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1.
Water Res ; 191: 116765, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33412419

RESUMEN

The removal of micropollutants from wastewater is an emerging issue that currently concerns the wastewater sector the most. Granular Activated Carbon (GAC) has gained recognition as a suitable technology for dealing with this problem. This study assesses the performance of six GAC-filters for the removal of micropollutants installed as final treatment step at a municipal wastewater treatment plant. The influence of the GAC-type and the Empty Bed Contact Time (EBCT) on the filter performance was evaluated. The breakthrough behaviour of 13 selected micropollutants as well as the removal of the Dissolved Organic Carbon (DOC) and UV absorption at 254 nm were investigated. Besides, the adsorbed DOC (qDOC) was introduced as assessment parameter (adsorbed and biodegraded DOC), instead of the commonly used treated bed volume. Finally, Size Exclusion Chromatography (SEC) with online DOC and UV254nm detection was applied for a better understanding of the influent and effluent characteristics. The results showed that the pore size distribution is a crucial feature of the activated carbon. A balanced proportion of macro-, meso­ and micropores may play a role in the better removal of micropollutants in presence of DOC. Regardless of the GAC-type, a minimum EBCT between 20 - 30 min was necessary. We proved that a short EBCT would not fully use the sorption capacity, whereas a long EBCT would increase the carbon demand without improving of the removal. Lastly, according to the SEC results, after a short operation time no difference between the influent and effluent chromatographable fractions (DOC and UV254nm) was observed.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Carbón Orgánico , Aguas Residuales , Contaminantes Químicos del Agua/análisis
2.
Mol Psychiatry ; 26(3): 864-874, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-31138890

RESUMEN

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4 ± 13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9 ± 13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET)/magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared with controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region's functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.


Asunto(s)
Dolor Crónico , Adulto , Encéfalo/diagnóstico por imagen , Dolor Crónico/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neuroglía , Tomografía de Emisión de Positrones , Receptores de GABA
3.
Water Res ; 189: 116588, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33221588

RESUMEN

Granulated Activated Carbon (GAC) filtration is a common process for advanced wastewater treatment. In such filters, the removal of organic substances results from adsorptive as well as biological processes. This work investigated the potential of biological processes and their influence on GAC-filter performance. During 32 months, the removal of micropollutants,Dissolved Organic Carbon (DOC) and the spectral absorption coefficient was monitored in six GAC-filters. The effects of pre-treatment (cloth- and/or membrane-filtration), EBCT (from 6 - 35 min) and GAC-type were evaluated. Likewise, the impact of the influent´s fluctuations in temperature, flow and concentration (ammonia, nitrate, and soluble reactive phosphorus (sRP)) were analysed. Biological processes were tracked by the frequency of backwashing, oxygen consumption, removal of poorly absorbable micropollutants and production of transformation products. Pre-treatment influenced biofilm growth significantly. Membrane filtration delayed the first backwashing event by 122 d in comparison to cloth-filtration, where the first backwash was conducted after only 21 d. Removal of poorly absorbable substances was observed early on (40 - 50 d). Parallel operation contributed to a better utilisation of the GAC-capacity and the biological removal potential. Influent nitrogen species > 0.5 mg N/L promoted biofilm growth, whereas sRP seemed to have no effect. The developed biofilm and optimal operating conditions led to longer life spans of the GAC-filters, making carbon usage rates comparable to those from PAC applications. The results suggest that biological processes accounted for about 25 - 42% of the totally removed DOC at the end of the operation.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Carbón Orgánico , Filtración , Aguas Residuales , Contaminantes Químicos del Agua/análisis
4.
Comput Biol Med ; 122: 103797, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32658723

RESUMEN

A deep learning pipeline was developed and used to localize and classify a variety of implants in the femur contained in whole-body post-mortem computed tomography (PMCT) scans. The results provide a proof-of-principle approach for labelling content not described in medical/autopsy reports. The pipeline, which incorporated residual networks and an autoencoder, was trained and tested using n = 450 full-body PMCT scans. For the localization component, Dice scores of 0.99, 0.96, and 0.98 and mean absolute errors of 3.2, 7.1, and 4.2 mm were obtained in the axial, coronal, and sagittal views, respectively. A regression analysis found the orientation of the implant to the scanner axis and also the relative positioning of extremities to be statistically significant factors. For the classification component, test cases were properly labelled as nail (N+), hip replacement (H+), knee replacement (K+) or without-implant (I-) with an accuracy >97%. The recall for I- and H+ cases was 1.00, but fell to 0.82 and 0.65 for cases with K+ and N+. This semi-automatic approach provides a generalized structure for image-based labelling of features, without requiring time-consuming segmentation.


