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Biomedical subjects

Gaetano Crepaldi

Publications and source records attributed to Gaetano Crepaldi.

At least 19 recordsLinked to original sources

The effect of age, weight, and lifestyle factors on calcaneal quantitative ultrasound: the ESOPO study.

Quantitative ultrasound (QUS) techniques have been shown to be as good as bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), in predicting fracture risk: QUS technique could increase substantially the accessibility to a reliable bone osteoporosis risk evaluation, but little is know regarding the relationship of QUS to risk factors that have been found to predict DXA-BMD values and this is even more true in men. We studied 6,811 postmenopausal women 40 to 80 years of age and 4,981 men 60-80 years of age representative of the general population of all regions of Italy. All participants were questioned on lifestyle habits and on their medical history. After a physical examination "bone stiffness" (called here for simplicity, stiffness), which is derived from the values of broadband ultrasound attenuation (BUA) and speed of sounds (SoS) was measured by a heel QUS device (Achilles apparatus, Lunar, Madison, USA). The most common recognized determinants of bone mass (either categorical or continuous variables) were modeled with stiffness by multiple regression analysis or ANOVA. Stiffness was strongly related to age and weight. After adjusting for these variables, the women who had taken hormone replacement therapy for more than a year had significantly higher stiffness values. The difference versus nonusers remained significant for up to 20 years-since-menopause (YSM). This effect was so strong that for further analysis these women were excluded. By multivariate analysis, stiffness was then found to be significantly related to recalled body weight at 25 years of age, actual and past cigarettes smoked per day, and dairy calcium intake. Stiffness was also associated with a number of categorial factors adjusted for age, weight, and YSM: prior ovariectomy, history of more than 2 months confined to bed, outdoor physical activity, smoking, chronic use of any drug, and past corticosteroid use. All these categorial and continuous variables predicted stiffness equally in men and women. In conclusion, QUS bone measurements discriminate postmenopausal women according to past use of hormone replacement therapy. Risk factors usually associated to BMD as measured by DXA are also associated to calcaneal bone stiffness as measured by QUS, and most risk factors for osteoporosis usually observed in women are equally applicable to men.

Adrenal Cortex Hormones↗

Cognitive functions are not affected by dietary fatty acids in elderly subjects in the Pro.V.A. study population.

BACKGROUND AND AIMS: Environmental, life-style, and dietary factors, including the type of dietary fatty acids consumed, may influence the onset of dementia. The aim of the present study was therefore to examine whether type of dietary fats consumed is associated with cognitive performance. METHODS: Using gaschromatography, plasma phospholipid fatty acid composition was determined in a sample of subjects (age > or = 65 years) randomly selected from the general Pro.V.A. study population. Plasma phospholipid fatty acid composition is a reliable marker of the type of fats present in the diet. The subjects' cognitive capacity was tested using the Mini-Mental State Examination (MMSE). RESULTS: At multiple regression analysis, the MMSE score variance was correlated with age and education level In 30% of cases, whereas the other variables considered (including type of fatty acids consumed) had an almost negligible effect. CONCLUSIONS: In free-living elderly subjects, moderate to severe cognitive impairment is not associated with dietary fatty acids.

Aged↗

Injectable bisphosphonates in the treatment of postmenopausal osteoporosis.

Osteoporosis is a "silent" disease and the patient has usually no clue of it until the occurrence of a fragility fracture. Prevention requires a continuous daily treatment that could be uncomfortable to the patient. Besides the recently introduced weekly oral schedules, injectable bisphosphonates have often been used as an off-label option to ameliorate compliance. In general, although with different efficiency, almost all injectable bisphosphonates can improve bone mineral density and suppress bone resorption markers. The effect of intravenous infusions of bisphosphonates are, to a large extent, similar to equivalent intramuscular administrations, but doses and dosing intervals represent the critical issues. Pain at the injection site and acute phase reactions are relatively common to intramuscular clodronate and intravenous infusions of nitrogen-containing bisphosphonates, respectively. Under certain circumstances, intermittent treatment with injectable bisphosphonates might represent a feasible alternative when compliance is at risk.

Anti-Inflammatory Agents↗

Predicting mortality in older patients. The VELCA Study.

