RESUMO
The effect of CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-versus-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological malignancies who received peripheral blood stem cell (PBSC) grafts from sibling donors. Myeloablative conditioning was used in 88 cases and 101 received reduced intensity conditioning. The median CD34+ cell dose was 5.6 × 106/kg (0.6-17.0). In the multivariate analysis, a CD34 cell dose of 6-7 × 106/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × 106/kg led to increased relapse and reduced chronic GVHD (cGVHD). A high CD34 cell-dose (>6.5 × 106/kg) correlated with less acute GVHD (aGVHD) II-IV. We conclude that the CD34 cell dose has an impact on the outcome of HSCT from sibling donor PBSCs.
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Reduced-intensity conditioning (RIC) allo-SCT is a potentially curative treatment approach for patients with relapsed Hodgkin's or non-Hodgkin's lymphoma. In the present study, 37 patients underwent RIC allo-SCT after induction treatment with EPOCH-F(R) using a novel form of dual-agent immunosuppression for GVHD prophylaxis with CsA and sirolimus. With a median follow-up of 28 months among survivors, the probability for OS at 3 and 5 years was 56%. Treatment-related mortality was 16% at day +100 and 30% after 1 year of transplant. Acute GVHD grades II-IV developed in 38% of patients, suggesting that the regimen consisting of CsA and an ultra-short course of sirolimus is effective in the prevention of acute GVHD.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Imunossupressores/administração & dosagem , Linfoma não Hodgkin/terapia , Sirolimo/administração & dosagem , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/cirurgia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Rituximab , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vincristina/administração & dosagem , Adulto JovemRESUMO
Requests for participation of unrelated stem cell donors in research transplant protocols are becoming more frequent. World Marrow Donor Association calls on donor registries to participate in research activities. Here, we discuss various implications of research participation and make some recommendations as how to make this possible.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Experimentação Humana/ética , Sujeitos da Pesquisa , Doadores de Tecidos , Árvores de Decisões , Declaração de Helsinki , Experimentação Humana/legislação & jurisprudência , Humanos , Consentimento Livre e Esclarecido , Agências Internacionais , Internacionalidade , Guias de Prática Clínica como Assunto , Sistema de Registros/normas , Sujeitos da Pesquisa/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/éticaRESUMO
BACKGROUND: The HLA (human leukocyte antigen) class II genes DQB1 and DRB1 and the Tumor Necrosis Factor alpha gene (TNFA) within the HLA complex (chromosome 6p21) have been associated with asthma and allergy. Due to the strong linkage disequilibrium characterizing this complex and the multiple asthma/allergy expressions, we aimed to determine which of these genes were primarily involved in specific asthma/allergy traits. METHODS: The DRB1-DQB1 alleles and TNFA-308 polymorphism were genotyped in 959 children from the Environment and Childhood Asthma study and analyzed for possible associations with allergic and non-allergic asthma (with/without at least one positive skin prick test for allergens) and specific allergic sensitization, as well as bronchial hyperresponsiveness and total IgE, using both allele and extended haplotype analyses. RESULTS: Different genes within the HLA complex were associated with separate asthma and allergy traits. Nonallergic asthma was associated with both the TNFA-308A allele [Odds ratio (OR) 1.7 (1.3-2.3)] and DRB1 03 allele [OR 1.6(1-2.6)], but extended DRB1 03-TNFA-308 haplotype analysis suggested that the DRB1-DQB1 association was secondary to linkage disequilibrium with the TNFA-308 polymorphism. Allergies were associated with HLA class II alleles only; birch sensitization with DQB1 0603-DRB1 13 [OR 2.3 (1.4-4.0)] and mugwort sensitization with DQB1 0609-DRB1 13 [OR 7.1 (1.9-27.0)] and DQB1 0501-DRB1 01 [OR 2.0 (1.0-4.0)]. CONCLUSIONS: Our data suggests that asthma is not associated with DRB1 or DQB1 but rather TNFA or a gene(s) in linkage disequilibrium, while sensitization to specific allergens is associated with particular alleles at the DQ and/or DR loci. A novel association between DQB1 0603-DRB1 13 and birch allergy is identified.