Asunto(s)
Aprendizaje Profundo , Autopsia , Fémur/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Imagen de Cuerpo Entero
5.
Z Orthop Unfall ; 157(5): 515-523, 2019 Oct.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-30736086

RESUMEN

PURPOSE: This study was aimed to determine the impact of bioregenerative operations in case of degenerative cartilage lesions within the media knee compartment. MATERIAL AND METHODS: The CartilageRegistry DGOU was founded in 2013. At the deadline August 2016 a total of 1847 patients were included. A total of 23.3% (n = 432) was suffering from a degenerative cartilage lesion in the medial compartment. Follow-up was performed after 6, 12, and 24 months (online evaluation). The patients were asked for their subject feeling as well as the KOOS (Knee injury and Osteoarthritis Outcome Score) was determined. RESULTS: Most of the patients (n = 358) suffered from a single femoral lesion. In 25 cases single tibial and in 49 cases combined defects ("kissing lesions") were addressed by different treatment options: 39.9% autologous chondrocyte transplantation, in 8.1% in combination with a spongiosa plasty. Other treatments were drilling, microfracturing with or without matrix. In 17.9% the surgeons had chosen combined methods. The bioregenerative treatment was combined with a concomitant operation in 39.7% in patients with medial, in 56.0% in patients with a tibial, and in 67.9% in patients with combined defects. The mostly performed additional operations were osteotomies. There were no gender differences at baseline or during follow-up. The history of patients with femoral defects was shorter than in the other groups. The patients with medial defects judged the subjective outcome significant more frequently better after 6, 12, or 24 months compared with the other groups. The KOOS raised from baseline (median 52 points) to a median of 75 after 6, to 78 points after 12, and to 80 points after 24 months. Patients with femoral defects had a better KOOS-outcome in tendency. Revision operations were required in 7.1%. CONCLUSIONS: The treatment of degenerative cartilage lesions (respective early OA) by bioregenerative procedures are well-established measures. These treatments are sufficient to produce high patients' satisfaction and acceptable short/midterm results.


Asunto(s)
Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Adolescente , Adulto , Anciano , Enfermedades de los Cartílagos/fisiopatología , Cartílago Articular/patología , Cartílago Articular/fisiología , Femenino , Fémur/fisiopatología , Fémur/cirugía , Humanos , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/fisiopatología , Regeneración , Sistema de Registros , Tibia/fisiopatología , Tibia/cirugía , Adulto Joven
6.
J Oral Rehabil ; 45(5): 399-405, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29573454

RESUMEN

The determination of the occlusal vertical dimension (OVD) in edentulous patients is based on clinical assessment with high variability. This study tested the hypothesis: The average OVD in edentulous patients with conventional dentures is too low compared to orthodontic norms, when only clinical parameters are used for the determination of the OVD. Edentulous patients with conventional full dentures were enrolled. Clinical parameters were judged by two senior prosthodontists. Digital lateral cephalograms were taken and served to calculate the OVD according to the lower face height angle (ANS-Xi-D) taking tooth-independent facial growth patterns into account. The ANS-Xi-D angle was compared with reference values by applying one-sample mean comparison tests. Thirty-six participants (17 female, 19 male; mean age 65.3 ± 10.6 years) were enrolled in this study. Clinically, the OVD of four dentures was judged too low, in one case too high, and in the other 31 cases as correct. The mean ANS-Xi-D angle was 48.28°±4.86 and statistically not different to the norm value of 49°±4 (n.s.). There was a tendency that the ANS-Xi-D angle was different between participants with different tooth-independent facial growth patterns (ANOVA, P = .0548). Predominantly, clinically sufficient prostheses show adequate ANS-Xi-D angles. Short-face type denture patients are often restored to comply with mesiofacial norms. The determination of the OVD based on lateral cephalography is not recommendable to be a standard diagnostic parameter. Orthodontic norms are derived from dentate cohorts and might not take the continuing facial growth and other confounding factors of edentulous subjects into account.


