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Biomedical subjects

A Piccoli

Publications and source records attributed to A Piccoli.

At least 73 records · Page 4Linked to original sources

Therapy for idiopathic membranous nephropathy: tailoring the choice by decision analysis.

Two Italian controlled trials demonstrated that the difference in remission rates obtained with six months of methylprednisolone and chlorambucil (MP+Ch) compared to MP was smaller than MP+Ch versus symptomatic therapy in the treatment of idiopathic membranous nephropathy nephrotic syndrome (NS). A decision analysis was used to compare the three treatment strategies, assuming triple probabilities and costs for MP+Ch complications compared to MP, with no risk for supportive therapy, referring to an average 40-year-old patient and using the quality-adjusted life expectancy year (QALY) as the utility scale. With MP+Ch the difference in expected QALY was 7.2 years compared to supportive therapy, and 2.6 years compared to MP. To offset the longer survival obtained with MP+Ch versus MP, it was assumed that all patients treated with MP+Ch would undergo either fatal (5% vs. 0.3% with MP) or non-fatal complications (95% vs. 15% with MP). This threshold denotes a great stability of the inequality in the expected QALY. Consequently, treatment with MP or with MP+Ch is justified if their side effects are considered to be a suitable trade-off for a five or seven QALY, respectively, longer survival. Only an absurd increase in the death rate with MP+Ch could offset the difference.

Adolescent↗

Proliferating cell nuclear antigen (PCNA) and recurrence in patients with cutaneous melanoma.

A positive correlation between PCNA and the most important histoprognostic factors of cutaneous melanoma has been demonstrated. The aim of our work was to evaluate the efficacy of PCNA in predicting melanoma recurrence and to compare it with that of Breslow thickness. One-hundred and fifteen patients (75 women, 40 men; mean age 50 years) with primary cutaneous melanoma were retrieved. pTNM stages were as follows: stage I, 54 patients; stage II, 31 patients; stage III, 26 patients; and stage IV, four patients. The mean follow-up period was 55 months (range 2-260). Six patients developed lymph node metastases and 28 developed distant metastases; 27 patients died within 2-202 months from diagnosis. Tumour thickness was re-evaluated for each case. PCNA immunostaining was performed using the avidin-biotin complex method and the percentage of PCNA-positive tumour cells was indicated as the PCNA index. In order to evaluate and compare the PCNA index and Breslow thickness as predictors of recurrence, the receiver-operating characteristic (ROC) curve method, based on true-positive and false-positive rates was used. The PCNA index showed the highest true-positive rates and the lowest false-positive rates in the 5-30 interval. The PCNA index optimal cut-off is 20, characterized by 70% sensitivity and 80% specificity; Breslow thickness optimal cut-off is 3.5 mm, with 40% sensitivity and 90% specificity. Our results indicate that the PCNA index has a higher efficacy in predicting locoregional and distant recurrences in patients presenting primary cutaneous melanoma.

Adult↗

Polymorphonuclear leukocytes enhance release of growth factors by cultured endothelial cells.

Porcine aortic endothelial cells (PAECs) in culture constitutively secrete polypeptide (endothelium-derived) growth factors (EDGFs) into the surrounding medium. Incubation of PAECs with human peripheral blood polymorphonuclear leukocytes (PMNs) caused a significant increase in EDGF release as assessed by [3H]thymidine incorporation into BALB/c 3T3 mouse fibroblasts and cell proliferation assay. The effect was time dependent and correlated with the number of PMNs, reaching a maximum with a 1:1 PAEC to PMN ratio. Generation of mitogenic activity was prevented by cycloheximide, indicating a requirement for de novo protein synthesis. Antibody-mediated inhibition assays suggested that mitogenic activity was due to platelet-derived growth factor and basic fibroblast growth factor. When supernatant from N-formyl-methionyl-leucyl-phenylalanine-stimulated PMNs was substituted for PMNs during incubation with PAECs, powerful mitogenic activity was generated, indicating the involvement of soluble mediators. A role for free oxygen radicals was ruled out by experiments in which superoxide dismutase and catalase did not prevent the increase in mitogenic activity. By contrast, serine protease inhibitors such as soybean trypsin inhibitor, alpha 1-antitrypsin, and eglin C reduced the PMN-stimulating activity by 70%, 80%, and 100%, respectively. The possible involvement of cathepsin G and elastase was investigated. Cathepsin G and elastase, when substituted for PMNs, increased the release of EDGFs in a dose-dependent fashion, mimicking the effect of PMNs. These findings suggest a new role for leukocyte-vessel wall interactions in the proliferative feature of atherosclerosis.

