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Biomedical subjects

A Girolami

Publications and source records attributed to A Girolami.

At least 145 records · Page 8Linked to original sources
PubMed1998

Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?

The pathogenesis of thrombocytopenia associated with TAD and the occurrence of overlapping traits between TAD and AITP are still a matter of debate. For this reason, we investigated for the presence and specificity of platelet and thyroid autoantibodies in 18 TAD patients with thrombocytopenia, 19 TAD patients without thrombocytopenia and in 22 patients with primary AITP without clinical signs of TAD. Platelet-associated IgG and/or specific circulating platelet autoantibodies were detected in 83% of patients with TAD and thrombocytopenia, in 10% of patients with TAD without thrombocytopenia and in 86% of patients with primary AITP. The reactivity of serum autoantibodies, assayed by MoAb immobilization of platelet antigens (MAIPA), was directed against platelet glycoproteins Ib and/or IIb/IIIa in 50% of the patients with TAD and thrombocytopenia, as in 46% of the patients with primary AITP. Thyroid autoantibodies were found in 89% of patients with TAD and thrombocytopenia, in 95% of patients with TAD without thrombocytopenia, and in 18% of patients with primary AITP. Thyrotropin (TSH) levels determined in three of four AITP patients with thyroid autoantibodies revealed a subclinical hyperthyroidism in one patient. The present study supports the autoimmune aetiology of thrombocytopenia associated with TAD, since the prevalence and specificity of platelet autoantibodies are similar in TAD and primary AITP. The results indicate also that there exists an overlap between thyroid and platelet autoimmunity with or without clinical manifestations.

Adult↗
PubMed1998

A simple clinical model for the diagnosis of deep-vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process.

OBJECTIVES: We recently demonstrated the utility of a clinical model combined with ultrasonography to assist the diagnostic approach in patients with suspected deep-vein thrombosis (DVT). In this study we also sought to demonstrate that the model is useful with impedance plethysmography, a less accurate and less utilized diagnostic test. The original clinical model is slightly cumbersome to use; thus at the completion of the study we attempted to develop a simpler scoring system with a goal of maintaining accuracy. DESIGN: An open, nonrandomized, multicentre trial. SETTING: Three centres, two in Canada, and one in Italy. SUBJECTS: Ambulatory patients with suspected deep-vein thrombosis. INTERVENTIONS: All patients were assessed clinically to determine the probability for deep-vein thrombosis prior to performing impedance plethysmography and venography. We compared the accuracy of impedance plethysmography between the three pretest probability categories of high, moderate and low. All of the above were performed and interpreted by independent observers. When the study was completed, we revised the clinical model by first performing a simple regression analysis then a multiple logistic regression analysis; a scoring system was devised using the latter. RESULTS: Impedance plethysmography is significantly more sensitive and less specific for all DVT in patients with high pretest probability for deep-vein thrombosis (P = 0.001). The post- test probability (positive predictive value) for deep-vein thrombosis with an abnormal impedance plethysmography result was significantly different (P = 0.0001) between the three pretest probability categories. Multiple regression analysis has provided a new model with only nine variables and a simple scoring system. The retrospective application of the revised clinical model, which is simpler to use, suggests it will provide similar results as the original clinical model when combined with impedance plethysmography. The combination of impedance plethysmography and the clinical model suggests patients are likely to have false positive results if they have a low or moderate pretest probability for deep-vein thrombosis and false negative results if the pretest probability is high. The combination of a low pretest probability and a normal impedance plethysmography result may exclude the need for serial testing, and represented more than 50% of our patient population. CONCLUSIONS: The use of the clinical model in conjunction with impedance plethysmography would decrease the number of false positive and negative diagnoses and could markedly decrease the need for serial impedance plethysmography. Combining the clinical model with impedance plethysmography could overcome the fact that impedance plethysmography is clearly less accurate than venous ultrasound imaging. The use of the revised clinical model may increase acceptability and utility, but prospective testing is required before widespread use.

