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Biomedical subjects

M Ruggeri

Publications and source records attributed to M Ruggeri.

At least 55 records · Page 3Linked to original sources
PubMed1998

Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.

The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.

Adolescent↗
PubMed1998

No treatment for low-risk thrombocythaemia: results from a prospective study.

Essential thrombocythaemia (ET) is a chronic myeloproliferative disorder characterized by the occurrence of thromboembolic episodes, particularly in patients aged > 60 years or with a previous history of thrombosis, and/or by haemorrhages in patients with an exceedingly high platelet count. In these subgroups of patients the use of cytoreductive therapy is beneficial in terms of risk/benefit ratio. Only limited anecdotal data are available on the thrombotic or haemorrhagic risk and survival in young asymptomatic ET patients with a platelet count < 1500 x 10(9)/l. Therefore the optimal management of these patients is unknown. To assess the incidence of thrombosis and haemorrhages in this group of patients we carried out a prospective observational study in a cohort of 65 patients with ET, aged < 60 years, with no history of thrombosis or haemorrhage and platelet count < 1500 x 10(9)/l, and in 65 age- and sex-matched controls. Patients were not treated with cytoreductive therapy until the occurrence of thrombosis or haemorrhage. Arterial or venous thrombotic events were objectively documented both in cases and in controls. The median follow-up was 4.1 years, with an incidence of thrombosis in patients and controls of 1.91 and 1.50 cases/100 patient-years, respectively. The age- and sex-adjusted risk rate ratio was 1.43 (95% CI 0.37-5.4). Only three minor haemorrhagic episodes occurred in patients, with an incidence of 1.12 cases/100 patient-years. Pregnancy and surgery were not associated with thrombosis in these patients. We conclude that the thrombotic risk in young ET patients, with no thrombotic history and a platelet count < 1500 x 10(9)/l, is not increased compared to the normal population and that a conservative therapeutic approach should therefore be considered in these patients.

Adolescent↗
PubMed1997

Botulinum toxin in upper limb spasticity: study of reciprocal inhibition between forearm muscles.

To establish whether botulinum A toxin (BTX-A) acts on modifying reciprocal inhibition between forearm muscles in spasticity, 20 patients with post-stroke upper limb spasticity lasting for more than 1 year were studied. Clinical examination, physiotherapeutic evaluation, standardized video-tape assessment and electrophysiological testing (flexor carpi radialis muscle M and H responses with study of reciprocal inhibition) were performed at baseline and 2 weeks, 1, 2, 3, 4 months after BTX-A treatment. BTX-A induced a significant decrease of tone and an improvement of motility and functional status, with a significant decrease of the M wave and the H reflex. The reduction in both inhibitory phases of reciprocal inhibition did not change after BTX-A treatment differently from that reported in upper limb dystonia. These findings indicate that the efficacy of BTX-A in upper limb spasticity is mainly due to peripheral effects.

Aged↗
PubMed1997

Occurrence and clinical relevance of an interleukin-4 gene polymorphism in patients with multiple sclerosis.

An epistatic gene interaction has been advocated to explain disease susceptibility in multiple sclerosis (MS). Cytokine genes are possible candidates due to the central role played by cytokines in the regulation of the immune-mediated pathogenetic process leading to central nervous system demyelination in these patients. Since interleukin (IL)-4 gene polymorphisms have been associated with immune-mediated diseases, we have analysed the relationship between a variable number of tandem repeat polymorphism of the IL-4 gene and clinical and physiological features of 256 sporadic MS patients and 146 healthy controls. Genotype frequencies were similar between the MS group and healthy controls. However, in MS patients a positive and significant correlation (r = 0.91; p < 0.001) was found between the carriage rate of the IL-4 B1 allele (from 0.21 to 0.36) and age of disease onset. No association was found between IL-4 alleles and disease progression, sex or ethnic background of the patients. Our results show that the IL-4 B1 allele is associated with late onset of MS and therefore might represent a modifier of age of onset rather than a susceptibility factor for patients with MS.

Adult↗
PubMed1997

Low prevalence of thrombophilic coagulation defects in patients with deep vein thrombosis of the upper limbs.

While many studies have demonstrated the pathogenetic role of inherited deficiency of natural clotting inhibitors in patients in the development of deep vein thrombosis of lower limbs, no data are available on the prevalence of these abnormalities in patients with upper vein thrombosis. In this study, antithrombin III, protein C, protein S, plasminogen, resistance to activated protein C and factor V Leiden mutation were assayed in 27 consecutive patients with thrombosis of upper extremities. Only two patients (7.4%) showed a congenital defect (one patient with deficiency of protein C, confirmed by family study, and one patient with factor V Leiden mutation). Anticardiolipin antibodies were also measured and four patients (14.8%) had increased levels, confirmed on a subsequent occasion 3 months later. Eighteen out of 27 (67%) had a predisposing or triggering factor, thus emphasizing the role of physical stress in the development of upper vein thrombosis. At variance with what is observed in deep vein thrombosis of the lower limbs, inherited clotting abnormalities seem to be rarely responsible for upper vein thrombosis, whereas anticardiolipin antibodies and cancer are implicated in a significant proportion of cases.

