Disappearance of FVIII inhibitors in a severe hemophilia A neonate after steroid treatment correlated with a cytokine shift toward a T-helper 2 pattern.
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Antibodies↗
Biomedical subjects
F Vianello
Publications and source records attributed to F Vianello.
Anti-beta2-glycoprotein I antibodies in patients with acute venous thromboembolism: prevalence and association with recurrent thromboembolism.
To establish the prevalence of antibodies against beta2-glycoprotein I (beta2GPI) in unselected patients with venous thromboembolism, as well as the association with antiphospholipid antibodies (aPL) and a history of previous thromboembolism, we investigated the presence of these antibodies in 227 consecutive patients with acute deep vein thrombosis or pulmonary embolism, of whom 63 were carriers of aPL with or without lupus anticoagulant (LA), and seven were carriers of LA alone. The presence of antibodies against beta2GPI was demonstrated in 19 patients [8.4%; 95% confidence interval (CI), 4.5-11.3%]. All of them belonged to the group of 63 patients with aPL (30.2%). A history of a previous thromboembolism was identified in 11 of the 19 patients with anti-beta2GPI antibodies (57.9%) and in 45 of the 208 patients without these antibodies [21.6%; odds ratio (OR)=4.98; 95% CI, 1.89-13.1; p<0.0005]. In the subgroup of patients with aPL and/or LA, the rate of recurrent thromboembolism among patients with anti-beta2GPI antibodies (11 of 19, 57.9%) was significantly higher than that observed in patients without these antibodies (15 of 51, 29.4%; OR=3.3; 95% CI, 1.1-9.83; p=0.28). We conclude that in patients with acute venous thromboembolism the prevalence of antibodies against beta2GPI is unexpectedly high. The presence of these antibodies seems to identify a subgroup of patients with antiphospholipid antibodies who have a peculiarly high risk of thrombotic recurrences. Further prospective studies are indicated to better define the role of anti-beta2GPI antibodies in the development of recurrent thromboembolism.
Acute Disease↗
An ESR assay for alpha-amylase activity toward succinylated starch, amylose and amylopectin.
The esterification of the three polysaccharides, starch, amylose and amylopectin was carried out in pyridine-DMSO by succinic anhydride. The carboxylic groups in the succinylated polysaccharides were measured by FT-IR spectroscopy. The succinic derivatives were tested as alpha-amylase (1,4-alpha-D-glucan glucano hydrolase, E.C. 3.2.1.1) substrates. A colorimetric assay of the alpha-amylase activity indicated that this enzyme is active on succinic esters of starch and amylose and that the activity shows a linear decrease with the number of succinic units introduced into the polysaccharide. Since the colorimetric test was not suitable for the detection of the alpha-amylase activity when succinylated amylopectin was the substrate, we set-up an assay based on the labeling by a paramagnetic probe of the free carboxylic groups of succinylated polysaccharides. The kinetics of the alpha-amylase reaction were monitored by ESR spectroscopy through the increase of the mobility of the paramagnetic probe. The spin label used was the commercially available 4-amino-tempo. By this method we demonstrated that alpha-amylase is active on succinylated amylopectin. The utility of the assay for monitoring alpha-amylase activity when other methods (i.e. colorimetric tests) fail, is discussed.
Amylopectin↗
Purification and characterization of amine oxidase from pea seedlings.
A novel, simple, and rapid procedure for the purification of pea seedling amine oxidase is reported. The crude enzyme, obtained by ammonium sulfate fractionation, was purified in two steps: the first one by anion-exchange chromatography and the second one by affinity chromatography. The first chromatography step was carried out on a diethylaminoethyl-cellulose column. By lowering the amount of protein loaded on the column and the buffer concentration it was possible to obtain an enzyme pure at 95% (sp act 1.2 microkat/mg). To achieve a higher degree of purification various affinity resins were prepared and tested. The resins were obtained by covalent immobilization of polyamines on Sepharose according to three different procedures. The best results were obtained with 6-aminohexyl-Sepharose 2B, prepared using CNBr as coupling agent, and eluting the enzyme by a solution containing 1, 4-diaminocyclohexane. This last compound was found to be a relatively strong competitive inhibitor of the oxidative deamination of cadaverine catalyzed by pea seedling amine oxidase (Ki = 32 microM). According to this procedure an electrophoretically homogeneous enzyme, characterized by a specific activity of 1.63 microkat/mg, was obtained.
