Biomedical subjects

Giovanni Zuliani

Publications and source records attributed to Giovanni Zuliani.

16 recordsLinked to original sources

PubMed2006

Enhanced soluble CD40 ligand and Alzheimer's disease: evidence of a possible pathogenetic role.

It has been suggested that cerebrovascular factors contribute to Alzheimer's disease. Soluble CD40 ligand (sCD40L) is directly involved in the development of vascular damage. We tested the hypothesis that sCD40L may be enhanced in Alzheimer's disease and predictive of its clinical course. Plasma sCD40L levels were evaluated in three groups of 40 consecutive patients each referring for mild or moderate or severe Alzheimer's disease, as assessed by the Clinical Dementia Rating (CDR), and in 40 healthy subjects. Seventy-seven patients with mild or moderate disease were re-evaluated after 2 years. Cross-sectional comparisons revealed higher plasma sCD40L levels in Alzheimer's disease patients than in controls (9.3+/-4.7 ng/mL versus 3.4+/-1.3 ng/mL, p<0.0001). Circulating sCD40L levels significantly increased through the three CDR stages (p=0.0011 or less) and were correlated with MMSE (r=-0.574, p<0.0001) and ADAS-cog subscale (r=0.538, p<0.0001) scores. Longitudinal evaluation identified sCD40L as an independent predictor of MMSE (beta=-0.157, t=-3.650, p=0.0005) and ADAS-cog subscale (beta=0.484, t=3.890, p=0.0002) score changes after 2 years. Patients with plasma sCD40L level>or=6.0 ng/mL, identified by ROC curve analysis as the best discriminating value for disease progression, had a three-fold increase in the risk of progression toward a worse CDR stage (odd ratio: 3.0, C.I. 95% 1.2-8.1). In conclusion, circulating sCD40L is enhanced in patients with Alzheimer's disease and independently associated with the severity and progression of the disease. These data might suggest a pathogenetic role for sCD40L in Alzheimer's disease.

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PubMed2006

Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study.

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (>/=65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.

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PubMed2006

High interleukin-6 plasma levels are associated with low HDL-C levels in community-dwelling older adults: the InChianti study.

BACKGROUND: Low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased incidence of coronary heart disease (CHD). A better understanding of the mechanisms leading to low HDL-C and CHD is essential for planning treatment strategies. Clinical studies have demonstrated that cytokines might affect both concentration and composition of plasma lipoproteins, including HDLs. METHODS: We investigated the possible association between low HDL-C levels, defined as < or =10th gender specific percentile, and circulating markers of inflammation (IL-1beta, TNF-alpha, IL-6, IL-10, IL-18, and CRP) in a population of 1044 community dwelling older Italian subjects from the InChianti study. RESULTS: Using logistic regression analysis we demonstrated that IL-6 levels (III versus I tertile, OR: 2.10; 1.10-3.75), TG (III versus I tertile OR: 27.45; 8.47-88.93), fasting insulin (III versus I tertile OR: 2.84; 1.50-5.42), and age (OR: 1.038; 1.002-1.075) were associated with low HDL-C independent of smoking, BMI, waist circumference, hypertension, diabetes, physical activity, alcohol intake, oral hypoglycaemics, CRP, IL-18, and TNF-alpha levels. The adjusted attributable risk of low HDL-C in the exposed group (III tertile of IL-6) was 54%. CONCLUSIONS: The present study provides the epidemiological evidence that besides triglycerides, fasting insulin, and age, IL-6 is one of the main correlates of low HDL-C levels in older individuals.

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PubMed2006

Anaemia increases the risk of dementia in cognitively intact elderly.

Although cross-sectional studies found an association between anaemia and dementia, longitudinal studies provided contradictory results. We hypothesize that anaemia might increase the risk of developing dementia because of chronic brain hypo-oxygenation. Using baseline data from a community-based longitudinal study, the Kungsholmen Project, Stockholm, Sweden, we clinically followed 1435 non demented subjects aged 75-95 years for 3 years to detect incident dementia cases (DSM-III-R criteria). Subjects that fulfilled WHO criteria for anaemia, baseline haemoglobin concentration; 130 g/L (men) and 120 g/L (women), had a higher hazard ratios (HR) of developing dementia 3 years later (HR 1.6, 95% CI: 1.1-2.4). In persons with good baseline cognition (MMSE>or=26, n=1139), the association was stronger and still significant after adjustments for conditions potentially related to anaemia and dementia, such as chronic diseases, inflammatory markers, and indicators of nutritional status. The HR was increased even when different haemoglobin cut offs for anaemia definition were used. Thus, anaemia is suggested to be a new potential modifiable risk factor for dementia.

