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2.
Br J Oral Maxillofac Surg ; 57(3): 246-250, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30851998

RESUMO

Many indices and scoring systems exist for assessing skeletal patterns and malocclusion but none have been universally adopted by teams providing orthognathic surgery in the UK. Using a standardised objective measure of a patient's condition is important both for service provision, treatment allocation, and other clinical governance domains. The Severity and Outcome Assessment tool (SOA) developed by the British Orthodontic Society (BOS) and British Association of Oral and Maxillofacial Surgeons (BAOMS) provides a standardised method of assessing patients throughout the orthognathic pathway and lends itself to case selection, resource allocation and auditing treatment outcomes. The SOA uses 7 cephalometric skeletal, dental and soft tissue measures to produce an overall score.The SOA has been used by the current NHS Tayside orthognathic team since August 2006 to audit treatment outcomes. While we recognise that cephalometric analysis forms only one part of orthognathic treatment we believe that having an objective measure on which to assess treatment is useful. We present our experience of using this quick, simple and reproducible tool in auditing orthognathic treatment outcomes.


Assuntos
Má Oclusão , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Cefalometria , Humanos , Sociedades Odontológicas , Resultado do Tratamento
3.
Implement Sci ; 14(1): 24, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30845958

RESUMO

BACKGROUND: Post-stroke disability is common, costly, and projected to increase. Acute stroke treatments can substantially reduce post-stroke disability, but few patients take advantage of these cost-effective treatments. Practical, cost-efficient, and sustainable interventions to address underutilized acute stroke treatments are currently lacking. In this context, we present the Stroke Ready project, a stepped wedge design, multi-level intervention that combines implementation science and community-based participatory research approaches to increase acute stroke treatments in the predominately African American community of Flint, Michigan, USA. METHODS: Guided by the Tailored Implementation of Chronic Disease (TICD) framework, we begin with optimization of acute stroke care in emergency departments, with particular attention given to our safety-net hospital partners. Then, we move to a community-wide, multi-faceted, stroke preparedness intervention, with workshops led by peer educators, over 2 years. Measures of engagement of the safety-net hospital and the feasibility and sustainability of the implementation strategy as well as community intervention reach, dose delivered, and satisfaction will be collected. The primary outcome is acute stroke treatment rates, which includes both intravenous tissue plasminogen activator, and endovascular treatment. The co-secondary outcomes are intravenous tissue plasminogen activator treatment rates and the proportion of stroke patients who arrive by ambulance. DISCUSSION: If successful, Stroke Ready will increase acute stroke treatment rates through emergency department and community level interventions. The stepped wedge design and process evaluation will provide insight into how Stroke Ready works and where it might work best. By exploring the relative effectiveness of the emergency department optimization and the community intervention, we will inform hospitals and communities as they determine how best to use their resources to optimize acute stroke care. TRIAL REGISTRATION: ClinicalTrials.gov Trial Identifier NCT03645590 .


Assuntos
Acidente Vascular Cerebral/terapia , Doença Aguda , Afro-Americanos/etnologia , Ensaios Clínicos como Assunto/métodos , Análise Custo-Benefício , Humanos , Michigan , Anos de Vida Ajustados por Qualidade de Vida , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/etnologia , Resultado do Tratamento
4.
J Oncol Pharm Pract ; 25(6): 1425-1433, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30924737

RESUMO

BACKGROUND: Lanreotide and octreotide acetate suspension for injectable (LAR) are both recommended for clinical use in patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors. However, each agent possesses unique attributes in terms of their drug-delivery characteristics. The study objective was to compare overall drug-delivery efficiency between lanreotide and octreotide LAR in gastroenteropancreatic neuroendocrine tumor patients. METHODS: This study employed an observational time and motion design among patients treated with lanreotide or octreotide LAR across five US cancer centers. Baseline patient data collection included age, disease grade and duration, prior therapies and performance status. Drug-delivery time (drug preparation and administration), total patient time and resource use data were collected for gastroenteropancreatic neuroendocrine tumors receiving lanreotide (n = 22) or octreotide LAR (n = 22). Following each administration, qualitative data on the drug-delivery experience was collected from patients and nurses. RESULTS: Lanreotide was associated with a significant reduction in mean delivery time (2.5 min; 95% CI:2.0 to 3.1) compared to octreotide LAR (6.2 min; 95%CI: 4.4 to 7.9; p = 0.004). The mean total patient time for lanreotide and octreotide LAR was comparable between groups (32.1 vs. 36.6 minutes; p = 0.97). Nurses reported increased concerns with octreotide LAR related to needle clogging (p = 0.034) and device failures (p = 0.057). Overall, lanreotide had a median satisfaction score of 5.0 compared to a score of 4.0 with octreotide LAR (p = 0.03). CONCLUSIONS: Lanreotide was associated with significant reductions in drug-delivery time compared to octreotide LAR, which contributed to an improvement in overall healthcare efficiency. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03017690.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Sistemas de Medicação/organização & administração , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Composição de Medicamentos , Falha de Equipamento , Feminino , Recursos em Saúde/estatística & dados numéricos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Agulhas/efeitos adversos , Satisfação do Paciente , Estudos Prospectivos , Somatostatina/uso terapêutico , Estudos de Tempo e Movimento
5.
Eur J Neurol ; 26(7): 969-e71, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30685877

