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Biomedical subjects

M Marchetti

Publications and source records attributed to M Marchetti.

At least 19 recordsLinked to original sources

Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with type II diabetes.

AIMS/HYPOTHESIS: To determine whether raxofelast, a new water soluble antioxidant decreases oxidative stress and improves endothelial function in men with Type II (non-insulin dependent) diabetes mellitus. METHODS: We treated ten normotensive, normocholesterolaemic men with Type II diabetes and as controls ten healthy men matched with them for age with raxofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF(2a), a non-enzymic oxidation product of arachidonic acid was measured by gas chromatography/mass spectrometry as an index of oxidative stress. Forearm vasodilator responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 microg min(-1)) and of the nitric oxide donor nitroprusside (1, 3 and 10 microg min(-1)) were measured by strain gauge plethysmography. RESULTS: Plasma concentrations of 8-epi-PGF(2a), were greater in diabetic than in control men (0.99 +/- 0.20 vs 0.18 +/- 0.01 nmol 1(-1), means +/- SEM, p < 0.001) and fell after raxofelast (from 0.99 +/- 0.20 to 0.47 +/- 0.07 nmol 1(-1), p < 0.05) in diabetic men but not in control men. Blood flow responses to acetylcholine were lower (p < 0.05) in diabetic than in control men (7.4 +/- 1.0 vs 12.9 +/- 2.3 ml min(-1) x 100 ml(-1) for the highest dose). In diabetic men, but not in control men, raxofelast increased (p < 0.05) blood flow responses to acetylcholine (from 7.4 +/- 1.0 m x min(-1) x 100 ml(-1) to 11.3 +/- 2.3 ml x min(-1) x 100 ml(-1) at highest dose). Blood flow responses to nitroprusside were similar in control and diabetic men and in both groups were similar before and after raxofelast. CONCLUSION/INTERPRETATION: Oral treatment with raxofelast for 1 week reduces oxidative stress and improves endothelial function in men with Type II diabetes.

Acetylcholine↗

Walking index for spinal cord injury (WISCI): an international multicenter validity and reliability study.

STUDY DESIGN: Construction of an international walking scale by a modified Delphi technique. OBJECTIVE: The purpose of the study was to develop a more precise walking scale for use in clinical trials of subjects with spinal cord injury (SCI) and to determine its validity and reliability. SETTING: Eight SCI centers in Australia, Brazil, Canada (2), Korea, Italy, the UK and the US. METHODS: Original items were constructed by experts at two SCI centers (Italy and the US) and blindly ranked in an hierarchical order (pilot data). These items were compared to the Functional Independence Measure (FIM) for concurrent validity. Subsequent independent blind rank ordering of items was completed at all eight centers (24 individuals and eight teams). Final consensus on rank ordering was reached during an international meeting (face validation). A videotape comprised of 40 clips of patients walking was forwarded to all eight centers and inter-rater reliability data collected. RESULTS: Kendall coefficient of concordance for the pilot data was significant (W=0. 843, P<0.001) indicating agreement among the experts in rank ordering of original items. FIM comparison (Spearman's rank correlation coefficient=0.765, P<0.001) showed a theoretical relationship, however a practical difference in what is measured by each scale. Kendall coefficient of concordance for the international blind hierarchical ranking showed significance (W=0.860, P<0.001) indicating agreement in rank ordering across all eight centers. Group consensus meeting resulted in a 19 item hierarchical rank ordered 'Walking Index for Spinal Cord Injury (WISCI)'. Inter-rater reliability scoring of the 40 video clips showed 100% agreement. CONCLUSIONS: This is the first time a walking scale for SCI of this complexity has been developed and judged by an international group of experts. The WISCI showed good validity and reliability, but needs to be assessed in clinical settings for responsiveness.

Australia↗

Cost-effectiveness of epoetin and autologous blood donationin reducing allogeneic blood transfusions incoronary artery bypass graft surgery.

