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Biomedical subjects

A Pasternack

Publications and source records attributed to A Pasternack.

At least 91 records · Page 5Linked to original sources
PubMed1997

Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with acute myocardial infarction treated with alteplase and streptokinase.

Peak serum C-reactive protein concentrations were measured in 146 patients randomized to receive streptokinase, alteplase, or a combination of streptokinase and alteplase in the GUSTO-I trial. Those receiving alteplase treatment had lower values than those receiving streptokinase or the combination treatment. Irrespective of treatment, complete reperfusion of the infarct-related artery (TIMI grade 3 flow) was associated with low peak serum C-reactive protein values.

Aged↗
PubMed1997

Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group.

BACKGROUND: Studies have shown that treatment of hyperlipidemia, especially lowering of plasma LDL levels, retards the progression of coronary atherosclerosis and prevents clinical cardiovascular events. No such studies have focused on subjects with low levels of HDL cholesterol. METHODS AND RESULTS: We randomly assigned 395 post-coronary bypass men, who had an HDL cholesterol concentration < or = 1.1 mmol/L and LDL cholesterol < or = 4.5 mmol/L, to receive gemfibrozil 1200 mg/d or placebo. Coronary angiography was performed at baseline and after, on average, 32 months of therapy. Changes in coronary dimensions were assessed by computer-assisted analysis. Average on-trial serum triglyceride concentrations were 1.69+/-0.68 and 1.02+/-0.37, total cholesterol 5.48+/-0.68 and 4.83+/-0.63, LDL cholesterol 3.84+/-0.59 and 3.39+/-0.56, and HDL cholesterol 0.88+/-0.15 and 0.98+/-0.17 mmol/L in the placebo and gemfibrozil groups, respectively (mean+/-SD, each P<.001). The change in per-patient means of average diameters of native coronary segments was -0.04+/-0.11 mm in the placebo group and -0.01+/-0.10 mm in the gemfibrozil group (P=.009). The equivalent changes in minimum luminal diameters of stenoses were -0.09+/-0.18 and -0.04+/-0.15 mm, respectively (P=.002). A similar, albeit nonsignificant, trend toward treatment benefit was found in the predefined primary study end point, segments unaffected by grafts and those distal to graft insertions. In aortocoronary bypass grafts, 23 subjects (14%) assigned to placebo had new lesions in the follow-up angiogram, compared with 4 subjects (2%) assigned to gemfibrozil (P<.001). CONCLUSIONS: Gemfibrozil therapy retarded the progression of coronary atherosclerosis and the formation of bypass-graft lesions after coronary bypass surgery in men with low HDL cholesterol as their main lipid abnormality.

Aged↗
PubMed1997

Fast 5-hour determination of angiotensin-converting enzyme genotypes from blood by SDS-PAGE using PhastSystem.

Polymorphism in the angiotensin-converting enzyme (ACE) gene has been shown to correlate with circulating ACE concentrations in plasma, and also to be an independent risk factor in the development of many cardiovascular diseases. However, methods available today for ACE genotyping are still laborious and time-consuming. Here we report a sensitive, simple and non-isotopic procedure with commercially available gels for the identification of ACE insertion/ deletion polymorphism. This technique includes rapid extraction of the DNA by the QIAamp Blood Kit prior to polymerase chain reaction, followed by sodium dodecylsulphate polyacrylamide gel electrophoresis using the PhastSystem (Pharmacia). The procedure can be accomplished in five-hours from drawing the blood samples to the final result.

Aged↗
PubMed1997

Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of severe disease with associated nephropathy.

OBJECTIVE: To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy. METHODS: A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay. RESULTS: Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (+/- SD) pANCA log titers (103 +/- 5.6 versus 27 +/- 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA-associated nephropathy. CONCLUSION: Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.

Adolescent↗
PubMed1997

A study to determine the response of coronary atherosclerosis to raising low high density lipoprotein cholesterol with a fibric-acid derivative in men after coronary bypass surgery. The rationale, design, and baseline characteristics of the LOCAT Study. Lopid Coronary Angiography Trial.

