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Biomedical subjects

R Klein

Publications and source records attributed to R Klein.

At least 37 records · Page 2Linked to original sources
PubMed1992

Alcohol consumption and the prevalence of diabetic retinopathy.

OBJECTIVE: To determine if alcohol consumption is associated with the prevalence of diabetic retinopathy. PARTICIPANTS: This study surveyed a 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 completed by 996 and 891 (730 by persons age 21 or older) younger-onset persons, respectively, and 1370 and 987 older-onset persons, respectively. Data analyzed are from the 4-year follow-up examination. Questionnaires concerning consumption were completed at follow-up. MAIN OUTCOME MEASURE: Diabetic retinopathy as determined from stereographic fundus photography. RESULTS: After controlling for known risk factors in the adult younger-onset group, average alcohol consumption, as determined by questionnaire, was inversely associated with prevalence of proliferative diabetic retinopathy (PDR), odds ratio, 0.49; 95% confidence interval, 0.27 to 0.92. The trend was similar for recent consumption, odds ratio, 0.63; confidence interval, 0.37 to 1.09. In the older-onset groups taking or not taking insulin, average or recent alcohol consumption or usage history were not significantly associated with the prevalence of any retinopathy or PDR. CONCLUSIONS: Alcohol consumption does not appear to increase the risk of retinopathy and may have a beneficial effect in younger-onset persons, although further study is needed.

Adolescent↗
PubMed1992

Prevalence of age-related lens opacities in a population. The Beaver Dam Eye Study.

Age-related lens opacities are common and are a frequent cause of loss of vision. The Beaver Dam Eye Study was designed to estimate the prevalence and severity of lens opacities in a rural community in the United States. Adults between the ages of 43 and 84 years, identified by private census, were examined and participated in the study (n = 4926). Photographs were taken of the lenses and were graded in masked fashion according to a standardized protocol. For nuclear sclerosis, more severe levels occurred more commonly in older age groups and in women. Overall, 17.3% had nuclear sclerosis more severe than level 3 in a 5-step scale of severity. Cortical opacities increased with increasing age and were more common in women. They were found in 16.3% of the population. Posterior subcapsular opacities occur in 6.0% of the population. There was a significant trend of greater prevalence at older ages, but no sex effect. The frequency of early cataract increased in both sexes through the age group 65 to 74 years, but declined in those 75 years of age and older. The frequency of late cataract increased consistently with age. Women were more severely affected than men. This study confirms that lens opacities are common in adults in the United States. These data are important for providing for social and health care needs. It is important to determine causes of cataracts in order to develop preventive programs.

Adult↗
PubMed1992

The Beaver Dam Eye Study. Retinopathy in adults with newly discovered and previously diagnosed diabetes mellitus.

The prevalence of diabetic retinopathy was examined in people with newly discovered noninsulin-dependent diabetes mellitus (NIDDM) (n = 50) and in those with previously diagnosed diabetes (n = 395) in a population-based study of people between the ages of 43 and 86 years who lived in Beaver Dam, Wisconsin between 1988 and 1990. Retinopathy was determined from stereoscopic fundus photographs. The prevalence of any retinopathy was 10.2% in those with newly diagnosed NIDDM, none had proliferative retinopathy, and 2.0% had macular edema. These data suggest that asymptomatic people discovered to have NIDDM during epidemiologic studies may not need immediate ophthalmoscopic examination at the time of their diagnosis because they have a relatively low risk of danger of visual loss due to diabetic retinopathy at that time.

Adult↗
PubMed1992

Effects of captopril on metabolic and hemodynamic alterations in global ischemia and reperfusion in the isolated working rat heart.

