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1.
Osteoarthritis Cartilage ; 21(6): 823-30, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23541875

RESUMO

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. DESIGN: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. RESULTS: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. CONCLUSION: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.


Assuntos
Arginina/análogos & derivados , Progressão da Doença , Lisina/análogos & derivados , Osteoartrite do Quadril/metabolismo , Osteoartrite do Joelho/metabolismo , Pele/química , Idoso , Arginina/análise , Cromatografia Líquida de Alta Pressão , Colágeno Tipo II/urina , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Lisina/análise , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Osteófito/metabolismo , Radiografia
2.
Osteoarthritis Cartilage ; 18(10): 1329-36, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20673850

RESUMO

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the aetiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced-glycation-endproducts (AGEs). Since, cartilage tissue is not readily available from patients for studying AGE levels, alternative approaches such as analyzing skin and urine are needed to study the role of cartilage AGE levels in OA. METHODS: Paired human skin and cartilage samples were obtained post mortem. Paired skin and urine samples were obtained from the CHECK cohort (early OA patients). Pentosidine levels were measured by high-performance liquid chromatography (HPLC). As marker of cumulative cartilage damage X-rays of both knees and hips were scored. Urinary CTXII (uCTXII) levels were measured, to assess current cartilage breakdown. RESULTS: Cartilage and skin pentosidine correlate well (R=0.473, P=0.05). Skin pentosidine was higher in mild (summed (Kellgren & Lawrence K&L) over four large joints ≥4) compared to no (summed K&L≤3) radiographic OA (P=0.007). Urinary pentosidine was not different between these two groups. Skin pentosidine levels were not related to cartilage breakdown (highest vs lowest tertile of uCTXII). Urinary pentosidine, however, was higher in the highest compared to the lowest uCTXII tertile (P=0.009). Multiple regression analysis showed age to be the only predictor of the summed K&L score and age, creatinine clearance and urinary pentosidine as predictors of uCTXII. CONCLUSION: The higher skin and urinary pentosidine levels in those with mild compared to no radiographic joint damage and low vs high cartilage breakdown respectively suggest that AGEs may contribute to disease susceptibility and/or progression. However, relations are weak and cannot be used as surrogate markers of severity of OA.


Assuntos
Arginina/análogos & derivados , Lisina/análogos & derivados , Osteoartrite do Quadril/metabolismo , Osteoartrite do Joelho/metabolismo , Pele/química , Adulto , Idoso , Arginina/análise , Arginina/urina , Biomarcadores/análise , Biomarcadores/urina , Cartilagem Articular/química , Estudos de Coortes , Colágeno Tipo II/urina , Feminino , Humanos , Lisina/análise , Lisina/urina , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/urina , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/urina , Radiografia , Índice de Gravidade de Doença
3.
Int Arch Occup Environ Health ; 83(8): 913-21, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20490537

RESUMO

OBJECTIVE: The prevalence of osteoarthritis (OA) increases, but the impact of the disorder on peoples' functional capacity is not known. Therefore, the objective of this study was to compare self-reported health status and functional capacity of subjects with early OA of hip and/or knee to reference data of healthy working subjects and to assess whether this capacity is sufficient to meet physical job demands. METHODS: Self-reported health status and functional capacity of 93 subjects from the Cohort Hip and Cohort Knee (CHECK) were measured using the Short-Form 36 Health Survey and 6 tests of the Work Well Systems Functional Capacity Evaluation. Results were compared with reference data from 275 healthy workers, using t-tests. To compare the functional capacity with job demands, the proportions of subjects with OA performing lower than the p(5) of reference data were calculated. RESULTS: Compared to healthy workers, the subjects (mean age 56) from CHECK at baseline reported a significantly worse physical health status, whereas the women (n = 78) also reported a worse mental health status. On the FCE female OA subjects performed significantly lower than their healthy working counterparts on all 6 tests. Male OA subjects performed lower than male workers on 3 tests. A substantial proportion of women demonstrated functional capacities that could be considered insufficient to perform jobs with low physical demands. CONCLUSIONS: Functional capacity and self-reported health of subjects with early OA of the hips and knees were worse compared to healthy ageing workers. A substantial proportion of female subjects did not meet physical job demands.


