Biomedical subjects

B Andersson

Publications and source records attributed to B Andersson.

At least 19 recordsLinked to original sources

PubMed2006

On-site gamma-ray spectroscopic measurements of fission gas release in irradiated nuclear fuel.

An experimental, non-destructive in-pool, method for measuring fission gas release (FGR) in irradiated nuclear fuel has been developed. Using the method, a significant number of experiments have been performed in-pool at several nuclear power plants of the BWR type. The method utilises the 514 keV gamma-radiation from the gaseous fission product (85)Kr captured in the fuel rod plenum volume. A submergible measuring device (LOKET) consisting of an HPGe-detector and a collimator system was utilised allowing for single rod measurements on virtually all types of BWR fuel. A FGR database covering a wide range of burn-ups (up to average rod burn-up well above 60 MWd/kgU), irradiation history, fuel rod position in cross section and fuel designs has been compiled and used for computer code benchmarking, fuel performance analysis and feedback to reactor operators. Measurements clearly indicate the low FGR in more modern fuel designs in comparison to older fuel types.

Gases↗

PubMed2006

A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis.

We performed a network-based analysis of DNA microarray data from allergen-challenged CD4(+) T cells from patients with seasonal allergic rhinitis. Differentially expressed genes were organized into a functionally annotated network using the Ingenuity Knowledge Database, which is based on manual review of more than 200,000 publications. The main function of this network is the regulation of lymphocyte apoptosis, a role associated with several genes of the tuber necrosis factor superfamily. The expression of TNFRSF4, one of the genes in this family, was found to be 48 times higher in allergen-challenged cells than in diluent-challenged cells. TNFRSF4 is known to inhibit apoptosis and to enhance Th2 proliferation. Examination of a different material of allergen-stimulated peripheral blood mononuclear cells showed a higher number of interleukin-4(+) type 2 CD4(+) T (Th2) cells in patients than in controls (P<0.01), as well as a higher number of non-apoptotic Th2 cells in patients (P<0.01). The number of Th2 cells expressing TNFRSF4, TNFSF7 and TNFRSF1B was also significantly higher in patients. Treatment with anti-TNFSF4 resulted in a significantly decreased number of Th2 cells (P<0.05). A logical inference from all this is that the proliferation of allergen-challenged Th2 cells is associated with a decreased apoptosis of Th2 cells and an increase in TNFRSF4 signalling.

Adolescent↗

PubMed2006

Induction of apoptosis by intracellular potassium ion depletion: using the fluorescent dye PBFI in a 96-well plate method in cultured lung cancer cells.

Depletion of intracellular potassium ions (K+) is necessary for cells to shrink, activate caspases and induce DNA fragmentation, events which are features of apoptosis. Here we describe a 96-well plate method using the cell permeable form of K+ binding benzofuran isophtalate (PBFI-AM) to measure intracellular K+ content in relation to untreated control. Cultured human pulmonary mesothelioma cells (P31) and small-cell lung cancer cells (U1690) were treated with K+ flux modulators in order to deprive the cells of intracellular K+. The combination of K+ influx inhibition with 10 micromol/L bumetanide plus 10 micromol/L ouabain and K+ efflux stimulation with 3 mg/L amphotericin B or 5 micromol/L nigericin efficiently reduced the intracellular K+ content after 3 h. Manipulation of K+ fluxes with subsequent intracellular K+ depletion induced apoptosis of lung cancer cells, as detected by caspase-3 activity after 3 h K+ depletion followed by 24 h proliferation and TUNEL positive staining after 48 h proliferation. We concluded that the PBFI-AM assay was a useful tool to determine intracellular K+ content in relation to untreated control, and that intracellular K+ depletion of lung cancer cells by clinically used drugs of relevant concentrations induced apoptosis. These findings may lead to novel therapeutic strategies in the treatment of lung cancer.

Apoptosis↗

PubMed2006

Long-term outcome in heart failure patients evaluated for heart transplantation but considered too well.

Patients referred for heart transplantation evaluation may be accepted for transplantation, or denied due to existing contraindications or judged to be too well. There is little knowledge about long-term outcome in patients considered too well for transplantation. Ninety-five patients (mean age 47 +/- 12 years, 73% men) judged "too well" at evaluation were included in this study. Acceptance for transplantation followed international guidelines. The follow-up (mean 4.5 years) was complete. Twenty of the 95 patients (21%) were eventually accepted for transplantation during the follow-up period. Twenty-one patients (22%) died, 13 without preceding acceptance for transplantation, 4 on the waiting list for transplantation, and 4 after transplantation. Cumulative and transplant-free survival at 1, 5, and 10 years were 91%, 82%, and 65%, and 90%, 70%, and 50%, respectively. In conclusion, long-term survival in patients considered too well for transplantation is better than in most contemporary series of heart transplant recipients, which suggests that the guidelines for acceptance are appropriate. However, almost one fifth of the patients die without preceding acceptance for transplantation or while on the waiting list, which illustrates the need for frequent reevaluation and tools to identify heart failure patients with an increased risk for sudden death.

Adult↗

PubMed2006

The direct pathway of human T-Cell allorecognition is not tolerized by stimulation with allogeneic peripheral blood mononuclear cells irradiated with high-dose ultraviolet B.

Transfusions of high-dose (> or =10,000 Joule/m(2)) ultraviolet-B (UVB)-irradiated allogeneic leukocytes in rodent models have been shown to induce immunologic tolerance that is mediated by allospecific regulatory CD4(+) T cells. Whether these regulatory T cells recognize alloantigens through the direct or indirect pathway of allorecognition is controversial. Here, we demonstrate that the proliferative response obtained in standard primary mixed leukocyte reactions (MLRs) with human peripheral blood mononuclear cells (PBMCs) reflected a CD4(+) T-cell-dependent direct pathway of allorecognition and that high-dose UVB irradiation of PBMCs totally inhibited their capacity to induce a proliferative alloresponse. Re-stimulation with gamma-irradiated PBMCs from the same allogeneic donor (secondary MLR) elicited a proliferative and Th1-deviated response that was similar to the response induced in unprimed PBMCs. Finally, high-dose UVB was found to induce a rapid and massive apoptosis of irradiated PBMCs. Collectively, these data indicate that leukocytes irradiated with high-dose UVB are unable to prime for unresponsiveness or immune deviation in T cells directly recognizing allogeneic major histocompatibility complex molecules. Because it is well-established that antigens within transfused apoptotic cells are captured by resident tolerogenic spleen dendritic cells, we propose that tolerance induced by transfusions of high-dose UVB-irradiated leukocytes primarily involve T cells indirectly recognizing alloantigens.

Apoptosis↗

PubMed2005

Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.

OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

Adolescent↗

PubMed2005

Temporal profile of ultrastructural changes in cortical neurones after a compression lesion.

We studied the occurrence of apoptosis and secondary delayed cell death at various time points in the penumbra zone, which is the target for therapeutic intervention after stroke. A compression lesion was induced in the right sensory motor cortex of rat brains. At 0.5, 1, 3, 6, 12, 24, 48 and 72 h after lesioning, motor functions were evaluated by behavioral tests, and cortical layers IV and V were examined by electron microscopy. Behavioral recovery was observed at 48 h after lesioning. At 0.5-1 h in the lesioned area, the neuropil was expanded and contained affected cells. Apoptotic cells were found between 0.5-72 h, and at 12 h, 47.3 % of the total cell number was apoptotic cells. On the contralateral side, cells showed an enlarged endoplasmic reticulum at 3 h, indicating secondary delayed cell death. Our results show that a compression lesion is a useful model for studying ultrastructural changes in injured cells. The lesion results in the penumbra zone with apoptotic cell death between 0.5-72 h. As secondary delayed cell death occurred on the contralateral side at three hours after lesioning might be the time period during which injured, but still viable, neurons can be targets for acute treatment.

Animals↗

PubMed2005

Gastrointestinal complications after cardiac surgery.

BACKGROUND: Gastrointestinal complications after cardiac surgery are often difficult to diagnose, and are associated with high morbidity and mortality rates. The aim of this study was to determine risk factors for these complications. METHOD: Between 1996 and 2001 data were collected prospectively from 6119 patients who underwent 6186 cardiac surgical procedures. Data from patients who experienced major gastrointestinal complications were analysed retrospectively by univariate and multivariate analysis. RESULTS: Fifty major gastrointestinal complications were identified in 47 patients (incidence 0.8 per cent). Thirteen of these patients died within 30 days. The most common complication was upper gastrointestinal bleeding (16 patients). Intestinal ischaemia was the most lethal complication (eight of ten patients died). Abdominal surgical operations were performed in 12 patients. Multivariate analysis identified nine variables that independently predicted major gastrointestinal complications: age over 80 years, active smoker, need for preoperative inotropic support, New York Heart Association class III-IV, cardiopulmonary bypass time more than 150 min, postoperative atrial fibrillation, postoperative heart failure, reoperation for bleeding and postoperative vascular complications. CONCLUSION: Nine risk factors for the development of major gastrointestinal complications after cardiac surgery were identified. Gastrointestinal complications were often lethal but did not independently predict death within 30 days.

Aged↗

PubMed2005

Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin's disease: low transplant-related mortality and impact of intensity of conditioning regimen.

A total of 40 patients with relapsed/refractory Hodgkin's disease (HD) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). Disease status at allo-SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens were fludarabine-cyclophosphamide+/-antithymocyte globulin (n=14), a less intensive regimen, and fludarabine-melphalan (FM) (n=26), a more intensive one. The two groups had similar prognostic factors. The median time to neutrophil recovery (ie absolute neutrophil count >/=500/microl) was 12 days (range 10-24). The median time to platelet recovery (ie platelet count >/=20 000/microl) was 17 days (range 7-132). Day 100 and cumulative (18-month) transplant-related mortalities (TRMs) were 5 and 22%. Twenty-four patients (60%) are alive (14 in complete remission or complete remission, unconfirmed/uncertain) with a median follow-up of 13 months (4-78). In all, 16 patients expired (TRM n=8, disease progression n=8). FM patients had better overall survival (73 vs 39% at 18 months; P=0.03), and a trend towards better progression-free survival (37 vs 21% at 18 months; P=0.2). RIC allo-SCT is feasible in relapsed/refractory HD patients with a low TRM. The intensity of the preparative regimen affects survival.

Adolescent↗

PubMed2005

Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia.

The major cause of failure after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) is disease relapse or progression. We analyzed the outcome of second HSCT for treatment of patients with relapsed, refractory AML/myelodysplastic syndrome (MDS) at our institution. A total of 72 patients were eligible for this analysis. In all, 25 (35%) patients received salvage chemotherapy prior to the second transplant procedure and only two (3%) patients were in complete remission at the time of the second transplant. A total of 20 patients (28%) had low leukemia burden as measured by the absence of peripheral blood blasts and <or=5% blasts in the bone marrow at the time of the second transplant. Although, the overall median survival after the second transplant was 6 months, a subset of patients who had low leukemia burden at the time of the second transplant had a 5-year survival of 25 vs 12% in those with a high leukemia burden. Thus, a second transplant may offer the possibility of long-term disease control in a subset of patients who have a 'low bulk' disease at the time of transplantation.

Adolescent↗

PubMed2005

Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid-resistant cGVHD. Thirty-five patients who developed GVHD after day 100 post-transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count > or = 100 x 10(9)/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD-free survival are warranted.

Adult↗

PubMed2005

Direct allorecognition promotes activation of bystander dendritic cells and licenses them for Th1 priming: a functional link between direct and indirect allosensitization.

T-cell sensitization to indirectly presented alloantigens (indirect pathway of allorecognition) plays a critical role in chronic rejection. The usual very efficient priming of such self-restricted, T helper type 1 (Th1)-deviated CD4+ T cells obviously conflicts with the fact that allogeneic MHC molecules are poorly immunogenic per se. The aim of the present study is to elucidate whether direct allosensitization induces production of inflammatory mediators that may affect recruitment and activation of immature bystander (host) dendritic cells (DC). These potential mechanisms were studied in vitro by conducting primary allogeneic mixed leucocyte reactions (MLR), mimicking the priming phase in secondary lymphoid organs, and secondary MLR, mimicking the effector phase within the graft. Primary, and particularly secondary, MLR supernatants were found to contain high levels of monocyte/immature DC-recruiting CC chemokines and pro-inflammatory cytokines. Exposure of immature DC to primary or secondary MLR supernatants was found to upregulate CD40 expression and further enhanced lipopolysaccharide-induced interleukin-12 (IL-12) p70 production. Secondary MLR supernatants additionally induced upregulation of CD86 and deviated allogeneic T-cell responses towards Th1 (enhanced interferon-gamma production without concomitant induction of detectable IL-4 or IL-10 production). These findings indicate that direct allorecognition may act as a Th1-deviating adjuvant for indirect allosensitization.

Antigen Presentation↗

PubMed2004

Effect of carvedilol on diastolic function in patients with diastolic heart failure and preserved systolic function. Results of the Swedish Doppler-echocardiographic study (SWEDIC).

AIM: The purpose of this study was to investigate the effects of carvedilol on diastolic function (DF) in heart failure patients with preserved left ventricular (LV) systolic function and abnormal DF. PATIENTS AND METHODS: We randomised 113 patients with diastolic heart failure (DHF) (symptomatic, with normal systolic LV function and abnormal DF) into a double blind multi-centre study. The patients received either carvedilol or matching placebo in addition to conventional treatment. After uptitration, treatment was continued for 6 months. Two-dimensional and Doppler echocardiography were used for quantification of LV function at baseline and at follow-up. Four different DF variables were evaluated by Doppler echocardiography: mitral flow E:A ratio, deceleration time (DT), isovolumic relaxation time (IVRT) and the ratio of systolic/diastolic pulmonary venous flow velocity (pv-S/D). Primary endpoint was change in the integrated quantitative assessment of all four variables during the study. RESULTS: Ninety-seven patients completed the study. A mitral flow pattern reflecting a relaxation abnormality was recorded in 95 patients. There was no effect on the primary endpoint, although a trend towards a better effect in carvedilol treated patients was noticed in patients with heart rates above 71 beats per minute. At the end of the study, there was a statistically significant improvement in E:A ratio in patients treated with carvedilol (0.72 to 0.83) vs. placebo (0.71 to 0.76), P<0.05. CONCLUSIONS: Treatment with carvedilol resulted in a significant improvement in E:A ratio in patients with heart failure due to a LV relaxation abnormality. E:A ratio was found to be the most useful variable to identify diastolic dysfunction in this patient population. This effect was observed particularly in patients with higher heart rates at baseline.

Adrenergic beta-Antagonists↗

PubMed2004

Disease perception and social behaviour in persistent rhinitis: a comparison between patients with allergic and nonallergic rhinitis.

BACKGROUND: Although the understanding of the pathophysiology and pharmacology of rhinitis has increased within recent years, few studies have examined the impact of rhinitis on patients' behaviour. AIM: To compare perennial allergic rhinitis (PAR) and perennial nonallergic rhinitis (PNR) in terms of patients' perception of their disease and its psychosocial concomitants. METHODS: Thirty-one PAR patients and 32 PNR patients responded to a standard symptom list and were interviewed in-depth regarding their complaints and the impact of rhinitis on their daily lives. RESULTS: PAR and PNR patients reported similar somatic and psychosocial complaints. In both disease groups the adverse effects of rhinitis were reported to be substantially limiting, particularly in social contacts, the impact appearing to be more severe in the women. CONCLUSION: Rhinitis has a severe impact on the daily lives of patients, women reporting more severe psychosocial effects. Disease perception and social adjustment appear to not depend appreciably on whether or not an objective diagnosis of rhinitis can be established.

Female↗

PubMed2004

Incidence, management and recurrence rate of acute pancreatitis.

BACKGROUND: Acute pancreatitis is a common condition that is still associated with substantial morbidity and mortality rates. Management, outcome and recurrence rate in acute pancreatitis in a clinical setting using a conservative management approach are described. METHODS: A total of 1376 consecutive cases representing 2211 hospitalizations due to acute pancreatitis treated at the Dept. of Surgery, Lund University Hospital, Lund, were reviewed retrospectively. Management, outcome and recurrence rate were recorded. RESULTS: Incidence, including recurrences, was 300 per million per year; 21% of patients had recurrent (> or =2) attacks. In relapsing disease, two-thirds of patients had the first attack within 3 months. Mortality decreased over the period studied, but overall it was 4.2%; mortality in relapsing attacks was 2.5%, related to multiple organ dysfunction (MODS) in 67% and occurring within the first week in 36%. CONCLUSIONS: Despite a conservative approach in the management of acute pancreatitis, mortality is still substantial, frequently occurs early after admission, is associated with MODS and is also seen in relapsing disease. Early cholecystectomy and bile duct clearance could decrease recurrent attacks of biliary pancreatitis.

Acute Disease↗

PubMed2004

Class separation of buildings with high and low prevalence of SBS by principal component analysis.

In this study, we were able to separate buildings with high and low prevalence of sick building syndrome (SBS) using principal component analysis. The prevalence of SBS was defined by the presence of at least one typical skin, mucosal and general (headache and fatigue) symptom. Data from the Swedish Office Illness Study describing the presence and level of chemical compounds in outdoor, supply, and room air, respectively, were evaluated together with information about the buildings in six models. When all data were included the most complex model was able to separate 71% of the high prevalence buildings from the low prevalence buildings. The most important variable that separates the high prevalence buildings from the low prevalence buildings was a more frequent occurrence or a higher concentration of compounds with shorter retention time in the high prevalence buildings. Elevated relative humidity in supply and room air and higher levels of total volatile organic compounds in outdoor and supply air were more common in high prevalence buildings. Ten building variables also contributed to the separation of the two classes of low and high prevalence buildings.

Air Pollutants↗

PubMed2004

Cartilage oligomeric matrix protein increases in serum after the start of growth hormone treatment in prepubertal children.

Both GH and IGF-I stimulate bone growth, but the molecular mechanisms mediating their effects on the growth plate are not fully understood. We measured gene expression by microarray analysis in primary cultured human chondrocytes treated with either GH or IGF-I. One of the genes found to be up-regulated by both GH and IGF-I was that encoding cartilage oligomeric matrix protein (COMP). This protein is predominantly found in the extracellular matrix of cartilage. Mutations in the COMP gene have been associated with syndromes of short stature. To verify that COMP is regulated by GH in vivo, we measured COMP levels in serum in short children treated with GH. The study included 113 short prepubertal children (14 girls and 99 boys) with a mean (+/- sd) age of 8.84 +/- 2.76 yr, height sd score of -2.74 +/- 0.67, and IGF-I sd score of -1.21 +/- 1.07 at the start of GH administration. Serum levels of COMP were 1.58 +/- 0.28, 1.83 +/- 0.28 (P < 0.0001), 1.91 +/- 0.28 (P < 0.0001), 1.78 +/- 0.28 (P < 0.001), and 1.70 +/- 0.24 (P < 0.05) microg/ml at baseline and after 1 wk and 1, 3, and 12 months, respectively. In conclusion, we have demonstrated that COMP expression is up-regulated by both GH and IGF-I in primary cultured human chondrocytes. Furthermore, serum levels of COMP increase after the start of GH treatment in short children.

Body Height↗

PubMed2004

Reducing the total discharge from a large WWTP by separate treatment of primary effluent overflow.

At many large wastewater treatment plants (WWTPs) the increased hydraulic load, caused by combined sewer systems during storm events, results in primary effluent overflow when the capacity of further treatment is exceeded. Due to stringent effluent standards, regulating the total discharge from the WWTPs, the Rya WWTP in Göteborg and the Sjölunda WWTP in Malmö will have to reduce the impact of primary effluent overflow. Separate, high rate, precipitation processes operated only during high flow conditions have been investigated in pilot units at the two WWTPs. Precipitation in existing primary settlers operated at a surface loading of 3.75 m/h removed phosphorus to 0.35 mg/l. The Actiflo process was also shown to remove suspended solids and phosphorus well. BOD was reduced by 50-60%. With such processes the overall effluent concentrations from the plants can be reduced significantly. Key upgrading features are small footprints, short start up time and high efficiency.

Bioreactors↗