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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 595 records · Page 33Linked to original sources

Making sense of inequalities: a response to Peter Townsend.

This article addresses the continuing controversy generated by the Black Report on Inequalities in Health, published in Britain in 1980, in response to the defense offered by Professor Peter Townsend. The author argues that Townsend's riposte to the critics of the Black Report is flawed in at least two respects. First, Townsend fails to acknowledge that the Black Report was as much an exercise in policy advocacy as in scholarly analysis, making rather large assumptions about the links in the reasoning leading to its recommendations for a massive program of income redistribution. Second, Townsend's defense of Black's use of social class as its main tool for analyzing health inequalities dismisses too easily much of the evidence; for example, the effects of social mobility and the historical dimension. Moreover, by concentrating on social class, a heterogeneous category, analysis may ignore what is most relevant for policy-making: i.e., specific factors associated with specific forms of deprivation, located within social classes or particular geographical communities. It would therefore be more constructive if scholars were to accept and research this complexity, rather than defending the Black Report as though it were a definitive (not to say sacred) text.

Adolescent↗

Association of elevated IGF-I levels with increased retinopathy in late-onset diabetes.

Insulinlike growth factor I (IGF-I) has been suggested to play a role in the pathogenesis of proliferative diabetic retinopathy (PDR). We determined IGF-I levels in subjects in a large population-based study of 928 people with diabetes diagnosed at 30 yr of age or older. PDR was found in 15.7% of the insulin-using group (n = 517) and in 2.8% of those not using insulin (n = 397). The mean serum level of IGF-I was 208 micrograms/L in individuals using insulin and 222 micrograms/L in those not using insulin, both significantly lower than in a nondiabetic comparison group (278 micrograms/L, P less than 0.0001). Logistic regression analysis was used to examine the relationship between IGF-I and PDR while controlling for other factors associated with the presence of PDR. After controlling for duration of diabetes, glycosylated hemoglobin, systolic blood pressure, presence of proteinuria, and age at diagnosis, higher levels of IGF-I were significantly associated with an increased frequency of PDR (P = 0.025) in the group using insulin. In individuals not using insulin, higher levels of IGF-I were associated with an increased frequency of PDR or moderate non-PDR (P = 0.08). These data suggest that higher IGF-I levels may be a risk factor for the development of severe retinopathy in people with diabetes diagnosed at 30 yr of age or older.

Adult↗

Visual impairment and retinopathy in people with normal glucose tolerance, impaired glucose tolerance, and newly diagnosed NIDDM.

OBJECTIVE: Prevalence rates of visual impairment and retinopathy were compared in 1992 people with normal glucose tolerance, impaired glucose tolerance (IGT), or newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Glucose tolerance status was based on an oral glucose tolerance test after exclusion of those with a history of diabetes and/or diabetes medication use in an upper middle-class community of older white adults in southern California between 1984 and 1987. RESULTS: Although many sex-specific comparisons were made between glucose tolerance groups, only a few emerged as statistically significant. Among those, women with IGT had significantly higher age-adjusted rates of visual impairment (10.8%) than women with normal glucose tolerance (4.4%). Among men, those with IGT had significantly higher age-adjusted rates of visual impairment (7.9%) than men with newly diagnosed NIDDM (4.0%). CONCLUSIONS: Low frequencies of retinopathy were found in all three glucose tolerance groups.

Age Factors↗

Factors determining recall of examination results in diabetic population.

OBJECTIVE: To determine factors influencing recall of examination results after 4 yr. RESEARCH DESIGN AND METHODS: At two examinations that were 4 yr apart, a diabetic population was asked, "Have you been told that your diabetes has affected the back of your eyes, that is the retina?" Participants were informed by letter whether they had retinopathy. Subjects in this study included younger-onset (n = 311) and older-onset (n = 279) diabetic subjects who had retinopathy at baseline and did not know it. RESULTS: Forty-two percent of younger-onset and 29% of older-onset subjects recalled at follow-up that they had been told their diabetes had affected their eyes. People in both groups were more likely to recall they had retinopathy if they had more severe retinopathy, had more symptoms of neuropathy and peripheral vascular disease, had seen an ophthalmologist within 2 yr, or monitored their blood glucose more often. In addition, younger-onset diabetic subjects with poorer visual acuity or who were on a combination insulin regimen and older-onset people taking insulin, having more education, or who were younger were more likely to recall they had retinopathy. Factors not associated with recall in either group included sex, duration of diabetes, proteinuria, glycosylated hemoglobin, and family income. CONCLUSIONS: These results underscore the need to develop better methods to deliver health-care information to people who have diabetes.