Diagnosis, Differential↗
PubMed1998

Acute coronary disease in essential thrombocythemia and polycythemia vera.

OBJECTIVES: The aim of this study is to report our experience on myocardial infarction (MI) in patients with essential thrombocythemia (ET) and polycythemia vera (PV). DESIGN: Patients with PV and ET consecutively diagnosed and followed in authors' Department between 1 July 1986 and 30 June 1996. SUBJECTS: Over the past 10 years we have followed 170 patients with ET and 149 with PV, diagnosed according to the Polycythemia Vera Study Group (PVSG) criteria. The patients were divided into 3 groups on the basis of the age at diagnosis (group A < 40, B 41-65, C > 65 years). INTERVENTIONS: In all patients with PV phlebotomies and/or myelosuppressive therapy were used to keep haematocrit level lower than 45%. Hydroxyurea was given to patients with ET with a positive history for major vascular complications or with an extreme thrombocytosis. Aspirin therapy (ASA) (100 mg per day) was administered in patients with microvascular disturbances or previous thrombosis (in patients with PV also in the presence of atherosclerotic risk factors). MAIN OUTCOME MEASURES: Frequency of MI in patients with ET and PV with and without ASA therapy. RESULTS: 9.4% of patients with ET and 11.4% of those with PV had MI. 17.6% of patients with PV were younger than 40 years at the moment of MI in contrast to 0% of those with ET. 75% of patients with ET and 70.6% of those with PV with MI had atherosclerotic risk factors such as smoking, hypertension, diabetes, dyslipidaemia. All patients with MI received ASA 100 mg daily after thrombosis and four of the ET group developed a transient ischaemic attack (TIA) afterwards. Four subjects with PV during the follow-up had TIAs and two peripheral arteriopathy in spite of ASA treatment. CONCLUSIONS: MI is less common in patients with ET younger than 40 years than in older patients. Association of MI and cardiovascular risk factors is frequent in patients with ET and PV. A low dose of ASA could be able to reduce the number of coronary thrombosis without increasing bleeding complications in patients with elevated platelet count and common atherosclerotic risk factors. However, a larger population must be evaluated to confirm our hypothesis.

Adult↗
PubMed1998

The evaluation of factor VIII binding activity of von Willebrand factor by means of an ELISA method: significance and practical implications.

One of the functions of von Willebrand factor (vWF) is to serve as a carrier of clotting factor VIII (FVIII). Deficiency of this function results in the von Willebrand disease (vWD) variant type 2N, which resembles hemophilia A. We describe a new sandwich enzyme-linked immunosorbent assay (ELISA) to study the ability of vWF to bind exogenous recombinant FVIII (rFVIII), in which anti-vWF-coated plates are incubated with plasma vWF, followed by exogenous FVIII and a peroxidase-coupled anti-FVIII antibody. Dose-response curves obtained using normal plasma vWF and purified normal vWF revealed a hyperbolic relationship between the optical density and the vWF concentration. The assay allows the quantification of FVIII binding with values expressed in U/dL; 100 U/dL was the amount present in normal plasma. The sensitivity and specificity of the method are demonstrated by its ability to measure binding levels as low as 1 to 2 U/dL and the fact that no FVIII binding was observed using plasma known to contain less than 1 U/dL vWF. To verify the accuracy of the assay, three patients with type 2N vWD with characterized vWF gene mutations were studied using an existing chromogenic assay and our ELISA. A patient who was homozygous for the R53W mutation and had no FVIII binding capacity according to the chromogenic method showed undetectable FVIII binding by ELISA. The remaining two patients, one who was homozygous for the R91Q mutation and one with compound heterozygosity for the R91Q and R53W mutations, showed markedly decreased FVIII binding by the chromogenic method and yielded ELISA values ranging from 4 to 8 U/dL. Therefore, although the two methods produce qualitatively similar results, the ELISA method offers the advantage of allowing quantification of the FVIII binding function. FVIII binding was also analyzed in 20 patients with type 1 vWD; we found a decrease of FVIII binding that was proportionate to the decrease in vWF levels, showing a normal FVIII binding activity/vWF molecule ratio. We define the binding activity measured by this assay as vWF:FVIII binding activity and propose its use in the functional analysis of vWF.