RESUMO

BACKGROUND AND PURPOSE: Pre-surgical evaluation of pediatric patients with drug-resistant focal epilepsy and negative (non-lesional) magnetic resonance imaging (MRI) is particularly challenging. Focal cortical dysplasia (FCD), a frequent pathological substrate in such setting, may be subtle on MRI and evade detection. The aim of this study was to use voxel-based MRI postprocessing to improve the detection of subtle FCD in pediatric surgical candidates. METHODS: A consecutive cohort of pediatric patients undergoing pre-surgical evaluation with a negative MRI by visual analysis was included. MRI postprocessing was performed using a voxel-based morphometric analysis program (MAP) on T1-weighted volumetric MRI, with comparison to an age-specific normal pediatric database. The pertinence of MAP-positive areas was confirmed by surgical outcome and pathology. RESULTS: A total of 78 patients were included. Forty-four patients (56%) had positive MAP regions. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome compared with the no/partial resection group (P < 0.001). Patients with no/partial resection of the MAP-positive regions had worse seizure outcomes than the MAP-negative group (P = 0.002). The MAP-positive rate was 100%, 77%, 63% and 40% in the 3-5, 5-10, 10-15 and 15-21 year age groups, respectively. MAP-positive rates were 45% in patients with temporal resection and 63% in patients with extratemporal resection. Complete resection of the MAP-positive regions was positively associated with seizure-free outcome in the extratemporal group (P = 0.001) but not in the temporal group (P = 0.070). CONCLUSION: Our data suggest the importance of using MRI postprocessing in the pre-surgical evaluation process of pediatric epilepsy patients with apparently normal MRI.

6.
J Thromb Thrombolysis ; 47(1): 166, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30478721

RESUMO

Unfortunately the author list in the original article is incomplete. The correct list of contributing authors is given in this Correction.

7.
J Theor Biol ; 444: 108-123, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29407269

RESUMO

A multiphasic constitutive model of the skin that implicitly accounts for the process of intrinsic (i.e. chronological) ageing via variation of the constitutive parameters is proposed. The structurally-motivated constitutive formulation features distinct mechanical contributions from collagen and elastin fibres. The central hypothesis underpinning this study is that the effects of ageing on the mechanical properties of the tissue are directly linked to alterations in the microstructural characteristics of the collagen and elastin networks. Constitutive parameters in the model, corresponding to different ages, are identified from published experimental data on bulge tests of human skin. The numerical results demonstrate that degradation of the elastin meshwork and variations in anisotropy of the collagen network are plausible mechanisms to explain ageing in terms of macroscopic tissue stiffening. Whereas alterations in elastin affect the low-modulus region of the skin stress-strain curve, those related to collagen have an impact on the linear region.


Assuntos
Envelhecimento , Fenômenos Biomecânicos/fisiologia , Modelos Biológicos , Pele/ultraestrutura , Animais , Anisotropia , Colágeno/metabolismo , Elastina/metabolismo , Análise de Elementos Finitos , Humanos
8.
Biochem Pharmacol ; 148: 88-99, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29248595