Assuntos
Asma/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Hipersensibilidade/genética , Glicoproteínas de Membrana/genética , Fator de Necrose Tumoral alfa/genética , Adolescente , Asma/epidemiologia , Criança , Feminino , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Haplótipos , Humanos , Hipersensibilidade/epidemiologia , Desequilíbrio de Ligação , Masculino , Noruega/epidemiologia , Polimorfismo GenéticoRESUMO
OBJECTIVE: To test whether postnatal psychological distress in parents of babies with congenital malformations is reduced by prenatal diagnosis. METHODS: A prospective observational longitudinal cohort study was conducted at two Norwegian hospitals. We included 293 parents of babies with congenital malformations (prenatal detection rate: 36.5%) referred for neonatal surgery and 249 parents of healthy babies (comparison group). Parental psychological responses were assessed on three postnatal occasions by psychometric instruments (GHQ-28, STAI-X1, and IES). RESULTS: Significantly increased psychological distress (GHQ-28) was reported by parents who received prenatal diagnosis as compared to postnatal diagnosis; acutely 28.9 versus 24.4, P = 0.006 (comparison group: 19.6); at 6 weeks 26.8 versus 21.5, P < 0.001 (comparison group: 17.7); and at 6 months 22.6 versus 18.7, P = 0.015 (comparison group: 16.6). Mothers consistently reported higher levels of distress than fathers. Multiple linear regression analysis showed that prenatal diagnosis and being a mother significantly predicted severity of acute psychological distress. At 6 weeks and 6 months, mortality and associated anomalies were significant independent predictors of psychological distress. CONCLUSION: Controlling for other covariates, we found that prenatal diagnosis of congenital malformations was a significant independent predictor of acute parental psychological distress after birth.
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Anormalidades Congênitas/diagnóstico , Pais/psicologia , Diagnóstico Pré-Natal/psicologia , Estresse Psicológico/epidemiologia , Adulto , Anormalidades Congênitas/psicologia , Feminino , Humanos , Modelos Lineares , Masculino , Mães/psicologia , Gravidez , Estudos Prospectivos , Testes PsicológicosRESUMO
The article presents views and recommendations of the World Marrow Donor Association regarding the need for donor and liability insurance for hematopoietic stem cell donor registries, and donor and collection centers.
Assuntos
Transplante de Células-Tronco Hematopoéticas/normas , Seguro de Responsabilidade Civil/normas , Sistema de Registros/normas , Doadores de Tecidos/ética , Saúde Global , Transplante de Células-Tronco Hematopoéticas/ética , Transplante de Células-Tronco Hematopoéticas/legislação & jurisprudência , Humanos , Seguro de Responsabilidade Civil/ética , Seguro de Responsabilidade Civil/legislação & jurisprudência , Imperícia , Sistema de Registros/ética , Doadores de Tecidos/legislação & jurisprudênciaRESUMO
The article discusses views and recommendations of the World Marrow Donor Association concerning ethical issues related to the donation of hematopoietic stem cell products with respect to recruitment, evaluation, workup, and follow-up of unrelated donors. Particular emphasis is placed upon commitment of individual donors, in particular, with respect to the needs of patients to find HLA-matched donors, who may be asked to donate stem cell and other cell products more than once for given patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/ética , Sistema de Registros/ética , Doadores de Tecidos/ética , Humanos , Consentimento Livre e EsclarecidoRESUMO
A total of 61 consecutive adult patients with haematological malignancies with an HLA-identical or one antigen-mismatched haploidentical family donor were randomised to allogeneic transplantation with blood stem cells (BSC) or bone marrow (BM). The median observation time was 5 years. Apart from engraftment parameters and acute graft-versus-host disease (GVHD), transplant-related mortality (TRM), incidence and severity of chronic GVHD, relapse, leukaemia-free survival (LFS) and overall survival (OS) were recorded. In the BSC and BM group, respectively, TRM was 8/30 and 4/30 (P=0.405), the incidence of chronic GVHD was 15/26 and 11/30 (P=0.138), extensive chronic GVHD was 10/26 and 4/30 (P=0.034), and relapse one and 10 patients (P=0.007). In log-rank test restricted to the cases allografted from HLA-identical donors, the difference remained significant with regard to relapse incidence (P=0.039), but not extensive chronic GVHD (P=0.072). No difference in LFS and OS was observed. In conclusion, our study strongly indicates an enhanced graft-versus-leukaemia effect in BSC recipients, which is not expressed in increased survival. The increased chronic GVHD in these patients may contribute, but the relation is complex and not yet understood.
