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1.
Surg Endosc ; 38(2): 679-687, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38017156

RESUMO

OBJECTIVES: Lung volume reduction surgery (LVRS) has proven an effective treatment for emphysema, by decreasing hyperinflation and improving lung function, activity level and reducing dyspnoea. However, postoperative air leak is an important complication, often leading to reoperation. Our aim was to analyse reoperations after LVRS and identify potential predictors. METHODS: Consecutive single-centre unilateral VATS LVRS performed from 2017 to 2022 were included. Typically, 3-5 minor resections were made using vascular magazines without buttressing. Data were obtained from an institutional database and analysed. Multivariable logistic regression was used to identify predictors of reoperation. Number and location of injuries were registered. RESULTS: In total, 191 patients were included, 25 were reoperated (13%). In 21 patients, the indication for reoperation was substantial air leak, 3 patients bleeding and 1 patient empyema. Length of stay (LOS) was 21 (11-33) vs. 5 days (3-11), respectively. Only 3 injuries were in the stapler line, 13 within < 2cm and 15 injuries were in another site. Multivariable logistic regression analysis showed that decreasing DLCO increased risk of reoperation, OR 1.1 (1.03, 1.18, P = 0.005). Resections in only one lobe, compared to resections in multiple lobes, were also a risk factor OR 3.10 (1.17, 9.32, P = 0.03). Patients undergoing reoperation had significantly increased 30-day mortality, OR 5.52 (1.03, 26.69, P = 0.02). CONCLUSIONS: Our incidence of reoperation after LVRS was 13% leading to prolonged LOS and increased 30-day mortality. Low DLCO and resections in a single lobe were significant predictors of reoperation. The air leak was usually not localized in the stapler line.


Assuntos
Pneumonectomia , Enfisema Pulmonar , Humanos , Pneumonectomia/efeitos adversos , Reoperação , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/cirurgia , Cirurgia de Second-Look , Resultado do Tratamento
2.
Front Oncol ; 13: 1256760, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37766866

RESUMO

Background: FLASH radiotherapy (RT) is a novel method for delivering ionizing radiation, which has been shown in preclinical studies to have a normal tissue sparing effect and to maintain anticancer efficacy as compared to conventional RT. Treatment of head and neck tumors with conventional RT is commonly associated with severe toxicity, hence the normal tissue sparing effect of FLASH RT potentially makes it especially advantageous for treating oral tumors. In this work, the objective was to study the adverse effects of dogs with spontaneous oral tumors treated with FLASH RT. Methods: Privately-owned dogs with macroscopic malignant tumors of the oral cavity were treated with a single fraction of ≥30Gy electron FLASH RT and subsequently followed for 12 months. A modified conventional linear accelerator was used to deliver the FLASH RT. Results: Eleven dogs were enrolled in this prospective study. High grade adverse effects were common, especially if bone was included in the treatment field. Four out of six dogs, who had bone in their treatment field and lived at least 5 months after RT, developed osteoradionecrosis at 3-12 months post treatment. The treatment was overall effective with 8/11 complete clinical responses and 3/11 partial responses. Conclusion: This study shows that single-fraction high dose FLASH RT was generally effective in this mixed group of malignant oral tumors, but the risk of osteoradionecrosis is a serious clinical concern. It is possible that the risk of osteonecrosis can be mitigated through fractionation and improved dose conformity, which needs to be addressed before moving forward with clinical trials in human cancer patients.

3.
Biomed Hub ; 8(1): 46-53, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37405232

RESUMO

Bronchoscopic lung volume reduction (BLVR) for emphysematous hyperinflation has evolved during the last two decades as an alternative to lung volume reduction surgery (LVRS) with lower morbidity and mortality. Emphysematous lung sealant (ELS) is a form of BLVR specifically aimed at patients with collateral ventilation (CV), shown to have favorable outcomes in lung function up to two years. This case series presents four emphysema patients treated bilaterally with ELS, with a follow-up period up to six years. Two of the patients had previously undergone LVRS and BLVR with valves. Following ELS installment, all patients showed positive changes in spirometric values, with varying durability between one and five years. Three patients reported an overall improvement in subjective symptoms after treatment as measured by the COPD Assessment Test (CAT), one of which had lasting improvement even after five years (CAT from 20 to 13). Two of the four treated patients suffered recurrent respiratory exacerbations and pneumonias requiring hospitalization. They both went on to receive lung transplantation within one and three years. This report concludes that ELS has a meaningful effect on reducing hyperinflation in emphysema with improving pulmonary function tests, and relieving symptoms of dyspnea for up to five years. Unfortunately, some patients develop complications leading to recurrent exacerbations. We were not able to show a survival benefit with ELS treatment. This article highlights the need for further research in order to predict who will benefit from this treatment and how to handle CV-positive patients.