Amine Oxidase (Copper-Containing)↗
Enzyme mimics complexing Cu(II) ion: structure-function relationships.
Five peptides containing (His-X2)-His or (His-X3)-His motifs have been designed and synthesized to coordinate Cu(II). Structural information was obtained by various spectroscopic techniques and was used as constraint to search for local conformational energy minima by molecular mechanics. Thermodynamic stability constants of the Cu(II) chelates was obtained by 19F-NMR. The synthesized Cu(II)-peptide chelates were tested as catalysts of some important red-ox processes occuring in biological systems, in particular oxidation of ascorbate and dismutation of superoxide ion. The catalytic efficiency of the five chelates was much lower than that of ascorbate oxidase. On the contrary, two of them showed kinetic constants for superoxide dismutation about one order of magnitude lower than that of the enzyme Cu,Zn superoxide dismutase. In both cases, the catalytic properties were dependent on the peptide sequence. The relationships between structure and activity are discussed to find the structural parameters crucial for catalytic activity that can be modulated by appropriate design and synthesis of the peptides.
Amino Acid Sequence↗
Serological markers of autoimmunity in patients with hemophilia A: the role of hepatitis C virus infection, alpha-interferon and factor VIII treatment in skewing the immune system toward autoreactivity.
The aim of this study was to investigate whether the immune system of patients with hemophilia A is skewed toward an aspecific activation and to identify the causative factors. It is well known that an immune derangement does exist in patients with hemophilia A. At least three factors potentially play a role: hepatitis C virus (HCV) infection, alpha-interferon therapy and the administration of factor VIII (FVIII). Sixty human immunodeficiency virus (HIV)-negative patients with severe or moderate hemophilia A were studied retrospectively. The serological markers of autoimmunity were evaluated and the results correlated with anti-HCV antibodies, FVIII treatment and alpha-interferon therapy. The role of these factors in the development of the anti-FVIII antibody was estimated concomitantly. The prevalence of autoantibodies and anti-FVIII antibodies was higher in HCV-positive than in HCV-negative patients before any treatment, although the difference was not statistically significant. The administration of FVIII further influenced the development of autoantibodies both in HCV-negative and HCV-positive patients, with no difference being observed between the two groups. As expected, fewer HCV-negative than HCV-positive patients developed anti-FVIII antibodies after administration of FVIII (31.8% versus 38%, respectively). Therapy with alpha-interferon did not seem to enhance significantly the risk of developing autoantibodies nor anti-FVIII antibodies. We observed a high prevalence of humoral signs of autoimmunity among patients with hemophilia A. Treatment with FVIII concentrate is probably the most important triggering factor. Monitoring these patients for autoimmune manifestations is recommended.
Adolescent↗
Continuous flow immunosensor for atrazine detection.
The hapten atrazine was detected under continuous flow conditions using a micro-column which contained immobilized monoclonal antibodies (Ab) against atrazine and atrazine labeled with alkaline phosphatase (An*). The equilibrium of the antibody-hapten system, was achieved by a continuous flow of the tracer An* through the micro-column containing the immobilized antibodies. The activity of the tracer was monitored continuously, after the micro-column, by an amperometric detector using p-hydroquinone phosphate as substrate. When pulses of unlabeled atrazine (An) were added to the An* flowing continuously through the micro-column, An* bound to the antibody was displaced, with a consequent change of the detector signal. By this method atrazine concentrations in the range 9-180 micrograms/l were monitored under conditions of continuous operation. Since the equilibrium condition for the system Ab-An* was continuously restored by the flow of An* through the micro-column the regeneration of the antibody was not required.
Animals↗
Myasthenic syndrome and oligoclonal lymphocytosis: evolution into chronic lymphocytic leukemia.
