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Biomedical subjects

G Pagano

Publications and source records attributed to G Pagano.

At least 109 records · Page 6Linked to original sources

Activated protein C resistance in type I diabetes.

OBJECTIVE: To compare activated protein C (aPC) sensitivity in 37 type I diabetic patients and 33 healthy control subjects. RESEARCH DESIGN AND METHODS: In this study, 37 type I diabetic patients and 33 healthy control subjects without personal or familial history of venous thrombosis and coagulation disorders, infections, intercurrent conditions, serum lupus anticoagulant, clinical cardiovascular complications, or drugs were examined. RESULTS: The aPC ratio (aPTT [activated partial thromboplastin time] with and without aPC) was significantly lower in the type I diabetic patients than in the control subjects (P = 0.005). CONCLUSIONS: These results suggest that the final steps of the protein C/S inhibiting system could be abnormal in type I diabetes.

Adult↗

[LKM (Liver-Kidney-Microsome) antibodies and hepatitis C virus. Description of a clinical case].

BACKGROUND: Diagnostic and therapeutic issues related to hepatitis C virus infection and autoimmune hepatitis are discussed. The authors report a 56 year old female patient with chronic hepatitis and both HCV-RNA positivity and a high titer of LKM-1 antibody on blood samples. METHODS: In the absence of clinical signs of autoimmunity the patient was started on interferon treatment. After four months she experienced a flare-up with a sharp increase of transaminases and a concomitant rise in LKM-1 titer. Viremia was persistently detected by PCR. As interferon therapy was discontinued transaminases and autoantibody titer fell to baseline values. A few months later she received immunosuppressive therapy, that resulted in a decrease in LKM1 titer and complete normalization of liver enzymes. Anti LKM-1 antibody was detected by indirect immunofluorescence, serum immunoblot assay (Western Blot), and enzyme immunoassay (ELISA). RESULTS AND CONCLUSIONS: Therapy of patients with HCV/LKM positive chronic hepatitis should be settled on an individual basis. Patients eligible for interferon treatment should be carefully selected and closely monitored because of the risk of adverse reaction.

English Abstract↗

A re-evaluation of glycohaemoglobin standardisation: the Italian experience with 119 laboratories and 12 methods.

The effect of calibration on glycohaemoglobin results was investigated in 119 laboratories where glycohaemoglobin (HbA1c) percentages were determined in triplicate in two samples and in two calibrators. The materials were human lyophilized haemolysates home-prepared with a novel protocol. The HbA1c content was assigned to calibrators using 4 HPLC methods with the data obtained from 11 laboratories. Intra-laboratory variation was low, although in 14 out of 119 laboratories CV values greater than 3.5% were reported. Calibration decreased inter-method variation from 16.3% to 5.6%, and from 15.3% to 4.2% for samples with low and high HbA1c content, respectively. Calibration decreased overall inter-laboratory variation from 18.7% to 7.4%, and from 17.2% to 5.4%. The calibrated results obtained with all methods, including Abbott IMx and Vision, were comparable.

