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Biomedical subjects

L Puccetti

Publications and source records attributed to L Puccetti.

At least 19 recordsLinked to original sources

Cardiac papillary fibroelastoma: an unusual source of cerebral embolism solved with local fibrinolysis.

Fibroelastoma is an infrequent tumor affecting mainly cardiac valves. Before echocardiography, it was an occasional autoptic finding. With the development of ultrasonographic techniques, it is currently possible to carry out diagnosis in vivo. We report the case of a young woman with cerebral ischemia who was successfully treated by intra-arterial fibrinolysis with complete clinical resolution. Transesophageal echocardiography (TEE) identified a papillary fibroelastoma on the posterior leaflet of the mitral valve. Surgical excision of the tumor was performed. Sudden cerebral or peripheral embolization is frequently linked to thrombotic material which surrounds the neoplasm, and thus can be successfully treated with local fibrinolysis.

Female↗

Role of platelets in tissue factor expression by monocytes in normal and hypercholesterolemic subjects. In vitro effect of cerivastatin.

Thrombosis is a complication of atherosclerosis and monocytes play a determinant role either in the progression of atherosclerotic plaque or in blood coagulation by way of tissue factor expression. Platelets play a direct role in thrombosis and a hyperfunctional state has been described in hypercholesterolemic subjects. Moreover, platelets seem to be able to enhance monocyte activity. Cholesterol-lowering molecules (statins) are reported to reduce cardiovascular risk, either by decreasing the circulating level of cholesterol or by non-lipidic actions such as the reduction of monocyte and platelet activity. The aim of our study was to investigate the influence of platelets on the expression of tissue factor by monocytes and the effect induced by cerivastatin. We measured tissue factor levels by ELISA and the procoagulant activity of stimulated monocytes by a clotting assay on cellular preparations and whole blood in 40 hypercholesterolemic subjects (22 male, 18 female, mean age 52.7 +/- 12 years, total cholesterol 251.6 +/- 19.9 mg/dl) before and after cerivastatin addition. Tissue factor expression was enhanced in hypercholesterolemic subjects compared with normal subjects (31.6 +/- 7.6 vs. 23 +/- 5.8 pg/cells, P < 0.01). The presence of platelets increased the amount of tissue factor (55.3 +/- 7.3 pg/cells, P < 0.001) and cerivastatin reduced the expression of tissue factor in isolated monocytes, in the mixed cellular system, and in whole blood (19.6 +/- 4.1 pg/cells, P < 0.001). In conclusion, tissue factor expression by monocytes is enhanced in hypercholesterolemic subjects compared with normal controls. Platelets enhance monocyte production of tissue factor, and cerivastatin is able to counteract this prothrombotic mechanism.

Adult↗

Complement activation in hypercholesterolemia.

BACKGROUND AND AIM: Inflammatory and lipid factors share an important role in atherosclerosis. This study evaluates their relations in dyslipidemic subjects. METHODS AND RESULTS: We compared the complement system (serum hemolytic activity CH50, C3 and C4 fractions and terminal complex sC5b-9) in 30 hypercholesterolemic patients with elevated cholesterol and decreased HDL-cholesterol levels, 30 normolipemic patients with clinical atherosclerosis and 30 matched normal subjects. In addition we evaluated the circulating immune complexes containing cholesterol (chol-CIC) on the assumption that they might be important in complement activation, and the circulating levels of the adhesion molecule ICAM-1 (sICAM-1) as a sign of endhotelial dysfunction. We found a significant increase of sC5b-9 (but not of CH50 and C3, C4) in the hypercholesterolemics compared with the other groups. The plasma sC5b-9 level was inversely and significantly related to HDL-chol (regression analysis), whereas no direct significant relation was found between sC5b-9 and cholesterol. Chol-CIC were also significantly increased in this group. The atherosclerosis patients also presented a significant increase of sC5b-9. Lastly, both patient groups displayed a significant increase of sICAM-1. CONCLUSIONS: We suggest that complement activation in dyslipidemics may be induced by their increased immune complexes. However, the decrease of complement regulatory proteins carried by HDL is another important factor, while complement changes may be related to variations of other humoral and cell systems (endothelium, coagulative/fibrinolytic system), whose involvement is suggested in our study by the changes of sICAM-1.

Adult↗

Systemic adenosine increase during cold pressor test is dependent on sympathetic activation.

