Biomedical subjects

Bo Nilsson

Publications and source records attributed to Bo Nilsson.

At least 55 records · Page 3Linked to original sources

PubMed2004

Left ventricular longitudinal relaxation velocity: a sensitive index of diastolic function.

OBJECTIVE: The aim of the present study was to evaluate maximal longitudinal relaxation velocity of the left ventricle as an index of diastolic function. DESIGN: Sixty-four consecutive patients with known or suspected heart failure, referred to echocardiography, were investigated by M-mode recordings and pulsed tissue Doppler recordings of the maximal early diastolic velocity of the mitral annulus. The classification as true positive or true negative cases was done using age-related reference values of mitral inflow and pulmonary vein flow. RESULTS: A rather high sensitivity of 89% was found for M-mode recordings and a slightly lower sensitivity of 81% for pulsed tissue Doppler recordings. A moderate high specificity was found: 81% for M-mode recordings and 78% for tissue Doppler recordings. The velocities recorded by pulsed tissue Doppler were about 30% higher than velocities recorded by M-mode. CONCLUSION: Maximal relaxation velocity in the long axis of the left ventricle, recorded by either M-mode or tissue Doppler, can be used for assessment of diastolic function but reference values cannot be used interchangeably.

Adult↗

PubMed2004

Interobserver reproducibility of percent Gleason grade 4/5 in prostate biopsies.

PURPOSE: Percent Gleason grade 4/5 (GG4/5) has been proposed as a predictor of prognosis in prostate cancer and it has been shown to add prognostic information to that given by Gleason score (GS). We recently noted that the interobserver reproducibility of percent GG4/5 in total prostatectomy specimens is at least as good as that of the GS. However, to our knowledge the reproducibility of percent GG4/5 in needle biopsies has not yet been investigated. MATERIALS AND METHODS: A consecutive series of needle biopsies from 69 men with prostate cancer was reviewed. Biopsies were taken according to a standardized octant protocol. All 279 slides containing cancer were circulated among 4 genitourinary pathologists, who assessed GS and percent GG4/5. Results were compared pairwise and weighted kappa was calculated. RESULTS: The 4 observers had a mean weighted kappa for GS and percent GG4/5 of 0.48 to 0.55 (overall mean 0.51) and 0.52 to 0.68 (overall mean 0.60), respectively. There was less disagreement in percent GG4/5 when a single biopsy was positive for cancer than when 6 or more biopsies were positive. The number of positive biopsies showed a stronger correlation with a discrepancy in percent GG4/5 than cancer length. Disagreement was worse when cribriform or fusion patterns were present. CONCLUSIONS: Interobserver reproducibility of percent GG4/5 on prostate biopsies is at least as good as that of GS. Hence, concern about interobserver variability should not deter pathologists from using percent GG4/5. Grading appears to be most difficult when cancer is present in multiple biopsies or it contains cribriform or fusion patterns.

Aged↗

PubMed2004

Thrombotic disease in systemic lupus erythematosus is associated with a maintained systemic platelet activation.

Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis. Platelet-induced extracellular phosphorylation of plasma proteins suggests that this is due to persistent activation of the platelets. We examined 30 SLE patients (15 with thrombotic disease), 18 non-SLE patients with deep vein thrombosis (DVT) and 50 healthy controls by analysing beta-thromboglobulin, activated factor XI-antithrombin complexes and fibrinogen-bound phosphate. All parameters were elevated in SLE patients, particularly those with thrombosis, but normal in DVT cases and healthy controls. We conclude that thrombotic disease in SLE patients is associated with a persistent systemic platelet activation that may lower the threshold for induction of thrombosis.

Adult↗

PubMed2004

Anti-EpCAM monoclonal antibody (MAb17-1A) based treatment combined with alpha-interferon, 5-fluorouracil and granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal carcinoma.

