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Biomedical subjects

M Johannesson

Publications and source records attributed to M Johannesson.

At least 19 recordsLinked to original sources
PubMed2006

Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.

The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL.

Adolescent↗
PubMed2006

Genetics of autoimmune diseases: a multistep process.

It has so far been difficult to identify genes behind polygenic autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), and type I diabetes (T1D). With proper animal models, some of the complexity behind these diseases can be reduced. The use of linkage analysis and positional cloning of genes in animal models for RA resulted in the identification of one of the genes regulating severity of arthritis in rats and mice, the Ncf1 gene. The Ncf1 gene encodes for the Ncf1 protein that is involved in production of free oxygen radicals through the NADPH oxidase complex, which opens up a new pathway for therapeutic treatment of inflammatory diseases. In most cases, however, a quantitative trait locus (QTL) is the sum effect of several genes within and outside the QTL, which make positional cloning difficult. Here we will discuss the possibilities and difficulties of gene identification in animal models of autoimmune disorders.

Animals↗
PubMed2005

Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice.

Identification of genes controlling complex diseases has proven to be difficult; however, animal models may pave the way to determine how low penetrant genes interact to promote disease development. We have dissected the Cia5/Eae3 susceptibility locus on mouse chromosome 3 previously identified to control disease in experimental models of multiple sclerosis and rheumatoid arthritis. Congenic strains showed significant but small effects on severity of both diseases. To improve the penetrance, we have now used a new strategy that defines the genetic interactions. The QTL interacted with another locus on chromosome 15 and a partial advanced intercross breeding of the two congenic strains for eight generations accumulated enough statistical power to identify interactions with several loci on chromosome 15. Thereby, three separate loci within the original QTL could be identified; Cia5 affected the onset of arthritis by an additive interaction with Cia31 on chromosome 15, whereas the Cia21 and Cia22 affected severity during the chronic phase of the disease through an epistatic interaction with Cia32 on chromosome 15. The definition of genetic interactions was a prerequisite to dissect the Cia5 QTL and we suggest the partial advanced intercross strategy to be helpful also for dissecting other QTL controlling complex phenotypes.

Animals↗
PubMed2005

Gene expression profiling of arthritis using a QTL chip reveals a complex gene regulation of the Cia5 region in mice.

One of the major quantitative trait loci (QTLs) associated with arthritis in crosses between B10.RIII and RIIIS/J mice is the Cia5 on chromosome 3. Early in the congenic mapping process it was clear that the locus was complex, consisting of several subloci with small effects. Therefore, we developed two novel strategies to dissect a QTL: the partial advanced inter-cross (PAI) strategy, with which we recently found the Cia5 region to consist of three loci, Cia5, Cia21 and Cia22, and now we introduce the QTL-chip strategy, where we have combined congenic mapping with a QTL-restricted expression profiling using a novel microarray design. The expression of QTL genes was compared between parental and congenic mice in lymph node, spleen and paw samples in five biological replicates and in dye-swapped experiments at three time points during the induction phase of arthritis. The QTL chip approach revealed 4 genes located in Cia21, differently expressed in lymph nodes, and 14 genes in Cia22, located within two clusters. One cluster contains six genes, differently expressed in spleen, and the second cluster contains eight genes, differently expressed in paws. We conclude the QTL-chip strategy to be valuable in the selection of candidate genes to be prioritized for further investigation.

Animals↗
PubMed2003

Genetic heterogeneity of autoimmune disorders in the nonobese diabetic mouse.

The nonobese diabetic mouse is highly susceptible not only to diabetes but to several autoimmune diseases, and one might suspect that these are controlled by a shared set of genes. However, based on various gene-segregation experiments, it seems that only a few loci are shared and that each disorder is influenced also by a unique set of genes.

Animals↗
PubMed2002

Predictors of deterioration of lung function in cystic fibrosis.

