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PURPOSE: To systematically review the literature to assess the heterogeneity of platelet-rich plasma (PRP) preparation and composition reporting for the treatment of musculoskeletal/orthopaedic pathologies. METHODS: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify Level I and Level II studies from 2016 to 2022 that evaluated the use of PRP therapy for musculoskeletal pathologies. The search phrase used was "platelet-rich plasma clinical studies." Studies were assessed based on their reporting of the PRP preparation methods and reporting of PRP composition. RESULTS: One hundred twenty-four studies (in 120 articles) met inclusion criteria for analysis. Of these studies, 15 (12.1%) provided comprehensive reporting, including a clear, well-described, and reproducible preparation protocol that future investigators can follow. Thirty-three studies (26.6%) quantitatively reported the final PRP product composition. CONCLUSIONS: Among the studies using PRP for the treatment of musculoskeletal/orthopaedic pathologies, less than 20% provided a clear, well-described, and reproducible PRP preparation protocol, and only one-fourth of studies reported on the final PRP product composition. CLINICAL RELEVANCE: A diverse current reporting of PRP composition between studies provides a high heterogeneity of the term "PRP," which becomes a limitation for a comparison of studies using PRP.
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PF-05212377 (SAM760) is a potent and selective 5-HT6 antagonist, previously under development for the treatment of Alzheimer's disease. In vitro, PF-05212377 was determined to be a P-gp/non-BCRP human transporter substrate. Species differences were observed in the in vivo brain penetration of PF-05212377 with a ratio of the unbound concentration in brain/unbound concentration in plasma (Cbu /Cpu ) of 0.05 in rat and 0.64 in non-human primates (NHP). Based on pre-clinical evidence, brain penetration and target engagement of PF-05212377 was confirmed in NHP using positron emission tomography (PET) measured 5-HT6 receptor occupancy (%RO). The NHP Cpu EC50 of PF-05212377 was 0.31 nM (consistent with the in vitro human 5HT6 Ki : 0.32 nM). P-gp has been reported to be expressed in higher abundance at the rat BBB and in similar abundance at the BBB of non-human primates and human; brain penetration of PF-05212377 in humans was postulated to be similar to that in non-human primates. In humans, PF-05212377 demonstrated dose and concentration dependent increases in 5-HT6 RO; maximal 5-HT6 RO of â¼80% was measured in humans at doses of ≥15 mg with an estimated unbound plasma EC50 of 0.37 nM (which was similar to the in vitro human 5HT6 binding Ki 0.32 nM). In conclusion, cumulative evidence from NHP and human PET RO assessments confirmed that NHP is more appropriate than the rat for the prediction of human brain penetration of PF-05212377, a P-gp/non-BCRP substrate. Clinical trial number: NCT01258751.
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Encéfalo , Serotonina , Humanos , Ratos , Animais , Serotonina/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Primatas/metabolismoRESUMO
Muscarinic acetylcholine receptors (mAChR), including M4, draw attention as therapeutic targets for several neurodegenerative diseases including Alzheimer's disease (AD). PET imaging of M4 positive allosteric modulator (PAM) allows qualification of the distribution as well as the expression of this receptor under physiological conditions and thereby helps to assess the receptor occupancy (RO) of a drug candidate. In this study, our aims were (a) to synthesize a novel M4 PAM PET radioligand [11C]PF06885190 (b) to evaluate the brain distribution of [11C]PF06885190 in nonhuman primates (NHP) and (c) to analyze its radiometabolites in the blood plasma of NHP. Radiolabeling of [11C]PF06885190 was accomplished via N-methylation of the precursor. Six PET measurements were performed using two male cynomolgus monkeys, where three PET measurements were at baseline, two after pretreatment with a selective M4 PAM compound CVL-231 and one after pretreatment with donepezil. The total volume of distribution (VT) of [11C]PF06885190 was examined using Logan graphical analysis with arterial input function. Radiometabolites were analyzed in monkey blood plasma using gradient HPLC system. Radiolabeling of [11C]PF06885190 was successfully accomplished and the radioligand was found to be stable in the formulation, with radiochemical purity exceeding 99% 1 h after the end of the synthesis. [11C]PF06885190 was characterized in the cynomolgus monkey brain where a moderate brain uptake was found at the baseline condition. However, it showed fast wash-out as it dropped to half of the peak at around 10 min. Change of VT from baseline was around -10% after pretreatment with a M4 PAM, CVL-231. Radiometabolite studies showed relatively fast metabolism. Although sufficient brain uptake of [11C]PF06885190 was observed, these data suggest that [11C]PF06885190 might have too low specific binding in the NHP brain to be further applied in PET imaging.
