controlling for additional risk indicators. CONCLUSIONS: Some risk factors for cardiovascular disease were associated with increased frequency of age-related lens opacities. Age and sex influenced these relationships but did not entirely explain them. Longitudinal follow-up is necessary to determine antecedent-consequent relationships that may suggest causal associations.
Adult↗
The relation of cardiovascular disease and its risk factors to the 5-year incidence of age-related maculopathy: the Beaver Dam Eye Study.
OBJECTIVE: The purpose of the study is to examine the association between cardiovascular disease and its risk factors and the incidence of age-related maculopathy. PARTICIPANTS: A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied at baseline and 5 years later. METHODS: Standardized protocols for physical examination, blood collection, administration of a questionnaire, and stereoscopic color fundus photography to determine age-related maculopathy were used. Standard univariate and multivariate analyses were performed. MAIN OUTCOME MEASURES: Incidence and progression of age-related maculopathy were measured. RESULTS: After controlling for age and gender, the authors found both higher systolic blood pressure (odds ratio [OR] per 10 mmHg, 1.16; 95% confidence interval [CI] 1.05, 1.27) and uncontrolled treated hypertension (OR 1.98, 95% CI 1.00, 3.94) were related to the incidence of retinal pigment epithelial depigmentation. After controlling for age and gender, the authors found that both blood pressure and uncontrolled treated hypertension were not significantly associated with an increased risk of having exudative macular degeneration develop (for systolic blood pressure, OR 1.18, 95% CI 0.95, 1.45; for uncontrolled treated hypertension, OR 2.10, 95% CI 0.54, 8.11). After controlling for age and gender, the authors found higher pulse pressure was significantly associated with increased incidence of retinal pigment epithelial depigmentation (OR per 10 mmHg 1.27, 95% CI 1.14, 1.42) and exudative macular degeneration (OR per 10 mmHg 1.29, 95% CI 1.02, 1.65). These relations remained significant after controlling for other risk factors in multivariable analyses. CONCLUSIONS: These findings indicate modest relations between higher pulse pressure (a presumed indicator of atherosclerotic vascular disease) and uncontrolled hypertension with increased 5-year incidence of retinal pigment epithelial depigmentation. Overall, however, data from this study show neither consistent nor strong relations between cardiovascular disease and most of its risk factors with the incidence of lesions associated with age-related maculopathy.
Adult↗
How should we evaluate a cohort study? Study design.
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Cohort Studies↗
Incident cataract surgery: the Beaver Dam eye study.
PURPOSE: The authors describe the incidence of cataract surgery in participants of the Beaver Dam Eye Study. METHODS: Objective evidence of cataract extraction as obtained at follow-up examinations of participants of a population-based cohort is given. Participants included all adults 43 to 84 years of age who lived in the city or township of Beaver Dam, Wisconsin. RESULTS: Age-adjusted incidence is significantly greater for women, for those with lower diastolic blood pressure, for those with hypertension, widows/widowers, and for those who report that their vision is worse than it had been. Multivariate analyses disclose that the following characteristics (with their respective odds ratios) are significantly associated with incident cataract surgery: age (odds ratio [OR] for 10 years 1.40; 95% confidence interval [CI] 1.02, 1.91); cigarette smoking (> or = 35 pack years; OR 1.91; 95% CI 1.16, 3.17); nuclear cataract (OR 35.58; 95% CI 10.12, 125.17 at age 50 years); cortical cataract (OR 3.75; 95% CI 2.40, 5.88); posterior subcapsular cataract (OR 15.51; 95% CI 8.27, 29.09); impaired vision (OR 3.76; 95% CI 2.33, 6.05); intraocular pressure (> or = 14 mmHg; OR 2.56; 95% CI 1.50, 4.38); visual sensitivity to light (OR 1.94; 95% CI 1.19, 3.17); refractive error (myopic) (OR 1.99; 95% CI 1.22, 3.24); yellow color (OR 1.69; 95% CI 1.02, 2.81); and being examined by an ophthalmologist within 2 years (OR 1.54; 95% CI 1.03, 2.30). CONCLUSIONS: Many factors are associated with cataract surgery, but the prior presence of posterior subcapsular cataract is the most important lens opacity. In addition, visual function changes, which may be relatively mild, are associated with subsequent incident surgery.
Adult↗
The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study.
PURPOSE: The aim of the study was to describe the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. POPULATION: A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period. METHODS: Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older had a significantly (P < 0.01) higher 5-year incidence of the following characteristics than people 43 to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or = 250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs. 0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the incidence of early age-related maculopathy was 2.2 times (95% confidence interval 1.6, 3.2) as likely in women 75 years of age or older compared with men this age. At follow-up, late age-related macular degeneration was more likely to develop in eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions. CONCLUSIONS: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older, and in women compared with men that age. The findings demonstrate that the presence of soft drusen and pigmentary abnormalities significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.
Adult↗