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Biomedical subjects

M Barbieri

Publications and source records attributed to M Barbieri.

135 records · Page 8Linked to original sources

Age-related insulin resistance: is it an obligatory finding? The lesson from healthy centenarians.

It is widely known that advancing age is associated with impaired glucose handling. A unifying hypothesis explaining the relationship between aging and insulin resistance might encompass four main pathways, namely: (a) anthropometric changes (relative and absolute increase in body fat combined with a decline in fat free mass) which could be the anatomic substrate for explaining the reduction in active metabolic tissue; (b) environmental causes, mainly diet style and physical activity; (c) neuro-hormonal variations [decline in plasma dehydroepandrosterone sulphate (DHEAS) and IGF-1]; and finally (d) the rise in oxidative stress. Indeed previous studies have also investigated the occurrence and the degree of insulin resistance in healthy centenarians. Such data demonstrated that age-related insulin resistance is not an obligatory finding in the elderly and that healthy centenarians have a preserved insulin action compared to aged subjects. Why insulin action is preserved in centenarians is still not known. Nevertheless, a possible approach to the question is to outline the centenarians' anthropometric, endocrine and metabolic characteristics in order to design a clinical picture of such metabolic "successful aging". According to the remodeling theory of age, the preserved insulin action in centenarians might be the net result of the continuous adaptation of the body to the deleterious changes that occur over time. Nevertheless, only future longitudinal studies specifically designed to investigate the relationship between extreme old age and degree of insulin sensitivity will provide a conclusive answer with regard to the pathophysiology of adaptive metabolic changes occurring in the elderly.

Adipose Tissue↗

Cellular electrophysiological aspects of myocardial protection.

Oxygen radicals (OR) generated at the time of reflow of the ischaemic myocardium may cause 'reperfusion injury'. To protect myocardium from this injury, it is important to understand how OR cause their deleterious effects on myocytes. Here we describe the basic electrophysiological alterations caused by OR in patch-clamped ventricular myocytes isolated from the rat heart. Oxygen radicals generated by dihydroxyfumarate (DHF) caused a lengthening of action potential duration (APD) and the appearance of arrhythmogenic alterations such as early and delayed afterdepolarizations. Prolongation of APD was accompanied by a reduction in calcium and potassium currents. When intracellular calcium levels were kept constantly low by 500 microM EGTA in the pipette solution, the effects of DHF on action potential duration and the occurrence of early afterdepolarizations were largely prevented. It is concluded that exposure to OR may induce electrophysiological alterations in isolated myocytes. They are related to changes in specific ionic currents and in levels of intracellular calcium.

Action Potentials↗

Analytic choices in economic models of treatments for rheumatoid arthritis: What makes a difference?

OBJECTIVES: To compare the analytic judgments, data, and assumptions of different models used in the economic evaluation of infliximab, one of a new class of drugs for rheumatoid arthritis (RA). METHODS: A detailed assessment was made of 4 models, 1 submitted (in a reimbursement dossier) by the manufacturer, 1 produced by an independent academic group, and 2 recently published in the literature. Factors considered included the key data inputs, assumptions about the sequencing of treatments for RA, the methods used to calculate health utilities, and the estimation of cost offsets. RESULTS: Two of the 4 models, although embodying different methodological approaches, gave fairly similar results (approximately 25,000 pounds- 35,000 pounds cost per additional quality-adjusted life year [QALY] gained). The other 2 models, both by an independent academic group, gave much higher estimates, ranging from 50,000 pounds to 60,000 pounds to more than 100,000 pounds per additional QALY. The differences appeared to depend mainly on differences in model structure, the assumptions about the positioning of infliximab in the treatment sequence, and the relationship between Health Assessment Questionnaire (HAQ) states and QALYs. CONCLUSIONS: Economic models of treatments for RA incorporate different key data inputs and analytic judgments. However, convergence was observed in some of the estimates produced by the models, particularly when adjustments were made for some of the differences in input parameters. Nevertheless, differences in the choice of model structure and in key assumptions also had a major impact on results. Therefore, more discussion is needed to reach a consensus on some of these methodological issues.

Antibodies, Monoclonal↗

Cell kinetics analysis in patients affected by squamous cell carcinoma of the head and neck treated with primary surgery and adjuvant radiotherapy.

