Warfarin for non-valvar atrial fibrillation: still underused in the 21st century?
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
G Pagano
Publications and source records attributed to G Pagano.
Maternal low birth weight and gestational hyperglycemia.
We aimed to investigate whether birth weight could predict the subsequent risk of gestational diabetes and impaired glucose tolerance. Consecutive women with a singleton pregnancy and gestational diabetes (n = 50), impaired glucose tolerance (n = 50) and normoglycemia (n = 200) were included in the study. Birth data were collected from original hospital records of the women. Women with gestational hyperglycemia were significantly older and heavier than those with normoglycemia. Maternal birth weights significantly declined for each class of glucose tolerance (3389 +/- 644; 3184 +/- 583 and 3077 +/- 661, respectively for women with normoglycemia, impaired glucose tolerance and gestational diabetes). After adjustment for age, gestational age and weight gain, maternal diabetes, and pre-pregnancy body mass index, maternal birth weight was negatively related to impaired glucose tolerance (OR 0.88, 95% CI 0.81-0.97) and to gestational diabetes (OR 0.82, 95% CI 0.74-0.91) in a multiple logistic regression model. These findings suggest that women with low birth weight constitute a group at increased risk for both gestational impaired glucose tolerance and diabetes.
Age Factors↗
Data sources and validity of epidemiological studies on diabetes.
Explore the source record for details and available documents.
Blindness↗
Higher lipoprotein (a) levels in atherothrombotic than lacunar ischemic cerebrovascular disease.
To investigate the role of plasma lipid abnormalities in ischemic cerebrovascular disease related to primary vessel disease, the authors assess lipid profiles in a hospital-based cohort of 202 consecutive patients with atherothrombotic or lacunar stroke subtypes. Lipoprotein (a) was the unique lipid parameter that differs between these two subtypes being its value twofold higher in patients with atherothrombotic than in lacunar stroke. This suggests that lipoprotein (a) promotes large vessel atheromatosis rather than small vessel arteriolosclerosis and favors thrombosis on atheromatous plaques by suppressing local fibrinolysis.
Adult↗
Plasma homocysteine, methylenetetrahydrofolate reductase gene polymorphism and carotid intima-media thickness in Italian type 2 diabetic patients.
BACKGROUND: Moderately elevated levels of homocysteine have been associated with an increased cardiovascular risk in type 2 diabetic patients. The role of methylenetetrahydrofolate reductase gene polymorphism is less clear. MATERIALS AND METHODS: We investigated the contribution of plasma homocysteine levels and the methylenetetrahydrofolate reductase gene polymorphism to the variability of carotid intima-media thickness in 124 consecutive Italian patients with type 2 diabetes mellitus. Fasting plasma homocysteine was measured by high-pressure liquid chromatography with an electrochemical detector; methylenetetrahydrofolate reductase genotypes were determined by polymerase chain reaction and restriction enzyme digestion. The carotid intima-media thickness was evaluated with high-resolution B-mode ultrasonography. RESULTS: Age, creatinine and plasma homocysteine levels showed a positive correlation with mean carotid intima-media thickness values, but only age and creatinine levels were still associated with mean carotid intima-media thickness values in the multivariate analysis. Plasma homocysteine levels were significantly higher in the patients bearing the 677T/677T genotype of the methylenetetrahydrofolate reductase polymorphism; mean carotid intima-media thickness values were not different in the three different methylenetetrahydrofolate reductase genotypes. CONCLUSION: In 124 Italian patients with type 2 diabetes mellitus, basal levels of plasma homocysteine, as well as methylenetetrahydrofolate reductase gene polymorphism, did not explain the variability of mean carotid intima-media thickness.
Aged↗
Type 2 diabetes with onset in the elderly is not a benign disease.
Explore the source record for details and available documents.
Adult↗
Redox-modulated xenobiotic action and ROS formation: a mirror or a window?
