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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 181 records · Page 10Linked to original sources
PubMed1999

Pigs aerogenously immunized with genetically inactivated (ghosts) or irradiated Actinobacillus pleuropneumoniae are protected against a homologous aerosol challenge despite differing in pulmonary cellular and antibody responses.

Aerosol immunization is a safe way to induce complete protection against pleuropneumonia in pigs caused by the lung pathogenic bacterium Actinobacillus pleuropneumoniae. In order to determine the local immune responses of vaccinees in concomitant with protection, lung lining fluid before and 3 weeks after immunization from pigs immunized three times with aerosols of either genetically inactivated ghosts which represent whole cell envelope preparations, or irradiated bacteria were examined following an homologous aerosol challenge. Specific antibody isotypes in the bronchoalveolar lavage were assayed by whole cell ELISAs. Total and relative numbers of cells including lymphocyte subsets were determined. In both vaccinated groups a net influx of plasma cells and lymphocytes, as well as a significant increase of specific IgG occurred. Concurrently, the CD4+/CD8+ ratio was found to increase after aerosol immunization. The lymphocyte subsets of IgG+ and IgA+ cells were found significantly higher in the group immunized with irradiated bacteria when compared to pigs immunized with bacterial ghosts. The latter group showed a significant increase of IgA, IgM, and a net influx of lymphoid blasts and granulocytes in the bronchoalveolar lining fluid. Although differences between the local immune responses of both immunized groups occurred, a significant increase of specific IgG and a net influx of plasma cells and lymphocytes were found to be associated with complete protection against a homologous aerosol challenge infection.

Actinobacillus Infections↗
PubMed1999

Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study.

Narrowing and other changes in retinal arterioles may reflect damage due to hypertension, which may predict stroke and other cardiovascular diseases independently of blood pressure level. Newly developed quantitative methods of assessing retinal narrowing are used to determine whether this sign is related only to current blood pressure or whether it also independently reflects the effects of previous blood pressure. Retinal photography was performed at the third examination of Atherosclerosis Risk in Communities (ARIC) Study in 1993-1995, and results are presented for the 9,300 nondiabetic participants aged 50-71 years. Generalized narrowing of smaller arterioles was strongly and monotonically related to current blood pressure in men and women, whether they were taking antihypertensive medications or not, and, independent of current blood pressure, was consistently and monotonically related to blood pressure levels measured 3 and 6 years before the retinal assessment. Arteriovenous nicking was also independently related to both current and previous blood pressures. The patterns of association suggested that these signs reflect both transient and persisting structural effects of elevated blood pressure, in agreement with the scant pathologic literature available. The findings suggest that retinal assessment may be useful for research on the microvascular contributions to clinical cardiovascular diseases.

Aged↗
PubMed1999

Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus.

CONTEXT: Despite nutrition information and guidelines that advise against depriving diabetic patients of the potential benefit of moderate alcohol intake against cardiovascular events, the association between alcohol consumption and risk of cardiovascular outcomes in diabetic individuals has not been determined. OBJECTIVE: To examine the relationship between alcohol intake and coronary heart disease (CHD) mortality in persons with older-onset diabetes. DESIGN: Population-based, prospective cohort study conducted from 1984 through 1996, with a follow-up of up to 12.3 years. SETTING AND PARTICIPANTS: A total of 983 older-onset diabetic individuals (mean [SD] age, 68.6 [11.0] years; 45.2% male; 98.5% white) were interviewed about their past-year intake of alcoholic beverages during the 1984-1986 follow-up examination of a population-based study of diabetic persons in southern Wisconsin. MAIN OUTCOME MEASURE: Time to mortality from CHD by category alcohol intake. RESULTS: Alcohol use was inversely associated with risk of CHD mortality in older-onset diabetic subjects. The CHD mortality rates for never and former drinkers were 43.9 and 38.5 per 1000 person-years, respectively, while the rates for those with alcohol intakes of less than 2, 2 to 13, and 14 or more g/d were 25.3, 20.8, and 10.0 per 1000 person-years, respectively. Compared with never drinkers and controlling for age, sex, cigarette smoking, glycosylated hemoglobin level, insulin use, plasma C-peptide level, history of angina or myocardial infarction, digoxin use, and the presence and severity of diabetic retinopathy, former drinkers had a relative risk (RR) of 0.69 (95% confidence interval [CI], 0.43-1.12); for those who drank less than 2 g/d (less frequent than 1 drink a week), the RR was 0.54 (95% CI, 0.33-0.90); for 2 to 13 g/d, it was 0.44 (95% CI, 0.23-0.84); and for 14 or more g/d (about 1 drink or more a day), it was 0.21 (95% CI, 0.09-0.48). Further adjustments for blood pressure, body mass index, education, physical activity, diabetes duration, hypertension history, overt nephropathy, peripheral neuropathy, lipid measures, or intake of medications such as aspirin and antihypertensive agents did not change the associations observed. CONCLUSION: Our results suggest an overall beneficial effect of alcohol consumption in decreasing the risk of death due to CHD in people with older-onset diabetes.

