Search PubMed⌕ Search

Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 163 records · Page 9Linked to original sources
PubMed2000

Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study.

The objective of this study was to describe associations of retinal arteriolar abnormalities with clinical and subclinical manifestations of atherosclerosis and a broad group of risk factors for vascular disease. A biracial population of 8772 adults (aged 48 to 72 years) living in 4 communities was examined from 1993 to 1995 were studied for that purpose. Retinal arteriovenous nicking and focal arteriolar narrowing were determined by light-box grading of a 45 degrees fundus photograph by use of a standardized protocol. Diameters of arterioles and venules were measured in digitized photographs, and a summary arteriolar-to-venular ratio was derived as an index of generalized arteriolar narrowing. Focal arteriolar narrowing was associated only with hypertension. Generalized arteriolar narrowing was associated with carotid plaque but not with any other evidence of atherosclerosis, either clinical (cardiovascular disease or stroke) or subclinical (carotid or popliteal artery thickness or lower limb obstructive disease), or with plasma cholesterol. It was also associated with smoking, with inflammatory markers (white blood cell count, fibrinogen, and reduced albumin), and with the triglyceride and high density lipoprotein cholesterol changes associated with inflammation. Arteriovenous nicking was inconsistently associated with subclinical atherosclerosis. It was not associated with cardiovascular disease, stroke, or plasma cholesterol. Arteriovenous nicking was associated with markers of inflammation and vascular endothelial dysfunction (von Willebrand factor and factor VIII). Arteriolar narrowing and nicking appear to be related to hypertension and inflammatory factors. Nicking may also be related to endothelial dysfunction. Results suggest that these arteriolar changes are pathologically distinct from atherosclerosis. Including their measurement in population studies may permit evaluation of the independent contribution of arteriolar disease to various ischemic diseases of the heart, brain, and other organs.

Aged↗
PubMed2000

The branchial arches and HGF are growth-promoting and chemoattractant for cranial motor axons.

During development, cranial motor neurons extend their axons along distinct pathways into the periphery. For example, branchiomotor axons extend dorsally to leave the hindbrain via large dorsal exit points. They then grow in association with sensory ganglia, to their targets, the muscles of the branchial arches. We have investigated the possibility that pathway tissues might secrete diffusible chemorepellents or chemoattractants that guide cranial motor axons, using co-cultures in collagen gels. We found that explants of dorsal neural tube or hindbrain roof plate chemorepelled cranial motor axons, while explants of cranial sensory ganglia were weakly chemoattractive. Explants of branchial arch mesenchyme were strongly growth-promoting and chemoattractive for cranial motor axons. Enhanced and oriented axon outgrowth was also elicited by beads loaded with Hepatocyte Growth Factor (HGF); antibodies to this protein largely blocked the outgrowth and orientation effects of the branchial arch on motor axons. HGF was expressed in the branchial arches, whilst Met, which encodes an HGF receptor, was expressed by subpopulations of cranial motor neurons. Mice with targetted disruptions of HGF or Met showed defects in the navigation of hypoglossal motor axons into the branchial region. Branchial arch tissue may thus act as a target-derived factor that guides motor axons during development. This influence is likely to be mediated partly by Hepatocyte Growth Factor, although a component of branchial arch-mediated growth promotion and chemoattraction was not blocked by anti-HGF antibodies.

Animals↗
PubMed2000

Immunomodulatory properties of rumalon, a glycosaminoglycan peptide complex, in patients with osteoarthritis: activation of T helper cell type 2 cytokines and antigen-specific IgG4 antigen-specific igG4 antibodies.

OBJECTIVE: To assess the immunogenic properties of the glycosaminoglycan peptide complex Rumalon, an aqueous extract of bovine cartilage and bone marrow frequently used in patients with osteoarthritis (OA). METHODS: Sera from 31 patients with OA who had received several series of Rumalon injections (Group 1, n = 17: before therapy and after one injection series; Group 2, n = 6: after 2-3 injection series; Group 3, n = 4: after 4-8 injection series; Group 4, n = 4: after 9-18 injection series) were tested by ELISA for antibodies against Rumalon and its components as well as by a double sandwich ELISA for type 1 [interferon-gamma, interleukin 2 (IL-2)] and type 2 cytokines (IL-4, IL-5, IL-10, IL-13). RESULTS: After the first injection series antibodies to Rumalon were induced in 7 of the 17 patients that were all negative before therapy. The antibodies were preferentially of the IgG4 type. IgG4 levels were increased during therapy (ELISA optical density x 1000 in Group 1: 73.9 +/- 209.5; Group 4: 1354.5 +/- 307.6), and in Group 4 all patients had developed these antibodies. Upon analysis of cytokine levels, there was a significant increase in IL-5 (Group 1 before therapy 407.4 +/- 257.1 pg/ml, Groups 3 and 4: 1409.4 +/- 963.1 pg/ml; p < 0.001) and to a lesser extent of IL-10 during therapy (Group 1 before therapy 950.2 +/- 867.8 pg/ml, Groups 3 and 4: 2817.8 +/- 3127.3 pg/ml; p < 0.05), while type 1 cytokines were not affected. CONCLUSION: Rumalon appears to have immunomodulatory properties and preferentially stimulates IgG4 antibodies via the activation of type 2 cytokines in vivo. Whether these phenomena can be correlated with the postulated therapeutic effect of Rumalon in patients with OA remains to be seen, but pain relief via release of endorphins by Th2 cells could be one explanation.

