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INTRODUCTION: The current literature describes various operative stabilization strategies which achieve good clinical outcomes after acute acromioclavicular joint (ACJ) dislocation. The aim of this study was to compare the mid-term clinical and sonographic treatment outcomes after minimally invasive mini-open and arthroscopic reconstruction. MATERIALS AND METHODS: We conducted a retrospective two-center study of patients with acute ACJ dislocation. Surgical treatment was performed using either a mini-open approach (MIOP) or an arthroscopic technique (AR). The primary outcome parameters of this study were the sonographically measured acromioclavicular (ACD) and coracoclavicular distances (CCD). Secondary outcome parameters included the Constant-Murley score (CS), range of motion (ROM), postoperative pain scale (VAS), return to daily routine, return to sports, complications, as well as operative revisions. RESULTS: After a mean follow-up of 29 months, 30 patients were included in this study with an average age of 41.3 ± 14.8 years (MIOP) and 41.2 ± 15.4 years (AR). The sonographic ACD (MIOP 9.11 mm vs. AR 8.93 mm, p = 0.41) and CCD (MIOP 25.08 mm vs. AR 24.36 mm, p = 0.29) distances showed no statistically significant differences. Furthermore, there was no statistically significant difference when compared to the contralateral side (p = 0.42). With both techniques, patients achieved excellent clinical outcome parameters without statistically significant differences in CS (MIOP 95 vs. AR 97, p = 0.11) and VAS (MIOP 1.76 vs. AR 1.14, p = 0.18). The return to daily activity and return to sport rates did not differ. There were neither complications nor revisions in both groups. CONCLUSION: Both minimally invasive techniques for acute ACJ stabilization achieved excellent clinical and sonographic outcomes without one technique being statistically superior to the other.
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Articulação Acromioclavicular , Artroplastia de Substituição , Luxações Articulares , Luxação do Ombro , Humanos , Adulto , Pessoa de Meia-Idade , Articulação Acromioclavicular/diagnóstico por imagem , Articulação Acromioclavicular/cirurgia , Luxações Articulares/cirurgia , Estudos Retrospectivos , Artroscopia/métodos , Luxação do Ombro/cirurgia , Resultado do TratamentoRESUMO
There is growing need for new drug delivery systems for intracochlear application of drugs to effectively treat inner ear disorders. In this study, we describe the development and characterization of biodegradable, triamcinolone-loaded implants based on poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) respectively, prepared by hot-melt extrusion. PEG 1500 was used as a plasticizer to improve flexibility and accelerate drug release. The sterilization process was performed by electron beam irradiation, resulting in minimal but acceptable polymer degradation for PEG-PLGA implants. The implants have been characterized by texture analysis, differential scanning calorimetry and X-ray powder diffraction. Compared to PLGA implants, PEG-PLGA implants offer similar flexibility but with improved mechanical stability, which will ease the handling and intracochlear application. A controlled release over three months was observed for dexamethasone and triamcinolone extrudates (drug load of 10%) with similar release profiles for both drugs. PEG-PLGA implants showed an initial slow release rate over several days regardless of the amount of PEG added. Mathematical simulations of the pharmacokinetics of the inner ear based on the in vitro release kinetics indicate a complete distribution of triamcinolone in the whole human scala tympani, which underlines the high potential of the developed formulation.
