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1.
J Laryngol Otol ; 137(11): 1226-1232, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36876328

RESUMO

OBJECTIVES: To evaluate the incidence of inadvertent parathyroidectomy, identify risk factors, determine the location of inadvertently excised glands, review pathology reporting in inadvertent parathyroidectomy, and explore relationships between inadvertent parathyroidectomy and post-surgical hypoparathyroidism or hypocalcaemia. METHODS: A retrospective cohort study of 899 thyroidectomies between 2015 and 2020 was performed. Histopathology slides of patients who had an inadvertent parathyroidectomy and a random sample of patients without a reported inadvertent parathyroidectomy were reviewed. RESULTS: Inadvertent parathyroidectomy occurred in 18.5 per cent of thyroidectomy patients. Central neck dissection was an independent risk factor (inadvertent parathyroidectomy = 49.4 per cent with central neck dissection, 12.0 per cent without central neck dissection, p < 0.001). Most excised parathyroid glands were extracapsular (53.3 per cent), followed by subcapsular (29.1 per cent) and intrathyroidal (10.9 per cent). Parathyroid tissue was found in 10.2 per cent of specimens where no inadvertent parathyroidectomy was reported. Inadvertent parathyroidectomy was associated with a higher incidence of six-month post-surgical hypoparathyroidism or hypocalcaemia (19.8 per cent who had an inadvertent parathyroidectomy, 7.7 per cent without inadvertent parathyroidectomy). CONCLUSION: Inadvertent parathyroidectomy increases the risk of post-surgical hypoparathyroidism or hypocalcaemia. The proportion of extracapsular glands contributing to inadvertent parathyroidectomy highlights the need for preventative measures.


Assuntos
Hipocalcemia , Hipoparatireoidismo , Humanos , Glândulas Paratireoides/cirurgia , Glândula Tireoide/cirurgia , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Estudos Retrospectivos , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/cirurgia , Tireoidectomia/efeitos adversos , Paratireoidectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
2.
Pulmonology ; 29 Suppl 4: S70-S79, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34642125

RESUMO

INTRODUCTION: In Portugal, lung cancer (LC) is the first cause of cancer-related death and of death and disability combined. This study aims to analyze the overall survival (OS) and relative survival (RS) of patients diagnosed with LC in 2009-2011 by socio-demographic and tumor characteristics, and analyze sex-specific patterns. METHODS: We estimated 5-year OS using the Kaplan-Meier method and 5-year net survival through the RS framework. Cox regression modeling was used to determine the hazard ratio (HR) of death associated with each independent variable. FINDINGS: For the 11,523 cases analyzed, median 5-year OS was 264 days (95% confidence interval [CI]: 254.8-273.2), the cumulative OS was 13.6% and RS was 15.1%. Males had a lower median survival (237 days; 95% CI: 228.2-245.7) compared to females (416 days; 95% CI: 384.4-447.6) (p < 0.0001) and lower 5-year RS proportions (12.1% vs. 24.9%). RS progressively decreased with age (41.7% for age-group <40 to 7.2% for ≥80) and stage (66.6% for stage I to 2.4% for stage IV). As predictors of decreased survival, we identified male gender, increasing age >50, histologic types (squamous cell carcinoma, non-small cell lung cancer not otherwise specified, other unspecified and small cell lung cancer), and increasing stage. Compared to women, the risk of death in men was 37.7% higher (HR = 1.386; 95% CI: 1.295-1.484). CONCLUSIONS: The differences between OS and RS were small, reflecting the high lethality of LC. Male gender and older age are factors related to poor prognosis. Histology also plays a role in survival prognosis and varies with gender, but the factor related to the worst survival is stage. Although the study reflects data from a decade ago, and major changes occurred in diagnosis, staging and treatment, particularly for advanced disease, as LC mortality is strongly correlated with late stage diagnosis, all efforts should be made to secure early diagnosis and improve survival prospects.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Neoplasias Pulmonares/patologia , Portugal/epidemiologia , Estadiamento de Neoplasias , Estudos Retrospectivos
3.
Respir Physiol Neurobiol ; 302: 103913, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35436602