Assuntos
Nível de Saúde , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Trabalho/fisiologia , Idoso , Envelhecimento , Estudos de Coortes , Avaliação da Deficiência , Feminino , Humanos , Remoção , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/psicologia , Osteoartrite do Joelho/psicologia , Perfil de Impacto da Doença , Trabalho/psicologia , Avaliação da Capacidade de Trabalho
4.
Arthritis Care Res (Hoboken) ; 62(5): 683-9, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20191474

RESUMO

OBJECTIVE: To examine the work participation of Dutch people with early osteoarthritis (OA) in hips or knees and compare this with data from the American Osteoarthritis Initiative (OAI) cohort. The influence of health status and personal factors on work participation was analyzed. METHODS: In the Cohort Hip and Cohort Knee (CHECK) study, 1,002 subjects were included. Baseline questionnaire data from 970 subjects were analyzed. Rate ratios were calculated to compare work participation with the general Dutch population, after correcting (by stratifying) for age, sex, and education. Health status was measured using the Short Form 36 health survey and the Western Ontario and McMaster Universities Osteoarthritis Index. Groups were compared (CHECK versus OAI, workers versus nonworkers) using t-tests. RESULTS: The mean age of the subjects was 56 years and 79% were women. Overall participation was 51%, similar to the general Dutch population and lower than in the OAI (76%). Point prevalence of sick leave because of hip/knee symptoms was 2%, and year prevalence was 12%. Of the subjects, 14% had made work adaptations. Workers reported significantly better health status (corrected for age, sex, and education) than nonworkers. CONCLUSION: Work participation of Dutch people with early OA is similar to the general population and significantly lower than American subjects. Increasing age, female sex, and lower education level were related to lower participation. Societal factors appear to have had more effect on work participation than health status in this stage of OA. The better health status of workers could not be explained solely by selection bias, but may be a result of work.


Assuntos
Atividades Cotidianas/psicologia , Efeitos Psicossociais da Doença , Osteoartrite do Quadril/psicologia , Osteoartrite do Joelho/psicologia , Trabalho/psicologia , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Países Baixos , Osteoartrite do Quadril/patologia , Osteoartrite do Joelho/patologia , Estudos Prospectivos , Índice de Gravidade de Doença , Estados Unidos
5.
Osteoarthritis Cartilage ; 18(5): 605-12, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20175979

RESUMO

CONTEXT: Molecules that are released into biological fluids during matrix metabolism of articular cartilage, subchondral bone, and synovial tissue could serve as biochemical markers of the process of osteoarthritis (OA). Unfortunately, actual breakthroughs in the biochemical OA marker field are limited so far. OBJECTIVE: By reviewing the status of commercially available biochemical OA markers according to the "Burden of disease, Investigative, Prognostic, Efficacy of intervention, and Diagnostic" ("BIPED") classification, future use of this "BIPED" classification is encouraged and more efficient biochemical OA marker research stimulated. DATA SOURCES: Three electronic databases [PubMed, Scopus, EMBASE (1997-May 2009)] were searched for publications on blood and urinary biochemical markers in human primary knee and hip-OA. STUDY SELECTION: Stepwise selection of original English publications describing human studies on blood or urinary biochemical markers in primary knee or hip-OA was performed. Selected articles were fully read to determine whether biochemical markers were investigated on performance within any of the "BIPED" categories. Eighty-four relevant publications were identified. DATA EXTRACTION: Data from relevant publications were tabulated according to the "BIPED" classification. Individual analyses within a publication were summarized in general "BIPED" scores. DATA SYNTHESIS: An uneven distribution of scores on biochemical marker performance and heterogeneity among the publications complicated direct comparison of individual biochemical markers. Comparison of categories of biochemical markers was therefore performed instead. In general, biochemical markers of cartilage degradation were investigated most extensively and performed well in comparison with other categories of biochemical markers. Biochemical markers of bone metabolism performed less adequately. Biochemical markers of synovial tissue metabolism were not investigated extensively, but performed quite well. CONCLUSIONS: Specific biochemical markers and categories of biochemical markers as well as their nature, origin and metabolism, need further investigation. International standardization of future investigations should be pursued to obtain more high-quality, homogenous data on the full spectrum of biochemical OA markers.