Asunto(s)
Cefalometría , Dentadura Completa , Cara/diagnóstico por imagen , Boca Edéntula/diagnóstico por imagen , Lengua/diagnóstico por imagen , Anciano , Relación Céntrica , Diseño de Dentadura , Cara/anatomía & histología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Boca Edéntula/fisiopatología , Propiedades de Superficie , Lengua/anatomía & histología , Dimensión Vertical
7.
Sci Rep ; 8(1): 3933, 2018 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-29500454

RESUMEN

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients. Abdominal subcutaneous AT biopsies were collected before and after intervention to determine the AT transcriptome and expression of proteins involved in lipolysis, NP signaling and mitochondrial oxidative metabolism. Both sacubitril/valsartan and amlodipine treatment did not significantly induce AT transcriptional changes in pathways related to lipolysis, NP signaling and oxidative metabolism. Furthermore, protein expression of adipose triglyceride lipase (ATGL) (Ptime*group = 0.195), hormone-sensitive lipase (HSL) (Ptime*group = 0.458), HSL-ser660 phosphorylation (Ptime*group = 0.340), NP receptor-A (NPRA) (Ptime*group = 0.829) and OXPHOS complexes (Ptime*group = 0.964) remained unchanged. In conclusion, sacubitril/valsartan treatment for 8 weeks did not alter the abdominal subcutaneous AT transcriptome and expression of proteins involved in lipolysis, NP signaling and oxidative metabolism in obese hypertensive patients.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Hipertensión/tratamiento farmacológico , Neprilisina/antagonistas & inhibidores , Obesidad/metabolismo , Proteínas/metabolismo , Tetrazoles/uso terapéutico , Transcriptoma , Tejido Adiposo/metabolismo , Adulto , Aminobutiratos/farmacología , Amlodipino/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Compuestos de Bifenilo , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Grasa Subcutánea/metabolismo , Tetrazoles/farmacología , Valsartán
8.
Z Gerontol Geriatr ; 51(6): 642-649, 2018 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-27342103

RESUMEN

BACKGROUND: Even though the intervention effects on cognitively impaired care recipients are of interest, the evaluation in dementia caregiver studies on caregiver outcomes is often limited. Furthermore, the comparison of studies and interventions is difficult because of the large variance of endpoints and assessments used in this field. OBJECTIVE: The aim of this study was to give an overview on the most prevalent outcomes for cognitively impaired care recipients and expert based recommendations for assessment. MATERIAL AND METHODS: A written Delphi survey was carried out on 16 assessments from 5 dimensions with 14 experts working in different disciplines in German healthcare and research institutes. RESULTS: The most important outcomes and best rated assessments were 1) for problem behavior: revised memory and behavior problem checklist and neuropsychiatric inventory Q, 2) for depressive symptoms: geriatric depression scale, 3) for quality of life: quality of life in Alzheimer's disease, 4) for cognition: mini mental state examination and 5) for ADL/IADL: Katz activities of daily living and Lawton instrumental activities of daily living. CONCLUSION: Due to the varying experiences of the experts with particular assessments, the ratings were in some cases relatively heterogeneous. Overall previous international recommendations could be confirmed. There is particular need of German validation studies on internationally used instruments within the dimensions of problem behavior and quality of life.


