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1.
Acta Anaesthesiol Scand ; 62(9): 1194-1199, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29932207

RESUMO

BACKGROUND: In Norway, each municipality is responsible for providing first line emergency healthcare, and it is mandatory to have a primary care physician/general practitioner on call continuously. This mandate ensures that a physician can assist patients and ambulance personnel at the site of severe injuries or illnesses. The compulsory presence of the general practitioner at the scene could affect different parts of patient treatment, and it might save resources by obviating resources from secondary healthcare, like pre-hospital anaesthesiologists and other specialized resources. This systematic review aimed to examine how survival, time spent at the scene, the choice of transport destination, assessment of urgency, the number of admissions, and the number of cancellations of specialized pre-hospital resources were affected by the presence of a general practitioner at the scene of a suspected severe injury. METHODS: We searched for published and planned systematic reviews and primary studies in the Cochrane Library, Medline, Embase, OpenGrey, GreyLit and trial registries. The search was completed in December 2017. Two individuals independently screened the references and assessed the eligibility of all potentially relevant studies. RESULTS: The search for systematic reviews and primary studies identified 5981 articles. However, no studies met the pre-defined inclusion criteria. CONCLUSION: No studies met our inclusion criteria; consequently, it remains uncertain how the presence of a general practitioner at the injury scene might affect the selected outcomes.


Assuntos
Clínicos Gerais/legislação & jurisprudência , Política de Saúde/legislação & jurisprudência , Ferimentos e Lesões/terapia , Hospitalização/estatística & dados numéricos , Humanos , Noruega
2.
Acta Oncol ; 55(5): 547-53, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27123741

RESUMO

Background This study examined employment patterns and associated factors in lymphoma survivors treated with high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT) from diagnosis to a follow-up survey at a mean of 10 years after HDT-ASCT. Patients and methods All lymphoma survivors aged ≥18 years at HDT-ASCT in Norway from 1987 to 2008, and alive at the end of 2011 were eligible for this cross-sectional study performed in 2012/2013. Participants completed a mailed questionnaire. Job status was dichotomized as either employed (paid work) or not-employed (disability and retirement pension, on economic support, home-makers, or students). Results The response rate was 78%, and the sample (N = 312) contained 60% men. Mean age at HDT-ASCT was 44.3 and at survey 54.0 years. At diagnosis 85% of survivors were employed, 77% before and 77% after HDT-ASCT, and 58% at follow-up. Forty seven percent of the survivors were employed at all time points. The not-employed group at survey was significantly older and included significantly more females than the employed group. No significant between-group differences were observed for lymphoma-related variables. Fatigue, mental distress and type D personality were significantly higher among those not-employed, while quality of life was significantly lower compared to the employed group. Older age at survey, being female, work ability and presence of type D personality remained significantly related to being not-employed at survey in the multivariable analysis. Conclusions Our findings show that not-employed long-term survivors after HDT-ASCT for lymphoma have more comorbidity, cognitive problems and higher levels of anxiety/depression than employed survivors. These factors should be checked and eventually treated in order to improve work ability.


Assuntos
Emprego/estatística & dados numéricos , Linfoma/epidemiologia , Sobreviventes/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Antineoplásicos/uso terapêutico , Comorbidade , Estudos Transversais , Feminino , Seguimentos , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Qualidade de Vida , Estudos Retrospectivos , Fatores Sexuais , Transplante de Células-Tronco , Inquéritos e Questionários , Sobreviventes/psicologia , Transplante Autólogo , Resultado do Tratamento , Desemprego/estatística & dados numéricos
3.
Ann Oncol ; 24(5): 1385-92, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23247661

RESUMO

BACKGROUND: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. RESULTS: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. CONCLUSIONS: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov. identifier NCT01502982.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Sistema Nervoso Central/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Anticorpos Monoclonais Murinos/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Imunoterapia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab , Vincristina/uso terapêutico , Adulto Jovem
4.
Leuk Lymphoma ; 64(12): 1927-1937, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37683053

RESUMO

The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/- interferon).


