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1.
Clin Radiol ; 76(12): 941.e19-941.e24, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34548172

RESUMO

AIM: To evaluate the safety and efficacy of treatment of patients presenting with acute aneurysmal subarachnoid haemorrhage (SAH) with primary flow-diverting stents (FDS; with or without adjuncts), with comparison to the published literature. MATERIALS AND METHODS: A retrospective single-centre review was undertaken of prospectively obtained data on patients treated for SAH over a 60-month period. Of 354 patients treated for SAH during that time period, 24 patients with a total of 25 aneurysms were identified. Baseline patient demographics were recorded and clinical and imaging outcomes assessed. RESULTS: Eighty-eight per cent (22/25) of the aneurysms were completely occluded (Raymond-Roy 1) at mean 12-month follow-up. The minor complication rate was 12.5% (3/24) without permanent morbidity. Mortality rate was 4% (1/25) after one patient died following aneurysmal rebleed on day 7 post-procedure. Forty-two per cent (10/24) of patients had a high-pressure shunt placed prior to endovascular treatment, no haemorrhagic complications of neurosurgical intervention were observed. CONCLUSION: The necessity of dual antiplatelet therapy (DAPT) therapy when deploying FDS will rightly continue to limit their use in the acutely ruptured setting to a case-by-case basis whereby other treatment options are deemed unsafe. Methods employed to minimise subsequent haemorrhagic risks from DAPT in these patients may be worthy of further investigation.


Assuntos
Aneurisma Roto/cirurgia , Procedimentos Endovasculares , Aneurisma Intracraniano/cirurgia , Stents , Hemorragia Subaracnóidea/cirurgia , Adulto , Idoso , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Feminino , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia , Fatores de Tempo , Resultado do Tratamento
2.
Surgeon ; 17(1): 1-5, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29807673

RESUMO

INTRODUCTION: Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. METHODS: Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. RESULTS: Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36-264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients (p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36-172). Mean serum creatinine was 72.6 ± 21.6 µmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. CONCLUSION: En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.


Assuntos
Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Doadores de Tecidos , Adulto , Fatores Etários , Idoso , Pré-Escolar , Feminino , Humanos , Lactente , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos/classificação , Resultado do Tratamento
3.
Int J Obes (Lond) ; 41(12): 1782-1789, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28769120

RESUMO

BACKGROUND: Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli. METHODS: Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. RESULTS: Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.


Assuntos
Adiponectina/metabolismo , Resistência à Insulina/fisiologia , Insulina/metabolismo , Interferon gama/metabolismo , Omento/citologia , Gordura Subcutânea Abdominal/metabolismo , Imunidade Adaptativa/fisiologia , Índice de Massa Corporal , Células Cultivadas , Humanos , Imunidade Inata/fisiologia , Imuno-Histoquímica , Fenótipo , Gordura Subcutânea Abdominal/fisiopatologia
4.
Int J Obes (Lond) ; 40(4): 706-13, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26499445

RESUMO

AIMS: The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. METHODS: Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed. RESULTS: In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum. INTERPRETATION: The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.


Assuntos
Gangliosídeo G(M3)/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Lipídeos/química , Obesidade/metabolismo , Fosfatidiletanolaminas/metabolismo , Adipócitos/metabolismo , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Inflamação/metabolismo , Gordura Intra-Abdominal/citologia , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo
5.
Osteoarthritis Cartilage ; 23(10): 1743-54, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26045176

RESUMO

OBJECTIVE: To describe gene expression in murine chondrocytes stimulated with IL-6 family cytokines and the impact of deleting Suppressor of Cytokine Signaling-3 (SOCS-3) in this cell type. METHOD: Primary chondrocytes were isolated from wild type and SOCS-3-deficient (Socs3(Δ/Δcol2)) mice and stimulated with oncostatin M (OSM), IL-6 plus the soluble IL-6 receptor (IL-6/sIL-6R), IL-11 or leukemia inhibitory factor (LIF) for 4 h. Total RNA was extracted and gene expression was evaluated by microarray analysis. Validation of the microarray results was performed using Taqman probes on RNA derived from chondrocytes stimulated for 1, 2, 4 or 8 h. Gene ontology was characterized using DAVID (database for annotation, visualization and integrated discovery). RESULTS: Multiple genes, including Bcl3, Junb, Tgm1, Angptl4 and Lrg1, were upregulated in chondrocytes stimulated with each gp130 cytokine. The gene transcription profile in response to OSM stimulation was pro-inflammatory and was highly correlated to IL-6/sIL-6R, rather than IL-11 or LIF. In the absence of SOCS-3, OSM and IL-6/sIL-6R stimulation induced an interferon (IFN)-like gene signature, including expression of IL-31ra and S100a9. CONCLUSION: While each gp130 cytokine induced a transcriptional response in chondrocytes, OSM- and IL-6/sIL-6R were the most potent members of this cytokine family. SOCS-3 plays an important regulatory role in this cell type, as it does in hematopoietic cells. Our results provide new insights into a hierarchy of gp130-induced transcriptional responses in chondrocytes that is normally restrained by SOCS-3 and suggest therapeutic inhibition of OSM may have benefit over and above antagonism of IL-6 during inflammatory arthritis.


