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Biomedical subjects

A Pasternack

Publications and source records attributed to A Pasternack.

At least 55 records · Page 3Linked to original sources
PubMed1999

Pharmacokinetics of clodronate in haemodialysis patients.

BACKGROUND: Clodronate is a bisphosphonate used in the treatment of hypercalcaemia of various aetiologies. The major route of elimination of clodronate is renal excretion. The aim of the study was to derive data for the adjustment of dosage in haemodialysis patients. METHODS: The pharmacokinetic parameters describing the fate of an intravenous infusion of 300 mg clodronate disodium were studied in 10 haemodialysis patients. Clodronate disodium in serum, urine and dialysate samples was analysed by capillary gas chromatography with mass-selective detection. RESULTS: Of the 300 mg clodronate infused, 159 mg (53%) was excreted into dialysate within 4 h. Clearance by haemodialysis (CLD) was 87.8+/-16.2 ml/min, accounting for 84% of total serum clearance (CLtot). Non-renal, non-dialysis clearance (CL(NRD)) represents the removal of the drug via other routes than dialysis or kidneys. The greatest CL(NRD) was observed in patients with most severe hyperparathyroidism. There was a positive correlation between CL(NRD) and plasma intact PTH concentration. CONCLUSIONS: According to the present findings, standard haemodialysis removes clodronate effectively from the circulation, and total clearance in haemodialysis patients on a dialysis day is not very different from that in healthy subjects. The regimen of dosing intravenous clodronate in hypercalcaemia can also be used in haemodialysis patients. The portion of clodronate eliminated by routes other than via dialysate or kidneys, i.e. predominantly via skeletal deposition, was related to the severity of hyperparathyroidism.

Aged↗
PubMed1999

The occurrence of renal involvement in primary Sjögren's syndrome: a study of 78 patients.

OBJECTIVE: To ascertain the occurrence of renal involvement in patients with primary Sjögren's syndrome (pSS). METHODS: Urinary total protein excretion from 24 h urine collection, as well as urinary excretion rates of albumin, alpha-1 microglobulin (alpha1m) and IgG from overnight 8 h collections, were determined from 78 pSS patients (75 females, three males). Urine acidification capacity after oral ammonium chloride load was tested in 55 of these patients. RESULTS: Mild proteinuria (0.15-0.42 g/24 h) was observed in 34 patients (44%). Increased urinary excretion rates of albumin (>/=20 microgram/min), alpha1m (>/=7.0 microgram/min) or IgG (>/=5.0 microgram/min) were detected in nine (12%), nine (12%) and 11 patients (14%), respectively. Latent or overt distal renal tubular acidosis (dRTA) was observed in 18 out of 55 patients with pSS (33%). These patients had a longer duration of the disease (10+/-4 vs 8+/-4 yr; P</=0.05); they also had proteinuria (67 vs 27%; P</=0.025) and hypertension (44 vs 14%; P</=0.05) more frequently, and significantly higher serum creatinine (92+/-39 vs 78+/-13 micromol/l; P</=0.025) and serum beta-2 microglobulin (beta2m) levels (3.3+/-1.6 g/l vs 2.6+/-0. 6 g/l; P</=0.025) as compared to patients with normal urine acidification capacity. CONCLUSIONS: Inadequate renal acidification capacity, as well as mild proteinuria, were frequently found in patients with pSS. Those with dRTA had longer disease duration, a higher level of serum beta2m, and they had proteinuria and hypertension more frequently than those with normal renal acidification capacity.

Acidosis, Renal Tubular↗
PubMed1999

Clinical follow up study of 87 patients with sicca symptoms (dryness of eyes or mouth, or both).

