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Biomedical subjects

O Zettervall

Publications and source records attributed to O Zettervall.

At least 19 recordsLinked to original sources
PubMed1997

Quality of life in young patients with chronic myelocytic leukaemia during intensive treatment including interferon.

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.

Adult↗
PubMed1997

Poor survival in t(8;21) (q22;q22)-associated acute myeloid leukaemia with leukocytosis.

Twenty-nine consecutive cases with a t(8;21)(q22;q22) in the bone marrow (BM) karyotype were retrospectively studied concerning clinical, morphological and cytogenetic data. All had been diagnosed as acute myeloid leukaemia (AML), 27 FAB subtype M2 and two M1, comprising 5% of all cytogenetically analysed AML during 18 yr. Auer rods were the most consistent t(8;21)-associated morphological finding and were demonstrated in 92% of the reviewed BM specimens, whereas BM eosinophilia was seen in only 24%. The median age was 53 yr, and 30% of the patients were > 60 yr old. Twenty-four patients had received induction chemotherapy; 22 of these (91%) entered a complete remission (CR). The median survival time in treated patients was 18 months. Leukocytosis at diagnosis (> or = 20 x 10(9)/1) was significantly (p = 0.01) associated with shorter survival time. All four children are still in first CR after 9-80 months. Seven cases (25%) developed granulocytic sarcomas, discovered either at diagnosis (n = 4) or at first relapse (n = 3). Secondary chromosome abnormalities were found in 62% of the cases, most often loss of a sex chromosome. The presence of such secondary aberrations did not correlate with any morphological or clinical characteristics, including survival. This first Scandinavian study of AML with t(8;21) corroborates the previous findings that these AMLs are characterized by distinct morphological features, a high frequency of CR and a striking tendency to develop extramedullary leukaemic manifestations. Leukocytosis at diagnosis indicates a less favourable prognosis.

Adolescent↗
PubMed1992

Incidence of polycythemia vera in a defined population.

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.

Adult↗
PubMed1990

Noncoagulation inhibitory factor VIII antibodies after induction of tolerance to factor VIII in hemophilia A patients.

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.

Antigen-Antibody Complex↗
PubMed1988

Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII.

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.

Adolescent↗
PubMed1987

A sulfhydryl-rich IgM protein with multiple serological specificities.

A monoclonal IgM lambda protein from a patient (E.T.) suffering from a lymphocytic lymphoma agglutinated Salmonella typhi bacteria and uncoated acryl particles. The antigenic determinant on Salmonella typhi bacteria was found to be 0-12 (alpha-D-Galp-(1-2)-alpha-D-Manp) while the structure on acryl particles recognized by IgM ET has not been defined. Both binding sites for bacteria and acryl particle determinants are localized on the same IgM molecule. The uncommon affinity of this IgM protein for some divalent heavy metal ions led to the finding of an unusually high content of sulfhydryl groups in the Fab portion of the molecule.

Acrylates↗
PubMed1986

The N-terminal propeptide of collagen type III in serum as a prognostic indicator in primary biliary cirrhosis.

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.

Adult↗
PubMed1986

Induction of split tolerance and clinical cure in high-responding hemophiliacs with factor IX antibodies.

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.

Adolescent↗
PubMed1985

Characterisation of the tolerant state in a patient with haemophilia B after removal of high-titre factor IX antibodies.

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.

Adult↗
PubMed1985

High expression of lymphocyte surface immunoglobulin in chronic lymphocytic leukaemia may be a bad prognostic sign.

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.

Aged↗
PubMed1984

Comparison of trends in the incidence of multiple myeloma in Malmö, Sweden, and other countries, 1950-1979.

Dramatic increases in mortality from multiple myeloma have been reported in the United States and the United Kingdom over the past three decades. To assess what fraction of this increase, if any, might be attributable to a change in the incidence of this disease, we examined the incidence of multiple myeloma during 1950 to 1979 in Malmö, Sweden, a city chosen because of its medical community's longstanding interest in this disease. The average annual incidence rates per 100,000 population were 4.9 for males and 3.7 for females (adjusted to the European age-standardized population). These rates are among the highest in the world. Unlike secular trends for myeloma in the United States and the United Kingdom, where large increases in mortality rates have been reported, the rates in Malmö have increased only slightly, and the increase was restricted to males, suggesting the possibility of environmental causes. We suggest that the rates in Malmö may represent the asymptote of myeloma's incidence that will be approached in other white populations as case ascertainment among them becomes complete.

Adult↗
PubMed1981

Cellular expression of the non-HLA-DR B-cell antigen 7420: studies on non-lymphoid cells and on lymphocytes from different species.

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.

Absorption↗
PubMed1979

Heterologous B-cell antisera may detect non-Ig, non-HLA-DR antigens.

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.

Animals↗
PubMed1979

An IgM monoclonal protein with multiple serological specificities.

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.

Acrylates↗