Modulation of serum eosinophil cationic protein levels by cyclosporin in severe atopic dermatitis.
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Adolescent↗
Biomedical subjects
G Cappelli
Publications and source records attributed to G Cappelli.
No direct evidence of increased lipid peroxidation in hemodialysis patients.
Lipid peroxidation, as measured by the thiobarbituric acid test, has been reported to have increased in hemodialysis (HD) patients, even though the test has low specificity in vivo. Conjugated diene fatty acid (CDFA) hydroperoxides are formed during lipid peroxidation, but not all conjugated dienes (CD) detected in humans originate from lipid peroxidation: octadeca-9,11-dienoic acid, a nonhydroperoxide CD derivative of linoleic acid (CDLA), has a dietary origin. We evaluated CDFA hydroperoxides, CDLA and linoleic acid, using high-performance liquid chromatography, in lipids extracted from plasma, adipose tissue and RBC membranes obtained from 25 patients treated with HD, 16 patients treated with hemodiafiltration (HDF) and 29 controls. No differences in the levels of CDFA hydroperoxides and linoleic acid were seen in any of the groups. Concentrations of CDLA were found to be significantly high in the adipose tissue and low in the RBC membranes of HD patients. HDF-treated patients showed the same results as HD patients. No direct evidence of increased lipid peroxidation was found in HD patients. This does not exclude the possibility that lipid peroxidation is increased and escapes direct detection due to the body's homeostatic control eliminating the increased production of hydroperoxides. Both HD- and HDF-treated patients showed a significant change in CDLA concentrations, either in the adipose tissue, or in the RBC membranes. These dietary CD may be mistaken for markers of lipid peroxidation by conventional methodologies.
Adipose Tissue↗
Tumor markers in breast cancer follow-up: a potentially useful parameter still awaiting definitive assessment. Forza Operativa Nazionale sul Carcinoma Mammario (FONCaM).
BACKGROUND: Although tumor markers are frequently used in the follow-up of patients with breast cancer, two points are still being debated: 1) their cost/effectiveness has been neither demonstrated nor disproved; 2) the reliability of the currently used dichotomous division into a positive/negative cut-off should be definitely validated. Dynamic criteria of interpretation based on serial serum samples would probably be more effective for early detection of relapse. PATIENTS AND METHODS: The aim of the present study was to compare the dichotomous cut-off based decision criteria to a dynamic serial sample based assessment of tumor markers. Since 1989, 794 patients have been followed in 11 institutions. CEA and CA15.3 were measured once a month for three months before every clinical examination. The present paper concerns the evaluation variability in 405 patients without evidence of disease in the first three institutions joining the study. RESULTS: In patients without evidence of disease, the coefficient of variation of all samples for every patient showed a median value of 19 for CEA and 21 for CA15.3. Variability was negatively associated with the antigen level and was most likely due to the analytical component. This was also confirmed by the significant difference in variability among the three institutions evaluated. The median value of the critical difference was 53% for CEA and 57% for CA15.3. CONCLUSIONS: 1) Individually tailored dynamic decision criteria are applicable in about 50% of the cases. 2) The problem of improving the precision of tumor marker assays in the low dose range must be urgently addressed to the manufacturers of tumor markers by the scientific community in order to apply individually tailored decision criteria for patients in whom the serum level of biological markers is low.
Biomarkers, Tumor↗
Serum eosinophil cationic protein (ECP) in bullous pemphigoid.