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Ácido Láctico , Ácido Poliglicólico , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Preparações Farmacêuticas , Ácido Poliglicólico/química , Ácido Láctico/química , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Portadores de Fármacos , Implantes de MedicamentoRESUMO
PURPOSE: Biomechanical evaluation of three different suture button devices used in acromioclavicular joint repair and analysis of their effect on post-testing tunnel widening. METHODS: Eighteen human shoulder girdles were assigned into three groups with a similar mean bone mineral density. Three different single-tunnel acromioclavicular repair devices were tested: (1) AC TightRope® with FiberWire; (2) AC Dog Bone™ Button with FiberTape; (3) Low Profile AC Repair System. Biomechanical testing was performed simulating the complex movement of the distal clavicle as follows. A vertical load of 80 N was applied continuously. The rotation of the clavicle about its long axis was set at 10° anterior and 30° posterior for 2500 cycles at 0.25 Hz. The horizontal translation of the clavicle was set at 6 mm medial and 6 mm lateral for 10,000 cycles at 1 Hz. The coracoclavicular distance was measured before and after testing. After testing, each sample underwent micro-CT analysis. Following 3D reconstruction, the area of the bone tunnels was measured at five defined cross sections. RESULTS: In TightRope® and Dog Bone™ groups, all samples completed testing, whereas in the Low Profile group, three out of six samples showed system failure. The mean absolute difference of coracoclavicular distance after testing was significantly greater in the Low Profile group compared to TightRope® and Dog Bone™ groups (4.3 ± 1.3 mm vs 1.9 ± 0.7 mm vs 1.9 ± 0.8 mm; p = 0.001). Micro-CT analysis of the specimens demonstrated significant tunnel widening in the inferior clavicular and superior coracoid regions in all three groups (p < 0.05). CONCLUSION: Significant tunnel widening can be observed for all devices and is primarily found in the inferior parts of the clavicle and superior parts of the coracoid. The Low Profile AC Repair System showed inferior biomechanical properties compared to the AC TightRope® and AC Dog Bone™ devices. Therefore, clinicians should carefully select the type of acromioclavicular repair device used and need to consider tunnel widening as a complication.
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Articulação Acromioclavicular , Luxações Articulares , Humanos , Articulação Acromioclavicular/cirurgia , Clavícula/cirurgia , Extremidade Superior/cirurgia , Técnicas de Sutura , Suturas , Luxações Articulares/cirurgia , Ligamentos Articulares/cirurgia , CadáverRESUMO
OBJECTIVE: Stepwise reconstruction of knee stability and physiological kinematics in acute knee dislocation. INDICATIONS: The operative technique is demonstrated in a case of multiligamentous injury of the knee with involvement of both cruciate ligaments and additional medial and lateral peripheral injuries (type IV according to Schenck classification). CONTRAINDICATIONS: Critical soft tissue conditions, infections, old age, obesity, lack of compliance. SURGICAL TECHNIQUE: Time-limited arthroscopy in order to primarily identify and treat posterior horn/root injuries of the meniscus and concomitant intra-articular injuries. Anatomical placement of anterior cruciate ligament (ACL) drill wires for later ACL tunnel drilling is arthroscopically guided. Subsequent conversion to an anteromedial arthrotomy and ligament bracing of the posterior cruciate ligament. The ACL is reconstructed using the ipsilateral semitendinosus tendon. Medial and lateral peripheral injures are anatomically reconstructed followed by a posterolateral augmentation in a technique described by Arciero. FOLLOW-UP: Limited weight bearing for 6 weeks and stepwise increase of flexion using a standard knee brace and close clinical monitoring. EVIDENCE: Ligament bracing of both cruciate ligaments is an established treatment technique in acute knee dislocations and has been proven to achieve good to excellent clinical results. In an ongoing clinical study primary ACL reconstruction as a modified treatment approach indicated superior stability in a 12-month follow-up in patients with acute knee dislocations.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Luxação do Joelho , Ligamento Cruzado Posterior , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Artroscopia , Humanos , Luxação do Joelho/cirurgia , Articulação do Joelho/cirurgia , Ligamento Cruzado Posterior/cirurgia , Resultado do TratamentoRESUMO
Drug delivery to the inner ear is an important and very challenging field. The cochlea is protected by several barriers that need to be overcome in the drug delivery process. Local drug delivery can avoid undesirable side effects arising from systemic drug delivery. We developed a biodegradable dexamethasone-loaded Round Window (RW) Disk based on poly(D,L-lactic-co-glycolic acid) (PLGA) for local drug therapy to the inner ear by RW membrane administration by a film-casting method. The optimal drying time was characterized by thermogravimetric analysis and differential scanning calorimetry. In addition, the mass and polymer degradation over time of drug release was measured in vitro showing a total mass loss of 70% after 3 weeks. Dexamethasone release was determined by a RW model setup using a polyethylene terephthalate membrane. We achieved a controlled release over 52 days. Ex vivo implantation of a RW Disk onto a guinea pig RW membrane indicated well-fitting properties of the drug delivery device leading to a close surface contact with the membrane and the successful proof of concept. The developed RW Disks could be new and promising drug delivery device to achieve effective local drug delivery to the inner ear for an extended time.
