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Biomedical subjects

L Hansson

Publications and source records attributed to L Hansson.

At least 19 recordsLinked to original sources

Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody).

Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor 'first dose' reactions. All 5 patients responded with a >or=2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4-7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2-12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.

Aged↗

BALF-derived fibroblasts differ from biopsy-derived fibroblasts in systemic sclerosis.

Growth of fibroblasts from bronchoalveolar lavage fluid (BALF) in patients with systemic sclerosis (SSc) has previously been described. The purpose of the present study was to characterise fibroblasts from BALF and bronchial biopsies from SSc patients with alveolitis and from controls, to analyse fibroblast proliferation, migration, stress fibres and proteoglycan production. BALF and bronchial biopsies were collected from 10 patients with SSc and alveolitis and from 15 controls. Outgrowth of fibroblasts was observed from the BALF of four patients, particularly in those with a markedly increased percentage of eosinophils in BALF, but not in any member of the control group. Increased levels of granulocyte-macrophage colony-stimulating factor, correlating with the percentage of eosinophils in BALF, were found in patients when compared with controls. Fibroblasts from BALF showed an elongated, mobile phenotype and increased proteoglycan production compared to the corresponding biopsy fibroblasts. In conclusion, outgrowth of fibroblasts with an altered phenotype is reported from bronchoalveolar lavage fluid in systemic sclerosis patients with alveolitis and an increased percentage of eosinophils in the bronchoalveolar lavage fluid. These findings indicate a possible role for eosinophil-fibroblast interaction in pulmonary fibrosis in systemic sclerosis.

Adult↗

A comparative study of the anti-settlement properties of mytilid shells.

Marine organisms have evolved defence mechanisms to prevent epibiosis. This study investigated the anti-settlement properties of natural periostracal microtopographies of two mytilid species, Mytilus edulis (from North, Baltic and White Seas) and Perna perna (from the SW Atlantic). Resin replicas of shells were exposed to cyprids of the barnacle Semibalanus balanoides. Replicas with intact isotropic microtopographies and smooth controls were much less fouled than roughened anisotropic surfaces. This indicates that in both M. edulis and P. perna the periostracum possesses a generic anti-settlement property, at least against S. balanoides cyprids, which is not regionally adapted. Such a potential globally effective anti-settlement mechanism possibly contributes to the invasive success of Mytilidae.

Animals↗

Determinants of quality of life in people with severe mental illness.

OBJECTIVE: The objective of this article was to review some methodological issues in this field and give an overview of empirical research findings with a special focus on factors associated with or affecting subjective quality of life in people with a severe mental illness. METHOD: A selective review of relevant scientific literature on quality of life in severe mental illness was conducted. RESULTS: Subjective quality of life in people with a severe mental illness is only to a lesser extent related to external life conditions. Major determinants are psychopathology, especially symptoms of depression and anxiety, and aspects of the social network. Personality related factors such as self-esteem are also influential. Comparative studies have further shown that patients in community care settings have a better subjective quality of life than patients in hospital settings. CONCLUSION: Efforts to improve subjective quality of life in people with severe mental illness should include a careful monitoring of depressive and anxiety symptoms, and pay particular attention to assessment of and interventions against unmet needs. Further, such interventions should stress a strengthening of the social support of the clients. It is also important to pay attention to mediators of changes in subjective quality of life such as self-esteem, mastery, autonomy, and self-efficacy.

Anxiety Disorders↗

Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines.

In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes' B) and 3 (Dukes' C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use.

Antigens, Tumor-Associated, Carbohydrate↗

Personality and self-variables: important determinants of subjective quality of life in schizophrenia out-patients.

OBJECTIVE: To investigate factors determining severely mentally ill patients' self-rated quality of life. The study hypothesized that objective life circumstances, personality, self-variables, and psychopathology would be determinants of quality of life. METHOD: A total of 117 individuals with schizophrenia and related disorders were investigated. Structural equation modelling was used to: 1). investigate if one or more subfactors best described the covariance within each potential determinant and quality of life, 2). explore the relations between all variables and factors extracted in step 1. RESULTS: A multi-factorial model indicated that a self-factor and two psychopathology factors worked as mediators of self-rated quality of life, in turn composed of an internal and an external aspect. Personality dimensions and objective life circumstances accounted directly or indirectly for substantial parts of quality of life. CONCLUSION: The relative importance of individual characteristics and objective indices was shown. Trait-like properties, such as the self-factor and personality, explained most of the variation in self-rated quality of life.

Adult↗

Health economics in the Hypertension Optimal Treatment (HOT) study: costs and cost-effectiveness of intensive blood pressure lowering and low-dose aspirin in patients with hypertension.

