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1.
Tech Coloproctol ; 28(1): 66, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850445

RESUMO

BACKGROUND: We aimed to compare outcomes and cost effectiveness of extra-corporeal anastomosis (ECA) versus intra-corporeal anastomosis (ICA) for laparoscopic right hemicolectomy using the National Surgical Quality Improvement Programme data. METHODS: Patients who underwent elective laparoscopic right hemicolectomy for colon cancer from January 2018 to December 2022 were identified. Non-cancer diagnoses, emergency procedures or synchronous resection of other organs were excluded. Surgical characteristics, peri-operative outcomes, long-term survival and hospitalisation costs were compared. Incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness. RESULTS: A total of 223 patients (175 ECA, 48 ICA) were included in the analysis. Both cohorts exhibited comparable baseline patient, comorbidity, and tumour characteristics. Distribution of pathological TMN stage, tumour largest dimension, total lymph node harvest and resection margin lengths were statistically similar. ICA was associated with a longer median operative duration compared with ECA (255 min vs. 220 min, P < 0.001). There was a quicker time to gastrointestinal recovery, with a shorter median hospital stay in the ICA group (4.0 versus 5.0 days, P = 0.001). Overall complication rates were comparable. ICA was associated with a higher surgical procedure cost (£6301.57 versus £4998.52, P < 0.001), but lower costs for ward accommodation (£1679.05 versus £2420.15, P = 0.001) and treatment (£3774.55 versus £4895.14, P = 0.009), with a 4.5% reduced overall cost compared with ECA. The ICER of -£3323.58 showed ICA to be more cost effective than ECA, across a range of willingness-to-pay thresholds. CONCLUSION: ICA in laparoscopic right hemicolectomy is associated with quicker post-operative recovery and may be more cost effective compared with ECA, despite increased operative costs.


Assuntos
Anastomose Cirúrgica , Colectomia , Neoplasias do Colo , Laparoscopia , Duração da Cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anastomose Cirúrgica/economia , Anastomose Cirúrgica/métodos , Colectomia/economia , Colectomia/métodos , Neoplasias do Colo/cirurgia , Neoplasias do Colo/economia , Análise de Custo-Efetividade , Procedimentos Cirúrgicos Eletivos/economia , Procedimentos Cirúrgicos Eletivos/métodos , Custos Hospitalares/estatística & dados numéricos , Laparoscopia/economia , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/economia , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
2.
Sci Rep ; 14(1): 11033, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744912

RESUMO

The presented paper discusses the production of radioactive ion beams of francium, radium, and actinium from thick uranium carbide (UC x ) targets at ISOLDE, CERN. This study focuses on the release curves and extractable yields of francium, radium and actinium isotopes. The ion source temperature was varied in order to study the relative contributions of surface and laser ionization to the production of the actinium ion beams. The experimental results are presented in the form of release parameters. Representative extractable yields per µ C are presented for 222 - 231 Ac, several Ra and Fr isotopes in the mass ranges 214 ≤ A ≤ 233 and 205 ≤ A ≤ 231 respectively. The release efficiency for several isotopes of each of the studied elements was calculated by comparing their yields to the estimated in-target production rates modeled by CERN-FLUKA. The maximal extraction efficiency of actinium was calculated to be 2.1(6)% for a combination of surface ionization using a Ta ion source and resonant laser ionization using the two-step 438.58 nm, and 424.69 nm scheme.

