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Biomedical subjects

M Marchetti

Publications and source records attributed to M Marchetti.

At least 73 records · Page 4Linked to original sources
PubMed1999

Long-term cost-effectiveness of low molecular weight heparin versus unfractionated heparin for the prophylaxis of venous thromboembolism in elective hip replacement.

BACKGROUND AND OBJECTIVE: Either low molecular weight heparin (LMWH) or unfractionated heparin (UH) may be used for the prophylaxis of post-operative venous thromboembolic disease (VTD) in elective hip replacement. This study was aimed at assessing the cost-effectiveness of LMWH over UH from the society perspective, which considers all the outcomes occurring in the life-long time horizon. DESIGN AND METHODS: A decision tree modeled the clinical outcomes and resources used in consequence of restricted (2 weeks) and extended (4 weeks) prophylaxis of VTD with LMWH or UH. RESULTS: In the studied population, that of 67 year-old patients, restricted prophylaxis with LMWH saved 25 quality-adjusted days and $75 over UH. Extended prophylaxis provided a small additional benefit with additional cost savings. The incremental outcomes of the model proved independent of most parameters. INTERPRETATION AND CONCLUSIONS: We conclude that LMWH has considerable advantages over UH in the prophylaxis of VTD following elective hip replacement, and should be recommended in clinical practice.

Aged↗
PubMed1999

Decision support systems in health economics.

This article describes a system addressed to different health care professionals for building, using, and sharing decision support systems for resource allocation. The system deals with selected areas, namely the choice of diagnostic tests, the therapy planning, and the instrumentation purchase. Decision support is based on decision-analytic models, incorporating an explicit knowledge representation of both the medical domain knowledge and the economic evaluation theory. Application models are built on top of meta-models, that are used as guidelines for making explicit both the cost and effectiveness components. This approach improves the transparency and soundness of the collaborative decision-making process and facilitates the result interpretation.

Computer Simulation↗
PubMed1999

The cardiovascular work of competitive dinghy sailing.

BACKGROUND: Hiking is the special manoeuvre, which the dinghy sailor uses to counterbalance the capsizing effect of the wind on the boat. In the present research the work required of the heart by this exercise was studied in the laboratory using a boat simulator. METHODS: Seven Laser male sailors selected from those in the first places in the junior national rank participated in this study. Their endurance, at different levels of isometric hiking efforts, was measured. Energy expenditure due to hiking was estimated from measurements of oxygen consumption, carbon dioxide elimination and blood lactate concentration. The cardiac load was evaluated by measuring blood pressure using the conventional method and heart rate measured by electrocardiography. Cardiac output was measured using the CO2 re-breathing method. Left ventricular work was then calculated as cardiac output multiplied by mean arterial pressure. RESULTS: The most relevant result was that, while whole body cost of hiking was relatively low (about 1 IO2 min-1), the power of the heart was very significant: cardiac output almost doubled with respect to that at rest and arterial mean pressure rose from 12.5 kPa (rest) to 18.5 kPa (hiking). Thus, left ventricular power rose from 1.2 Watt to 3.2 Watt, which is a typical cardiovascular response to muscular isometric contraction. CONCLUSIONS: These results assume relevance when a person's eligibility for sailing sports is evaluated.

Adolescent↗
PubMed1998

Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells.

All-trans-retinoic acid (ATRA) downregulates the expression of two cellular procoagulants, tissue factor (TF) and cancer procoagulant (CP), in human promyelocytic leukemia cells. To evaluate whether or not changes of the procoagulant activities (PCAs) may share mechanisms with the ATRA-induced cyto-differentiation process, we have characterized the effect of ATRA on the TF and CP expression by NB4 cells, an ATRA maturation-inducible cell line, and two NB4-derived cell lines resistant to ATRA-induced maturation, the NB4. 306 and NB4.007/6 cells. Next, we evaluated the effect on the PCAs of the NB4 parental cells of three synthetic retinoid analogues, ie: AM580 (selective for the retinoic acid receptor [RAR] alpha), capable to induce the granulocytic differentiation of NB4 cells; and CD2019 (selective for RARbeta) and CD437 (selective for RARgamma), both lacking this capability. Cells were treated with either ATRA or the analogues (10(-6) to 10(-8) mol/L) for 96 hours. The effect on cell differentiation was evaluated by morphologic changes, cell proliferation, nitro blue tetrazolium reduction assay, and flow cytometry analysis of the CD33 and CD11b surface-antigen expression. PCA was first measured in 20 mmol/L Veronal Buffer cell extracts by the one-stage clotting assay of normal and FVII-deficient plasmas. Further TF and CP have been characterized and quantified in cell-sample preparations by chromogenic and immunological assays. In the first series of experiments, ATRA downregulates both TF and CP in NB4 parental cells, as expected. However, in the differentiation-resistant cell lines, it induced a significant loss of TF but had little or no effect on CP. In a second series of experiments, in the NB4 parental cells, the RARalpha agonist (AM580) induced cell maturation and reduced 91% CP expression, whereas CD437 and CD2019 had no cyto-differentiating effects and did not affect CP levels. On the other hand, in the same cells the TF expression was reduced by ATRA and AM580, but also by the RARbeta agonist CD2019, which did not induce cell maturation. These data indicate that in NB4 cells, ATRA modulation of CP occurs in parallel with signs of cell differentiation, while the regulation of TF appears to be at least in part independent from these processes, and involves both alpha and beta nuclear retinoid receptors.

