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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 271 records · Page 15Linked to original sources
PubMed1998

Self-rated health and diabetes of long duration. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

OBJECTIVE: To evaluate the self-reported quality of life in individuals with diabetes of long duration. RESEARCH DESIGN AND METHODS: An interview was administered 14 years after baseline to two cohorts of individuals with diabetes who have been followed in an epidemiological study periodically since 1980. Responses to the Medical Outcomes Study Short Form 36 as related to complications of diabetes, age, glycosylated hemoglobin level, and other characteristics were assessed. RESULTS: Physical function, physical role, general health scales, and a general question about health were related to diabetes characteristics in older- and younger-onset individuals. Symptoms of sensory neuropathy were associated with the four measures in both younger- (n = 645) and older-onset (n = 292) individuals. Other descriptive variables in the younger-onset group were the presence of nephropathy, cardiovascular disease, smoking, peak expiratory flow, physical activity, and glycosylated hemoglobin. Hypoglycemic reactions were of only borderline significance and that for only one scale (physical role). In older-onset individuals, cardiovascular disease, physical activity, and sex were descriptive of responses to the quality-of-life questions. CONCLUSIONS: Factors related to diabetes contribute to self-assessed health. some of these factors may be modifiable, which, if altered, may lead to improved quality of life.

Activities of Daily Living↗
PubMed1998

Relation of glycemic control to diabetic complications and health outcomes.

Data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) demonstrated that the incidence of diabetic complications is directly related to glycemic control. The results of the Diabetes Control and Complications Trial and Stockholm Study showed that intensive insulin therapy and improved glycemic control reduced diabetic complications in people with type 1 diabetes. Results of the U.K. Prospective Diabetes Study Group and the Kumamoto trial also support the relationship between glycemic control and diabetic complications in individuals with type 2 diabetes. Preliminary WESDR health outcomes data suggest that higher levels of glycemia are related to a decreasing quality of life. This study and others showing that higher levels of glycemia are associated with an increased incidence of complications suggest that it is the complications of diabetes that contribute to a decrease in quality of life. Despite evidence of the benefits of improved glycemic control, a large percentage of people with diabetes maintain poor glucose control in part because of the limitations of the therapies available for diabetes management.

Albuminuria↗
PubMed1998

Development and application of a model to estimate the impact of type 1 diabetes on health-related quality of life.

OBJECTIVE: To develop a simulation model to assess the impact of type 1 diabetes and its associated complications on health-related quality of life of a population. RESEARCH DESIGN AND METHODS: The methodology builds upon 1) an existing population model of type 1 diabetes progression, 2) an empirical study designed to measure state- and age-specific health statuses of type 1 diabetes, and 3) existing literature to quantify quality of life of the corresponding health status. Health statuses were measured in a group of type 1 diabetic patients using the Medical Outcomes Study short form 36 (SF-36). A published empirical regression equation was then used to predict corresponding Quality of Well-Being Index (QWB) scores from these assessments. The QWB scores were incorporated into a previously developed type 1 diabetes progression and cost simulation model. Sensitivity analyses on key parameters were performed, and the model was found to be robust. RESULTS: The augmented model can estimate quality-adjusted life years (QALYs) as well as costs associated with type 1 diabetes on any population of interest over any period of time. The model is used to compare intensive versus conventional treatment strategies using a simplified set of assumptions regarding the relative effects of these alternative treatments. With these assumptions, intensive strategy produces more QALYs than does conventional strategy and is cost-beneficial after 5 years. CONCLUSIONS: The model enables health planners to perform cost-effectiveness analyses to compare alternative treatment strategies for type 1 diabetes and support subsequent decision making.

Adult↗
PubMed1998

Development of proliferative diabetic retinopathy in African-Americans and whites with type 1 diabetes.

OBJECTIVE: To investigate the comparable risk of developing proliferative diabetic retinopathy (PDR) in African-Americans and whites with type 1 diabetes. RESEARCH DESIGN AND METHODS: Using a cohort design with the sample drawn from medical records, the sample consisted of 312 people with type 1 diabetes (97 African-Americans, 215 whites) having at least two visits to a Model Demonstration Unit with gradeable fundus photographs (stereo, color, 7 standard fields). Excluded were subjects with preexisting or treated PDR or hemoglobinopathy. Masked grading of the fundus photographs was conducted at the Wisconsin Reading Center. RESULTS: At baseline, African-Americans had poorer glycemic control (mean HbA1 of 11.3 vs. 10.0%, P < 0.0001), higher systolic blood pressure (mean of 117 vs. 110 mmHg, P < 0.001), and were older (mean of 26.8 vs. 19.3 years, P < 0.0001) than the white subjects. African-Americans also tended to have slightly longer duration of diabetes and length of follow-up. In the African-Americans, 17.5% developed PDR, compared with 10.2% in the 215 whites, for an odds ratio (OR) of 1.86 (95% CI 0.93-3.70). When adjusted for baseline glycemic control, retinopathy grade, and length of follow-up, race was not a significant risk factor (OR = 0.73, 95% CI 0.30-1.78). CONCLUSIONS: African-Americans with type 1 diabetes may have a higher rate of developing PDR. The observed racial difference, however, is attributable to the presence of a worse risk factor profile, especially to poorer glycemic control. Efforts should be expanded to improve the care for all individuals with poor glycemic control.