Calibration↗

Association of fibrinogen with glycemic control and albumin excretion rate in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: The high prevalence of classic cardiac risk factors in patients with non-insulin-dependent diabetes mellitus does not explain the increased cardiovascular-related morbidity and mortality in these patients. Fibrinogen may have a role in this excess risk. OBJECTIVE: To evaluate the following in patients with non-insulin-dependent diabetes mellitus: 1) the distribution of plasma fibrinogen levels and the prevalence of hyperfibrinogenemia and 2) the association of fibrinogen level with hemoglobin A1c value and albumin excretion rate. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rural area in northern Italy. PATIENTS: 1574 patients with non-insulin-dependent diabetes mellitus who represented 81% of the initial cohort of 1967 patients. MEASUREMENTS: Albumin excretion rate was measured in urine samples obtained during an overnight collection. Venous blood samples were collected while patients fasted. RESULTS: Fibrinogen levels were available for 1525 of the 1574 patients who were examined (669 men and 856 women). The mean age (+/- SD) was 67.3 +/- 10.3 years for men and 70.7 +/- 10.7 years for women. The mean plasma fibrinogen level (+/- SD) was 3.6 +/- 0.9 g/L; levels slightly differed between men and women. In 50.3% of patients, plasma fibrinogen level exceeded 3.5 g/L. In men, fibrinogen level increased with age (P < 0.001). In both men and women, fibrinogen level adjusted for age and sex was significantly and linearly related to hemoglobin A1c value (P < 0.001) and albumin excretion rate (P < 0.001). In a multiple regression analysis, hemoglobin A1c value (b = 0.06; P < 0.001) and albumin excretion rate (b = 0.09; P = 0.005) were associated with fibrinogen level independent of other cardiovascular risk factors (sex, age, hypertensive status, total cholesterol level, smoking habit, and body mass index). CONCLUSIONS: Patients with non-insulin-dependent diabetes mellitus had a high prevalence of hyperfibrinogenemia. Fibrinogen level was independently associated with hemoglobin A1c value and albumin excretion rate, which suggests that fibrinogen may be involved in the increased cardiovascular risk of patients with diabetes mellitus.

Adult↗

Low prevalence of microalbuminuria in young Italian insulin-dependent diabetic patients with short duration of disease: a population-based study. Piedmont Study Group for Diabetes Epidemiology.

Objectives of this study were to determine the prevalence of microalbuminuria and the level of glycaemic control obtained in a young Italian population-based cohort of subjects with short duration of insulin-dependent diabetes mellitus (IDDM). Out of 298 subjects with onset of IDDM in the period 1984-88, 211 were examined (71%) in 1991-92 (duration of disease 3-9 years). Microalbuminuria was defined as albumin excretion rate (AER) 20-200 micrograms min-1 in an overnight urine collection or alb/creat > 2.5 mg mmol-1 in men and > 4.5 mg mmol-1 in women in one first morning urine sample. Twelve subjects had AER 20-200 micrograms min-1 and 4 had elevated alb/creat ratio. Prevalence of microalbuminuria was 7% (95% Cl 4.0-11.1) in subjects with duration of IDDM 3-9 years and 4% (0.3-7.7) in subjects with duration 3-5 years. Only 1 microalbuminuric subject was found out of 52 aged < or = 14 years. Duration of IDDM was significantly higher (6.9 +/- 1.9 years vs 5.7 +/- 1.6, p = 0.007) and HDL-cholesterol lower (1.22 +/- 0.21 mM vs 1.42 +/- 0.34, p = 0.025) in micro- than in normoalbuminuric subjects, even after adjustment for age, systolic and diastolic blood pressure, BMI, and HbA1c. In almost 50% of the cohort, HbA1c levels were over 9%, whereas only in 10.9% HbA1c levels were lower than 6.6% (mean +3 SD). In conclusion, this Italian population-based study showed low prevalence of microalbuminuria in young subjects with short duration of IDDM, even if the glycaemic control obtained was far from ideal.

Adolescent↗

Cytogenetic, developmental, and biochemical effects of aluminum, iron, and their mixture in sea urchins and mussels.

