Gianfranco Salvioli

Cross-calibration of eight-polar bioelectrical impedance analysis versus dual-energy X-ray absorptiometry for the assessment of total and appendicular body composition in healthy subjects aged 21-82 years.

Aim: To calibrate eight-polar bioelectrical impedance analysis (BIA) against dual-energy X-ray absorptiometry (DXA) for the assessment of total and appendicular body composition in healthy adults. Research design: A cross-sectional study was carried out. Subjects: Sixty-eight females and 42 males aged 21-82 years participated in the study. Methods: Whole-body fat-free mass (FFM) and appendicular lean tissue mass (LTM) were measured by DXA; resistance ( R ) of arms, trunk and legs was measured by eight-polar BIA at frequencies of 5, 50, 250 and 500 kHz; whole-body resistance was calculated as the sum R of arms, trunk and legs. Results: The resistance index (RI), i.e. the height 2 /resistance ratio, was the best predictor of FFM and appendicular LTM. As compared with weight (Wt), RI at 500 kHz explained 35% more variance of FFM ( vs 0.57), 45% more variance of LTM arm ( vs 0.48) and 36% more variance of LTM leg ( vs 0.50) ( p < 0.0001 for all). The contribution of age to the unexplained variance of FFM and appendicular LTM was nil or negligible and the RI 2 sex interactions were either not significant or not important on practical grounds. The percent root mean square error of the estimate was 6% for FFM and 8% for LTM arm and LTM leg. Conclusion: Eight-polar BIA offers accurate estimates of total and appendicular body composition. The attractive hypothesis that eight-polar BIA is influenced minimally by age and sex should be tested on larger samples including younger individuals.

Diagnosis and Characteristics of Syncope in Older Patients Referred to Geriatric Departments

OBJECTIVES: To test the applicability and safety of a standardized diagnostic algorithm in geriatric departments and to define the prevalence of different causes of syncope in older patients.

Importance of serum anticholinergic activity in the assessment of elderly patients with delirium.

To evaluate the importance of serum anticholinergic activity (SAA) in elderly patients who developed delirium fol lowing hospital admission, we performed a cross-sectional study with consecutively referred inpatients in a university geriatric medical ward. Sixty-one patients aged 66 to 95 years (mean age: 79.2 ± 11.6; 54% females) were recruited. Delirium was assessed by means of the Confusion Assessment Method, SAA determination, questionnaire for cur rent drug treatment, past medical history and clinical examination, and blood chemistries. Patients were divided into two groups according to the absence (N = 49) or the presence (N = 12) of delirium. Delirious patients showed a significantly higher SAA (23.0 vs 3.9 pmol/mL atropine equivalents, P < .004); they were using antibiotics (P < .05), neuroleptics (P < .002), barbiturates (P < .004), and benzodiazepines (P < .005) more frequently. Subjects with delir ium were more likely to have infections and a lower Body Mass Index; they had higher plasma glucose and creatinine. The multivariate analysis identified SAA and use of neuroleptics, and benzodiazepines as the most important fea tures independently associated with delirium. SAA may be a suitable marker for identifying people at risk of developing delirium. Moreover, neuroleptics and benzodiazepines must be carefully used in the elderly because of their relationship with the onset of delirium. (J Geriatr Psychiatry Neurol 1999; 12:82-86).

Thymic output and functionality of the IL‐7/IL‐7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life

During aging, the thymus undergoes a marked involution that is responsible for profound changes in the T‐cell compartment. To investigate the capacity of the thymus to produce new cells at the limit of human lifespan, we analyzed some basic mechanisms responsible for the renewal and maintenance of peripheral T lymphocytes in 44 centenarians. Thymic functionality was analyzed by the quantification of cells presenting the T‐cell receptor rearrangement excision circles (TREC). A new method based upon real‐time PCR was used, and we found that most centenarians (84%) had undetectable levels of TREC+ cells. Six‐color cytofluorimetric analysis revealed that centenarians had an extremely low number of naïve T cells; central memory and effector memory T cells were greatly increased, while terminally differentiated cells were as numerous as in young (aged 20–45) or middle‐aged (aged 58–62) donors. Interleukin (IL)‐7 and IL‐7 receptor α‐chain (CD127) levels were the same at all ages, as shown by ELISA, flow cytometry and real‐time PCR. However, IL‐7 plasma levels were higher in centenarian females than males. The presence of TREC+ cells and of very few naïve T lymphocytes suggests that in centenarians such cells could either derive from residues of thymic lymphopoietic islets, or even represent long‐living lymphocytes that have not yet encountered their antigen. IL‐7 could be one of the components responsible, among others, for the higher probability of reaching extreme ages typical of females.

Hyperhomocysteinemia and Other Newly Recognized Inherited Coagulation Disorders (Factor V Leiden and Prothrombin Gene Mutation) in Patients with Idiopathic Cerebral Vein Thrombosis

Background: Idiopathic cerebral vein thrombosis (iCVT) represents approximately 30% of the cases of cerebral vein thrombosis (CVT). New, inherited – factor V Leiden (FVL) and prothrombin gene mutation (PTHRA20210) – and inherited/acquired – hyperhomocysteinemia (HHcy) – prothrombotic conditions have been detected recently. Methods: We assessed fasting plasma homocysteine (Hcy) levels and main Hcy determinants, FVL and PTHRA20210 in 30 patients with documented iCVT and 40 age- and sex-matched healthy subjects. Results: A strong and significant association of PTHRA20210 [30% (9/30) vs. 2.5% (1/40) iCVT vs. controls, respectively, p = 0.001; OR = 16.174, p = 0.002] and HHcy [13/30 (43.3%) vs. 4/40 (10%) iCVT vs. controls, respectively; p = 0.002, OR = 6.88, p = 0.002] with iCVT was found. Conclusions: PTHRA20210 and HHcy should be considered when screening for thrombophilia and should be assessed in patients with a family or personal history of CVT.

Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading

Hyperhomocysteinemia is a risk factor for vascular disease, although its mechanism of action is not fully clear. Different experimental studies have suggested that homocysteine (Hcy) exerts a pro-oxidant effect in the presence of metal ions (Fe and Cu). To test for a similar effect in vivo, we studied plasma markers of lipid and protein oxidation during hyperhomocysteinemia induced by an oral methionine load. Twenty-nine subjects (aged 61 +/- 25 years; 17 women), 25 of whom underwent oral methionine (100 mg/kg) loading, were studied; in every case, we measured total plasma Hcy, malondialdehyde (MDA), conjugated dienes (DIE), and oxidized protein ([PTOX] carbonylic groups) in basal conditions and 4, 6, 8, and 24 hours after methionine loading. Four participants acted as controls. In every case, we also measured total plasma antioxidant capacity (ANTOX) in basal conditions and 8 hours after methionine loading. Eight hours after methionine loading, plasma Hcy increased from 17.6 +/- 11.4 to 54.3 +/- 31.6 nmol/mL, PTOX from 0.33 +/- 0.18 to 0.71 +/- 0.33 nmol/mg protein, DIE from 493 +/- 163 to 590 +/-202 optical density units, and MDA from 1.66 +/- 0.81 to 2.1 +/- 0.93 nmol/mL. There was a significant correlation (Spearmans r) between Hcy and both PTOX (r = .86, P = .01) and MDA (r = .47, P < .05) 8 hours after methionine loading. No significant modifications of the plasma parameters were found during the observation period in controls. ANTOX at 8 hours was significantly (paired ttest) reduced in probands (from 1.74 +/- 0.59 to 1.14 +/- 0.55 mmol/mL, P = .014); no significant difference was observed for plasma ANTOX in controls. Hyperhomocysteinemia due to oral methionine loading induced an increase in plasma oxidation markers. In the absence of hyperhomocysteinemia, no significant modifications were observed. These findings, together with the decrease in ANTOX and the corresponding increase in total plasma Hcy, are consistent with a pro-oxidant effect of acute hyperhomocysteinemia in vivo.

Orthostatic Hypotension As Cause of Syncope in Patients Older Than 65 Years Admitted to Emergency Departments for Transient Loss of Consciousness

BACKGROUND Syncope due to orthostatic hypotension (OH) refers to loss of consciousness caused by hypotension induced by the upright position; it is an important risk factor for fall-related physical injuries, especially in the elderly adults. We evaluated the prevalence of OH syncope and the clinical characteristics of patients older than 65 years with syncope due to OH in the Evaluation of Guidelines in Syncope Study 2 group population. METHODS Two hundred fifty nine patients older than 65 years consecutively admitted to the emergency department because of loss of consciousness in a period of a month were submitted to a standardized protocol approved by the European Task Force for the diagnosis of syncope; all the patients were studied by a trained physician who interacted with a central supervisor as the management of syncope was concerned, using a decision-making software. RESULTS Prevalence of OH syncope was 12.4%. Patients with OH syncope were more likely to be affected by Parkinsons disease and by other neurological diseases. ST changes and longer values of QTc were found in OH syncope group, and they took a greater number of diuretics, nitrates, and digoxin. In multivariate analysis, Parkinsons disease (p = .001) and use of nitrates (p = .001) and diuretics (p = .020) were independently related to OH syncope. CONCLUSIONS In patients older than 65 years, Parkinsons disease and neurological comorbidity are strictly related to OH syncope. Moreover, this study suggests the independent link between OH syncope and the use of vasoactive drugs, identifying the majority of cases as adverse drug reaction, a preventable risk factor for syncope and falls in the older population.