Antineoplastic Agents↗
PubMed1998

Aspirin increases the bleeding side effects in essential thrombocythemia independent of the cyclooxygenase pathway: role of the lipoxygenase pathway.

Acetylsalicylic acid (ASA) is currently recommended as an antithrombotic for patients with essential thrombocythemia (ET) who are at an increased risk of thrombotic events. However, ASA is also associated with an increased risk of bleeding in these patients as compared to the risk of bleeding in other patients treated with ASA. Recent data suggest that while ASA inhibits platelet thromboxane A2 (TxA2) synthesis in all individuals, ASA has little effect or inhibits the lipoxygenase pathway (i.e., 12-hydroxyeicosatetranoic acid or 12-HETE synthesis) in some individuals, and enhances 12-HETE synthesis in others. These differential effects are associated with a pronounced prolongation of the bleeding time vs. no prolongation of the bleeding time, respectively, i.e., in ASA responders and ASA nonresponders, respectively. To determine if the increased risk of ASA-induced bleeding seen in ET patients is associated with an effect on 12-HETE synthesis, we compared the relative effects of ASA on the bleeding time, platelet TxA2 and 12-HETE synthesis, and platelet aggregation and adhesion in ET patients and healthy volunteers. ASA (300 mg, taken orally) prolonged the bleeding time in 82% of the ET patients but only 27% of the healthy volunteers although platelet TxA2 synthesis and ADP- and collagen-induced aggregation were inhibited significantly in both groups. In contrast, platelet 12-HETE synthesis was unchanged and platelet adhesion was decreased in those patients and volunteers whose bleeding times were prolonged by ASA, whereas platelet 12-HETE synthesis was increased significantly and platelet adhesion was unaffected in those patients and volunteers whose bleeding times were not prolonged, and in some cases shortened by ASA. These results confirm previous data that demonstrate that ASA has different effects on platelet 12-HETE synthesis and platelet adhesion in different individuals, i.e., inhibitory or no effect in ASA responders (in whom ASA prolonged bleeding) vs. enhancing effects in ASA nonresponders (in whom ASA did not prolong bleeding). These results also indicate that there is a greater percentage of ASA responders in patients with ET than that seen in the general population, a difference that is associated with an effect of ASA on the lipoxygenase pathway. This may explain the increased bleeding side effects seen in the ET patient population.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1998

Oxidative stress, antioxidant defences and aging.

Apoptosis and aging share common mechanisms in oxidative stress and mitochondrial involvement. Treatment of cultured neuroblastoma cells with a radical initiator induced apoptosis; raise in hydrogen peroxide and release of cytochrome c from mitochondria preceded collapse of mitochondrial potential and cell death. In rat hepatocytes treated with adriamycin incubation with exogenous Coenzyme Q10 counteracted the drug-induced increase of hydrogen peroxide and the fall of the mitochondrial potential, thus demonstrating the quinone antioxidant effect. Complex I activity and its rotenone sensitivity decreased in brain cortex non-synaptic mitochondria from old rats; a 5 kb mitochondrial DNA deletion was found only in the old rats. A similar behavior was found in human platelets from old individuals. The postulated energy decline was confirmed by the inhibitor sensitivities of platelet aggregation and lactate production. The lack of the 5 kb deletion in platelets throws doubts on mitochondrial DNA lesions as the only causes of mitochondrial dysfunction in aging.

Aging↗
PubMed1998

Protection against Helicobacter pylori infection in mice by intragastric vaccination with H. pylori antigens is achieved using a non-toxic mutant of E. coli heat-labile enterotoxin (LT) as adjuvant.