Adolescent↗
PubMed1997

Inherited abnormalities of blood coagulation in juvenile stroke. A case-control study.

The nature of the relationship between inherited abnormalities of the clotting system and the occurrence of cerebrovascular accidents in young subjects is controversial. To evaluate the risk of cerebrovascular disease associated with such abnormalities, we analyzed a series of 23 consecutive patients in a case-control study with ischemic stroke proven by computerised tomography and aged below 45 years at admission, and a control group of 115 age- and sex-matched controls from the general population. No differences in antithrombin, protein C, protein S, heparin cofactor II, plasminogen or response to activated protein C were observed between cases and controls. None of the patients had a history of personal or familial thrombosis, and none had a reduction in the considered clotting factor below the reference range. We conclude that abnormalities of the clotting system are not associated with the occurrence of cerebrovascular abnormalities in the young and that routine screening for inherited thrombophilia is not appropriate in young patients with cerebrovascular disease.

Adult↗
PubMed1997

Apolipoproteins B and E, and angiotensin I-converting enzyme (ACE) genetic polymorphisms in Italian women with coronary artery disease (CAD) and their relationships with plasma lipid and apolipoprotein levels.

The XbaI, EcoRI and the signal peptide insertion/deletion (I/D) polymorphic sites of APOB gene, the CfoI polymorphic site of apolipoprotein E gene (APOE), and the insertion/deletion polymorphism of angiotensin I-converting enzyme (ACE) gene were studied using polymerase chain reaction (PCR) in 55 postmenopausal women with coronary artery disease (CAD) and in 119 control women of equivalent age. Patients and controls were recruited from the population of Rome, considered representative of Central and Southern Italy. There were no significant differences in allele frequencies between the two groups, though APOB X-, R- and I, APOE*3, and ACE D alleles were slightly more frequent in the cases than in the controls. The patients did not differ from the controls for plasma total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, and apoAI values, while they presented significantly higher levels of triglycerides and apoB, and lower apoE levels. TC, apoE, and apoB quantitative values, adjusted for age, varied significantly among APOB XbaI and APOE genotypes. APOB X-X- genotype was associated in patients with a significantly lower mean TC concentration than the other two genotypes pooled together. APOE 3-2 genotype in the controls had significantly lower TC levels with respect to the other two pooled genotypic classes and higher apoE levels compared to 3-3 and 4-3 genotypes. In the patients, 3-2 genotype had significantly lower apoB levels than the pooled 3-3 and 4-3 class. We conclude that in the Italian women the DNA polymorphisms studied in this work do not seem to be important risk factors for CAD occurrence; that apoE quantitation could be another useful parameter to identify subjects at risk of CAD; and that APOB X- and APOE*2 are the alleles that most influence the interindividual plasma lipid variation among CAD female patients.

Aged↗
PubMed1997

[Prevention of hemorrhage and dental treatment of patients with congenital or acquired coagulopathies].

The physiopathology of the hemorrhagic blood coagulation disorders caused by genetic or aquired problems is described. Among the former the most frequent ones include the hemophilia of type A-B and the von Willebrand disease, among the latter the use of oral anticoagulant constitutes the most frequent cause. If the are not subjected to an adequate haemostatic prophylaxis, both patients with hemophilia and von Willebrand disease present a serious haemorrhagic risk as a consequence of dental practice. As far as the use of anticoagulants is concerned, a periodical monitoring of the time of prothrombin (PT) is needed to find the right dosage (TP between 20%-30% or INR--international normalized radio between 2 and 3.5). Values over this range cause an increase of the hemorrhagic risk, while lower values involve an increased risk of thrombotic events. According to the authors the patients with the hemorrhagic diathesis show a precise handicap, caused both by his illness and by environmental elements, such as the fear of doctors for the haemorrhagic complications consequent to a therapeutical operation, fear that often leads to neglect important medical measures, in particular dental measures. The specialized dental surgeon has to mantain a strict cooperation with the hematologist in order to arrange an appropriate procedure of the prophylaxis. As far as the hemostatic prophylaxis is concerned, the use of the dermopressin (DDAVP), in patients with hemophilia A and von Willebrand disease, guarantees the realisation of dental practice without hemorrhagic risk. On the contrary, the use of the tranhexanic acid on patients in an anticoagulant oral treatment gives hemostatic security and makes it possible to carry on the therapy and the out-patient treatment.