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PubMed2006

Risk factors for short-term mortality in older subjects with acute ischemic stroke.

BACKGROUND: Stroke is the third cause of death in older individuals living in Western Countries. The identification of predictors for mortality after stroke has a major importance for clinicians in order to allow the implementation of therapeutic and preventive strategies. OBJECTIVE: To evaluate the association between clinical and laboratory parameters and 30-days total mortality in a large sample of older patients with stroke. METHODS: 469 older patients (median age: 80.0 years) consecutively hospitalized for acute ischemic stroke were enrolled. The data recorded included: (1) clinical features of stroke; (2) routine clinical chemistry analyses; (3) medical history, and (4) 12-lead ECG. All patients underwent computed tomography scan of the brain. Stroke type was classified by the Oxfordshire Community Stroke Project system. RESULTS: 130 subjects died within 30 days after stroke, with an overall mortality of 27.7%. At univariate analysis, altered levels of consciousness (ALC), congestive heart failure, atrial fibrillation, previous stroke, high blood glucose, fibrinogen and blood sedimentation rate levels, higher white blood cell count, lower serum albumin and iron levels were associated with mortality. Multivariate logistic regression analysis indicated that short-term mortality was associated with ALC (OR: 11.80; CI 95%: 5.50-24.00), congestive heart failure (OR: 3.06; CI 95%: 1.04-8.80), and age (OR: 1.04; CI 95%: 1.002-1.09) independent of gender, previous stroke, AF, fasting blood glucose, serum albumin, serum iron, and white blood cell count. In patients with ALC (high-mortality rate: 63.6%), only hyperglycemia (III vs. I tertile, OR: 9.60; CI 95%: 1.65-52.50) was associated with mortality after multivariate adjustment. CONCLUSION: Our study highlights the role of ALC and congestive heart failure in the short-term prognostic stratification of older patients with acute ischemic stroke. Furthermore, our results support the value of post-stroke hyperglycemia as a marker for short-term mortality also in advanced age, and particularly in the presence of ALC and in nondiabetic individuals.

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PubMed2005

Treatment with angiotensin-converting enzyme inhibitors is associated with a reduction in short-term mortality in older patients with acute ischemic stroke.

BACKGROUND: Stroke is the third cause of death in older people living in Western countries. We tested the hypothesis that angiotensin-converting enzyme inhibitors (A-I) might affect short-term (30 day) mortality in older persons with severe acute ischemic stroke. METHODS: We analyzed data from a retrospective study including 475 consecutive older patients hospitalized for acute ischemic stroke. Mean age was 78.4 +/- 9.2 years; 58.2% were female. Stroke type was classified according to the Oxford Community Stroke Project (OCSP). RESULTS: Mortality rate was 28%. Thirty-two percent of patients were treated with A-I; mortality was 16.5% in patients treated compared with 33.3% in those not treated (chi(2) p =.001). The odds ratio for mortality in treated patients was: 0.47 (0.25-0.89) after full adjustment (age, sex, mean diastolic and systolic blood pressure, previous stroke and/or transient ischemic attack, congestive heart failure, atrial fibrillation, diabetes, hypertension, coronary heart disease, and previous treatment with A-I); 0.29 (0.09-0.89) in patients with altered level of consciousness after full adjustment; 0.60 (0.33-1.12) after adjustment for OCSP classification, age, and sex; and 0.30 (0.08-0.97) in total anterior circulation infarction stroke type after full adjustment. CONCLUSIONS: Our data suggest that treatment with A-I might reduce short-term mortality in older patients with acute ischemic stroke. Randomized clinical trials should confirm this possible specific effect of A-I.

Age Factors↗

PubMed2005

Executive function correlates with walking speed in older persons: the InCHIANTI study.

OBJECTIVES: To study the association between performance on psychological tests of executive function and performance on lower extremity tasks with different attentional demands in a large sample of nondemented, older adults. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: Nine hundred twenty-six persons aged 65 and older, without dementia, stroke, parkinsonism, visual impairment, or current treatment with neuroleptics, enrolled in a large epidemiological study. MEASUREMENTS: Trail Making Test (TMT) parts A and B and two performance-based measures of lower extremity function that require different executive/attentional-demanding skills: walking speed on a 4-m course at usual pace and walking speed on a 7-m obstacle course at fast pace. A difference score (Delta TMT), obtained by subtracting time to perform part A from time to perform part B of the TMT, was used as an indicator of executive function. Based on Delta TMT, subjects were divided into poor performance, intermediate performance, and good performance. RESULTS: After adjustment, no association between Delta TMT and 4-m course usual-pace walking speed was found. Participants with poor Delta TMT and with intermediate Delta TMT performance were more likely to be in the lowest tertile for 7-m obstacle course walking speed. CONCLUSION: In nondemented older persons, executive function is independently associated with tasks of lower extremity function that require high attentional demand.