A number of xenobiotics require redox reactions to form the reactive intermediates involved in the ultimate toxic events (e.g., adduct formation). The same mechanisms lead to the formation of reactive oxygen species (ROS), which can themselves exert direct toxicity including, e.g., DNA oxidative damage or glutathione depletion. The occurence of both mechanistic features in xenobiotic activation and toxicity may raise some difficulties in ascertaining the respective roles of reactive intermediates versus ROS-related mechnisms. An example is provided by the toxicity mechanisms of mitomycin C (MMC) and diepoxybutane (DEB), which are commonly referred to as 'cross-linkers'. Their toxic actions, however, are well-known to be modulated via redox parameters, such as oxygen tension, antioxidants levels, or thioredoxin overexpression. The diagnostic assessment of Fanconi's anaemia (FA) relies on MMC and DEB sensitivity, which is usually referred to as 'cross-linker sensitivity'; thus the redox-dependent toxicities of MMC and DEB may have direct implications for the definition of FA phenotype. Another major aspect in ROS formation relies on the extensive evidence pointing to the requirement for oxidative, as well as nitrosative activities in triggering a number of key events in cell division and differentiation, and in early embryogenesis. In turn, antioxidants that may prevent ROS-associated cellular damage in adult cells may prove to exert adverse or fatal outcomes when administered in early life stages. The overall information available on xenobiotic redox biotransformation and on the physiopathological roles of ROS points to the need of addressing ad hoc studies that should take into account the multiplicity of mechanistic events involved.
Cell Differentiation↗
Low socioeconomic status as a risk factor for gestational diabetes.
Explore the source record for details and available documents.
Adult↗
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.
This study evaluated dual protease inhibitor (PI) regimens containing amprenavir (APV) in PI-naive, HIV-1-infected patients over 48 weeks. Patients were randomized to 800-mg APV combined with 800-mg indinavir (IDV), 750-mg nelfinavir (NFV), or 800-mg saquinavir-soft gel capsule (SGV-SGC), all three times daily without nucleoside reverse transcriptase inhibitors, or APV given alone for 3 weeks and then with 150-mg lamivudine (3TC) and 300-mg zidovudine (ZDV), twice daily. Dual PI therapy demonstrated substantial antiviral activity and was generally safe and well tolerated. Eight patients had virologic failure; 5 were receiving dual PI therapy and 3 were in the APV/3TC/ZDV arm. The protease I50V mutation characteristic of APV resistance was not observed, although other key PI mutations were selected in 4 patients failing therapy, 2 of whom had PI resistance at baseline.
Adult↗
The effects of atrial fibrillation on functional recovery in post-stroke patients.
PURPOSE: This study evaluates the negative effects of atrial fibrillation (AF) on after stroke recovery and its relationship with age and other concomitant diseases. METHOD: One hundred and ninety-nine consecutive inpatients, after their first stroke, were enrolled and entered a rehabilitation program lasting 60 days. The mean interval since the stroke was 19 days. The disability, both at admission and at discharge, was assessed by Functional Independence Measure (FIM). Atrial fibrillation was diagnosed at admission on the basis of electrocardiographic recordings. Gender, age, blood pressure and blood sugar level were also taken into account. RESULTS: Stroke patients suffering from AF, when compared to those lacking AF, have higher disability at admission as well as at discharge and had a lesser gain in functional recovery. No statistical difference of the AF occurrence was found between male and female patients. The negative correlation between age and functional gain was found only in AF patients. There was also a significant association between AF and hypertension, but not between AF and diabetes. At the beginning and at the end of the study, the median FIM scores of all the patients with AF were quite similar irrespective of manifesting hypertension, diabetes or neither of these two. CONCLUSIONS: The presence of AF has a negative prognostic value on post stroke outcome, particularly in the elderly patients. The pattern of recovery of stroke subjects having AF is not influenced by concomitant diseases like hypertension or diabetes.
Animals↗
The role of oxidative stress in developmental and reproductive toxicity of tamoxifen.
