RESUMO
The aim of this study was to evaluate to what extent the quality of life (QOL) of young patients with chronic myelocytic leukemia (CML) was affected by treatment with interferon (IF) and intensive chemotherapy. In a main study performed by The Swedish CML Group, aiming at reduction of the malignant pH+ cell clone by treatment with hydroxyurea and IF followed by ABMT, QOL was evaluated with VAS scales and the Life Ingredient Profile in 44% of the patients. The intensive treatment did not lead to intolerable suffering or protracted reduction in QOL. However, 80% of the patients were on sick leave during the first year of treatment.
Assuntos
Transplante de Medula Óssea , Interferons/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Qualidade de Vida , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Interferons/efeitos adversos , Masculino , Pessoa de Meia-Idade , Licença Médica , Transplante AutólogoAssuntos
Neoplasias Encefálicas/metabolismo , Transtornos Cerebrovasculares/metabolismo , Falência Renal Crônica/metabolismo , Proteínas/metabolismo , Proteínas Sanguíneas/análise , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/urina , Proteínas do Líquido Cefalorraquidiano/análise , Transtornos Cerebrovasculares/sangue , Transtornos Cerebrovasculares/líquido cefalorraquidiano , Transtornos Cerebrovasculares/urina , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/líquido cefalorraquidiano , Falência Renal Crônica/urina , Peso Molecular , Proteinúria/diagnósticoAssuntos
Doenças Hematológicas/terapia , Hepatite C/transmissão , Reação Transfusional , Doenças Hematológicas/complicações , Doenças Hematológicas/imunologia , Hepacivirus/imunologia , Hepatite C/epidemiologia , Hepatite C/imunologia , Humanos , Técnicas Imunológicas , Estudos Retrospectivos , Testes Sorológicos , Suécia/epidemiologiaRESUMO
Lymphocytes from 27 patients with B-type chronic lymphocytic leukaemia (CLL) were tested with immunofluorescence for expression of surface membrane immunoglobulin (SmIg) and the B cell antigen 7420. When age at time of testing, sex, clinical stage according to Binet, disease progression according to Levin and percentage of SmIg and 7420 antigen-expressing cells were used as explanatory variables for survival in a linear logistic regression model, only the SmIg variable was significant (p less than 0.025). A high proportion of SmIg bearing cells (greater than 61%) was associated with short survival, large tumour mass and aggressive disease. The tentative conclusion is drawn that the differentiation stage of the tumour cells in CLL determines the clinical course of the disease and is inversely correlated to the SmIg expression.
Assuntos
Leucemia Linfoide/diagnóstico , Receptores de Antígenos de Linfócitos B/análise , Idoso , Transformação Celular Neoplásica , Feminino , Humanos , Expectativa de Vida , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , PrognósticoRESUMO
In this retrospective investigation from Malmö, a city well-suited for epidemiologic studies, 177 patients (88 males and 89 females) with polycythemia vera (PV) were identified between 1950 and 1984. The incidence rate (number of cases/100,000/yr) in both sexes increased significantly, being 1.0 in 1950-1959 and 2.6 in 1980-1984 (adjusted to the European age-standardized population). This is the highest rate reported to date. In 1970-1984 the highest age-specific incidence rates (number of cases/100,000/yr) were found in males greater than or equal to 80 yr and females 70-79 yr of age, being 18.3 and 14.6, respectively. A subgroup of 12 (7%) was identified where the PV diagnosis was not obvious on entry into the study but where it became clear during follow-up. 16 PV patients (9%) had verified or suspected arterial hypoxemia caused by a concomitant condition. We conclude that the increasing PV incidence rates, mainly confined to older age groups, are probably due to better case ascertainment.
