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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 559 records · Page 31Linked to original sources
PubMed1992

The prevalence and incidence of lower extremity amputation in a diabetic population.

OBJECTIVE: To describe the incidence of lower extremity amputations and sores or ulcers and investigate risk factors for these complications. DESIGN: Cohort. SETTING: Primary care. PARTICIPANTS: Population-based sample (N = 1210) of younger-onset diabetic persons (diagnosed before age 30 years and taking insulin) and a stratified random sample (N = 1780) of older-onset diabetic persons (diagnosed after age 30 years). Baseline and 4-year follow-up examinations were completed by 996 and 891 younger-onset persons, respectively, and by 1370 and 987 older-onset persons, respectively. MAIN OUTCOME MEASURES: Amputations and sores or ulcers of the lower extremities. RESULTS: Four-year incidence of amputations was 2.2% in both groups. Incidence of sores or ulcers was 9.5% in younger-onset and 10.5% in older-onset persons. In younger-onset persons, significant risk factors for amputation with odds ratios (and 95% confidence intervals) include age, 2.0 for 10 years (1.2 to 3.1), history of sores or ulcers, 10.5 (3.7 to 29.8), diastolic blood pressure, 2.1 for 10 mm Hg (1.3 to 3.5), and pack-years smoked, 1.3 for 10 years (1.0 to 1.6). Risk factors for sores or ulcers include glycosylated hemoglobin, 1.6 for 2% (1.3 to 2.0), retinopathy, 1.3 for two steps (1.1 to 1.6), and current smoking, 2.3 (1.0 to 5.6). In older-onset persons, risk factors for amputation are history of sores or ulcers, 4.6 (1.7 to 12.2), proteinuria, 4.3 (1.6 to 11.5), glycosylated hemoglobin, 1.5 for 2% (1.0 to 2.2), sex, 2.8 for males (1.0 to 7.5), and duration of diabetes, 1.8 for 10 years (1.0 to 3.2). For sores or ulcers, risk factors are glycosylated hemoglobin, 1.6 for 2% (1.3 to 2.0), duration, 1.5 for 10 years (1.0 to 2.1), proteinuria, 2.2 (1.1 to 4.3), and diastolic blood pressure, 0.8 for 10 mm Hg (0.6 to 1.0). CONCLUSIONS: Several factors offer potential for modification for the prevention of amputations but require further study. These include blood pressure, glycosylated hemoglobin, and smoking.

Adolescent↗
PubMed1992

Intraocular pressure in an American community. The Beaver Dam Eye Study.

The Beaver Dam Eye Study is a population-based study of age-related eye diseases in persons 43-86 yr of age. Applanation tonometry was done on all study subjects. Mean intraocular pressure (IOP) increased significantly with age. Mean IOP differed little between the sexes and was not significantly different after age adjustment (in right eyes of 2721 women, it was 15.5 mm Hg, and in right eyes of 2135 men, it was 15.3 mm Hg). There was an association of IOP with systolic and diastolic blood pressures, body mass index, hematocrit, serum glucose, glycohemoglobin, cholesterol level, pulse, nuclear sclerosis, season, and time of day of measurement. These data confirm that, in a general population, IOP is associated with important systemic and ocular characteristics. Those characteristics should be considered in further research on determinants of IOP.

Adult↗
PubMed1992

Microalbuminuria in a population-based study of diabetes.

The prevalence of microalbuminuria in younger-onset diabetic participants in a large population-based study of diabetic retinopathy was determined, and the relationships of microalbuminuria to blood pressure and other risk factors were investigated. Using an agglutination inhibition test (AlbuScreen), the frequency of microalbuminuria was 21.2%. To evaluate the association of several characteristics with the presence of microalbuminuria, multivariate models based on logistic regression were developed. Microalbuminuria was associated with having higher systolic or diastolic blood pressure and higher glycosylated hemoglobin. These findings give further impetus to efforts to reduce controllable risk factors in younger-onset diabetic persons.

Adult↗
PubMed1991

The validity of self-reported and surrogate-reported cataract and age-related macular degeneration in the Beaver Dam Eye Study.