Assuntos
Osteoartrite do Quadril/diagnóstico , Osteoartrite do Joelho/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Osso e Ossos/metabolismo , Cartilagem Articular/metabolismo , Efeitos Psicossociais da Doença , Humanos , Prognóstico , Membrana Sinovial/metabolismo
6.
Ann Rheum Dis ; 68(9): 1413-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18772189

RESUMO

OBJECTIVE: To describe the osteoarthritis study population of CHECK (Cohort Hip and Cohort Knee) in comparison with relevant selections of the study population of the Osteoarthritis Initiative (OAI) based on clinical status and radiographic parameters. METHODS: In The Netherlands a prospective 10-year follow-up study was initiated by the Dutch Arthritis Association on participants with early osteoarthritis-related complaints of hip and/or knee: CHECK. In parallel in the USA an observational 4-year follow-up study, the OAI, was started by the National Institutes of Health, on patients with or at risk of symptomatic knee osteoarthritis. For comparison with CHECK, the entire cohort and a subgroup of individuals excluding those with exclusively hip pain were compared with relevant subpopulations of the OAI. RESULTS: At baseline, CHECK included 1002 participants with in general similar characteristics as described for the OAI. However, significantly fewer individuals in CHECK had radiographic knee osteoarthritis at baseline when compared with the OAI (p<0.001). In contrast, at baseline, the CHECK cohort reported higher scores on pain, stiffness and functional disability (Western Ontario and McMaster osteoarthritis index) when compared with the OAI (all p<0.001). These differences were supported by physical health status in contrast to mental health (Short Form 36/12) was at baseline significantly worse for the CHECK participants (p<0.001). CONCLUSION: Although both cohorts focus on the early phase of osteoarthritis, they differ significantly with respect to structural (radiographic) and clinical (health status) characteristics, CHECK expectedly representing participants in an even earlier phase of disease.


Assuntos
Osteoartrite do Quadril/diagnóstico , Osteoartrite do Joelho/diagnóstico , Idoso , Avaliação da Deficiência , Progressão da Doença , Métodos Epidemiológicos , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/complicações , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Dor/etiologia , Prognóstico , Amplitude de Movimento Articular
7.
Rheumatology (Oxford) ; 46(11): 1712-7, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17956917

RESUMO

OBJECTIVE: To examine the efficacy of short-term intensive exercise training (IET) directly following hospital discharge. METHODS: In the Disabled Arthritis Patients Post-hospitalization Intensive Exercise Rehabilitation (DAPPER) study, patients with rheumatoid arthritis or osteoarthritis were eligible when they needed hospitalization for either a flare-up in disease, elective hip or knee arthroplasty. The intervention group received IET for 3 weeks immediately after discharge; the control group was treated with the usual care (UC). The intensive exercise was provided in a resort. Outcomes were assessed at baseline, after 3, 13, 26 and 52 weeks. Range of motion was measured using the Escola Paulista de Medicina-Range of Motion scale (EPM-ROM), disability was measured using the HAQ and the McMaster Toronto Arthritis Patient Preference Disability Questionnaire (MACTAR), and for health-related quality of life (HRQoL), the Research and Development 36-Item Health Survey (RAND-36) was used. RESULTS: The IET showed a better and faster improvement than UC on all outcome measures except for HRQoL. Up to 52 weeks after baseline, the EPM-ROM and the MACTAR remained favourable in IET compared with UC. At 3 weeks, the MACTAR improved significantly more in the IET compared with the UC: mean difference -5.5 (95% CI -8.4 to -2.2). At 26 weeks, the mean difference remained significant (-5.2; 95% CI -10.0 to -0.34). At 52 weeks, the effect was not significant; however, the mean difference in improvement between the groups can be considered clinically relevant. At 3 weeks, the IET had improved significantly more on the HAQ walking and rising subscales. CONCLUSION: Intensive short-term exercise training of arthritis patients, immediately after hospital discharge results in improved regain of function. The DAPPER programme has a direct effect, which lasts up to 52 weeks.


