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1.
Artigo em Inglês | MEDLINE | ID: mdl-38873914

RESUMO

OBJECTIVES: Data regarding the occurrence of complications specifically during pediatric anesthesia for endoscopic procedures is limited. By evaluating such data, factors could be identified to assure proper staffing and preparation to minimize adverse events and improve patient safety during flexible endoscopy. METHODS: This retrospective cohort study included children undergoing anesthesia for gastroscopy, colonoscopy, bronchoscopy, or combined endoscopic procedures over 10-year period. The primary study aim was to evaluate the incidence of complications and identify risk factors for adverse events. RESULTS: Overall, 2064 endoscopic procedures including 1356 gastroscopies (65.7%), 93 colonoscopies (4.5%), 235 bronchoscopies (11.4%), and 380 combined procedures (18.4%) were performed. Of the 1613 patients, 151 (7.3%) patients exhibited an adverse event, with respiratory complications being the most common (65 [3.1%]). Combination of gastrointestinal endoscopies did not lead to an increased adverse event rate (gastroscopy: 5.5%, colonoscopy: 3.2%). Diagnostic endoscopy as compared to interventional had a lower rate. If bronchoscopy was performed, the rate was similar to that of bronchoscopy alone (19.5% vs. 20.4%). Age < 5.8 years or body weight less than 20 kg, bronchoscopy, American Society of Anesthesiologists status ≥ 2 or pre-existing anesthesia-relevant diseases, and urgency of the procedure were independent risk factors for adverse events. For each risk factor, the risk for events increased 2.1-fold [1.8-2.4]. CONCLUSIONS: This study identifies multiple factors that increase the rate of adverse events associated anesthesia-based endoscopy. Combined gastrointestinal procedures did not increase the risk for adverse events while combination of bronchoscopy to gastrointestinal endoscopy showed a similar risk as bronchoscopy alone.

2.
Mol Genet Metab ; 139(3): 107610, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37245379

RESUMO

PMM2-CDG is the most common defect among the congenital disorders of glycosylation. In order to investigate the effect of hypoglycosylation on important cellular pathways, we performed extensive biochemical studies on skin fibroblasts of PMM2-CDG patients. Among others, acylcarnitines, amino acids, lysosomal proteins, organic acids and lipids were measured, which all revealed significant abnormalities. There was an increased expression of acylcarnitines and amino acids associated with increased amounts of calnexin, calreticulin and protein-disulfid-isomerase in combination with intensified amounts of ubiquitinylated proteins. Lysosomal enzyme activities were widely decreased as well as citrate and pyruvate levels indicating mitochondrial dysfunction. Main lipid classes such as phosphatidylethanolamine, cholesterol or alkyl-phosphatidylcholine, as well as minor lipid species like hexosylceramide, lysophosphatidylcholines or phosphatidylglycerol, were abnormal. Biotinidase and catalase activities were severely reduced. In this study we discuss the impact of metabolite abnormalities on the phenotype of PMM2-CDG. In addition, based on our data we propose new and easy-to-implement therapeutic approaches for PMM2-CDG patients.


Assuntos
Defeitos Congênitos da Glicosilação , Fosfotransferases (Fosfomutases) , Humanos , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/terapia , Defeitos Congênitos da Glicosilação/metabolismo , Glicosilação , Fosfotransferases (Fosfomutases)/genética , Aminoácidos/metabolismo , Lipídeos
3.
Knee Surg Sports Traumatol Arthrosc ; 31(9): 3799-3805, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36820902

RESUMO

PURPOSE: The anterolateral ligament (ALL) is an important structure for controlling anterolateral rotatory stability of the knee. Its assessment, however, is difficult using standardized MRI images. The goal of this study was to assess the reliability of judging the integrity of the ALL on multi-planar reformatted (MPR) MRI images and on standard coronal reformatted (SCR) MRI images in knees with an anterior cruciate ligament (ACL) rupture. METHODS: Forty-eight patients (14 females, 34 males, 30 ± 6 years (mean age ± standard deviation)) with acute ACL ruptures (< 2 weeks) and no additional knee injuries (except segond fractures) were included. Images were assessed by two independent raters twice with at least a 2-week interval in between. The assessment was first performed on SCR images and thereafter on MPR images. Images were judged for assessability of the ALL and then the integrity of the ALL was rated. RESULTS: Depending on rater and read, the ALL was judged as "torn" in between 5 (10.4%) and 11 (22.9%) patients out of 48 patients on SCR images. On MRP images, the ALL was judged as "torn" in between 5 (10.4%) and 6 (12.5%) patients out of 48 patients, depending on rater and read. Inter- and intra-rater reliability for the assessment of the ALL using MPR images was "substantial" to "almost perfect". Inter- and intra-rater reliability for the assessment using SCR was "fair" to "substantial". CONCLUSION: MPR images should be used when assessing the integrity of the ALL. Assessment quality is independent of patient positioning during MRI acquisition and the ALL can be displayed in full length on one image. LEVEL OF EVIDENCE: Level III.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho , Masculino , Feminino , Humanos , Reprodutibilidade dos Testes , Articulação do Joelho/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Ligamentos , Imageamento por Ressonância Magnética/métodos
4.
Eur J Orthop Surg Traumatol ; 33(2): 415-424, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35041071