OBJECTIVE: To assess the prognosis of patients with sicca symptoms and to identify the clinical and immunological factors that most sensitively predict the later development of primary Sjögren's syndrome (SS) or other connective tissue diseases. METHODS: Eighty seven patients (72 female, 15 male) with sicca symptoms were re-evaluated after a median follow up time of 11 years (range 8-17). The clinical examination included ophthalmological examination (Schirmer's test, break up time and Rose-Bengal staining). Labial salivary gland biopsy was performed and histological findings graded according to the Chisholm-Mason scale. The immunoserological tests included determination of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-extractable nuclear antigen-antibodies (ENA), serum immunoglobulins IgA, IgG, and IgM, and serum beta2-microglobulin (beta2m). RESULTS: At follow up 31 patients (36%) fulfilled modified Californian criteria (salivary flow measurements were not performed and Chisholm-Mason grades 3-4 were regarded as diagnostic histological findings) for possible or definite SS. Likewise, a significant progression of the histological findings was observed. Labial salivary gland re-biopsy was performed in 42 patients with grade 0-2 findings at baseline, progression to grades 3-4 being observed in 21 (50%) at follow up. The patients who later developed SS were at baseline significantly older (mean (SD) 52 (9) v 44 (14) years, p</=0.005) compared with those not fulfilling the SS criteria at follow up; they also had significantly higher serum beta2m (p</=0.0005) and IgG concentrations (p</=0.005), and they had positive ANA more frequently (p</=0.01). CONCLUSION: These results suggest that high age, increased values of serum beta2m, ANA positivity and increased concentrations of serum IgG, might be useful indicators for the subsequent development of SS in patients with sicca symptoms. The prognosis of patients with these symptoms was favourable, and the clinical course was benign even in the 36% of patients who developed SS. No cases of lymphoma were observed.

Adult↗
PubMed1999

QRS amplitude and volume changes during hemodialysis.

BACKGROUND: According to several studies the QRS amplitude of the ECG increases during hemodialysis. The detailed background to this phenomenon has not been defined. Two main mechanisms have been suggested: myocardial ischemia and volume changes. New noninvasive technologies make possible a comparison of QRS complex changes synchronously with myocardial ischemia and extracellular water (ECW)/blood volume (BV) changes during hemodialysis. METHODS: In this study hemodialysis-related changes in body weight, biochemical blood variables, BV, ECW, ST segment and QRS complex were analyzed in 15 patients (age 36-76, time on dialysis 0-6 years) undergoing chronic hemodialysis treatment. QRS complex and ST segment changes were measured using a dynamic vectorcardiographic monitoring system. The ECG parameters measured were QRS vector difference (QRS-VD) and ST vector magnitude (ST-VM6). Bioimpedance analysis was used to detect changes in the ECW. Continuous measurement of BV changes was implemented using an on-line optical reflection method based on the reflection of infrared light by erythrocyte membranes. Blood hemoglobin (B-Hb), hematocrit (B-Hcr), plasma sodium (P-Na), chloride (P-Cl), magnesium (P-Mg), potassium (P-K), ionized calcium (P-iCa), phosphate (P-Pi), creatinine (P-Crea) and urea (S-Urea) were monitored. RESULTS: The mean QRS-VD increase during the dialysis session was almost fourfold (372 +/- 300%) from 4.16 +/- 2. 40 to 15.60 +/- 7.0 microVs (p < 0.001). This change was due to a change in amplitude, since the duration of the QRS complex did not alter significantly. The correlation between the changes in QRS-VD and body weight from the start to the end of the dialysis session was moderate and statistically significant (r = -0.55, p < 0.05). The correlation between the changes in QRS-VD and ECW varied from r = -0.67 to -0.97, being statistically significant in all patients (p < 0.001). The correlation between BV and QRS-VD was assessed at one minute intervals during the dialysis and varied from r = -0.22 to -0. 98, being significant in 14 of the 15 patients (p < 0.001). Significant ST segments alterations (ST-VM6 elevation > 100 microV) did not occur during dialysis. Laboratory parameters reflecting volume and osmotic changes during hemodialysis correlated with QRS-VD change: B-Hcr (r = 0.56, p < 0.05), B-Hb (r = 0.63, p < 0.05), P-Na (r = 0.62, p < 0.05) and S-Urea (r = -0.62, p < 0.05). CONCLUSIONS: The increase in QRS complex amplitude during hemodialysis is correlated to reduced ECW. The mechanism involved is most probably augmentation of electrical resistance of the tissues around the heart caused by loss of interstitial fluid.

