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.

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.

The effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones in men.

To investigate the effects of aging on the secretion of the common alpha-subunit of the glycoprotein hormones, we measured basal levels of luteinizing hormone (LH), testosterone (T) and alpha-subunit in 176 normal men aged 19 to 89 years. In addition, in two groups of young (less than 65 years; n = 25) and old (greater than 65 years; n = 15) subjects, the effects of luteinizing hormone-releasing hormone (LHRH) on LH and alpha-subunit secretion were determined. Age-related increases in serum alpha-subunit and LH were noted only in the oldest men while T levels decreased progressively with advancing age. LHRH stimulation resulted in significantly greater secretion of alpha-subunit in the old subjects while no difference in LH release between young and old men was observed. Moreover, there was a delay to peak LH and alpha-subunit levels after LHRH in the old subjects. These data suggest that the aging process in males involves deficits in both testicular and gonadotroph functions as demonstrated by (1) the relative hypogonadotropic hypogonadism seen until the ninth decade; (2) the hypergonadotropic hypogonadism apparent in men greater than 80 years; (3) the delay in the timing of peak responses of LH and alpha-subunit after LHRH administration; and (4) the disproportionate increase in the secretion of alpha subunit relative to intact LH.

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.

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.

Obstacles to integrating disabled students in a "two-roof" elementary school.

This article describes a 5-year effort to integrate special and regular students on a campus where special and regular education students are housed in separate but adjacent facilities with separate administrators. Observational data and questionnaires revealed almost total segregation at the end of 3 years. An intensive intervention program, Project L.E.A.D., generated promising short-term movement toward integration, but there were few enduring effects. Physical, social, and psychological barriers created by the two-roof school erect almost insurmountable obstacles to integration. Future efforts should concentrate on building one-roof schools with a single facility and administration.

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.

The role of overweight and glucose tolerance in the impaired pituitary-gonadal axis of obese males.

In a group of 30 obese male patients (160.2% of ideal body weight), an impaired function of the pituitary-gonadal axis has been demonstrated. Decreased testosterone and increased estradiol basal levels, increased LH and FHS responsiveness to gonadotropin-releasing hormone, and increased basal prolactin (PRL) levels are the most significant findings. The overweight factor seems to account for the documented decreased testosterone and increased estrogen levels through a modulation of peripheral steroid metabolism. These peripheral steroid patterns might affect gonadotropin and PRL secretions as well; nevertheless an interference with the metabolism of cerebral neurotransmitters, perhaps related to a nutritional component (impaired glucose tolerance), cannot be completely excluded.

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.

The effects of ACTH 1-17 on GH secretion in vitro.

Recently we demonstrated that ACTH 1-17 infusion in normal subjects is able to stimulate growth hormone (GH) secretion. In order to study the mechanism by which ACTH 1-17 induces this hormonal secretory pattern, we examined the effects of ACTH 1-17 addition to primary cultures of rat anterior pituitary cells and of two human pituitary adenomas (a mixed GH- and PRL-secreting adenoma and a prolactinoma) on GH and PRL secretion. Normal rat pituitary cells responded to rGRF with a dose-dependent increase of rGH: ACTH 1-17 induced a slight not significant increase of rGH secretion even at micromolar concentrations. Furthermore no additive effect of ACTH 1-17 on rGRF-stimulated GH release was observed. No significant stimulatory effect was also documented in the human tumors studied. These results suggest that the GH releasing activity of ACTH 1-17 observed in vivo is mediated via a direct action on CNS.

Acute infusion of hCG and thyroid hormone pattern before and after bilateral orchiectomy.

An acute infusion of 5000 IU of hCG was given to a group of 10 elderly men affected by prostatic carcinoma prior to and 1 month after castration to evaluate the possibility of any aspecific effect on thyroid hormones. No significant change was documented for TT4 and TT3, and a significant increase in fT4 occurred only in the presurgical experiment. From these results the authors conclude that the thyroid movement documented may be correlated to the decreased binding capacity of thyroxine-binding globulins promoted by the increase in Te levels.

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.