RESUMO

PURPOSE: Providing long-term outcome data after rTKA and compare one- versus two-stage and septic versus aseptic revisions. METHODS: This study represents a single-center retrospective study of first rTKAs performed for any reason with a final follow-up of a minimum of five years. Outcome parameters included stability assessment ROM, radiologic assessment, HSS score, KSS score, OKS score, EQ-5D-3L and VAS. 44 patients were included in the study. Subgroups analysis of one- versus two-stage revision and septic versus aseptic revision was performed. RESULTS: The leading causes of rTKA in this mean 11 year follow-up study were aseptic loosening (36%) and periprosthetic joint infection (27%). At the final follow-up, there was a 89% survivorship of the implants. Patients showed a ROM of 114 ± 13°, HSS score of 78 ± 12, KKS objective score of 77 ± 16, KSS expectation and satisfaction score of 32 ± 11, KSS functional activity score of 50 ± 20, OKS of 30 ± 9, VAS of 53 ± 25 and EQ-5D index of 0.649. Functional outcome scores were not significantly altered in the analyzed subgroups. CONCLUSIONS: In our 11 years follow-up, we obtained 89% implant survivorship. Measurements regarding functional outcome and pain showed results in the medium range of the respective scores, while patient satisfaction lay in the upper third. No significant differences in outcome scores between one- and two-stage revisions and septic versus aseptic revisions were observed. Level of Evidence Level III, retrospective cohort study.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Seguimentos , Estudos Retrospectivos , Articulação do Joelho , Prótese do Joelho/efeitos adversos , Reoperação/métodos , Resultado do Tratamento , Falha de Prótese
5.
Eur J Orthop Surg Traumatol ; 33(5): 1885-1894, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35989369

RESUMO

PURPOSE: The purpose of this study is to report and compare outcome data of both primary and revision cases using a rotating hinge knee (RHK) implant. METHODS: This study retrospectively analyzed 63 cases (19 primary, 44 revisions) at a mean follow-up of 34 ± 8 months after RHK implantation. Outcome parameters were stability, range of motion (ROM), loosening, Hospital of Special Surgery Score (HSS), Knee Society Score (KSS), Oxford Knee Score (OKS), EQ-5D-3L, and Visual Analog Scale (VAS) for overall function. Revision rates and implant survival are reported. RESULTS: Eleven percent showed medio-lateral instability < 5 mm, a mean ROM of 115° ± 17° and radiologic loosening occurred in 8% (2% symptomatic). PROMS showed the following results: HSS 79 ± 18, KSS 78 ± 27, OKS 26 ± 10, EQ-5D index 0.741 ± 0.233 and VAS 70 ± 20. Primary cases revealed better outcomes in HHS (p = .035) and OKS (p = 0.047). KSS, EQ-5D index and VAS did not differ between primary and revision cases (p = 0.070; p = 0.377; p = 0.117). Revision rate was 6.3% with an implant survival of 96.8%. CONCLUSIONS: RHK arthroplasty can be performed with good clinical outcome and low revision rate in revision and complex primary cases. RHK is an option in cases where standard arthroplasty and even implants with a higher degree of constraint have reached their limits. LEVEL OF EVIDENCE: Level III, retrospective cohort study.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Estudos Retrospectivos , Artroplastia do Joelho/efeitos adversos , Reoperação , Prótese do Joelho/efeitos adversos , Amplitude de Movimento Articular , Resultado do Tratamento , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia
6.
Langenbecks Arch Surg ; 407(7): 2915-2927, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35678902