We have previously shown that infection of mice with H. pylori can be prevented by oral immunization with H. pylori antigens given together with E. coli heat-labile enterotoxin (LT) as adjuvant. Since LT cannot be used in humans because of its unacceptable toxicity, we investigated whether protection of mice could be achieved by co-administration of antigens with non-toxic LT mutants. Here we show that CD1/SPF mice are protected against infection after oral vaccination with either purified H. pylori antigens (native and recombinant VacA, urease and CagA), or whole-cell vaccine formulations, given together with the non-toxic mutant LTK63 as a mucosal adjuvant. Furthermore we show that such protection is antigen-specific since immunization with recombinant or native VacA plus LTK63 conferred protection against infection by an H. pylori Type I strain, which expresses VacA, but not against challenge with a Type II strain which is not able to express this antigen. These results show that: (1) protection against H. pylori can be achieved in the mouse model of infection using subunit recombinant constructs plus non-toxic mucosal adjuvants; and (2) this mouse model is an useful tool in testing H. pylori vaccine formulations for eventual use in humans.

Adjuvants, Immunologic↗
PubMed1998

Metal complexes of bovine lactoferrin inhibit in vitro replication of herpes simplex virus type 1 and 2.

The inhibitory effect of bovine lactoferrin (BLf) saturated with ferric, manganese or zinc ions, on the infection of Vero cells by human herpes simplex virus type 1 (HSV1) and 2 (HSV2) was investigated. Viral infectivity determined by intracellular antigen synthesis and plaque formation was efficiently inhibited by metal saturated lactoferrins in a dose-dependent manner. Effective BLf concentrations which reduced the infection by 50% ranged from 5.2 to 31 micrograms ml-1 and were far below the cytotoxicity threshold. Fe3+BLf and Mn2+BLf exhibited selectivity indexes higher than Zn2+BLf and apoBLf for both viruses and the effect was mainly directed towards the early steps of infection. The slight viral inhibition shown by the citrate complexes of the different metals could indicate that the antiviral effect was not significantly influenced by Fe3+, Mn2+ or Zn2+ ions delivered by BLf into the cells.

Animals↗
PubMed1998

Cost-effectiveness of recombinant human erythropoietin in the prevention of chemotherapy-induced anaemia.

Recombinant human erythropoietin (rHuEPO) has been advocated for the treatment of anaemia in patients submitted to cancer chemotherapy. We used decision analysis to compare the cost-effectiveness of rHuEPO supplemented with red blood cell (RBC) transfusions with conventional treatment with RBC transfusions alone. At baseline, we analysed the use of rHuEPO as secondary prophylaxis according to effectiveness estimates from a community-based oncology study. In order to reduce the probability of transfusions from 21.9% to 10.4%, and the number of RBC units per patient per month from 0.55 to 0.29, 150 units kg(-1) s.c. rHuEPO three times per week for 4 months resulted in an incremental cost of $189,652 per quality-adjusted life year (QALY). In patients treated with cisplatin-containing chemotherapy, rHuEPO added $190,142 per QALY. In a hypothetical scenario of a transfusion pattern that maintained the same haemoglobin level of rHuEPO-responsive patients, the marginal cost of rHuEPO was always greater than $100,000 per QALY. Results were stable with regard to variations in the probability of blood-borne infections, quality of life of responding patients and cancer-related mortality. The additional cost could be lowered to less than $100,000 per QALY by saving 4.5 RBC units over 4 months for any patient treated. In conclusion, according to current use, rHuEPO is not cost-effective in the treatment of chemotherapy-induced anaemia. More tailored utilization of the drug and better consideration of predictive response indicators may lead to an effective, blood-sparing alternative.

Aged↗
PubMed1998

Prophylactic splenectomy and cholecystectomy in mild hereditary spherocytosis: analyzing the decision in different clinical scenarios.

OBJECTIVES: Patients with mild hereditary spherocytosis (HS), i.e. with haemolysis without anaemia. have an increased risk of gallstone formation, erythroid aplasia and haemolytic crisis. Since the effect of prophylactic splenectomy on life expectancy has not been established, we conducted a decision analysis comparing prophylactic splenectomy and cholecystectomy with no surgery. DESIGN: The available data on surgery and disease outcomes were modelled to estimate the effects of the different interventions on the quality-adjusted life expectancy. The early phase outcomes depicted surgery-related mortality and incorporated compliance and the adverse effects of prophylaxis against post splenectomy infections. The late phase outcomes were framed by a Markov cohort analysis. RESULTS: For patients without gallstones, surgery was of no benefit. For those with gallstones the preferred strategies were found to be splenectomy and cholecystectomy before the age of 39 when asymptomatic, and before 52 when accompanied by occasional biliary colic. Cholecystectomy alone proved to be the preferred strategy in older patients with occasional biliary colic. For patients of up to 52 years of age and candidates for cholecystectomy because of recurrent biliary colic, the best strategy was to combine this procedure with splenectomy. Sensitivity analysis showed that the results were sensitive to the incidence of post cholecystectomy syndrome. Most remarkably an extreme sensitivity to compliance with post splenectomy infection prophylaxis was demonstrated. CONCLUSIONS: Our model suggested that combined prophylactic splenectomy and cholecystectomy provide a substantial gain in quality-adjusted life expectancy for young patients and adults with mild HS and gallstones.

