Heart transplantation and biomarkers: a review about their usefulness in clinical practice.

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice.

Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Pulsed electromagnetic fields and platelet rich plasma alone and combined for the treatment of wear-mediated periprosthetic osteolysis: An in vivo study.

Wear-mediated osteolysis is a common complication occurring around implanted prosthesis, which ultimately leads to bone loss with mechanical instability and the need for surgical revision. At the moment, revision surgery is the only effective treatment. The aim of this study was to assess the efficacy of pulsed electromagnetic fields (PEMFs) and platelet rich plasma (PRP), alone and in association, in a clinically relevant in vivo model of periprosthetic osteolysis. Titanium alloy pins were implanted intramedullary in distal femurs of male inbred rats and, after osseointegration, polyethylene particles were injected intra-articularly to induce osteolysis. Animals were divided in four groups of treatment: PEMFs, PRP, PEMFs + PRP and no treatment. Microtomography was performed during the course of experiments to monitor bone stock and microarchitecture. Histology, histomorphometry, immunohistochemistry and biomechanics were evaluated after treatments. Biophysical and biological stimulations significantly enhanced bone to implant contact, bone volume and bone microhardness and reduced fibrous capsule formation and the number of osteoclasts around implants. Among treatments, PEMFs alone and in association with PRP exerted better results than PRP alone. Present data suggest that biophysical stimulation, with or without the enrichment with platelet derived growth factors, might be a safe, mini-invasive and conservative therapy for counteracting osteolysis and prompting bone formation around implants. STATEMENT OF SIGNIFICANCE: Pulsed electromagnetic fields (PEMFs) and platelet rich plasma (PRP) show anabolic and anti-inflammatory effects and they are already been used in clinical practice, but separately. To date, there are no preclinical in vivo studies evaluating their combined efficacy in periprosthetic osteolysis, in bone tissue microarchitecture and in biomechanics. The aim of the present study was to evaluate the effects of PEMFs and PRP in vivo, when administered individually and in combination in the treatment of periprosthetic wear mediated ostelysis, and in restoring the osteogenetic properties of perimplant bone tissue and its biomechanical competence. The combination of PEMFs and PRP could be employed for counteracting the ostelysis process in a conservative and non surgical manner.

Mesenchymal Stem Cells for the Treatment of Spinal Arthrodesis: From Preclinical Research to Clinical Scenario.

The use of spinal fusion procedures has rapidly augmented over the last decades and although autogenous bone graft is the "gold standard" for these procedures, alternatives to its use have been investigated over many years. A number of emerging strategies as well as tissue engineering with mesenchymal stem cells (MSCs) have been planned to enhance spinal fusion rate. This descriptive systematic literature review summarizes the in vivo studies, dealing with the use of MSCs in spinal arthrodesis surgery and the state of the art in clinical applications. The review has yielded promising evidence supporting the use of MSCs as a cell-based therapy in spinal fusion procedures, thus representing a suitable biological approach able to reduce the high cost of osteoinductive factors as well as the high dose needed to induce bone formation. Nevertheless, despite the fact that MSCs therapy is an interesting and important opportunity of research, in this review it was detected that there are still doubts about the optimal cell concentration and delivery method as well as the ideal implantation techniques and the type of scaffolds for cell delivery. Thus, further inquiry is necessary to carefully evaluate the clinical safety and efficacy of MSCs use in spine fusion.

When size matters: differences in demineralized bone matrix particles affect collagen structure, mesenchymal stem cell behavior, and osteogenic potential.

Demineralized bone matrix (DBM) is a natural, collagen-based, osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM cytocompatibility and osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1-2 mm), medium (M, 0.5-1 mm), and small (S, <0.5 mm). After demineralization, the chemical-physical analysis clearly showed a particle size-dependent alteration in collagen structure, with DBM-M being altered but not as much as DBM-S. DBM-M displayed a preferable trend in almost all biological characteristics tested, although all DBM particles revealed an optimal cytocompatibility. Subcutaneous implantation of DBM particles into immunocompromised mice resulted in bone induction only for DBM-M. When sheep MSC were seeded onto particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM-M and DBM-S. In conclusion, the collagen alteration in DBM-M is likely the best condition to promote bone induction in vivo. Furthermore, the choice of 0.5-1 mm particles may enable to obtain more efficient and consistent results among different research groups in bone tissue-engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1019-1033, 2017.

