Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1999
The serotonin syndrome is a rare, but potentially fatal complication to treatment with serotonin ... more The serotonin syndrome is a rare, but potentially fatal complication to treatment with serotonin reuptake inhibitors. Due to increasing prescription of these drugs the condition must be expected to occur more often. Symptoms include changes in mental status (confusion, agitation and restlessness), neuromuscular symptoms (shivering, ataxia, myoclonus and hyperreflexia) and autonomic dysfunction (fever, diaphoresis, hypertension and tachycardia). The syndrome is most often produced by concurrent use of two or more drugs that enhance serotonin neurotransmission. Monotherapy may also elicit the syndrome. We report the development of serotonin syndrome with a fatal outcome in a patient treated with paroxetin++. Interactions with alimemazin++, melperon++ and karbamazepin may have contributed to the outcome. The serotonin syndrome usually resolves within 24 hours when the suspected drugs are discontinued. However, there may be a dramatic progression of symptoms requiring intensive supporti...
Extracorporeal photopheresis (ECP) is an immunomodulatory alternative for treatment of graft vers... more Extracorporeal photopheresis (ECP) is an immunomodulatory alternative for treatment of graft versus host disease (GVHD). The blood is then separated into its various components through apheresis; buffy coat cells are thereafter treated with 8-methoxypsoralen before exposure to ultraviolet light and finally reinfused into the patient. There is a general agreement that this treatment has an anti-GVHD effect, but the mechanisms of action behind this effect are only partly understood. However, altered maturation of dendritic cells (DC) and thereby indirect modulation of T-cell reactivity seems to be one important mechanism together with DC-presentation of antigens derived from apoptotic donor T cells and induction of regulatory T cells. The treatment has been best studied in patients with chronic GVHD (both pediatric and adult patients), but most studies are not randomized and it is difficult to know whether the treatment is more effective than the alternatives. The clinical studies of ECP in adults with acute GVHD are few and not randomized; it is not possible to judge whether this treatment should be a preferred second- or third-line treatment. There is no evidence for increased risk of leukemia relapse or suppression of specific graft versus leukemia reactivity by this treatment, so specific antileukemic immunotherapy may still be possible. Thus, even though the treatment seems effective in patients with GVHD, further clinical (especially randomized) as well as biological studies with careful standardization of the treatment are needed before it is possible to conclude how ECP should be used in acute and chronic GVHD.
Homozygosity for a novel D180G mutation in the protease domain of protein C, associated with plas... more Homozygosity for a novel D180G mutation in the protease domain of protein C, associated with plasma protein C activity and antigen levels of 8% of normal was identified in a thrombosis prone family. Transient expression of protein C in HK-293 cells and analysis of protein C antigen in culture media and cell lysates showed that the secretion of mutant protein as compared with wild-type protein was reduced by 79% while the intracellular contents were similar. Computer analysis of the X-ray structure of activated protein C and of a theoretical model of the zymogen predicts that the mutation destabilises the molecule locally. Our results are compatible with a relatively unstable mutant molecule that could be trapped inside the cell and degraded. However, if secreted the mutant molecule could have a relatively normal catalytic activity and structure consistent with the plasma levels of protein C activity and the late onset of thrombosis.
BACKGROUND Allogeneic stem cell transplantation (ASCT) has been a treatment option for patients w... more BACKGROUND Allogeneic stem cell transplantation (ASCT) has been a treatment option for patients with serious diseases of the blood and haematopoietic organs in Norway since 1985. Such treatment is potentially curative for selected patients who have a relatively short predicted survival with other treatment modalities. This article summarises the experience and results from ASCT at Oslo University Hospital Rikshospitalet. MATERIAL AND METHOD The study included all of the 734 adult patients who had undergone allogeneic stem cell transplantation at the Department of Haematology, Rikshospitalet, later Oslo University Hospital Rikshospitalet, from November 1985 to October 2012. RESULTS At the time of analysis, altogether 384 patients were alive, and the five and ten-year survival rates were 54% and 48% respectively. The median follow-up time was six years. A total of 339 patients (46%) had developed acute graft-versus-host disease (GvHD), and 250 (73%) of these had GvHD ≥ grade II. Altogether 280 out of 602 patients who lived ≥ 100 days after the transplantation (46.5%) developed chronic GvHD. The most frequent causes of death included recurrence of the initial disease in 116 patients (33.1 %), multi organ failure after transplantation in 88 patients (25.4%), infections in 54 patients (16%) and GvHD in 33 patients (9.4%). INTERPRETATION ASCT is a treatment option with a curative potential for patients with serious haematological diseases when other forms of treatment provide few prospects for recovery. The total survival rate in our study is in accordance with international results for the same time period, and the indications have consistently been in line with what is accepted internationally.
