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Biomedical subjects

M Plebani

Publications and source records attributed to M Plebani.

At least 199 records · Page 11Linked to original sources

Human natriuretic factor in cirrhotic patients undergoing orthotopic liver transplantation.

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P < 0.05). Concurrently, an increase in CVP (P < 0.05) and a decrease in SVRI were observed without any significant increase in diuresis. These data suggest that ANF might play a role in the development of the reperfusion syndrome.

Adult↗

Influence of Helicobacter pylori on tryptase and cathepsin D in peptic ulcer.

We here ascertain whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (CD, a lysosomal hydrolase that seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori (Hp) infection. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer, and 11 with duodenitis. Tryptase and CD were measured in mucosal biopsies (body and antrum of the stomach and duodenum) using IRMA methods. Hp infection was histologically evaluated (Giemsa). Tryptase and CD levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. In Hp-positive patients the CD mucosal content was higher while tryptase mucosal levels were lower than in Hp-negative patients. Tryptase was correlated with gastrin content. CD seems to be mainly related to the phlogistic reaction of the mucosa to Hp infection; tryptase may reflect an indirect link between Hp infection, gastrin release, and the function of mast cells.

Adult↗

Gastrin stimulates gastric mast cells in rabbits.

In a previous study we demonstrated that in human gastric mucosa tryptase was localized only in mast cells and that its levels were correlated with serum gastrin, suggesting a link between gastrin action and mucosal mast cell function. The aim of the present study was to discover whether pentagastrin injection could stimulate gastric mucosal mast cells in rabbits. Ten female rabbits (group S) were injected s.c. with pentagastrin (10 mu g/kg); another group of ten animals (group C) was injected s.c. with an equal volume of saline solution. One hour after the injection the rabbits were sacrificed and their stomachs removed. Antrum (A), corpus (C) and fundus (F) mucosal homogenates were assayed for total protein, tryptase, pepsinogen A (PGA), histamine and gastrin. Histamine tissue levels were significantly lower in group S than in group C in the antrum (Mann-Whitney test: U = 82, P < 0.01) and in the corpus (U = 83, P < 0.005). Tryptase levels were significantly higher in group S than in group C in all gastric areas (antrum: U = 95, P < 0.001; corpus: U = 85, P < 0.005 and fundus: U = 75, P < 0.05). Total protein, PGA and gastrin did not vary significantly between groups. In group C, no significant correlations were found among the five parameters. In group S, corpus tryptase was correlated with fundus tryptase (Spearman's r = 0.831, P < 0.01). The same relationship was observed for histamine (r = 0.672, P < 0.05). In group S, antrum gastrin was inversely correlated with antrum tryptase (r = -0.903, P < 0.001), and with corpus PGA (r = -0.806, P < 0.05). This study demonstrates that bolus pentagastrin administration stimulates gastric mucosal mast cells in the rabbit.

Animals↗

Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes.

We evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread.

Adult↗

Coagulation and plasma fibronectin parameters in HELLP syndrome.

OBJECTIVES: HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) has a high fetal mortality and maternal morbidity, partly due to its late diagnosis. In order to facilitate earlier diagnosis, we studied the changes occurring in natural coagulation inhibitors, fibronectin and haptoglobin as potential early markers of endothelial damage, coagulation cascade activation and intravascular hemolysis. METHODS: The study compared antithrombin (AT-III), protein C and S activity, plasma fibronectin, 'prothrombin time' and 'partial prothrombin time' (AST, ALT), lactate dehydrogenase (LDH), bilirubin and serum haptoglobin in 17 asymptomatic controls, 19 preeclampsia patients and 11 HELLP syndrome patients. RESULTS: HELLP syndrome patients had higher fibronectin and D-dimer values, lower AT-III and protein C activity, a lower platelet count and higher LDH than healthy controls; only 25% had raised bilirubin. Serum haptoglobin was lower in HELLP syndrome. CONCLUSIONS: Early on in HELLP syndrome, there is probably a pro-coagulatory imbalance in the placental microcirculation. Endothelial damage causes tissue thromboplastin release and coagulation cascade activation due to collagen exposure; the vascular lesion increases thromboplastin in the bloodstream and triggers distant coagulation processes, suggesting compensated disseminated intravascular coagulopathy. Measuring plasma fibronectin and coagulation inhibitors should be supported by testing haptoglobin as a marker of intravessel hemolysis to differentiate conventional preeclampsia from HELLP.