4.
Plast Reconstr Surg Glob Open ; 11(6): e5046, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37305199

RESUMO

Patients undergoing plastic surgery of the breasts often communicate their size expectations as a brassiere cup size. However, multiple factors may cause a miscommunication between the surgeon and patient when brassiere cup size is used as a measure of results. The aim of this study was to determine the degree of agreement between disclosed and estimated brassiere cup size and also interrater agreement. Methods: Three-dimensional (3D) scans of 32 subjects were evaluated by 10 plastic surgeons estimating cup size using the American brassiere system. The surgeons were blinded to all parameters, including the 3D surface software-derived volume measures of the Vectra scan. The 3D scans of the anterior torsos were viewed. The plastic surgeons' estimations were compared with the cup sizes stated by the subjects (disclosed cup size), using simple and weighted Kappa statistics. Results: Agreement between the estimated and disclosed brassiere sizes was only slight (0.1479 ± 0.0605) using a simple Kappa analysis. Even when a Fleiss-Cohen-weighted comparison was used, only moderate agreement (0.6231 ± 0.0589) was found. The interrater agreement intraclass correlation coefficient was 0.705. Rater accuracy varied. The percentage of time spent in cosmetic practice and gender were not significantly correlated with accuracy. Conclusions: Agreement between cup size disclosed by subjects and estimates by plastic surgeons was low. A miscommunication between the surgeon and patient may occur when using brassiere sizes to communicate wishes and estimates in procedures that involve changes in breast volume.

5.
Med Phys ; 50(7): 4047-4054, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37190907

RESUMO

BACKGROUND: During recent years FLASH radiotherapy (FLASH-RT) has shown promising results in radiation oncology, with the potential to spare normal tissue while maintaining the antitumor effects. The high speed of the FLASH-RT delivery increases the need for fast and precise motion monitoring to avoid underdosing the target. Surface guided radiotherapy (SGRT) uses surface imaging (SI) to render a 3D surface of the patient. SI provides real-time motion monitoring and has a large scanning field of view, covering off-isocentric positions. However, SI has so far only been used for human patients with conventional setup and treatment. PURPOSE: The aim of this study was to investigate the performance of SI as a motion management tool during electron FLASH-RT of canine cancer patients. METHODS: To evaluate the SI system's ability to render surfaces of fur, three fur-like blankets in white, grey, and black were used to imitate the surface of canine patients and the camera settings were optimized for each blanket. Phantom measurements using the fur blankets were carried out, simulating respiratory motion and sudden shift. Respiratory motion was simulated using the QUASAR Respiratory Motion Phantom with the fur blankets placed on the phantom platform, which moved 10 mm vertically with a simulated respiratory period of 4 s. Sudden motion was simulated with an in-house developed phantom, consisting of a platform which was moved vertically in a stepwise motion at a chosen frequency. For sudden measurements, 1, 2, 3, 4, 5, 6, 7, and 10 Hz were measured. All measurements were both carried out at the conventional source-to-surface distance (SSD) of 100 cm, and in the locally used FLASH-RT setup at SSD = 70 cm. The capability of the SI system to reproduce the simulated motion and the sampling time were evaluated. As an initial step towards clinical implementation, the feasibility of SI for surface guided FLASH-RT was evaluated for 11 canine cancer patients. RESULTS: The SI camera was capable of rendering surfaces for all blankets. The deviation between simulated and measured mean peak-to-peak breathing amplitude was within 0.6 mm for all blankets. The sampling time was generally higher for the black fur than for the white and grey fur, for the measurement of both respiratory and sudden motion. The SI system could measure sudden motion within 62.5 ms and detect motion with a frequency of 10 Hz. The feasibility study of the canine patients showed that the SI system could be an important tool to ensure patient safety. By using this system we could ensure and document that 10 out of 11 canine patients had a total vector offset from the reference setup position <2 mm immediately before and after irradiation. CONCLUSIONS: We have shown that SI can be used for surface guided FLASH-RT of canine patients. The SI system is currently not fast enough to interrupt a FLASH-RT beam while irradiating but with the short sampling time sudden motion can be detected. The beam can therefore be held just prior to irradiation, preventing treatment errors such as underdosing the target.


