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Biomedical subjects

F Ferrando

Publications and source records attributed to F Ferrando.

36 records · Page 2Linked to original sources
PubMed1998

Hemorheological alterations and hypercoagulable state in deep vein thrombosis.

Deep vein thrombosis (DVT) seems to be related to a hypercoagulation and definite hemorheological alterations, but the importance of these alterations in the development of thrombotic events in the deep vein system has not been established. The present study examines both aspects in a group of 55 patients with DVT; the presence of a hypercoagulable state was assessed by quantifying the prothrombin fragment 1+2 (F1+2) and the thrombin-antithrombin III complex (T-AT), and the main hemorheological parameters were evaluated in the acute state and 6 and 12 months later. The results show marked hemorheological, F1+2, and TAT alterations in the acute phase. After 12 months the pattern shows a modest improvement, but erythrocyte aggregation, fibrinogen, F1+2 and T-AT remain increased with respect to the control group (8.51 +/- 1.43; 331 +/- 81 mg/dl; 1.33 +/- 0.60 nmol/l; 3.54 +/- 1.71 ng/ml vs. 8.10 +/- 1.40; 230 +/- 38; 0.94 +/- 0.40; 1.56 +/- 0.59, respectively). These data suggest that the thrombotic event could be influenced by the previous rheological situation and hypercoagulable state.

Acenocoumarol↗
PubMed1997

High-dose mitoxantrone with peripheral blood progenitor cell rescue: toxicity, pharmacokinetics and implications for dosage and schedule.

The optimal use of mitoxantrone (NOV) in the high-dose range requires elucidation of its maximum tolerated dose with peripheral blood progenitor cell (PBPC) support and the time interval needed between drug administration and PBPC reinfusion in order to avoid graft toxicity. The aims of this study were: (1) to verify the feasibility and haematological toxicity of escalating NOV up to 90 mg m(-2) with PBPC support; and (2) to verify the safeness of a short (96 h) interval between NOV administration and PBPC reinfusion. Three cohorts of ten patients with breast cancer (BC) or non-Hodgkin's lymphoma (NHL) received escalating doses of NOV, 60, 75 and 90 mg m(-2) plus melphalan (L-PAM), 140-180 mg m(-2), with PBPC rescue 96 h after NOV. Haematological toxicity was evaluated daily (WHO criteria). NOV plasma pharmacokinetics was also evaluated, as well as NOV cytotoxicity against PBPCs. Haematological recovery was rapid and complete at each NOV dose level without statistically significant differences, and there were no major toxicities. NOV plasma concentrations at the time of PBPC reinfusion were below the toxicity threshold against haemopoietic progenitors. It is concluded that, when adequately supported with PBPCs, NOV can be escalated up to 90 mg m(-2) with acceptable haematological toxicity. PBPCs can be safely reinfused as early as 96 h after NOV administration.

Antineoplastic Agents↗
PubMed1997

Standard-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows safe and repeated administration of high-dose cyclophosphamide, etoposide, and cisplatin (CEP).

High-dose chemotherapy often requires hematopoietic progenitor cell reinfusion, but drugs with extramedullary dose-limiting toxicity may be administered in the high-dose range by simple growth factor support. In this study, we evaluated the feasibility and toxicity of a three-drug high-dose regimen supported by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Ten patients with histologically proven malignancy were enrolled. Eight had breast cancer, one non-Hodgkin's lymphoma, and one a mediastinal tumor of unknown origin. The regimen included cyclophosphamide (C) 5 g/m2, etoposide (E) 1.5 g/m2, and cisplatin (P) 150 mg/m2 (CEP), administered in a 3-day schedule followed by rhG-CSF, 300 micrograms once a day, beginning from day +5 (36 h after the end of chemotherapy). The cycle was repeated as clinically needed up to three times. After the first course, hematologic recovery was rapid and complete without documented infections, and no relevant extramyeloid toxicities were observed. Eight of 10 patients received a second course with comparably low toxicity, and three of them received a third course. We concluded that CEP therapy can be administered safely and even repeatedly, by simple growth factor support, in good performance status cancer patients.