Asunto(s)
Enfermedad de Alzheimer , Cuidadores , Actividades Cotidianas , Anciano , Enfermedad de Alzheimer/enfermería , Humanos , Evaluación de Resultado en la Atención de Salud , Calidad de Vida
9.
Clin Pharmacol Ther ; 101(2): 254-263, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27542885

RESUMEN

Natriuretic peptide (NP) deficiency and sustained renin-angiotensin system activation are associated with impaired oxidative metabolism and predispose to type-2 diabetes. We hypothesized that sacubitril/valsartan (LCZ696), which augments NP through neprilysin inhibition while blocking angiotensin II type-1 (AT1 )-receptors, improves insulin sensitivity, lipid mobilization, and oxidation. After 8 weeks of treatment of obese patients with hypertension, sacubitril/valsartan 400 mg q.d., but not amlodipine 10 mg q.d., was associated with a significant increase from baseline in the insulin sensitivity index (hyperinsulinemic-euglycemic clamp), and tended to be higher in patients treated with sacubitril/valsartan compared to amlodipine. Abdominal adipose tissue interstitial glycerol concentrations increased with sacubitril/valsartan, but decreased with amlodipine. Whole-body lipolysis and substrate oxidation did not change with either treatment. Results confirm that sacubitril/valsartan treatment leads to a metabolic benefit in the study population and supports the relevance of neprilysin inhibition along with AT1 -receptor blockade in the regulation of human glucose and lipid metabolism.


Asunto(s)
Aminobutiratos/farmacología , Antihipertensivos/farmacología , Resistencia a la Insulina/fisiología , Neprilisina/antagonistas & inhibidores , Obesidad/metabolismo , Tetrazoles/farmacología , Tejido Adiposo/efectos de los fármacos , Adulto , Aminobutiratos/uso terapéutico , Amlodipino/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/metabolismo , Compuestos de Bifenilo , Combinación de Medicamentos , Metabolismo Energético/efectos de los fármacos , Femenino , Glicerol/análisis , Humanos , Hipertensión/tratamiento farmacológico , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Péptidos Natriuréticos/genética , Péptidos Natriuréticos/metabolismo , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Tetrazoles/uso terapéutico , Valsartán
10.
Z Orthop Unfall ; 155(1): 92-99, 2017 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-27769090

RESUMEN

Background: Osteochondral lesions (OCL) of the ankle are a common cause of ankle pain. Although the precise pathophysiology has not been fully elucidated, it can be assumed that a variety of factors are responsible, mainly including traumatic events such as ankle sprains. Advances in arthroscopy and imaging techniques, in particular magnetic resonance imaging (MRI), have improved the possibilities for the diagnosis of OCLs of the ankle. Moreover, these technologies aim at developing new classification systems and modern treatment strategies. Material and Methods: This article is a review of the literature. Recommendations of the group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) for the treatment of OCLs of the ankle are presented. The review gives a concise overview on the results of clinical studies and discusses advantages and disadvantages of different treatment strategies. Results: Non-operative treatment shows good results for selected indications in children and adolescents, especially in early stages of osteochondritis dissecans (OCD). However, surgical treatment is usually indicated in OCLs in adolescents and adults, depending on the size and location of the lesion. Various arthroscopic and open procedures are frequently employed, including reattachment of the fragment, local debridement of the lesion with fragment removal and curettage of the lesion, bone marrow-stimulation by microfracture or microdrilling (antegrade or retrograde), and autologous matrix-induced chondrogenesis (AMIC®) - with or without reconstruction of a subchondral bone defect or cyst by autologous cancellous bone grafting. Isolated subchondral cysts with an intact cartilage surface can be treated by retrograde drilling and possibly additional retrograde bone grafting. For larger defects or as salvage procedure, osteochondral cylinder transplantation (OATS® or Mosaicplasty®) or matrix-induced autologous chondrocyte transplantation (MACT) are recommended. Transplantation of so-called (osteochondral) mega grafts, such as autologous bone grafts or allografts, are used for very large osteochondral defects that cannot be reconstructed otherwise. Implantation of the so-called "small metal implants" - such as HemiCAP Talus® - is reserved for selected cases after failed primary reconstruction. Corrective osteotomies are indicated in accompanying axial malalignments. Conclusions: There are several different treatment strategies for OCLs, but clinical studies are rare and evidence is limited. Therefore, interventional studies, e.g. randomised controlled trials (RCTs), but also observational studies, e.g. based on data of the Cartilage Registry of the German Society of Orthopaedics and Traumatology (www.knorpelregister-dgou.de), are needed and are recommended by the authors.