Assuntos
Artrite/reabilitação , Terapia por Exercício/métodos , Idoso , Idoso de 80 Anos ou mais , Artrite/fisiopatologia , Artrite/cirurgia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/reabilitação , Artroplastia de Quadril/reabilitação , Artroplastia do Joelho/reabilitação , Avaliação da Deficiência , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Quadril/reabilitação , Osteoartrite do Quadril/cirurgia , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/reabilitação , Osteoartrite do Joelho/cirurgia , Alta do Paciente , Qualidade de Vida , Amplitude de Movimento Articular , Resultado do Tratamento
8.
Ned Tijdschr Geneeskd ; 151(21): 1178-85, 2007 May 26.
Artigo em Holandês | MEDLINE | ID: mdl-17557758

RESUMO

OBJECTIVE: To compare the effects of alendronate and alfacalcidol in the prevention ofglucocorticoid-related osteoporosis in patients with a rheumatic disease. DESIGN: Randomised, double-blind, double-placebo clinical trial (www. clinicaltrials.gov; number: NCT00138983). METHODS: A total of 201 patients with rheumatic disease who were starting glucocorticoid treatment at a daily dose that was equivalent to at least 7.5 mg of prednisone were randomised to alendronate (10 mg) and a placebo capsule ofalfacalcidol daily (n = 100) or alfacalcidol (1 microg) and a placebo tablet ofalendronate daily (n = 101) for 18 months. Primary outcome was change in lumbar spine bone mineral density at 18 months. The main secondary outcome was the incidence of morphometrically confirmed vertebral deformities. RESULTS: Overall, 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1% (95% CI: 1.1-3.1) in the alendronate group and decreased by 1.9% (95% CI: -3.I--0.7) in the alfacalcidol group. At 18 months the mean difference in change in bone mineral density between the two groups was 4.0% (95% CI: 2.4-5-5). Three patients in the alendronate group had a new vertebral deformity, compared with 8 patients in the alfacalcidol group, including 5 symptomatic vertebral fractures in 3 patients; the hazard ratio was 0.4 (95% CI: 0.1-1.4). CONCLUSION: Alendronate was more effective than alfacalcidol in preventing glucocorticoid-induced bone loss during this 18-month trial in patients with rheumatic diseases who were starting glucocorticoid treatment.

9.
Leukemia ; 20(7): 1217-20, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16642044

RESUMO

In acute myeloid leukemia (AML), activating mutations in the fms-like tyrosine kinase 3 (FLT3) gene predict poor prognosis. We determined FLT3 internal tandem duplications (FLT3/ITD) and D835 point mutations in paired initial and relapse samples from 80 pediatric and adult AML patients. One D835 point mutation was found in an initial pediatric AML sample. Fms-like tyrosine kinase 3/ITDs were present in 21 initial and 22 relapse samples (26.3 and 27.5%, respectively). Interestingly, FLT3/ITD positivity was related to a significantly shorter time to relapse, most pronounced when the ITD-positive status was found at relapse (P<0.001). However, FLT3/ITD status changed between diagnosis and relapse in 14 cases. In four patients, the FLT3/ITD became undetectable at relapse in five patients FLT3/ITDs were only detected at relapse, and in five patients the length or number of FLT3/ITDs changed. Gain of FLT3/ITDs may suggest oligoclonality with selective outgrowth of the FLT3/ITD-positive clone, whereas losses may reflect ITDs in the more mature leukemic cells rather than in the leukemic stem cell, or, alternatively, that other genetic aberrations provided a greater selective advantage. Studying FLT3/ITD kinetics in minimal residual disease setting may provide some answers for the changes we observed. Fms-like tyrosine kinase 3/ITD is a relevant marker for prognosis, and remains an important target for therapeutic inhibition.