Adult↗
PubMed1998

Congenital deficiencies and abnormalities of prothrombin.

Prothrombin (factor II) deficiency was first described in 1947 by Quick et al., although the first prothrombin abnormality was reported in 1969 by Shapiro et al. The condition is still considered very rare. In spite of its rarity, the defect has allowed important improvements in our understanding of both congenital and acquired prothrombin deficiencies. The diagnosis of prothrombin deficiency or abnormality can be made using a combination of clotting, chromogenic and immunological assays. In cases of true deficiency, a parallel decrease in all these assays is observed, regardless of the activating agent. If discrepancies among the clotting assays are noted, particularly using viper venoms, a dysprothrombinemia should be suspected. Usually, activity levels less than 10% of normal are found in homozygotes, and between 40 and 60% in heterozygotes. Factor II levels in congenital dysprothrombinemias are more variable since one may encounter homozygotes, heterozygotes and compound heterozygotes between a heterozygous abnormality and heterozygous 'true' deficiency or between two distinct abnormalities. Usually the levels of factor II vary between 1 and 50% of normal. Antigen levels in congenital dysprothrombinemias will be normal, near normal or slightly decreased but always higher than the clotting counterpart. Cases with a parallel decrease in prothrombin activity and antigen should not be considered as examples of hypoprothrombinemia. The gene involved in the synthesis of prothrombin is located in chromosome 11. It is composed of 10 exons and 8 introns. Molecular biology studies have discovered several point mutations in some of the dysprothrombinemias. Bleeding manifestations may be severe in homozygous 'true' deficiency and may be more variable in dysprothrombinemias. Heterozygotes are usually asymptomatic. Prognosis is variable and generally in agreement with the prothrombin activity level. In homozygous true deficiency, hemarthroses and intracranial bleeding have been described. Substitution therapy is based on the administration of prothrombin complex concentrates or of plasma. The long half-life of prothrombin injected, about 70 h, allows the achievement of hemostatically effective levels (about 50% of normal) without difficulty.

Adolescent↗
PubMed1998

Glycocalicin in the diagnosis and management of immune thrombocytopenia.

We studied glycocalicin (GC), expressed as plasma GC concentration and as GC index (ratio to platelet count), in 129 thrombocytopenic patients (platelet count < 100 x 10(9)/l) and 60 sex- and age-matched controls. Seventy-two patients had idiopathic immune thrombocytopenia, 32 secondary immune thrombocytopenia, 8 microangiopathic thrombocytopenia and 17 thrombocytopenia secondary to bone marrow aplasia. Patients with immune thrombocytopenia (ITP) were also subclassified, according to their clinical behaviour, as having active disease or being in spontaneous or therapy-induced partial remission. A significant correlation was found between glycocalicin levels and platelet count both in normals and in patients with bone marrow aplasia (r = 0.75). ITP patients showed a GC index significantly higher than controls (6.02+/-7.87 vs. 0.9+/-0.2, p<0.001). When ITP patients with similar platelet count (30-50 x 10(9)/l) were studied, the mean level of GC and the GC index were significantly higher in those patients with active disease than in those in remission (0.97+/-0.38 vs. 0.58+/-0.17 microg/ml, p <0.05; 6.41+/-2.64 vs. 3.44+/-0.94, p<0.05, respectively). A longitudinal study performed in 10 patients with different subtypes of ITP suggested a positive correlation between GC index and the activity of the disease. The GC value and GC index were significantly higher in patients with microangiopathic thrombocytopenia than in controls (1.44+/-0.73 vs. 0.8+/-0.16 microg/ml, p < 0.01; and 18.77+/-22.23 vs. 0.9+/-0.2, p<0.001, respectively). The GC value was significantly lower in bone marrow failure (0.15+/-0.04 microg/ml, p<0.01) compared to controls, while no difference was observed in the GC index. Our data confirm that the GC index is helpful in differentiating thrombocytopenia due to increased platelet destruction from the one due to impaired production. In addition, the assay has been proven useful in the differential diagnosis of different ITP subtypes and their follow-up.

