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Biomedical subjects

G Zuliani

Publications and source records attributed to G Zuliani.

At least 19 recordsLinked to original sources
PubMed2007

High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia.

In older individuals, inflammatory mechanisms have been linked to the pathogenesis of both dementia and functional impairment. In this cross-sectional study we have investigated the possible association between some markers of systemic inflammation and functional status, in a sample of one hundred and forty older demented patients including 60 patients with late onset Alzheimer's disease (LOAD) and 80 with vascular dementia (VD). Functional status was evaluated by Barthel Index (BI); the total score ranged from 0 (total dependency) to 20 (total autonomy). Interleukin-1beta, Tumor Necrosis Factor-alpha, Interleukin- 6, Interleukin- 8, and Transforming Grow Factor beta were quantified by ELISA. Among the cytokines evaluated, only IL-6 was correlated with the BI (r: -0.32, p < 0.001). The mean levels of IL-6 progressively decreased from I (9.50 pg/mL), to II (6.40 pg/mL), to III BI tertile (4.80 pg/mL) (p < 0.02). At multiple regression analysis, IL-6 was associated with BI in the whole sample and in VD, but not in LOAD, independent of age, gender, smoking, alcohol consumption, hypertension, diabetes, coronary heart disease, previous stroke, and mini mental state examination score. Our study suggests the existence of an independent and negative relationship between IL-6 plasma levels and functional status in older individuals with vascular dementia. This finding might contribute to explain the 'excess of disability' phenomenon described in older demented patients.

Activities of Daily Living↗
PubMed2006

Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia.

Some cytokines have been involved in the pathogenesis of late onset Alzheimer's disease (LOAD). A possible increase in plasma cytokines levels has been reported in LOAD and vascular dementia (VD), but the results of previous studies are conflicting. We evaluated the plasma levels of IL-6, TNF-alpha, IL-1beta, and IL-10 in four groups of older individuals: 60 patients with LOAD, 80 patients with VD, 40 subjects with cerebrovascular disease but without dementia (CDND), and 42 controls (C). By analysis of covariance (adjustment for age, gender, coronary heart disease, diabetes, hypertension, smoking, and alcohol consumption) we found that: *IL-1beta was higher in VD, LOAD, and CDND compared with controls (p<0.005). *TNF-alpha was higher in VD and LOAD compared to C (p<0.05), and in VD compared to LOAD (p<0.03). *IL-6 was higher in VD compared with LOAD (p<0.03). No differences in IL-10 values were found (Kruskal-Wallis, Asymp. Sig. 0.14). By logistic regression analysis, we demonstrated that high levels (defined as above the median) of IL-1beta and TNF-alpha, but not of IL-6, were associated with increased likelihood of having VD and LOAD compared to C, while high IL-6 levels were associated with a increased probability of having VD, compared with LOAD. Our study support the notion of a low-grade systemic inflammation in older patients with LOAD or VD, characterized by an increase in plasma IL-1beta and TNF-alpha levels. The high IL-6 levels found in VD might be not a specific finding, as it might come from several conditions including atherosclerosis and related vascular risk factors, comorbidity, and frailty.

Aged↗
PubMed2005

Role of antioxidants in atherosclerosis: epidemiological and clinical update.