Assuntos
Condrócitos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores do Crescimento/farmacologia , Interleucina-11/farmacologia , Interleucina-6/farmacologia , Fator Inibidor de Leucemia/farmacologia , Oncostatina M/farmacologia , RNA Mensageiro/efeitos dos fármacos , Proteínas Supressoras da Sinalização de Citocina/genética , Proteína 4 Semelhante a Angiopoietina , Angiopoietinas/genética , Animais , Proteína 3 do Linfoma de Células B , Calgranulina B/efeitos dos fármacos , Calgranulina B/genética , Cartilagem Articular/citologia , Condrócitos/metabolismo , Glicoproteínas/efeitos dos fármacos , Glicoproteínas/genética , Inflamação/genética , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina/efeitos dos fármacos , Receptores de Interleucina/genética , Receptores de Interleucina-6 , Proteína 3 Supressora da Sinalização de Citocinas , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/genética , Transglutaminases/efeitos dos fármacos , Transglutaminases/genética , Regulação para Cima
6.
Clin Oncol (R Coll Radiol) ; 36(6): e154-e162, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38553363

RESUMO

BACKGROUND AND PURPOSE: For high-risk neuroblastoma, planning target volume coverage is often compromised to respect adjacent kidney tolerance. This trial investigated whether intensity-modulated arc radiotherapy techniques (IMAT) could facilitate dose escalation better than conventional techniques. MATERIALS AND METHODS: Children with high-risk abdominal neuroblastoma referred for radiotherapy to the primary tumour site and involved regional lymph nodes were randomised to receive either standard dose (21 Gy in 14 fractions) or escalated dose (36 Gy in 24 fractions) radiotherapy. Dual planning with both a conventional anterior-posterior parallel opposed pair radiotherapy technique and an IMAT technique was performed. The quality of target volume and organ-at-risk delineation, and dosimetric plans, were externally reviewed. Dosimetric parameters were used to judge the superior technique for treatment. This feasibility trial was not powered to detect improvement in outcome with dose escalation. RESULTS: Between 2017 and 2020, 50 patients were randomised and dual-planned. The IMAT technique was judged more favourable in 48 patients. In all patients randomised to receive 36 Gy, IMAT would have permitted delivery of the full dose (median D50% 36.0 Gy, inter-quartile range 36.0-36.1 Gy) to the target volume, whereas dose compromise would have been required with conventional planning (median D50% 35.6 Gy, inter-quartile range 28.7-35.9 Gy). CONCLUSION: IMAT facilitates safe dose escalation to 36 Gy in patients receiving radiotherapy for neuroblastoma. The value of dose escalation is now being evaluated in a current prospective phase III randomised trial.


Assuntos
Estudos de Viabilidade , Neuroblastoma , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Humanos , Neuroblastoma/radioterapia , Radioterapia de Intensidade Modulada/métodos , Masculino , Feminino , Pré-Escolar , Criança , Lactente , Planejamento da Radioterapia Assistida por Computador/métodos , Órgãos em Risco/efeitos da radiação
7.
Clin Transplant ; 27(6): E665-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24125166

RESUMO

OBJECTIVE: To review the incidence and long-term outcomes of squamous cell carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS: Between January 1976 and March 2013, five patients from one center (0.0013%) developed SCC of the bladder after undergoing a deceased donor kidney transplant. Their relevant risk factors included long-term self-intermittent catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome variables were overall patient survival and latency period between transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up was 94 ± 89 (range: 4-239) months. The latency period between transplantation and bladder SCC was 87 ± 87 (range: 2-228) months, and all five patients were immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four patients had suspected metastases upon presentation, and one patient presented with organ-confined disease. This patient underwent a radical cystectomy and remains disease free eight months post-operatively. Despite radical treatment, the remaining four patients died from metastatic disease 7 ± 4.4 (range: 2-11) months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor prognosis particularly in renal transplant patients. Early detection with flexible cystourethroscopy in patients with risk factors for SCC may improve long-term outcomes in this patient cohort.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Transplante de Rim , Neoplasias da Bexiga Urinária/epidemiologia , Adolescente , Adulto , Idoso , Cadáver , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Pré-Escolar , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Imunossupressores , Incidência , Irlanda/epidemiologia , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Doadores de Tecidos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/etiologia
8.
Surgeon ; 11(6): 300-3, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23877024

RESUMO

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.