RESUMO

Continuous positive airway pressure (CPAP) is a primary non-invasive mode of respiratory support for preterm infants. However, emerging evidence suggests CPAP could be an underlying contributor to the unintended pathophysiology of wheezing and associated airway hyperreactivity (AHR) in former preterm infants. The therapeutic benefits of mesenchymal stem cells (MSCs) have been demonstrated in a variety of animal models and several clinical trials are currently underway to assess their safety profiles in the setting of prematurity and bronchopulmonary dysplasia (BPD). In the present study, using a mouse model of neonatal CPAP, we investigated whether conditioned medium harvested from cultures of human bone-marrow derived mesenchymal stem cells (hMSC) could rescue the CPAP-induced AHR, based upon previous observations of their anti-AHR properties. Newborn mice (male and female) were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for the first 7 postnatal days. At postnatal day 21 (two weeks after CPAP ended), lungs were removed, precision-cut lung slices were sectioned and incubated for 48 h in vitro in conditioned medium collected from cultures of three different hMSC donors. As expected, CPAP resulted in AHR to methacholine compared to untreated control mice. hMSC conditioned medium from the cultures of all three donors completely reversed AHR. These data reveal potential therapeutic benefits of hMSC therapy, which may be capable of rescuing the long-term adverse effects of neonatal CPAP on human airway function.


Assuntos
Displasia Broncopulmonar , Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório do Recém-Nascido , Animais , Medula Óssea , Displasia Broncopulmonar/etiologia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Meios de Cultivo Condicionados/farmacologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino
4.
Rev Gastroenterol Mex (Engl Ed) ; 87(1): 20-28, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34635446

RESUMO

INTRODUCTION AND AIMS: Foreign body (FB) ingestion is a common problem in children under 5 years of age and is one of the main indications for endoscopy. The aim of the present study was to describe the clinical, radiographic, and endoscopic characteristics of patients with FB ingestion, as well as the factors associated with the anatomic location and the type of object ingested. MATERIALS AND METHODS: An analytic cross-sectional study was conducted on all patients with FB ingestion seen at the gastroenterology service from January 2013 to December 2018. The data were analyzed using the SPSS program, obtaining frequencies, percentages, medians, and interquartile ranges. Associations were assessed through the chi-square test. RESULTS: Eighty-five patients (52 males and 33 females) were included, with a median age of 4 years. The most common symptom was vomiting (29.4%). Two radiographic projections were carried out in 72.9% of the cases and the stomach was the site where the FB was most frequently visualized (32.9%). The objects most commonly ingested were coins (36%), with esophageal location (p<0.05), as well as objects with a diameter larger than 2cm (p<0.05). An endoscopic procedure was performed on 76 patients (89.4%) for FB extraction, with findings of erythema (28.9%), erosion (48.6%), ulcer (10.5%) and perforation (1.3%). CONCLUSIONS: Numerous factors should be taken into account in the approach to FB ingestion in pediatric patients, including type and size of the FB, time interval from ingestion to hospital arrival, and patient clinical status and age.


Assuntos
Corpos Estranhos , Criança , Pré-Escolar , Estudos Transversais , Ingestão de Alimentos , Endoscopia Gastrointestinal , Feminino , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária
6.
Radiat Oncol ; 15(1): 171, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32653003