Assuntos
Policitemia Vera/epidemiologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Incidência , Leucocitose/epidemiologia , Leucocitose/etiologia , Masculino , Pessoa de Meia-Idade , Policitemia Vera/fisiopatologia , Caracteres Sexuais , Esplenomegalia/epidemiologia , Esplenomegalia/etiologia , Suécia/epidemiologia , Trombocitose/epidemiologia , Trombocitose/etiologia , População UrbanaRESUMO
The serum level of N-terminal propeptide of collagen III (Col 1-3) has received increasing attention as a possible marker of liver fibrosis. Elevated levels have been reported in patients with primary biliary cirrhosis (PBC). We measured Col 1-3 levels in 24 patients with PBC (mean age 56 +/- 8 years) and compared their value as a prognostic marker with serum bilirubin and IgM levels, the aminopyrine demethylating capacity (ABT) and presence of clinical symptoms. Mean observation time was 5.1 +/- 2.7 years. When these parameters and age were evaluated as predictive factors for survival, only bilirubin, Col 1-3 levels and symptom status variables were found to be significant. When tested as explanatory variables for survival in a stepwise linear logistic regression model Col 1-3 was identified as the strongest significant (P less than 0.001) explanatory variable followed by bilirubin (P less than 0.01) whereas the symptom status emerged as a non-significant variable. The results suggest that the serum level of Col 1-3 may be a useful prognostic indicator in PBC, which is independent of the bilirubin level.
Assuntos
Cirrose Hepática Biliar/sangue , Pró-Colágeno/sangue , Adulto , Fatores Etários , Idoso , Bilirrubina/sangue , Feminino , Humanos , Imunoglobulina M/análise , Cirrose Hepática Biliar/mortalidade , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , PrognósticoRESUMO
We recently reported on a heterologous antiserum (antiserum 7420), raised against chronic lymphocytic leukaemic lymphocytes, that reacts with B-lymphocyte antigen(s) different from known B-cell markers such as HLA-DR (Ia-like) antigens, surface immunoglobulin, and the Fc receptor. This antiserum is now shown to react also with a C3-receptor-positive population of lymphocytes from the dog, monkey, ox and sheep but not from rodents and avians. The antiserum does not react with the non-lymphoid human cells mature granulocytes, thrombocytes, erythrocytes, or spermatozoa, nor with the cultured cell lines tested, i.e. fibroblasts, melanoma cells, HeLa cells and green monkey kidney cells. This reactivity pattern differs somewhat from that reported for HLA-DR antiserum. The antigen(s) defined by the 7420 antiserum and the C3 receptor are different, since they redistribute independently on the lymphocyte surface.
Assuntos
Linfócitos B/imunologia , Antígenos de Histocompatibilidade Classe II , Absorção , Animais , Plaquetas/imunologia , Bovinos , Linhagem Celular , Galinhas , Chlorocebus aethiops , Cães , Eritrócitos/imunologia , Sangue Fetal/imunologia , Granulócitos/imunologia , Cobaias , Humanos , Fragmentos Fab das Imunoglobulinas , Masculino , Camundongos , Coelhos , Ratos , Saimiri , Ovinos , Espermatozoides/imunologiaRESUMO
A 67-year-old man with malignant lymphoma and acquired von Willebrand's disease is described. His bleeding symptoms started late in life and at this time a monoclonal IgGK serum protein was found. He had a prolonged bleeding time, decreased platelet adhesiveness, low values for factor VIII clotting activity (VIII:C), factor VIII related antigen (VIIIR:Ag) and ristocetin co-factor activity (VIII:Rcof). Infusion of factor VIII concentrates (fraction I-0) did not correct the abnormalities. No inhibitory activity in vitro of the patient's plasma or IgG fraction could be demonstrated against VIII:C, VIIIR:Ag and VIII:Rcof. In order to demonstrate an antibody that binds factor VIII without inhibiting its biological activities in vitro, advantage was taken of the fact that staphylococcal protein A strongly binds the Fc part of IgG molecules. Addition of staphylococci to mixtures of patient IgG and a factor VIII preparation resulted in removal of all factor VIII activities (VIII:C, VIIIR:Ag, VIII:Rcof) from the supernatant at sedimentation of the bacteria. The active binding principle was the M-component, i.e. probably a monospecific antibody molecule. We hypothesize that the complex is formed in vivo and eliminated at an accelerated rate.