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Orelha Interna , Janela da Cóclea , Animais , Dexametasona , Sistemas de Liberação de Medicamentos , Cobaias , Ácido LácticoRESUMO
Cationic liposomes composed of a novel lipid (N-{6-amino-1-[N-(9Z) -octadec9-enylamino] -1-oxohexan-(2S) -2-yl} -N'- {2- [N, N-bis(2-aminoethyl) amino] ethyl} -2-hexadecylpropandiamide) (OO4) and dioleoylphosphatidylethanolamine (DOPE) possess high amounts of amino groups and are promising systems for lipofection. Moreover, these cationic liposomes can also be used as a polycationic entity in multilayer formation using layer-by-layer technique (LbL), which is a method to fabricate surface coatings by alternating adsorption of polyanions and polycations. Since liposomes are suitable for endocytosis by or fusion with cells, controlled release of their cargo on site is possible. Here, a polyelectrolyte multilayer (PEM) system was designed of chondroitin sulfate (CS) and collagen type I (Col I) by LbL technique with OO4/DOPE liposomes embedded in the terminal layers to create an osteogenic microenvironment. Both, the composition of PEM and cargo of the liposomes were used to promote osteogenic differentiation of C2C12 myoblasts as in vitro model. The internalization of cargo-loaded liposomes from the PEM into C2C12 cells was studied using lipophilic (Rhodamine-DOPE conjugate) and hydrophilic (Texas Red-labeled dextran) model compounds. Besides, the use of Col I and CS should mimic the extracellular matrix of bone for future applications such as bone replacement therapies. Physicochemical studies of PEM were done to characterize the layer growth, thickness, and topography. The adhesion of myoblast cells was also evaluated whereby the benefit of a cover layer of CS and finally Col I above the liposome layer was demonstrated. As proof of concept, OO4/DOPE liposomes were loaded with dexamethasone, a compound that can induce osteogenic differentiation. A successful induction of osteogenic differentiation of C2C12 cells with the novel designed liposome-loaded PEM system was shown. These findings indicate that designed OH4/DOPE loaded PEMs have a high potential to be used as drug delivery or transfection system for implant coating in the field of bone regeneration and other applications.
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The effective treatment of diseases of the inner ear is currently an unmet medical need. Local controlled drug delivery to the cochlea is challenging due to the hidden location, small volume and high sensitivity of this organ. A local intracochlear delivery of drugs would avoid the problems of intratympanic (extracochlear) drug application, but is more invasive. The requirements for such a delivery system include a small size and appropriate flexibility. The delivery device must be rigid enough for surgical handling but also flexible to avoid traumatizing cochlear structures. We developed biodegradable dexamethasone loaded PLGA extrudates for the controlled intracochlear release. In order to achieve the desired flexibility, Polyethylene glycol (PEG) was used as a plasticizer. In addition to the drug release, the extrudates were characterized in vitro by differential scanning calorimetry (DSC) and texture analysis. Simulation of the pharmacokinetics of the inner ear support the expectation that a constant perilymph drug level is obtained after few hours and retained over several weeks. Ex vivo implantation of the extrudates into a guinea pig cochlea indicate that PEG containing extrudates have the desired balance between mechanical strength and flexibility for direct implantation into the cochlea. The location of the implant was visualized by computer tomography. In summary, we postulate that intracochlear administration of drug releasing biodegradable implants is a new and promising approach to achieve local drug delivery to the cochlea for an extended time.
