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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 253 records · Page 14Linked to original sources
PubMed1998

The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes.

OBJECTIVE: To examine the 14-year incidence and progression of diabetic retinopathy and macular edema and its relation to various risk factors. DESIGN: Population-based incidence study. SETTING: The study was conducted in an 11-county area in southern Wisconsin. PARTICIPANTS: Six hundred thirty-four insulin-taking persons with diabetes diagnosed before age 30 years participated in baseline, 4-year, 10-year, and 14-year follow-up examinations. MAIN OUTCOME MEASURES: The 14-year progression of retinopathy, progression to proliferative retinopathy, and incidence of macular edema were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. RESULTS: The 14-year rate of progression of retinopathy was 86%, regression of retinopathy was 17%, progression to proliferative retinopathy was 37%, and incidence of macular edema was 26%. Progression of retinopathy was more likely with less severe retinopathy, being male, having higher glycosylated hemoglobin or diastolic blood pressure at baseline, an increase in the glycosylated hemoglobin level, and an increase in diastolic blood pressure level from the baseline to the 4-year follow-up. Increased risk of proliferative retinopathy or incidence of macular edema was associated with more severe baseline retinopathy, higher glycosylated hemoglobin at baseline, and an increase in the glycosylated hemoglobin between the baseline and 4-year follow-up examination. The increased risk of proliferative retinopathy was associated with the presence of hypertension at baseline, whereas the increased risk of a participant having macular edema develop was associated with the presence of gross proteinuria at baseline. Lower glycosylated hemoglobin at baseline was associated with improvement in retinopathy. CONCLUSIONS: These data suggest relatively high 14-year rates of progression of retinopathy and incidence of macular edema. These data also suggest that a reduction of hyperglycemia and hypertension may result in a beneficial decrease in the progression to proliferative retinopathy.

Adolescent↗
PubMed1998

Performance-based and self-assessed measures of visual function as related to history of falls, hip fractures, and measured gait time. The Beaver Dam Eye Study.

OBJECTIVE: The purpose of the study is to report relationships between visual function parameters and falls, hip fractures, and gait time in adults. DESIGN: Population-based study. PARTICIPANTS: The 3722 persons who participated in the 5-year follow-up of the Beaver Dam Eye Study cohort. MAIN OUTCOME MEASURES: The visual functions measured at the examination were best-corrected visual acuity, current binocular acuity, near acuity, contrast sensitivity, and visual threshold to light. Information on falls and hip fractures was obtained by structured interview. Gait time was measured by standardized protocol. RESULTS: History of falls and hip fractures increased with age, as did time to walk a measured course. Falls were more commonly reported for all persons who had poorer visual function, although not all relationships were significant in persons less than 60 years of age. In persons 60 years of age and older, hip fractures after the age of 40 were significantly related to all measures of visual function. Time to walk a measured course was significantly related to all measures of visual function. CONCLUSIONS: These data indicate a consistent relationship between falls, fractures, gait time, and visual functions. Longitudinal data are necessary to accurately determine temporal relationships and to determine the likelihood of a causal association. In the interim, these data suggest that improving visual function may have benefits such as decreased traumatic events and improved mobility.

Accidental Falls↗
PubMed1998

Alcohol consumption and the 5-year incidence of age-related maculopathy: the Beaver Dam eye study.

OBJECTIVE: This study evaluated alcohol consumption as a risk factor for incidence of age-related maculopathy (ARM). DESIGN: Persons aged 43 to 86 years in 1988 in Beaver Dam, Wisconsin, were examined from 1988 through 1990 and 1993 through 1995, n = 3684. The presence and severity of ARM at both examinations were determined from gradings of stereoscopic fundus photographs using the Wisconsin Age-related Maculopathy Classification System. Alcohol consumption was determined by self-report. RESULTS: Men drinking at least 78 g/week of alcohol from beer had a higher 5-year age-adjusted incidence of early ARM (10.6%) than did men who did not drink beer (6.9%), but the test for trend was only borderline significant (P = 0.08). However, incidence of soft indistinct drusen (P = 0.01), increased drusen area (P < 0.01), and confluent drusen (P = 0.02) are all associated with beer drinking in men. Increased retinal pigment and retinal pigment epithelial depigmentation are not associated with beer drinking in men or women nor are any lesions associated with total alcohol consumption or consumption from liquor or wine in either men or women. CONCLUSIONS: Except for an association of beer drinking with retinal drusen in men, consumption of alcoholic beverages is not likely to be an important risk factor for incidence of ARM.

