MMP8 increases tongue carcinoma cell-cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5.

Matrix metalloproteinases (MMPs) modify bioactive factors via selective processing or degradation resulting in tumour-promoting or tumour-suppressive effects, such as those by MMP8 in various cancers. We mapped the substrates of MMP8 to elucidate its previously shown tumour-protective role in oral tongue squamous cell carcinoma (OTSCC). MMP8 overexpressing (+) HSC-3 cells, previously demonstrated to have reduced migration and invasion, showed enhanced cell-cell adhesion. By analysing the secretomes of MMP8 + and control cells with terminal amine isotopic labelling of substrates (TAILS) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS), we identified 36 potential substrates of MMP8, including FXYD domain-containing ion transport regulator 5 (FXYD5). An anti-adhesive glycoprotein FXYD5 has been previously shown to predict poor survival in OTSCC. Cleavage of FXYD5 by MMP8 was confirmed using recombinant proteins. Furthermore, we detected a loss of FXYD5 levels on cell membrane of MMP8 + cells, which was rescued by inhibition of the proteolytic activity of MMP8. Silencing (si) FXYD5 increased the cell-cell adhesion of control but not that of MMP8 + cells. siFXYD5 diminished the viability and motility of HSC-3 cells independent of MMP8 and similar effects were seen in another tongue cancer cell line, SCC-25. FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility. FXYD5 being a known prognostic factor in OTSCC, our findings strengthen its potential as a therapeutic target.

Does the Introduction of Laparoscopic Distal Pancreatectomy Jeopardize Patient Safety and Well-Being?

BACKGROUND/PURPOSE: Despite retrospective data indicating short-term superiority for laparoscopic distal pancreatectomy compared to open distal pancreatectomy, the implementation of the procedure has been slow. The aim of this study was to investigate whether patients operated with laparoscopic distal pancreatectomy during the early phase of introduction are at higher risk for complications than patients operated with open distal pancreatectomy. METHODS: A retrospective single-center analysis of patients operated with laparoscopic distal pancreatectomy (n = 37) from the introduction of the procedure and comparison regarding demographic data, preoperative data, operative factors, and postoperative outcomes to patients operated with open distal pancreatectomy was done. RESULTS: Operation duration shortened (195 vs 143 min, p = 0.04) and severe complications reduced (37% vs 6%, p = 0.02) significantly in the laparoscopic distal pancreatectomy group between the first half of the study and the second half. Blood loss was significantly (p < 0.001) lower in the laparoscopic distal pancreatectomy group (75 mL) than in the open distal pancreatectomy group (550 mL), while complication rate and hospital stay as well as the percentage of radical resections were the same. CONCLUSION: Laparoscopic distal pancreatectomy can be introduced without jeopardizing patient safety and well-being during the early learning curve. The procedures should be compared in a prospective randomized manner.

Reconstructive vascular surgery and the extent of tissue damage due to diabetic foot ulcers relates to risk of new ulceration in patients with PAD.

OBJECTIVE: There is limited information regarding new ulceration following the healing of ischaemic foot ulcers in diabetic patients. Our aim is to study new ulcerations in the same foot as the previous ulcer(s) in patients with diabetes and severe peripheral artery disease (PAD). METHOD: Patients with diabetes and severe PAD who healed from previous ulcer(s) (Wagner grade 1-5, at or below the ankle), were recruited for the prospective study from the time of healing of their ulcer. Patients were followed up regarding new ulceration, and their treatments and ulcer status noted either directly or on examination of medical records. RESULTS: We analysed the data on 602 patients with diabetes and severe PAD with healed foot ulcers, either primarily (n=443, 74%) or after minor amputation (n=159, 26%). Of these 51% (n=305) had revascularisation before healing from the previous ulcer, 34% (n=202) developed a new ulcer on the same foot within 15 months (range 0-106). Amputation was required by 22% (n=45) of patients, with a new ulcer on the same foot. The median survival time of all patients (n=602) was 54 months. By regression analysis, a low maximal Wagner grade for the previous ulcer and reconstructive vascular surgery was related to a decreased risk of developing new ulcers in the same foot. CONCLUSION: Patients with diabetes and ischaemic foot ulcers have a high-risk for developing new ulcers and amputation in the same foot after healing. The extent of tissue involvement in the previous ulcer and reconstructive vascular surgery affected the risk for development of new ulcers.

