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Biomedical subjects

A Butti

Publications and source records attributed to A Butti.

104 records · Page 6Linked to original sources
PubMedDate not supplied

Effects of a supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters.

In a phase I trial effects of a new supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters were investigated in healthy volunteers. Parameters studied were activated partial thromboplastin time (aPTT), thrombin time, Heptest, anti-activated factor II (anti-FIIa) and anti-activated factor X (anti-FXa) activity, platelet adhesion, platelet count, platelet-induced thrombin generation time (PITT), bleeding time, antithrombin III, fibrinogen and several safety parameters. After single intravenous (i.v.) injections of IK-SSH (0.14, 0.33 and 0.66 mg/kg) aPTT, Heptest and PITT were strongly and dose-dependently prolonged. After ascending subcutaneous (s.c.) doses of IK-SSH (0.33, 0.66 and 1 mg/kg) aPTT, Heptest and PITT were prolonged in a dose-dependent manner. Repeat s.c. injections of 1 mg/kg IK-SSH for 5 days markedly prolonged aPTT, Heptest and PITT. No cumulative effects were observed. Anti-FIIa and anti-FXa activity were not or only slightly increased. Bleeding time, thrombin time and platelet adhesion were not significantly changed after i.v. and s.c. injections of IK-SSH. However, tissue factor pathway inhibitor (TFPI) concentration was markedly increased after each injection of IK-SSH and returned to the preinjection value 24 h later. IK-SSH prolongs aPTT, Heptest and PITT in a similar manner as other low molecular weight heparins but without significantly affecting thrombin time, FIIa and FXa activity. The release of TFPI may well be responsible for the prolongation of aPTT, Heptest and PITT. IK-SSH may be further developed as an antithrombotic agent.

Adult↗
PubMedDate not supplied

A recombinant hirudin (IK-HIR02) in healthy volunteers. I. Effects on coagulation parameters and bleeding time.

The pharmacodynamic effects of different intravenous and subcutaneous doses of a recombinant hirudin (r-hirudin; IK-HIR02) on clotting parameters and bleeding time were investigated in 24 healthy volunteers in a bicenter study. Single intravenous bolus injections of 0.1, 0.2 and 0.3 mg/ kg IK-HIR02 caused a prolongation of thrombin time (TT) and aPTT in a dose-dependent manner and led to an increase in hirudin plasma levels > 6 micrograms/ml. The plasma half-life of IK-HIR02 was calculated as 1.3 h. A continuous infusion of 0.03 mg/kg/h of IK-HIR02 for 4 h significantly prolonged TT and aPTT. At the end of the hirudin infusion, a mean plasma level of 0.19 +/- 0.13 microgram/ml was measured. Single subcutaneous doses of 0.1, 0.25 and 0.5 mg/kg markedly prolonged the coagulation tests. The highest increase in hirudin plasma levels was found 2 h after injection. At this time the aPTT was doubled after 0.5 mg/kg. After repeat subcutaneous injections of 0.3 mg/kg b.i.d., aPTT was doubled, and TT increased to about 200 s, 2 h after the injections. At this time the mean plasma level was 0.5-0.6 microgram/ml. There was no cumulative effect after multiple injections. Bleeding time was not changed after the 4-hour intravenous infusion and after repeat subcutaneous injections of 0.3 mg/kg IK-HIR02. Bleeding time was moderately but significantly prolonged after the highest single intravenous and subcutaneous hirudin doses tested. Other than very minor local bleeding in some volunteers, IK-HIR02 was well tolerated. Biochemical blood and urine parameters did not change. In conclusion, r-hirudin (IK-HIR02) obtained by a new technique was well tolerated in healthy volunteers after single intravenous and subcutaneous injections, after repeat subcutaneous doses and during continuous intravenous infusion. Measurement of aPTT and anti-IIa activity, using a chromogenic substrate test, can be used to monitor hirudin effects if doses similar to those tested here are administered.

Adult↗
PubMedDate not supplied

A recombinant hirudin (IK-HIR02) in healthy volunteers. II. Effects on platelet adhesion and platelet-induced thrombin generation time.

The pharmacodynamic effects of different intravenous and subcutaneous doses of a new recombinant hirudin (IK-HIR02) on platelet adhesion, platelet-induced thrombin formation and on platelet count have been studied in 18 healthy volunteers in a bicenter study. Single intravenous bolus injections of 0.1, 0.2 and 0.3 mg/kg IK-HIR02 in 6 volunteers caused a significant dose-dependent prolongation of platelet-induced thrombin generation time (PITT) and a significant inhibition of platelet adhesion to glass. Single subcutaneous doses of 0.1, 0.25 and 0.5 mg/kg IK-HIR02 slightly prolonged PITT and inhibited platelet adhesion to glass for up to 8 h. Repeat subcutaneous injections of 0.3 mg/kg IK-HIR02 b.i.d. in 6 healthy volunteers led to a prolongation of PITT and also to a reduction of platelet adhesion. In platelet-rich plasma (PRP) from blood samples which had been collected using hirudin as anticoagulant (0.7 micrograms/ml), the platelet count was constantly higher than in citrate PRP which had been sampled at the same time. The recombinant hirudin IK-HIR02 inhibits platelet adhesion to glass and also PITT. Both effects which have not been described before are most likely due to a direct inhibition of thrombin-induced platelet activation. These effects may contribute to the antithrombotic action of hirudin and probably have to be considered when hirudin is used in higher doses as an antithrombotic agent together with platelet function inhibitors to avoid excessive bleeding.