3.
Scand J Gastroenterol ; 58(12): 1499-1504, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37464727

RESUMO

BACKGROUND: Drug-induced liver injury (DILI) remains a challenging diagnosis due to an absence of specific biomarkers. DILI due to volatile anaesthetics (VA-DILI) is characterised by trifluoroacetyl and CYP2E1 antibodies, but may not be seen for weeks after injury. Interleukin-4 (IL-4) may be involved in the production of these antibodies and may serve as a clinically useful early biomarker of VA-DILI. AIM: To prospectively compare serum IL-4 levels between patients who develop VA-DILI and controls following exposure to the volatile anaesthetic. METHODS: A nested case-control study of patients exposed to VA during surgery was conducted. Thirteen DILI cases were identified from the original cohort, and 26 controls were matched according to age, sex and VA agent. Serum samples were collected before and 48-96 h after VA exposure, and analysed for IL-4 using quantitative enzyme-linked immunosorbent assay techniques. RESULTS: There was a statistically significant difference in serum IL-4 in post-VA samples between DILI cases and controls (control: 0.030 pg/mL, IQR: 0.030 - 0.030 pg/mL vs DILI: 0.044 pg/mL, IQR: 0.030 - 0.061 pg/mL; p = 0.039). A greater proportion of DILI cases had post-VA IL-4 levels above the assay lower limit of detection compared to controls (control: 23% vs DILI: 69%; p = 0.013). CONCLUSION: IL-4 is a potential biomarker of DILI. Clinical diagnosis and understanding of DILI disease mechanisms may be improved by further investigation of novel biomarkers, and this IL-4 signal in serum is important as proof of concept for prospective study designs.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Interleucina-4 , Humanos , Estudos de Casos e Controles , Estudos Prospectivos , Biomarcadores , Anticorpos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Fígado
4.
Phys Rev Lett ; 131(2): 022502, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37505949

RESUMO

The excitation energy of the 1/2^{-} isomer in ^{99}In at N=50 is measured to be 671(37) keV and the mass uncertainty of the 9/2^{+} ground state is significantly reduced using the ISOLTRAP mass spectrometer at ISOLDE/CERN. The measurements exploit a major improvement in the resolution of the multireflection time-of-flight mass spectrometer. The results reveal an intriguing constancy of the 1/2^{-} isomer excitation energies in neutron-deficient indium that persists down to the N=50 shell closure, even when all neutrons are removed from the valence shell. This trend is used to test large-scale shell model, ab initio, and density functional theory calculations. The models have difficulties describing both the isomer excitation energies and ground-state electromagnetic moments along the indium chain.

5.
Eur Rev Med Pharmacol Sci ; 24(21): 11365-11373, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33215457

RESUMO

OBJECTIVE: This experimental study explored the potential of oral zinc sulfate to protect the gut mucosa from 5-fluorouracil (5-FU)-induced degenerative lesions in Wistar rats. MATERIALS AND METHODS: Female Wistar rats were used and divided into 2 interventional groups (Z with 6 animals and F with 5 animals) and one control group (M with 5 rats). After 2 hours of fasting, group Z received via oral gavage 1.5 ml of solution, corresponding to 15 mg zinc sulfate for 9 consecutive days. Groups F and M received only the vehicles. On day 3, 400 mg/kg of 5-FU was administered intraperitoneally to groups Z and F. Tissue samples were collected from the duodenum, jejunum, colon and liver. Histological assessment for each gastrointestinal tract segment was determined semi-quantitatively by rating 11 histological features from normal (0) to severe (3). The independent groups were analyzed using the Kruskal-Wallis test and the Mann-Whitney U-test, with a Bonferroni correction for alpha (p ≤ 0.016). RESULTS: In group F the jejunum was the most affected area with a mean histological score of  27 (25-32). In the Z group, significantly lower histological scores were obtained compared with group F (duodenum Z vs. F: U = 0, p = 0.004; jejunum Z vs. F: U = 0, p = 0.006 and colon: Z vs. F: U = 0, p = 0.005). Graded liver necro-inflammatory lesions were significantly lower in group Z compared with group F (U = 0, p = 0.004), suggesting fewer bacterial intestinal translocation processes. CONCLUSIONS: Zinc sulfate has a beneficial role, decreasing the severity of gut mucosal injuries induced by 5-FU in Wistar rats.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Mucosite/tratamento farmacológico , Sulfato de Zinco/farmacologia , Administração Oral , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Modelos Animais de Doenças , Feminino , Fluoruracila/administração & dosagem , Trato Gastrointestinal/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Mucosite/induzido quimicamente , Mucosite/patologia , Ratos , Ratos Wistar , Sulfato de Zinco/administração & dosagem
6.
Osteoarthritis Cartilage ; 28(12): 1559-1571, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32858189