RESUMO

11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1; EC 1.1.1.146) generates active glucocorticoid hormones. Small molecule inhibitors have been developed to target 11ß-HSD1 for the treatment of dementia; these must enter brain subregions, such as the hippocampus, to be effective. We previously reported mass spectrometry imaging measurement of murine tissue steroids, and deuterated steroid tracer infusion quantification of 11ß-HSD1 turnover in humans. Here, these tools are combined to assess tissue pharmacokinetics and pharmacodynamics of an 11ß-HSD1 inhibitor that accesses the brain. [9,11,12,12-2H]4-Cortisol was infused (1.75 mg/day) by minipump for 2 days into C57Bl6 mice (male, age 12 weeks, n = 3/group) after which an 11ß-HSD1 inhibitor (UE2316) was administered (25 mg/kg oral gavage) and animals culled immediately or 1, 2 and 4 h post-dosing. Mice with global genetic disruption of Hsd11B1 were studied similarly. Turnover of d4-cortisol to d3-cortisone (by loss of the 11-deuterium) and regeneration of d3-cortisol (by 11ß-HSD1-mediated reduction) were assessed in plasma, liver and brain using matrix assisted laser desorption ionization coupled to Fourier transform cyclotron resonance mass spectrometry. The tracer d4-cortisol was detected in liver and brain following a two day infusion. Turnover to d3-cortisone and on to d3-cortisol was slower in brain than liver. In contrast, d3-cortisol was not detected in mice lacking 11ß-HSD1. UE2316 impaired d3-cortisol generation measured in whole body (assessed in plasma; 53.1% suppression in rate of appearance in d3-cortisol), liver and brain. Differential inhibition in brain regions was observed; active glucocorticoids were suppressed to a greater in extent hippocampus or cortex than in amygdala. These data confirm that the contribution of 11ß-HSD1 to the tissue glucocorticoid pool, and the consequences of enzyme inhibition on active glucocorticoid concentrations, are substantial, including in the brain. They further demonstrate the value of mass spectrometry imaging in pharmacokinetic and pharmacodynamic studies.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Encéfalo/enzimologia , Pirazóis/farmacologia , Tiofenos/farmacologia , Animais , Cortisona/metabolismo , Hidrocortisona/metabolismo , Marcação por Isótopo , Fígado/metabolismo , Espectrometria de Massas , Camundongos , Estrutura Molecular
9.
Biomech Model Mechanobiol ; 17(2): 479-497, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29139052

RESUMO

The flow rate inside arteriovenous fistulas is many times higher than physiological flow and is accompanied by high wall shear stress resulting in low patency rates. A fluid-structure interaction finite element model is developed to analyse the blood flow and vessel mechanics to elucidate the mechanisms that can lead to failure. The simulations are validated against flow measurements obtained from magnetic resonance imaging data.


Assuntos
Vasos Sanguíneos/fisiologia , Análise de Elementos Finitos , Modelos Cardiovasculares , Diálise Renal , Algoritmos , Fenômenos Biomecânicos , Calibragem , Cateteres , Simulação por Computador , Humanos , Imageamento Tridimensional , Imagem por Ressonância Magnética , Análise Numérica Assistida por Computador , Pressão , Reprodutibilidade dos Testes , Estresse Mecânico , Sístole
11.
Am J Transplant ; 17(2): 451-461, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27456745

RESUMO

Clinical islet transplantation achieves insulin independence in selected patients, yet current methods for extracting islets from their surrounding pancreatic matrix are suboptimal. The islet basement membrane (BM) influences islet function and survival and is a critical marker of islet integrity following rodent islet isolation. No studies have investigated the impact of islet isolation on BM integrity in human islets, which have a unique duplex structure. To address this, samples were taken from 27 clinical human islet isolations (donor age 41-59, BMI 26-38, cold ischemic time < 10 h). Collagen IV, pan-laminin, perlecan and laminin-α5 in the islet BM were significantly digested by enzyme treatment. In isolated islets, laminin-α5 (found in both layers of the duplex BM) and perlecan were lost entirely, with no restoration evident during culture. Collagen IV and pan-laminin were present in the disorganized BM of isolated islets, yet a significant reduction in pan-laminin was seen during the initial 24 h culture period. Islet cytotoxicity increased during culture. Therefore, the human islet BM is substantially disrupted during the islet isolation procedure. Islet function and survival may be compromised as a consequence of an incomplete islet BM, which has implications for islet survival and transplanted graft longevity.


Assuntos
Membrana Basal/metabolismo , Separação Celular , Colágeno Tipo IV/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Ilhotas Pancreáticas/metabolismo , Laminina/metabolismo , Proteínas de Membrana/metabolismo , Adulto , Células Cultivadas , Feminino , Humanos , Ilhotas Pancreáticas/citologia , Transplante das Ilhotas Pancreáticas , Masculino , Pessoa de Meia-Idade
12.
Clin Genet ; 91(5): 708-716, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27718516

RESUMO

Post-translational protein modifications exponentially expand the functional complement of proteins encoded by the human genome. One such modification is the covalent addition of a methyl group to arginine or lysine residues, which is used to regulate a substantial proportion of the proteome. Arginine and lysine methylation are catalyzed by protein arginine methyltransferase (PRMTs) and protein lysine methyltransferase proteins (PKMTs), respectively; each methyltransferase has a specific set of target substrates. Here, we report a male with severe intellectual disability, facial dysmorphism, microcephaly, short stature, brachydactyly, cryptorchidism and seizures who was found to have a homozygous 15,309 bp deletion encompassing the transcription start site of PRMT7, which we confirmed is functionally a null allele. We show that the patient's cells have decreased levels of protein arginine methylation, and that affected proteins include the essential histones, H2B and H4. Finally, we demonstrate that patient cells have altered Wnt signaling, which may have contributed to the skeletal abnormalities. Our findings confirm the recent disease association of PRMT7, expand the phenotypic manifestations of this disorder and provide insight into the molecular pathogenesis of this new condition.