Assuntos
Linfoma Folicular , Humanos , Rituximab , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Variações do Número de Cópias de DNA , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Interferons/uso terapêutico , Biópsia , Expressão Gênica
5.
Ann Oncol ; 23(5): 1254-1259, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21926399

RESUMO

BACKGROUND: From 1999, Norwegian guidelines recommend two escalated (esc) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) followed by six standard (s) BEACOPP for patients with advanced-stage classical Hodgkin lymphoma (HL) with an international prognostic score (IPS) ≥ 4. We evaluated retrospectively the experience with this recommendation at the Norwegian Radium Hospital, also including all IPS 3 patients treated with the same regimen. PATIENTS AND METHODS: Forty-seven patients were treated between June 1999 and December 2008. IPS was 3 in 10 patients and ≥ 4 in 37. RESULTS: Thirty-five patients received eight cycles of BEACOPP, 12 patients received one to six cycles only, mainly due to toxicity. Sixty percent of patients had dose reductions. With median follow-up of survivors of 89 months, 5-year progression-free and overall survival are 84% [95% confidence interval (CI) 73% to 95%] and 91% (95% CI 82% to 100%), respectively. Toxicity was considerable with grade 3 or more infections/febrile neutropenia in 66% of patients, including one death and three cases of Pneumocystis jiroveci pneumonia. Of note, 10 patients (21%) experienced symptomatic aseptic osteonecrosis, of whom 3 have had hip replacement surgery after treatment. CONCLUSION: Two escBEACOPP plus six sBEACOPP is efficacious in advanced-stage high-risk HL. We document a high incidence of aseptic bone necrosis, possibly related to prednisolone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Osteonecrose/induzido quimicamente , Adolescente , Adulto , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Progressão da Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Osteonecrose/diagnóstico , Osteonecrose/etiologia , Osteonecrose/mortalidade , Guias de Prática Clínica como Assunto/normas , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Estudos Retrospectivos , Risco , Análise de Sobrevida , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
6.
N Engl J Med ; 359(22): 2313-23, 2008 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-19038878

RESUMO

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.


Assuntos
Perfilação da Expressão Gênica , Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Células Estromais/metabolismo , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Progressão da Doença , Doxorrubicina , Matriz Extracelular/genética , Regulação Neoplásica da Expressão Gênica , Genes MHC da Classe II , Centro Germinativo , Humanos , Fatores Imunológicos/administração & dosagem , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Pessoa de Meia-Idade , Análise Multivariada , Neovascularização Patológica/genética , Prednisona , Prognóstico , Rituximab , Células Estromais/patologia , Vincristina
7.
Scand J Immunol ; 74(6): 632-9, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21883353

RESUMO

We evaluated inflammatory markers in febrile neutropenic lymphoma patients undergoing high-dose chemotherapy with autologous stem cell support. Based on MASCC scores, our patients had a low risk of serious complications and a perspective of a benign initial clinical course of the febrile neutropenia. We also studied the impact of tobramycin given once versus three times daily on these immune markers. Sixty-one patients participating in a Norwegian multicentre prospective randomized clinical trial, comparing tobramycin once daily versus three times daily, given with penicillin G to febrile neutropenic patients, constituted a clinically homogenous group. Four patients had bacteraemia, all isolates being Gram-positive. Thirty-two patients received tobramycin once daily, and 29 patients received tobramycin three times daily. Blood samples were taken at the onset of febrile neutropenia and 1-2 days later. All samples were frozen at -70 °C and analysed at the end of the clinical trial for C-reactive protein (CRP), procalcitonin (PCT), complement activation products, mannose-binding lectin (MBL) and 17 cytokines. We found a mild proinflammatory response in this series of patients. CRP was non-specifically elevated. Ten patients with decreased MBL levels showed the same mild clinical and proinflammatory response. Patients receiving tobramycin once daily showed a more pronounced proinflammatory response compared with patients receiving tobramycin three times daily. Overall, febrile neutropenic cancer patients with a benign clinical course show a mild proinflammatory immune response.