BACKGROUND AND AIMS: Mortality at older age, during and after hospitalization, can be determined by several factors, beyond the direct cause for hospital admission, which are not yet fully understood. The aim of this study was to assess predictors of inpatient mortality and one-year mortality in older Italians, hospitalized for dementia, heart failure, chronic obstructive pulmonary disease, stroke, hip fracture and myocardial infarction at the Verona Teaching Hospital, Northern Italy. METHODS: At admission, 429 patients aged 65 years and older reported information on: sociodemographic characteristics, Barthel index at admission and two weeks before, and severity of investigated diagnosis; at discharge: diagnosis, comorbid conditions, complications from hospital records, drug therapy, and Barthel index. One year after discharge, an ad hoc questionnaire for those subjects found to have died on phone contact was administered to a proxy to collect data on new hospital admissions, onset of new conditions, need for formal care, a short version of the Barthel index one month before death, and the place of death. RESULTS: Sex and specific diseases at admission were not significant predictors of inpatients, nor was one-year mortality in this cohort, whereas the presence of any comorbid conditions doubled the risk of mortality at one year compared with patients without comorbidity. Those patients who had moderate to severe/total dependency in ADL at admission were three times more likely to have died at discharge than those who were independent. The same risk for mortality at one-year follow-up was found in those patients who were severely or totally dependent at preadmission, at admission, or at discharge. CONCLUSIONS: Functional status and comorbidity are key risk factors for mortality in the elderly. Therefore, multidimensional assessment, including functional status prior to hospitalization should always be assessed, and should be considered a relevant predictor of short- and long-term outcomes.

Activities of Daily Living↗

Hepatic lipase: a marker for cardiovascular disease risk and response to therapy.

PURPOSE OF REVIEW: Hepatic lipase plays a key role in the metabolism of pro-atherogenic and anti-atherogenic lipoproteins affecting their plasma level as well as their physico-chemical properties. However, controversial evidence exists concerning whether hepatic lipase is pro or anti-atherogenic. The goal of this review is to summarize recent evidence that connects the enzyme to cardiovascular disease. The potential impact of genetic determinants of hepatic lipase activity in modulating both the development of coronary and carotid atherosclerosis will be discussed based on hepatic lipase proposed roles in lipoprotein metabolism. RECENT FINDINGS: Twenty to 30% of individual variation of hepatic lipase activity is accounted for by the presence of a common polymorphism in the promoter region (-514 C to T) of the hepatic lipase gene (LIPC). This polymorphism, via its impact on hepatic lipase synthesis and activity, appears to contribute to (1) individual susceptibility to cardiovascular disease: the presence of the T allele (low hepatic lipase activity) may carry a marginally increased risk of atherosclerosis; (2) carotid plaque composition and individual susceptibility to cerebrovascular events: the presence of the C allele (high hepatic lipase activity) is associated with increased carotid intima-media thickness and abundance of macrophages in the carotid plaque (unstable plaque); and (3) response of cardiovascular disease patients to lipid-lowering therapy: patients with the CC genotype have the greatest clinical benefit from intensive lipid-lowering therapy. SUMMARY: Convincing evidence shows that hepatic lipase plays a key role in remnant lipoprotein catabolism as well as in remodeling of LDL and HDL particles. The anti or pro-atherogenic role of hepatic lipase is likely to be modulated by the concurrent presence of other lipid abnormalities (i.e. increased LDL cholesterol levels) as well as by the genetic regulation of other enzymes involved in lipoprotein metabolism. Characterization of patients by their LIPC genotype will contribute to a better definition of individual risk of coronary and cerebrovascular events, specifically in patients with qualitative (small, atherogenic LDL and low HDL2 cholesterol) rather than quantitative lipid abnormalities for whom the routine lipid profile may underestimate the risk of coronary and cerebrovascular disease.

Animals↗

Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis.

OBJECTIVE AND DESIGN: The prevalence and the effects of hypercalciuria on bone in patients with primary osteoporosis are poorly defined. We therefore retrospectively analyzed the data of 241 otherwise healthy women. They were 45-88 years of age and had been referred for their first visit to our Unit for Metabolic Bone Diseases over a 2-year period because of primary osteoporosis (bone density T-score < -2.5). METHODS: The main parameters of calcium and skeletal metabolism had been analyzed in all subjects. This population was then divided into two groups, according to the presence (HC+) or absence (HC-) of hypercalciuria. RESULTS: Elevated urinary calcium was present in 19% of the subjects. Due to the selection criteria, spinal and femoral bone loss was similar in the two groups. Urinary calcium, phosphate and fractional calcium excretion were higher in hypercalciuric patients. In a logistic regression model, the higher the Tm of phosphate, the lower the risk of hypercalciuria (odds ratio 0.33, confidence interval 0.18-0.62). On the contrary, hypercalciuria was the most important predictor of low bone mass in HC+ (accounting for more than 50% of the variance in spinal bone density). CONCLUSIONS: Hypercalciuria is a common feature in postmenopausal bone loss. Since increased urinary calcium excretion and low bone mass appear to be linked, hypercalciuria seems to be an important determinant of reduced bone density in this setting as well.