Age of Onset↗
PubMed1999

A Bayesian approach to modelling the natural history of a chronic condition from observations with intervention.

To assess the costs and benefits of screening and treatment strategies, it is important to know what would have happened had there been no intervention. In today's ethical climate, however, it is almost impossible to observe this directly and therefore must be inferred from observations with intervention. In this paper, we illustrate a Bayesian approach to this situation when the observations are at separated and unequally spaced time points and the time of intervention is interval censored. We develop a discrete-time Markov model which combines a non-homogeneous Markov chain, used to model the natural progression, with mechanisms that describe the possibility of both treatment intervention and death. We apply this approach to a subpopulation of the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a population-based cohort study to investigate prevalence, incidence, and progression of diabetic retinopathy. In addition, posterior predictive distributions are discussed as a prognostic tool to assist researchers in evaluating costs and benefits of treatment protocols. While we focus this approach on diabetic retinopathy cohort data, we believe this methodology can have wide application.

Age of Onset↗
PubMed1999

Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study.

The relation of antioxidant nutrients to the incidence of nuclear cataracts was investigated in a cohort of adults aged 43-84 years in the Beaver Dam Eye Study (Beaver Dam, Wisconsin). Nuclear opacity was assessed on a five-point ordinal scale using lens photographs taken at baseline (1988-1990) and at follow-up (1993-1995). Of the 1,354 persons eligible, 246 developed a nuclear cataract (level 4 or 5 opacity) in at least one eye. Antioxidant intakes were assessed using a food frequency questionnaire administered at baseline for time points corresponding to intake during the year preceding baseline and 10 years before baseline (the distant past). Lutein-zeaxanthin was the only carotenoid, out of five examined, that was associated with nuclear cataracts. Persons in the highest quintile of lutein intake in the distant past were half as likely to have an incident cataract as persons in the lowest quintile of intake (95% confidence interval 0.3-0.8). In the overall group, nuclear cataracts were not significantly related to intake of vitamin C or vitamin E. However, vitamins C and E were inversely associated with opacities in persons who had some other risk factors for cataracts. While results of this short term follow-up study are consistent with a possible protective influence of lutein and vitamins E and C on the development of nuclear cataracts, the evidence in the present study provides weak support for these associations.

Adult↗
PubMed1999

Tyro-3 family receptors are essential regulators of mammalian spermatogenesis.