Early revascularization after admittance to a diabetic foot center affects the healing probability of ischemic foot ulcer in patients with diabetes.

OBJECTIVES: There is limited information about whether time from recognition of decreased perfusion to revascularization affects the probability of healing in a patient with a diabetic foot ulcer. The aim of the present study was to examine whether time to revascularization after referral to a multidisciplinary foot center was related to the outcome of foot ulcers in patients with diabetes and severe peripheral arterial disease (PAD). METHODS: Patients with diabetes, a foot ulcer, and a systolic toe pressure <45 mmHg or an ankle pressure <80 mmHg were prospectively included at the foot center, and considered for revascularization according to a preset protocol. All patients underwent invasive revascularization, either percutaneous transluminal angioplasty (PTA) or reconstructive vascular surgery. All patients had continuous follow-up until healing or death irrespective of the type of revascularization. RESULTS: A total of 478 patients were included (age 74 [range 66-80] years, 60% males), of whom 315 patients (66%) had PTA, and 163 (34%) had reconstructive surgery. Of the 478 patients, 217 (45%) healed primarily, 88 (19%) healed after a minor amputation, 76 (16%) healed after a major amputation and 92 patients (19%) died unhealed. The median time from inclusion in the study to revascularization was 8 weeks (3-18 weeks). Time to vascular intervention within 8 weeks (p < .001), maximum Wagner grade reached <3 (p < .001), absence of peripheral edema (p = .033), and presence of intermittent claudication (p = .001) were related to a higher probability of healing. CONCLUSIONS: Time to revascularization and extent of tissue damage were related to the probability of healing of ischemic foot ulcer in patients with diabetes over time. In the presence of a decreased perfusion in a patient with diabetes and a foot ulcer not only revascularization per se but also timing of revascularization is important for the possibility of healing without a major amputation.

Toll-like receptor 9 ligands enhance mesenchymal stem cell invasion and expression of matrix metalloprotease-13.

Human mesenchymal stem cells (hMSCs) are multipotent cells that are found in the bone marrow. Inflammation and tissue damage mobilize MSCs and induce their migration towards the damaged site through mechanisms that are not well defined. Toll-like receptor-9 (TLR9) is a cellular receptor for microbial and vertebrate DNA. Stimulation of TLR9 induces inflammatory and invasive responses in TLR9-expressing cells. We studied here the expression of TLR9 in human MSCs and the effects of synthetic TLR9-agonists on their invasion. Constitutive expression of TLR9 was detected in human MSCs but the expression was suppressed when MSCs were induced to differentiate into osteoblasts. Using standard invasion assays and a novel organotypic culture model based on human myoma tissue, we discovered that stimulation with the TLR9 agonistic, CpG oligonucleotides increased the invasion capacity of undifferentiated MSCs. Simultaneously, an increase in MMP-13 synthesis and activity was detected in the CpG-activated MSCs. Addition of anti-MMP-13 antibody significantly diminished the CpG-induced hMSC invasion. We conclude that treatment with TLR9-ligands increases MSC invasiveness, and this process is at least partially MMP-13-mediated.

Parental expectations, experiences and reactions, sense of coherence and grade of anxiety related to routine ultrasound examination with normal findings during pregnancy.

