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1.
Cureus ; 15(7): e42409, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37502467

RESUMO

Introduction In the setting of nasal surgeries, the use of opioid-free anesthesia involving the use of dexmedetomidine, and lignocaine is being investigated as a potential alternative to opioids. This combination of drugs provides sympatholysis, pain relief, and sedative properties, thereby aiming at reducing the negative effects commonly associated with opioid usage. The objective of this study is to evaluate and compare the effectiveness of opioid-free anesthesia using dexmedetomidine and lignocaine versus conventional opioid anesthesia with fentanyl for nasal surgeries. The comparison will be based on the primary outcome of postoperative visual analog scale (VAS) scores. Secondary outcomes assessed were the amount of rescue analgesic consumption, intraoperative sevoflurane usage, intraoperative blood loss, hemodynamic stability, postoperative nausea and vomiting (PONV) scores, and postoperative Ramsay Sedation Scores. Methods A triple-blind, prospective, randomized, parallel arm study in which 48 patients planned for elective nasal surgery were allocated randomly to one of two groups. In the study, the population labeled as Group D, comprising 24 participants, received dexmedetomidine at a dosage of 1 mcg.kg-1 via intravenous infusion lasting for a duration of 10 minutes prior to the induction of anesthesia. This was followed by a continuous infusion of 0.6 mcg.kg-1 h-1 throughout the intraoperative period, and intravenous Lignocaine 1.5 mg.kg-1 was administered three minutes prior to induction, subsequently an intraoperative infusion of 1.5 mg.kg-1 h-1. In Group F, consisting of 24 participants, intravenous fentanyl of 2 mcg.kg-1 was administered three minutes before the induction. This was subsequently followed by a fentanyl infusion of 0.5 mcg.kg-1h-1 in the intraoperative period. Results The study findings indicate that Group D had considerably lower postoperative VAS scores from 30 minutes to two hours compared to Group F (p<0.05). The utilization of sevoflurane during the intraoperative period was comparatively reduced in Group D in order to achieve the desired bispectral index (BIS) range of 40-60 (p<0.01). Mean intraoperative blood loss was also lower in Group D (85 ml) compared to Group F (115 ml )(p<0.01). Additionally, Group D had significantly lower rescue analgesic consumption and lower incidence of PONV up to 60 minutes compared to Group F (P-value <0.01). A statistically significant difference was observed between Group D and Group F in terms of lower mean values of both mean arterial pressure (MAP) and heart rate in Group D (p<0.01). The results indicate that the postoperative sedation scores within the first two hours were significantly greater in Group D compared to Group F (p<0.01). Conclusion The usage of opioid-free anesthesia has been found to be superior to a traditional opioid-based approach in various aspects, including the provision of sufficient pain relief after surgery, maintenance of stable hemodynamics during the operation, and reduction in occurrences of postoperative nausea and vomiting.

2.
Case Rep Gastrointest Med ; 2022: 5703407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669380

RESUMO

Malignancies of the small intestine are rare. Signet-ring cell carcinoma (SRCC) is one of the rarest forms of adenocarcinoma that can arise in the small intestines. We present a case of a patient who originally presented with abdominal pain and radiographic findings suggestive of ileal congestion. The ileal biopsy specimens were nonspecific, and the patient began a trial of corticosteroid treatment for suspected Crohn's disease. A repeat colonoscopy yielded biopsies that were positive for malignancy. The patient then underwent an exploratory laparotomy which led to the diagnosis of SRCC. Given their similar presentations and the extreme rarity of this unusual malignancy, it can be difficult to differentiate between new-onset Crohn's disease and SRCC. A review of the literature was conducted to provide us with an improved understanding of previously documented cases of SRCC.