We have generated and analysed null mutations in the mouse genes encoding three structurally related receptors with tyrosine kinase activity: Tyro 3, Axl, and Mer. Mice lacking any single receptor, or any combination of two receptors, are viable and fertile, but male animals that lack all three receptors produce no mature sperm, owing to the progressive death of differentiating germ cells. This degenerative phenotype appears to result from a failure of the tropic support that is normally provided by Sertoli cells of the seminiferous tubules, whose function depends on testosterone and additional factors produced by Leydig cells. Tyro 3, Axl and Mer are all normally expressed by Sertoli cells during postnatal development, whereas their ligands, Gas6 and protein S, are produced by Leydig cells before sexual maturity, and by both Leydig and Sertoli cells thereafter. Here we show that the concerted activation of Tyro 3, Axl and Mer in Sertoli cells is critical to the role that these cells play as nurturers of developing germ cells. Additional observations indicate that these receptors may also be essential for the tropic maintenance of diverse cell types in the mature nervous, immune and reproductive systems.

Animals↗
PubMed1999

Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis.

Eph receptor tyrosine kinases and their cell-surface-bound ligands, the ephrins, regulate axon guidance and bundling in the developing brain, control cell migration and adhesion, and help patterning the embryo. Here we report that two ephrinB ligands and three EphB receptors are expressed in and regulate the formation of the vascular network. Mice lacking ephrinB2 and a proportion of double mutants deficient in EphB2 and EphB3 receptor signaling die in utero before embryonic day 11.5 (E11.5) because of defects in the remodeling of the embryonic vascular system. Our phenotypic analysis suggests complex interactions and multiple functions of Eph receptors and ephrins in the embryonic vasculature. Interaction between ephrinB2 on arteries and its EphB receptors on veins suggests a role in defining boundaries between arterial and venous domains. Expression of ephrinB1 by arterial and venous endothelial cells and EphB3 by veins and some arteries indicates that endothelial cell-to-cell interactions between ephrins and Eph receptors are not restricted to the border between arteries and veins. Furthermore, expression of ephrinB2 and EphB2 in mesenchyme adjacent to vessels and vascular defects in ephB2/ephB3 double mutants indicate a requirement for ephrin-Eph signaling between endothelial cells and surrounding mesenchymal cells. Finally, ephrinB ligands induce capillary sprouting in vitro with a similar efficiency as angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), demonstrating a stimulatory role of ephrins in the remodeling of the developing vascular system.

Animals↗
PubMed1999

Association of ocular disease and mortality in a diabetic population.

OBJECTIVE: To investigate the association of ocular disease with all-cause and cause-specific mortality in a diabetic population. DESIGN: Geographically defined population-based cohort study. SETTING: An 11-county area in Wisconsin. STUDY POPULATION: Participants were all younger-onset diabetic persons (diagnosed as having diabetes at <30 years of age and taking insulin) and a random sample of older-onset diabetic persons (diagnosed as having diabetes at > or =30 years of age). Diabetic retinopathy, macular edema, visual acuity, and cataract were measured using standardized protocols at baseline examinations from 1980 to 1982, in which 996 younger-onset and 1370 older-onset persons participated. Participants were followed up for 16 years. MAIN OUTCOME MEASURE: All-cause and cause-specific mortality as determined from death certificates. RESULTS: In the younger-onset group, after controlling for age and sex, retinopathy severity, macular edema, cataract, history of cataract surgery, and history of glaucoma at baseline were associated with all-cause and ischemic heart disease mortality. In the older-onset group, after controlling for age and sex, retinopathy and visual impairment were related to all-cause, ischemic heart disease, and stroke mortality. No ocular variable under study was related to cancer mortality in the older-onset group. After controlling for systemic risk factors, visual impairment was associated with all-cause and ischemic heart disease mortality in the younger-onset group. In the older-onset group, retinopathy severity was related to all-cause and stroke mortality, and visual impairment was related to all-cause, ischemic heart disease, and stroke mortality. CONCLUSIONS: Presence of more severe retinopathy or visual impairment in diabetic patients is a risk indicator for increased risk of ischemic heart disease death. Presence of these ocular conditions may identify individuals who should be under care for cardiovascular disease.

Adolescent↗
PubMed1999

Retinal emboli and stroke: the Beaver Dam Eye Study.

