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Biomedical subjects

G Fonte

Publications and source records attributed to G Fonte.

At least 19 recordsLinked to original sources
PubMed2003

Quantitative determination of paclitaxel in human plasma using semi-automated liquid-liquid extraction in conjunction with liquid chromatography/tandem mass spectrometry.

This paper describes a high-throughput sample preparation procedure combined with LC-MS/MS analysis to measure paclitaxel in human plasma. Paclitaxel and an internal standard were extracted from plasma by a semi-automated robotic method using liquid-liquid extraction. Thereafter compounds were separated on a RP C18 column. Detection was by a PE Sciex API 3000 mass spectrometer equipped with a TurboIonSpray interface. The compounds were detected in positive ion mode using the mass transition m/z 854.6-->286.2 and m/z 831.6-->263.2 for paclitaxel and the internal standard, respectively. The limit of quantitation for paclitaxel was 1 ng/ml with an imprecision of 5.2% following extraction of 0.1 ml of plasma. Linearity was confirmed over the whole calibration range (1-1000 ng/ml) with correlation coefficients higher than 0.99 indicating good fits of the regression models. The inter and intra-day precision was better than 9.5% and the accuracy ranged from 90.3 to 104.4%. The assay was simple, fast, specific and exhibited excellent ruggedness.

Animals↗
PubMed1999

Determination of 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyldaunorubicin+ ++ and its 13-hydroxy metabolite by direct injection of human plasma into a column-switching liquid chromatography system with mass spectrometric detection.

A selective, sensitive and fully automated column-switching LC system using direct injection of human plasma followed by mass spectrometry (MS) detection was developed and validated to determine the concentrations of 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methylsulphonyldaunorubicin++ + (PNU-159548) and its 13-hydroxy metabolite (PNU-169884). A 50-microl human plasma sample was directly introduced into a C4-alkyl-diol silica clean-up column separating analytes from proteins and polar endogenous compounds using water and methanol as the mobile phase. The fraction containing PNU-159548 and its metabolite was back-flushed and transferred to the analytical column. The compounds were separated using a Zorbax SB C8 column (150x4.6 mm, 5 microm) under gradient conditions with the mobile phase containing acetonitrile and 2 mM ammonium formate, pH 3.5. MS detection was by atmospheric pressure ionisation with multiple reaction monitoring in positive ion mode. Linearity was demonstrated over the calibration range of 0.051-10.291 ng/ml for PNU-159548 and 0.104-10.434 ng/ml for PNU-169884. The assay was validated with respect to accuracy, precision and analyte stability. On the basis of the validation data, the developed analytical method was found to be suitable for use in Phase I clinical studies.

Antibiotics, Antineoplastic↗
PubMed1999

Cholesterol and long-term mortality after acute myocardial infarction in elderly patients.

METHOD: We investigated the association of total serum cholesterol concentrations and subsequent overall and coronary mortality in 304 patients aged > or =65 discharged from hospital after acute myocardial infarction. RESULTS: There was no association between total cholesterol concentrations and mortality due to either coronary heart disease or to all causes in all patients or, separately, in men, women, patients younger than 75 and patients aged 75 years and older.

Aged↗
PubMed1997

A case-control study on lymphocytic subsets in elderly bearing a gastroenteric cancer.

The aim of this work is to evaluate the differences in lymphocytic sub-classes between elderly patients with gastroenteric cancer and elderly patients with a non neoplastic disease. A group of 88 patients over 60, consecutively admitted to the III Division General Surgery for gastro-enteric cancer has been collected for the study, the control group consisted of 74 patients also over 60, consecutively admitted over the same period for benign abdominal diseases. In all patients the following data were measured: body mass index (BMI), white blood cells (WBC), total lymphocytes, total T lymphocytes (CD3+), helper T lymphocytes (CD4+), suppressor T lymphocytes (CD8+), CD4+/CD8+ ratio, B lymphocytes, CD5+ B lymphocytes, activated T lymphocytes (CD3+ HLA-DR+), CD4+ "naive" lymphocytes (CD4+ CD45 RA+), CD4+ "memory" lymphocytes (CD4+ CD45 RO+), NK lymphocytes (CD16+ 56+), red blood cells (RBC), total serum cholesterol, albumin, total serum proteins. The main lymphocytic subsets were on an average lower in the cancerous elderly group with respect to the non cancerous. As the tumour progressively increases in size (T), total lymphocytes significantly decrease, while CD4+ progressively decreases with nodal involvement (N). In the cancerous elderly, we found a lower immune response. The immune system appears to be less efficient also in association with tumor growth, especially when T and N get worse. The response of effector cells to the tumour seems not specific.

