Effects of build orientation and element partitioning on microstructure and mechanical properties of biomedical Ti-6Al-4V alloy produced by laser sintering.

Direct Metal Laser Sintering (DMLS) technology was used to produce tensile and flexural samples based on the Ti-6Al-4V biomedical composition. Tensile samples were produced in three different orientations in order to investigate the effect of building direction on the mechanical behavior. On the other hand, flexural samples were submitted to thermal treatments to simulate the firing cycle commonly used to veneer metallic devices with ceramics in dental applications. Roughness and hardness measurements as well as tensile and flexural mechanical tests were performed to study the mechanical response of the alloy while X-ray diffraction (XRD), electron microscopy (SEM, TEM, STEM) techniques and microanalysis (EDX) were used to investigate sample microstructure. Results evidenced a difference in the mechanical response of tensile samples built in orthogonal directions. In terms of microstructure, samples not submitted to the firing cycle show a single phase acicular α' (hcp) structure typical of metal parts subject to high cooling rates. After the firing cycle, samples show a reduction of hardness and strength due to the formation of laths of the ß (bcc) phase at the boundaries of the primary formed α' plates as well as to lattice parameters variation of the hcp phase. Element partitioning during the firing cycle gives rise to high concentration of V atoms (up to 20wt%) at the plate boundaries where the ß phase preferentially forms.

Effects of thermal treatments on microstructure and mechanical properties of a Co-Cr-Mo-W biomedical alloy produced by laser sintering.

Direct Metal Laser Sintering (DMLS) technology based on a layer by layer production process was used to produce a Co-Cr-Mo-W alloy specifically developed for biomedical applications. The alloy mechanical response and microstructure were investigated in the as-sintered state and after post-production thermal treatments. Roughness and hardness measurements, and tensile and flexural tests were performed to study the mechanical response of the alloy while X-ray diffraction (XRD), electron microscopy (SEM, TEM, STEM) techniques and microanalysis (EDX) were used to investigate the microstructure in different conditions. Results showed an intricate network of ε-Co (hcp) lamellae in the γ-Co (fcc) matrix responsible of the high UTS and hardness values in the as-sintered state. Thermal treatments increase volume fraction of the ε-Co (hcp) martensite but slightly modify the average size of the lamellar structure. Nevertheless, thermal treatments are capable of producing a sensible increase in UTS and hardness and a strong reduction in ductility. These latter effects were mainly attributed to the massive precipitation of an hcp Co3(Mo,W)2Si phase and the contemporary formation of Si-rich inclusions.

Structural characterization of biomedical Co-Cr-Mo components produced by direct metal laser sintering.

Direct metal laser sintering (DMLS) is a technique to manufacture complex functional mechanical parts from a computer-aided design (CAD) model. Usually, the mechanical components produced by this procedure show higher residual porosity and poorer mechanical properties than those obtained by conventional manufacturing techniques. In this work, a Co-Cr-Mo alloy produced by DMLS with a composition suitable for biomedical applications was submitted to hardness measurements and structural characterization. The alloy showed a hardness value remarkably higher than those commonly obtained for the same cast or wrought alloys. In order to clarify the origin of this unexpected result, the sample microstructure was investigated by X-ray diffraction (XRD), electron microscopy (SEM and TEM) and energy dispersive microanalysis (EDX). For the first time, a homogeneous microstructure comprised of an intricate network of thin ε (hcp)-lamellae distributed inside a γ (fcc) phase was observed. The ε-lamellae grown on the {111}γ planes limit the dislocation slip inside the γ (fcc) phase, causing the measured hardness increase. The results suggest possible innovative applications of the DMLS technique to the production of mechanical parts in the medical and dental fields.

Outcome predictors of rehabilitation for first stroke in the elderly.