Adult↗
PubMed1999

Retinopathy is independently related to microalbuminuria in type 2 diabetes mellitus.

UNLABELLED: AIM, SUBJECTS AND METHODS: To evaluate whether microalbuminuria is related to retinopathy in type 2 diabetes, we studied a sample of 125 known diabetic subjects with a mean disease duration of 11 years (range 5-22 years), aged 46-71 years, by ophthalmoscopy, fundus photography and fluoresceine angiography. Urinary albumin excretion rate (UAER) was measured by nephelometry and the fractional clearance of albumin, i.e. in relation to creatinine was calculated from spot samples. The subjects were classified into groups based on the UAER/24 h. RESULTS: Microalbuminuria was present if UAER was 30-300 mg/24 h and overt nephropathy when UAER > or = 300 mg/24 h. Background (> or = 2 microaneurysms or > or = 2 hemorrhages or > or = 1 more advanced lesions, except proliferative changes) and proliferative retinopathies were found in 21% and in 3%, respectively. Subjects with microalbuminuria (p = 0.026) and overt nephropathy (p = 0.002) had more frequently background retinopathy than their counterparts with a normal UAER (chi2-test). A multivariate logistic regression model was obtained for background retinopathy (chi2 = 37.5, p = 0.0000039, OR 14.9, correct prediction of negative outcome in 97% and of positive outcome in 30.4%) including the following variables. The fractional clearance of albumin independently explained background retinopathy (OR 3.9, 95% CI 1.3-12, p = 0.028). Insulin therapy (p = 0.0017), diabetes duration (p = 0.048), blood glucose at 2 h in standard oral glucose tolerance test (p = 0.009) and low fasting serum HDL cholesterol (p = 0.023) also independently explained retinopathy. Age, gender, BMI, systolic blood pressure, ACE inhibitor therapy, fasting serum total cholesterol and triglyceride, blood glucose or insulin, hemoglobin A1c, glucagon-stimulated C peptide response, glomerular filtration rate or smoking habits did not independently explain retinopathy. CONCLUSION: We conclude that microalbuminuria is related to background retinopathy in type 2 diabetes.

Aged↗
PubMed1999

Increased in vitro production of interleukin 6 in response to trimethoprim among persons with trimethoprim induced systemic adverse reactions.

OBJECTIVE: Trimethoprim occasionally triggers a systemic adverse reaction including fever, malaise, head and backache, and even overt meningeal irritation, particularly in women with an autoimmune rheumatic disease. To study the unknown pathogenesis of the reaction we measured the effect of trimethoprim upon the cytokine [interleukin (IL) 2, 6, 10, and tumor necrosis factor-alpha] production of trimethoprim reactive and tolerant persons' peripheral blood mononuclear cells in vitro. METHODS: Peripheral blood mononuclear cells from 12 women reactive to trimethoprim (3 with primary Sjögren's syndrome, 3 with systemic lupus erythematosus, 1 with systemic scleroderma, 5 with no rheumatic disease) were cultured in the presence of trimethoprim, and the cytokine production was measured. Eleven women who tolerated trimethoprim (6 with Sjögren's syndrome and 5 with no rheumatic disease) served as controls. RESULTS: Therapeutic trimethoprim concentration induced in the mononuclear cells of the trimethoprim reactive patients significantly higher IL-6 production [mean +/- SD (median), 2034+/-2965 (572) pg/ml] versus cells of the trimethoprim tolerant subjects [954+/-2552 (89) pg/ml; p = 0.036]. No significant differences in the production of other cytokines were detected. CONCLUSION: Trimethoprim induces IL-6 production in the peripheral blood mononuclear cells of trimethoprim reactive persons. We suggest that IL-6 production is the probable trigger leading to the clinical reaction.