Several clinical trials have shown that reducing serum cholesterol levels retards the progression of coronary atherosclerosis assessed by serial angiography. By contrast, as yet no studies have addressed the impact of increasing high density lipoprotein (HDL) cholesterol levels on progression of coronary artery disease (CAD). As HDL cholesterol is inversely related to the risk of CAD, we hypothesize that an intervention that raises low HDL cholesterol concentrations may have a beneficial effect on the course of CAD. Lopid Coronary Angiography Trial (LOCAT) was designed to test this hypothesis. Three hundred and ninety-five men, aged < or = 70 years, all of whom had previously undergone coronary bypass surgery, were randomly assigned to receive either slow-release gemfibrozil, 1200 mg once daily, or a matching placebo for on average 2 1/2 years. The lipid inclusion criteria were HDL cholesterol concentration < or = 1.1 mmol/L, low density lipoprotein (LDL) cholesterol < or = 4.5 mmol/L, and serum triglyceride < or = 4.0 mmol/L. Subjects were not accepted if they had manifest diabetes, body mass index > 30 kg/m2, uncontrolled hypertension, or if they were regular smokers. All randomized subjects underwent baseline coronary angiography, which will be repeated at the end of the study. The angiograms will be analyzed using the Cardiovascular Measurement System, a validated computer-assisted image-analysis and quantitation package. The primary endpoints are the changes in the per-patient mean of 1) the average diameter of evaluable native coronary segments, and 2) the minimal luminal diameter of evaluable stenoses, and 3) the appearance of new lesions. Extensive lipoprotein and other metabolic studies and analyses of genetic polymorphisms are carried out to study the determinants of CAD progression. At baseline, the study subjects were 59.1 +/- 6.8 (mean +/- standard deviation) years old, had a body mass index 26.4 +/- 2.2 kg/m2, and serum triglyceride, serum cholesterol, HDL cholesterol, and LDL cholesterol concentrations 1.64 +/- 0.64, 5.17 +/- 0.64, 0.82 +/- 0.14, and 3.61 +/- 0.53 mmol/L, respectively.

Cholesterol, HDL↗
PubMed1997

The influence of peritoneal dialysis and the use of subcutaneous and intraperitoneal insulin on glucose metabolism and serum lipids in type 1 diabetic patients.

BACKGROUND: Intraperitoneally administered insulin is regarded as the most physiological replacement therapy, leading to lower peripheral insulin concentrations and equal or better glycaemic control than subcutaneous insulin. This two-part study was undertaken to evaluate the effect of CAPD, as well as the use of subcutaneous vs. intraperitoneal insulin on insulin sensitivity, glycaemic control and serum lipids in type 1 diabetes. METHODS: Eleven patients with type 1 diabetes mellitus and chronic renal failure participated the studies. Glycated haemoglobin (HbA1c), euglycaemic hyperin-sulinaemic clamp, serum lipids, and patient well-being were measured. During CAPD all patients were first treated with subcutaneous insulin and then with intraperitoneal insulin. The metabolic studies were repeated after both treatment periods for at least 3 months. Metabolic studies were performed on six of the patients also before initiation of CAPD. RESULTS: HbA1c rose after the initiation of CAPD from 8.85 +/- 0.54% to 9.58 +/- 0.66%, NS) and improved after changing from subcutaneous to intraperitoneally administered insulin (from 9.49 +/- 0.43% to 8.13 +/- 0.39%, P < 0.01). Insulin dose increased by 15% after initiation of CAPD and 128% after switching from subcutaneous to intraperitoneal insulin. Glucose disposal rate enhanced by 39% (P = 0.05) and 14% respectively (P < 0.01). Initiation of CAPD had no significant effects on serum lipids but intraperitoneally administered insulin reduced HDL cholesterol and increased LDL/HDL ratio significantly. CONCLUSIONS: Intraperitoneal insulin therapy offers better glycaemic control and insulin sensitivity than subcutaneous insulin. Deterioration of HbA1c after initiation of CAPD while patients remained on subcutaneous insulin may be partly due to absorbed energy from the dialysate. Intraperitoneal insulin therapy seems to have detrimental effects on serum lipids. The clinical significance in modifying the risk of atherosclerosis remains unclear.