1. Following local vasoconstriction-inducing stimuli, such as the cold pressor test (CPT), significant changes occur in haemodynamics, with a rise in arterial blood pressure and heart rate (HR) due to the activation of the sympathetic nervous system. Among the compensatory mechanisms to local ischaemia, the endogenous nucleoside adenosine (ADO) has been suggested to play a relevant role by contributing to sympathetic stimulation. The possibility was investigated that CPT-induced increases in plasma ADO levels were not only an expression of the increased production of ADO in the ischaemic area, but also a consequence of systemic sympathoexcitatory mechanisms, thus showing a bidirectional involvement of the mechanisms of ADO formation. 2. The CPT was performed in 15 volunteers and mean arterial blood pressure (MABP) and HR were evaluated, together with plasma levels of noradrenaline (NA) and ADO in the tested and contralateral arm. The 15 subjects were then divided into three groups of five that were treated with either 5 mg transdermal clonidine weekly, 100 mg atenolol daily or 600 mg aminophylline twice daily. After 1 week treatment, the same test was repeated in the respective groups. 3. The CPT induced a rise in MABP and HR and an increase in plasma levels of NA and ADO. Increases in ADO were more pronounced in the tested arm. Clonidine blunted the haemodynamic response and NA release, while increases in ADO increase were reduced to a greater extent in the contralateral arm rather than the tested arm. Atenolol only affected MABP and HR without any effect on NA and ADO levels. Theophylline did not show any effect on CPT-induced changes. 4. In conclusion, local vasoconstriction and ischaemia induced in one arm following CPT are associated with haemodynamic changes dependent on the activation of the sympathetic system. The observed increase in plasma levels of ADO seems to be, in part, a direct expression of local responses to ischaemia (pre-dominant in the tested arm), but also appears as the consequence of systemic sympathoexcitatory mechanisms. Such increases in ADO are not dependent on a beta 1-adrenoceptor-mediated mechanism. Finally, theophylline, at a therapeutic dose, has no effect on the response to CPT.

Adenosine↗

[Effectiveness and tolerability of heparan sulfate in the treatment of superficial thrombophlebitis. Controlled clinical study vs sulodexide].

One of the most interesting glycosaminoglycans (GAGs) is heparansulphate, known as the physiological activator of antithrombin III and involved in the maintenance of the antithrombotic potential of uninjured endothelium. The aim of our study was to evaluate the tolerability and effectiveness of heparansulphate with respect to sulodexide, another GAG suitable for the treatment of venous diseases. The study was performed in a open-label, controlled, with parallel and randomized groups, design. Thirty patients (aged 32-72 years) suffering from superficial thrombophlebitis were treated for two weeks with heparansulphate 100 mg t.i.d. or sulodexide 250 LSU b.i.d., both given orally. Some coagulative and fibrinolytic parameters (PT; aPTT; fibrinogen; euglobulin lysis time; t-PA; PAI-1; ATIII; alpha 2-antiplasmin; D-Dimer and platelets count) were assayed at the beginning and at the end of the study. Moreover signs and symptoms of disease (skin trophism; local pain; itch and oedema) were assessed. Heparansulphate and sulodexide were able to reduce signs and symptoms with similar degree and to significantly modify t-PA, alpha 2-antiplasmin and ATIII levels without any difference between treatments. Our issues show that heparansulphate can be useful in superficial thrombophlebitis management.

Adult↗

A placebo-controlled study on urokinase therapy in systemic sclerosis.

A 4-month randomized placebo controlled trial on urokinase therapy in 36 consecutive systemic sclerosis patients randomly treated with urokinase or placebo was conducted. While patients on placebo did not show any significant improvement, in those following urokinase therapy there was a noticeable improvement in skin sclerosis observed via hand-print and ultrasonography of the skin. Vascular involvement improved: this was demonstrated by capillaroscopy results, showing an improvement in pattern and signs of revascularization and the resolution of skin ulcers. Vascular damage is a typical occurrence in systemic sclerosis cases and various vasoactive drugs are used symptoms for some such as Raynaud's syndrome or skin ulcers. At the moment these drugs seem to constitute the most effective therapy, and have few side effects. We have found only one previous study utilizing urokinase therapy for acute digital ischemia in systemic sclerosis. Our study is the first in which urokinase therapy has been used for the treatment of systemic sclerosis in a large number of patients.

Adult↗

D-penicillamine and gold salt treatments were complicated by myasthenia and pemphigus, respectively, in the same patient with rheumatoid arthritis.

A 53-year-old woman with rheumatoid arthritis developed myasthenia gravis after 6 months of therapy with D-penicillamine. Nineteen months after D-penicillamine was discontinued and 12 months after the beginning of gold therapy, she developed pemphigus vulgaris. This is the first reported case of gold-induced pemphigus in rheumatoid arthritis. This study further underlines the complex interactions between the effects of treatment with sulfhydryl-disulfide exchange drugs and the altered immunological system of patients affected by rheumatoid arthritis.