The validity of reported ocular disease was investigated in a population-based epidemiologic study of persons aged 43-86 years residing in Beaver Dam, Wisconsin. In a telephone survey conducted from September 1987 through May 1988, histories of cataract and age-related macular degeneration were obtained from the subject for 2,155 cases and from a surrogate for 1,433 cases. Within 2 years, these persons underwent a complete ocular examination. At that time, an "in-person" self-reported history of eye disease was obtained and disease presence was determined based on ocular photographs. The reporting methods, telephone versus in-person and surrogate versus subject, were compared and the validity of each assessed. Reporting methods were in agreement in better than 90% of all cases. Reporting of cataract showed a sensitivity of 20.4 for surrogate by telephone, 30.2 for self-report by telephone, and 37.8 for self-report at the examination. Sensitivity of reported age-related macular degeneration was poorer, with the highest rate of 17.9 for the "in-person" self-report. Specificity was better than 90.0 for all reporting methods for both cataract and age-related macular degeneration. These data suggest that estimates of prevalence of ocular disease should not be based solely on reported histories, and that clinical determinations are necessary.

Adult↗
PubMed1991

trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3.

We report the isolation and molecular characterization of trkC, a new member of the trk family of tyrosine protein kinase genes. trkC is preferentially expressed in the brain. In situ hybridization studies revealed trkC transcripts in the hippocampus, cerebral cortex, and the granular cell layer of the cerebellum. The product of the trkC gene has been identified as a glycoprotein of 145,000 daltons, gp145trkC, which is equally related to the previously characterized gp140trk and gp145trkB tyrosine kinases. gp145trkC is a functional receptor for neurotrophin-3 (NT-3). However, gp145trkC does not bind the highly related neurotrophic factors NGF or BDNF. In proliferating cells, the interaction between gp145trkC and NT-3 elicits a more efficient biological response than when NT-3 binds to its other receptors gp140trk and gp145trkB. These results indicate that gp145trkC may play an important role in mediating the neurotrophic effects of NT-3.

Amino Acid Sequence↗
PubMed1991

2,4-diamino-7-hydroxy-pteridines, a new class of catabolites of methotrexate.

Methotrexate remains a commonly used drug in the chemotherapy of various malignancies. The known catabolites are 7-hydroxy-methotrexate, formed in the liver, and diamino-methyl-pteroic acid formed in the gut. We report for the first time evidence that 2,4-diamino-7-hydroxy-pteridine derivatives are present in the biological fluids of patients on high-dose methotrexate protocols. So far, two major derivatives have been identified as 2,4-diamino-6-hydroxymethyl-7-hydroxy-pteridine and 2,4-diamino-6-methyl-7-hydroxy-pteridine. In regard to the actual knowledge of the catabolism of pteridines, these compounds are presumably formed by intestinal bacteria during enterohepatic circulation of the drug. Their slow clearance from the body raises the question of possible interference of these compounds on pteridine-dependent enzymes, which might explain in part some of the toxic effects of methotrexate.

Adolescent↗
PubMed1991

Explaining outputs of primary health care: population and practice factors.

OBJECTIVE: To examine whether variations in the activities of general practice among family health service authorities can be explained by the populations characteristics and the organisation and resourcing of general practice. DESIGN: The family health services authorities were treated as discrete primary health care systems. Nineteen performance indicators reflecting the size, distribution, and characteristics of the population served; the organisation of general practice (inputs); and the activities generated by general practitioners and their staff (output) were analysed by stepwise regression. SETTING: 90 family health services authorities in England. MAIN OUTCOME MEASURES: Rates of cervical smear testing, immunisation, prescribing, and night visiting. RESULTS: 53% of the variation in uptake of cervical cytology was accounted for by Jarman score (t = -3.3), list inflation (-0.41), the proportion of practitioners over 65 (-0.64), the number of ancillary staff per practitioner (2.5), and 70% of the variation in immunisation rates by standardised mortality ratios (-6.6), the proportion of practitioners aged over 65 (-4.8), and the number of practice nurses per practitioner (3.5). Standardised mortality ratios (8.4), the number of practitioners (2.3), and the proportion over 65 (2.2), and the number of ancillary staff per practitioner (-3.1) accounted for 69% of variation in prescribing rates. 54% of the variation in night visiting was explained by standardised mortality ratios (7.1), the proportion of practitioners with lists sizes below 1000 (-2.2), the proportion aged over 65 (-0.4), and the number of practice nurses per practitioner (-2.5). CONCLUSIONS: Family health services authorities are appropriate systems for studying output of general practice. Their performance indicators need to be refined and to be linked to other relevant factors, notably the performance of hospital, community, and social services.