Assuntos
Antineoplásicos/efeitos adversos , Linfoma , Neutropenia/tratamento farmacológico , Tobramicina/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Citocinas/imunologia , Feminino , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Fatores de Risco , Tobramicina/administração & dosagem , Tobramicina/efeitos adversos , Adulto Jovem
9.
Br J Cancer ; 101(4): 575-81, 2009 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-19623176

RESUMO

PURPOSE: Hodgkin's lymphoma survivors (HLSs) have an elevated risk for cardiovascular diseases that appear several years after radiotherapy. This study examined the time-dependent development and evolution of valvular and myocardial function related to treatment with mediastinal radiotherapy and anthracyclines in HLSs. PATIENTS AND METHODS: In 1993, echocardiography was performed in 116 HLSs median 10 years (range 6-13 years) after treatment with mediastinal radiotherapy. None of the 116 patients had valvular stenosis in 1993 whereas 36 (31%) had moderate valvular regurgitation. In 2005-2007, 51 of 57 invited patients were included in a second echocardiographic study - median 22 years (range 11-27 years) after treatment. Of these patients, 28 (55%) had also received anthracyclines. The patients were selected on the basis of the presence or absence of moderate valvular regurgitation in 1993. RESULTS: The second echocardiographic study demonstrated that 10 out of 27 (37%) patients with only mild or no aortic or mitral regurgitation in 1993 had developed moderate regurgitation in either or both the aortic or mitral valve. Of the 24 patients with moderate (n=23) or severe (n=1) regurgitation in the aortic or mitral valve in 1993, 8 (33%) had progressed to severe regurgitation, developed moderate regurgitation in a previously normal or mild regurgitant valve or had received valvular replacement. In total, of all patients, 20 (39%) had developed mild to severe aortic stenosis and 3 patients had received valvular replacement. In a multiple linear regression the use of anthracyclines predicted left ventricular remodelling between ECHO 1993 and 2005 as demonstrated by increased left ventricular end systolic diameter (beta =0.09 (95% CI 0.01-0.17), P=0.04) and reduced thickness of the left ventricular posterior wall (beta =-0.18 (95% CI -0.33 to -0.03), P=0.02) and interventricular septum (beta =-0.16 (95% CI -0.30 to -0.03), P=0.02). CONCLUSION: Given the progressive nature of valvular dysfunction and left ventricular remodelling 20-30 years after diagnosis, we recommend life-long cardiological follow-up of HLSs treated with mediastinal radiotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Doenças das Valvas Cardíacas/etiologia , Ventrículos do Coração/patologia , Doença de Hodgkin/terapia , Neoplasias do Mediastino/terapia , Radioterapia/efeitos adversos , Adolescente , Adulto , Antraciclinas/efeitos adversos , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/efeitos da radiação , Ecocardiografia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/efeitos da radiação , Doença de Hodgkin/patologia , Humanos , Pessoa de Meia-Idade , Valva Mitral/efeitos dos fármacos , Valva Mitral/efeitos da radiação , Estadiamento de Neoplasias , Sobreviventes , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/efeitos da radiação , Adulto Jovem
10.
Leuk Lymphoma ; 48(3): 570-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17454601

RESUMO

There is no consensus on the optimal chemotherapy regimen for Hodgkin's lymphoma patients > or = 60 years. We present our institution's results of 5 years, using CHOP-21 as standard for this patient group. Twenty-nine patients with a median age of 71 years (range, 60 - 91) were included in this cohort. Fifty-five percent had known co-morbidities. Stage I/IIA patients (38%) were treated with 2 - 4 cycles of CHOP followed by radiotherapy. Stage IIB - IV patients (62%) received 6 - 8 cycles of CHOP and for the majority (13/18 pts) no radiotherapy. Two treatment-related deaths occurred. Febrile neutropenia was the most common toxicity (31%). The complete response rate after CHOP +/- radiotherapy was 93%. With a median follow-up of 41 months, five patients have relapsed and four have died from Hodgkin's lymphoma. So far, no relapses have occurred after 2 years from the end of therapy. Overall survival and progression-free survival at 3 years were 79% and 76%, respectively. We conclude that CHOP-21 is a well-tolerated and effective treatment for elderly patients with Hodgkin's lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Indução de Remissão , Taxa de Sobrevida , Vincristina/uso terapêutico
11.
Mol Cell Biol ; 11(6): 3384-9, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2038340

