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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 361 records · Page 20Linked to original sources
PubMed1996

Follistatin concentrations in male sheep increase following sham castration/castration or injection of interleukin-1 beta.

Plasma follistatin (FS) concentrations were determined after castration (n = 5) or sham castration (n = 4) of mature rams. Both treatments resulted in a prolonged increase in FS between 7 and 19 h after surgery, which returned to pretreatment concentrations by 24 h. Tumour necrosis factor-alpha (TNF-alpha), a sensitive maker of an acute-phase response, was undetectable in plasma, indicating that the FS response was not induced by trauma due to surgery. In a second experiment, injection of castrated rams (n = 4) with ovine recombinant interleukin-1 beta, an acute-phase mediator, resulted in a sustained rise in FS concentrations within 4 h of injection. Plasma TNF-alpha concentrations increased transiently within 1 h of interleukin-1 beta injection, indicating that an acute-phase response had been initiated. Plasma follicle-stimulating hormone (FSH) concentrations were significantly decreased at 8 and 24 h after interleukin-1 beta injection, strongly suggestive of an inhibitory effect of increased FS concentrations on the secretion of FSH. Injection of castrated rams (n = 2) with a control preparation of recombinant interleukin-2 did not induce an acute-phase response, and plasma FS and FSH concentrations were unaffected. These data show that the testis is not a major source of circulating FS, that the increase in circulating FS following sham castration/castration is not due to an acute-phase response, but that conversely FS concentrations are modulated by the acute-phase mediator, interleukin-1 beta.

Acute-Phase Reaction↗
PubMed1996

Sex hormones and DHEA-SO4 in relation to ischemic heart disease mortality in diabetic subjects. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

OBJECTIVE: Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a group with very high levels of IHD. RESEARCH DESIGN AND METHODS: We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject). RESULTS: In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may be associated with worse IHD risk factors. CONCLUSIONS: This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.

Adult↗
PubMed1996

Evaluations of retinopathy in the VA Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM). A feasibility study.

OBJECTIVE: The main goal of the study of 153 male veterans was to determine whether a statistically and clinically significant difference in HbA1c could be achieved between a standard therapy and an intensively treated group of patients with type II diabetes. A second major goal was to assess the feasibility of collecting reliable high-quality endpoint data, including microvascular and macrovascular events. Retinopathy was defined as a key microvascular endpoint. RESEARCH DESIGN AND METHODS: This was a randomized prospective trial of 153 men between the ages of 40 and 69 years, with type II diabetes for 15 years or less. Of the patients, 78 were assigned to the standard therapy arm and 75 to the intensive therapy arm. The goal of standard therapy was good general medical care and well-being and avoiding excessive hyperglycemia, glycosuria, ketonuria, or hypoglycemia. This was generally accomplished with one shot of insulin per day. The goal of intensive therapy was to obtain an HbA1c within two standard deviations of the mean of nondiabetic subjects (4.0-6.1%). This was obtained by a four-step management technique, with patients moving to the next step only if operational goals were not met. The steps were as follows: step 1: evening intermediate or long-acting insulin only; step 2: evening insulin with daytime glipizide; step 3: insulin, twice a day, no glipizide; and step 4: more than two injections of insulin, no glipizide. Retinopathy was assessed at baseline, 12, and 24 months by seven-field stereo fundus photography done at each of the five participating VA medical centers and read at the Central Reading Center at the Department of Ophthalmology, University of Wisconsin Medical School, Madison. Visual acuity was determined by ophthalmologists at each of the participating hospitals. RESULTS: After the 6th month of the 24-month study, an average HbA1c of approximately 7.1% in the intensively treated group was sustained for the full study and was significantly lower than that seen in the standard group (9.2%, P < 0.001). Compliance in obtaining fundus photographs was excellent. Near normalization of glycemia did not cause transient worsening of retinal morphology nor did it prevent the onset or delay the progression of retinopathy. There was no effect on visual acuity. CONCLUSIONS: 1) A glycemic control intervention study in people with type II diabetes is feasible and safe; 2) intensive control did not cause transient deterioration of retinopathy; and 3) although no improvement was seen in retinopathy, the follow-up was 24 months, an interval shorter than the 3 years or more of intensive therapy before improvement is seen in type 1 diabetic studies. This does not rule out the possibility that longer periods of intensive therapy would have improved retinopathy. A full-scale intervention trial in type II diabetes is needed to resolve this issue.