BACKGROUND: The increasing complexity of management strategies for patients with head and neck squamous cell carcinoma (HN-SCC) calls for the investigation of new objective prognostic parameters to subdivide patients according to the tumor's biological aggressiveness. METHODS: We evaluated in 35 HN-SCC patients the pretreatment cell kinetics parameters and DNA ploidy after in vivo infusion of bromodeoxyuridine and flow cytometric analysis. Patients were treated with radical surgery followed by conventional radiation therapy. Locoregional control data are available for follow-up times above five years. RESULTS: We found that the likelihood of locoregional control for patients with rapidly proliferating HN-SCC characterized by a short potential doubling time (Tpot <5 days) was significantly smaller than for HN-SCC patients with slow tumor proliferation (Tpot >5 days). Moreover, when patients were stratified according to DNA ploidy and Tpot value, we found that the locoregional failure rate for rapidly proliferating tumors was significantly higher for diploid HN-SCCs than for aneuploid HN-SCCs. CONCLUSION: The present data suggest that patients with resectable HN-SCC characterized by fast growth might have a worse prognosis after surgery and adjuvant conventional radiotherapy and might benefit from more aggressive radiotherapeutic modalities.

Adult↗

[Validazione della versione italiana del Brief Pain Inventory nei pazienti con dolore cronico].

BACKGROUND: The purpose of this study has been the validation of an Italian version of the Brief Pain Inventory (BPI), Breve Questionario per la valutazione del Dolore (BQVD), in patients with chronic pain not-caused by neoplastic illness. METHODS: The analysis has been proposed to 113 patients affected by different kinds of chronic pain of non-neoplastic origin while hospitalized, both as outpatients or as in-patients. The descriptive analysis of the specimen and of each item of the BPI has been carried out. Moreover, the psychometric characteristics of the analysis, intended as an instrument to describe intensity of pain and its interference in the various aspects of life have been investigated, evaluating with factorial analysis its validity both as a construct, and its internal coherence calculating the Cronbach's alpha of the whole instrument and of each identifier with factorial analysis. RESULTS: From the factorial analysis emerged a frame with three factors that have been identified as Pain intensity, Pain interference in emotional sphere and Interference in working activities. CONCLUSIONS: The Brief Pain Inventory can be considered a suitable useful instrument in the global evaluation of patients affected by chronic pain since its allows a contemporaneous analysis of three factors that characterize the phenomenon and contribute equally in defining the various facet of the pain universe. The Italian version of the BPI may be included in the essential evaluation instruments in the diagnosis and therapy of chronic pain.

Adult↗

[The prognostic role of the parameters of cellular kinetics in head and neck tumors treated solely by radiotherapy].

Cell cycle and cell population characteristics, as obtained for head and neck cancers by flow-cytometry analysis of a single tumor sample, after in vivo bromodeoxyuridine (Burd) infusion, were proposed for their prognostic value and for their potentials for radiotherapy planning (conventional vs accelerated) and monitoring. DNA ploidy, the S phase fraction labeling index (LI), and duration (Ts) as well as cell population potential doubling time (Tpot) were measured in 42 head and neck squamous cell carcinoma patients and analyzed along with histopathological and clinical data. Twenty-seven patients received standard radiotherapy (70 Gy/35 fractions/7 weeks) whereas 15 patients were treated with the concomitant boost technique (75 Gy/40 fr/6 weeks). The univariate analysis of 31 patients, for whom all the cell kinetic parameters were available, indicated that local control probability was strongly affected by lymph node status (p = 0.05) and by potential doubling time (p = 0.04). Patients having tumor Tpot < 5 days had markedly lower two-year local control rate (13%) than patients with Tpot > 5 days (68%). Furthermore, tumors with Tpot < or = 5 days exhibited a trend toward better local control after concomitant boost regimen compared with the patients treated with standard regimen (p = 0.06). These preliminary results point out that Tpot could play a role as additional prognostic factor influencing disease outcome in head and neck carcinomas treated by radiotherapy. In patients with fast growth-rate tumors (Tpot < or = 5 days) a more aggressive radiotherapy combination or chemo-radiotherapy should be suggested.

Actuarial Analysis↗