Assuntos
Braquidactilia/genética , Deficiência Intelectual/genética , Microcefalia/genética , Proteína-Arginina N-Metiltransferases/genética , Anormalidades Múltiplas/genética , Arginina/metabolismo , Pré-Escolar , Cromossomos Humanos Par 16 , Face/anormalidades , Feminino , Dedos/anormalidades , Deleção de Genes , Humanos , Lactente , Recém-Nascido , Masculino , Sítio de Iniciação de Transcrição , Via de Sinalização Wnt/genética
13.
J Therm Biol ; 62(Pt B): 201-209, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27888934

RESUMO

The modelling and computation of the coupled thermal and mechanical response of human skin at finite deformations is considered. The model extends current thermal models to account for thermally- and mechanically-induced deformations. Details of the solution of the highly nonlinear system of governing equations using the finite element method are presented. A representative numerical example illustrates the importance of considering the coupled response for the problem of a rigid, hot indenter in contact with the skin.


Assuntos
Modelos Biológicos , Fenômenos Fisiológicos da Pele , Temperatura Cutânea , Simulação por Computador , Elasticidade , Análise de Elementos Finitos , Humanos
14.
Transpl Infect Dis ; 18(1): 63-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26606757

RESUMO

BACKGROUND: Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients. METHODS: A single-institution retrospective review of electronic medical records was conducted for patients who underwent allo-HSCT between January 2001 and May 2013 and who had received at least 1 dose of IV PEN for PJP prophylaxis. Data collected included patient demographics, diagnosis, previous chemotherapy, pre-transplant conditioning regimen, other medications, microbiology test results, and clinical outcomes. RESULTS: A total of 113 patients were included in the study. The median number of PEN doses administered per patient was 3 (range 1-23). IV PEN was primary PJP prophylaxis in 74 of the patients (65%) and second-line prophylaxis in 39 (35%) post transplant, with the majority switching from oral TMP-SMX. Side effects of IV PEN administration were minimal. No patients who received IV PEN prophylaxis developed PJP infection. No case of PJP was seen in patients who received other agents for PJP prophylaxis. CONCLUSION: This retrospective study showed that IV PEN is very effective and well-tolerated prophylaxis for PJP; IV PEN can be considered a favorable alternative for PJP in situations where other agents might be contraindicated. Our findings provide strong support for prospective studies of IV PEN for PJP prophylaxis in adult HSCT recipients.


Assuntos
Antifúngicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Oportunistas/tratamento farmacológico , Pneumonia por Pneumocystis/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Atovaquona/administração & dosagem , Criança , Pré-Escolar , Dapsona/administração & dosagem , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/etiologia , Infecções Oportunistas/microbiologia , Pentamidina/administração & dosagem , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/microbiologia , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Adulto Jovem
16.
Br J Cancer ; 112(8): 1301-5, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25791875

RESUMO

BACKGROUND: The combination of nab-paclitaxel plus gemcitabine (NAB-P+GEM) has shown superior efficacy over GEM monotherapy in metastatic pancreas cancer (MPC). Independent cost-effectiveness/utility analyses of NAB-P+GEM from the payer perspective have not been conducted for the UK. METHODS: A Markov model simulating the health outcomes and total costs was developed to estimate the life years gained (LYG) and quality-adjusted life years gained (QALY) and incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) for patients with MPC in a base case and in a probabilistic (PSA) sensitivity analysis. Total cost included the cost of supportive care medications, administration, chemotherapy, disease monitoring, and adverse reactions; and was discounted at 3.5% per year. A full lifetime horizon and third party payer perspective was chosen. RESULTS: The total cost of NAB-P+GEM was £5466 higher than the cost for GEM. Respectively, LYGs were 0.97 vs 0.79 and QALYs were 0.52 vs 0.45, with ICER of £30 367/LYG and ICUR of £78 086/QALY, confirmed by PSA. CONCLUSIONS: The superior survival efficacy of NAB-P+GEM over GEM in the management of MPC is associated with positive cost-effectiveness and cost-utility.