Antirheumatic Agents↗

Polymyositis-like syndrome in hypothyroidism: report of two cases.

An increase of muscle enzymes in hypothyroidism has sometimes been correlated with a polymyositis-like syndrome and hypothyroid patients have been misdiagnosed and mismanaged as suffering from polymyositis. Actually, muscle symptoms, such as aches and pain, stiffness, weakness and cramps or, more rarely, hypertrophy, are observed in hypothyroidism and increased serum muscle enzyme values, particularly the level of creatine phosphokinase (CPK), indeed seem to suggest polymyositis. The muscular groups most commonly affected by the above mentioned symptomatology are those of the shoulder and pelvic girdles. In this report two hypothyroid patients complaining of muscle symptoms, whose serum muscle enzymes were particularly elevated, are described. In the first case the patient had been suffering from pain and weakness of the thenar eminence for about 4 months. The clinical features suggested a diagnosis of Carpal Tunnel Syndrome, but thyroid function tests revealed primary hypothyroidism. In the second case the patient had been afflicted with muscular weakness of the shoulder girdle for 2 months and was unable to keep his arms raised over his head. A study of thyroid function demonstrated a picture of hypothyroidism. Both patients were treated with L-thyroxine and in a relatively short time biochemical parameters improved remarkably, and the symptoms disappeared. The hypothesis that a muscular effort of long duration by hypothyroid patients may have been responsible for the muscular damage and the symptoms may explain why only a few hypothyroid patients develop a clinical picture similar to polymyositis.

Adult↗

Double-blind comparison of the efficacy and safety of etodolac SR 600 mg u.i.d. and of tenoxicam 20 mg u.i.d. in elderly patients with osteoarthritis of the hip and of the knee.

Etodolac SR is the sustained-release formulation of etodolac, an effective anti-inflammatory drug used in the treatment of various rheumatic diseases. The efficacy and safety of etodolac SR were compared with those of tenoxicam in 120 elderly patients with radiographic and clinical evidence of active osteoarthritis (OA) of the knee and/or the hip. This was a double-blind, double-dummy, randomized, parallel-group, multicentre study conducted at 4 Italian rheumatic-disease units. Sixty patients received 600 mg of etodolac SR once daily (u.i.d.) for 8 weeks; the remaining 60 patients received 20 mg of tenoxicam u.i.d. Significant improvements in all 6 efficacy parameters (viso-analogic scale of the global pain, pain at active movements, night pain, joint tenderness, joint motility, and Lequesne's algofunctional index) were observed within each of the treatment groups even after the first 2 weeks of therapy. There were no significant differences in the therapeutic response between the two groups for any efficacy parameters. Adverse reactions, mostly regarding the G-I tract, were significantly more frequent in the tenoxicam group than in the etodolac group: 23.3% vs 8.3% respectively, albeit in the majority of the cases they were not considered to be so severe as to cause the interruption of the study. There were no clinically important changes from baseline in laboratory tests performed during the study. Endoscopy of the upper G-I tract was performed both at baseline and after 8 weeks of therapy in 30 patients per treatment group in order to obtain a reliable comparative evaluation of the G-I safety of the two drugs. Both drugs were found to be well tolerated; only 2 ulcers were observed after therapy in both groups, but minor lesions were more frequently detected in the mucosa of the stomach in the patients who received tenoxicam. The cumulative endoscopic index that reflected both the erosive and the haemorrhagic lesions found in the stomach taken as a whole was significantly (p < 0.03) higher after therapy in the tenoxicam group. These results indicate that 600 mg of etodolac SR u.i.d. for 8 weeks is as effective as 20 mg of tenoxicam u.i.d. in the treatment of OA of the knee and/or of the hip. Both the overall and the G-I specific safety profiles were found to be more favourable in patients treated with etodolac SR. Renal function was not substantially affected in either treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Evaluation of the effectiveness and safety of etodolac in prolonged treatment of active osteoarthritis.