Adult↗
PubMed1998

The 14-year incidence of visual loss in a diabetic population.

OBJECTIVE: The purpose of the study was to estimate the 14-year incidence of visual loss in a diabetic population and to examine its relationship to potential risk factors. DESIGN: Cohort study. PARTICIPANTS: A population-based sample of younger onset diabetic persons diagnosed younger than 30 years of age and taking insulin (n = 880) were examined at baseline, 4 years, 10 years, and 14 years. INTERVENTION: Visual acuity (VA) as measured by the Early Treatment Diabetic Retinopathy Study protocol was performed. MAIN OUTCOME MEASURES: Visual impairment (VI), defined as a VA of 20/40 or worse in the better eye; blindness, defined as a VA of 20/200 or worse in the better eye; and doubling of the visual angle were measured. RESULTS: Cumulative 14-year incidences of VI, doubling of the visual angle, and blindness were 12.7%, 14.2%, and 2.4%, respectively. In univariate analyses, loss of vision as measured by doubling of the visual angle is associated with older age, longer duration of diabetes, higher glycosylated hemoglobin, higher systolic and diastolic blood pressure, presence of proteinuria, more pack-years smoked, presence of macular edema, and more severe retinopathy. In logistic regression analyses, incidence of doubling of the visual angle is associated independently with retinopathy (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03, 1.11 for each level), glycosylated hemoglobin (OR, 1.46; 95% CI, 1.28, 1.66 for each 1%), proteinuria (OR, 2.32; 95% CI, 1.39, 3.88 for presence), and age (OR, 1.45; 95% CI, 1.20, 1.75 for 10 years). In addition, a change in glycosylated hemoglobin from baseline to the 4-year examination is associated with loss of vision (OR, 1.15; 95% CI, 1.02, 1.30 for a 1% increase). CONCLUSIONS: Loss of vision continues to be significant in persons with diabetes. These results suggest that prevention of retinopathy through control of glycemia will have a beneficial effect on visual outcome.

Adolescent↗
PubMed1998

The economic effect of child abuse in the burn unit.

The financial burden imposed on society by abusing children through burn injury is unknown. This study retrospectively evaluates the economic impact and demographics of such abuse on patients and their families treated at Children's Hospital Medical Center of Akron (CHMCA) from four counties over a 5 year period. The inclusive group consisted of all children evaluated during the stated period referred to Social Services for possible child abuse. There were 104 children (55 females and 49 males, 46% black and 56% white) with a mean age of 3.76 years. 71% of the patients came from single parent homes (all single mothers). There were a total of 58 admissions with a mean length of stay of 10.53 days. Total cost for all patients was approximately 1.2 million dollars for health care, of which 65% was government funded. In addition to hospital costs, the perpetrators incurred court costs and jail costs, all of which were the financial responsibility of Summit County. Child abuse through burns imposes a potentially preventable financial burden. This study does not take into account the socioeconomic and psychological impact on the abused victims through life, which is incalculable. By increasing awareness about the demographics and financial burden of child abuse, this paper may serve as a focus for further study and prevention of such abuse.

Burn Units↗
PubMed1998

Multiple roles for hepatocyte growth factor in sympathetic neuron development.

We have studied the role of hepatocyte growth factor (HGF)/Met signaling in the development of sympathetic neuroblasts and neurons. Anti-HGF antibodies reduced the number of sympathetic neuroblasts that differentiated into neurons, but neither anti-HGF antibodies nor HGF affected neuroblast proliferation. Anti-HGF antibodies also reduced the survival of neuroblasts but not sympathetic neurons. HGF greatly enhanced the neurite outgrowth of NGF-dependent sympathetic neurons throughout development. These in vitro effects of anti-HGF antibodies and HGF were abolished by a disabling mutation of Met, the HGF receptor tyrosine kinase. The Met mutation also increased sympathetic neuroblast apoptosis in vivo. Because Met and HGF are expressed in sympathetic ganglia throughout development, it is possible that the multiple effects of HGF/Met signaling on sympathetic neuroblasts and neurons occur in part by an autocrine mechanism.