Absorptiometry, Photon↗

Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes.

Podocyte structural changes have been suggested to be involved in the pathogenesis of albuminuria in diabetes. We evaluated podocytes density, number, and structure in 67 white patients with type 2 diabetes: 21 normoalbuminuric (NA), 23 microalbuminuric (MA), and 23 proteinuric (P). Kidney function and biopsy studies were performed; 20 kidney donors served as control subjects. Electron microscopic morphometric analysis was used to estimate numerical density of podocytes per glomerulus [Nv(epi/glom)], filtration slit length density per glomerulus (FSLv/glom), and foot process width (FPW). The number of podocytes per glomerulus (Epi N/glom) was obtained by multiplying Nv(epi/glom) by mean glomerular volume. Nv(epi/glom) was significantly decreased in all type 2 diabetic groups compared with control subjects and was lower in MA and P than in NA (P < 0.0001, ANOVA). Epi N/glom was lower in MA and P patients compared with control subjects (P < 0.002, ANOVA); however, there were no significant differences among the type 2 diabetic groups. In addition, MA and P had decreased FSLv/glom and increased FPW compared with NA (P < 0.005 for both, ANOVA). The albumin excretion rate was inversely related to Nv(epi/glom) and FSLv/glom and directly to FPW (P < 0.0005 for all), whereas there was no correlation with Epi N/glom. In conclusion, changes in podocyte structure and density occur since the early stages of diabetic nephropathy and might contribute to increasing albuminuria in type 2 diabetic patients. These findings also suggest that in white type 2 diabetic patients, the density of podocytes may be functionally more relevant than the absolute number.

Aged↗

Association between the --514 C-->T polymorphism of the hepatic lipase gene promoter and unstable carotid plaque in patients with severe carotid artery stenosis.

OBJECTIVE: We investigated the potential association between -514 C-->T polymorphism in the promoter of the hepatic lipase gene (LIPC) and the prevalence of inflammatory cells in the plaque of patients with severe carotid artery stenosis. BACKGROUND: This common LIPC polymorphism has been related to the presence of an atherogenic lipoprotein pattern. METHODS: We studied 68 consecutive patients undergoing carotid endarterectomy. The LIPC genotype was determined by polymerase chain reaction. Endarterectomy specimens were examined by immunocytochemistry using monoclonal antibodies for smooth muscle cells, macrophages, or lymphocytes. RESULTS: In 50 of 68 patients who had evidence of previous ipsilateral ischemic events, 36 (72%) were carriers of the CC genotype, whereas only 14 (28%) were carriers of the CT/TT genotype (p = 0.002). Among the 18 patients without evidence of events, the two genotypes were equally distributed (9 vs. 9). The low-density lipoprotein (LDL) particles were denser in CC than in CT/TT genotype carriers (flotation rate: 0.315 +/- 0.025 vs. 0.356 +/- 0.019, p < 0.0005). The CC genotype was associated with an abundance of macrophages (6.7 +/- 3.5 vs. 2.1 +/- 2.1 cells/area unit in the CT/TT group, p < 0.0005) and a reduced number of smooth muscle cells (6.9 +/- 6.2 vs. 14.5 +/- 6.4 in the CT/TT group, p < 0.0005) in the plaque. An inverse relationship was found between LDL buoyancy and the number of macrophages in the plaque (r = -0.639, p < 0.0005). CONCLUSION: We provide evidence, for the first time, that LIPC promoter -514 C-->T polymorphism, by modulating LDL density, significantly affects the number of macrophages in the plaque and possibly affects the occurrence of cerebrovascular events in patients with carotid artery stenosis.

Aged↗

The fatty acid composition of plasma phospholipids and the insulin sensitivity in elderly diabetic patients. The Pro.V.A. study.

BACKGROUND AND AIMS: The prevalence of diabetes is increasing worldwide indicating that life-style habits are important determinants for this disease. The aim of this study was to examine the effects of dietary fats on insulin sensitivity in diabetic patients. METHODS: In a randomly selected sample of population aged 65 and older, plasma phospholipid fatty acid composition was determined by gaschromatography. The plasma phospholipid fatty acid composition is a reliable marker of the type of fats present in the diet. Insulin resistance was estimated with the Homeostasis Model Assessment (HOMA). RESULTS: Body weight, height, body mass index (BMI), waist circumference, serum cholesterol as well as fasting insulin, and the HOMA index were lower in the older groups. With increasing age, there was an increase in the monounsaturated fatty acid content and a decrease in the polyunsaturated and n-6 polyunsaturated fatty acids. In the linear regression analysis, saturated fatty acids were significantly related to waist circumference, fasting glucose, fasting insulin, and HOMA. Significant relations were also obserued between HOMA and BMI, triglycerides, waist circumference, and age. Triglycerides and HDL cholesterol were strongly interrelated as well as BMI and waist circumference. In the multiple regression analysis including age, BMI, waist circumference, triglycerides, HDL cholesterol, and saturated fatty acids, the HOMA index was predicted significantly only by age, BMI, and triglycerides. This model explained 28% of the HOMA variance. CONCLUSIONS: In elderly diabetic patients insulin sensitivity is modulated by age, BMI, and triglycerides, but the type of dietary fats is not independently associated with insulin sensitivity.