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Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adolescente , Adulto , Transplante de Medula Óssea/mortalidade , Doença Crônica , Feminino , Seguimentos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Recidiva , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Single-photon emission computed tomography (SPECT) is used to study cerebral blood flow and cerebral metabolism in various neuropsychiatric disorders. Reduced regional cerebral blood flow has been demonstrated in patients with depression and chronic fatigue, symptoms that are common in primary hyperparathyroidism. The aim of this study was to reveal possible changes in regional cerebral blood flow in patients with primary hyperparathyroidism before and after operative treatment. METHODS: This was a prospective study of regional cerebral blood flow in 16 consecutive women of median age 72 (range 50-82) years using SPECT with (99m)Tc-labelled hexamethylpropylenamine-oxime. The measurements were performed before and 2, 4 and 12 months after parathyroidectomy. The Montgomery and Asberg depression rating scale (MADRS) depression score was used as a parallel clinical test. RESULTS: Reduced (pathological) regional cerebral blood flow was seen before operation in 14 patients, 13 with a solitary adenoma and one with double adenoma. After surgery, this improved to normal values in 13, but was further reduced in one. In two patients with preoperative normal regional cerebral blood flow, both of whom were asymptomatic and had diffuse hyperplasia, a slight reduction was demonstrated. Eight patients had a pathological preoperative MADRS score, which normalized in seven after surgical treatment. CONCLUSION: The finding of reduced regional cerebral blood flow in patients with primary hyperparathyroidism followed by significant improvement after operation might influence the case for surgical treatment.
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Circulação Cerebrovascular/fisiologia , Hiperparatireoidismo/cirurgia , Paratireoidectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperparatireoidismo/diagnóstico por imagem , Hiperparatireoidismo/fisiopatologia , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Exametazima , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
The Ethics Working Group of the World Marrow Donor Association (WMDA) was established to address the increasing and complex number of ethical issues surrounding unrelated haematopoietic stem cell donation where the selected donor and recipient reside in different countries. This paper considers the topic of informed donor consent, but recognises that the recommendations contained within the paper may be subject to cultural variances in interpretation, and to adjustment to meet the legal requirements of individual countries. Nevertheless, the extent of international cooperation establishes sufficient common denominators for the recommendations to be widely adhered to in the interests of best practice.
Assuntos
Transplante de Células-Tronco Hematopoéticas/ética , Transplante de Células-Tronco Hematopoéticas/normas , Consentimento Livre e Esclarecido/ética , Consentimento Livre e Esclarecido/normas , Doadores de Tecidos/ética , Humanos , Seleção de PacientesRESUMO
Increased body mass index (BMI) is claimed to be a complication among survivors of testicular cancer (TCSs), especially after receiving cisplatin-based chemotherapy. This study compares changes in BMI (kg m(-2)) in TCSs with those observed in age-matched men from the population (controls). Associations between treatment, age and potential BMI changes were sought. In 1999, a survey was performed at the NRH of 444 unilaterally orchiectomised TCSs treated from 1980 to 1990. BMI at survey was recorded in each TCS. Information on principal treatment (surgery only: SURG; radiotherapy only: RAD; chemotherapy +/- surgery or radiotherapy: CHEM+/-) and pretreatment BMI was retrieved from the medical records. The age-matched controls had BMI measurements from population surveys from 1985 and 1996. The annual BMI increase was calculated based on the difference in the two BMI measurements divided by observation time. TCSs displayed a lower pretreatment mean BMI than the controls, whereas no difference was found post-treatment. However, the annual BMI increase in TCSs exceeded that of the controls (0.19 vs 0.15, P=1.4 x 10(-7)). The SURG and CHEM+/- groups showed the greatest annual BMI increase. The multiple regression analysis showed that young TC patients who received chemotherapy displayed an excessive annual BMI increase. Oncologists and young TCSs should be aware of the risk of excessive BMI increase, in particular, after the use of chemotherapy.