Assuntos
Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Mutação Puntual , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Feminino , Marcadores Genéticos , Predisposição Genética para Doença/epidemiologia , Humanos , Leucemia Eritroblástica Aguda/genética , Leucemia Megacarioblástica Aguda/genética , Leucemia Monocítica Aguda/genética , Leucemia Mielomonocítica Aguda/genética , Leucemia Promielocítica Aguda/genética , Masculino , Neoplasia Residual/epidemiologia , Neoplasia Residual/genética , Prognóstico , Recidiva , Fatores de Risco , Sequências de Repetição em Tandem
12.
Leukemia ; 17(1): 175-84, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12529676

RESUMO

Recognition events between hematopoietic progenitor cells (HPC) and bone marrow endothelial cells (BMEC) initiate homing of HPC to the bone marrow. The chemokine SDF-1 is present on BMEC and plays a crucial role in bone marrow engraftment. We studied the role of proteoglycans (PGs) on BMEC in binding and presentation of SDF-1. SDF-1 mRNA was present in three human BMEC cell lines. Competition experiments showed that 125I-SDF-1 alpha binding to the BMEC cell line 4LHBMEC was inhibited by heparins, heparan sulfate (HS) intestinal mucosa, chondroitin and dermatan sulfate (CS/DS), but not by HS bovine kidney. Pretreatment of 4LHBMEC with glycosaminoglycan (GAG)-degrading enzymes or sodium chlorate demonstrated that SDF-1 bound to both HSPGs and CS/DSPGs in a sulfation-dependent manner, as determined with an SDF-1 antibody recognizing the CXCR4-binding site. 4LHBMEC bound four-fold more SDF-1 than HUVEC. Isolated endothelial PGs did not bind SDF-1 in a filter or microplate-binding assay, suggesting the necessity of membrane association. In flow adhesion experiments, endothelial arrest of CXCR4+ KG-1 and not of CXCR4- KG-1a cells increased significantly when SDF-1 was presented on 4LHBMEC. In conclusion, SDF-1 is produced by BMEC and binds to the BMEC cell surface via HS and CS/DS-GAGs, thereby presenting its CXCR4 binding site to HPC contributing to their arrest.


Assuntos
Células da Medula Óssea/metabolismo , Quimiocinas CXC/metabolismo , Endotélio Vascular/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Proteoglicanas de Heparan Sulfato/fisiologia , Animais , Bovinos , Quimiocina CXCL12 , Quimiocinas CXC/genética , Cloratos/farmacologia , Sulfatos de Condroitina/farmacologia , Primers do DNA/química , Dermatan Sulfato/farmacologia , Citometria de Fluxo , Proteoglicanas de Heparan Sulfato/farmacologia , Heparitina Sulfato/farmacologia , Humanos , Reação em Cadeia da Polimerase , Ligação Proteica , Células Estromais/metabolismo
13.
Ann Neurol ; 50(4): 468-75, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11601499