Assuntos
Pacientes Internados , Medicina/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Centros de Atenção Terciária , Doenças Urológicas/diagnóstico , Urologia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Agendamento de Consultas , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga de Trabalho , Adulto Jovem
9.
Clin Oncol (R Coll Radiol) ; 34(4): 211-219, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35063327

RESUMO

AIMS: To determine if multi-isocentric volumetric modulated arc radiotherapy for craniospinal irradiation (CSI-VMAT) can be implemented safely and accurately using robust optimisation in a commercially available treatment planning system. Our initial clinical experience is reported for the first 20 patients treated with the technique. MATERIALS AND METHODS: Patients received between 23.4 and 39.6 Gy (mode 23.4 Gy) in 13-22 fractions with CSI-VMAT. The heart mean dose was 4.2-10.3 Gy (median 5.3 Gy) for patients prescribed up to 24 Gy and 6.5-16.3 Gy (median 10.1 Gy) for patients receiving 35 Gy or more. The lung mean dose was 5.5-7.6 Gy (median 6.8 Gy) for patients prescribed up to 24 Gy and 6.9-11.1 Gy (median 10.0 Gy) for patients receiving 35 Gy or more. The robustness of the planning target volume D0.1cm3 and D99% to systematic errors in the isocentre superoinferior position of up to 5 mm was evaluated. These remained acceptable but were correlated to the length of the available beam overlap through the neck. RESULTS: As of January 2021, one patient was deceased after 508 days and one patient was lost to follow-up after completing treatment. The median follow-up was 399 days (range 175-756 days) and progression-free survival was 131 days (34-490 days). Acute toxicities at Common Terminology Criteria for Adverse Events v5.0 grade 3+ included lowered white blood cell count (16/20), decreased platelet count (8/20), nausea (5/20), vomiting (2/20), pharyngeal mucositis (1/20) and oral mucositis (1/20). Three patients developed grade 4 neutropenia or decreased white blood cell count. CONCLUSIONS: CSI-VMAT can be implemented safely and accurately using robust optimisation functions in a commercially available treatment planning system.


Assuntos
Radiação Cranioespinal , Radioterapia de Intensidade Modulada , Radiação Cranioespinal/efeitos adversos , Radiação Cranioespinal/métodos , Coração , Humanos , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos
10.
J Neurol Neurosurg Psychiatry ; 80(11): 1202-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19286742

RESUMO

BACKGROUND: An fMRI study is described in which a postencephalitic woman with amnesia used a wearable camera which takes photographs passively, without user intervention, to record and review recent autobiographical events. "SenseCam" generates hundreds of images which can subsequently be reviewed quickly or one by one. RESULTS: Memory for a significant event was improved substantially when tested after 4.5 weeks, if the patient viewed SenseCam images of the event every 2 days for 3 weeks. In contrast, after only 3.5 weeks, her memory was at chance levels for a similarly significant event which was reviewed equally often, but using a written diary. During the fMRI scan, the patient viewed images of these two events, plus images of an unrehearsed event and images from a novel "control" event that she had never experienced. There was no difference in behavioural responses or in activation when the unrehearsed and novel conditions were compared. Relative to the written-rehearsed condition, successful recognition of the images in the SenseCam-rehearsed condition was associated with activation of frontal and posterior cortical regions associated with normal episodic memory. CONCLUSION: SenseCam images may provide powerful cues that trigger the recall and consolidation of stored but inaccessible memories.


Assuntos
Amnésia/terapia , Córtex Cerebral/fisiopatologia , Encefalite Límbica/complicações , Psicoterapia/métodos , Idoso , Amnésia/complicações , Amnésia/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Fotografação
11.
Nat Commun ; 10(1): 1945, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31019194

RESUMO

The original version of this Article contained an error in Fig. 4. In the left histogram of the right panel of Fig. 4d, several data points were inadvertently deleted from the histogram during the production process. This error has been corrected in both the PDF and HTML versions of the Article. The original, incorrect version of Fig. 4 is presented in the accompanying Publisher Correction.