Animals↗
PubMed1998

Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responses.

Neurotrophins are a family of soluble ligands that promote the survival and differentiation of peripheral and central neurons and regulate synaptic function. The two neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), bind and activate a single high-affinity receptor, TrkB. Experiments in cell culture have revealed that an intact Shc adaptor binding site on TrkB and subsequent activation of the Ras/MAPK pathway are important for neuronal survival and neurite outgrowth. To elucidate the intracellular signaling pathways that mediate the diverse effects of BDNF and NT4 in vivo, we have mutated in the mouse germline the Shc binding site in the trkB gene. This trkB(shc) mutation revealed distinctive responses to BDNF and NT4. While nearly all NT4-dependent sensory neurons were lost in trkB(shc/shc) mutant mice, BDNF-dependent neurons were only modestly affected. Activation of MAP kinases and in vitro survival of cultured trkB(shc/shc) neurons were reduced in response to both neurotrophins, with NT4 being less potent than BDNF, suggesting differential activation of TrkB by the two ligands. Moreover, while the Ras/MAPK pathway is required for in vitro differentiation of neuronal cells, trkB(shc/shc) mutant mice do not show any defects in BDNF-dependent differentiation of CNS neurons or in the function of sensory neurons that mediate innocuous touch.

Animals↗
PubMed1998

Signaling by Eph receptors and their ephrin ligands.

What are the mechanisms by which Eph receptor tyrosine kinases guide axons and migrating cells? Recent results show that Eph receptors bind some of the well-known effector molecules that are implicated in the organization of the actin cytoskeleton; moreover, biochemical and genetic evidence suggests a signaling role for transmembrane ephrin ligands in axon pathfinding.

Animals↗
PubMed1998

Aging and high-frequency hearing sensitivity.

As part of a large population-based study of hearing and aging, ultra high-frequency (9-20 kHz) threshold measures are reported for 3396 participants grouped by age (48-59 years, n = 1233; 60-69 years, n = 1031; 70-79 years, n = 851; 80-92 years, n = 281). Ultra high-frequency (UHF) thresholds were higher for older age groups. The percentage of unmeasurable responses also was significantly higher for older age groups and for higher frequencies in the UHF range. The observed age effects remained significant after adjusting for gender. In general, UHF thresholds were significantly higher for men compared to those for women at lower UHF frequencies (9-14 kHz), but were not significantly different by gender for the highest UHF frequencies (16, 18, and 20 kHz). After accounting for hearing loss at traditional audiometric frequencies (250-8000 Hz), the age effect still remained; even for comparable degrees of sensorineural hearing loss, participants in older age groups evidenced higher UHF thresholds.

Adult↗
PubMed1998

Anti-mitochondrial antibodies in patients with dilated cardiomyopathy (anti-M7) are directed against flavoenzymes with covalently bound FAD.

Anti-mitochondrial antibodies (anti-M7) in sera from patients with dilated cardiomyopathy and myocarditis recognize, besides mitochondrial antigens, bacterial sarcosine dehydrogenase. The common target antigen was identified as the covalently bound FAD of mitochondrial and bacterial flavoenzymes. Thus, anti-M7-positive serum reacted on Western blots exclusively with covalently flavinylated enzymes. The antigenic specificity of anti-M7 sera was reproduced by an antiserum raised in rabbits with 6-hydroxy-D-nicotine oxidase. The heart mitochondrial membrane antigen recognized by anti-M7 serum was identified as the flavoprotein subunit of succinate dehydrogenase, the antigens in rat liver mitochondrial matrix as the flavoenzymes dimethylglycine dehydrogenase and sarcosine dehydrogenase. Anti-M7 serum contained a specific anti-flavoenzyme antibody fraction. Nanomolar concentrations of FAD and riboflavin inhibited the immune reaction on Western blots and in ELISA, and incubation with FAD-agarose depleted the anti-M7 activity of the serum. N-terminally deleted dimethylglycine dehydrogenase proteins were only immunoprecipitated by anti-M7 sera when the FAD was covalently incorporated. An affinity constant (KD) of 10(-8) M was established for the anti-flavoenzyme antibodies by competitive ELISA. Of patients with cardiomyopathy and myocarditis, 36% and 25%, respectively, were anti-flavoenzyme-positive by Western blot and ELISA, but only two of 15 patients with other heart diseases and none of 50 healthy controls.

