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Biomedical subjects

J Abrahamsson

Publications and source records attributed to J Abrahamsson.

At least 19 recordsLinked to original sources
PubMed2005

Long-term results in children with AML: NOPHO-AML Study Group--report of three consecutive trials.

In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.

Acute Disease↗
PubMed2004

Internal standard in surface-enhanced Raman spectroscopy.

A method is presented for the use of SAM layers as internal standards for calibration in surface-enhanced Raman spectroscopy. Three cyano-containing compounds were attached to gold colloids via a metal-sulfur bond and evaluated for spectral stability and normalization capacity. The results show that the analyte, rhodamine 6G, and the internal standard signal enhancement covaried, and it was possible to quantify the analyte with PLS. The fact that the enhancing substrate was chaotic assemblies with large variation in signal enhancement shows the versatility of this method.

Journal Article↗
PubMed2003

NESP55, a novel chromogranin-like peptide, is expressed in endocrine tumours of the pancreas and adrenal medulla but not in ileal carcinoids.

Neuroendocrine secretory protein 55, NESP55, is an acidic protein belonging to the chromogranin family. The distribution of NESP55 in human tumours is not known. The aim of the present study was to study the expression of NESP55 in human gastrointestinal, pancreatic and adrenal tumours. A total of 118 human endocrine and nonendocrine tumours were examined by immunocytochemistry, and compared to the expression of chromogranin A (CgA) in the same tumours. Pancreatic endocrine tumours (14 out of 25), pheochromocytomas (19 out of 19), and neuroblastomas (seven out of 14) expressed NESP55, with the same strong labelling pattern in both benign and malignant tumours. Expression of NESP55 in pancreatic endocrine tumours and pheochromocytomas was confirmed by Western and Northern blot analysis. Immunocytochemical analysis demonstrated no labelling in ileal carcinoids (zero out of 15), and adrenocortical adenomas (zero out of 15). The majority of gastrointestinal and pancreatic carcinomas were negative for NESP55, with focal staining observed in two out of 30 tumours. In contrast, CgA was present in all neuroendocrine tumours examined (25 out of 25 pancreatic endocrine tumours, 19 out of 19 pheochromocytomas, 14 out of 14 neuroblastomas and 15 out of 15 ileal carcinoids). Thus, the expression of NESP55 in endocrine tumours of the gastrointestinal tract, pancreas and adrenals differs from that of CgA. Neuroendocrine secretory protein 55 is found in a subset of neuroendocrine tumours showing differentiation towards adrenal chromaffin cells and pancreatic islets cells.

Adolescent↗
PubMed2003

Vincristine in childhood leukaemia: no pharmacokinetic rationale for dose reduction in adolescents.

AIM: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. METHODS: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on day 1 of induction therapy. Plasma samples were drawn before and 10, 30, 360 and 1380 min after injection of vincristine 2.0 mg/m2 (maximum dose 2.0 mg) and analysed by high-performance liquid chromatography. RESULTS: The median value (and range) for distribution half-life was 6.4 min (0.8-11.8), elimination half-life 1014 min (258-2570), volume of distribution 445 L/m2 (137-1241) and total body clearance 362 ml/min/m2 (134-2553). No correlation was found between age and any of these pharmacokinetic parameters. The area under the concentration time curve (AUC) was significantly correlated to age (p = 0.002; p - 0.31), as expected from the dosage of vincristine. The lower AUC in children with a body surface area > 1 m2, which is reached at 8-9 y of age, indicates that they received a less intense treatment because of the capping of the vincristine dose at 2.0 mg. CONCLUSIONS: Vincristine pharmacokinetics were not age dependent in this paediatric population. Thus, we found no pharmacokinetic rationale for dose reduction in adolescents. The common practice of limiting the vincristine dose to 2.0 mg should be carefully reconsidered.

Adolescent↗
PubMed2002

Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia: multi-institutional collaborative study.