Adult↗

Clinical evaluation of seven tumour markers in lung cancer diagnosis: can any combination improve the results?

In this study we compared the diagnostic utility of: (1) neuron-specific enolase (NSE); (2) squamous cell carcinoma antigen (SCC); (3) carcinoembryonic antigen (CEA); and (4) cytokeratin markers (CYFRA 21-1, TPA, TPM, TPS) in patients with small-cell lung cancer (SCLC) (21 cases) and non-small-cell lung cancer (94 cases). For comparison we also studied 66 patients with benign lung diseases and nine with pleural mesothelioma. NSE levels in SCLC patients were significantly higher than those in all the other groups studied. No significant variations were found among the SCC levels in all groups. CEA levels in patients with adenocarcinoma were significantly higher than those in all other groups studied. CYFRA 21-1 serum levels significantly increased in patients with squamous cell carcinoma and mesothelioma, while TPA, TPS and TPM increased in patients with lung cancer irrespective of the histological type. In patients with SCLC, high levels of all markers except SCC were found when the disease was extensive. In patients with non-SCLC, the highest levels of all tumour markers were usually found in those with advanced disease, although CYFRA 21-1 gave a sensitivity of 44% when a specificity of 95% was fixed in stage I non-SCLC patients. An analysis of receiver operating characteristic curves revealed that the highest diagnostic accuracies in distinguishing benign from malignant lung diseases were achieved with TPM (81%), CYFRA 21-1 (72%), CEA (78%) or TPA (78%) when using cut-off values of 46 Ul-1, 3.0 micrograms l-1, 2.0 micrograms l-1 and 75 Ul-1 respectively. When all patients were considered, the combined evaluation of more than one marker did not significantly improve the results obtained with TPM alone. However, taking into consideration the fact that CYFRA 21-1 is the most sensitive index of early lung tumours and that its combined determination with TPM did not worsen the overall sensitivity and specificity of the latter, the combined use of these two markers may be suggested as a useful took for the diagnosis of lung tumours.

Adult↗

Effects of pancreaticobiliary duct obstruction on the exocrine and endocrine rat pancreas.

Experimentally, biliary obstruction can produce morphological and functional changes in the pancreatic gland, whereas pancreatic obstruction may have short-term (hyperamylasemia, pancreatic edema, and lysosomal hydrolase redistribution) or long-term (acinar cell atrophy and interstitial fibrosis) effects. We created a pancreaticobiliary duct obstruction in rats to evaluate (a) exocrine and endocrine anatomobiochemical pancreatic modifications; (b) structural and functional liver alterations; and (c) the relationship, if any, between the alterations found in the two organs. Forty-five male Sprague-Dawley rats were subdivided on the basis of period of obstruction (from 1 to 28 days). In each rat serum we evaluated amylase, cholestatic and cytolytic indices, and glucose. In frozen pancreatic samples we measured insulin, glucagon, and DNA; in the liver the DNA content was determined. Histologically, ductal dilation and proliferation were evaluated for the liver, zymogen granules, and Langerhans' islets, and atrophy for the pancreas. Fibrosis was evaluated for both the liver and the pancreas. Short-term common pancreaticobiliary duct ligation caused an increase in serum amylase levels and mild pancreatic edema. Longer-term obstruction had either similar or different effects on the two organs. In the pancreas it caused fibrosis and exocrine and endocrine atrophy, but not acute pancreatitis. In the liver the main phenomena observed were fibrosis, ductal dilation, and proliferation.