OBJECTIVE: To investigate parents' expectations, experiences and reactions, sense of coherence and anxiety before and after a second-trimester routine ultrasound examination, with normal findings. METHODS: Before and after ultrasound questionnaires including the scales parents' expectations, experiences and reactions to routine ultrasound examination (PEER-U state of mind index), sense of coherence (SOC) and state and trait anxiety inventory (STAI), were sent to a 1-year cohort of women and their partners. Replies received were 2183. RESULTS: Both parents had significantly less worried state of mind (PEER-U) after the examination than before. Women had a lower grade of state anxiety after than before, but for men there was no significant change. Before the ultrasound, women had a higher degree of worried state of mind, as well as a higher grade of state and trait anxiety and a lower sense of coherence, than men. The women showed a greater reduction in worried state of mind than the men after the ultrasound examination. There were no significant differences in sense of coherence before and after ultrasound. CONCLUSIONS: Women and men are affected in their psychological well-being in relation to a routine ultrasound examination, but their sense of coherence remains stable.

Complexity of factors related to outcome of neuropathic and neuroischaemic/ischaemic diabetic foot ulcers: a cohort study.

AIMS/HYPOTHESIS: We sought to identify factors related to short-term outcome of foot ulcers in patients with diabetes treated in a multidisciplinary system until healing was achieved. METHODS: Consecutively presenting patients with diabetes and worst foot ulcer (Wagner grade 1-5, below ankle) (n = 2,511) were prospectively followed and treated according to a standardised protocol until healing was achieved or until death. The number of patients lost to dropout was 31. The characteristics of the remaining 2,480 patients were: 1,465 men, age 68 +/- 15 years (range 18-96), type 1 diabetes 18%, type 2 diabetes 82% and insulin-treated 62%. RESULTS: The healing rate without major amputation in surviving patients was 90.6% (n = 1,867). Sixty-five per cent (n = 1,617) were healed primarily, 9% (n = 250) after minor amputation and 8% after major amputation; 17% (n = 420) died unhealed. Out of 2,060 surviving patients, 1,007 were neuroischaemic (48.8%). In a multiple regression analysis, primary healing was related to co-morbidity, duration of diabetes, extent of peripheral vascular disease and type of ulcer. In neuropathic ulcers, deep foot infection, site of ulcer and co-morbidity were related to amputation. Amputation in neuroischaemic ulcers was related to co-morbidity, peripheral vascular disease and type of ulcer. Age, sex, duration of diabetes, neuropathy, deformity and duration of ulcer or site of ulcer did not have an evident influence on probability of amputation. CONCLUSIONS/INTERPRETATION: Patients with diabetic foot ulcer suffer from multi-organ disease. Factors related to outcome are correspondingly complex.

Sociodemographic risk factors of metabolic syndrome in middle-aged women: results from a population-based study of Swedish women, The Women's Health in the Lund Area (WHILA) Study.

BACKGROUND: Metabolic syndrome (MS) is a common health problem in menopausal women. According to The Adult Treatment Panel (ATP) III, MS includes the combination of three or more of the following risk factors: abdominal obesity, glucose intolerance, high blood pressure, high serum triglycerides and low levels of high density lipoprotein cholesterol. OBJECTIVES: To assess the prevalence of the MS in middle-aged women, and the relationships of sociodemographic factors to the MS. METHODS: This analysis covers 10,766 women born between December 2, 1935 and December 1, 1945, living in the Lund area of Sweden by December 1, 1995. RESULTS: We found that 11.6% of women with a mean (+/-standard deviation) age of 56.9 +/- 3.06 years had MS. Women with MS were older and had higher scores for body weight, body mass index, waist/hip ratio, pulse rate, pulse pressure, serum triglycerides and total serum cholesterol (p < 0.001 for all) compared to the control group. More MS women were smokers, less often consumers of alcohol, and less qualified. In addition, they had low-intensity physical activity at leisure time (p < 0.001) and high-intensity physical activity at work (p = 0.009). Premenopausal women and those treated with hormones had less MS (p < 0.001). Education, physical activity at leisure time, moderate intensity of physical activity at work, alcohol intake and smoking had strong association with MS but work status, household status and dietary habits had no significant association with MS. CONCLUSIONS: Sociodemographic features may contribute to MS. Hence, prevention of MS should encompass sociodemographic features.

Could androgens protect middle-aged women from cardiovascular events? A population-based study of Swedish women: The Women's Health in the Lund Area (WHILA) Study.