BACKGROUND: The importance of eosinophils in the pathogenesis of the major forms of pemphigoid (bullous pemphigoid, cicatricial pemphigoid, herpes gestationis) remains to be confirmed. METHODS: To evaluate the role of eosinophilic infiltrates in these diseases and to detect the presence and activity of eosinophils, we compared the serum levels of eosinophil cationic protein (ECP), an eosinophil-derived protein, in 11 healthy subjects and in 10 patients with pemphigoid diseases (8 with bullous pemphigoid, one with cicatricial pemphigoid, and one with herpes gestationis). The serum of two patients with epidermolysis bullosa acquisita (EBA) and one with linear IgA bullous dermatosis (LABD) were utilized as a further control. RESULTS: There was a significant difference between the mean of serum ECP levels in patients with pemphigoid diseases (25.1 +/- 12.3 micrograms/L, M = SD) and control subjects (2.30 +/- 2.41, micrograms/L +/- SD 2.41) (T = 4.272 P < 0.0001). The two patients with EBA (10.8 and 17.7 micrograms/L) showed contrasting results; the patient with LABD had normal ECP serum levels. The serum levels of ECP were not significantly correlated with the blood eosinophil count (R = 0.103; P = 0.777) in any of the cases. CONCLUSIONS: In pemphigoid disease, the serum levels of ECP seem to be correlated with the activated secreting and tissue-damaging eosinophils found in the dermis, supporting the concept of an active participation of eosinophils in generating cutaneous lesions.
Adult↗
Leaching and corrosion of polyvinyl chloride (PVC) tubes in a dialysis water distribution system.
PVC tubes, from the dialysis water distribution system of a 14 and a 7 year old plant, were analysed by scanner electron microscopy (SEM) and X-ray microanalysis (EDAX). Results showed that the leaching of material occurs depending on time of use. The phenomenon does not modify the chemical composition of the material. Results suggest that PVC alterations, induced by time, could support bacterial proliferation thus reducing the quality of dialysate.
Corrosion↗
Amniotic fluid levels of CA 19.9 and CA 15.3 in normal and Down's syndrome pregnancies.
CA 125, CA 19.9 and CA 15.3 are antigenic determinants on glycoproteins commonly used as serum markers in gynecologic oncology. CA 125 was also investigated in the amniotic compartment of Down's syndrome pregnancies. The objective of this study was to evaluate the concentration of CA 19.9 and CA 15.3 in the amniotic fluid of normal and Down pregnancies. The concentration of these antigens was measured in stored amniotic fluid samples from 15-19 weeks pregnancies with and without Down's syndrome fetuses and expressed in multiples of the median for normal pregnancies of the same gestational age. The study group included 20 samples selected from single Down's syndrome pregnancies. Each of these samples were matched with three control samples from unaffected pregnancies, matched for maternal age, gestational age and duration of storage of the sample. The median MoM values of CA 19.9 and CA 15.3 in Down's syndrome pregnancies were respectively 1.11 MoM and 1.16 MoM, not significantly different from those of unaffected pregnancies (CA 19.9: 1.02 MoM; CA 15.3: 0.99 MoM). In the present study we have not found significantly different levels of CA 19.9 and CA 15.3 in the amniotic fluid of fetuses affected by Down's syndrome and in the controls.
Amniotic Fluid↗
How alternative are immunoassay systems employing non-radioisotopic labels? A comparative appraisal of their main analytical characteristics.