Adolescent↗
PubMed1998

Vitamin B6 deficiency affects antioxidant defences in rat liver and heart.

We have evaluated the effects of a diet containing normal amounts of lipids and a marginal content of vitamin B6 on lipid peroxidation. Pyridoxal phosphate concentrations of plasma and liver indicated that an initial deficiency state was reached. Vitamin B6 deficiency led to peroxidative stress: TBARS production was higher in the liver (+18.6%) and even more in the heart (+61%) of deficient rats as compared with controls. Furthermore, significant stimulation of glutathione-dependent enzymes occurred in both heart and liver of deficient rats: glutathione peroxidase activity increased in heart (+144%) and liver (+505%); glutathione reductase increased in heart (+54.9%) and liver (+15.5%). No difference in the total glutathione content of the organs of the two groups was observed. The reduced glutathione/oxidized glutathione ratio was significantly lower in deficient rats. Although the activity of glutathione-dependent enzymes was significantly greater in deficient rats than in controls, this stimulation was only partially able to counteract the peroxidative damage due to vitamin B6 deficiency.

Animals↗
PubMed1998

The value of the prognostic factors in ovarian granulosa cell tumors.

The malignant potential of granulosa cell tumors (GCT) of the ovary is much debated. This study includes 18 patients with a diagnosis of GCT of the ovary. Clinical and pathologic data from patients were compared with flow cytometry ploidy, Ki-67 reactivity and p53 overexpression in order to determine their prognostic usefulness. There was no correlation between ploidy and stages or between ploidy and biological behavior. On the other hand, mitotic count, Ki-67 reactivity and p53 overexpression were associated with stages of disease, recurrent onset and survival. We believe that ploidy, Ki-67 and p53 should be considered important prognostic factors for GCT in association with the other more studied prognostic factors, even if no conclusions can be reached.

Adult↗
PubMed1998

Malignant ovarian tumors: conservative surgery and quality of life in young patients.

Better knowledge and adequate treatment of malignant ovarian tumors have improved the quality of life of young women--especially of child-bearing age. Nowadays preservation of ovarian function in women with tumors in early stage (I) or, in selected cases even in advanced stage (II-III), must be evaluated for conservative surgery (sometimes expressly requested by the patient herself). In our Institute we have followed this philosophy for many years and our experience confirms its value: 42 patients under age 40 (36 in stage I and 6 in advanced stage) underwent conservative surgery: 12 subsequently became pregnant and another 12 are able to conceive. Five- and ten-year survival rates are very good with 89.2% and 83.3% for all stages and 96.9% and 95% for early stages.

Adult↗
PubMed1998

Intrauterine ectopic pregnancy. A case report.

A case of vaginal bleeding occurring in a patient with a cervico-isthmic pregnancy located in a previous caesarean section scar was treated with curettage and systemic methotrexate. Metrorrhagia and uterine rupture are severe complications of this kind of ectopic pregnancy and sometimes require demolitive surgery, still today. Early ultrasonographic diagnosis is necessary to allow conservative treatment.

Adult↗
PubMed1997

Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non-synaptic mitochondria of aged rats.

We investigated NADH oxidation in non-synaptic and synaptic mitochondria from brain cortex of 4- and 24-month-old rats. The NADH oxidase activity was significantly lower in non-synaptic mitochondria from aged rats; we also found a significant decrease of sensitivity of NADH oxidation to the specific Complex I inhibitor, rotenone. Since the rotenone-binding site encompasses Complex I subunits encoded by mtDNA, these results are in accordance with the mitochondrial theory of aging, whereby somatic mtDNA mutations are at the basis of cellular senescence. Accordingly, a 5 kb deletion was detected only in the cortex of the aged animals.

Aging↗
PubMed1997

Coenzyme Q changes in liver and plasma in the rat after partial hepatectomy.

The levels of coenzyme Q were determined in blood plasma and regenerating liver mitochondria of hepatectomized rats, using as controls either sham-operated or non-operated animals. Mitochondrial CoQ9 content increased in sham-operated rats, whereas it was significantly lower in hepatectomized with respect to non-operated animals. Plasma CoQ9 levels decreased dramatically in hepatectomized animals, but increased strongly in sham-operated in comparison with non-operated rats. The data suggest the possibility of a rate-limiting step in CoQ biosynthesis in hepatectomized animals.

Animals↗