Patrizio Ferrari

VASCULAR DEMENTIA ITALIAN SULODEXIDE STUDY (VA.D.I.S.S.) CLINICAL AND BIOLOGICAL RESULTS.

In order to evaluate the biological effects on some haemostasis factors of antithrombotic-hemorheological treatments on patients with vascular dementia, a multicenter, randomized, double-blind, double-dummy, study comparing sulodexide (Sdx, 50 mg bid orally for 6 months) and pentoxifylline (Ptx, 400 mg tid orally for six months) was carried out. Eighty-six patients, 46 in Sdx group, 40 in Ptx group, fulfilling the NINDS-AIREN criteria for probable vascular dementia were evaluated. Plasma fibrinogen levels showed a significant reduction in both groups, in patients with high basal levels (> or = 350 mg/dl), the reduction being earlier in Sdx group (2nd month of therapy) than in Ptx group (4th month of therapy). In Sdx group a significant reduction in factor VII-Ag (baseline 102.8 U/dl; 6th month 90.1 U/dl) was also observed. Both drugs induced a slight reduction in activated factor VII levels as well. A parallel improvement of G.B.S. Rating Scale for dementia scores was observed in Sdx group. These results seem to indicate that sulodexide treatment can have positive effects in vascular dementia.

Medroxyprogesterone acetate (MAP) plasma levels after multiple high-dose administration in advanced cancer patients.

SummaryMedroxyprogesterone acetate plasma levels were measured in advanced cancer patients after multiple PO or IM administration (500, 1000, 2000, 3000, 4000, and 5000 mg/day PO and 500, 1000, 2000 mg/day IM for 30 days). After PO administration, the plasma concentration rises quickly and plateau level is reached in 4–10 days. Discontinuation of the treatment produces a fast decay (t1/2=62.4 h) of the drug levels. When medroxyprogesterone acetate is given IM plasma levels steadily increase and after drug discontinuation no noticeable decay is observed for at least 6 months; plateau plasma levels are about three times higher than after the corresponding PO treatment. Extremely high interpatient variation in bioavailability is present with both administration routes. These data may well rationalize the results of previous clinical trials and will help in planning treatment schedules.

Home therapy with LMWH in deep vein thrombosis: randomized study comparing single and double daily administrations.

The aim of this study was to assess the effectiveness of low-molecular-weight heparin (LMWH) treatment of deep vein thrombosis (DVT) in terms of the evolution of thrombosis, the incidence of adverse events, and compliance with heparin treatment using 2 types of LMWH available on the market administered in therapeutic doses throughout the period of treatment (Nadroparin) or at therapeutic doses only during the first month of treatment followed by a prophylactic phase at half dose (Parnaparin). A randomized prospective study was carried out on patients under observation with a recent diagnosis of DVT. The objectives of the study were to confirm the effectiveness of therapy with LMWH in terms of prevention of the risk of thromboembolism, of relapse of DVT, and of hemorrhagic complications, and to complete an evaluation of venous recanalization and residual valve competence in the 2 groups of patients. From December 2002 to June 2005, we randomized a total of 91 patients (51 in the Parnaparin group and 40 in the Nadroparin group). Overall, there was 1 case of nonfatal pulmonary embolism (1.1%) at 7 days into therapy with LMWH. There were 3 cases (3.3%) of progression of thrombosis despite therapy with LMWH, 2 cases (5%) in the Nadroparin group, and 1 case (2%) in the Parnaparin group (P = NS), and after suspension of the therapy, there was 1 case of relapse of thrombosis. Three of the 4 thrombotic events occurred in patients with active neoplasia. Moreover, only 1 major hemorrhagic event (1.1%) required blood transfusion. The Doppler ultrasound in the follow-up showed a complete resolution of 56% of the vein thromboses at an average of 6.1 ± 4.6 (mean ± SD) months. Valve competence recovered in 65.9% of cases with no significant difference between the 2 heparin groups. Home treatment of sural and femoral-popliteal DVT using LMWH represents a safe and effective method in the prevention of pulmonary embolism and encourages the process of recanalization of the thrombosed vessel, especially in cases of sural and/or popliteal DVT. Administration can be carried out with the same degree of safety at the therapeutic dose throughout the period of treatment or can be halved after the first month of treatment. In patients with active neoplasia, treatment with oral anticoagulant therapy must be considered.

Medroxyprogesterone acetate bioavailability after high-dose intraperitoneal administration in advanced cancer

SummaryAdministration of medroxyprogesterone acetate IP in advanced cancer with peritoneal metastases and ascitic effusion generates considerably higher drug plasma levels than those observed after PO or IM treatment. Comparison of areas under the time-concentration curves (AUC) with reference to the three administration routes indicates that after oral administration only 0.2%–17.4% (mean 5.7%; SD 3.77; 40 patients) of the administered dose is absorbed; after IM treatment a daily absorption of 0.7%–7.7% (mean 2.5%; SD 1.66; 30 patients) of the administered dose per injection site was computed.

Prophylaxis of venous thromboembolism in minor orthopedic surgery with parnaparin.

This study analyzed the efficacy of venous thromboembolism prophylaxis in knee arthroscopy in 509 patients who received Parnaparin (Alfa Wassermann, Bologna, Italy), 3200 IU to 4250 IU daily, after minor arthroscopic knee surgery. No proximal deep venous thrombosis or other thromboembolic events occurred. Adverse events related to the treatment with Parnaparin were observed in 2 of 172 patients treated with 3200 IU/d and in 6 of 337 patients treated with 4250 IU/d, without any evidence of dose-proportionality in the incidence. Prophylaxis with a low-molecular-weight heparin such as Parnaparin should be considered in all patients who will be undergoing a procedure in which a tourniquet is used. If Parnaparin is used, it should be started immediately after knee arthroscopy at doses of 3200 to 4250 IU/d, according to the characteristics of the patients. Depending on the patients risk factors, postoperative prophylaxis for 10 days may be appropriate.