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Encéfalo , Tomografia por Emissão de Pósitrons , Animais , Masculino , Macaca fascicularis , Radioisótopos de Carbono/química , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/químicaRESUMO
Regular monitoring and timely repair of concrete cracks are required to minimize further deterioration. Self-healing of cracks has been proposed as an alternative to the crack maintenance procedures. One of the proposed techniques is to use axenic cultures to exploit microbial-induced calcite precipitation (MICP). However, such healing agents are not cost-effective for in situ use. As the market for bio-based self-healing concrete necessitates a low-cost bio-agent, nonaxenic sulfate reducing bacterial (SRB) granules were investigated in this study through cultivation in an upflow anaerobic sludge blanket reactor. The compact granules can protect the bacteria from adverse conditions without encapsulation. This study investigated the microbial activities of SRB granules at different temperatures, pH, and chemical oxygen demand concentrations which the microbes would experience during the concrete casting and curing process. The attenuation and recovery of microbial activities were measured before and after the exposure. Moreover, the MICP yield was also tested for a possible use in self-healing bioconcrete. The results consistently showed that SRB granules were able to survive starvation, high temperature (50-60°C), and high pH (12), together with scanning electron microscope/energy dispersive spectrometry/X-ray diffraction analysis evidence. Microbial staining analysis demonstrated the formation of spores in the granules during their exposure to harsh conditions. SRB granule was thus demonstrated to be a viable self-healing nonaxenic agent for low-cost bioconcrete.
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Materiais de Construção , Sulfatos , Bactérias , Carbonato de Cálcio , Materiais de Construção/análise , Materiais de Construção/microbiologia , Esgotos/microbiologiaRESUMO
PURPOSE: Beta-secretase 1 (BACE1) enzyme is implicated in the pathophysiology of Alzheimer's disease. [18F]PF-06684511 is a positron emission tomography (PET) radioligand for imaging BACE1. Despite favorable brain kinetic properties, the effective dose (ED) of [18F]PF-06684511 estimated in non-human primates was relatively high. This study was therefore designed to evaluate the whole-body distribution, dosimetry, quantification, and test-retest reliability of imaging brain BACE1 with [18F]PF-06684511 in healthy volunteers. METHODS: Five subjects were studied for the dosimetry study. Whole-body PET was performed for 366 min with 4 PET-CT sessions. Estimates of the absorbed radiation dose were calculated using the male adult model. Eight subjects participated in the test-retest study. Brain PET measurements were conducted for 123 min with an interval of 5 to 19 days between test and retest conditions. The total distribution volume (VT) was estimated with one-tissue (1T), two-tissue (2T), compartment model (CM), and graphical analysis. Test-retest variability (TRV) and intraclass correlation coefficient (ICC) of VT were calculated as reliability measures. RESULTS: In the dosimetry study, the highest uptake was found in the liver (25.2 ± 2.3 %ID at 0.5 h) and the largest dose was observed in the pancreas (92.9 ± 52.2 µSv/MBq). The calculated ED was 24.7 ± 0.8 µSv/MBq. In the test-retest study, 2TCM described the time-activity curves well. VT (2TCM) was the highest in the anterior cingulate cortex (6.28 ± 1.09 and 6.85 ± 0.81) and the lowest in the cerebellum (4.23 ± 0.88 and 4.20 ± 0.75). Mean TRV and ICC of VT (2TCM) were 16.5% (12.4-20.5%) and 0.496 (0.291-0.644). CONCLUSION: The ED of [18F]PF-06684511 was similar to other 18F radioligands, allowing repeated PET measurements. 2TCM was the most appropriate quantification method. TRV of VT was similar to other radioligands without a reference region, albeit with lower ICC. These data indicated that [18F]PF-06684511 is a suitable radioligand to measure BACE1 level in the human brain. TRIAL REGISTRATION: EudraCT 2016-001110-19 (registered 2016-08-08).