Assuntos
Elétrons , Neoplasias , Humanos , Animais , Cães , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Neoplasias/veterinária , Diagnóstico por Imagem , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos
6.
Eur Clin Respir J ; 10(1): 2178600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36861118

RESUMO

Introduction: Long-term High Flow Nasal Cannula (LT-HFNC), defined as High Flow Nasal Cannula treatment provided to patients with chronic pulmonary conditions during stable phases, has emerged as a home treatment in different categories of patients with chronic lung diseases in recent years. Methods: This paper summarizes the physiological effects of LT-HFNC and evaluates the clinical knowledge to date about treatment in patients with chronic obstructive lung disease, interstitial lung disease and bronchiectasis. The guideline is translated and summarized in this paper and presented unabridged as an appendix to the paper. Results: The paper describes the working process behind the Danish Respiratory Society's National guideline for treatment of stable disease, which has been written to support clinicians in both evidence-based decision making and practical issues concerning the treatment.

7.
Methods Mol Biol ; 2551: 461-479, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36310220

RESUMO

Protein misfolding and self-assembling into amyloid structures are associated with a number of diseases. Characterization of protein amyloid formation reactions is a challenging task as transient populations of multiple species are involved. Here we outline a method for identification and characterization of the individual soluble states during protein amyloid formation. The method combines NMR translational diffusion measurements with multilinear data analysis.


Assuntos
Amiloide , Proteínas Amiloidogênicas , Superóxido Dismutase-1/metabolismo , Amiloide/química , Espectroscopia de Ressonância Magnética , Difusão
8.
Transplant Proc ; 54(8): 2329-2336, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36127173

RESUMO

BACKGROUND: Post-transplantation anemia (PTA) is frequent among solid organ transplant recipients and has been associated with increased morbidity and mortality. However, the prevalence and impact of PTA in lung transplant recipients is still not elucidated. METHODS: We performed a retrospective cohort study of adult Danish lung transplant recipients between January 2010 and December 2019. The prevalence and severity of PTA were determined during the first three years post-transplantation. Associations between PTA and selected risk factors were established using uni- and multivariate logistic regression models. RESULTS: A total of 278 patients were included. At one and three years post-lung transplantation the prevalence of PTA was 75% and 52%, respectively. Male sex was associated with increased odds of PTA at all time points (aOR ranging from 2.3, 95% CI 1.1-4.6, P = 0.02 to 5.9, 95% CI 2.6-14, P < .001). Cystic fibrosis was also associated with anemia at one-year post-transplantation (aOR 4.3, 95% CI 1.2-17, P = 0.03). We found no strong associations between PTA and renal function or viral infections. Excess mortality in recipients with moderate or severe anemia compared to patients with mild or no anemia was borderline statistically significant at one-year post-lung transplantation (aHR 2.0, 95% CI 0.9-4.4, P = 0.07). DISCUSSION: Post-transplantation anemia is very common in Danish lung transplant recipients. Male sex and cystic fibrosis are independent risk factors for development of anemia. Further investigation on PTA, the underlying mechanisms, and its clinical impact is needed.


Assuntos
Anemia , Fibrose Cística , Transplante de Rim , Transplante de Pulmão , Adulto , Humanos , Masculino , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Fibrose Cística/complicações , Fatores de Tempo , Anemia/diagnóstico , Anemia/epidemiologia , Anemia/etiologia , Fatores de Risco , Transplante de Pulmão/efeitos adversos
9.
Eur J Midwifery ; 6: 12, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350798

RESUMO

INTRODUCTION: Breastfeeding and factors influencing breastfeeding are essential when considering the association between parity and neonatal and maternal morbidity risks when mothers are discharged within 24 hours after birth. However, there is a lack of studies examining the effect of parity and breastfeeding in a setting where all healthy mothers are recommended discharge four hours after birth. Therefore, this study examined the association between parity and the time for discharge, breastfeeding, and factors influencing breastfeeding. METHODS: The study was designed as a prospective cohort study. Data were obtained from questionnaires at one and at six weeks after birth, and combined with registered data. All 147 included mothers were healthy, with an uncomplicated birth and a healthy newborn, discharged within 24 hours after birth. RESULTS: This study documented that primiparous women had a higher relative risk (RR=2.62; 95% CI: 1.35-5.10) of having doubts about infant feeding after discharge than multiparous women. Furthermore, 54% of primiparous women contacted the maternity ward after discharge compared to 27% of multiparous women. Twice as many primiparous than multiparous women felt anxious or depressed at one and at six weeks after birth. Finally, the study documented that 13% of primiparous women and 5% of multiparous women discharged within six hours after birth perceived the time before discharge to be too short. CONCLUSIONS: Primiparous women differ from multiparous women regarding breastfeeding, insecurity, and anxiety. Special attention towards primiparous women and a follow-up strategy that allows the mothers to contact the maternity ward after early discharge is recommended.