Adult↗

Association of cigarette smoking with diabetic retinopathy.

OBJECTIVE: To determine whether cigarette smoking is associated with the incidence and progression of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Younger-onset diabetic subjects who had been diagnosed at less than 30 yr of age and taking insulin (n = 1210) and a random sample of older-onset diabetic subjects diagnosed at greater than or equal to 30 yr of age (n = 1780) were selected. Baseline examinations were conducted on 996 younger- and 1370 older-onset subjects. Incidence of retinopathy was based on 138 younger-onset and 154 older-onset insulin-taking subjects and 321 older-onset non-insulin-taking subjects who were free of retinopathy at baseline. Progression of retinopathy was based on 530 younger-onset and 418 older-onset insulin-taking subjects and 486 older-onset non-insulin-taking subjects with less than proliferative diabetic retinopathy at baseline. RESULTS: Baseline smoking history was categorized by status (nonsmoker, ex-smoker, current smoker) and pack-years smoked while diabetic. Retinopathy was documented by stereoscopic fundus photography. In univariate analyses, the only significant association was between pack-years and progression to proliferative diabetic retinopathy in older-onset insulin-taking subjects (P less than 0.01). After controlling for known risk factors for the incidence and progression of retinopathy, pack-years smoked was borderline significant (P = 0.052) in predicting incidence of retinopathy in younger-onset subjects. Smoking was not associated with incidence in older-onset subjects or with progression or progression to proliferative diabetic retinopathy in any of the groups. CONCLUSIONS: Smoking is not likely to be an important risk factor for diabetic retinopathy.

Adult↗

Antibodies against central nervous system tissue (anti-CNS) detected by ELISA and western blotting: marker antibodies for neuropsychiatric manifestations in connective tissue diseases.

Organ specific antibodies against epitopes of the central nervous system (CNS) tissue were detected by ELISA and Western blotting (WB) in sera from patients with ANA positive collagen disorders using a 100,000 g supernatant from beef or rat brain. The corresponding CNS-antigens consist of six major determinants at molecular weights 29, 48, 56, 68 kD and six minor determinants at 130, 110, 86, 60, 38, 34 kD. All except the 38 kD polypeptide were organ specific. Forty-six of 91 patients with ANA positive collagen disorders reacted with at least one of these determinants; 43 of them had cerebral symptoms in contrast to only three of the 43 anti-CNS negative patients. Sera from patients with other disorders did not react with these epitopes. We conclude that anti-CNS antibodies detected by Western blotting may be marker for neuropsychiatric manifestations in patients with collagen disorders.

Adolescent↗

Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis.

Antibodies against neutrophils have been detected in sera from patients with primary sclerosing cholangitis and inflammatory bowel diseases either by immunofluorescence or by enzyme-linked immunosorbent assay. To assess primary sclerosing cholangitis-specific antibodies, we examined sera from 30 patients with clinically and morphologically well-established primary sclerosing cholangitis by Western blotting against neutrophils and compared these results with those obtained by testing sera from patients with inflammatory bowel diseases. By Western blot using sonified neutrophils, 24 (80%) of 30 primary sclerosing cholangitis sera were positive. Five antigenic determinants at 95, 60, 55, 40 and 30 kD were visualized. Twenty-eight of the primary sclerosing cholangitis sera also showed the characteristic perinuclear fluorescence pattern by immunofluorescence on neutrophils. Thus a serological diagnosis of primary sclerosing cholangitis could be made in 80% of patients based on these two methods. In contrast, only 9% of 23 patients with ulcerative colitis and 10% of 60 patients with Crohn's disease were positive by Western blot, and these patients also showed positive perinuclear fluorescence pattern by immunofluorescence, suggesting an overlap between inflammatory bowel diseases and primary sclerosing cholangitis. Although some patients with classical primary biliary cirrhosis and autoimmune chronic active hepatitis had antibodies against primary sclerosing cholangitis epitopes, none of the patients with obstructive bile duct disorders, collagen diseases, Wegener's granulomatosis or other hepatic and nonhepatic disorders were positive by Western blot, indicating the specificity of these five primary sclerosing cholangitis-related neutrophilic epitopes.