RESUMO

PURPOSE: Right colectomy (RC) is a frequently performed procedure. Beneath standard conventional open surgery (COS), various minimally invasive techniques had been introduced. Several advantages had recently been described for robotic approaches over COS or conventional laparoscopy. Nevertheless, novel minimally invasive techniques require continuous benchmarking against standard COS to gain maximum patient safety. Bowel dysfunction is a frequent problem after RC. Together with general complication rates postoperative bowel recovery are used as surrogate parameters for postoperative patient outcome in this study. METHODS: Retrospective, 10-year single-center analysis of consecutive patients who underwent sequentially either COS (n = 22), robotic-assisted (ECA: n = 39), or total robotic surgery (ICA: n = 56) for oncologic RC was performed. RESULTS: The conversion from robotic to open surgery rate was low (overall: 3.2%). Slightly longer duration of surgery had been observed during the early phase after introduction of the robotic program to RC (ECA versus COS, p = 0.044), but not anymore thereafter (versus ICA). No differences were observed in oncologic parameters including rates of tumor-negative margins, lymph node-positive patients, and lymph node yield during mesocolic excision. Both robotic approaches are beneficial regarding postoperative complication rates, especially wound infections, and shorter length of in-hospital stay compared with COS. The duration until first postoperative stool is the shortest after ICA (COS: 4 [2-8] days, ECA: 3 [1-6] days, ICA: 3 [1-5] days, p = 0.0004). Regression analyses reveal neither a longer duration of surgery nor the extent of mesocolic excision, but the degree of minimally invasiveness and postoperative systemic inflammation contribute to postoperative bowel dysfunction, which prolongs postoperative in-hospital stay significantly. CONCLUSION: The current study reflects the institutional learning curve of oncologic RC during implementation of robotic surgery from robotic-assisted to total robotic approach without compromises in oncologic results and patient safety. However, the total robotic approach is beneficial regarding postoperative bowel recovery and general patient outcome.


Assuntos
Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Curva de Aprendizado , Estudos Retrospectivos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Colectomia/efeitos adversos , Colectomia/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Resultado do Tratamento
7.
J Shoulder Elbow Surg ; 30(2): e60-e68, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32540315

RESUMO

BACKGROUND: The rotator cuff (RC) and the deltoid muscle are 2 synergistic units that enable the functionally demanding movements of the shoulder. A number of biomechanical studies assume similar force contribution of the force couple (RC and deltoid) over the whole range of motion, whereas others propose position-dependent force distribution. There is a lack of in vivo data regarding the deltoid's contribution to shoulder flexion and abduction strength. This study aimed to create reliable in vivo data quantifying the deltoid's contribution to shoulder flexion and abduction strength throughout the range of motion. METHODS: Active range of motion and isometric muscle strength of shoulder abduction and flexion in 0°, 30°, 60°, 90°, and 120° of abduction/flexion as well as internal and external rotation in 0° and 90° of abduction were obtained in 12 healthy volunteers on the dominant arm before and after an ultrasound-guided isolated axillary nerve block. Needle electromyography was performed before and after the block to confirm deltoid paralysis. Radiographs of the shoulder and an ultrasonographic examination were used to exclude relevant shoulder pathologies. RESULTS: Active range of motion showed a minimal to moderate reduction to 94% and 88% of the preintervention value for abduction and flexion. Internal and external rotation amplitude was not impaired. The abduction strength was significantly reduced to 76% at 0° (P = .002) and to 25% at 120° (P < .001) of abduction. The flexion strength was significantly reduced to 64% at 30° (P < .001) and to 30% at 120° (P < .001) of flexion. The strength reduction was linear, depending on the flexion/abduction angle. The maximal external rotation strength showed a significant decrease to 53% in 90° (P < .001) of abduction, whereas in adduction no strength loss was observed (P = .09). The internal rotation strength remained unaffected in 0° and 90° of abduction (P = .28; P = .13). CONCLUSION: The deltoid shows a linear contribution to maximal shoulder strength depending on the abduction or flexion angle, ranging from 24% in 0° to 75% in 120° of abduction and from 11% in 0° to 70% in 120° of flexion, respectively. The overall contribution to abduction strength is higher than to flexion strength. The combination of deltoid muscle and teres minor contributes about 50% to external rotation strength in 90° of abduction. The internal rotation strength is not influenced by a deltoid paralysis. This study highlights the position-dependent contribution of the shoulder muscles to strength development and thereby provides an empirical approach to better understand human shoulder kinematics.