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PubMed2004

Prescription of antithrombotic therapy in older patients hospitalized for transient ischemic attack and ischemic stroke: the GIFA study.

BACKGROUND AND PURPOSE: Antithrombotic therapy has been demonstrated as an effective tool for secondary ischemic stroke prevention. Nevertheless, scant data are available on actual prescription of this therapy in clinical practice. METHODS: A total of 17 337 patients admitted to geriatric and internal medicine wards participating in the study in the 1993 to 1998 survey period were analyzed. Patients with coded diagnoses of ischemic stroke and transient ischemic attack (TIA) were selected. Data recorded included demographic and clinical characteristics and medication prescription during hospital stay and at discharge. Logistic regression analyses were used to identify conditions associated with the prescription of antiplatelet or anticoagulant drugs. RESULTS: Among 946 patients with diagnosis of stroke or TIA (mean age 78 years), >40% was discharged without antithrombotic prescription. Conditions that made the prescription more unlikely were diagnosis of stroke (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.44 to 0.86), presence of anemia (OR: 0.70; 95% CI: 0.49 to 0.98), severe disability (OR: 0.48; 95% CI: 0.30 to 0.75), and cognitive impairment (OR: 0.58; 95% CI: 0.43 to 0.75). There was an independent and additive association of physical and cognitive status with antithrombotic therapy prescription. CONCLUSIONS: A high rate of patients affected by stroke or TIA are discharged from the hospital without antithrombotic therapy. The most important correlates of the likelihood of not receiving an antithrombotic medication were cognitive and functional status.

Acute Disease↗

PubMed2004

Combined measurement of serum albumin and high-density lipoprotein cholesterol strongly predicts mortality in frail older nursing-home residents.

BACKGROUND AND AIMS: The aim of this study was to verify the hypothesis that a combined measurement of albumin and HDL-C might predict total mortality in institutionalized frail older residents. METHODS: Participants were 344 older subjects (272 F, 72 M), living in the "Istituto Riposo Anziani" (I.R.A.), a nursing-home located in Padova, North-east Italy. Functional status, comorbidity, and clinical chemistry parameters were evaluated at entry. All-cause mortality was evaluated after 2 and 4 years. The sample was divided into 4 groups by using the 50 degrees percentile of albumin and HDL-C as cut-off value. The mortality odds ratio (OR) was estimated by multivariate logistic regression analysis. RESULTS: Total mortality was 36.8% after 2 years and 51.8% after four years. A trend toward an increase in mortality from group 1 to 4 was observed (p for trend: 0.01). The OR for 2 and 4 years mortality was 3.83 (95% CI 1.86-7.58) and 2.66 (95% CI 1.37-5.17), respectively, in group 4 compared with group 1, after adjustment for age, gender, number of chronic diseases, functional status, BMI, diabetes, dementia, stroke, CHD, CHF, hypertension, depression, COPD, and total cholesterol levels. CONCLUSIONS: Among frail older nursing-home residents, simple measurement of serum albumin and HDL-C levels may be useful in identifying varying degrees of frailty.

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PubMed2004

Low cholesterol levels are associated with short-term mortality in older patients with ischemic stroke.

BACKGROUND: The possible relationship between serum total cholesterol (TC) levels and outcome following ischemic stroke is still controversial. We evaluated the association between TC levels and 30-day mortality in a sample of older patients with acute ischemic stroke. METHODS: We enrolled 490 older patients with severe ischemic stroke consecutively admitted to University Hospital's Internal Medicine or Geriatrics Department. Stroke type was classified according to the Oxfordshire Community Stroke Project. The data recorded included clinical features, medical history, electrocardiogram, and blood analyses. Patients were divided into three groups by TC levels: group I (TC<4.1 mmol/L), group II (TC 4.1-5.2 mmol/L), and group III (TC>5.2 mmol/L). RESULTS: The overall mortality was 27.7%. Mortality was higher in patients with low TC levels (47.4%) compared with those with normal and high TC levels (23.0% and 24.1%, respectively). The odds ratio (OR) for short-term death was 2.17 (95% confidence interval [CI] 1.22-3.85) in group I compared with group III, after adjustment for age and gender. This result did not change after adjustment for possible confounders (OR 2.87; 95% CI 1.23-6.68). A similar trend was observed after adjustment for the Oxfordshire classification, age, and gender (OR 1.67; 95% CI 0.83-3.33). CONCLUSIONS: Short-term mortality following ischemic stroke is higher in older participants with low TC levels, independent of a large number of factors. Low TC levels might be useful in identifying frail older participants at high risk of stroke short-term mortality.