12.
Nat Commun ; 10(1): 766, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30770823

RESUMO

Primary triple negative breast cancers (TNBC) are prone to dissemination but sub-clonal relationships between tumors and resulting metastases are poorly understood. Here we use cellular barcoding of two treatment-naïve TNBC patient-derived xenografts (PDXs) to track the spatio-temporal fate of thousands of barcoded clones in primary tumors, and their metastases. Tumor resection had a major impact on reducing clonal diversity in secondary sites, indicating that most disseminated tumor cells lacked the capacity to 'seed', hence originated from 'shedders' that did not persist. The few clones that continued to grow after resection i.e. 'seeders', did not correlate in frequency with their parental clones in primary tumors. Cisplatin treatment of one BRCA1-mutated PDX model to non-palpable levels had a surprisingly minor impact on clonal diversity in the relapsed tumor yet purged 50% of distal clones. Therefore, clonal features of shedding, seeding and drug resistance are important factors to consider for the design of therapeutic strategies.


Assuntos
Células Clonais , Neoplasias de Mama Triplo Negativas/genética , Animais , Proteína BRCA1/genética , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Mutação/genética , Recidiva Local de Neoplasia/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Mol Cell Cardiol ; 44(2): 270-80, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18191142

RESUMO

Impaired glucose uptake is associated with both cardiac hypertrophy and contractile dysfunction, but whether there are common underlying mechanisms linking these conditions is yet to be determined. Using a 'gene dose' Cre-Lox GLUT4-deficient murine model, we examined the effect of suppressed glucose availability on global myocardial gene expression and glycolysis substrate bypass on the function of isolated perfused hearts. Performance of hearts from 22- to 60-week-old male GLUT4 knockout (KO, >95% reduction in GLUT4), GLUT4 knockdown (KD, 85% reduction in cardiac GLUT4) and C57Bl/6 wild-type (WT) controls was measured ex vivo in Langendorff mode perfusion. DNA microarray was used to profile mRNA expression differences between GLUT4-KO and GLUT4-KD hearts. At 22 weeks, GLUT4-KO hearts exhibited cardiac hypertrophy and impaired contractile function ex vivo, characterized by a 40% decrease in developed pressure. At 60 weeks, dysfunction was accentuated in GLUT4-KO hearts and evident in GLUT4-KD hearts. Exogenous pyruvate (5 mM) restored systolic pressure to a level equivalent to WT (GLUT4-KO, 176.8+/-13.2 mmHg vs. WT, 146.4+/-9.56 mmHg) in 22-week-old GLUT4-KO hearts but not in 60-week-old GLUT4-KO hearts. In GLUT4-KO, DNA microarray analysis detected downregulation of a number of genes centrally involved in mitochondrial oxidation and upregulation of other genes indicative of a shift to cytosolic beta-oxidation of long chain fatty acids. A direct link between cardiomyocyte GLUT4 deficiency, hypertrophy and contractile dysfunction is demonstrated. These data provide mechanistic insight into the myocardial metabolic adaptations associated with short and long-term insulin resistance and indicate a window of opportunity for substrate intervention and functional 'rescue'.


Assuntos
Transportador de Glucose Tipo 4/deficiência , Glucose/metabolismo , Miocárdio/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Miocárdica/efeitos dos fármacos , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Ácido Pirúvico/farmacologia , Especificidade por Substrato/efeitos dos fármacos , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos
14.
Ir J Med Sci ; 186(4): 835-840, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27796665

RESUMO

BACKGROUND: Radical prostatectomy for prostate cancer is associated with significant complications, such as urinary incontinence and erectile dysfunction. Debate remains regarding the influence of surgical technique on these important functional outcomes. AIM: The aim of this study was to compare the early functional outcomes following robotic-assisted (RARP), laparoscopic (LRP), and open radical prostatectomy (ORP) in a rapid access cohort. METHODS: A retrospective review of a prospectively maintained database was performed between 2011 and 2014. Functional status was objectively assessed using the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5), and a self-reported continence score. RESULTS: Two hundred and ninety-two patients underwent RP (85 RARP, 100 LRP, 107 ORP). The mean age was 61.3 years with a mean initial PSA was 6.2 ng/ml. There was no difference noted in urinary function between ORP, LRP, and RARP at 3 months (p = 0.894), 6 months (p = 0.244), 9 months (p = 0.068) or 12 months (p = 0.154). All men noted a deterioration in erectile function; however, there was no difference at 3 months (p = 0.922), 6 months (p = 0.723), 9 months (p = 0.101) or 12 months (p = 0.395), CONCLUSION: Equivalent good early functional outcomes are being achieved in patients undergoing RP irrespective of surgical approach. Longer follow-up in a prospective randomized fashion is required to fully assess the most appropriate surgical technique.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Resultado do Tratamento
15.
Cancer Res ; 59(17): 4325-33, 1999 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10485480