OBJECTIVE: To describe the prevalence at baseline and the 5-year incidence of retinal emboli, associated risk factors, and the relationship of retinal emboli at baseline to stroke and ischemic heart disease mortality. METHODS: The Beaver Dam Eye Study is a large (N = 4926) population-based study of persons aged 43 to 86 years at the baseline examination. Retinal emboli were detected at baseline (1988-1990) and at a 5-year follow-up (1993-1995) by grading of stereoscopic 30 degrees color fundus photographs using standardized protocols. Cause-specific mortality was determined from death certificates. RESULTS: The prevalence of retinal arteriolar emboli was 1.3%, and the 5-year incidence was 0.9%. After adjustments were made for age and sex, the prevalence of retinal emboli was associated with higher pulse pressure, hypertension, diabetes mellitus, past and current smoking, cardiovascular disease, and the presence of retinopathy. After adjustments were made for age and sex, the incidence of retinal emboli was associated with past and current smoking and a history of coronary artery bypass surgery. After age, sex, and systemic factors were controlled for, people with retinal emboli had a significantly higher hazard of dying with a mention of stroke on the death certificate (hazard ratio = 2.61, 95% confidence interval = 1.12-6.08) than those without retinal emboli. CONCLUSIONS: Persons with retinal emboli are at an increased risk of stroke-related death. Data also show an association of smoking, hypertension, and cardiovascular disease with the prevalence of retinal emboli. CLINICAL RELEVANCE: Data from this population-based study suggest that after discovery of retinal emboli in the asymptomatic patient, referral for possible medical intervention to control hypertension, if present, may be beneficial.

Adult↗
PubMed1999

Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To describe the prevalence of age-related maculopathy (ARM) in blacks and whites and its relation to macrovascular disease and risk factors thereof in a population studied for cardiovascular disease risk factors and outcomes. POPULATION: A biracial population of 11532 adults (ranging from 48-72 years of age; 8984 whites and 2548 blacks) living in 4 US communities (Forsyth County, North Carolina; the city of Jackson, Miss; selected suburbs of Minneapolis, Minn; and Washington County, Maryland) were examined during the interval from 1993 to 1995. METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of 1 eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System. RESULTS: The overall prevalence of any ARM was lower in blacks (3.7%) than whites (5.6%). After controlling for age and sex, the odds ratio for any ARM in blacks compared with whites was 0.73 (95% confidence interval, 0.58-0.91; P = .006). Few associations between atherosclerosis and its risk factors and the presence of early ARM or its component lesions were found. After adjusting for age, race, and sex, carotid artery plaque (odds ratio, 1.77; 95% confidence interval, 1.18-2.65) and focal retinal arteriolar narrowing (odds ratio, 1.79; 95% confidence interval, 1.07-2.98) were associated with retinal pigment epithelial depigmentation. CONCLUSIONS: This population-based study documents the higher prevalence of early ARM in whites compared with blacks. Measures of atherosclerosis and its risk factors were generally unrelated to ARM and do not explain these racial differences.

Aged↗
PubMed1999

Is it necessary to test patients with immune thrombocytopenic purpura (ITP) for seropositivity to HTLV-1?

HTLV-111 (HIV-1) has been shown to be associated with thrombocytopenia of a type resembling immune thrombocytopenic purpura (ITP). HTLV-1 is a retrovirus similar to HIV-I (HTLV-III) in a number of features, such as CD4 tropism. It is responsible for several clinical entities, including adult T-cell leukemia/lymphoma. The relationship, if any, of HTLV-1 and thrombocytopenia has not been systematically studied. To determine how frequently ITP patients are commonly infected with HTLV-1, the following study was performed. Frozen serum samples from 123 randomly selected patients with ITP were thawed and tested for antibodies to HTLV-1 by enzyme-linked immunoabsorbent assay. Positives were confirmed by Western blot. Three patients were initially found to be positive for HTLV-1. One was a female of Caribbean ancestry, one was a male HIV-1+ patient, and one was an adolescent female with no known risk factors for HIV-1. The two females later tested negative for HTLV-1. As a screening program for HTLV-1 antibodies was not introduced into blood banks until November 1988, there may have been passive transfer of the virus from intravenous immunoglobulin that these patients had received. This study of a large number of ITP patients shows that it is extremely unlikely that they are infected with HTLV-1, and, therefore, it is unnecessary to screen ITP patients for seropositivity to HTLV-1.