Assuntos
Articulação do Ombro , Ombro , Fenômenos Biomecânicos , Músculo Deltoide , Humanos , Amplitude de Movimento Articular , Rotação , Manguito Rotador , Articulação do Ombro/diagnóstico por imagem
8.
Molecules ; 26(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917726

RESUMO

This paper studies the influence of hydroxyethyl methyl cellulose (HEMC) on the properties of calcium sulfoaluminate (CSA) cement mortar. In order to explore the applicability of different HEMCs in CSA cement mortars, HEMCs with higher and lower molar substitution (MS)/degree of substitution (DS) and polyacrylamide (PAAm) modification were used. At the same time, two kinds of CSA cements with different contents of ye'elimite were selected. Properties of cement mortar in fresh and hardened states were investigated, including the fluidity, consistency and water-retention rate of fresh mortar and the compressive strength, flexural strength, tensile bond strength and dry shrinkage rate of hardened mortar. The porosity and pore size distribution were also analyzed by mercury intrusion porosimetry (MIP). Results show that HEMCs improve the fresh state properties and tensile bond strength of both types of CSA cement mortars. However, the compressive strength of CSA cement mortars is greatly decreased by the addition of HEMCs, and the flexural strength is decreased slightly. The MIP measurement shows that HEMCs increase the amount of micron-level pores and the porosity. The HEMCs with different MS/DS have different effects on the improvement of tensile bond strength in different CSA cement mortars. PAAm modification can improve the tensile bond strength of HEMC-modified CSA cement mortar.

9.
Arch Orthop Trauma Surg ; 141(12): 2185-2194, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34269891

RESUMO

INTRODUCTION: Total knee arthroplasty (TKA) has historically been the preferred solution for any type of knee osteoarthritis, independently of the number of compartments involved. In these days of patient-specific medicine, mono-compartmental disease could also be approached with a more individualized treatment, such as partial knee arthroplasty (PKA). Off-the-shelf (OTS) implants are often the compromise of averages and means of a limited series of anatomical parameters retrieved from patients and the pressure of cost control by limited inventory. Personalized medicine requires respect and interest for the individual shape and alignment of each patient. MATERIALS AND METHODS: A Pubmed and Google Scholar search were performed with the following terms: "patient-specific knee" and "arthroplasty" and "custom implant" and "total knee replacement" and "partial knee replacement" and "patellofemoral knee replacement" and "bicompartmental knee replacement". The full text of 90 articles was used to write this narrative review. RESULTS: Unicondylar, patellofemoral and bicompartmental knee arthroplasty are successful treatment options, which can be considered over TKA for their bone and ligament sparing character and the superior functional outcome that can be obtained with resurfacing procedures. For TKA, where compromises dominate our choices, especially in patients with individual variations of their personal anatomy outside of the standard, a customized implant could be a preferable solution. CONCLUSION: TKA might not be the only solution for every patient with knee osteoarthritis, if personalized medicine wants to be offered. Patient-specific mono-compartmental resurfacing solutions, such as partial knee arthroplasty, can be part of the treatment options proposed by the expert surgeon. Customized implants and personalized alignment options have the potential to further improve clinical outcome by identifying the individual morphotype and respecting the diversity of the surgical population.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Joelho , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Resultado do Tratamento
10.
Eur J Orthop Surg Traumatol ; 31(7): 1387-1393, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33555443

RESUMO

PURPOSE: The purpose of this study was to outline an indirect sign of advanced Achilles tendinopathy on magnetic resonance imaging (MRI), based on the hypothesis that these patients would present with secondary hypertrophy of the flexor hallucis longus muscle (FHL). METHODS: MRI scans of Achilles tendon were analyzed retrospectively in two cohorts. The study group consisted of consecutive patients presenting with clinical signs of Achilles tendinopathy and no previous surgeries, while the control group were patients that had an MRI due to other reasons and no signs of tendinopathy. Two parameters from two muscle bellies were measured and compared on axial MRI scans 4-5 cm above the ankle joint line at the level of greatest thickness: area and diameter of the triceps surae (TS) and of the FHL muscle. Ratios (FHL/TS) were calculated for area (Ar) and diameter (Dm) measurements. Interobserver agreement was analyzed. A receiver operating characteristic (ROC) curve was created for both ratios to assess potential cutoff points to differentiate between the groups. RESULTS: A total of 60 patients for each study group were included. Both ratios Ar(FHL/TS) and Dm(FHL/TS) showed significant higher values in the tendinopathy group (p < 0.001). There were strong to very strong intraclass correlation coefficients (ICC = 0.75-0.93). A diameter ratio Dm (FHL/TS) of 2.0 or higher had a sensitivity of 49% and specificity of 90% for concomitant Achilles tendinopathy. CONCLUSION: In our patient cohort, FHL hypertrophy was observed in patients with Achilles tendinopathy as a possible compensatory mechanism. Measuring a diameter ratio Dm(FHL/TS) of 2.0 or higher on an axial MRI, may be indicative as an indirect sign of functional deterioration of the Achilles tendon.


