Introduction FNAIT is associated with severe bleeding, especially intracranial hemorrhage (ICH), ... more Introduction FNAIT is associated with severe bleeding, especially intracranial hemorrhage (ICH), in the fetus and/or newborn. More than 75% of ICHs occur in utero and up to 50% before 32 weeks gestation. The consequences of ICH include death (35%) or serious neurological sequelae in survivors (83%). FNAIT requires prompt identification and treatment antepartum, postpartum and in subsequent pregnancies. An international panel was convened by the International Collaboration for Transfusion Medicine Guidelines (ICTMG) to develop evidence based recommendations for diagnosis and management of FNAIT. Methods The international panel consisted of specialists in adult and pediatric hematology, maternal fetal medicine (MFM), neonatology, methodology, transfusion medicine, and a patient representative. Clinical questions were developed for diagnostic testing, antenatal screening and management, and postnatal interventions. A systematic search for articles published between 1946 and June 2017 i...
2889 GSK-3β is a multifunctional kinase that plays a role in several signaling pathways. Due to t... more 2889 GSK-3β is a multifunctional kinase that plays a role in several signaling pathways. Due to the contradictory roles of GSK-3β as a mediator of both cell survival and apoptosis, we have examined the role of GSK-3β for proliferation and apoptosis in leukemic cell lines KG1a, K562 and CMK. GSK-3β was selectively inhibited by the small-molecule SB-415286. Treatment of leukemia cells with SB-415286 (40 μM) for 72 hr approximately halved cell growth in all three cell lines. SB-415286 also showed a concentration-dependent stabilization of intracellular β-catenin: In KG1a cells the mean fluorescence intensity (MFI) [± 95% CI] was 3.1 [± 1.7] in untreated cells vs. 423 [± 24] in treated cell. The figures for the K562 and CMK cell lines were: 2.8 [± 1.6] vs. 353.2 [± 11.1], and 6.8 [± 4.0] vs. 320.2 [± 23.7], respectively. Cell cycle analysis was carried out to examine if the growth inhibition was caused by arrest in cell cycle and/or induction of apoptosis. We found that SB-415286 caused...
NAITP is suspected if a neonate unexpectedly presents with petecchiae and is severely trombocytop... more NAITP is suspected if a neonate unexpectedly presents with petecchiae and is severely trombocytopenic. The thrombocytopenia is caused by maternal alloantibodies to platelet-specific antigens, most often anti-HPA 1a. A mother who has previously given birth to an affected child is usually considered at high risk for giving birth to a trombocytopenic child also in the subsequent pregnancy. The aim of the present study was to compare to what extent quantification of anti-HPA 1a versus obstetric history can predict the severity of thrombocytopenia in new-borns. Anti-HPA 1a was repeatedly quantified in 152 immunized pregnant women who were included in a large Norwegian prospective study. Sixty-eight of the women gave birth to thrombocytopenic children of which 42 suffered severe thrombocytopenia (plt. count <50x109/l). Ten women had previously given birth to children with symptomatic NAITP. Five of these did not give birth to children with severe thrombocytopenia in their subsequent pr...
Key Points HLA-DRB3*01:01 has a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immuniz... more Key Points HLA-DRB3*01:01 has a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immunized women giving birth to an HPA-1a–positive child. HLA-DRB3*01:01 has a dose-dependent impact on the neonatal platelet counts in HPA-1a–positive children born of HPA-1a–immunized women.
Acta obstetricia et gynecologica Scandinavica, Jan 7, 2018
An important issue on human platelet antigen (HPA)-1a screening has recently been addressed in Ac... more An important issue on human platelet antigen (HPA)-1a screening has recently been addressed in Acta Obstetrica et Gynecologica Scandinavia. Winkelhorst et al. reported that the vast majority of women in the general pregnant population were positive about screening (1). Here we report that there was also a positive attitude towards screening among Norwegian HPA-1a-immunized pregnant women. Further, we report that insufficient information may have led to unnecessary anxiety in this high-risk population. This article is protected by copyright. All rights reserved.