Age Factors↗

The effect of cardiovascular and osteoarticular diseases on disability in older Italian men and women: rationale, design, and sample characteristics of the Progetto Veneto Anziani (PRO.V.A.) study.

OBJECTIVES: Describe the methodology and preliminary results of the Progetto Veneto Anziani (PRO.V.A.) Study, an observational study of the Italian population aged 65 and older DESIGN: Cross-sectional cohort observation. SETTING: Northern Italy. PARTICIPANTS: Italians aged 65 and older, living in both the community and nursing homes. MEASUREMENTS: At baseline, participants were interviewed at their homes and subsequently examined by nurses and physicians at the two study clinics using an extensive battery of clinical, instrumental, biochemical, and physical performance tests. Hand, knee, hip, and chest x-rays and bone densitometry were performed in 92% of the participants, and 99% of the participants consented to blood drawing and deoxyribonucleic acid analyses. The physician who performed the physical examination determined disease presence based on several components of the interview and examination. A further, comprehensive determination was performed with standardized algorithms using all the information collected on each participant, including hospital records surveillance, standardized x-ray readings, and blood assays. In one of the study sites, a brain magnetic resonance imaging was performed in a subsample of the participants (820 persons). RESULTS: Overall response rate to the baseline clinic visit was 77% for men and 64% for women. Co-presence of at least one cardiovascular disease (CVD) and at least one osteoarticular disease (OAD) was identified in 10%, 22%, and 29% of men and 9%, 24%, and 40% of women aged 65 to 74, 75 to 84, and 85 and older, respectively. Overall, the mean number of coexisting chronic conditions was 1.8 for men and 2.4 for women. CONCLUSIONS: The PRO.V.A. study has the potential to provide an original contribution to clarify the mechanisms whereby diseases cause disability in older men and women; the particular focus on CVD and OADs will make it possible to comprehensively evaluate the development of disability as it relates to these two important conditions.

Aged↗

Prevalence rate and correlates of depressive symptoms in older individuals: the Veneto Study.

BACKGROUND: Depressive symptoms (DS) are very common in elders, particularly among women, and their prevalence rates vary widely across countries. METHODS: A random sample of noninstitutionalized men (n = 867) and women (n = 1531), aged 65 years and older, from the Veneto region, northeastern Italy, were interviewed and participated in a brief physical examination in their homes. The prevalence rates of DS and the associated physical, social, and psychological factors were analyzed. RESULTS: The overall prevalence rate of DS was 58% in women and 34% in men (p <.0001), but there was no significant trend with age. Women were at higher risk of DS (OR = 1.63) than men, even after adjusting for traditional risk factors, such as fair-poor self-rated health, sleep disturbances and use of sleep medications, lack of support from social and family network, and physical and cognitive impairment. CONCLUSIONS: This study provides evidence that older women more frequently report DS than men, independently from the presence of traditional risk and associated factors. Cultural and lifestyle factors throughout life might explain this gender difference.

Aged↗

Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: the Di.N.A.S. randomized trial.