Animals↗
PubMed1998

Usual consumption of plant foods containing phytoestrogens and sex hormone levels in postmenopausal women in Wisconsin.

Consumption of phytoestrogens may reduce hormone-dependent cancer risk through alterations in the actions or metabolism of steroid hormones. Studies in humans of phytoestrogen-hormone interactions have been limited and inconsistent. Relations between the consumption of phytoestrogen-containing foods and serum sex hormones and sex hormone-binding globulin were studied in a population-based sample of postmenopausal women who participated in the Nutritional Factors in Eye Disease Study of the Beaver Dam Eye Study. Information on phytoestrogen-containing foods (broccoli, carrots, cauliflower, chili, dark bread, peas, and dried beans) was collected by interviewer-administered food-frequency questionnaires. Estrone, sex hormone-binding globulin, dehydroepiandrosterone sulfate, and total and free testosterone were measured. Analyses included 246 postmenopausal women not taking hormone replacements. Partial correlations between hormones and intake of phytoestrogen-containing foods were computed, with adjustment for age, body mass index, years since menopause, and total energy intake. Number of standard servings per week of whole-grain products from the dark bread group was inversely associated with total testosterone (r = -0.20, p = 0.002). Although not statistically significant, other hormones displayed similar inverse associations with dark bread consistent with a common metabolic pathway. Although the magnitude of association was small, the data are consistent with the possibility that consumption of some phytoestrogen-containing foods may affect levels of testosterone in postmenopausal women.

Adult↗
PubMed1998

Weight change and glycemic control in a population-based sample of adults with older-onset diabetes.

BACKGROUND: Numerous clinic-based studies have observed improved glycemic control with even moderate weight reductions, for periods up to 1 year, in obese subjects with noninsulin-dependent diabetes mellitus (NIDDM). Similar benefits of weight loss have not been well documented in free-living populations, particularly in older persons with NIDDM of long duration. METHODS: Relations between weight change and glycosylated hemoglobin were evaluated in a population-based sample of persons with older-onset diabetes. Persons participating in baseline (1980-1982, n = 1370) and two follow-up examinations (1984-1986, n = 987; 1990-1992, n = 550) were included. Mean glycosylated hemoglobin levels among those losing, gaining, or remaining within 5 kg were compared in all subjects combined and stratified by insulin use, using ordinary least-squares regression to adjust for confounding variables. RESULTS: Subjects who lost weight had higher mean glycosylated hemoglobin compared to those who gained weight (baseline to second exam only). This pattern remained in those not using insulin. Weight change was not related to glycosylated hemoglobin in persons using insulin. CONCLUSIONS: Associations suggest that in older persons not using insulin, moderate weight loss over periods of 4-6 years has little beneficial impact on glycosylated hemoglobin. Weight loss may be reflecting disease processes that also result in poor glycemic control. Intentional weight loss achieved over a shorter time period and maintained through the later years in older diabetic persons remains to be evaluated.

Adult↗
PubMed1998

Supplement users differ from nonusers in demographic, lifestyle, dietary and health characteristics.

This study delineates demographic, lifestyle, dietary and health factors associated with the use of supplements at varying levels. Data are from a population-based cohort of 2,152 middle- to older-age adults living in Beaver Dam, Wisconsin. Information was collected by in-person interviews between 1988-1990. Associations were adjusted for gender and age. Use of supplements was more prevalent among women, persons with more than 12 years of education, those with relatively low body mass indices, persons with active lifestyles, and persons who never smoked as compared to current smokers (P </= 0.05). Supplement users had higher intakes of most of the micronutrients from food that were examined in this study, including the antioxidant vitamins C and E and certain carotenoids (P </= 0.05). Intakes of dairy products and also foods that are important sources of vitamin C and carotenoids were higher among users of supplements, but relationships differed by gender and by the type and level of supplement intake. These findings suggest that several factors need to be considered potential confounders in observational studies that examine the etiologic role of supplements in the occurrence of chronic disease.

Adult↗
PubMed1998

Low prevalence of hearing aid use among older adults with hearing loss: the Epidemiology of Hearing Loss Study.