Patients affected by osteoarthritis totalling 358 (142 males and 216 females) were recruited in an open study which lasted up to three months. All patients started treatment with etodolac 600 mg/die per os. 74 patients were treated and followed for 15 days, 94 for one month, 54 for two months, and 132 for three months. Clinical evaluations, performed at baseline and after 15, 30, 60, and 90 days of treatment were made on the following parameters: intensity of pain, index of sleep disturbance caused by symptoms related to osteoarthritis, investigator's evaluation of the global patient's condition, patient's self-evaluation about his own condition, presence and duration of morning stiffness, presence and duration of stiffness at rest, and finally the investigator's integrated evaluation about the effectiveness tolerance of etodolac during the study. All the parameters showed a noticeable and significant improvement in all groups of patients, stratified by sex, age, and duration of the disease. The younger patients and those patients with osteoarthritis of a less prolonged duration achieved the best results. Only slight differences were registered by examining the baseline values of the various parameters or the extent of the different improvements achieved, on the basis of sex, and duration of osteoarthritis and the non-steroidal anti-inflammatory drugs previously used. Among the 27 patients who withdrew, eight dropped out for clinical inefficacy and 15 for intolerance. In all these latter cases a prompt and complete resolution of the adverse reaction was achieved and maintained after the interruption of therapy. In the 49 patients who presented side-effects, these were almost always related to the gastrointestinal tract and of slight intensity. A complete resolution was promptly achieved in 25 cases, while in 17 other patients the side-effect persisted during the course of the study, but it was considered not worthy of the patient dropping out. The profile of routine laboratory parameters, measured both at inception and at the end of the study, did not show relevant changes after treatment with etodolac. In conclusion this study demonstrated that etodolac is effective and well tolerated in the prolonged treatment of patients with active osteoarthritis.

Adult↗

Effectiveness and safety of etodolac in treatment of rheumatoid arthritis: a multicentre two-months' open study.

One hundred and seventeen outpatients (87 females and 30 males; mean age 53.5 +/- 13.2 years) encompassing the 1987 American Rheumatism Association criteria for rheumatoid arthritis were admitted into a multicentre open study. All patients were evaluated at baseline and after two months of therapy with etodolac (400 or 600 mg/die per os). Clinical evaluation was performed by using the following indicators: viso-analogic scale of global pain; index of pain on active movements; index for sleep disturbances, and duration of morning stiffness. The erythrocyte sedimentation rate was chosen for the laboratory evaluation of the activity of the disease. One hundred patients received 400 mg/die, while only 17 patients received 600 mg/die; 115 patients undertook the evaluation after treatment, whereas two patients were considered "lost to follow-up". One hundred and five patients completed the study while ten patients withdrew (seven because of inefficacy and three because of intolerance of the gastrointestinal tract). Only nine patients presented side-effects, among these: five were judged etodolac-related, whereas four were not. A complete resolution of all these side-effects was achieved in all cases. Significant improvements were registered for all the four clinical variables. At the end of the study 56.5% of patients expressed a preference for etodolac, 16.5% for one of the non-steroidal anti-inflammatory drugs previously taken and 27% did not answer or were not able to express any definite preference. Strict concordance was found between the degree of clinical improvement achieved and the preferences expressed. The laboratory parameters did not reveal any variation at the end of the study in comparison with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Etodolac versus diclofenac: double-blind cross-over study in rheumatoid arthritis.

A 14-day double-blind clinical study was conducted on 16 patients with clinically active rheumatoid arthritis to compare the effects of etodolac (600 mg daily) and diclofenac (150 mg daily). Admission criteria were: functional impairment between Steinbrocker's classes I to III, Ritchie's index greater than 10 and erythrocyte sedimentation rate greater than 25 mm/h, and finally active involvement of the small joints of the hands. Following a wash-out period of at least two days from their previous non-steroidal anti-inflammatory drugs, trial patients received etodolac or diclofenac for five consecutive days by random allocation; after that, and after another two day wash-out period, all patients were crossed-over to the alternate drug for another five consecutive days. One day before intake and on the last day of each treatment lap, each patient was examined in regard to the circadian grip strength (of the more severely affected hand), Ritchie's index and acute phase reactants; at the end of the second treatment period, subjective drug preference was explored. Grip strength was assessed by the patients themselves with a dynamometer at 08h00 and every two hours thereafter until 20h00. The overall daily value was calculated by measuring the area under curve (AUC) depicting the grip strength profile. Both groups of patients showed significant improvement of the Ritchie's index (p less than 0.01) and grip strength AUC (p less than 0.05), while taking medication, whereas no significant variations were noted in regard to the values of the acute phase parameters both between the two treatment groups, and within each treatment group. At termination, four patients expressed preference for etodolac, eight were in favour of diclofenac, and four gave an indifferent judgement. No statistically significant differences were detected between the two treatment groups; also no adverse events were seen in this short-term study. The results confirm the effectiveness and tolerability of etodolac in the acute stage of rheumatoid arthritis.

Adult↗

Plasma levels of fibronectin in polymyalgia rheumatica giant cell arteritis.