Adjuvants, Immunologic↗
PubMed1995

Four-step high-dose sequential chemotherapy with double hematopoietic progenitor-cell rescue for metastatic breast cancer.

PURPOSE: High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast cancer (BC). A current issue is the possibility that these patients may have an even better prognosis with multiple high-dose treatments. In this study, we evaluated the feasibility of a four-step, high-dose sequential chemotherapy (HDSC) with double autologous hematopoietic progenitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment with cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with closely timed repeated courses of several non-cross-resistant agents. PATIENTS AND METHODS: The treatment plan included CY 7 g/m2, followed by GM-CSF 5 to 7 micrograms/kg/d administered by continuous intravenous (i.v.) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) harvest; mitoxantrone (NOV) 60, 75, or 90 mg/m2 plus melphalan (L-PAM) 140 to 180 mg/m2 with hematopoietic rescue; methotrexate (MTX) 8 g/m2 plus vincristine (VCR) 1.4 mg/m2; and etoposide (VP-16) 1.5 g/m2 plus carboplatin (PP) 1.5 g/m2 with hematopoietic rescue. RESULTS: All 15 patients enrolled completed the entire treatment and there were no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/microL and platelet count less than 20,000/microL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP. The main non-hematologic toxicity was mucositis, while organ toxicity was mild and reversible. CONCLUSION: This regimen is feasible, with acceptable toxicity. GM-CSF and PBPCs have a pivotal role, as they hasten hematologic reconstitution, abate toxicity, and allow rapid recycling.

Adult↗
PubMed1995

[Long term central venous catheterization revisited].

The authors describe their experience about long-term VAD (Venous Access Devices) placement and in particular of placement techniques types of catheters, complications, and risk and benefit. 243 placements of VAD in 112 males and 131 females mainly affected by leukemia or breast cancer have been analyzed. 145 Leonard, 54 Groshong and 44 Hickman type silicon catheters have been implanted. The preferred access vein was the right internal jugular vein in 75% of patients and the right subclavian vein in the remained. The results show implant success in 98.7% of the patients. Complications have been rare and not serious and they have been divided into: 1) complications due to venipuncture, 2) complications during implant, 3) complications during the staying of catheter, 4) complications during the removal. The authors underline the advantages of puncture access through the right internal jugular vein in comparison with access through the right subclavian vein. Groshong type catheter is better than Leonard and Hickman. Very few infections have been noticed and patients seem to accept more willingly percutaneous placement than surgical one.

Adolescent↗
PubMed1992

Influence of ST 789 on human neutrophil function in vitro.

We report the results of our in vitro experiments on the effects of an L-Arg terminal synthetic hypoxanthine derivative (ST 789) on human neutrophil function. To verify the hypothesis that the reported immunomodulatory effects of ST 789 in vivo are accounted for, at least in part, by effects on phagocytic cells, we experimented in parallel also with methisoprinol, a well known stimulator of neutrophil chemotaxis, structurally related to ST 789. Our results demonstrate that ST 789 is able to improve the true chemotactic response of human neutrophils without interfering with other phagocytic functions, following a pattern largely shared by methisoprinol. Accordingly, ST 789 may be able, when used in vivo, to prime neutrophils for timely and efficient migration to inflammatory sites, and it could be considered for therapeutic use in patients with impaired inflammatory response or severe infections.

Adjuvants, Immunologic↗
PubMed1992

[Hemostasis screening in the emergency laboratory].