RAW 264.7 co-cultured with ultra-high molecular weight polyethylene particles spontaneously differentiate into osteoclasts: an in vitro model of periprosthetic osteolysis.

Wear-particle osteolysis affects prosthesis survival leading to implant loosening up to 70% of revisions. Therapeutic strategies are increasing, however alternative testing methods to experimentally evaluate such treatments are lacking. The aim of this study was to reproduce an in vitro osteolysis model recapitulating the events that, starting from the exposure of macrophages to polyethylene, lead to the establishment of osteoclastogenesis and inflammation. Responses to polyethylene, at 3 and 7 days, in a macrophage cell line, RAW 264.7, were determined by DNA quantification, immunofluorescence, pit assay, gene expression, cytokine production and NF-kB activation. Results showed that 3 days exposure to particles could induce a significant production of Tumor Necrosis Factor alpha (p < 0.0005) and Prostaglandin E2 (p < 0.005) compared to controls. Particles also induced macrophages to spontaneously differentiate into mature and active osteoclasts, in terms of identification of multinucleated cells by Phalloidin staining and by the analysis of osteoclast-specific gene markers. In particular, at 3 days polyethylene induced a significant up-regulation of Nuclear Factor of Activated T-cells, cytoplasmic 1, Receptor Activator of Nuclear factor Kappa-B and Receptor Activator of Nuclear Factor Kappa-B Ligand genes (p < 0.0005) compared to controls. At protein level, the particles induced a significant increase of Receptor Activator of Nuclear Factor Kappa-B Ligand at day 7 over controls (p < 0.0005). Osteoclasts were capable to resorb bone even in absence of differentiating factors. The possible mechanism, beside spontaneous osteoclastogenesis mediated by wear debris, was identified in an autocrine up-regulation of Receptor activator of nuclear factor kappa-B ligand gene expression and protein synthesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 510-520, 2017.

Comparisons of physical activity, adipokines, vitamin D status and dietary vitamin D intake among adolescents.

BACKGROUND: Considering that lifestyle and diet are key factors responsible for the increases in adiposity in youth, it is important to understand how vitamin D, adipokines and markers of glucose metabolism are related to physical activity level (PAL) during growth. The present study aimed to investigate associations between physical activity level, adiponectin/leptin ratio, vitamin D status and dietary vitamin D intake among adolescents. METHODS: A cross-sectional study was conducted with adolescents aged 14-18 years old who were living in São Paulo, Brazil. Serum 25 hydroxyvitamin D [25(OH)D], adiponectin (A), leptin (L), glucose and insulin were obtained after 12 h of fasting. Dietary calcium and vitamin D intake were measured by 24-h food record, as repeated in 62.6% of the sample. PAL was measured by the International Physical Activity Questionnaire (IPAQ). Pearson's chi-square test, Pearson correlation and linear regression analysis were performed. RESULTS: A total of 198 subjects, mean (SD) age 16.3 (1.4) years, 51% male, were enrolled in the study. Some 9% of participants were sedentary, 22% were insufficiently active (IA), 51% were active and 18% were very active (VA). The A/L ratio was lower among sedentary/IA subjects [2.2 (4.0) versus 5.6 (12.3); P = 0.01] compared to active/VA subjects. PAL was not associated with vitamin D status or markers of glucose metabolism. Serum 25(OH)D positively associated with vitamin D intake, after adjusting for sex, sun exposure and season of the year in regression analysis (partial r2 =0.026, P = 0.02). CONCLUSIONS: Low PAL was associated with a lower A/L ratio. Vitamin D status was not associated with sun exposure habits, although it was positively correlated with vitamin D intake.

