Colony-Stimulating Factor-1: A Potential Biomarker for Lupus Nephritis

A noninvasive means to predict the onset and recurrence of lupus nephritis (LN) before overt renal injury is needed to optimize and individualize treatment. Colony-stimulating factor-1 (CSF-1) is expressed by kidney tubules at the onset of LN, increases with disease progression, and spills into the circulation in lupus-prone mice. We tested the hypothesis that amplified expression of CSF-1 detected in the serum or urine correlates with intrarenal CSF-1 expression and histopathology (increased macrophage accumulation, activity indices) and clinical kidney disease activity and predicts the onset and recurrence of nephritis in patients with systemic lupus erythematosus (SLE). We found increased serum or urine CSF-1 levels in patients with cutaneous, serositis, and musculoskeletal disease; however, the increase in CSF-1 levels was far greater in LN. Moreover, an elevation in serum or urine CSF-1 levels correlated with increasing intrarenal CSF-1 expression and histopathology. By longitudinally tracking patients, we found that elevated serum CSF-1 heralded the initial onset of disease, and a rise in serum or urine CSF-1 predicted recurrences of LN before clinical evidence of glomerular dysfunction and conventional serologic measures, even in patients with other manifestations of SLE. These findings indicate that serial monitoring for a rise in serum or urine CSF-1 levels in patients with SLE reflects kidney histopathology and may predict renal disease activity and the onset and recurrence of LN more accurately than conventional laboratory measures.     

Donor sepsis is not a contraindication to cadaveric organ donation

Systemic donor infection is regarded as being an absolute contraindication to cadaveric organ donation for transplantation. This is largely due to fear of transmitting pathogenic organisms to the immunosuppressed recipient. However, due to the current shortage of organs available for transplantation, clinicians are faced with the option of using organs from 'non-ideal' donors, such as those patients with documented evidence of infection. We report the successful outcome of six orthotopic liver transplants, 11 renal transplants, one combined heart lung transplant and one simultaneous kidney and pancreas transplant with organs from eight donors in whom bacterial meningitis (n = 7) and acute bacterial epiglottitis (n = 1) were the antecedent causes of death.      

Serum selenium and serum lipids in US adults

BACKGROUND: Selenium, an essential micronutrient, has received considerable attention for its antioxidant properties. In addition, selenium may affect several cardiometabolic risk factors, such as glucose homeostasis and lipid concentrations. However, the effects of selenium intake on the lipid profile in selenium-replete populations, such as the United States, are largely unknown. OBJECTIVE: We examined the relation of serum selenium concentrations with serum lipids in a representative sample of US adults. DESIGN: This was a cross-sectional analysis of 5452 men and women aged >/= 20 y participating in the third National Health and Nutrition Examination survey. Serum selenium was measured by atomic absorption spectrometry. RESULTS: The multivariable adjusted differences in total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I) comparing the highest with the lowest quartile of serum selenium were 16.6 mg/dL (95% CI: 11.6, 21.4 mg/dL), 10.9 mg/dL (95% CI: 6.4, 15.4 mg/dL), 3.2 mg/dL (95% CI: 1.6, 5.0 mg/dL), 8.9 mg/dL (95% CI: 5.6, 12.2 mg/dL), and 6.9 mg/dL (95% CI: 1.7, 12.1 mg/dL), respectively. Participants in the highest quartile of serum selenium had 10% higher concentrations of triacylglycerols than did participants in the lowest quartile (ratio of triacylglycerol concentrations: 1.10; 95% CI: 1.05, 1.17). The difference in the ratios of LDL cholesterol to HDL cholesterol and apo B to apo A-I that compared the highest with the lowest selenium quartiles were 0.11 (95% CI: -0.02, 0.25) and 0.03 (95% CI: 0.00, 0.06), respectively. CONCLUSION: Elevated serum selenium was associated with elevated serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, apo B, and apo A-I among US adults, a selenium-replete population. Experimental studies are needed to determine cause and effect relations and the potential mechanisms underlying these associations.     

Improving outpatient treatment in schizophrenia: effects of computerized guideline implementation—results of a multicenter-study within the German Research Network on Schizophrenia

Schizophrenia clinical practice guidelines are developed to provide expert- and evidence-based advice to practicing psychiatrists in order to improve the management of this disorder. However, the application of these guidelines in everyday health care can still be described as nonsatisfying. Within the project “Guideline-supported quality management in outpatient treatment”, we investigated whether guideline adherence and quality of outcome can be improved by implementing a computer-based, guideline-oriented decision-support system. Therefore, a disease-specific decision-support system was developed interactively presenting guidelines to support the physicians decision-making process during the treatment of schizophrenia patients. We evaluated the system in a control group design: An experimental group consisting of 15 psychiatrists in private practice used the decision-support system, thus documenting the treatment of schizophrenic patients. Guideline-based algorithms were interactively and case specifically displayed on the PC-screen as soon as predefined triggers were met. A first control group in Munich provided treatment-as-usual, documenting the treatment via paper–pencil. Two further physician groups served as additional comparison groups: one also documented electronically using the decision-support system, however without receiving electronic guideline support, the second group carried out traditional quality circles while also using the paper–pencil approach. As a result of the intervention, we observed a strong initial but time-limited improvement with respect to the core aspects of outpatient treatment in schizophrenia in the experimental group. The findings suggest that decision-support systems, despite their limitations, can be used to enhance treatment outcome in schizophrenia outpatient care.     

Lipopolysaccharide-Activated Macrophages Stimulate the Synthesis of Collagen Type I and C-Fibronectin in Cultured Pancreatic Stellate Cells

We have recently identified and characterized pancreatic stellate cells (PSC) in rats and humans (Gastroenterology 1998, 15:421-435). PSC are suggested to represent the main cellular source of extracellular matrix in chronic pancreatitis. Now we describe a paracrine stimulatory loop between human macrophages and PSC (rat and human) that results in an increased extracellular matrix synthesis. Native and transiently acidified supernatants of cultured macrophages were added to cultured PSC in the presence of 0.1% fetal calf serum. Native supernatants of lipopolysaccharide-activated macrophages stimulated the synthesis of collagen type I 1.38 +/- 0.09-fold of control and c-fibronectin 1.89 +/- 0.18-fold of control. Transiently acidified supernatants stimulated collagen type I and c-fibronectin 2.10 +/- 0.2-fold and 2.80 +/- 0.05-fold of control, respectively. Northern blot demonstrated an increased expression of the collagen-I-(alpha-1)-mRNA and fibronectin-mRNA in PSC 10 hours after addition of the acidified macrophage supernatants. Cell proliferation measured by bromodeoxyuridine incorporation was not influenced by the macrophage supernatants. Unstimulated macrophages released 1.97 pg TGFbeta1/microgram of DNA over 24 hours and lipopolysaccharide-activated macrophages released 6.61pg TGFbeta1/microgram of DNA over 24 hours. These data together with the results that, in particular, transiently acidified macrophage supernatants increased matrix synthesis, identify TGFbeta as the responsible mediator. In conclusion, our data demonstrate a paracrine stimulation of matrix synthesis of pancreatic stellate cells via TGFbeta1 released by activated macrophages. We suggest that macrophages might play a pivotal role in the development of pancreas fibrosis.     

Budd-Chiari syndrome in a premature infant receiving total parenteral nutrition

A premature infant who developed Budd-Chiari syndrome as a complication of total parenteral nutrition through an inferior vena cava catheter is presented. A novel approach to the treatment of this otherwise lethal condition is described. This very unusual complication in pediatric patients may be seen with increased frequency as more premature infants are treated with central vein total parenteral nutrition.