Low density lipoprotein (LDL) oxidative modification in the vascular wall seems to be a key factor in atherosclerosis development. Oxidised LDLs might recruit monocytes and favour their transformation into foam cells through a receptor-mediated intake (scavenger pathway). Moreover oxidised LDLs show cytotoxic potential which is probably responsible for endothelial cell damage and macrophage degeneration in the atherosclerotic human plaque. Following the oxidation hypothesis of atherosclerosis the role of natural antioxidants, i.e. Vitamin C, Vitamin E and carotenoids, has been investigated in a large number of epidemiological, clinical and experimental studies. Animal studies indicate that dietary antioxidants may reduce atherosclerosis progression, and observational data in humans suggest that antioxidant vitamin ingestion is associated with reduced cardiovascular disease, but the results of randomised controlled trials are mainly disappointing. It has been suggested that natural antioxidants may be effective only in selected subgroups of patients with high levels of oxidative stress or depletion of natural antioxidant defence systems. The favourable effects shown by some studies relating antioxidant dietary intake and cardiovascular disease, may have been exerted by other chemicals present in foods. Flavonoids are the ideal candidates, since they are plentiful in foods containing antioxidant vitamins (i.e. fruits and vegetables) and are potent antioxidants. Tea and wine, rich in flavonoids, seem to have beneficial effects on multiple mechanisms involved in atherosclerosis. Future studies should probably select patients in a context of high-oxidative stress / low-antioxidant defence, to verify if antioxidants may really prove useful as therapeutic anti-atherosclerotic agents.

Animals↗
PubMed2003

Clinical and biochemical characterisation of patients with autosomal recessive hypercholesterolemia (ARH).

BACKGROUND AND AIM: Inherited hypercholesterolemias are common disorders characterised by elevated LDL-C levels and premature coronary heart disease. We have recently described a recessive form of hypercholesterolemia (autosomal recessive hypercholesterolemia, ARH) in which LDL catabolism is reduced because of a mutation in the gene coding for an adaptor protein that impairs LDL-receptor (LDL-R) activity in the liver. The aim of this study was to characterise in detail the phenotypes of subjects with homozygous and heterozygous ARH. METHODS AND RESULTS: We have so far identified six Italian families with ARH and studied the clinical and biochemical characteristics of 11 homozygotes (age 13-47 years) and 12 obligate heterozygotes (age 42-83 years). The study protocol included an evaluation of the lipoprotein profile, LDL-R activity in fibroblasts, LDL binding activity, and apo E genotype; a structured questionnaire (CHD risk factors, medical history, current medications); a physical examination, resting and stress ECG, ultrasound examinations (heart, carotid arteries, Achilles tendons) and coronary angiography. The pedigrees were characterised by the absence of vertical transmission; consanguinity was documented in two families. Only the two previously described Sardinian mutations, ARH1 (c.432insA) and ARH2 (c.65G > A), were identified in the probands. All of the ARH homozygotes had large tendinous xanthomas, two had exertional angina, and four a positive stress ECG. None had experienced myocardial infarction or stroke. More than half had instrumental signs of atherosclerosis such as a positive stress ECG or positive carotid echo-doppler examination. The ARH heterozygotes were consistently normal and had a normal lipid profile. CONCLUSIONS: The ARH phenotype resembles that of familial hypercholesterolemia (FH) homozygotes, but ARH may be a less serious illness. The absence of vertical transmission, and the presence of mild coronary heart disease and consanguinity, can suggest a possible diagnosis of ARH. ARH might be considered a phenocopy of FH but heterozygous subjects seem to have a consistently normal phenotype.

Adolescent↗
PubMed2001

Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein.

Atherogenic low density lipoproteins are cleared from the circulation by hepatic low density lipoprotein receptors (LDLR). Two inherited forms of hypercholesterolemia result from loss of LDLR activity: autosomal dominant familial hypercholesterolemia (FH), caused by mutations in the LDLR gene, and autosomal recessive hypercholesterolemia (ARH), of unknown etiology. Here we map the ARH locus to an approximately 1-centimorgan interval on chromosome 1p35 and identify six mutations in a gene encoding a putative adaptor protein (ARH). ARH contains a phosphotyrosine binding (PTB) domain, which in other proteins binds NPXY motifs in the cytoplasmic tails of cell-surface receptors, including the LDLR. ARH appears to have a tissue-specific role in LDLR function, as it is required in liver but not in fibroblasts.

Adolescent↗
PubMed2001

Predictors of two-year mortality in older nursing home residents. The IRA study. Istituto di Riposo per Anziani.