A new bi-layered scaffold for osteochondral tissue regeneration: In vitro and in vivo preclinical investigations.

Current treatments for acute or degenerative chondral and osteochondral lesions are in need of improvement, as these types of injuries lead to disability and worsen the quality of life in a high percentage of patients. The aim of this study was to develop a new bi-layered scaffold for osteochondral tissue regeneration through a "biomimetic" and "bioinspired" approach. For chondral regeneration, the scaffold was realized with an organic compound (type I collagen), while for the regeneration of the subchondral layer, bioactive magnesium-doped hydroxyapatite (Mg/HA) crystals were co-precipitated with the organic component of the scaffold. The entire scaffold structure was stabilized with a cross-linking agent, highly reactive bis-epoxyde (1,4-butanediol diglycidyl ether - BDDGE 1wt%). The developed scaffold was then characterized for its physico-chemical characteristics. Its structure and adhesion strength between the integrated layers were investigated. At the same time, in vitro cell culture studies were carried out to examine the ability of chondral and bone scaffold layers to separately support adhesion, proliferation and differentiation of human mesenchymal stem cells (hMSCs) into chondrocytes and osteoblasts, respectively. Moreover, an in vivo study with nude mice, transplanted with osteochondral scaffolds plain or engineered with undifferentiated hMSCs, was also set up with 4 and 8-week time points. The results showed that chondral and bone scaffold layers represented biocompatible scaffolds able to sustain hMSCs attachment and proliferation. Moreover, the association of scaffold stimuli and differentiation medium, induced hMSCs chondrogenic and osteogenic differentiation and deposition of extracellular matrix (ECM). The ectopic implantation of the engineered osteochondral scaffolds indicated that hMSCs were able to colonize the osteochondral scaffold in depth. The scaffold appeared permissive to tissue growth and penetration, ensuring the diffusion of nutrients and oxygen, as also suggested by the presence of a neo-angiogenesis process, especially at 4weeks. Moreover, the in vivo results further confirmed the great potential of the scaffold in tissue engineering, as it was able to support the initial formation of new bone and chondral tissue, confirming the importance of combined and innovative strategies to improve the available therapeutic strategies for chondral and osteochondral regeneration.

Production of nabumetone nanoparticles: Effect of molecular weight, concentration and nature of cellulose ether stabiliser.

The ability of a range of hydrophilic nonionic cellulose ethers (CEs) (namely methylhydroxethylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose) to prepare stable nabumetone nanoparticles (<1000nm, as measured by laser diffraction) using wet-bead milling has been investigated. Due to the limited range of CE molecular weights commercially available, the CEs were degraded using ultrasonication for varying lengths of time to yield CEs of lower molecular weight. Of the CEs tested, only hydroxyethylcellulose was found not to stabilise the production of nabumetone nanoparticles at any of the molecular weights tested, namely viscosity average molecular weights (Mv) in the range of 236-33kg/mol. All other CEs successfully stabilised nabumetone nanoparticles, with the lower molecular weight/viscosity polymers within a series being more likely to result in nanoparticle production than their higher molecular weight counterparts. Unfortunately due to the nature of the ultrasonication process, it was not possible to compare the size of nabumetone particles produced using polymers of identical Mv. There was, however, enough similarity in the Mv of the various polymers to draw the general conclusion that there was no strong correlation between the Mv of the various polymers and their ability to produce nanoparticles. For example hydroxypropylcellulose of 112.2kg/mol or less successfully produced nanoparticles while only ethylhydroxyethylcellulose and hydroxypropylmethyl polymers of 52 and 38.8kg/mol or less produced nanoparticles. These results suggest that polymer molecular weight is not the only determinant of nanoparticle production and that structure of the polymer is at least as important as its molecular weight. In particular the hydrophobic nature of the CE was thought to be an important factor in the production of nabumetone nanoparticles: the more hydrophobic the polymer, the stronger its interaction with nabumetone and the greater its ability to produce nanoparticles. In this context HPC was the most hydrophobic polymer and HEC the least hydrophobic.