RESUMO

BACKGROUND: To date, only limited magnetic resonance imaging (MRI) data are available concerning tumor regression during neoadjuvant radiochemotherapy (RCT) of rectal cancer patients, which is a prerequisite for adaptive radiotherapy (RT) concepts. This exploratory study prospectively evaluated daily fractional MRI during neoadjuvant treatment to analyze the predictive value of MR biomarkers for treatment response. METHODS: Locally advanced rectal cancer patients were examined with daily MRI during neoadjuvant RCT. Contouring of the tumor volume was performed for each MRI scan by using T2- and diffusion-weighted-imaging (DWI)-sequences. The daily apparent-diffusion coefficient (ADC) was calculated. Volumetric and functional tumor changes during RCT were analyzed and correlated with the pathological response after surgical resection. RESULTS: In total, 171 MRI scans of eight patients were analyzed regarding anatomical and functional dynamics during RCT. Pathological complete response (pCR) could be achieved in four patients, and four patients had a pathological partial response (pPR) following neoadjuvant treatment. T2- and DWI-based volumetry proved to be statistically significant in terms of therapeutic response, and volumetric thresholds at week two and week four during RCT were defined for the prediction of pCR. In contrast, the average tumor ADC values widely overlapped between both response groups during RCT and appeared inadequate to predict treatment response in our patient cohort. CONCLUSION: This prospective exploratory study supports the hypothesis that MRI may be able to predict pCR of rectal cancers early during neoadjuvant RCT. Our data therefore provide a useful template to tailor future MR-guided adaptive treatment concepts.


Assuntos
Quimiorradioterapia , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/terapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia
7.
Am J Physiol Regul Integr Comp Physiol ; 319(2): R233-R242, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32579854

RESUMO

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.


Assuntos
Alprostadil/farmacologia , Tronco Encefálico/efeitos dos fármacos , Cafeína/farmacologia , Ventilação Pulmonar/efeitos dos fármacos , Respiração/efeitos dos fármacos , Animais , Tronco Encefálico/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Pletismografia Total , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Proto-Oncogênicas c-sis/metabolismo , Antagonistas de Receptores Purinérgicos P1/farmacologia , Ratos , Ratos Sprague-Dawley
8.
BMJ Open ; 7(3): e012935, 2017 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-28341685

RESUMO

OBJECTIVES: To develop a computerised decision aid (DA) to inform the decision process on adjuvant chemotherapy in patients with stage II colorectal cancer, and examine perceived usefulness, acceptability and areas for improvement of the DA. DESIGN: Mixed methods. SETTING: Single outpatient oncology department in central London. PARTICIPANTS: Consecutive recruitment of 13 patients with stage II colorectal cancer, 12 of whom completed the study. Inclusion criteria were: age >18 years; complete resection for stage II adenocarcinoma of the colon or rectum; patients within 14-56 days after surgery; no contraindication to adjuvant chemotherapy; able to give written informed consent. Exclusion criterion: previous chemotherapy. PRIMARY OUTCOMES: Patient perceived usefulness (assessed by the PrepDM questionnaire) and acceptability of the DA. RESULTS: PrepDM scores, measuring the perceived usefulness of the DA in preparing the patient to communicate with their doctor and make a health decision, were above those reported in other patient groups. Patient acceptability scores were also high; however, interviews showed that there was evidence of a lack of understanding of key information among some patients, in particular their baseline risk of recurrence, the net benefit of combination chemotherapy and the rationale for having chemotherapy when cancer had apparently gone. CONCLUSIONS: Patients found the DA acceptable and useful in supporting their decision about whether or not to have adjuvant chemotherapy. Suggested improvements for the DA include: sequential presentation of treatment options (eg, no treatment vs 1 drug, 1 drug vs 2 drugs) to enhance patient understanding of the difference between combination and single therapy, diagrams to help patients understand the rationale for chemotherapy to prevent a recurrence and inbuilt checks on patient understanding of baseline risk of recurrence and net benefit of chemotherapy.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Técnicas de Apoio para a Decisão , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
9.
Science ; 349(6253): 1228-32, 2015 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-26229117

RESUMO

Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development.


Assuntos
Infecções por HIV/imunologia , HIV-1/metabolismo , Herpes Simples/imunologia , Herpesvirus Humano 1/metabolismo , Interferon beta/imunologia , Nucleotídeos Cíclicos/metabolismo , Sistemas do Segundo Mensageiro , Vírion/metabolismo , Vacinas contra a AIDS/imunologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Genes Reporter , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Células HEK293 , Infecções por HIV/metabolismo , Infecções por HIV/prevenção & controle , HIV-1/genética , Herpes Simples/prevenção & controle , Vacinas contra o Vírus do Herpes Simples/imunologia , Herpesvirus Humano 1/genética , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Interferon beta/genética , Regiões Promotoras Genéticas , Ativação Transcricional , Vírion/genética
10.
Int J Comput Assist Radiol Surg ; 10(7): 1127-40, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25408305