BACKGROUND: In adults, it has been shown that the pharmacokinetics of doxorubicin are highly variable, despite standardization of the dose based on body surface area (BSA). The purpose of this study was to determine the plasma concentrations of doxorubicin and its active metabolite doxorubicinol in children treated for acute lymphoblastic leukemia (ALL). PROCEDURE: Children, 107 in number, aged 1.3-17.3 years, were studied at Day 1 of induction therapy according to the current Nordic protocol. Five infants, 3-9 months old, were also included. Plasma samples were drawn 23 hr after the start of a 24-hr infusion of doxorubicin 40 mg/m(2), and analyzed by reversed-phase liquid chromatography. RESULTS: There was a more than 10-fold difference between patients in dose normalized plasma concentration of doxorubicin, median 62.8 ng/ml, range 22.6-334 ng/ml. The doxorubicin concentrations differed significantly between age groups (P = 0.003). Children aged 4-6 years had the highest doxorubicin concentrations, median 77.9 ng/ml, followed by 2-4-year-old children, median 64.3 ng/ml. Both younger and older children had median values of about 50 ng/ml. Patients with white blood cell (WBC) count > 50 x 10(9)/L at diagnosis had significantly lower doxorubicin concentrations, median 55.3 ng/ml, than those with WBC count < 10 x 10(9)/L, median 64.4 ng/ml (P = 0.015). There was no difference in doxorubicin concentration between boys and girls. No correlation was found between doxorubicin levels and serum aminotransferases or serum creatinine. The concentration of doxorubicinol was 13% (median value) of that of doxorubicin. Four infants, 7-9 months old, had plasma clearance between 350-431 ml/min/m(2), which is in the same range as in older children. A 3-month-old infant had a clearance of 181 ml/min/m(2). CONCLUSIONS: The age groups who had the highest doxorubicin concentrations, (2-) 4-6-year-old children, are known to make up a large proportion of standard risk ALL cases with good prognosis. The correlation between doxorubicin plasma levels and clinical effect needs further study. The influence of age, body composition, and tumor burden on the pharmacokinetics of antineoplastic drugs should also be further explored, aiming at improvements in the current dosing regimen based on BSA.

Adolescent↗
PubMed2001

No disadvantage in outcome of using matched unrelated donors as compared with matched sibling donors for bone marrow transplantation in children with acute lymphoblastic leukemia in second remission.

PURPOSE: We evaluated the outcome of children with acute lymphoblastic leukemia (ALL) in second remission (2CR), comparing bone marrow transplantation (BMT) using either matched sibling donors or unrelated donors (URDs). PATIENTS AND METHODS: A total of 65 patients, aged 2 months to 20 years at BMT, with ALL in 2CR underwent allogeneic BMT at seven Nordic centers during 1990 to 1997. Of the first relapses, 85% were in bone marrow; 46% occurred on therapy, and 54%, off therapy. The preparative regimens were cyclophosphamide plus total-body irradiation +/- antithymocyte/antilymphocyte globulin, busulfan plus cyclophosphamide +/- antithymocyte/antilymphocyte globulin, or cytarabine plus total-body irradiation. Of the allografts, 37 were from HLA-matched siblings and 28 were from URDs. RESULTS: In the sibling versus URD graft recipient groups, the posttransplantation 5-year event-free survival was 39% versus 54% (P =.4), the estimated posttransplantation relapse rate was 76% versus 40% (P = not significant [NS]), and the toxic death rate was 19% versus 11% (P = NS). The incidence of significant (grade 2 to 4) acute graft-versus-host disease (GVHD) was 38% versus 64% (P <.05) and was 14% versus 32% (P <.10) for severe (grade 3 to 4) acute GVHD; the incidence of chronic GVHD was 26% versus 57% (P <.05) and was 13% versus 22% (P = NS) for extensive chronic GVHD in the sibling and URD groups. CONCLUSION: BMT with matched URD allografts offers at least equal survival for children with ALL in 2CR, as compared with allografts from matched sibling donors. URD allografts were not associated with a higher toxic mortality rate, although both acute and chronic GVHD were more frequent with URD. Indications for using matched URD allografts in ALL 2CR can be considered the same as for using matched sibling donors.

Adolescent↗
PubMed2001

Proinflammatory cytokines mediate the systemic inflammatory response associated with high-dose cytarabine treatment in children.

