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J Samuelsson

Publications and source records attributed to J Samuelsson.

At least 19 recordsLinked to original sources
PubMed2003

No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: better outcome in patients with less proliferative disease.

In this prospective randomized multicenter trial 93 patients, median age 72 years, with RAEB-t (n=25) and myelodysplastic syndrome (MDS)-AML (n=68) were allocated to a standard induction chemotherapy regimen (TAD 2+7) with or without addition of granulocyte-macrophage-CSF (GM-CSF). The overall complete remission (CR) rate was 43% with no difference between the arms. Median survival times for all patients, CR patients, and non-CR patients were 280, 550, and 100 days, respectively, with no difference between the arms. Response rates were significantly better in patients with serum lactate dehydrogenase (S-LDH) levels </=9.5 microkat/l, bone marrow cellularity </=70%, and WBC counts <4.0 x 10(9)/l, but S-LDH was the only variable independently associated with response by logistic regression analysis. Cox's regression analysis identified four significant prognostic factors for survival: bone marrow cellularity, S-LDH, cytogenetic risk group (International Prognostic Scoring System), and age. Only bone marrow cellularity (P=0.01) and S-LDH (P=0.0003) retained statistical significance in the log-rank test. Severe adverse events were significantly more common in the GM-TAD arm (P=0.01). Thus, addition of GM-CSF to chemotherapy showed no clinical benefit in terms of response but carried an increased risk for side effects. We present a clinically useful tool to predict response to chemotherapy and survival in elderly patients with transforming MDS, favoring patients with features of less proliferative disease.

Acute Disease↗
PubMed2001

Measurements of methane emissions from landfills using a time correlation tracer method based on FTIR absorption spectroscopy.

Methane is an important climate gas contributing significantly to global warming. A large part of the anthropogenic emissions of methane comes from landfills. Due to the biogenic origin of these emissions and the inhomogeneous characteristics of landfills and their soil cover, these emissions show large spatial variation. Thus, development of reliable and cost-effective methods for measurements of these emissions is an important task and a challenge to the scientific community. Traditionally, field chamber methods have been used but also different area integrating methods based on downwind plume measurements. These measurements have been supported by meteorological data either directly from local measurements or by controlled release of tracer gas from the landfill providing the dispersion characteristics of the plume. In this paperwe describe a method,the Time Correlation Tracer method, combining controlled tracer gas release from the landfill with time-resolved concentration measurements downwind the landfill using FTIR absorption spectroscopy. The method has been tested and used on measurements at a landfill in southern Sweden over the past 1.5 years. The method has proven to be a usable method for measurements of total methane emission from landfills, and under favorable meteorological conditions we estimate an achievable accuracy of 15-30%. The real time analysis capability of the FTIR makes it possible to judge the success of the measurement already on site and to decide whether more measurements are necessary. The measurement strategy is relatively simple and straightforward, and one person can make a measurement from a medium sized landfill (1-4 ha) within a few days to a week depending on the meteorological situation.

Air Pollutants↗
PubMed2001

Quantitative evaluation of microplankton palaeobiogeography in the Ordovician-Early Silurian of the northern Trans European Suture Zone: implications for the timing of the Avalonia-Baltica collision.