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PubMed2004

Body mass index, body cell mass, and 4-year all-cause mortality risk in older nursing home residents.

OBJECTIVES: To investigate the relationship between body composition (assessed using body mass index (BMI) and body cell mass (BCM)) and all-cause mortality in a sample of older nursing home residents. DESIGN: Prospective study with a median follow-up period of 3.5 years. SETTING: Istituto di Riposo per Anziani, Padua, Italy. PARTICIPANTS: A total of 344 participants (79.1% women) aged 65 and older at baseline. MEASUREMENTS: Anthropometric, nutritional, and metabolic parameters were measured at baseline. BCM was measured using tetrapolar bioelectric impedance analysis. Up to 4 years of follow-up data for vital status were available. Survival analysis was conducted using Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS: During the follow-up period, there were 179 deaths. After adjustment for age and sex, subjects with low BMI and low BCM (lowest sex-specific tertiles) had significantly higher mortality than those with higher BMI or BCM levels. In a fully adjusted regression model, there was no association between BMI levels and risk of mortality, with subjects in the top tertile having the same likelihood of mortality as subjects in the lowest tertile (relative risk (RR)=0.94, 95% confidence interval (CI)=0.61-1.43). Conversely, there was a strong and significant inverse association between BCM levels and mortality (RR for tertile III=0.55, 95% CI=0.35-0.87; P<.01). Furthermore, participants who had high BCM had comparable survival rates in all BMI tertiles. CONCLUSION: In this sample of older nursing home residents, BCM was a strong and independent risk factor for mortality. BCM assessment might provide more useful prognostic information for clinicians than BMI.

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PubMed2004

Prescription of anti-oedema agents and short-term mortality in older patients with acute ischaemic stroke.

BACKGROUND AND OBJECTIVE: In Western countries, stroke is the third most common cause of death and one of the main causes of disability in individuals aged over 65 years. Mortality at 1 month after stroke is still high, at around 25-30%. Despite the widespread use of anti-oedema agents in clinical practice, there are only a few studies that have investigated the effect of these drugs on stroke outcome. In this study we evaluated the effect of intravenously administered glycerol or mannitol individually and in combination with corticosteroids, on short-term mortality (30 days). The sample included patients aged over 65 years who were admitted to hospital for acute ischaemic stroke. STUDY DESIGN: This was a retrospective cohort study. The odds ratio, estimated by means of multivariate logistic regression method, was used to compare short-term mortality risk across treatment groups after adjusting for possible confounders. METHODS: This study included 442 consecutive patients aged over 65 years with severe ischaemic stroke who were admitted to either the University School of Internal Medicine (Ferrara) or the Geriatric Department (Perugia), Italy, over a 4-year period (1996-2000). All patients underwent a computed tomography (CT) scan of the brain within 72 hours of admission. Stroke type was classified according to the system used by the Oxfordshire Community Stroke Project. The data recorded included: (i) clinical features of stroke; (ii) detailed medical history, including vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, coronary heart disease, congestive heart failure, alcohol abuse, smoking, previous transient ischaemic attacks or stroke); (iii) 12-lead ECG; and (iv) routine blood analysis and urine tests. RESULTS: No reduction in short-term mortality risk was observed in patients treated with intravenous (IV) glycerol. However, an increase in short-term mortality risk was observed in the patients who were concurrently treated with IV corticosteroids. Similarly, treatment with mannitol did not reduce the risk of short-term mortality; however, concurrent treatment with IV corticosteroids did not show a significant rise in short-term mortality risk. When treatment with IV glycerol and mannitol was considered together, the treatment did not decrease short-term mortality risk, while concurrent therapy with corticosteroids was associated with an increase in short-term mortality risk. CONCLUSION: This study does not support the use of IV osmotic agents such as glycerol or mannitol in the prevention of short-term mortality in older patients with acute ischaemic stroke. Furthermore, our data suggest a possible harmful effect of IV corticosteroids on short-term mortality risk.

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PubMed2003

Emotional vitality and change in lower extremity function after acute medical illness and hospitalization.

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PubMed2002

Molecular mechanisms of autosomal recessive hypercholesterolemia.