Aged↗
PubMed1997

[In-hospital mortality of elderly patients with myocardial infarct. Difference between the sexes].

The number of women who become ill and die from acute myocardial infarction (AMI) increases steadily with age. It is not yet clearly defined whether and why women suffer from a higher in-hospital mortality rate after AMI. In this study we evaluated the importance of the female sex as a risk factor for in-hospital mortality in elderly patients suffering from AMI. A retrospective study was performed in 724 patients (429 males, 295 females) aged > or = 65 years (mean age 74.9 +/- 6.3 years) consecutively admitted to San Giovanni Battista Hospital in Turin during the period 1988-1991 with validated primary discharge diagnosis of AMI. In-hospital mortality was significantly higher in females (34.6%) compared to males (25.6%, p > 0.01). After multivariate analysis female sex was not independent predictive for in-hospital death. Multivariate analysis was therefore repeated in the various sections of the history of AMI (anamnestic variables, including age and sex: physical signs on admission, ECG findings, laboratory tests, clinical progress, including complications and treatment) in order to identify the factors responsible for the higher mortality rate in women. These were found to be low hemoglobin values (< 12 g/dl) on admission, development of cardiac failure disorders and rhythm disturbances during hospitalization, and differences in therapeutic procedures. In spite of the absence of an independent unfavourable effect of female sex, elderly women with AMI have a higher in-hospital mortality rate. A more precarious state of health on admission, a peculiar susceptibility to severe complications during hospital-stay and differences in therapeutic procedures appear to be the factors responsible for this increased mortality rate in women.

Age Factors↗
PubMed1995

[Course of peripheral arterial diseases].

During January and November 1983 we examined 230 patients by means of doppler evaluation for suspect of peripheral arterial disease. We identified 105 subjects with peripheral arterial disease. During September and November 1993 we tried to convoke again all 230 subjects. Altogether we followed 215 subjects (95 with peripheral arterial disease and 120 without). Sixty-three patients died and we analysed the cause of death. Forty-seven out of 95 patients (49.5%) with peripheral arterial disease died and only 16 out of 120 subjects (13.3%) without peripheral arterial disease. Twenty-five out of 47 deaths (53.2%) happened among the patients with peripheral arterial disease. Age, severity of peripheral arterial disease (measured by ankle-arm pressure ratio) and the presence of a carotid bruit were associated with death. The natural history of peripheral arterial disease has been characterized by a worsening of the intermittent claudication in 52.1% of patients but only 18.6% presented a progression toward a superior class of the Fontaine classification. In conclusion, the peripheral arterial disease, despite his apparently benign course, represents a clinical event that must not be overlooked, because the risk of cardiovascular mortality is high. The measurement of ankle-arm pressure ratio allows a good definition of the severity of peripheral arterial disease and therefore represents a valid prognostic criterion.

Aged↗
PubMed1995

[Associations between arterial hypertension and other cardiovascular risk factors in subjects over 65 years of age].

The goal of this study was to evaluate whether in subjects aged 65 or over hypertensive patients have a greater prevalence of risk factors than normotensives. 1369 subjects, aged 65 or over, have been retrospectively investigated. The following risk factors were considered: cigarette smoking, left ventricular hypertrophy, diabetes mellitus and atrial fibrillation (analyzed as dichotomous variables), B.M.I., blood concentration of total, -LDL-HDL cholesterol, triglycerides and total/HDL cholesterol ratio (analyzed as continuous variables). The mean number of risk factors was calculated in hypertensive and normotensive subjects; the association between hypertension and risk factors was evaluated using univariate and multiple logistic regression analysis. 451 subjects (32.9%) were found to be hypertensives. The average number of risk factors was significantly greater in hypertensive than in normotensive subjects (1.85 +/- 1.27 vs 1.39 +/- 1.15, p < 0.001), and, in both groups, in men than in women. Left ventricular hypertrophy (p < 0.001), total cholesterol (p < 0.001), diabetes mellitus (p < 0.001) and atrial fibrillation (p < 0.01) were found to be independently associated with the presence of hypertension. We concluded that among the elderly there is a greater prevalence of risk factors in hypertensive than in normotensive subjects and that some risk factors--left ventricular hypertrophy, atrial fibrillation, diabetes mellitus, and blood levels of atherogenic lipids--are independently associated with the presence of hypertension.