The present study was undertaken to evaluate the toxicity of aluminum sulfate, ferric chloride and their 1:1 mixture (Mix) on early development, fertilization and offspring quality in three sea urchins species (Sphaerechinus granularis, Paracentrotus lividus, Psammechinus microtuberculatus) and in mussels (Mytilus galloprovincialis). The endpoints were the following: a) larval malformations; b) developmental arrest; c) embryonic mortality; d) fertilization success; e) cytogenetic effects, and f) luminol-dependent chemiluminescence (LDCL). Overall data point to the induction of developmental defects in both sea urchin and mussel embryos following exposure of embryos to Al(III) or Fe(III) (10(-7) to 10(-6) M), whereas Mix caused varied effects vs. Al(III) or Fe(III) alone, from scarce or no additive effects (M. galloprovincialis and P. lividus) to a dramatic rise in embryolethality even at nominal levels of 10(-8) M (Ps. microtuberculatus).S. granularis sperm underwent a dose-dependent decrease in fertilization success following exposure to Al(III), or Fe(III), or Mix at levels ranging from 10(-8) to 10(-5) M. A significant increase of developmental defects was observed in the offspring of S. granularis sperm exposed to micromolar levels of the agents, suggesting an Al(III)- and Fe(III)-related transmissible damage to sperm. The cytogenetic analysis of Al(III)-, Fe(III)-, or Mix-exposed S. granularis embryos showed a significant increase in mitotic aberrations. A relevant feature of the observed cytogenetic damage included scattered chromosomes, suggesting cytoskeleton damage. The LDCL emission in S. granularis embryos showed a dose-related inhibition by agent levels ranging from 10(-7) to 10(-5) M; this held true for both spontaneous and, to a larger extent, for horseradish peroxidase (HRP)-activated LDCL. LDCL associated with fertilization was affected by Al(III), Fe(III) and Mix, with a time- and dose-related shift from stimulation to inhibition. The changes observed in LDCL emission suggested that the observed damage to embryogenesis, fertilization and mitotic activity may be related, at least partly, to alterations of the embryo prooxidant state. The present data point to developmental, cytogenetic and biochemical changes related to realistic levels of Al(III), Fe(III) and their mixtures, raising concern as to their environmental, occupational and iatrogenic exposures.

Alum Compounds↗

Lipoprotein(a) after acute exercise in healthy subjects.

Some acute-phase proteins increase during exercise, and lipoprotein(a) has been considered an acute-phase protein on the basis of an increase in its serum level after acute cardiovascular episodes or surgery. We found no significant effect of acute physical exercise (600 kpm/min for 20 min) on lipoprotein(a) levels in ten healthy subjects [pre exercise 6.25 (0.1-14), median (range), mg/dl; at the end of exercise 6 (0.1-12) mg/dl; 30 min post exercise 5.9 (0.1-23) mg/dl; 60 min post exercise 5.95 (0.1-11) mg/dl]. This suggest that activation of the adrenergic system does not induce changes in lipoprotein(a) levels.

Adult↗

Postprandial triglyceride-rich lipoprotein changes in elderly and young subjects.

To determine whether an increased risk for atherosclerosis in older humans is related to changes in postprandial lipoprotein metabolism, we compared the dynamic profiles (0-10 hours) of triglyceride (Tg)-rich lipoproteins and the Tg content in VLDL subfractions in elderly and young subjects after an oral fat load. The plasma Tg response curves displayed significant differences between the groups at all times. Postprandial triglyceridemia was quantified from the plasma response curves as an incremental area, and was significantly different in the two groups (young subjects 231.9 +/- 199.6 vs elderly subjects 511.0 +/- 305.6 mg/dL x 10 hr, p = 0.036). The more scattered VLDL-Tg values were significantly different compared to values at baseline and 6 hours after fat load. Tg baselines in the four VLDL subfractions (expressed as percentages) were higher in the larger particles (B Sf = 175-400) in the elderly subjects, and in the smaller, denser particles (D Sf = 20-100) in the young subjects. In both groups, postprandial hyperlipidemia increased the Tg content of the larger, less dense particles (Sf more than 400), and reduced that of the denser particles. These variations usually coincided with the plasma Tg and VLDL peaks: 63% to 70% above the Tg baseline between the 2nd and 4th hour in all the young subjects: 48% to 68% above the baseline between the 4th and the 6th hour in all the elderly subjects. Total cholesterol variations showed no significant differences between the two groups at any time. All subjects tested for the missense mutation at codon 188 of the human lipoprotein lipase (LPL) gene resulted noncarriers of LPL mutant alleles. Our data show that, after a fatty meal, healthy elderly subjects tend to present prolonged postprandial hypertriglyceridemia, suggesting an atherogenic behavior of their lipid metabolism.

Adult↗

Insulin resistance shows selective metabolic and hormonal targets in the elderly.