OBJECTIVES: To investigate the marginal cost-effectiveness of different targets for the reduction of blood pressure and the cost-effectiveness of adding acetylsalicylic acid (ASA) to the treatment of hypertension. DESIGN: Patients with hypertension were randomized to three target groups for blood pressure; < or =90, < or =85 and < or =80 mmHg. Patients were also randomly assigned ASA and placebo. The average follow-up time was 3.8 years. The direct costs for drugs, visits, hospitalizations, and side-effects were calculated and related to clinical outcome. SETTING: Resource utilization data from all the 26 countries in the study were pooled, and Swedish unit costs were applied to the aggregated resource utilization. SUBJECTS: A total of 18 790 patients, 50-80 years of age (mean 61.5 years), with a diastolic blood pressure between 100 and 115 mmHg (mean 105 mmHg). INTERVENTIONS: Antihypertensive treatment with the long-acting calcium antagonist felodipine was given to all patients. Additional therapy and dose increments in four further steps were prescribed to reach the randomized target blood pressure. Fifty per cent of the patients were randomized to a low dose, 75 mg daily, of acetylsalicylic acid. MAIN OUTCOME MEASURES: Direct health care costs, major cardiovascular (CV) events (myocardial infarction and stroke) and CV death. RESULTS: The average cost of drugs and visits increased with more intensive treatment. The increase in treatment costs was partly but not fully offset by a nonsignificant reduction in the cost of CV hospitalizations. For patients with diabetes there were no significant differences in total cost between the target groups. The cost of avoiding a major CV event was negative in the base case analysis, SEK -10 360 (CI: -78 195, 75 630), and SEK 18 450 (CI: -88 789, 192 980) in a sensitivity analysis. For patients on ASA, costs were slightly but significantly higher than for patients on placebo. The estimates of the cost of avoiding a major CV event varied between SEK 41 600 and SEK 477 400, with very wide confidence intervals. CONCLUSIONS: The treatment cost increases as the target for hypertension treatment is lowered. In patients with diabetes, intensive treatment to a lower target is cost-effective. Because of the nonsignificant difference in events, no conclusion can be made for all patients in the study. Furthermore, no conclusive evidence was found regarding the cost-effectiveness of adding ASA to the treatment of hypertension.

Aged↗

Kinetics of cytokine gene expression in human CD4+ and CD8+ T-lymphocyte subsets using quantitative real-time PCR.

The time kinetics of five cytokines [interleukin-2 (IL-2), IL-5, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha)] and one cytotoxic effector protein (granzyme B) was analysed by real-time quantitative polymerase chain reaction (PCR) following in vitro stimulation of human CD4 and CD8 T lymphocytes. Two stimuli were used, a mitogen [phytohemagglutinin (PHA)] and a recall antigen [purified protein derivative (PPD)]. The pattern of cytokine mRNA expression was found to be dependent on the T-cell subset and stimulus used. A wide interindividual variability in the cytokine gene expression pattern was demonstrated. Two expression patterns were observed. A bell-shaped expression profile was seen for most cytokines upon PHA activation in both subsets and PPD-activated CD4 T cells, whereas a biphasic/multiphasic expression pattern was noted in CD8 T cells upon PPD stimulation. For most cytokines, the time to induction was within 30 min of activation, and maximum accumulation seemed to be obtained after 4-8 h of activation. A sustained high level could, however, be noticed for up to 24 h. Granzyme B gene expression was also induced within 30 min of activation but showed a continuous gradual increase and late maximal accumulation (48-72 h). The findings of the present study are of importance when designing studies using the cytokine gene expression profile as a marker for antigen-specific T lymphocytes. It might be recommended that cytokine gene expression (IL-2, IL-5 and IFN-gamma) should be measured after 4-8 h of specific activation but also up to 24 h of stimulation is acceptable. Granzyme B should preferentially be measured after 48-72 h of activation.

CD4-Positive T-Lymphocytes↗

Bronchodilation by an inhaled VPAC(2) receptor agonist in patients with stable asthma.