RESUMO

The human apolipoprotein E4 (ApoE4) isoform is associated with genetic risk for Alzheimer's disease. To assess the effects of different ApoE isoforms on amyloid plaque formation, human ApoE3 and ApoE4 were expressed in the brains of transgenic mice under the control of the human transferrin promoter. Mice were crossed with transgenic mice expressing human amyloid precursor protein containing the Swedish mutation (APPsw), which facilitates amyloid beta peptide (A beta) production. The following progeny were selected for characterization: APPsw+/- x ApoE3+/- and APPsw+/-, APPsw+/- x ApoE4+/- and APPsw+/- littermates. All mice analyzed were wild type for the endogenous mouse APP and ApoE genes. Mice expressing ApoE4 in combination with APPsw have accelerated A beta deposition in the brain as assessed by enzyme immunoassay for A beta40 and A beta42 extractable in 70% formic acid, by assessment of amyloid plaque formation using thioflavin-S staining, and by immunohistochemical staining with antibodies specific for A beta40 or A beta42 and the 4G8 monoclonal or 162 polyclonal antibody. No difference in the rate of A beta deposition in the brain was seen in mice expressing ApoE3 in combination with APPsw. Thus, our data are consistent with the observation in Alzheimer's disease that ApoE4 is associated with increased accumulation of A beta in the brain relative to ApoE3.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Apolipoproteínas E/genética , Química Encefálica/genética , Fragmentos de Peptídeos/metabolismo , Fatores Etários , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/imunologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Anticorpos Monoclonais , Apolipoproteína E4 , Encéfalo/metabolismo , Encéfalo/patologia , Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/imunologia , Placa Amiloide/química , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Receptores Imunológicos/metabolismo
14.
Bone Marrow Transplant ; 28(2): 145-55, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11509932

RESUMO

Autologous stem cell transplantation using unprocessed, G-CSF-mobilized whole blood (WB) is a simple, cost-reducing procedure and supports high-dose chemotherapy regimens not exceeding 72 h. Thereafter, clonogenic capacity rapidly decreases if routine anticoagulants are used for storage. In order to increase clinical applicability, we investigated the requirements for optimal preservation of unprocessed WB for 7 days. During storage at 22 degrees C in CPDA-1, a decrease in pH was noted, which was at least partially responsible for the low recovery of clonogenic cells. Subsequently, WB cells were stored in various cell culture media (RPMI 1640, alpha-MEM, X-VIVO15, CellGro SCGM and Leibovitz's L15 medium) containing either serum, serum-free substitutes or no additives. Leibovitz's L15 showed significantly better CFU-GM recoveries than the other media. Using a calcium-free modification of L15 medium (added 3:10 to WB), 94 +/- 24% of CD34(+) cells, 41 +/- 14% of BFU-E, 56 +/- 17% CFU-GM and 90 +/- 14% of LTC-IC were preserved during storage for 7 days at 22 degrees C. Storage at 4 degrees C was also feasible, but showed less optimal recoveries of 52 +/- 29% (CD34), 32 +/- 10% (BFU-E), 13 +/- 7% (CFU-GM) and 58 +/- 9% (LTC-IC). The expression of CD38, Thy-1, c-kit, AC133, L-selectin and CXCR4 on CD34-positive cells remained unchanged. In conclusion, a modified Leibovitz's L15 medium better meets the metabolic requirements of a high-density cell culture and allows safe storage of G-CSF mobilized WB for at least 7 days. The results encourage further exploration of WB transplants stored for 7 days for clinical use.


Assuntos
Preservação de Sangue/métodos , Meios de Cultura Livres de Soro , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Neoplasias/terapia , Proteínas Recombinantes/uso terapêutico , Adenina , Antígenos CD/sangue , Antígenos CD34/sangue , Neoplasias da Mama/terapia , Técnicas de Cultura de Células/métodos , Citratos , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura , Feminino , Filgrastim , Glucose , Humanos , Lenograstim , Linfoma não Hodgkin/terapia , Compostos Orgânicos , Fosfatos , Transplante Autólogo
15.
Scand J Rheumatol ; 30(1): 25-30, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11252688