The severity of lung disease in cystic fibrosis (CF) may be related to the type of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and to environmental and immunological factors. Since pulmonary disease is the main determinant of morbidity and mortality in CF, it is important to identify factors that can explain and predict this variation. The aim of this longitudinal study of the whole Swedish CF population over age 7 years was to correlate genetic and clinical data with the rate of decline in pulmonary function. The statistical analysis was performed using the mixed model regression method, supplemented with calculation of relative risks for severe lung disease in age cohorts.The severity of pulmonary disease was to some extent predicted by CFTR genotype. Furthermore, the present investigation is the first long-term study showing a significantly more rapid deterioration of lung function in patients with concomitant diabetes mellitus. Besides diabetes mellitus, pancreatic insufficiency and chronic Pseudomonas colonization were found to be negative predictors of pulmonary function. In contrast to several other reports, we found no significant differences in lung function between genders. Patients with pancreatic sufficiency have no or only a slight decline of lung function with age once treatment is started, but an early diagnosis in this group is desirable.

Adolescent↗
PubMed2002

Exhaled carbon monoxide is not elevated in patients with asthma or cystic fibrosis.

Increased levels of exhaled carbon monoxide (fractional concentration of CO in expired gas (FE,CO)), measured with an electrochemical sensor, have been reported in patients with inflammatory airway disorders, such as asthma, rhinitis and cystic fibrosis. This study aimed to evaluate these findings by using a fast-response nondisperse infrared (NDIR) analyser, and to compare these measurements with the fractional concentration of nitric oxide in exhaled air (FE,NO). Thirty-two steroid-naïve asthmatics, 24 steroid-treated asthmatics (16 patients with allergic rhinitis, nine patients with cystic fibrosis), and 30 nonsmoking healthy controls were included. CO measurements with the NDIR analyser were performed simultaneously with nitric oxide (NO) analysis (chemiluminescence technique). After 15 s of breath-hold, single-breath exhalations over 10 s were performed at two flow rates and end-tidal plateau concentrations were registered. An electrochemical CO sensor was used independently with an exhalation to residual volume, after a 15 s breath-hold. None of the two CO analysers gave a significant increase in FE,CO in the groups of patients with inflammatory airway disorders compared to controls. FE,NO was significantly elevated in steroid-naïve asthmatics and subjects with allergic rhinitis, but not in steroid-treated asthmatics and subjects with cystic fibrosis. Reducing exhalation flow rate by 50% gave a two-fold increase in FE,NO, while FE,CO was unaffected. A significant increase was seen in FE.CO, but not in FE,NO, when comparing with and without a 10 s breath-hold. In conclusion, the fractional concentration of carbon monoxide in expired gas was not increased in any of the patient groups, while the fractional concentration of nitric oxide in expired gas was significantly elevated in patients with steroid-naïve asthma and allergic rhinitis. Moreover, carbon monoxide was unaffected by flow rate but increased with breath-hold, suggesting an origin in the alveoli rather than the conducting airways.

Adolescent↗
PubMed2001

Genetic control of collagen-induced arthritis in a cross with NOD and C57BL/10 mice is dependent on gene regions encoding complement factor 5 and FcgammaRIIb and is not associated with loci controlling diabetes.

The nonobese diabetic (NOD) mouse spontaneously develops autoimmune-mediated diseases such as diabetes and Sjögren's syndrome. To investigate whether NOD genes also promote autoimmune-mediated arthritis we established a NOD strain with an MHC class II fragment containing the A(q) class II gene predisposing for collagen induced arthritis (NOD.Q). However, this mouse was resistant to arthritis in contrast to other A(q) expressing strains such as B10.Q and DBA/1. To determine the major resistance factor/s, a genetic analysis was performed. (NOD.Q x B10.Q)F1 mice were resistant, whereas 27% of the (NOD.Q x B10.Q)F2 mice developed severe arthritis. Genetic mapping of 353 F2 mice revealed two loci associated with arthritis. One locus was found on chromosome 2 (LOD score 9.8), at the location of the complement factor 5 (C5) gene. The susceptibility allele was from B10.Q, which contains a productive C5 encoding gene in contrast to NOD.Q. The other significant locus was found on chromosome 1 (LOD score 5.6) close to the Fc-gamma receptor IIb gene, where NOD carried the susceptible allele. An interaction between the two loci was observed, indicating that they operate on the same or on interacting pathways. The genetic control of arthritis is unique in comparison to diabetes, since none of these loci have been identified in analysis of diabetes susceptibility.