Animals↗

Atrial natriuretic factor in hypertensive and normotensive diabetic patients.

OBJECTIVE: To evaluate plasma atrial natriuretic factor (ANF) behavior in hypertensive patients with either insulin-dependent (type I) or non-insulin-dependent (type II) diabetes. RESEARCH DESIGN AND METHODS: Plasma ANF levels were measured in euglycemic normotensive patients (n = 18) and hypertensive patients (n = 18), in diabetic normotensive patients (type I diabetes, n = 12; type II diabetes, n = 12), and in diabetic hypertensive patients (type I diabetes, n = 12; type II diabetes, n = 22). In all groups, plasma ANF levels were determined at the end of a normal NaCl diet period (120 mmol NaCl per day for 10 days) in both the supine and the upright positions. RESULTS: Plasma ANF levels were significantly higher (P < 0.05) in hypertensive euglycemic patients (supine vs. upright: 13.4 +/- 6.7 vs. 8.5 +/- 4.3 fmol/ml) than in normotensive type I diabetic patients (supine vs. upright: 8.6 +/- 2.2 vs. 5.9 +/- 2.9 fmol/ml) but not in euglycemic normotensive subjects (supine vs. upright: 11.4 +/- 5.1 vs. 7.6 +/- 5.8 fmol/ml) and normotensive type II diabetic patients (supine vs. upright: 10.1 +/- 4.1 vs. 7.9 +/- 4.1 fmol/ml). Moreover, in the normotensive groups plasma ANF levels did not significantly differ among euglycemic type I and type II diabetic patients. However, the highest levels of plasma ANF were observed in hypertensive type II diabetic patients (supine vs. upright: 16.9 +/- 7.4 fmol/ml [P < 0.01 vs. euglycemic normotensive subjects, P < 0.0001 vs. normotensive type I diabetic patients, P < 0.01 vs. hypertensive type I diabetic patients and normotensive type II diabetic patients] vs. 11.6 +/- 2.9 fmol/ml [P < 0.005 vs. normotensive type I diabetic patients, P < 0.01 vs. hypertensive type I diabetic patients]). On the contrary, plasma ANF levels were higher (P < 0.05) in hypertensive type I diabetic patients (supine vs. upright: 10.8 +/- 1.9 vs. 6.4 +/- 2.2 fmol/ml) compared with normotensive type I diabetic patients, but not with any other patient group. A significant correlation between supine ANF and insulin levels was found in both type II diabetic (r = 0.457; P < 0.05) and nondiabetic hypertensive patients (r = 0.716; P < 0.0001). CONCLUSIONS: These findings indicate that circulating ANF levels are markedly elevated in type II diabetic patients affected by essential hypertension. On the contrary, plasma ANF levels are in the range of normality in normotensive type I and type II diabetic patients.

Adult↗

Lipid peroxidation and renal tubular damage in chronic pancreatic diseases: is there any relationship?

Lipid peroxidation is one of the most important expression of oxidative stress induced by oxygen-derived free radicals. Here we evaluate the behavior of malondialdehyde (MDA) in the serum and urine from patients with chronic pancreatic diseases, with respect to patients with extra-pancreatic digestive diseases and glomerulonephritis. Serum and urinary phospholipase A2 (PLA2) activity was also determined, since this enzyme contributes to damage of plasma membranes. MDA and PLA2 levels increased in the sera from most of the patients with pancreatic and extra-pancreatic digestive diseases. In glomerulonephritis, pathological MDA levels (36%), but not PLA2 levels, were found. Serum MDA correlated with gamma-glutamyl transpeptidase (GGT), while PLA2 correlated with alanine-phosphodiesterase (ALP), GGT, alanine-aminotransferase (ALT) and creatinine. In urine, MDA and PLA2 behaved differently from the corresponding serum values. MDA increased in some patients with pancreatic cancer, extra-pancreatic diseases and glomerulonephritis. PLA2 levels did not significantly vary between groups. Urinary MDA correlated with some indicators of renal tubular damage [urinary ribonuclease, beta-2-microglobulin (B-2-M) and N-acetyl-glucosaminidase (NGA)] and with serum bilirubin. Urinary PLA2 correlated only with ribonuclease (RNase). We conclude that serum MDA increases aspecifically in pancreatic and extra-pancreatic diseases, probably reflecting an aspecific phlogistic phenomenon; PLA2, although sharing a similar pattern with MDA, seems mainly related to hepato-biliary damage. Urinary MDA reflects the presence of renal tubular damage, which may be the cause or a consequence of lipid peroxidation; little variations in PLA2 are recorded in urine, and mainly reflect the presence of impaired tubular function.