Assuntos
Antimetabólitos Antineoplásicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Albuminas/administração & dosagem , Albuminas/economia , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise Custo-Benefício , Desoxicitidina/administração & dosagem , Desoxicitidina/economia , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econômicos , Metástase Neoplásica , Paclitaxel/administração & dosagem , Paclitaxel/economia , Neoplasias Pancreáticas/economia , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida , Reino Unido
18.
Osteoarthritis Cartilage ; 23(2): 203-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25464166

RESUMO

OBJECTIVES: Osteoarthritis (OA) has a genetic component but it is uncertain if the offspring of those with knee OA are at a greater risk. The aim of this study was to describe radiographic OA (ROA) progression and cartilage loss over 10 years in a midlife cohort with some having a family history of OA and some community based controls. METHODS: 220 participants [mean-age 45 (26-61); 57% female] were studied at baseline and 10 years. Half were adult offspring of subjects who underwent knee replacement for OA and the remainder were randomly selected controls. Joint space narrowing (JSN) and osteophytes were assessed on radiographs and cartilage volume (tibial, femoral and patellar), cartilage defects, bone marrow lesions (BMLs) and meniscal tears were assessed on Magnetic resonance imaging (MRI). RESULTS: For ROA, there was a significant difference between offspring and controls in unadjusted analysis for change in total ROA, medial JSN, total medial, total lateral and total osteophyte scores. This difference persisted for medial JSN (difference in ratios = +1.93 (+1.04, +3.51)) only, after adjustment for confounders and baseline differences. In unadjusted analysis for cartilage loss, offspring lost more cartilage at the medial tibial (difference in means = -79.13 (-161.92, +3.71)) site only. This difference became of borderline significance after adjustment for baseline differences (P = 0.055). CONCLUSION: The offspring of subjects having a total knee replacement have a greater worsening of ROA (both JSN and osteophytes) and higher medial tibial cartilage volume loss over 10 years. Most of these changes are mediated by differences in baseline characteristics of offspring and controls except for increase in medial JSN.


Assuntos
Artroplastia do Joelho , Cartilagem Articular/patologia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/cirurgia , Adulto , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Osteoartrite do Joelho/diagnóstico por imagem , Radiografia , Tíbia , Fatores de Tempo
19.
Bone Marrow Transplant ; 49(8): 1052-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24797182

RESUMO

In an otherwise eligible patient, inadequate mobilization of PBSCs is a limiting factor to proceeding with an auto-ASCT. In such situations, plerixafor is commonly added to improve PBSC collection yields along with cytokine (G-CSF alone) or chemomobilization (chemotherapy+G-CSF). Individually, both strategies are proven to be safe and effective. Here we report six patients who underwent successful mobilization with combination chemomobilization plus plerixafor after upfront failure of cytokine mobilization plus plerixafor. The median CD34(+) cell yield after chemomobilization was 2.48 × 10(6)/kg (range 0.99-8.49) after receiving one to two doses of plerixafor. All patients subsequently underwent ASCT without major unforeseen toxicities and engrafted successfully. No significant delays in time to neutrophil recovery were observed. Our experience highlights the safety and effectiveness of chemomobilization with plerixafor after G-CSF plus plerixafor (G+P) failure and suggests this is a viable salvage strategy after initial failed G+P mobilization.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/administração & dosagem , Linfoma/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Autoenxertos , Feminino , Humanos , Linfoma/sangue , Masculino , Pessoa de Meia-Idade
20.
Animal ; 7(5): 778-83, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23171533

RESUMO

Erythropoietin (EPO) gene therapy can be used for several purposes; however, its effects on reproductive performance are unknown. The aim of this study was to evaluate the toxicological effects of non-viral (EPO) gene transfer on sperm motility, viability, morphology and concentration. Rabbit EPO cDNA was cloned into a pTarget mammalian expression vector. Rabbits were administered with: (1) pTarget/EPO vector, (2) recombinant human EPO (rHuEpo) and (3) saline (control). Both pTarget/EPO and rHuEpo significantly increased (P < 0.05) hematocrit levels 1 week after injection and they remained significantly higher than the control for up to 5 weeks (P < 0.05), showing that both EPO treatments were effective in stimulating the production of red blood cells in rabbits. The EPO gene transfer or rHuEPO administration had no significant effect (P > 0.05) on sperm motility, vigor, viability, concentration or morphology in the testis.


Assuntos
Eritropoetina/genética , Terapia Genética/veterinária , Motilidade Espermática/fisiologia , Espermatozoides/citologia , Espermatozoides/fisiologia , Animais , Clonagem Molecular , Terapia Genética/métodos , Células HeLa , Humanos , Masculino , Coelhos , Testículo
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