OBJECTIVE: The aim of this analysis was to delineate perceived associations between androgens and cardiovascular events in perimenopausal women. DESIGN: A cross-sectional, population-based study of 6440 perimenopausal women aged 50-59 years, living in Southern Sweden. In all, 461 (7.1%) women were premenopausal (PM), 3328 (51.7%) postmenopausal without hormone therapy (HT) (PM0) and 2651 (41.2%) postmenopausal with HT (PMT). For further comparisons, 104 women (1.6%) who reported cardiovascular disease (CVD) were studied in detail; 49 had had a myocardial infarction, 49 a stroke and six women both events. For each woman with CVD, two matched controls were selected (n=208). RESULTS: In the matched controlled series, androstenedione levels were lower (p<0.005) in cases. Cases with hormone therapy had also lower testosterone levels than matched controls (p=0.05). In the total cohort, by using multiple logistic regression analyses, testosterone was positively associated with low density lipoprotein cholesterol (p<0.001) and high density lipoprotein cholesterol (HDL-C) (p<0.001) in all women, but negatively associated with levels of triglycerides in both the PM0 (p<0.001) and PMT (p<0.001) groups. Androstenedione levels were positively associated with HDL-C (p<0.05) and negatively with triglycerides (p<0.05) in the PM group. CONCLUSION: Women with cardiovascular disease had lower serum androgen levels, particularly women using hormone replacement therapy, even when controlled for lipids and other potential risk factors.

Obstructive airways diseases, smoking and use of inhaled corticosteroids in southern Sweden in 1992 and 2000.

OBJECTIVE: To examine the prevalence of obstructive pulmonary diseases, respiratory symptoms, smoking habits and pulmonary medication in an adult population, and to compare the results with a study performed in the same geographical area in 1992. DESIGN: In 2000, a postal questionnaire was sent to a randomly selected population of 5179 subjects aged 20-59 years living in southern Sweden. RESULTS: The participation rate was 71.3%. Self-reported asthma was reported by 8.5% of all respondents (vs. 5.5% in 1992, P < 0.001) and 14.5% of females aged 20-29 years. Self-reported chronic bronchitis and/or emphysema and/or chronic obstructive pulmonary disease (CBE/COPD) was reported by 3.6% (vs. 4.6% in 1992, non-significant) with the highest prevalence (5.7%) in the 50-59 year cohort. Smoking decreased from 33.3% in 1992 to 28.4% in 2000 (P < 0.05). About 46% of asthmatics reported nocturnal respiratory symptoms, and 69% reported having had asthma symptoms in the last 12 months. Use of inhaled steroids increased in subjects with asthma and CBE/COPD from 19.4% to 36.5% (P < 0.05) and from 8.6% to 30.0% (P < 0.05), respectively. CONCLUSIONS: Self-reported asthma increased significantly between 1992 and 2000, but the prevalence of CBE/COPD was unchanged. The high proportion of reported symptoms in asthmatics despite an increased use of steroids suggests that further efforts are needed to improve asthma treatment.

Is increased segmental motion early after lumbar discectomy related to poor clinical outcome 5 years later?

The purpose of the study was to compare segmental motion in the early postoperative phase after lumbar discectomy to the outcome 5 years postoperatively. The study population had radiologically verified symptomatic L4-L5 or L5-S1 lumbar disc herniation and was referred with an indication for lumbar discectomy. Radiostereometry was performed in the supine and standing positions. The L4-L5 and L5-S1 segments were analysed separately. L4-L5 segments adjacent to the operated L5-S1 segment constituted a reference segment for the operated L4-L5 and vice versa. Twenty-one patients were available for the follow-up at 5 years. Outcome was classified as functionally good or poor. Repeated or planned repeat surgery at the same level during follow-up was considered as poor outcome. The L4-L5 segments in the poor group showed different direction of sagittal rotation (anterior versus posterior) of L4 on L5 compared with the good group (p<0.01). On the L5-S1 segment, patients with poor outcome displayed an increased anterior translation of about 1 mm (p<0.01) compared with the reference segments. Our study suggests that increased inducible vertebral displacement in the early postoperative phase after discectomy is associated with a poor clinical outcome.