Monoclonal antibodies (MAbs) have different modes of action and toxicity profile compared to chemotherapeutics, which makes it interesting to combine these drugs. Addition of cytokines to MAb therapy may also augment immune effector functions utilized by MAb. In an effort to improve the therapeutic effect of a MAb-based regimen in colorectal carcinoma (CRC) patients, the effects of a combination of alpha-interferon (alpha-IFN), 5-fluorouracil (5-FU), granulocyte-macrophage colony-stimulating factor (GM-CSF) and mouse MAb17-1A was evaluated in 27 patients with metastatic disease. alpha-IFN was given s.c. once daily for 5 consecutive days and at days 4 and 5, 5-FU was administered as a daily i.v. bolus injection. After 2 days rest, GM-CSF was given s.c. once daily, days 8-14 and on day 10, MAb17-1A was given i.v. The treatment cycle was repeated every 4th week. One patient achieved a partial remission and 13 patients showed a minor response or stable disease >3 months, inducing an overall response rate of 54%. Responding patients survived significantly longer than non-responding patients (p=0.021). Median overall survival time for all patients was 75 weeks and progression-free survival time 15 weeks. Adverse events related to alpha-IFN, GM-CSF and 5-FU were as expected. The frequency of patients with an immediate-type allergic reaction (ITAR) against MAb17-1A at the 1st, 2nd, 3rd and 4th treatment cycles was 11%, 52%, 62% and 64% respectively. The planned MAb17-1A dose had to be reduced by repeated infusions. No patient received full dose of MAb17-1A from the 3rd cycle and onward. Compared to historical control patients treated with MAb17-1A alone, the present combination regimen seemed to improve the response rate (54% vs 15%) as well as progression-free survival (15 vs 7 weeks; p<0.05).

Adult↗

PubMed2003

Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation.

BACKGROUND: Islet-produced tissue factor (TF) triggers an adverse clotting reaction, the instant blood-mediated inflammatory reaction (IBMIR), providing a likely explanation for the need of tissue from multiple donors in clinical islet transplantation. In this study, the authors investigated whether compounds previously shown to affect TF and macrophage chemoattractant protein (MCP)-1 expression in monocytes and endothelial cells have the same effect in human islet cells. METHODS: Islets were cultured in the presence of l-arginine, cyclosporine A, enalapril, or nicotinamide for 48 hr, after which the TF content and MCP-1 expression were assessed. The effect of nicotinamide on IBMIR was evaluated by exposing the treated islets to fresh human ABO-compatible blood in an in vitro loop model. RESULTS: Nicotinamide was the only compound that significantly reduced both TF and MCP-1. This reduction was dose-dependent. The level of MCP-1 was strongly correlated with TF expression (r2=0.98). In addition, the level of TF was also correlated with the ability of the islets to initiate IBMIR (r2=0.94). CONCLUSIONS: TF and MCP-1 expression in human islets can be decreased by adding nicotinamide to the culture medium. These observations indicate that the adverse effects of IBMIR in clinical islet transplantation could be reduced without endangering the recipient using antithrombotic drugs.

Arginine↗

PubMed2003

Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro.

Contact between blood and a biomaterial surface takes place in many applications and is known to activate the coagulation and complement systems. Heparin surface coatings have been shown to reduce blood activation upon contact with artificial surfaces. To establish the optimal heparin surface concentration, blood was incubated in a tubing loop model at 37 degrees C. The tubing was coated with different surface concentrations of heparin and rotated at three different velocities. We demonstrate that the blood compatibility of a surface with regard to coagulation, complement, and platelet activation can be improved by increasing the heparin surface concentration in the 6-12 pmol antithrombin/cm2 concentration interval. The binding of factor H is not influenced by the increased heparin surface concentration, suggesting that this factor is not the primary regulator of complement on heparin surfaces. In addition, the heparin coating has no effect on the complement activation that occurs on gas surfaces in extracorporeal circuits.

Antithrombins↗

PubMed2003

Quality of life in women with breast cancer during the first year after random assignment to adjuvant treatment with marrow-supported high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin or tailored therapy with Fluorouracil, epirubicin, and cyclophosphamide: Scandinavian Breast Group Study 9401.