RESUMO

This article describes the effects of sulfasalazine (SSZ) treatment on serum immunoglobulin (Ig) levels in 6 children with oligoarticular- or polyarticular onset juvenile chronic arthritis (JCA). None of the children who developed dysimmunoglobulinemia during treatment showed clinical symptoms of this adverse event, in particular none developed severe infections. All patients regained normal immunoglobulin levels after discontinuing SSZ treatment. One patient with a partial IgA deficiency at the start of SSZ treatment showed a slow increase in the IgA level during treatment. During follow-up (4-6 years), one patient spontaneously developed a dysimmunoglobulinemia and one patient developed diabetes mellitus. Based on these case reports and review of the literature we advocate monitoring of serum immunoglobulin levels while on SSZ treatment.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Imunoglobulinas/sangue , Sulfassalazina/uso terapêutico , Artrite Juvenil/sangue , Criança , Pré-Escolar , Ensaios Clínicos Controlados como Assunto , Disgamaglobulinemia/induzido quimicamente , Feminino , Humanos , Lactente
16.
J Hematother Stem Cell Res ; 10(6): 795-806, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11798506

RESUMO

The colony-forming unit (CFU) assay is exposed to a lot of variation, part of which is introduced by several enrichment strategies that are routinely performed before assessment of clonogenic capacity in mobilized peripheral blood (PB), bone marrow (BM), or cord blood (CB). We investigated the possibility to perform a single-step CFU assay by direct plating of PB, BM, or CB into CFU culture medium to obtain more reproducible results than after a standard Ficoll or lysis procedure. Direct plating implies the presence of red blood cells (RBC), white blood cells (WBC), and plasma in the CFU assay, which could possibly influence the outcome of the assay. Of all components, only the RBC was found to negatively influence CFU-GM growth if a concentration of > 0.02 x 10(9)/ml was present in the CFU culture medium. Subsequently, depending on the RBC concentration PB, BM, and CB samples were prediluted in triplicate or quadruplicate and plated into CFU medium. Lysis and/or Ficoll procedures were also performed in triplicate or quadruplicate on the same samples, and the mean colony number and coefficient of variation (CV) of the three techniques were compared. Significantly smaller CV values were found using the direct plating technique (all assays, mean 7.5%, range 1.6-15.6%) than after Ficoll separation (mean 18.0%, range 2.2-62.5%). Intermediate results were obtained with the lysis method (mean CV 11.6%, range 3.3-29%). In most samples, and especially in those with a very low number of clonogenic cells per milliliter, more colonies were detected with the direct plating method than with either the lysis or Ficoll method. In conclusion, the single-step direct plating method significantly enhances reproducibility of the CFU assay for PB, BM, and CB samples in comparison with standard techniques by circumvention of loss of colony formation and by decreasing variability. Furthermore, the direct plating technique is a timesaving assay.


Assuntos
Ensaio de Unidades Formadoras de Colônias/métodos , Células Progenitoras Mieloides/citologia , Células Sanguíneas/citologia , Células da Medula Óssea/citologia , Contagem de Células , Técnicas de Cultura de Células , Separação Celular/métodos , Ensaio de Unidades Formadoras de Colônias/normas , Sangue Fetal/citologia , Mobilização de Células-Tronco Hematopoéticas , Humanos , Reprodutibilidade dos Testes
17.
Semin Arthritis Rheum ; 30(1): 52-69, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10966213