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The linear polyester poly(glycerol adipate) (PGA) with its free pendant hydroxyl groups was covalently grafted with indomethacin which yields polymeric prodrugs. It was possible to produce nanospheres with narrow particle size distribution of these polymer-drug conjugates with an optimized interfacial deposition method. Nanospheres were characterized by zeta potential measurements, dynamic light scattering, electron microscopy and nanoparticle tracking analysis. Moreover, cell viability studies and cytotoxicity tests in three different cell lines were carried out showing low toxicity for three different degrees of grafting. In addition, the nanospheres had (in contrast to the free drug) low hemolytic activity in vitro. Release studies of nanodispersions are challenging. The use of a specially developed setup with highly porous aluminum oxide membranes enabled us to overcome problems associated with other setups (e.g. dialysis membranes). A slow and controlled release profile without any burst was observed over 15â¯days. The results indicate that indomethacin-PGA conjugates can be formulated successfully as nanospheres with the desired characteristics of small size with narrow distribution, controlled drug release and low toxicity. The newly developed particles have the potential to improve the therapy of inflammation and associated diseases.
Assuntos
Inibidores de Ciclo-Oxigenase/química , Portadores de Fármacos , Indometacina/química , Nanopartículas , Poliésteres/química , Células A549 , Óxido de Alumínio/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica/métodos , Inibidores de Ciclo-Oxigenase/toxicidade , Preparações de Ação Retardada , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Indometacina/toxicidade , Cinética , Células LLC-PK1 , Membranas Artificiais , Nanotecnologia , Poliésteres/toxicidade , Porosidade , Solubilidade , SuínosRESUMO
OBJECTIVE: Mechanical overloading induces a degenerative cell response in the intervertebral disc. However, early changes in the extracellular matrix (ECM) are challenging to assess with conventional techniques. Fourier Transform Infrared (FTIR) imaging allows visualization and quantification of the ECM. We aim to identify markers for disc degeneration and apply these to investigate early degenerative changes due to overloading and katabolic cell activity. DESIGN: Three experiments were conducted; Exp 1.: In vivo, lumbar spines of seven goats were operated: one disc was injected with chondroitinase ABC [cABC (mild degeneration)] and compared to the adjacent disc (control) after 24 weeks. Exp 2a: Ex vivo, caprine discs received physiological loading (n = 10) or overloading (n = 10) in a bioreactor. Exp 2b: Cell activity was diminished prior to testing by freeze-thaw cycles, 18 discs were then tested as in Exp 2a. In all experiments, FTIR images (spectral region: 1000-1300 cm-1) of mid-sagittal slices were analyzed using multivariate curve resolution. RESULTS: In vivo, FTIR was more sensitive than biochemical and histological analysis in identifying reduced proteoglycan content (P = 0.046) and increased collagen content in degenerated discs (P < 0.01). Notably, FTIR analysis additionally showed disorganization of the ECM, indicated by increased collagen entropy (P = 0.011). Ex vivo, the proteoglycan/collagen ratio decreased due to overloading (P = 0.047) and collagen entropy increased (P = 0.047). Cell activity affected collagen content only (P = 0.044). CONCLUSION: FTIR imaging allows a more detailed investigation of early disc degeneration than traditional measures. Changes due to mild overloading could be assessed and quantified. Matrix remodeling is the first detectable step towards intervertebral disc degeneration.
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Colágeno/metabolismo , Matriz Extracelular/metabolismo , Degeneração do Disco Intervertebral/diagnóstico , Disco Intervertebral/metabolismo , Vértebras Lombares/diagnóstico por imagem , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Modelos Animais de Doenças , Cabras , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismoRESUMO
The linear biodegradable polyester poly(glycerol adipate) (PGA) was synthesized via enzymatic polycondensation using lipase B from Candida antarctica (CAL-B). Every monomer unit of PGA possesses a pendant hydroxyl group which is responsible for the hydrophilic character and moisture swelling. These OH groups were esterified to different degrees with the anti-inflammatory drug indomethacin in order to create a prodrug with a pH-sensitive linker for modified drug release. The structure of the conjugates was determined via ATR FT-IR spectroscopy, NMR spectroscopy, GPC and UV/VIS spectroscopy. The physical properties of polymers with different drug load were investigated using DSC, contact angle measurements and oscillatory rheology. Drug release was monitored over one month in vitro. A very slow, but continuous release was observed in PBS. Slightly acidic conditions and lipase activity are accelerating the indomethacin release. Therefore, poly(glycerol adipate) - indomethacin conjugates are promising prodrugs for the local sustained release of indomethacin.