RESUMO

PURPOSE: Minimal invasion computer-assisted neurosurgical procedures with various tool insertions into the brain may carry hemorrhagic risks and neurological deficits. The goal of this study is to investigate the role of computer-based surgical trajectory planning tools in improving the potential safety of image-based stereotactic neurosurgery. METHODS: Multi-sequence MRI studies of eight patients who underwent image-guided neurosurgery were retrospectively processed to extract anatomical structures-head surface, ventricles, blood vessels, white matter fibers tractography, and fMRI data of motor, sensory, speech, and visual areas. An experienced neurosurgeon selected one target for each patient. Five neurosurgeons planned a surgical trajectory for each patient using three planning methods: (1) conventional; (2) visualization, in which scans are augmented with overlays of anatomical structures and functional areas; and (3) automatic, in which three surgical trajectories with the lowest expected risk score are automatically computed. For each surgeon, target, and method, we recorded the entry point and its surgical trajectory and computed its expected risk score and its minimum distance from the key structures. RESULTS: A total of 120 surgical trajectories were collected (5 surgeons, 8 targets, 3 methods). The surgical trajectories expected risk scores improved by 76% ([Formula: see text], two-sample student's t test); the average distance of a trajectory from nearby blood vessels increased by 1.6 mm ([Formula: see text]) from 0.6 to 2.2 mm (243%). The initial surgical trajectories were changed in 85% of the cases based on the expected risk score and the trajectory distance from blood vessels. CONCLUSIONS: Computer-based patient-specific preoperative planning of surgical trajectories that minimize the expected risk of vascular and neurological damage due to incorrect tool placement is a promising technique that yields consistent improvements.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Técnicas Estereotáxicas , Cirurgia Assistida por Computador/métodos , Adulto , Idoso , Encéfalo/cirurgia , Criança , Pré-Escolar , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Adulto Jovem
11.
J Occup Environ Med ; 55(7): 746-51, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23787563

RESUMO

OBJECTIVE: Despite reduced workplace exposures, beryllium sensitization and chronic beryllium disease still occur. Effective health and safety training is needed. METHODS: Through an Occupational Safety and Health Administration (OSHA) Targeted Topic Training grant and company partners, we developed a training program. Evaluation and validation included knowledge and training reaction assessments and training impact survey. RESULTS: We describe herein the iterative, five-pronged approach: (1) needs assessment; (2) materials development; (3) pilot-testing, evaluation, and material revisions; (4) worker training; and (5) evaluation and validation. Mean posttraining test score increased 14% (82% to 96%; P < 0.005) and were unchanged at 90-day follow-up (94%; P = 0.744). In addition, 49% reported making changes in work practices. CONCLUSIONS: The use of a five-pronged training program was effective and well received and resulted in improved work practices. These materials are available on the OSHA Web site.


Assuntos
Beriliose/prevenção & controle , Serviços de Saúde do Trabalhador/métodos , Saúde Ocupacional/educação , Avaliação Educacional , Humanos , Comunicação Interdisciplinar , Avaliação das Necessidades , Projetos Piloto , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Reprodutibilidade dos Testes , Estados Unidos , United States Occupational Safety and Health Administration
12.
Z Gastroenterol ; 51(5): 450-7, 2013 May.
Artigo em Alemão | MEDLINE | ID: mdl-23681899

RESUMO

Patients with ulcerative colitis and Crohn's colitis are at increased risk of colorectal cancer (CRC). This risk is dependent on the duration and extent of disease, inflammatory activity and possible additional risk factors. Thus, the aim is to reduce this risk and to detect dysplastic and malignant lesions at an early stage. The working group for Inflammatory Bowel Diseases (IBD) of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) has developed consensus statements on the following topics: risk of colorectal cancer, screening and surveillance, procedure of surveillance colonoscopy, dysplasia and its management, and chemoprevention. This consensus is intended to increase awareness of the increased risk of CRC in IBD and to support a standardised approach in cancer prevention.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/normas , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/prevenção & controle , Vigilância da População/métodos , Guias de Prática Clínica como Assunto , Áustria/epidemiologia , Neoplasias Colorretais/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Prevalência
13.
Br J Cancer ; 108(6): 1252-9, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23449352