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Índice de Massa Corporal , Intervalo Livre de Doença , Neoplasias Testiculares/complicações , Peso Corporal , Tratamento Farmacológico , Humanos , Masculino , Qualidade de Vida , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/psicologiaRESUMO
BACKGROUND: Primary sclerosing cholangitis (PSC) confers a high risk of cholangiocarcinoma (CC) development. Since patients at risk of CC may be selected for early liver transplantation, it is a challenge to identify any predisposing factors. We compared the presentation and natural history of a large number of PSC patients with and without later CC development to identify features associated with risk of CC. METHODS: Clinical and laboratory data from presentation and follow-up were collected from 394 PSC patients from five European countries. The cohort included 48 (12.2%) patients with CC. RESULTS: CC was diagnosed within the first year after diagnosis of PSC in 24 (50%) cases and in 13 (27%) patients at intended liver transplantation. Jaundice, pruritus, abdominal pain and fatigue were significantly more frequent at diagnosis of PSC in the group that developed CC, but not after exclusion of cases diagnosed within the first year. Inflammatory bowel disease was diagnosed at least 1 year before PSC more often among patients with CC development than among those without (90% and 65%, respectively: P = 0.001). The duration of inflammatory bowel disease before diagnosis of PSC was significantly longer in patients who developed CC than in the remaining group (17.4 years and 9.0 years, respectively: P=0.009 in multivariate analysis). CONCLUSIONS: A high proportion of CC cases is diagnosed within the first year after diagnosis of PSC. A long history of inflammatory bowel disease is a risk factor for CC development.
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Neoplasias dos Ductos Biliares/etiologia , Neoplasias dos Ductos Biliares/fisiopatologia , Ductos Biliares Intra-Hepáticos/fisiopatologia , Colangiocarcinoma/etiologia , Colangiocarcinoma/fisiopatologia , Colangite Esclerosante/complicações , Colangite Esclerosante/fisiopatologia , Adulto , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Colangite Esclerosante/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Fatores de Risco , Taxa de Sobrevida , Fatores de TempoRESUMO
Biological consequences and physical complaints were compared for donors randomly assigned either to blood stem cell (BSC) or bone marrow (BM) donation. In the period 1994-1999, 61 consecutive donors were included. The BSC donors were given G-CSF 10 microg/kg s.c., daily during 5 days before the first leukapheresis. Nineteen donors had one leukapheresis, 10 required two and one donor needed three leukaphereses in order to reach the target cell number of 2 x 10(6) CD34(+) cells/kg bw of the recipient. A median platelet nadir of 102 x 10(9)/l was reached shortly after the last leukapheresis. Three weeks post harvest, 17 of 30 BSC donors had a mild leukopenia. Six had a leukopenia lasting more than a year before returning to normal values. Both groups were monitored prospectively through a standardised questionnaire completed by the donors. BSC donation was significantly less burdensome than BM donation and was preferred by the donors. The short-term risks of BSC mobilisation and harvest seem negligible. The potential long-term effects of G-CSF are unresolved and the donors must be followed closely.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas , Coleta de Tecidos e Órgãos/efeitos adversos , Adolescente , Adulto , Contagem de Células Sanguíneas , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucaférese , Leucopenia/sangue , Leucopenia/etiologia , Leucopenia/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Coleta de Tecidos e Órgãos/métodosRESUMO
BACKGROUND: An improvement of prognostic models in primary sclerosing cholangitis (PSC) is needed. In particular, inclusion of prognostic markers that are independent of the disease stage would be advantageous. We investigated whether HLA class II genes associated with PSC are also related to disease progression. METHODS: The study included 265 PSC patients from five European countries with a median follow-up of 9.1 years. The end-points were death (n = 38) or liver transplantation (n = 52). Thirty patients developed cholangiocarcinoma during follow-up. RESULTS: The DRB1*03,DQA1*0501, DQB1*02 (i.e. DR3,DQ2) heterozygous genotype was associated with an increased risk of death or liver transplantation (hazard ratio = 1.63; 95% confidence interval (CI) = 1.06-2.52). The presence of a DQ6 encoding haplotype (DQB1*0603 or DQB1*0602) in DR3,DQ2 negative individuals was associated with a reduced risk of death or liver transplantation (hazard ratio = 0.57; 95% CI = 0.36-0.88). There was a trend towards an increased risk of developing cholangiocarcinoma among DR4,DQ8 positive patients, but this did not reach significance (odds ratio = 2.27; 95% CI = 0.78-6.62). CONCLUSION: The DR3,DQ2 heterozygous genotype is associated with a more rapid progression of PSC, whereas HLA-DQ6 is associated with a retarded disease progression. It is possible that the DR4,DQ8 haplotype is related to cholangiocarcinoma development.