AIM: The prediction of stroke outcome in the elderly can be rather difficult, due to the potential interference into disability and handicap development of several clinical modifiers, such as comorbidity, medical complications, neuropsychological impairment proper to the aging brain and social issues. These factors can strongly affect old patient response to rehabilitation and need to be taken into account, along with ageing per se, to optimize health resource efficiency for the care of disability due to stroke. In this study, we tried to identify outcome determinants of stroke rehabilitation specific for the elderly. METHODS: A total of 359 first-stroke patients aged 75 years, admitted for active rehabilitation treatment to hospital rehabilitation wards, were enrolled into a multicenter cohort (prospective) study. They all underwent a comprehensive medical rehabilitation program. We considered as primary outcomes the frequency of home discharge and the extent of functional recovery, assessed by Functional Independence Scale (FIM) and expressed as the Montebello Rehabilitation Factor Score (MRFS) efficacy. Each measure of outcome was related to age, as well as other potential clinical and functional confounders, according to a multivariate model. For each dependent variable, two models were developed, using either FIM total score or FIM domains scores at admission among predictors. RESULTS: FIM total score increased from 55.8+/-24 to 75.3+/-30 (P<0.0001), with a mean MRFS efficacy of 0.33+/-0.25. Most patients (79.9%) were discharged home. Age turned out as independently and inversely related to MRFS, explaining at the most 3.6% of its variance, although FIM at admission was its most powerful predictor. Home discharge was not related to age, but to social issues, such as living in family before admission, and cognition. CONCLUSION: The present study suggests that rehabilitation can be effective in elderly stroke patients, in improving function as well as in favorably affecting discharge destination. In fact, age per se predicts the outcome at a lesser extent than other clinical covariates, such as functional and cognitive status at admission and social situation.

The PADAM syndrome and its clinical manifestations: the muscle mass.

Many animal and in vitro studies suggest that testosterone can affect body composition. Therefore, the age-related decline in testosterone (T) likely contributes to the concomitant decrease in lean mass documented in men. While observational data in humans are not conclusive, intervention studies suggest that aged men could benefit from T replacement in term of muscle mass preservation. However, its potential positive impact on strength and functional status is unproven.

Changes in HDL-cholesterol and lipoprotein Lp(a) after 6-month treatment with finasteride in males affected by benign prostatic hyperplasia (BPH).

Androgen effects on lipoproteins, mainly high density lipoprotein (HDL), could be exerted by a direct interaction of testosterone (T) or dihydrotestosterone (DHT) with liver androgen receptors. To assess if T needs to be converted into DHT to affect lipid metabolism, 13 patients were studied, affected with benign prostatic hyperplasia (BPH) and treated with an inhibitor of 5 alpha-reductase (finasteride). They were compared with 15 untreated controls. At baseline and after 3 and 6 months of therapy, each patient was evaluated as for lipoprotein and hormone concentrations, as well as for nutritional status. Body composition was assessed by anthropometry and bio-impedance analysis (BIA). Treatment was associated with a significant increase of HDL-cholesterol (HDL-C), mainly HDL3 subclass, and lipoprotein(a) (Lp(a)), as well as a decline of DHT, whereas no significant changes were apparent for T, estradiol (E2), sex hormone binding hormone (SHBG) and body composition indexes. However, no significant associations between DHT and lipid relative changes were apparent at bivariate correlation analysis. This finding was confirmed by comparing patient subsets identified by cluster analysis, according to HDL subclass individual responses. Rather, a slight association with E2 for HDL2 (positive) and HDL3 (negative) was found. In conclusion, finasteride can modify HDL and Lp(a) concentrations. However, by the data, these effects cannot be definitively attributed to the changes in DHT synthesis induced by finasteride, since a direct and non-specific interference of the drug on liver metabolism cannot be excluded.

Aging-related decline of gonadal function in healthy men: correlation with body composition and lipoproteins.

OBJECTIVE: To assess if androgen decline in physiological aging contributes to the concomitant changes in body composition and lipoprotein levels. DESIGN: Cross-sectional, observational study. SETTING: A university-based outpatient center. SUBJECTS: The study comprised 206 healthy volunteers (aged 18-95 years). MEASUREMENTS: Blood samples were drawn after an overnight fast for the assay of hormones (free testosterone (FT), estradiol (E2), and sex hormone-binding globulin (SHBG)) and lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and lipoprotein Lp(a)). At the same time, body composition was assessed by both anthropometry (fat mass percentage (FM%) estimated from four measures of skinfold thickness using the Durnin and Womersley equation and the Siri equation) and by bioimpedance analysis (FM% estimated using the Segal or Deurenberg equations, respectively, for subjects younger or older than 62 years). RESULTS: A significant age-related decline was found for FT and E2 concentrations, whereas SHBG levels were related positively with age. No significant association was apparent between hormonal changes and the concomitant modifications of body composition and lipoproteins. Only SHBG showed a significant inverse association between FM% and the waist-to-hip ratio, independent of age. The comparison between older hypogonadal (with FT levels below the lower limit of the normality range assessed in younger subjects) and eugonadal men did not show any significant differences in body composition or lipid profile. CONCLUSIONS: This study suggests that, in men, androgen decline caused by normal aging does not significantly affect some targets of testosterone action, such as body composition and lipid metabolism. Therefore, androgen supplementation in hypogonadal older men cannot be expected to influence nutritional status and body composition to the same extent that it does other main targets of testosterone action, such as sexual activity and muscle strength. However, we cannot exclude that selected subsets of older patients with low testosterone levels, especially if affected by catabolic disease, could benefit from the effects of androgen administration on nutritional status.