We report a patient with myasthenic syndrome who, 2 years after diagnosis, developed an oligoclonal lymphocytosis. This disorder was sustained by both kappa+ and lambda+ CD5+ B-cell clones; over the following year, the white blood cell count increased and phenotypic characterization revealed a clear imbalance in the immunoglobulin light chain ratio (84% kappa+). Accordingly, persistence of a kappa+ B-cell clone was disclosed by molecular analysis of immunoglobulin heavy chain gene rearrangements. Our results may suggest that prolonged immune system stimulation due to an autoimmune disease can drive a benign lymphoproliferation into a B-cell neoplastic process.
B-Lymphocytes↗
Optimal PPI-based triple therapy for the cure of Helicobacter pylori infection: a single center comparison of four 14-day schedules.
BACKGROUND: Helicobacter pylori eradication is accomplished using a wide array of drugs combined in a multitude of dosage schedules. The aim of the present study was to define the best 14-day eradication schedule using a PPI plus either two antibiotics or one antibiotic and bismuth. MATERIAL AND METHODS: For this study, 367 subjects (198 males, 169 females, age 22-87 years) with document H. pylori infection of the stomach were recruited from out-patients of the Gastroenterology Department of the Venezia Hospital. In all patients, H. pylori infection was identified by histology and the CLO-test. Patients were treated as follows: 1) PPI (P) plus clarithromycin (C) 250 mg plus amoxicillin (A) 1000 mg bid (P + C + A); 2) P plus C plus bismuth subcitrate (B) 120 mg qid (P + C + B); 3) P plus C plus tinidazole (T) 500 mg bid (P + C + T); and 4) P plus A plus T bid (P + A + T). After two months, an upper gastrointestinal endoscopy was repeated for end point histological evaluation and the CLO- test. Positivity of one of the two methods was considered sufficient to define H. pylori as "not eradicated". STATISTICS: Chi-squared test and Fisher exact test. RESULTS: Thirty-three subjects dropped out (six due to adverse events). P + C + B was proven significantly less effective than P + C + A, P + C + T and P + A + T, eradication rates being, respectively, 75.0%, 90.5%, 87.6%, 92.0%, (p = .005, per protocol analysis). CONCLUSIONS: All PPI-based triple therapies tested in this study were effective in curing H. pylori infection; however, P + C + B resulted in rates too low (< 85%) to be recommended. P + C + A and P + A + T resulted in the high cure rates and thus may be considered the treatment of choice.
Adult↗
Low dose of clarithromycin in triple therapy for the eradication of Helicobacter pylori: one or two weeks?
The aims of this pilot study were: (i) to compare the efficacy of low-dose clarithromycin (250 mg twice daily) for 1 or 2 weeks; and (ii) to evaluate possible therapeutic advantages in associating the low-dose clarithromycin with an anti-secretory agent or tripotassium dicitrate bismuthate (De Nol; Yamanouchi Pharm, Corugate Milano, Italy). A prospective, randomized, open trial was carried out on consecutive outpatients with dyspeptic symptoms and Helicobacter pylori infection. We enrolled 129 patients in one of the following schedules: (A) De Nol 120 mg q.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; (B) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; or (C) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 1 week. Results were evaluated by Per Protocol (PP) and Intention-To-Treat analysis (ITT). Eradication rate was 100% after treatment A, 92.6% after treatment B and 86.5% after treatment C by PP and 83.3, 75.7, and 68.1%, respectively by ITT. Side effects were reported by 16 subjects: 26.6% in group A; 9.1% in group B; and 7.5% in group C; in two cases side effects led to the withdrawal of the treatment. In conclusion, 500 mg clarithromycin per day in association with omeprazole and metronidazole, for 1 week gave comparable results to the same schedule for a 2 week period. The use of clarithromycin with bismuth and metronidazole produced a therapeutic gain compared with both of the anti-secretory schedules, although this was not statistically significant.
Adult↗
Detection of B-cell monoclonality in fine needle aspiration by PCR analysis.