Aged↗
PubMed1994

Radioimmunoassay for the testosterone 5 alpha-reductase inhibitor turosteride in biological fluids.

An antiserum against turosteride (code name FCE 26073), a potent testosterone 5 alpha-reductase inhibitor, has been raised in rabbits by immunization with an immunogen produced by conjugation of a derivative of FCE 26073 (FCE 27424) to bovine serum albumin. The antiserum was able to distinguish FCE 26073 from its derivatives modified at the 17 beta position and from all the endogenous steroids tested. A radioimmunoassay for the determination of FCE 26073 in human plasma and urine was developed using this antiserum and tritium labeled turosteride. FCE 26073 was extracted from 50 microliters of plasma or 25 microliters of urine using ethyl-ether with a recovery greater than 90%. Using this procedure it was possible to achieve a final limit of quantitation of 142 pg/ml in plasma and 284 pg/ml in urine. The assay was validated in terms of reproducibility, accuracy and precision in the range 3.9-250 pg/50 microliters of plasma and 25 microliters of urine. The plasma concentration of FCE 26073 in a healthy male volunteer who received 0.2 mg of the drug was measured using the radioimmunoassay.

5-alpha Reductase Inhibitors↗
PubMed1994

Carotid plaque, aging, and risk factors. A study of 457 subjects.

BACKGROUND AND PURPOSE: The aim of this study was to assess the prevalence of extracranial carotid artery atherosclerosis and its relation to principal cardiovascular risk factors at different ages in a sample of the general population. METHODS: B-mode ultrasonography was used to investigate the carotid district in 457 subjects (231 men and 226 women; mean age, 55.4 +/- 18.7 years; range, 18 to 97 years) in the metropolitan area. The ultrasonographic findings were then related to risk factors. RESULTS: Carotid plaques were found in 178 subjects (38.9%). The prevalence of atherosclerosis, number of plaques, and severity of stenosis were observed to increase with age. Age (P < .0001), cigarette smoking (P < .0001), male sex (P < .001), total cholesterol (P < .05), and, inversely, the ratio of high-density lipoprotein cholesterol to total cholesterol (P < .05) were found to be independently associated with carotid atherosclerosis. Stratified analysis by sex and age showed effect modifications by age on cigarette smoking, total cholesterol, and the ratio of high-density lipoprotein cholesterol to total cholesterol. After multivariate analysis including interaction terms, cigarette smoking and cholesterol levels were not longer found to be associated with carotid atherosclerosis in elderly subjects. Age (P < .01), total cholesterol (P < .05), and diabetes (P < .05) were positively related to the severity of vascular narrowing. CONCLUSIONS: There is a high prevalence of asymptomatic carotid atherosclerosis in the general population, particularly among the very old. The association between risk factors and carotid atherosclerosis is less pronounced in the elderly than in younger subjects.

Adolescent↗
PubMed1994

Risk factors for atherosclerosis and aging.

In order to investigate the association between atherosclerosis and risk factors in aged subjects, Doppler ultrasound scans were used to identify the presence and severity of carotid and femoral atherosclerosis in a sample of 457 community living subjects (mean age 55.4 +/- 18.7 years) of the metropolitan area; the ultrasonographic findings were then related to primary cardiovascular risk factors. Carotid and femoral plaques were found respectively in 178 (38.5%) and in 180 (39.4%) subjects. Prevalence of atherosclerosis, number of plaques and percentage of stenosis have been observed to increase with age. All the main cardiovascular risk factors (age, male sex, hypertension, cigarette smoking, diabetes and hypercholesterolemia) resulted significantly associated with both carotid and femoral atherosclerosis in the total series and, more strongly, in subjects aged under 65. On the contrary, most of these associations disappeared in subjects aged 65 or more. Multiple logistic regression analysis confirmed that in this age group only age and male sex were independently associated with carotid and femoral atherosclerosis; of the other risk factors cigarette smoking alone was an independent risk factor for femoral atherosclerosis. We conclude that in the elderly, in spite of the age-related increase in carotid and femoral atherosclerosis, the association between risk factors and atherosclerotic disease is less relevant than at younger ages.

Age Factors↗
PubMed1993

Autopsy and multiple pathology in the elderly.