Effects of aging on dehydroepiandrosterone sulfate in relation to fasting insulin levels and body composition assessed by bioimpedance analysis.

Insulin can inhibit dehydroepiandrosterone (DHEA) biosynthesis in humans, as suggested by several studies performed in induced or spontaneous hyperinsulinemia. The increased insulin resistance documented throughout aging, with its accompanying hyperinsulinemia, may contribute to the age-related decline in DHEA synthesis. The aim of this study was to assess if the aging-related differences in DHEA sulfate (DHEA-S) serum levels can be associated with differences in fasting insulin levels, as well as body composition. Two hundred fifty-two healthy subjects of both sexes aged 19 to 90 years with a body mass index (BMI) less than 30 (mean +/- SD, 23.5 +/- 2.4) were studied DHEA-S and insulin serum levels were determined by a radioimmunologic procedure; body composition was assessed by anthropometry (fat mass percentage [FM%] estimated from four skinfold thicknesses by Durnin and Womersley and Siri equations [FM%-SKF]) and by bioimpedance analysis (BIA) (FM% estimated by equations developed by Segal et al and Deurenberg et al for subjects < and > 62 years, respectively [FM%-BIA]). DHEA-S levels were significantly and inversely related to age in both sexes. No significant aging-related differences were found in fasting insulin levels, although a trend toward an increase was apparent in the women on simple regression analysis. No significant associations were found between DHEA-S and insulin levels. As for body composition, a positive relationship to age was apparent for FM%-SKF, FM%-BIA, and waist to hip ratio (WHR), whereas BMI and phase angle ([PA] a bioelectric parameter considered an index of the ratio between intracellular and extracellular water) were inversely related to age. Fasting insulin levels were positively related to FM% as estimated by both BIA and anthropometry, independently of age in both sexes; in addition, a positive correlation with WHR and with the subscapular to triceps skinfold thickness ratio (SS/TS) was found in men and women, respectively. No significant correlation was apparent between DHEA-S and body composition indices in men, whereas in women a slight negative correlation between DHEA-S and WHR was documented, and was still significant after adjustment for age and fasting insulin. Stepwise multiple regression analysis confirmed that DHEA-S levels are not related to fasting insulin, but are independently related to age and, in women only, to WHR. Our study suggests that the DHEA-S decline due to aging is independent of fasting insulin, at least in healthy, non-obese people. In addition, it is not related to the aging-dependent changes in body composition in terms of FM% and fat-free mass (FFM) percentage (FFM%). Only in women could changes in fat distribution be slightly associated with DHEA-S decline, although such a relation cannot be accounted for by changes in insulin levels.

Effects of androgen suppression by gonadotropin-releasing hormone agonist and flutamide on lipid metabolism in men with prostate cancer: focus on lipoprotein(a).

No clear relation between lipoprotein(a) [Lp(a)] and endogenous gonadal hormones has been demonstrated. In this study, we compared the effects on Lp(a) of pharmacological castration in 50 patients with prostate cancer who were undergoing therapy with a gonadotropin-releasing hormone agonist (goserelin), with effects on 58 age-matched controls. We also studied 16 untreated patients under baseline conditions and after 3 months of therapy with goserelin alone or combined with an antiandrogen (flutamide). Neither cross-sectional nor prospective studies showed any significant effects of therapy on Lp(a). However, cluster analysis identified a subgroup of patients showing slight but significant increases in Lp(a) concentrations, as well as greater declines of testosterone and estradiol, suggesting that androgen, like estrogen, can exert some slight, though not easily detectable, influence on Lp(a).

Escaping the cave to dream new dreams: a normative vision for learning disabilities.

This essay is predicated on two beliefs: (a) that special educators must critically examine the dominant view of reality undergirding the field of learning disabilities to see the false images built into it, and (b) we must seek a new, empowering vision of the purposes of education as we move into the twenty-first century. The purpose of the article is to analyze how the dominant image of reality in the field of learning disabilities is derived from the diagnostic model, and to propose an alternative, normative conception of education that emphasizes the importance of caring, social relatedness, and community participation.

