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Biomedical subjects

R Madonna

Publications and source records attributed to R Madonna.

11 recordsLinked to original sources

Insulin enhances vascular cell adhesion molecule-1 expression in human cultured endothelial cells through a pro-atherogenic pathway mediated by p38 mitogen-activated protein-kinase.

AIMS/HYPOTHESIS: Although hyperinsulinaemia in Type 2 diabetes in states of insulin resistance is a risk factor for atherosclerotic vascular disease, underlying mechanisms are poorly understood. We tested the hypothesis that insulin increases monocyte-endothelial interactions, which are implicated in atherosclerosis. METHODS: We treated human umbilical vein endothelial cells with insulin (10(-10) to 10(-7) mol/l) for 0 to 24 h. To dissect potentially implicated signal transduction pathways, we treated endothelial cells with known pharmacological inhibitors of two distinct insulin signalling pathways: the phosphatidylinositol-3'-kinase (PI3'-kinase) inhibitor wortmannin (3 x 10(-8) to 10(-6) mol/l), involved in insulin-induced endothelial nitric oxide synthase stimulation, and the p38 mitogen-activated protein (p38MAP) kinase inhibitor SB-203580 (10(-7) to 2 x 10(-6) mol/l). We measured adhesion molecule expression by cell surface enzyme immunoassays and U937 monocytoid cell adhesion in rotational adhesion assays. RESULTS: At pathophysiological concentrations (10(-9) to 10(-7) mol/l), insulin concentration-dependently induced vascular cell adhesion molecule (VCAM)-1 (average increase: 1.8-fold) peaking at 16 h. By contrast, the expression of intercellular adhesion molecule-1 and E-selectin were unchanged. The effect on VCAM-1 was paralleled by increased U937 cell adhesion. In the absence of cytotoxicity, wortmannin significantly potentiated the effect of insulin alone on VCAM-1 surface expression and monocytoid cell adhesion, whereas SB-203580 (10(-6) mol/l) completely abolished such effects. CONCLUSIONS/INTERPRETATION: These observations indicate that insulin promotes VCAM-1 expression in endothelial cells through a p38MAP-kinase pathway, amplified by the PI3'-kinase blockage. This could contribute to explaining the increased atherosclerosis occurring in subjects with hyperinsulinaemia, or in states of insulin resistance, which feature a defective PI3'-kinase pathway.

Androstadienes↗

N-Nitroso compounds, bacteria, and carcinoembryonic antigen in the gastric stump.

Analyses of biochemical and microbiological parameters such as pH, N-nitroso compound (NOC) concentration, carcinoembryonic antigen (CEA) level, and total viable counts (TVCs), and identification of microorganisms were carried out on 65 fasting gastric juice samples obtained at endoscopy from 45 patients previously submitted to partial gastrectomy for benign peptic ulcer disease (23 Billroth I, 22 Billroth II/Reichel-Polya) and 20 normal controls. Biopsy specimens were taken to determine histology, the Helicobacter pylori status, and both tissue CEA immunoreactivity and level. Significantly higher mean pH values, NOC and CEA concentrations, and TVCs were found in partial gastrectomies compared with normal controls. In relation to surgical methods, higher mean pH values, NOC concentrations, TVCs, and anaerobic bacterial counts were observed in the juice of patients with Billroth II compared with Billroth I gastrectomies. Mild CEA immunoreactivity and apical CEA localization were found significantly more often in Billroth II than in Billroth I stumps. Intensive CEA immunoreactivity and cytoplasmatic localization were found significantly more often in Billroth I than in Billroth II stumps. Independent of the type of surgical reconstruction, higher mean NOC levels were recorded in patients with more severe histological changes and H. pylori infection. Higher mean CEA levels in gastric juice and tissue were detected in the gastric stumps with more severe histological changes. All these data suggest that high levels of NOCs in the gastric juice could be a cofactor in gastric stump carcinogenesis and determination of CEA level in gastric juice and tissue could be included as a very useful marker in quantifying this process.

Adult↗

Mortality in psychiatric hospital patients: a cohort analysis of prognostic factors.

BACKGROUND: This work followed a group of patients living in a psychiatric hospital in Central Italy in 1978 at the time of enforcement of the Italian reform law (No. 180) for closing down mental hospitals. The study had the following aims: a) to compare in terms of mortality patients discharged into the community with patients who did not experience deinstitutionalization; b) to determine the survival of the cohort of patients and to analyse prognostic risk factors for death; c) to analyse differences in mortality rates between psychiatric patients and the general population. METHODS: The study was designed as an historical follow-up investigation. Univariate (product limit) and multivariate (proportional hazards model) methods were used to estimate prognostic variables and related death risks. Mortality was assessed using standardized mortality ratios (SMR) on the entire cohort as well as after stratification according to age, sex, cause of death and discharge status, assuming the Abruzzo Region's population as standard. RESULTS: Length of hospitalization and discharge from hospital are prognostic variables for death risk, with relative risks respectively of 4.22 (95% confidence interval [CI]: 2.41-7.40) for a length of hospitalization of 10-25 years, and 8.13 (95% CI: 4.73-13.88) for non-discharge. The global SMR of the cohort was 2.68 (95% CI: 2.42-3.07). Non-discharged patients showed higher SMR than discharged. Excess mortality was found both in males and females for circulatory, respiratory and undefined diseases. A significantly lower mortality for cancer was observed in male patients. A strong excess mortality was observed in younger patients (20-29 years: SMRmales = 43.57; SMRfemales = 97.52). CONCLUSIONS: Longer periods of hospitalization and non-discharge from hospital are the main risk factors for death in psychiatric patients, who globally experience higher death rates than the general population for a wide spectrum of causes of death, whatever their diagnosis or gender. These findings strongly suggest positive actions in order to overcome the effects of institutionalization.