Adult↗
PubMed1997

Renal and cardiovascular predictors of 9-year total and sudden cardiac mortality in non-insulin-dependent diabetic subjects.

BACKGROUND: The objective was to evaluate the impact of urinary albumin excretion rate (UAER), glomerular filtration rate (GFR) and subclinical autonomic neuropathy (SANP) on 9-year total (TM) and sudden cardiac mortality (SCM) in recently diagnosed (< 1 year; RD; n = 150) and known (mean duration 11 years; KD; n = 146) NIDDM subjects. METHODS: The study was prospective and controlled (n = 150). Mortality predictors were analysed by logistic regression analysis. The dependent variables were TM and SCM, the predictors were UAER, GFR, SANP, age, gender, BMI, mean arterial pressure (MAP), fasting serum cholesterol, HDL-cholesterol, triglycerides, insulin, haemoglobin A1c, diabetes duration, QTc-interval (ECG), coronary heart disease (CHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), congestive heart failure (CHF), antihypertensive therapy, and smoking habits. RESULTS: CHD predicted TM and SCM in both RD (P = 0.041 and 0.029) and KD (P = 0.034 and 0.006). PVD predicted TM and SCM in KD only (P = 0.001 and 0.003). CVD predicted TM and SCM in RD only (P = 0.001 and 0.017). In RD male gender (P = 0.049), fasting serum cholesterol (P = 0.007) and CHF (P = 0.001) predicted TM and in kDa haemoglobin A1c (P = 0.004), age (P = 0.001) and MAP (P = 0.014) predicted TM. Serum triglycerides predicted SCM in both RD and kDa (P = 0.001 and 0.003). SANP predicted TM (P = 0.009) and SCM (P = 0.044) in KD only. GFR (inverse value) predicted TM and SCM (P = 0.04 and 0.027) in kDa only. The UAER did not predict mortality in the diabetic subjects. CONCLUSION: SANP and a slightly reduced GFR still in the normal range predicted mortality in KD. Microalbuminuria (30 < UAER < 300 mg/24 h) did not independently predict 9-year mortality in the NIDDM subjects studied.

Adult↗
PubMed1997

Mesangial glomerulonephritis as an extra-articular manifestation of rheumatoid arthritis.

Mesangial glomerulonephritis (MesGN) is a frequent renal biopsy finding in patients with rheumatoid arthritis (RA) presenting with haematuria and/or proteinuria. The purpose of this study was to describe the mesangial immunofluorescence (IF) findings in 37 such RA patients, and to correlate the nature of the glomerular immunodeposits with clinical data, levels of serum immunoglobulins and the concentrations of serum rheumatoid factors (RFs). The serological findings in RA patients with MesGN were correlated with those of RA patients matched for age, sex and duration of RA, but without clinically evident renal disease. The most characteristic mesangial IF finding in 37 RA patients with MesGN was IgM observed in 29 specimens (78%). IgA (n = 16) and C3 (n = 15) deposits were also frequently found, whereas C1q (n = 3) and IgG (n = 2) deposits were only occasionally seen. Two main patterns of IF findings could be classified. (1) Granular IgM deposits as a sole or main finding (IgM GN; 25 specimens). The intensity of the mesangial IgM deposits did not correlate with the duration or severity of RA nor with the levels of serum immunoglobulins. However, a significant correlation with the intensity of mesangial IgM deposits and the levels of serum IgM class RF was observed. (2) Granular IgA deposits usually together with the complement component C3, i.e. IgA glomerulonephritis (IgA GN; nine specimens). The intensity of mesangial IgA deposits correlated significantly with the duration and severity of RA, and especially with serum IgA levels. Both RA patients with IgA GN or IgM GN were associated with a more frequent occurrence and higher titres of serum RFs when compared with the RA patients without nephropathy. The clinicopathological correlations and the association with RF support the concept that MesGN is related to the basic rheumatoid disease, and it should be regarded as an extra-articular manifestation of RA.