Adult↗

Therapy of lupus nephritis. A two-year prospective study.

The aim of our study was to compare the efficacy of 3 different therapeutic protocols in the treatment of patients with WHO class IV lupus nephritis and normal renal function. We carried out a randomized prospective trial. The treatment programs consisted of a standard therapy regimen alone (protocol A), plus plasmapheresis (protocol B) or pulse methylprednisolone (protocol C), followed by a slow (protocols A and B) or fast (protocol C) prednisone tapering schedule. Statistical analysis was performed, using univariate survival analysis according to Kaplan Meier and Breslow's test to compare survival curves. Eighteen patients entered the study: 6 protocol A, 5 protocol B and 7 protocol C. No patients developed renal insufficiency. Moreover, no statistical differences in the probability of inducing partial or complete disease remission and in reducing 24-hour urinary protein excretion to < or = 2 g per day were observed among the groups. Protocols A and B were more effective in comparison with protocol C in decreasing 24-hour urinary protein excretion to < or = 0.5 g and < or = 0.2 g per day. In conclusion, a slow prednisone tapering schedule is more effective in reducing 24-hour urinary protein excretion to < or = 0.5 and < or = 0.2 g per day as compared with a fast prednisone tapering schedule, even if it is preceded by methylprednisolone pulse therapy.

Adolescent↗

Ductal adenocarcinoma of the pancreas: clinicopathologic features and survival.

AIMS AND BACKGROUND: The prognosis after surgical resection for pancreatic cancer has not been clearly defined because conflicting results have been reported. METHODS: Fifty-five patients who underwent surgical resection for pancreatic carcinoma between 1970 and 1987 were retrospectively reviewed to determine factors influencing long-term survival. RESULTS: The actuarial 5-year survival rate for all 55 patients was 12.5%. Type of operation, tumor stage, direct extension into adjacent organs, grading and lymph node involvement were found to significantly influence survival. Age, sex, tumor site, size, invasion into peripancreatic tissue, invasion of lymphatic vessels and small veins, perineural infiltration, tumor necrosis, round cell infiltrate at the tumor margin, associated chronic pancreatitis, and atypia of pancreatic ductal epithelium demonstrated no predictive capacity. No 5-year survival was observed among the patients who underwent vascular resection. Three of 9 patients who underwent left-sided pancreatectomy for cancer of the tail of the pancreas survived more than 5 years. Multivariate analysis confirmed that lymph node involvement, moderate-poor histologic tumor differentiation, and treatment with total pancreatectomy were significantly associated with a worse prognosis. CONCLUSIONS: Lymph node status, grading of the tumor and type of operation have a significant impact on prognosis in resected pancreatic cancer.

Adult↗

Does acetylsalicylic acid interfere with stimulated pancreatic secretion? An experimental study in the rat.