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Composição de Medicamentos , Indometacina/química , Poliésteres/química , Preparações de Ação Retardada , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In-situ forming implant formulations based on poly(lactic-co-glycolic acid) (PLGA), acetyltributyl citrate (ATBC), minocycline HCl, N-methyl pyrrolidone (NMP) and optionally hydroxypropyl methylcellulose (HPMC) were prepared and thoroughly characterized in vitro. This includes electron paramagnetic resonance (EPR), nuclear magnetic resonance ((1)H NMR), mass change and drug release measurements under different conditions, optical microscopy, size exclusion chromatography (SEC) as well as antibacterial activity tests using gingival crevicular fluid samples from periodontal pockets of periodontitis patients. Based on these results, deeper insight into the physico-chemical phenomena involved in implant formation and the control of drug release could be gained. For instance, the effects of adding HPMC to the formulations, resulting in improved implant adherence and reduced swelling, could be explained. Importantly, the in-situ formed implants effectively hindered the growth of bacteria present in the patients' periodontal pockets. Interestingly, the systems were more effectively hindering the growth of pathogenic bacterial strains (e.g., Fusobacterium nucleatum) than that of strains with a lower pathogenic potential (e.g., Streptococcus salivarius). In vivo, such a preferential action against the pathogenic bacteria can be expected to give a chance to the healthy flora to re-colonize the periodontal pockets.
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Antibacterianos/administração & dosagem , Implantes de Medicamento/química , Derivados da Hipromelose/química , Ácido Láctico/química , Minociclina/administração & dosagem , Periodontite/tratamento farmacológico , Ácido Poliglicólico/química , Adesividade , Antibacterianos/química , Antibacterianos/farmacologia , Composição de Medicamentos , Liberação Controlada de Fármacos , Fusobacterium/efeitos dos fármacos , Fusobacterium/crescimento & desenvolvimento , Humanos , Testes de Sensibilidade Microbiana , Minociclina/química , Minociclina/farmacologia , Bolsa Periodontal/microbiologia , Periodontite/microbiologia , Transição de Fase , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade , Solventes/química , Streptococcus/efeitos dos fármacos , Streptococcus/crescimento & desenvolvimento , Propriedades de SuperfícieRESUMO
OBJECTIVE: The aim of this study was to establish and evaluate (colour Doppler-) high-resolution-ultrasound (hrUS) and bench-top magnetic resonance imaging (btMRI) as new methods to monitor experimental colitis. MATERIALS AND METHODS: hrUS, btMRI and endoscopy were performed in mice without colitis (n = 15), in mice with acute colitis (n = 14) and in mice with acute colitis and simultaneous treatment with infliximab (n = 19). RESULTS: Determination of colon wall thickness using hrUS (32 MHz) and measurement of the cross-sectional colonic areas by btMRI allowed discrimination between the treatment groups (mean a vs. b vs. c - btMRI: 922 vs. 2051 vs. 1472 pixel, hrUS: 0.26 vs. 0.45 vs. 0.31 mm). btMRI, endoscopy, hrUS and colour Doppler-hrUS correlated to histological scoring (p < 0.05), while endoscopy and btMRI correlated to post-mortem colon length (p < 0.05). CONCLUSIONS: The innovative in vivo techniques btMRI and hrUS are safe and technically feasible. They differentiate between distinct grades of colitis in an experimental setting, and correlate with established post-mortem parameters. In addition to endoscopic procedures, these techniques provide information regarding colon wall thickness and perfusion. Depending on the availability of these techniques, their application increases the value of in vivo monitoring in experimental acute colitis in small rodents. KEY POINTS: ⢠Improved in vivo monitoring might balance interindividual differences in murine colitis. ⢠In monitoring murine colitis, btMRI and hrUS are safe and technically feasible. ⢠Very short examination times underline the usefulness especially of hrUS. ⢠Results of btMRI and hrUS correlate with endoscopic and post-mortem findings.
