PubMed Health⌕ Search

Biomedical subjects

Gaetano Crepaldi

Publications and source records attributed to Gaetano Crepaldi.

30 records · Page 2Linked to original sources

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↗

The angiotensin-converting enzyme DD genotype is associated with glomerulopathy lesions in type 2 diabetes.

Genetic factors are important in conferring diabetic nephropathy (DN) risk. The insertion/deletion (I/D) polymorphism of the ACE gene has been described to be associated with DN risk and progression. The renal lesions underlying DN in type 2 diabetes are heterogeneous; only a subset of patients, characterized by a faster decline of renal function, have diabetic glomerulopathy. This study explored the relations between diabetic glomerulopathy and the ACE genotype distribution in 77 type 2 diabetic patients with an albumin excretion rate > or = 20 microg/min. Using morphometric analysis of kidney biopsies, mesangial and mesangial matrix fractional volumes [Vv(mes/glom) and Vv(MM/glom)] and glomerular basement membrane (GBM) width were estimated. We found that 13 patients were II, 30 were ID, and 34 were DD. Clinical features and renal function were similar in the three groups; in contrast, the DD patients had the highest Vv(MM/glom) and GBM width. Subdividing patients in tertiles of GBM width and Vv(MM/glom), from the lowest (I) to the highest (III) values, the DD carriers had an odds ratio of 6.11 (95% CI 1.84-20.3) and 10.67 (2.51-45.36), respectively, for the likelihood of being in tertile III than I for GBM width and Vv(MM/glom). Multiple regression analysis revealed the I/D polymorphism as an independent determinant of GBM thickening in addition to diabetes duration and HbA(1c). In conclusion, the ACE DD genotype is associated with diabetic glomerulopathy lesions, making the study of this polymorphism helpful in identifying those type 2 diabetic patients at higher risk of fast DN progression.

Albuminuria↗

Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients.

The efficacy and safety of lipid-lowering agents in elderly individuals have not been extensively assessed. This population generally takes more drugs concurrently than middle-aged patients, and are therefore at higher risk of drug-drug interactions. This large-scale, randomized, double-blind, placebo-controlled study investigated the efficacy and safety of extended-release (XL) fluvastatin 80 mg once daily for up to 1 year in elderly patients with primary hypercholesterolemia. A total of 1229 patients (mean age, 75.5 years) were randomized. After 2 months of treatment, fluvastatin XL 80 mg significantly decreased plasma lipid levels from baseline compared with placebo; fluvastatin reduced total cholesterol by 25% compared with a decrease of 2.5% in the placebo group, low-density lipoprotein cholesterol was -33% vs. -2.5%, respectively, and triglycerides were -13.3% vs. 2.9%, respectively (p<0.00001). The safety profile of fluvastatin XL was similar to that of placebo. Fluvastatin XL 80 mg once daily was well tolerated and effectively managed plasma lipid profiles in a large cohort of elderly patients. These findings are consistent with data obtained previously in younger recipients of fluvastatin XL 80 mg, and reinforce the safety of fluvastatin in a population at high risk of drug-drug interactions.

Aged↗