The aim of this study was to prospectively explore the detailed longitudinal development of plate... more The aim of this study was to prospectively explore the detailed longitudinal development of platelet increments in patients with chemotherapy-induced bone marrow aplasia during the first 24 hours after platelet transfusion. Patients admitted to the Haematology department during 7 months, and fulfilled inclusion criteria were divided into 4 groups: Group 1, patients with acute leukaemia; Group 2, patients after autologous stem cell transplantation (SCT); Group 3, patients after allogeneic SCT; and Group 4, patients given platelet transfusion prior to intervention. We used frequent blood sampling within 24 hours after platelet transfusion to investigate the kinetics of platelet counts following transfusion. Fifty-four platelet transfusion occasions in patients with chemotherapy-induced bone marrow aplasia were included. The decrease in corrected count increment (CCI) 1-24 hours after platelet transfusions in all groups could be described as linear functions. For patients in the aggregated Groups 1-3, the decline was 2.0% ± 0.6% (mean ± standard deviation) per hour. For patients in Group 4, the decline of CCI was 2.8% ± 1.2% per hour. We found no differences between the groups, either in the rate of platelet elimination from the bloodstream or in the mean CCI, in the first 24 hours post-transfusion.
Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in... more Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), and weekly maternal intravenous immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy are common options, but the optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and twenty-two non-randomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of antenatal management strategy applied; FBS, IUPT or IVIG with/without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. Fetal blood sampling or intrauterine platelet transfusion resulted in a relatively high compl...
We have developed a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA... more We have developed a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA) with enhanced sensitivity in detecting antibodies against human platelet antigens (HPA), using biotinylated monoclonal antibodies, streptavidin-coated beads and detection by flow cytometry. The beads-MAIPA gave superior signal-to-noise resolution (>10-fold higher) for detection of anti-HPA-1a and anti-HPA-5b compared with the in-house standard MAIPA. Also, efficient and reproducible detection of anti-HPA-15 (CD109) was shown. The enhanced sensitivity was confirmed using WHO International Reference Reagents for anti-HPA-1a, anti-HPA-3a and anti-HPA-5b, which allowed comparison of detection endpoints with other laboratories. Finally, the beads-MAIPA was validated for quantification of anti-HPA-1a. The lower limit of quantification was 0.4IU/mL for beads-MAIPA, compared to 1IU/mL previously reported for standard MAIPA. Based on improved performance against all HPA-antibodies tested, th...
Transfusion clinique et biologique : journal de la Société française de transfusion sanguine, 2005
The allo-immune thrombocytopenias are the major cause of severe thrombocytopenia in the fetus and... more The allo-immune thrombocytopenias are the major cause of severe thrombocytopenia in the fetus and the neonate. The frequency of this affection has been evaluated to be 1 out of 800 to 1000 live births. The deleterious consequences of severe thrombocytopenia are intracranial hemorrhages leading to death or neurological sequelae. Progress in platelet immunology and antenatal medicine has allowed a better diagnosis of this affection and development of the antenatal management of high-risk pregnancies. Nevertheless there are unsolved questions, particularly concerning the mechanism of the maternal immunization, the laboratory difficulties for the identification of the alloantibodies, the absence of antenatal management standardization.
The dietary treatment of rheumatoid arthritis is a controversial issue. Several patients have exp... more The dietary treatment of rheumatoid arthritis is a controversial issue. Several patients have experienced that their diet does affect the disease activity. For many years this has been explained by rheumatologists either as a result of natural variations in the disease activity, or as reflecting a placebo effect. In recent years several clinical trials seem to support patients&#39; claims of an interrelation between their diet and the disease activity. Possible explanations of this interrelation are: 1) food allergy/intolerance, 2) dietary factors which modify the inflammatory process, 3) dietary factors which modify the bacterial flora in the gastrointestinal tract. In this article we sum up the results of several clinical trials on the dietary treatment of rheumatoid arthritis, and discuss the three possible explanations of the effects.
... fJowever, we found HLA-DR' synovial Tyd cells all but one Page 8. 658 J. KjeUhen-Kragh e... more ... fJowever, we found HLA-DR' synovial Tyd cells all but one Page 8. 658 J. KjeUhen-Kragh el al. palieni. and IL-2 reccpior-positive J/6 cells could be dcleclcd in one-third urthc synoviiil samples. ... iflhritis RlHuni.M.?\f,. 19SS. 4 Borst. J,. van Dongen. JJM. Bolhuis. RLH. I'L'ters. ...