Assuntos
Imunoglobulina G , Linfoma/imunologia , Neoplasias Gástricas/imunologia , Doenças de von Willebrand/etiologia , Idoso , Sítios de Ligação de Anticorpos , Testes de Coagulação Sanguínea , Fator VIII/análise , Fator VIII/imunologia , Humanos , Fragmentos Fc das Imunoglobulinas , Imunoglobulina G/isolamento & purificação , Linfoma/sangue , Linfoma/complicações , Masculino , Proteína Estafilocócica A/imunologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/complicações , Doenças de von Willebrand/sangue , Doenças de von Willebrand/imunologiaRESUMO
A heterologous antiserum (antiserum 7420) against B-lymphocyte antigen(s) was raised in a rabbit by immunization with peripheral blood lymphocytes from a patient with chronic lymphocytic leukaemia (CLL). After absorptions with pooled normal human serum, IgA, IgD, and IgM M-components, the fluorescein isothiocyanate-conjugated F(ab')2 fragments were prepared and further absorbed with normal peripheral blood leucocytes. The F(ab')2 fragments, studied in direct immunofluorescence, reacted with both normal and CLL B lymphocytes but not with T lymphocytes. Comparative studies with an HLA-DR antiserum showed that the antigen(s) detected by 7420 antiserum did not redistribute together with HLA-DR antigens in cocapping experiments, nor did the HLA-DR antiserum block the reaction of 7420 F(ab')2 fragments with B lymphocytes. The 7420 F(ab')2 fragments prcipitated detergent-solubilized B-cell membrane material with a molecular weight of around 40,000 and 150,000 daltons. The conclusion drawn is that the 7420 and HLA-DR antigens are different. The 7420 antigen was also shown to be different from classical HLA antigens, beta 2-microglobulin, surface immunoglobulin, the Fc receptor, and HC protein.
Assuntos
Linfócitos B/imunologia , Epitopos , Soros Imunes , Animais , Antígenos de Superfície/análise , Imunofluorescência , Antígenos HLA , Humanos , Imunização , Fragmentos Fab das Imunoglobulinas , Fragmentos Fc das Imunoglobulinas , Leucemia Linfoide/imunologia , CoelhosRESUMO
One IgG1(kappa), one IgM(kappa), and one IgA1(kappa) monoclonal (M)-component were purified from one human serum. Rabbit antisera were raised against the IgG and IgM M-components and were absorbed until specific for idiotypic determinants on these molecules. All three M-components gave reactions of immunological identity when tested by double radial immunodiffusion with either of the two idiotype-specific antisera. Both heavy and light chains were isolated from each of the three M-components and all preparations inhibited formation of idiotypic precipitates. None of these preparations formed precipitates with idiotype-specific antisera alone. When heavy or light chains of one M-component were hybridized with light or heavy chains from the other M-components the resultant molecules precipitated with anti-idiotypic serum. Hybrids with chains from polyclonal IgG were not precipitable with such antiserum. These results indicate that the variable region of the heavy chains of these M-components of three different immunoglobulin classes are closely similar, if not identical.
Assuntos
Epitopos , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Idoso , Humanos , Imunodifusão , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , MasculinoRESUMO
A new micro-method for the quantitative measurement of phagocytosis by neutrophils is described. The material used for phagocytosis consists of a radioactive oil emulsion coated with E. coli lipopolysaccharide. Uptake of radioactive material is a function of cell number, duration of incubation, dilution of serum used for opsonization, content of lipopolysaccharide and concentration of emulsion. This method can be used to quantify rapidly and precisely phagocytosis rates of as few as 5 x 10(4)-10(6) polymorphonuclear leucocytes and the opsonic activity of 10 microliter serum.
