PubMed Health⌕ Search

Biomedical subjects

Amos Pasternack

Publications and source records attributed to Amos Pasternack.

At least 19 recordsLinked to original sources
PubMed2006

Insulin resistance and the progression of IgA glomerulonephritis.

BACKGROUND: IgA glomerulonephritis (IgAGN) has a highly variable prognosis with 15-40% of patients progressing to end-stage renal disease. Hypertension, proteinuria and renal insufficiency are risk factors associated with poor prognosis. The role of insulin resistance is unclear in IgAGN. METHODS: From a retrospective cohort of IgAGN patients, a total of 174 patients (104 males) were invited for two visits at the clinic, 11 and 16 years (median times) after IgAGN was diagnosed in renal biopsy. Of all the patients, 63% had been diagnosed at least 10 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the first and second visits, or kidney transplantation or start of dialysis. Plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index and cystatin-C were obtained for analysis from 118 patients. RESULTS: IgAGN was progressive in 19.5% of the patients on the second visit. Insulin level and HOMA-IR of the first visit showed significant association with the progression of IgAGN (P = 0.019 and 0.005, respectively). CONCLUSIONS: Our results show that in addition to the known risk factors age, hypertension, proteinuria and hyperuricaemia, plasma insulin level and calculated HOMA-IR are associated with the progression of IgAGN.

Adolescent↗
PubMed2006

Mortality in patients with rheumatoid arthritis treated with low-dose oral glucocorticoids. A population-based cohort study.

OBJECTIVE: To evaluate mortality and causes of death in patients with rheumatoid arthritis (RA) treated with low-dose oral glucocorticoids. METHODS: Mortality was analyzed in population-based data of 604 patients with RA. In the original study in 1988, state of general health, severity of RA, and treatment including the use of oral glucocorticoids were recorded. In 1999 vital status and causes of death were evaluated. Mortality in patients with RA who had not received glucocorticoids (Group A, n = 209) was compared to that in patients treated with glucocorticoids for less than 10 years (Group B, n = 276) or for more than 10 years (Group C, n = 119). RESULTS: From onset of RA to 1999, 395 (65%) patients had been treated with oral glucocorticoids. In 1999 a total of 160 (26%) patients had died, 23% of patients in Group A, 21% in Group B, and 45% in Group C. In multivariate Cox regression analysis, male sex (hazard ratio 2.50; 95% CI 1.74-3.59), impaired functional capacity by Health Assessment Questionnaire (HR 2.11; 95% CI 1.65-2.96), heart failure (HR 1.96; 95% CI 1.36-2.84), and diabetes (HR 1.87; 95% CI 1.17-3.01) predicted increased mortality. In the same analysis glucocorticoid treatment for 1 year increased the mortality risk by 14% (HR 1.14; 95% CI 0.98-1.27, p = 0.057) and treatment over 10 years by 69% (HR 1.69; 95% CI 1.12-2.56, p = 0.011) compared to RA patients without treatment. The major cause of death was cardiovascular disease in all groups, but infections and intestinal perforations due to amyloidosis were more frequent in patients with long-lasting glucocorticoid therapy. Lymphomas were more frequent in all patients treated with glucocorticoids (Groups B and C) than in those not receiving glucocorticoids. CONCLUSION: Patients with RA treated with low-dose oral glucocorticoids for more than 10 years had increased mortality compared to those who did not receive glucocorticoids or whose duration of treatment was less than 10 years. The increased mortality was related mainly to infections and complications caused by systemic amyloidosis.

Administration, Oral↗
PubMed2006

Vascular diseases and their risk factors in IgA nephropathy.