In a controlled, double blind, clinical trial we tested the effect of dietary omega-3 fatty acid ... more In a controlled, double blind, clinical trial we tested the effect of dietary omega-3 fatty acid supplementation with and without naproxen and placebo, respectively, in 67 patients with active rheumatoid arthritis. The patients were randomized into 3 groups that received the following treatment: Group 1, corn oil (&quot;placebo omega-3 fatty acids&quot;), 7 g/day for 16 weeks, and naproxen, 750 mg/day for 10 weeks followed by a stepwise reduction to 0 mg/day during the following 3 weeks; Group 2, omega-3 fatty acids, 3.8 g of eicosapentaenoic acid plus 2.0 g of docosahexaenoic acid, and naproxen, 750 mg/day for 16 weeks; and Group 3, omega-3 fatty acids as Group 2 and naproxen as Group 1. At the end of the trial, patients in Group 2 had improved with respect to duration of morning stiffness and global assessment by physician and patient. In Groups 1 and 3 there was a significant deterioration for most of the variables measured. However, for duration of morning stiffness the deterioration was significantly less pronounced in Group 3 compared with Group 1. These effects might be ascribed to the dietary omega-3 fatty acid supplementation.
During the last 10-20 years it has become clear that the immune system not only protects the indi... more During the last 10-20 years it has become clear that the immune system not only protects the individual against potentially harmful intruders but also interacts with both the nervous and endocrine systems. Today we know that immune competent cells have receptors for hormones and neurotransmitters, and that cytokine receptors are expressed in certain areas of the brain. Furthermore, in many animal models immune suppression has been induced by classical conditioning. Several in vitro studies have shown signs of reduced immunity in individuals during acute and chronic stress. Some studies have also indicated that chronic stress may increase the risk of infections and cancer. On the other hand, various psychotherapeutic techniques appear to strengthen the immune system. As for immunological disease, we know that psychological factors are important in the case of allergic asthma. Moreover, serious life events prior to onset of disease are reported more frequently by seronegative than by seropositive rheumatoid arthritis patients. Prospective studies have shown that psychotherapeutic intervention can reduce disability in rheumatoid arthritis patients, but disease activity is diminished only rarely.
To investigate the effects of either a 7-day fast or a 7-day ketogenic diet upon serum interleuki... more To investigate the effects of either a 7-day fast or a 7-day ketogenic diet upon serum interleukin-6 (IL-6) and dehydroepiandrosterone sulphate (DHEAS) in RA patients. We measured serum concentrations of DHEAS and IL-6 in 23 RA patients with active disease, 10 of whom followed a 7-day sub-total fast and 13 of whom consumed a ketogenic diet (isoenergetic, carbohydrate &lt; 40 g/day) for 7 days. Clinical and laboratory variables were measured at baseline, on day 7 and after re-feeding on day 21. Correlation analyses were used to assess the associations between serum IL-6, DHEAS and disease activity variables at each timepoint. Fasting, but not the ketogenic diet, decreased serum IL-6 concentrations by 37% (p &lt; 0.03) and improved disease activity at day 7. Both fasting and the ketogenic diet increased serum DHEAS levels by 34% as compared with baseline (both p &lt; 0.006). Levels of IL-6, but not DHEAS, correlated with several disease activity variables. Both fasting and a ketogenic diet significantly increased serum DHEAS concentrations in RA patients. Only fasting significantly decreased serum IL-6 levels and improved disease activity. As the increases in serum DHEAS were similar in response to both fasting and a ketogenic diet, it is unlikely that the fall in serum IL-6 or clinical improvements after fasting were directly related to increases in serum DHEAS. The fasting-induced fall in serum IL-6 may underlie the fall in CRP and ESR observed in RA patients in response to a 7-day fast.
Paroxysmal nocturnal haemoglobinuria is a clonal, acquired disease affecting the membrane of the ... more Paroxysmal nocturnal haemoglobinuria is a clonal, acquired disease affecting the membrane of the blood cells, arising from a somatic mutation at the haematopoietic stem cell level. It results in clones of blood cells deficient in membrane bound proteins, such as the complement regulating molecules Decay Accelerating Factor (DAF = CD55) and Membrane Inhibitor of Reactive Lysis (MIRL = CD59). For many years, Ham&#39;s test has been essential for diagnostic testing of erythrocytes for paroxysmal nocturnal haemoglobinuria. We present a 3-colour flowcytometry method used for quantification of CD59-negative erythrocytes and CD55/CD59-negative leukocytes. The results from analysis of blood samples from six patients suffering from paroxysmal nocturnal haemoglobinuria and six healthy blood donors, using the flowcytometry method, Ham&#39;s test and a microtyping gelcard method are compared. Our flow cytometric method, using directly conjugated monoclonal antibodies to test both erythrocytes and leukocytes, is the most sensitive method. It is specific and delivers fast results. The method involves a minimum of manipulation of the fragile cells and can be recommended as an alternative to Ham&#39;s test and the gelcard test.