Long-term in vivo experimental investigations on magnesium doped hydroxyapatite bone substitutes.

Despite several efforts to find suitable alternatives to autologous bone, no bone substitute currently available provides the same characteristics and properties. Nevertheless, among the wide range of materials proposed as bone substitutes, calcium phosphate materials represent the most promising category and the present study is aimed at improving the knowledge on non-stoichiometric magnesium-doped hydroxyapatite substitutes (Mg-HA), tested in two different formulations: Mg-HA Putty and Mg-HA Granules. These bone substitutes were implanted bilaterally into iliac crest bone defects in healthy sheep and comparative histological, histomorphometric, microhardness and ultrastructural assessments were performed 9, 12, 18 and 24 months after surgery to elucidate bone tissue apposition, mineralization and material degradation in vivo. The results confirmed that the biomimetic bone substitutes provide a histocompatible and osteoconductive structural support, during the bone formation process, and give essential information about the in vivo resorption process and biological behavior of biomimetic bone substitutes.

Can early diagnosis and partial meniscectomy improve quality of life in patients with lateral discoid meniscus?

OBJECTIVES: To evaluate clinical and radiographic mid-term outcomes and improvement in quality of life in pediatric patients affected by LDM and who underwent partial or total/subtotal meniscectomy. MATERIALS AND METHODS: 28 patients (12 M, 16 F), mean age 8.3 years old (range: 6-13) affected by LDM with symptoms and/or meniscal tears, mean follow up: 2 years and 4 months (range: 24-52 months). Symptoms included: pain, swelling, articular block, limitation to knee extention, meniscal instability and formation of meniscal cysts. 23 patients treated with partial meniscectomy, 5 by total/subtotal meniscectomy. All of them have been clinically evaluated using the Ikeuchi scale and the POSNA questionnaire; for radiological evaluation we used the Tapper-Hoover grading scale. RESULTS: Ikeuchi: In 23 patients underwent partial meniscectomy: 21 excellent and 2 good; in 5 patients underwent total/subtotal meniscectomy: 1 excellent, 2 good and 2 average. POSNA presurgical mean score: partial meniscectomy: 70 (range 66.8-73.6), total/subtotal meniscectomy: 58.7 (56.9-62.2). POSNA presurgical mean score: partial meniscectomy: 92.4 (range 88.7-98), total/subtotal meniscectomy: 81.2 (range 78.3-85.6). Tapper-Hoover: in 23 patients underwent partial meniscectomy: 17 were classified grade I, 5 grade II, 1 grade III; in 5 patients underwent total/subtotal meniscectomy: 2 were classified grade II and 3 grade III. These ones evidenced further signs of chondromalacia on articular surfaces, in the lateral area of knee joint. DISCUSSION: Significant improvement in quality of life, evidenced in all patients (p = 0.048 in those underwent total/subtotal meniscectomy, p = 0.011 in those underwent partial meniscectomy), but especially in patients who underwent partial meniscectomy with absence of meniscal tears (p = 0.033), supports how important can be early diagnosis of LDM in childhood. We assert that early diagnosis and conservative treatment (partial meniscectomy) could reduce risks in development of chondromalacia, in those patients affected by LDM, because of its association with better clinical, radiographic and in quality of life mid-term results.

Nutritional intake according to injury extent in ulcerative colitis patients.