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Colite/diagnóstico , Doença Aguda , Animais , Colite/induzido quimicamente , Colo/irrigação sanguínea , Colonoscopia/métodos , Estudos Transversais , Sulfato de Dextrana/toxicidade , Diagnóstico Diferencial , Estudos de Viabilidade , Fármacos Gastrointestinais/farmacologia , Infliximab/farmacologia , Irritantes/toxicidade , Imageamento por Ressonância Magnética/métodos , Masculino , Camundongos Endogâmicos BALB C , Imagem Multimodal/métodos , Ultrassonografia Doppler em CoresRESUMO
Periodontitis is the primary cause of tooth loss in adults and a very wide-spread disease. Recently, composite implants, based on a drug release rate controlling polymer and an adhesive polymer, have been proposed for an efficient local drug treatment. However, the processes involved in implant formation and the control of drug release in these composite systems are complex and the relationships between the systems' composition and the implants' performance are yet unclear. In this study, advanced characterization techniques (e.g., electron paramagnetic resonance, EPR) were applied to better understand the in-situ forming implants based on: (i) different types of poly(lactic-co-glycolic acid) (PLGA) as drug release rate controlling polymers; (ii) hydroxypropyl methylcellulose (HPMC) as adhesive polymer; and (iii) doxycycline or metronidazole as drugs. Interestingly, HPMC addition to shorter chain PLGA slightly slows down drug release, whereas in the case of longer chain PLGA the release rate substantially increases. This opposite impact on drug release was rather surprising, since the only difference in the formulations was the polymer molecular weight of the PLGA. Based on the physico-chemical analyses, the underlying mechanisms could be explained as follows: since longer chain PLGA is more hydrophobic than shorter chain PLGA, the addition of HPMC leads to a much more pronounced facilitation of water penetration into the system (as evidenced by EPR). This and the higher polymer lipophilicity result in more rapid PLGA precipitation and a more porous inner implant structure. Consequently, drug release is accelerated. In contrast, water penetration into formulations based on shorter chain PLGA is rather similar in the presence and absence of HPMC and the resulting implants are much less porous than those based on longer chain PLGA.
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Adesivos/química , Antibacterianos/química , Implantes de Medicamento , Derivados da Hipromelose/química , Ácido Láctico/química , Ácido Poliglicólico/química , Adulto , Idoso , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Química Farmacêutica , Doxiciclina/química , Doxiciclina/farmacologia , Liberação Controlada de Fármacos , Feminino , Líquido do Sulco Gengival/microbiologia , Humanos , Masculino , Metronidazol/química , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Periodontite/tratamento farmacológico , Periodontite/microbiologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , PorosidadeRESUMO
PURPOSE: To assess the accuracy of surgeons in identifying elbow rotation axis (RA) on fluoroscopic images and to measure the interobserver variability. METHODS: Five healthy subjects underwent 3-dimensional computed tomography (CT) analysis of their nondominant elbow. Real-time rotation software enabled surgeons to approximate the elbow RA on CT-reconstructed fluoroscopy, which was repeated twice with different starting positions to increase the number of observations. The surgeons used anatomical landmarks of choice. Analysis of variance (ANOVA) was used to determine structural error differences between surgeons, and intraclass correlation coefficients (ICCs) were used to determine the corresponding interobserver variability. RESULTS: Eight subspecialty-trained trauma surgeons (P.K., N.W.L.S., V.M.d.J., P.J., G.M.K., R.W.P., T.S., B.A.v.D.) participated and attempted to identify the RA on reconstructed fluoroscopy. A total of 15 RA definitions on 5 elbows were recorded per surgeon. The surgeons had a mean rotational error of 5° (range, < 1°-13°) and mean translational error of 1 mm (range, < 1-8 mm), compared with the true elbow RA as measured by the 3-dimensional CT analysis. The ANOVA showed structural differences between surgeons in rotational and translational errors, indicating that some surgeons consistently had more accurately identified the elbow RA than others. The ICC was 0.12 for rotational error and 0.10 for translational error, indicating a large interobserver variability. CONCLUSIONS: We show in this in vivo study that identification of the elbow RA on fluoroscopy is associated with substantial rotational errors and large inconsistencies among surgeons. Implementation of standardized anatomical landmarks is required to improve surgeons' accuracy. These landmarks should preferably take into account both the coronal and the sagittal planes, using the orientation of the capitellum and trochlea as well as the posterior distal humeral cortex. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.