BACKGROUND: The synthetic vasoactive intestinal peptide (VIP) analogue Ro 25-1553 is a selective VIP-PACAP type 2 (VPAC(2)) receptor agonist that causes a bronchodilatory effect in guinea pigs in vivo. The effect of Ro 25-1553 given by inhalation to patients with asthma was studied and compared with that of a long acting beta(2) adrenoceptor agonist. METHODS: Twenty four patients with moderate stable asthma participated in a double blind, randomised, placebo controlled, crossover study. The primary variable was bronchodilatory effect (increase in forced expiratory volume in 1 second, FEV(1)) after inhalation of Ro 25-1553 (100 microg or 600 microg) and formoterol (4.5 microg), respectively. Putative side effects were characterised by monitoring sitting blood pressure, serum potassium, electrocardiography and echocardiography. RESULTS: Inhalation of 600 microg Ro 25-1553 caused a rapid bronchodilatory effect (geometric mean increase in FEV(1) compared with placebo) within 3 minutes of 6% (95% CI 4 to 9), as did inhalation of formoterol (8% (95% CI 5 to 10)). The corresponding maximum bronchodilatory effect during 24 hours was similar for 600 microg Ro 25-1553 (7% (95% CI 4 to 10)) and the reference bronchodilator formoterol (10% (95% CI 7 to 12)). However, for both doses of Ro 25-1553 the bronchodilatory effect was attenuated 5 hours after inhalation whereas formoterol still had a bronchodilatory effect 12 hours after inhalation. Neither Ro 25-1553 nor formoterol produced any clinically relevant side effects. No drug related difference in adverse events was observed. CONCLUSION: Inhalation of a synthetic selective VPAC(2) receptor agonist constitutes a promising approach for bronchodilation in patients with asthma.

Administration, Inhalation↗

Predictors of improvement in quality of life of long-term mentally ill individuals receiving case management.

One hundred and thirteen long-term mentally ill clients receiving case management were investigated with regard to psychosocial and clinical predictors of changes in subjective quality of life during an 18-month follow-up. Better psychosocial functioning and fewer psychiatric symptoms at baseline predicted a greater improvement in quality of life. A larger decrease in symptom severity and a greater improvement in the social network during the follow-up were identified as the most important predictors of a greater improvement in subjective quality of life. The results of the study suggest that an emphasis should be put on effective symptom management, a reduction of needs for care and social support in order to fulfill the aims of improving subjective quality of life in patients receiving case management.

Adult↗

Living situation, subjective quality of life and social network among individuals with schizophrenia living in community settings.

OBJECTIVE: To investigate the relationships between characteristics of the living situation in the community and subjective quality of life and social network among community-based individuals with schizophrenia. METHOD: A total of 418 individuals with schizophrenia from 10 sites were interviewed with regard to quality of life, psychopathology, social network and needs for care. Characteristics of the living situation investigated were: living alone or not, living with family or not, and having an independent or a sheltered housing situation. RESULTS: An independent housing situation was related to a better quality of life concerning living situation and living with the family to a better quality of life concerning family relations. An independent housing situation was associated with a better social network regarding availability and adequacy of emotional relations. CONCLUSION: People with schizophrenia with an independent housing situation have a better quality of life associated with more favorable perceptions of independence, influence, and privacy. Their social network is better irrespective of whether they live alone or not, or with family or not.

Activities of Daily Living↗

Comparison of user assessed needs for care between psychiatric inpatients and supported community residents.

The aim of the present study was to compare user assessed needs for care for psychiatric patients in inpatient settings with that of residents in supported community residences. The Camberwell Assessment of Need was administered to 75 patients and residents in different housing settings. Residents in supported community settings had more needs for care (8.1), than patients in inpatient settings (5.8), partly because of differences in duration of illness. A greater proportion of those living in supported community residences reported needs in the areas of psychotic symptoms, accommodation, food, daytime activities, sexual expression and looking after the home. There were no differences in numbers of unmet needs. Relatives and friends provided emotional and social support predominantly in the areas of company and psychological distress. In conclusion, living in supported community residences does not imply more unmet needs, or less adequate response to needs from services, despite a greater number of needs being reported. In some areas of need, relatives and friends play an important role in the provision of support.

Adolescent↗

Effects of formoterol (Oxis Turbuhaler) and ipratropium on exercise capacity in patients with COPD.

Although long-acting inhaled beta 2-agonists improve various outcome measures in COPD, no double-blind study has yet shown a significant effect of these drugs on exercise capacity. In a randomized, double-blind, placebo-controlled, crossover study, patients received formoterol (4, 5, 9, or 18 micrograms b.i.d. via Turbuhaler), ipratropium bromide (80 micrograms t.i.d. via pMDI with spacer), or placebo for 1 week. Main endpoint was time to exhaustion (TTE) in an incremental cycle ergometer test. Secondary endpoints were Borg dyspnoea score during exercise, lung function, and adverse events. Thirty-four patients with COPD were included, mean age 64.8 years, FEV1 55.6% predicted, reversibility 6.1% predicted. All doses of formoterol, and ipratropium significantly improved TTE, FEV1, FEF25-75%, FRC, IVC, RV and sGAW compared with placebo. A negative dose-response relationship was observed with formoterol. Ipratropium increased time to exhaustion more compared with formoterol, 18 micrograms, but not with formoterol, 4.5 and 9 micrograms. No changes in Borg score were found. There was no difference in the adverse event profile between treatments. In conclusion, 1 week of treatment with formoterol and ipratropium significantly improved exercise capacity and lung function compared with placebo. However, a negative dose-response relation for formoterol was unexpected and needs further investigation.