Adolescent↗
PubMed1998

Cerebral vascular accidents in young patients with essential thrombocythemia: relation with other known cardiovascular risk factors.

BACKGROUND AND PURPOSE: Since the advent of routine automated blood cell counts, an increased platelet count often is detected fortuitously in asymptomatic individuals. In the past, essential thrombocythemia (ET) was thought to be linked to an increase incidence of hemorrhagic complications, whereas thrombosis is now considered more frequently. Actually, the risk of thrombosis cannot be predicted in an asymptomatic patient with essential thrombocythemia. PATIENTS AND METHODS: A total of 41 young patients (age range, 18 to 45 years) affected by ET and diagnosed in agreement with the Polycythemia Vera Study Group criteria are reported. Common risk factors, such as hypertension, smoke, obesity, dyslipidemia, and diabetes, have been registered. Particular attention has been given to cerebral vascular accidents (CVA) both of the arterial and venous systems. Platelet number, platelet serotonin content, and platelet aggregation under collagen, adenosine diphosphate (ADP), and adrenalin stimuli were evaluated. RESULTS: Nine out of the 41 patients affected by ET had CVAs, four of which occurred in the venous system. No difference in platelet function tests has been observed between patients with or without CVA. Six out of the 9 patients with ET and CVA had at least one atherosclerotic risk factor: four were heavy smokers, one had hypertension, and one had hypertension and obesity. CONCLUSIONS: Cerebral vascular accidents are confirmed to be frequent in patients with essential thrombocythemia, even at a young age. However, the presence of at least one atherosclerotic risk factor associated with increased platelet number seems to favor thrombotic complications. In particular, cigarette smoking seems to be related to arterial CVAs in essential thrombocythemia.

Adult↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

A founder effect is proposed for factor XIII B subunit deficiency caused by the insertion of triplet AAC in exon III encoding the second Sushi domain.

We previously concluded that genetic defects in the B subunit of factor XIII were the basis for former Type I deficiency (i.e. factor XIII B subunit deficiency). When we examined an Italian patient with the disease at the DNA level, restriction digestion and sequencing analyses of amplified DNAs revealed that the proband and her family members possessed an AAC insertion within the codon for Tyr-80 in exon III in the gene for the B subunit. a nucleotide polymorphism (A-G) in its 3'-noncoding region in exon XII, and a short tandem repeat polymorphism of (TTTA9, in the 3'-flanking region. These mutations and 3'-polymorphisms were also identified in another Italian family reported in a previous study (10). suggesting that a founder effect is responsible for factor XIII B subunit deficiency in Italians.

DNA Transposable Elements↗
PubMed1998

Molecular bases of pseudo-homozygous APC resistance: the compound heterozygosity for FV R506Q and a FV null mutation results in the exclusive presence of FV Leiden molecules in plasma.