10.
Plast Reconstr Surg Glob Open ; 9(10): e3826, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34712540

RESUMO

BACKGROUND: The 21-cm notch-to-nipple distance has been accepted without academic scrutiny as a key measure in breast aesthetics. The Fibonacci sequence and phi ratio occur frequently in nature. They have previously been used to assess aesthetics of the face, but not the breast. This study aims to assess if the static 21-cm measure or the proportional phi ratio is associated with ideal breast aesthetics. METHOD: Subclavicular-breast height and breast width were used to calculate the aesthetic ratio. Subjects were subsequently aesthetically rated. A one-sample t-test was used to determine if the ratio for each breast differed from phi. Breast scores with one, both, or no breasts were compared with an optimal phi ratio. Analysis of variance was performed. Tukey-Kramer adjustment for multiple comparisons was used when pairwise comparisons were conducted. RESULTS: Five subjects (14%) had bilateral optimal phi ratio breasts. Four subjects (11%) had one breast with an optimal phi ratio. Subjects with bilateral optimal phi ratios had significantly higher overall breast scores than those with only one optimal breast (Δ = 0.86, P = 0.025) or no optimal breast (Δ = 0.73, P = 0.008). Distance from optimal Fibonacci nipple position was moderately to strongly correlated with aesthetic score (-0.630, P = 0.016). No correlation was found between 21-cm notch-to-nipple distance and aesthetic score. CONCLUSION: The bilateral optimal phi ratio is correlated with high overall aesthetic scores, as is the optimal Fibonacci nipple position. No correlation was found between 21-cm notch-to-nipple distance and overall aesthetic score.

11.
Front Oncol ; 11: 658004, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055624

RESUMO

FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.

12.
Plast Reconstr Surg Glob Open ; 8(10): e3173, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173686

RESUMO

Background: There is little consensus about the relative determinative value of each individual factor in female breast aesthetics. When performing breast surgery with an aesthetic goal, certain factors will be more important than others. The purpose of this study was to make an aesthetic factor rank list to determine the relative contributions to overall breast aesthetics. Method: Volunteers were scanned using the 3-dimensional Vectra system. Ten Scandinavian plastic surgeons rated 37 subjects, using a validated scoring system with 49 scoring items. The correlation between specific aesthetic factors and overall breast aesthetic scores of the subjects were calculated using Pearson's r, Spearman's ρ, and Kendall's τ. Results: A very strong correlation was found between overall breast aesthetic score and lower pole shape (0.876, P < 0.0001). This was also true for upper pole shape (0.826, P < 0.0001) and breast height (0.821, P < 0.0001). A strong correlation was found between overall breast aesthetic score and nipple position (0.733, P < 0.0001), breast size (0.644, P < 0.0001), and breast width (0.632, P < 0.0001). Factors that were only moderately correlated with aesthetic score were intermammary distance (0.496, P = 0.002), nipple size and projection (0.588, P < 0.0001), areolar diameter (0.484, P < 0.0001), and areolar shape (0.403, P < 0.0001). Perceived symmetry was a weak factor (0.363, P = 0.027). Conclusions: Aesthetic factors of the female breast can be ranked in a priority list. Shape of the lower pole and upper pole and breast height are primary factors of female breast aesthetics. These should be prioritized in any aesthetic breast surgery. Vertical dimensional factors seem to be more determinative than horizontal factors.

13.
Methods Mol Biol ; 2141: 629-650, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32696381

RESUMO

Many intrinsically disordered proteins (IDPs) adopt a well-defined structure upon binding to their interaction partners. Kinetic characterization is a requirement for the investigation of the dynamics and mechanisms of these folding-upon-binding reactions. Here a protocol is described for the investigation of binding kinetics of bimolecular binding and folding reactions of IDPs to their ligand partner under pseudo-first-order conditions using stopped-flow mixing and fluorescence detection.


