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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 433 records · Page 24Linked to original sources
PubMed1994

Relationship of hyperglycemia to the long-term incidence and progression of diabetic retinopathy.

BACKGROUND: The object was to examine the relationship of hyperglycemia, as measured by glycosylated hemoglobin level, to the incidence and progression of diabetic retinopathy over a 10-year period. METHODS: Patients who were younger (n = 682) and older (n = 834) than 30 years at onset of diabetes participated in baseline (1980-1982) and follow-up (1984-1986 and 1990-1992) examinations of a population-based cohort study. Glycosylated hemoglobin levels were measured by microcolumn. Retinopathy was determined from stereoscopic fundus photographs. RESULTS: Persons with glycosylated hemoglobin levels in the highest quartile at baseline were more likely to have progression of retinopathy than persons with levels in the lowest quartile (younger-onset group: relative risk [RR], 2.9; 95% confidence interval [CI], 2.3 to 3.5; older-onset group taking insulin: RR, 2.1; 95% CI, 1.6 to 2.8; and older-onset group not taking insulin: RR, 4.3; 95% CI, 3.0 to 6.2) and were more likely to develop proliferative diabetic retinopathy (younger-onset group: RR, 7.1; 95% CI, 4.6 to 11.1; older-onset group taking insulin: RR, 3.1; 95% CI, 1.5 to 6.1; and older-onset group not taking insulin: RR, 13.8; 95% CI, 4.8 to 39.5). These relations were significant (P < .005) in all groups examined, even after controlling for other risk variables. CONCLUSIONS: These data are compatible with the hypothesis that long-term control of hyperglycemia, as measured by glycosylated hemoglobin levels, is a significant risk factor for the long-term progression of diabetic retinopathy and that lower levels of glycosylated hemoglobin, even later in the course of diabetes, may modify the risk imposed by higher levels earlier in the course of disease in people with both younger- and older-onset diabetes.

Adult↗
PubMed1994

Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene.

Nerve growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons in culture. In vivo, NGF decreases the extent of naturally occurring cell death in developing sympathetic ganglia and protects cholinergic neurons of the basal forebrain and caudatoputamen. NGF interacts with the low-affinity p75 receptor and with Trk, a receptor tyrosine kinase encoded by the trk proto-oncogene. To study the role of Trk in vivo, we have ablated the gene in embryonic stem cells by homologous recombination. Mice lacking Trk have severe sensory and sympathetic neuropathies and most die within one month of birth. They have extensive neuronal cell loss in trigeminal, sympathetic and dorsal root ganglia, as well as a decrease in the cholinergic basal forebrain projections to the hippocampus and cortex. These findings demonstrate that Trk is the primary mediator of the trophic actions of NGF in vivo and that this signalling pathway plays a crucial role in the development of both the peripheral and the central nervous systems.

Acetylcholinesterase↗
PubMed1994

Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements.

The trkC gene is expressed throughout the mammalian nervous system and encodes a series of tyrosine protein kinase isoforms that serve as receptors for neurotrophin-3 (NT3), a member of the nerve growth factor (NGF) family of neurotrophic factors. One of these isoforms, gp145trkC/TrkC K1, mediates the trophic properties of NT3 in cultured cells. Here we show that homozygous mice defective for TrkC tyrosine protein kinase receptors lack Ia muscle afferent projections to spinal motor neurons and have fewer large myelinated axons in the dorsal root and posterior columns of the spinal cord. These mice display abnormal movements and postures, indicating that NT3/TrkC-dependent sensor; neurons may play a primary role in proprioception, the sense of position and movement of the limbs.

Amino Acid Sequence↗
PubMed1994

Is there evidence of an estrogen effect on age-related lens opacities? The Beaver Dam Eye Study.

