RESUMEN
BACKGROUND: Matrix metalloproteinase 9 (MMP-9) has been reported to be correlated with declines in hippocampal volume and cognitive function in ApoE4-positive MCI patients. OBJECTIVES: The present study was aimed to investigate the effects of plasma matrix MMP-9 on the conversion risk between mild cognitive impairment (MCI) patients with and without ApoE4. DESIGN AND SETTING: Retrospective observational study using the data extracted from the Alzheimer's Disease Neuroimaging Initiative database. PARTICIPANTS: We included 211 ApoE4-positive MCI subjects (ApoE4+ MCI) and 184 ApoE4-negative MCI subjects (ApoE4- MCI). MEASUREMENTS: We obtained demographic and data including plasma MMP-9 levels at baseline and longitudinal changes in Clinical Dementia Rating (CDR) up to 15 years. We compared conversion rates between ApoE4+ MCI and ApoE4- MCI by the Log-rank test and calculated the hazard ratio (HR) for covariates including age, sex, educational attainment, drinking and smoking histories, medications, and plasma MMP-9 levels using a multiple Cox regression analysis of ApoE4+ MCI and ApoE4- MCI. RESULTS: No significant differences were observed in baseline plasma MMP-9 levels between ApoE4+ MCI and ApoE4- MCI. High plasma MMP-9 levels increased the conversion risk significantly more than low plasma MMP-9 levels (HR, 2.46 [95% CI, 1.31-4.48]) and middle plasma MMP-9 levels (HR, 1.67 [95% CI, 1.04-2.65]) in ApoE4+ MCI, but not in ApoE4- MCI. CONCLUSION: Plasma MMP-9 would be the risk of the future conversion to dementia in ApoE4+ MCI.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Progresión de la Enfermedad , Humanos , Metaloproteinasa 9 de la Matriz , NeuroimagenRESUMEN
INTRODUCTION: Cementless femoral revision total hip arthroplasty (RTHA) after periprosthetic fracture, aseptic loosening or infection is a challenging surgical procedure. The aim of this study was to evaluate the incidence and reasons for failure after two-stage septic revision, periprosthetic fracture or aseptic loosening that may reveal a rationale for cementless RTHA in two-stage revisions. MATERIALS AND METHODS: A consecutive series of 105 cases using cementless femoral revision prostheses were evaluated retrospectively. Indications for revision were 39 two-stage revisions after infection, 49 aseptic loosenings, and 17 periprosthetic fractures. A Kaplan-Meier analysis was performed using infection with or without removal of the implant as an endpoint. RESULTS: Incidence of infection with or without implant removal was significantly higher in patients treated for periprosthetic fractures compared to two-stage revisions or aseptic loosening (log-rank P < 0.0001). The mean follow-up period was 6.4 (2.0-13.7) years. Using infection with or without implant removal as the endpoint, 12 patients were diagnosed after the index operation resulting in a cumulative risk after 13.7 years of 29.9% (95% CI 0-61.2). CONCLUSION: Cementless revision using a modular tapered device is reliable with respect to reinfection risk in two-stage procedures.
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Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Fracturas Periprotésicas , Artroplastia de Reemplazo de Cadera/métodos , Estudios de Seguimiento , Prótesis de Cadera/efectos adversos , Humanos , Fracturas Periprotésicas/epidemiología , Fracturas Periprotésicas/etiología , Fracturas Periprotésicas/cirugía , Diseño de Prótesis , Falla de Prótesis , Reoperación/efectos adversos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
To clarify the role of concomitant carpal lesions in dislocated distal radius fractures (DRF), 104 consecutive patients with DRF underwent a preoperative morphological examination using CT and MRI. The study was performed between 2004 and 2006 with the aim of recording all types of concomitant carpal lesions as well as their consequences after 1 year. Carpal lesions of different types were found in all treated cases of dislocated DRF. A clinical follow-up 1 year (13.9 ± 6.5 months) after surgical treatment showed no correlation between the carpal lesions and the treatment outcome (previously described by Gologan et al. 2011). A second follow-up study ( > 10 years postoperative, range 11.2 ± 0.9 years) was initiated to find suspected later decompensations of the concomitant carpal lesions. A total of 37 of the original 104 patients could potentially be followed up: 22 patients had passed through both follow-ups and 15 could only be contacted with restrictions. 27 patients had died, 24 patients were excluded due to the presence of dementia or explicit rejection, and 16 patients could no longer be found. Using the Castaing score, the first follow-up after 1 year resulted in an average of 4.95 ± 3.1 points (range 0-12; "good result") and the second follow-up after 10 years in an average of 5.91 ± 2.9 points (range 2-14; "good result"). Again, there were no correlations with the primarily recognized carpal lesions [comparable groups 22 vs 22 (identical patients in both follow-ups); lost to follow-up rate 15.4%]. These results suggest that concomitant carpal lesions are primarily prevalent and detectable in (nearly) all dislocated DRF cases. However, with the usual protection of the wrist and the carpus after surgical treatment of DRF, these lesions often do not decompensate or require treatment, even after 10 years.
