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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 217 records · Page 12Linked to original sources

Atrial natriuretic factor increases in response to an acute glucose load.

OBJECTIVE: To evaluate the effects of an acute glucose load on circulating atrial natriuretic factor (ANF) levels. METHODS: We investigated plasma ANF, glucose and insulin levels before and after intravenous administration of 50% D-glucose (300 mg/kg body weight) in healthy, normal volunteers. RESULTS: In study group A (n = 30) plasma ANF was found to be increased significantly 30 min after the glucose load. In study group B (n = 55) the response of plasma ANF over time was assessed. A peak plasma ANF response was observed 10 min after intravenous glucose loading; thereafter, plasma ANF levels returned gradually to basal levels at 50 min after glucose injection. The latter produced in both study groups a similar acute hyperglycaemia, and in group B the expected concomitant hyperinsulinaemia. CONCLUSION: These observations demonstrate that, in normal humans, acute marked hyperglycaemia is accompanied by a rapid increase in circulating ANF levels. In this metabolic interaction, ANF might counteract the renal sodium-retaining effect of acute hyperglycaemia and hyperinsulinaemia.

Adult↗

[HPV genital infections + CIN. The immunological patterns, loop electroablation and beta-interferon].

Sixteen patients with genital HPV associated with CIN were treated with electroablation using a diathermic loop and immunomodulation with human beta interferon. Changes in immunological, cyto-histological and clinical parameters were observed pre- and post-treatment. Thirteen cases showed an excellent response. Disease was persistent in three cases. The authors report an improvement, even if statistically non-significant, in some immune parameters and confirm the value of associating physical therapy with immunomodulating treatment.

Adult↗

IgG antibodies to papillomavirus genus-antigens in adult men with cancer of the urinary bladder.

Forty-five sera from men with bladder cancer were examined in a micro solid-phase enzyme-linked immunosorbent assay (ELISA) and in a Western-blotting (WB) assay for the presence of IgG antibodies to papillomavirus (PV) genus-antigens of bovine origin. The ELISA detected PV antibodies in 75.6% of cancer patients. This antibody frequency was significantly higher than that found in both healthy males (22.7%) and patients with urological disorders (24%). A similar correlation among the PV antibody frequencies of the three groups was found with WB assay: 60% of the neoplastic group showed PV antibodies versus 17.3% in healthy males and 32.6% in non-neoplastic patients. Within the same group, 78% to 87% sera showed the same reactivity to both assays. Of these concordant sera, PV positive sera were 55.6% in cancer patients, 13.3% in healthy adults and 19.6% in patients with urological disorders. ELISA PV antibody level in the cancer group was higher than in each of the two control groups. The meaning of the humoral response to PV genus-antigens in men with bladder cancer is discussed.

Adult↗

Combination treatment in M1 prostate cancer.

The treatment of advanced prostate cancer is based on hormone manipulation to eliminate the trophic effect of testosterone on sensitive androgen tissue of the tumor. In this study, we evaluated the efficacy of the partial androgen blockage versus the complete androgen blockage. One hundred, twenty-two patients were entered in this study and randomly were treated with buserelin alone or with buserelin and flutamide. The group that received buserelin was given cyproterone acetate (200 mg/day) during first 3 weeks of treatment to avoid "flare-up". During the follow-up (range 0-244 +/- 1 weeks), we evaluated 59 patients (61.4%) that had positive response and 37 patients (38.6%) that showed progressive disease: There were no statistically significant differences between the two treatment groups, not even in the evaluation of median time to response and of median time to treatment failure. In conclusion, the results emphasize that total androgenic blockage is as effective as a luteinizing hormone-releasing hormone analog used alone.

Aged↗

[Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study].

Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA-reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average -9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated.

Cholesterol, HDL↗

Insulin sensitivity and body fat distribution in normotensive offspring of hypertensive parents.

Lean, healthy normotensive sons of essential hypertensive parents (OHyp) have lower insulin sensitivity (SI) than sons of normotensive parents (ONorm). We have tried to find out whether this disturbance in insulin metabolism is related to altered body fat distribution, fuel metabolism, or both. 21 OHyp and 21 ONorm of similar age and body-mass index were investigated after fasting overnight. Body composition was assessed by dual-energy X-ray absorptiometry and fuel metabolism by indirect calorimetry and urinary nitrogen excretion. Plasma insulin and glucose concentrations were measured during the frequent sampling intravenous glucose tolerance test, and SI was calculated by the minimum model method. Systolic blood pressure and heart rate were slightly but not significantly higher in OHyp than ONorm but the groups did not differ in fasting plasma insulin or glucose concentrations, carbohydrate or lipid oxidation, lean and fat mass, bone mineral content, or distribution of body fat. By contrast, SI was significantly lower in OHyp than ONorm (8.2 [0.7] vs 13.4 [1.5] 10(-4) L mU-1 min-1, p < 0.01). Within the whole study population upper-body fat mass was positively correlated with fasting plasma insulin (r = 0.33, p < 0.03) and lipid oxidation was positively correlated with SI (r = 0.35, p < 0.04) and negatively correlated with subscapular/triceps skinfold thickness (r = -0.43, p < 0.01). Thus, impairment of SI precedes both the development of overt hypertension and gain or redistribution of body fat. Therefore, the concept that SI is low as a result of altered fat distribution has to be reconsidered, at least in young male offspring of hypertensive parents.