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Secretases da Proteína Precursora do Amiloide , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Ácido Aspártico Endopeptidases , Encéfalo/diagnóstico por imagem , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Radiometria , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Distribuição Tecidual , Tomografia Computadorizada por Raios XRESUMO
AIMS/HYPOTHESIS: The progressive loss of beta cell function is part of the natural history of type 2 diabetes. Autopsy studies suggest that this is, in part, due to loss of beta cell mass (BCM), but this has not been confirmed in vivo. Non-invasive methods to quantify BCM may contribute to a better understanding of type 2 diabetes pathophysiology and the development of therapeutic strategies. In humans, the localisation of vesicular monoamine transporter type 2 (VMAT2) in beta cells and pancreatic polypeptide cells, with minimal expression in other exocrine or endocrine pancreatic cells, has led to its development as a measure of BCM. We used the VMAT2 tracer [18F]fluoropropyl-(+)-dihydrotetrabenazine to quantify BCM in humans with impaired glucose tolerance (prediabetes) or type 2 diabetes, and in healthy obese volunteers (HOV). METHODS: Dynamic positron emission tomography (PET) data were obtained for 4 h with metabolite-corrected arterial blood measurement in 16 HOV, five prediabetic and 17 type 2 diabetic participants. Eleven participants (six HOV and five with type 2 diabetes) underwent two abdominal PET/computed tomography (CT) scans for the assessment of test-retest variability. Standardised uptake value ratio (SUVR) was calculated in pancreatic subregions (head, body and tail), with the spleen as a reference region to determine non-specific tracer uptake at 3-4 h. The outcome measure SUVR minus 1 (SUVR-1) accounts for non-specific tracer uptake. Functional beta cell capacity was assessed by C-peptide release following standard (arginine stimulus test [AST]) and acute insulin response to the glucose-enhanced AST (AIRargMAX). Pearson correlation analysis was performed between the binding variables and the C-peptide AUC post-AST and post-AIRargMAX. RESULTS: Absolute test-retest variability (aTRV) was ≤15% for all regions. Variability and overlap of SUVR-1 was measured in all groups; HOV and participants with prediabetes and with type 2 diabetes. SUVR-1 showed significant positive correlations with AIRargMAX (all groups) in all pancreas subregions (whole pancreas p = 0.009 and pancreas head p = 0.009; body p = 0.019 and tail p = 0.023). SUVR-1 inversely correlated with HbA1c (all groups) in the whole pancreas (p = 0.033) and pancreas head (p = 0.008). SUVR-1 also inversely correlated with years since diagnosis of type 2 diabetes in the pancreas head (p = 0.049) and pancreas tail (p = 0.035). CONCLUSIONS/INTERPRETATION: The observed correlations of VMAT2 density in the pancreas and pancreas regions with years since diagnosis of type 2 diabetes, glycaemic control and beta cell function suggest that loss of BCM contributes to deficient insulin secretion in humans with type 2 diabetes.
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Diabetes Mellitus Tipo 2/metabolismo , Pâncreas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Proteínas Vesiculares de Transporte de Monoamina/metabolismo , Feminino , Humanos , Células Secretoras de Insulina/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
The Massachusetts General Hospital Radiochemistry Program, in collaboration with Pfizer, has developed unique 11C and 18F-labeling strategies to synthesize isotopologs of lorlatinib (PF-06463922) which is undergoing phase III clinical trial investigations for treatment of non-small-cell lung cancers with specific molecular alterations. A major goal in cancer therapeutics is to measure the concentrations of this drug in the brain metastases of patients with lung cancer, and penetration of the blood-brain barrier is important for optimal therapeutic outcomes. Our recent publication in Nature Communications employed radiolabeled lorlatinib and positron emission tomography (PET) studies in preclinical models including nonhuman primates (NHPs) that demonstrated high brain permeability of this compound. Our future work with radiolabeled lorlatinib will include advanced PET evaluations in rodent tumor models and normal NHPs with the goal of clinical translation.
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Encéfalo/metabolismo , Lactamas Macrocíclicas/farmacologia , Tomografia por Emissão de Pósitrons , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Aminopiridinas , Quinase do Linfoma Anaplásico , Animais , Encéfalo/efeitos dos fármacos , Humanos , Lactamas , Lactamas Macrocíclicas/síntese química , Lactamas Macrocíclicas/química , Macaca mulatta , Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Pirazóis , Receptores Proteína Tirosina Quinases/metabolismoRESUMO
Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact.This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.