PURPOSE: To compare, in high-risk breast cancer patients, the effects on health-related quality of life (HRQoL) of two adjuvant treatments. Treatments were compared at eight points during the first year after random assignment to treatment with tailored fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy for nine courses versus induction FEC therapy for three courses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb) supported by peripheral-blood stem cells. PATIENTS AND METHODS: From March 1994 to March 1998, 525 breast cancer patients (estimated relapse risk > 70% within 5 years with standard therapy) were included in the Scandinavian Breast Group 9401 study. HRQoL evaluation, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Breast Cancer Module-23, included 408 of 446 eligible patients in Finland, Norway, and Sweden. RESULTS: Eighty-four percent to 95% of the patients completed questionnaires at eight points of assessment. Nostatistically significant overall differences were found between the tailored FEC group and the CTCb group for any of the HRQoL variables. Statistically significant differences over time were found for all HRQoL variables. HRQoL in the CTCb group demonstrated a steeper decrease, but a faster recovery than in the tailored FEC group. Emotional functioning improved with increased time from randomization. Higher levels of problems in body image and arm symptoms were reported in the tailored FEC group compared with the CTCb group. Sexual functioning and satisfaction were impaired during the study period. CONCLUSION: Both treatments had a negative influence on HRQoL during the treatment period. Despite the aggressive therapies, the patient's HRQoL returned to levels found at inclusion on most variables.

Adult↗

PubMed2003

Inflammatory mediators expressed in human islets of Langerhans: implications for islet transplantation.

Expression of immune modulating mediators in human Islets of Langerhans could have important implications for development of autoimmunity in type 1 diabetes and influence the outcome of clinical islet transplantation. Islets obtained from five donors were analyzed at various times after isolation using cDNA array technology. The Atlas Human Cytokine/Receptor and Hematology/Immunology nylon membranes representing 268 genes and 406, respectively, were used and the relative expression of each gene analyzed. Of the 51 gene products identified, high mRNA expression of MCP-1, MIF, VEGF, and thymosin beta-10 was detected in all islet samples. IL-8, IL-1-beta, IL-5R, and INF-gamma antagonist were expressed in islets cultured for 2 days. IL-2R was expressed in islets cultured for more than 6 days. In conclusion, several inflammatory mediators were expressed in isolated islets, particularly at an early stage after isolation, indicating that a few days of culture could be beneficial for the outcome of islet transplantation.

Cells, Cultured↗

PubMed2003

Natural killer (NK) cell function is a strong prognostic factor in colorectal carcinoma patients treated with the monoclonal antibody 17-1A.

Tumor cells might be susceptible to different effector functions of the immune system. This cytotoxic capacity has been utilized to analyze the prognostic significance of peripheral blood mononuclear cells (PBMC) in patients with metastatic colorectal carcinoma (CRC) treated with the monoclonal antibody (MAb)17-1A. Such analysis might form the basis for future patient selection and may lead to improvements in therapeutic strategies. Between 1986 and 1998, 73 patients were treated with regimens containing MAb17-1A. Prior to therapy, the lytic capability of PBMC was assayed against: K562 (4 hr assay), the CRC cell line SW948 (4 hr and 18 hr assays) and antibody-dependent cellular cytotoxicity (ADCC, 18 hr assay). Since the study was performed over 13 years, the assays were checked for time-related bias. Reproducibility over time was satisfactory. Patients exhibited a significantly higher cytotoxic capability in all 4 assays compared to healthy control donors. No correlation to clinical outcome was noted for 18 hr ADCC and 18 hr spontaneous cytotoxicity. Pretreatment natural killer (NK) cell cytotoxicity (K562) was significantly related to overall survival (OS), progression-free survival (PFS), and response rate. OS for patients with high and low NK cell cytotoxicity was 71 vs. 30 weeks, respectively (p = 0.007). NK cell cytotoxicity (K562) was an independent prognostic factor for OS (p = 0.016). Pretreatment NK cell activity is a strong prognostic factor for patients with metastatic CRC receiving MAb17-1A therapy and is a predictor for OS, PFS and response. These results should be considered when designing antibody-based therapeutic protocols.