Quantitative analysis of assemblage similarity among chitinozoan and acritarch associations recovered from various sedimentary sequences across the Trans European Suture Zone (TESZ; southern Baltic Sea and northern Germany region), permits evaluation of changes in microplankton palaeobiogeography during the Ordovician in the study area. The present data confirm strong palaeobiogeographic differences between the lower Ordovician of the Rügen area, and the coeval domains of the East European Platform (EEP), corroborating the idea that the subsurface of Rügen should be considered palaeogeographically as the eastern extension of Avalonia.Cluster analysis of chitinozoan assemblages from numerous wells in the Rügen area, and one well from the southern margin of the EEP indicates that chitinozoan bioprovincialism reached its maximum during the Llanvirn; during this period, the Rügen microplankton communities were clearly Gondwanan in character. Calculations using the coefficient of similarity support the conclusion of a high similarity between Llanvirn acritarch assemblages from the Rügen subsurface and from coeval Perigondwana localities (e.g. Tunisia). Since the early Caradoc, this Gondwanan affinity of the Rügen microfossils starts to lessen, and becomes negligible during the late Caradoc. During latest Caradoc-early Ashgill through Llandovery times the chitinozoan assemblages from either side of the TESZ are undistinguishable. If palaeobiogeographical differentiation is primarily related to palaeolatitudinal distance, then the present data support closure of the Tornquist Ocean during late Caradoc-Ashgill times. The presence of reworked Llanvirn acritarchs of Perigondwanan affinity in middle Ashgill sedimentary sequences at the southern margin of the EEP, clearly shows that by this time erosion of an uplifted area was taking place. Accordingly, the closure of the Tornquist Ocean, and consequent Avalonia-Baltica collision must have taken place during the time interval between the middle Caradoc and the early middle Ashgill (Rawtheyan).New chitinozoan data from boreholes H 2 and K 5, offshore of Rügen Island, northern Germany, allow for precise biostratigraphic dating. In the pre-Devonian part of H 2, Siphonochitina formosa indicates an Abereiddian (Early Llanvirn) age, facilitating correlation with boreholes Binz 1/73 and Lohme 2/70 of Rügen. In borehole K 5, the occurrence of Belonechitina robusta and Tanuchitina bergstroemi permits attribution of the investigated pre-Carboniferous sequence to the middle-late Caradoc, and, possibly, early Ashgill.

Journal Article↗
PubMed2000

Ordovician chitinozoan biozonation of the Brabant Massif, Belgium.

Chitinozoans from seven Ordovician units (Abbaye de Villers, Tribotte, Rigenée, Ittre, Bornival, and Brutia formations and a new unnamed unit, here provisionally called the Asquempont unit) belonging to the mainly concealed Brabant Massif, Belgium are described herein. Fifty-six samples were taken from rocks cropping out at the south-eastern rim of the massif in the Orneau, Dyle-Thyle and Senne-Sennette valleys. Microfossil preservation is moderate to poor, and the chitinozoans occur in low numbers. Taxonomically, the recovered chitinozoans are distributed into 29 taxa, some placed under open nomenclature. Together with earlier published graptolite and acritarch data, the analysis of the chitinozoan assemblages resulted in an improved chronostratigraphy of the investigated formations. We propose a local chitinozoan biozonation with 11 zones for the Brabant Massif. The oldest investigated units yielded chitinozoans typical for North Gondwana, and younger units (starting in the middle Caradoc), yielded some taxa also common in Baltica. As the Brabant Massif formed part of the microcontinent Avalonia, the chitinozoan assemblages recovered from the massif support the inferred drifting of Avalonia from high latitudes towards middle latitudes in the Ordovician as was suggested earlier.

Journal Article↗
PubMed2000

Chitinozoan faunas from the Rügen Ordovician (Rügen 5/66 and Binz 1/73 wells), NE Germany.

The island of Rügen (NE Germany), situated close to the Trans-European Suture Zone (TESZ), in the southern Baltic Sea is underlain by sedimentary rocks of an Early Palaeozoic age, known only from boreholes. The wells, Rügen 5/66 and Binz 1/73, were investigated for their chitinozoan assemblages to improve the earlier biostratigraphic dating (graptolites and acritarchs) and to facilitate comparisons with other chitinozoan assemblages on both sides of the TESZ. In the lower part of the Rügen 5/66 core (3794.7-3615.8m), Lagenochitina destombesi Elaouad-Debbaj is indicative of an early late Tremadoc age. In the upper part of the same well (3287.3-1709.7m), the observed chitinozoan taxa suggest an age spanning the early Llanvirn to the Caradoc. The entire sampled interval of the Binz 1/73 core (5217.6-5041.8m) is interpreted as belonging to the Siphonochitina formosa Biozone (early-early late Abereiddian, corresponding to the early Llanvirn). The chitinozoan data corroborate the earlier suggested biostratigraphic ages, based on acritarchs and graptolites. The chitinozoans from the Binz 1/73 well point to a high latitude provenance of the investigated host sediments at time of deposition.

Journal Article↗
PubMed2000

Defective platelet aggregation in polycythaemia vera is not caused by impaired calcium signaling, phospholipase D activation or decreased amounts of focal adhesion proteins.