The antiestrogen tamoxifen (TAM) is widely used as a drug against breast cancer and is currently being tested as a chemopreventive agent. However, a number of studies showed genotoxic and carcinogenic effects of TAM. These effects are thought to be related to oxygen radical overproduction which occurs during TAM metabolic activation. There is no evidence, thus far, on TAM toxicity to embryos and gametes. The present study was designed to elucidate the mechanisms of TAM-induced developmental, reproductive and cytogenetic toxicity towards sea urchin (SU) embryos with regard to the possibility of TAM-initiated oxidative stress. Embryo cultures from SU were subjected to long-term (throughout embryogenesis) or short-term (two hours) incubation with TAM at concentrations from 10(-8) to 10(-5) M. The experiments on TAM-induced toxicity to gametes were carried out with SU sperm, or unfertilized eggs, suspended in TAM (10(-8) to 10(-6) M). To assess the effects of TAM to embryos or to gametes, developmental defects, embryonic mortality, fertilization success, and cytogenetic abnormalities were scored. Oxidative damage to DNA and lipids was detected by measurements of 8OHdG levels and lipid peroxidation, respectively. Reactive oxygen species (ROS) production by eggs and embryos was recorded by luminol-dependent chemiluminescence (LDCL) and cytochrome c reduction methods. The changes in activities of SU superoxide dismutase (SOD) and catalase were also evaluated. TAM exerted: a) early embryonic mortality to exposed embryos and to the offspring of exposed eggs; b) developmental defects to the offspring of exposed sperm; c) decrease in sperm fertilization success, and d) cytogenetic effects in the offspring of exposed sperm or eggs. These morphological effects corresponded to the state of oxidative stress in SU embryos (increased oxidative damage to DNA and lipids and induction of antioxidant enzymes). Since TAM did increase significantly ROS production by embryos, it is suggested that TAM may be metabolically activated by SU embryonic oxidases and peroxidases, which in turn could be induced by TAM. The present study provides further support to the utilization of the SU system as a useful model to help elucidate mechanisms of chemical teratogenesis and carcinogenesis.
Animals↗
Increasing trend of type I diabetes in children and young adults in the province of Turin (Italy). Analysis of age, period and birth cohort effects from 1984 to 1996.
AIMS/HYPOTHESIS: This study aimed to determine if the incidence of Type I (insulin-dependent) diabetes mellitus increased over time and if the time trend is attributable to linear trend, calendar period or birth cohort effects. METHODS: This study was based on a cohort of subjects aged 0-29 years from 1984 to 1996, who resided in the province of Turin, Italy. Poisson regression models were used to estimate the effect of sex, age, calendar time and cohorts on incidence rates. RESULTS: The mean incidence rate in the age group of 0 to 29 years was 7.78 of 100,000 person-years (95% confidence interval: 7.26-8.32), with a lower risk in women than in men [rate ratio (RR): 0.76 (0.67-0.88)]. We found a trend of incidence increasing over time (annual increase of risk 2.25 % a year, 95 % CI 0.44-4.10). In Poisson regression analysis we found that the best model was the one with sex, age and a linear term attributable to either calendar period or cohort effects. The linear term corresponds to a RR of 1.12 (1.02-1.22,p = 0.015) for each 5-year age span. CONCLUSION/INTERPRETATION: We found that the time trend in this Mediterranean area was similar in magnitude to that reported in northern European countries. The increase was linear in pattern, each birth cohort and each calendar period showing a higher risk than the preceeding one with some evidence of two steep increases in the incidence of Type I diabetes centered on the years 1964 and 1984. We found that the incidence of diabetes increased in the 0 to 14 age group and also in the older age group of 15 to 29 years and that the age-period models were not statistically significantly better than the age-cohort models.
Adolescent↗
Dietary fat and gestational hyperglycaemia.
AIMS/HYPOTHESIS: The purpose of this study was to investigate the relation between life-style habits and glucose abnormalities in Caucasian women with and without conventional risk factors for gestational diabetes. METHODS: A total of 126 pregnant women with gestational diabetes, 84 with impaired glucose tolerance and 294 with normal glucose tolerance, identified by sequential screening, were interviewed to determine their usual weekly food pattern, amount of exercise, smoking habits and alcohol intake. RESULTS: Patients with glucose abnormalities were older and shorter in height and had significantly higher BMI before pregnancy, percentage of diabetic first-degree relatives and higher intake of saturated fat. Patients without known risk factors for gestational diabetes (i. e. younger than 35 years of age, BMI < 25 kg/m2, no first-degree diabetic relatives) included 40 with impaired glucose tolerance or gestational diabetes. In a multiple logistic regression model age, short stature, familial diabetes, BMI and percentages of saturated fat were associated with impaired glucose tolerance or gestational diabetes in all patients, after adjustment for gestational age. In patients without conventional risk factors only percentages of saturated fat (OR = 2.0; 95 %-CI = 1.2-3.2) and polyunsaturated fat (OR = 0.85; 95 %-CI = 0.77-0.92) were associated with gestational hyperglycaemia, after adjustment for age, gestational age and BMI. CONCLUSION/INTERPRETATION: Saturated fat has an independent role in the development of gestational glucose abnormalities. This role is more important in the absence of conventional risk factors suggesting that glucose abnormalities could be prevented during pregnancy, at least in some groups of women.