The immunoassay is one of the most sensitive and reliable analytical techniques available in the clinical laboratory. The original label for immunoassays was radioisotopes, and these methods, radioimmunoassay (RIA) and immunoradiometric assay (IRMA) are still the reference methods, because of invulnerability of the radioactive emission with respect to environmental interference. Labels other than radioisotopes have been tested for use in immunoassay to improve the sensitivity and reliability and to avoid some of the disadvantages of radioisotopic techniques. New labels have continued to be developed (Horseradish peroxidase-HPR-, pyrophosphatase, luciferases, pyrodopirazines, europium cryptates, porphirins, phosphors) and new label detection methods have been set up (e.g. chemiluminescence assay, thermometric assay, NADP+ and FADP- based coupled assay). New immunoassay strategies such as simultaneous multianalyte automated test have been developed and the reliability of the assays has in some cases caused division among researchers about the choice between the radioisotopic immunoassay or the non-radioisotopic immunoassay, as considerable effort and investment had been devoted to the search for more sensitive and practicable tests than the classic RIA-IRMA methods. The evolution of immunoassays (Monoclonal Antibodies, non-radioactive tracers, automation) has produced systems which allow a large number of laboratories to determine a great number of analytes with very good practicability. The availability of fully automated systems has generated the opinion that analytical performance of immunoassays can be considered similar to that of many traditional parameters of clinical chemistry. This conclusion seems however too optimistic, in fact data collected from interlaboratory studies demonstrate that problems concerning the analytical reliability of the measurements still remain not completely solved. In the authors' opinion, this opposition between immunological assay based on isotopic or non-isotopic labels is misleading, because each assay (whether it uses isotopic, enzymatic, fluorimetric or luminescent labels) has its own analytical characteristics and performance. For this reason the term "alternative", used to indicate all non-isotopic assays as a unique class of tests, should be abandoned. From a theoretical point of view the choice should not be between isotopic and non isotopic techniques. For each analyte to be tested, it is advisable to use the immunological assay that suits the requirements of the laboratory, irrespective of type of label. From a practical point of view, the choice should be based on the analytical performance and on the characteristics of each assay, on its cost and the type of instrumentation available in the laboratory, and on the experience and the knowledge of the laboratory personnel.
Costs and Cost Analysis↗
Selective expansion of cytotoxic T lymphocytes with a CD4+CD56+ surface phenotype and a T helper type 1 profile of cytokine secretion in the liver of patients chronically infected with Hepatitis B virus.
Highly purified CD4+ T cells isolated from liver biopsies of patients with hepatitis B virus-induced CAH had a strong cytotoxic activity and were comprised of a substantial number of cells (25%-40%) expressing CD56 surface marker. These cells were absent in CD4+ T cells from the peripheral blood of CAH patients or normal controls and these suspensions did not have cytotoxic activity. CD4+CD56+ T cells were further characterized by studies at the clonal level. A total of 71 hepatitis B envelope antigen-specific CD4+ T cell clones was investigated (23 from liver biopsies, 48 from peripheral blood of patients or normal vaccinated individuals). A total of 16 out of 23 (69.5%) of the clones from liver biopsies, but only 4.1% (2 out of 48) of those from PBLs, expressed CD56. A clone was defined as CD56+ when 40% or more of the cells expressed the marker. Production of TNF-alpha, IL-4, IL-5, IL-2, and IFN-gamma was investigated in 15 CD4+CD56+ and in 18 CD4+CD56- T cell clones, which shared the same HLA restriction element (DR2w15) and the same fine specificity (peptide 193-207 of the S region). All of the clones from the two groups released TNF-alpha and IL-2. However, all of the CD4+CD56+ T cell clones produced IFN-gamma but not IL-4 and IL-5 (Th1-like cell clones). Fourteen of the CD4+CD56- clones released IFN-gamma, IL-4, and IL-5 (Th0-like cell clones); three produced IL-4 and IL-5 but not IFN-gamma (Th2-like cell clones); and only one had a Th1 cytokine secretion profile. Cell fractionating studies within single CD4+CD56+ T cell clones showed that cells expressing high density CD56 had a stronger cytotoxic activity and produced higher levels of IFN-gamma than cells with low density CD56, thus further supporting a correlation between CD56 expression and cell functions. The results indicate that: 1) in CAH patients, cytotoxic CD4+ T cells with a Th1 cytokine secretion profile are compartmentalized in the liver, 2) these cells may be identified by the expression of CD56, 3) the expansion of these cells may be facilitated by antigenic stimulation within the inflammatory environment of the liver, and 4) CD4+CD56+ cells may play a pathogenetic role in hepatitis B virus infection.
Adult↗
Mathematical model application to the kinetic study of tumor markers.