To evaluate the extent of food allergy/intolerance in rheumatoid arthritis, an elemental (hypoall... more To evaluate the extent of food allergy/intolerance in rheumatoid arthritis, an elemental (hypoallergenic) diet was studied in a controlled, double-blind pilot study. Ten patients were allocated to an experimental group and 7 to a control group. The patients in the experimental group received an elemental diet for 3 weeks, whereas the patients in the control group received a control soup consisting of milk, meat, fish, shellfish, orange, pineapples, tomatoes, peas and flour of wheat and corn. During the 4th week of the study the patients in both groups resumed their regular diet. A significant improvement was found in the number of tender joints (p = 0.04) in the experimental group, whereas improvement was found in the erythrocyte sedimentation rate (ESR) (p = 0.03) and in the thrombocyte count (p = 0.02) in the control group. Three patients in the elemental diet group and 2 patients in the control group improved in all of the measured disease variables during the dietary treatment period. There was no significant difference in disease activity variables between the two groups. These results suggest that some RA patients may respond to the elimination of offending food items. However, the results do not encourage treatment with an elemental diet in unselected RA patients.
Approximately one third of the Norwegian blood donor population has been tested for infection wit... more Approximately one third of the Norwegian blood donor population has been tested for infection with human T-lymphotropic virus type I and II (HTLV-I/II). This study was initiated to provide an indication as to whether or not the Norwegian transfusion service should screen the entire donor population for HTLV I/II. No HTLV-I infections were found among the blood donors. One new donor was confirmed HTLV-II positive. This individual had previously used drugs intravenously. HTLV-I/II infection can be regarded as a marker for risk behaviour, and testing can be of significance in the quality assurance of the transfusion service. We recommend that the entire blood donor population be tested for HTLV-I/II infections, and thereafter only new donors. The benefit of this scheme should be evaluated in the future.
Introduction FNAIT is associated with severe bleeding, especially intracranial hemorrhage (ICH), ... more Introduction FNAIT is associated with severe bleeding, especially intracranial hemorrhage (ICH), in the fetus and/or newborn. More than 75% of ICHs occur in utero and up to 50% before 32 weeks gestation. The consequences of ICH include death (35%) or serious neurological sequelae in survivors (83%). FNAIT requires prompt identification and treatment antepartum, postpartum and in subsequent pregnancies. An international panel was convened by the International Collaboration for Transfusion Medicine Guidelines (ICTMG) to develop evidence based recommendations for diagnosis and management of FNAIT. Methods The international panel consisted of specialists in adult and pediatric hematology, maternal fetal medicine (MFM), neonatology, methodology, transfusion medicine, and a patient representative. Clinical questions were developed for diagnostic testing, antenatal screening and management, and postnatal interventions. A systematic search for articles published between 1946 and June 2017 i...
2889 GSK-3β is a multifunctional kinase that plays a role in several signaling pathways. Due to t... more 2889 GSK-3β is a multifunctional kinase that plays a role in several signaling pathways. Due to the contradictory roles of GSK-3β as a mediator of both cell survival and apoptosis, we have examined the role of GSK-3β for proliferation and apoptosis in leukemic cell lines KG1a, K562 and CMK. GSK-3β was selectively inhibited by the small-molecule SB-415286. Treatment of leukemia cells with SB-415286 (40 μM) for 72 hr approximately halved cell growth in all three cell lines. SB-415286 also showed a concentration-dependent stabilization of intracellular β-catenin: In KG1a cells the mean fluorescence intensity (MFI) [± 95% CI] was 3.1 [± 1.7] in untreated cells vs. 423 [± 24] in treated cell. The figures for the K562 and CMK cell lines were: 2.8 [± 1.6] vs. 353.2 [± 11.1], and 6.8 [± 4.0] vs. 320.2 [± 23.7], respectively. Cell cycle analysis was carried out to examine if the growth inhibition was caused by arrest in cell cycle and/or induction of apoptosis. We found that SB-415286 caused...