The success rate for chemotherapy of adults with acute lymphoblastic leukaemia in Norway compares... more The success rate for chemotherapy of adults with acute lymphoblastic leukaemia in Norway compares favourably with that in international reports, but improvements are still needed. Allogeneic stem cell transplantation is an option for patients up to 60 years and may contribute to improving the outcome for these patients. Allogen stem cell transplantation was performed in 61 high-risk patients (38 men and 23 women) with acute lymphoblastic leukaemia at Rikshospitalet between 1985 and 2005. 19 patients were transplanted in first remission and 42 at a later stage of the disease. At the end of 2006, 26 patients (43%) were alive; 21 (35%) in complete remission and 5 with relapse. Median survival time was 1.5 years. Relapse was the most important cause of treatment failure (38%), but transplantation-related mortality (25%) was also a substantial problem. Estimated 5-year actuarial leukemia-free survival was 35 %. Our results are in line with international reports on the results of allogen ...
Mutated oncogene peptides may be presented to T cells by HLA molecules. To be able to design the ... more Mutated oncogene peptides may be presented to T cells by HLA molecules. To be able to design the optimal peptides for stimulation of T cells in individuals with different HLA molecules, it is important to analyse the binding characteristics of oncogene peptides to HLA. HLA-DQ6 (DQ(alpha 1*0102,beta 1*0602)) and HLA-DR1 (DR(alpha,beta 1*0101)) molecules were purified from lysates of homozygous EBV-transformed cell lines. Purified HLA molecules were then tested for their ability to bind synthetic peptides in gel filtration assays. A p21 ras oncogene peptide (previously found to stimulate DQ6-restricted T-cell clones) and an influenza matrix peptide were labelled with 125I and served as indicator peptides for binding to DQ6 and DR1 respectively. Binding of homologous truncated and mutated p21 ras peptides and unrelated peptides was then evaluated by their capacity to inhibit binding of the indicator peptides. p21 ras-derived peptides were found to bind to both DQ6 and DR1 molecules indicating the existence of a promiscuous binding motif in these peptides. The binding affinities seemed to vary between the different peptides, but the amino acid substitutions resulting from natural mutations were not critical for binding. Notably, the results obtained for DQ6 in the biochemical peptide binding assay correlated well with results obtained in a functional assay using T-cell clones as probes.
A 58-yr-old woman was diagnosed with Ph(+) chronic myeloid leukaemia in May 2001. She was initial... more A 58-yr-old woman was diagnosed with Ph(+) chronic myeloid leukaemia in May 2001. She was initially treated with hydroxyurea and subsequently with interferon-alpha (IFN-alpha). Imatinib mesylate was started in April 2002 after failure of IFN-alpha to induce a cytogenetic response. The patient remained on treatment with imatinib mesylate for 3 months during which she suffered daily fever resulting in discontinuation of the treatment. Response evaluation performed shortly after discontinuing imatinib mesylate revealed a complete cytogenetic remission and a substantial molecular response. Fifteen months later, she was still enjoying a major cytogenetic response. This case illustrates that a short course of imatinib mesylate may result in a sustained haematological and cytogenetic response.
Key Points Bortezomib consolidation after ASCT improves PFS in myeloma. Improvement of response i... more Key Points Bortezomib consolidation after ASCT improves PFS in myeloma. Improvement of response is seen with bortezomib consolidation after ASCT in myeloma.