Adult↗
PubMed1996

Prevalence of self-reported erectile dysfunction in people with long-term IDDM.

OBJECTIVE: The purpose of this report is to examine the prevalence of erectile dysfunction and relationships to other characteristics in men with younger-onset diabetes. RESEARCH DESIGN AND METHODS: In a population-based cohort study in southern Wisconsin, prevalence of erectile dysfunction was measured based on self reports in men who were 21 years of age or older, were < 30 years of age at diagnosis of diabetes, had 10 or more years of diabetes, and were taking insulin (n = 365). RESULTS: Of the study group, 20% reported a history of erectile dysfunction. The prevalence of erectile dysfunction increased with increasing age (from 1.1% in those 21-30 years of age to 47.1% in those 43 years of age or older, P for trend < 0.0001) and with increasing duration of diabetes (P for trend < 0.0001). Erectile dysfunction was associated with presence of severe diabetic retinopathy, a history of peripheral neuropathy, amputation, cardiovascular disease, a higher glycosylated hemoglobin, use of antihypertensive medications, and higher BMI. CONCLUSIONS: These data suggest that tighter glycemic control and careful selection of antihypertensive medications might prove beneficial.

Adult↗
PubMed1996

The medical management of hyperglycemia over a 10-year period in people with diabetes.

OBJECTIVE: The purpose of the study was to examine changes in the medical management of glycemia in diabetes and its relation to changes in hyperglycemia as measured by glycated hemoglobin. RESEARCH DESIGN AND METHODS: A total of 765 patients with younger-onset diabetes diagnosed before 30 years of age and 533 older-onset diabetic patients participated in a population-based study in southern Wisconsin, at baseline (1980-1982), at 4 years (1984-1986), and at 10 years (1990-1992). Glycated hemoglobin, the presence of complications, and information regarding medical management of glycemia, hypoglycemic reactions, and socioeconomic factors were determined using standardized protocols at the three examinations. RESULTS: In the younger-onset group, there was a significant increase (P < 0.001) in the use of three or more insulin injections per day or in the use of an insulin infusion pump from 3.6% of the cohort at baseline to 24.4% at the 10-year follow-up. This increase was associated with female sex, the presence of gross proteinuria, more education, and better glycemic control at baseline. In the older-onset group, there was a significant (P < 0.05) increase in the proportion of patients taking insulin, from 49.2% at baseline to 61.9% at the 10-year follow-up. This was associated with being younger, having a longer duration of diabetes, having higher glycated hemoglobin values, and having more education at baseline, or developing proliferative diabetic retinopathy or macular edema between baseline and the 4-year follow-up. CONCLUSIONS: These data suggest a change in the pattern of use of insulin to treat people with diabetes. However, there is still a large number of individuals with poorly controlled diabetes in the population.

Adolescent↗
PubMed1996

Parental history of diabetes in a population-based study.

OBJECTIVE: To evaluate the relative frequency of parental history of diabetes in a population-based study of younger- and older-onset groups of individuals with diabetes and a comparison group of individuals without diabetes. RESEARCH DESIGN AND METHODS: Study participants were queried about a family history of diabetes. The frequencies of positive responses for parents and siblings were compared between younger- and older-onset groups. RESULTS: At least one parent had diabetes in 18.6% of the families of younger-onset individuals and in 38.6% of the families of older-onset individuals. For those of younger-onset diabetes, 9.1% of fathers, 8.3% of mothers, and 1.3% of both parents had diabetes; the corresponding percentage for those of older-onset diabetes were 11.5, 23.5, and 3.6%, respectively. The difference between frequencies in mothers and fathers was significant (P < 0.0001) in the older-onset group. In the nondiabetic comparison group, for those of similar ages to the younger- and older-onset groups, the corresponding frequencies were 6.2 and 9.0% and 7.7 and 9.8% for fathers and mothers, respectively. The greater frequencies of diabetes in mothers of older-onset diabetic individuals were not accounted for by maternal age. In younger-onset individuals, the relative risk (RR) of diabetes in a sibling if the father had diabetes was 1.22 (95% CI, 0.72-2.05); if the mother had diabetes, the RR was 2.39 (95% CI, 1.64-3.48); and, if both parents had diabetes, the RR was 5.61 (95% CI, 3.37-9.34). In the older-onset individuals, the corresponding RR values were 1.69 (95% CI, 1.35-2.13) for fathers, 1.72 (95% CI, 1.44-2.06) for mothers, and 2.42 (95% CI, 1.81-3.25) for both parents. CONCLUSIONS: These data confirm a familial influence on the frequency of diabetes. The excess of cases in mothers of older-onset diabetic individuals is compatible with both environmental and genetic influences.