Adolescent↗
PubMed1999

Is there any relationship between eosinophilia myalgia syndrome (EMS) and fibromyalgia syndrome (FMS)? An analysis of clinical and immunological data.

The eosinophilia-myalgia syndrome (EMS) caused by intake of contaminated L-tryptophan resembles in its clinical presentation the fibromyalgia syndrome (FMS). We, therefore, analysed clinical and immunological parameters in 16 patients with chronic EMS and 100 patients with FMS in order to see whether there may be a relationship between both disorders. From 12 FMS patients and 12 controls also peripheral blood mononuclear cells (PBMC) were obtained. Myalgia and arthralgia was observed in chronic EMS in the same incidence as in patients with FMS (81%). Also antibodies to serotonin, gangliosides and phospholipids were present in both groups. In vitro stimulation of PBMC with different L-tryptophan preparations revealed in six of the 12 FMS patients but only two of the control individuals a production of type 2 cytokines (IL-5, IL-10). We, therefore, conclude that EMS may have developed in patients suffering primarily from FMS as an allergic reaction towards a more immunogenic L-tryptophan preparation.

Adult↗
PubMed1999

Is serum cholesterol associated with progression of diabetic retinopathy or macular edema in persons with younger-onset diabetes of long duration?

PURPOSE: To quantitate the relationships of total cholesterol and high-density lipoprotein cholesterol to the incidence and progression of diabetic retinopathy and macular edema 5 years later in those with younger-onset diabetes of long duration. METHODS: Casual serum specimens for lipid values and fundus photography at the time of the lipid determinations were evaluated with regard to retinal lesions in photographs taken 5 years later during the course of a population-based cohort study. RESULTS: Univariable associations were significant for associations of incident retinal lesions with total cholesterol/high-density lipoprotein cholesterol, but multivariable associations considering covariates were not significant. CONCLUSION: Our data suggest that lowering cholesterol by therapeutic means may not be indicated for the sole purpose of decreasing the incidence or progression of these retinal lesions.

Age of Onset↗
PubMed1999

The effects of retroperitoneal carbon dioxide insufflation on hemodynamics and arterial carbon dioxide.

BACKGROUND: Laparoscopic techniques are being increasingly used for retroperitoneal surgery. However, hemodynamic and ventilatory efforts of retroperitoneal carbon dioxide (CO2) insufflation have not been studied. We hypothesized that differences in absorptive surface, anatomy, and compartment compliance could result in different hemodynamic and ventilatory effects between retroperitoneal and intraperitoneal insufflation. METHODS: Pigs (n = 7) were anesthetized and stabilized. The peritoneal cavity was incrementally insufflated with CO2 to a maximum pressure of 25 cm H2O and the gas released. Hemodynamics and arterial blood gas values were recorded initially, at each level of insufflation, and following the pneumoperitoneum release until baseline values were reached. This insufflation protocol was repeated in the retroperitoneum. RESULTS: Mean arterial pressure (111 mm Hg, 95% confidence interval 99 to 156) and cardiac output (3.7 L/min, 2.8 to 5.2) did not change with increasing insufflation pressure of either intraperitoneum or retroperitoneum. PaCO2 was directly related to insufflation pressure in both spaces, increasing from 41.2 mm Hg (37.3 to 43.4) at baseline to 57.7 mm Hg (47.6 to 82.1) at insufflation pressure of 25 cm H2O. After release of the insufflation gas, time to return to baseline PaCO2 was slightly less from the retroperitoneal space (73 minutes, 45 to 105) than the intraperitoneal (107 minutes, 35 to 175). CONCLUSIONS: The effects of CO2 insufflation on hemodynamics and PaCO2 are the same in the retroperitoneal and intraperitoneal spaces.