PURPOSE: While automation of laboratories is of great value for analysts, as it makes technical work easier, and for clinicians, as the results are available in a shorter time, the requests increase strikingly bringing about higher costs. The emergency laboratory is an example of what happens in the general laboratory. In order to make an estimate of this subject, the haemostasis screening was chosen since it is a recently automated technique in that laboratory, attention being paid to the aim and indication of the screening and its economical burden. MATERIAL AND METHODS: A study of the haemostasis screening performed during July 1990 was carried out of considering the 24 hours per day work. The requests were classified, in accordance with their indication, as diagnostic, pre-surgical, therapeutic or unknown; the justification and purpose of those requests was also examined. RESULTS: The total number of studies performed in that month was 1,273, with a daily mean of 41, as opposed to 2,095 performed in the haemostasis laboratory in the same period. According to the American Medical Association criteria only 48% of the requests could be warranted, and abnormal findings appeared in only 10% of them. CONCLUSIONS: The cost per isolated parameter is low, but it increases greatly when compared with the benefit that it reports to the patient because, as those biological tests indirectly measure the concentration of clotting factors, they are subjected to error when performed by non-specialized personnel; on the other hand, the most valuable information for detecting haemorrhagic troubles comes from the patient's history. The economical burden in the month studied amounted to 985,879 PTA; one year later, the same laboratory, in the same month, had a 50% increase of studies.

Blood Coagulation Disorders↗
PubMed1991

Tumor cell lysis by activated human neutrophils: analysis of neutrophil-delivered oxidative attack and role of leukocyte function-associated antigen 1.

The lysis of tumor cells, and other nucleated mammalian cells, by neutrophilic polymorphonuclear leukocytes (PMNs) triggered by phorbol myristate acetate (PMA) represents a widely used model system to dissect the PMN cytolytic armamentarium, potentially responsible for the cell damage at tissue sites of PMN activation. Although oxidants are generally considered to be instrumental in the target lysis by PMNs, the mediators actually involved remain a matter of controversy. Moreover, other factors potentially crucial to the lysis have not been clearly identified. In order to reexamine the determinants of the cytolytic process, we studied the events underlying the PMA-triggered PMN-delivered attack against two different targets, selected on the basis of preliminary experiments (B lymphoblastoid Daudi cells and erythroleukemic K 562 cells). The results suggest that the lysis is promoted by hypochlorous acid (HOCl) or a compound with characteristics very similar to HOCl itself. No evidence was obtained for the intervention or contribution of hydrogen peroxide (H2O2), hydroxyl (OH.) radicals, and the major HOCl-derived chloramines. PMNs appeared to use 35% of the generated H2O2 to produce HOCl, while the remainder appears to be consumed by PMNs themselves and target cells as well. Moreover, PMNs and target cells coaggregated at an early step of the cytolytic reaction, through a process efficiently prevented by a monoclonal antibody (MoAb J-90) directed against leukocyte function-associated antigen-1 (LFA-1). The inhibition of the PMN-target aggregation by the MoAb J-90 resulted in the impairment of the lysis, despite a normal generation of HOCl. Thus, the data demonstrate that the PMA-triggered lysis of tumor target cells by PMNs requires at least two events, occurring simultaneously: the LFA-1-mediated effector-target adherence and the PMN production of HOCl. The intervention of the LFA-1-mediated PMN-target adherence in the PMA-triggered lysis is likely to allow PMNs to focus HOCl on the target cell surface and suggests that the process requires a sort of molecule to molecule recognition at the effector-target surface level.

Antibodies, Monoclonal↗
PubMed1990

Cytoprotection against neutrophil derived hypochlorous acid: a potential mechanism for the therapeutic action of 5-aminosalicylic acid in ulcerative colitis.

The aim of the present study was to investigate the effects of 5-aminosalicyclic acid (5-ASA) on the cell injury mediated by activated neutrophils. We used a system constituted of neutrophils, triggered with phorbol myristate acetate, and 51Cr-labelled Daudi cells as targets. The results show that 5-ASA is capable of efficiently preventing neutrophil-mediated lysis. 5-ASA was up to 10-fold more effective than taurine, which acts as an hypochlorous acid scavenger. Moreover, 5-ASA was found to compete with taurine for the neutrophil derived hypochlorous acid. The results are consistent with the conclusion that 5-ASA is capable of limiting the neutrophil mediated cell damage by scavenging the generated hypochlorous acid. This may represent a potential mechanism for the therapeutic action of 5-ASA in ulcerative colitis.

