Prevalence of serum apolipoprotein E4 isoprotein is not increased in rheumatoid arthritis patients with amyloidosis: comment on the article by Hasegawa et al.
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Alleles↗
Biomedical subjects
A Pasternack
Publications and source records attributed to A Pasternack.
Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM.
The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been shown to be associated with cardiovascular and renal diseases in diabetes mellitus, but the mechanism underlying this association is not known. In addition, recent studies of the effect of the ACE gene on blood pressure have yielded conflicting results. Therefore, we studied the association of the ACE gene I/D polymorphism with glucose intolerance and insulin resistance, and the contribution of this locus to genetic susceptibility to hypertension in non-insulin-dependent diabetic mellitus (NIDDM). We analysed the ACE genotype in 84 unrelated NIDDM patients with a known disease duration of less than 1 year and in 115 age- and sex-matched controls. The I/D polymorphism was determined by the polymerase chain reaction. There were no differences in ACE genotype distribution and allele frequencies between patients with NIDDM and nondiabetic controls. The frequencies of the D and I alleles in both groups were identical, viz., 0.65 and 0.35, respectively. The NIDDM patients with the DD genotype had significantly higher blood glucose levels in the oral glucose tolerance test than those with the other genotypes; the incremental glucose area under the curve in the order of II, ID, and DD was 7.2+/-2.4, 9.2+/-4.0, and 10.7+/-2.7 mmol/l x h (II vs ID vs DD, P=0.0066 by ANOVA). No significant difference was found between the ACE genotype and serum insulin values. Similarly, there were no differences in body mass index, blood pressure, or serum lipids between the three genotypes. Among the non-diabetic controls, there was no statistically significant association of the I/D polymorphism with serum lipids, blood glucose levels, serum insulin concentrations, or blood pressure values. In conclusion, NIDDM patients with the DD genotype have higher blood glucose levels and are more glucose intolerant; this may help to explain the reported association between the D allele and vascular complications in NIDDM.
Diabetes Mellitus, Type 2↗
The 5A/6A polymorphism in the promoter of the stromelysin-1 (MMP-3) gene predicts progression of angiographically determined coronary artery disease in men in the LOCAT gemfibrozil study. Lopid Coronary Angiography Trial.
The relationship between the 5A/6A stromelysin-1 promoter polymorphism and progression of angiographically determined coronary artery disease (CAD) has been examined in men treated for 32 months with gemfibrozil or placebo in the Lopid Coronary Angiography Trial (LOCAT). The frequency of the 5A allele was 0.40 (95%, CI, 0.36-0.43), and in the sample as a whole 12% of the men were homozygous for the 5A allele. In the placebo group, diffuse progression of disease was, on average, completely prevented in men with the genotype 5A/5A as measured by a 0.30% increase in mean average diameter of the coronary artery segments (ADS), compared with a mean 1.79% decrease in the combined group with the genotype 5A6A or 6A6A (mean +/- S.E.M., +0.007 +/- 0.020 mm vs. -0.043 +/- 0.0.08 mm, P = 0.03). A similar relationship with genotype was seen for disease progression determined by the mean minimal luminal diameter (MLD); with the 5A5A group decreasing by an average of 1.72% compared with 5.54% in the 5A/6A plus 6A/6A group (-0.029 +/- 0.034 mm vs. -0.102 +/- 0.013 mm, P = 0.06). In the gemfibrozil-treated group, the effect on disease progression associated with the 5A/6A alleles was of a similar pattern as in the placebo group, but the effect was less marked and was not statistically significant. This study confirms the previously reported beneficial effect on disease progression associated with the 5A allele and raises the possibility that patients with CAD who are homozygous for the 6A allele, and who represent 25-30% of the population, may be at particular risk of rapid progression of disease and may require particularly aggressive lipid lowering therapy to prevent disease progression.
Aged↗
Angiotensin-converting enzyme gene polymorphism is associated with coronary heart disease in non-insulin-dependent diabetic patients evaluated for 9 years.