In order to overcome the inefficient cutoff criterion in the management of neoplastic patients after therapy, in follow-up, in recurrence and in monitoring treatment, we have analysed some mathematical models to evaluate serial determinations of tumor markers, with the aim to ascertain the radicality of surgery or the presence of recurrences. Since a tracer study of the biological system of tumor markers is impossible, some information, such as rate factor and half-life, is obtained by determination of the marker after radical treatment. In steady state with two or more samples in time it is possible with adequate statistical models to establish a significant increase in the marker. In recurrence, if it is true that the secretion rate of the marker by a tumor is proportional to tumor mass, then increasing concentrations of the tumor marker would be a phenotypic expression of tumor growth. Therefore some mathematical models are proposed to evaluate the kinetics of tumor growth.
Biomarkers, Tumor↗
On line filtration of dialysate: structural and functional features of an asymmetric polysulfone hollow fiber ultrafilter (Diaclean).
The endotoxin transfer across dialysis membranes has been investigated using specific in vitro circuits. Backdiffusion and backfiltration have been analyzed and most dialysis membranes have shown to be permeable to LAL positive substances. Synthetic membranes however display the better capacity of retention of these products despite their higher porosity and permeability. For such reason synthetic polysulfone ultrafilters are used as pyrogen filters to obtain ultrapure dialysate. We have investigated the characteristics of a polysulfone ultrafilter named Diaclean and manufactured by Amicon Ireland. The capacity of endotoxin retention has been investigated both in filtration and backfiltration modes on new and used ultrafilters. The capacity of endotoxin adsorption was investigated as well. Used ultrafilters appeared to maintain the retention capacity and the adsorption capacity up to 4 months of use. Only slight differences were noted from the baseline values (p = n.s.). The best adsorption capacity is always displayed by the outer layer of the membrane suggesting its best utilization in back filtration mode with tangential flow. No morphological changes were observed in the used membrane analyzed by scanning electron microscopy.
Diffusion↗
Effects of low-dose captopril on renal hemodynamics and function in patients with cirrhosis of the liver.
BACKGROUND: In cirrhotic patients with ascites, captopril has deleterious effects on renal function, which have been referred to as captopril-induced arterial hypotension. The effects of this drug on renal function in cirrhosis were evaluated using low-dose captopril, thereby avoiding any change in arterial pressure. METHODS: In a randomized, double-blind, placebo controlled, cross-over trial, the effects of 12.5 mg captopril on renal plasma flow, glomerular filtration rate (measured by radioisotopic techniques), and sodium excretion in healthy controls and cirrhotic patients with and without ascites were determined. RESULTS: In healthy subjects, captopril only induced a significant, 18% increase in renal plasma flow. In contrast, glomerular filtration rate significantly decreased in patients with (from 108 +/- 7 to 78 +/- 9 mL/min) and without ascites (from 102 +/- 4 to 88 +/- 3 mL/min), whereas renal plasma flow did not change. Urinary sodium excretion also significantly decreased in ascitic patients (from 43.8 +/- 4.4 to 30.6 +/- 3.8 mumol/min). CONCLUSIONS: These data suggest that angiotensin II contributes to maintain renal hemodynamics in cirrhosis with and without ascites.
Aged↗
Conjugated diene fatty acids in patients with chronic renal failure: evidence of increased lipid peroxidation?