BACKGROUND: Coronary artery bypass graft (CABG) surgery accounts for a substantial portion of all allogeneic units of blood transfused. Drugs and autologous blood donation (ABD) are alternative or adjunctive methods for reducing complications and costs induced by allogeneic blood transfusions. Recombinant human erythropoietin (epoetin) has the potential to decrease perioperative need for allogeneic blood during CABG, but its high cost calls for a careful economic evaluation before it can be recommended for widespread use. STUDY DESIGN AND METHODS: A decision tree was used to compare a hypothetical strategy of no epoetin with one in which epoetin was utilized to control blood transfusion needs in CABG; each strategy was tested with and without ABD. The impact of these strategies on both the quality-adjusted life years (QALYs) and costs ($US) was calculated. RESULTS: Using epoetin alone and with ABD, respectively, avoided the transfusion of 0.61 and 1.35 units of allogeneic blood per patient and saved 0.000086 and 0.000146 QALYs per patient. This made cost-effectiveness (CE) higher than $7 million and $5 million for each QALY saved, respectively. ABD alone cost more than $1 million per QALY saved. If the risk of bacterial infections following allogeneic transfusions was included in the model, epoetin alone cost $6288 per QALY saved, while ABD, both alone and with epoetin, saved money. CONCLUSION: On the basis of the existing evidence, neither of the blood-saving strategies modeled was a cost-effective means of avoiding the deleterious health effects of perioperative blood transfusions in CABG. However, if allogeneic blood-related infections were to be considered, both ABD and epoetin would be acceptable interventions.

Aged↗

Infection of human enterocyte-like cells with rotavirus enhances invasiveness of Yersinia enterocolitica and Y. pseudotuberculosis.

Mixed infection with rotavirus and either Yersinia enterocolitica or Y. pseudotuberculosis was analysed in Caco-2 cells, an enterocyte-like cell line highly susceptible to these pathogens. Results showed an increase of bacterial adhesion and internalisation in rotavirus-infected cells. Increased internalisation was also seen with Escherichia coli strain HB101 (pRI203), harbouring the inv gene from Y. pseudotuberculosis, which is involved in the invasion process of host cells. In contrast, the superinfection with bacteria of Caco-2 cells pre-infected with rotavirus resulted in decreased viral antigen synthesis. Transmission electron microscopy confirmed the dual infection of enterocytes. These data suggest that rotavirus infection enhances the early interaction between host cell surfaces and enteroinvasive Yersinia spp.

Adhesins, Bacterial↗

Prognostic value of bcl-2, p53 and Ki-67 in invasive squamous carcinoma of the uterine cervix.

The aim of this study was to evaluate the immunohistochemical expression of the markers bcl-2, p53 and Ki67 and their relation to the classical clinical-pathological prognostic factors in invasive squamous cellular carcinoma of the cervix. Since bcl-2 and p53 are implicated in the regulation of programmed cell death, very probably they play a role in carcinogenesis and consequently become prognostic factors.

Adult↗

Bovine lactoferrin peptidic fragments involved in inhibition of herpes simplex virus type 1 infection.

Bovine lactoferrin (BLf) prevents the infection of some enveloped and naked viruses. To identify BLf sequences responsible for the antiviral activity, we tested 31 HPLC fractions, derived from tryptic digestion of BLf, toward herpes simplex virus type 1 (HSV-1). Only a few HPLC purified fragments were active against HSV-1, even if at lower extent than the native undigested BLf. Two large fragments, one corresponding to the C-lobe (amino acid sequence 345-689) and the other corresponding to a large portion of the N-lobe (1-280), were inhibitors of HSV-1 infection, while a smaller part of the N-lobe (86-258) was ineffective. Among the low-molecular-weight fragments, only two small peptides, which coeluted in a single chromatographic peak, were effective towards HSV-1. These peptides, both present in the N-lobe, were identified as peptides 222-230 (ADRDQYELL) and 264-269 (EDLIWK). The same peptides, chemically synthesised, were able to inhibit HSV-1 infection only when they were assayed in association.