OBJECTIVE: To evaluate a possible association between estrogen and lens opacities. DESIGN: A prevalence survey of age-related eye disease. SETTING: Beaver Dam, Wis. PARTICIPANTS: A total community sample of persons 43 through 84 years of age at the time of a private census were recruited for examination, medical history, and photographs of the lenses of the eyes. Data from women are included in this report. MAIN OUTCOME MEASURES: Photographs were graded by protocol for the presence and severity of age-related lens opacities. RESULTS: Current use of postmenopausal estrogens was associated with a decreased risk of more severe nuclear sclerosis. Younger age at menarche was also associated with a protective effect regarding nuclear sclerosis. Older age at menopause was associated with a decreased risk of cortical opacities. CONCLUSION: These data are suggestive of a modest protective effect of estrogen exposure on the lenses of women. Further evaluation of this may be possible in studies currently under way in which postmenopausal estrogens are being tested for other (protective) effects.

Adult↗
PubMed1994

Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population.

OBJECTIVE: To investigate the relationship of various retinal lesions to systemic hypertension in the population-based Beaver Dam Eye Study. DESIGN: In this cross-sectional population-based study, blood pressure was measured using standardized protocols. Using standardized protocols, stereoscopic color fundus photographs were graded in a masked fashion to determine the presence of retinopathy (defined as retinal microaneurysms only, blot hemorrhages only, hemorrhages and/or microaneurysms, cotton-wool spots, hard exudates, intraretinal microvascular abnormalities, venous beading, and retinal new vessels), retinal arteriolar narrowing, and arteriovenous nicking. PARTICIPANTS: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, between 1987 and 1988 were examined between 1988 and 1990. People with diabetes or retinal vascular occlusions were excluded. RESULTS: Retinopathy was present in 336 subjects (7.8%), arteriolar narrowing in 582 subjects (13.5%), and arteriovenous nicking in 95 subjects (2.2%) in the nondiabetic population. Hypertension was associated with increased frequency of retinopathy, arteriolar narrowing, and arteriovenous nicking. After adjusting for age, hypertension was associated with the presence of retinopathy (in men: relative risk [RR], 1.47; 95% confidence interval [CI], 1.10 to 1.96; in women: RR, 1.69; 95% CI, 1.26 to 2.27), arteriolar narrowing (in men: RR, 1.34; 95% CI, 1.03 to 1.74; in women: RR, 1.37; 95% CI, 1.14 to 1.64), and arteriovenous nicking (in men: RR, 1.87; 95% CI, 0.99 to 3.54; in women: RR, 1.65; 95% CI, 1.00 to 2.73). Retinopathy, arteriolar narrowing, and arteriovenous nicking were more frequent in those subjects whose blood pressure was elevated despite use of antihypertensive medications compared with those subjects whose blood pressure was controlled with antihypertensive medications or those who were normotensive. CONCLUSIONS: These data suggest that retinopathy and retinal arteriolar narrowing are common in people with hypertension. Further longitudinal study is necessary to evaluate the public health significance of these retinal lesions regarding possibly increased risk of renal and cardiovascular disease.

Adult↗
PubMed1994

Is age-related maculopathy associated with cataracts?

OBJECTIVE: To evaluate the relationship between three types of cataract or cataract surgery and age-related maculopathy. DESIGN: Population-based prevalence study. PARTICIPANTS: A total of 4926 people participating in The Beaver Dam Eye Study from 1988 through 1990. MAIN OUTCOME MEASURES: Grading of photographs for nuclear sclerosis, cortical cataract, and posterior subcapsular cataract and signs of age-related maculopathy was performed using standardized protocols. RESULTS: After adjusting for other risk factors, nuclear sclerosis was associated with increased odds of early age-related maculopathy (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.28 to 3.01) but not of late age-related maculopathy (OR, 1.38; 95% CI, 0.52 to 3.63). Neither cortical nor posterior subcapsular cataracts were related to age-related maculopathy. There were increased odds of early age-related maculopathy in eyes that had undergone cataract surgery. CONCLUSION: These data suggest a possible commonly shared pathogenesis between nuclear sclerotic cataract and age-related maculopathy.

Adult↗
PubMed1994

The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy.