Adult↗
PubMed1996

Recurrent first trimester spontaneous abortion associated with antiphospholipid antibodies: a pilot study of treatment with intravenous immunoglobulin.

BACKGROUND: Antiphospholipid antibodies, unassociated with an underlying connective tissue disease, have repeatedly been detected in women suffering from recurrent spontaneous abortions. Several therapeutic regimens have been advocated for pregnant women with recurrent fetal loss and antiphospholipid antibodies. However, most of these approaches were empirical, using several drugs simultaneously, and most reports describe single cases or limited series. PATIENTS AND INTERVENTIONS: In a pilot study, thirty-eight women with a history of three or more consecutive first trimester spontaneous abortions and antiphospholipid antibodies were treated with intravenous immunoglobulin. As soon as pregnancy had been confirmed, intravenous immunoglobulin was administered at a dose of 300 mg/kg bodyweight, and infusions were repeated at three-weekly intervals until the 16th-17th week of pregnancy. RESULTS: Pregnancy proceeded beyond the first trimester in 34 of the patients (89.4%), and 31 patients (81.4%) gave birth to healthy infants at 37 to 42 weeks' gestation. CONCLUSIONS: Although the results are promising, randomized placebo-controlled trials are necessary to exclude the influence of other factors (e.g. intense obstetric supervision and psychological factors) on pregnancy outcome and confirm the effectiveness of intravenous immunoglobulin in patients with recurrent spontaneous abortions and antiphospholipid antibodies.

Abortion, Habitual↗
PubMed1996

Visual sensitivity and age-related eye diseases. The Beaver Dam Eye Study.

OBJECTIVE: To evaluate the relationships between visual sensitivity and age-related ocular disorders. DESIGN: Prevalence survey of age-related eye diseases. SETTING: Beaver Dam, Wisconsin. PARTICIPANTS: A total community sample of persons 43-84 at the time of the census (1987-1988) was invited to participate (n = 5.926). MAIN OUTCOME MEASURE: Visual sensitivity was measured by a perimeter. Sensitivities were evaluated with regard to age, sex and age-related eye diseases. RESULTS: Sensitivity was inversely associated with age and was lower in women in each age stratum. Central cataract, cataract surgery, and late age-related maculopathy were significantly related to decreased sensitivity in multivariate analyses. CONCLUSIONS: Visual sensitivity, an indication of the ability of the eye to detect a light stimulus, was diminished in those with central cataract, cataract surgery, and late age-related maculopathy. This may be related to diminished vision in environmental conditions of low illumination. Since visual sensitivity is relative easy to determine, this test may have use as a surrogate to assess functional vision loss. Also, although cataract surgery often leads to improved high contrast acuity, there may be a loss in low contrast settings.

Adult↗
PubMed1996

Dictyopterin appears at amoebae emergence during spore germination in Dictyostelium.

Intracellular dictyopterin, which is present in reduced form, mainly as tetrahydrodictyopterin, both in vegetative cells and in starved cells, could neither be detected in dormant spores nor in unswollen or swollen activated spores. Synthesis of tetrahydrodictyopterin starts with emergence of nascent amoebae during spore germination. Tetrahydrodictyopterin levels in cell-free extracts vary as a function of the percent emerged amoebae in spore suspension. These data are consistent with a requirement for tetrahydrodictyopterin during vegetative growth.

Amoeba↗
PubMed1996

Interexaminer reliability of otoscopic signs and tympanometric measures for older adults.

To accurately classify hearing loss and otic disorders among older adults, examiners must be able to consistently assess otoscopic signs and perform middle-ear screening tympanograms. As part of a population-based study of hearing loss in Beaver Dam, Wisconsin, the interexaminer reliability of otoscopic examinations and screening tympanograms was evaluated using 45 replicate examinations. Data from 1941 participants 48 to 91 years of age were used to compare otoscopic and tympanometric results. Overall agreement for nine otoscopic signs ranged from 73 percent (vascularity) to 100 percent (drainage). There were small examiner differences in tympanometric measures of equivalent ear-canal volume (Vea) and tympanogram width. No significant differences were observed for peak compensated static acoustic admittance and tympanogram peak pressure. Our findings suggest that examiners can be trained to consistently and accurately assess otoscopic signs and obtain reliable tympanometric results.