Adolescent↗
PubMed1998

Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes? A U.S. population study.

OBJECTIVE: To compare the risk for diabetic retinopathy in non-Hispanic white, non-Hispanic black, and Mexican-American adults with type 2 diabetes in the U.S. population. RESEARCH DESIGN AND METHODS: Representative population-based samples of people aged > or = 40 years in each of the three racial/ethnic groups were studied in the 1988-1994. Third National Health and Nutrition Examination Survey (NHANES III). Diagnosed diabetes was ascertained by medical history interview, and undiagnosed diabetes by measurement of fasting plasma glucose. A fundus photograph of a single eye was taken with a nonmydriatic camera, and a standardized protocol was used to grade diabetic retinopathy. Information on risk factors for retinopathy was obtained by interview and standard laboratory procedures. RESULTS: Prevalence of any lesions of diabetic retinopathy in people with diagnosed diabetes was 46% higher in non-Hispanic blacks and 84% higher in Mexican Americans, compared with non-Hispanic whites. Blacks and Mexican Americans also had higher rates of moderate and severe retinopathy and higher levels of many putative risk factors for retinopathy. Blacks had lower retinopathy prevalence among those with undiagnosed diabetes. In logistic regression, retinopathy in people with diagnosed diabetes was associated only with measures of diabetes severity (duration of diabetes, HbA1c, level, treatment with insulin and oral agents) and systolic blood pressure. After adjustment for these factors, the risk of retinopathy in Mexican Americans was twice that of non-Hispanic whites, but non-Hispanic blacks were not at higher risk for retinopathy. These risks were similar when people with undiagnosed diabetes were included in the logistic regression models. CONCLUSIONS: The prevalence and severity of diabetic retinopathy is greater in non-Hispanic blacks and Mexican Americans with type 2 diabetes in the U.S. population than in non-Hispanic whites. For blacks, this can be attributed to their higher levels of risk factors for retinopathy, but the excess risk in Mexican Americans is unexplained.

Adult↗
PubMed1998

Association of NIDDM and hearing loss.

OBJECTIVE: To evaluate the association of NIDDM with hearing loss in a large population-based study. RESEARCH DESIGN AND METHODS: Data from population-based longitudinal studies of aging conducted in Beaver Dam, Wisconsin, were used in these analyses. Hearing thresholds were determined by pure-tone air- and bone-conduction audiometry performed by trained technicians following American Speech-Language-Hearing Association specifications. Hearing loss was defined as the pure-tone average of the frequencies 500, 1,000, 2,000, and 4,000 Hz greater than 25 decibels hearing level in the worse ear. Diabetes status was determined by self-report of physician-diagnosed diabetes or by elevated glucose or glycated hemoglobin levels at examination. RESULTS: Of 3,571 study participants, 344 were classified as having NIDDM. Subjects with NIDDM were more likely to have a hearing loss than were subjects without diabetes (59 vs. 44%). After results were adjusted for age, this difference was not statistically significant. After individuals with hearing loss patterns inconsistent with presbycusis were excluded, there was an association between NIDDM and hearing loss when controlling for potential confounders (odds ratio [OR] 1.41, 95% CI 1.05-1.88). There was no association between duration of diabetes or glycemic control and hearing loss. Individuals with NIDDM and nephropathy were more likely to have a hearing loss than were those with NIDDM but no nephropathy (OR 2.28, 95% CI 1.04-5.00). CONCLUSIONS: These data are suggestive of a weak association between NIDDM and hearing loss.

Adult↗
PubMed1998

Aging and word recognition in competing message.

As part of an epidemiologic study of hearing disorders in older adults, word recognition performance (NU-6 word lists in quiet and in competing message) was evaluated for 3189 adults grouped by age (48-59 years, n = 1176; 60-69 years, n = 979; 70-79 years, n = 794; 80-92 years, n = 240). Overall, scores for all measures were worse for older age groups and worse for men than for women. Word recognition scores in competing message were poorer than word recognition scores in quiet for all subjects and age groups. Further, differences in scores across age groups and gender were greater for the word recognition test in competing message than for the word recognition test in quiet. Although degree of hearing loss accounted for the largest portion of variation in word recognition scores, the observed age and gender differences remained significant after adjusting for the degree of sensorineural hearing loss.