Assuntos
Técnicas Imunológicas , Fagocitose , Albuminas/farmacologia , Contagem de Células , Emulsões , Humanos , Radioisótopos do Iodo , Neutrófilos/citologia , Neutrófilos/imunologia , Proteínas Opsonizantes/análiseRESUMO
The development of antibodies to factor VIII is a serious complication of the treatment of patients with hemophilia A. We successfully induced immune tolerance in patients with such antibodies with a new treatment protocol, which combined factor VIII, cyclophosphamide, and high-dose intravenous IgG, followed by regular prophylactic treatment with factor VIII. This protocol has now been used in 11 patients with hemophilia A, of whom 9 had a strong antibody response. When the initial concentration of antibodies exceeded 3 Malmö inhibitor units (corresponding to about 10 Bethesda units) per milliliter, treatment was preceded by adsorption of antibody to protein A. After two to three weeks of the combined treatment, factor VIII coagulant antibodies had disappeared in 9 of the 11 patients; in 8 of these 9 patients the half-life of infused factor VIII had normalized. The tolerant state appears to be stable after a median of 30 months. Two patients did not respond to the treatment. Because earlier treatment with factor VIII and cyclophosphamide or with factor VIII and IgG had been ineffective in these patients, our experience suggests that all three components of the protocol are required for the successful induction of tolerance to factor VIII.
Assuntos
Anticorpos/análise , Ciclofosfamida/administração & dosagem , Fator VIII/administração & dosagem , Hemofilia A/terapia , Tolerância Imunológica , Imunoglobulina G/administração & dosagem , Adolescente , Adulto , Pré-Escolar , Esquema de Medicação , Quimioterapia Combinada , Fator VIII/imunologia , Hemofilia A/imunologia , Humanos , Pessoa de Meia-IdadeRESUMO
In a patient with severe haemophilia B and antibodies against factor IX in high titre, and known for many years to be a really high responder, it was possible to suppress the secondary antibody response after treatment with high doses of intravenous IgG (Gammonativ, KabiVitrum AB) combined with factor IX and cyclophosphamide. After 2 further treatments, including IgG, a total disappearance of the IX:C inhibitor was noted. The patient now treats himself at home with weekly infusions of only factor IX concentrate. Survival of IX:C is normal, though IX antigen (IX:Ag), as measured with the original antibody in an immunoradiometric assay, persists for at least a week after concentrate infusion. We have not been able to demonstrate an antiidiotypic antibody. Instead the antigenic factor IX material circulates complexed to a 'new' antibody without anticoagulant activity. Theoretically at least, the persistence of such immune complexes may be important for sustaining the patient's tolerance to the anticoagulant antibody's epitope. The initial IgG treatment appears as a crucial factor for induction of tolerance in this case.
Assuntos
Autoanticorpos/isolamento & purificação , Fator IX/imunologia , Hemofilia A/sangue , Adulto , Ciclofosfamida/uso terapêutico , Fator IX/uso terapêutico , Hemofilia A/imunologia , Hemofilia A/terapia , Humanos , Imunoglobulinas/análise , Imunoterapia , Masculino , Valores de Referência , gama-Globulinas/administração & dosagemRESUMO
An approach to the problem of inducing tolerance in patients with hemophilia complicated by high-responding antibodies is described. Thus, in four patients with severe hemophilia B and high-responding antibodies against factor IX, it has been possible to modify the immune response by giving high doses of intravenous IgG in combination with cyclophosphamide and factor IX, followed by regular factor IX treatment. In three of the patients, the in vivo recovery and half-life of infused factor IX coagulant activity (IX:C) are now normal, while the fourth patient has been converted to a low responder. Hip replacement surgery has been performed successfully in one patient. The tolerant state in these four patients is characterized, and they have all been found to have complexes between factor IX antigen and a "new" antibody without IX:C inhibitory activity. The disappearance rate of the complexed factor IX antigen (i.e., lacking IX:C activity) is considerably prolonged, and the persistence in the circulation of this (probably modified) factor IX molecule may be crucial, since tolerance to factor IX treatment was only induced when immunocomplexes were produced. Since earlier treatment of the patients with cyclophosphamide and factor IX, but without IgG, failed to induce tolerance, it appears to be the IgG that is the prerequisite.