BACKGROUND: Ulcerative colitis (UC) is often associated with nutritional deficiency, which appears to contribute to the progression of UC severity. The present study aimed to evaluate nutritional status and dietary intake in UC remission patients. METHODS: The present study comprised a cross-sectional study in which variables such as extent of disease (distal colitis, left-sided colitis, pancolitis), remission period, sex and age were recorded. Extent of disease was assessed by the results of a colonoscopy and dietary intake was evaluated by using 3-day, 24-h recalls. A Kruskall-Wallis test was used to compare the intake of macro- and micronutrients among the three study groups. The analysis was complemented by the Mann-Whitney test. A logistic regression analysis was performed to identify predictive factors of extent of disease (pancolitis versus left-sided colitis versus distal colitis). RESULTS: The median (range) age of the 59 patients was 49.0 (37.0-63.0) years and 53.3% were female. Twenty-six (44.1%) patients had distal colitis, 11 (18.6%) patients had left-sided colitis and 22 (37.3%) patients had pancolitis. A high probability of an inadequate intake of fibre (100%), fat soluble vitamins (>40% for vitamin A and >95% for vitamin E), vitamin C (>34%), calcium (>90%) and magnesium (>50%) was identified in the study group. Vitamin D intake (odds ratio = 0.60; 95% confidence interval = 0.39-0.94; P < 0.05) was significantly associated with increased intestinal damage. CONCLUSIONS: A large number of individuals showed an inadequate intake of nutrients. In addition, the consumption of vitamin D was significantly associated with extent of disease.

Toxocariasis/cysticercosis seroprevalence in a long-term rural settlement, São Paulo, Brazil.

Seroprevalence of Toxocara and Taenia solium and risk factors for infection with these parasites were explored in a long-term rural settlement in São Paulo state, Brazil. An ELISA for the detection of anti-Toxocara IgG and IgE and anti-T. solium cysticerci was standardized using Toxocara excretory-secretory antigens (TES) obtained from the cultured second-stage larvae of T. canis and by vesicular fluid antigen from Taenia crassiceps cysticerci (VF). For cysticercosis, the reactive ELISA samples were assayed by Western blot using 18 kDa and 14 kDa proteins purified from VF. Out of 182 subjects, 25 (13.7%) presented anti-Toxocara IgG and a positive correlation between total IgE and the reactive index of specific anti-TES IgE (P=0.0265) was found amongst the subjects found seropositive for anti-Toxocara IgG. In these individuals 38.0% showed ocular manifestations. The frequency of anti-T. solium cysticerci confirmed by Western blot was 0.6%. Seropositivity for Toxocara was correlated with low educational levels and the owning of dogs. Embryonated eggs of Toxocara spp. were found in 43.3% of the analysed areas.

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS).

UNLABELLED: The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. INTRODUCTION: The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. METHODS: A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. RESULTS: The average of age, height and weight for men and women were 58.4 +/- 12.8 and 60.1 +/- 13.7 years, 1.67 +/- 0.08 and 1.56 +/- 0.07 m and 73.3 +/- 14.7 and 64.7 +/- 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06-2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1-2.8), early menopause (OR = 1.7; 95% CI 1.02-2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02-2.7), poor quality of life (OR = 1.9; 95% CI 1.2-2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2-2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01-8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1-3.6) and recurrent falls (OR = 2.4; 95% CI 1.2-5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7-6.1), current smoking (OR = 3.5; 95% CI 1.28-9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27-13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1-36.1). CONCLUSION: Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.

[Collet-Sicard syndrome after carotid artery dissection]. / Syndrome de Collet-Sicard après dissection carotidienne.

Collet-Sicard syndrome is a rare condition, defined as unilateral palsy of the last four cranial nerves. It differs from Villaret syndrome because of absence of sympathetic involvement. Collet-Sicard syndrome is most often caused by skull tumors, carotid artery dissections or head and neck trauma. We report the case of a 57-year-old man who presented palsy of the left lower cranial nerves IX-XII linked to carotid artery dissection after trivial neck injury.

Effect of polymer molecular weight on the production of drug nanoparticles.