We have previously demonstrated that platelets in polycythaemia vera (PV) exhibit decreased aggregation after stimulation with platelet activating factor (PAF) and reduced expression of GPIIIa on both resting and stimulated platelets. In the present study, we investigated if these results were related to changes in the mobilization of intracellular calcium, activation of phospholipase D (PLD) or amounts of GPIIIa and the intracellular tyrosine kinases Fak, Syk, Grb2, Shc and rhoA. Intracellular calcium levels were not different in resting platelets from 14 PV patients and 15 healthy controls (median 43 nmol/L, range 10-114, vs. 36 nmol/L, range 10-119). After stimulation with PAF (1 micromol/L) an equal increase was seen (125 nmol/L for PV platelets, range 67-257, vs. 113 nmol/L for controls, range 60-250). Also formation of phosphatidyl ethanol (PEt) was similar after exposure to 0.5 U/ml thrombin (0.28% PEt of total phospholipid, range 0.16-1.10, vs. 0.24 for controls, range 0.11-2.3) and 1 micromol/L PMA (0.25, range 0.16-0.32, vs. 0.14, range 0.09-0.6). In contrast to the reduced amount of GPIIIa on the surface of PV platelets, immunoblotting on whole cell lysates showed no reduction in PV patients compared to controls, indicating the possibility of an impaired incorporation of GPIIIa to the cell membrane. Levels of Fak, Syk, Shc, Grb2 and rhoA appeared equal in patients and controls. Similar intracellular proteins were tyrosine phosphorylated after stimulation with thrombin, PAF and PMA. In summary, defective platelet aggregation after stimulation with PAF is caused by neither defective mobilization of intracellular calcium nor, in contrast to the situation in PV granulocytes, an impaired activation of PLD. Moreover, no apparent differences in the intracellular amounts of Fak, Syk Shc, Grb2 and rhoA could be detected between PV and control platelets.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Marked heterogeneity in protein levels and functional integrity of the thrombopoietin receptor c-mpl in polycythaemia vera.

Polycythaemia vera (PV) is a myeloproliferative disorder (MPD) characterized by an increased production of mature blood cells. The underlying pathogenic mechanisms behind PV are largely unknown. Thrombopoietin (TPO) is the most important cytokine for stimulation of megakaryocyte growth and formation of functional platelets. Recently, it has been shown that the receptor for TPO, c-mpl, is expressed on haematopoietic stem cells, and that TPO promotes the growth of these stem cells via binding to c-mpl. Quantitative or qualitative abnormalities of c-mpl function could thus theoretically play a role in the pathogenesis of different MPDs. Previous studies of the integrity of the c-mpl system in PV have produced conflicting results. We therefore studied c-mpl protein expression using immunoblot analysis in 15 PV patients and 10 healthy controls. Seven out of 15 PV patients (47%) exhibited similar c-mpl protein levels to the controls, whereas eight out of 15 patients (53%) showed either markedly reduced or absent levels of c-mpl. Five of the seven c-mpl-positive patients had only been treated by phlebotomy, whereas six out of eight c-mpl-negative patients were receiving treatment with hydroxyurea, anagrelide or alpha-interferon. Disease duration tended to be slightly longer in c-mpl-negative patients compared with c-mpl-positive patients (mean = 55 vs. 43 months). Tyrosine phosphorylation of JAK-2 in immunoprecipitates of platelets obtained after stimulation with TPO (100 and 1000 ng/ml) was normal in c-mpl-positive patients, whereas it could not be detected in c-mpl-negative patients. We therefore conclude that there exists a marked heterogeneity in c-mpl protein levels and functional integrity in PV. However, it seems less likely that c-mpl abnormalities per se are directly involved in the pathogenesis leading to the occurrence of PV, as c-mpl levels were similar to those seen in healthy individuals in about half of the patients under study.

Aged↗
PubMed1999

Unusual clinical presentation in a patient with myelodysplastic syndrome, with subsequent hematological remission and suppression of the malignant clone following treatment with cyclosporine A, erythropoietin and granulocyte colony-stimulating factor.

A 35-year-old female presented with isolated thrombocytopenia of autoimmune origin. One and a half years later, hypoplastic myelodysplastic (MDS) was diagnosed. Following treatment with cyclosporin A, erythropoietin and granulocyte colony-stimulating factor, the patient has achieved a sustained hematological remission which is still ongoing after 3 years. Furthermore, to the best of our knowledge, this is the third case described in the literature where treatment with cytokines alone or in combination with immunosuppressive agents has resulted in a long standing cytogenetic response in MDS.