Cytologic examination of fine-needle aspiration (FNA) sometimes fails to diagnose the malignant nature of B-cell proliferations. In this study we analyzed the Ig gene rearrangement of 49 FNA samples by polymerase chain reaction (PCR) in order to evaluate whether molecular analyses can improve the accuracy of FNA. Twenty-six patients had non-Hodgkin's lymphoma, 11 had reactive lymphoid diseases, 5 had chronic inflammation and 7 had carcinoma. A semi-nested PCR was performed using an oligoprimer specific for consensus sequences of the V regions (FR3A) and two oligoprimers derived from conserved sequences of the J regions (LJH and VLJH). Histologic examination always followed the molecular and cytologic analysis. The sensitivity of PCR and FNA morphological examination in detecting a neoplastic pattern was 92% and 78%, respectively. When samples were considered inadequate for cytologic examination, PCR always reached a diagnosis consistent with the histologic features. Our results demonstrate that PCR analysis of FNA specimens is a reliable and sensitive method capable of enhancing the diagnostic accuracy of cytologic examination.
B-Lymphocytes↗
Contraceptive and therapeutic effectiveness of two low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsute patients.
OBJECTIVE: To compare the effectiveness of two very low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsutism. PATIENTS: Eighteen hirsute women were randomized into two different regimens of cyproterone acetate and ethinylestradiol in a reverse sequential pattern: group 1 (0.28 mg ethinylestradiol monthly), group 2 (0.32 mg ethinylestradiol monthly). Both groups received 12.5 mg/day cyproterone acetate for the first 10 days of treatment each month. MAIN OUTCOME MEASURES: Hirsutism scores were measured according to the Ferriman and Gallwey scoring system and side-effects and complications were recorded during the 6 months of therapy. Ovulation was monitored by radioimmunoassay of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone levels. The pituitary response was studied using a gonadotropin releasing hormone test. RESULTS: Hirsutism scores decreased significantly in both groups at the end of the 6 months (-30%). All patients were anovulatory, as documented by the reduction of the LH, FSH, estradiol and progesterone levels. Pretreatment basal LH and FSH levels were higher than LH and FSH levels during the treatment. Side-effects were observed only occasionally with some differences between the two therapeutic regiments. CONCLUSION: Both treatments greatly improve hirsutism, reduce clinical problems and side-effects, guarantee both anovulation and contraceptive effectiveness and afford an optimal control of the menstrual cycle.
Adult↗
Prevalence and patterns of symptomatic thromboembolism in oncohematology.
BACKGROUND AND OBJECTIVE: Approximately 15% of patients with cancer will experience a thrombotic episode at some time. Some patients are at particularly high risk depending on the histology of the malignant disease. The aim of the study was to determine the actual prevalence of thrombotic episodes in oncohematologic patients. DESIGN AND METHODS: We conducted a retrospective cohort analysis on a total of 515 patients that were admitted to the out-patients clinic (Institute of Medical Semeiotics) from January 1, 1986 to January 31, 1996. Two main groups were selected for this study: 133 patients suffering from a myeloproliferative disorder and 382 patients affected by a lymphoproliferative disorder. Follow-up lasted a median of 33 months in both groups (range 3-144 months). The difference between the observed events for each group was estimated by the odds ratio and chi square. Age and sex distribution were estimated by the Mann-Whitney test. Distribution of overall survival was estimated by the Kaplan-Meier method and compared between groups (DVT patients and non DVT patients) by the log-rank test. RESULTS: Twenty-three patients experienced a venous thrombotic disorder. The prevalence of deep vein thrombosis (DVT) in myeloproliferative and lymphoproliferative disorders was 8.27% (n = 11) and 3.14% (n = 12) respectively (odds ratio = 0.36; 95% CI = 0.14-0.90; chi-square = 4.94 p = 0.028). DVT was apparently idiopathic in 17 cases. In 4 patients another cancer was present; in the remaining 2 patients the thrombotic episode was associated with other predisposing factors. Although 7 of the 23 patients with DVT died, we cannot find any difference in the overall survival compared to oncohematologic patients who did not experience DVT. INTERPRETATION AND CONCLUSIONS: The prevalence of symptomatic DVT in the oncohematological patients is lower than reported for solid tumor. Patients affected by myeloproliferative disease have a higher risk of developing thrombosis. DVT if well-treated does not influence the survival of oncohematological patients.
Adolescent↗
Clinical and laboratoristic remission after cryosupernatant plasma exchange in thrombotic thrombocytopenic purpura.