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Huesos del Carpo , Luxaciones Articulares , Fracturas del Radio , Huesos del Carpo/diagnóstico por imagen , Huesos del Carpo/cirugía , Estudios de Seguimiento , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugía , Imagen por Resonancia Magnética , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The population structure of the Pacific cod Gadus macrocephalus was examined using 15 microsatellite loci and mitochondrial DNA (ND2 region). In total, 274 individuals were sampled from 16 locations around Japan to estimate the level of genetic differentiation and effective population size (Ne ). Pairwise FST , analysis of molecular variance and Bayesian clustering analysis suggested the presence of two genetically distinct groups in waters around Japan, with a higher Ne value in the eastern group than in the western group. A possible factor that restricts gene flow between groups may be related to the water temperature differences in the south-western part of the Sea of Japan, where the Tsushima Warm Current flows around the area inhabited by the western group, which may limit migration between the west and east.
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Gadiformes/genética , Variación Genética , Animales , Teorema de Bayes , ADN Mitocondrial/genética , Genética de Población , Japón , Repeticiones de Microsatélite/genética , Océano PacíficoRESUMEN
INTRODUCTION: Septic ankle joint arthrodesis is a good therapeutic option in cases of infection after trauma or orthopedic surgical procedures. Many different procedures have been described, but external fixation seems to be standard. Aim of this study is to identify risk factors for complications in septic ankle joint arthrodesis with the external AO frame fixator. MATERIALS AND METHODS: Patients who received septic ankle joint arthrodesis between January 2008 and December 2012 were included in this study. Patients were evaluated clinically and with radiographs or CT scans. RESULTS: Follow-up of 74 of 79 patients with an external AO frame fixator could be evaluated; follow-up was 411 days (105-991). The mean age at surgery was 57.7 years (19-87). At this time, complications occurred in 41 patients (52 %) with wound healing problems (17 patients, 22 %) and non-union (12 patients, 15 %), and some needed surgical revision. In our collective, men had a significant higher non-union rate (p = 0.031), age or BMI showed no difference. Patients with diabetes and alcohol consumption showed a higher risk for complications (p = 0.049 and p = 0.031, respectively). 62 % of primary arthrodesis showed union, whereas in the case of revision, arthrodesis only 39 % showed union. CONCLUSIONS: Septic ankle joint arthrodesis with the external AO frame fixator is a probable tool to achieve union. This study showed that there is a high complication rate and some risk factors for complications could be identified. A blinded and prospective study is needed to compare intramedullary nailing and external fixation to evaluate the possible advantage of intramedullary devices in septic ankle arthrodesis.