Adult↗
PubMed1999

Acute quadriplegic myopathy following autologous peripheral blood stem cell transplantation for breast cancer.

Autologous peripheral blood stem cell transplantation (APSCT) is increasingly used in the treatment of breast cancer. We report a patient who experienced septic shock, and after treatment with antibiotics, high-dose corticosteroids and mechanical ventilation due to respiratory insufficiency, developed quadriplegia. Electroneurophysiological examination, as well as a muscle biopsy, showed a typical picture of acute quadriplegic myopathy with loss of thick filament proteins. This is, to the best of our knowledge, the first reported case of this complication following APSCT.

Acute Disease↗
PubMed1999

The measurement of venous haematocrit in patients with polycythaemia vera.

OBJECTIVE: In clinical practice, patients with polycythaemia vera (PV) are monitored by measurement of venous packed cell volume (PCV). However, whereas treatment recommendations are still based upon studies in which the results were obtained with the centrifuged microhaematocrit, currently in most instances automated blood cell counters are used to calculate PCV. In a group of patients with polycythaemia we therefore compared the results obtained by the microhaematocrit method with PCV calculated by haematology analysers. DESIGN: The study was carried out on a prospective basis. Duplicate venous blood samples were collected. The centrifuged microhaemotocrit was obtained by using an IEC Micro-MB Centrifuge. Depending on different routine methods used in the participating hospitals, the blood cell counter PCV was calculated using Coulter STKS, Bayer Technicon H2 or H3. SETTING: Patients were included from four Swedish university hospitals: Akademiska (Uppsala), Huddinge and Karolinska (Stockholm) and Sahlgrenska (Göteborg). SUBJECTS: Seventy-four patients with PV and 10 patients with secondary polycythaemia were included and a total of 150 duplicate blood samples were analysed from these subjects. RESULTS: In the 150 measurements the mean blood cell counter calculated PCV was 0.448 +/- 0.037; the mean for centrifuged microhaematocrit was 0.467 +/- 0. 037 and the difference between means was highly significant (P = 6.8 x 10-25). The means for centrifuged haematocrit and calculated PCV differed significantly in the groups of PV patients treated with phlebotomy only, hydroxyurea or radiophosphorous (P < 0.0001, respectively). In PV patients treated with alpha-interferon and in patients with secondary polycythaemia the difference in means did not reach statistical significance (P = 0.07 and P = 0.13, respectively). The groups of patients with MCV <80 fL and >/=80 fL both presented significant differences between means for calculated PCV and centrifuged haematocrit. CONCLUSIONS: If PV patients are monitored with blood cell counter calculated PCV it appears that the therapeutic goal should be to maintain the calculated PCV below 0.43, provided the local differences in calculated PCV and centrifuged haematocrit are of the same magnitude as in this study.

Aged↗
PubMed1998

Impaired platelet binding of fibrinogen due to a lower number of GPIIB/IIIA receptors in polycythemia vera.

We have previously described a stimulus-specific defect in platelet aggregation in polycythaemia vera (PV) after stimulation with surface receptor dependent agonists such as platelet activating factor (PAF). In contrast, responses to phorbol myristate acetate (PMA) were normal. We now report that after PAF stimulation, using flow cytometry, the amount of fibrinogen bound to its receptor was significantly lower in PV platelets with a median MFI of 6.0 (range 4.1-17.3) compared to controls, 12.8 (range 8-21.3; n=11; p<0.01). We found no evidence of preactivation of PV platelets. Quantitative analysis of GPIIIa gave a significantly lower number of GPIIIa on resting PV platelets, 14300 subunits of GPIIIa (range 8500-15500) vs. 19800 for controls (range 13400-26800; n=12; p<0.01). Both patients and controls increased their number of receptors on the cell surface after stimulation with PAF and PMA, but the significant difference in the number of receptors per cell remained. Indirect evaluation of PAF receptor function showed that activation of CD 62 did not differ in PV and controls after PAF stimulation. Additionally, although the basal level of serotonin in platelet-rich plasma was significantly lower in PV, there was a threefold increase of the basal level after stimulation with PAF for both PV and control platelets, also indicating a normal interaction of PAF with its receptor. Although our results indicate both an impaired PAF induced aggregation in PV and a lower number of GPIIb/IIIa complexes on single platelets, whether these phenomena are related remains uncertain.