Adjuvants, Immunologic↗
PubMed2000

Efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles in the preoperative embolization of meningiomas.

BACKGROUND AND PURPOSE: Trisacryl gelatin microspheres are a new, commercially available nonabsorbable embolic agent. The purpose of this study was to evaluate their efficacy in the preoperative embolization of meningiomas as compared with polyvinyl alcohol (PVA) particles of various sizes. METHODS: In 30 consecutive patients, trisacryl gelatin microspheres (150-300 microm) were used for the preoperative superselective embolization of meningiomas (group 1). Thirty other consecutive patients had embolization with PVA particles of 45 to 150 microm (n = 15, group 2) and of 150 to 250 microm (n = 15, group 3). Extent of devascularization, intraoperative blood loss, blood transfusion, and hemostasis at the time of surgery were recorded for every patient. The inflammatory reaction, the extent of necrotic areas, and the most distal intravascular location of the embolic agent (arterial, arteriolar, precapillary, capillary) were recorded. RESULTS: There was no significant difference in the extent of angiographic devascularization among the groups. Intraoperative blood loss differed significantly between groups 1 and 2 and groups 1 and 3, but not between groups 2 and 3. The trisacryl gelatin microspheres were located more distally in tumor vessels than were the PVA particles of either size. The extent of intratumoral necrosis was not significantly different between the two embolic agents. In all groups there was a mild inflammatory tissue reaction in the vicinity of the embolic agent. CONCLUSION: Trisacryl gelatin microspheres may be effective in the preoperative embolization of meningiomas, producing significantly less blood loss at surgery than seen with PVA particles of either size, possibly because of the significantly more distal vascular penetration of the microspheres.

Acrylates↗
PubMed2000

MR spectroscopy in gliomatosis cerebri.

BACKGROUND AND PURPOSE: The diagnosis of gliomatosis cerebri with MR imaging is known to be difficult. We report on the value of MR spectroscopy in the diagnosis, grading, and biopsy planing in eight patients with histopathologically proved gliomatosis cerebri. METHODS: Patients underwent MR imaging and MR spectroscopy (single-voxel point-resolved spectroscopy [PRESS] at 1500/135, and chemical-shift imaging [CSI] PRESS at 1500/135) before open (n = 4) or stereotactic (n = 4) biopsy. In six patients who underwent CSI, biopsy samples were taken from regions of maximally elevated levels of choline/N-acetylaspartate (Cho/NAA). RESULTS: All patients showed elevated Cho/creatine (Cr) and Cho/NAA levels as well as varying degrees of decreased NAA/Cr ratios, which were most pronounced in the anaplastic lesions. In low-grade lesions, there was a maximum Cho/NAA ratio of 1.3, whereas in anaplastic tumors, the maximum Cho/NAA level was at least 2.5. Spectra in two patients with grade III lesions revealed a lactate peak; lactate and lipid signals were seen in two patients with grade IV lesions. Biopsy specimens from regions with maximally elevated levels of Cho/NAA showed dense infiltration of tumor cells. CONCLUSION: MR spectroscopy might be used to classify gliomatosis cerebri as a stable or a progressive disease indicating its potential therapeutic relevance.

Adolescent↗
PubMed2000

Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development.

p38alpha MAP kinase is activated in response to many cellular stresses and also regulates the differentiation and/or survival of various cell types in vitro, including skeletal muscle cells and cardiomyocytes. Here we show that targeted inactivation of the mouse p38alpha gene results in embryonic lethality at midgestation correlating with a massive reduction of the myocardium and malformation of blood vessels in the head region. However, this defect appears to be secondary to insufficient oxygen and nutrient transfer across the placenta. When the placental defect was rescued, p38alpha(-/-) embryos developed to term and were normal in appearance. Our results indicate that p38alpha is required for placental organogenesis but is not essential for other aspects of mammalian embryonic development.

Animals↗
PubMed2000

The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study.