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Articulação do Cotovelo/diagnóstico por imagem , Adulto , Pontos de Referência Anatômicos , Articulação do Cotovelo/fisiologia , Articulação do Cotovelo/cirurgia , Fluoroscopia , Voluntários Saudáveis , Humanos , Imageamento Tridimensional , Masculino , Variações Dependentes do Observador , Interpretação de Imagem Radiográfica Assistida por Computador , Rotação , Software , Tomografia Computadorizada por Raios XRESUMO
Utilizing poorly soluble drug candidates in pharmacokinetic studies remains challenging in preclinical drug development. We investigated a nanosuspension-based delivery system to achieve constant drug plasma levels by applying the nanoparticles via subcutaneously implanted micro-osmotic pumps. Various nanosuspension formulations were characterized in vitro prior to Alzet® pump release by means of dynamic light scattering (DLS), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and rheological measurements. In vitro formulation release was checked by HPLC/UV. The in vivo experiments compared plasma-concentration time profiles of subcutaneously injected nanosuspensions with those of formulations delivered by pumps. Two Poloxamer 338 containing nanosuspensions with different viscosities were found to be stable over observation time, physically resistant against biorelevant media and showed only a low amorphous part after preparation. The more viscous nanosuspension with 31.65 mPas revealed in vitro the expected zero-order release, while the low viscous formulation with 2.18 mPas showed first order release. In in vivo experiments, the higher viscous nanosuspension released from osmotic pumps exhibited elevated plasma levels compared to the lower viscous formulation. Compared to bolus injected nanosuspensions constant plasma levels could be maintained by adapting the viscosity of the nanosuspension. Subcutaneously implanted osmotic pumps prove to be a valuable delivery system for nanosuspensions in pharmacokinetic studies by consideration of the key parameter viscosity in release kinetics.
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Sistemas de Liberação de Medicamentos , Nanopartículas , Preparações Farmacêuticas/administração & dosagem , Animais , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Implantes de Medicamento , Estabilidade de Medicamentos , Feminino , Injeções Subcutâneas , Luz , Camundongos , Microscopia Eletrônica de Varredura , Osmose , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Poloxâmero/química , Reologia , Espalhamento de Radiação , Solubilidade , Suspensões , Fatores de Tempo , ViscosidadeRESUMO
In research and development sufficiently high and constant plasma levels of drug candidates are often requested, but simple solutions of hydrophobic drugs delivered from the commonly used micro-osmotic pumps cannot meet these demands. Nanosuspensions released from implanted osmotic devices can be a strategy to overcome this challenge but little is known about their pharmacokinetic behavior after subcutaneous application. In the current study, four different nanosuspension formulations containing iodinated fenofibrate were prepared, physicochemically characterized and investigated concerning their in-vitro release kinetics from osmotic pumps. One nanosuspension of lower viscosity exhibited thereby an unexpectedly first order release kinetics, whereas the higher viscous counterpart was released in the expected zero-order manner. To assess the relation of the in-vitro release kinetics to the in-vivo fate of nanosuspensions, various [(131)I] iodinated fenofibrate formulations were subcutaneously applied to mice. The biodistribution was followed by means of γ-scintigraphy and γ-scintillation. Two different nanosuspensions released from osmotic pumps were compared to bolus injections of a nanosuspension and an organic drug solution. The distribution and elimination of the bolus injected drug solution were almost completed within 48h. In contrast, a long lasting (>1week) depot at the injection site was formed by the bolus injected nanosuspension. Ex vivo examination of the organs showed a sustained, but exponential decrease of the radiolabel concentration. More constant drug levels in the organs were achieved within the nanosuspensions released from osmotic pumps. The organ levels of [(131)I] labeled fenofibrate were found to be more constant in case of the pump with the higher viscous nanosuspension in contrast to the lower viscous counterpart. However, the very different release profiles of the lower and higher viscous nanosuspension observed in-vitro were not observed in-vivo, as both pumps showed zero order release. In conclusion, nanosuspensions of poorly soluble compounds released from subcutaneously implanted osmotic pumps can be a suitable approach in pharmacokinetic studies. Although the in-vivo release of nanosuspensions differed in the expected release profile from the in-vitro test results, these in-vitro release tests present a valuable tool for the pre-selection of suitable nanosuspension candidates.