Acoustic Impedance Tests↗
PubMed1996

Tympanometric measures in older adults.

Tympanometric measures were obtained in 1240 adults (2147 ears) ranging in age from 48 to 90 years. All subjects reported a negative history of otic disease, passed an otoscopic examination, and did not present a significant air-bone gap based on pure-tone audiometry. Relative to findings for younger adults, tympanometric measures for older adults in the present study showed greater variability, a slightly lower mean peak compensated static acoustic admittance (peak Ytm), and a significantly higher mean equivalent ear-canal volume (Vea). Across age in the present study, Vea tended to decrease with age and tympanogram width (TW) tended to increase with age. Relative to measures for females, males in the present study tended to have higher peak Ytm values, higher Vea values, and slightly lower TW values. Overall, our findings indicate a need to adopt criteria that account for age and gender effects in tympanometry protocols for older adults.

Acoustic Impedance Tests↗
PubMed1996

Pattern of age-related maculopathy in the macular area. The Beaver Dam Eye Study.

PURPOSE: To describe the distribution of lesions associated with age-related maculopathy by location in the macula in a population of adult Americans. METHODS: Four thousand nine hundred twenty-six persons ranging in age from 43 to 84 years and living in Beaver Dam, Wisconsin, at the time of a census (1987-1988) were examined from 1988 to 1990. Lesions typical of age-related maculopathy were determined by masked grading of stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. The extent and prevalence of different types of lesions were determined for each of nine macular subfield regions: central, inner superior, inner nasal, inner inferior, inner temporal, outer superior, outer nasal, outer inferior, and outer temporal. RESULTS: Lesions associated with early age-related maculopathy were distributed in specific patterns. Soft indistinct drusen were more prevalent in the temporal and superior quadrants than in the nasal and inferior quadrants, whereas pigmentary abnormalities associated with age-related maculopathy were more prevalent in the superior or nasal quadrants than in the inferior or temporal quadrants. After weighting for subfield area, all types of lesions were most prevalent in the central macular region. CONCLUSION: Various lesions associated with early age-related maculopathy were located in specific patterns in the macula. It is not known whether these patterns resulted from environmental, anatomic, or physiologic factors.

Adult↗
PubMed1996

Similarities and Differences in the Way Transmembrane-Type Ligands Interact with the Elk Subclass of Eph Receptors

The Eph family of receptor tyrosine kinases and their cell surface bound ligands have been implicated in a number of developmental processes, including axon pathfinding and fasciculation, as well as patterning in the central nervous system. To better understand the complex signaling events taking place, we have undertaken a comparative analysis of ligand-receptor interactions between a subset of ligands, those that are tethered to the cell surface via a transmembrane domain, and a subset of Eph receptors, the so-called Elk subclass. Based on binding characteristics, receptor autophosphorylation, and cellular transformation assays, we find that the transmembrane-type ligands Lerk2 and Elf2 have common and specific receptors within the Elk subclass of receptors. The common receptors Cek10 and Elk bind and signal in response to Lerk2 and Elf2, whereas the Myk1 receptor is specific for Elf2. Elf2, however, fails to signal through Cek5 in a cellular transformation assay, suggesting that Lerk2 may be the preferred Cek5 ligand in vivo. A recently identified third transmembrane-type ligand, Elf3, specifically, but weakly, binds Cek10 and only induces focus formation when activated by C-terminal truncation. This suggests that the physiological Elf3 receptor may have yet to be identified. Knowledge regarding functional ligand-receptor interactions as presented in this study will be important for the design and interpretation of in vivo experiments, e.g., loss-of-function studies in transgenic mice.

Journal Article↗
PubMed1995

Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor.

Various in vitro studies have suggested that ErbB4 (HER4) is a receptor for the neuregulins, a family of closely related proteins implicated as regulators of neural and muscle development, and of the differentiation and oncogenic transformation of mammary epithelia. Here we demonstrate that ErbB4 is an essential in vivo regulator of both cardiac muscle differentiation and axon guidance in the central nervous system (CNS). Mice lacking ErbB4 die during mid-embryogenesis from the aborted development of myocardial trabeculae in the heart ventricle. They also display striking alterations in innervation of the hindbrain in the CNS that are consistent with the restricted expression of the ErbB4 gene in rhombomeres 3 and 5. Similarities in the cardiac phenotype of ErbB4 and neuregulin gene mutants suggest that ErbB4 functions as a neuregulin receptor in the heart; however, differences in the hindbrain phenotypes of these mutants are consistent with the action of a new ErbB4 ligand in the CNS.