Assuntos
Tendão do Calcâneo , Tendinopatia , Tendão do Calcâneo/diagnóstico por imagem , Estudos de Casos e Controles , Humanos , Hipertrofia , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Ruptura , Tendinopatia/diagnóstico por imagem , Tendinopatia/etiologia , Transferência Tendinosa
11.
Ann Surg Oncol ; 27(4): 1147-1155, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31646454

RESUMO

BACKGROUND: Surgical resection is associated with the best long-term results for intrahepatic cholangiocarcinoma (ICC); however, long-term outcomes are still poor. OBJECTIVE: The primary aim of this study was to validate the recently proposed MEGNA score and to identify additional prognostic factors influencing short- and long-term survival. PATIENTS AND METHODS: This was a retrospective analysis of a German multicenter cohort operated at 10 tertiary centers from 2004 to 2013. Patients were clustered using the MEGNA score and overall survival was analyzed. Cox regression analysis was used to identify prognostic factors for both overall and 90-day survival. RESULTS: A total of 488 patients undergoing liver resection for ICC fulfilled the inclusion criteria and underwent analysis. Median age was 67 years, 72.5% of patients underwent major hepatic resection, and the lymphadenectomy rate was 86.9%. Median overall survival was 32.2 months. The MEGNA score significantly discriminated the long-term overall survival: 0 (68%), I (48%), II (32%), and III (19%) [p <0.001]. In addition, anemia was an independent prognostic factor for overall survival (hazard ratio 1.78, 95% confidence interval 1.29-2.45; p <0.01). CONCLUSION: Hepatic resection provides the best long-term survival in all risk groups (19-65% overall survival). The MEGNA score is a good discriminator using histopathologic items and age for stratification. Correction of anemia should be attempted in every patient who responds to treatment. Perioperative liver failure remains a clinical challenge and contributes to a relevant number of perioperative deaths.


Assuntos
Anemia/complicações , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Oncologia/métodos , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Alemanha/epidemiologia , Hepatectomia , Humanos , Excisão de Linfonodo , Masculino , Oncologia/normas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo
12.
J Shoulder Elbow Surg ; 29(3): 516-520, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31563506

RESUMO

BACKGROUND: Shoulder joint aspirations are frequently performed to rule out infection. In case of unsuccessful aspiration, physicians often augment the aspiration liquid by injecting saline solution. METHODS: We performed shoulder joint aspirations by fluoroscopic assistance and analyzed the value of an additional saline solution irrigation in patients undergoing revision shoulder surgery. Native joints and post-fracture repair, post-arthroscopy, and post-arthroplasty shoulders were included. A minimum of 3 deep intraoperative tissue samples served as the microbiological gold standard. RESULTS: We performed 106 aspirations occurring between 0 and 179 days before revision surgery. Among them, we could sample intra-articular liquid directly in 60 cases and after saline solution injection in 43 cases, whereas 3 cases remained unsuccessful. According to intraoperative samples, 24 shoulders were infected but only 10 of 24 (42%) yielded pathogens in the aspirate. Moreover, of the 43 saline solution-enforced irrigations, none revealed bacteria but 8 (17%) confirmed infection in intraoperative samples. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of presurgical aspirations were 33%, 98%, 80%, and 83%, respectively. CONCLUSION: When surgical revision is planned, presurgical shoulder joint aspiration is not reliable to sufficiently exclude shoulder joint infection. Nevertheless, a positive aspiration finding can guide clinical decision making, so we propose to perform aspiration only if there is a clinically high index of suspicion for an infection. Irrigation after unsuccessful primary aspiration is futile.