Alcohol Drinking↗
Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients.
Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.
Adult↗
Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes.
BACKGROUND AND DESIGN: Conflicting data exist about uric acid levels in type 2 diabetes mellitus, as low levels were found in diabetic patients, while elevated serum uric acid is a feature of hyperinsulinemia and impaired glucose tolerance. The present study was addressed to evaluate the relation between uric acid and metabolic parameters, creatinine clearance and albumin excretion rate in a cohort of type 2 diabetic patients. RESULTS: Hyperuricemic patients were older and had higher values of body mass index (BMI), systolic and diastolic blood pressure, triglycerides, albumin excretion rate, C-peptide and prevalence of hypertension, metabolic syndrome and macroalbuminuria and lower values of high-density lipoprotein (HDL)-cholesterol, creatinine clearance and glycated haemoglobin (HbA1c). The correlations between uric acid levels and triglycerides, BMI, systolic blood pressure, albumin excretion rate, C-peptide, creatinine clearance, HDL-cholesterol and HbA1c remained significant in a multiple regression analysis after adjustment for age, sex and duration of diabetes. After performing multiple logistic regression analyses, uric acid levels were independently associated with hypertension [odds ratio (OR) = 1.8; 95% confidence interval (CI) 1.6--2], after adjustment for age, sex, duration of diabetes and macroalbuminuria (OR = 1.5; 95% CI 1.1--2.0), after adjustment for age, sex, HbA1c levels, creatinine clearance, duration of diabetes and blood pressure levels and the metabolic syndrome (OR = 1.6; 95% CI 1.5--1.8), after adjustment for age, sex and creatinine clearance. CONCLUSIONS: In type 2 diabetes, hyperuricemia seems to be associated with the insulin-resistant syndrome and with early onset or increased progression to overt nephropathy, while hypouricemia is associated with worse metabolic control, hyperfiltration and a late onset or decreased progression to overt nephropathy.
Aged↗
Myocardial infarction before the age of 40 years is associated with insulin resistance.
Insulin resistance is associated with atherosclerosis, and hyperinsulinemia is predictive of coronary heart disease. However, a quantitative estimation of in vivo insulin sensitivity in juvenile myocardial infarction is still lacking and the mechanism of hyperinsulinemia is unknown. We estimated insulin sensitivity, beta-cell secretion, and hepatic insulin extraction using the minimal model analysis of a frequently sampled intravenous glucose tolerance test (FSIGT) in 25 normal-weight subjects without glucose intolerance and hypertension who had an acute myocardial infarction before the age of 40 years, and 10 control subjects comparable for age, sex, body mass index, and blood pressure. All patients underwent a coronary angiography. Insulin sensitivity was significantly lower in patients than in control subjects (mean +/- SEM, 4.6 +/- 0.6 v8.5 +/- 1.2 10(-4). min(-1)(microU/mL), P = .002). The basal C-peptide secretion rate (P = .02), total C-peptide secretion (P = .005), area under the curve (AUC) of insulin (P = .04) and C-peptide (P = .01), and hepatic insulin extraction (P = .04) were higher in patients versus control subjects. In conclusion, insulin resistance is evident in subjects with early myocardial infarction accurately selected to avoid the influence of other factors known to reduce insulin sensitivity, and hyperinsulinemia is due to an increase in beta-cell secretion rather than a decrease in hepatic insulin extraction.
Adult↗
The metabolic syndrome in twins: a consequence of low birth weight or of being a twin?
BACKGROUND: To evaluate if being a twin is a condition at risk of developing metabolic abnormalities in the adult life 'per se' or as a consequence of the lower birth weight. METHODS: 48 monozygotic twins and 50 non-twin controls, both with parental diabetes, were compared; the two groups were comparable for age, sex and body mass index. RESULTS: Twins showed higher values of blood pressure, triglycerides, insulin resistance, fasting insulin, insulin AUCs and higher prevalence of the metabolic syndrome, and, inversely, lower birth weight. After adjustment for birth weight, no significant association was evident with the twin status. Birth weight was inversely associated with the presence of the metabolic syndrome or of at least one or more of its components, while the positive association with the twin status was not significant. CONCLUSIONS: Our data suggest that low birth weight is more relevant than the twin status as a risk factor for the metabolic syndrome and its components.
Adolescent↗
Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).
The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.
AIDS-Related Opportunistic Infections↗