RESUMO

A complex of polyinosinic-polycytidylic acid [poly(I) x poly(C)] and cationic liposome (LIC) inhibited the growth of many tumor cell lines at low concentration in vitro, but poly(I) x poly(C) alone had no such antiproliferative effect. The IC50 values of LIC against the tumor cells ranged from 0.1 to 1000 ng/ml. LIC had strong cytotoxic effects on malignant cells of epithelial and fibroblastic origin from various tissues and was also effective against Adriamycin-resistant tumor cells. LIC did not significantly affect the growth of lymphoma cells, leukemia cells, normal diploid fibroblasts, or primary liver cells at concentrations up to 10 microg/ml. The mechanism of the antiproliferative effect of LIC against malignant cells was the induction of apoptosis. LIC induced the fragmentation of nuclear DNA and the degradation of rRNA in tumor cells. The DNA fragmentation occurred within 1-5 h after the addition of LIC, and both the fragmentation and the inhibition of cancer-cell growth were suppressed by a nuclease inhibitor. In contrast, caspase inhibitors did not affect the antiproliferative activity of LIC. These results suggest that LIC induced apoptosis in malignant cells through the direct activation of nucleases and not through the activation of caspases. LIC reduced the incidence and the size of metastatic liver-cancer tumors in two different mouse metastatic liver-cancer models using human colon carcinoma cells. Histochemical analysis revealed that the KM12-HX cells in the tumor nodules were undergoing apoptosis; therefore, LIC also induced the apoptosis of tumor cells in vivo. In these animal models, LIC caused no observed changes in normal hepatocytes.


Assuntos
Antineoplásicos/farmacologia , Poli I-C/farmacologia , Animais , Apoptose/efeitos dos fármacos , Inibidores de Caspase , Divisão Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Humanos , Lipossomos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microinjeções , Poli I-C/farmacocinética , RNA Ribossômico/metabolismo , Células Tumorais Cultivadas
16.
Aust Vet J ; 94(1-2): 4-11, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26726106

RESUMO

OBJECTIVE: To collate data on the numbers of applications, offers, acceptances, students and graduates at Australian veterinary schools between 2001 and 2013. METHOD: Data were obtained from the Australian Department of Education, the Australian Bureau of Statistics, Graduate Careers Australia and the Australian Veterinary Association Ltd. RESULTS: The number of eligible applicants for veterinary science courses increased from 1540 in 2001 to 2243 in 2013 (46% increase). Offers for places ranged from 400 in 2001 to 643 in 2013 (61% increase) and acceptances ranged from 254 in 2001 to 457 in 2013 (80% increase).The total number of students enrolled ranged from 1641 in 2001 to 3036 in 2013 (85% increase). Female students increased from 1195 in 2001 to 2340 in 2013 (96% increase) and male students increased from 446 to 696 (56%) over this time period. Domestic students numbered 1411 in 2001 and 2391 in 2013 (69% increase). International students increased from 230 in 2001 to 643 in 2013 (180% increase). Students entering veterinary courses numbered 389 in 2001 and increased to 688 in 2013 (77% increase). Graduates increased from 312 in 2001 to 561 in 2013 (80% increase). Percent of recent veterinary graduates seeking full-time employment was 7.6% in 2001 and increased to 21.2% in 2013. Median starting salaries for veterinary graduates in Australia were A$34,000 in 2001 and A$46,000 in 2013 (35% increase). CONCLUSIONS: These data provide additional information about the ongoing increase in the numbers of domestic and international students studying veterinary science at Australian universities. Between 2001 and 2013 the numbers of Australian veterinary students and graduates increased at a greater rate than the Australian population.