In the isolated working rat heart model, we studied metabolic and hemodynamic effects of 5- and 30-min global ischemia followed by reperfusion and assessed the potentially beneficial effect of captopril 80 micrograms/ml added throughout the experiment. Creatine kinase (CK) and catecholamines were measured in coronary effluent. De novo eicosanoids (prostaglandin E2) synthesis was assessed in endocardial explants. Hemodynamic alterations occurred after 30-min ischemia and were reflected most dramatically by a reduction in cardiac output (CO 72 +/- 10% of baseline values in captopril vs. 68 +/- 16% in controls) without significant differences as a result of treatment. Captopril shortened reperfusion ventricular fibrillation (VF) duration (6.9 +/- 1.2 vs. 13.6 +/- 8.7 min, p less than 0.05) but had no effect on VF incidence. No differences occurred in norepinephrine (NE) outflow, whereas total CK release was greater in controls. Five controls versus none of the treated hearts (p less than 0.05) released trace amounts of epinephrine during reperfusion. Increased de novo PGE2 synthesis was demonstrated after 5-min I (465 +/- 168 vs. 238 +/- 75 pg/100 mg tissue per hour, p less than 0.01). Captopril stimulated production of PGE2 in normoxic hearts (p less than 0.02), but the difference was no more apparent in ischemic hearts. We conclude that captopril produces some biochemical and electrophysiologic evidence of myocardial salvage, but these effects are not sufficient to induce hemodynamic improvement after global ischemia and reperfusion.

Animals↗
PubMed1992

Excretion of anthranilate and 3-hydroxyanthranilate by Saccharomyces cerevisiae: relationship to iron metabolism.

Resting suspensions of cells of Saccharomyces cerevisiae grown in iron-rich or iron-deficient conditions were studied by following the fluorescence emission changes (lambda em. 400-460 nm, lambda exc. 300-340 nm) occurring in these suspensions upon addition of glucose and ferric iron. The results show that, in addition to NAD(P)H, metabolites of the aromatic amino acid pathway interfere with the fluorescence measurements, and that they could be involved in ferric iron reduction. Wild-type strains of S. cerevisiae are known to excreted anthranilic acid and 3-hydroxyanthranilic acid in response to glucose. The major fluorescing compound excreted by a chorismate-mutase-deficient mutant strain of S. cerevisiae was identified as anthranilic acid. The excretion of anthranilic and 3-hydroxyanthranilic acids was correlated with the ferric-reducing capacity of the extracellular medium. Excretion during growth was much greater by cells cultured in iron-rich medium than by cells grown in iron-deficient medium. The possibility was examined that a link could exist between the biosynthesis of aromatics and the ferri-reductase activity of the cells, via chorismate synthase and its putative diaphorase-associated activity. Two ferri-reductase-deficient mutants excreted much less 3-hydroxyanthranilate than did the parental wild-type strains. However, the ferri-reductase activity of a chorismate-synthase-deficient mutant was comparable to that of the parental strain.

3-Hydroxyanthranilic Acid↗
PubMed1992

Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants.

In previous studies it was demonstrated that antibodies in sera from patients with primary biliary cirrhosis (PBC) and their relatives can recognize two different antigen systems in the ATPase fraction prepared from beef heart mitochondria, namely the PBC-related M2- and the naturally occurring mitochondrial antigen (NOMAg)-related epitopes. Since separation of these two antigen systems could not be achieved using mammalian mitochondria, mitochondria from a wide spectrum of plants were analysed with respect to the presence of mitochondrial antigens. Mitochondria from 29 species of plants were prepared and tested by ELISA and Western blot using marker sera from patients with PBC reacting in the Western blot with M2a,b,c,d (alpha-ketoacid-dehydrogenase complex) and NOMAg-specific sera recognizing the three major epitopes epsilon, zeta, and eta at 65, 61 and 58 kD. Naturally occurring mitochondrial antibody (NOMA)-positive marker sera reacted in the ELISA with mitochondria from all plants, and the zeta/eta positive sera gave also a positive reaction at 61/58 kD in the Western blot while the epsilon epitope could not be visualized by this method. In contrast, the M2 antigen was detected preferentially in lower plants such as algae, fungi, and ferns. Analysing these data with respect to the evolution of proteins one would have to assume that the M2 antigen was lost in most higher plants or underwent some structural alterations. Furthermore, considering the fact that the M2- and the NOMAg-related epitopes could be only partially separated, i.e. there were no plant mitochondria showing only M2 but no NOMAg, one could speculate that anti-M2 antibodies are derived from the pool of naturally occurring antibodies.