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Articulación del Tobillo/cirugía , Artritis Infecciosa/cirugía , Artrodesis , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Artritis Infecciosa/complicaciones , Artrodesis/instrumentación , Artrodesis/métodos , Fijadores Externos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
INTRODUCTION: The aim of the study was to determine predictive risk factors for revision surgery in patients with septic orthopaedic implant removal of the lower leg. MATERIALS AND METHODS: A total of 196 patients with septic removal of orthopaedic implants after primary trauma of the lower leg between 2008 and 2012 were evaluated. Patients with endoprosthesis infection were excluded from this study. RESULTS: Thirteen patients (22.4 %) had infectious complications with revision surgery. We found 14 patients with soft tissue infections, 10 patients with osteomyelitis, 19 patients with wound-healing problems, 10 patients with pin track infections and two patients with fistulas. High complication rates were associated with severity of the initial trauma, localisation, and the state of union or non-union. Patients with peripheral arterial disease, anaemia and smoking showed a significantly higher risk for revision surgery; whereas patients with diabetes and arterial hypertension did not. A total of 22.6 % had open fractures as an initial trauma. In 76 %, bacteria could be detected. The complication rate was 41.2 % after initial open fractures and 19.6 % after initial closed fractures. A higher grade of soft tissue damage showed no increasing complication rate (p > 0.05). CONCLUSIONS: In this study, complications after septic implant removal of the lower leg were evaluated and risk factors were determined. The awareness of the risks for complications after septic orthopaedic implant removal can lead to a better treatment for patients. Decision-making can be based on scientific results to prevent patients suffering from further severe disease progression.
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Peroné/lesiones , Fracturas Óseas/cirugía , Traumatismos de la Pierna/cirugía , Infecciones Relacionadas con Prótesis/cirugía , Fracturas de la Tibia/cirugía , Adolescente , Adulto , Anciano , Remoción de Dispositivos , Femenino , Curación de Fractura , Fracturas Cerradas/cirugía , Fracturas Abiertas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/cirugía , Infecciones Relacionadas con Prótesis/epidemiología , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Infecciones de los Tejidos Blandos/cirugíaRESUMEN
OBJECTIVES: To assess the effect of the major efavirenz metabolizing enzyme (CYP2B6) genotype and the effects of rifampicin co-treatment on induction of CYP3A by efavirenz. PATIENTS AND METHODS: Two study arms (arm 1, n = 41 and arm 2, n = 21) were recruited into this study. In arm 1, cholesterol and 4ß-hydroxycholesterol were measured in HIV treatment-naive patients at baseline and then at 4 and 16 weeks after initiation of efavirenz-based antiretroviral therapy. In arm 2, cholesterol and 4ß-hydroxycholesterol were measured among patients taking efavirenz during rifampicin-based tuberculosis (TB) treatment (efavirenz/rifampicin) just before completion of TB treatment and then serially following completion of TB treatment (efavirenz alone). Non-linear mixed-effect modelling was performed. RESULTS: A one-compartment, enzyme turnover model described 4ß-hydroxycholesterol kinetics adequately. Efavirenz treatment in arm 1 resulted in 1.74 (relative standard error = 15%), 3.3 (relative standard error = 33.1%) and 4.0 (relative standard error = 37.1%) average fold induction of CYP3A for extensive (CYP2B6*1/*1), intermediate (CYP2B6*1/*6) and slow (CYP2B6*6/*6) efavirenz metabolizers, respectively. The rate constant of 4ß-hydroxycholesterol formation [mean (95% CI)] just before completion of TB treatment [efavirenz/rifampicin co-treatment, 7.40 × 10(-7) h(-1) (5.5 × 10(-7)-1.0 × 10(-6))] was significantly higher than that calculated 8 weeks after completion [efavirenz alone, 4.50 × 10(-7) h(-1) (4.40 × 10(-7)-4.52 × 10(-7))]. The CYP3A induction dropped to 62% of its maximum by week 8 of completion. CONCLUSIONS: Our results indicate that efavirenz induction of CYP3A is influenced by CYP2B6 genetic polymorphisms and that efavirenz/rifampicin co-treatment results in higher induction than efavirenz alone.