NAITP is suspected if a neonate unexpectedly presents with petecchiae and is severely trombocytop... more NAITP is suspected if a neonate unexpectedly presents with petecchiae and is severely trombocytopenic. The thrombocytopenia is caused by maternal alloantibodies to platelet-specific antigens, most often anti-HPA 1a. A mother who has previously given birth to an affected child is usually considered at high risk for giving birth to a trombocytopenic child also in the subsequent pregnancy. The aim of the present study was to compare to what extent quantification of anti-HPA 1a versus obstetric history can predict the severity of thrombocytopenia in new-borns. Anti-HPA 1a was repeatedly quantified in 152 immunized pregnant women who were included in a large Norwegian prospective study. Sixty-eight of the women gave birth to thrombocytopenic children of which 42 suffered severe thrombocytopenia (plt. count <50x109/l). Ten women had previously given birth to children with symptomatic NAITP. Five of these did not give birth to children with severe thrombocytopenia in their subsequent pr...
Key Points HLA-DRB3*01:01 has a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immuniz... more Key Points HLA-DRB3*01:01 has a dose-dependent impact on HPA-1a antibody levels in HPA-1a–immunized women giving birth to an HPA-1a–positive child. HLA-DRB3*01:01 has a dose-dependent impact on the neonatal platelet counts in HPA-1a–positive children born of HPA-1a–immunized women.
Acta obstetricia et gynecologica Scandinavica, Jan 7, 2018
An important issue on human platelet antigen (HPA)-1a screening has recently been addressed in Ac... more An important issue on human platelet antigen (HPA)-1a screening has recently been addressed in Acta Obstetrica et Gynecologica Scandinavia. Winkelhorst et al. reported that the vast majority of women in the general pregnant population were positive about screening (1). Here we report that there was also a positive attitude towards screening among Norwegian HPA-1a-immunized pregnant women. Further, we report that insufficient information may have led to unnecessary anxiety in this high-risk population. This article is protected by copyright. All rights reserved.
The aim of this study was to prospectively explore the detailed longitudinal development of plate... more The aim of this study was to prospectively explore the detailed longitudinal development of platelet increments in patients with chemotherapy-induced bone marrow aplasia during the first 24 hours after platelet transfusion. Patients admitted to the Haematology department during 7 months, and fulfilled inclusion criteria were divided into 4 groups: Group 1, patients with acute leukaemia; Group 2, patients after autologous stem cell transplantation (SCT); Group 3, patients after allogeneic SCT; and Group 4, patients given platelet transfusion prior to intervention. We used frequent blood sampling within 24 hours after platelet transfusion to investigate the kinetics of platelet counts following transfusion. Fifty-four platelet transfusion occasions in patients with chemotherapy-induced bone marrow aplasia were included. The decrease in corrected count increment (CCI) 1-24 hours after platelet transfusions in all groups could be described as linear functions. For patients in the aggregated Groups 1-3, the decline was 2.0% ± 0.6% (mean ± standard deviation) per hour. For patients in Group 4, the decline of CCI was 2.8% ± 1.2% per hour. We found no differences between the groups, either in the rate of platelet elimination from the bloodstream or in the mean CCI, in the first 24 hours post-transfusion.
Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in... more Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), and weekly maternal intravenous immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy are common options, but the optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and twenty-two non-randomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of antenatal management strategy applied; FBS, IUPT or IVIG with/without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. Fetal blood sampling or intrauterine platelet transfusion resulted in a relatively high compl...
We have developed a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA... more We have developed a modified monoclonal antibody immobilization of platelet antigens assay (MAIPA) with enhanced sensitivity in detecting antibodies against human platelet antigens (HPA), using biotinylated monoclonal antibodies, streptavidin-coated beads and detection by flow cytometry. The beads-MAIPA gave superior signal-to-noise resolution (>10-fold higher) for detection of anti-HPA-1a and anti-HPA-5b compared with the in-house standard MAIPA. Also, efficient and reproducible detection of anti-HPA-15 (CD109) was shown. The enhanced sensitivity was confirmed using WHO International Reference Reagents for anti-HPA-1a, anti-HPA-3a and anti-HPA-5b, which allowed comparison of detection endpoints with other laboratories. Finally, the beads-MAIPA was validated for quantification of anti-HPA-1a. The lower limit of quantification was 0.4IU/mL for beads-MAIPA, compared to 1IU/mL previously reported for standard MAIPA. Based on improved performance against all HPA-antibodies tested, th...
