Danazol in refractory pruritus of myeloproliferative disorders.
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Biomedical subjects
Publications and source records attributed to F Fabris.
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OBJECTIVES: A cost-effectiveness analysis on osteoporosis treatment has been carried out as the basis for an estimate of the cost per avoided hip fracture (CPAHF) in Italy. METHODS: We have assumed as correct, reported data on the efficacy of calcitonin in preventing hip fractures in European women over 50 (Mediterranean Osteoporosis Study). Health-care costs were calculated using Weinstein and Stason's equation. RESULTS: Given the incidence of such fractures in Italy and their cost to the health service, we calculate that in order to prevent one hip fracture 1285 women need to be treated with calcitonin at a cost of over two million dollars. The introduction of an element of screening (bone mass measurement to select a high risk subpopulation) would reduce the CPAHF by 65%. Choice of a more effective treatment (as the hormone replacement therapy) would be cost-neutral. CONCLUSIONS: Drug-related costs, selection of high risk subpopulations and drug efficacy have important implications in the estimation of optimal CPAHF.
In human ageing and with many pathologies correlated to the senile functional decay of cells, membrane damage often occurs in some organ or tissue, which provokes lipid peroxidation in the membrane and accelerates the disorder in structure and function of the membrane. When lipid peroxides accumulate sufficiently, they leak from the organ or tissue into the bloodstream and increase the lipid peroxide level in blood lipoproteins. The increased lipid peroxides in the blood attack the blood vessel and promote atherogenesis. This paper describes the possible involvement of free radicals in this damage, both to tissues and to blood vessels, which contributes to the senile functional decay of the tissues.
An excess of free-radical production has been linked to many diseases and to the ageing process. Oxidant by-products of normal metabolism can cause extensive damage to DNA, protein and lipid. Exposure to ultraviolet light, cigarette smoke and other environmental pollutants may also increase the free radical burden. The accumulation of unrepaired oxidative damage products is likely to be a major factor in cellular ageing. Many repair processes are available to the cell, including enzyme and structural defences. The large group of natural antioxidants is also part of a protective mechanism. High consumption of fruit and vegetables in the diet is associated with a lowered risk of degenerative diseases. At present, however, there are few data to support the routine use of exogenous antioxidants to prevent and treat these diseases.
We studied 47 subjects belonging to 13 unrelated families with a history of mild haemorrhagic diathesis and chronic thrombocytopenia. 36 patients presented some degree of thrombocytopenia: 7/36 (19%) had slight thrombocytopenia (100-150 x 10(9)/L); 26/36 (72%) had mild thrombocytopenia (50-100 x 10(9)/L) and 3/36 (8%) had severe thrombocytopenia (< 50 x 10(9)/L). No correlation was observed between platelet count and the degree of haemorrhagic diathesis, which was mild in the majority of patients. Transmission was autosomal dominant. Platelet anisocytosis, increased percentage of large platelets and absence of leukocyte inclusions were observed in 26/30 (87%) of the examined blood smears. The ultrastructural appearance of platelets was normal. Megakaryocytes appeared normal in number in 10/10 patients, but showed asynchronous nuclear-cytoplasm maturation and mainly nonlobulated nuclei. Platelet aggregation was studied in 26 patients and either increased or decreased curves were variably observed in response to different aggregating agents. Platelet-associated IgG (PAIgG) was increased in 18/31 (58%) patients, while serum autoantibodies against platelet glycoproteins Ib/IX or IIb/IIIa were demonstrable in only 1 case. An increased expression of platelet surface glycoproteins Ib and IIb/IIIa, as studied by murine monoclonal antibodies binding in 17 cases, was observed. Platelet survival performed by 111Inoxine-labelled autologous platelets was normal in the 3 studied patients. Congenital macrothrombocytopenia confirms to be a distinct clinical disorder for which the name of "chronic isolated hereditary macrothrombocytopenia" is proposed.