RESUMO

OBJECTIVES: This study aimed to investigate the role of endothelin-1 (ET-1), originally known as the potent vasoconstrictor, and its receptors in chondrocyte senescence and osteoarthritis (OA) development. METHOD: Temporal changes of ET-1 and its receptors with OA development were characterized in a posttraumatic OA (PTOA) mouse model at time zero, 1-month and 4-month after surgical induction via destabilization of medial meniscus (DMM). A transgenic ET-1 overexpression (TET-1) mouse model was deployed to assess the impact of upregulated ET-1 on chondrocyte senescence and cartilage degradation. Effects of endothelin receptor blockade on chondrocyte senescence and OA development were further examined both in vitro and in vivo. RESULTS: Local expression of ET-1 in subchondral bone and synovium upregulated after DMM with an increase of plasma ET-1 level from 3.18 ± 0.21 pg/ml at time zero to 6.47 ± 0.34 pg/ml at 4-month post-surgery. Meanwhile, endothelin type B receptor (ETBR) (53.31 ± 2.42% to 83.8 ± 2.65%) and p16INK4a (10.91 ± 1.07% to 28.2 ± 1.0%) positve chondrocytes accumulated in articular cartilage since 1-month prior to cartilage loss at 4-month post-surgery. Overexpressed ET-1 promoted p16INK4a-positive senescent chondrocytes accumulation and cartilage degradation in TET-1 mice. Selective blockade of ETBR, but not ETAR, lowered the expression of p16INK4a in ET-1 or H2O2-induced chondrocyte senescence model, and mitigated the severity of murine PTOA. Intriguingly, reactive oxygen species (ROS) scavenger, Vitamin C, could rescue ET-1-induced chondrocyte senescence in vitro associated with restoration of mitochondrial dynamics. CONCLUSION: ET-1 could induce chondrocytes senescence and cartilage damages via ETBR in PTOA.


Assuntos
Cartilagem Articular/metabolismo , Senescência Celular/fisiologia , Condrócitos/fisiologia , Endotelina-1/metabolismo , Osteoartrite/fisiopatologia , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Senescência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Receptores de Endotelina/metabolismo , Regulação para Cima/fisiologia
7.
Genet Med ; 21(4): 1008-1014, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30166628

RESUMO

PURPOSE: Developmental and epileptic encephalopathies (DEEs) are severe clinical conditions characterized by stagnation or decline of cognitive and behavioral abilities preceded, accompanied or followed by seizures. Because DEEs are clinically and genetically heterogeneous, next-generation sequencing, especially exome sequencing (ES), is becoming a first-tier strategy to identify the molecular etiologies of these disorders. METHODS: We combined ES analysis and international data sharing. RESULTS: We identified 11 unrelated individuals with DEE and de novo heterozygous truncating variants in the interferon regulatory factor 2-binding protein-like gene (IRF2BPL). The 11 individuals allowed for delineation of a consistent neurodevelopmental disorder characterized by mostly normal initial psychomotor development followed by severe global neurological regression and epilepsy with nonspecific electroencephalogram (EEG) abnormalities and variable central nervous system (CNS) anomalies. IRF2BPL, also known as enhanced at puberty protein 1 (EAP1), encodes a transcriptional regulator containing a C-terminal RING-finger domain common to E3 ubiquitin ligases. This domain is required for its repressive and transactivating transcriptional properties. The variants identified are expected to encode a protein lacking the C-terminal RING-finger domain. CONCLUSIONS: These data support the causative role of truncating IRF2BPL variants in pediatric neurodegeneration and expand the spectrum of transcriptional regulators identified as molecular factors implicated in genetic developmental and epileptic encephalopathies.