To evaluate the effect of the prostaglandin inhibitor acetylsalicylic acid (ASA) on rat exocrine pancreas secretion, three groups of rats were administered ASA by infusion: Groups 1-3, 50, 100, and 200 mg/kg body wt, respectively; Group 4 received saline. Twenty minutes later these ASA-pretreated groups were given intraarterial secretin (18 CU/kg) and cholecystokinin (CCK) (18 micrograms/kg). In an additional three groups of seven rats each, saline solution rather than secretin-CCK was given after ASA pretreatment. Pancreatic juice was collected every 10 min by means of a chronic pancreatic fistula. Bicarbonate and protein concentrations were measured and variations in outputs observed. No significant variations were found in the bicarbonate concentrations and outputs of rats with different types of pharmacological treatment, while protein concentrations and outputs were found to vary with time and type of experiment. There was, however, no interaction between these two variables. At lower ASA dosages, the bicarbonate and protein concentrations and outputs of secretin-CCK-stimulated rats were higher than the basal values and the levels of rats without hormonal stimulation. At higher dosages, no difference was found between the two groups. In conclusion, ASA seems to interfere with stimulated pancreatic exocrine secretion of proteins, even when its effect on bicarbonate concentration is factored in, and its effect seems to be present at the highest dosages considered in the study. Among the various hypotheses that may explain this phenomenon, an antagonizing effect of ASA on secretin-CCK action should be the first to be considered.

Animals↗

Oxygen administration increases plasma digoxin-like substance and renal sodium excretion in chronic hypoxic patients.

Despite the absence of cardiac or renal pathologies, edema and mild hyponatremia may often occur in patients affected by chronic obstructive pulmonary disease (COPD). Therefore, it has been suggested that hypoxia may influence the release of different hormones regulating renal sodium handling. To evaluate the effect of hyperoxia and O2 removal on plasma digitalis-like substance (DLS) levels, 9 patients affected by COPD and 7 normal subjects were studied. After 1 h in supine position, O2 was administered for 3 h by a tight-fitting face-mask. Blood samples for plasma DLS were taken at time 0, 60, 180 min and then for 3 h after O2 removal. In normal subjects, plasma DLS did not vary after O2 administration (from basal values of 162.25 +/- 8.59 to 107.75 +/- 6.65 pg/ml at 180 min; NS), and O2 removal (143.7 +/- 16.87 pg/ml after 3 h from O2 removal; NS). On the contrary, in patients affected by COPD, plasma DLS levels increased during O2 administration (from basal values of 138.98 +/- 8.31 to 202.14 +/- 8.21 pg/ml at 180 min; p < 0.05), and returned to baseline levels (142.59 +/- 8.28 pg/ml) 3 h after O2 removal. In the same patients, DLS increase was accompanied by a rise in Na+ excretion (from 0.08 +/- 0.01 at time 0 to 0.16 +/- 0.02 mEq/min after 3 h of O2 administration; p < 0.05). In conclusion, our findings showed an oxygen-related increase in plasma DLS levels and in urinary Na+ excretion in patients affected by COPD. This phenomenon could promote Na+ urinary loss during prolonged O2 therapy in these patients and should be taken into account in their management.

Blood Proteins↗

The influence of salt sensitivity on the blood pressure response to exogenous kallikrein in essential hypertensive patients.

In order to verify the influence of salt sensitivity on the blood pressure response to orally administered kallikrein, we evaluated the efficacy of glandular kallikrein (derived from porcine pancreas) in 28 essential hypertensives (21 males and 9 females) aged between 40 and 62 years. After a placebo run-in period, the patients were assigned to receive oral kallikrein therapy (150 IU 3 times a day; n = 18 patients) or placebo (n = 10 patients) over a period of 8 days in a random double-blind fashion. In the salt-resistant patients (n = 8), kallikrein administration did not modify blood pressure levels. In the same group, natriuresis increased significantly after the treatment [from 94.51 +/- 10.76 to 111.65 +/- 23.19 mEq/24 h (mmol/24 h), p < 0.039]. In the salt-sensitive patients (n = 10), blood pressure decreased with the kallikrein therapy (systolic: from 158.50 +/- 9.20 to 144.50 +/- 10.12 mm Hg, p < 0.005; diastolic: from 99.50 +/- 2.16 to 90.0 +/- 3.67 mm Hg, p < 0.024). In the same patients, urinary Na+ excretion increased considerably after the kallikrein treatment (from 101.07 +/- 18.36 to 134.34 +/- 18.27 mEq/24 h, p < 0.0001). Therefore, our data indicate that the oral kallikrein administration reduces blood pressure levels only in the salt-sensitive hypertensives. In both the salt-sensitive and the salt-resistant groups a marked increase in the 24-hour urinary excretion of sodium was observed after the kallikrein treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Enhanced blood pressure response to cyclooxygenase inhibition in salt-sensitive human essential hypertension.

