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Biomedical subjects

F Vianello

Publications and source records attributed to F Vianello.

At least 55 records · Page 3Linked to original sources

Hypertriglyceridemia during long-term interferon-alpha therapy in a series of hematologic patients.

Adverse reactions to interferon-alpha (IFN-alpha) therapy include flu-like syndrome, bone marrow suppression, neurotoxic effects, and autoimmunity. A slight increase in triglyceride levels has been described less frequently during IFN-alpha administration. The incidence of IFN-alpha-induced hypertriglyceridemia seems variable, and there are no clear data on how to treat it. We report the effect of long-term (more than 12 months) IFN-alpha treatment on triglyceride levels in 43 patients suffering from hairy cell leukemia (18), multiple myeloma (10), chronic myelogenous leukemia (6), cryoglobulinemia (5), non-Hodgkin's lymphoma (3), and Sezary syndrome (1). Hypertriglyceridemia was found in 6 patients (15%). In 3 patients, gemfibrozil restored normal triglyceride values. This study suggests that hypertriglyceridemia is a minor side effect of long-term IFN-alpha therapy and that gemfibrozil might be considered the treatment of choice.

Adult↗

Remission in hairy cell leukemia-variant following splenic radiotherapy alone.

The therapeutic approach to hairy cell leukemia (HCL) is in some instances still debated. A variant form of HCL (HCL-V) characterized by high white cell count, splenomegaly, hypercellular and aspirable bone marrow has been described; differential diagnosis often arises with some other B-cell disorders which also show circulating hairy or villous lymphocytes. Conventional treatment for HCL is often less effective in HCL-V. In this report we describe a case with features consistent with HCL-variant treated with splenic radiotherapy. We not only obtained an hematological response but also the near total disappearance of bone marrow infiltration, compatible with a clinical complete remission. Clinical and biological implications of this phenomenon are discussed on the basis of this unexpected therapeutic result, obtained with splenic radiotherapy alone.

Aged↗

Short-term treatment of gastric ulcer. A meta-analytical evaluation of blind trials.

Gastric ulcer is relatively infrequent, and clinical trails are often based on small-sized samples. The aim of this study was to define the "gold standard" therapy of active gastric ulcer. We included all single- or double-blind clinical trials on the short-term treatment of gastric ulcer. All the articles published over the period 1977-1994 were reviewed. Meta-analysis was done with both fixed and random effect models; results were shown using Galbraith's radial plot. Forty-eight papers comprising 52 studies were evaluated. Cimetidine, ranitidine, and famotidine proved significantly better than placebo [odds ratio (OR) and 95% confidence interval (CI 95%) at four to six weeks were: 2.67 (2.03-3.52), 3.94 (2.28-6.80), 1.76 (1.08-2.88), respectively]. Cimetidine and ranitidine had results comparable with the newer H2 blockers [OR (CI 95%) at four weeks: 1.16 (0.91-1.47), 1.11 (0.80-1.55), respectively]. H2 blockers were proved comparable with either sucralfate [OR (CI 95%) at eight weeks: 0.81 (0.37-1.79)] or bismuth [OR (CI 95%) at four to six weeks: 0.67 (0.37-1.20)]. Omeprazole is more effective than H2 blockers [OR (CI 95%) at four weeks: 2.00 (1.57-2.55)]. It is concluded that H2 blockers are preferred to either a placebo or sucralfate for short-term gastric ulcer treatment; the newer H2 blockers do not have significant advantages over the older types; omeprazole can be regarded as the "gold standard" for active gastric ulcer treatment.

Antacids↗

Do concomitant diseases and therapies affect the persistence of ulcer symptoms in the elderly?

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study; 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size.

Aged↗

High incidence of anti-FVIII antibodies against non-coagulant epitopes in haemophilia A patients: a possible role for the half-life of transfused FVIII.