Assuntos
Proteínas de Transporte/genética , Epilepsia/genética , Transtornos do Neurodesenvolvimento/genética , Proteínas Nucleares/genética , Convulsões/genética , Adolescente , Adulto , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/patologia , Criança , Eletroencefalografia , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Feminino , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/fisiopatologia , Fenótipo , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Sequenciamento do Exoma , Adulto Jovem
8.
Nanoscale ; 10(27): 13074-13082, 2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-29961799

RESUMO

The large-scale production and ecotoxicity of urea make its removal from wastewater a health and environmental challenge. Whereas the industrial removal of urea relies on hydrolysis at elevated temperatures and high pressure, nature solves the urea disposal problem with the enzyme urease under ambient conditions. We show that CeO2-x nanorods (NRs) act as the first and efficient green urease mimic that catalyzes the hydrolysis of urea under ambient conditions with an activity (kcat = 9.58 × 101 s-1) about one order of magnitude lower than that of the native jack bean urease. The surface properties of CeO2-x NRs were probed by varying the Ce4+/Ce3+ ratio through La doping. Although La substitution increased the number of surface defects, the reduced number of Ce4+ sites with higher Lewis acidity led to a slight decrease of their catalytic activity. CeO2-x NRs are stable against pH changes and even to the presence of transition metal ions like Cu2+, one of the strongest urease inhibitors. The low costs and environmental compatibility make CeO2-x NRs a green urease substitute that may be applied in polymer membranes for water processing or filters for the waste water reclamation. The biomimicry approach allows the application of CeO2-x NRs as functional enzyme mimics where the use of native or recombinant enzyme is hampered because of its costs or operational stability.


Assuntos
Cério/química , Nanotubos , Ureia/isolamento & purificação , Urease , Hidrólise , Água , Purificação da Água
11.
Br J Pharmacol ; 169(1): 143-55, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23351143

RESUMO

BACKGROUND AND PURPOSE: Adrenomedullin (AM) is a peptide hormone whose receptors are members of the class B GPCR family. They comprise a heteromer between the GPCR, the calcitonin receptor-like receptor and one of the receptor activity-modifying proteins 1-3. AM plays a significant role in angiogenesis and its antagonist fragment AM22-52 can inhibit blood vessel and tumour growth. The mechanism by which AM interacts with its receptors is unknown. EXPERIMENTAL APPROACH: We determined the AM22-52 binding epitope for the AM1 receptor extracellular domain using biophysical techniques, heteronuclear magnetic resonance spectroscopy and alanine scanning. KEY RESULTS: Chemical shift perturbation experiments located the main binding epitope for AM22-52 at the AM1 receptor to the C-terminal 8 amino acids. Isothermal titration calorimetry of AM22-52 alanine-substituted peptides indicated that Y52, G51 and I47 are essential for AM1 receptor binding and that K46 and P49 and R44 have a smaller role to play. Characterization of these peptides at the full-length AM receptors was assessed in Cos7 cells by cAMP assay. This confirmed the essential role of Y52, G51 and I47 in binding to the AM1 receptor, with their substitution resulting in ≥100-fold reduction in antagonist potency compared with AM22-52 . R44A, K46A, S48A and P49A AM22-52 decreased antagonist potency by approximately 10-fold. CONCLUSIONS AND IMPLICATIONS: This study localizes the main binding epitope of AM22-52 to its C-terminal amino acids and distinguishes essential residues involved in this binding. This will inform the development of improved AM receptor antagonists.