The number of women who become ill and die from acute myocardial infarction (AMI) increases steadily with age. It is not yet clearly defined whether and why women suffer from a higher in-hospital mortality rate after AMI. In this study we evaluated the importance of the female sex as a risk factor for in-hospital mortality in elderly patients suffering from AMI. A retrospective study was performed in 724 patients (429 males, 295 females) aged > or = 65 years (mean age 74.9 +/- 6.3 years) consecutively admitted to San Giovanni Battista Hospital in Turin during the period 1988-1991 with validated primary discharge diagnosis of AMI. In-hospital mortality was significantly higher in females (34.6%) compared to males (25.6%, p > 0.01). After multivariate analysis female sex was not independent predictive for in-hospital death. Multivariate analysis was therefore repeated in the various sections of the history of AMI (anamnestic variables, including age and sex: physical signs on admission, ECG findings, laboratory tests, clinical progress, including complications and treatment) in order to identify the factors responsible for the higher mortality rate in women. These were found to be low hemoglobin values (< 12 g/dl) on admission, development of cardiac failure disorders and rhythm disturbances during hospitalization, and differences in therapeutic procedures. In spite of the absence of an independent unfavourable effect of female sex, elderly women with AMI have a higher in-hospital mortality rate. A more precarious state of health on admission, a peculiar susceptibility to severe complications during hospital-stay and differences in therapeutic procedures appear to be the factors responsible for this increased mortality rate in women.
The presence and specificity of antiplatelet autoantibodies in 32 patients with primary and 18 patients with secondary autoimmune thrombocytopenic purpura (AITP), as well as 11 non-thrombocytopenic patients with systemic autoimmune diseases, were studied. By means of the direct and indirect monoclonal antibody immobilization of platelet antigen (MAIPA) assay, antiplatelet autoantibodies were detected using monoclonal antibodies specific for platelet glycoproteins (GPs) Ib, IIb/IIIa, Ia/IIa, and IV. Serum antiplatelet autoantibodies were found in 18 of 32 primary AITP patients (56%), 6 of 18 secondary AITP patients (33%), and 5 of 11 nonthrombocytopenic patients (45%). Platelet-associated autoantibodies were detected in five of eight patients with primary (62%) and in four of eight patients with secondary AITP (50%) and in two of four patients without thrombocytopenia (50%). Multiple antibody reactivity, mainly against GPs IIb/IIIa and Ib and, in a few patients, against Ia/IIa, was found. Using MAIPA, platelet xylene eluates from 20 patients were also studied. Antiplatelet elutable autoantibodies were related to thrombocytopenia; autoantibodies against membrane GPs Ib and IIb/IIIa were demonstrable in 84 and 63% of eluates from patients with primary and secondary AITP, respectively, but not in eluates from nonthrombocytopenic patients. The presence of antiplatelet antibodies thus appears to be a common feature of many autoimmune diseases apart from the thrombocytopenia, but the (primary or secondary) etiology of the immune thrombocytopenia cannot be differentiated on the grounds of their specificity.
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AIM: Evaluation of fracture incidence in the institutionalized elderly and analysis of associated risk factors. EXPERIMENTAL DESIGN: Longitudinal and prospective study with 3-year follow-up. SETTING: Old people's home in Turin for patients who are no longer self-sufficient. PARTICIPANTS: 197 subjects (47 males and 150 females) aged between 61-98 years old, dependent in at least two basic daily activities. PARAMETERS: At the time of enrollment, the following parameters were evaluated: age, weight, height, degree of walking autonomy, bone mineral density at proximal and distal radius. The number of falls and fractures were recorded during follow-up. RESULTS: A total of 46 fractures (22 femoral and 24 in other sites) were recorded with an annual incidence of 7.8%. Femoral fractures only occurred in females. The following risk factors were associated with femoral fractures: very old age (relative risk = 2.6; 95% confidence interval = 1.1-6.4), low body mass index levels (RR = 3.3; 95% CI = 1.3-8.7), low bone mineral density levels at the proximal radius (RR = 2.6; 95% CI = 1.1-6.3), autonomous walking capacity (RR = 3.7; 95% CI = 1.1-12.0) and recurrent falls (RR = 2.7; 95% CI = 1.2-6.2). The following risk factors were associated with non-femoral fractures: autonomous deambulation (RR = 5.7; 95% CI = 1.4-23.7) and recurrent falls (RR = 6.4; CI = 2.3-18.3). CONCLUSIONS: Institutionalized elderly patients present numerous risk factors for femoral fractures. Fractures in other sites are only associated with risk factors that express a tendency to fall.