BACKGROUND: Treatment with high-dose cytarabine (1-beta-D-arabinofuranosylcytosine) is often associated with an acute febrile reaction sometimes including abdominal pain, myalgia, and rash. The similarity of these symptoms to those caused by hypersecretion of cytokines in the systemic inflammatory response syndrome (SIRS) prompted us to investigate the plasma levels of proinflammatory cytokines during treatment of children with high-dose cytarabine. PROCEDURE: Sixteen children treated for hematological malignancies and in clinical remission were studied during treatment with six infusions of cytarabine given every 12 hr at a dose of 2 g/m(2). Blood samples for analysis of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1gamma (IL-1gamma), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and interleukin-1 receptor antagonist (IL-1ra) were obtained prior to treatment and subsequently at 12, 36 and 60 hr. Additional samples were collected as soon as fever occurred. RESULTS: Thirteen of 16 patients developed fever at a median time of 30 hr following start of treatment. At 12 hr levels of TNF-alpha were elevated followed by a rise in IL-6, IFN-alpha, and IL-1ra, peaking at the onset of fever. Thereafter these levels slowly declined whereas low IL-10 levels became detectable. CONCLUSIONS: We conclude that high-dose cytarabine treatment often induces release of TNF-alpha followed by the sequential release of other proinflammatory cytokines. Most likely these cytokines mediate the development of symptoms comprising the cytarabine syndrome.

Adolescent↗
PubMed2001

Multivariate evaluation of doxorubicin surface-enhanced Raman spectra.

Multivariate evaluation of surface-enhanced Raman spectra of doxorubicin in plasma was performed. In a principal component analysis (PCA) all spectral features were modelled into three principal components. The major variation of the data was shown to be the variation of doxorubicin Raman signal together with the doxorubicin fluorescence, whereas the variation due to plasma was of minor importance. It was also shown that the surface-enhanced Raman scattering (SERS) measurements were independent on such factors as measurement occasion and silver colloids. The presented results show that with some improvements, quantification of doxorubicin directly in plasma could be possible.

Animals↗
PubMed1999

Serum antibody levels and avidities to Escherichia coli O antigens and poliovirus type 1 antigen are increased in children treated for malignant disease.

BACKGROUND: Treatment of malignant disease in children is often associated with low serum immunoglobulin and reduced specific antibody levels. The aim of this study was to investigate if the functional affinity of specific antibodies in serum and saliva is reduced as well and to evaluate if antigenic exposure or treatment duration affects this antibody avidity. PROCEDURE: Serum samples were obtained from 45 children and salivary specimens from 30 children with malignant disease. The children were tested either prior to, during, or after chemotherapy. Levels of antibody to E. coli O and to poliovirus type 1 antigens were determined using an ELISA and isotype-specific relative antibody avidity was measured using thiocyanate to elute antibodies from solid-phase immobilized antigens. RESULTS: Children with malignant disease had higher levels and relative avidity indexes of serum antibodies to both antigens as compared to controls. The duration of treatment and type of malignant disease were unrelated to these parameters. In saliva, the level of antibodies to E. coli O antigens, but not to poliovirus type 1 antigen, increased during treatment. CONCLUSIONS: Both the amount and avidity of serum antibodies to these antigens are increased in children with malignant disease. This may be due to a dysregulation of the immune system caused by the malignancy and seems not to be dependent on exposure. In contrast, the avidity and levels of these antibodies in saliva seem to correlate with the presence of antigenic exposure.

Adolescent↗
PubMed1998

Loss of heterozygosity of 3p markers in neuroblastoma tumours implicate a tumour-suppressor locus distal to the FHIT gene.

Neuroblastoma is a heterogeneous childhood tumour of the sympathetic nervous system, in which deletions of chromosomal region 1p and amplification of the MYCN oncogene correlate with aggressive tumour behaviour. However, the majority of neuroblastoma tumours show neither of these aberrations, indicating that other chromosomal regions may be involved in tumorigenesis. Here, we report findings of loss of heterozygosity (LOH) on chromosome 3. In our neuroblastoma material, nine of 59 (15.3%) tested tumours showed allelic loss of chromosome 3p markers. We found significant clinical and biological differences between tumours with the loss of one entire chromosome 3 vs tumours with partial loss in chromosome region 3p. All children with tumours with whole chromosome 3 loss are long-term survivors, whereas all children with tumours showing partial 3p LOH have died from tumour progression. A consensus region found to be deleted in all the tumours with 3p deletions was defined by markers D3S1286 and D3S1295, i.e. 3p25.3-p14.3, distal to the FHIT gene.

Acid Anhydride Hydrolases↗
PubMed1998

Bone marrow fibrosis and radiological changes of the long bones in children with acute megakaryocytic leukaemia.