RESUMO

The expression and distribution of DNA polymerase alpha was measured by cytometry and confocal laser scanning microscopy. Expression was proportional to DNA content in proliferating cells, while only S-phase cells retained DNA polymerase alpha after detergent extraction. Nuclear DNA polymerase alpha binding may be one of the key events of S-phase entry.


Assuntos
Ciclo Celular , Núcleo Celular/fisiologia , DNA Polimerase II/metabolismo , Animais , Linfócitos B/citologia , Linfócitos B/enzimologia , Linhagem Celular , Núcleo Celular/ultraestrutura , Células Cultivadas , Citometria de Fluxo , Fase G1 , Humanos , Lasers , Fase S
12.
Blood Cancer J ; 7(8): e596, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28841210

RESUMO

Effect of alternative splicing (AS) on diffuse large B-cell lymphoma (DLBCL) pathogenesis and survival has not been systematically addressed. Here, we compared differentially expressed genes and exons in association with survival after chemoimmunotherapy, and between germinal center B-cell like (GCB) and activated B-cell like (ABC) DLBCLs. Genome-wide exon array-based screen was performed from samples of 38 clinically high-risk patients who were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis. The exon expression profile separated the patients according to molecular subgroups and survival better than the gene expression profile. Pathway analyses revealed enrichment of AS genes in inflammation and adhesion-related processes, and in signal transduction, such as phosphatidylinositol signaling system and adenosine triphosphate binding cassette transporters. Altogether, 49% of AS-related exons were protein coding, and domain prediction showed 28% of such exons to include a functional domain, such as transmembrane helix domain or phosphorylation sites. Validation in an independent cohort of 92 DLBCL samples subjected to RNA-sequencing confirmed differential exon usage of selected genes and association of AS with molecular subtypes and survival. The results indicate that AS events are able to discriminate GCB and ABC DLBCLs and have prognostic impact in DLBCL.


Assuntos
Processamento Alternativo , Éxons , Genes Neoplásicos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Idoso , Neoplasias do Sistema Nervoso Central , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
13.
Clin Microbiol Infect ; 23(3): 179-187, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27793737

RESUMO

OBJECTIVES: In Norway, initial treatment of febrile neutropenia (FN) has traditionally been benzylpenicillin plus an aminoglycoside. Internationally, FN is often treated with a broad-spectrum ß-lactam antibiotic. We aimed to compare these two regimens in a prospective, randomized, trial in patients with lymphoma or leukaemia with an expected period of neutropenia ≥7 days, and a suspected bacterial infection. METHODS: Adult neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection, were randomized for treatment with benzylpenicillin plus an aminoglycoside or meropenem. The primary endpoint was clinical success, defined as no modification of antibiotics and clinical stability 72 h after randomization. RESULTS: Among 322 randomized patients, 297 proved evaluable for analyses. Fifty-nine per cent (95% CI 51%-66%), (87/148) of the patients given benzylpenicillin plus an aminoglycoside were clinically stable, and had no antibiotic modifications 72 h after randomization, compared with 82% (95% CI 75%-87%), (122/149) of the patients given meropenem (p <0.001). When the antibiotic therapy was stopped, 24% (95% CI 18%-32%), (36/148) of the patients given benzylpenicillin plus an aminoglycoside, compared with 52% (95% CI 44%-60%), (78/149) of the patients given meropenem, had no modifications of their regimens (p <0.001). In the benzylpenicillin plus an aminoglycoside arm, the all-cause fatality within 30 days of randomization was 3.4% (95% CI 1.2%-7.9%), (5/148) of the patients, compared with 0% (95% CI 0.0%-3.0%), (0/149) of the patients in the meropenem arm (p 0.03). CONCLUSION: Clinical success was more common in FN patients randomized to meropenem compared with the patients randomized to benzylpenicillin plus an aminoglycoside. The all-cause fatality was higher among the patients given benzylpenicillin plus an aminoglycoside.