Adult↗

[The assessment of the operative risk in vascular surgery].

Atherosclerosis is a polydistrectual disease. The patients with peripheral, carotid or aortoiliac pathology suffer frequently from coronary disease; so, a careful evaluation of operative risk is indispensable related to the anatomic district that we intend submit to surgery. In this work we separately explore the risk related to peripheral revasculations, aortic surgery and carotid surgery following the current literature and our experience.

Aorta↗

Kinetics of fenfluramine isomers in the rat.

The kinetics of fenfluramine isomers were studied in the rat following oral doses of racemic fenfluramine. The data, analyzed using an analogue computer, indicate that the d-fenfluramine is metabolised and excreted at a slower rate than the 1-isomer, resulting in higher plasma and brain concentrations. The kinetic parameters of both isomers were dose-dependent. The rates of disappearance decreased as the dose was raised. The increase in brain area under the curves (AUC) was much greater than the increase of the dose. These findings suggested the rat has a limited capacity for disposition of fenfluramine.

Animals↗

[Epidemiological monitoring of psychological, neurological and sensory handicaps in the 0-24-year-old Abruzzo population (Italy). Preliminary results].

OBJECTIVE: To describe the setting up of the Abruzzo Region (Italy) Service for Prevention and Epidemiological Register of Handicaps, to show prevalence data of occurring diseases and fit regression models aimed at explicating disease occurrence in terms of risk factors; to discuss services access data in terms of their efficacy in fitting social and health needs. SETTING AND DESIGN: We managed data obtained from a regional information system, based upon primary information sources operating in the Local Health Agencies (i.e. school medicine services, general practitioners, paediatricians, familiar counseling services, rehabilitation centers) and specialistic structures for diagnostic detection (multidisciplinary school équipes, hospital division of infant neuropsychiatry, outpatient infant neuropsychiatry services). The data managing model is a population-based epidemiological register. The target population is the 0-24 years population of the Abruzzo Region. MAIN OUTCOME MEASURES: Occurrence data are expressed as prevalence rates, using standardisation according to the global population of the area of interest. Diagnoses have been defined according to the standard ICD-9 and ICD-10 criteria; definition of handicaps has been made according to the WHO classification (1981). Association between indicator (socio-demographic and anamnestic) variables and occurrence of disease has been fitted by logistic regression models. RESULTS: Prevalence estimates obtained for the main infant neuropsychiatric diseases, as well as for the main handicap-determining genetic and/or congenital diseases, are consistent with the findings of literature in similar settings. An exception is the high occurrence of hyperkinetic disorders in both sexes. Rehabilitation is the main health need for all diagnostic axes. With respect to social needs, school and home personal care seem to be scarcely relevant if related to disease prevalence. Logistic regression analysis indicates socio-economic status and presence of handicapped relatives in the family as factors associated with the occurrence of disease. Respectively, the two factors are negatively associated with the occurrence of hyperkinetic disorders and positively associated with occurrence of mental retardation. Moreover, living in a natural family is negatively associated with evolutive disorders. CONCLUSIONS: This is a report about the preliminary results obtained by a specialised register for infant psychological and neurological handicaps. The findings suggest, as operating indications, the standardisation of diagnostic procedures and the definition of common managing guidelines in different areas. Anyhow, the findings of this report highlight the importance of an epidemiological knowledge of handicap in order to design correct prevention strategies and health services planning.

Adolescent↗

[Value of cardiac scintigraphy using thallium dipyridamole in the preoperative diagnosis of vascular diseases].

The authors assess the value of cardiac scintigraphy using thallium dipyridamidole in the preoperative examination of vascular patients. Data from the literature indicate the real possibility of cardiac complications in major vascular surgery. These complications, which range from simple arrhythmias to lethal myocardial infarctions, have an incidence of 0.5-2% in aortic surgery, 0.6-3% in peripheral revascularisation increasing to 2.6-8.3% in distal revascularisation, although they are less important in carotid surgery. From January 1993 to March 1994 cardiac risk was evaluated in 44 patients due to undergo major vascular surgery using cardiac scintigraphy with thallium dipyridamidole. The test was negative in 14 cases. The presence of one or more redistribution areas was observed in 23 cases, and a fixed zone in 7 cases. In line with the proposals made by Eagle, the authors conclude that it is necessary to restrict the indications for this test to those cases presenting at least two risk factors.

Arrhythmias, Cardiac↗