Assuntos
Artrite Infecciosa/diagnóstico , Artrocentese , Articulação do Ombro , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Infecciosa/cirurgia , Artroplastia , Artroscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
13.
Plant J ; 95(3): 458-473, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29763523

RESUMO

Cytokinin plays diverse roles in plant growth and development, generally acting by modulating gene transcription in target tissues. The type-B Arabidopsis response regulators (ARR) transcription factors have emerged as primary targets of cytokinin signaling and are required for essentially all cytokinin-mediated changes in gene expression. The diversity of cytokinin function is likely imparted by the activity of various transcription factors working with the type-B ARRs to alter specific sets of target genes. One potential set of co-regulators modulating the cytokinin response are the BARLEY B-RECOMBINANT/BASIC PENTACYSTEINE (BBR/BPC) family of plant-specific transcription factors. Here, we show that disruption of multiple BPCs results in reduced sensitivity to cytokinin. Further, the BPCs are necessary for the induction of a subset of genes in response to cytokinin. We identified direct in vivo targets of BPC6 using ChIP-Seq and found an enrichment of promoters of genes differentially expressed in response to cytokinin. Further, a significant number of BPC6 regulated genes are also direct targets of the type-B ARRs. Potential cis-binding elements for a number of other transcription factors linked to cytokinin action are enriched in the BPC binding fragments, including those for the cytokinin response factors (CRFs). In addition, several BPCs interact with a subset of type-A ARRs. Consistent with these results, a significant number of genes whose expression is altered in bpc mutant roots are also mis-expressed in crf1,3,5,6 and type-A arr3,4,5,6,7,8,9,15 mutant roots. These results suggest that the BPCs are part of a complex network of transcription factors that are involved in the response to cytokinin.


Assuntos
Proteínas de Arabidopsis/metabolismo , Citocininas/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas/genética , Glucosiltransferases/metabolismo
14.
Transpl Infect Dis ; 21(5): e13138, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31278878

RESUMO

Human cytomegalovirus (HCMV) infections and reactivations are common after lung transplantation and are associated with the development of bronchiolitis obliterans syndrome. Against this background, temporary HCMV prophylaxis is an established standard regimen after lung transplantation in most centers. However, the optimal duration of prophylaxis is unclear. We conducted a retrospective two-center study to determine the efficacy of indefinite lifelong HCMV prophylaxis with oral valganciclovir in a cohort of 133 lung transplant recipients with a mean follow-up time of approximately 5 years. During the follow-up period, HCMV DNA was detected in 22 recipients (16.5%). In one case, HCMV pneumonitis developed after prophylaxis had been terminated. We observed a beneficial safety profile and tolerability in our cohort, as the majority of patients still received valganciclovir after a 1- and 3-year observation period, respectively. Compared to the literature, these data indicate a beneficial effect of extended valganciclovir prophylaxis with an acceptable safety profile.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Transplante de Pulmão , Valganciclovir/administração & dosagem , Adulto , Idoso , Citomegalovirus , Infecções por Citomegalovirus/complicações , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transplantados , Adulto Jovem
15.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1863(9): 1016-1028, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29902569

RESUMO

Inflammatory disorders such as sepsis are a major cause of morbidity and mortality. Mitochondrial dysfunction is considered a key factor in the pathogenesis of severe inflammation. In the present study, we aimed to investigate the impact of arachidonic acid, omega-3 (n-3) fatty acids, and n-3-derived lipid mediators 18R-HEPE and resolvin (Rv) E1 on mitochondrial function in experimental inflammation. The results revealed that, in contrast to n-6 and n-3 fatty acids, both 18R-HEPE and RvE1 possess anti-inflammatory and anti-apoptotic properties. Both mediators are able to restore inflammation-induced mitochondrial dysfunction, which is characterized by a decrease in mitochondrial respiration and membrane potential, as well as an imbalance of mitochondrial fission and fusion. Furthermore, inhibition of mitochondrial fission by Mdivi-1 and Dynasore reduces levels of the pro-inflammatory cytokines IL-6 and IL-8. These results suggest a novel functional mechanism for the beneficial effects of RvE1 in inflammatory reactions.