The effect of standard lumbar discectomy on segmental motion: 5-year follow-up using radiostereometry.

We measured the effects of lumbar discectomy on segmental motion over a period of 5 years. Twenty-four patients with lumbar disc herniation were treated by standard lumbar discectomy at the L4-L5 or L5-S1 level. Peroperatively, tantalum markers were inserted into L4, L5, and the sacrum. Radiostereometric analysis was performed at discharge from hospital and 5 years postoperatively. The treated level was compared with the corresponding untreated level. Thus, patients who had discectomy at the L4-L5 level served as controls for patients with L5-S1 lesions and vice versa. The relative rotation and translation in relation to the three cardinal axes were calculated. Inducible displacements over the two discs were calculated between the supine and standing positions. At the L4-L5 level, there were no differences in inducible displacements between the operated and control levels at discharge or 5 years postoperatively. At the L5-S1 level we found decreasing inducible movement in the sagittal plane over time for discectomy patients. The reason for decreasing mobility over time after discectomy at the L5-S1 but not at the L4-L5 level is unknown. Mechanical factors caused by the more vertical orientation of the L5-S1 disc in combination with degenerative changes could be one explanation.

Cardiovascular risk factors in middle-aged women and the association with use of hormone therapy: results from a population-based study of Swedish women. The Women's Health in the Lund Area (WHILA) Study.

OBJECTIVE: Cardiovascular diseases in women are multifactorial. Women carry different risk factors compared to men and these specific risk factors need to be delineated, particularly in relation to the hormonal situation, and effects of diet and lifestyle. METHODS: Out of the total cohort of 10,766 women born 1935-1945 living in the Lund area of southern Sweden, 6917 women completed a generic questionnaire and underwent a physical and laboratory assessment. According to hormonal status, 492 women were premenopausal (PM), 3600 were postmenopausal without hormone therapy (HT) (PM0) and 2816 were postmenopausal with ever-use of HT (PMT). Major cardiovascular risk factors as well as level of education, diet, and degree of physical activity were assessed in relation to hormonal status. RESULTS: Compared to the PM0 group, the women in the PMT group had a higher level of education, more often worked full time, more often had sedentary work and lived a more regular life. They also had a lower rate of cigarette consumption, lower waist-to-hip ratio and lower body mass index than women in the PM0 group. The PMT group had lower levels of serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides than the PM0 group and also had lower systolic and diastolic blood pressures, a lower prevalence of type II diabetes mellitus, of deep venous thrombosis and of coronary artery disease. Low-risk factors for cardiovascular disease and high level of education were still associated with HT, after adjustment by multiple logistic regression. Major risk factors for coronary heart disease were similar between the PM and the PMT groups. CONCLUSION: Use of HT is accompanied by a lower risk profile for cardiovascular disease and also by several factors indicating a healthier lifestyle.

Examination on Candida spp. in refractory periapical granulomas.

AIM: To examine the occurrence of Candida spp. in refractory periapical granulomas. METHODOLOGY: One hundred and three surgically removed periapical granulomas were subjected to molecular analysis for the occurrence of Candida albicans. DNA was extracted from the samples using a modified phenol/chloroform/isoamyl alcohol method and was subjected to polymerase chain reaction (PCR) with OPA-03 and repetitive sequence (GACA)4 primers. The PCR products were separated in agarose gel electrophoresis, stained with ethidium bromide, visualized using UV light and the sequences were analysed. Samples indicating possible occurrence of Candida were further investigated by histological and immunohistological methods. Periodic acid-Shiff staining (PAS) was used to detect yeast cells and hyphae, and specific monoclonal antibodies to recognize high molecular mass mannoproteins present in the C. albicans cell wall. DNA extraction was controlled by running PCR using beta-actin primers (a housekeeping gene). C. albicans CCUG19915, C. tropicalis ATCC750, C. krusei ATCC6258, C. guilliermondii ATCC6260 and C. glabrata CCUG32725 served as positive controls in PCR. A tissue preparation of chronic atrophic candidosis in oral buccal mucosa served as a positive control for histological and immunohistological examinations. RESULTS: Polymerase chain reaction with beta-actin primers indicated successful DNA extraction in 68 out of 103 samples. The majority of the samples (50) were negative whereas 18 of the samples showed PCR products indicating possible occurrence of Candida spp. PAS-staining and immunohistological examination of these samples were, however, negative. Further analysis of the PCR products revealed sequences not typical for Candida spp. CONCLUSIONS: Candida spp. do not seem to occur in periapical granuloma.