Assuntos
Aminoglicosídeos/administração & dosagem , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Leucemia/complicações , Linfoma/complicações , Penicilina G/administração & dosagem , Tienamicinas/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Meropeném , Pessoa de Meia-Idade , Mortalidade , Neutropenia/complicações , Noruega , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
14.
Cancer Res ; 48(23): 6708-14, 1988 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-3263191

RESUMO

The chromatin structure of a diploid precursor B-cell line (REH), in vitro-stimulated normal B-lymphocytes, and reactive and malignant lymph node B-lymphocytes was studied by staining formaldehyde-fixed, permeabilized cells with the DNA-specific fluorophore 7-aminoactinomycin D (7-AMD) and measuring single-cell fluorescence by flow cytometry. Resting peripheral blood B- and T-lymphocytes (G0 cells) bound low amounts of 7-AMD (7-AMD- phenotype), while G1 REH cells and purified B-cells stimulated with anti-mu + B-cell growth factor bound nearly twice as much 7-AMD (7-AMD+ phenotype). 7-AMD binding increased up to threefold and the differences in binding between G0 and G1 cells were nearly abolished when nuclei were isolated prior to fixation or when fixed whole cells were treated with DNase 1. 7-AMD binding increased in parallel with autofluorescence and approximately linearly with time during the G0-G1 transition of in vitro stimulated B-cells, as was determined by simultaneous measurements of 7-AMD fluorescence and autofluorescence or fluorescence of fluorescein isothiocyanate-labeled antibodies to the early activation antigen 4F2 and to the transferrin receptor. In cell suspensions from lymph node biopsies, the 7-AMD+ phenotype was a property of tumor cells in patients with high grade non-Hodgkin's lymphoma (H-NHL, Kiel classification, 5/5); cells with this phenotype were only found in one of nine low grade non-Hodgkin's lymphoma samples (L-NHL, 1/9). The other (8/9) L-NHL samples and the reactive lymph node contained only 7-AMD- cells. All tumors were diploid. The correlation observed between 7-AMD binding and DNase 1 susceptibility of DNA in chromatin (P less than 0.001) suggests that 7-AMD binding is a marker of general transcriptional activity. Surprisingly, the percentage of tumor cells in S phase did not correlate significantly with 7-AMD stainability (P = 0.07), while the light scattering (cell size) of G0/G1 cells was highly correlated to 7-AMD binding (P less than 0.001).


Assuntos
Linfócitos B/metabolismo , Cromatina/metabolismo , Dactinomicina/análogos & derivados , Citometria de Fluxo , Ativação Linfocitária , Ciclo Celular , Dactinomicina/metabolismo , Humanos , Técnicas In Vitro , Transcrição Gênica
15.
Cancer Res ; 52(18): 5007-12, 1992 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-1516056

RESUMO

Chromatin structure-dependent binding of the DNA-specific dye 7-aminoactinomycin D (7-AMD) in leukemic and normal cells in bone marrow aspirates from childhood acute leukemia patients and patients without bone marrow neoplasia was assessed by multiparameter flow cytometry. Simultaneous staining with fluorescein isothiocyanate-labeled antibodies was needed in many cases for determination of the immunophenotype of the cells that exhibited differential binding of 7-AMD. 7-AMD binding was enhanced in normal (4 patients) and malignant (8 patients) myeloid cells, and was generally low in normal and leukemic lymphocytes and normoblasts. Four of 18 aspirates from 16 patients with acute lymphoblastic leukemia contained neoplastic cells with increased 7-AMD binding capability. The 7-AMD binding of the leukemic cells was not correlated to S-phase fraction (P = 0.07), but was significantly correlated to cell size as measured by forward angle light scattering (r = 0.49, P = 0.007). Patients with tumor cells exhibiting low 7-AMD binding at last aspirate survived significantly longer than the patients with leukemic cells binding high amounts of 7-AMD (P = 0.03). Neither cell size, S-phase fraction, nor ploidy status predicted patient survival in this small scale study.