Adipose Tissue↗

Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension.

To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg once daily in 14 patients who were hypertensive after 8 weeks on the lower dosage. At entry (before placebo), SI was slightly but not significantly lower in group A than B [2.7 vs. 3.6 x 10(-4) ml.microU-4.min-1]; fasting plasma insulin was 13.6 vs. 12.9 microU.ml-1. After 6 weeks on placebo, S1 averaged 3.7 in group A and 4.4 x 10(-4) microU.ml-1.min-1 in group B; fasting plasma insulin was 14.6 vs. 15.1 microU.ml-1, and glucose 5.5 vs. 5.5 mmol.l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine↗

Characteristics of a ouabain-like factor from Milan hypertensive rats.

Ouabain-like factor (OLF) has been extracted from hypothalamus and adrenal glands of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive controls (MNS). OLF was identified by its ability (a) to inhibit ouabain-sensitive 86Rb uptake into human erythrocytes, (b) to displace [3H]ouabain binding, and (c) to inhibit purified dog kidney Na-K-ATPase. Rat and bovine OLF have similar characteristics. Those that are close to ouabain are (a) ligand conditions for maximal inhibitory activity, (b) high-performance liquid chromatography retention time, (c) reversibility of inhibitory activity on Na-K-ATPase, (d) reduced Na-K-pump inhibitory activity by K+, (e) high affinity for Na-K-ATPase, and (f) no activity on Ca(2+)-ATPase. OLF does not resemble ouabain because the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform is greater than that of ouabain. The yield of OLF is greater from MHS than MNS hypothalamic and adrenal extracts. These findings represent the first direct evidence that a higher amount of OLF is present in tissues from genetically hypertensive rats than from their inbred normotensive controls, maintained under the same dietary and environmental conditions. This further supports previous observations on the role of OLF in the pathogenesis of MHS hypertension.

Adrenal Glands↗

Serum lipoproteins during treatment with antihypertensive drugs.

Several drugs used for antihypertensive therapy may modify the lipoprotein metabolism. Thiazides in high dosage and loop diuretics can increase serum low-density lipoprotein (LDL) cholesterol and/or very-LDL cholesterol and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio, while HDL cholesterol is largely unchanged; triglycerides (Tg) are also often elevated. Premenopausal women may be protected from this side effect. Whether diuretic-induced dyslipidemia is dose-dependent and low thiazide doses (i.e., hydrochlorothiazide < or = 12.5 mg daily) are interacting less, awaits clarification. beta-Blockers without intrinsic sympathomimetic activity increase serum triglycerides and tend to lower the potentially antiatherogenic HDL cholesterol. The diuretic-antihypertensive agent indapamide, given at a dose of 2.5 mg/day, is neutral with regard to serum lipoprotein and glucose metabolism. The potassium-sparing diuretic spironolactone, conventional sympatholytic agents, calcium-channel blockers, and probably the serotonin2-receptor antagonist ketanserin, exert no relevant effects on the lipoprotein profile. Angiotensin-converting enzyme inhibitors may slightly decrease serum triglycerides. alpha 1-Receptor blockers slightly decrease LDL cholesterol and Tg and increase HDL cholesterol. Drug-induced development or aggravation of dyslipidemia represents a potentially adverse influence. In the hypertensive population, effective blood pressure control with traditional drug therapy based on thiazide-type diuretics in high dosage led to a distinct decrease in cerebrovascular morbidity and mortality, but failed to satisfactorily reduce coronary complications. The prognostic relevance of drug-induced changes in serum lipoproteins, carbohydrate metabolism and other risk factors or correlates awaits further clarification.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

[Genetic hypertension in the rat is partially dependent of parathyroid glands. Results of a crossed transplantation trial].

The parathyroid hypertensive factor (PHF) is present in the plasma of SHR rats. The authors of this study set out to determine whether this factor was also present in the Lyon (LH male and female) and Milan (MHS male) hypertensive rats. Five week old normotensive rats (LN and MNS) were transplanted with the parathyroid glands of LH and MHS rats immediately after parathyroidectomy (PTX). Plasma calcium fell rapidly after PTX but returned to physiological levels, confirming the functional activity of the graft. Systolic blood pressures of transplanted rats were significantly higher than normotensive LN and MNS controls. These results confirm the role of the parathyroid glands in the genesis of hypertension in Lyon and Milan male and female rats. They suggest that PHF may be implicated in the hypertensive mechanisms of these two models of genetic hypertension.