Adult↗
PubMed1997

[Diabetic nephropathy--screening, follow-up and treatment. Nephropathy Study Groups of The Finnish Diabetes Organization].

Owing to advances in the diagnosis and treatment of diabetic nephropathy, its management has become more active and is now initiated earlier after the presence of microalbuminuria has been established. In 1996 the Finnish Diabetic Association's nephropathy group issued recommendations concerning screening for diabetic nephropathy, and treatment and follow-up of patients with the disease.

Adolescent↗
PubMed1997

Evaluation of the calcium-PTH axis and renal handling of phosphate by calcium and citrate clamp techniques in normal subjects and in patients with heavy proteinuria.

We studied the effect of induced hyper- and hypocalcemia on parathyroid function and renal handling of phosphate in healthy subjects (n = 10) and in patients with heavy proteinuria, mean 5.6 +/- 1.9 g/24 hours (n = 5). We used calcium and citrate clamp techniques. Hypercalcemia was rapidly induced by calcium infusion and maintained for 120 min, and correspondingly, hypocalcemia by citrate infusion. The suppression of intact PTH secretion during calcium clamp was similar (to the level of < or = 0.8 pmol/l) in both groups. The response of the parathyroid glands to hypocalcemia was similar in normal subjects and proteinuric patients. Both groups showed a peak of PTH secretion at 10 min, 18.9 +/- 6.7 pmol/l in healthy subjects and 20.4 +/- 7.4 pmol/l in patients. The peak levels were 4.8-7.2 times and 4.0-6.7 times the baseline level, respectively. Thereafter the plasma PTH concentration declined to a fairly constant steady-state level (twice the baseline level) in spite of maintained hypocalcemia. The area under the curve of the plasma concentrations of intact PTH at various times (AUC0-120) was 890 +/- 324 pmol/l/min in normal subjects and 989 +/- 331 pmol/l/min in proteinuric patients, the difference between the groups being again not significant. The renal threshold phosphate concentration (TmPO4/GFR) increased during calcium infusion and decreased during citrate infusion in both groups. During recovery from hypocalcemia PTH levels were lower than during hypocalcemic induction at corresponding serum calcium levels. Using calcium and citrate clamp techniques, we found that the response of the parathyroid glands in acute and maintained hypercalcemia and hypocalcemia, and renal phosphate handling in patients with heavy proteinuria was not different from that of healthy subjects.

Adult↗
PubMed1996

Cytokines, adhesion molecules, and cellular infiltration in nephropathia epidemica kidneys: an immunohistochemical study.

Puumala hantavirus-induced nephropathia epidemica (NE) is an important cause for an acute reversible renal failure in Scandinavia, European Russia, and the Balkans. The characteristic histopathological renal finding is an acute tubulointerstitial nephritis. Mild to massive proteinuria, hematuria, and a rise in the serum creatinine level are typically seen. The pathogenetic mechanisms of NE kidney failure are incompletely understood. Therefore we studied the infiltrating cell populations and local expression of cytokines and growth factors in the kidney during the acute disease. Results of the histological and immunohistological studies of eight kidney biopsies show mild to moderate interstitial infiltration of lymphocytes, plasma cells, monocytes/macrophages, and polymorphonuclear leukocytes, mainly eosinophilic granulocytes and neutrophils. An increased expression of the cytokines tumor necrosis factor-alpha, transforming growth factor-beta, and platelet-derived growth factor was seen at the same sites mainly in the peritubular area of the distal nephron. Concomitantly also at the same locations expression of the endothelial adhesion molecules ICAM-1, VCAM, and PECAM was seen. Light microscopic changes in tubuli were common. Interestingly, despite the often massive transient proteinuria, no marked changes were seen in the glomeruli of NE kidneys. No evidence of Puumala virus was found in the kidney biopsies.