Animals↗

Determinants for the development of chronic atrophic gastritis and intestinal metaplasia in the stomach.

This study aimed to identify the factors associated with the development of gastric precancerous changes, in a prospective series of patients undergoing endoscopy. Risk factors and associated mucosal changes were evaluated in 134 endoscoped patients affected by chronic non-atrophic (n = 76) or atrophic gastritis (CAG) (n = 32), with or without intestinal metaplasia (IM), or lacking any major histological changes (n = 26). The following variables were taken into account: age, alcohol consumption, smoking habit, vitamin C intake (using a questionnaire), gastric juice vitamin C (HPLC on gastric juice samples obtained at endoscopy), H. pylori infection, gastric mucosa malondialdehyde (MDA; a measure of free radical production) and extent of CAG in gastric biopsies (only for IM). Tissue MDA levels were significantly higher, and vitamin C levels significantly lower in CAG and IM patients (P = 0.01). Multiple regression analysis showed significant correlations for: CAG vs age (P < 0.02), MDA (< 0.02) and gastric vitamin C (< 0.05); IM vs age (P < 0.0005), CAG (< 0.0005) and MDA (< 0.001). Using stepwise discrimination analysis, the independent variables included in the model were: for CAG, age (P < 0.003), MDA (< 0.05), gastric juice vitamin C (< 0.05); for IM, CAG (P < 0.0005), age (< 0.001), MDA (< 0.03) and vitamin C intake (< 0.05). H. pylori was not included. The major determinants for CAG and IM were age, free radical production (as measured by MDA), vitamin C (for CAG) and vitamin C intake and CAG (for IM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Full automation in allergy testing: measurement of specific IgE by the ENEA System.

UNLABELLED: We evaluated the ENEA System, a fully automated instrument for the measurement of specific IgE antibodies. The instrument dispenses sera and reagents, incubates, washes, and reads and prints results automatically. The "core" of the instrument is the reactive unit called ACE (Allergy Chamber Enzymatic), which is a new solid phase to which the allergens are linked. The system uses calibration curves specific for the major allergen families, and data are supplied qualitatively (five classes) and quantitatively. We evaluated the analytic efficiency of the system and its correlation with the in vivo test (skin prick test (SPT)) results in 60 patients with inhalant allergic diseases and in 20 controls. RESULTS: 450 results were available within 4 h. A satisfactory within-run (CVs between 1.58 and 6.2%) and between-run (CVs 6.3-11.5%) precision was found. No significant carry-over was observed. A wide linearity of the assay was demonstrated. With the concordance between the clinical history and SPT as the reference value, the clinical sensitivity of the ENEA System was 84.1%, the specificity 82.8%, and the overall efficiency 83.4%. Finally, a good agreement with the results of another technique for the in vitro measurement of specific IgE (Pharmacia CAP System) was proven.

Adolescent↗

Eosinophil cationic protein in tears of normal subjects and patients affected by vernal keratoconjunctivitis.

The objectives of this study were to determine: 1) levels of tear eosinophil cationic protein (ECP) in patients with vernal keratoconjunctivitis (VKC); 2) the effect of pharmacologic therapy on ECP release; and 3) the correlation of this mediator with the severity of the disease. Tears were collected from 10 controls and 20 VKC patients before and after therapy for cytologic analysis and ECP measurement by radioimmunoassay. Ocular signs and symptoms were evaluated before tear collection. Mean ECP levels in controls were 7.5 +/- 0.4 microgram/l, and in VKC patients, 988.3 +/- 128 micrograms/l before therapy (P < 0.001) and 566.3 +/- 121 micrograms/l after therapy (P < 0.005). In dexamethasone (Dex) 0.1% or cyclosporin A (CsA) 2% patients (five per group), tear ECP decreased significantly after 7-14 days of treatment. Disodium cromoglycate (DSCG) 4% (five patients) for 14 days did not significantly affect ECP levels. ECP levels were significantly correlated with allergic signs (P < 0.001), symptoms (P < 0.001), and the number of eosinophils in tears (P < 0.005). The results of this study suggest that tear ECP levels accurately reflect the clinical status of VKC patients. The measurement of ECP may prove useful not only in the diagnosis and monitoring of allergic disease, but also as an objective parameter for the evaluation of new antiallergic therapies.