3.
Chemosphere ; 304: 135331, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35709842

RESUMO

In the latest times, considerable studies have been performed closer to detecting emerging pollutant such as paracetamol in wastewater. Electrochemical sensor developments have recently started to determine in fewer concentrations effectively. The detection of paracetamol using standard protocols corresponding to electroanalytical techniques has a greater impact noticed in directing the detecting process toward biosensors. Non-enzymatic sensors are the peak of all electro analysis approaches. Functionalized materials, such as metal oxide nanoparticles, conducting polymers, and carbon-based materials for electrode surface functionalization have been used to create a fortification for distributing passive enzyme-free biosensors. Synergic effects are possible by enhancing loading capacity and mass transfer of reactants for attaining high analytical sensitivity using a variety of nanomaterials with large surface areas. The main focus of this study is to address the prevailing issues in the identification of paracetamol with the tasks in the non-enzymatic sensors field, followed by the useful methods of electro analysis studies.


Assuntos
Técnicas Biossensoriais , Poluentes Ambientais , Nanopartículas Metálicas , Acetaminofen/análise , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Poluentes Ambientais/análise , Óxidos , Água
5.
ESMO Open ; 6(3): 100101, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33901870

RESUMO

BACKGROUND: Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. METHODS: The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. RESULTS: A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. CONCLUSIONS: In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Axitinibe , Carcinoma de Células Renais , Neoplasias Renais , Sunitinibe , Protocolos de Quimioterapia Combinada Antineoplásica , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Sunitinibe/uso terapêutico
6.
Math Biosci Eng ; 18(3): 2384-2400, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33892551

RESUMO

In this work, we study the problem of p-th moment global exponential stability for functional differential equations and scalar chaotic delayed equations under random impulsive effects. Meanwhile, the p-th moment global exponential synchronization for the proposed equations is also discussed, whereas the main results are proved by using Lyapunov function and Razumikhin technique. Furthermore, the impact of fixed and random time impulses are presented by applying the results to Mackey Glass blood cell production model and Ikeda bistable resonator model. Finally, the effectiveness of fixed and random impulses are depicted via graphical representations.

7.
Mar Pollut Bull ; 160: 111562, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32853841

RESUMO

The concentration of Acid Leachable Trace Metals (ALTMs) was assessed in urbanized tourist beaches (96 samples from Marina beach, 34 samples from Edward Elliot's beach, and 28 samples from Silver beach) of southeast coast of India. The concentration of metals accumulated in the beach sediment was less than the Upper Continental Crust (UCC) background reference values. The mean enrichment of ALTMs in the studied urban tourist beaches showed the following descending order: Marina beach - Cr > Pb > Ni > Zn > Cu > Mn > Co; Edward Elliot's beach - Cr > Pb > Ni > Mn > Co > Zn > Cu; Silver beach - Cr > Pb > Ni > Co > Mn > Cu > Zn. The ALTMs such as Fe, Mn, Co, Cu, and Zn were probably derived from natural weathering and mild anthropogenic influences whereas other metals were derived from anthropogenic induced factors.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Monitoramento Ambiental , Sedimentos Geológicos , Índia , Metais Pesados/análise , Poluentes Químicos da Água/análise
8.
J Hazard Mater ; 384: 121316, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31607578

RESUMO

In this study, Staphylococcus aureus biofilms, which are considered a foe for being pathogenic, were tested for their uranium bioremediation capacity to find out if they can turn out to be a friend. Acid phosphatase activity, which is speculated to aid in bio-precipitation of U(VI) from uranyl nitrate solution, was assayed in biofilms of seven different S. aureus strains. The presence of acid phosphatase enzyme was detected in the biofilms of all S. aureus strains (in the range of 3.1 ± 0.21 to 26.90 ± 2.32 µi.u./g), and found to be higher when compared to that of their planktonic phenotypes. Among all, S. aureus V329 biofilm showed highest biofilm formation ability along with maximum phosphatase activity (26.9 ± 2.32 µi.u./g of biomass). Addition of phosphate enhanced the U(VI) remediation when treated with uranyl nitrate solution. S. aureus V329 biofilm showed significant U tolerance with only a 3-log reduction when exposed to 10 ppm U(VI) for 1 h. When treated in batch mode, V329 biofilm successfully remediated up to 47% of the 10 ppm U(VI). This new approach using the acid phosphatase from the S. aureus V329 biofilm presents an alternative method for the remediation of uranium contamination.