Adult↗
PubMed1996

Genetic susceptibility to severe course of nephropathia epidemica caused by Puumala hantavirus.

Nephropathia epidemica (NE) caused by Puumala hantavirus is one type of hemorrhagic fever with renal syndrome (HFRS). There is considerable variability in the clinical severity of NE. Many infections are subclinical but the disease can even be fatal. We questioned whether the wide spectrum in the outcome of NE is dependent, on host-related immunological factors by determining the major histocompatibility complex markers (MHC) in 74 adult patients with NE. Patients with the most severe course of the disease had a very high frequency of HLA B8, C4A*Q0, and DRB1*0301 alleles. HLA B8 was found in all 7 (100%) patients with shock and in 9 of the 13 (69%) patients who required dialysis, versus in only 25 of 74 (34%) in the entire population, and in 14 of 93 (15%) controls. In addition, various other clinical findings pointing to a severe form of NE were found to be associated with these alleles. Interestingly, the same MHC alleles are risk factors for various autoimmune diseases. This is the first study where a certain HLA haplotype is found to be associated with the clinical course of an acute viral disease or acute nephritis.

Acute Kidney Injury↗
PubMed1996

Plasma atrial natriuretic peptide, body weight and twenty-four-hour blood pressure monitoring in chronic hemodialysis patients.

In this study we investigated the interactions between volume changes (body weight), plasma atrial natriuretic peptide (pANP) and ambulatory blood pressure (BP) in 10 patients with end-stage renal disease undergoing regular hemodialysis (HD) treatment three times weekly. Most patients retained their diurnal BP variation when their BP was adequately controlled. Interdialytic weight gain was 1.3 +/- 0.2 kg and the day-time systolic BP increased 12.5 +/- 4.8 mm Hg on the second interdialytic day. pANP did not correlate (r = -0.07, p = 0.85) with this BP elevation, but there was a fairly strong positive correlation (r = 0.61, p = 0.06) between interdialytic weight gain and systolic BP. The mean pANP level decreased from 149.7 +/- 18.2 to 117 +/- 0.1 ng/l during HD and continued its decrease to 83 +/- 12.2 ng/l at 20 h after an HD session. The total decrease from 149.7 +/- 18.2 to 83 +/- 12.2 ng/l was statistically significant (p = 0.001). Since the lowest pANP value was found 20 h after completion of the dialysis session, body weight is a more reliable indicator of volume reduction during HD than pANP. The results indicate that in HD patients weight gain between two dialysis sessions increases the day-time systolic BP but not the diastolic BP. Diurnal BP variation is maintained as long as BP is adequately controlled either by volume control or by drug treatment.

Adult↗
PubMed1996

Intravenous calcitriol therapy restores reduced antigen-induced T-lymphocyte response in 1,25-(OH)2D3-deficient hemodialysis patients.

Ten hemodialysis patients were treated with intravenous calcitriol (1-1.5 micrograms 3 times per week) for 3 months and parameters reflecting cell-mediated immunity were measured before and at the end of treatment. Peripheral blood CD4+ cells increased from 33.1 +/- 14.2 to 43.8 +/- 5.8% (p < 0.05) causing a comparable increase in CD3+ cells (67.3 +/- 14.3 vs. 77.1 +/- 7.9%, p < 0.05), whereas CD8+ cells did not change significantly (22.2 +/- 5.4 vs. 25.5 +/- 3.0%). Mitogen-induced lymphocyte stimulation responses were normal even before treatment and did not change. Antigen-induced T-cell responses were very heterogeneous before calcitriol therapy; those 5 with initially unmeasurably low serum 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) had a weaker response than the other patients (3,873 +/- 1,528 vs. 22,948 +/- 13,684 cpm, p < 0.05). After calcitriol treatment the patients with pretherapy unmeasurably low serum 1,25-(OH)2D3 had a comparable response to other patients (16,220 +/- 9,674 vs. 22,064 +/- 10,331 cpm). Our study shows that calcitriol therapy restores the depressed antigen-induced T-cell response of the hemodialysis patients most deficient in 1,25-(OH)2D3.