Mutations in the phosphotyrosine-binding domain protein ARH cause autosomal recessive hypercholesterolemia (ARH), an inherited form of hypercholesterolemia due to a tissue-specific defect in the removal of low density lipoproteins (LDL) from the circulation. LDL uptake by the LDL receptor (LDLR) is markedly reduced in the liver but is normal or only moderately impaired in cultured fibroblasts of ARH patients. To define the molecular mechanism underlying ARH we examined ARH mRNA and protein in fibroblasts and lymphocytes from six probands with different ARH mutations. None of the probands had detectable full-length ARH protein in fibroblasts or lymphoblasts. Five probands were homozygous for mutations that introduced premature termination codons. No relationship was apparent between the site of the mutation in ARH and the amount of mRNA. The only mutation identified in the remaining proband was a SINE VNTR Alu (SVA) retroposon insertion in intron 1, which was associated with no detectable ARH mRNA. (125)I-LDL degradation was normal in ARH fibroblasts, as previously reported. In contrast, LDLR function was markedly reduced in ARH lymphoblasts, despite a 2-fold increase in LDL cell surface binding in these cells. These data indicate that all ARH mutations characterized to date preclude the synthesis of full-length ARH and that ARH is required for normal LDLR function in lymphocytes and hepatocytes, but not in fibroblasts. Residual LDLR function in cells that do not require ARH may explain why ARH patients have lower plasma LDL levels than do patients with homozygous familial hypercholesterolemia who have no functional LDLRs.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Autosomal recessive hypercholesterolaemia in Sardinia, Italy, and mutations in ARH: a clinical and molecular genetic analysis.

BACKGROUND: Autosomal recessive hypercholesterolaemia (ARH) is caused by mutations in a putative adaptor protein called ARH. This recessive disorder, characterised by severe hypercholesterolaemia, xanthomatosis, and premature coronary artery disease, is rare except on the island of Sardinia, Italy. Our aim was to ascertain why ARH is more common on Sardinia than elsewhere. METHODS: We obtained detailed medical histories, did physical examinations, measured concentrations of lipoproteins, and harvested genomic DNA from 28 Sardinians with ARH from 17 unrelated families. We sequenced the coding regions and consensus splice sites of ARH in probands from these families, and from 40 individuals of non-Sardinian origin who had an autosomal recessive form of hypercholesterolaemia of unknown cause. FINDINGS: Two ARH mutations, a frameshift mutation (c432insA) in exon 4 (ARH1) and a nonsense mutation (c65G-->A) in exon 1 (ARH2), were present in all of the 17 unrelated families with ARH. Three of the ARH alleles contained both mutations, as a result of an ancient recombination between ARH1 and ARH2. No regional clustering of the three mutant alleles within Sardinia was apparent. Furthermore, four Italians from the mainland with autosomal recessive hypercholesterolaemia were homozygous for ARH1. INTERPRETATION: The small number, high frequency, and dispersed distribution of ARH mutations on Sardinia are consistent with these mutations being ancient and maintained in the Sardinian population because of geographic isolation.

Adolescent↗

PubMed2002

Genetic factors associated with the absence of atherosclerosis in octogenarians.

BACKGROUND: Atherosclerosis (ATS) is a common age-related disease of large arteries. The prevalence of older subjects with vascular successful aging (VaSA), defined as the absence of clinical symptoms and instrumental signs of ATS, is low in Western countries. The possible contribution of genetics to the VaSA phenomenon is not known. METHODS: We investigated the distribution of four genetic polymorphisms (angiotensin converting enzyme [ACE], methylenetetrahydrofolate reductase [MTHFR], apolipoprotein E [apo E], and paraoxonase [PON] genes) in 30 subjects with VaSA, 30 subjects with moderate carotid atherosclerosis (ATS group), and 161 controls with a negative history for cardiovascular disease. Clinical examination; ultrasonographic examination of carotid, vertebral, abdominal aortic, iliac, and femoral arteries; and electrocardiogram were performed. RESULTS: The frequency of PON 192 B allele was lower in VaSA patients (13%) compared with ATS patients (37%) and controls (46%) ( p =.06 and.006, respectively); B/B homozygotes were 27% in the ATS group, 12% in controls, and 0% in the VaSA group. The frequency of the MTHFR thermolable + allele was higher in VaSA (0.51) compared with ATS (0.39) and controls (0.40) (VaSA vs C, p =.006). No differences in the distribution of ACE I/D and apo E alleles emerged between the three groups. CONCLUSIONS: The low prevalence of the PON 192 B allele in the VaSA subjects suggests that this polymorphism might have an important role in VaSA, probably by hydrolyzing lipid peroxides and thus preventing low-density lipoprotein from undergoing the oxidative modification. This finding further supports the oxidative hypothesis of ATS.

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