BACKGROUND: Many studies have focused on risk factors for renal insufficiency in IgA nephropathy (IgAN). We recently found metabolic factors, especially uric acid, to predict progression and marked histopathological lesions in IgAN. Since vascular diseases (VDs), in addition to renal insufficiency, affect the overall survival of IgAN patients, we studied the occurrence of and risk factors underlying VDs in IgAN. METHODS: In this study, VDs here comprised the presence of coronary heart disease (CHD) and/or cerebrovascular disease (CeVD). We correlated clinical, metabolic and histopathological findings with the occurrence of VDs in 221 adult patients with IgAN. Seven histopathological parameters were semiquantitatively graded. Logistic regression analysis was used to evaluate independent predictors of VDs in these patients. The occurrence of VDs in IgAN patients > or = 30 years of age was studied and compared with that in the general population drawn from the same area. RESULTS: VDs were notably common in IgAN patients. Patients with IgAN had significantly more frequent VDs, CHD and CeVD than the general population (P < 0.01 to < 0.001). Of > or = 30 years of age IgAN patients, 25% had some VD at the end of follow-up, while only 9% of the general population had VDs [odds ratio, OR 4.6 (2.2-9.4)]. Old age, male gender, hypertension, proteinuria, renal insufficiency, hyperuricaemia, hypertriglyceridaemia, diabetes, smoking and high body mass index correlated with the occurrence of VDs in univariate analysis. In all patients initial renal insufficiency and smoking were independently associated with some VD, male gender with CHD and hypertension with CeVD. In the multivariate analysis model including patients with initially normal renal function, male gender was independently associated with some VD, and hypertriglyceridaemia with CHD. CONCLUSION: VDs, especially CeVD, would seem to be particularly common in patients with IgAN. Patients with progressive renal disease run a significantly elevated risk of developing VD. Many previously known risk factors for VD were also associated with the occurrence of some VD in the present study. Vascular changes seen in renal biopsy in patients with IgAN signify an elevated risk of VDs.

Adolescent↗
PubMed2006

Effects of erythropoietin treatment on cell-mediated immune responses in predialysis patients.

OBJECTIVE: The effects of erythropoietin (EPO) treatment on the immune functions of dialysis patients have been shown to be controversial and there are only limited data concerning predialysis patients. MATERIAL AND METHODS: Twenty-four predialysis patients with renal anemia were assigned to subcutaneous EPO treatment, and those in need (n=19) were additionally treated with i.v. iron every other week. We analyzed the effect of the start of EPO treatment on (i) lymphocyte and lymphocyte subclass counts, (ii) lymphocyte stimulation functions and (iii) persisting IgG-class antibody levels to the viral antigens of Epstein-Barr virus and cytomegalovirus. RESULTS: Our main findings were a decrease in the absolute lymphocyte count, combined with decreases in all the main lymphocyte subclass counts. The absolute number of cells with activation and memory markers remained constant, and therefore their proportion slightly increased. The proliferation responses to phytohemagglutinin, tuberculin and tetanus declined significantly, while the amount of IgG-class viral antibodies remained unchanged, meaning that the humoral side of immunity was not affected by the start of the EPO treatment. Similarly, the proliferation response to pokeweed mitogen, a B-cell mitogen, was unchanged. CONCLUSIONS: EPO treatment has a suppressive effect on cellular immune functions of predialysis patients. This suppression does not correlate with erythropoiesis, kidney function or iron status.

Adult↗
PubMed2006

[Not Available].

Explore the source record for details and available documents.

Journal Article↗
PubMed2005

High serum C3 predicts poor outcome in IgM nephropathy.