Adenocarcinoma↗

PubMed2003

[Injuries and mortality in motorcycle and moped accidents in Sweden 1987-1994. Advanced age and male sex are risk factors of fatal moped and motorcycle accidents].

Data from the Swedish Hospital Discharge Registry were analysed, years 1987-1994 inclusive. The registry includes all living patients admitted to Swedish hospitals. Patients admitted after moped or motor-cycle accidents were studied. A total of 4,716 mopedists and 8,927 motor-cycle riders were admitted in the given time frame. The median age of mopedists was 16 and that of motor-cycle riders 22 years. 85% of mopedists were male, while 95% of motor-cycle drivers and 55% of motor-cycle passengers were male. The injury distribution in both groups was quite similar with fractures and cerebral concussion dominating, although fractures of the arm and vertebrae were considerably more common in motor-cycle riders. The incidence of hospital admission after accidents did not change over time in mopedists, but decreased in motorcyclists. Accidents involving both types of vehicles occurred more commonly in the countryside. High age and male sex was associated with increased mortality in mopedists, while high age and being a passenger was associated with higher death rates in admitted motor-cyclists.

Accidents, Traffic↗

PubMed2003

[A nationwide study in primary health care: One out of four patients suffers from anxiety and depression].

Anxiety and depression in Swedish primary care has rarely been studied. A national sample of 131 primary care physicians and their 1,348 patients during one day in September 2001 responded to questionnaires on somatic disease, social conditions, treatments, and symptoms of anxiety and depression. A total of 23% of the patients had generalized anxiety and/or depression with or without receiving treatment, i.e. the most common category following musculoskeletal conditions. The appointment was caused by anxiety in 7.1% of the patients, depression in 8.5%, and insomnia in 11%. This group of patients did not deviate much in terms of somatic and social conditions, except being younger. Doctors were confident in diagnosing and treating them. Five key questions can be used in primary care to screen for these common psychiatric conditions.

Adult↗

PubMed2003

Uveal melanoma survival in Sweden from 1960 to 1998.

PURPOSE: To investigate the crude and relative survival rates in patients with uveal melanoma in Sweden during the period from 1960 to 1998. METHODS: A population-based national survey revealed 2997 cases of uveal melanoma in the Swedish Cancer Registry. The survival rates were calculated by the Hakulinen life-table method, using relative survival as an estimate for deaths due to uveal melanoma. The excess mortality rates were calculated with confidence intervals for the first 15 years after diagnosis. Multivariate regression analysis was undertaken to evaluate the influence of gender, age, and calendar period on relative survival the first 5 years after diagnosis. The underlying causes of deaths in the patients with uveal melanoma, as found in the Cause of Death Registry were also investigated. RESULTS: Up to December 31, 1998, 2003 patients had died. The 5-year crude survival rate was 60.3% and the relative survival 70.1%. After 10 years, the rates were 42.5% and 59.4%, respectively. Significant excess mortality existed up to 5.5 years after diagnosis. In the multivariate model, younger age (P < 0.001) and later calendar period (P = 0.002), but not gender (P = 0.117), were associated with better relative survival. Deaths due to uveal melanoma were misclassified in the Cause of Death Registry in more than half of the cases. CONCLUSIONS: This study, covering more than 95% of the uveal melanoma cases in the Swedish population revealed an improvement in relative survival rates for patients with uveal melanoma over time and a significant excess mortality up to 5.5 years after diagnosis.

Adolescent↗

PubMed2003

Hodgkin's lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis.