Animals↗
PubMed2001

Hypothetical versus real willingness to pay in the health care sector: results from a field experiment.

We conducted a field experiment comparing hypothetical and real purchase decisions for a pharmacist provided asthma management program among 172 subjects with asthma. Subjects received either a dichotomous choice contingent valuation question or were given the opportunity to actually enroll in the program. Three different prices were used: US$ 15, 40, and 80. In the hypothetical group, 38% of subjects said that they would purchase the good at the stated price, but only 12% of subjects in the real group purchased the good (p = 0.000). We cannot, however, reject the null hypothesis that "definitely sure" hypothetical yes responses, as identified in a follow-up question, correspond to real yes responses. We conclude that the dichotomous choice contingent valuation method overestimates willingness to pay, but that it may be possible to correct for this overestimation by sorting out "definitely sure" yes responses.

Adolescent↗
PubMed2001

Health-related quality of life by disease and socio-economic group in the general population in Sweden.

Measuring health-related quality of life (HRQoL) on population level, is becoming increasingly important for priority setting in health policy. In the health economics field, it is common to measure HRQoL in terms of health-state utilities or QoL weights. This study investigates the feasibility of obtaining mean QoL weights by mapping survey data to the generic HRQoL measure EQ-5D and to describe the HRQoL in terms of mean QoL weights in certain disease and socio-economic groups. Data from the 1996-1997 Survey of Living Conditions, interviews with a representative sample (16-84 years) of the Swedish population (n=11 698) were used. The mean QoL weight decreased from 0.91 among the youngest to 0.61 among the oldest, and was lower for women than for men. The QoL weight was 0.88 in the highest socio-economic group and 0.78 in the lowest socio-economic group. The QoL weight was lowest (0.38) among persons with depression and highest among persons with hypertension (0.71). The QoL weight decreased from 0.95 for persons with very good global self-rated health to 0.20 for persons with very poor global self-rated health. The results support the feasibility and validity of the mapping approach. HRQoL varies greatly between socio-economic groups and different disease groups.

Activities of Daily Living↗
PubMed2001

Swedish population health-related quality of life results using the EQ-5D.

Health-related quality of life (HRQoL) measured on population level may be useful to guide policies for health. This study aims to describe the HRQoL; in EQ-5D dimensions, mean rating scale (RS) scores and mean EQ-5D index values, in the general population, by certain disease and socio-economic groups, in Stockholm County 1998. The EQ-5D self-classifier and a RS were included in the 1998 cross-sectional postal Stockholm County public health survey to a representative sample (n = 4950, 20-88 years), 63% response rate. Mean RS score ranged from 0.90 (20-29 years) to 0.69 (80-88 years), mean EQ-5D index value ranged from 0.89 (20-29 years) to 0.74 (80-88 years). For different diseases mean RS scores ranged from 0.80 (asthma) to 0.69 (angina pectoris), mean EQ-5D index values ranged from 0.79 (asthma) to 0.66 (low back pain). The mean health state scores (RS and EQ-5D index) were 0.06 lower in the unskilled manual group than in the higher non-manual group after controlling for age and sex (p < 0.0001). This difference was 0.03 after controlling also for different diseases (p < 0.0001). In conclusion, our results show that the HRQoL varies greatly between socio-economic and disease groups. Furthermore, after controlling for age, sex and disease, HRQoL is lower in manual than in non-manual groups.

Adult↗
PubMed2001

Influence of CD4 or CD8 deficiency on collagen-induced arthritis.