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1999
The serotonin syndrome is a rare, but potentially fatal complication to treatment with serotonin ... more The serotonin syndrome is a rare, but potentially fatal complication to treatment with serotonin reuptake inhibitors. Due to increasing prescription of these drugs the condition must be expected to occur more often. Symptoms include changes in mental status (confusion, agitation and restlessness), neuromuscular symptoms (shivering, ataxia, myoclonus and hyperreflexia) and autonomic dysfunction (fever, diaphoresis, hypertension and tachycardia). The syndrome is most often produced by concurrent use of two or more drugs that enhance serotonin neurotransmission. Monotherapy may also elicit the syndrome. We report the development of serotonin syndrome with a fatal outcome in a patient treated with paroxetin++. Interactions with alimemazin++, melperon++ and karbamazepin may have contributed to the outcome. The serotonin syndrome usually resolves within 24 hours when the suspected drugs are discontinued. However, there may be a dramatic progression of symptoms requiring intensive supporti...
Extracorporeal photopheresis (ECP) is an immunomodulatory alternative for treatment of graft vers... more Extracorporeal photopheresis (ECP) is an immunomodulatory alternative for treatment of graft versus host disease (GVHD). The blood is then separated into its various components through apheresis; buffy coat cells are thereafter treated with 8-methoxypsoralen before exposure to ultraviolet light and finally reinfused into the patient. There is a general agreement that this treatment has an anti-GVHD effect, but the mechanisms of action behind this effect are only partly understood. However, altered maturation of dendritic cells (DC) and thereby indirect modulation of T-cell reactivity seems to be one important mechanism together with DC-presentation of antigens derived from apoptotic donor T cells and induction of regulatory T cells. The treatment has been best studied in patients with chronic GVHD (both pediatric and adult patients), but most studies are not randomized and it is difficult to know whether the treatment is more effective than the alternatives. The clinical studies of ECP in adults with acute GVHD are few and not randomized; it is not possible to judge whether this treatment should be a preferred second- or third-line treatment. There is no evidence for increased risk of leukemia relapse or suppression of specific graft versus leukemia reactivity by this treatment, so specific antileukemic immunotherapy may still be possible. Thus, even though the treatment seems effective in patients with GVHD, further clinical (especially randomized) as well as biological studies with careful standardization of the treatment are needed before it is possible to conclude how ECP should be used in acute and chronic GVHD.
Homozygosity for a novel D180G mutation in the protease domain of protein C, associated with plas... more Homozygosity for a novel D180G mutation in the protease domain of protein C, associated with plasma protein C activity and antigen levels of 8% of normal was identified in a thrombosis prone family. Transient expression of protein C in HK-293 cells and analysis of protein C antigen in culture media and cell lysates showed that the secretion of mutant protein as compared with wild-type protein was reduced by 79% while the intracellular contents were similar. Computer analysis of the X-ray structure of activated protein C and of a theoretical model of the zymogen predicts that the mutation destabilises the molecule locally. Our results are compatible with a relatively unstable mutant molecule that could be trapped inside the cell and degraded. However, if secreted the mutant molecule could have a relatively normal catalytic activity and structure consistent with the plasma levels of protein C activity and the late onset of thrombosis.
BACKGROUND Allogeneic stem cell transplantation (ASCT) has been a treatment option for patients w... more BACKGROUND Allogeneic stem cell transplantation (ASCT) has been a treatment option for patients with serious diseases of the blood and haematopoietic organs in Norway since 1985. Such treatment is potentially curative for selected patients who have a relatively short predicted survival with other treatment modalities. This article summarises the experience and results from ASCT at Oslo University Hospital Rikshospitalet. MATERIAL AND METHOD The study included all of the 734 adult patients who had undergone allogeneic stem cell transplantation at the Department of Haematology, Rikshospitalet, later Oslo University Hospital Rikshospitalet, from November 1985 to October 2012. RESULTS At the time of analysis, altogether 384 patients were alive, and the five and ten-year survival rates were 54% and 48% respectively. The median follow-up time was six years. A total of 339 patients (46%) had developed acute graft-versus-host disease (GvHD), and 250 (73%) of these had GvHD ≥ grade II. Altogether 280 out of 602 patients who lived ≥ 100 days after the transplantation (46.5%) developed chronic GvHD. The most frequent causes of death included recurrence of the initial disease in 116 patients (33.1 %), multi organ failure after transplantation in 88 patients (25.4%), infections in 54 patients (16%) and GvHD in 33 patients (9.4%). INTERPRETATION ASCT is a treatment option with a curative potential for patients with serious haematological diseases when other forms of treatment provide few prospects for recovery. The total survival rate in our study is in accordance with international results for the same time period, and the indications have consistently been in line with what is accepted internationally.
