Correlates of vascular access occlusion in hemodialysis.

Vascular access occlusion results in significant morbidity in hemodialysis patients. Age, diabetes, and synthetic grafts (polytetrafluoroethylene [PTFE]) have been associated with vascular access occlusion in univariate analysis. However, the independent risk associated with each of these factors has not been assessed adjusting for confounding among the factors or by other variables, such as blood pressure (BP) or hematocrit. The influence of serum lipoprotein(a) [Lp(a)] and fibronectin on vascular access occlusion has not been widely studied despite their theoretical or demonstrated importance in vascular bypass occlusion. In a cohort study of 124 hemodialysis patients monitored for up to 14 months, we reported that Lp(a) values in the upper tertile (> or = 57 mg/dL) were associated with vascular access occlusion risk in white and Hispanic patients, but not in black patients. We now report an expanded analysis of this data set to determine the independent correlates of vascular access occlusion. Variables tested included age, race, gender, diabetes, access type (PTFE v endogenous), treatment time, systolic BP, hematocrit, heparin and erythropoietin dosage, and serum levels of Lp(a) and fibronectin. In univariate analysis, access occlusion was associated with age, diabetes, PTFE, Lp(a) > or = 57 mg/dL, serum fibronectin, and reduced BP. The independent correlates of first access occlusion were determined with the Cox proportional hazards model. Since the overall model included a significant race x Lp(a) interaction term, we stratified by race. In black patients, risk correlated directly with PTFE (P < 0.01) and inversely with systolic BP (P < 0.001), whereas for white and Hispanic patients, age (P = 0.04) and Lp(a) > or = 57 mg/dL (P = 0.05) were associated with increased risk. In summary, vascular access occlusion was found to be associated with a number of factors. Important independent correlates were PTFE and lower BP in black patients, and age and serum Lp(a) > or = 57 mg/dL in white and Hispanic patients. Diabetes mellitus and increased serum fibronectin may contribute additional risk.

Prealbumin and lipoprotein(a) in hemodialysis: relationships with patient and vascular access survival.

The high morbidity and mortality of hemodialysis patients has led to a search for early markers of risk. Because cardiovascular and nutritional risk are prevalent in this population, we examined the prognostic value of the serum levels of two markers of risk in the general population: (1) lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle linked to myocardial infarction and coronary bypass stenosis, and (2) prealbumin, a marker of visceral protein status, with a shorter half-life than that of serum albumin. Baseline demographics, clinical information, dialysis prescription, and serum biochemistry measurements of 125 hemodialysis patients followed for up to 14 months were recorded on enrollment. Vascular access events and deaths were recorded prospectively. The hypotheses tested were that increased serum Lp(a) levels would predict cardiovascular mortality and vascular access stenosis and thrombosis, and that reduced serum prealbumin levels would predict mortality risk independently of established risk predictors. Cross-sectional analysis of serum Lp(a) demonstrated a skewed distribution with a median value of 38.3 mg/dL (upper tertile, > or = 57 mg/dL). Lipoprotein(a) was significantly higher in black patients (P < 0.001) and was significantly correlated (P < 0.005) with total cholesterol and apoprotein B (apoB), but not with a history of prior coronary disease. Serum prealbumin was strongly correlated with serum albumin (r = 0.49, P < 0.001). However, prealbumin correlated (P < 0.001) more strongly with other serum nutrition markers (total cholesterol, apoB, creatinine, urea) than did serum albumin. Fourteen-month cumulative survival was 80%. Age, diabetes, and serum levels of albumin, prealbumin, creatinine, total cholesterol and apoB, but not Lp(a), were correlated with survival in univariate analysis. Using the Cox proportional hazards model, independent predictors of mortality risk were prealbumin less than 15 mg/dL versus higher values (relative risk [RR] = 4.48, P < 0.01), apoB (RR = 0.97 per 1 mg/dL increase, P < 0.02), creatinine less than 10 mg/dL versus higher values (RR = 3.51, P = 0.04), and age (RR = 1.04 per year, P = 0.10). Thirty-eight patients experienced at least one vascular access thrombosis (n = 33) or stenosis (n = 5) during the study. Patients with Lp(a) > or = 57 mg/dL had decreased vascular access event-free survival compared with patients with Lp(a) less than 57 mg/dL (56% v 73%, P < 0.06). This trend was increased in magnitude and statistically significant for white and Hispanic patients (31% v 79%, P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of a nisin-based germicidal formulation on teat skin of live cows.

A purified preparation of the nontoxic antimicrobial peptide, nisin (AMBICIN N), was used in the formulation of a germicidal sanitizer suitable for use on cow teats. The germicidal activity of the formulation against mastitis pathogens was measured on teat skin of live cows. The nisin-based formulation gave a mean log reduction of 3.90 against Staphylococcus aureus and 4.22 log reduction against Escherichia coli after exposure for 1 min to the germicide. This activity was comparable with that exhibited by a 1% iodophor teat dip but was significantly greater than that exhibited by the .1 and .5% iodophors and by the .5% chlorhexidine digluconate teat dips. The nisin-based formulation showed little or no potential for skin irritation after multiple application to skin, but iodophor and chlorhexidine digluconate teat dips showed significant potential for skin irritation in comparable studies.

Class 1 (unique) tumor antigens of human melanoma: identification of unique and common epitopes on a 90-kDa glycoprotein.

Antibodies present in the serum of melanoma patient FD detect an antigenic determinant (FD) restricted to the autologous melanoma cell line SK-MEL-131. This cell-surface determinant is carried on a glycoprotein of 90 kDa, designated gp90. Mice were immunized with a partially purified preparation of gp90 derived from SK-MEL-131 clone 1.5, and three murine hybridomas (KF23, KF26, and KF104) secreting monoclonal antibodies (mAbs) detecting this antigen have been generated. Sequential immunoprecipitation experiments demonstrate that the three mAbs and human FD serum react with the same gp90 species. The mAbs, in contrast to FD serum, react with a broad range of cultured cells in assays for cell-surface antigens and immunoprecipitate a gp90 component from radiolabeled extracts of these cells, including autologous FD B cells. We conclude that gp90 from SK-MEL-131 has two types of determinants: restricted (detected by FD serum) and common (detected by the mouse mAbs). gp90 molecules from cell lines other than SK-MEL-131 carry only the common determinant(s). Immunoperoxidase analysis of frozen tissue sections with mAb KF23 demonstrated a restricted gp90 expression in normal tissues (capillary endothelial cells, duct epithelium in sweat glands, breast, and pancreas). Melanomas and sarcomas showed strong gp90 expression, suggesting up-regulation of gp90 synthesis in certain human cancers.

Calmodulin increases in selective brain regions with opioid dependence.

Acute challenge of thalamic membranes with opioid agonists displaces calcium and prevents isoproterenol stimulation of adenylate cyclase. Chronic morphine administration for three days or three weeks results in significant increases in the level of calmodulin in membranes of thalamus, but not in periaqueductal gray, striatum, amygdala or hypothalamus.