Blood Coagulation Disorders↗
PubMed1996

Assessment of exposure to inorganic arsenic, a human carcinogen, due to the consumption of seafood.

To assess whether regular consumption of seafood, particularly fish and shellfish, by humans may lead to an overexposure to inorganic arsenic, a well-established human carcinogen, the urinary excretion of the relevant As metabolites (Asi, inorganic form; MMA, monomethylarsonic acid; DMA, dimethylarsinic acid) was compared in groups of subjects with different seafood consumption habits and in volunteers after ingestion of a known amount of seafood arsenicals. Studies of Italian cohorts, involving five groups of +/-30 subjects with different seafood consumption habits, and balance studies in Belgian volunteers failed to show a biologically significant absorption of inorganic arsenic either present as such in the food or formed from organoarsenicals during cooking or digestion. The results suggest that the digestion of some seafood, especially mussels, may increase the urinary excretion of the dimethylated arsenic metabolite. Therefore, the biological monitoring of exposure to inorganic arsenic in an industrial context should mainly rely upon specific measurement of the unmetabolized form when recent ingestion of seafood cannot be excluded.

Arsenic↗
PubMed1996

Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry.

PURPOSE: To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies. PATIENTS AND METHODS: Three hundred sixty consecutive patients (118 males, 242 females, median age 39 years [range 2 to 78]) fulfilling the currently accepted criteria for diagnosis of lupus anticoagulant (LAC) (n = 326) and/or raised immunoglobulin G anticardiolipin antibodies (IgG ACA) (n = 185) were collected from 16 Italian institutions and prospectively observed for a median of 3.9 years (range 0.5 to 5). Main endpoints were the occurrence of arterial or venous thrombosis, the outcome of pregnancies, and any severe complications leading to hospitalization or death. RESULTS: Thirty-four patients developed a thrombotic complication, with a total incidence of 2.5% patient-years. Multivariate logistic regression analysis identified two independent risk factors for thrombotic events: a previous thrombosis (RR 4.9; 95% CI, 1.76 to 13.7; P < 0.005) and IgG ACA titer above 40 units (RR 3.66; 95% CI, 1.24 to 10.8; P < 0.01). A total of 28 pregnancies were observed in 25 women and 11 (39%) were abortive. Adverse pregnancy outcomes were significantly more frequent in women with a history of miscarriage or vascular occlusion (9/16, 56%) than in asymptomatic women (2/12, 17%) (P = 0.035). Four patients developed non-Hodgkin's lymphoma during the follow-up. Eighteen patients died. Vascular events and hematological malignancies represented the most frequent causes of death (n = 5 for each). CONCLUSIONS: The present study shows that: (a) previous thrombosis and ACA titer > 40 U are independent predictors of thrombosis; (b) history of miscarriage or vascular disease is significantly associated with adverse pregnancy outcome; (c) hematological malignancies can develop during follow-up in patients with antiphospholipid antibodies.

Adolescent↗
PubMed1996

Clinical usefulness of desmopressin for prevention of surgical bleeding in patients with symptomatic heterozygous factor XI deficiency.

Heterozygous factor XI (FXI) deficiency is sometimes associated with a significant bleeding tendency. Fresh frozen plasma of FXI concentrates are the mainstay of treatment in patients with a clear bleeding history, especially prior to surgery. However, these treatments are not completely free of risk. Furthermore, thrombosis has been reported in patients with FXI deficiency infused with FXI concentrate. No data are available on the possible efficacy of desmopressin in these patients. Two patients with a clear bleeding history associated with FXI deficiency and no additional haemostatic defects agreed to be treated with desmopressin before carpal tunnel surgery and dental extraction. The reduced basal FXI activity and antigen levels slightly increased after infusion, reaching borderline values. No bleeding was observed after surgical procedures. Desmopressin treatment seems a reasonable and useful choice in symptomatic, heterozygous FXI-deficient patients, thus reducing the cost of treatment, the risk of transmission of blood-borne viruses, and of thrombosis.

Blood Loss, Surgical↗
PubMed1996

The natural history of monoclonal villous lymphocytosis: a chronic lymphoproliferative disorder of CD11c+ B cells.

The long-term outcome of three asymptomatic subjects with isolated persistent lymphocytosis of monoclonal villous B-cells (MVL) is reviewed. After 7.5 years, evolution to a splenic lymphoma variant (SLVL) was documented in only one patient, accompanied by a loss of interleukin-1beta autocrine production, confirming that MVL can be an early form of a malignant disorder. The clinical course was uneventful in the other two cases; a progressive lowering of lymphocyte count being noted in one. While the strict relationship of MVL to SLVL is confirmed, time to progression is unpredictable and the mechanisms by which it occurs still remain to be elucidated.

