Cardiopulmonary bypass increases permeability of the blood-cerebrospinal fluid barrier.

BACKGROUND: The integrity of the blood-cerebrospinal fluid (CSF) barrier during cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) has not been systematically studied, especially in children. We tested the hypothesis that the blood-CSF barrier is disrupted by CPB. METHODS: The study randomized 25 piglets (mean weight, 11 kg) to five groups (5 per group): anesthesia alone (control); CPB at 37 degrees C with full-flow (FF); CPB at 25 degrees C with very low flow (LF); and HCA at 15 degrees C and 25 degrees C. pH-stat strategy was applied during CPB. An epidural catheter was inserted into the cisterna magna for collection of CSF. CSF and blood samples were collected at seven points: after induction of anesthesia (baseline), at 10, 50 and 115 minutes after start of CPB, just before the end of CPB, and at 30 and 120 minutes after CPB. Albumin levels in CSF and plasma were measured to assess blood-CSF barrier integrity and the albumin ratio (CSF/plasma) was calculated (Q(Alb)). RESULTS: In both HCA groups, the Q(Alb) was significantly higher than in the control and 37 degrees C FF groups (all p < 0.05), whereas Q(Alb) in the 37 degrees C group was not significantly different vs control. CONCLUSIONS: The blood-CSF barrier is impaired by CPB with 1 hour of 15 degrees C or 25 degrees C HCA. Further investigations are needed to understand the behavior of the blood-CSF barrier during CPB and its role in neuroprotection.

Correlation between cystatin C- and renal scan-determined glomerular filtration rate in children with spina bifida.

We report on the relationships between serum cystatin C level, glomerular filtration rate (GFR) estimated from a cystatin C-based prediction equation (that of Filler and Lepage), GFR calculated by the Schwartz formula and technetium 99m-diethylene triamine penta-acetic acid ((99)Tc-DTPA)-determined GFR in 28 children with spina bifida. All children underwent measurement of height, weight, serum cystatin C level, and serum creatinine level at the time of their renal scan. The relationship between variables was assessed by Pearson correlation. Pearson correlation for the relationship between (99)Tc-DTPA GFR and GFR calculated by the cystatin C-based equation was significant and higher than that of the relationship between (99)Tc-DTPA GFR and GFR calculated by the Schwartz equation, which was not statistically significant. The correlation for Filler GFR was 0.42 (P = 0.03) and for Schwartz GFR was 0.21 (P = 0.28). Although we use renal scan determination of GFR as the best measure, and a creatinine-based formula as the most practical measure, perhaps a formula such as that published by Filler and Lepage, which is not dependent on anthropometric data, might be a more useful (and accurate) tool for establishing GFR in children with spina bifida.

[Interest of cystatin C for individual dosing of anticancer drugs cleared by the kidneys]. / Intérêt de la cystatine C pour l'adaptation de posologie des médicaments anticancéreux à élimination rénale.

Cystatin C is a protein freely filtered in the renal glomerulus, then reabsorbed and completely metabolised within the tubular cells. The possibility to predict the clearance of compounds eliminated by the kidneys (and then to control their interindividual variability) was evaluated for two cytotoxic drugs (carboplatin and topotecan) in adults and EDTA (ethylene diamine tetraacetic acid), a compound used to determine the glomerular filtration rate in children. The population pharmacokinetic approach based on NONMEM program was used. For each of the three compounds, the cystatin C serum level was better predictive of clearance than that of creatinine. Moreover, for carboplatin and EDTA, the best equation between clearance and patients' characteristics included both cystatin C and creatinine level. A generalisation of cystatin C assay would contribute to standardise the clinical practices in Oncology.

High resolution protein electrophoresis of 100 paired canine cerebrospinal fluid and serum.