Assuntos
Cromatina/ultraestrutura , DNA/metabolismo , Dactinomicina/análogos & derivados , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Antígenos CD/análise , Ciclo Celular , Criança , Cromatina/metabolismo , Dactinomicina/metabolismo , Citometria de Fluxo , Células-Tronco Hematopoéticas/imunologia , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Análise de Sobrevida , Transcrição Gênica
16.
J Clin Oncol ; 19(11): 2927-36, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11387366

RESUMO

PURPOSE: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. PATIENTS AND METHODS: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. RESULTS: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71). CONCLUSION: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Idoso , Transplante de Medula Óssea , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Prospectivos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
17.
Hypertension ; 29(1 Pt 1): 53-7, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9039080

RESUMO

We studied the role of nitric oxide and adrenergic activation in the blood pressure (BP) response to exogenous bradykinin in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Rats were pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the alpha-adrenergic receptor antagonist phentolamine together with L-NAME, or phentolamine alone. Sham-injected rats were used as controls. All rats subsequently received bradykinin (3, 6, and 30 micrograms/kg i.v.). Bradykinin induced a concentration-dependent fall in BP in both WKY and SHR (P < .0005). The change in BP was greater in SHR than WKY (P < .0001). BP before bradykinin administration was elevated in the L-NAME group in both strains. In WKY, L-NAME or L-NAME plus phentolamine did not alter the delta BP concentration-response curve to bradykinin (P = NS), whereas in SHR, the delta BP concentration-response curve was attenuated (P < .0048). The attenuation was observed for the two lower bradykinin doses (P < .0005) but not the highest. In SHR, phentolamine alone reduced BP before bradykinin to the same level as in WKY controls, and its delta BP concentration-response curve was not different from that of the normotensive controls or L-NAME and L-NAME plus phentolamine SHR groups. No difference was observed in the duration of the hypotensive response in SHR compared with WKY. The present results confirm that in normotensive rats, the hypotensive effect of bradykinin was mediated by an unknown mechanism other than through the release of nitric oxide. However, in SHR, this mechanism was amplified by additional activation of nitric oxide synthesis. This bradykinin-activated nitric oxide production may be a pressure-induced mechanism to counteract the hypertensive condition.


Assuntos
Bradicinina/farmacologia , Hipertensão/metabolismo , Hipotensão/induzido quimicamente , Óxido Nítrico/biossíntese , Antagonistas Adrenérgicos alfa/administração & dosagem , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Bradicinina/administração & dosagem , Bradicinina/uso terapêutico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Hipertensão/tratamento farmacológico , Injeções Intravenosas , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase/antagonistas & inibidores , Fentolamina/administração & dosagem , Fentolamina/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
18.
Eur J Cancer ; 36(14): 1762-8, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10974623