Asunto(s)
Artroplastia de Reemplazo de Tobillo/normas , Artroscopía/normas , Desbridamiento/normas , Prótesis Articulares/normas , Ortopedia/normas , Osteocondritis Disecante/terapia , Traumatología/normas , Trasplante Óseo/normas , Condrocitos/trasplante , Terapia Combinada/normas , Alemania , Humanos , Osteocondritis Disecante/diagnóstico , Osteotomía/normas , Guías de Práctica Clínica como Asunto , Procedimientos de Cirugía Plástica/normas , Sociedades Médicas
11.
Knee ; 23(3): 426-35, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26947215

RESUMEN

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.


Asunto(s)
Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Condrocitos/trasplante , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Trasplante Autólogo/métodos , Humanos
12.
Z Orthop Unfall ; 153(1): 67-74, 2015 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-25723583

RESUMEN

The German Cartilage Registry (KnorpelRegister DGOU) has been introduced in October 2013 and aims on the evaluation of patients who underwent cartilage repair for symptomatic cartilage defects. It represents a nation-wide cohort study which has been introduced by the working group "Tissue Regeneration" of the Germany Society of Orthopaedic Surgery and Traumatology and is technically based upon a web-based remote data entry (RDE) system. The present article describes first experiences with the registry including patient and treatment characteristics. Between October 2013 and April 2014, a total of 230 patients who had undergone surgical cartilage repair for symptomatic full-thickness cartilage defects of the knee has been included in the German Cartilage Registry from 23 cartilage repair centres. Mean age was 37.11 years (SD 13.61) and mean defect size was 3.68 cm(2) (SD 0.23). Since the introduction of the KnorpelRegister DGOU the total number of registered patients has increased steadily up to the most recent figure of 72 patients within one month. Patients were treated mainly according to the recommended therapies. The highest percentage in therapy is represented by the bone marrow stimulation techniques (55.02 %) as well as by the autologous chondrocyte transplantation (34.92 %). Unlike the patient collective in the majority of prospective randomised controlled trials, the patient population within the registry shows a high proportion of patients with accompanying pathologies, with an age of more than 50 years at the time of treatment and with unfavourably assessed accompanying pathologies such as an affection of the opposite cartilage surface or a previously resected meniscus. In summary, the technical platform and forms of documentation of the KnorpelRegister DGOU have proved to be very promising within the first six months. Unlike data from other clinical trials, the previous analysis of the patients' data and therapies reflects successfully the actual medical care situation of patients with cartilage defects of the knee joint. This analysis also provides new information on subgroups of patients that have not yet been recorded in the scientific literature. This will be part of the first analysis of clinical treatment data. An expansion of the KnorpelRegister DGOU to patients with cartilage defects of the ankle and hip joints is already decided upon and initialised.


Asunto(s)
Artroplastia/estadística & datos numéricos , Fracturas del Cartílago/epidemiología , Fracturas del Cartílago/cirugía , Traumatismos de la Rodilla/epidemiología , Traumatismos de la Rodilla/cirugía , Sistema de Registros/estadística & datos numéricos , Adulto , Femenino , Fracturas del Cartílago/diagnóstico , Alemania/epidemiología , Humanos , Masculino , Proyectos Piloto , Prevalencia , Resultado del Tratamiento
13.
Oncogene ; 33(17): 2245-54, 2014 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-23708654

RESUMEN

Human colorectal cancers are known to possess multiple mutations, though how these mutations interact in tumor development and progression has not been fully investigated. We have previously described the FCPIK3ca* murine colon cancer model, which expresses a constitutively activated phosphoinositide-3 kinase (PI3K) in the intestinal epithelium. The expression of this dominantly active form of PI3K results in hyperplasia and invasive mucinous adenocarcinomas. These cancers form via a non-canonical mechanism of tumor initiation that is mediated through activation of PI3K and not through aberrations in WNT signaling. Since the Adenomatous Polyposis Coli (APC) gene is mutated in the majority of human colon cancers and often occurs simultaneously with PIK3CA mutations, we sought to better understand the interaction between APC and PIK3CA mutations in the mammalian intestine. In this study, we have generated mice in which the expression of a constitutively active PI3K and the loss of APC occur simultaneously in the distal small intestine and colon. Here, we demonstrate that expression of a dominant active PI3K synergizes with loss of APC activity resulting in a dramatic change in tumor multiplicity, size, morphology and invasiveness. Activation of the PI3K pathway is not able to directly activate WNT signaling through the nuclear localization of CTNNB1 (ß-catenin) in the absence of aberrant WNT signaling. Alterations at the transcriptional level, including increased CCND1, may be the etiology of synergy between these activated pathways.