Antigens↗
PubMed1992

Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.

The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction.

Adolescent↗
PubMed1992

Antimitochondrial antibodies in primary biliary cirrhosis and other disorders: definition and clinical relevance.

The nine different antimitochondrial antibody specificities found in non-hepatic and hepatic disorders are described. Anti-M1 and anti-M7 antibodies are associated with infectious disorders such as syphilis or myocarditis. Anti-M3 and anti-M6 have been found in the course of a drug allergic disease due to Venocuran and iproniazid, and anti-M5 antibodies seem to occur occasionally in some forms of ANA-positive and ANA-negative collagen disorders. The M1- and M7-antigens are biochemically defined as cardiolipin and sarcosine dehydrogenase, respectively. Anti-M2, anti-M4, anti-M8, anti-M9 are associated with primary biliary cirrhosis (PBC). M2 was identified as alpha-ketoacid-dehydrogenase complex of the inner mitochondrial membrane, anti-M4 as sulfite oxidase, an enzyme of the mitochondrial intermembrane space, and anti-M9 as glycogen phosphorylase, a cytoplasmic enzyme. M8 copurifies with outer mitochondrial membranes derived from pig kidney. Anti-M9 can occur in the absence of anti-M2 while anti-M4 and anti-M8 are always associated with anti-M2. A progressive course of PBC can be predicted with high probability even at early stages of the disease when complement fixing antibodies against M2, M4 and/or M8 are present in patients' sera. In contrast, the presence of anti-M2/M9 antibodies heralds a benign course. The etiopathogenesis of PBC is still unknown. In PBC contact persons a strong stimulation of naturally occurring mitochondrial antibodies (NOMA) has been observed which was in contrast to the lack of this antibody type in PBC patients. Considering the generally accepted role of those antibodies in protecting individuals from infections, the failure of NOMA production may be a predisposing factor to acquire PBC more easily.

Autoantibodies↗
PubMed1992

Ultraviolet light exposure and lens opacities: the Beaver Dam Eye Study.

OBJECTIVES: Exposure to sunlight may be a risk factor for the development of cataract. The relationships between exposure to sunlight and to the ultraviolet-B (UVB) component of light and the prevalence of lens opacities were examined in the Beaver Dam Eye Study. METHODS: Persons 43 to 84 years of age residing in Beaver Dam, Wisconsin, were examined using standardized photographic assessments of lens opacities. A questionnaire about medical history and exposure to light was administered. RESULTS: After adjusting for other risk factors, men who had higher levels of average annual ambient UVB light were 1.36 times more likely to have more severe cortical opacities than men with lower levels. However, UVB exposure was not found to be associated with nuclear sclerosis or posterior subcapsular opacities in men. Moreover, no associations with UVB exposure were found for women, who were less likely to be exposed to UVB. CONCLUSIONS: Exposure to UVB light may be associated with the severity of cortical opacities in men. However, the lack of an association in women, the group more likely to have cortical opacities, suggests that other factors may be more important in the pathogenesis of lens opacities.

Adult↗
PubMed1992

Use of cardiovascular disease medications and mortality in people with older onset diabetes.

Mortality follow-up for a cohort defined in 1980 with diabetes diagnosed at 30 years of age or older has been completed through 1988. History of medication use was obtained during the initial evaluation. There were 605 (44.2%) confirmed deaths; heart disease was the underlying cause in 49.9% of the deaths. Use of loop diuretics was associated with an odds ratio of death of 1.8 (95% CI = 1.4, 2.2). Although a causal relationship cannot be inferred, it is reasonable to suggest that blood chemistries be monitored regularly in persons on these drugs since electrolyte imbalance may be related to death.

Adult↗
PubMed1992

Genetic marker associations with proliferative retinopathy in persons diagnosed with diabetes before 30 yr of age.