Assuntos
Fator IX/imunologia , Hemofilia B/imunologia , Imunoglobulina G/uso terapêutico , Adolescente , Adulto , Anticorpos Anti-Idiotípicos/imunologia , Ciclofosfamida/uso terapêutico , Hemofilia B/terapia , Humanos , Idiótipos de Imunoglobulinas/imunologia , Terapia de Imunossupressão , Masculino , Pessoa de Meia-IdadeRESUMO
We recently described tolerance induction with factor VIII/IX, cyclophosphamide, and high-dose intravenous IgG in hemophilia A or B patients with coagulation inhibitory antibodies. Circulating noninhibitory antibodies complexed with factor IX have been demonstrated in tolerant hemophilia B patients. Similar findings are now described in six tolerant hemophilia A patients. Complexes between factor VIII and the 'tolerant' antibody were demonstrated by subjecting plasma to gel filtration chromatography, void fractions containing factor VIII/vWF complexes being collected and adsorbed to protein A. Using 125I-labeled F(ab')2 fragments against IgG subclass and factor VIII antigen, complexes between an IgG4 antibody and factor VIII were found to adsorb to protein A. After infusion of factor VIII to tolerant patients, all factor VIII circulated in complex with IgG4 antibody. In three of the patients, the 'tolerant' antibodies inhibited an ELISA specific for factor VIII light chain but, unlike the pretolerant antibodies, did not bind radiolabeled factor VIII heavy chain. Although after induction of tolerance the patients still have circulating IgG4 antibodies against factor VIII, the antibodies differ in specificity, lack coagulation inhibitory activity, and do not enhance the rate of elimination of factor VIII.
Assuntos
Coagulação Sanguínea , Fator VIII/imunologia , Hemofilia A/terapia , Complexo Antígeno-Anticorpo/análise , Complexo Antígeno-Anticorpo/imunologia , Reações Antígeno-Anticorpo , Cromatografia em Gel , Fator VIII/administração & dosagem , Fator VIII/farmacocinética , Humanos , Imunoglobulina G/imunologia , Terapia de Imunossupressão , SolubilidadeRESUMO
A case with clinical and histological features resembling angioimmunoblastic lymphadenopathy, but with a very marked decrease in B-lymphocytes instead of T-lymphocytes is presented.
Assuntos
Linfócitos B/imunologia , Linfadenopatia Imunoblástica/imunologia , Idoso , Humanos , Linfadenopatia Imunoblástica/patologia , Linfonodos/patologia , MasculinoRESUMO
An IgM lambda M-component with a false Wasserman reaction and 'false' rheumatoid factor activity from a patient suffering from a well-differentiated lymphocytic lymphoma is presented. The monoclonal protein showed antibody activity against cardiolipin and cross-reacted with acryl particles, not with human IgG. Both these activities were found in the Fab fragment. The reduction of the 19S IgM to 7S IgM subunits was responsible for a strong decrease in activity. The importance of the IgM quaternary structure in determining antibody affinity is emphasized.
Assuntos
Imunoglobulina M/imunologia , Linfoma não Hodgkin/imunologia , Acrilatos , Afinidade de Anticorpos , Sítios de Ligação de Anticorpos , Cardiolipinas/imunologia , Reações Cruzadas , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Fragmentos Fc das Imunoglobulinas/imunologia , Cadeias lambda de Imunoglobulina , Fator ReumatoideRESUMO
The authors review 18 patients with multiple myeloma who had bone destruction of a kind that indicated surgical therapy. Eight patients had paralegic myelopathy and one had compression of the cauda equina. Four of them displayed partial to complete regression. One patient lived for 77 months after the operation, most of the time in excellent condition. The operative technique is discussed, with laminectomy, exeresis, filling of bone with cement and, in some instances, mechanical support from metal plates. Early diagnosis and operation is imperative, postoperative irradiation obligatory in severe cases. Radiation alone may be the method of choice in early stages. The other 9 patients were operated upon for bone destruction in the limbs. A Moore operation on the destroyed hip was performed in one patient, who lived in excellent condition for about four years. Active surgical therapy combined with radiation and cytostatics seems to be of value in many patients with multiple myeloma.