Stable, polymer-coated nanoparticles of two hydrophobic drugs, namely nabumetone and halofantrine, have been prepared by a wet-bead milling process performed in the presence of a stabilizing homopolymer, either hydroxypropylmethylcellulose (HPMC) or polyvinylpyrrolidone (PVP), of differing molecular weights and concentrations. Although nabumetone nanoparticles could only be produced when HPMC was used as stabilizing polymer, halofantrine nanoparticles could be prepared using either HPMC or PVP. Stable nanoparticles of nabumetone could be produced using a HPMC solution of viscosity average molecular weight, M(v), of 5 kg/mol over an approximate four fold polymer concentration range (0.63-2.5% w/w) when a drug loading of 20% w/w was used. Increasing the molecular weight of HPMC up to a limiting M(v) of 89 kg/mol did not result in the formation of nanoparticles at any of the polymer concentrations examined. The amount of polymer absorbed onto the nanoparticles was determined by measuring the depletion of polymer from solution based on either an ultra-violet (PVP) or optical rotatory dispersion (ORD) (HPMC) assay. The slightly lower concentration of HMPC found to be present on the surface of the halofantrine nanoparticles compared with the nabumetone nanoparticles suggested a differing affinity of the polymer for the surface of the two drugs.

Surgical approach to concealed penis: technical refinements and outcome.

OBJECTIVES: A concealed penis is defined as a phallus of normal size buried in prepubic tissue (buried penis), enclosed in scrotal tissue (webbed penis), or trapped by scar tissue after penile surgery (trapped penis). We report our results using a standardized surgical approach that was highly effective in both functional and cosmetic terms. METHODS: From January 2002 to December 2005, 56 patients (median age 7 years) underwent surgery for a buried penis, 11 (median age 5 years) for a webbed penis, and 20 (median age 8 years) for a trapped penis. All 20 patients with a trapped penis had previously undergone circumcision for phimosis, except for 3 (1 for multioperated lymphangioma, 1 for repaired hypospadias, and 1 for corrected glanular epispadia). All webbed penises were phimotic, requiring circumcision. The surgical technique consisted of complete exteriorization of the shaft and reconstruction of the penopubic and penoscrotal angles. These maneuvers, however, proved extremely straightforward, with the addition of an incision along the scrotal raphe without any incision of the penile skin. RESULTS: All the patients were observed for at least 1 year after repair. Recurrence was observed in 3 boys with a buried penis (5.3%); all 3 boys were obese. Two cases of a trapped penis (10.0%) recurred, but no case of a webbed penis recurred. Regarding complications, 2 patients with a buried penis presented with mild lymphatic stasis of distal shaft that spontaneously subsided within a few months. CONCLUSIONS: The scrotal approach we have described has simplified the complete exteriorization of the penile shaft, with easy bleeding control, avoiding the use of flaps, grafts, and additional ventral Z-plasty often described in published reports. In addition, the cosmetic results were judged to be good by the parents.

Desenvolvimento de equação para estimativa da gordura corporal de mulheres idosas com osteoporose e osteopenia através da espessura de dobras cutâneas tendo como referência absorciometria por dupla emissão de raios X / Development of an equation for measurement of bodyfat mass of elderly women with osteoporosis or osteopenia through skin fold thickness using dual energy X-ray absorptiometry as a reference

INTRODUÇÃO E OBJETIVO: A composição corporal vem sendo descrita como importante fator relacionado à densidade mineral óssea. Assim, o presente estudo teve como objetivo desenvolver equação preditiva para percentagem de gordura corporal através da espessura de dobras cutâneas tendo como referência a absorciometria por dupla emissão de raios X (DXA), em mulheres com osteoporose e osteopenia. METODOLOGIA: Foram analisadas 29 mulheres com idade entre 67 e 84 anos, atendidas no Ambulatório de Osteoporose da Disciplina de Reumatologia da Faculdade de Medicina da Universidade de São Paulo. Foram mensuradas as espessuras de quatro dobras cutâneas (bíceps, tríceps, subescapular e supra-ilíaca) e realizada a avaliação da composição corporal pela DXA. A análise estatística constou do teste de Kolmogorov-Smirnov, coeficiente de correlação de Pearson, análise de regressão linear simples, coeficiente de correlação intraclasse, teste t de Student, teste de Bland-Altman e cálculo do erro total da equação de acordo com Lohman (1992). RESULTADOS: O modelo de espessura de dobras cutâneas que melhor explicou o percentual de gordura corporal incluiu a soma das dobras supra-ilíaca, bicipital e tricipital, determinando em até 72 por cento a percentagem de gordura corporal. Os valores médios da gordura corporal em quilograma, estimados pelas dobras e medidos pela DXA, não foram estatisticamente diferentes e estiveram altamente correlacionados (r = 0,82; p < 0,001). Comparando-se o percentual de gordura corporal avaliado pela equação proposta e o medido pela DXA, o erro total foi de 0,7 por cento e 0,4kg. CONCLUSÃO: Em vista dos presentes resultados, a equação resultante do modelo de regressão linear é adequada para as mulheres idosas com osteoporose e osteopenia, podendo ser uma alternativa para a estimativa de gordura corporal nesse tipo de população.