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Several 'capture' assays are currently employed to identify specific platelet antibodies, but all require the use of murine monoclonal antibodies (MoAbs) against the antigen of interest. We have developed a new antigen capture assay for the detection of platelet reactive antibodies, based on platelet surface sialoglycoprotein labelling with biotin hydrazide, and a following immobilization of the biotinylated platelet proteins to microtiter wells that had been coated with streptavidin. The resulting solid phase can then be used in a simple ELISA to detect serum and platelet associated antibodies. We describe here two versions of this biotin-avidin immobilization of platelet glycoproteins (BAIPG) assay. In BAIPG assay type I, the test sera are directly incubated in microtiter wells previously coated with streptavidin plus biotinylated platelet proteins. The BAIPG type II procedure involves the incubation of sera with biotinylated platelets before platelet solubilization, and, after platelet lysis, the immobilization of the immune complexes to streptavidin-coated wells. In both cases, the bound antibodies are determined by alkaline phosphatase conjugated anti-human IgG. Using BAIPG type I, positive results were obtained in 7/33 patients with idiopathic thrombocytopenic purpura (ITP), 1/10 patients with secondary immune thrombocytopenia (SIT) and 4/17 with non-immune thrombocytopenia (NIT). The BAIPG type II test was positive in 13 out of 33 patients with ITP, in six out of ten patients with SIT, and in three out of the 17 patients with NIT. A comparison between BAIPG and monoclonal antibody immobilization of platelet antigens (MAIPA) assays showed a high degree of correlation between the two methods. These results suggest that the BAIPG assay is a valuable new tool for the detection of anti-platelet antibodies.
A 3-year prospective study was performed to evaluate the incidence of fractures in institutionalized elderly and associated risk factors. A total of 197 subjects (47 males and 150 females, mean age 81.5 +/- 8.0 years) were included in the study. The annual fracture incidence was 7.8%. All hip fractures occurred in female subjects (annual incidence = 3.7%). As expected, the incidence of fractures is higher in walking subjects. In walking subjects (n = 128) logistic regression analysis showed falls [adjusted relative risk (RR) = 3.3; 95% confidence interval (CI) = 1.3-8.4] and age (adjusted RR = 1.7; 95% CI = 1.1-2.3) to be variables independently and significantly associated with fractures, after adjusting for baseline bone mineral density (BMD) and sex. Hip fractures were associated with age (RR = 1.6; 95% CI = 1.1-2.3), and non-hip fractures with falls (RR = 4.1; 95% CI = 1.3-13.4). The importance of low BMD as a risk factor for fractures is reduced in the institutionalized elderly. However, other fracture-site-specific risk factors exert a greater influence.
During January and November 1983 we examined 230 patients by means of doppler evaluation for suspect of peripheral arterial disease. We identified 105 subjects with peripheral arterial disease. During September and November 1993 we tried to convoke again all 230 subjects. Altogether we followed 215 subjects (95 with peripheral arterial disease and 120 without). Sixty-three patients died and we analysed the cause of death. Forty-seven out of 95 patients (49.5%) with peripheral arterial disease died and only 16 out of 120 subjects (13.3%) without peripheral arterial disease. Twenty-five out of 47 deaths (53.2%) happened among the patients with peripheral arterial disease. Age, severity of peripheral arterial disease (measured by ankle-arm pressure ratio) and the presence of a carotid bruit were associated with death. The natural history of peripheral arterial disease has been characterized by a worsening of the intermittent claudication in 52.1% of patients but only 18.6% presented a progression toward a superior class of the Fontaine classification. In conclusion, the peripheral arterial disease, despite his apparently benign course, represents a clinical event that must not be overlooked, because the risk of cardiovascular mortality is high. The measurement of ankle-arm pressure ratio allows a good definition of the severity of peripheral arterial disease and therefore represents a valid prognostic criterion.