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Fármacos Anti-VIH/farmacocinética , Antituberculosos/farmacocinética , Benzoxazinas/farmacocinética , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP3A/metabolismo , Hidroxicolesteroles/análisis , Rifampin/farmacocinética , Adulto , Alquinos , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Benzoxazinas/uso terapéutico , Ciclopropanos , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológicoRESUMEN
BACKGROUND: When performing minimally invasive spine surgery in trauma patients, a short operation time and a perfect positioning of pedicle screws are demanded. In this study, we show that a Minimally Invasive Pedicle Screw System allows both. METHODS: One hundred and twenty-one patients (131 fractures) with fractures between Th 3 and L 5 were treated. The most common fracture type was A3. We treated 52 females and 69 men with a mean age of 56.7 years. In 72% of the cases, the procedure was performed by two experienced spine surgeons. Postoperatively, all patients were examined using a CT-scan. In 61 patients, an anterior stabilization was additionally performed in 33 patients, vertebroplasty or cyphoplasty was performed. Fifteen patients underwent laminectomy. RESULTS: No patient postoperatively developed any additional neurological compromise. In total, 682 screws were placed. In the postoperative CT-scan, we found 16 screws (2.2%) in suboptimal position, 8 with medial and 8 with lateral deviation. DISCUSSION: With the Minimally Invasive Pedicle Screw System used in this study, spinal fractures can be treated in a short operation time with percutaneous stabilization and a correct positioning of the pedicle screws in almost 98%. In our study, no screw was so much malpositioned that revision surgery would have been necessary. LEVEL OF EVIDENCE: Level III - Case-control study.
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Tornillos Óseos , Fijación Interna de Fracturas/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Fracturas de la Columna Vertebral/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fracturas de la Columna Vertebral/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Soft tissue defects in the distal lower leg region are challenging to treat, especially in trauma cases. To achieve early closure of the defect, pediculated adipofascial or muscle flaps can be used as well as free flaps. The pediculated adipofascial suralis flap has a reliable blood supply and a broad radius so this flap can be used for almost every defect location on the distal lower leg except for defects larger than 10 × 10 cm. The donor site defect does not lead to major problems and is well tolerated. The soleus flap can cover defects in the middle third and proximal distal third of the lower leg with its muscle. The donor site defect is occasionally associated with reduced calf functioning but is tolerated well most of the time. Because of these advantages, the pediculated adipofacial suralis flap and the soleus muscle flap can be used instead a microvascular free flap for the closure of defects in the distal lower leg region.
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Traumatismos de la Pierna/cirugía , Procedimientos de Cirugía Plástica/instrumentación , Procedimientos de Cirugía Plástica/métodos , Traumatismos de los Tejidos Blandos/cirugía , Colgajos Quirúrgicos , HumanosRESUMEN
OBJECTIVE: Soft-tissue defect coverage with well vascularized tissue (musculocutaneous or fasciocutaneous) in the arthroplasty setting. Where arthroplasty has been removed due to infection, as a muscle flap to close infected cavities. INDICATIONS: Soft tissue defects, wound-edge necrosis in arthroplasty, and persistent infection in Girdlestone patients. CONTRAINDICATIONS: Moribund patients. SURGICAL TECHNIQUE: Pedicled flap: as far as possible, lift the flap as an island flap to increase coverage. Then suture the flap into the defect (split skin graft where appropriate). Free flap: lift the flap and prepare a vascular pedicle for anastomosis. Suture the flap into the site and create arterial and vascular micro-anastomoses (split skin graft where appropriate). POSTOPERATIVE MANAGEMENT: Position the extremity according to the flap type used. Use 500 ml HES (hydroxyethyl starch) 6% for 5 days. Avoid compression of the pedicle or anastomosis area. Flaps are generally autonomous after 3 weeks. RESULTS: The survival rate for both flap types, free and pedicled, is >90%. The flap survival rate should not be confused with the healing rate for infected arthroplasty.
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Artroplastia/métodos , Prótesis Articulares/efectos adversos , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugía , Infecciones de los Tejidos Blandos/etiología , Infecciones de los Tejidos Blandos/cirugía , Colgajos Quirúrgicos , Artroplastia/instrumentación , Humanos , Resultado del TratamientoRESUMEN
SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p=0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p=0.0067, OR 2.65, 95% CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE.