Adult↗
PubMed1996

Glomerular filtration rate and kidney size after six years disease duration in non-insulin-dependent diabetic subjects.

The objective of the present study was to estimate how glomerular filtration rate and kidney size change after six years of diabetes in subjects with non-insulin-dependent disease. It is a population-based prospective study of a cohort of non-insulin diabetic patients (n = 150) diagnosed 1985-1988. The baseline studies utilized a non-diabetic control group, whose basic characteristics were equal to the study group. The setting was a primary health care center in an urban area. Main outcome measures were the glomerular filtration rate and its relation to renal area, mean blood pressure, hemoglobin A1c, serum insulin and cholesterol. Seventeen patients had died and 109 were eligible for evaluation at follow-up. The mean (standard deviation) of the glomerular filtration rate (ml/min/1.73 m2) remained elevated at follow-up, 118 (28), just as it was at baseline, 118 (28) in the diabetic subjects compared to matched non-diabetic subjects, 103 (24) (p = 0.0000). Kidney size (cm2) was larger in diabetic subjects at follow-up, 114 (19) than at baseline, 109 (18) (p = 0.0000) and in non-diabetic subjects 98 (14) (p < 0.0000). This resulted in a decline in glomerular filtration rate per unit renal area in the diabetic subjects at follow-up, 1.0 (0.23) compared to at baseline, 1.09 (0.23) (p = 0.002) and to non-diabetic subjects, 1.07 (0.23). The renal area at baseline was directly and significantly related to the glomerular filtration rate at follow-up (p < 0.001). The relation of baseline serum cholesterol, hemoglobin A 1c and mean arterial blood pressure to the glomerular filtration rate at follow-up was inverse and reached significance in those diabetic subjects having had high filtration rates at baseline but displaying a faster decline than on average i.e. in those patients who were at increased risk of renal insufficiency. We conclude that after the first six years of non-insulin-dependent diabetes the glomerular filtration rate remains high. Kidney size increases further from the attained increase at diagnosis and is an important determinant of continuing hyperfiltration. The deleterious effect of serum cholesterol and high blood glucose on the glomerular filtration rate at this early stage of diabetic kidney disease is suggestive.

Analysis of Variance↗
PubMed1996

Subcutaneous and intraperitoneal insulin therapy in diabetic patients on CAPD.

We evaluated in a cross-over manner the consequences of subcutaneously and intraperitoneally given insulin on glucose control, insulin sensitivity, and serum lipids in 8 type I diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The patients were treated with both subcutaneous and intraperitoneal insulin for at least three months. After each period, metabolic studies were performed. Despite significantly improved glycemic control (Hb A1c 10.00 +/- 0.38% after subcutaneous and 8.40 +/- 0.36% after intraperitoneal insulin, p = 0.01), serum lipids showed unfavorable changes. High-density lipoprotein (HDL)-cholesterol was significantly lower (1.28 +/- 0.18 mmol/L vs 0.88 +/- 0.06 mmol/L, p = 0.03) and low-density lipoprotein (LDL)/HDL-cholesterol ratio was higher (p = 0.025) during intraperitoneal insulin. Total cholesterol, LDL-cholesterol, and triglycerides were higher during intraperitoneal insulin administration. Severe hypoglycemic episodes were more common during subcutaneous than intraperitoneal insulin. It is concluded that, although intraperitoneal insulin administration offers significantly better glycemic control and insulin sensitivity than subcutaneous insulin, the effect of serum lipids is more disadvantageous possibly via a direct effect of insulin on the liver.

Adult↗