The diagnosis of acute megakaryocytic leukaemia (AMkL) may be difficult to establish owing to difficulties in obtaining adequate bone marrow aspirates secondary to bone marrow fibrosis. We describe three children without Down's syndrome under 2 y of age with AMkL. Although none of the patients had the non-random t(1;22) (p13;q13) translocation, bone marrow cells from all patients exhibited chromosome abnormalities with complex karyotypes, including trisomy 21 in two cases. All patients had profound bone marrow fibrosis and characteristic lamellar diaphyseal radiological changes of the long bones.

Bone Marrow↗
PubMed1997

Epinephrine and sodium bicarbonate independently and additively increase survival in experimental amitriptyline poisoning.

OBJECTIVES: Cardiac depression is the main adverse effect of severe tricyclic antidepressant poisoning. The aim of this study was to investigate whether treatment with epinephrine or norepinephrine increases survival as compared with standard treatment with sodium bicarbonate in experimental amitriptyline poisoning. DESIGN: Nonrandomized, controlled intervention trial. SETTING: University laboratory. SUBJECTS: Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 91). INTERVENTIONS: Rats subjected to a 60-min infusion of amitriptyline (2 mg/kg/min) were treated with a continuous infusion of either epinephrine, norepinephrine, sodium bicarbonate, epinephrine plus sodium bicarbonate, norepinephrine plus sodium bicarbonate, or placebo. MEASUREMENTS AND MAIN RESULTS: Inotropic drug treatment was associated with an increased survival rate as compared with treatment with sodium bicarbonate and treatment with placebo. Epinephrine treatment was superior to norepinephrine. Additional treatment with sodium bicarbonate increased survival rate for each inotropic drug. Sodium bicarbonate and inotropic drug treatment independently increased the survival rate (p < .001 for both effects). No interaction between these two treatment effects was observed. CONCLUSIONS: Both epinephrine and norepinephrine increased the survival rate in tricyclic antidepressant poisoning in rats. Sodium bicarbonate increased the survival rate independent of inotropic drug treatment. Furthermore, epinephrine was superior to norepinephrine when used both with and without sodium bicarbonate, and the most effective treatment was epinephrine plus sodium bicarbonate.

Amitriptyline↗
PubMed1997

Bone marrow immunoglobulin-secreting cells are not reduced in children with leukaemia as compared to children with solid tumours.

Children with leukaemia exhibit multiple immunological disturbances, including low circulating levels of immunoglobulins, caused by both the disease and chemotherapy. We investigated the number of isotype-specific immunoglobulin-secreting cells (ISCs) in the bone marrow at the time of diagnosis in 32 children and during therapy in 12 children with leukaemia. We compared these to the number of ISCs in 17 untreated children with solid tumours and related the ISCs to serum immunoglobulin levels, lymphocyte subsets, response to mitogenic stimulation and serum cytokine levels. Bone marrow specimens were analysed for isotype-specific (immunoglobulins G, A and M) ISCs using the ELISPOT method. At the time of diagnosis, for all isotypes, the total number of ISCs per millilitre of bone marrow in children with leukaemia was no different from that in children with solid tumours. Chemotherapy significantly decreased the number of ISCs. The quantitative relationship between the different isotypes was unaffected by both tumour type and therapy. It can be concluded that in childhood leukaemia, tumour replacement of bone marrow cells does not cause a decreased number of ISCs and can therefore not account for the low serum immunoglobulin levels observed at time of diagnosis. Chemotherapy reduces the number of ISCs without changing the isotype distribution.

Adolescent↗
PubMed1997

Interleukin 6, but not tumour necrosis factor-alpha, is a good predictor of severe infection in febrile neutropenic and non-neutropenic children with malignancy.

OBJECTIVE: Interleukin-6 (IL6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important mediators of the inflammatory response in human infection. The aim of this study was to determine the relationship between serum levels of IL6, TNF-alpha, IFN-gamma and CRP in febrile children with malignant disease, and relate these levels to aetiology of fever, presence of neutropenia and the effect of untreated malignancy. METHODS: 110 febrile episodes in 70 children with malignant disease were included. Cytokine analyses were performed with sensitive immunoradiometric methods using double monoclonal antibodies. RESULTS: IL6 had a sensitivity of 74% in detecting sepsis in children with fever and malignant disease. This sensitivity was not influenced by the presence of neutropenia or newly diagnosed malignancy. A positive correlation between IL6 and the CRP levels on the following day was observed (r = .53). TNF-alpha was elevated in 22% of the episodes and mean levels were significantly higher in untreated malignancy but lower in neutropenic patients. IFN-gamma was elevated in 18% of cases and correlated strongly with mean TNF-alpha levels. CONCLUSIONS: IL6 is a sensitive and early predictor of bacterial infection in both neutropenic and non-neutropenic febrile children with malignancy. It is more sensitive than CRP in detecting sepsis, but the predictive value is too low to allow IL6 levels to influence initial treatment decisions in patients with granulocytopenia. TNF-alpha production seems to be impaired in neutropenic children and serum TNF-alpha cannot be employed as an indicator of bacterial infection.