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Péptidos y Proteínas de Señalización Intracelular/genética , Lupus Eritematoso Sistémico/genética , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Intrones , Japón , Células Jurkat , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Luciferasas , Lupus Eritematoso Sistémico/metabolismo , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Proteína Asociada a la Molécula de Señalización de la Activación LinfocitariaRESUMEN
The objective of this study was to assess the incidence, timing and identify pharmacogenetic, efavirenz (EFV) pharmacokinetic and biochemical predictors of EFV-based antiretroviral therapy (ART) drug-induced liver injury (DILI). ART-naïve HIV patients (n = 285) were prospectively enrolled. Pretreatment laboratory evaluations included hepatitis B surface antigen and C antibody, CD4 count and viral load. Liver tests were done at baseline, 1st, 2nd, 4th, 8th, 12th, 24th and 48th weeks during ART. Plasma EFV and 8-hydroxyefvairenz concentration was determined at week 4 using liquid chromatography-mass spectrometry. CYP2B6, CYP3A5, ABCB1 3435C/T and UGT2B7*2 genotyping was done using Taqman genotyping assay. Data were analyzed using survival analysis and Cox proportional hazards model. The incidence of DILI was 15.7% or 27.9 per 100 person-years and that of severe injury was 3.4% or 6.13 per 100 person-years. The median time for the development of DILI and severe injury was 2 and 4 weeks after initiation of ART, respectively. There was significant association of DILI with lower baseline platelet, albumin, log plasma viral load and CD4 count (P = 0.031, 0.037, 0.06 and 0.019, respectively). Elevated baseline alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, plasma EFV level and CYP2B6*6 were good predictors for the development of DILI (P = 0.03, 0.01, 0.016, 0.017 and 0.04, respectively). We report for the first time CYP2B6*6 as a putative genetic marker and high plasma EFV concentration as intermediate biomarker for vulnerability to EFV-induced liver injury in HIV patients. CYP2B6 genotyping and/or regular monitoring of EFV and lever enzymes level during early therapy is advised for early diagnosis and management of DILI.
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Terapia Antirretroviral Altamente Activa/efectos adversos , Hidrocarburo de Aril Hidroxilasas/genética , Benzoxazinas/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Infecciones por VIH/tratamiento farmacológico , Oxidorreductasas N-Desmetilantes/genética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Adulto , Alquinos , Benzoxazinas/sangre , Estudios de Cohortes , Ciclopropanos , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A/genética , Femenino , Genotipo , Humanos , Masculino , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction.
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Antibióticos Antituberculosos/uso terapéutico , Hidrocarburo de Aril Hidroxilasas/genética , Benzoxazinas/sangre , Oxidorreductasas N-Desmetilantes/genética , Inhibidores de la Transcriptasa Inversa/sangre , Rifampin/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Alquinos , Alelos , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/metabolismo , Fármacos Anti-VIH/uso terapéutico , Antibióticos Antituberculosos/sangre , Terapia Antirretroviral Altamente Activa , Benzoxazinas/metabolismo , Benzoxazinas/uso terapéutico , Ciclopropanos , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A/genética , Interacciones Farmacológicas , Inducción Enzimática , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Inhibidores de la Transcriptasa Inversa/metabolismo , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Rifampin/sangre , Tuberculosis/tratamiento farmacológico , Tuberculosis/genéticaRESUMEN
We evaluated the potential of a vastus lateralis muscle flap in controlling infection after resection arthroplasty of the hip. We retrospectively reviewed 119 patients with 120 chronic infections after resection arthroplasty treated with this procedure. The flap was fixed with Mitek anchors in the acetabular cavity. The mean duration of infection after resection before the muscle flap procedure was 6.5 months (2 to 13). The patients had previously undergone a mean of 4.9 operations (2 to 25). In all patients the infected cavity was the origin of the persistent infection. The mean follow-up was for 2.6 years (1.0 to 4.7). No patient had recurrent infection post-operatively and all had an improvement in the pain and better quality of life.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Prótesis de Cadera/efectos adversos , Infecciones Relacionadas con Prótesis/cirugía , Músculo Cuádriceps/trasplante , Colgajos Quirúrgicos , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/métodos , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias , Infecciones Relacionadas con Prótesis/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We investigated the influence of gender and pharmacogenetic variations on long-term efavirenz autoinduction and disposition among patients with HIV in Tanzania (N = 129). Plasma concentrations (at 16 h) of efavirenz and 8-hydroxyefavirenz were quantified at weeks 4 and 16 of therapy. Genotyping was performed to identify cytochrome P450 (CYP) 2B6*6, CYP3A5*3, *6, and *7, and ABCB1-3435 C/T genotypes. There were reductions in the median efavirenz concentration (Wilcoxon matched-pair test P < 0.001) and efavirenz/8-hydroxyefavirenz ratio (P < 0.001) by 19 and 32%, respectively, at week 16 as compared with week 4. The proportion of patients with efavirenz concentration <1 µg/ml at week 16 was higher by 67, 25, and 5% in CYP2B6*1/*1, *1/*6, and *6/*6 genotypes, respectively. The defined therapeutic range based on observed plasma concentrations is affected by the time point of sampling and the CYP2B6 genotype. The effect of efavirenz autoinduction on reducing plasma exposure continues up to week 16 and predominantly affects CYP2B6 extensive metabolizers. Among CYP2B6 slow metabolizers, the presence of a CYP3A5 genotype allele is associated with greater effects of efavirenz autoinduction on plasma concentrations of the drug. The cumulative induction may influence the long-term antiretroviral therapy outcome, particularly in CYP2B6*1 carriers.