Diabetic nephropathy may be effectively prevented and treated by controlling glycemia and administering angiotensin-converting enzyme (ACE) inhibitors. However, strict metabolic control can be difficult, and ACE inhibitors may be poorly tolerated and only partially effective, particularly in diabetes mellitus type 2 (DM2), warranting the search for ancillary treatment. Sulodexide is a glycosaminoglycan, a new class of drug that has demonstrated nephroprotective activity in experimental investigations. The Di.N.A.S. study was a randomized, double-blind, placebo-controlled, multicenter, dose-range finding trial to evaluate the extent and duration of the hypoalbuminuric effect of oral sulodexide in diabetic patients. A total of 223 microalbuminuric and macroalbuminuric DM1 and DM2 patients with serum creatinine < or =150 micromol/L and stable BP and metabolic control were recruited. They were randomly allocated to one of four groups: 50 mg/d, 100 mg/d, or 200 mg/d sulodexide daily or placebo for 4 mo (T0 to T4), with 4 mo of follow-up after drug suspension (T4 to T8). Treatment with 200 mg/d sulodexide for 4 mo significantly reduced log albumin excretion rate (logAER) from 5.25 +/- 0.18 at T0 to 3.98 +/- 0.11 at T4 (P < 0.05), which was maintained till T8 (4.11 +/- 0.13; P < 0.05 versus T0). Moreover, the sulodexide-induced percent reductions in AER at T4 were significantly different from the placebo value at T4 and approximately linear to dose increments (30% [confidence limits, 4 to 49%], P = 0.03; 49% [30 to 63%], P = 0.0001; and 74% [64 to 81%], P = 0.0001 in the sulodexide 50, 100, and 200 mg/d groups, respectively. At T8, the sulodexide 200 mg/d group maintained a 62% (45 to 73%) AER significant reduction versus placebo (P = 0.0001). Subanalysis by type of diabetes (DM1 versus DM2, microalbuminuric versus macroalbuminuric, or on concomitant ACE inhibitors versus not on ACE inhibitors) demonstrated similar findings. These effects were obtained without any significant variation in metabolic control and BP or serum creatinine. Very few adverse events were reported; none were serious. In conclusion, a 4-mo course of high doses of sulodexide significantly and dose-dependently improves albuminuria in DM1 and DM2 patients and micro- or macroalbuminuric patients with or without concomitant ACE inhibition. The effect on albuminuria is long-lasting and seemingly additive to the ACE inhibitory effect.

Administration, Oral↗

The effects of vitamin D receptor polymorphism on secondary hyperparathyroidism and bone density after renal transplantation.

Immunosuppresive treatment and secondary hyperparathyroidism (SHPT) are considered among the most important pathogenetic factors for postrenal transplant bone disease. The aim of this study was to investigate the relationships among vitamin D receptor (VDR) gene polymorphism, parathyroid hormone (PTH) levels, and bone density in renal transplant recipients. We enrolled 69 patients (47 men and 22 women; mean age, 47 +/- 11 years) who had undergone kidney transplantation 51 +/- 5 months before. All patients underwent an evaluation of the main biochemical parameters of bone metabolism as well as bone densitometry. VDR alleles were typed by a polymerase chain reaction (PCR) assay based on a polymorphic BsmI restriction site. When the patients were categorized according to the VDR genotype (BB, Bb, and bb), serum creatinine, and the cumulative doses of immunosuppressive drugs were similar across the groups. PTH levels higher than 80 pg/ml were found in 53.6% of the patients, with the highest values being detected in the bb VDR genotype (p < 0.05). PTH was significantly correlated to urinary type I collagen cross-linked N-telopeptide (NTx) values. Bone density was low in the whole population; however, spinal bone density was lower in the bb subgroup (p < 0.02). In the whole population, only PTH (p < 0.05) and body mass index (BMI; p < 0.01) were independent predictors of spinal bone density. When grouping the patients by the VDR gene polymorphism, only PTH continued to be an independent predictor of spinal bone density in the bb allele subgroup (R2 adj. = 0.17). We can conclude that the VDR genotype polymorphism affects bone density of renal transplant recipients via its effects on the severity of SHPT.

Absorptiometry, Photon↗

Nitric oxide modulation of renal and cardiac hemodynamics in type 2 diabetes.

OBJECTIVE: To evaluate endothelial function in type 2 diabetic patients with and without diabetic nephropathy. METHODS: We studied the effects of systemic infusion of the nitric oxide (NO) synthase inhibitor NG-monomethyl-l-arginine (L-NMMA) on cardiovascular and renal hemodynamics in six type 2 diabetic patients with microalbuminuria (D2-MA), six type 2 diabetic patients with normoalbuminuria (D2-NA) and five control subjects. Both type 2 diabetic patients and control subjects had mild arterial hypertension. RESULTS: L-NMMA infusion decreased the cardiac index in all groups. A reduction in glomerular filtration rate (GFR) and an increase in filtration fraction were observed only in controls. Renal plasma flow decreased in controls and D2-NA patients and renal vascular resistance increased in all groups. CONCLUSIONS: The effect of L-NMMA on cardiac output was similar in controls and type 2 diabetic patients with and without diabetic nephropathy. In contrast, the effect on GFR was impaired in both diabetic groups, suggesting that glomerular NO homeostasis is altered in type 2 diabetes. Moreover the discrepancy, in diabetic patients, between cardiac and renal effects during L-NMMA infusion suggests that the modulation of glomerular hemodynamics is independent from NO-regulated cardiac output.

Adult↗