OBJECTIVE: To examine the 10-year incidence and progression of diabetic retinopathy. DESIGN: Population-based incidence study. PARTICIPANTS: Seven hundred sixty-five insulin-taking diabetic persons diagnosed before age 30 years, 251 insulin-taking diabetic persons diagnosed at age 30 years or older, and 282 non-insulin-taking diabetic persons diagnosed at age 30 years or older who participated in baseline, 4-year, and 10-year follow-up examinations. MAIN OUTCOME MEASURES: The 10-year incidence of any retinopathy, progression of retinopathy, and progression to proliferative retinopathy were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study severity scheme. RESULTS: The 10-year incidence of retinopathy (89%, 79%, and 67%), progression of retinopathy (76%, 69%, and 53%), and progression to proliferative retinopathy (30%, 24%, and 10%) were highest in the group diagnosed before age 30 years, intermediate in the insulin-taking group diagnosed at age 30 years or older, and lowest in the non-insulin-taking group, respectively. Increased risk of proliferative retinopathy was associated with more severe retinopathy at baseline. CONCLUSIONS: These data suggest relatively high 10-year rates of incidence and progression of retinopathy, and despite changes in the treatment of diabetes, there has been little change in the incidence and progression of diabetic retinopathy during the 10-year study period.

Adolescent↗
PubMed1994

Chiral lumazines: preparation, properties, enantiomeric separation.

Optically active lumazines (biolumazine, dictyolumazine, monalumazine, and neolumazine) are prepared from the corresponding pterins by enzymatic reaction, using pterin deaminase excreted by Dictyostelium discoideum. The fluorescence properties, circular dichroism spectra, and chromatographic behavior of these lumazines are studied. D- and L-enantiomers of biolumazine, dictyolumazine, and monalumazine are separated using a chiral flavoprotein column. This column also separates the enantiomeric pterins of the threo form: monapterin and dictyopterin. However, the column does not separate the enantiomeric pterins of the erythro form: neopterin and biopterin. By coupling a reverse-phase column to the flavoprotein column, the separation of pterins and lumazines in function of their hydrophobicity, as well as the separation of the diastereomers, is achieved. This coupled achiral/chiral high-performance liquid chromatography method enables determination of the stereoconfiguration of natural lumazines by comparison with optically pure compounds. A lumazine derivative, present in the extracellular medium of Dictyostelium discoideum, is identified as D-dictyolumazine, i.e., 6-(D-threo-1,2-dihydroxypropyl)-lumazine.

Animals↗
PubMed1994

Sibling correlations and segregation analysis of age-related maculopathy: the Beaver Dam Eye Study.

Sibling correlations were evaluated and segregation analysis was performed on age-dependent maculopathy scores of the right and left eyes of individuals from 564 families in the Beaver Dam Eye study. There is evidence of significant sibling correlations. The data fit a mixture of two normal distributions, especially after undergoing the Box and Cox power transformation. In each eye, the hypothesis of mendelian transmission of a major effect cannot be rejected under the tau AB free model, but is rejected under the tau's free model. The hypothesis of a random environmental major effect is rejected. Similar major gene parameter estimates are found for both eyes. The results are consistent with a major effect accounting for 62% and 59%, in the right and left eyes, respectively, of the determination of age-related maculopathy scores. A single major gene can account for about 89% and 97% of this variability due to a major effect, or for about 55% and 57% of the total variability, in the right and left eyes, respectively.

Adult↗
PubMed1994

A comparative study on antibodies to nucleoli and 5-hydroxytryptamine in patients with fibromyalgia syndrome and tryptophan-induced eosinophilia-myalgia syndrome.

Eosinophilia myalgia syndrome (EMS) has been related to intake of "contaminated" L-tryptophan, and an alteration in tryptophan 5-hydroxytryptamine (5-HT, serotonin) metabolism has been reported in EMS patients. Recently we found that a defined autoantibody pattern consisting of antibodies to nucleoli, gangliosides, and phospholipids is closely related to the fibromyalgia syndrome (FS) which clinically resembles the EMS. We were therefore interested to see whether these antibodies can also be detected in patients with EMS. Studied were 27 patients with acute EMS (13 of whom were also examined 2 years after acute onset), 100 patients with FS, and 40 patients with progressive systemic sclerosis (PSS). As controls, sera from 100 blood donors were analyzed. Antibodies to nucleoli were demonstrated by immunofluorescence test on cell cultures in 52% of patients with acute EMS, 62% of patients with chronic EMS, and 37% of FS patients. Western blotting with a nuclear extract from HeLa cells revealed in both diseases the same epitopes at 63, 57, and 53 kDa. Antibodies to 5-HT, gangliosides (Gm1), and phospholipids were determined by enzyme-linked immunosorbent assay. Among patients with FS 73% had antibodies to 5-HT, in contrast to only 19% of patients with acute EMS. However, 77% of the 13 EMS patients analyzed 2 years later had become anti-5-HT antibody positive during that time. Also the incidence of antibodies to Gm1 increased from 37% at acute onset to 69% in patients with chronic EMS (30%). The various antibodies were detected in only 18% of healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Transcranial Doppler sonography during isoflurane/N2O anaesthesia and surgery: flow velocity, "vessel area" and "volume flow".