Adolescent↗

Altered lipid peroxidation/glutathione ratio in experimental extrahepatic cholestasis.

1. Lipid peroxidation can occur in the presence of a cellular antioxidant-oxidant imbalance, but the role of lipid peroxides in cholestasis is not well understood. 2. This study was undertaken in order to: (i) evaluate the behaviour of a product of lipid peroxidation (thiobarbituric acid-reactive species), and of an important antioxidant tripeptide, reduced glutathione, in the course of experimental extrahepatic cholestasis; and (ii) ascertain whether there was a link between this aspect and the alterations in liver morphology. 3. Forty-five male Sprague-Dawley rats (250-300 g) were double bile duct ligated and followed from 1 to 28 days. At the end of each experimental period, blood and liver samples were collected for thiobarbituric acid-reactive species and glutathione determinations. 4. Bile duct ligated rats showed a marked increase in liver weight which was related to cholestasis duration and to some anatomical alterations such as bile duct proliferation and dilation and liver fibrosis (periportal, perivenular, perineoductular and parenchymal). 5. An increase in serum lipid peroxidation was also observed but this was not linked to hepatic thiobarbituric acid-reactive species. Erythrocyte and hepatic glutathione decreased in relation to cholestasis duration. Serum lipid peroxides and erythrocyte glutathione were correlated with liver cell necrosis. 6. In conclusion, experimental extrahepatic cholestasis determines bile duct proliferation and fibrosis, the degree of which is directly related to the duration of cholestasis itself and to liver cell necrotic phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal functional alterations in extrahepatic cholestasis: can oxidative stress be involved?

Renal function may be compromised by extrahepatic cholestasis. In this context, the nephrotoxic role of bile salts is well known. Recently, however, it has been claimed that other factors, such as lipid peroxides, are involved. We therefore created bile duct ligation in 40 Sprague-Dawley rats. During the follow-up (from 1 to 28 days), significant variations were found in liver histological parameters, but not in renal morphology. Fourteen days after ligation, significant increases were found in serum and urinary thiobarbituric-acid-reactive species and phospholipase A2 (indirect indices of lipid peroxidation), whereas 8-10 days after ligation, a significant decrease was observed in erythrocytic and hepatic GSH levels. The variations in urinary thiobarbituric-acid-reactive species and in phospholipase A2 were not correlated with concomitant variations in the sera. Urinary lipid peroxides were directly correlated with the degree of liver morphological alterations and inversely with circulating GSH. Urinary outputs of lipid peroxides, phospholipase A2 and N-acetyl-glucosaminidase were correlated with each other. These results suggest that there is an imbalance in the oxidative-antioxidant hepatic system in experimental extrahepatic cholestasis. The reduced bioavailability of blood GSH may alter the oxidative equilibrium in other organs, such as the kidney, triggering and favoring the lipoperoxidative cascade.

Animals↗

Effect of octreotide acetate on pancreatic exocrine and endocrine functions after pancreatoduodenal resection.

In view of forecasting the effect of octreotide acetate (Sandostatin) in preventing fistula formation after pancreatic surgery, 9 patients, who had pancreatoduodenectomy 8-12 days before, underwent a 2-day study. The first day, by means of a catheter located in the jejunal loop separately anastomosed to the pancreatic remnant, basal and after secretin stimulation pancreatic secretion was evaluated. During the 2nd day the possible inhibitory effect of octreotide on basal and stimulated secretion was investigated. Under the experimental conditions of the study Sandostatin showed little effect on the water and bicarbonate increase as stimulated by secretin. A greater hormone inhibitory effect on amylase production and pancreatic endocrine function was seen. On the basis of these results the use of Sandostatin can hardly be seen as useful in preventing fistula formation after pancreatic resection.