The role of T cells in the mouse collagen-induced arthritis (CIA) model for rheumatoid arthritis is not clarified, and different results have been reported concerning the role of CD4 and CD8 T cells. To address this issue, we have investigated B10.Q mice deficient for CD4 or CD8. The mice lacking CD4 were found to be less susceptible to disease, but not completely resistant, whereas the CD8 deficiency had no significant impact on the disease. No difference in the development of late occurring relapses was noted. Interestingly, the CD4-deficient mice had a severely reduced response to the glycosylated form of the immunodominant type II collagen (CII) 256-270 peptide whereas the response to the non-glycosylated peptide was not significantly different. Furthermore, CD4-deficient mice had lower antibody responses to CII, explaining the lower disease susceptibility. In comparison with previously reported results, it is apparent that the lack of CD4 molecules has a different impact on CIA if present on different genetic backgrounds, findings that could possibly be related to the occurrence of different disease pathways of CIA in different mouse strains.

Animals↗
PubMed2001

At what coronary risk level is it cost-effective to initiate cholesterol lowering drug treatment in primary prevention?

BACKGROUND: The entire risk factor profile should be taken into account when considering initiating cholesterol lowering drug treatment. Recent treatment guidelines are therefore based on the absolute risk of coronary heart disease. We estimated at what coronary risk it is cost-effective to initiate cholesterol lowering drug treatment in primary prevention for men and women of different ages in Sweden. METHODS: The cost-effectiveness was estimated as the incremental cost per quality-adjusted life-year (QALY) gained of cholesterol lowering drug treatment. Treatment was assumed to lower the risk of coronary heart disease by 31%. The analysis was carried out from a societal perspective including both direct and indirect costs of the intervention and morbidity, and the full future costs of decreased mortality. The coronary risk, in a Markov model of coronary heart disease, was raised until the cost per QALY gained corresponded to a specific threshold value per QALY gained. Three different threshold values were used: $40,000, $60,000 and $100,000 per QALY gained. RESULTS: The risk cut-off value for when treatment is cost-effective varied with age and gender. If society is willing to pay $60,000 to gain a QALY it was cost-effective to initiate treatment if the 5-year-risk of coronary heart disease exceeded 2.4% for 35-year-old men, 4.6% for 50-year-old men, and 10.4% for 70-year-old men. The corresponding risk cut-off values for women were 2.0%, 3.5% and 9.1%. CONCLUSIONS: The results can serve as a basis for treatment guidelines based on cost-effectiveness.

Adult↗
PubMed2000

Income-related inequality in life-years and quality-adjusted life-years.

We estimate the income-related inequality in Sweden with respect to life-years and quality-adjusted life-years (QALYs). We use a large data set from Sweden with over 40,000 individuals followed up for 10-16 years, to estimate the survival and quality-adjusted survival in different income groups. For both life-years and QALYs, we discover inequalities in health favouring the higher income groups. For men (women) in the youngest age-group (20-29 years), the number of QALYs is 43.7 (45.7) in the lowest income decile and 47.2 (49.0) in the highest income decile.

Adult↗
PubMed2000

Cost-effectiveness of intense insulin treatment after acute myocardial infarction in patients with diabetes mellitus; results from the DIGAMI study.

AIMS: The aim of the present analysis was to estimate the cost-effectiveness of intense insulin treatment after acute myocardial infarction in patients with diabetes mellitus based on the results of the Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. In this study 620 patients with diabetes mellitus and acute myocardial infarction were randomized to intense insulin treatment (insulin group) or to serve as controls given standard antidiabetic therapy. Mortality was significantly reduced in the insulin group. METHODS AND RESULTS: The cost-effectiveness ratio was estimated as the incremental cost per life-year and quality-adjusted life-year gained of intense insulin treatment. The incremental costs were estimated as the difference in health care costs and indirect costs (labour production) during the first year of follow-up plus the future costs of increased survival. The life-years gained were based on the 5-year long-term follow-up experience and an assumed annual 20% mortality risk for all patients thereafter. The health care costs were Euro 975 higher in the insulin group during the first year of follow-up, mainly due to a longer period of initial hospitalization related to the institution of multidose insulin. The estimated discounted gain in life-years of the insulin treatment was 0.94 years without and 0.66 with quality of life adjustment, respectively. The cost per life-year gained by intense insulin treatment was Euro 16 900 and the cost per quality-adjusted life-year gained was Euro 24 100. Thus the estimated cost-effectiveness ratios were relatively low. CONCLUSION: The results of the DIGAMI study indicate that intense insulin treatment after an acute myocardial infarction in patients with diabetes mellitus has an acceptable level of cost-effectiveness.