Assuntos
Colangite Esclerosante/genética , Antígenos HLA-DQ/genética , Antígeno HLA-DR3/genética , Heterozigoto , Adolescente , Adulto , Idoso , Criança , Colangite Esclerosante/imunologia , Progressão da Doença , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoRESUMO
PURPOSE: The aim of this study was to review all available studies reported in the English-language literature from 1975 through 1998, and by meta-analysis assess the importance of prenatal diagnosis, associated malformations, side of hernia, timing of surgery, and study population on mortality rates in patients with congenital diaphragmatic hernia (CDH). METHODS: One-hundred-two studies were identified, and 51 studies (2,980 patients) fulfilled the prespecified inclusion criteria. Studies were grouped according to study population into: (I) fetuses diagnosed prenatally; (II) neonates admitted to a treatment center; and (III) population-based studies. RESULTS: Pooled total mortality rate was significantly higher in category I than in category III (75.6% v 58.2%, P < .001). Pooled hidden postnatal mortality rate (deaths before admittance to a treatment center) in population-based studies was 34.9%. Prenatally diagnosed patients in both category II and III had significantly higher mortality rates than those diagnosed postnatally. Mortality rates were significantly higher among CDH infants with associated major malformations compared with isolated CDH in all 3 categories. An increased mortality rate in right-sided CDH was found in category II and III. CONCLUSIONS: Prenatal diagnosis of CDH, presence of associated major malformations, and the study population have a major influence on mortality rate. The very high mortality rate in studies of fetuses with a prenatal diagnosis of CDH should be taken into account in prenatal counselling.
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Hérnia Diafragmática/mortalidade , Hérnias Diafragmáticas Congênitas , Anormalidades Múltiplas/mortalidade , Estudos de Casos e Controles , Feminino , Hérnia Diafragmática/diagnóstico por imagem , Humanos , Recém-Nascido , Gravidez , Prevalência , Ultrassonografia Pré-NatalRESUMO
Sixty-one consecutive adult patients with leukaemia, primary myelofibrosis or myelodysplastic syndrome with an HLA-identical or one antigen mismatched family donor were randomised to allogeneic transplantation with PBPC or BM. Progenitor cells were mobilised into the blood by giving the donors 10 microg/kg/day G-CSF subcutaneously for 5-7 days. G-CSF was not given to patients after transplantation. The time to neutrophil counts >0.5 x 109/l was 17 days (95% CI 15.2-18.8 days) in the PBPC group compared to 23 (95% CI 20.3-25.7 days) in the BM group (P = 0.0005). The time to platelet counts >20 x 109/l was 13 days (95% CI 11.7-14.3 days) in the PBPC group and 21 days (95% CI 18.7-23.3 days) in the BM group (P = 0.0005). Acute GVHD of grades II-IV developed in six patients transplanted with PBPC and three patients transplanted with BM. The numbers of patients with chronic GVHD were 15 and 8, respectively. Transplant-related mortality and leukaemia-free survival showed no significant differences. Transplantation with PBPC appears preferable for the recipient due to faster neutrophil and platelet recovery. However, the final conclusion can not be drawn before long-term results on chronic GVHD and relapse incidence in longer randomised trials are available.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Mielofibrose Primária/terapia , Adolescente , Adulto , Células da Medula Óssea , Ciclosporina/uso terapêutico , Família , Doença Enxerto-Hospedeiro/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/uso terapêutico , Leucemia/sangue , Leucemia/mortalidade , Contagem de Leucócitos , Doadores Vivos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/mortalidade , Contagem de Plaquetas , Mielofibrose Primária/sangue , Mielofibrose Primária/mortalidade , Análise de Sobrevida , Transplante HomólogoRESUMO