Adult↗

Neutrophil NADPH oxidase activity in chronic myeloproliferative and myelodysplastic diseases by microscopic and photometric assays.

Neutrophil NADPH oxidase is a membrane-bound enzyme complex responsible for the reduction of oxygen to superoxide anion in the respiratory burst. Impaired neutrophil function has often been reported in myeloproliferative diseases and myelodysplastic syndromes (MDSs), but its laboratory features have not been well characterized. Traditionally, NADPH oxidase activity has been evaluated with a microscopic method by nitroblue tetrazolium salt reduction to blue-black insoluble formazan granules identified in positive neutrophils by microscopy. We investigated neutrophil NADPH oxidase in 22 patients with chronic myeloproliferative disorders (cMPDs) and 15 patients with MDSs, using the microscopic method as well as a photometric microplate assay, which monitored the cytochemical reaction for 30 min. The relationship between cMPD and patient susceptibility to infections was also investigated. In the photometric assay, the mean enzyme activity in MDSs and cMPDs was lower than in normal subjects. NADPH oxidase activity was greater in cMPDs (except myelofibrosis) than in MDSs (except chronic myelomonocytic leukemia), and these differences were less evident with microscopy. Moreover, for cMPDs, patients with susceptibility to infections showed a lower NADPH oxidase activity than patients without infections.

Adult↗

Multicentre evaluation of the Serono SR1 assay for prostate specific antigen.

This report describes the findings of an evaluation of the validity of the new, highly automated Serono SR1 enzyme immunoassay for prostate specific antigen performed at three European sites. Within-run precision was below 5.5% at the clinically important decision point of 4 micrograms/l, less than 10% below 3 micrograms/l and less than 5% above 4 micrograms/l. Between-run precision was below 12% at each site and between-site precision was less than 14%. Dilution series were shown to be parallel to the standard curve on 12 samples with neat prostate specific antigen concentrations ranging from 20 to 88 micrograms/l (linear regression slopes and correlation coefficients of 1.00 to 1.06 and 0.972 to 1.000 respectively). Comparisons with Hybritech Tandem-E and -R and Roche Cobas Core prostate specific antigen methods used routinely at the three sites were good (linear regression slopes 1.04 to 1.13, correlation coefficients 0.96 to 0.99), but results were significantly lower than the Ciba Corning ACS180 (slope 0.66, correlation coefficient 0.99). The assay presents a precise, robust and valid diagnostic tool offering additional advantages of non-isotope automation.

Cross Reactions↗

Clinical efficiency of in vitro and in vivo tests for allergic diseases.

BACKGROUND: Specific serum IgE determination is widely used in the diagnosis of IgE-mediated allergic diseases but the relative merits of in vitro measurement of IgE antibody in comparison to in vivo skin tests are still debated. OBJECTIVE: The aim of this study was to investigate the clinical efficiency of a "second generation" technique for in vitro analysis of IgE antibody (Pharmacia CAP System). METHODS: Eighty-six patients with suspected inhalant and/or food allergies and 20 asymptomatic subjects for a total of 655 tests were evaluated. Sera with divergent results between in vitro and in vivo techniques were further analyzed by using ImmunoCAP inhibition and immunoblotting. For the calculation of sensitivity and specificity of both in vitro and in vivo tests we considered as true value (reference value) either the concordant results or, in case of discordance, the datum confirmed by ImmunoCAP inhibition or immunoblot (ie, vitro positive, vivo negative, ImmunoCAP inhibition positive; true result: positive). RESULTS: The obtained results demonstrate that the in vitro results correlate well in terms of specificity and sensitivity to this new reference standard. In particular a higher specificity for Pharmacia CAP System in comparison to in vivo skin prick test for grass pollens and a better sensitivity for mites and cat allergens were found. CONCLUSIONS: Our results suggest that the in vitro "second generation" testing provides reliable results in all clinical situations.

Adolescent↗