Assuntos
Ácido Eicosapentaenoico/análogos & derivados , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Ácido Araquidônico/farmacologia , Respiração Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Humanos , Inflamação , Interleucina-6/biossíntese , Interleucina-6/metabolismo , Interleucina-8/biossíntese , Interleucina-8/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Mitocôndrias/metabolismo , Modelos Biológicos , Cultura Primária de Células , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
16.
J Surg Res ; 223: 230-236, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29433879

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most dismal of human malignancies. Neuropeptides have shown to be implicated in angiogenesis, tumor growth, and formation of distant metastases in various solid tumors. In the present study, we used a genetically engineered mouse model of pancreatic cancer to evaluate the impact of neuropeptide Y (NPY) and its receptors 1 (Y1) and 2 (Y2) in preneoplastic lesions and pancreatic cancer as a potential target with antiproliferative properties. In addition, human PDAC tissue was analyzed. MATERIALS AND METHODS: By interbreeding conditional LsL-Trp53R172H,LsL-KrasG12D and Pdx1-Cre strains, we obtained LsL-KrasG12D;LsL-Trp53R172H;Pdx1-Cre(KPC), LsL-KrasG12D;Pdx1-Cre(KP) and control mice (n = 8 each). Mice were then followed in a longitudinal study for 3 to 6 mo. Pancreata were analyzed in regard to pancreatic intraepithelial neoplasia (PanIN) lesions and invasive carcinoma. Corresponding sections were then assessed by immunohistochemistry and quantitative polymerase chain reaction for NPY, Y1 and Y2 expression in murine and human samples. RESULTS: NPY and Y1 expressions were detected in human and murine pancreatic samples, but expression levels were similar in neoplastic and non-neoplastic tissue. Y2 revealed a significant increase of expression in the transgenic mouse model in PanIN lesions and pancreatic cancer compared to control. This holds also true for human samples of pancreatic cancer. Immunohistochemistry of Y2 in murine and human samples of PanINs and pancreatic carcinoma revealed an increased expression in PanIN lesions and pancreatic cancer. CONCLUSIONS: Y2 is strongly overexpressed in pancreatic cancer and may modulate angiogenesis.


Assuntos
Carcinoma in Situ/química , Neuropeptídeo Y/análise , Neoplasias Pancreáticas/química , Receptores de Neuropeptídeo Y/análise , Animais , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pâncreas/química
17.
Int J Colorectal Dis ; 33(11): 1551-1557, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30112664

RESUMO

PURPOSE: Postoperative gut dysmotility is a physiologic and frequent temporary reaction after major abdominal surgery. If paralysis merges into a prolonged ileus state, it causes significant morbidity and subsequently worse outcome and discomfort for the patients. Pathophysiology of pathologic prolonged postoperative paralytic ileus remains multifactorial. METHODS: We present a retrospective single-center analysis of patients, who underwent a primary open oncologic anterior rectal resection with primary anastomosis with or without defunctioning loop ileostomy during a 43-month period of observation. Primary endpoint was the rate of prolonged postoperative paralytic ileus, defined by the intravenous administration of neostigmine. Confounders for regression analysis were assessed by univariate analysis and correlations between confounders were examined. Odds ratio for prolonged postoperative paralytic ileus in patients with defunctioning loop ileostomy was estimated by a logistic regression model. RESULTS: Of 101 patients (62 male), 62 (61.39%) received defunctioning loop ileostomy. In univariate analysis, male gender and patients with ileostomy showed more frequently prolonged paralysis by tendency (both p = 0.07). Logistic regression analysis proves the influence of a defunctioning ileostomy on the development of prolonged postoperative paralytic ileus after oncologic rectal resection (p = 0.047). Odds ratio for prolonged postoperative paralytic ileus in patients with ileostomy was 4.96 [95% CI 1.02-24.03]. CONCLUSIONS: Although the construction of defunctioning loop ileostomies during rectal resection is a safe, uncomplicated surgical procedure, they can cause significant postoperative morbidity for the patients. High fluid and electrolyte loss are well-known complications, but herewith we raise the evidence for prolonged gut paralysis in patients with defunctioning loop ileostomy.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Ileostomia , Pseudo-Obstrução Intestinal/etiologia , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/complicações , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
Surg Endosc ; 32(6): 2664-2675, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29218675