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Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adulto , Alquinos , Terapia Antirretroviral Altamente Activa , Hidrocarburo de Aril Hidroxilasas/genética , Hidrocarburo de Aril Hidroxilasas/metabolismo , Benzoxazinas/administración & dosificación , Benzoxazinas/sangre , Biotransformación , Ciclopropanos , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Esquema de Medicación , Femenino , Genotipo , Infecciones por VIH/sangre , Humanos , Hidroxilación , Masculino , Persona de Mediana Edad , Oxidorreductasas N-Desmetilantes/genética , Oxidorreductasas N-Desmetilantes/metabolismo , Fenotipo , Estudios Prospectivos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/sangre , Factores Sexuales , TanzaníaAsunto(s)
Antirreumáticos/uso terapéutico , Antituberculosos/uso terapéutico , Cooperación del Paciente/estadística & datos numéricos , Enfermedades Reumáticas/tratamiento farmacológico , Tuberculosis Pulmonar/prevención & control , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Periprosthetic infection remains a major complication in arthroplasty; increasing numbers of primary and revision arthroplasties are being followed by increasing numbers of periprosthetic infections. In cases of possible infection, the surgeon must have a treatment concept that can be individually adjusted. Diagnosis is a challenge and should include a variety of investigations. In early and secondary infections, component retention can be successful. Surgical debridement is the key to success. All late and chronic infections should be treated by explantation of all components because of infection with biofilm-producing microbes. The individual patient's situation and the surgeon's experience should determine whether to choose direct single-stage or two-stage revision. New diagnostic and therapeutic procedures can improve outcomes but cannot replace the need for prophylactic efforts.
Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Desbridamiento/métodos , Prótesis de Cadera/efectos adversos , Inestabilidad de la Articulación/cirugía , Falla de Prótesis , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/terapia , Humanos , Inestabilidad de la Articulación/complicaciones , Selección de Paciente , Reoperación/instrumentación , Reoperación/métodosRESUMEN
In regenerative medicine, there is an approach to avoid expansion of the mesenchymal stem cell (MSC) before implantation. The aim of this study was to compare methods for instant MSC therapy by use of a portable, automatic and closed system centrifuge that allows for the concentration of MSCs. The main outcome measures were the amount of MSCs per millilitre of bone marrow (BM), clusters of differentiation (CD), proliferation and differentiation capacities of the MSC. A volume reduction protocol was compared to the traditional laboratory methods of isolation using a Ficoll gradient and native BM. Fifty millilitres of BM were obtained from haematologically healthy male Caucasians (n=10, age 8 to 49 years). The number of colony forming units-fibroblast (CFU-F)/ml BM was highest in the centrifuge volume reduction protocol, followed by the native BM (not significant), the centrifuge Ficoll (p=0.042) and the manual Ficoll procedure (p=0.001). The MSC of all groups could differentiate into the mesenchymal lineages without significant differences between the groups. The CD pattern was identical for all groups: CD13+; CD 44+; CD73 +; CD90+; CD105+; HLA-A,B,C+; CD14-; CD34-; CD45-; CD271-; HLA-DR-. In a further clinical pilot study (n=5) with 297 ml BM (SD 18.6), the volume reduction protocol concentrated the MSC by a factor of 14: there were 1.08 x 10(2) MSC/ml BM (standard deviation (SD) 1.02 x 10(2)) before concentration, 14.8 x 10(2) MSC/ ml BM (SD 12.4 x 10(2)) after concentration, and on average 296 x 10(2) MSC (SD 248.9 x 10(2), range 86.4-691.5 x 10(2)) were available for MSC therapy. The volume reduction protocol of the closed centrifuge allows for the highest concentration of the MSC, and therefore, is a promising candidate for instant stem cell therapy.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Medicina Regenerativa/métodos , Células de la Médula Ósea/citología , Diferenciación Celular , Proliferación Celular , Separación Celular/métodos , Centrifugación , Ficoll , HumanosRESUMEN