Transcranial Doppler sonography (TCD) constitutes an advance in noninvasive monitoring of the cerebral circulation. However, as long as the diameter and cross-sectional area of the insonated middle cerebral artery (MCA) remain unknown, the derived flow velocities (v) are not informative. It is not known how the human MCA is influenced by anaesthetic agents. However, a TCD-modification allows noninvasive determination of "vessel area" (VA) and "volume flow" (VF) in MCA by analysing the backscattered Doppler power. This investigation evaluates the effects of isoflurane (in combination with N2O and surgery) on v, VA and VF. In 14 patients (ASA I) scheduled for minor surgical or gynaecological operations, anaesthesia was induced with droperidol, alfentanil, thiopentone and vecuronium. After intubation ventilation with N2O:O2 = 3:2 was adjusted, to maintain endexpiratory carbon dioxide (FECO2) constant between 4 and 5%. Baseline values of heart rate (HR), oscillometric mean arterial pressure (MAP), and TCD variables (v, VA VF) were measured before adding 2.4% isoflurane to the inspiratory mixture. Further measurements-were made 3, 6, 10, and 20 min after starting isoflurane. Surgery commenced between the sixth and tenth minute after isoflurane application. The MAP, FECO2, and v showed only minor alterations; HR increased after 6, 10 and 20 min. Transcranial "vessel area" and "volume flow" showed increases after isoflurane inhalation. The increase of "vessel area" supports the assumption that isoflurane greater than 1 MAC dilates large human cerebral arteries, so that if flow velocities are considered alone, alterations of cerebral blood flow may easily be underestimated.

Anesthesia, Inhalation↗
PubMed1994

Can we restrict the health care menu?

The case of Britain's National Health Service is used to illuminate the cross-national debate about whether the availability of health care should be restricted and, if so, how this should be done. Traditionally, the NHS relied on implicit rationing by clinicians within budgetary constraints set by government. However, the logic of the 1989 reforms appeared to require explicit decisions about the packages of health care to be provided to local populations. In practice, purchasers have refused to define such packages. Explicit rationing remains very much the exception. Exploring the reasons for this suggests that defining a restricted menu of health care, by adopting a cost-utility approach and excluding specific procedures or forms of treatment on the Oregon model, is only one of many policy options. There is a large repertory of policy tools for balancing demands and resources, ranging from diluting the intensity of treatment to its earlier termination. Given that health care is characterised by uncertainty, lack of information about outcomes and patient heterogeneity, it may therefore be more 'rational' to diffuse decision-making among clinicians and managers than to try to move towards a centrally determined menu of entitlements.

Cost-Benefit Analysis↗
PubMed1994

The relation of socioeconomic factors to age-related cataract, maculopathy, and impaired vision. The Beaver Dam Eye Study.

PURPOSE: To investigate the relations between socioeconomic factors and the prevalence of age-related cataract, maculopathy, and visual impairment. METHODS: A population-based sample of 4926 people 43 to 86 years of age was examined from 1988 to 1990. Education, income, employment status, marital status, nuclear sclerosis, cortical, and posterior subcapsular cataract, age-related maculopathy, and impaired vision were all ascertained using standard protocols. RESULTS: While controlling for age, sex, diabetes status, multivitamin use, alcohol consumption, and cigarette smoking, less education was significantly associated with nuclear and cortical cataract, and lower income was significantly associated with cortical and posterior subcapsular cataract and impaired vision. There was a "U-shaped" relation between income and cataract surgery. Neither income nor education was related to age-related maculopathy. There was no relation of marital status to cataract status or age-related maculopathy. CONCLUSION: These data suggest that education and income are associated with cataract, cataract surgery, and impaired vision. These relations were not explained by other risk factors measured in the study.