RESUMO

BACKGROUND: Pleural empyema is an infectious disease of the chest cavity, with a high morbidity and mortality. According to the American Thoracic Society, pleural empyema gets graduated into three stages, with surgery being indicated in intermediate stage II and chronic stage III. Evidence for the feasibility of a minimally-invasive video-assisted thoracoscopic approach in stage III empyema for pulmonary decortication is still little. METHODS: Retrospective single-center analysis of patients conducted to surgery for chronic stage III pleural empyema from 05/2002 to 04/2014 either by video-assisted thoracoscopic surgery (VATS, n = 110) or conventional open surgery by thoracotomy (n = 107). Multiple regression analysis and propensity score matching was used to evaluate the influence of operation technique (thoracotomy versus VATS) on the length of post-operative hospitalization. RESULTS: Operation time was longer in the thoracotomy-group (p = 0.0207). Conversion rate from VATS to open surgery by thoracotomy was 4.5%. Post-operative complication- (61 patients in thoracotomy- and 55 patients in VATS-group), recurrence- (3 patients in thoracotomy- and 5 in VATS-group) and mortality-rates (6.5% in thoracotomy- and 9.5% in VATS-group) did not differ between both groups; the length of (post-operative) stay at intensive care unit was longer in the VATS-group (p = 0.0023). Duration of chest tube drainage and prolonged air leak rate were similar among both groups, leading to a similar overall and post-operative length of hospital stay in both groups. Adjusted to clinically and statistically relevant confounders, multiple regression analysis showed an influence of the surgical technique on length of post-operative stay after pair matching of the patients (n = 84 in each group) by propensity score (B = - 0.179 for thoracotomy = 0 and VATS = 1, p = 0.032) leading to a reduction of 0.836 days after a VATS-approach compared to thoracotomy. CONCLUSIONS: VATS in late stage (III) pleural empyema is feasible and safe. The decrease in post-operative hospitalization demonstrated by adjusted multiple regression analysis may indicate the minimally-invasive approach being safe, more tolerable for patients, and more effective.


Assuntos
Empiema Pleural/cirurgia , Cirurgia Torácica Vídeoassistida , Toracotomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Empiema Pleural/patologia , Estudos de Viabilidade , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Thorac Cardiovasc Surg ; 66(7): 603-606, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-28582786

RESUMO

Persistent air leaks (PALs) are regarded as a frequent complication after thoracic surgery resulting in prolonged hospitalization and increased morbidity. Several more or less invasive therapeutic approaches are available for treatment of PAL with varying degrees of success. The endoscopic placement of one-way intrabronchial valves in the segment(s) in which the air leak has been located offers a highly effective and well-tolerated minimal invasive option for patients with PAL.


Assuntos
Broncoscopia/instrumentação , Pneumotórax/terapia , Implantação de Prótese/instrumentação , Broncoscopia/efeitos adversos , Remoção de Dispositivo , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Fatores de Risco , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Resultado do Tratamento
20.
Neurocrit Care ; 29(2): 291-301, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29949006

RESUMO

BACKGROUND: A novel multiparameter brain sensor (MPBS) allows the simultaneous measurement of brain tissue oxygenation (ptiO2), cerebral blood flow (CBF), intracranial pressure (ICP), and brain temperature with a single catheter. This laboratory investigation evaluates the MPBS in an animal model in relation to established reference probes. METHODS: The study group consisted of 17 juvenile male pigs. Four MPBS and four reference probes were implanted per pig and compared simultaneously. The measured parameters were challenged by standardized provocations such as hyperoxia, dobutamine, and norepinephrine application, hypercapnia and hypoxia in combination with and without a controlled cortical impact (CCI) injury. Mean values over 2 min were collected for predefined time points and were analyzed using Bland-Altman plots. RESULTS: The protocol was successfully conducted in 15 pigs of which seven received CCI. ICP and ptiO2 were significantly influenced by the provocations. Subtraction of MPBS from reference values revealed a mean difference (limits of agreement) of 3.7 (- 20.5 to 27.9) mm Hg, - 2.9 (- 7.9 to 2.1) mm Hg, and 5.1 (- 134.7 to 145.0) % for ptiO2, ICP, and relative CBF, respectively. CONCLUSIONS: The MPBS is a promising measurement tool for multiparameter neuromonitoring. The conducted study demonstrates the in vivo functionality of the probe. Comparison with standard probes revealed a deviation which is mostly analogous to other multiparameter devices. However, further evaluation of the device is necessary before it can reliably be used for clinical decision making.


Assuntos
Temperatura Corporal/fisiologia , Lesões Encefálicas/fisiopatologia , Encéfalo/fisiologia , Circulação Cerebrovascular/fisiologia , Pressão Intracraniana/fisiologia , Monitorização Neurofisiológica/instrumentação , Consumo de Oxigênio/fisiologia , Animais , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Modelos Animais de Doenças , Fluxometria por Laser-Doppler , Masculino , Monitorização Neurofisiológica/métodos , Suínos
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