RESUMO

BACKGROUND: Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC). METHODS: We conducted a randomised phase II/III trial in patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4-6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322. RESULTS: The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P=0.019). End-of-treatment RECIST response (CR+PR) was 13.2 and 32.6% (P=0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P=0.74) months and 7.2 vs 7.5 (P=0.59), respectively. CONCLUSION: Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Cisplatino/uso terapêutico , Embolização Terapêutica , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Taxa de Sobrevida , Fatores de Tempo
14.
Br J Cancer ; 108(2): 402-8, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23322209

RESUMO

BACKGROUND: Experimental studies have established a causal connection between tumour hypoxia, hypoxia-associated proteome changes and downregulation of E-cadherin, the final common pathway of epithelial-to-mesenchymal transition (EMT). Our study aimed at elucidating the interrelationship of these processes in cancers of the uterine cervix in vivo. METHODS: Tumour oxygenation was assessed in 48 squamous cell carcinomas (SCC) of the uterine cervix using polarographic needle electrodes. The expression pattern of E-cadherin was investigated by immunohistochemistry and western blotting, and was compared with that of the hypoxia-inducible proteins glucose transporter (GLUT)-1 and carbonic anhydrase (CA) IX in biopsy specimens of the oxygenation measurement tracks. RESULTS: The majority of cervical cancers (52%) were E-cadherin positive, with a complete absence of the antigen in only 10% of the tumours. No correlation was found between the level of E-cadherin expression and the oxygenation status (mean pO(2), median pO(2) and hypoxic fractions). In patients showing partial expression of E-cadherin (38%), staining was not preferentially diminished in GLUT-1- or CA IX-positive areas, and loss of E-cadherin occurred independently of tumour cell scattering. CONCLUSION: Our data provide no evidence in favour of a hypoxia-induced EMT as a mechanistic basis of cervical cancer invasiveness.


Assuntos
Caderinas/metabolismo , Hipóxia Celular , Transição Epitelial-Mesenquimal , Neoplasias do Colo do Útero/metabolismo , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Anidrase Carbônica IX , Anidrases Carbônicas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Colo do Útero/metabolismo , Colo do Útero/patologia , Regulação para Baixo , Feminino , Transportador de Glucose Tipo 1/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade
16.
Transplantation ; 92(10): 1140-6, 2011 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-21946173

RESUMO

BACKGROUND: Donation after cardiac death (DCD) has reemerged as potential way to increase donor liver availability. Earlier, programs with DCD liver transplantation used conservative donor criteria to allow safe results. Successful initial outcomes allowed extended DCD criteria to address transplant demand. METHODS: A total of 63 DCD liver grafts were used during the study period in carefully selected recipients. These were divided into two groups: "Standard" DCD within conservative criteria (n=33; age ≤60 years, body mass index <30 kg/m(2), donor warm ischemia time ≤30 min, and cold ischemia time ≤8 hr) and "Extended" DCD beyond these criteria (n=30). We compared donor and recipient characteristics and postoperative outcomes, including patient and graft survival. RESULTS: Both groups had satisfactory initial function; liver graft function at 1, 7, and 30 days after liver transplantation were similar. Median follow-up period was 25 and 18.5 months for Standard and Extended criteria DCD grafts, respectively, with 1-year patient and graft survival of 88% and 82% for the Standard group vs. 90% and 90% for the Extended. Overall, 8 of 63 (13%) patients developed biliary complications; however, the incidence was not different between the Standard and Extended groups. Seven early deaths occurred, four and three in the Standard and Extended groups, respectively. CONCLUSIONS: Recipients of DCDs beyond conventional acceptance criteria have equivalent early outcomes to standard DCD grafts. With careful selection of donors and recipients, these grafts can be safely used to expand the donor pool.