Aminosalicylic Acids↗
PubMed1990

Inactivation of neutrophil-derived hypochlorous acid by nimesulide: a potential mechanism for the tissue protection during inflammation.

The anti-inflammatory drug nimesulide was found to effectively reduce the availability of hypochlorous acid, the most potent chlorinated oxidant generated by the myeloperoxidase system of activated neutrophils. Such an effect was observed at concentrations achievable in vivo after the oral administration of the drug. Higher concentrations of nimesulide were also found to limit both the oxygen consumption and the superoxide anion/hydrogen peroxide production by neutrophils. Taken together, the results suggest that nimesulide is endowed with a high potential to efficiently control the harmful effects of oxidants produced by neutrophils at inflammatory tissue sites.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Effector-target co-aggregation as a crucial step in the neutrophil-mediated tumour cell lysis.

The Daudi cell lysis by human neutrophils, incubated with phorbol myristate acetate (PMA), was inhibited by amino acids (taurine, methionine), consistent with the involvement of hypoclorous acid (HOCl) in the lytic process. Also, the lysis was inhibited by a monoclonal antibody (mAb J-90) directed against the leukocyte function-associated antigen-1 (LFA-1). The inhibition of the target cell lysis by mAb J-90 is not due to a HOCl-scavenging mechanism, as suggested by the use of control mAb Dako M-1 (anti CD-15). As detected by the microscopic examination of samples from test tubes and measured by monitoring the light transmission from the cell suspensions, neutrophils and Daudi cells were found to co-aggregate during the lytic reaction. Co-aggregation was efficiently inhibited by the mAb J-90. The results suggest that tumour cell lysis by PMA-triggered human neutrophils involves at least two events: production of HOCl and LFA-1-mediated effector-target adhesion.

Antibodies, Monoclonal↗
PubMedDate not supplied

Increase in thrombin generation after coronary thrombolysis with rt-PA or streptokinase with simultaneous heparin versus heparin alone.

This study compares the extent of inhibition of thrombin generation and activity achieved in patients with acute myocardial infarction receiving fibrinolytic treatment (streptokinase SK, or rt-PA) and concomitant intravenous heparin treatment adjusted to the patients' weight with that achieved with the same heparin regimen but without fibrinolytic therapy. The study involved 90 patients, grouped according to their treatment: SK+heparin; rt-PA+heparin, and heparin without thrombolytic agents. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), fibrinopeptide A (FPA) and activated partial thromboplastin time were measured. Patients treated with SK+heparin or rt-PA+heparin and higher F1+2 plasma levels than the patients treated with heparin alone at 12, 48 and 72 h in the case of SK+heparin, and at 12, 24, 48 and 72 h in that of rt-PA+heparin. Compared to baseline, the plasma levels of FPA were decreased in the three treatment groups at 24-48 h. There were no significant changes in TAT and FPA plasma levels among the three treatment groups at the different times. After thrombolytic therapy with both SK and rt-PA, there was an increase in thrombin generation, although high-dose intravenous heparin inhibited the different increases in thrombin associated with the thrombolytic agents to the same extent.

Acute Disease↗
PubMedDate not supplied

Elevated thrombotic activity after myocardial infarction: A 2-year follow-up study.