Administration, Inhalation↗

Accuracy of a first diagnosis of asthma in primary health care.

BACKGROUND: In a postal questionnaire study, the prevalence of asthma in southern Sweden has been found to be 5.5%. However, the register prevalence of asthma obtained from the medical records in the same municipality and age groups was found to be only 2.1%. OBJECTIVES: The aims of the study were to investigate whether the low register prevalence of asthma was caused by an underdiagnosis of asthma in primary health care and to validate a first diagnosis of asthma set by GPs in primary health care. METHODS: During a period of 3 months in 1997, all patients seeking care in the primary health care units of the municipality of Lund (population 171 877) with upper or lower airway infections, prolonged cough, allergic rhinitis, fatigue or a first positive diagnosis of asthma were recorded ( n = 3025). RESULTS: In the whole group of 3025 patients, 99 patients were found to have received a diagnosis of asthma for the first time during the study period. The diagnosis was verified in 52 of those 68 patients who attended a follow-up and examination by a respiratory physician. Among the remaining 2926 patients, 221 patients were selected randomly to constitute a control group. In this group, three patients were found to have asthma. Thus, the specificity of an asthma diagnosis set in primary health care was 0.99 [95% confidence interval (CI) 0.99-1.00] and the sensitivity was 0.59 (95% CI 0.31-0.81). CONCLUSIONS: The GPs in this study were good at excluding those who did not have asthma (specificity 99%) but less good in correctly diagnosing those who actually had current asthma (sensitivity 59%), which suggests an underdiagnosis of asthma.

Adult↗

'Why don't you do as I tell you?' Compliance and antihypertensive regimens.

Although hypertension is recognised as one of the major health hazards in the developed world, compliance with antihypertensive regimens is still undesirably low. This brings important costs, both to patients in increased morbidity and mortality, and to society in hospitalisations and lost productivity. This review surveys possible reasons for non-compliance with treatments generally and antihypertensive medications specifically. It also looks at how insights into reasons for non-compliance can help us design more effective treatments, and discusses current and emerging medications in the context of compliance. As one of the reasons for low compliance is thought to be the impact of a drug on the patient's lifestyle, recently developed agents such as angiotensin II-receptor blockers may be expected to have less effect on patients' daily lives than earlier treatments, which brings hope for increased compliance with these regimens.

Antihypertensive Agents↗

[Are newer antihypertensive agents better than the older ones? Results of trials (CAPPP, STOP-2, NORDIL, INSIGHT and ALLHAT) with newer antihypertensive agents].

Until recently, no morbidity-mortality study had examined the effects of "newer" drugs, like angiotensin-converting enzyme inhibitors, calcium antagonists, and alpha-blockers compared to "old", but well-proven, thiazide diuretics, and beta-blockers in the treatment of essential hypertension. The prospective and randomised clinical trials, CAPPP, STOP-2, NORDIL, INSIGHT, and one arm of ALLHAT, with a total of about 58,000 middle-aged or elderly hypertensive patients have now been published. The primary outcome, composite cardiovascular (CV) death, cerebral stroke, and myocardial infarction, or composite fatal coronary heart disease and myocardial infarction, was the same, irrespective of the drug in all trials. Thus, prevention of CV complications depends on the lowering of blood pressure with well-tolerated medication, irrespective of class.

Adult↗

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗

Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial.

BACKGROUND: Is cancer related to hypertension and blood pressure? Do antihypertensive drugs promote cancer? Do antihypertensive drugs protect against cancer? We previously analysed the frequency of cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 (STOP-Hypertension-2). We have also looked at the frequency of cancer in these patients. METHODS: We randomly assigned 6614 elderly patients with hypertension (mean age 76 years, median time of follow-up 5.3 years) to one of three treatment strategies: conventional drugs (diuretics or b-blockers), calcium antagonists, or ACE inhibitors. We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age, sex, and calendar-year-specific reference frequencies for the general Swedish population. We also compared the number of cancers between the three treatment groups. FINDINGS: At baseline, 607 (9%) patients had previous malignant disease. Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients. During follow-up, there were 625 new cases of cancer in 590 patients. The frequency of cancer did not differ significantly between the treatment strategies, including all cancers and those at individual sites. The standardised incidence ratios (SIRs) for all cancers were also close to unity: 0.92 (95% CI 0.80-1.06) for conventional drugs, 0.96 (0.83-1.10) for calcium antagonists, and 0.99 (0.86-1.13) for ACE inhibitors. INTERPRETATIONS: No difference in cancer risk was seen between patients randomly assigned to conventional drugs, calcium antagonists, or ACE inhibitors. Thus, the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer.

Aged↗