INTRODUCTION AND OBJECTIVE: The body composition has been intensively investigated as a determinant of bone mineral density. The present study was developed in order to propose a predictive equation to calculate body fat percentage by means of skin folds thickness using bone densitometry (DXA) as a reference in a group of elderly women with osteoporosis and osteopenia. METHODOLOGY: Twenty-nine women, mean age 67 to 84 years old, in attendance at the Osteoporosis Clinic at Rheumatology Division, School of Medicine, University of Sao Paulo, were evaluated. Four skin folds thickness were measured (biceps, triceps, subscapular and suprailiac) and body composition by DXA was evaluated. The statistical analysis consisted of Kolmogorov-Smirnov test, Pearson's coefficient correlation, simple linear regression analysis, intra-class correlation coefficient, t Student test, Bland-Altman test and calculus of equation total error according to Lohman (1992). RESULTS: The best skinfold model that explained the percentage of body fat mass included the suprailiac, bicipital and tricipital values, determining up to 72 percent of body fat mass. The fat mass average values in kilograms estimated by the skin folds and measured by DXA were not statistically different and had been highly correlated (r = 0.82; p < 0.001). Comparing the fat mass percentage evaluated by the proposed equation and the percentage measured by DXA, the total error was of 0.7 percent and 0.4 kg. CONCLUSION: In view of the presented results, the resultant equation of the regression model is adequate for elderly women with osteoporosis and osteopenia, and may be an alternative for the body fat mass estimate in this population.

INTRODUCCION Y OBJETIVO: La composición corporal viene siendo descrita como un importante factor relacionado a la densidad mineral ósea. De este modo el presente estudio ha tenido como objetivo desarrollar una ecuación predictiva para el porcentaje de grasa corporal a través de la espesura de los dobleces cutáneos con bases en la absorciometría por doble emisión de rayos X (DXA), en mujeres con osteoporosis y osteopenia. METODOLOGíA: Fueron analizadas 29 mujeres con edades entre 67 y 84 años, atendidas en Ambulatorio de Osteoporosis de la Disciplina de Reumatología de la Facultad de Medicina de la Universidad de San Pablo. Fueron medidas las espesuras de cuatro dobleces cutáneos (bíceps, tríceps, subescapular y suprailiaca) y realizada la evaluación de la composición corporal por DXA. El análisis estadístico constó del test de Kolmogorov-Smirnov, el coeficiente de correlación de Pearson, el análisis de regresión lineal simple, el coeficiente de correlación intraclase, el test t de Student, el test de Bland-Altman y el cálculo del error total de la ecuación de acuerdo a Lohman (1992). RESULTADOS: El modelo de espesura de dobleces cutáneos que mejor explicó el porcentaje de grasa corporal incluyó la suma de los dobleces suprailiaco, bicipital y tricipital, determinando en hasta 72 por ciento el porcentaje de grasa corporal. Los valores medios de grasa corporal en kilogramos, estimados por los dobleces y medidos por el DXA, no fueron estadísticamente diferentes y estuvieron altamente correlacionados (r = 0,82; p < 0,001). Al compararse el porcentaje de grasa corporal evaluado por la ecuación propuesta y el medido por el DXA, el error total fue de 0,7 por ciento y 0,4 kg. CONCLUSION: A la luz de los resultados obtenidos, la ecuación resultante del modelo de regresión lineal es adecuada para las mujeres ancianas con osteoporosis y osteopenia siendo incluso una alternativa para la estimativa de la grasa corporal en este tipo de población.