Adult↗
PubMed1994

The association of alcohol consumption with the incidence and progression of diabetic retinopathy.

PURPOSE: To investigate the association of alcohol consumption with the incidence and progression of diabetic retinopathy. METHODS: The population consisted of a cohort of adult younger-onset (diagnosis received before 30 years of age and taking insulin, n = 439) and older-onset (diagnosis received after 30 years of age, n = 478) persons with diabetes examined from 1984 to 1986 and again from 1990 to 1992. The outcomes were incidence of retinopathy, progression, and progression to proliferative retinopathy. Retinopathy was determined by grading of stereoscopic color fundus photographs. Alcohol consumption was determined by questionnaire and summarized as average or recent consumption. The proportion of heavier drinkers was small, 6% of younger-onset and 4% of older-onset persons. RESULTS: In the younger-onset group, progression of retinopathy occurred in 62%, 51%, 61%, and 71% of nondrinkers, light, moderate, and heavier drinkers, respectively, based on average intake (P = 0.28). Based on recent intake, 55%, 46%, 63%, and 69% of nondrinkers, light, moderate, and heavier drinkers, respectively, progressed (P = 0.10). A similar trend is seen for incidence of retinopathy, but the sample sizes are small. No association is seen with progression to proliferative diabetic retinopathy. After controlling for age, sex, and glycemia in a logistic regression model, alcohol intake is not associated with progression of retinopathy. In the older-onset group, alcohol intake is not related to the incidence or progression of retinopathy. CONCLUSION: Alcohol consumption in moderation (< or = 1 oz/day) does not appear to affect the occurrence of diabetic retinopathy.

Adult↗
PubMed1994

Open-angle glaucoma and older-onset diabetes. The Beaver Dam Eye Study.

PURPOSE: To evaluate the relation of older-onset diabetes to open-angle glaucoma. METHODS: During a population-based study of age-related eye disease (n = 4926), participants were evaluated for the presence of glaucoma. Glycosylated hemoglobin levels were measured, and a medical history was obtained. RESULTS: Rates of persons meeting optic disc, visual field, and intraocular pressure criteria for definite glaucoma were more common in those with older-onset diabetes than in those without (4.2% versus 2.0%; P = 0.004). When persons with a history of treated glaucoma, despite whether they met the other criteria for glaucoma, were included, rates were 7.8% in those with diabetes compared with 3.9% in those without diabetes (P = 0.0005). CONCLUSIONS: The presence of open-angle glaucoma is increased in people with older-onset diabetes.

Adult↗
PubMed1994

The influence of combined kidney-pancreas transplantation on the progression of diabetic retinopathy. A case series.

PURPOSE: To evaluate the impact of combined kidney and pancreas transplantation on the progression of advanced diabetic retinopathy. METHODS: The changes in diabetic retinopathy severity in patients with insulin-dependent diabetes mellitus who had kidney-pancreas transplantation (n = 51) and in those who had kidney transplantation only (n = 21) were compared. Patients were invited to baseline and 1 year follow-up examinations. Fundus photographs were graded in a masked fashion using standardized protocols. RESULTS: The mean age and duration of diabetes were similar for both groups. After combined transplantation, none of the patients used insulin, and their mean glycosylated hemoglobin was significantly lower (6.4% versus 10.6%) than those who underwent only kidney transplantation. There was a nonsignificant difference in overall progression of retinopathy for combined transplantation compared with kidney transplantation only (risk ratio = 0.73; 95% confidence interval, 0.31, 1.71). CONCLUSION: The authors found no evidence that the normalization of glycemia associated with a combined kidney-pancreas transplantation in patients with advanced proliferative diabetic retinopathy (mostly treated with photocoagulation) accelerated retinopathy progression. These data suggest that the normalization of glycemia associated with a combined kidney-pancreas transplantation does not have beneficial influence on the progression of advanced diabetic retinopathy.

Adult↗