There has been no simultaneous evaluation of different aspects of insulin action in ageing. We studied 12 elderly (77 +/- 2 years) and 12 young (26 +/- 1 years) subjects with normal glucose tolerance and matched for sex, body mass index, lean body mass (LBM), blood pressure and physical activity, using a euglycaemic-hyperinsulinaemic clamp at about 350 pmol L-1 in combination with [3H]-glucose infusion. In the elderly group, hepatic glucose production was normal, fasting serum insulin and C-peptide were significantly increased (P = 0.001) and glucose utilization (34.4 +/- 2.4 vs. 44.4 +/- 3.2 mumol kg-1 LBM min-1, P = 0.02) and the percentage maximal suppression of C-peptide (58 +/- 6% vs. 79 +/- 5%, P = 0.02) during the clamp were reduced. Fasting plasma free fatty acid (FFA) and glycerol levels were similar in the two groups, but their percentage maximal suppression during the clamp was reduced in the elderly group (FFA 45 +/- 5% vs. 77 +/- 6%, P = 0.001; glycerol 43 +/- 5% vs. 76 +/- 3%, P = 0.001). Branched-chain amino acids (valine, leucine, isoleucine) and glucagon levels were similar in the two groups, both while fasting and during the clamp. Thus, insulin resistance in ageing appears selective on glucose utilization, inhibition of lipolysis and feedback inhibition of the B-cell secretion.

Adult↗

Prevalence and risk factors for micro- and macroalbuminuria in an Italian population-based cohort of NIDDM subjects.

OBJECTIVE: To determine the prevalence of micro- and macroalbuminuria in NIDDM and their relationship with some known and putative risk factors. RESEARCH DESIGN AND METHODS: Out of a population-based cohort of 1,967 NIDDM subjects, 1,574 were investigated (80%). Albumin excretion rate (AER) was evaluated on an overnight urine collection, and plasma and urine determinations were centralized. RESULTS: The prevalences of microalbuminuria (AER 20-200 micrograms/min), macroalbuminuria (AER > 200 micrograms/min), and hypertension were 32.1% (95% CI 29.8-34.4), 17.6% (15.7-19.5), and 67% (64.6-69.3), respectively. Apart from prevalence of hypertension, which after adjustment for age, BMI, and duration of diabetes was 2.3 times higher in women, rates were higher in men (odds ratio [OR] 1.31, 95% CI 1.04-1.66 for microalbuminuria and OR 1.63, 1.22-2.17 for macroalbuminuria). In comparison with normoalbuminuric subjects, both micro- and macroalbuminuric diabetic subjects had significantly longer duration of diabetes, higher levels of systolic blood pressure, fasting plasma glucose, HbA1c, triglycerides, and uric acid; in macroalbuminuric subjects only, levels of apolipoprotein B and HDL cholesterol were, respectively, higher and lower than in normo- and microalbuminuric subjects. In logistic regression, variables independently related to both micro- and macroalbuminuria were age, HbA1c, cigarette smoking habits, plasma uric acid, and diastolic blood pressure, after adjustment for plasma creatinine and diabetic treatment. In addition, duration of diabetes and HDL cholesterol levels were associated with macroalbuminuria. CONCLUSIONS: This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.

Aged↗

Apolipoprotein H: a two-step isolation method.

A new method for the purification of apolipoprotein H by affinity chromatography followed by continuous-elution electrophoresis is described. It is both simpler and less complicated than the chromatographic and electrophoretic methods usually used. In addition, apolipoprotein H is isolated in a pure, structurally uncleaved form. This is of importance, as impairment has been detected in commercial preparations. The separation and purification of apolipoprotein H is a necessary prelude to its quantitative determination and phenotyping, and hence the clarification of its physiopathological mechanisms in lipid metabolism.

Amino Acid Sequence↗

Changes in tRNA pattern in ethionine-induced rat putative preneoplastic hepatocyte nodules.