OBJECTIVES: To measure the prevalence of hearing aid use among older adults with hearing loss and to identify factors associated with those currently using hearing aids. DESIGN: Population-based cohort study. SETTING: The south-central Wisconsin community of Beaver Dam. PARTICIPANTS: A total of 1629 adults, aged 48 to 92 years, who have hearing loss and are participating in the Epidemiology of Hearing Loss Study and the Beaver Dam Eye Study. MEASUREMENTS: A hearing-related risk factor and medical history questionnaire, the Hearing Handicap Inventory for the Elderly (screening version), screening tympanometry, pure-tone air- and bone-conduction audiometry, and word recognition tests were administered by trained examiners using standard protocols. RESULTS: The prevalence of current hearing aid use among those with a hearing loss (pure-tone average > 25 decibels hearing level over 500, 1000, 2000, and 4000 Hertz, worse ear) was 14.6%. The prevalence was 55% in a subset of the most severely affected participants. In univariate analyses, current hearing aid use was associated with age, severity of loss, word recognition scores, self-reported hearing loss, self-perceived hearing handicap, and history of noise exposure. Factors associated with current hearing aid use in multivariate logistic regression models were age, severity of loss, education, word recognition scores, Hearing Handicap Inventory for the Elderly (screening version) score, and self-report of a hearing loss. CONCLUSIONS: Few older adults with hearing loss are currently utilizing hearing aids. Improved screening and intervention programs to identify older adults who would benefit from amplification are needed to improve hearing-related quality of life for this large segment of the population.

Age Factors↗
PubMed1998

Outcome states of colorectal cancer: identification and description using patient focus groups.

OBJECTIVE: Utilities for the outcome states of colorectal cancer must be measured to evaluate the cost-utility of screening and surveillance strategies for this disease. We sought to identify these outcome states, define their associated areas of morbidity, and construct representative descriptions of them for use in a utilities assessment instrument. METHODS: We identified candidate colorectal cancer outcome states based on a review of the literature and interviews with health care professionals. We organized patient focus groups from each of the candidate outcome states to examine their homogeneity and define their associated areas of morbidity. After analyzing the focus group transcripts, we identified and described outcome states of colorectal cancer for future incorporation into a utilities assessment instrument. RESULTS: Six candidate outcome states of colorectal cancer were identified based on disease stage and location at diagnosis. Thirty-eight patients then participated in six focus groups. Analysis of the focus group transcripts revealed seven areas of morbidity associated with colorectal cancer. These areas included problems with social interaction and cognition, fear of cancer recurrence, pain, fatigue, changes in bowel habits, and sexual dysfunction. Based on differences in the intensity and frequency of the symptoms reported in each of these areas, seven distinct outcome states of colorectal cancer were identified and described. CONCLUSION: Clinically distinct outcome states of colorectal cancer are determined by the stage and location of the cancer at the time of diagnosis. Descriptions of these outcome states were created using data collected from patient focus groups. These descriptions can be incorporated into a utilities assessment instrument.

Aged↗
PubMed1998

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Adult↗
PubMed1998

The Onchocerciasis Elimination Program for the Americas: a history of partnership.

The decision in 1987 by the pharmaceutical firm Merck & Co. to provide Mectizan (ivermectin) free of charge to river blindness control programs has challenged the international public health community to find effective ways to distribute the drug to rural populations most affected by onchocerciasis. In the Americas, PAHO responded to that challenge by calling for the elimination of all morbidity from onchocerciasis from the Region by the year 2007 through mass distribution of ivermectin. Since 1991, a multinational, multiagency partnership (consisting of PAHO, the endemic countries, nongovernmental development organizations, the Centers for Disease Control and Prevention in Atlanta, Georgia, as well as academic institutions and funding agencies) has developed the political, financial, and technical support needed to move toward the realization of that goal. This partnership is embodied in the Onchocerciasis Elimination Program for the Americas (OEPA), which is supported by the River Blindness Foundation (RBF) and now by the Carter Center. OEPA was conceived as a means of maintaining a regional initiative to eliminate what is otherwise a low priority disease. Since its inception in 1993, the OEPA has provided more than US$ 2 million in financial, managerial, and technical assistance to stimulate and/or support programs in Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela, so as to take full advantage of the Merck donation. Now halfway into a five-year, US$ 4 million grant provided through the Inter-American Development Bank, the OEPA's capacity to support the regional initiative is assured through 1999.

Americas↗