BACKGROUND AND OBJECTIVES: In general, elderly patients with Hodgkin's lymphoma (HL) have a less favorable prognosis than do younger ones. Inadequate therapy, often due to decreased tolerance to treatment, contributes to the poor outcome. This study was undertaken to evaluate potential clinical factors of importance for prognosis with special reference to relative dose intensity (RDI) of chemotherapy (CT). DESIGN AND METHODS: Eighty-eight consecutive elderly (>60 years) HL patients diagnosed between 1973-1994 who received up-front CT+/-radiotherapy (RT) were included (median age 72 years, range 60-92; median follow-up time 78 months, range 49-206). The calculations of RDI of CT were based on Hryniuk's model. RESULTS: The 5-year overall (OS) and cause-specific (CSS) survival was 39% and 51%, respectively, in patients who received CT+/-RT. Nine of the 14 patients who only received 1 cycle of CT died within 6 months from diagnosis without achieving complete remission (CR). However, the remaining 5 patients in this group survived 14-97+ months. Patients with a RDI >65% had a significantly better OS (p=0.029) and CSS (p=0.024) than those with a RDI 65%. Patients who received ABVD-based CT with a RDI >65% had a significantly better OS (p=0.0011) than those who were treated with ABVD-based CT with a RDI 65%, or MOPP-like therapy, irrespective of received RDI. INTERPRETATION AND CONCLUSIONS: Prognosis remains heterogeneous and the significance of established prognostic factors is limited in elderly HL patients. Patients who received a low RDI of CT and those receiving non-ABVD-based treatment fared worse. However, also elderly patients can enjoy long-standing complete remission following minimal treatment.

Aged↗

PubMed2002

[Marked injury decline among pedestrians 1987-1994].

A retrospective case study from The Swedish Hospital Discharge Register was performed. There were 8,684 pedestrians in collision with motor vehicles, a total of 12,036 episodes, treated in Swedish hospitals from 1987-1994. Fifty three percent were men and 47% women, having a median age of 47 (range 1-100) years. In average, 17.6 persons were admitted/100,000 population/year. The annual incidence of injured pedestrians in Sweden decreased significantly during this period. Injuries to the extremities were commonest (39% fractures), followed by injuries to the head and neck (34%). The total number of deaths in our series of patients was 444 (5%). Among these, more than half had head, 1/5 orthopaedic, 1/20 abdominal or thoracic injuries. Among pedestrians hit by motor vehicles injuries to the extremities were commonest, followed by injuries to the head and neck. The usual victim was an old person. Five percent of the patients treated in hospital died.

Accidents, Traffic↗

PubMed2002

Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients with severe sepsis.

INTRODUCTION: Treatment of patients with severe sepsis with agents antagonising the effects of C5a has been proposed based on beneficial effects in animal experiments and in vitro studies demonstrating upregulation of the C5a receptor (CD88) on granulocytes by endotoxin. MATERIALS AND METHODS: CD88 expression on leukocytes from 12 patients with severe sepsis or septic shock was analysed by flow cytometer, and serum complement factors C3a and C5b-9 were measured by enzyme immunoassay techniques. RESULTS: The granulocyte CD88 expression on day 1 was lowered (36; range, 2-59) in comparison with controls (63; range, 25-88) (P < 0.001), despite complement activation, while the monocyte CD88 expression was unchanged. The receptor reduction correlated significantly to the APACHE II score (r2 = 0.35, P < 0.05). The recovery of CD88 expression was slow. DISCUSSION: In contrast to the findings in animals, it is concluded that granulocyte CD88 expression is reduced at the time when the diagnosis of severe sepsis or septic shock can clinically be made. The reason for this needs further investigation but it may be due to a previous complement activation or to cytokine effects.

APACHE↗

PubMed2002

C3 adsorbed to a polymer surface can form an initiating alternative pathway convertase.

Contact between blood and a biomaterial surface induces an immediate complement-mediated inflammatory response. Under these conditions, the alternative pathway of complement is often initiated and amplified on the biomaterial surface. Adsorption of a protein such as C3 to a polymer surface induces conformational changes in the protein. Based on the expression on adsorbed C3 of conformational neoepitopes specific for bound C3 fragments, we have hypothesized that adsorbed C3 is able to bind factor B and form a functional C3,Bb convertase. Using a quartz crystal microbalance to monitor binding of proteins to a polymer surface, we have demonstrated that a functional C3-containing alternative pathway convertase can be formed, in particular, in the presence of properdin. These data indicate that adsorption of C3 induces conformational changes that turn C3 into a C3b-like molecule that is able to participate in the functioning of the alternative convertase, and they suggest a new mechanism for complement activation on a biomaterial surface.