Assuntos
Morte , Transplante de Fígado , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Adulto , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Pessoa de Meia-Idade , Reoperação
17.
Clin Hemorheol Microcirc ; 48(1): 57-63, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21876234

RESUMO

Cardiovascular implants such as stents or artificial vascular grafts established in clinical application to date are generally designed as long-term implants. An important requirement for the successful application of these devices is the haemocompatibility of their interface to the blood stream, which often is approached by polymeric coatings. Modern therapies are aiming at curative treatments (Regenerative Medicine) by inducing the in vivo formation of a new endothelial layer on the implant surface ensuring an optimal haemocompatibility based on the generated glycocalyx. A promising approach for providing the required biological stimulus is the secretion of pro-angiogenic factors (such as VEGF-A) by autologous CD14⁺ monocytes/macrophages (mo/mΦ), which can be induced by previous angiogenic stimulation. While protocols for negative and positive immune-isolation are already established, this study was aimed to evaluate the efficacy of a positive and a negative MACS based immune-isolation protocol by analysing the yield, the purity and the activation status of the isolated CD14 mo/mΦ. Both protocols enabled the isolation of more than 80% (positive isolation) and 86% (negative isolation) CD14⁺ mo/mΦ representing approximately 1.3 × 107 CD14⁺ mo/mΦ from 1 ml buffy coat. Less than 10% of these cells were also positive for CD69. Latter is an important selection criterion as CD69 is a marker characteristic for classically activated and catabolic active mo/mΦ which can negatively affect the endothelialisation process. As the negative immune-isolation protocol resulted in a cell fraction meeting the requirements on a pure cell fraction (percentage of contaminating cells < 15%) this isolation method is advantageous although it was more time consuming than the positive isolation protocol.


Assuntos
Separação Celular/métodos , Receptores de Lipopolissacarídeos/sangue , Macrófagos/citologia , Magnetismo , Monócitos/citologia , Citometria de Fluxo , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo
18.
Ann Surg ; 253(3): 553-60, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21217507

RESUMO

INTRODUCTION: A majority of bile duct injuries (BDI) sustained during laparoscopic cholecystectomy require formal surgical reconstruction, and traditionally this repair is performed late. We aimed to assess long-term outcomes after repair, focusing on our preferred early approach. METHODS: A total of 200 BDI patients [age 54(20-83); 64 male], followed up for median 60 (5-212) months were assessed for morbidity. Factors contributing to this were analyzed with a univariate and multivariate analysis. RESULTS: A total of 112 (56%) patients were repaired by specialist hepatobiliary surgeons [timing of repair: immediate, n = 28; early (<21 days), n = 43; and late (>21 days) n = 41], whereas 45 (22%) underwent repair by nonspecialist surgeons before specialist referral [immediate, n = 16; early, n = 26 and late, n = 03]. Outcomes after immediate and early repairs were comparable to late repairs when performed by specialists [recurrent cholangitis:11%, 12%, and 10%; P = 0.96, NS; re-stricture:18%,5%, and 29%; P = 0.01; nonsurgical intervention: 14%, 5%, and 24%; P<0.03; redo surgery: 4%, 2%, and 5%; P = 0.81, NS; overall morbidity: 21%, 14%, and 39%; P<0.02]. On multivariate analysis, immediate and early repairs done by nonspecialist surgeons were independent risk factors (P < 0.05) for recurrent cholangitis [50% and 27%], re-stricturing (75% and 61%), redo reconstructions (31% and 61%), and overall morbidity (75% and 84%). CONCLUSION: Immediate and early repair after BDI results in comparable, if not better long-term outcomes compared to late repair when performed by specialists.