Besides functional impairment, several factors have been associated with mortality in institutionalized older subjects, including advanced age, gender, comorbidity, and malnutrition. We investigated the possible association of a large number of factors, including functional, anthropometric, nutritional, metabolic, clinical, and demographic variables, with two-year all-cause mortality in a sample of 344 institutionalized older subjects (> or = 65 years) without evidence of acute illness at the time of observation. Although a number of factors were associated with mortality risk, multivariate analysis showed that only severe disability (6 vs 0-1 lost ADL, O.R.: 3.37, C.I. 95%: 1.76-7.3) and low albumin levels (lowest vs highest tertile: O.R.: 3.0, C.I. 95%: 1.65-5.43) were independent predictors of outcome. Moreover, in the analysis stratified for degree of disability and albumin tertiles, we found a strong gradient in mortality risk with increasing disability and decreasing albumin levels. These results further support the value of these two simple parameters in identifying frail institutionalized older individuals.

Aged↗
PubMed2001

Genetic polymorphisms in older subjects with vascular or Alzheimer's dementia.

OBJECTIVES: Paraoxonase, angiotensin-converting enzyme (ACE), methylenetetrahydrofolate reductase (MTHFR), and apo E gene polymorphisms were evaluated in older patients with vascular dementia (VD) or late-onset Alzheimer's disease (LOAD). MATERIAL AND METHODS: Sixty patients with VD, 45 patients with LOAD, and 54 non-demented controls were compared. RESULTS: No differences in the distribution of paraoxonase, ACE, and MTHFR polymorphisms were found. The overall frequency of apo E epsilon4 allele was "low"; epsilon4 allele was more frequent in LOAD (17.5%) and VD (13.3%) compared with controls (9.2%), but the difference was not statistically significant. CONCLUSION: Paraoxonase, ACE, and MTHFR polymorphisms were not associated with VD or LOAD; these common polymorphisms might have a marginal role in the pathogenesis of dementia in older subjects. In spite of a "low" frequency of the apo E epsilon4 allele in our sample, the frequency of epsilon4 allele was about double in LOAD compared with controls.

Age of Onset↗
PubMed2001

Vitamin E and lipid peroxide plasma levels predict the risk of cardiovascular events in a group of healthy very old people.

OBJECTIVES: To assess whether systemic oxidative stress can predict the risk of first myocardial infarction, ischemic stroke, and congestive heart failure. DESIGN: A longitudinal study started in 1992 and completed in 1997. SETTING: Community-based, outpatient. PARTICIPANTS: 102 apparently healthy, community-dwelling subjects age 80 and older from the Vibrata valley, Teramo, Italy. MEASUREMENTS: Plasma vitamin E, beta-carotene, vitamin C, fluorescent products of lipid peroxidation (FPLPs), and serum lipids were determined at enrollment. RESULTS: Thirty-two cardiovascular events were recorded in 47.4 months of follow-up. The subjects with vitamin E levels in the highest quartile had a risk of cardiovascular events one-sixth those with vitamin E levels in the lowest quartile (relative risk (RR) = 0.16; 95% confidence interval (CI) = 0.04-0.55). The subjects with FPLPs in the highest quartile had a risk seven times greater than those with FPLPs in the lowest quartile (RR = 7.61; 95% CI = 2.23-25.96). No association was observed for vitamin C, beta-carotene, or total cholesterol. Multivariate adjustment for known risk factors did not significantly change the results. CONCLUSIONS: Our results suggest that in apparently healthy, community-dwelling very old subjects, base-line plasma concentration of vitamin E and FPLPs predicts the risk of future cardiovascular events. We confirm previous data showing that total cholesterol is not a predictor of cardiovascular disease in people age 80 and older.

Age Distribution↗
PubMed2001

High vitamin E plasma levels and low low-density lipoprotein oxidation are associated with the absence of atherosclerosis in octogenarians.