Haemopoietic progenitor cells (HPCs) express the CD34 molecule, a heavily glycosylated transmembrane protein displaying three main classes of epitopes. The CD34 epitope class expression may vary between different subsets of HPCs. The aim of this study was to characterise the subsets of HPCs expressing CD34 class II and III epitopes. The cells were studied for coexpression of activation-, lineage- and adhesion-associated molecules, and their clonogenic ability and morphological features were examined. CD34+ HPCs expressing class III epitopes outnumbered those expressing class II. Class III expressing HPCs were enriched for CFU-GM and BFU-E and cells coexpressing CD13, CD33, c-kit and CD71 compared to class II expressing HPCs. CD34+ cells exclusively expressing class III epitopes uniformly displayed CD13 and CD33; they had a high clonogenic capacity and morphological characteristics of promyelocytes and myelocytes. The data show that class III epitopes are distributed more broadly on CD34+ HPCs than are class II epitopes, and that lack of class II epitopes is confined to CD34+ HPCs at a late stage of myeloid differentiation. The higher number of class III expressing HPCs coexpressing c-kit and CD71 suggests that these cells exhibit a higher proliferative or differential potential than do HPCs expressing class II epitopes.
Assuntos
Antígenos CD34/imunologia , Linhagem da Célula , Epitopos/imunologia , Hematopoese/imunologia , Células-Tronco Hematopoéticas/imunologia , Adesão Celular , Moléculas de Adesão Celular/imunologia , Diferenciação Celular , Divisão Celular , Células-Tronco Hematopoéticas/citologia , HumanosRESUMO
BACKGROUND: The effect of percutaneous transluminal coronary angioplasty (PTCA) on physiologic measurements has previously been shown, but the relation between physiologic response and degree of change in coronary luminal diameter is not known. We studied the relation between exercise capacity and minimal luminal diameter before and after PTCA. We also explored the usefulness of measurement of attenuation in exercise capacity after PTCA to predict the likelihood of restenosis. METHODS: Bicycle exercise testing was performed 2 weeks before and 2 and 20 weeks after PTCA in 395 consecutively enrolled patients. Angiograms obtained before and after PTCA and 20 weeks afterward were analyzed by quantitative coronary angiography. Restenosis was defined as both angiographic (>/=50% diameter stenosis at follow-up angiography) and clinical (target-vessel revascularization), after successful PTCA. Exercise capacity was defined as the cumulative work performed divided by body weight (watt x minutes x kilograms(-1)). RESULTS: Exercise capacity increased 43% (P <.0001) from before PTCA to 2 weeks after PTCA (early increase) and decreased 4% (P =.01) from 2 to 20 weeks after PTCA (late decrease). The gain in minimal luminal diameter (Minimal luminal diameter after - Minimal luminal diameter before) was 0.92 +/- 0.46 mm. The loss in minimal luminal diameter (Minimal luminal diameter after PTCA - Minimal luminal diameter at follow-up examination) was 0.27 +/- 0.42 mm. Exercise capacity and minimal luminal diameter measured before PTCA were positively correlated (coefficient 3.3; R = 0.12; P =.01). Gain in minimal luminal diameter correlated with the early increase in exercise capacity (coefficient -3.8; R = 0.23; P <.0001). Loss in minimal luminal diameter correlated with the late decrease in exercise capacity (coefficient 3.3; R = 0.20; P <.0001). Multivariate logistic regression analysis revealed that the late decrease in exercise capacity was independently predictive of both angiographically (odds ratio 1.13; P <.0001) and clinically (odds ratio 1.12; P <.0001) defined restenosis. CONCLUSIONS: The results demonstrated a linear relation between the severity of coronary stenosis and exercise capacity measured before PTCA. The degree of coronary luminal enlargement achieved with angioplasty and the luminal reduction that occurred between PTCA and follow-up evaluation correlated with increases and decreases in exercise capacity. Attenuation in exercise capacity was found to be a strong predictor of restenosis.