Influence of heavy traffic, city dwelling and socio-economic status on nasal symptoms assessed in a postal population survey.

BACKGROUND: The association between social position, living environment and nasal symptoms is inconsistent. We wanted to test how living environment, occupation and social position were associated with nasal symptoms. METHODS: In a postal survey study of a random sample of 12,079 adults, aged 20-59 years living in the southern part of Sweden the relationship between nasal symptoms, socio-economic status and environmental factors was analysed. RESULTS: The response rate was 70% (n = 8469) of whom 33% reported significant nasal symptoms. Nasal discharge, thick yellow discharge, a blocked nose, sneezing and itching were strongly associated with living close to heavy traffic or living in cities. Most of the nasal symptoms provoked by extrinsic factors were more frequently reported among subjects who lived close to heavy traffic and in cities. Apart from thick yellow discharge and nasal symptoms provoked by damp/cold air which were more common in the socio-economic position "low" no relation to the socio-economic group was found. The prevalence of self-reported hay fever was neither affected by site of living nor by socio-economic status. Nasal symptoms evoked by "allergic" factors were linked to asthma but symptoms evoked by non-allergic factors were linked to chronic bronchitis/emphysema CBE. CONCLUSIONS: To conclude, we found a strong relation between geographical site and the prevalence of self-reported nasal symptoms which emphasizes the environment as a risk factor for nasal symptoms. Only by merging the socio-economic groups into "low" and "middle/high" an association to nasal symptoms was apparent. Nasal symptoms evoked by "allergic" factors were linked to asthma but symptoms evoked by "non allergic factors" were linked to CBE.

Socio-demographic and psychosocial factors are associated with features of the metabolic syndrome. The Women's Health in the Lund Area (WHILA) study.

AIM: The aim was to analyse any associations between socio-demographic and psychosocial factors and different features of the metabolic syndrome in a geographically well-defined population of middle-aged women. METHODS: A population of 10 766 Caucasian women aged 50-59 years was investigated regarding biological and socio-demographic conditions, physical activity, dietary habits, aspects of quality of life, and subjective physical and mental symptoms. The screening instrument was used to discriminate subjects as positive or negative on one or more of a total of eight variables considered to be linked to the metabolic syndrome. The cut-off values for positive screening were non-fasting capillary blood glucose >/= 8.0 mmol/l and serum triglycerides >/= 2.3 mmo/l, BMI >/= 30 kg/m2, WHR >/= 0.90, blood pressure >/= 160 and/or 95 mmHg, a family history of diabetes, and pharmacological treatment for hypertension or hyperlipidaemia. RESULTS: Altogether 6805 women (63.2%) participated: 3535 with positive and 3270 with negative screening. Multiple logistic regression analyses showed that comprehensive (OR 1.62, 95% CI 1.41-1.87) and upper secondary (1.40, 1.24-1.57) school, low physical quality of life (1.41, 1.23-1.61) and high sum of subjective physical symptoms (1.06, 1.04-1.08) were positively associated with one or more features of the metabolic syndrome, while high leisure-time exercise and healthy diet (0.84, 0.71-0.99), and low (

MMP-9 activation by tumor trypsin-2 enhances in vivo invasion of human tongue carcinoma cells.