Transfusion clinique et biologique : journal de la Société française de transfusion sanguine, 2005
The allo-immune thrombocytopenias are the major cause of severe thrombocytopenia in the fetus and... more The allo-immune thrombocytopenias are the major cause of severe thrombocytopenia in the fetus and the neonate. The frequency of this affection has been evaluated to be 1 out of 800 to 1000 live births. The deleterious consequences of severe thrombocytopenia are intracranial hemorrhages leading to death or neurological sequelae. Progress in platelet immunology and antenatal medicine has allowed a better diagnosis of this affection and development of the antenatal management of high-risk pregnancies. Nevertheless there are unsolved questions, particularly concerning the mechanism of the maternal immunization, the laboratory difficulties for the identification of the alloantibodies, the absence of antenatal management standardization.
The dietary treatment of rheumatoid arthritis is a controversial issue. Several patients have exp... more The dietary treatment of rheumatoid arthritis is a controversial issue. Several patients have experienced that their diet does affect the disease activity. For many years this has been explained by rheumatologists either as a result of natural variations in the disease activity, or as reflecting a placebo effect. In recent years several clinical trials seem to support patients&#39; claims of an interrelation between their diet and the disease activity. Possible explanations of this interrelation are: 1) food allergy/intolerance, 2) dietary factors which modify the inflammatory process, 3) dietary factors which modify the bacterial flora in the gastrointestinal tract. In this article we sum up the results of several clinical trials on the dietary treatment of rheumatoid arthritis, and discuss the three possible explanations of the effects.
... fJowever, we found HLA-DR' synovial Tyd cells all but one Page 8. 658 J. KjeUhen-Kragh e... more ... fJowever, we found HLA-DR' synovial Tyd cells all but one Page 8. 658 J. KjeUhen-Kragh el al. palieni. and IL-2 reccpior-positive J/6 cells could be dcleclcd in one-third urthc synoviiil samples. ... iflhritis RlHuni.M.?\f,. 19SS. 4 Borst. J,. van Dongen. JJM. Bolhuis. RLH. I'L'ters. ...
In a controlled, double blind, clinical trial we tested the effect of dietary omega-3 fatty acid ... more In a controlled, double blind, clinical trial we tested the effect of dietary omega-3 fatty acid supplementation with and without naproxen and placebo, respectively, in 67 patients with active rheumatoid arthritis. The patients were randomized into 3 groups that received the following treatment: Group 1, corn oil (&quot;placebo omega-3 fatty acids&quot;), 7 g/day for 16 weeks, and naproxen, 750 mg/day for 10 weeks followed by a stepwise reduction to 0 mg/day during the following 3 weeks; Group 2, omega-3 fatty acids, 3.8 g of eicosapentaenoic acid plus 2.0 g of docosahexaenoic acid, and naproxen, 750 mg/day for 16 weeks; and Group 3, omega-3 fatty acids as Group 2 and naproxen as Group 1. At the end of the trial, patients in Group 2 had improved with respect to duration of morning stiffness and global assessment by physician and patient. In Groups 1 and 3 there was a significant deterioration for most of the variables measured. However, for duration of morning stiffness the deterioration was significantly less pronounced in Group 3 compared with Group 1. These effects might be ascribed to the dietary omega-3 fatty acid supplementation.
During the last 10-20 years it has become clear that the immune system not only protects the indi... more During the last 10-20 years it has become clear that the immune system not only protects the individual against potentially harmful intruders but also interacts with both the nervous and endocrine systems. Today we know that immune competent cells have receptors for hormones and neurotransmitters, and that cytokine receptors are expressed in certain areas of the brain. Furthermore, in many animal models immune suppression has been induced by classical conditioning. Several in vitro studies have shown signs of reduced immunity in individuals during acute and chronic stress. Some studies have also indicated that chronic stress may increase the risk of infections and cancer. On the other hand, various psychotherapeutic techniques appear to strengthen the immune system. As for immunological disease, we know that psychological factors are important in the case of allergic asthma. Moreover, serious life events prior to onset of disease are reported more frequently by seronegative than by seropositive rheumatoid arthritis patients. Prospective studies have shown that psychotherapeutic intervention can reduce disability in rheumatoid arthritis patients, but disease activity is diminished only rarely.