Assuntos
Proteínas Intrinsicamente Desordenadas/metabolismo , Ligação Proteica , Dobramento de Proteína , Desenho de Equipamento , Proteínas Intrinsicamente Desordenadas/química , Cinética , Ligantes , Modelos Moleculares , Conformação Proteica , Espectrometria de Fluorescência/métodos , Termodinâmica
14.
BMC Microbiol ; 20(1): 9, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924162

RESUMO

After publication of our article [1] it came to our notice that the source of the sequence for the control plasmid, pNeo (Materials and methods: Controls) was incorrectly stated as AB094461. The correct accession number is AB074461. The authors apologize for any confusion this may have caused.

15.
J Am Chem Soc ; 141(47): 18649-18652, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31702142

RESUMO

Amyloid fibril formation is a hallmark of neurodegenerative disease caused by protein aggregation. Oligomeric protein states that arise during the process of fibril formation often coexist with mature fibrils and are known to cause cell death in disease model systems. Progress in this field depends critically on development of analytical methods that can provide information about the mechanisms and species involved in oligomerization and fibril formation. Here, we demonstrate how the powerful combination of diffusion NMR and multilinear data analysis can efficiently disentangle the number of involved species, their kinetic rates of formation or disappearance, spectral contributions, and diffusion coefficients, even without prior knowledge of the time evolution of the process or chemical shift assignments of the various species. Using this method we identify oligomeric species that form transiently during aggregation of human superoxide dismutase 1 (SOD1), which is known to form misfolded aggregates in patients with amyotrophic lateral sclerosis. Specifically, over a time course of 42 days, during which SOD1 fibrils form, we detect the disappearance of the native monomeric species, formation of a partially unfolded intermediate in the dimer to tetramer size range, subsequent formation of a distinct similarly sized species that dominates the final spectrum detected by solution NMR, and concomitant appearance of small peptide fragments.


Assuntos
Amiloide/química , Agregados Proteicos , Difusão , Humanos , Espectroscopia de Ressonância Magnética , Solubilidade , Superóxido Dismutase-1/química
16.
BMC Microbiol ; 19(1): 199, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462211

RESUMO

BACKGROUND: Candidatus Neoehrlichia mikurensis is an emerging tick-borne pathogen. It is widely distributed in Ixodes ricinus ticks in Europe, but knowledge of its distribution in Norway, where I. ricinus reaches its northern limit, is limited. In this study we have developed a real time PCR test for Ca. N. mikurensis and used it to investigate the distribution of Ca. N. mikurensis in Norway. RESULTS: Real time PCR targeting the groEL gene was developed and shown to be highly sensitive. It was used to detect Ca. N. mikurensis in 1651 I. ricinus nymphs and adults collected from twelve locations in Norway, from the eastern Oslo Fjord in the south to near the Arctic Circle in the north. The overall prevalence was 6.5% and varied locally between 0 and 16%. Prevalence in adults and nymphs was similar, suggesting that ticks acquire Ca. N. mikurensis predominantly during their first blood meal. In addition, 123 larvae were investigated; Ca. N. mikurensis was not found in larvae, suggesting that transovarial transmission is rare or absent. Sequence analysis suggests that a single variant dominates in Norway. CONCLUSIONS: Ca. N. mikurensis is widespread and common in ticks in Norway and reaches up to their northern limit near the Arctic Circle. Ticks appear to acquire Ca. N. mikurensis during their first blood meal. No evidence for transovarial transmission was found.


Assuntos
Anaplasmataceae/isolamento & purificação , Chaperonina 60/genética , Ixodes/microbiologia , Larva/microbiologia , Ninfa/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Regiões Árticas , Noruega
17.
J Phys Chem B ; 123(9): 1920-1930, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30753785