Adult↗
PubMed1998

Associations between lipoproteins and the progression of coronary and vein-graft atherosclerosis in a controlled trial with gemfibrozil in men with low baseline levels of HDL cholesterol.

BACKGROUND: Lipid-lowering secondary-prevention trials of coronary artery disease (CAD) have implicated triglyceride-rich lipoproteins as the main determinants of angiographic progression after elevated LDL cholesterol levels have been lowered with therapy. The present study focuses on the lipoprotein determinants of angiographic CAD progression in men with low HDL cholesterol concentration as their main baseline lipid abnormality who underwent 32 months of randomized therapy with gemfibrozil or placebo. METHODS AND RESULTS: Men who had undergone coronary bypass surgery (n=372) completed a randomized, placebo-controlled study with gemfibrozil 1200 mg/d. They were selected primarily for HDL cholesterol levels that corresponded to the lowest third for middle-aged men. Average baseline lipid and lipoprotein levels were serum triglyceride, 1.60; serum cholesterol, 5.17; ultracentrifugally separated LDL cholesterol, 3.43; HDL2 cholesterol, 0.41; and HDL3 cholesterol, 0. 61 mmol/L. In the gemfibrozil group, these levels were reduced on average by 40%, 9%, and 6% or increased by 5% and 9%, respectively. On-trial IDL and LDL triglyceride and cholesterol levels significantly predicted global angiographic progression, taking into account changes in native segments and in bypass grafts. HDL3 but not HDL2 cholesterol concentration was associated with protection against progression, especially focal disease in native coronary lesions. VLDL was the lipoprotein most predictive of new lesions in vein grafts; IDL was also significantly related. CONCLUSIONS: This study expands the previous evidence of the triglyceride-rich lipoproteins, especially IDL, as predictors of angiographic progression of CAD but does not negate the significance of mildly elevated LDL levels. Of the HDL subfractions, only HDL3 was protective in this group of men selected for their low initial HDL levels.

Apolipoproteins↗
PubMed1998

Susceptibility of LDL to oxidation is not associated with the presence of coronary heart disease or renal dysfunction in NIDDM patients.

Coronary heart disease (CHD) is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM) and the oxidation of low-density lipoprotein (LDL) may be an essential factor in the development of atherosclerotic lesions. Therefore, we studied the in vitro susceptibility of LDL to copper-induced oxidation in 72 NIDDM patients and 94 well-matched non-diabetic control subjects. There was no significant difference in the lagtime of LDL oxidation between NIDDM patients and control subjects (68.1+/-8.8 vs. 66.7+/-9.2 min, respectively, P=0.29). The plasma alpha-tocopherol/LDL-ratio was the most significant determinant of the lagtime in multiple regression analysis. High level of serum triglycerides was associated with decreased lagtime in control subjects, but not in NIDDM patients. Blood glucose balance was not associated with LDL susceptibility to oxidation in NIDDM patients. Subjects with CHD did not have LDL susceptibility to oxidation different from that of subjects without CHD in either of the study groups. Urinary albumin excretion or glomerular filtration rate was not associated with the lagtime of LDL oxidation in NIDDM patients. In conclusion, these data suggest that diabetes and hyperglycemia per se do not affect the susceptibility of LDL to oxidation. The presence of CHD or renal dysfunction were not associated with LDL susceptibility to oxidation.

Aged↗
PubMed1998

Information under load.

That's what happens when your clinical and business people don't speak the same language. Without that, clinical data can't become grist for business decisions, and business strategies lack key clinical goals, such as reducing service delays or mortality following heart surgery.

Budgets↗
PubMed1998

6 new buying rules.

Times change--and so does software purchasing. Buying in bulk, paying top dollar for what a system does, trusting a vendor to watch out for you--that's old input. Here are six fresh rules for the buying game.

Contract Services↗