Urinary and Plasma Homocysteine and Cysteine Levels during Prolonged Oral N-Acetylcysteine Therapy

Acute administration of N-acetylcysteine (NAC) may induce alterations in plasma and urinary levels of homocysteine (Hcy) and cysteine (Cys). We studied the effects of continuous oral NAC therapy on different Hcy and Cys plasma and urinary forms in 40 healthy subjects assigned to three groups (groups A: n = 13, no therapy; group B: n = 14, NAC 600 mg/day, and group C: n = 14, NAC 1,800 mg/day) for 1 month (T1). After a 1-month washout period without therapy (T2), all subjects were treated with oral NAC (1,800 mg/day) for 2 months and (T3 and T4) reassessed monthly for plasma and urinary thiols. The treated subjects showed a significant decrease in plasma total Hcy and a slight increase in total Cys levels; the alterations of different forms of plasma thiols suggested an NAC-induced increase in disulfide forms and an increase in urinary Hcy and Cys excretion as disulfide forms. The effects appeared to be dose dependent, being more marked in subjects treated with higher dosages. This approach may be important, as an association or alternative therapy in hyperhomocysteinemic conditions of poor responses to vitamins.

Continuous combined hormone replacement therapy with oral 17beta-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women.

ObjectiveTo evaluate the effect of a continuous combined oral hormone replacement therapy (HRT) on basal and post-methionine load homocysteine levels in postmenopausal women. DesignTwenty-two postmenopausal women (PMW) were randomly allocated to receive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of norethisterone acetate;n = 11) or no treatment (controls, n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed in each subject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by high-performance liquid chromatography) and B12 and folate (both by ELISA) were assayed in samples collected at time 0. ResultsSerum levels of glucose and body mass index increased in treated PMW, whereas folate decreased in controls. In treated PMW, basal homocysteine tended to decrease (10.6 ± 3.3 &mgr;mol/L vs. 9.62 ± 2.8 &mgr;mol/L, p = 0.062), whereas in controls it significantly increased (10.7 ± 2.65 &mgr;mol/L vs. 12.17 ± 3.89 &mgr;mol/L, p < 0.05). This increase was not significant after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 ± 13.53 &mgr;mol/L vs. 39.83 ± 22.53 &mgr;mol/L, p < 0.05) and 8 h (35.1 ± 13.13 vs. 43.34 ± 22.15 &mgr;mol/L) after methionine, and integrated homocysteine response to methionine (392.5 ± 133.8 &mgr;mol/24 h vs. 458.8 ± 104.8 &mgr;mol/24 h;p < 0.05), were significantly reduced in HRT-treated, but not in untreated, PMW. ConclusionsContinuous combined oral HRT with17&bgr;-estradiol plus norethisterone acetate reduces homocysteine levels, mainly after a methionine load. This effect seems to be independent of vitamin status and may have positive implications for the prevention of cardiovascular diseases in PMW.

Relationship between body composition and bone mineral content in young and elderly women.

Primary objective : To study the relationship between bone mineral content (BMC), lean tissue mass (LTM) and fat mass (FM) in a large sample of young and elderly women. Research design : Cross-sectional. Methods and procedures : BMC, LTM and FM were measured by dual-energy X-ray absorptiometry in 2009 free-dwelling Caucasian women aged 63 - 7 years (mean - SD; range: 37-88 years). The majority of women were postmenopausal (96%). Results : LTM explained 13% more variance of BMC than FM ( R 2 adj = 0.39 vs 0.26, p < 0.0001) but weight (Wt) explained 5% more variance of BMC than LTM ( R 2 adj = 0.44, p < 0.0001). The prediction of BMC obtained from LTM and FM ( R 2 adj = 0.46, p < 0.0001) was only slightly better than that obtained from Wt. After the effects of age, Wt and height (Ht) on BMC were taken into account by multiple regression, the contribution of LTM and FM to BMC was just one-fifth of that of Wt ( R 2 adj for full models r 0.56, p < 0.0001). After a further correction for bone area (BA), the contribution of LTM and FM to BMC was just one-tenth of that of BA and not different from that of Wt and Ht on practical grounds ( R 2 adj for full models = 0.84, p < 0.0001). Thus, after inter-individual differences in age, Wt, Ht (and bone size) are taken into account, the relationship between body composition and BMC is substantially weakened. Conclusions : In Caucasian women, (1) LTM is a stronger predictor of BMC than FM, but (2) Wt is a better predictor of BMC than body composition for practical purposes, and (3) Wt and body composition are not able to explain more than 46% of BMC variance.