The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. Recent studies have found the ACE D allele to be associated with an increased risk for coronary heart disease (CHD) in diabetic and nondiabetic subjects. This association has not been evaluated in prospective studies. We therefore studied the relationship between ACE gene I/D polymorphism and CHD in patients with non-insulin-dependent diabetes mellitus (NIDDM) evaluated for 9 years. The I/D polymorphism was determined by polymerase chain reaction (PCR). Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primers and inclusion of 5% dimethylsulfoxide (DMSO). Eighty-three patients were evaluated for a mean period of 9.1 years (range, 7.4 to 10.5). Among them, 64 patients showed no CHD at entry. During the follow-up period, 21 patients (37.5%) developed CHD. The systolic blood pressure (P = .046), fasting blood glucose (P < .01), and prevalence of hypertension (P < .001) increased, while high-density lipoprotein (HDL) cholesterol (P < .001) decreased. Patients who developed CHD were older than those who did not; the mean age was 59.3 and 53.2 years, respectively (P = .003). The prevalence of albuminuria at follow-up examination was higher in CHD subjects versus non-CHD subjects (61.9% v 20.9%, P = .012). The D allele of the ACE gene was significantly more frequent in subjects with CHD versus those without CHD in both follow-up (P = .028, chi2 test) and cross-sectional (P = .033, chi2 test) settings. No difference could be detected between the three genotypes in age, body mass index (BMI), blood pressure, or plasma lipid levels. In our logistic regression analysis, the best model selected the DD genotype (P = .0105) and age (P = .0407) as significant risk factors for CHD. This model classified 89% of the subjects correctly. In conclusion, this 9-year prospective study supports the hypothesis that the ACE I/D polymorphism is an important and independent risk factor for CHD in patients with NIDDM.
Adult↗
Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus.
Both the severe course of nephropathia epidemica (NE) caused by Puumala hantavirus, and the fast progression of human immunodeficiency virus (HIV) disease, are associated with the HLA B8 DRB1*0301 haplotype. As HLA B27, on the contrary, is associated with the slow progression of HIV disease, we wanted to test whether the same is true for NE. Only six (8%) NE patients, half the figure expected, had the HLA B27 allele in 74 randomly selected hospital-treated patients. All six had a benign overall clinical course of NE; none had any severe complications, the severity of renal failure was also mild, and the treatment time at the hospital was half that needed for HLA B27- patients (P = 0.004). Patients who were HLA B27 had maximal blood leucocyte count > 10.000 x 10(9)/L (P = 0.020) more often, probably reflecting differences in immune response. Thus, similar HLA associations can be found in both HIV infection and NE caused by Puumala virus.
Adult↗
The association between the total antioxidant potential of plasma and the presence of coronary heart disease and renal dysfunction in patients with NIDDM.
Oxidative stress may be an important pathogenetic factor in the development of diabetic vascular complications. The total antioxidative potential of plasma reflects the ability of an individual to resist oxidative stress. We measured the plasma total peroxyl radical-trapping potential (TRAP) and the concentrations of four plasma chain-breaking antioxidants in 81 patients with non-insulin-dependent diabetes mellitus (NIDDM) nine years after diagnosis and in 102 well-matched non-diabetic control subjects. The association between the total antioxidative potential and the presence of coronary heart disease (CHD) and diabetic kidney disease were also studied. There were no significant differences in plasma TRAP between NIDDM patients and control subjects (1250+/-199 vs. 1224+/-198 microM). Nor were there any significant differences in the concentrations of plasma uric acid, ascorbic acid, alpha-tocopherol, and protein thiols between NIDDM patients and control subjects. Patients with a low glomerular filtration rate and/or high urinary albumin excretion had elevated plasma uric acid. Plasma TRAP was not, however, associated with renal dysfunction. The plasma of NIDDM patients with CHD had a significantly higher value of unidentified antioxidative potential than that of patients without CHD. This relation was strongly dependent upon smoking. In conclusion, these data demonstrate that there are no major defects in the antioxidative potential of plasma caused by NIDDM per se. CHD and diabetic renal dysfunction were not associated with changes in plasma TRAP.
Aged↗
Epidemiology of hantavirus infections in Europe.
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Animals↗
The Met54Leu polymorphism of paraoxonase (PON) enzyme gene is not a genetic risk factor for non-insulin-dependent diabetes mellitus in Finns.
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Alleles↗
Evaluation of infectious etiology in subacute thyroiditis--lack of association with coxsackievirus infection.