We examined autopsy reports and the clinical diagnoses of 600 patients (200 in 1967 and 400 in 1987). For each patient we considered age, diagnostic error, main diseases and presence of multiple pathology. The number of diagnostic errors increased from 1967 to 1987. The diagnostic error was particularly high for pulmonary embolism and septic shock and significantly higher in patients > 65 than < or = 65 years old. Multiple pathology was higher in old patients: we found 4 or more diseases in 195/270 (72.2%) patients > 65 years and in only 135/330 (40.9%) patients < or = 65 years. The average period of hospitalization was directly proportional to the number of diseases present in the same patient.

Age Factors↗
PubMed1993

Risk factors for atherosclerosis: ultrasound evaluation of carotid and femoral arteries in patients examined by coronary angiography.

The carotid and femoral arteries of 209 subjects (161 men and 48 women), consecutively tested by coronary angiography during the first four months of 1990, were examined using a B-Mode Echo-doppler. The angiographic examination was performed for suspected ischemic disease or to complement hemodynamic tests for valvular cardiopathy. The relationship between the main risk factors and the degree of atherosclerotic vascular involvement in the coronary, carotid and femoral districts was examined using standardised partial correlation coefficients. Cigarette smoke (expressed as number of cigarettes per day or as duration of exposure to smoke), total blood cholesterol concentration and age were positively correlated with the degree of atherosclerotic involvement in all three vascular regions; triglyceridemia values were correlated only in the coronary region. These relations were observed both in patients below and above 65 years of age; in the elderly group no correlation was found between blood cholesterol concentration and coronary involvement and between triglycerides levels and atherosclerotic disease in the three districts. Our results suggest that some risk factors (high blood cholesterol concentration and history of smoking) correlate with severity of atherosclerotic involvement even in advanced age.

Age Factors↗
PubMed1993

[Ischemic stroke and transient ischemic attacks: a case-control study of the risk factors in elderly hospitalized patients].

We have evaluated in a case-control study the association of the main risk factors with cerebrovascular ischemic accidents in elderly patients. Two hundred and twenty patients aged 65 year or more (average age 77.3 +/- 7.3 yr, 93 males and 127 females) admitted to our Division for stroke (122) or transient ischemic attacks (TIA) (98) were enrolled: 220 hospitalized patients, age and sex-matched, without actual or previous cardiovascular clinical manifestations were the control group. Advanced senile decay, hepatic or renale failure and malignancies were considered exclusion criteria for both groups. The following risk factors have been considered: family history, obesity, cigarette smoking, diabetes, hypercholesterolemia, hypertriglyceridemia, atrial fibrillation, left ventricular hypertrophy, and related continuous variables. After logistic multiple regression analysis, atrial fibrillation, hypertension and blood cholesterol concentration above 240 mg/dl were significantly and independently associated with stroke, while only hypertension and hypercholesterolemia were associated with TIA. The unexpected finding of a significant association between hypercholesterolemia and cerebrovascular ischemia seems attributable to the choice of hospitalized patients as control group. These results indicate that hypertension and atrial fibrillation are independently associated with ischemic stroke even in advanced age.

Aged↗
PubMed1992

Radioimmunoassay for the synthetic ergoline derivative cabergoline in biological fluids.

An antiserum against cabergoline, a powerful dopamine-agonist under clinical trials for the treatment of Parkinson's disease and hyperprolactinemia, has been raised in rabbits by immunization with an immunogen produced by conjugation of cabergoline to bovine serum albumin. The antiserum was able to bind a derivative of cabergoline labelled with tritium and was able to distinguish the drug molecule from some of its close related compounds and from other agents that could be simultaneously present in plasma from patients undergoing treatment with cabergoline. The antiserum and the tritium labelled hapten were used to develop a radioimmunoassay for cabergoline determination in human plasma and urine. A linear relationship between cabergoline added and % radioactivity bound was found in the range 1.9-500 pg/tube. The addition in the assay of 200 microliters human plasma or 25 microliters urine did not affect the specific and the non-specific binding of the radiolabelled hapten so enabling us to obtain a final sensitivity of about 12 pg/ml plasma and 120 pg/ml urine. The assay was validated in terms of reproducibility, precision and accuracy over the whole range of concentrations tested both in plasma and urine. The plasma concentrations at the steady state in a patient with Parkinson's disease who had received the drug at single oral daily doses of 3, 5 and 7 mg were determined using the assay.

Aged↗