Lumbar total disc replacement is an increasingly common way of treating degenerative lumbar disc disease while preserving mobility. The aim of this analysis was to survey evidence-based data to classify the procedure. Based on a MEDLINE inquiry, 38 clinical trials dealing with lumbar total disc replacement were selected and analyzed by the criteria of indication, preoperative procedure, and clinical follow-up. These data represent 3,180 patient-related evaluations with follow-up of 5.9 to 204 months. We also included ten retrospective studies. Patient satisfaction was a mean of 90.73%, and the Oswestry Disability Index and Visual Analog Scale were significantly lower. High rates of revision surgery, explantation surgery, and secondary fusions are linked to wrong preoperative indication. According to evidence criteria, the results show that lumbar total disc replacement is a safe procedure with a high rate of success. There is clear evidence that both imprecise indication and the choice of too-small implants significantly reduce the prospect of surgical success and increase the rates of reintervention.
Asunto(s)
Artroplastia de Reemplazo/instrumentación , Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Prótesis e Implantes , Espondilosis/cirugía , Evaluación de la Discapacidad , Medicina Basada en la Evidencia , Estudios de Seguimiento , Humanos , Estudios Multicéntricos como Asunto , Dimensión del Dolor , Complicaciones Posoperatorias/etiología , Diseño de Prótesis , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Maxacalcitol is a vitamin D analogue, which is administered intravenously for secondary hyperparathyroidism in dialysis patients as well as calcitriol. However, few dose-comparison clinical studies have been reported for these drugs. The present multicenter, randomized crossover study was conducted to determine the equivalence of maxacalcitol and calcitriol doses. METHODS: Subjects comprised 31 patients on chronic hemodialysis with secondary hyperparathyroidism who had not received maxacalcitol or calcitriol in the previous 3 months. Patients were randomly divided into two groups, and maxacalcitol or calcitriol was administered in a crossover design for 12 weeks each. Maxacalcitol and calcitriol doses were adjusted based on serum levels of calcium and intact parathyroid hormone. RESULTS: After the 12-week maxacalcitol/calcitriol administration, there were no significant differences in levels of calcium (maxacalcitol 2.40+/-0.22 mmol/1 (9.6+/-0.9 mg/dl), calcitriol 2.42 + 0.25 mmol/l (9.7+/-1.0 mg/dl), p = 0.71), phosphate (maxacalcitol 1.97 + 0.42 mmol/l (6.1+/-1.3 mg/dl), calcitriol 2.00+/-0.48 mmol/l (6.2+/-1.5 mg/dl), p = 0.64), intact parathyroid hormone (maxacalcitol 267+/-169 pg/ml, calcitriol 343+/-195 pg/ml, p = 0.11) in serum or other bone-metabolic parameters such as serum alkaline phosphatase. The doses ofmaxacalcitol and calcitriol were 49.3+/-23.7 microg/month and 9.0+/-3.8 microg/month, respectively, and maxacalcitol : calcitriol dose ratio was 5.5: 1. No severe adverse reactions were seen for either maxacalcitol or calcitriol during the study period. CONCLUSIONS: Comparable therapeutic efficacy can be obtained in the treatment of secondary hyperparathyroidism using either maxacalcitol or calcitriol at a dose ratio of 5.5 : 1.