OBJECTIVES: To identify the biological characteristics of older subjects with vascular successful aging (VASA), defined as the absence of instrumental signs and clinical symptoms of atherosclerosis in the extracoronary and coronary vessels. DESIGN: A cross-sectional study. SETTING: A university-affiliated outpatient clinic. PARTICIPANTS: Sixty older subjects (30 with VASA and 30 controls with moderate carotid atherosclerosis (AG group)) from a sample of 705 subjects age 75 and older consecutively screened. MEASUREMENTS: Clinical examination; ultrasonographic examination of carotid, vertebral, abdominal aortic, iliac, and femoral arteries; electrocardiogram; and laboratory evaluation (lipid profile, lipophilic antioxidants, and markers of low-density lipoprotein (LDL) oxidation). RESULTS: Compared with controls, there were more females in the VASA group (82% vs 50%, P <.01), and fewer previous smokers (20.5% vs 52.5%, P <.01). Vitamin E/total cholesterol levels both in plasma (4.81 vs 3.51 micromol/mmol, P <.001) and in isolated LDLs (2.71 vs 1.86 microg/mg LDL cholesterol (LDL-C), P <.01), were higher in the VASA group, as was the resistance of LDLs to in vitro oxidation (as indicated by a longer duration of the lag phase: 80.2 vs 65.6 minutes, P <.001). The level of fluorescent products of lipid peroxidation (FPLPs) in native LDLs was lower in the VASA group (13.5 vs 18.8 URF/mg LDL-C, P <.001). Multivariate logistic regression analysis showed that only plasma vitamin E level (odds ratio (OR) = 6.04, 95% confidence interval (CI) = 1.48-24.63) and FPLPs in LDLs (OR = 0.53, 95% CI = 0.31-0.91) were independently associated with VASA. CONCLUSIONS: These results suggest that an appropriate level of vitamin E and a low level of LDL oxidation might be important for reaching advanced age without developing atherosclerosis.

Aged↗
PubMed2001

Nutritional parameters, body composition, and progression of disability in older disabled residents living in nursing homes.

BACKGROUND: The evaluation of nutritional status is one of the primary components of multidimensional geriatric assessment. We investigated the relationship between some markers of malnutrition and the modifications in functional status in a sample of older disabled residents living in nursing homes. METHODS: Ninety-eight subjects who were independent in at least two activities of daily living (ADLs) were enrolled in a 2-year longitudinal study. Anthropometric, nutritional, and metabolic parameters, as well as body composition, were measured at baseline and after 2 years. RESULTS: Deteriorating functional status (> or =2 additional lost ADLs) was associated with baseline albumin levels (Tertile 3 vs Tertile 1; odds ratio [OR] 0.16, 95% confidence interval [CI] 0.04-0.67) and subscapular skinfold thickness (Tertile 3 vs. Tertile 1; OR 0.06, 95% CI 0.006-0.50). After multivariate adjustment, the OR for increasing disability was >4 in subjects with decreasing body cell mass (BCM), compared with subjects with a stable BCM. The degree of BCM reduction was strongly related to the number of additional ADLs lost at follow-up (test for trend, p = .003). CONCLUSIONS: In a sample of older disabled nursing home residents, signs of malnutrition seem to predict further worsening in functional status. Furthermore, BCM declines proportionally to the loss in ADLs, suggesting the existence of a strong relationship between BCM loss and the progressive deterioration of functional status.

Activities of Daily Living↗
PubMed2001

Lipoprotein profile in older patients with vascular dementia and Alzheimer's disease.