To investigate the effects of either a 7-day fast or a 7-day ketogenic diet upon serum interleuki... more To investigate the effects of either a 7-day fast or a 7-day ketogenic diet upon serum interleukin-6 (IL-6) and dehydroepiandrosterone sulphate (DHEAS) in RA patients. We measured serum concentrations of DHEAS and IL-6 in 23 RA patients with active disease, 10 of whom followed a 7-day sub-total fast and 13 of whom consumed a ketogenic diet (isoenergetic, carbohydrate &lt; 40 g/day) for 7 days. Clinical and laboratory variables were measured at baseline, on day 7 and after re-feeding on day 21. Correlation analyses were used to assess the associations between serum IL-6, DHEAS and disease activity variables at each timepoint. Fasting, but not the ketogenic diet, decreased serum IL-6 concentrations by 37% (p &lt; 0.03) and improved disease activity at day 7. Both fasting and the ketogenic diet increased serum DHEAS levels by 34% as compared with baseline (both p &lt; 0.006). Levels of IL-6, but not DHEAS, correlated with several disease activity variables. Both fasting and a ketogenic diet significantly increased serum DHEAS concentrations in RA patients. Only fasting significantly decreased serum IL-6 levels and improved disease activity. As the increases in serum DHEAS were similar in response to both fasting and a ketogenic diet, it is unlikely that the fall in serum IL-6 or clinical improvements after fasting were directly related to increases in serum DHEAS. The fasting-induced fall in serum IL-6 may underlie the fall in CRP and ESR observed in RA patients in response to a 7-day fast.
Paroxysmal nocturnal haemoglobinuria is a clonal, acquired disease affecting the membrane of the ... more Paroxysmal nocturnal haemoglobinuria is a clonal, acquired disease affecting the membrane of the blood cells, arising from a somatic mutation at the haematopoietic stem cell level. It results in clones of blood cells deficient in membrane bound proteins, such as the complement regulating molecules Decay Accelerating Factor (DAF = CD55) and Membrane Inhibitor of Reactive Lysis (MIRL = CD59). For many years, Ham&#39;s test has been essential for diagnostic testing of erythrocytes for paroxysmal nocturnal haemoglobinuria. We present a 3-colour flowcytometry method used for quantification of CD59-negative erythrocytes and CD55/CD59-negative leukocytes. The results from analysis of blood samples from six patients suffering from paroxysmal nocturnal haemoglobinuria and six healthy blood donors, using the flowcytometry method, Ham&#39;s test and a microtyping gelcard method are compared. Our flow cytometric method, using directly conjugated monoclonal antibodies to test both erythrocytes and leukocytes, is the most sensitive method. It is specific and delivers fast results. The method involves a minimum of manipulation of the fragile cells and can be recommended as an alternative to Ham&#39;s test and the gelcard test.
To evaluate the extent of food allergy/intolerance in rheumatoid arthritis, an elemental (hypoall... more To evaluate the extent of food allergy/intolerance in rheumatoid arthritis, an elemental (hypoallergenic) diet was studied in a controlled, double-blind pilot study. Ten patients were allocated to an experimental group and 7 to a control group. The patients in the experimental group received an elemental diet for 3 weeks, whereas the patients in the control group received a control soup consisting of milk, meat, fish, shellfish, orange, pineapples, tomatoes, peas and flour of wheat and corn. During the 4th week of the study the patients in both groups resumed their regular diet. A significant improvement was found in the number of tender joints (p = 0.04) in the experimental group, whereas improvement was found in the erythrocyte sedimentation rate (ESR) (p = 0.03) and in the thrombocyte count (p = 0.02) in the control group. Three patients in the elemental diet group and 2 patients in the control group improved in all of the measured disease variables during the dietary treatment period. There was no significant difference in disease activity variables between the two groups. These results suggest that some RA patients may respond to the elimination of offending food items. However, the results do not encourage treatment with an elemental diet in unselected RA patients.
Approximately one third of the Norwegian blood donor population has been tested for infection wit... more Approximately one third of the Norwegian blood donor population has been tested for infection with human T-lymphotropic virus type I and II (HTLV-I/II). This study was initiated to provide an indication as to whether or not the Norwegian transfusion service should screen the entire donor population for HTLV I/II. No HTLV-I infections were found among the blood donors. One new donor was confirmed HTLV-II positive. This individual had previously used drugs intravenously. HTLV-I/II infection can be regarded as a marker for risk behaviour, and testing can be of significance in the quality assurance of the transfusion service. We recommend that the entire blood donor population be tested for HTLV-I/II infections, and thereafter only new donors. The benefit of this scheme should be evaluated in the future.
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