Asunto(s)
Adenocarcinoma/genética , Proteína de la Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales/genética , Fosfatidilinositol 3-Quinasas/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Animales , Núcleo Celular/metabolismo , Fosfatidilinositol 3-Quinasa Clase I , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Ciclina D1/metabolismo , Modelos Animales de Enfermedad , Epistasis Genética , Femenino , Expresión Génica , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Inestabilidad de Microsatélites , Fosfatidilinositol 3-Quinasas/metabolismo , Carga Tumoral , Vía de Señalización Wnt , beta Catenina/metabolismo
14.
Unfallchirurg ; 117(3): 235-41, 2014 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-23179821

RESUMEN

BACKGROUND: Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. MATERIAL AND METHODS: Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. RESULTS: There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. CONCLUSIONS: This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).


Asunto(s)
Enfermedades de los Cartílagos/terapia , Trasplante de Células/rehabilitación , Trasplante de Células/normas , Condrocitos/trasplante , Ortopedia/normas , Guías de Práctica Clínica como Asunto , Rehabilitación/normas , Enfermedades de los Cartílagos/patología , Alemania , Trasplante Autólogo/rehabilitación , Trasplante Autólogo/normas
15.
Dtsch Arztebl Int ; 110(33-34): 550-6, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24069079

RESUMEN

BACKGROUND: The incidence of decubitus ulcers is an established quality indicator for external quality assurance in the inpatient setting. Epidemiologic analyses of the frequency of, and risk factors for, decubitus ulcers in routine care are lacking. METHOD: We analyzed routine decubitus-ulcer documentation data relating to all inpatients of the University Hospital of Dresden, Germany, from 2007 to 2011 (n = 246 162 patients). The prevalence and incidence of decubitus ulcers and demographic and illness-related risk factors for them were determined with the use of descriptive techniques and logistic regression models. The effort-to-benefit ratio of documenting decubitus ulcers in various care scenarios was calculated in terms of the number of additional patients to be documented for each patient with incident decubitus ulcer. RESULTS: The prevalence of decubitus ulcers was 1.21%, and their incidence during inpatient treatment was 0.78%, with significant differences across clinical care units (range of ward-specific incidences: 0.0% to 12.7%). Predictors for the development of a new decubitus ulcer during a hospital stay included higher age (odds ratio [OR] 1.03 per year, 95% confidence interval [CI] 1.02-1.03), longer hospital stay (OR 1.03 per day, 95% CI 1.031-1.033), treatment in an intensive care unit (OR 2.88, 95% CI 2.58-3.22), and transfer to the hospital from a residential nursing-care facility (OR 6.05, 95% CI 5.13-7.11). The patient's sex and the severity of disease were not correlated with the incidence of decubitus ulcers. The effort-to-benefit ratio could be improved if wards with a low incidence of decubitus ulcers (<0.5%) either entirely discontinued the current hospital-wide procedure for documenting decubitus ulcers (with one new ulcer for every 645 patients) or continued it only for patients aged 65 or older (with one new ulcer for every 902 patients). CONCLUSION: There are major differences between clinical care units in the risk of decubitus ulcers. Epidemiological analysis of routine quality management data is useful to assess the benefit of measures taken in medical care. Continuing evaluation is essential.