The success rate for chemotherapy of adults with acute lymphoblastic leukaemia in Norway compares... more The success rate for chemotherapy of adults with acute lymphoblastic leukaemia in Norway compares favourably with that in international reports, but improvements are still needed. Allogeneic stem cell transplantation is an option for patients up to 60 years and may contribute to improving the outcome for these patients. Allogen stem cell transplantation was performed in 61 high-risk patients (38 men and 23 women) with acute lymphoblastic leukaemia at Rikshospitalet between 1985 and 2005. 19 patients were transplanted in first remission and 42 at a later stage of the disease. At the end of 2006, 26 patients (43%) were alive; 21 (35%) in complete remission and 5 with relapse. Median survival time was 1.5 years. Relapse was the most important cause of treatment failure (38%), but transplantation-related mortality (25%) was also a substantial problem. Estimated 5-year actuarial leukemia-free survival was 35 %. Our results are in line with international reports on the results of allogen ...
Mutated oncogene peptides may be presented to T cells by HLA molecules. To be able to design the ... more Mutated oncogene peptides may be presented to T cells by HLA molecules. To be able to design the optimal peptides for stimulation of T cells in individuals with different HLA molecules, it is important to analyse the binding characteristics of oncogene peptides to HLA. HLA-DQ6 (DQ(alpha 1*0102,beta 1*0602)) and HLA-DR1 (DR(alpha,beta 1*0101)) molecules were purified from lysates of homozygous EBV-transformed cell lines. Purified HLA molecules were then tested for their ability to bind synthetic peptides in gel filtration assays. A p21 ras oncogene peptide (previously found to stimulate DQ6-restricted T-cell clones) and an influenza matrix peptide were labelled with 125I and served as indicator peptides for binding to DQ6 and DR1 respectively. Binding of homologous truncated and mutated p21 ras peptides and unrelated peptides was then evaluated by their capacity to inhibit binding of the indicator peptides. p21 ras-derived peptides were found to bind to both DQ6 and DR1 molecules indicating the existence of a promiscuous binding motif in these peptides. The binding affinities seemed to vary between the different peptides, but the amino acid substitutions resulting from natural mutations were not critical for binding. Notably, the results obtained for DQ6 in the biochemical peptide binding assay correlated well with results obtained in a functional assay using T-cell clones as probes.
A 58-yr-old woman was diagnosed with Ph(+) chronic myeloid leukaemia in May 2001. She was initial... more A 58-yr-old woman was diagnosed with Ph(+) chronic myeloid leukaemia in May 2001. She was initially treated with hydroxyurea and subsequently with interferon-alpha (IFN-alpha). Imatinib mesylate was started in April 2002 after failure of IFN-alpha to induce a cytogenetic response. The patient remained on treatment with imatinib mesylate for 3 months during which she suffered daily fever resulting in discontinuation of the treatment. Response evaluation performed shortly after discontinuing imatinib mesylate revealed a complete cytogenetic remission and a substantial molecular response. Fifteen months later, she was still enjoying a major cytogenetic response. This case illustrates that a short course of imatinib mesylate may result in a sustained haematological and cytogenetic response.
Key Points Bortezomib consolidation after ASCT improves PFS in myeloma. Improvement of response i... more Key Points Bortezomib consolidation after ASCT improves PFS in myeloma. Improvement of response is seen with bortezomib consolidation after ASCT in myeloma.
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