Animals↗

Neutrophil activation and hemostatic changes in healthy donors receiving granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) enhances neutrophil functions in vitro and in vivo. It is known that neutrophil-derived products can alter the hemostatic balance. To understand whether polymorphonuclear leukocyte (PMN) activation, measured as PMN degranulation and phenotypical change, may be associated to hemostatic alterations in vivo, we have studied the effect of recombinant human G-CSF (rHuG-CSF) administration on leukocyte parameters and hemostatic variables in healthy donors of hematopoietic progenitor cells (HPCs). Twenty-six consecutive healthy donors receiving 10 micrograms/kg/d rHuG-CSF subcutaneously for 5 to 7 days to mobilize HPCs for allogeneic transplants were included in the study. All of them responded to rHuG-CSF with a significant white blood cell count increase. Blood samples were drawn before therapy on days 2 and 5 and 1 week after stopping rHuG-CSF treatment. The following parameters were evaluated: (1) PMN activation parameters, ie, surface CD11b/CD18 antigen expression, plasma elastase antigen levels and cellular elastase activity; (2) plasma markers of endothelium activation, ie, thrombomodulin (TM) and von Willebrand factor (vWF) antigens; (3) plasma markers of blood coagulation activation, ie, F1+2, TAT complex, D-dimer; and (4) mononuclear cell (MNC) procoagulant activity (PCA) expression. The results show that, after starting rHuG-CSF, an in vivo PMN activation occurred, as demonstrated by the significant increment of surface CD11b/CD18 and plasma elastase antigen levels. Moreover, PMN cellular elastase activity, which was significantly increased at 1 day of treatment, returned to baseline at day 5 to 6, in correspondence with the elastase antigen peak in the circulation. This change was accompanied by a parallel significant increase in plasma levels of the two endothelial and the three coagulation markers. The PCA generated in vitro by unstimulated MNC isolated from rHuG-CSF-treated subjects was not different from that of control cells from untreated subjects. However, endotoxin-stimulated MNC isolated from on-treatment individuals produced significantly more PCA compared with both baseline and control samples. All of the parameters were decreased or normal 1 week after stopping treatment. These data show that rHuG-CSF induces PMN activation and transiently affects some hemostatic variables in healthy HPC donor subjects. The clinical significance of these findings remains to be established.

Adolescent↗

Inhibition of poliovirus type 1 infection by iron-, manganese- and zinc-saturated lactoferrin.

In this study we investigated the inhibitory activity of different milk proteins on poliovirus infection in Vero cells. Proteins analyzed were mucin, alpha-lactalbumin, beta-lactoglobulin, and bovine and human lactoferrin. Viral cytopathic effect was not prevented by mucin, alpha-lactalbumin or beta-lactoglobulin, whereas the lactoferrins tested were able to inhibit the replication of poliovirus in a dose-dependent manner. Further experiments were carried out in which apo- and native lactoferrin or lactoferrin fully saturated with ferric, manganese or zinc ions were added to the cells during different phases of viral infection. Results obtained demonstrated that all lactoferrins were able to prevent viral replication when present during the entire cycle of poliovirus infection or during the viral adsorption step. Only zinc lactoferrin strongly inhibited viral infection when incubated with the cells after the viral attachment, being the inhibition directly correlated with the degree of zinc saturation. Our results demonstrated that all lactoferrins interfered with an early phase of poliovirus infection; zinc lactoferrin was the sole compound capable of inhibiting a phase of infection subsequent to virus internalization into the host cells.

Animals↗

Force generation performance and motor unit recruitment strategy in muscles of contralateral limbs.