Animals↗
PubMed1999

Clearance of fetal products and subsequent immunoreactivity of blood salvaged at cesarean delivery.

OBJECTIVE: To determine if fetal products can be detected after postplacental, intraoperative blood salvage, and if the product is immunoreactive with maternal serum. METHODS: We suctioned the shed blood of 27 term gravidas with intact membranes who had cesareans, beginning 4 minutes after placenta removal, into a COBE BRAT-2 salvage system (COBE Cardiovascular, Arvada, CO). Preoperative maternal and fetal cord blood samples were collected. Preprocessing and postprocessing salvaged blood was analyzed for alpha-fetoprotein (AFP), hemoglobin, hematocrit, and plasma-free hemoglobin. Papanicolaou smears and immunodiffusion using Ouchterlony methods for detection of protein-protein interactions were run on maternal serum. Postprocess salvaged blood was subjected to Kleihauer-Bethke tests, typed, and crossmatched with maternal serum, including mixed fields. No women were transfused. RESULTS: Ten of 27 women shed enough postprocess salvaged blood for analysis. Alpha-fetoprotein was cleared, but Kleihauer-Bethke analyses were positive in all postprocessing specimens. Anucleate squamous cells were detected by Papanicolaou smears in four of ten preprocessed specimens, with one cleared by processing. No antigen-antibody reaction between maternal and preprocessed or postprocessed salvaged blood was found by the Ouchterlony method. Crossmatching of the final product with maternal serum was successful, with negative mixed fields in all cases. CONCLUSION: Fetal debris was present in blood salvaged 4 minutes after removal of placenta. Despite clearance of humoral material, fetal blood cells were detectable in all postprocess salvaged blood. The product was compatible with maternal blood by crossmatching and its supernate did not immunoreact with maternal serum.

Blood↗
PubMed1999

Age-related maculopathy in a multiracial United States population: the National Health and Nutrition Examination Survey III.

OBJECTIVE: To investigate the prevalence of and risk factors for age-related maculopathy (ARM) in three racial/ethnic groups: non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. DESIGN: A nationally representative population-based, cross-sectional study. PARTICIPANTS: A total of 8270 persons 40 years of age or older, a sample of the Third National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: Age-related maculopathy was determined by the grading of fundus photographs using a standardized protocol. RESULTS: The prevalence of any ARM in the civilian noninstitutionalized United States population including those 40 years of age or older was 9.4% (95% confidence interval [CI], 8.2, 10.6) as estimated from the sample. After adjusting for age, there was no difference in the prevalence of early ARM (defined largely by the presence of soft drusen) by ethnic/racial group. However, for the less frequent component lesions of early ARM (increased retinal pigment and retinal pigment epithelial depigmentation), the odds ratios (95% CIs) comparing non-Hispanic blacks to non-Hispanic whites were 0.47 (0.31, 0.74) and 0.59 (0.33, 1.04), respectively, and for comparing Mexican-Americans to non-Hispanic whites, they were 0.41 (0.21, 0.81) and 0.72 (0.44, 1.19), respectively. For late ARM, the odds ratio (95% CI) for non-Hispanic blacks compared to non-Hispanic whites was 0.34 (0.10, 1.18) and for Mexican-Americans compared to non-Hispanic whites, it was 0.25 (0.07, 0.90). Other than age, none of the personal, medical, or physiologic variables studied were statistically significantly associated with any of the ARM endpoints in any of the three races/ethnic groups. CONCLUSION: Overall, rates of any ARM (including all early and late lesions) are not significantly different among non-Hispanic blacks, Mexican-Americans, and non-Hispanic whites. However, the rates of individual lesions suggest that non-Hispanic whites and Mexican-Americans may be protected against retinal pigment abnormalities and lesions associated with late ARM. There appears to be little influence of personal, medical, and environmental factors studied on these results. Further studies in larger populations of older persons in these ethnic groups would likely clarify these relations.

Adult↗