PURPOSE: To describe the prevalence and the 5-year incidence of retinal central and branch vein occlusion and associated risk factors. METHODS: The Beaver Dam Eye Study (n = 4,926) is a population-based study in which retinal vein occlusions were detected at baseline (1988-1990) and at a 5-year follow-up examination (1993-1995) by grading of 30 degrees color fundus photographs. RESULTS: The prevalence and 5-year incidence of retinal branch vein occlusion were each 0.6%. The prevalence of retinal central vein occlusion was 0.1%, and the 5-year incidence was 0.2%. While adjusting for age, the prevalence of branch vein occlusion was associated with hypertension (odds ratio [OR] 5.42, 95% confidence interval [CI] 2.18, 13.47), diabetes mellitus (OR 2.43, 95% CI 1.04, 5.70), pulse pressure (OR 1.24 for 10 mm Hg, 95% CI 1.03, 1.48), ocular perfusion pressure (OR 2.09 for 10 mm Hg, 95% CI 1.45, 3.01), arteriovenous nicking (OR 16.75, 95% CI 7.33, 38.24), and focal arteriolar narrowing (OR 22.86, 95% CI 8.43, 62.03). The age-adjusted incidence of retinal branch vein occlusion was associated with current smoking (OR 4.43 95%, CI 1.53, 12.84) compared with nonsmokers and to focal arteriolar narrowing (OR 5.24, 95% CI 1.97, 13.94) at baseline. While controlling for age, the incidence of branch vein occlusion was not associated with serum lipid levels, body mass index, white blood cell count, alcohol consumption, aspirin use, glaucoma, intraocular pressure, or ocular hypertension. CONCLUSIONS: Retinal vein occlusion is infrequent in the population. These data suggest a strong association between retinal branch vein occlusion and retinal arteriolar changes. Data from larger populations are needed to further assess associations between risk factors and the incidence of retinal vein occlusions.

Adult↗
PubMed1999

North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.

PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.

Adolescent↗
PubMed1999

Epidemiology of age-related macular degeneration.

For more than two decades, researchers have sought to identify "risk factors" for age-related macular degeneration (AMD), a major cause of irreversible vision loss in the Western world, particularly in the elderly. Two issues have complicated this search: failure to differentiate between different stages of AMD and misinterpretation of measures of association (odds ratios) and risk (risk ratios) derivable from different research designs. Fortunately, in more recent epidemiologic studies, more attention has been given to these issues. Three groups of potential "risk factors" that have been studied were reviewed: those known to be risk factors for cardiovascular disease, environmental factors, and racial and ethnic factors. Of these, only tobacco smoking, a known risk factor for cardiovascular disease, has been demonstrated to be associated with AMD consistently across many studies of different design, carried out within different populations. The available evidence supports at least a doubling of risk of late AMD associated with long-term smoking, a factor that is under the control of the individual. The preponderance of evidence has not supported other factors to the same degree. Presently, racial and ethnic factors are high priorities for further research.

Age Factors↗
PubMed1999

Risk factors for hospitalization in people with diabetes.

OBJECTIVE: To determine factors predicting hospitalization in people with diabetes. METHODS: Two population-based groups with diabetes were examined at baseline (1980-1982), 4 years (1984-1986), and 10 years (1990-1992). The younger-onset group (n = 777) consisted of all persons diagnosed as having diabetes before age 30 years who were taking insulin, and the older-onset group (n = 542) consisted of a sample of persons diagnosed after age 30 years. At the 10-year examination, participants were asked if they had been hospitalized in the previous year. Factors from the 4-year examination were examined for their ability to predict hospitalization at the 10-year examination. RESULTS: In the younger-onset group, 25.5% reported being hospitalized. In logistic models, glycosylated hemoglobin level (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.16-1.39 for a 1% increment) and hypertension (OR, 1.60; 95% CI, 1.08-2.38) predicted hospitalization. Factors that were not significant included age, sex, systolic and diastolic blood pressures, body mass, smoking status, and alcohol consumption. In the older-onset group, 30.8% reported being hospitalized. In logistic models, only glycosylated hemoglobin level (OR, 1.16; 95% CI, 1.06-1.29 for a 1% increment) predicted hospitalization. CONCLUSIONS: Glycemic control is subject to intervention. Better control may decrease hospitalization among people with diabetes. Thus, there is considerable potential for reducing health care costs.

Adult↗
PubMed1999

Bidirectional signals establish boundaries.

Recent studies have shown that the formation of boundaries between the segments - rhombomeres - of the vertebrate hindbrain depends on bidirectional signalling between neighbouring cells. This signalling is mediated by Eph receptors and their ligands, which has been found to restrict cell intermingling in vitro.

Animals↗
PubMed1999

Independent sector regulation. Privates on parade.

The government's proposal to set up a new regulatory body for the private and voluntary sectors is regrettable. The major hospital groups in the private sector could undertake some system of clinical governance. Whatever form regulation takes, it must be supported by much better information on the private sector, including consultants' activity rates and rates of re-admission and numbers of transfers to NHS hospitals.

Facility Regulation and Control↗