Assuntos
Adrenomedulina/metabolismo , AMP Cíclico/metabolismo , Epitopos/metabolismo , Fragmentos de Peptídeos/metabolismo , Receptores de Adrenomedulina/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Células COS , Calorimetria/métodos , Chlorocebus aethiops , Imageamento por Ressonância Magnética/métodos , Ligação Proteica
12.
Arch Orthop Trauma Surg ; 131(11): 1509-18, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21805361

RESUMO

AIM: Delayed fracture healing and non-unions of the femoral neck after lag screw osteosynthesis occur particularly in multiply injured young patients, and then surgical revision is often required. Currently no evidence-based treatment guidelines exist and therapeutic options include both hip arthroplasties and femoral head-maintaining operations. Here we report on young patients with delayed fracture healing of the femoral neck. Patients underwent revision surgery by autologous bone cylinder transplantation with mechanical re-stabilisation by cannulated lag screws. MATERIAL AND METHODS: We reviewed all patients after femoral neck screw osteosynthesis and identified eight patients at 7.3 [3-24] months after initial osteosynthesis with persisting, or reoccurring postoperative pain. Average patient age was 43 [35-57] years and patient Harris Hip Score (HHS) numbers were low (52 ± 19). Before revision surgery the preoperative CT scans showed a partial bone consolidation (anterior and/or posterior cortices) in the absence of a complete bone consolidation of all cortices. Seven patients were treated by bone cylinder transplantation from the patient's own iliac crest; one patient underwent an inverse bone cylinder procedure. Seven patients were additionally treated by re-insertion of 1-2 lag screws to increase mechanical stability. RESULTS: After revision surgery the average patient follow-up period was 42 [12-89] months. Five patients achieved favourable clinical and radiographic outcome with both complete bone union and return to work within 7.2 ± 2.75 months. One patient showed fracture healing but developed an aseptic femoral head osteonecrosis. Two patients failed to achieve complete bone consolidation. The postoperative HHS was 92 ± 4 in patients with favourable clinical outcome (n = 5) and 89 ± 2 after second revision surgery (2 hip arthroplasties; 1 valgus osteotomy). Both groups had significantly better HHS numbers compared with before surgical revision (p < 0.05). DISCUSSION: These data show that in this difficult-to-treat subset of young patients with delayed fracture healing of the femoral neck, autologous bone cylinder transplantation with mechanical re-stabilisation should be considered as a promising surgical revision strategy before hip arthroplasty.


Assuntos
Parafusos Ósseos , Transplante Ósseo/instrumentação , Fraturas do Colo Femoral/cirurgia , Consolidação da Fratura , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
13.
Bone Marrow Transplant ; 46(10): 1369-73, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21132024

RESUMO

Bronchiolitis obliterans syndrome (BOS) is a devastating pulmonary complication affecting long-term survivors of allogeneic hematopoietic cell transplantation. Treatment of BOS with prolonged courses of high dose corticosteroids is often associated with significant morbidity. Reducing the exposure to corticosteroids may reduce treatment-related morbidity. Our institution has recently begun to treat patients with emerging therapies in an effort to diminish corticosteroid exposure. We retrospectively reviewed the 6-month corticosteroid exposure, lung function and failure rates in eight patients with newly diagnosed BOS who were treated with a combination of fluticasone, azithromycin and montelukast (FAM) and a rapid corticosteroid taper. These patients were compared with 14 matched historical patients who received high-dose corticosteroids, followed by a standard taper. The median 6-month prednisone exposure in FAM-treated patients was 1819 mg (0-4036 mg) compared with 7163 mg (6551-7829 mg) in the control group (P=0.002). The median forced expiratory volume in 1 s (FEV(1)) change in FAM-treated patients was 2% (-3 to 4%] compared with 1% (-4 to 5%) in the control group (P=1.0). Prednisone exposure in FAM patients was one quarter that of a retrospective-matched group of patients, with minimal change in median FEV(1), suggesting that BOS may be spared of the morbidities associated with long-term corticosteroid use by using alternative agents with less side effects.