BACKGROUND: Some alterations of the lipoprotein profile have been associated with cerebrovascular disease. Recently, it has been suggested that cerebrovascular disease might play a role in the pathogenesis of both vascular dementia (VD) and Alzheimer's disease (AD). Nevertheless, the possible association of dyslipidemias with VD or AD is still a controversial issue. METHODS: We investigated the lipoprotein profile in 100 older patients with vascular dementia (VD; no degrees: 60) or Late Onset Alzheimer's Disease (LOAD; no degrees: 40). The patients were compared with 54 community dwelling non-demented older controls. RESULTS: After adjustment for functional status, blood sedimentation rate, and serum albumin levels, no differences in lipoprotein profile emerged between the three groups, with the exception of HDL-C that was lower in VD compared with controls. Low HDL-C (< 45 mg/dL) was associated with VD (O.R.: 6.52, C.I. 95%: 1.42-30.70 vs controls, and 4.31, C.I. 95%: 0.93-19.82 vs LOAD), after multivariate adjustment. No differences in plasma lipid levels emerged between the three groups after stratification for apo E4 genotype. CONCLUSIONS: In this cross-sectional study low HDL-C levels are associated with VD, but not with LOAD, in a sample of older subjects.

Journal Article↗
PubMed2001

Cystocerebral syndrome: a case report and literature review.

Delirium is a frequent cause of hospitalization in the elderly patient, and can be sustained by several factors, which are not always evident. In 1990 Blackburn and Dunn described a clinical picture characterized by the presence of acute urinary retention presenting as delirium, and named it "cystocerebral syndrome". In 1991 Liem and Carter advanced a possible pathophysiological explanation for this phenomenon, suggesting that adrenergic tension might increase in the central nervous system when micturition cannot occur at the usual threshold. The consequent increase in catecholamines level might produce delirium. We report the case of a very old subject with delirium and acute urinary retention, suggestive of the "cystocerebral syndrome", in order to call the attention of geriatricians to acute urinary retention as a possible precipitating factor of delirium.

Acute Disease↗
PubMed2001

White blood cell count is associated with some features of metabolic syndrome in a very old population.

BACKGROUND AND AIMS: Although the association between white blood cell (WBC) counts and the risk of cardiovascular disease has been repeatedly described, its biological mechanism is still unclear. A significant correlation has been demonstrated in adults between WBC counts and some risk factors for coronary heart disease (CHD), including insulin resistance. The aims of this study were: 1) to investigate the association between WBC count and some risk factors for atherosclerosis in a sample of octo-nonagenarians; and 2) to test the hypothesis of an association between WBC count and "metabolic syndrome", a clinical condition mediated by insulin resistance. METHODS AND RESULTS: The study involved 160 free-living healthy octo-nonagenarians participating in the Val Vibrata Aging Project, whose WBC count, and anthropometric and metabolic parameters were measured using standardised methods. WBC count correlated positively with the logarithm of triglyceride, apoprotein B and glucose levels, and negatively with high-density lipoprotein cholesterol: the subjects with low high-density lipoprotein and high triglyceride levels had higher WBC count than normal subjects. The WBC count were significantly higher in the subjects with four or more of six features of metabolic syndrome than in those with three or less. CONCLUSIONS: The results of this study support the existence of a significant association between WBC count and some of the typical features of metabolic syndrome in very old subjects.

Aged↗
PubMed2000

Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production : key role of L-arginine availability.