The occurrence of antibodies (Abs) capable of inhibiting factor VIII (FVIII) coagulant activity is a severe complication in haemophilia A, leading to the inhibition of transfused FVIII activity. It is not known whether, or to what extent, post-transfusion antibodies may also arise against non-coagulant epitopes. Therefore we set up a system capable, in theory, to detect all the FVIII-induced antibodies by use of an enzyme-linked immunoassorbent assay (ELISA) based on coating human recombinant FVIII onto polystyrene microtitre plates. Serum samples from 23 patients affected by haemophilia A of different gravity (22 referred to our Centre and one to the Bari Centre) were analysed. Although only one patient was positive at Bethesda assay, the presence of antibodies in ELISA was detected in 39% of patients in variable degrees; transfusion with FVIII was found to induce a raise in antibody titre, arguing in favour of the specificity of the phenomenon. The clinical relevance of these non-inhibitory antibodies was evaluated in three patients; although half-life did not show any change in the patients without or with low amount of antibodies, FVIII clearance was found enhanced in the patient displaying high titre antibodies. We propose detection of anti-FVIII antibodies by ELISA when routinely assessing haemophilia A patients.

Adolescent↗

Azithromycin for the cure of Helicobacter pylori infection.

OBJECTIVES: Azithromycin, a new antibiotic chemically related to erythromycin, has been proposed for the cure of Helicobacter pylori, achieving high gastric tissue levels (above the MIC for H. pylori) after oral administration. The aim of the study was to establish whether azithromycin plus metronidazole in association with either omeprazole or bismuth subcitrate is useful in curing H. pylori infection of the stomach. PATIENTS AND METHODS: The study involved 132 dispeptic patients who proved to be H. pylori infected by antral and corpus histology (Giemsa, modified) and rapid urease test (CLOtest); the Sydney system was used to classify the gastritis. Sixty-three patients received bismuth subcitrate 120 mg q.i.d. for 14 days plus azithromycin 500 mg o.d. for the first 3 days plus metronidazole 250 mg q.i.d. for the first 7 days; 69 patients received omeprazole 40 mg for 14 days plus azithromycin 500 mg o.d. for the first 3 days plus metronidazole 250 mg q.i.d. for the first 7 days. Patients were well matched for common clinical variables. Cure of H. pylori infection was assessed by the same methods 2 months after completion of treatment. RESULTS: Eleven patients dropped out of the study, only one reporting side effects (nausea, vomiting, and epigastric pain). Cumulative "per protocol" cure rate was 66.1% (CI 95%, 58.5-75.3%). There was no statistically significant difference between the two treatment groups: 58.9% (CI 95% 48.4-74.6%) versus 72.3% (CI 95%, 60.7-82.5%). Intention to treat does not substantially modify results. Few side effects were recorded. Cured patients showed a significant reduction in the activity of gastritis. CONCLUSION: Azithromycin, combined with omeprazole and metronidazole, the cure rate of H. pylori was about 70%. The cure of H. pylori infection improves the activity of gastritis.

Adult↗

Thermodynamic analysis of the oxidative deamination of polyamines by bovine serum amine oxidase.

The effect of incubation temperature on the activity of bovine serum amine oxidase was studied using natural substrates of this enzyme, namely spermine and spermidine. The activity behavior was found to be rather complex and different from that observed using benzylamine as substrate. The enzyme is fully active after 3 min incubation at temperatures up to 60 degrees C, while at higher temperatures it shows an S-shaped irreversible decrease of the activity with a T50 of about 70 degrees C. The dependence of the kinetic parameters Kcat and Km on temperature was also studied in the range 5-66 degrees C, measuring the initial rates of oxidation of spermidine. The Arrhenius plot of kcat shows a continuous bend in the thermal stability range of the enzyme. This nonlinearity is due to the dramatic change of kcat activation entropy (from +11 eu at 8 degrees C, to -31 eu at 50 degrees C) and indicates that kcat is a composite constant, involving two or more successive steps characterized by different kinetic parameters. In the case of the ratio kcat/Km, which for natural substrates of bovine serum amine oxidase was shown that its dependence on ionic strength gives information on the influence of electrostatic field on k1 (Stevanato et al. (1994) Biochem. J. 299, 317-320), where k1 is the kinetic constant of interaction between the polyamine and the enzyme, the Arrhenius plot is linear in the range 12-45 degrees C, and an activation entropy of 18.8 eu was calculated at 37 degrees C. This value is in accord with a mechanism involving the formation of a polyamine-enzyme complex which is accompanied by neutralization of charges between the polycationic substrate and negatively charged groups of the enzyme.

Amine Oxidase (Copper-Containing)↗

Kinetic characterization of soybean seedling amine oxidase.