Assuntos
Acetatos/uso terapêutico , Corticosteroides/efeitos adversos , Androstadienos/uso terapêutico , Azitromicina/uso terapêutico , Bronquiolite Obliterante/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Quinolinas/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Bronquiolite Obliterante/etiologia , Ciclopropanos , Feminino , Fluticasona , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sulfetos , Transplante Homólogo , Adulto Jovem
14.
Cell Prolif ; 41(6): 843-858, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19040565

RESUMO

OBJECTIVES: Islet-like clusters (ILCs), differentiated from human embryonic stem cells (hESCs), were characterized both before and after transplantation under the kidney capsule of streptozotocin-induced diabetic immuno-incompetent mice. MATERIALS AND METHODS: Multiple independent ILC preparations (n = 8) were characterized by immunohistochemistry, flow cytometry and cell insulin content, with six preparations transplanted into diabetic mice (n = 42), compared to controls, which were transplanted with either a human fibroblast cell line or undifferentiated hESCs (n = 28). RESULTS: Prior to transplantation, ILCs were immunoreactive for the islet hormones insulin, C-peptide and glucagon, and for the ductal epithelial marker cytokeratin-19. ILCs also had cellular insulin contents similar to or higher than human foetal islets. Expression of islet and pancreas-specific cell markers was maintained for 70 days post-transplantation. The mean survival of recipients was increased by transplanted ILCs as compared to transplanted human fibroblast cells (P < 0.0001), or undifferentiated hESCs (P < 0.042). Graft function was confirmed by secretion of human C-peptide in response to an oral bolus of glucose. CONCLUSIONS: hESC-derived ILC grafts continued to contain cells that were positive for islet endocrine hormones and were shown to be functional by their ability to secrete human C-peptide. Further enrichment and maturation of ILCs could lead to generation of a sufficient source of insulin-producing cells for transplantation into patients with type 1 diabetes.


Assuntos
Células-Tronco Embrionárias/citologia , Células Endócrinas/citologia , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas/citologia , Animais , Diferenciação Celular , Linhagem Celular , DNA/metabolismo , Células-Tronco Embrionárias/ultraestrutura , Células Endócrinas/ultraestrutura , Citometria de Fluxo , Humanos , Insulina/metabolismo , Ilhotas Pancreáticas/ultraestrutura , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos NOD
15.
Clin Vaccine Immunol ; 14(6): 775-81, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17442847

RESUMO

In the context of a larger clinical study in Nouna, Burkina Faso, we evaluated a simplified dual-platform (DP) flow cytometric (FCM) method that allows the determination of major lymphocyte subsets in a single test tube. We compared the phenotyping of lymphocytes with DP FCM and simultaneous measurements with standard single-platform (SP) FCM for samples from 177 individuals. Analysis of the comparative measurements revealed that DP FCM systematically underestimates the proportion of NK cells, overestimates the percentage of CD3(+) CD8(+) lymphocytes, and yields proportions of B cells and CD4(+) T cells comparable with the results from SP FCM. Bland-Altman analysis showed a low bias between both methods and an acceptable precision for percent values of CD4(+) T cells (bias +/- precision, -1% +/- 6%) and CD8(+) T cells (-3% +/- 6%). The absolute cell numbers of all lymphocyte subpopulations, however, were systematically biased towards lower values being obtained by DP FCM. Reference values for the distribution of T-cell maturation phenotypes in 177 healthy adults were calculated using DP FCM. The mean +/- standard deviation (SD) CD4(+)-to-CD8(+) T-cell ratio was 1.61 +/- 0.61, the mean percentage +/- SD of CD4(+) T cells was 42% +/- 7%, and that of CD8(+) T cells 29% +/- 7%. Among CD4(+) lymphocytes, 28% +/- 7% were classified as central memory (CD45RA(low) CCR7(+)), 22% +/- 10% as naïve (CD45RA(high) CCR7(+)), 45% +/- 12% as effector memory (CD45RA(low) CCR7(-)); and 5% +/- 3% as terminally differentiated effector memory expressing CD45RA (CD45RA(high) CCR7(-)). Among CD8(bright) lymphocytes, 3% +/- 2% had a central memory phenotype, 27% +/- 13% were naïve, 37% +/- 13% had an effector memory phenotype, and 34% +/- 12% were terminally differentiated effector memory cells expressing CD45RA.