Assuntos
Fosfatase Ácida/química , Biofilmes , Recuperação e Remediação Ambiental/métodos , Staphylococcus aureus/enzimologia , Urânio , Biodegradação Ambiental , Plâncton/química , Nitrato de Uranil/química
9.
In. The University of the West Indies, Faculty of Medical Sciences. Faculty of Medical Sciences, Research Day. St. Augustine, Caribbean Medical Journal, March 21, 2019. .
Não convencional em Inglês | MedCarib | ID: biblio-1023475

RESUMO

Objectives: To investigate the epidemiology, management and predictors of mortality in severe sepsis. Design and Methodology: Prospective observational study in 4 Trinidadian Intensive Care Units (ICU) over a one year period August 2017-August 2018. Physiologic and treatment data was collected on admission to ICU and patients were followed up until ICU discharge and then at 28 days to determine mortality. Results: 163 patients fit the criteria for severe sepsis and were enrolled. Twenty-eight day and ICU mortality rate were 42% (68) and 34 % (56) respectively. Case distribution by the various hospitals were San Fernando General Hospital 62% (101), Port of Spain General Hospital 16% (26), Eric Williams Medical Sciences Complex 12.3% (20) and Sangre Grande Hospital 9.8% (16). The most common source of sepsis was pulmonary (54%) followed by abdominal (17%) and urological sepsis (14%). Acute Kidney Injury (AKI) was present in 71% (115) patients and 43% (46) of patients with stage 2 and above AKI received Renal Replacement Therapy (RRT) in the ICU. In the regression model, the only factors that were found to predict both 28 day and ICU mortality were stage 2 AKI [OR 6.2 (95% CI 1.7- 23.1, p = .007)], stage 3 AKI [OR 7.2 (95% CI, 2.1-24.0, p=.001)] , mean arterial pressure of < 60mmHg in the first 24 hours [OR 10.8 (95% CI 1.7-68.1, p= .001)], presence of either moderate-severe Acute Respiratory Distress Syndrome [OR 4.1 (95% CI 1.8 ­ 9.2, p = .002)] and Acute Physiology, Age, Chronic Health Evaluation (APACHE) II score [OR 1.08 (95% CI, 1.0-1.2, p=.039)]. Conclusion: Severe sepsis is associated with a high hospital mortality rate and this sepsis burden varies according to region. Limited access to RRT remains a problem in certain centers.


Assuntos
Humanos , Sepse , Choque Séptico , Trinidad e Tobago , Epidemiologia
10.
Clin Exp Immunol ; 194(2): 259-272, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30246373

RESUMO

Memory T cell (Tmem) responses play a critical role in the outcome of allo-transplantation. While the role of the T-box transcription factor Eomesodermin (Eomes) in the maintenance of antigen-specific Tmem is well studied, little is known about Eomes+ CD8+ T cell responses after transplantation. We evaluated the phenotype and function of allo-reactive Eomes+ CD8+ T cells in healthy volunteers and kidney transplant patients and their relation to transplant outcome. High Eomes expression by steady-state CD8+ T cells correlated with effector and memory phenotype. Following allo-stimulation, the expression of both the T-box proteins Eomes and T-bet by proliferating cells increased significantly, where high expression of Eomes and T-bet correlated with higher incidence of allo-stimulated IFNγ+ TNFα+ CD8+ T cells. In patients with no subsequent rejection, Eomes but not T-bet expression by donor-stimulated CD8+ T cells, increased significantly after transplantation. This was characterized by increased Eomeshi T-bet-/lo and decreased Eomes-/lo T-bethi CD8+ T cell subsets, with no significant changes in the Eomeshi T-bethi CD8+ T cell subset. No upregulation of exhaustion markers programmed-death-1 (PD-1) and cytotoxic-T-lymphocyte-associated-antigen-4 (CTLA4) by donor-stimulated Eomes+ CD8+ T cells was observed. Before transplantation, in patients without rejection, there were higher incidences of Eomeshi T-bet-/lo , and lower incidences of Eomeshi T-bethi and Eomes-/lo T-bethi donor-stimulated CD8+ T cell subsets, compared to those with subsequent rejection. Overall, our findings indicate that high Eomes expression by allo-stimulated T-bet+ CD8+ T cells is associated with enhanced effector function, and that an elevated incidence of donor-stimulated CD8+ T cells co-expressing high levels of Eomes and T-bet before transplantation, may correlate with an increased incidence of acute cellular rejection.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Rim , Proteínas com Domínio T/metabolismo , Subpopulações de Linfócitos T/imunologia , Proliferação de Células , Células Cultivadas , Sobrevivência de Enxerto , Voluntários Saudáveis , Humanos , Memória Imunológica , Interferon gama/metabolismo , Isoantígenos/imunologia , Ativação Linfocitária , Proteínas com Domínio T/genética , Transplantados , Fator de Necrose Tumoral alfa/metabolismo
11.
Clin Genet ; 94(1): 159-164, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29566257