Normal electrocardiographic criteria in the elderly are not well defined. The prevalence of electrocardiographic abnormalities is three times higher in subjects over 85 years than in subjects 65-69 years old. With aging the heart rate does not vary during rest and sinus rhythm is prevalent, although sinus pauses, overall at night, are frequently seen. First degree atrio-ventricular block is present in 8.1%-19% of the elderly. 11% of subjects over 70 years suffer from left anterior hemiblock. 4.3% of subjects over 65 years and 7% of those over 85 present a right bundle branch block. 1.7% of subjects older than 65 years and 9% of those older than 85 are affected by a left bundle branch block. Atrial ectopic contractions are present in 8.8% of subjects over 60 years and in all older subjects. Atrial fibrillation is more common as age increases, being found in 2% of under 75s, in 5% of all subjects over this age, in 14% over 85 years and in 27% of patients hospitalized or institutionalized aged over 90 years. The prevalence of ventricular ectopic contractions varies from 76% in studies performed with baseline electrocardiogram to 96% in studies performed with portable monitoring electrocardiogram. Major ST-T wave alterations are present in 6.3%-13% of the elderly. In 340 patients over 80 years, hospitalized for diseases, other than cardiovascular, we found atrial fibrillation in 27.9% of subjects, ectopic beats in 26.2%, first degree atrioventricular block in 8.5%, right bundle branch block in 11.2%, left bundle branch block in 5.9%, left anterior hemiblock in 8.2%, ST-T wave alterations in 23.8% of the population.
BACKGROUND: Thrombocytosis can be present in patients with myeloproliferative disorders or can accompany various conditions, in particular chronic inflammatory diseases, namely chronic bowel diseases, rheumatoid arthritis, and nephritis. OBJECTIVE: We report our experience in 55 patients younger than 45 years of age with increased platelet counts (over 500 X 10(9)/L). Thirty-three were affected by essential thrombocytemia in agreement with polycytemia vera study group criteria and 22 by reactive thrombocytosis. Serotonin concentration has been determine in all the patients. RESULTS: Serotonin was decreased as expected in 23 out of the 33 patients with essential thrombocytemia. In the remaining ten subjects, serotonin was within normal limits as in reactive thrombocytosis. Eight of these subjects had positive histories for allergic rhinitis and two for atopic dermatitis. CONCLUSIONS: Chronic inflammation, present in patients with diseases of the immune system may cause an increased platelet number. One should consider with caution patients with thrombocytosis and positive histories for diseases of the immune system; probably a diagnosis of essential thrombocytemia is not justified.
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By means of immunoblotting and monoclonal antibody immobilization of platelet antigens (MAIPA) we have studied the specificity of antiplatelet antibodies in patients with antiphospholipid antibodies and thrombocytopenia defined as presence of anticardiolipin IgG and a platelet count below 100 x 10(9)/l. The study group consisted of 10 patients with systemic lupus erythematosus (SLE), 8 patients with primary anti-phospholipid syndrome (PAPS) and 16 patients with idiopathic thrombocytopenic purpura (ITP). The comparison group was formed by 17 patients with classical chronic ITP without anticardiolipin IgG. We identified the 80-100, 130-150 and 150-170 KD surface proteins that comigrate with GPIIIa, GPIIb and GPIb and a 50-70 KD cytoplasm band by immunoblot. In patients with classical chronic ITP, the prevalence of the antiplatelet antibodies against GPIIIa was 53% on immunoblot assay and 47% on MAIPA. In ITP patients who had also anti-phospholipid antibodies in serum, the percentage of reactivity to GPIIIa declined to 37% on immunoblot and 21% on MAIPA but it was not statistically different from the percentage observed in patients with classical ITP. Autoantibodies to platelet surface glycoproteins were almost absent in SLE and PAPS patients, who showed a significant prevalence (78%) of IgG reactivity to the 50-70 KD internal platelet protein which was frequently encountered also in patients with ITP and aPL (56%). Our study provides additional evidence that platelet antigens in patients with phospholipid-associated secondary immune thrombocytopenia are different from those of primary ITP, and that surface glycoproteins were not involved.