This study examines the evolution of the thrombotic activity in patients with myocardial infarction (MI) treated with aspirin (200 mg/day) for 2 years after MI. Plasma samples of 10 patients were collected at 7, 30, 60, 90, 120, 150, 180, 360 and 720 days. In all the samples we measured fibrinogen (Fg), high molecular weight Fg (HMW-Fg), fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), beta-thromboglobulin (beta-TG), von Willebrand factor (vWF), tissue factor (TF) and TF pathway inhibitor (TFPI). The plasma Fg, HMW-Fg, FPA, F1+2, beta-TG and vWF levels were significantly elevated in the patients at the beginning of the study as compared to the normal group. The 95% confidence intervals were Fg 277-333 mg/dl, HMW-Fg 200-244 mg/dl, FPA 5.3-16.5 ng/ml, F1+2 1.4-1.8 nmol/l, beta-TG 110-118 IU/ml and vWF 139-195%. At thirty days Fg and HMW-Fg returned to normal levels, whereas the increase in FPA and F1+2 levels persisted throughout the study. At 120 and 150 days, respectively, beta-TG and vWF returned to normal levels. The increase in thrombin generation and activity pointed to a persistent hypercoagulable state 2 years after MI. Plasma levels of TF and TFPI showed no statistically significant variations with respect to the normal values over the 2-year period studied. In conclusion, these results suggest a persistent generation and activity of thrombin and cellular activation in these patients after MI.

Aged↗
PubMedDate not supplied

High-dose cyclophosphamide followed by GM-CSF is a safe and effective procedure for the recruitment of trilineage circulating progenitor cells.

BACKGROUND: Several methods for the recruitment of circulating progenitor cells (CPC) to be used for hemopoietic rescue after myeloablative therapy have been described. The present study was designed to verify the effectiveness and safeness of one of such procedures, involving the administration of high-dose cyclophosphamide (HD-CTX) and granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Eight tumor patients were treated with HD-CTX (7 g/m2), followed by GM-CSF (7 mcg/Kg/day, continuous infusion) from day +2 to the completion of leukocyte recovery, when aphereses for CPC harvesting were performed. CPC were evaluated by clonogenic assay for granulocyte-macrophage colony-forming units (CFU-GM), megakaryocyte colony-forming units (CFU-Meg) and erythrocyte burst-forming units (BFU-E) before therapy as well as during the hemopoietic recovery. RESULTS: In each patient, a significant increase of trilineage CPC was observed, at a mean of 14 days from HD-CTX, with peak increment of 224, 268 and 230-fold for CFU-GM, CFU-Meg and BFU-E respectively. The mean duration of leukocyte count < or = 0.5 x 10(9)/l was 6.6 days, with severe thrombocytopenia (grade 4 WHO) lasting 2.8 days in 5 patients. GM-CSF infusion was well tolerated without any need for dose reduction or discontinuation. CONCLUSION: The administration of HD-CTX and GM-CSF induces a significant enhancement of CPC including CFU-Meg other than CFU-GM and BFU-E. The procedure is suitable for the recruitment of CPC in patients with CTX sensitive tumors.

Adult↗
PubMedDate not supplied

[Study of oligosaccharides in human urothelial membrane by means of lectins].

We have used four lectins (PHA-L, HPA, RCA-120 and PNA) to characterise the oligosaccharides present in the membrane of the different cell layers of the human vesical urothelium, obtained from 27 normal biopsies of vesical mucus. In all the patients studied the PHA-L and HPA lectins showed an affinity for all the urothelial layers, and a progressive increase in fluorescence is observed from the basal to the surface stratum. The pattern observed when using lectin RCA-120 was a positive marking of all the urothelial layers studied, with a homogeneous intensity in all of them. The PNA lectin did not show reactivity to the normal urothelium in none of the cases studied. We comment on the applications of this type of study both for characterizing the glycid composition of the urothelial cell membrane and for ascertaining its variations in accordance with cell differentiation.

Acetylgalactosamine↗
PubMedDate not supplied

The surgical correction of varicocele: multidisciplinary study on semen evaluation and prognostic factors for fertility.

The seminal pattern was studied in a group of 52 patients before and six months after sclerotherapy of varicocele. In this series, we studied the differences in clinical and seminal characteristics between the group that succeeded in obtaining a pregnancy and the group that remained infertile after 1 year follow-up. The difference in pregnancy rate is discussed between the operated group and a control group of pz, who refused any form of surgery, after 1 year follow-up.

Evaluation Studies as Topic↗