RESUMO

The location and/or type of variants in FLNB result in a spectrum of osteochondrodysplasias ranging from mild forms, like spondylocarpotarsal synostosis syndrome and Larsen syndrome, to severe perinatal lethal forms, such as atelosteogenesis I and III and Boomerang dysplasia. Spondylocarpotarsal synostosis syndrome is characterized by disproportionate short stature, vertebral anomalies and fusion of carpal and tarsal bones. Biallelic loss-of-function variants in FLNB are known to cause spondylocarpotarsal synostosis syndrome and 9 families and 9 pathogenic variants have been reported so far. We report clinical features of 10 additional patients from 7 families with spondylocarpotarsal synostosis syndrome due to 7 novel deleterious variants in FLNB, thus expanding the clinical and molecular repertoire of spondylocarpotarsal synostosis syndrome. Our report validates key clinical (fused thoracic vertebrae and carpal and tarsal coalition) and molecular (truncating variants in FLNB) characteristics of this condition.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Alelos , Filaminas/genética , Variação Genética , Vértebras Lombares/anormalidades , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/genética , Escoliose/congênito , Sinostose/diagnóstico , Sinostose/genética , Vértebras Torácicas/anormalidades , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Linhagem , Fenótipo , Radiografia , Escoliose/diagnóstico , Escoliose/genética , Síndrome
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 193: 344-348, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29268234

RESUMO

In the evolution of nanotechnology research for smart and precise sensor fabrication, here we report the implementation of simple logic gate operations performing by luminescent nanostructures in biomolecule environment based on photoluminescence (PL) technique. This present work deals with the luminescence property of α-Bi2O3 and Ag modified α-Bi2O3 nanostructures for d-glucose and Bovine serum albumin (BSA) sensing applications. These nanostructures are prepared by simple co-precipitation method and their morphology are examined using transmission electron microscope (TEM). We explore the PL characteristics of the prepared nanostructures and observe their change in PL intensity in the presence of d-glucose and BSA molecules. Enhancement in PL intensity is observed in the presence of d-glucose and BSA. Based on the PL response of prepared nanostructures in the biomolecule environment, we demonstrate biophotonic logic gates including YES, PASS 0, OR and INHIBIT gates.

13.
West Indian med. j ; 67(spe): 488-492, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-1045874

RESUMO

ABSTRACT Increasing life-expectancy globally and in the Caribbean region has led to an increased proportion of the population being categorized as elderly. The ageing population frequently require elective and emergency surgical procedures often with considerable morbidity and mortality. The amount of strain this paradigm can cause in any healthcare system is a huge challenge for the coming generations. In the Caribbean Islands, these challenges are compounded by several unique factors. This article reviews the impact of ageing upon surgery and associated specialties including anaesthesia and intensive care, with special reference to the Caribbean healthcare sector and attempts to provide some suggestions to mitigate such challenges in the near future.