Conjugated diene fatty acids (CDFA) were evaluated by second derivative spectrophotometry in the plasma and adipose tissue of 42 chronic renal failure (CFR) patients in conservative treatment, 40 patients treated by hemodialysis (HD) with cuprophane, cellulose acetate or hemophan, 29 treated by hemodiafiltration (HDF) with polysulfone, polyacrylonitrile or polyamide, and 28 healthy controls. Plasma CDFA were also evaluated at the beginning, at 30 min and at the end of the dialytic session. CDFA were unchanged in CRF patients with creatinine clearance (Ccr) > 10 ml/min respect to the controls, CRF patients with Ccr < 10 ml/min showed a higher level of CDFA both in plasma and adipose tissue (p < 0.02). HD patients showed values similar to those of the control group. The lowest level of CDFA was found in HDF patients (p < 0.01 for plasma, p < 0.05 for adipose tissue versus both control and any other group). A significant relationship between plasma and adipose tissue CDFA was found in all groups. In the group of CRF patients with Ccr < 10 ml/min, females exhibited a higher level of CDFA both in plasma and adipose tissue. No significant change was found during dialytic session, independently from the membrane used. CDFA are not only primary products of lipid peroxidation, but also have a dietary origin, primarily from dairy products. Taking into account the reduced dietary intake, the increase in end-stage CRF may be due to an enhanced oxidative stress and/or to abnormalities in CDFA metabolism. Uremic patients, particularly in the predialytic stage, should be considered at risk for increased oxidative stress. HDF treatment better corrects the abnormality compared to conventional HD.
Adipose Tissue↗
Variability of tumor markers in the follow-up of patients radically resected for breast cancer.
The biological and analytical components of variability of tumor markers should be distinguished from the variations due to tumor progression. The aim of the present study was to evaluate tumor marker variability in the follow-up of patients resected for breast cancer. So far, we have carried out 2,085 CEA and 2,550 CA 15-3 determinations in 435 patients. The total variability of both CEA and CA 15-3 was widely scattered among different subjects (CEA coefficient of variation 0-105%; CA 15-3 coefficient of variation 0-89.2%). The biological variability of CA 15-3, which was calculated in a limited number of cases, was scattered between 0 and 23% and was higher than the intra-assay variability. From these findings we conclude that when evaluating serial marker assays the intra-individual variability should be assayed initially to obtain a reference value of individual variability in relapse-free conditions.
Analysis of Variance↗
Removal of limulus reactivity and cytokine-inducing capacity from bicarbonate dialysis fluids by ultrafiltration.
Bicarbonate-based dialysate solutions support the rapid growth of bacteria. The long-term (360-h) efficacy of ultrafiltration by two polysulphone ultrafilters in removing not only endotoxin but also the cytokine(IL-1, TNF)-inducing capacity was evaluated using an experimental circuit contaminated with Pseudomonas aeruginosa filtrates. One of the polysulphone ultrafilters was submitted to a standard sanitization procedure every 12 h (hypochlorite 1.2% solution for 5 min and rinsing for 20 min). Endotoxin was detected by the kinetic quantitative chromogenic limulus amoebocyte lysate (LAL) assay. Immunoreactive IL-1 and TNF were evaluated in the lysates of peripheral blood mononuclear cells containing 5 x 10(5) human monocytes. The results of the present studies show that although LAL-reactive bacterial products were significantly removed in post-ultrafilter samples, they remained detectable, albeit below the upper limit accepted by the present European pharmacopeias (< 0.125 EU/ml). The removal of cytokine-inducing capacity was time-dependent and correlated with time of use in the case of the sanitized ultrafilter. Beyond the time of use, two other factors emerged as possibly capable of reducing the efficacy of the ultrafilter in removing LAL-reactive bacterial components, namely the pressure and the cytokine-inducing activity in pre-ultrafilter samples. Preincubation with polymyxin B, an agent that irreversibly binds lipid A and blocks lipid A-induced biological activities, did not abrogate the cytokine-inducing capacity in all post-ultrafilter samples; this suggests that either low-molecular-weight endotoxin subunits or lipid A-unrelated components may be responsible for the residual biological activity in post-ultrafilter samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylmuramyl-Alanyl-Isoglutamine↗
Ultrafiltration and endotoxin removal from dialysis fluids.