Adsorption↗

PubMed2002

The significance of serum CA 125 elevation in malignant and nonmalignant diseases.

OBJECTIVES: The aims of the study were to investigate whether an elevated CA 125 level signals malignancies other than ovarian cancer and to find the cause of death for 247 women with elevated values among the 5550 women screened in 1986-1988 in the Stockholm population. METHODS: The Swedish Regional Cancer Registry delivered malignancy diagnoses among the 5550 women screened. The Cause of Death Registry gave the cause of death among the women with elevated CA 125 values. RESULTS: Patients with ovarian cancer were excluded. In 44 women with elevated CA 125 values other malignancies were reported to the Cancer Registry. They represent 18% of the entire group with elevated values. Among the 5297 women with normal CA 125 values 13% developed various malignancies. The difference between incidence of malignant disease in women with elevated values and women with normal values is significant, P = 0.02. Especially during the test-related period, from 1 year before to 1 year after the test, malignancies were detected in 6.9% of the population with elevated values and in only 1.6% with normal values (P = < 0.001). Breast cancer and lung cancer were overrepresented among women with elevated CA 125 values (P = 0.015 and < 0.001, respectively). Of the total 5500 women screened, 358 women died with different diagnoses. Elevated CA 125 values had been noted earlier in 25 women, and of these 20 died of malignant diseases, predominantly ovarian, breast, and lung cancer. CONCLUSIONS: Asymptomatic postmenopausal women with elevated CA 125 levels in ovarian carcinoma screening trials should, if ovarian cancer is excluded, be investigated for possible breast or lung cancer. The findings also suggest that elevated CA 125 level is a risk factor for death from malignant disease.

Breast Neoplasms↗

PubMed2002

Interobserver reproducibility of percent Gleason grade 4/5 in total prostatectomy specimens.

PURPOSE: Recently the percent Gleason grade 4/5 was proposed as a predictor of the outcome of prostate cancer and it has been shown that it adds prognostic information to that given by Gleason score. To our knowledge the interobserver variability of percent Gleason grade 4/5 has not yet been investigated. We assessed the percent Gleason grade 4/5, including the identification of high grade patterns and estimation of the percent tumor area, which is potentially more difficult than conventional Gleason grading. MATERIALS AND METHODS: A consecutive series of 69 total prostatectomy specimens was reviewed. A single slide per specimen was circulated among 4 genitourinary pathologists, who assessed Gleason score and the percent Gleason grade 4/5. Results were compared pairwise and a weighted kappa was calculated for Gleason score and the percent Gleason grade 4/5. RESULTS: The 4 observers had a mean weighted kappa for Gleason score and the percent Gleason grade 4/5 of 0.52 to 0.66 (overall mean 0.56) and 0.58 to 0.72 (overall mean 0.66), respectively. The best agreement for percent Gleason grade 4/5 was in 2 pathologists at the same department (weighted kappa 0.86). Transition zone tumors had a lower weighted kappa for Gleason score but a higher weighted kappa for percent Gleason grade 4/5 than peripheral zone tumors. In cases of the greatest disagreement in the percent Gleason grade 4/5 crush artifact, cribriform cancer and high grade PIN within the tumor were significantly more common. An intraobserver reproducibility of weighted kappa 0.91 was achieved for Gleason score and the percent Gleason grade 4/5. CONCLUSIONS: Interobserver reproducibility of the percent Gleason grade 4/5 is substantial and at least as good as that of the Gleason score. Hence, concern about interobserver variability should not deter pathologists from using the percent Gleason grade 4/5 as a prognostic marker for prostate cancer.

Aged↗