It has been suggested that HLA-DR4 is a marker of genetic predisposition to proliferative retinopathy. To investigate this relationship and potential associations between other polymorphic genes and proliferative retinopathy, a sample (n = 428) of participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy was selected for typing for HLA-A, -B, -C, and -DR and a panel of other polymorphic genes. The presence of proliferative retinopathy was determined from grading of stereoscopic color fundus photographs taken at 2 examinations, 4 yr apart. In logistic regression models with repeated measures, persons with HLA-DR4 who were negative for DR3 were five times more likely to have proliferative retinopathy than those negative for both antigens after adjusting for other potential risk factors (Odds ratio = 5.43, 95% Confidence Interval (Cl) = 1.04, 28.30). HLA-C2, AK-2, and MNSs-S also were associated positively with proliferative retinopathy, and HLA-DR8 was associated inversely with this complication of diabetes in each case before adjusting for the number of comparisons. These data suggest that the genetically determined immunopathic mechanisms leading to diabetes, and in linkage disequilibrium with DR4, may independently contribute to the development of proliferative retinopathy.

Adolescent↗
PubMed1992

Physical activity and proliferative retinopathy in people diagnosed with diabetes before age 30 yr.

OBJECTIVE--To examine the relationships of past and current physical activity to the prevalence of PDR. RESEARCH DESIGN AND METHODS--Individuals diagnosed with diabetes less than 30 yr of age (n = 818), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984-1986. Stereoscopic fundus photographs were graded for presence of PDR. Physical activity was assessed by an interviewer-administered standardized questionnaire. RESULTS--Women diagnosed with diabetes less than 14 yr of age who reported a history of participation in team sports in high school or college were less likely to have PDR at examination (OR 0.46, 95% CI 0.23, 0.93). Those women who reported current strenuous activity levels were less likely to have PDR (OR 0.34, 95% CI 0.13, 0.87). There were no significant associations between past or current physical activity and PDR in men. Current levels of energy expenditure were not related to PDR in either sex. CONCLUSIONS--Higher levels of physical activity may be associated with a reduced risk of having PDR in women. However, the lack of similar findings in men suggests that physical activity may be a relatively unimportant factor in the etiology of PDR.

Adolescent↗
PubMed1992

Epidemiology of proliferative diabetic retinopathy.

OBJECTIVE: This review examines recent epidemiological data about the prevalence and incidence of and risk factors for proliferative diabetic retinopathy. In addition, the relation of proliferative retinopathy to other systemic complications associated with diabetes is reviewed. RESEARCH DESIGN AND METHODS: The data come mostly from the baseline and 4-yr follow-up examinations of a large population-based study, the WESDR, which involved 996 younger-onset insulin-dependent people whose diabetes was diagnosed at < 30 yr of age and 1370 older-onset people whose diabetes was diagnosed at > or = 30 yr of age, and who were taking or not taking insulin. RESULTS: The major finding is that proliferative retinopathy is a prevalent complication (23% in the WESDR younger-onset group, 10% in the WESDR older-onset group that takes insulin, and 3% in the group that does not take insulin). Hyperglycemia, longer duration of diabetes, and more severe retinopathy at baseline were associated with an increased 4-yr risk of developing proliferative retinopathy. However, higher blood pressure at baseline was associated only with the development of proliferative retinopathy in the younger-onset group. The presence of proliferative diabetic retinopathy was associated with an increased 4-yr risk of loss of vision, cardiovascular disease, diabetic nephropathy, and mortality. In the WESDR, a significant number of diabetic people with proliferative retinopathy at risk for vision loss were not under the care of an ophthalmologist or had not undergone panretinal photocoagulation. CONCLUSIONS: These data suggest that hyperglycemia and, possibly, high blood pressure are related to proliferative retinopathy. They also suggest that once proliferative diabetic retinopathy is detected, people should have a medical evaluation, because it is a strong indicator for the presence and development of systemic disease. These data also indicate that diabetic patients and their physicians should be aware of the need for routine ophthalmological examinations to detect and treat proliferative retinopathy.