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Desenvolvimento de Medicamentos/métodos , Imagem Molecular/métodos , Desenvolvimento de Medicamentos/tendências , Humanos , Imagem Molecular/tendências , Técnicas de Sonda Molecular , Imagem Multimodal , Medicina de Precisão , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
1. Unbound brain drug concentration (Cb,u), a valid surrogate of interstitial fluid drug concentration (CISF), cannot be directly determined in humans, which limits accurately defining the human Cb,u:Cp,u of investigational molecules. 2. For the H3R antagonist (1R,3R)-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-lmethyl)phenyl]cyclobutane-1-carboxamide (PF-03654746), we interrogated Cb,u:Cp,u in humans and nonhuman primate (NHP). 3. In rat, PF-03654746 achieved net blood-brain barrier (BBB) equilibrium (Cb,u:Cp,u of 2.11). 4. In NHP and humans, the PET receptor occupancy-based Cp,u IC50 of PF-03654746 was 0.99 nM and 0.31 nM, respectively, which were 2.1- and 7.4-fold lower than its in vitro human H3 Ki (2.3 nM). 5. In an attempt to understand this higher-than-expected potency in humans and NHP, rat-derived Cb,u:Cp,u of PF-03654746 was integrated with Cp,u IC50 to identify unbound (neuro) potency of PF-03654746, nIC50. 6. The nIC50 of PF-03654746 was 2.1 nM in NHP and 0.66 nM in human which better correlated (1.1- and 3.49-fold lower) with in vitro human H3 Ki (2.3 nM). 7. This correlation of the nIC50 and in vitro hH3 Ki suggested the translation of net BBB equilibrium of PF-03654746 from rat to NHP and humans, and confirmed the use of Cp,u as a reliable surrogate of Cb,u. 8. Thus, nIC50 quantitatively informed the human Cb,u:Cp,u of PF-03654746.
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Ciclobutanos/farmacocinética , Antagonistas dos Receptores Histamínicos H3/farmacocinética , Pirrolidinas/farmacocinética , Animais , Transporte Biológico , Barreira Hematoencefálica , Encéfalo , Humanos , RatosRESUMO
Up to 14% of individuals with systemic AL amyloidosis develop acquired factor X deficiency, which occurs due to adsorption of factor X onto amyloid fibrils. Although baseline factor X levels are not predictive of bleeding risk in these patients, serious hemorrhagic complications can occur, particularly during invasive procedures. Optimal management strategies to attenuate bleeding risk in these patients are unknown. We describe our experience in the management of acquired factor X deficiency, secondary to systemic AL amyloidosis, in a case series of three patients who received prothrombin complex concentrates (PCCs) for treatment and prevention of bleeding events. We performed a retrospective review extracting information on baseline demographics, laboratory data, pharmacokinetic (PK) studies, and clinically documented bleeding events. Our case series demonstrates that individuals with acquired factor X deficiency secondary to amyloidosis have variable laboratory and clinical responses to PCCs. This is likely due to distinct amyloid loads and fibril sequences, leading to different binding avidities for factor X. Our data emphasize the importance of performing PK testing prior to any invasive procedures to determine the dose and frequency interval to achieve adequate factor X levels for hemostasis, given the variable response between individuals.
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Amiloidose , Fatores de Coagulação Sanguínea , Deficiência do Fator X , Adulto , Idoso , Amiloidose/sangue , Amiloidose/complicações , Amiloidose/tratamento farmacológico , Fatores de Coagulação Sanguínea/administração & dosagem , Fatores de Coagulação Sanguínea/farmacocinética , Deficiência do Fator X/sangue , Deficiência do Fator X/tratamento farmacológico , Deficiência do Fator X/etiologia , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: [(18)F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test-retest reproducibility of [(18)F]FPEB in the human brain. METHODS: Seven healthy male subjects were scanned twice, 3 - 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [(18)F]FPEB. Four methods were used to estimate volume of distribution (V T): equilibrium analysis (EQ) using arterial (EQA) or venous input data (EQV), MA1, and a two-tissue compartment model (2 T). Binding potential (BP ND) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test-retest variability (aTRV) of V T and BP ND were calculated for each method. Venous blood measurements (C V) were compared with arterial input (C A) to examine their usability in EQ analysis. RESULTS: Regional V T estimated by the four methods displayed a high degree of agreement (r (2) ranging from 0.83 to 0.99 among the methods), although EQA and EQV overestimated V T by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V T were 11 % by EQA, 12 % by EQV, 14 % by MA1 and 14 % by 2 T. Regional BP ND also agreed well among the methods and mean aTRV of BP ND was 8 - 12 % (CWM) and 7 - 9 % (CGM). Venous and arterial blood concentrations of [(18)F]FPEB were well matched during equilibrium (C V = 1.01 · C A, r (2) = 0.95). CONCLUSION: [(18)F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [(18)F]FPEB is an excellent PET imaging tracer for mGluR5 in humans.