To evaluate the influence of salt sensitivity on the blood pressure response to oral indomethacin treatment, we studied 35 hospitalized essential hypertensive patients (24 men and 11 women, aged from 40 to 55 years). During a normal NaCl intake (120 mmol Na+ per day), patients were assigned to receive in a randomized double-blind fashion either 200 mg indomethacin (25 patients) or placebo (10 patients) for 5 days. Two weeks after the interruption of indomethacin treatment, during which the normal NaCl intake was continued, salt sensitivity was assessed by giving each patient a high (220 mmol Na+ per day for 10 days) and then a low (20 mmol Na+ per day for 10 days) NaCl diet. Blood pressure changes were evaluated, and the measurement taken at the end of the 2 weeks under normal sodium intake was considered baseline blood pressure. Patients were classified as salt sensitive when a diastolic blood pressure change of 10 mm Hg or more occurred after both low and high periods of sodium intake. In salt-resistant patients treated with indomethacin (n = 12, nine men and three women, mean age 50.5 +/- 3.7 years), neither blood pressure (systolic blood pressure from 150.8 +/- 11.2 to 154.6 +/- 9.3 mm Hg, NS; diastolic blood pressure from 99.3 +/- 2.1 to 101.1 +/- 4.4 mm Hg, NS) nor the urinary Na+ excretion (from 108.1 +/- 20.9 to 97.9 +/- 9.1 mmol/24 hr, NS) was significantly affected by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reduction in urinary prostaglandin excretion in the premenstrual syndrome.

The purpose of the present work was to study some factors involved in renal handling of salt and water in the premenstrual syndrome (PMS), in which salt and water retention is frequently observed. In 18 women with PMS and in 18 healthy women we studied the levels of cyclic adenosine monophosphate, aldosterone, prostaglandin E2, prostaglandin F2 alpha and kallikrein in urinary samples collected during the luteal phase. There was no difference between the two groups regarding sodium, aldosterone and kallikrein urinary excretion. In the PMS group there was a significant reduction in urinary excretion of cyclic adenosine monophosphate, prostaglandin E2 and prostaglandin F2 alpha with respect to the control group. At multivariate analysis sodium urinary excretion proved not to be the same as the model validated in healthy women. There may be different renal handling of water and electrolytes during the luteal phase of the menstrual cycle in women with PMS.

Adult↗

Evidence of a link between erythrocyte band 3 phosphorylation and anion transport in patients with 'idiopathic' calcium oxalate nephrolithiasis.

This study was carried out to verify the hypothesis of a link between faster endogenous phosphorylation of band 3 protein, the anion carrier, and anomalous oxalate transmembrane self-exchange found in erythrocyte from calcium oxalate renal stone formers. Agents able to modify 32P-labelling of band 3 protein induced a concurrent modification in oxalate transmembrane flux. Cyclic AMP- and phospholipid-sensitive Ca(2+)-independent protein kinases seem to be critical modulators of band 3 function. These observations demonstrate a close link between the band 3 phosphorylation state and its anion transport function, and provide new insights into the pathogenetic mechanisms of the cellular anomalies observed in calcium-oxalate renal stone disease.

Anion Exchange Protein 1, Erythrocyte↗

Relationship between plasma leucine concentration and clearance in normal and type 1 diabetic subjects.

In a series of studies in normal and type 1 diabetic subjects, we analysed the relationship between isotope-calculated leucine clearance and plasma leucine concentration. All studies were performed under euglycaemic conditions. Plasma leucine concentrations were either experimentally decreased by means of insulin infusion, or increased by means of exogenous amino acid infusion in the presence of hyperinsulinaemia. Leucine clearance rates were compared in normal and diabetic subjects at similar plasma insulin levels. The effect of hyperinsulinaemia was examined by measuring clearance rates in normal subjects at comparable leucine levels but different insulin concentrations. Our data show that leucine clearance is inversely related to leucine concentration, and that it is not independently stimulated by hyperinsulinaemia. Type 1 diabetes is not associated with decreased leucine clearance. A general equation relating leucine concentration and clearance is proposed. These data support the view that peripheral leucine utilization is not decreased in type 1 diabetes mellitus.

Adult↗