Adolescent↗

Risks and benefits of comparative studies: notes from another shore.

The fascination of American and British scholars with each other's health care systems is a case study of the risks and benefits of the comparative approach. The risks stem from the temptation to seek solutions to national problems in the experience of other countries in a way that ignores the fact that whereas institutions may, in theory at least, be exportable, their social, political, and economic environment is not. The benefits derive from the fact that only a comparative approach can hope to identify the factors that are specific to national health care systems, as distinct from being common to all such systems. Finally, a comparative perspective can extend national ideas about what is possible and at the same time provide the understanding that must precede prescription.

Cross-Cultural Comparison↗

[Photoablative, refractive keratectomy in treatment of myopia. A case study of 134 myopic eyes with 6-months follow-up].

A total of 106 myopic eyes and 134 eyes with sight were operated on with photorefractive keratectomy. To perform these operations the two surgeons used an excimer laser made by Aesculap-Meditec, emitting a wavelength of 193 nm. Patients were assigned to one of four groups according to refraction. The majority of patients had moderately high to high myopia, i.e., over 6 D. All patients could no longer wear spectacles or had developed contact lens intolerance. The follow-up period extended over 6 months. Depending upon the amount of correction desired in myopia, i.e., between -3D and -15 D, we ablated between 30 and 130 microns of the central corneal stroma after abrading the epithelium. The optical zone had a diameter of 5 mm. Three months after the operation a reduction of myopia by 10.6 D had been achieved in the group with moderately high myopia (10-20 D). In the group of high myopia (over 20 D), the mean correction was 13.4 D. In the group with refraction between 0 and 6 D, 88% of the eyes treated had attained a correction between -1 and +1 D 3 months postoperatively. The results in the group with myopia between 6 to 10 D were similar attaining a refraction of -1 and +1 D. Regression of 2 to 5 D occurred in all patients during the follow-up period of 6 months, depending on the degree of correction. We noted a slight subepithelial reticular haze in all eyes. In 98% of the cases the haze was clinically irrelevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The trk family of oncogenes and neurotrophin receptors.

To date more than twenty five different oncogenes have been identified in human neoplasias. One of these oncogenes is trk, a transforming gene originally isolated from a colon carcinoma biopsy by using gene transfer assays. This oncogene encodes a chimeric molecule that contains the 221 amino terminal residues of a non-muscle tropomyosin followed by the transmembrane and cytoplasmic domains of the trk proto-oncogene product, a tyrosine protein kinase receptor. trk oncogenes have also been identified in a significant fraction of thyroid papillary carcinomas. Some of these trk oncogenes contain sequences derived from genes other than tropomyosin. One such gene is tpr, a gene first identified as a component of the human met oncogene. The trk proto-oncogene, non-muscle tropomyosin and tpr map in the long arm of chromosome 1. Therefore, trk oncogenes are likely to result from internal rearrangements or from unequal cross-overs between two chromosome 1s. Recent studies have demonstrated that the product of the trk proto-oncogene, gp140trk, is the functional receptor for nerve growth factor (NGF). NGF elicits the rapid phosphorylation of gp140trk on tyrosine residues. Moreover, addition of NGF to NIH3T3 cells expressing gp140trk induces the transient expression of c-Fos, DNA synthesis and morphologic transformation. Finally, transfection of the trk proto-oncogene into NGF non-responsive PC12 mutant cells restores NGF responsiveness. Two additional genes designated trkB and trkC have recently been isolated in our laboratory. These genes are highly related to the trk proto-oncogene and encode tyrosine protein kinases which serve as functional receptors for the NGF-related neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophic-3 (NT-3), respectively. Whether mutations in these novel members of the trk family of receptor genes are also implicated in human cancer remains to be determined.