Biocompatibility in hemodialysis is now regarded as a multifactorial problem and dialysate represents a main risk. Pyrogenic fractions mostly coming from gram-negative bacteria easily pass through dialysis membrane, either by backdiffusion or by backfiltration, and induce blood cell activation. To demonstrate the long-term efficiency of a 2 m2 polyamide ultrafilter in producing a pyrogen free solution, we used an experimental circuit ultrafiltering for 240 hours (500 ml/min) a bicarbonate dialysate contaminated (5 to 48 EU/ml) by a Pseudomonas aeruginosa filtrate. The efficiency was monitored by LAL-test and IL-1 PBMC so to detect not only lipid A containing endotoxins but also other cytokines inducing bacterial fractions. At the post-ultrafilter sampling port the LAL-test was < 0.005 to 0.034 EU/ml; IL-1 PBMC was below the detection limit (20 pg/ml) being 27 to 63 pg/ml at the pre-ultrafilter level. Polyamide ultrafiltration represents an efficient system to obtain an endotoxin-free dialysate and a single filter works up to 240 hours.
Cells, Cultured↗
Red cell membrane during erythropoietin therapy in hemodialysis and in hemodiafiltration.
This study assessed the effect of recombinant human erythropoietin (r-HuEPO) on red cell membrane behaviour in patients undergoing hemodialysis (HD) and hemodiafiltration (HDF). We studied erythrocyte osmotic fragility (EOF), mechanical fragility (EMF) and deformability (ED) before and after r-HuEPO therapy in patients on conventional dialysis treatment with a cuprophan membrane and in subjects undergoing HDF with a polyacrylonitrile membrane. Non-uremic, non-anemic subjects were enrolled as controls. Red cell membrane defects were more evident in HD than in HDF; r-HuEPO seemed to improve deformability in both groups compared to controls (p less than 0.005) possibly through the great production of red cells during this therapy.
Anemia↗
Acute Fisher's syndrome during the course of chronic uremia: is the hemodialysis implicated in onset and relapses?
An uremic patient, in chronic dialytic treatment, developed a Miller-Fisher's syndrome acutely after a dialysis. Clinical diagnosis was supported by findings of persistent conduction block in upper and lower extremities and by raised proteins in CSF. Contrast-enhanced CT and MRI scans excluded lesions in the brain stem. The course of this illness was characterized by waxing and waning in cranial nerve deficits, in relation with the hemodialytic treatments. We suggest that, when the patient recovered, reversible changes occurred in the nerves, either due to reversibly impaired sodium permeability or to an ischemic process related to the ultrafiltration dialysis.
Acute Disease↗
Improved biocompatibility by modified cellulosic membranes: the case of hemophan.
The rising problem of biocompatibility is encouraging the development of new dialysis membranes, but the high cost of synthetic ones precludes their wide use. The authors compared the biocompatibility of cuprophan (CU), cellulose acetate (CA), and hemophan (HE), evaluating both in vitro and in vivo polymorphonuclear leukocyte (PMN) oxidative metabolism activation by resting chemiluminescence and complement activation by C3a; in vivo PMN counts during dialysis were also performed. The lowest increase in in vitro PMN resting chemiluminescence using HE was + 71.3% with CA, +49.3% with CU, and + 21.4% with HE (p less than 0.001 versus CA and CU); furthermore, HE did not significantly stimulate PMN resting chemiluminescence during in vivo hemodialysis: + 56.6% with CA, + 38.8% with CU, and + 3.7% with HE (p less than 0.01 versus CU and p less than 0.001 versus CA). C3a concentration increased with all membranes both in vitro and in vivo, but HE (in both experimental conditions) showed the lowest increase at any time (p less than 0.001 versus CA and CU). After 15 min of dialysis, PMN count dropped to 20.3% of basal values with CU, to 49.8% with CA, and to 76.5% with HE (p less than 0.001 versus CU and CA). Among cellulosic membranes, HE is the most biocompatible and appears to be an important step in preventing blood-membrane interactions and related complications.
Biocompatible Materials↗