The purpose of the present study was to determine whether the motor unit (MU) recruitment strategy of the agonist and antagonist muscles in the dominant arm differs from that in the non-dominant arm. The median frequency (MF) of the power density spectrum (PDS) of the electromyogram (EMG) was used as a tracking parameter to describe the MU recruitment. In 8 subjects the EMG was recorded from the biceps brachii and triceps brachii of each limb during isometric elbow flexion performed in a ramp fashion. Force was increased from 0 to 100% of the maximum voluntary contraction (MVC) in 3 s following a track displayed on an oscilloscope. When comparing the dominant versus non-dominant arm we found no statistical difference in the MU recruitment pattern of the biceps brachii and the triceps. Because the dominant arm was not always the better performing arm, we grouped the data according to the ability of the subjects to track the ramp signal. In this case we found a statistically significant difference between the better and worse performing arm in the full MU recruitment of the biceps. A more precise and accurate control of the increase in force was obtained when the central nervous system selected a slower and prolonged recruitment of MUs in the agonist muscle.

Adult↗

Cost of walking and locomotor impairment.

The aim of the present study was to evaluate the importance and the necessity of metabolic measurements to quantify locomotor impairment in a clinical context. Oxygen consumption, heart rate, pulmonary ventilation and walking speed were measured during locomotion in 14 normal subjects, used as a control group, and 82 patients with different pathologies [hemiparetic, paraparetic, tetraparetic, orthopaedic and paraplegic patients, who walked using a reciprocating gait orthosis (RGO)]. The subjects were characterized on the basis of a cumulative impairment score (CIS), based on clinical scales commonly used to evaluate impairment and disability in locomotion. Appropriate indices of energy, cardiac and ventilatory costs expressed per metre walked, globally called physiological costs, were obtained. It resulted that the most comfortable speed (MCS) of normal subjects was significantly higher than that of each group of patients. Normal subjects' physiological costs were found to be significantly lower than those of patients who needed either a device or the help of a person to walk. All measured parameters correlated significantly with each other. The MCS was found to be the most correlated parameter with the CIS (r = 0.8), and therefore it must be considered the best single measurement, if only one is to be used. Measurements more precise than MCS, such as the physiological costs, may be necessary in clinical trials.

Adult↗

Influence of dietary n-3 polyunsaturated fatty acids on plasma lipemic effect of vitamin B6 deficiency.

Since many connections exist between vitamin B6 and lipid metabolism, we aim to investigate the lipemic effect of different dietary intakes of polyunsaturated fatty acids in rats fed a vitamin B6 deficient diet. Diets were either vitamin B6 deficient (-B6) or vitamin B6 sufficient, pair-fed to the deficient group (PF) and ad libitum (N). The diets were combined with normal lipid (LC: soya bean-coconut-palm oils) and fish oil (FO: soya bean-fish oil). The fish oil diet with sufficient vitamin B6 content caused an increase in n-3 long chain polyunsaturated fatty acids and a decrease in arachidonic acid. In the -B6 group fed a normal lipid diet, the arachidonic acid percentage decreased and the linoleic acid percentage increased; in the -B6 group fed fish oil these changes in fatty acid composition, already consequent upon dietary intake of n-3 long chain polyunsaturated fatty acids, did not show further variations. In the dietary condition of vitamin B6 deficiency, plasma cholesterol content increased in rats fed a lipid control diet, whereas no hypocholesterolemic effect was observed in those fed a fish oil diet. Plasma triglyceride contents were not influenced by dietary lipid quality because, in all conditions, the lower food intake of the PF groups caused a decrease and vitamin B6 deficiency caused an elevation in triglyceride contents which reached those of the ad libitum groups. The study highlights the interaction between vitamin B6 and polyunsaturated fatty acids and the opportunity of dietary intake of fish oil to counterbalance some effects of vitamin B6 deficiency.

Animals↗

A model for analysing the cost of autologous peripheral blood progenitor cell (PBPC) transplantation.