The kinetic characterization of soybean seedling amine oxidase (SSAO) and the effect of ionic strength and pH on the enzyme activity have been studied. A strong dependence of the activity on the carbon chain length of alpha-omega diamines, peaking at C8 and at C5, for Km and kc, respectively, was found. The analysis of ionic strength effects on activity showed a high sensitivity of Km and an insensitivity of kc to this parameter. This behavior and the different dependence of Km and kc on the carbon chain length suggest a two-stage equilibrium model for the oxidative deamination of polyamines by SSAO. The formation of the first intermediate (complex amine-enzyme) is controlled mainly by ionic interactions and by the structure of the polyamine, while the formation of the second intermediate depends only on the length of the carbon chain of the diamine. The molecular dissociation constants of the system soybean seedling amine oxidase-cadaverine were obtained from the dependence of kc, Km, and kc/Km on pH. A mechanism of the initial steps of reaction, involving a two-stage equilibrium model, is proposed.

Amine Oxidase (Copper-Containing)↗

CD25-negative hairy cell leukaemia: intracytoplasmic detection of Tac antigen and interferon-induced surface expression.

Hairy cell leukaemia (HCL) is a chronic lymphoproliferative disease of B-cell lineage. One of the peculiar immunophenotypic markers is the strong expression of the p55 chain of the interleukin-2 receptor (IL2R), recognized by anti-CD25 (or anti-Tac) monoclonal antibody. However, it is known that in rare cases CD25 may not be detectable, even when variant forms of HCL are excluded. The possibility has not been investigated that in these situations CD25 is present in the cytoplasm of the neoplastic cells. This paper describes a case in which the clinical, histological, and electron microscopic features were consistent with a typical HCL. Immunophenotype analysis showed the whole spectrum of markers of HCL, except for the expression of IL2R. The soluble form of the molecule was, however, increased in the patient's serum. Cytospin staining of the neoplastic B cells with anti-CD25 clearly demonstrated the presence of IL2R in the cytoplasm of hairy cells. When the cells were cultivated in vitro in the presence of interferon-alpha 2b, CD25 was detectable at the membrane level. These findings suggest that at least some cases of CD25-negative HCL may express cytoplasmic IL2R.

Aged↗

Failure of B cells of chronic lymphocytic leukemia in presenting soluble and alloantigens.

B-cell-type chronic lymphocytic leukemia (B-CLL) patients have immunological abnormalities of both B and T lymphocytes. Since T cell defects might depend upon a defective accessory function of neoplastic B lymphocytes, we analyzed the ability of peripheral blood B cells of seven B-CLL patients to stimulate allogenic normal T cells in mixed lymphocyte reaction (MLR) and to present tetanus toxoid (TT) to autologous T cells. In both systems, neoplastic B lymphocytes show a defective antigen-presenting function, which is more evident with disease progression. Such a defect cannot be ascribed to a decreased MHC class II molecule expression nor to an abnormal IL-1 beta production, but it can be partially accounted for by a low B7 expression. Pretreatment of neoplastic B cells with interleukin-4 (IL-4) restores primary MLR, but has little effect on the response to TT. The effect of IL-4 is not mediated by quantitative modifications of class II and B7 molecule expression or of IL-1 beta production.

Antigen Presentation↗

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↗

Kinetics of nitroxide spin label removal in biological systems: an in vitro and in vivo ESR study.

A systematic study on the disappearance of the electron spin resonance (ESR) signal of nitroxides based on six-or five-membered ring and bearing various charges was carried out in vitro and in vivo. The second-order kinetic rate constants of the reaction of spin probes with ascorbate were measured in vitro at various temperatures in phosphate buffered saline, and the relative activation energies were calculated. Clearance rates of the nitroxide radicals in rat brain homogenates and in blood indicate that the ascorbate contribution to nitroxide removal is about 50-70% in brain and 50-90% in blood. These rates can be easily calculated on the basis of the ascorbate concentration and of the second-order kinetic rate constants measured in phosphate buffered saline. ESR spectra acquired in vivo in rat head and tail, by an L-band resonator, indicated that the nitroxide decay rate is a first-order kinetic process in both domains and that the positively charged nitroxides are not retained in the brain, whereas the anionic and uncharged nitroxides are. Once nitroxides with piperidine ring enter the brain, their decay appears controlled mainly by ascorbate, while the ascorbate has a negligible influence on disappearance in brain of five-membered ring proxyl nitroxides.

Animals↗