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Encéfalo/metabolismo , Imagem Molecular/métodos , Nitrilas/administração & dosagem , Nitrilas/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Piridinas/administração & dosagem , Piridinas/farmacocinética , Receptor de Glutamato Metabotrópico 5/metabolismo , Adulto , Encéfalo/diagnóstico por imagem , Humanos , Infusões Intravenosas , Masculino , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Adulto JovemRESUMO
INTRODUCTION: Kappa opioid receptors (KOR) are implicated in several brain disorders. In this report, a first-in-human positron emission tomography (PET) study was conducted with the potent and selective KOR agonist tracer, [(11)C]GR103545, to determine an appropriate kinetic model for analysis of PET imaging data and assess the test-retest reproducibility of model-derived binding parameters. The non-displaceable distribution volume (V(ND)) was estimated from a blocking study with naltrexone. In addition, KOR occupancy of PF-04455242, a selective KOR antagonist that is active in preclinical models of depression, was also investigated. METHODS: For determination of a kinetic model and evaluation of test-retest reproducibility, 11 subjects were scanned twice with [(11)C]GR103545. Seven subjects were scanned before and 75 min after oral administration of naltrexone (150 mg). For the KOR occupancy study, six subjects were scanned at baseline and 1.5 h and 8 h after an oral dose of PF-04455242 (15 mg, n=1 and 30 mg, n=5). Metabolite-corrected arterial input functions were measured and all scans were 150 min in duration. Regional time-activity curves (TACs) were analyzed with 1- and 2-tissue compartment models (1TC and 2TC) and the multilinear analysis (MA1) method to derive regional volume of distribution (V(T)). Relative test-retest variability (TRV), absolute test-retest variability (aTRV) and intra-class coefficient (ICC) were calculated to assess test-retest reproducibility of regional VT. Occupancy plots were computed for blocking studies to estimate occupancy and V(ND). The half maximal inhibitory concentration (IC50) of PF-04455242 was determined from occupancies and drug concentrations in plasma. [(11)C]GR103545 in vivo K(D) was also estimated. RESULTS: Regional TACs were well described by the 2TC model and MA1. However, 2TC VT was sometimes estimated with high standard error. Thus MA1 was the model of choice. Test-retest variability was ~15%, depending on the outcome measure. The blocking studies with naltrexone and PF-04455242 showed that V(T) was reduced in all regions; thus no suitable reference region is available for the radiotracer. V(ND) was estimated reliably from the occupancy plot of naltrexone blocking (V(ND)=3.4±0.9 mL/cm(3)). The IC50 of PF-04455242 was calculated as 55 ng/mL. [(11)C]GR103545 in vivo K(D) value was estimated as 0.069 nmol/L. CONCLUSIONS: [(11)C]GR103545 PET can be used to image and quantify KOR in humans, although it has slow kinetics and variability of model-derived kinetic parameters is higher than desirable. This tracer should be suitable for use in receptor occupancy studies, particularly those that target high occupancy.
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Compostos de Bifenilo/farmacocinética , Piperazinas , Pirrolidinas , Receptores Opioides kappa/efeitos dos fármacos , Sulfonamidas/farmacocinética , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Piperazinas/farmacocinética , Tomografia por Emissão de Pósitrons , Pirrolidinas/farmacocinética , Receptores Opioides kappa/antagonistas & inibidores , Receptores Opioides kappa/metabolismo , Reprodutibilidade dos TestesRESUMO
Anterior knee pain is a common musculoskeletal complaint that is often due to an excessively tight lateral retinaculum, which normally plays a role in patellar tracking and stabilization. Several etiologies underlie lateral soft-tissue tightness in the knee, including lateral patellar compression syndrome, patellofemoral arthritis, patellofemoral instability, and patellofemoral pain syndrome. Stretching the lateral retinaculum through conservative treatment may be helpful, but lateral retinacular lengthening may be indicated. Since this surgical procedure has classically been performed in an open fashion, the purpose of this Technical Note is to describe an arthroscopic technique designed to limit complications, improve patient outcomes, and reduce operative and recovery times.