Various human cancer cells express tumor-associated trypsinogen-2 (TAT-2), which can efficiently activate matrix metalloproteinases (MMPs) in vitro. MMP-2 and MMP-9 are particularly associated with the invasive malignant potential of several tumors. To investigate the role of TAT-2 in tumor invasion, we overexpressed TAT-2 in two malignant human squamous cell carcinoma cell lines of tongue and in non-malignant human papilloma virus transformed gingival keratinocytes. The TAT-2 overexpression significantly increased the levels of active MMP-9 in the most malignant cell line. TAT-2-transfected cells intravasated (invaded blood vessels) up to 60% more efficiently than did the control cells in an in vivo chick embryo chorioallantoic membrane invasion model. This increased intravasation was almost completely abolished by a specific tumor-associated trypsin inhibitor (TATI). These results indicate that TAT-2 has a role in the invasive growth of tumors, either alone or in cascade with gelatinases, especially by generating active MMP-9.

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.

Prevalence of obstructive lung diseases and respiratory symptoms in relation to living environment and socio-economic group.

We wanted to test whether living environment, occupation and social position are risk factors for asthma and chronic bronchitis/emphysema (CBE). The prevalence of bronchial asthma, CBE, respiratory symptoms and smoking habits in a random sample of 12,071 adults aged 20-59 years was assessed in a postal survey with a slightly modified questionnaire previously used in central and northern Sweden (The OLIN studies). Occupation was coded according to a socio-economic classification system. Six different living environment areas were defined; city-countryside, seaside-not seaside and living close to heavy traffic-not living close to heavy traffic. Multiple logistic regression analysis (forward conditional) was applied to estimate the association between the proposed set of risk factors and self-reported obstructive lung diseases and lower respiratory symptoms controlling for age, gender and smoking. After two reminders, the response rate was 70.1% (n=8469); 33.8% of the responders were smokers. In all, 469 subjects (5.5%) stated that they had asthma and 4.6% reported CBE. Besides smoking, which was a risk for both asthma and CBE, there were different risk patterns for self-reported asthma and CBE. In the economically active population there was a tendency that CBE was more common among 'unskilled and semi-skilled workers'. This fact was further emphasized when the population was merged into the two groups 'low social position' and 'middle/high social position', with 'low social position' as a risk for CBE (OR=1.35, 95% CI=1.06-1.72). No social risk factors were identified for asthma. Living close to heavy traffic was a risk factor for asthma (OR=1.29, 95% CI=1.02-1.62) but not for CBE. Apart from this no living environmental risk factors for obstructive pulmonary diseases were identified. Asthma symptoms and long-standing cough were more common among those subjects living close to heavy traffic compared to those not living close to heavy traffic. To conclude, low social position was a risk factor for CBE and living close to heavy traffic was a risk factor for asthma.

Cost of illness of adult diabetes mellitus underestimated if comorbidity is not considered.

OBJECTIVE: To determine costs of illness for adult diabetes mellitus (DM), including complications caused by DM. DESIGN: A population-based multicentre cross- sectional study including an interview and a physical examination of patients identified as having DM. The patients' medical records were analysed regarding diagnoses and complications attributable to DM. SETTING: Eight health care centres of six primary care districts in Southern Sweden. SUBJECTS: 1677 adults aged 25+, cared for at the health care centres, entered the study. MAIN OUTCOME MEASURES: Utilization of health care and care from relatives and the municipality, absence of short- and long-term sickness, cost of illness. RESULTS: The average annual direct and indirect costs for an adult with DM were calculated to be 61 700 Swedish Kronor (SEK) or 2.5 times higher than earlier estimates. The incremental cost of DM was 34 100 SEK. The cost distribution was 28% for health care, 31% for the municipality and relatives and 41% lost productivity. CONCLUSIONS: Calculations for the cost of illness of DM are underestimated if comorbidity caused by DM is not considered. When DM-related complications are included to identify the actual burden of disease to society, the cost of illness as a result of DM in Sweden is substantially higher than previously estimated.