The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it is postulated to be associated with viral infections and genetic factors. In the present study, the possibility of an infectious etiology was prospectively studied in 27 consecutive patients with SAT. Special emphasis was put on the role of enteroviruses. Coupled sera (interval one month) were taken from all patients and single sera from 29 control subjects for virus antibody determinations. Stool samples were collected for virus isolation and fine-needle aspiration samples from thyroid gland for the detection of enterovirus RNA using RT-PCR were taken from SAT patients. Enteroviral antibodies were tested using three different methods: indirect EIA, heavy chain capture RIA, and standard complement fixation (CF) test. Antibodies against other common viral pathogens, including enteroviruses, were screened using the CF test and those against Mycoplasma pneumoniae and Chlamydia pneumoniae using EIA and microimmunofluorescence techniques, respectively. Common respiratory viruses were also screened from nasopharyngeal suction samples by antigen detection EIA. Based on serological findings, one patient had acute Cytomegalovirus infection. All other patients were negative in antibody tests, virus isolation, RT-PCR, and antigen detection. Enterovirus RNA was not detected by PCR in the thyroid tissue in any of the fine-needle aspiration samples. There was no evidence of recent enteroviral infections in SAT patients. The results suggest that SAT is not usually associated with acute infections. No evidence was obtained to support the proposed role of enteroviruses as an important etiologic agent of SAT.
Adult↗
Effect of intravenous calcitriol on cardiac systolic and diastolic function in patients on hemodialysis.
The systolic and diastolic function of the heart of hemodialysis (HD) patients and the effect of intravenous vitamin D therapy on cardiac function was studied by Doppler and digitized M-mode echocardiography in 10 HD patients before and after 3-4.5 months of calcitriol therapy. Calcitriol was administered intravenously 1-3 times a week at a dose of 1-2 microg after the dialysis sessions. Ten age- and sex-matched healthy controls were also examined echocardiographically. Before calcitriol therapy cardiac wall thicknesses (interventricular septum, posterior wall) and left ventricle (LV) dimensions (end diastolic, end systolic) were greater, and LV diastolic (peak late diastolic velocity, peak early diastolic velocity/peak late diastolic velocity ratio, isovolumic relaxation time) and systolic (fractional shortening) function was impaired in HD patients as compared to controls. The LV posterior wall thickness was related to plasma parathyroid hormone (PTH; r = 0. 70, p = 0.01) in the patients. Calcitriol therapy raised serum ionized Ca from 1.23+/-0.04 to 1.33 +/- 0.04 mmol/l and reduced PTH from 41.1+/-10.7 to 34.2+/-11.7 pmol/l (29+/-11%). Calcitriol therapy did not cause any significant changes in cardiac function in the whole patient group. However, in a subgroup of 5 patients with severe but controllable hyperparathyroidism (PTH >3 times upper normal margin) the LV dimensions and systolic function improved (LV end systolic dimension from 39.0 +/- 4.0 to 31.3 +/- 2.9 mm, p = 0. 03; LV end diastolic dimension from 57.7 +/- 3.1 to 53.4 +/- 3.0 mm, p = 0.06; fractional shortening from 33 +/- 4 to 42 +/- 3%, p = 0. 03). The diastolic indices improved also, but not significantly. In conclusion, left ventricle hypertrophy and systolic and diastolic dysfunction was observed in HD patients. Intravenous calcitriol therapy improved cardiac function in patients with severe secondary hyperparathyroidism.
Adult↗
Nephrotic syndrome, hyperreninemia and multiple transplant renal arterial stenoses in a patient with diabetes.
Nine months after cadaveric renal transplantation the nephrotic syndrome developed in a patient with insulin-dependent diabetes. Renal biopsy ruled out tissue lesions induced by cyclosporine, chronic rejection, recurrence of diabetic kidney disease and de novo glomerulopathies. Captopril-enhanced nephrography and a high plasma renin response suggested renal artery disease. Angiography revealed five intrarenal arterial stenoses. Four were successfully dilated with a prompt diuretic response and diminished proteinuria. Late angiography showed a moderate restenosis in two of the dilated arteries. Due to persistent proteinuria, elevated blood pressure and higher serum creatinine levels than at nadir after transplantation low-dose ACE inhibitor therapy was started. This normalized proteinuria, blood pressure and serum creatinine levels. This beneficial response to combined renal artery balloon angioplasty and medical treatment has been sustained for 2.5 years.