Pseudo-homozygous APC resistance, the condition resulting from compound heterozygosity for FV R506Q (FV Leiden) and quantitative FV deficiency, provides a natural model to study the interaction between procoagulant and anticoagulant defects. This paper reports a complete FV characterization of a pseudo-homozygous APC resistant thrombotic patient. The expression of the patient's non-Leiden gene was found to be severely impaired both at the mRNA and protein levels. In particular, only FV Leiden molecules were detected in the patient's plasma by immunoblotting, which accounts for the observed marked APC resistance. Analysis of the FV cDNA obtained by reverse transcription of platelet RNA revealed that the mRNA of the non-Leiden gene was extremely reduced in amount. A PAC clone containing the whole FV gene was used to design primers for a complete FV exon scanning. A 2-bp insertion at nucleotide 3706 in the large exon 13 of the non-Leiden gene, predicting a frame-shift and premature termination of protein synthesis, was identified as responsible for the FV defect. Failure to find any case of pseudo-homozygous APC resistance in a large sample (6,804) of blood donors suggests that this condition is extremely rare among normal controls and that its detection is favoured by the thrombotic risk that it may confer.

Aged↗
PubMed1998

4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep vein thrombosis.

A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression. A relationship between 4G/5G polymorphism and PAI-1 levels was found in patients with cardiovascular and metabolic diseases, but not in healthy subjects. In the present work we studied the distribution of PAI-1 4G/5G genotype and its relation to fibrinolytic capacity in 70 unrelated patients with deep vein thrombosis. Each patient was assayed before and after 20 min. Venous occlusion for euglobulin lysis time, t-PA antigen and activity, and PAI-1 antigen and activity. The prevalence of 5G homozygous carriers was significantly lower in patients than in controls (10% vs. 26%, p=0.009). The 5G allele frequency was reduced, even though not significantly, in DVT patients compared to healthy subjects (0.40 vs. 0.51, respectively). In the patient group, the mean PAI-1 antigen and activity levels were significantly higher than among controls and related to the 4G/5G polymorphism. In patients with 4G/5G and 4G/4G genotype a significant correlation was found between PAI-1 levels and the global fibrinolytic activity as evaluated by euglobulin lysis time. The prevalence of a reduced fibrinolytic potential due to PAI-1 excess was 45.7% among DVT patients. Moreover, the prevalence of PAI-1 induced hypofibrinolysis was strongly related to PAI-1 polymorphism, since it was significantly lower in 5G homozygous patients (28.6%) than in both 4G/5G carriers (55.3%, p <0.001) and 4G homozygous patients (57.9%, p <0.001). In conclusion, in patients with deep vein thrombosis the 4G polymorphism of PAI-1 gene promoter may influence the expression of PAI-1 and it should be taken into consideration as a facilitating condition for pathological fibrinolysis together with other environmental and genetic factors. Whether this has any significance in regard to the pathogenesis of venous thrombosis remains to be proven.

Adult↗
PubMed1997

Impairment of fibrinolytic potential in long-term steroid treatment after heart transplantation.

Thrombotic complications constitute an important risk in transplant recipients, in whom a hypercoagulable state and hypofibrinolysis have been associated with immunosuppressive treatment, especially with cyclosporine. In no case have clotting and fibrinolytic abnormalities been correlated with steroid immunosuppression, even though steroids were always administered. Previous studies found a relationship between hypercorticism and hypofibrinolysis both in Cushing's disease and after renal transplantation. The aim of this investigation was to compare fibrinolytic potential using the venous occlusion test in two similar groups of heart transplant patients treated with or without steroids. Euglobulin lysis time, tissue-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) activities, and antigens were determined before and after the venous occlusion test. A reduced fibrinolytic potential (significant prolongation of lysis time) due to a significant increase in PAI-1 activity and antigen levels was found in heart transplant patients treated with steroids, as compared with patients without steroid treatment and control subjects. The prevalence of reduced fibrinolytic potential was 69.2% (18 cases) in the steroid-treated group and 34.8% (8 cases) in the non-steroid-treated group. In every case, the impaired fibrinolytic potential was due to high basal PAI-1 levels. Our results are compatible with the presence of a hypofibrinolytic state secondary to long-term steroid treatment. In heart transplant recipients, steroid-induced hypofibrinolysis may constitute a further risk factor for thrombotic disease.

Adolescent↗