Age Distribution↗
PubMed1998

Correlates of lens thickness: the Beaver Dam Eye Study.

PURPOSE: To evaluate the relationships of lens thickness to age, to the presence of a nuclear, cortical, or posterior subcapsular cataract, and to other personal characteristics in participants in the Beaver Dam Eye Study. METHODS: Slit lamp photographs taken during a population-based prevalence study were measured for lens thickness. In addition, slit lamp photographs were graded for nuclear cataracts, and retroillumination photographs were graded for cortical and posterior subcapsular cataracts. A questionnaire was administered, and height, weight, and blood pressure were measured by protocol. RESULTS: Lens thickness increased systematically with age in men and women. In multivariate analysis, age, sex (male), cortical cataract, diabetes, nuclear cataract, and former cigarette smoking were related significantly to lens thickness. CONCLUSIONS: Age was the most significant personal characteristic associated with lens thickness among those subjects considered. In addition, other characteristics, including specific cataract types and risk factors for cataracts, also were associated with thickness. Whether lens thickness among people of the same age is associated prospectively with these characteristics requires a longitudinal follow-up.

Adult↗
PubMed1998

Renal function abnormalities and incident cataract after a five-year interval: The Beaver Dam Eye Study.

PURPOSE: To evaluate the relationship between renal function abnormalities and incidence of age-related cataract. METHODS: In a population-based epidemiologic study of age-related eye disease, cataract was classified based on lens photographs. Standard methods of grading were used. Blood urea nitrogen, serum creatinine, and gross proteinuria were measured using standard protocols. RESULTS: Cortical cataract was associated with increased BUN, but after controlling for age, this relationship was no longer significant. In those with diabetes, elevated BUN or elevated creatinine was associated with increased odds of posterior subcapsular cataract, but these relationships were not significant. CONCLUSION: Renal function abnormalities were not significantly associated with incidence of cataract after controlling for age and gender. However, the power to test these associations was limited. Further longitudinal follow-up of this cohort as well as other studies designed to evaluate these associations are needed.

Adult↗
PubMed1998

Disease progression and cost of insulin dependent diabetes mellitus: development and application of a simulation model.

This paper presents the development and application of a Markov model that simulates the onset and progression of insulin dependent diabetes mellitus (IDDM) and its sequelae. The model estimates direct medical costs resulting from different patterns of health states during the course of the disease. The model is user-friendly and allows for changes in the input variables to be specified, thereby providing a frame-work for sensitivity analysis. The Markov process moves a cohort of individuals through six different health states: Healthy, IDDM without chronic microvascular complications, IDDM with retinopathy alone, IDDM with neuropathy alone or with retinopathy, IDDM with nephropathy, and death. Epidemiologic data were obtained from governmental sources as well as the medical literature. Transition probabilities were estimated using data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Direct medical costs were estimated from actual charges from a local health maintenance organization in Wisconsin. The validity of the model was tested in several ways including a comparison with an independent cost estimate made by the Wisconsin Department of Health and Family Services. The model appears to be useful in estimating the progression and associated costs of IDDM for any large population over any period of time and in allowing changes in the inputs to evaluate their impact thus providing pertinent information to healthcare decision-makers and health planners.

Age Factors↗
PubMed1997

Met receptor signaling is required for sensory nerve development and HGF promotes axonal growth and survival of sensory neurons.

The development of the nervous system is a dynamic process during which factors act in an instructive fashion to direct the differentiation and survival of neurons, and to induce axonal outgrowth, guidance to, and terminal branching within the target tissue. Here we report that mice expressing signaling mutants of the hepatocyte growth factor (HGF) receptor, the Met tyrosine kinase, show a striking reduction of sensory nerves innervating the skin of the limbs and thorax, implicating the HGF/Met system in sensory neuron development. Using in vitro assays, we find that HGF cooperates with nerve growth factor (NGF) to enhance axonal outgrowth from cultured dorsal root ganglion (DRG) neurons. HGF also enhances the neurotrophic activities of NGF in vitro, and Met receptor signaling is required for the survival of a proportion of DRG neurons in vivo. This synergism is specific for NGF but not for the related neurotrophins BDNF and NT3. By using a mild signaling mutant of Met, we have demonstrated previously that Met requires signaling via the adapter molecule Grb2 to induce proliferation of myoblasts. In contrast, the actions of HGF on sensory neurons are mediated by Met effectors distinct from Grb2. Our findings demonstrate a requirement for Met signaling in neurons during development.

Animals↗
PubMed1997

A role for the Ras signalling pathway in synaptic transmission and long-term memory.