BACKGROUND: IgM nephropathy (IgMN) is an idiopathic glomerulonephritis with mesangial IgM deposition. The etiology of the depositions and possible association of serum and mesangial immunoglobulins and complement findings with renal outcome in IgMN remain unknown. Here we brought out data supplementary to our previous findings by reporting associations of immunological parameters with the outcome of IgMN. METHODS: Serum IgA, IgG, IgM, C3 and C4 were measured in 110 IgMN patients by single radial immunodiffusion or nephelometry. Mesangial IgA, IgG, IgM, C1q and C3 assessed in immunofluorescent study were graded as +/-. Seven histopathological parameters were semiquantitatively graded into three classes. The relationship of serum and mesangial immunoglobulin and complement findings with the clinical outcome and prognosis of IgMN was examined. RESULTS: We found significantly lower serum IgG and higher serum C3 levels in patients with nephrotic syndrome. Serum C3 correlated with the severity of glomerular histopathological changes. Of immunological parameters evaluated a low serum IgG/C3 ratio correlated best with the progression of renal disease. However, serum C3 was associated independently with progression in the case of patients without nephrotic syndrome. CONCLUSIONS: In addition to previously reported factors, immunological parameters may also be helpful in determining the prognosis in IgMN. High serum C3 predicts poor outcome in IgMN, being associated with high-grade proteinuria, severe histopathological changes and progression.

Adolescent↗
PubMed2004

Uric acid correlates with the severity of histopathological parameters in IgA nephropathy.

BACKGROUND: Immunoglobulin-A nephropathy (IgAN) is the most common chronic glomerulonephritis worldwide. Many clinical and histopathological risk factors for progression have been found previously. Recently, metabolic risk factors, such as hyperuricaemia and hypertriglyceridaemia, also have been associated with the progression of IgAN. METHODS: In the present study we correlated clinical and metabolic risk factors with histopathological parameters in 202 patients with IgAN. Morphological changes in glomerular, tubulointerstitial and vascular tissue were semiquantitatively graded into three classes. Mesangial proliferation activity and the amount of inflammatory cells were also evaluated by immunohistochemical staining of Ki-67 (MIB-1), CD45 (LCA) and CD68 stainings. Serum uric acid, triglycerides and cholesterol, urine protein excretion (UPE), blood pressure and body mass index (BMI) were measured. Smoking habits and occurrence of diabetes mellitus also were evaluated. The independent role of serum uric acid in the development of renal morphological changes was evaluated in multivariate analysis. RESULTS: Serum uric acid and UPE level correlated with several histological parameters. Uric acid level showed the strongest correlation with tubulointerstitial changes and UPE with glomerulosclerosis. The level of serum triglycerides correlated with interstitial fibrosis and hyaline arteriolosclerosis. Blood pressure correlated with hyaline arteriolosclerosis, glomerulosclerosis and tubulointerstitial changes. BMI and diabetes mellitus correlated with both tubulointerstitial and vascular changes. We found no significant correlations between histopathological parameters and smoking habits or serum cholesterol level. Serum uric acid had independent associations with the presence of tubular atrophy and interstitial fibrosis and inflammation. CONCLUSIONS: We conclude that many metabolic factors are univariately associated with renal morphological findings in IgAN. These same factors are central in the metabolic or insulin resistance syndrome and may have a pathogenetic role in the progression of IgAN. Serum uric acid may have an independent role in development of tubulointerstitial lesions as well as being associated with inflammation in renal tissue of patients with IgAN.

Adolescent↗
PubMed2004

APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study.

Animal and human studies support a role for apolipoprotein A-V (apoA-V) in triglyceride (TG) metabolism. We examined the relationship of APOA5 -1131T>C and S19W with lipid subfractions and progression of atherosclerosis in the Lopid Coronary Angiography Trial. Compared with -1131TT men (n = 242), carriers of the -1131C allele (n = 54) had significantly higher total TG (P = 0.03), reflected in significantly increased VLDL mass [higher VLDL-TG, VLDL-cholesterol, VLDL-protein, and surface lipids (all P < 0.05)]. Because apoB levels were unaffected by genotype, this suggests an increase in VLDL size and not number. Compared with 19SS men (n = 268), 19W carriers (n = 44) had higher intermediate density lipoprotein (IDL)-TG, IDL-cholesterol (P = 0.04), and IDL-surface components [free cholesterol (P = 0.005) and phospholipids (P = 0.017)] but not protein content, suggesting an increase in IDL lipid enrichment resulting in an increase in IDL size. 19W carriers also showed a trend toward increased progression of atherogenesis, as measured by change in average diameter of segments (-0.46 +/- 0.011 mm compared with -0.016 +/- 0.006 mm) in 19SS men (P = 0.08). There was no effect of genotype on the response of these parameters to gemfibrozil treatment. These results shed new light on the role of APOA5 variants in TG metabolism and coronary heart disease risk.