Aged↗
PubMed1996

Molecular diagnosis and clinical relevance of t(9;22), t(4;11) and t(1 ;19) chromosome abnormalities in a consecutive group of 141 adult patients with acute lymphoblastic leukemia.

Over a time period of five years leukemic blast samples from 141 consecutive patients with adult ALL were referred to our laboratory, for molecular evaluation of chromosome abnormalities. The t(9;22), t(4;11) and t(1;19) which are most commonly found in adult ALL with a B-precursor phenotype were molecularly analyzed by similar RT-PCR based protocols. BCR-ABL transcripts generated by the t(9;22) translocation were demonstrated in 36 patients (25%) and were restricted to the 109 patients with B precursor ALL (33% of this group). Of 83 patients showing a, common phenotype (CD10+), 34 were BCR-ABL positive (41%) whereas only 2 out of 26 with Null ALL (HLADr+, CD19+, CD10) were positive. Interestingly, the percent of BCR-ABL positive CD1O+ ALL increases significantly with age being 20% in patients less than 30 years old and more than 50% in older patients. None of the T-ALL (24 patients) and B-ALL (8 patients) were positive. The majority of cases (67%) showed the p190 gene subtype. The cytogenetic diagnosis of Philadelphia chromosome was always confirmed by the molecular analysis and this approach allowed for the detection of the presence of the BCR-ABL rearrangement in 26 patients when a negative result or no metaphases were obtained. The complete remission rate was similar among BCR-ABL positive and negative patients but a shorter remission duration was observed in those showing molecular evidence of t(9;22) and this finding was significantly evident in CD1O+ ALL patients. By means of comparison, in most of the same adult ALL patients, we analyzed the yet unrecognized prevalence of the t(4;11) and t(1;19) translocations by the molecular analysis of their chromosomal breakpoints. Rearrangements of the ALL-1 gene on 11q23 band and ALL- l1AF.4 fusion transcripts specific for the t(4;11) were demonstrated in 7 out of the 21 Null ALL investigated, with no additional positive cases found among the other ALL subgroups. Overall the clinical behavior of t(4; 11) positive patients was dismal with a very short CR duration. Chimeric E2A-PBX1 transcripts generated by the t(1;19) were found in only two of the 87 B-precursor ALL analyzed. The presented results provide further evidence for the utility of RT-PCR based methods for the molecular diagnosis of chromosome translocations in ALL. The identification of such abnormalities can significantly contribute to the identification of more appropriate therapeutic options for standard and high risk ALL patients

Adolescent↗
PubMed1996

[Henoch-Schonlein purpura. Considerations about 95 pediatric cases].

The authors present their considerations about 95 cases of Henoch-Schonlein purpura, occurring in children between 6 months and 14 years old, admitted in their Pediatric Division over the years 1984-1994. The authors have studied the risk factors, the typical clinical picture including purpuric rash, abdominal pain and arthritis or arthralgia, the atypical clinical presentations, the renal involvement and its sequelae, the therapy and the recurrence. They also have examined the presence of group A Strepto beta in their children with Henoch-Schonlein purpura. The authors emphasize the distinction between the lack of serious sequelae on long-term follow-up in their children and other reports of the literature.

Anti-Inflammatory Agents↗
PubMed1995

Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis.

BACKGROUND: Abnormalities in the number and function of platelets may contribute to thromboembolic complications in patients with essential thrombocythemia. We assessed whether maintaining the platelet count below 600,000 per cubic millimeter with hydroxyurea reduces the incidence of thrombosis in patients with essential thrombocythemia and a high risk of thrombosis. METHODS: A total of 114 patients with essential thrombocythemia (77 women and 37 men; median age, 68 years; range, 40 to 85) and a median platelet count of 788,000 per cubic millimeter (range, 533,000 to 1,240,000 per cubic millimeter) were randomly assigned to receive hydroxyurea (56 patients) or no myelosuppressive therapy (58 patients). Ninety-seven (85 percent) were over 60 years old, and 52 (46 percent) had had thrombosis. The two groups were matched for age, sex, and platelet count at randomization. Antiplatelet prophylaxis with aspirin or ticlopidine was not stopped. Follow-up lasted a median of 27 months in both groups. RESULTS: Two patients (3.6 percent) treated with hydroxyurea had thrombotic episodes (one stroke and one myocardial infarction), whereas 14 patients (24 percent) in the control group had thrombotic episodes (one stroke, five transient ischemic attacks, five peripheral arterial occlusions, one deep-vein thrombosis, and two cases of superficial thrombophlebitis). The difference (20.4 percentage points; 95 percent confidence interval, 8.5 to 32 percent) was statistically significant (chi-square with Yates' correction, 8.3; 1 df; P = 0.003). CONCLUSIONS: Hydroxyurea is effective in preventing thrombosis in high-risk patients with essential thrombocythemia.

Adult↗