Members of the Ras subfamily of small guanine-nucleotide-binding proteins are essential for controlling normal and malignant cell proliferation as well as cell differentiation. The neuronal-specific guanine-nucleotide-exchange factor, Ras-GRF/CDC25Mm, induces Ras signalling in response to Ca2+ influx and activation of G-protein-coupled receptors in vitro, suggesting that it plays a role in neurotransmission and plasticity in vivo. Here we report that mice lacking Ras-GRF are impaired in the process of memory consolidation, as revealed by emotional conditioning tasks that require the function of the amygdala; learning and short-term memory are intact. Electrophysiological measurements in the basolateral amygdala reveal that long-term plasticity is abnormal in mutant mice. In contrast, Ras-GRF mutants do not reveal major deficits in spatial learning tasks such as the Morris water maze, a test that requires hippocampal function. Consistent with apparently normal hippocampal functions, Ras-GRF mutants show normal NMDA (N-methyl-D-aspartate) receptor-dependent long-term potentiation in this structure. These results implicate Ras-GRF signalling via the Ras/MAP kinase pathway in synaptic events leading to formation of long-term memories.

3T3 Cells↗
PubMed1997

Elongation factor Ts of Chlamydia trachomatis: structure of the gene and properties of the protein.

A putative structural gene cluster containing four open reading frames (ORFs) located downstream of the omp1 gene of Chlamydia trachomatis mouse pneumonitis (MoPn) was cloned and sequenced. A GenBank survey indicated that the identified cluster is similar to the rpsB-tsf-pyrH(smbA)-frr region of Escherichia coli. The second ORF was 846 bp encoding a 282-amino-acid polypeptide with a calculated M(r) 30,824. Alignment of this deduced protein sequence and E. coli elongation factor Ts (EF-Ts, product of tsf) demonstrated 34% identity and an additional 14% similarity. The putative chlamydial tsf gene was expressed in E. coli as a nonfusion protein and as a 6x His-tagged fusion protein. By SDS-PAGE analysis, the molecular weights of the nonfusion recombinant protein and a protein of chlamydial elementary bodies (EBs), which was recognized by monoclonal antibodies derived from the nonfusion recombinant protein, are 34 kDa. The purified recombinant 6x His-tagged fusion protein increased the rate of GDP exchange with both Chlamydia and E. coli elongation factor Tu (EF-Tu). These data show that the second gene of the identified cluster is tsf. Unlike EF-Ts from any other species, its activity was comparable to that of E. coli EF-Ts in exchange reaction with E. coli EF-Tu.

Amino Acid Sequence↗
PubMed1997

The N-terminal globular domain of Eph receptors is sufficient for ligand binding and receptor signaling.

The Eph family of receptor protein-tyrosine kinases (RTKs) have recently been implicated in patterning and wiring events in the developing nervous system. Eph receptors are unique among other RTKs in that they fall into two large subclasses that show distinct ligand specificities and for the fact that they themselves might function as 'ligands', thereby activating bidirectional signaling. To gain insight into the mechanisms of ligand-receptor interaction, we have mapped the ligand binding domain in Eph receptors. By using a series of deletion and domain substitution mutants, we now report that an N-terminal globular domain of the Nuk/Cek5 receptor is the ligand binding domain of the transmembrane ligand Lerk2. Using focus formation assays, we show that the Cek5 globular domain is sufficient to confer Lerk2-dependent transforming activity on the Cek9 orphan receptor. Extending our binding studies to other members of both subclasses of receptors, it became apparent that the same domain is used for binding of both transmembrane and glycosylphosphatidyl-anchored ligands. Our studies have determined the first structural elements involved in ligand-receptor interaction and will allow more fine-tuned genetic experiments to elucidate the mechanism of action of these important guidance molecules.

3T3 Cells↗
PubMed1997

Using smoothing spline anova to examine the relation of risk factors to the incidence and progression of diabetic retinopathy.

Smoothing spline ANOVA (ANalysis Of VAriance) methods provide a flexible alternative to the standard parametric GLIM (generalized linear models) methods for analysing the relationship of predictor variables to outcomes with data from large epidemiologic studies. These methods allow the visualization of relationships not readily fit by simple GLIM models, and provide for the ability to visualize interactions between the variables. At the same time, they reduce to GLIM models if the data suggest that the added flexibility is unwarranted. Using this method, we investigate risk factors for incidence and progression of diabetic retinopathy in a group of patients with older onset diabetes from the Wisconsin Epidemiological Study of Diabetic Retinopathy. We carry out four analyses to illustrate various properties of this class of methods. Some of the results confirm previous findings with use of standard methods, while others allow the visualization of more complex relationships not evident from the application of parametric methods.

Adult↗