England↗
PubMed1991

The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3.

trkB is a tyrosine protein kinase gene highly related to trk, a proto-oncogene that encodes a receptor for nerve growth factor (NGF) and neurotrophin-3 (NT-3). trkB expression is confined to structures of the central and peripheral nervous systems, suggesting it also encodes a receptor for neurotrophic factors. Here we show that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation on tyrosine of gp145trkB, one of the receptors encoded by trkB. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells that express gp145trkB. Cotransfection of plasmids encoding gp145trkB and BDNF or NT-3 leads to transformation of recipient NIH 3T3 cells. In these assays, BDNF elicits a response at least two orders of magnitude higher than NT-3. Finally, 125I-NT-3 binds to NIH 3T3 cells expressing gp145trkB; binding can be competed by NT-3 and BDNF but not by NGF. These findings indicate that gp145trkB may function as a neurotrophic receptor for BDNF and NT-3.

Animals↗
PubMed1991

The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3.

The product of the trk proto-oncogene encodes a receptor for nerve growth factor (NGF). Here we show that NGF is a powerful mitogen that can induce resting NIH 3T3 cells to enter S phase, grow in semisolid medium, and become morphologically transformed. These mitogenic effects are absolutely dependent on expression of gp140trk receptors, but do not require the presence of the previously described low affinity NGF receptor. gp140trk also serves as a receptor for the related factor neurotrophin-3 (NT-3), but not for brain-derived neurotrophic factor. Both NGF and NT-3 induce the rapid phosphorylation of gp140trk receptors and the transient expression of c-Fos proteins. However, NT-3 appears to elicit more limited mitogenic responses than NGF. These results indicate that the product of the trk proto-oncogene is sufficient to mediate signal transduction processes induced by NGF and NT-3, at least in proliferating cells.

Animals↗
PubMed1991

The trk proto-oncogene encodes a receptor for nerve growth factor.

Two classes of receptors with distinct affinities for nerve growth factor (NGF) have been identified. The low affinity receptor (Kd approximately 10(-9) to 10(-8) M) is a cysteine-rich glycoprotein encoded by the previously characterized LNGFR gene. The structural nature of the high affinity receptor (Kd approximately 10(-11) to 10(-10) M) has yet to be established. In this study we show that the product of the human trk proto-oncogene (gp140trk) binds NGF with high affinity. Moreover, NGF could be chemically cross-linked to the endogenous gp140trk present in rat PC12 pheochromocytoma cells as well as to gp140trk ectopically expressed in mouse fibroblasts and in insect Sf9 cells. High affinity binding of NGF to gp140trk can occur in the absence of low affinity LNGFR receptors, at least in nonneural cells. Addition of NGF to PC12 cells elicits rapid phosphorylation of gp140trk on tyrosine residues and stimulates its tyrosine kinase activity. These results indicate that gp140trk is a functional NGF receptor that mediates at least some of the signal transduction processes initiated by this neurotrophic factor.

Adrenal Gland Neoplasms↗
PubMed1991

The epidemiology of diabetes complications study. IV. Correlates of diabetic background and proliferative retinopathy.

The roles of potential risk factors for background and proliferative retinopathy were evaluated in cross-sectional analyses from the Epidemiology of Diabetes Complications Study, Pittsburgh, Pennsylvania. This report presents results from the 657 insulin-dependent diabetic participants seen at the baseline examination (1986-1988). The presence of and severity of retinopathy were judged from stereoscopic photographs of three views of the ocular fundus using the modified Airlie House classification system. Fifty-three percent of the participants had background retinopathy, and 31% had proliferative retinopathy. Logistic regression analyses showed that among participants aged less than 18 years, those with background retinopathy were older and had higher levels of glycosylated hemoglobin compared with those without retinopathy. In the 18-29-year age group, participants with background retinopathy had a longer duration of diabetes, higher low density lipoprotein (LDL) cholesterol levels, and lower high density lipoprotein cholesterol levels and were more likely to have microalbuminuria compared with those without retinopathy. Participants aged 18-29 years with proliferative retinopathy had a longer duration of diabetes, higher diastolic blood pressure, and higher fibrinogen and LDL cholesterol levels than those with background retinopathy. In the age group greater than or equal to 30 years, diabetes duration, diastolic blood pressure, and fibrinogen, LDL cholesterol, and triglyceride levels were increased in participants with proliferative retinopathy versus those with background retinopathy. In a multivariate model of proliferative retinopathy, controlling for concurrent renal disease weakened the influence of blood pressure, fibrinogen, triglycerides, and LDL cholesterol and improved the overall fit of the model. These results suggest that diabetic nephropathy may contribute to the development of proliferative (but not background) retinopathy by increasing blood pressure and fibrinogen, by altering the lipoprotein profile, and possibly through other mechanisms.

Adolescent↗