Asunto(s)
Centros Médicos Académicos/estadística & datos numéricos , Unidades Hospitalarias/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Transferencia de Pacientes/estadística & datos numéricos , Úlcera por Presión/epidemiología , Úlcera por Presión/prevención & control , Gestión de la Calidad Total/estadística & datos numéricos , Centros Médicos Académicos/normas , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Documentación/normas , Documentación/estadística & datos numéricos , Femenino , Alemania/epidemiología , Unidades Hospitalarias/normas , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Gestión de la Calidad Total/métodos , Adulto Joven
16.
Arch Orthop Trauma Surg ; 133(10): 1469-75, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23880842

RESUMEN

STUDY DESIGN: Case report. CLINICAL QUESTION: Traumatic articular cartilage defects predispose to secondary osteoarthritis accompanied by impairment or complete loss of function in the corresponding joint. On this account, the timely and correct diagnosis as well as the selection of an appropriate therapy for reconstruction of articular cartilage defects is important. METHODS: A 22-year-old healthy male patient with history of traumatic intra-articular distal radius fracture is presented with in the course detectable 4° cartilage damage in the fovea scaphoidea and into the fovea lunata. For the first time, autologous chondrocyte implantation by the use of an in situ polymerizable albumin-hyaluronic acid gel was performed to restore the articular cartilage. RESULTS: The assessment 6 months after autologous chondrocyte implantation using the standard DASH questionnaire for upper extremity pointed out an improvement in the patient outcome (DASH score pre-operative: 10.8 and 6 months post-operative: 7.5). The clinical examination also showed an improvement in the range of movement of the wrist without pain. The radiological control investigation (MRI- examination) of the wrist 6 months after implantation also revealed a good integration of the implant. CONCLUSION: The case presented here demonstrates the first use of autologous chondrocyte implantation for cartilage reconstruction using an in situ polymerizable albumin-hyaluronic acid gel after traumatic cartilage lesion with 4° cartilage damage of the wrist in a 22-year-old non-smoking, active and healthy man. Initial results are promising in terms of mobility, pain and patient outcome. However, further clinical studies have to be performed with larger number of cases.


Asunto(s)
Cartílago Articular/lesiones , Condrocitos/trasplante , Fracturas Intraarticulares/complicaciones , Procedimientos Ortopédicos/métodos , Fracturas del Radio/complicaciones , Traumatismos de la Muñeca/cirugía , Cartílago Articular/cirugía , Humanos , Masculino , Trasplante Autólogo , Adulto Joven
17.
Z Orthop Unfall ; 151(1): 38-47, 2013 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-23423589

RESUMEN

Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI.


Asunto(s)
Enfermedades de los Cartílagos/cirugía , Condrocitos/trasplante , Articulación de la Rodilla/cirugía , Procedimientos Ortopédicos/normas , Ortopedia/normas , Guías de Práctica Clínica como Asunto , Traumatología/normas , Alemania , Humanos
18.
Z Orthop Unfall ; 150(4): 368-73, 2012 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-22753127

RESUMEN

INTRODUCTION: The high tibial osteotomy (HTO) is regarded as an established method for varus deformity. To quantify the varus deformity, the anatomic and the mechanical leg axis can be determined. The success of HTO depends on the correct assessment of the preoperative axis deviation and the exact as planned correction. The aim of the retrospective study was to verify the accuracy (± 1.5° of mechanical tibiofemoral angle tolerance compared to the planning) with the preoperative planning compared to the postoperative result after correction using the TomoFix™ plate in open wedge HTO. MATERIALS AND METHOD: A retrospective study of patients was carried out after open wedge HTO with the TomoFix™ plate. A full-weight bearing, long-standing anteroposterior radiograph of the whole lower extremity was performed before and after correction. The mechanical angles in the frontal plane were determined and compared with the plan as drawn. RESULTS: The preoperative mechanical tibiofemoral angle (mTFA) was -5.33 ± 3.29° (varus) and at follow-up -0.3 ± 3.0° (varus). The mean correction was 4.9 ± 2.9°. The planned mTFA was 2.2 ± 1.6°(valgus). The corrected lower extremity showed a mean difference of -2.5 ± 3.4° in angle correction of the varus deformity as preoperatively assumed to be the optimal correction compared to the planning. The planning goal was not achieved in 73 % of the cases. CONCLUSION: The results are comparable to those of other publications. However, taking into account the required accuracy of the drawn plan combined with the surgical precedure, it is not possible to achieve results within the desired tolerance.