Cost-Benefit Analysis↗
PubMed2000

Lung function changes in relation to menstrual cycle in females with cystic fibrosis.

Oestrogen and progesterone have been shown to have impact on cystic fibrosis transmembrane conductance regulator (CFTR) gene expression, tone of smooth muscle in the airways, immune response, exhaled nitric oxide and cytology in the tracheobronchial epithelium. The aim of this investigation was to study the influence of menstrual cyclicity on airway symptoms among cystic fibrosis (CF) females. Twelve CF women (mean age 30 years, mean Shwachman score 85) kept daily records during three menstrual cycles of lung function, sputum quality and need for intravenous antibiotics. Paired t-test was used as a statistical method to compare the airway symptoms between the time of ovulation (high levels of oestrogen and low levels of progesterone), the luteal phase (high levels of oestrogen and progesterone) and menstruation (low levels of oestrogens and progesterone). Forced expiratory volume in 1 sec (FEV1) was significantly higher during the luteal phase (66% of predicted) compared to during ovulation (63%) and menstruation (61%) (P<0.01). Forced vital capacity (FVC) showed the same pattern, being significantly higher during the luteal phase compared with during menstruation (mean 75% vs. 70%, P<0.01). In conclusion, lung function changes were found during menstrual cycles in women with cystic fibrosis. These changes are probably related to changes in progesterone levels during the menstrual cycles. This result warrants further studies to understand the complexity of CF lung disease in women.

Adolescent↗
PubMed2000

Resource utilization and costs of stroke unit care integrated in a care continuum: A 1-year controlled, prospective, randomized study in elderly patients: the Göteborg 70+ Stroke Study.

BACKGROUND AND PURPOSE: The aim of the present study was to examine resource utilization during a 12-month period after acute stroke in elderly patients randomized to care in an acute stroke unit integrated with a care continuum compared with conventional care in general medical wards. A secondary aim was to describe costs related to the severity of stroke. METHODS: Two hundred forty-nine consecutive patients aged >/=70 years with acute stroke within 7 days before admission, living in their own homes in Göteborg, Sweden, without recognized need of care were randomized to 2 groups: 166 patients were assigned to nonintensive stroke unit care with a care continuum, and 83 patients were assigned to conventional care. There was no difference in mortality or the proportion of patients living at home after 1 year. Main outcomes were costs from inpatient care, outpatient care, and informal care. RESULTS: Mean annual cost per patient was 170, 000 Swedish crowns (SEK) (equivalent to $25,373) and 191,000 SEK ($28,507) in the stroke unit and the general medical ward groups, respectively (P:=NS). Seventy percent of the total cost was for inpatient care, and 30% was for outpatient and informal care. For patients with mild, moderate, and severe stroke, the mean annual costs per patient were 107,000 SEK ($15,970), 263,000 SEK ($39, 254), and 220,000 SEK ($32,836), respectively (P:<0.001). There was no statistical difference in age or nonstroke diagnosis. CONCLUSIONS: The total costs the first year did not differ significantly between the treatment groups in this prospective study. The total annual cost per patient showed a very large variation, which was related to stroke severity at onset and not to age or nonstroke diagnoses. Costs other than those for hospital care constituted a substantial fraction of total costs and must be taken into account when organizing the management of stroke patients. The high variability in costs necessitates a larger study to assess long-term cost effectiveness.

Acute Disease↗