BACKGROUND: Native and oxidized LDLs (n-LDL and ox-LDL) are involved in the atherogenic process and affect endothelium-dependent vascular tone through their interaction with nitric oxide (NO). METHODS AND RESULTS: In this study we evaluated directly, by using a porphyrinic microsensor, the effect of increasing lipoprotein concentrations on endothelial NO and superoxide (O(2)(-)) production. We investigated where lipoproteins may affect the L-arginine-NO pathway by pretreating cells with L-arginine, L-N-arginine methyl ester (L-NAME), and superoxide dismutase. Bovine aortic endothelial cells were exposed for 1 hour to increasing concentrations of n-LDL (from 0 to 240 mg cholesterol/dL) and ox-LDL (from 0 to 140 mg cholesterol/dL). A stimulated (calcium ionophore) NO concentration decreased to 29% of the control at n-LDL concentration of 80 mg cholesterol/dL and to 15% of the control at 20 mg cholesterol/dL of ox-LDL. L-Arginine partially neutralized the inhibitory effect of n-LDL and ox-LDL on the NO generation. Superoxide dismutase pretreatment did not modify NO production, whereas L-NAME blunted NO generation at all LDL concentrations. O(2)(-) production was increased at low n-LDL and very low ox-LDL concentrations; this was reversed by L-arginine. CONCLUSIONS: These findings confirm the inhibitory role of n-LDL and ox-LDL on NO generation and suggest that lipoproteins may induce a decreased uptake of L-arginine. The local depletion of the L-arginine substrate may derange the NO synthase, leading to overproduction of O(2)(-) from oxygen, the other substrate of NO synthase.

Animals↗
PubMed2000

Benzodiazepines with different half-life and falling in a hospitalized population: The GIFA study. Gruppo Italiano di Farmacovigilanza nell'Anziano.

In recent years, the use of benzodiazepines has been recognized as an independent risk factor for falls among the elderly. To evaluate the role of different types of benzodiazepines in determining falls in a hospitalized geriatric population, we conducted a prospective study among 7908 patients consecutively admitted in 58 clinical centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA), during an 8-month observation period (1991 and 1993). Over 70% of the patients were older than 65 years, 50% were women, and 23. 6% had a benzodiazepine prescription during hospital stay. The number of patients who experienced one or more falls during follow-up was 174 (2.2%). Sixty falls occurred among patients taking benzodiazepines (3.2%) and 114 (1.9%) among those who did not use benzodiazepines; the crude odds ratio for users versus non-users was 1.7 (95% CI 1.2-2.3). Multivariate logistic regression analysis showed that benzodiazepines with very short (OR 1.9; CI 1.03-3.3) and short half-life (OR 1.8; CI 1.2-2.8) were positively associated with falls during hospital stay. Patients who used other psychotropic agents (OR 2.3; CI 1.7-3.4), antidiabetic agents (OR 1. 5; CI 1.03-2.2), patients with presence of cognitive impairment (OR 1.6; CI 1.08-2.3), high level of comorbidity (OR 1.7; CI 1.05-2.9), more advanced age (>80 years, OR 2.7; CI 1.5-4.7) and those who stayed in the hospital for 17 days or more (OR 2.1; CI 1.4-3.3) were also at a greater risk. These findings suggest that benzodiazepines with short and very short half-life are an important and independent risk factor for falls and their prescription to elderly hospitalized patients should be carefully evaluated.

Accidental Falls↗
PubMed2000

A new locus for autosomal recessive hypercholesterolemia maps to human chromosome 15q25-q26.

High serum cholesterol is an established risk factor for cardiovascular disease and is the prime target for therapeutic intervention in large groups of patients. The development of modern treatments for this major risk factor was propelled by the early realization that forms of severe hypercholesterolemia could be caused by dominantly inherited defects in the LDL receptor or in the APOB gene. Further understanding of the mechanisms contributing to early atherosclerosis will allow for new targets for therapy. We therefore identified and investigated the genetics of families from Sardinia that have recessive inheritance of precocious hypercholesterolemia. We used five families in an analysis of linkage of the autosomal recessive hypercholesterolemia locus, termed "ARH1," to chromosome 15q25-q26. A genomewide search mapped the disease-causing gene with a LOD score of 3.3 and excluded major contributions to the phenotype of other genes. A candidate gene present in the mapped chromosome region-the ligand-activated liver-transcription-factor gene ARP1 (apolipoprotein regulatory-protein gene)-has been excluded after DNA sequencing. The close-bred nature of the Sardinian population offers unique opportunities for isolation of this hypercholesterolemia-causing gene.

Adolescent↗