Assuntos
Faculdades de Medicina Veterinária/estatística & dados numéricos , Austrália , Coleta de Dados , Estudantes/estatística & dados numéricos
17.
Aust Vet J ; 94(3): 52-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26914949

RESUMO

OBJECTIVE: To obtain information on the types of Australian horses, how they are kept and their activities. METHODS: An invitation to participate in an opt-in, internet-based survey was sent to 7000 people who had registered an email address to receive information from the Australian Horse Industry Council Inc. RESULTS: There were 3377 (48%) useable responses from owners of 26,548 horses. Most horses were kept on small properties (usually 2-8 ha) in paddocks in rural areas of Queensland, New South Wales and Victoria. Most horses were female or geldings and the most common of 54 different activities was breeding. Owners reported 19,291 horses were used in different activities and 6037 (23%) horses were not kept for any stated purpose or activity. Owners used an average of 1.95 horses in 2.9 different types of activities. The most common of the 43 breeds were Thoroughbred, Australian Stock Horse and Australian Quarter Horse. Only 1% of the total numbers of Thoroughbreds and Standardbreds in this survey were used in horse racing, indicating there is a demand for these breeds in non-racing activities. Microchip was the most favoured method of horse identification and 36% favoured compulsory registration of horses. Most respondents reported owning some other animal species. CONCLUSIONS: There is a wide variation in horse breeds used in different activities by Australian horse owners. There are regional differences in various management systems. There needs to be considerable improvement in the collection and recording of information to improve the validity and reliability of horse industry data.


Assuntos
Criação de Animais Domésticos , Cavalos/fisiologia , Criação de Animais Domésticos/métodos , Criação de Animais Domésticos/estatística & dados numéricos , Animais , Austrália , Cruzamento , Demografia , Feminino , Cavalos/classificação , Internet , Masculino , Distribuição por Sexo , Inquéritos e Questionários
18.
Int J Impot Res ; 28(6): 205-208, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27225711

RESUMO

Controversy exists regarding optimal penile rehabilitation program following radical prostatectomy (RP). Vacuum erectile devices (VEDs) have become an important component of penile rehabilitation protocols. The aim of this study was to assess the efficacy and patient satisfaction of a dedicated VED clinic. A voluntary telephone questionnaire was performed of all patients who attended a VED clinic to date in two university teaching hospitals. Patient demographics, histopathological characteristics and functional status (International Index of Erectile Function (IIEF) scores) were obtained from a retrospective review of a prospectively maintained database. Sixty-five men attended the dedicated VED clinic in the two university teaching hospitals. Forty-men (76.3%) men purchased a VED following the dedicated clinic. There was significant differences noted between the mean preoperative and the 3-month postoperative IIEF scores (22.08±3.16 vs 11.3±3.08, P=0.0001) and between the 3-month postoperative IIEF score and the post-VED use IIEF score (11.3±3.08 vs 16.74±2.62, P=0.0001). Despite VED use, there was a significant reduction in erectile function from presurgery status (22.08±3.16 vs 16.74±2.62, P=0.0001). All patients reported that the dedicated VED was helpful and would recommend it to other patients. Our study demonstrates that, despite a reduction in erectile function after RP, successful erections are attainable with a VED. There is potential and need for the development of a standard penile rehabilitation program and treatment of ED after RP internationally.


Assuntos
Disfunção Erétil/reabilitação , Ereção Peniana/fisiologia , Prostatectomia/efeitos adversos , Disfunção Erétil/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/reabilitação , Prostatectomia/reabilitação , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Vácuo
19.
Ir J Med Sci ; 185(1): 121-5, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25472824

RESUMO

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.


Assuntos
Criopreservação/métodos , Função Retardada do Enxerto , Transplante de Rim/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Obtenção de Tecidos e Órgãos/métodos , Adenosina , Idoso , Alopurinol , Feminino , Glutationa , Sobrevivência de Enxerto , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos , Rafinose , Estudos Retrospectivos
20.
Transplant Proc ; 37(10): 4228-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16387085

RESUMO

Pediatric en bloc transplantation of infant organs into adult recipients is a recognized technique to expand the number of kidneys available for transplantation. We reviewed our experience with this technique over a 15-year period to determine the long-term outcomes. Twelve patients underwent pediatric en bloc transplantation from donors aged <4 years. All transplants functioned immediately with no graft thrombosis. Two patients died 12 and 10 years posttransplant with functioning grafts. The remaining 10 recipients experienced excellent graft function with a mean follow-up time of 73.8 months (range, 10 to 169 months) with no evidence of hyperfiltration injury. We conclude that pediatric en bloc transplantations achieve excellent long-term allograft function in selected recipients.


Assuntos
Transplante de Rim/métodos , Transplante de Rim/fisiologia , Doadores de Tecidos/estatística & dados numéricos , Adulto , Idoso , Cadáver , Causas de Morte , Criança , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Terapia de Imunossupressão/métodos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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