We describe a case of thrombotic thrombocytopenic purpura (TTP) resistant to conventional therapy with fresh-frozen plasma (FFP)-plasma exchange (PEX) as well as to steroids, immunoglobulins, vincristine, dipyridamole, dextran and iloprost, achieving complete remission with cryosupernatant-plasma exchange. Our case shows the effectiveness of cryosupernatant PEX, when FFP-PEX and alternative therapies have failed.
Adult↗
[Phenotypic changes in mucin-secreting cells in the ileal neobladder mucosa: a metaplastic or precancerous lesion?].
Colonic metaplasia with shifting from sialo-to sulfomucins was observed in 10/18 patients with ileal orthotopic neobladder; their median follow-up was 59 months. There is a significant statistical relationship (p = 0.002) between Colonic Metaplasia and a follow-up longer than 14 months. Diversion Cancer is nowadays a practical problem and probably urologists will be confronted with it in the future more than at present. A modification of established attitudes as regards urinary diversion in standard situations (i.e., 60 over years old patients with invasive bladder cancer) don't seems, at present, justified, although our study confirms the suspicion that ileal neobladder could be considered theoretically at risk for cancer onset.
Aged↗
Strategy for the retreatment of failed Helicobacter pylori eradication therapy: a case series.
BACKGROUND: Helicobacter pylori eradication therapy can be unsuccessful in 5 to 20% of patients. AIM: To investigate the validity of a strategy using triple therapies for the retreatment of patients with eradication failure, avoiding retreatment with antibiotics prone to induce resistance after use in the first treatment. PATIENTS AND METHODS: From a consecutive sampling of 108 patients still Helicobacter pylori-positive after a first course of antibiotic-based treatment, 74 (68.5%) agreed to a second course of triple therapy. Group 1 (N = 17): treatment failures on an imidazole (1)-based therapy were retreated with clarithromycin (C)-based regimen; Group 2 (N = 28): failures on a C-based therapy with an I-based regimen; Group 3 (N = 7): failures on an IC-based therapy using an I-based regimen and Group 4 (N = 22): failures on a non-I/non-C based therapy with either an I-based, C-based or IC-based regimen. The presence of Helicobacter pylori was assessed by histology and the CLO-test at study entry and two months after stopping therapy. RESULTS: Nine patients were withdrawn from the study (12.2%) due to a lack of end point endoscopy. Helicobacter pylori was cured after the second course of therapy in all but seven patients [10.7% failure by Per Protocol analysis, 21.6% by Intention-To-Treat analysis]. No statistically significant differences were found between the four groups (Group 1: 92.9% PP, 76.5% ITT; Group 2: 90.9% PP, 71.4% ITT; Group 3: PP and ITT 85.7%; Group 4: PP and ITT 86.4%). Minor adverse events were experienced in nine, none of whom required withdrawal from the drug therapy. CONCLUSIONS: A second course of triple therapy with alternate antibiotics effectively eradicated Helicobacter pylori, with only very few treatment failures. This suggests that the therapeutic strategy employed may be recommended.
Adult↗
Deuterium distribution in lactate as tracer of metabolic pathways.
2H-NMR spectroscopy has been used to study the distribution of 2H atoms in brain lactate, after intraperitoneal injection of 2H2O. Information on brain metabolism was obtained from the ratio [(3-2H) lactate]/[(2-2H)-lactate] which was found very sensitive to the PO2 in the breathing air. The dependence of this ratio on the rates of metabolic pathways is an example of the possibility to use the distribution of 2H atoms in a molecule to probe metabolic flow through different pathways.
Air↗
Prevalence of anti-FVIII antibodies in severe haemophilia A patients with inversion of intron 22.
The aim of our study was to investigate whether haemophilia A patients with inversion of intron 22 are at high risk for non-inhibitory anti-FVIII antibodies development detected by ELISA. It is known that patients with severe forms of haemophilia A are more likely to develop anti-FVIII antibodies. The incidence of inhibitory anti-FVIII antibodies in patients with factor VIII gene inversion has been extensively evaluated, but if this defect has to be considered a predisposing factor is still debatable. Non-inhibitory anti-FVIII antibodies are attracting interest, due to the potential influence on FVIII half-life. Our data show that FVIII gene inversion was a major predisposing factor for anti-FVIII antibodies development.
Adolescent↗