Aged↗
PubMed2004

Serum homocysteine concentrations, gemfibrozil treatment, and progression of coronary atherosclerosis.

The present study aimed to assess the effect of gemfibrozil on serum total homocysteine (tHcy) concentration and to evaluate the influence of tHcy on the angiographically determined progression of coronary atherosclerosis in a randomised, placebo-controlled trial of 395 post-coronary bypass men with low HDL cholesterol levels. The baseline levels of tHcy and those after 16 months of randomised therapy were measured by high-pressure liquid chromatography. Patients were genotyped for the thermolabile variant of N5,N10-methylenetetrahydrofolate reductase (MTHFR) (677C > T substitution). Gemfibrozil therapy was associated with a median 18% increase in tHcy levels (P < 0.01). In the gemfibrozil group increases in tHcy and HDL cholesterol were related (r = 0.217, P = 0.004), but changes in tHcy and triglycerides were not. Levels of tHCy were not associated with baseline extent or progression of coronary-artery disease. Subjects homozygous for the rare MTHFR T allele had 34% higher median tHcy concentrations than CC homozygotes or CT heterozygotes, but responses to gemfibrozil did not differ significantly among genotypes. The MTHFR genotype was not associated with extent or progression of coronary atherosclerosis. We conclude that gemfibrozil causes a significant elevation in tHcy levels, but the clinical relevance of this is unknown at present.

Cholesterol, HDL↗
PubMed2004

R643G polymorphism in PECAM-1 influences transendothelial migration of monocytes and is associated with progression of CHD and CHD events.

The 643R allele of R643G polymorphism (also known as R670G in the premature protein) in PECAM-1 has been associated with risk of myocardial infarction (MI), while the 643G allele has been associated with risk of coronary artery stenosis (CAS). The aim of this study was to investigate this apparently conflicting association. The association of R643G with risk of MI was determined in the second Northwick Park Heart study (2037 men with 138 CHD events; mean age: 56 years). Smokers homozygous for the 643R allele showed increased risk of MI with a hazard ratio of 2.47 (95% CI: 1.23-4.97; P=0.01) compared to smokers homozygous for the 643G allele. Progression of disease was determined in the Lopid Coronary Angiography Trial (279 men; mean age: 58.9 years). The 643G homozygotes showed greater focal (-0.08 +/- 0.02 mm) and diffuse (-0.01 +/- 0.01 mm) progression of CAS compared to 643R homozygotes (-0.02 +/- 0.02 mm and 0.001 +/- 0.01 mm, respectively; P=0.04). While there was no genotype effect on platelet aggregation, PECAM-1 tyrosine phosphorylation in HUVECs of GG genotype was 2.4-fold greater (P <0.01) than cells of RR genotype, and the level of transendothelial migration of monocytes of GG genotype was greater than that of monocytes of RR genotype following stimulation with either IL-1beta (12% higher, P <0.01) or TNF-alpha (10% higher, P=0.05). These data confirm the association of the R643G polymorphism with MI and CAS and suggest that greater influx of monocytes in individuals homozygous for the 643G may explain the association with CAS.

Cell Movement↗
PubMed2004

Urinary excretion of interleukin-6 correlates with proteinuria in acute Puumala hantavirus-induced nephritis.