Asunto(s)
Placas Óseas , Articulación de la Rodilla/anomalías , Articulación de la Rodilla/cirugía , Osteotomía/instrumentación , Osteotomía/métodos , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Implantación de Prótesis/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento
19.
Orthopade ; 41(3): 186, 188-94, 2012 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-22407093

RESUMEN

AIM: High tibial osteotomy (HTO) is an established treatment for varus osteoarthritis of the knee. The correction can be achieved by lateral closed wedge HTO or medial open wedge HTO techniques. Both techniques can change the patella position which influences alignment of the patella. Patella infera may compromise the result of secondary total knee prosthesis. An analysis of the current literature was carried out focusing on changes of patella position after HTO. METHOD: A literature search was performed in PubMed which identified 15 relevant publications and the Insall-Salvati-index, the Blackburne-Peel-index and the Caton-Deschamps-index were analyzed. RESULTS: Results after closed wedge HTO: the Insall-Salvati-index decreased in 7 papers, increased in 3 papers and was unchanged in 1 paper. The Blackburne-Peel-index increased in 5 papers and decreased in 2. The Caton-Deschamps-index decreased in 4 papers and increased in 2 papers. Results after open wedge HTO: the InsalI-Salvati-index decreased in 5 papers and increased in 2. The Blackburne-Peel-index decreased in all 7 papers and the Caton-Deschamps-index decreased in all 5 papers. The results of these studies vary significantly and there was a tendency to patella infera in both techniques. The Blackburne-Peel-index and the Caton-Deschamps-index may be biased by slope changes but the exact effect is not yet known. The Insall-Salvati-index seems to be independent of slope changes. The effect of different rehabilitation concepts on patella height is not known. CONCLUSION: The clinical relevance of the observed changes in patella position must be clarified by prospective studies with strict criteria.


Asunto(s)
Inestabilidad de la Articulación/epidemiología , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/cirugía , Osteotomía/estadística & datos numéricos , Rótula/cirugía , Complicaciones Posoperatorias/epidemiología , Tibia/cirugía , Comorbilidad , Humanos , Inestabilidad de la Articulación/cirugía , Prevalencia , Insuficiencia del Tratamiento , Resultado del Tratamiento
20.
J Neurosci Methods ; 201(2): 340-5, 2011 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-21875617

RESUMEN

An important consideration in any terminal experiment is the method used for euthanizing animals. Although the prime consideration is that the method is humane, some methods can have a dramatic impact on experimental outcomes. The standard inhalant anesthetic for experiments in brain slices is isoflurane, which replaced the flammable ethers used in the pioneer days of surgery. To our knowledge, there are no data available evaluating the effects of the method of euthanasia on plasticity changes in brain slices. Here, we compare the magnitude of long-term potentiation (LTP) and long-term depression (LTD) in the lateral nucleus of the amygdala (LA) after euthanasia following either ether or isoflurane anesthesia, as well as in mice decapitated without anesthesia. We found no differences in input-output curves using different methods of euthanasia. The LTP magnitude did not differ between ether and normal isoflurane anesthesia. After deep isoflurane anesthesia LTP induced by high frequency stimulation of cortical or intranuclear afferents was significantly reduced compared to ether anesthesia. In contrast to ether anesthesia and decapitation without anesthesia, the low frequency stimulation of cortical afferents induced a reliable LA-LTD after deep isoflurane anesthesia. Low frequency stimulation of intranuclear afferents only caused LTD after pretreatment with ether anesthesia. The results demonstrate that the method of euthanasia can influence brain plasticity for hours at least in the interface chamber. Therefore, the method of euthanasia is an important consideration when brain plasticity will be evaluated.


Asunto(s)
Amígdala del Cerebelo/fisiología , Eutanasia Animal/métodos , Isoflurano/farmacología , Plasticidad Neuronal/fisiología , Técnicas de Cultivo de Órganos/métodos , Amígdala del Cerebelo/efectos de los fármacos , Anestésicos por Inhalación/farmacología , Animales , Animales de Laboratorio , Estimulación Eléctrica/métodos , Éter/farmacología , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Depresión Sináptica a Largo Plazo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Plasticidad Neuronal/efectos de los fármacos , Técnicas de Cultivo de Órganos/normas
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