Adolescent↗
PubMed1995

Antiarrhythmic effects of magnesium sulphate. Report of three cases.

A wide variety of antiarrhythmic agents is used in treatment of both supraventricular and ventricular arrhythmias. Magnesium sulphate has previously been used mainly in the treatment of torsade de pointe arrhythmias but several reports show that this agent may be used in the treatment of arrhythmias of different aetiology. We describe 3 patients who exhibited arrhythmias affecting haemodynamic performance. Case #1 had a subarachnoid haemorrhage and developed a supraventricular tachycardia. In case #2, ventricular tachycardia appeared during the postoperative course after abdominal surgery. Case #3 experienced critical heart failure due to dilated cardiomyopathy and had an irregular heart rhythm with multiple ectopic beats. In all three cases the administration of intravenous magnesium sulphate was successful in treating the arrhythmias. Magnesium sulphate is an antiarrhythmic agent that is effective mainly in treatment of ventricular arrhythmias. The drug can also be employed as second-line treatment of supraventricular arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1995

Immunoglobulin levels and lymphocyte response to mitogenic stimulation in children with malignant disease during treatment and follow-up.

Intensification of chemotherapeutic regimens has improved survival in childhood malignant disease. To characterize the impact of this intensified therapy on some aspects of the immune system, we have, in an unselected material of 220 children with malignant disease, investigated serum immunoglobulin levels and lymphocyte response at diagnosis and then subsequently during and up to 4 years after cessation of therapy. In leukemia and Hodgkin's disease, all immunoglobulin isotypes decreased during therapy. A profound depression of immunoglobulin M levels, lasting well after completion of therapy, was seen in all tumor types. The mitogenic response was attenuated in patients with leukemia at diagnosis but was rapidly restored after institution of therapy. Patients with solid tumors, particularly Hodgkin's disease, had a reduced mitogenic response during therapy. Thus these patients exhibit multiple immunological disturbances. The basis of the pronounced immunoglobulin M deficiency remains unclear.

Adolescent↗
PubMed1994

Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat.

OBJECTIVES: Amitriptyline poisoning is associated with ventricular arrhythmias. Standard treatment is sodium bicarbonate but further intervention may be necessary. The present study compared the actions of lidocaine and magnesium sulfate on ventricular tachycardia induced by amitriptyline. DESIGN: Nonrandomized, controlled, intervention trial. SETTING: University laboratory. SUBJECTS: Thirty male Wistar rats anesthetized with pentobarbital and mechanically ventilated. INTERVENTIONS: After pretreatment with norepinephrine, the animals were subjected to a continuous infusion of amitriptyline. After the appearance of ventricular tachycardia, they were treated with magnesium sulfate (45 mg/kg + 15 mg/kg/min) or lidocaine (1 mg/kg + 0.5 mg/kg/min) or glucose infusion as a control. MEASUREMENTS AND MAIN RESULTS: In the group treated with magnesium sulfate, electrocardiogram tracings demonstrated that nine of ten animals converted from ventricular tachycardia to sinus rhythm compared with one of ten in both the lidocaine- and glucose-treated groups (p < .001). The animals treated with magnesium sulfate also had a significantly longer total time in sinus rhythm (10.0 +/- 1.6 mins) than those rats treated with lidocaine (1.7 +/- 1.5 mins) or glucose (1.5 +/- 1.5 mins). Magnesium sulfate significantly decreased blood pressure and heart rate, but no severe hemodynamic side effects were observed. CONCLUSIONS: Magnesium sulfate is effective in converting ventricular tachycardia in hyperadrenergic amitriptyline poisoning. In contrast, lidocaine had no effect on arrhythmias.

Amitriptyline↗