Age Factors↗
PubMed1992

Serum cholesterol in Wisconsin epidemiologic study of diabetic retinopathy.

OBJECTIVE: To describe serum total and high-density lipoprotein (HDL) cholesterol in a sample of people with diabetes. RESEARCH DESIGN AND METHODS: Subjects were those who participated in the 1984-1986 Wisconsin Epidemiologic Study of Diabetic Retinopathy. Data were from three groups of subjects: 304 younger-onset and 185 older-onset people taking insulin and 162 older-onset individuals not taking insulin. Serum lipids, duration of diabetes, glycosylated hemoglobin, diastolic blood pressure, sex, age, serum creatinine, units of insulin per kilogram per day, smoking status, serum C-peptide level, and alcohol use were analyzed statistically. RESULTS: In subjects taking insulin, glycosylated hemoglobin was correlated most strongly with total cholesterol. In those not taking insulin, C-peptide was correlated most strongly. In subjects taking insulin, the units used per day (fewer) and sex (female) were significantly associated with higher HDL cholesterol, and in both older-onset groups, serum C-peptide was significantly associated with lower HDL cholesterol. Mean total cholesterol levels were generally higher and mean HDL cholesterol levels were generally lower than those found in a nondiabetic comparison group. CONCLUSION: By the National Cholesterol Education Program guidelines, 17% of younger-onset and 30% of older-onset insulin users and 32% of older-onset subjects not taking insulin were in the high-risk range for total cholesterol. Lower levels of glycosylated hemoglobin might result in lower cholesterol levels.

Adult↗
PubMed1992

Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis.

OBJECTIVE: To investigate duration of the period between diabetes onset and its clinical diagnosis. RESEARCH DESIGN AND METHODS: Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. RESULTS: Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred approximately 4-7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9-12 yr before its clinical diagnosis. CONCLUSIONS: These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications.

Australia↗
PubMed1992

Glycemic control in early IDDM. The Wisconsin Diabetes Registry.

OBJECTIVE: A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. RESEARCH DESIGN AND METHODS: Unselected cases with IDDM, who were less than 30 yr of age, were identified at diagnosis from a 28-county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. RESULTS: In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P less than 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P greater than 0.10). Adolescent males (10-19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P less than 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children less than 10 yr of age (P less than 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. CONCLUSIONS: These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self-management.

Adolescent↗
PubMed1992

Epicardial versus endocardial "in mirror" changes in prostaglandin synthesis after short periods of ischemia and reperfusion.

Cardiac ischemia and reperfusion are associated with increased prostaglandin levels in the coronary venous effluent. This study implemented an in vivo-in vitro technique to investigate regional alterations in heart tissue PGE2 and PGF2 alpha de novo production. Canine endocardial and epicardial explants were incubated following 5 min regional ischemia, or 5 min ischemia with 10 min reperfusion, induced in vivo in two groups of animals (n = 10 and 6, respectively). Ischemia produced a significant upsurge in endocardial but not in epicardial prostaglandin synthesis as compared with the non-ischemic zone: 7.6 +/- 0.7 versus 4.5 +/- 0.5 pg/mg tissue per h in PGE2 (P < 0.001) and 8.8 +/- 1.2 versus 6.8 +/- 1.2 pg/mg per h PGF2 alpha (P < 0.01). Following reperfusion, PGE2 was higher in the apparently normal than in the affected endocardium (5.8 +/- 0.6 versus 4.4 +/- 0.5 pg/mg per h, P < 0.05). Opposite changes occurred in the reperfused epicardium: 8.2 + 0.9 versus 4.9 +/- 0.7 pg/mg per h PGE2 (P < 0.01) and 11.1 +/- 0.9 versus 6.0 +/- 0.6 pg/mg per h PGF2 alpha (P < 0.001), for the reperfused as compared to the "normal" region, respectively. Our findings imply that the left ventricular wall is not homogeneous in its eicosanoid response to ischemia and reperfusion. "In mirror" changes were found between endocardium end epicardium and between the injured and the apparently normal regions.

Animals↗