RESUMO

We examined retrospectively the outcome of patients with non-Hodgkin's lymphoma (NHL) with systemic involvement of the central nervous system (CNS) registered at The Norwegian Radium Hospital (NRH) from 1980 to 1996, in order to evaluate our treatment strategy for these patients. 170 of 2561 patients (6.6%) had CNS involvement, 140 (5.5%) systemic CNS lymphoma (SCNSL) and 30 (1.2%) primary CNS lymphoma (PCNSL). Description of the patients, time of SCNSL diagnosis, symptoms at CNS diagnosis, treatment and survival were registered. The overall median survival for the 140 patients with SCNSL was 2.6 months (95% confidence interval (CI) 2.1-3.2), only 12 patients are alive in complete remission (CR). Patients with CNS involvement at diagnosis, relapse or progression during treatment for NHL had a median survival of 5.4 months (95% CI: 0.3-10.6), 3.8 months (95% CI: 0.0-9.1), and 1.8 months (95% CI: 1.0-2. 7), respectively (P=0.001). 5 of the 8 patients consolidated with high-dose therapy (HDT) are in CR. Paresis was the only symptom that predicted survival for SCNSL. Patients above 60 years of age with CNS involvement at progression or relapse and those with paresis at the time of CNS diagnosis have a dismal prognosis. For these patients supportive therapy only should be considered. For patients under 60 years of age with chemosensitive disease, the trend was toward better prospects, and they should be offered intensive chemo-radiotherapy including HDT with autologous stem cell support.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Intervalo Livre de Doença , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/radioterapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos
19.
Eur J Cancer ; 34(12): 1865-70, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10023307

RESUMO

We present the socio-medical situation for 459 adult disease-free long-term survivors of Hodgkin's disease (HD) 3-23 years after first line curative treatment. In 1994, 557 patients were sent a self-report questionnaire relating to their social status and 459 patients (82%) replied. Educational or professional plans were changed due to HD in 142 patients (32%). After 6, 12 and 18 months from start of treatment, 52, 82 and 95% of the patients, respectively, had returned to their job or education. The sum of full-time and part-time employment was in men 78% at diagnosis and 85% at follow-up, and in women 57% at diagnosis and 64% at follow-up. Only 2% of men and 3% of women did not have a job at follow-up in 1994. At diagnosis 2% of the patients were permanently disabled versus 19% at follow-up in 1994. Age > 40 years at diagnosis, increased the total score of psychological distress and fatigue and long-term disablement after first line treatment were predictors for permanent disablement. Transient or permanent sexual problems were reported in 16% and 13%, respectively. MVPP (mustine, vinblastine, procarbazine and prednisone) or LVPP (chlorambucil, vinblastine, procarbazine and prednisone) chemotherapy was responsible for most cases of early menopause in women older than 30 years, and of infertility in both men and women. In summary, most long-term HD survivors had adapted well to their socio-medical situation except a high number of permanently disabled patients. By focusing more on factors predisposing for permanent disablement and early treatment for these, more patients may be helped to return to their job.


Assuntos
Emprego , Doença de Hodgkin/psicologia , Sobreviventes/psicologia , Adolescente , Adulto , Idoso , Escolha da Profissão , Pessoas com Deficiência/psicologia , Intervalo Livre de Doença , Saúde da Família , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Infertilidade/etiologia , Relações Interpessoais , Masculino , Casamento , Distúrbios Menstruais/etiologia , Pessoa de Meia-Idade , Disfunções Sexuais Fisiológicas/etiologia
20.
Eur J Cancer ; 33(14): 2380-3, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9616285

RESUMO

The aim of the study was to investigate the incidence rate and time trends in a national registry population of Hodgkin's disease (HD) and the effects of selection in a hospital population. A national registry population of all HD patients from Norway and a hospital population of HD patients treated at the Norwegian Radium Hospital (NRH) were studied retrospectively from 1971 to 1993. The incidence of non-Hodgkin's lymphomas (NHL) in Norway increased steadily from 1961 in contrast to a stable incidence pattern for HD before 1980 and a decreasing incidence since 1980. Due to improved diagnostic tools after 1980, an increasing proportion of patients previously diagnosed as lymphocyte depleted and unclassified HD were classified as NHL. As these histologies are dominant in older patients, the incidence of older patients with HD and the total population of HD have decreased since 1980. As a result, the proportion of young adults with a favourable histology has increased. These changes may partly explain the increased patient survival observed both in the national and the hospital population. The hospital population comprised 92% of patients aged 15-39 years, 80% of patients aged 40-59 years and 53% of patients aged > 60 years in the national population. The selection of younger patients in the hospital material may explain a higher survival rate as compared with the national population.


Assuntos
Doença de Hodgkin/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Feminino , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
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