Animals↗
PubMed1995

Relation of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to cardiovascular risk factors in postmenopausal women.

Sex hormones play a major role in determining the risk of cardiovascular disease. While several studies have shown that reduced sex hormone-binding globulin is associated with an atherogenic pattern of lipoproteins and increased glucose concentrations in premenopausal women, little data are available examining the association of sex hormone-binding globulin and sex hormones with cardiovascular risk factors in postmenopausal women, a group with high rates of cardiovascular disease. The investigators hypothesized that in postmenopausal women decreased sex hormone-binding globulin and increased testosterone would be associated with an atherogenic pattern of cardiovascular risk factors. The sex hormone-binding globulin, total and free testosterone, estrone, and dehydroepiandrosterone sulfate (DHEA-SO4) in 253 postmenopausal women who were not taking hormones were measured in a population-based study, the Beaver Dam Eye Study (Beaver Dam, Wisconsin, 1988-1990). Sex hormone-binding globulin was significantly inversely correlated with body mass index (r = -0.53, p 0.001), glycosylated hemoglobin (r = -0.34, p < 0.001), and diastolic blood pressure (r = -0.25, p < 0.001), and positively correlated with high density lipoprotein cholesterol (HDL cholesterol) (r = 0.31, p < 0.001), and HDL cholesterol/total cholesterol (r = 0.31, p < 0.001). Total (r = -0.20, p < 0.01) and free (r = -0.14, p < 0.05) testosterone were significantly inversely correlated with HDL cholesterol/total cholesterol ratio. Total testosterone concentrations were also significantly positively correlated with total cholesterol (r = 0.15), body mass index (r = 0.16), and systolic (r = 0.17) and diastolic (r = 0.18) blood pressures (all p < 0.01). DHEA-SO4 was not associated with any of the metabolic variables, while estrone was inversely associated only with the HDL cholesterol/total cholesterol ratio (r = 0.13, p < 0.05). The authors conclude that increased androgenization in postmenopausal women is associated with atherogenic changes in cardiovascular risk factors.

Adult↗
PubMed1995

High incidence of antibodies to 5-hydroxytryptamine, gangliosides and phospholipids in patients with chronic fatigue and fibromyalgia syndrome and their relatives: evidence for a clinical entity of both disorders.

The fibromyalgia syndrome (FMS) is one of the most frequent rheumatic disorders showing a wide spectrum of different symptoms. An association with the chronic fatigue syndrome (CFS) has been discussed. Recently, a defined autoantibody pattern consisting of antibodies to serotonin (5-hydroxytryptamine, 5-HT), gangliosides and phospholipids was found in about 70% of the patients with FMS. We were therefore interested in seeing whether patients with CFS express similar humoral immunoreactivity. Sera from 42 CFS patients were analysed by ELISA for these antibodies, and the results were compared with those previously observed in 100 FMS patients. 73% of the FMS and 62% of the CFS patients had antibodies to serotonin, and 71% or 43% to gangliosides, respectively. Antibodies to phospholipids could be detected in 54% of the FMS and 38% of the CFS patients. 49% of FMS and 17% of the CFS patients had all three antibodies in parallel, 70% and 55%, respectively had at least two of these antibody types. 21% of FMS and 29% of CFS patients were completely negative for these antibodies. Antibodies to 5-HT were closely related with FMS/CFS while antibodies to gangliosides and phospholipids could also be detected in other disorders. The observation that family members of CFS and FMS patients also had these antibodies represents an argument in favour of a genetic predisposition. These data support the concept that FMS and CFS may belong to the same clinical entity and may manifest themselves as 'psycho-neuro-endocrinological autoimmune diseases'.

Adult↗
PubMed1995

A comparison of methods for correlated ordinal measures with ophthalmic applications.

For many clinical trials and epidemiologic investigations in the field of ophthalmology, paired ordinal data are often collected through the detailed grading of retinal photographs. One method for analysis of these data is the extension of the generalized estimating equation (GEE) methodology to multinomial data with cumulative link functions. Prior to the development of this advanced technique, however, ophthalmologists developed a method of combining the ordinal responses of both eyes of a patient into a single person-level response on a new ordinal scale. A relationship between the regression coefficients of these two methods is derived as a function of the correlation between eyes. We investigate the applicability of this result and the relationship of the standard errors in simulation experiments and in an example from the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Diabetic Retinopathy↗