Animals↗

Prevention of deep venous thrombosis by a new low molecular weight heparin (Fluxum) in cardiac surgery.

The prophylactic deep venous antithrombotic efficacy of a low molecular weight heparin (LMWH) was compared with traditional unfractionated calcium heparin in 39 patients submitted to cardiac surgery. The patients were allocated at random to receive either LMWH-Fluxum 3200 IUaXa daily (Group A: 20 patients) or calcium heparin 5000 IU three times daily (Group B: 19 patients). Both treatments were started on the first day after surgery and continued over the fourth postoperative days. One or more risk factors for deep venous thrombosis in addition to the cardiac pathology were present in all the patients of group A and in 13 (72.2%) of group B. Mean times of surgery, blood loss during the perioperative period and number of blood units transfused in both groups were not statistically significant. The deep venous system was investigated by continuous wave Doppler and real time colour Echotomography. No evidence of thrombosis was detected in the two groups. Side effects and subcutaneous hematomas were present in only four patients of group B. Both drugs showed good tolerance, provoking no variations of the main laboratory parameters. We conclude that Fluxum (LMWH) for the efficacy and convenience given by a single daily dose, could represent an alternative choice in the prevention of deep venous thrombosis in cardiac surgery.

Female↗

Pharmacokinetics and bioavailability of metoclopramide nasal spray versus metoclopramide intravenous in healthy volunteers and cancer patients.

The kinetics and bioavailability of a new formulation of metoclopramide (CAS 364-62-5) nasal spray (MTC NS) were assessed in two separate studies versus the same drug administered intravenously (MTC IV) according to a balanced-block design where each study subject served as his own control. The first study involved 10 healthy subjects, each receiving metoclopramide NS 20 mg (one 10-mg puff per nostril) and metoclopramide IV 20 mg on two trial days separated by a 7-day washout period. On both occasions, blood samples were obtained at time 0 and at 20, 40, 60, 120, 150, 210, 280 and 360 min of dosing. Metoclopramide concentrations were assayed in plasma by HPLC. The second study involved 10 patients of oncologic domain, scheduled to receive mildly emetic chemotherapy regimes. The experimental design was similar to the one above except that blood was sampled at 0, 20, 40 and 60 min and again at 2, 3, 4, 6, and 8 h of dosing. All healthy subjects completed the trial without experiencing any adverse or untoward events; in the group of cancer patients, one subject dropped out after the nose spray treatment when he was removed to another department. This patient was replaced by another, and included in final data analysis only for the segment of treatment actually received. Metoclopramide kinetics after intravenous dosing were in good agreement with known data for the active substance, with no meaningful differences between healthy subjects and cancer patients. With MTC NS administration there was only a slight but significant difference of Cmax, being lower in the cancer patient group (p < 005).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

[Immunosuppressive therapy of glomerulonephritis--controlled studies].

Glucocorticoids, cytostatic agents and cyclosporin are frequently employed in the treatment of glomerular diseases of immunologic origin. In order to assess the efficacy of these drugs, we retrieved--with the help of a Medline-based search--and analysed all controlled studies published since 1966 dealing with immunosuppressive therapy of glomerulonephritis. Of the 34 identified controlled studies, only 27 had a prospective and randomized design. In patients with minimal-change glomerulonephritis, proteinuria decreases and disappears during therapy with prednisone. A comparable effect can be obtained with cyclosporin. Occasionally, there is a relapse of proteinuria after cessation of the immunosuppressive therapy in some patients. These relapses can be controlled with a chlorambucil-based regimen. Chlorambucil may be successfully utilized in the treatment of focal-segmental glomerulosclerosis, a form of glomerulonephritis which is more refractory to glucocorticoid therapy and is probably pathogenetically related to minimal-change glomerulonephritis. Patients with membranous glomerulonephritis and a nephrotic syndrome seem to benefit from an alternate month prednisone and chlorambucil regimen. However, an indiscriminate treatment of all patients with this regimen is not legitimate, because some patients would be overtreated as the disease may undergo spontaneous remission. There are no well-documented valuable therapies for the IgA-associated glomerulonephritis and the membranoproliferative glomerulonephritis. The combination of prednisone with cytotoxic substances, particularly cyclophosphamide and azathioprine, seem to remarkably improve the renal prognosis of the diffuse proliferative lupus glomerulonephritis. The efficacy of cyclophosphamide and prednisone with or without plasma exchange in the treatment of the rapidly progressive glomerulonephritis due to other systemic diseases (M. Wegener, panarteritis nodosa, Goodpasture syndrome) is a widely accepted therapeutic modality, although controlled studies are lacking. Immunosuppressive therapy of glomerulonephritis bears notable risks and sometimes questionable efficacy. Thus, before prescribing any immunosuppressive therapy, it is mandatory to evaluate in every single patient the prognostic factors of the underlying disease, the probability of the onset of severe side effects and the possible acceptance of a renal replacement therapy, including renal transplantation.

Autoimmune Diseases↗