Assuntos
Linfócitos T CD4-Positivos/classificação , Linfócitos T CD8-Positivos/classificação , Citometria de Fluxo/instrumentação , Citometria de Fluxo/métodos , Linfócitos T/imunologia , Adolescente , Adulto , Anticorpos Monoclonais/metabolismo , Burkina Faso , Relação CD4-CD8 , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Imunofenotipagem , Antígenos Comuns de Leucócito/análise , Contagem de Linfócitos , Masculino , Valores de Referência , População Rural , Linfócitos T/classificação , Linfócitos T/citologia
16.
Leukemia ; 20(4): 715-23, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16453006

RESUMO

The processes mediating genomic instability and clonal evolution are obscure in multiple myeloma (MM). Acquisition of new chromosomal translocations into the switch region of the immunoglobulin heavy chain (IgH) gene (chromosome 14q32) in MM, often heralds transformation to more aggressive disease. Since the combined effects of CD40 plus interleukin-4 (IL-4) mediate IgH isotype class switch recombination (CSR), and this process involves DNA double strand break repair (DSBR), we hypothesized that CD40 and/or IL-4 activation of MM cells could induce abnormal DNA DSBR and lead to genomic instability and clonal evolution. In this study, we show that MM cell lines that are optimally triggered via CD40 and/or IL-4 demonstrate abnormal decoupling of IL-4 signal transduction from CD40. Specifically, CD40 alone was sufficient to trigger maximal growth of tumor cells. We further demonstrate that CD40 triggering induced both DNA DSBs as well as newly acquired karyotypic abnormalities in MM cell lines. Importantly, these observations were accompanied by induction of activation induced cytidine deaminase expression, but not gross apoptosis. These data support the role of abnormal CD40 signal transduction in mediating genomic instability, suggesting a role for the CD40 pathway and intermediates in myelomagenesis and clonal evolution in vivo.


Assuntos
Antígenos CD40/imunologia , Ligante de CD40/farmacologia , Instabilidade Genômica , Cadeias Pesadas de Imunoglobulinas/imunologia , Interleucina-4/imunologia , Mieloma Múltiplo/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Aberrações Cromossômicas , Citidina Desaminase/biossíntese , Citidina Desaminase/efeitos dos fármacos , DNA/biossíntese , DNA/efeitos dos fármacos , Humanos , Cadeias Pesadas de Imunoglobulinas/efeitos dos fármacos , Cadeias Pesadas de Imunoglobulinas/genética , Interleucina-4/farmacologia , Mieloma Múltiplo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Regulação para Cima
17.
Disabil Rehabil ; 22(1-2): 43-56, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10661757

RESUMO

A community survey of 271 Chinese migrants aged 15 years and older living in Auckland was conducted to assess self-rated adjustment and health. The majority of respondents came from Hong Kong and Taiwan. Despite significant changes in their lives, including the absence of family members, unemployment and underemployment, most did not report major adjustment problems or regret having come to New Zealand. Few considered their health to be poor. Forty-two per cent reported having consulted a doctor within the past 12 weeks. Factors significantly associated with having experienced major problems included being aged 26-35 years, rejection from locals and having low English proficiency. Factors associated with poor adjustment included expectations not having been met, regretting coming, low proficiency in English, recent arrival in New Zealand, unemployment, younger age and lower levels of education. Self-rated fair or poor health was found to be associated with Chinese-only reading knowledge, residency of more than 5 years and regretting having come to New Zealand.