Diabetes Mellitus, Type 1↗
Angiotensin-converting enzyme insertion/deletion polymorphism and diabetic albuminuria in patients with NIDDM followed Up for 9 years.
Nephropathy is a major cause of premature morbidity and mortality in patients with non-insulin-dependent diabetes mellitus (NIDDM). The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) is a genetic determinant of plasma ACE levels. Recent studies have found I/D polymorphism of the ACE gene to be associated with nephropathy in NIDDM. This association has not been evaluated in prospective studies. We, therefore, studied the relationship between ACE gene I/D polymorphism and diabetic albuminuria and glomerular filtration rate (GFR) in 83 NIDDM patients followed up for 9 years. At baseline, 29% (24 of 83) of the diabetic patients had an increased (>30 mg/24 h) urinary albumin excretion rate (UAER) and the prevalence of albuminuria at the 9-year examination was 35% (29 of 83). During the follow-up period, systolic blood pressure (p = 0.044), prevalence of hypertension (p < 0.01), and fasting blood glucose levels (p < 0.01) increased, while high-density lipoprotein cholesterol (p < 0.01) decreased. The declines of GFR during the follow-up period were 8.5, 14.1, and 16.3% within genotype groups of II, ID, and DD, respectively (p values for decreases: NS for II, <0.001 for ID, and <0.001 for DD). Patients with the DD genotype tended to have a steeper decrease of GFR, but the change was not statistically significant between the genotype groups. The increases of UAER during the follow-up period were 35.1, 8.3, and 122.4% within genotype groups of II, ID, and DD, respectively, but p values for all increases were not significant. Parallel to GFR, patients with the DD genotype tended to have a steeper increase of UAER, but the change was not statistically significant between the genotype groups. There were no differences in the ACE genotype distribution and allele frequencies between the patients with or without albuminuria either at follow-up or in cross-sectional settings. In conclusion, this 9-year follow-up study does not support the hypothesis that the ACE I/D polymorphism is a major genetic marker of diabetic nephropathy in NIDDM patients.
Adult↗
Serum ionized versus total magnesium in patients with chronic renal disease.
BACKGROUND: Recent technology has made it possible to assess serum ionized magnesium with user-friendly ion-selective electrodes similar to measurement of the serum calcium concentration. METHODS: We measured the serum ionized (Mg2+) and total magnesium (tMg) concentration in 69 patients with chronic kidney disease (38 men, 31 women, age 22-85 years) and in 75 control subjects. RESULTS: In control subjects the reference ranges were as follows: serum Mg2+ 0. 45-0.67 mmol/l, and tMg 0.67-0.96 mmol/l. In patients with chronic renal failure serum Mg2+ was 0.57 +/- 0.05 mmol/l and tMg 0.80 +/- 0. 11 mmol/l, and in transplant recipients receiving cyclosporine 0.53 +/- 0.05 and 0.71 +/- 0.10 mmol/l, respectively. The correlation coefficient between serum Mg2+ and tMg was r = 0.73 (p < 0.001) in the patient group and r = 0.75 (p<0.001) in control subjects. Serum tMg was below the reference range in 15 of 69 measurements. However, serum Mg2+ was below the reference range in only 1 of these 15 samples. Hence, 14 of 69 cases with low tMg but normal Mg2+ were false-positive with respect to hypomagnesemia. CONCLUSION: We conclude that tMg may overestimate the incidence of hypomagnesemia, and the measurement of Mg2+ may be of benefit when studying patients with expected hypomagnesemia.
Adult↗
Mutation C677T of methylenetetrahydrofolate reductase gene is not associated with coronary artery disease, but possibly with albuminuria, in type 2 diabetic patients.