Animals↗

Anti-M4 antibodies in primary biliary cirrhosis react with sulphite oxidase, an enzyme of the mitochondrial inter-membrane space.

Testing three anti-M2/anti-M4-positive and three anti-M2 positive/anti-M4-negative primary biliary cirrhosis (PBC) marker sera against different mitochondrial enzymes by ELISA it could be shown that only the anti-M4-positive sera reacted with pyruvate dehydrogenase (M2) and sulphite oxidase (SO), an enzyme of the mitochondrial inter-membrane space in parallel. Absorption of these sera with SO abolished completely the anti-M4 antibodies but had no effect on the anti-M2 activity. The specificity of this reaction was also documented by examining 30 anti-M2/anti-M4-positive sera showing that 28 of them were positive with SO. Among ten anti-M2/anti-M8-positive but anti-M4-negative PBC sera, four became positive when tested against SO, indicating a higher sensitivity of SO for the demonstration of anti-M4. Retesting sera from 76 PBC patients with defined anti-mitochondrial antibody (AMA) profiles who had been followed for up to 18 years against SO by ELISA and complement fixation test (CFT), none of 32 patients with profile A B (positive for anti-M2 and/or anti-M9 by ELISA; benign course) but 33 of 44 patients with profile C/D (anti-M2/anti-M4 and or anti-M8 positive by CFT and or ELISA; progressive course) were positive. These data indicate that sulphite oxidase can be used in the ELISA for the detection of anti-M4 antibodies which may be of prognostic relevance.

Antibodies↗

The incidence of gross proteinuria in people with insulin-dependent diabetes mellitus.

Epidemiologic data on the incidence of gross proteinuria in people with diabetes are important in medical counseling, in projecting estimates of needs and costs of health care, and for developing approaches to prevent renal complications. We performed a population-based incidence study in southern Wisconsin of insulin-taking diabetic persons diagnosed before 30 years of age. The presence of gross proteinuria (greater than or equal to 0.30 g/L) was determined by means of a reagent strip. The incidence of proteinuria in a 4-year interval was 14.4% (95% confidence interval, 11.7% to 17.0%). The relative risk of developing proteinuria after 4 years for those with glycosylated hemoglobin levels in the highest quartile compared with those in the lowest quartile was 3.0 (95% confidence interval, 1.6 to 5.3). The incidence of proteinuria was also associated with higher diastolic blood pressure, being male, taking more insulin, and having more severe retinopathy at the baseline examination. The relationship between glycosylated hemoglobin level and the incidence of proteinuria was significant even after controlling for these other risk variables. These data suggest that hyperglycemia, as measured by glycosylated hemoglobin level, is a significant risk factor for the development of gross proteinuria.

Adolescent↗

Long-term effect of mexiletine on left ventricular function and relation to suppression of ventricular arrhythmia.

The effects of oral mexiletine on left ventricular (LV) ejection fraction (EF) and ventricular arrhythmias--and a possible relation between these effects--were evaluated during 3 months of therapy in 29 patients with chronic ventricular premature complexes (VPCs) and a moderately reduced to normal LVEF by 24-hour Holter monitoring and by radionuclide ventriculography at rest and during maximum tolerable exercise testing. After an average titration period of 13 days, a mean daily mexiletine dose of 739 mg was maintained throughout the treatment. At the end of titration and after 3 months of treatment, patients with a baseline LVEF less than or equal to 40% (group 2) responded with a median reduction of the hourly VPC rate by 90 and 81%, respectively, compared with 79 and 72% in those with a baseline LVEF greater than 40% (group 1). Couplets and runs of ventricular tachycardia were almost completely suppressed in nearly all patients. A single patient had a proarrhythmic increase in VPCs during treatment. Compared with baseline, there were no significant changes in resting or exercise LVEF after 1 or 3 months of treatment in either of the 2 groups of patients. No correlation was found between treatment-induced changes in arrhythmia frequency and in resting EF. No symptoms of congestive heart failure developed. The study confirms that long-term use of mexiletine is efficacious and relatively free of cardiac depressant effects even in patients with diminished LV function.

Aged↗

New lamps for old.

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Community Participation↗