Adult↗
PubMed1998

Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients.

Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months. The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates.

Aged↗
PubMed1998

Survival in a patient with polycythaemia vera for over thirty years: implications for treatment decisions in younger patients.

Modern treatment has dramatically improved the prognosis for patients with polycythaemia vera (PV). Here a patient is described who has been followed and treated for PV for over 30 years, demonstrating that very long term survival can be achieved in PV. However, effective treatment modalities such as radioactive phosphorus, alkylating agents and, most recently, hydroxyurea, have all been shown to increase the risk to develop acute leukaemia when used in the treatment of myeloproliferative disorders. Hopefully, the prolonged survival of this patient may help to emphasize the need to use non-leukaemogenic agents when treating younger PV patients.

Adult↗
PubMed1997

No evidence for an altered mRNA expression or protein level of haematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythaemia vera.

Polycythaemia vera (PV) is a myeloproliferative disorder characterized by haematopoietic progenitor cells being hypersensitive to cytokines such as erythropoietin, interleukin-3, stem cell factor and insulin-like growth factor 1, which results in an increased production of mature blood cells. The pathogenetic cellular mechanism(s) behind this hypersensitivity to cytokines is unknown, but the number of cytokine receptors and the interaction between ligand and receptor are normal in PV. Interest has therefore focused on post-receptor mechanism(s). Haematopoietic cell phosphatase (HCP) is an intracellular tyrosine phosphatase that has been demonstrated to regulate proliferative signals negatively induced by the cytokines mentioned above. Moreover, motheaten mice that genetically lack HCP have an increased amount of erythroid progenitors that are hypersensitive to Epo, and patients with familial polycythaemia have been shown to exhibit a mutation of the Epo receptor gene that includes the docking site for HCP. We therefore studied mRNA expression of HCP in pure populations of CD34+ cells, granulocytes, platelets and lymphocytes from patients with PV, chronic myeloid leukaemia (CML) or essential thrombocythemia (ET), as well as healthy controls. Using a polymerase chain reaction analysis employing specific primers for HCP, we failed to detect any abnormalities of HCP expression in PV in any of the cell populations that were examined. Moreover, HCP mRNA expression was similar in ET and CML compared to controls. Finally, Western blot analysis revealed a normal HCP protein content in PV granulocytes and platelets. We therefore conclude that neither an impaired expression of the HCP gene nor a defect in HCP protein synthesis is present in PV, and does not seem to play a role in the aetiology of this disorder.

Aged↗
PubMed1997

Spontaneous remission during two pregnancies in a patient with essential thrombocythaemia.

A woman with untreated essential thrombocythaemia (ET) exhibited spontaneous normalization of her elevated platelet count during two pregnancies. After delivery the platelet count increased rapidly to the same high level as before. Low platelet adhesion as well as adrenalin- and collagen-induced platelet aggregation, present before pregnancy, increased to normal values during pregnancy. Furthermore, no erythropoietin-independent colony growth was observed during pregnancy, while such colonies were clearly demonstrated when the patient was assayed after pregnancy. This is the second case in the literature demonstrating that remission of ET can occur without treatment during pregnancy.

Adult↗
PubMed1996

Fludarabine, as well as 2-chlorodeoxyadenosine, can induce eosinophilia during treatment of lymphoid malignancies.

We treated 25 patients suffering from low-grade lymphoid malignancies with nucleoside analogues. In 11 patients undergoing treatment with fludarabine, two patients with follicular lymphoma developed a marked absolute peripheral blood eosinophilia devoid of clinical symptoms which resolved without medical intervention. Of 15 patients treated with 2-chlorodeoxyadenosine, one patient with B-cell chronic lymphocytic leukaemia (CLL) experienced repeated episodes of eosinophilia that required steroid treatment. Eosinophilia in these three patients was not coupled to tumour lysis, and we found no correlation between the occurrence of eosinophilia and clinical response to treatment. Thus, for the first time, we can report eosinophilia as a side-effect of fludarabine treatment, and these are also the first published cases of this complication occurring in patients treated with nucleoside analogues for follicular lymphoma and CLL.

Aged↗