Data from autologous peripheral blood progenitor cell (PBPC) transplant recipients were used for cost analysis and modelling so as to link the main intervention procedures and clinical events to resource use and costs. This cohort consisted of 64 patients from 4 to 62 years old at transplantation (mean, 36.9 years) who underwent a first transplant between August 1994 and May 1997. The main indications for transplantation were non-Hodgkin's lymphomas (47%), multiple myeloma (30%) and Hodgkin's lymphomas (15%). The course of a patient during the whole transplant procedure was modelled using a Markov chain of six states of health: (1) mobilisation and recovery of PBPC; (2) post-mobilisation phase; (3) conditioning and transplant; (4) critical haematological reconstitution; (5) non-critical haematological reconstitution; (6) death. The probability of transition between the different health states, together with the estimated costs, were the input for the Markov model. The model also managed transition probabilities depending both on the current health state and on various demographic, clinical and procedure-related covariates unique to the patient. The expected time spent in each clinical state and the expected total cost were, therefore, estimated. This analysis gave an actual total cost per transplanted patient of $26,600 (95% range: $24,700 to $43,500) while mean duration was 197 days. The expenses for in-hospital stay accounted for 80% of the costs. Both the probability of staying in the different states, and the consequent cost were dependent on the number of CD34-positive cells collected, the phase and the type of the disease, the subset of patients (either children or adults), and the post-transplant G-CSF prophylaxis. The sensitivity of the estimates to alternative assumptions was studied, and the method of comparing alternative future scenarios by the model was explored.

Adolescent↗

Ambulation training of neurological patients on the treadmill with a new Walking Assistance and Rehabilitation Device (WARD).

STUDY DESIGN: Patients with neurological walking impairment were rehabilitated with a new system, consisting of an apparatus to constantly relieve the body weight and a treadmill: The Walking Assistance and Rehabilitation Device (WARD). Patients were evaluated before and after rehabilitation with clinical scales and physiological measurements. OBJECTIVES: To evaluate the effectiveness of the WARD in improving walking capability in these patients. SETTING: The study was carried out in a clinical environment (IRCCS S. Lucia, Rehabilitation Hospital, Rome, Italy). METHODS: Seven patients (six with spinal cord injuries, one with brain injury) underwent a 1 - 2 month training period with the WARD. During the WARD training the body weight constant unloading (BWCU) applied to the patient through the WARD was regularly evaluated. Oxygen consumption, carbon dioxide production and heart rate were measured in order to obtain energy and cardiac costs of walking. These measurements were carried out while walking with the WARD at an appropriate treadmill speed (ATS) and in the open field at the most comfortable speed (MCS). All measurements, in addition to clinical scores related to the walking capability, were carried out at the beginning of the WARD training period (BWT) and at the end (EWT). At the EWT the patients were tested walking with the WARD observing the same BWT conditions (same ATS and BWCU), referred to as beginning conditions second measurements (BCSM). The relationships between physiological costs and ATS were described through second order polynomial regression curves and studied. RESULTS: Comparing the data obtained at the BWT and EWT, the following results were found significantly different: (1) Clinical scores improved; (2) All patients increased their ATS; (3) The BWCU was reduced; (4) The Walking Energy Cost (WEC) and the Walking Cardiac Cost (WCC) measured when walking with the WARD at the ATS improved in all patients; and (5) The WEC and WCC measured in the open field improved in all patients. The WEC vs ATS curve found at the EWT in the BCSM was found significantly different from the BWT curve, demonstrating a major improvement due to the WARD training. CONCLUSION: Despite some limitations due to sample size and functional ambulation scale, this study has demonstrated that the WARD training is effective in improving the walking capability and efficiency of the patients.

Adult↗

Hormonal replacement therapy and gynecological cancer.

The problem of quality of life and lifestyle in elderly women is today a very important social problem all over the world but particularly in rich western countries. Life expectancy of the population will be longer and longer in the future and for both females and males the biological involution correlated with the aging process must be delayed. The gonadal hormones stimulate the healthy state of the entire body (heart, skin, brain, bones, urogenital apparatus and so on) and consequently hormonal replacement therapy (HRT) is mandatory. In women the biological clock of menopause allows us to intervene at the right time, with personalized estrogenic, estroprogestinic or estroandrogenic treatments. Health benefits and groundless risks allow today a careful hormonal management even in women treated for gynaecological cancers (breast and endometrium as well).

Aged↗

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↗

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↗

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↗