Assuntos
Ductos Biliares Extra-Hepáticos/lesões , Ductos Biliares Extra-Hepáticos/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar , Colecistectomia Laparoscópica/efeitos adversos , Doença Iatrogênica , Complicações Intraoperatórias/cirurgia , Equipe de Assistência ao Paciente , Complicações Pós-Operatórias/cirurgia , Especialidades Cirúrgicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Precoce , Inglaterra , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Encaminhamento e Consulta , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Int J Surg ; 9(2): 145-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21029795

RESUMO

OBJECTIVES: Whilst there are theoretical benefits from pre-operatively draining the biliary tree prior to pancreatoduodenectomy (PD), the current literature does not support this intervention. The aim of this study was to explore the relationship between pre-operative stenting, bactibilia and outcome in a large United Kingdom tertiary referral practice. METHODS: Patients undergoing PD were identified from a prospectively maintained database. The presence or absence of a stent prior to PD, and the results of bile cultures taken at PD were related to the subsequent post-operative course and the development of complications. RESULTS: 280 patients underwent PD for periampullary malignancies, all of whom presented with jaundice. 118 patients were stented prior to referral (98 ERCP, 20 PTC). Bile cultures were positive more frequently in the stent group (83% vs. 55%; p = 0.000002) and bactibilia was more common after ERCP than PTC (83% vs. 56%; p = 0.006). The overall prevalence of complications was 54% in the stented and 41% in the non-stented group (p = 0.03) with statistical significance achieved for pancreatic leak (p = 0.013) and haemorrhagic complications (p = 0.03). Comparing stent with no stent, there as no difference in the 30-day mortalities (8.5% vs. 6.8%; p = 0.6) or the 1-year mortality rates (35% vs. 28%; p = 0.21). Mortality rates in the infection versus no infection groups were comparable at 30 days (8.5% vs. 5.5%; p = 0.21), and at 1 year (30.7% vs. 26.4%; p = 0.25). CONCLUSIONS: Pre-operative stent insertion prior to PD is associated with increased morbidity but not mortality and this is greatest for stents placed at ERCP.


Assuntos
Pancreaticoduodenectomia , Complicações Pós-Operatórias/epidemiologia , Cuidados Pré-Operatórios/instrumentação , Stents/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bile/microbiologia , Colangiografia , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Stents/microbiologia
20.
Clin Hemorheol Microcirc ; 49(1-4): 423-30, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22214713

RESUMO

So called intermediate (MO2) monocytes/macrophages possess anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic, acrylamide-based hydrogel human intermediate (CD14++ CD16+) CD163++ monocytes/macrophages (aMO2) which were angiogenically stimulated, maintained a pro-angiogenic and non-inflammatory status for at least 14 days. Here we explored, whether this aMO2 subset can positively influence the proliferation of human umbilical venous endothelial cells (HUVECs) without switching back into a pro-inflammatory (MO1) phenotype. aMO2 or HUVEC were seeded alone on glass cover slips (0.5 × 10(5) cells / 1.33 cm(2)) in a HUVEC specific cell culture medium (EGM-2) for 3 hrs, 24 hrs and 72 hrs or under co-culture conditions (0.5 × 10(5) HUVEC + 0.25 × 10(5) aMO2 / 1.33 cm(2)) in EGM-2 for the same time window as well (n = 6 each). Under co-culture conditions the numbers of adherent HUVEC per unit area were significantly higher (p < 0.01; 525 ± 52 HUVEC/mm(2)) compared to control mono-cultures (473 ± 76 HUVEC/mm(2)) after 72 hrs of cultivation and showed their typically spread morphology. The aMO2 remained in their subset status and secreted VEGF-A165 without release of pro-inflammatory cytokines until the end of the 72 hrs cultivation time period, thereby supporting the HUVEC proliferation. These in vitro results might indicate that this MO subset can be used as cellular delivery system for pro-angiogenic and non-inflammatory mediators to support the endothelialisation of biomaterials like e.g. cPnBA.


Assuntos
Células Endoteliais da Veia Umbilical Humana/citologia , Macrófagos/citologia , Monócitos/citologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Materiais Biocompatíveis , Adesão Celular , Comunicação Celular , Divisão Celular , Células Cultivadas/citologia , Técnicas de Cocultura , Vidro , Humanos , Macrófagos/química , Macrófagos/metabolismo , Monócitos/química , Monócitos/metabolismo , Neovascularização Fisiológica , Fenótipo , Poliestirenos , Receptores de Superfície Celular/análise , Engenharia Tecidual/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo
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