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Octocrylene is a common sun filter ingredient used to protect the skin from damaging UV rays. Benzophenone is an impurity found in formulations containing octocrylene. [14C]-Benzophenone was spiked (0.1 g/L) into 2 commercial sunscreen formulations; Neutrogena® Beach Defense Sunscreen Spray Broad Spectrum SPF 70 Aerosol, Neutrogena® Ultra Sheer Body Mist Sunscreen Broad Spectrum SPF 30 Aerosol, and an acetone vehicle. The formulations were applied (ca 2 µL/cm2) to dermatomed human skin mounted in static diffusion cells in vitro. Receptor fluid was collected up to 24 h post dose. All samples were analyzed by liquid scintillation counting. The dermal delivery of [14C]-Benzophenone was 10.02, 9.04 and 5.19% for the 3 formulations. However, the [14C]-Benzophenone mass balances were low; 81.5, 85.3 and 8.02%, respectively. A volatility test was performed replacing skin with aluminum foil for the sunscreen formulations only. The [14C]-Benzophenone mass balance at dosing was 99% but fell to 56.9 and 60.6% at 24 h post dose, confirming the losses were due to [14C]-Benzophenone volatility. A conservative dermal absorption value of 12.42% was proposed to cover [14C]-Benzophenone containing formulations.
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Benzofenonas , Radioisótopos de Carbono , Absorção Cutânea , Pele , Protetores Solares , Benzofenonas/farmacocinética , Benzofenonas/administração & dosagem , Humanos , Protetores Solares/farmacocinética , Protetores Solares/química , Protetores Solares/administração & dosagem , Pele/metabolismo , Técnicas In Vitro , Acrilatos/química , Acrilatos/farmacocinéticaRESUMO
OBJECTIVE: To update estimates of cancer risk in SLE relative to the general population. METHODS: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). CONCLUSION: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
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Lúpus Eritematoso Sistêmico/epidemiologia , Neoplasias/epidemiologia , Adulto , Ásia/epidemiologia , Neoplasias da Mama/epidemiologia , Canadá/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Cooperação Internacional , Linfoma não Hodgkin/epidemiologia , Masculino , Neoplasias Ovarianas/epidemiologia , Risco , Estados Unidos/epidemiologiaRESUMO
Shoulder instability is the separation of the humeral head from the glenoid. Injury to the static and dynamic stabilizers can result in instability. Anterior shoulder instability is the predominant form of instability. It is usually a result of trauma. Posterior shoulder instability often presents with an insidious onset of pain. Multidirectional instability of the shoulder is symptomatic laxity in more than one plane of motion. The primary goal of rehabilitation is to restore pain-free mobility, strength, and functioning. Rehabilitation implements range of motion and strengthening exercises to restore proprioceptive control and scapular kinematics.
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Instabilidade Articular , Articulação do Ombro , Humanos , Ombro , Instabilidade Articular/terapia , Escápula , Modalidades de Fisioterapia , Amplitude de Movimento Articular , Fenômenos BiomecânicosRESUMO
The foundation of preventing and treating an on-field emergency is preparation and readiness. The sideline medical team should coordinate the utilization of an emergency action plan (EAP). A successful EAP is accomplished through attention to detail, rehearsal, and self-assessments. Every EAP should include site-specific implementation, personnel, equipment, communication, transportation, venue location, emergency care facilities, and documentation. Improvements and advancements can be made to the EAP by self-evaluation after each on-field emergency and yearly reviews. A competent sideline emergency medical team can enjoy the competition while being ready to respond to a catastrophic on-field emergency.
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Serviços Médicos de Emergência , Medicina Esportiva , Esportes , Humanos , EmergênciasRESUMO
Arthroscopic subscapularis repair continues to improve with the advancement of surgical technique and critical focus on careful intraoperative evaluation. As identification of these tears increases, there is an expected increase in repair rates as well. Anatomically, the upper border of the subscapularis and the long head of the biceps (LHB) tendon are in close relation. Many surgeons have advocated concomitant LHB tenotomy versus tenodesis in conjunction with operative subscapularis tears. We hypothesized that in the setting of a preserved anatomic biceps pulley and no LHB pathology, isolated subscapularis repair would result in excellent clinical outcomes when compared with subscapularis repair and biceps tenotomy or tenodesis.