RESUMO

OBJECTIVE: To review the value of magnetic resonance imaging (MRI) in diagnosis and evaluation of rheumatic diseases of the spine and sacroiliac joints. METHODS: A review of the literature on MRI of the spine and sacroiliac joints in rheumatoid arthritis (RA), ankylosing spondylitis (AS), infectious spondylodiscitis, infection of the sacroiliac joint (SIJ), gout, calcium pyrophosphate deposition disease, nontraumatic vertebral compression fractures, insufficiency fracture of the sacrum, avascular necrosis of the vertebral body, sarcoidosis, and Paget's disease was performed. The reports were obtained from a Medline search. RESULTS: In RA, AS, and crystal deposition disease, synovial tissue, atlantoaxial and subaxial subluxations, crystal deposition, and neurologic compromise can be adequately diagnosed with MRI of the cervical spine. Studies on MRI of SIJs in AS indicate that MRI enables early diagnosis of sacroiliitis. In most cases of infectious spondylodiscitis, avascular necrosis of the vertebral body, nontraumatic vertebral compression fractures, and insufficiency fractures of the sacrum characteristic findings on MRI suggest the correct diagnosis. Moreover, soft tissue abnormalities and neurologic compromise can be visualized. In infection of the SIJ, MRI shows findings suggesting an inflammatory process. In Paget's disease, MRI does not provide additional information as compared with plain radiography (PR) or computed tomography (CT). CONCLUSION: In evaluation of spinal and SIJ abnormalities in many rheumatic diseases, MRI, in addition to PR, can replace conventional tomography, CT, and myelography. Moreover, MRI can visualize soft tissue abnormalities and neurologic compromise without use of intrathecal contrast.


Assuntos
Artropatias/diagnóstico , Imageamento por Ressonância Magnética , Doenças Reumáticas/diagnóstico , Articulação Sacroilíaca/patologia , Doenças da Coluna Vertebral/diagnóstico , Humanos
19.
Leukemia ; 13(11): 1675-90, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10557039

RESUMO

In the last decade it has become clear that homeobox containing genes (HOX genes) not only play a significant role in regulating body formation, but in addition, they are contributing to organization and regulation of hematopoiesis. Modern molecular technologies showed that deregulated expression or disruption of Hox genes can lead to altered characteristics of blood cells or disturbance of blood cell development. In this paper we review the role of HOX proteins in hematopoiesis and leukemogenesis and speculate about their possible target genes and involvement in lymphomagenesis.


Assuntos
Genes Homeobox/genética , Neoplasias Hematológicas/genética , Hematopoese/genética , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem da Célula , Desenvolvimento Embrionário e Fetal/genética , Genes Homeobox/fisiologia , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Hematopoese/fisiologia , Humanos , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
J Rheumatol ; 26(9): 1953-8, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10493676

RESUMO

OBJECTIVE: To investigate the diagnostic value of magnetic resonance imaging (MRI) in the detection of early sacroiliitis. METHODS: Twenty-five consecutive HLA-B27 positive patients with inflammatory low back pain and < or = grade 2 unilateral sacroiliitis on conventional radiography (modified New York criteria) were studied. Erythrocyte sedimentation rate, C-reactive protein, plain radiography (PR), and MRI of the sacroiliac (SI) joints were obtained at study entry and PR of the SI joints after 3 years. Each radiograph and MR image set was interpreted independently. SI joints were scored according to the modified New York Criteria for radiological sacroiliitis. MRI scans were also scored for the presence of subchondral marrow edema. The relationship between > or = grade 2 sacroiliitis (by modified New York criteria for radiological sacroiliitis) shown on MRI and the subsequent development of > or = grade 2 sacroiliitis on PR after 3 years was investigated. RESULTS: At study entry > or = grade 2 sacroiliitis was found on MRI in 36 of 50 SI joints. Edema was found in 20 of 50 SI joints. After 3 years > or = grade 2 sacroiliitis was found on PR in 21 of 44 SI joints. The positive predictive value of > or = grade 2 sacroiliitis on MRI for the development of > or = grade 2 sacroiliitis on PR after 3 years was 60%; sensitivity was 85% and specificity 47%. CONCLUSION: Our data suggest that MRI of the SI joints can be used to identify sacroiliitis earlier than PR.


Assuntos
Imageamento por Ressonância Magnética , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia , Espondilite Anquilosante/diagnóstico , Adulto , Intervalos de Confiança , Feminino , Humanos , Estudos Longitudinais , Dor Lombar/diagnóstico , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Radiografia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Espondilite Anquilosante/complicações
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