Assuntos
Aculturação , Emigração e Imigração , Nível de Saúde , Saúde Mental , Adaptação Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/etnologia , Feminino , Serviços de Saúde/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nova Zelândia/epidemiologia , Razão de Chances , Fatores Socioeconômicos
18.
Nat Genet ; 23(2): 203-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10508518

RESUMO

Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.


Assuntos
Arabidopsis/genética , Marcadores Genéticos/genética , Genoma de Planta , Ascomicetos/crescimento & desenvolvimento , Mapeamento Cromossômico , DNA de Plantas/genética , Genes de Plantas/genética , Predisposição Genética para Doença , Genótipo , Análise de Sequência com Séries de Oligonucleotídeos , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Polimorfismo Genético
19.
J Formos Med Assoc ; 98(3): 190-4, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10365538

RESUMO

The objective of this study was to evaluate the incidence of and risk factors for femoral fracture in patients who underwent cementless hip arthroplasty during a 3-year period. Several predisposing factors have been reported; we tried to find another predictive indicator that could be recognized preoperatively. The records of all patients who underwent cementless hip arthroplasty from December 1993 to December 1996 were reviewed. The characteristics and clinical features (including age, gender, diagnosis, geometry of the proximal femur, and quality of bone) of the patients who had fractures were compared with those of patients who did not have fractures. During the 3-year study, 425 patients underwent a total of 454 cementless hip arthroplasties. There were 16 postoperative fractures (3.5%, 16 patients). Patients who suffered femoral fracture were significantly older than patients without fracture (65.6 +/- 10.9 yr vs 52.6 +/- 16.2 yr, p < 0.001). The fracture group had poorer preoperative bone quality compared with the nonfracture group (3.3 +/- 0.6 vs 3.8 +/- 0.7, Singh's Index of Osteoporosis, p < 0.01). The canal flare index of the proximal femur was significantly lower in the fracture group than in the nonfracture group (3.3 +/- 0.40 vs 3.8 +/- 0.7, p < 0.01). Our results indicate that old age and osteoporosis affect the likelihood of periprosthetic femoral fractures, and that a low flare index is a predictive indicator of femoral fracture. These factors should be taken into account during preoperative planning, and cemented arthroplasty should be considered for patients with these risk factors.


Assuntos
Artroplastia de Quadril , Fraturas do Fêmur/epidemiologia , Falha de Prótese , Idoso , Análise de Variância , Artroplastia de Quadril/métodos , Feminino , Fraturas do Fêmur/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
20.
Aust N Z J Psychiatry ; 33(1): 13-21, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10197881

RESUMO

OBJECTIVE: The purpose of this study was to identify and assess the relative importance of predictors of the self-rated adjustment and psychiatric morbidity of recent Chinese migrants. METHOD: Chinese migrants (n = 271) living in Auckland and aged 15 years or older completed a postal questionnaire that included the Chinese Health Questionnaire (CHQ). The majority of respondents came from Hong Kong and Taiwan. RESULTS: Most respondents did not report major adjustment problems. The psychiatric morbidity rate was 19%. Major predictors of experiencing problems included rejection by locals, being aged 26-35 years or over 45 years and low English proficiency. Major predictors of poor adjustment included unemployment, low English proficiency, lack of university education, younger age, shorter residency, expectations not met and regrets about coming to New Zealand. Predictors of minor mental disorder included regretting coming, female gender and younger age. For migrants resident 2 years or less, unemployment and underemployment were additional risk factors. Mothers with absent husbands and young people with absent parents also had elevated rates of mental disorder. CONCLUSIONS: Although the overall prevalence of mental disorder for this sample of recent migrants appears to be similar to that of the general population, significant risk factors were identified. The findings extend knowledge of the adjustment and the mental health of migrants and provide potential focal points for primary and secondary prevention interventions.


Assuntos
Transtornos Mentais/etnologia , Ajustamento Social , Migrantes/psicologia , Adolescente , Adulto , Fatores Etários , Atitude , Feminino , Hong Kong/etnologia , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Fatores Sexuais , Inquéritos e Questionários
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