In order to verify whether measurement of plasma fibronectin (Fn) could represent a useful tool in acute-phase-response assessment, Fn was measured in 16 previously untreated patients (group A) affected by polymyalgia rheumatica giant cell arteritis (PMR-GCA), both before, during, and after 45 days of steroid therapy, and its course was compared with the behavior of some acute-phase reactants such as erythrocyte sedimentation rate (ESR), fibrinogen (Fng), and prealbumin (Preal). No difference was detected between the baseline Fn levels found in patients and those registered in a control group composed of 15 sex- and age-matched healthy subjects; no correlation was found with the other acute-phase parameters considered, and no significant variation of plasma Fn levels was registered as a result of the steroid therapy administered. On the contrary, all the other parameters revealed a good degree of correlation and tended progressively and homogeneously towards normalization as a result of the therapy administered. Plasma Fn was also measured in another group of 16 PMR-GCA patients (group B), all of whom had pathological retinal fluoroangiographic findings, and its levels were compared with those of the von Willebrand factor antigen (vWfAg), a biochemical index of vascular damage. While the levels of Fn continued to be the same as those detected in the control group, the values of vWfAg registered in group B proved to be significantly different from those found in another homogeneous control group of 25 healthy subjects. Finally, no correlation could be detected between Fn and vWfAg, and neither of them showed any significant correlation with the ESR.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

Behavior of prealbumin in the acute phase of polymyalgia rheumatica treated with 6-methylprednisolone.

Serum levels of prealbumin, fibronectin, fibrinogen, alpha 1-acid glycoprotein, C-reactive protein, immunoglobulins, and white blood cell count were prospectively studied in 33 patients affected by polymyalgia rheumatica during the first 45 days of treatment with 6-methylprednisolone. Almost all parameters considered, except for fibronectin and IgM, settled within the normal range fairly quickly, while prealbumin showed a specular course compared with the other reactants. This behavior reflected the improvement of clinical symptoms registered in all patients after steroid treatment. Finally, the genesis of the low baseline prealbumin levels found in polymyalgia rheumatica/giant cell arteritis and their behavior during treatment are discussed.

Aged↗

Coagulative, fibrinolytic and metabolic pattern in patients with central retinal vein occlusion.

Central retinal vein occlusion (CRVO) is an important cause of visual loss. Many risk factors have been associated with CRVO onset at various ages. Among them diabetes mellitus, hypertension, immunologic disorders, increase in blood viscosity and coagulation, decrease of fibrinolysis have been reported in many subjects. The aim of our study was to detect the metabolic, coagulative and fibrinolytic pattern in 54 patients (26 men, 28 women, mean age 50.4 +/- 12.3) affected by CRVO. We excluded from the study patients with other ocular disorders. A fibrinolytic impairment is the most common feature in our population. It occurs either in dysmetabolic or in nonmetabolic subjects. Such data suggest a prominent role of the fibrinolytic system in the pathogenesis of CRVO.

Adult↗

Hypercoagulable state in hypercholesterolemic subjects assessed by platelet-dependent thrombin generation: in vitro effect of cerivastatin.

BACKGROUND: Hypercholesterolemia is an important risk factor to develop acute thrombotic complications of atherosclerosis like to myocardial infarction and ischemic stroke. Platelets and coagulation factors are strictly involved in the genesis of such thrombotic events and their hyperactivity in hypercholesterolemic patients has been previously reported. Moreover some cholesterol-lowering molecules (statins) seem to be able of reducing platelet activity. METHODS: We performed platelet-dependent thrombin generation (colorimetric method) to assess the coagulative potential of 40 caucasian hypercholesterolemic subjects with respect to normal controls and to the grade of hypercholesterolemia. Moreover we observed the effect of platelets from hypercholesterolemics on thrombin generation in plasma from normal subjects. The effect of Cerivastatin on thrombin generation was evaluated too. RESULTS: Our data show an increased thrombin generation both in mild and high hypercholesterolemic subjects with respect to controls (424.6+/-30.5 vs. 197.1+/-27.4 mIU/ml). No significant difference in the amount of thrombin generation was found between mild and high hypercholesterolemics (399.6+/-20.7 vs. 440.2+/-21.4 mIU/ml). Platelets directly influence thrombin generation and they present an intrinsic hyperactivity that can be modulated by Cerivastatin (223.6+/-24.8 vs. 424.6+/-30.5 mIU/ml). CONCLUSIONS: Mild hypercholesterolemia is associated with an increased thrombinic potential that may be considered an added risk factor to develop thrombotic events. Platelets directly influences this hypercoagulative state and Cerivastatin is able to reduce thrombin generation by way of a direct interaction with platelets.

Blood Coagulation Disorders↗