As part of a study to explore further the biochemical pathology of chemical hepatocarcinogenesis, cytoplasmic tRNA patterns have been studied in ethionine-induced rat putative preneoplastic nodules in comparison to surrounding non-nodular liver and control liver. A new h.p.l.c. methodology, able to resolve contemporaneously the numerous components in a tRNA population, has been used. The results obtained indicate the presence of marked differences in the chromatographic profiles of hepatocyte nodules, non-nodular surrounding liver and control liver. The differences are both quantitative and qualitative, with some chromatographic peaks showing increases and some decreases or absences. Also, new peaks are seen reproducibly in the nodules. The data show major changes in the tRNA population during hepatocarcinogenesis that might have mechanistic implications.

Animals↗

[Thrombophlebitis of the lower limbs: a convenient diagnosis?].

Venous thrombosis may expose the patient to short (pulmonary embolism) or long term complications (postphlebitic syndrome), invalidating and onerous for society. The main point is identifying or excluding this pathology by anamnesis, clinical findings and bloodless diagnostics as Doppler c.w. and vascular duplex scanner. We suggest a decision flow chart helpful for diagnosis and therapeutics.

Adult↗

Transferable clastogenic activity in plasma from patients with Fanconi anemia.

The present study was conducted on 13 patients with Fanconi anemia. 25 parents and 12 siblings. The chromosomal instability characteristic of this congenital breakage syndrome was associated with the presence of transferable clastogenic material in the plasma, as also reported previously for ataxia telangiectasia and Bloom's syndrome. While all plasma ultrafiltrates from homozygotes had chromosome damaging properties, the clastogenic material had to be concentrated in most heterozygotes to reach detectable levels. The clastogenic effect was exerted via the intermediacy of superoxide radicals, since it was regularly inhibited by superoxide dismutase (SOD). This adds further evidence for a prooxidant state in this hereditary disease. The autosustained clastogenic activity possibly plays a role in the progressive impairment of blood cell-producing bone marrow and may predispose patients to develop cancer and leukemia. Prophylactic use of antioxidants may be recommended, using clastogenic plasma activity as a guide.

Adolescent↗

Albumin excretion rate levels in non-diabetic offspring of NIDDM patients with and without nephropathy.

Familial clustering of diabetic nephropathy points to genetic susceptibility. The observation that in non-diabetic subjects microalbuminuria occurs more frequently in the presence of a parental history of diabetes supports this hypothesis. However, the role of inherited factors in poorly understood in non-insulin dependent diabetes mellitus (NIDDM). This study investigated the albumin excretion rate in non-diabetic offspring of NIDDM patients with increased albumin excretion rate (> 20 micrograms/min) or normal albumin excretion rate (< 20 micrograms/min). We recruited 20 offspring of NIDDM patients with increased albumin excretion rate (A-off) and 20 offspring rate (N-off), matched for age, sex, body mass index, blood pressure and estimated protein intake. All offspring were normotensive, had normal creatinine clearance, normal glucose tolerance and sterile urine collection. Albumin excretion rate was measured on three sterile overnight urine collections and median values were used for calculations. Albumin excretion rate was significantly higher in A-off than in N-off (7.7 +/- 1.2 vs 3.4 +/- 0.6 micrograms/min p<0.01) and significantly related to parents' albumin excretion rate (p<0.01, r=0.53). These results suggest that an increased glomerular permeability is present in non-diabetic offspring of NIDDM patients with increased albumin excretion rate.

Adult↗

Apolipoprotein E allele frequencies in an Italian population: relation to age and lipid profile.

Apo E phenotype and plasma Tg, Chol, LDL-Chol, HDL-Chol and Apo B levels were determined in a sample of 228 healthy Italian subjects (124 men and 104 women) aged 18-93. The allele frequencies were: epsilon 2 = 0.070; epsilon 3 = 0.829; epsilon 4 = 0.101 (among the lowest values in the literature). Division of the sample into four age groups indicated that epsilon 4 frequency decreased with age to 0 in persons aged over 75. Covariance analysis of the influence of each allele on plasma lipids showed that epsilon 4 was significantly associated with the highest Chol, LDL-Chol and Apo B levels. These data are evidence of the influence of epsilon 4 on Chol metabolism in an Italian population. They also show that its frequency decreases with age.

Adolescent↗