RESUMEN El aumento de la expectativa de vida tanto a nivel mundial como en la región del Caribe ha llevado a una mayor proporción de la población en la categoría de ancianos. La población en proceso de envejecimiento frecuentemente requiere procedimientos quirúrgicos electivos y de emergencia, acompañados a menudo de considerable morbilidad y mortalidad. La tremenda tensión que este paradigma puede causar en cualquier sistema de salud representa un desafío enorme para las generaciones venideras. En las islas del Caribe, estos desafíos se agravan por varios factores únicos. Este artículo examina el impacto del envejecimiento en la cirugía y las especialidades asociadas incluyendo anestesia y cuidados intensivos, con especial referencia al sector de la salud del Caribe, a la par que persigue brindar algunas sugerencias para mitigar estos desafíos en un futuro cercano.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Expectativa de Vida , Idoso Fragilizado , Mortalidade Hospitalar , Fatores de Risco
14.
Br Dent J ; 222(9): 683-687, 2017 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-28496231

RESUMO

Aims To compare the profile of paediatric patients receiving dental treatment under general anaesthesia (GA) or conscious sedation (CS). A second aim was to explore whether there is an overlap between the two patient groups.Design This service evaluation study was based on sociodemographic and clinical data extracted from clinical records of patients attending dental appointments for GA or CS services at King's College Hospital. Sociodemographic and clinical differences between GA and CS groups were explored using logistic regression models.Results Data from 113 children (58 GA and 55 CS) were analysed. There were differences between groups in terms of age and numbers of quadrants and teeth treated, but not in terms of sex, ethnicity or deprivation scores. In the adjusted model, older children and those having more teeth treated were more likely to be in the GA than in the CS group. An overlap between the GA and CS groups was found, with 50% of children aged four to nine years having two to four teeth treated in both groups.Conclusion Age and number of teeth treated were the main characteristics associated with receiving care under GA or CS. Some overlap between children receiving dental treatment under GA or CS existed despite demographic and clinical differences between both groups.


Assuntos
Anestesia Dentária/estatística & dados numéricos , Anestesia Geral/estatística & dados numéricos , Sedação Consciente/estatística & dados numéricos , Assistência Odontológica para Crianças/estatística & dados numéricos , Adolescente , Fatores Etários , Anestesia Dentária/métodos , Anestesia Geral/métodos , Criança , Pré-Escolar , Sedação Consciente/métodos , Assistência Odontológica para Crianças/métodos , Cárie Dentária/cirurgia , Feminino , Humanos , Masculino , Fatores Sexuais , Extração Dentária/métodos
15.
Thorax ; 71(11): 1012-1019, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27259338

RESUMO

BACKGROUND: Extreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This study examined respiratory mechanics and ventilatory response during exercise in a large cohort of children born extremely preterm (EP). METHODS: This cohort study included children 8-12 years of age who were born EP (≤28 weeks gestation) between 1997 and 2004 and treated in a large regionalised neonatal intensive care unit in western Canada. EP children were divided into no/mild bronchopulmonary dysplasia (BPD) (ie, supplementary oxygen or ventilation ceased before 36 weeks gestational age; n=53) and moderate/severe BPD (ie, continued supplementary oxygen or ventilation at 36 weeks gestational age; n=50). Age-matched control children (n=65) were born at full term. All children attempted lung function and cardiopulmonary exercise testing measurements. RESULTS: Compared with control children, EP children had lower airway flows and diffusion capacity but preserved total lung capacity. Children with moderate/severe BPD had evidence of gas trapping relative to other groups. The mean difference in exercise capacity (as measured by oxygen uptake (VO2)% predicted) in children with moderate/severe BPD was -18±5% and -14±5.0% below children with no/mild BPD and control children, respectively. Children with moderate/severe BPD demonstrated a potentiated ventilatory response and greater prevalence of expiratory flow limitation during exercise compared with other groups. Resting lung function did not correlate with exercise capacity. CONCLUSIONS: Expiratory flow limitation and an exaggerated ventilatory response contribute to respiratory limitation to exercise in children born EP with moderate/severe BPD.