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Fenofibrato/administração & dosagem , Bombas de Infusão Implantáveis , Animais , Sistemas de Liberação de Medicamentos , Feminino , Fenofibrato/química , Fenofibrato/farmacocinética , Isótopos de Iodo/química , Camundongos , Nanoestruturas , Suspensões , Distribuição TecidualRESUMO
Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to investigate the effects of three fatty acid esters on skin permeation. Propylene glycol diperlargonate (DPPG), isopropyl myristate (IPM) and isostearyl isostearate (ISIS) were selected as pharmaceutically relevant solvents with a range of lipophilicities and cyanophenol (CNP) was used as a model drug. The resultant data were compared with that obtained when water was used as the solvent. The diffusion of CNP, DPPG and IPM across epidermis was successfully described by a Fickian model. When ISIS was used as a solvent Fickian behaviour was only obtained across isolated stratum corneum suggesting that the hydrophilic layers of the epidermis interfere with the permeation of the hydrophobic ISIS. The diffusion coefficients of CNP across epidermis in the different solvents were not significantly different. Using chemometric data analysis diffusion profiles for the solvents were deconvoluted from that of the skin and modelled. Each of these solvents was found to diffuse at a faster rate across the skin than CNP. DPPG considerably increased the concentration of CNP in the stratum corneum in comparison with the other solvents indicating strong penetration enhancer potential. In contrast IPM produced a similar CNP concentration in the stratum corneum to water with ISIS resulting in a lower CNP concentration suggesting negligible enhancement and penetration retardation effects for these two solvents respectively.
Assuntos
Ácidos Graxos/administração & dosagem , Fenóis/administração & dosagem , Pele/metabolismo , Solventes/administração & dosagem , Difusão , Ácidos Graxos/química , Feminino , Humanos , Fenóis/química , Absorção Cutânea/efeitos dos fármacos , Solventes/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Although neonatal bloodstream infections may be caused by a variety of fungi, invasive fungaemia due to Candida pulcherrima in a premature neonate has not been previously reported. We describe such a case in which antifungal susceptibility test data led to successful therapy. A colonized catheter used for parenteral nutrition is presumed to have been the main source of this persistent infection.
Assuntos
Candida/classificação , Candida/isolamento & purificação , Candidemia/microbiologia , Doenças do Prematuro/microbiologia , Antifúngicos/uso terapêutico , Candida/genética , Candidemia/tratamento farmacológico , DNA Espaçador Ribossômico/análise , DNA Espaçador Ribossômico/genética , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
A stiff elbow is usually defined as having less than 30° in extension or less than 130° in flexion. Most activities of daily living are possible if the elbow has a range of motion of 100° (30-130° of flexion, Morrey's arc of motion). Loss of mobility of the elbow is not uncommon after trauma, burns or coma and severely impairs upper limb function. Loss of mobility may be difficult to avoid and is challenging to treat. Detailed analysis of the etiology and diagnostic evaluation is of utmost importance for planning any surgical intervention for elbow stiffness. Current operative techniques, such as closed distraction with external fixation (arthroplasty), are presented and evaluated. Elbow arthrolysis is a technically demanding procedure but if the indications and techniques are used correctly and the surgeon, physiotherapist and even the patient are familiar with the procedure, good long-term results may be achieved. Contraindications are poor compliance, poorly controlled diabetes mellitus, active hepatitis B and C infections, HIV infection and acute articular infections.
Assuntos
Artroplastia de Substituição do Tornozelo/métodos , Lesões no Cotovelo , Articulação do Cotovelo/cirurgia , Instabilidade Articular/cirurgia , Osteogênese por Distração/métodos , HumanosRESUMO
Closed and open dislocations of the knee joint with vascular and nerve injuries are treated immediately and may present an indication for external fixation. In acute trauma definitive treatment and reconstruction of the complex capsule and ligamentous injuries are often impossible. The application of a medial transarticular external fixator with motion capacity combines the treatment of remaining joint instability with the benefit of early joint movement. Disadvantages of prolonged joint immobilisation until definitive stabilisation of the knee are reduced.