This study was performed to investigate the diagnostic relevance of cerebrospinal fluid (CSF) high resolution electrophoresis. The laboratory technique was applied to 100 paired samples of canine CSF and serum, with paired samples tested during the same analytical run, as recommended in human medicine. Ninety four of the dogs had a neurological disease and 6 healthy dogs served as a control group. A strong linear correlation between CSF total protein concentration and the albumin quota (AQ) was found in the control group and in the inflammatory (infectious or noninfectious), neoplastic, and miscellaneous groups: AQ = 0.015 CSF total protein--0.102, r = 0.990. This correlation suggests that an increased CSF total protein concentration can be an indicator of blood brain barrier dysfunction. The highest median AQ value was found in the aseptic suppurative meningitis group, but no statistical differences were found between this and the other groups. The AQ, calculated with this technique, did not provide any additional information. Moreover, although unexpected, the electrophoretic profiles were not characteristic of any particular disease. In conclusion, this study did not confirm high resolution electrophoresis of paired CSF and serum samples to be a valuable ancillary diagnostic tool for canine neurological diseases.

Cystatin C and the risk of death and cardiovascular events among elderly persons.

BACKGROUND: Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community. METHODS: Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c). RESULTS: Higher cystatin C levels were directly associated, in a dose-response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66); quintile 5a, 1.77 (1.34 to 2.26); 5b, 2.18 (1.72 to 2.78); and 5c, 2.58 (2.03 to 3.27). In contrast, the association of creatinine categories with mortality from all causes appeared to be J-shaped. As compared with the two lowest quintiles combined (cystatin C level, < or =0.99 mg per liter), the highest quintile of cystatin C (> or =1.29 mg per liter) was associated with a significantly elevated risk of death from cardiovascular causes (hazard ratio, 2.27 [1.73 to 2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]), and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariate adjustment. The fifth quintile of creatinine, as compared with the first quintile, was not independently associated with any of these three outcomes. CONCLUSIONS: Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.

Comparison of cystatin C, creatinine and creatinine clearance vs. GFR for detection of renal failure in renal transplant patients.

BACKGROUND: Serum cystatin C (Scyst) has been suggested as an alternative index of glomerular filtration rate (GFR) and could be useful in renal transplant patients. METHODS: In a 60-subject cohort (40 +/- 12 years old), we compared the simultaneous measurements of Scyst, serum creatinine (Screat), creatinine clearance (Ccreat), Cockcroft and Gault's estimated clearance (Ccg) and GFR measured using inulin clearance (Cin). Receiver operating characteristic (ROC) analysis was performed using two Cin cut-off (60 and 90 mL/min/1.73 m2). RESULTS: A significant correlation was found among Cin on one hand and 1/Scyst, Ccreat, 1/Screat and Ccg on the other hand. Best fits (sensitivity/specificity) at 90 mL/min/1.73 m2 were 1.18 mg/L (0.72/0.80) for Scyst, 1.32 mg/dL (0.67/0.90) for Screat, 77 mL/min (0.80/0.70) for Ccg and 104 mL/min (0.88/0.80) for Ccreat. The areas under the ROC curves were not significantly different. CONCLUSIONS: This study provides cut-off values for Screat and Ccg for detection of renal failure in renal transplant patients. However, the results also suggest that Scyst is not a more sensitive marker than Screat or Ccg for detecting renal failure in renal transplant patients.

Serum and cerebrospinal fluid cystatin C levels in vascular and Alzheimer's dementia.

INTRODUCTION: Cystatin C, a cysteine protease inhibitor, has been implicated in the neurodegenerative and repair processes of the nervous system, and the deposition of the same protein together with beta amyloid peptide was found as cerebral amyloid angiopathy (CAA) in different types of dementias. OBJECTIVE AND METHODS: Because of the differential diagnostic importance, serum and cerebrospinal fluid (CSF) cystatin C levels of 24 late onset Alzheimer's demented (AD) and 16 ischemic type of vascular demented (VD) probands were compared with 17 aged control (AC) persons. RESULTS: The serum and CSF cystatin levels were found in the normal range in all groups. The ischemic VD probands had the tendency to have higher cystatin C levels than the AD. No correlation has been found with the severity and duration of dementia and with the other measured parameters. CONCLUSION: These results indicate that lower than normal CSF cystatin C level is not a diagnostic marker in ischemic VD and CAA related to AD.

