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Biomedical subjects

G Cappelli

Publications and source records attributed to G Cappelli.

At least 55 records · Page 3Linked to original sources

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↗

Polymorphonuclear oxygen free radical production and complement activation induced by dialysis membranes as assayed in an experimental model.

Activation of polymorphonuclear leukocytes with subsequent production of reactive oxygen metabolites has been reported to occur during hemodialysis related to a membrane bioincompatibility. We used an experimental dialysis model to evaluate, by chemiluminescence, the production of reactive oxygen metabolites and, by C3a, complement activation induced by cuprophan, cellulose acetate, hemophan, polysulfone, polyacrylonitrile, polymethylmethacrylate or polyvinyl chloride blood lines alone. No differences were obtained in the system, at time 30 min compared to initial values, as far as zymosan-activated chemiluminescence is concerned; resting chemiluminescence increased markedly with cellulose acetate (+71%), cuprophan (+49%), polymethylmethacrylate (+22%), hemophan (+21%) but had no variation with polysulfone, polyacrylonitrile and blood line. The time course of C3a levels up to 120 min showed a marked rise with cuprophan and cellulose acetate, a moderate increase with hemophan, polysulfone and blood line, and a decrease with polymethylmethacrylate and polyacrylonitrile. The results obtained documented a different behavior of the production of reactive oxygen metabolites compared to complement activation and support the hypothesis that the production of reactive oxygen metabolites by polymorphonuclear leukocytes is stimulated not only by complement activation but also by a direct dialysis membrane interaction.

Biocompatible Materials↗

Oxidative metabolism of polymorphonuclear leukocytes and serum opsonic activity in chronic renal failure.

Luminol-amplified chemiluminescence was used to study the oxidative metabolism of polymorphonuclear leukocytes (PMN), in resting state and in response to opsonized zymosan, in 65 patients with different degrees of chronic renal failure (CRF) or on regular dialysis treatment (RDT). Every patient was compared on the same day with a normal subject. Furthermore, the serum opsonic activity was evaluated, cross-matching zymosan opsonized by serum from CRF-RDT patients and normals with PMN from CRF-RDT patients and normals. PMN resting chemiluminescence showed a progressive increase inversely related to the glomerular filtration rate, and it remained high in patients on RDT. Zymosan-activated chemiluminescence indicated a deficit in phagocytosis for PMN of patients with a glomerular filtration rate lower than 10 ml/min, persisting in RDT patients. The serum opsonic activity was always significantly lower in CRF and in RDT patients than in the control group; this defect was already present in patients with mild renal impairment. Our findings suggest that PMN from CRF or RDT patients have an increased reactive oxygen metabolite production in the resting state that may cause cell and tissue damage; the opsonization impairment and the decreased PMN phagocytic activity contribute to increased vulnerability to infection in these patients.

Humans↗

Radioimmunoassay of gastrin in human saliva.

We have developed a personal procedure for the radioimmunoassay of gastrin (lower detection limit 3 pg/ml). Using 5-fold concentrated lyophilized salivary samples, we are able to detect the basal content of gastrin immunoreactivity in saliva of normal fasting people (mean +/- SD: 1.38 +/- 0.61 pg/ml) compared to plasma gastrin (mean +/- SD: 28.88 +/- 11.00 pg/ml). We found that after meal stimulus, the value of salivary as well as plasma gastrin concentration increased (the correlation coefficient r among salivary and plasma gastrin being 0.899; p less than 0.001). We believe that gastrin appears in a very low concentration in saliva and that it is not produced by the gland, but derives probably from the serum clearance.

Gastrins↗

Acid-base balance during biofiltration (BF).

Acid base balance during biofiltration (BF): Six patients on standard acetate hemodialysis (HD) were switched to BF with 1 m2 AN69-S membrane, 12 hours weekly (BF-4h) and, later on, to a stage with 1.2 m2 AN69-S, 9 hours weekly (BF-3h). During BF, in order not to exceed 25 mEq/l in intradialytic arterial HCO3, arterial acid-base was examined hourly and a mean of 178 and 199 mEq of HCO3 respectively were infused in BF-4h and BF-3h. We obtained a better control of acidosis with a reduction of the intradialytic pCO2 decrease and hypoxemia. The amount of HCO3 infused was related to the patients deficit in HCO3 total pool and therefore it can be predicted, to avoid postdialytic alkalosis.