Lipoprotein Lp(a) and cerebrovascular disease in the elderly: correlations with the severity of extracranial carotid atherosclerosis assessed by ultrasonography.

High levels of lipoprotein Lp(a) are related to cerebrovascular disease clinical manifestations, as well as to the severity of extracranial carotid atherosclerosis assessed by ultrasonography. In order to investigate the relationship of Lp(a) to the severity of carotid atherosclerosis in the elderly, 100 subjects, aged 78.5 +/- 0.6 yrs underwent an echo-color-doppler scanning of carotids; atherosclerosis severity, assessed as maximum percentage stenosis, presence of complicated plaque and Intima-Media Thickness (IMT), was related to Lp(a) levels, assayed by an immunoenzymatic procedure. A slight association between Lp(a) and CVD clinical manifestations was apparent only in subjects under 78 yrs and for Lp(a) values above 25 mg/dL. Lp(a) levels were not related either to the degree of stenosis, the presence of complicated plaque, or IMT. As for other selected risk factors, while no relationship was found for clinical CVD and IMT, the maximum percentage of stenosis and the presence of complicated plaques were positively related to LDL-cholesterol in subjects under 78 yrs. We can conclude that Lp(a), albeit unrelated to the severity of extracranial vessel atherosclerosis, maintains a role as cerebrovascular risk factor in the elderly, being slightly related to clinical manifestations; however its discriminant power is lower than in middle-aged people and further decreases throughout ageing.

Correlation between plasma lipoprotein Lp(a) and sex hormone concentrations: a cross-sectional study in healthy males.

High concentrations of lipoprotein Lp(a) have been related to atherosclerotic disease, both at coronary and cerebrovascular levels. Although Lp(a) levels are under a strict genetic control, being inversely related to the molecular weight of apo(a) isoforms, an interference of endogenous sex steroids on Lp(a) metabolism has been hypothesized. The aim of this study was to investigate the interrelationship between plasma Lp(a) and sex hormone concentrations in 98 healthy males, controlled as for their nutritional status by anthropometric measurements. Statistical evaluation was performed employing simple and multiple stepwise regression analysis. No significant correlation was found between Lp(a) levels and fT, E2 and gonadotropins, while they were positively and independently related to LDL-cholesterol and DHEA-S. As for the other lipoproteins, a positive correlation between HDL-cholesterol and E2 and an inverse correlation between triglycerides and SHBG were observed. These data suggest that endogenous testosterone and estradiol do not affect Lp(a) metabolism in males, at least in physiological concentrations. However Lp(a) might be affected by DHEA-S, the most abundant product of the adrenal gland. The positive correlation of HDL-cholesterol to E2 suggests that estrogens play a major role in lipid metabolism also in males, in spite of their low concentrations; more complex to be explained is the finding of an inverse relationship between Tg and SHBG. Further studies are needed in order to clarify the influence of sex steroids on lipid metabolism, mainly on Lp(a), under physiological conditions; population samples homogeneous in terms of apo a isoforms could be the ideal objects of such studies, in order to avoid the great interindividual variability of Lp(a) concentrations.

alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects.

Growth hormone (GH) secretion is decreased during aging in humans and in rodents. This decrease may be due to increased hypothalamic somatostatin release, which is inhibited by cholinergic agonists, or to decreased secretion of GHRH. Alpha-glyceryl-phosphorylcholine (alpha-GFC) is a putative acetylcholine precursor used in the treatment of cognitive disorders in the elderly. In order to learn what effect alpha-GFC had on GH secretion, GH-release hormone (GHRH) was given to young and old human volunteers, with or without the addition of alpha-GFC. GH secretion was greater in the younger subjects than in the old individuals, and both groups had a greater GH response to the GHRH+alpha-GFC than to GHRH alone. The potentiating effect of alpha-GFC on GH secretion was more pronounced in the elderly subjects. These findings confirm the observation that aged individuals respond less well to GHRH than younger subjects, and provides further evidence that increased cholinergic tone enhances GH release.

Effects of cytidine 5'-diphosphocholine administration on basal and growth hormone-releasing hormone-induced growth hormone secretion in elderly subjects.

The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'-diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69-84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'-diphosphocholine infusions. The infusion of cytidine 5'-diphosphocholine induced a 4-fold (p less than 0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2-fold greater in the cytidine 5'-diphosphocholine treated group (706.85 +/- 185.1 vs 248.9 +/- 61.4 micrograms.l-1.(120 min)-1; p = 0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear.