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Biomedical subjects

B Nilsson

Publications and source records attributed to B Nilsson.

At least 19 recordsLinked to original sources
PubMed2007

Quality of life in children with hypoplastic left heart syndrome.

AIM: To measure quality of life in children with hypoplastic left heart syndrome and their families. METHODS: A questionnaire exploring socioeconomic status, structure and function of networks and psychological well-being was completed by the families of all 18 patients older than 2 years (age range 2.7-10.6). The results were compared with those of 180 healthy Swedish children matched for age and sex. RESULTS: There were no significant differences between the groups in any of the aspects of socioeconomic status. Study group parents had not more available time for their child (p < 0.05) and more separations/divorces (p < 0.01). The patients had lower self-esteem (p < 0.05), more psychosomatic symptoms (p < 0.01) [corrected] and lower peer acceptance (p < 0.01) than control children. CONCLUSION: With regard to psychological well-being, quality of life was significantly lower in children with hypoplastic left heart syndrome than in healthy controls.

Cardiac Surgical Procedures↗
PubMed2006

Influence of electrodes on the photon energy deposition in CVD-diamond dosimeters studied with the Monte Carlo code PENELOPE.

A new dosimeter, based on chemical vapour deposited (CVD) diamond as the active detector material, is being developed for dosimetry in radiotherapeutic beams. CVD-diamond is a very interesting material, since its atomic composition is close to that of human tissue and in principle it can be designed to introduce negligible perturbations to the radiation field and the dose distribution in the phantom due to its small size. However, non-tissue-equivalent structural components, such as electrodes, wires and encapsulation, need to be carefully selected as they may induce severe fluence perturbation and angular dependence, resulting in erroneous dose readings. By introducing metallic electrodes on the diamond crystals, interface phenomena between high- and low-atomic-number materials are created. Depending on the direction of the radiation field, an increased or decreased detector signal may be obtained. The small dimensions of the CVD-diamond layer and electrodes (around 100 microm and smaller) imply a higher sensitivity to the lack of charged-particle equilibrium and may cause severe interface phenomena. In the present study, we investigate the variation of energy deposition in the diamond detector for different photon-beam qualities, electrode materials and geometric configurations using the Monte Carlo code PENELOPE. The prototype detector was produced from a 50 microm thick CVD-diamond layer with 0.2 microm thick silver electrodes on both sides. The mean absorbed dose to the detector's active volume was modified in the presence of the electrodes by 1.7%, 2.1%, 1.5%, 0.6% and 0.9% for 1.25 MeV monoenergetic photons, a complete (i.e. shielded) (60)Co photon source spectrum and 6, 18 and 50 MV bremsstrahlung spectra, respectively. The shift in mean absorbed dose increases with increasing atomic number and thickness of the electrodes, and diminishes with increasing thickness of the diamond layer. From a dosimetric point of view, graphite would be an almost perfect electrode material. This study shows that, for the considered therapeutic beam qualities, the perturbation of the detector signal due to charge-collecting graphite electrodes of thicknesses between 0.1 and 700 microm is negligible within the calculation uncertainty of 0.2%.

Diamond↗
PubMed2006

Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer.

The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB-IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (P=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT.

DNA Damage↗
PubMed2006

An oncolytic conditionally replicating adenovirus for hormone-dependent and hormone-independent prostate cancer.

The use of conditionally replicating adenoviruses offers an attractive complementary treatment strategy for localized prostate cancer. We have produced a replicating adenovirus, Ad[I/PPT-E1A], where E1A gene expression is controlled by a recombinant regulatory sequence designated PPT. The PPT sequence comprises a PSA enhancer, a PSMA enhancer and a T-cell receptor gamma-chain alternate reading frame protein promoter, and it is shielded from transcriptional interference from adenoviral backbone sequences by an H19 insulator. Ad[I/PPT-E1A] yields prostate-specific E1A protein expression, viral replication and cytolysis in vitro. Furthermore, Ad[I/PPT-E1A] considerably regresses the growth of subcutaneous LNCaP prostate cancer tumors in nude mice. Importantly, the viral replication and cytolytic effect of Ad[I/PPT-E1A] are independent of the testosterone levels in the prostate cancer cells. This may be beneficial in a clinical setting since many prostate cancer patients are treated with androgen withdrawal. In conclusion, Ad[I/PPT-E1A] may prove to be useful in the treatment of localized prostate cancer.

Adenoviridae↗
PubMed2006

Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours.

BACKGROUND: The aim of this retrospective population-based study, which was conducted before the introduction of imatinib, was to evaluate the role of surgery in patients with gastrointestinal stromal tumours (GISTs) and clarify which subgroups might benefit from adjuvant treatment. METHODS: Two hundred and fifty-nine patients with clinically detected GISTs were studied. Univariate and multivariate analyses were performed to identify predictors for recurrent disease and survival. RESULTS: Thirty of 48 patients with high-risk GISTs and all of those with overtly malignant tumours developed recurrent tumour after complete (R0) resection. Thirty-four of 38 first recurrences occurred within 36 months of surgery. No recurrence was observed after 72 months. R0 resection, achieved in 48 (80 per cent) of 60 patients with high-risk tumours, was significantly associated with a decreased risk of death from tumour recurrence (P = 0.008). CONCLUSION: Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.

Adolescent↗
PubMed2006

EUS-guided FNA immediately after unrevealing transbronchial needle aspiration in the evaluation of mediastinal lymphadenopathy: a prospective study.

BACKGROUND: Transbronchial needle aspiration (TBNA) and EUS-guided FNA (EUS-FNA) are minimally invasive diagnostic approaches to mediastinal lymphadenopathy. Rapid on-site cytopathologic evaluation (ROSE) may facilitate the decision whether to proceed to a second procedure in the same session. The aim of this study was to determine the utility of TBNA with ROSE, combined with the option for immediate EUS-FNA in a single-session approach to mediastinal lymphadenopathy. METHODS: We prospectively recruited 20 patients (12 men; mean age 66.7 +/- 10.2 years) with mediastinal lymphadenopathy on CT who required cytopathologic evaluation. Bronchoscopy was first performed with TBNA and ROSE. If this was unrevealing, EUS-FNA was performed immediately afterward with ROSE. All procedures were performed with the patient under local anesthesia and sedation. RESULTS: TBNA specimens were deemed adequate on-site in 13 patients, and EUS-FNA was performed in the remaining 7 patients. TBNA with ROSE was falsely negative in one patient. The diagnostic yield for TBNA and EUS-FNA alone was 65% and 86%, respectively. This single-session approach provided a yield of 90%, with no complications. The final diagnoses were 12 non-small-cell lung cancer, two small-cell lung cancer, one metastatic adenocarcinoma, two sarcoidosis, one tuberculosis, one lymphoma, and one with no definitive diagnosis. CONCLUSIONS: Combining TBNA with the option for EUS-FNA immediately after unrevealing TBNA gave a yield approaching that of mediastinoscopy and, therefore, may reduce the need for invasive mediastinal sampling. This single-session endoscopic approach was safe, required only local anesthesia and sedation, was convenient, and obviated the need for patients to return for a second procedure.

Aged↗
PubMed2006

Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation.

The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation.

Anticoagulants↗
PubMed2005

Current status of clinical islet transplantation.

Islet transplantation is currently being explored as a treatment for patients with type 1 diabetes. At present, the number of patients becoming insulin-independent is rapidly increasing world-wide applying the transplantation protocol originally described by the group in Edmonton. A hallmark in this procedure is repeated infusions of islets obtained from 2 to 4 donors until normoglycemia is achieved. In order to establish islet transplantation as a widely accepted treatment modality, and make tolerance induction regimes applicable, it is essential that the donor:recipient ratio is brought down to 1:1. A conceivable strategy to achieve this goal in clinical islet transplantation is discussed.

Animals↗
PubMed2005

Key factors for human islet isolation and clinical transplantation.

BACKGROUND: To further improve the outcome of clinical islet transplantation analysis of the impact of donor- and process-related factors could be of great importance. MATERIALS AND METHODS: Thirty-eight consecutive clinical islet transplantations were performed with consecutive islet isolations. Univariate analysis for donor- and isolation-related variables were correlated with recipient C-peptide levels at 2 and 4 weeks after transplantation. "Warm ischemia time" was defined as the time from start of University of Wisconsin solution perfusion in the donor until the pancreas was removed to the back table. RESULTS: Short "warm ischemia time" (WIT), low expression of tissue factor (TF) in pancreatic tissue, and high creatinine levels in the donor were variables related to high C-peptide values after islet transplantation. Furthermore, hospitalization length longer than 4 days was associated with low C-peptide levels. The number of islet equivalents (IEQ) did not correlate with the clinical outcome, possibly due to the fact that IEQ number was included in the release criteria for clinical islet transplantation CONCLUSIONS: Successful clinical islet transplantation is strongly correlated with donor and pancreas procurement factors rather than isolation process-related variables. "WIT" may induce TF expression in the pancreatic tissues. TF has been identified as the main trigger of the instant blood-mediated-inflammatory reaction in clinical islet transplantation. Therefore, assay of TF expression in pancreatic tissues could be applied as useful screening tool to identify "good" pancreata for clinical transplantation.

Analysis of Variance↗
PubMed2005

Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABO-compatible blood.

The poor outcome of intraportal islet transplantation may be explained by the instant blood-mediated inflammatory reaction (IBMIR), characterized by islet entrapment in blood clots, leucocyte infiltration and disruption of islet morphology. Here we employ a newly developed in vitro system to identify the blood cells involved in this process. Islets were mixed with ABO-compatible blood in heparinized tubes and incubated for various times up to 6 h. Clots were analysed immunohistochemically for detection of platelets (CD41a), leucocytes/lymphocytes (CD11b), granulocytes (CD16, lysozyme), neutrophilic granulocytes (neutrophil elastase), eosinophilic granulocytes (NaCN + H(2)O(2)), macrophages (CD68), dendritic cells (CD209/DC-SIGN), B cells (CD20) and T cells (CD4, CD8). Platelets were rapidly deposited around the islets in contact with the blood, reaching a maximum by 30 min. The first neutrophilic granulocytes appeared in the islets after 15 min, increased at 1 h and peaked at 2 h. Small numbers of macrophages were found infiltrating the islets already after 5 min, with a slight increase over time. However, control stainings of cultured islets and pancreas biopsies identified these cells as being largely of donor origin. No T cells, B cells, dendritic cells or eosinophilic granulocytes were detected during the 6 h observation time. Neutrophilic granulocytes were identified as the main infiltrating blood cell in islets exposed to blood, implying that these cells play a key role in clinical islet transplantation. Because islets are known to be exquisitely susceptible to oxidative stress, development of drugs targeting neutrophilic cytotoxicity could markedly improve the outcome of islet transplantation.

ABO Blood-Group System↗
PubMed2004

Individuals with an increased risk of colorectal cancer: perceived benefits and psychological aspects of surveillance by means of regular colonoscopies.

PURPOSE: To evaluate the psychological consequences of genetic counseling followed by a surveillance program using colonoscopy among individuals with increased risk of colorectal cancer. PATIENTS AND METHODS: Two hundred sixty-five individuals, participating in a surveillance program with colonoscopy, were mailed a survey questionnaire that assessed their experience of the surveillance program and their perception of the risk of colorectal cancer. The Hospital Anxiety and Depression scale and the Swedish Short Form-36 Health Survey was also included. RESULTS: Two hundred forty individuals completed the questionnaire and were divided into the following risk groups: risk group 1, an individual with a mutation in hMLH1 or hMSH2 and a lifetime colorectal cancer risk of 80% (n = 28); risk group 2, a lifetime colorectal cancer risk of 40% (n = 129); and risk group 3, a lifetime colorectal cancer risk of 20% (n = 83). Among all individuals, the mean for perceived benefit was 8.0, and the perception of discomfort was 3.3 on the visual analog scale (1-10). In risk group 1, 61% underestimated personal risks as being 40% or less. Approximately 50% of the subjects in risk groups 2 and 3 either under- or overestimated their lifetime risk. According to the Swedish Short Form-36 Health Survey and the Hospital Anxiety and Depression scale, the study sample resembled the reference population. CONCLUSION: A majority of the study sample understood why they were under surveillance, and regular colonoscopies were well-tolerated. The wide range of risk perception as well as low-risk perception in mutation positive subjects is acceptable, as long as these individuals adhere to surveillance programs and do not demonstrate increased levels of anxiety or depression.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618.

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate-high risk, based on stratified genetic information. METHODS: The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION: Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.

Adolescent↗
PubMed2004

Low-molecular weight dextran sulfate abrogates the instant blood-mediated inflammatory reaction induced by adult porcine islets both in vitro and in vivo.

BACKGROUND: One of the main obstacles to clinical application of islet xenotransplantation is the injurious inflammatory reaction elicited by porcine islets when they are exposed to fresh human blood in vitro and in vivo. This instant blood-mediated inflammatory reaction (IBMIR) causes rapid binding of platelets to the islet surface, activation of the coagulation and complement systems, and leukocyte infiltration of the islets. As a consequence of IBMIR, morphological destruction of porcine islets occurs within the first few hours after transplantation. MATERIALS AND METHODS: In the present study, by analyzing the plasma samples and performing immunohistochemical investigation, we assessed the effect of adding low-molecular weight dextran sulfate (LMW-DS) at 0.01-1 mg/mL to an in vitro tubing loop assay in which porcine islets were exposed to fresh human blood. The effect of LMW-DS also was investigated in an in vivo model using diabetic athymic mice, which provides an innate inflammatory milieu without influence of T cells. The possible toxicity of LMW-DS was assessed by culturing pig islets in the presence or absence of LMW-DS for 3 days. RESULTS: In the in vitro study, in the presence of LMW-DS at 0.01 mg/mL, platelet consumption, coagulation, and complement activation were reduced, and, at 0.1 mg/mL, LMW-DS totally prevented IBMIR. Immunohistochemical investigation showed that leukocyte infiltration was totally abrogated at the highest dose. A similar finding was observed in the in vivo study. No adverse effect of LMW-DS was observed on the quality of the islets. CONCLUSIONS: LMW-DS appears to be an effective drug candidate that is able to control the strong innate immune response induced by pig islets in contact with human blood.

Animals↗
PubMed2004

Oxygen affinity is decreased in patients with polycythaemia vera and essential thrombocythaemia.

The plasma erythropoietin (EPO) concentration is subnormal in the vast majority of all patients at the time of diagnosis of polycythaemia vera (PV) and in 33-50% of patients with essential thrombocythaemia (ET). At equivalent haemoglobin concentrations patients with PV and a substantial number of ET patients have subnormal EPO concentrations compared with those of healthy subjects. A possible explanation could be altered haemoglobin (Hb) oxygen affinity. Plasma EPO concentration and the oxygen pressure at 50% Hb saturation (p50) were measured in 29 patients with PV, 23 patients with ET and 34 healthy controls. There was no significant correlation between p50 and plasma EPO concentration. However, the mean p50 for PV patients exceeded the mean for healthy controls (p = 0.004). Furthermore, the mean p50 for ET patients significantly (p = 0.012) exceeded the mean for controls but there was no significant difference in p50 between patients with PV and ET. It could be hypothesized that the lower oxygen affinity to Hb in PV and ET patients partly explains the decreased EPO production.

Adult↗
PubMed2004

Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system.

Immune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fcgamma RII antibodies, whereas Fcgamma R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction.

Antigen-Antibody Complex↗
PubMed2004

A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma.

BACKGROUND: Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA). METHODS: A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI. RESULTS: A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period. CONCLUSIONS: A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.

Adolescent↗