The missense mutation in the 677th nucleotide (C677T) of methylenetetrahydrofolate reductase gene causes substitution of valine (V) for alanine (A) resulting in three genotypes VV, VA and AA. The VV genotype causes hyperhomocysteinemia and may be a risk factor for coronary artery disease. We determined genotypes by polymerase chain reaction and subsequent restriction fragment length analysis and compared them in 84 patients with type 2 diabetes and in 115 non-diabetic subjects with and without coronary disease. Fractional urinary excretion rate of albumin was assessed by nephelometry. The VV, VA, and AA frequencies in the diabetic and in the control groups were 0.095, 0.357, 0.548 and 0.061, 0.417, 0.522, respectively (p = NS, diabetic vs. controls, chi2 test). Genotype frequencies did not differ in either diabetic or control subjects between those with or those without coronary disease (chi2 test). The fractional urinary excretion rate of albumin (mean +/-SD) in diabetic patients with the VV genotype i.e. 1.59 +/-0.71 was lower (Kruskall-Wallis test p = 0.002) than in the other genotypes i.e. VA 5.98 +/-9.75 and AA 3.75 +/-4.77, respectively (post-hoc Mann-Whitney test VV vs. VA p = 0.005 and VV vs. AA p = 0.054, respectively). We found that in patients with type 2 diabetes the methylenetetrahydrofolate reductase VV genotype was associated with a low urinary albumin excretion but not with coronary artery disease or diabetes per se.
Adult↗
Serum ionized versus total magnesium in patients with intestinal or liver disease.
In serum, magnesium exists in three fractions: protein-bound, complex-bound and free ionized form. Only the free ionized fraction is biologically active. Until recently, only the measurement of serum total magnesium has been in clinical use. Now, commercially available instruments using new ion-selective electrodes for Mg++ have made possible the reliable measurement of serum ionized magnesium in clinical practice. For the measurement of serum ionized magnesium we used a magnesium-selective electrode installed in a six-channel electrolyte analyzer. We compared the use of ionized versus total magnesium measurement in 52 patients with intestinal disease, 54 with liver disease, and in 75 healthy control subjects. In the patients with alcoholic liver disease both serum ionized and total magnesium were lower, and in those with inflammatory bowel disease slightly higher than in control subjects. The correlation coefficient between serum ionized and total magnesium was r=0.87 (p<0.001) in the patients, and r=0.75 (p<0.001) in the controls. In the patient group the fraction of ionized magnesium in the total was negatively related to the serum albumin level (r=-0.41, p<0.001). Serum total magnesium was below the reference range in 30 out of 150 measurements, serum ionized magnesium in only 9 out of 150 measurements, respectively. Thus, 21 cases with low total but normal ionized magnesium (two thirds of hypomagnesemia according to serum total magnesium) were false positive. Total magnesium measurement may overestimate the incidence of hypomagnesemia when significant hypoalbuminemia is present. Measurement of serum ionized magnesium instead of total magnesium may therefore be of advantage in evaluating patients with hypoalbuminemia and when hypomagnesemia is expected.
Adolescent↗
[The basis of learning to be a doctor: science, clinical skills and humanism].
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Clinical Competence↗
The level of autoantibodies against oxidized LDL is not associated with the presence of coronary heart disease or diabetic kidney disease in patients with non-insulin-dependent diabetes mellitus.
Oxidation of low-density lipoprotein (LDL) may be an important factor in the development of diabetic macrovascular and renal complications. The level of autoantibodies against oxidized LDL (oxLDL-Ab) can be used as an index of LDL oxidation in vivo. The purpose of this study was to investigate the association between the level of oxLDL-Ab and the presence of coronary heart disease and renal dysfunction in patients with non-insulin-dependent diabetes mellitus (NIDDM). We determined the plasma levels of oxLDL-Ab in 46 NIDDM patients and 48 well matched nondiabetic control subjects. NIDDM patients had a moderately higher level of oxLDL-Ab than control subjects (0.083 +/- 0.051 vs. 0.062 +/- 0.045, p = 0.04). However, there was no difference in the level of oxLDL-Ab between subjects with and without coronary heart disease, and the level of oxLDL-Ab was not associated with indices of glomerular filtration rate or urinary albumin excretion.
Aged↗
New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus.
Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. We have investigated oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus (NIDDM) by urinary 8-OHdG assessments. We determined the total urinary excretion of 8-OHdG from 24 h urine samples of 81 NIDDM patients 9 years after the initial diagnosis and of 100 non-diabetic control subjects matched for age and gender. The total 24 h urinary excretion of 8-OHdG was markedly higher in NIDDM patients than in control subjects (68.2 +/- 39.4 microg vs. 49.6 +/- 37.7 microg, P = 0.001). High glycosylated hemoglobin was associated with a high level of urinary 8-OHdG. The increased excretion of urinary 8-OHdG is seen as indicating an increased systemic level of oxidative DNA damage in NIDDM patients.
8-Hydroxy-2'-Deoxyguanosine↗