Adult↗
PubMedDate not supplied

Central venous catheter disruption and embolization: percutaneous retrieval. A case report.

Disruption followed by intravasal embolization is a rare (0.5%) however possible complication secondary to the insertion of a central venous catheter. The carriers of these implantable systems are patients who, for their cure and at times even for their survival, require the chronic intravenous infusion of drugs and solutions. Therefore materials that can allow long-term insertion with a minimum of complications are the most suitable. There are several causes of disruption and embolization of cannulae. The most common are represented by the pinch-off syndrome and catheter disconnection from reservoir. The literature on the subject is illustrated and a personal case treated with intravascular retrieval is reported.

Adult↗
PubMedDate not supplied

[Prevention of extraskeletal calcifications in uremia].

Secondary hyperparathyroidism (HPTH) is a common feature in end-stage renal disease (ESRD) patients. The three main factors involved in secondary HPTH pathogenesis are high phosphate levels, hypocalcemia and vitamin D deficiency. Recently, many studies demonstrated a strong association between bone disease and cardiovascular events in chronic kidney disease patients. In addition, cardiovascular events are the most frequent cause of death in patients with chronic renal failure. Increased levels of serum phosphorus and calcium-phosphate product are directly involved in the pathogenesis of extraskeletal calcifications (blood vessels, soft tissues, etc) in dialyzed patients compared to the non-uremic population. Recent studies suggested that vascular calcification is due not only to a passive calcium-phosphate deposition on atherosclerotic arteries, but also to active mechanisms regulated by bone-associated genes. In particular, fetuin and matrix Gla-protein are two 'protective' proteins associated with reduced vascular calcification and could be the regulatory keys in preventing this process in renal failure. The limitations of calcium salts as phosphate-binders in patients with advanced renal failure have been thoroughly evaluated in the last 5 yrs. New phosphate binders, which do not contain aluminum or calcium, have been developed to reduce the risk of extraskeletal calcifications in ESRD.

Animals↗
PubMedDate not supplied

[New insights in the pathogenesis of secondary hyperparathyroidism].

Parathyroid gland growth is a major cause of secondary hyperparathyroidism in renal failure. It is well known that high serum phosphate levels, low serum calcium levels and vitamin D deficiency are the three promoters of parathyroid hyperplasia in renal failure. Recent studies have investigated in depth the potential role of growth factors (transforming growth factor alpha) and their receptors (epidermal growth factor receptor) in the pathogenesis of parathyroid cell hyperplasia in chronic renal failure. The identification of molecular mechanisms involved in calcium, phosphate and vitamin D manipulations in an experimental renal failure model could help design more effective therapy for secondary hyperparathyroidism in uremic patients.

Calcium↗
PubMedDate not supplied

Pulmonary vascular resistance changes in experimental hemorrhagic shock.

Hemorrhagic shock was experimentally induced in 40 mongrel dogs, and the resulting pulmonary vascular resistances studied. A mechanical test with closure of the left branch of the pulmonary artery and two pharmacological tests with isoproterenol (isuprel) and cyclic adenosine-monophosphate (cAMP) were performed. The results suggest that there is a block in the beta-control during prolonged shock, and that beta-control is restored by cAMP.

Animals↗
PubMedDate not supplied

[Neurinoma of the vagus nerve. Description of 2 cases and review of the literature].

The Authors report two rare cases of schwannoma of the cervical and thoracic portion of the vagus nerve. Schwannomas of the vagus nerve are particularly uncommon; patients suffering from these neurogenic tumors typically exhibit a paucity of symptoms and in the majority of cases they present with an asymptomatic mass noted on incidental chest X-ray. Chest pain and cough may occur with tumors arising next to and compressing the trachea or major bronchi. In the cases observed, schwannomas appeared like a mass whose size had increased during the last months without producing any clinical symptom. Clinical features of the mass, laboratory tests, ultrasound, CT scanning, magnetic resonance imaging were useful only to define its extension and relationships with the adjacent structures. Needle aspiration of these lesions is not indicated because of the paucity of the material obtained for the exact diagnosis. Surgery, with preservation of the vagus nerve when possible, is the treatment of choice also for a correct diagnosis of nature and to prevent further growth and compression on adjacent structures. When the individual fibers of the vagus nerve are displayed over the surface of the tumor within a discrete capsule nerve preservation is possible. On the contrary, when it is technically difficult to preserve the nerve trunk microsurgical procedures allow to reanastomose the cut ends. Injury of homolateral recurrent nerve often is the complication of a radical removal. Recurrence of benign lesions is not usual; malignant tumors carry a poor prognosis with patients rarely surviving beyond 1 year.

Adult↗