RESUMO

Using NMR and Monte Carlo (MC) methods, we investigate the stability and dynamics of superoxide dismutase 1 (SOD1) in homogeneous crowding environments, where either bovine pancreatic trypsin inhibitor (BPTI) or the B1 domain of streptococcal protein G (PGB1) serves as a crowding agent. By NMR, we show that both crowders, and especially BPTI, cause a drastic loss in the overall stability of SOD1 in its apo monomeric form. Additionally, we determine chemical shift perturbations indicating that SOD1 interacts with the crowder proteins in a residue-specific manner that further depends on the identity of the crowding protein. Furthermore, the specificity of SOD1-crowder interactions is reciprocal: chemical shift perturbations on BPTI and PGB1 identify regions that interact preferentially with SOD1. By MC simulations, we investigate the local unfolding of SOD1 in the absence and presence of the crowders. We find that the crowders primarily interact with the long flexible loops of the folded SOD1 monomer. The basic mechanisms by which the SOD1 ß-barrel core unfolds remain unchanged when adding the crowders. In particular, both with and without the crowders, the second ß-sheet of the barrel is more dynamic and unfolding-prone than the first. Notably, the MC simulations (exploring the early stages of SOD1 unfolding) and the NMR experiments (under equilibrium conditions) identify largely the same set of PGB1 and BPTI residues as prone to form SOD1 contacts. Thus, contacts stabilizing the unfolded state of SOD1 in many cases appear to form early in the unfolding reaction.


Assuntos
Aprotinina/metabolismo , Proteínas de Bactérias/metabolismo , Desdobramento de Proteína , Superóxido Dismutase-1/metabolismo , Animais , Aprotinina/química , Proteínas de Bactérias/química , Escherichia coli/genética , Humanos , Método de Monte Carlo , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Estabilidade Proteica , Estrutura Secundária de Proteína , Streptococcus/química , Superóxido Dismutase-1/química , Superóxido Dismutase-1/genética
18.
Clin Transplant ; 31(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27862341

RESUMO

Islet transplantation is a minimally invasive ß-cell replacement strategy. Islet transplantation is a reimbursed treatment in Norway. Here, we summarize the cost and clinical outcome of 31 islet transplantations performed at Oslo University Hospital (OUS) from January 2010 to June 2015. Patients were retrospectively divided into three groups. Thirteen patients received either one or two islet transplantation alone (ITA), while five patients received islet transplantation after previous solid organ transplantation. For the group receiving 2 ITA, Kaplan-Meier estimates show an insulin independence of 20% more than 4 years after their last transplantation. An estimated 70% maintain at least partial graft function, defined as fasting C-peptide >0.1 nmol L-1 , and 47% maintain a HbA1c below 6.5% or 2 percent points lower than before ITA. For all groups combined, we estimate that 44% of the patients have a 50% reduction in insulin requirement 4 years after the initial islet transplantation. The average cost for an islet transplantation procedure was 347 297±60 588 NOK, or 35 424±6182 EUR, of which isolation expenses represent 34%. We hereby add to the common pool of growing experience with islet transplantation and also describe the cost of the treatment at our center.


Assuntos
Diabetes Mellitus Tipo 1/economia , Rejeição de Enxerto/economia , Transplante das Ilhotas Pancreáticas/economia , Complicações Pós-Operatórias/economia , Adulto , Diabetes Mellitus Tipo 1/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Incidência , Transplante das Ilhotas Pancreáticas/métodos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
19.
J Diabetes Res ; 2016: 4196460, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26885529

RESUMO

Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 µg/L), sirolimus (30 µg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 µg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus.


Assuntos
Glucocorticoides/administração & dosagem , Ilhotas Pancreáticas/efeitos dos fármacos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Adulto , Apoptose , Índice de Massa Corporal , Células Cultivadas , Citocinas/metabolismo , Sinergismo Farmacológico , Feminino , Glucose/química , Humanos , Imunossupressores/uso terapêutico , Inflamação , Insulina/metabolismo , Secreção de Insulina , Transplante das Ilhotas Pancreáticas , Masculino , Metilprednisolona/química , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo
20.
Adv Exp Med Biol ; 875: 505-12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26610998

RESUMO

Hearing thresholds of a great cormorant (Phalacrocorax carbo) were measured in air and under water using psychophysics. The lowest thresholds were at 2 kHz (45 dB re 20 µPa root-mean-square [rms] in air and 79 dB re 1 µPa rms in water). Auditory brainstem response measurements on one anesthetized bird in air indicated an audiogram with a shape that resembled the one achieved by psychophysics. This study suggests that cormorants have rather poor in-air hearing abilities compared with other similar-size birds. The hearing capabilities in water are better than what would have been expected for a purely in-air adapted ear.


Assuntos
Ar , Aves/fisiologia , Audição/fisiologia , Água do Mar , Animais , Comportamento Animal/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Masculino , Espectrografia do Som , Gravação em Fita
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