Acetates↗

Effects of biofiltration versus hemofiltration in the treatment of chronic uremia.

Biofiltration (BF), a new depurative hemo-diafiltration employing a high efficiency membrane (acrylonitrile and metallylsulphonate of sodium) and reinfusion of 8-9 liters of fluid was tested as an alternative method to hemofiltration (HF). Sixteen uremic patients who showed circulatory instabilities during traditional hemodialysis (HD) were treated with HF (27 liters infused in postdilution), or BF (210 min/session) for 12 months. Low and middle molecular weight metabolites weekly clearances, calcium, phosphorus and bicarbonate serum levels in BF and HF showed no significant differences: in BF the incidence of symptomatic hypotension events and orthostatic changes of mean blood pressure were lower than in HD, but a little higher than in HF. Our results show that BF achieves satisfactory depuration of low and middle molecular weight metabolites in a shorter time than HF and an improvement of autonomic nervous system abnormalities is observed.

Acrylic Resins↗

Calcitonin increases peripheral plasma somatostatin-like immunoreactivity levels in humans.

Even though the inhibitory effects of CT on both hormone secretion and gastrointestinal functions have been well established, the exact mechanism of action still remains unclear. Since the effects of CT can be reproduced by somatostatin, we studied in man the effect of SCT on peripheral plasma SLI levels. Immediately after the onset of CT infusion SLI rose from its mean basal value of 45 +/- 5.5 pg/ml to a peak value of 91 +/- 11 pg/ml (p less than 0.005). SLI levels were still significantly elevated at 30 (p less than 0.05), 45 (p less than 0.05), 90 (p less than 0.005) and 120 min (p less than 0.02). Our results, in good agreement with the previous report by Chiba et al. on isolated perfused rat stomach, suggest that CT effects may, at least in part, be mediated by endogenous somatostatin release.

Adult↗

A new case of familial partial generalized resistance to thyroid hormones: study of 3,5,3'-triiodothyronine (T3) binding to lymphocyte and skin fibroblast nuclei and in vivo conversion of thyroxine to T3.

A clinically euthyroid 30-yr-old man with high serum levels of both total (T4, 14.5 micrograms/dl; T3, 272 ng/dl) and free (FT4, 33 pg/ml; FT3, 9.7 pg/ml) thyroid hormones and inappropriately normal TSH levels, both basally and after TRH stimulation, is described. Peripheral indices of thyroid hormone action and the patient's clinical status were not modified by the prolonged administration of supraphysiological doses of both T4 (up to 900 micrograms/day) and T3 (up to 80 micrograms/day), which decreased but did not completely abolish the TSH response to TRH. However, the TSH response to TRH was normally blunted by dexamethasone administration, which also reduced serum T4 and T3 levels to normal. T3 binding to nuclei of mononuclear leukocytes and cultured skin fibroblasts was normal. The overall pattern demonstrates that the patient was affected by partial peripheral resistance to thyroid hormone action. Study of the patient's family revealed the same hormone pattern in the patient's father, suggesting an autosomal dominant mode of inheritance. An in vivo study performed after the iv injection of tracer doses of [125I]T4 and [131I]T3, demonstrated increased production rates (PR) of both T4 [PR, 113.0 micrograms/day X m2; normal subjects, 55.4 +/- 12.3 (mean +/- SD); n = 13] and T3 (PR, 41.1 micrograms/day X m2; normal subjects, 16.3 +/- 2.7). In vivo conversion of T4 to T3 was also evaluated in the patient; a nearly normal T4 to T3 conversion factor was found (0.3108 vs. 0.2576 +/- 0.0422 in normal subjects). In four hyperthyroid patients, the T4 to T3 conversion factors were similar (0.2932 +/- 0.0600), while the PRs of T4 and T3 were increased (PR of T4, 308.6 +/- 85.6; PR of T3, 110.3 +/- 35.0 micrograms/day X m2) compared to those in the normal subjects.

Adult↗