Assuntos
Displasia Broncopulmonar/fisiopatologia , Exercício Físico/fisiologia , Lactente Extremamente Prematuro/fisiologia , Mecânica Respiratória/fisiologia , Canadá , Criança , Teste de Esforço , Feminino , Humanos , Masculino , Testes de Função Respiratória
16.
Artigo em Inglês | MEDLINE | ID: mdl-27031446

RESUMO

We report preparation of pure and surfactant added α-Bi2O3 microrods through simple chemical method at moderate temperature. Cetyltrimethyl ammonium bromide (CTAB) is used as a surfactant. X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, UV-Vis absorption and photoluminescence (PL) measurements were carried out to understand the effect of surfactant (CTAB) on structural, phonon and optical properties of the prepared material. It is observed that the crystallite size, optical band gap and the structural defects (oxygen vacancies) decreases due to the effect of surfactant. Raman spectral studies exhibit various phonon modes of Bi2O3 and also decrease in the FWHM of the phonon modes is observed after the addition of CTAB.

17.
Am J Transplant ; 16(5): 1503-15, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26602886

RESUMO

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor-recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long-term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor-specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM- (n = 454) recipients. Median follow-up is 7.1 years. FCXM+ recipients were significantly different from FCXM- recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA >80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5-year actual graft survival rates are 87% and 84%, respectively. AR <1 year occurred in 13% FCXM+ and 12% FCXM- recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor-recipient compatibility.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas , Rejeição de Enxerto/diagnóstico , Alocação de Recursos para a Atenção à Saúde/métodos , Teste de Histocompatibilidade/métodos , Isoanticorpos/imunologia , Transplante de Rim , Obtenção de Tecidos e Órgãos , Linfócitos B/imunologia , Feminino , Citometria de Fluxo/métodos , Seguimentos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
18.
J Plant Res ; 128(6): 953-74, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26459328

RESUMO

Rice (Oryza sativa L.) as a model and crop plant with a sequenced genome offers an outstanding experimental system for discovering and functionally analyzing the major cell cycle control elements in a cereal species. In this study, we identified the core cell cycle genes in the rice genome through a hidden Markov model search and multiple alignments supported with the use of short protein sequence probes. In total we present 55 rice putative cell cycle genes with locus identity, chromosomal location, approximate chromosome position and EST accession number. These cell cycle genes include nine cyclin dependent-kinase (CDK) genes, 27 cyclin genes, one CKS gene, two RBR genes, nine E2F/DP/DEL genes, six KRP genes, and one WEE gene. We also provide characteristic protein sequence signatures encoded by CDK and cyclin gene variants. Promoter analysis by the FootPrinter program discovered several motifs in the regulatory region of the core cell cycle genes. As a first step towards functional characterization we performed transcript analysis by RT-PCR to determine gene specific variation in transcript levels along the rice leaves. The meristematic zone of the leaves where cells are actively dividing was identified based on kinematic analysis and flow cytometry. As expected, expression of the majority of cell cycle genes was exclusively associated with the meristematic region. However genes such as different D-type cyclins, DEL1, KRP1/3, and RBR2 were also expressed in leaf segments representing the transition zone in which cells start differentiation.


Assuntos
Proteínas de Ciclo Celular/genética , Regulação da Expressão Gênica de Plantas , Oryza/genética , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Ciclo Celular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Oryza/classificação , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Filogenia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Análise de Sequência de DNA
19.
Br J Cancer ; 113(1): 12-9, 2015 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-26086878

RESUMO

BACKGROUND: We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials. METHODS: Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice. RESULTS: A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15-17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8-10.0) and 18.7 months (95% CI: 17.5-19.5). Median PFS in subgroups of interest: aged ⩾65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ⩾2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand-foot syndrome (each 7%). CONCLUSION: Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Metástase Neoplásica , Pirróis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/patologia , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Pirróis/efeitos adversos , Sunitinibe , Adulto Jovem
20.
Am J Transplant ; 15(4): 1014-20, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25736704

RESUMO

Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.


Assuntos
Anticorpos Neutralizantes/imunologia , Vírus BK/genética , Genes Virais , Genótipo , Imunoglobulinas/imunologia , Linhagem Celular , Humanos
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