BACKGROUND: Nephropathia epidemica (NE) is a mild type of hemorrhagic fever with renal syndrome caused by Puumala Hantavirus. Cytokines are thought to have an important role in the pathogenesis of NE. The aim of this study is to evaluate whether cytokines contribute to renal involvement in NE. METHODS: Overnight urinary excretion of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-6, tumor necrosis factor-alpha (TNF-alpha), albumin, immunoglobulin G (IgG), and alpha1-microglobulin and quantitative 24-hour urinary protein excretion were measured for 3 consecutive days from 70 hospitalized patients with acute NE (49 men, 21 women; age, 15 to 70 years; median age, 39 years). Plasma levels of the respective cytokines also were measured. Urinary collections were repeated after 1 year. The control group for blood samples included 400 healthy blood donors. RESULTS: Maximum median urinary IL-6 excretion in the acute phase of NE was increased compared with values detected after 1 year (49.5 versus 0.7 pg/min; P < 0.001). Correspondingly, maximum median plasma IL-6 concentration in patients was increased compared with controls (14.6 versus 1.2 pg/mL; P < 0.001). Urinary IL-6 excretion correlated with urinary albumin, IgG, and protein excretion (r = 0.79; P < 0.001; r = 0.76; P < 0.001; and r = 0.65; P < 0.001, respectively), but not plasma IL-6 levels (r = 0.18; P = 0.148). CONCLUSION: Plasma IL-6 concentrations and urinary IL-6 excretion were markedly increased in patients with acute NE, but there was no correlation between plasma and urinary IL-6 levels. The high urinary IL-6 levels might reflect local production of this proinflammatory cytokine in the kidneys during acute infection.

Adult↗
PubMed2004

The effect of isolated ultrafiltration on Doppler-derived indices of left ventricular diastolic function.

BACKGROUND: Haemodialysis (HD) is associated with acute changes simultaneously in fluid status (ultrafiltration) and in many biochemical parameters (dialysis). Reports on the effects of these changes on left ventricular (LV) diastolic function are scant. This study evaluated the effect of isolated ultrafiltration (UF) and subsequent HD with minimal fluid removal on Doppler-derived indices of LV diastolic function in patients who were asymptomatic and stable on HD. METHODS: In 11 HD cases, the 5 h treatment session was divided into a 2.5 h period of fluid removal without dialysis (UF phase) and 2.5 h of dialysis with minimal fluid removal (HD phase). We examined the following parameters of LV diastolic function echocardiographically: early rapid filling (Emax), atrial peak filling (Amax), Emax/Amax ratio, isovolumic relaxation time (IVRT) and deceleration time of the E-wave (DT). RESULTS: During the UF phase, Emax decreased from 0.82 +/- 0.2 to 0.62 +/- 0.2 m/s (P = 0.003), Amax decreased from 0.72 +/- 0.2 to 0.63 +/- 0.2 m/s (P = 0.042) and the ratio Emax/Amax did not change (P = NS). During the HD phase, Emax increased from 0.62 +/- 0.2 to 0.72 +/- 0.2 m/s (P = 0.018), Amax increased from 0.63 +/- 0.2 to 0.70 +/- 0.3 m/s (P = NS) and the Emax/Amax ratio remained unchanged (P = NS). IVRT was prolonged in 10 out of 11 patients at the start of the UF phase and it was further prolonged from 142 +/- 40 to 171 +/- 55 ms (P = 0.03) during the UF phase. IVRT did not alter during the HD phase (P = NS). During the UF phase, DT increased from 175 +/- 83 to 244 +/- 119 and it decreased from 244+/-119 to 209 +/- 98 in the HD phase, but both changes were statistically insignificant. No statistically significant correlations were observed between the changes in the Doppler indices of diastolic function and changes in biochemical parameters during the HD phase. CONCLUSIONS: UF affects the parameters Emax, Amax and IVRT used to evaluate LV diastolic function. The changes in Emax and Amax during the HD phase are due to fluid refilling from tissues into the blood space, HD as such having no effect on Doppler indices. However, isolated UF or HD does not affect the Emax/Amax ratio. Emax and IVRT seem to be the most volume-sensitive parameters.

Female↗