Dietary phylloquinone depletion and repletion in postmenopausal women: effects on bone and mineral metabolism.

INTRODUCTION: Vitamin K has been implicated in increased bone fracture risk. Despite a potential role of vitamin K in bone, little is known about the effects of altered dietary phylloquinone intake on the underlying components of bone and mineral metabolism. METHODS: A 84-day in-house dietary phylloquinone (vitamin K) depletion-repletion study was undertaken in 21 postmenopausal women (mean age: 70 years) to assess the effects of altered vitamin K status on intestinal calcium (Ca) absorption, urinary and serum Ca and phosphorus (P), serum calcemic hormones, and serum biomarkers of bone turnover [osteocalcin and N-telopeptide type 1 collagen cross-links (NTx)] and the response to 1,25-dihydroxyvitamin D treatment (1 microg/dayx7 d). RESULTS: The group receiving calcitriol treatment (n=11) had higher Ca absorption, urinary Ca, urinary and serum P and serum osteocalcin and lower serum parathyroid hormone (PTH). There were no significant effects of acute (4-week) phylloquinone depletion on response to 1,25-dihydroxyvitamin D treatment or on measures of bone formation or mineral metabolism. However, phylloquinone treatment had a significant effect (p<0.04) on serum NTx. Phylloquinone repletion, up to five times (450 microg phylloquinone per day) the currently recommended adequate intake level of dietary phylloquinone for women, significantly reduced serum NTx (16.8+/-0.9 nmol bone collagen equivalents (BCE) per liter following repletion vs 18.4+/-1.1 nmol BCE per liter following depletion; p<0.01). CONCLUSIONS: These findings suggest that altering vitamin K status in postmenopausal women by manipulating phylloquinone intake does not have an acute affect on intestinal Ca absorption, renal mineral excretion, or bone formation, but high phylloquinone intake may modestly reduce bone resorption. The impact of high phylloquinone intake on bone mineral density and fracture risk needs to be ascertained in randomized clinical trials.

Body composition changes in haemodialysis patients with secondary hyperparathyroidism after parathyroidectomy measured by conventional and vector bioimpedance analysis.

Considering the negative effects of secondary hyperparathyroidism (SHPT) in patients with chronic renal failure (CRF), the objective of the present study was to evaluate body composition changes using conventional and vector bioimpedance analysis in patients before and after parathyroidectomy (PTX). Twelve adult patients, mean age 43.4 (sd 12.7) years, were evaluated prior to and 6 months after PTX. Diets were assessed with 3 d dietary records, and mean energy, protein, calcium and phosphorus intake were estimated from these inventories. Weight, height, BMI and bioelectrical impedance were measured; and biochemical markers of nutritional status (albumin and total protein) and bone metabolism (calcium, phosphorus and intact parathyroid hormone) were determined. No significant differences were observed in mean energy, protein and phosphorus after surgery. There was a significant increase in calcium intake after PTX (382.3 (sd 209.6) mg to 656.6 (sd 313.8) mg; P<0.05). Mean weight, BMI, conventional bioelectrical impedance measurements, total body fat, lean body mass and total body water were unaffected by surgery. However, the phase angle and reactance significantly increased after PTX (5.0 degrees (sd 1.4) to 5.6 degrees (sd 1.3); 44.1 (sd 15.6) Omega to 57.1 (sd 14.4) Omega, respectively). The high levels of intact parathyroid hormone before surgery had a negative effect on total body fat (r -0.69, P<0.05). After PTX, the mean albumin significantly increased (3.9 (sd 0.4) g/dl to 4.2 (sd 0.6) g/dl; P<0.05). PTX for SHPT is associated with certain changes in laboratory values, dietary intake and body composition. The latter is best seen with bioimpedance vector analysis.