Cystatin C in paediatric nephrology. Present situation and prospects.

Cystatin C is a small basic protein with a MW of 13,359 Daltons, consisting of a non-glycosylated polypeptide chain containing 120 amino-acid residues. Cystatin C is produced in all the nucleated cells of the human body and its output rate is constant. The kidney is the main catabolic site of cystatin C, since the protein, by virtue of its low MW and its positive charge at normal pH, is freely filtered by the glomerulus and almost completely reabsorbed, catabolised and broken down in the cells of the proximal convoluted tubule. It is practically entirely filtered via the glomerular membrane, without any significant tubular secretion. The constant production rate of cystatin C in all the tissues, its elimination via the glomerular filter and its non-dependence on many extrinsic factors, including sex, age, diet, inflammation, are potentially ideal conditions for an endogenous biochemical marker of glomerular filtration. A recent method for determining cystatin C, is based on an immune reaction, could increase its clinical application. Not many studies have been conducted to date on cystatin C in children. The cystatin C concentration was higher during the first few days of life (range: 1.64-2.59 mg/L) with a rapid reduction during the first 4 months. Beyond the first year of life, cystatin C concentration became constant, with a reference range of 0.7-1.38 mg/L. On the basis of the data currently available, neonatal serum cystatin C would appear to derive from the newborn itself. In fact no correlations were found between maternal and neonatal serum cystatin C values. Cystatin C determination appears to be at least equivalent to serum creatinine measurement for the assessment of glomerular filtration rate in children. Further extended studies are needed to investigate these aspects more thoroughly in neonates.

Inverse correlation between disappearance of intrathecally injected 111In-DTPA from CSF with CSF protein content and CSF-to-serum albumin ratio.

By means of cerebrospinal fluid (CSF) scintigraphy with 111In-DTPA injected following lumbar puncture in 18 patients after meningitis (12), with traumatic head injury (4), cholesteatoma (1) or a communicating hydrocephalus (1) the hypothesis of whether slow movement of CSF may contribute to the elevation of CSF protein and albumin content in neurological diseases other than spinal block was tested. The ratios of the count rates over the head (geometric mean of anterior and posterior view) at 23-25 h to 4-6 h after 111In-DTPA application (C24 h/C5 h) and the ratio 47-49 h to 23-25 h after injection (C48 h/24 h) were taken as measures of the velocity of 111In-DTPA disappearance from CSF. Both the CSF protein content and the CSF-to-serum albumin ratio correlated with C24 h/C5 h and C48 h/C24 h. Assuming log-linear elimination between 24 and 48 h the elimination half-life of 111In-DTPA was estimated to be 12.4-131.1 h (median = 31.7 h). It was concluded that slow CSF kinetics probably are involved in the elevation of CSF protein content in several neurological diseases.

Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system.

Gamma-Trace was purified in large amounts from urine and used for the production of a specific rabbit antiserum. An enzyme immunoassay for quantitation of gamma-trace was developed using the pure protein as a primary standard. Its sensitivity was approximately 30 microgram/l. An enzyme amplified single radial immunodiffusion was developed as well. Its sensitivity was approximately 0.3 mg/l. These assays allowed quantitation of gamma-trace in normal human biological fluids. The following results were obtained (mean +/- SD): cerebrospinal fluid: 5.8 +/- 2.2 mg/l, plasma: 1.1 +/- 0.42 mg/l, saliva: 1.8 +/- 0.88 mg/l and urine: 0.095 +/- 0.057 mg/l. Plasma samples from patients with advanced renal failure revealed gamma-trace values up to 13 times the normal mean plasma value. The results indicate a production of gamma-trace in the central nervous system and that the protein is primarily catabolized by the kidney.