Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects.

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

Development of early PCLP1-expressing haematopoietic cells within the avian dorsal aorta.

The first haematopoietic stem cells (HSC) develop in the dorsal aorta as haematopoietic intra-aortic clusters (HIAC). To evaluate the initial steps of definitive haematopoiesis, we have studied the emergence and the expression profile of podocalyxin-like protein 1 (PCLP1)-expressing cells in early chick embryos. Here we demonstrate that at embryonic day 2 (E2), the PCLP1+ cells are present in the splanchnic mesoderm and in the ventral lining of the paired dorsal aorta. Following aortic fusion at E3, the PCLP1-expressing cells are exclusively found in the aortic floor and as the development proceeds, both the haematopoietic clusters and the aortic endothelial cells express PCLP1. In parallel with the early PCLP1 expression, bone morphogenetic protein 4 (BMP4) expression was detected in the splanchnopleura and thereafter in the densely packed mesenchymal cells beneath the HIAC. The microarray analyses of early E3 PCLP1+ cells revealed elevated expression of genes known to be involved in the stem cell function. These data suggest that splanchnopleura-derived PCLP1-expressing cells give rise to the earliest definitive haematopoietic progenitors.

Thalidomide therapy and polyneuropathy in myeloma patients.

Thalidomide is today an increasingly used therapy in advanced and refractory myeloma patients, especially in patients relapsing after high dose therapy. One important and well-known side effect of thalidomide is polyneuropathy (PNP). The purpose of this study was to investigate 1) how severe the thalidomide-induced PNP is in patients treated for myeloma 2) which neurophysiological tests and parameters are most sensitive in detecting the thalidomide-induced PNP and 3) how neuropathic symptoms correlate with neurophysiological changes. Twelve patients received thalidomide for treatment of relapsed multiple myeloma for at least 5 months. Prior to the thalidomide treatment, all patients had been treated with chemotherapy including vincristine, and seven patients had also received cisplatin. PNP symptoms, clinical findings and neurophysiological tests before and after the therapy were evaluated. Prior to thalidomide treatment, 7 patients had minimal and one patient slight PNP. After thalidomide treatment, 4 patients had minimal, 4 patients slight, and 3 patients moderate PNP. Thalidomide-induced PNP mainly affected sensory myelinated axons, but also alpha motor neuron axons were affected to some extent. Thermal thresholds were not altered, indicating that thin myelinated and unmyelinated axons are spared. The most sensitive parameter for detecting thalidomide-induced PNP was the sensory nerve compound action potential amplitude. The neuropathic symptoms deteriorated significantly during the therapy, but clinically, no patient developed a disabling PNP that would have required interrupting the therapy. The neuropathic side effects of thalidomide seem to be acceptable in myeloma patients.

Chicken B-cell-activating factor: regulator of B-cell survival in the bursa of fabricius.

Previous studies on mammals have demonstrated that a tumour necrosis factor family member, B-cell-activating factor (BAFF) (BlyS, TALL-1), is mainly produced by myeloid and dendritic cells and that BAFF promotes B-cell differentiation and survival in a paracrine fashion. We have recently shown that BAFF is upregulated at the bursal stage of the avian B-cell development. We now show that the avian bursal B cells and B-cell lines, RP-9, RP-13 and DT40, express chicken BAFF (cBAFF). In situ hybridization confirms strong cBAFF expression within the bursal follicles. Like mammals, cBAFF is expressed in the avian myeloblast and myelomonocytic cell lines but not in the peripheral blood alphabeta and gammadelta T cells. The binding of recombinant human BAFF (hBAFF) to the bursal B-cells indicates a conserved receptor-ligand binding. Furthermore, the recombinant hBAFF has a positive effect on bursal cell proliferation and transiently inhibits cell death in vitro. In conclusion, cBAFF is highly conserved structurally, but as a novel observation we suggest cBAFF to function in an autocrine fashion to promote the growth and maturation of follicular B cells in bursa of Fabricius.

The asthma programme of Finland: an evaluation survey in primary health care.

OBJECTIVE: To evaluate the basic structures and processes of asthma care 6 years after the launch of the Finnish Asthma Programme. The evaluation will serve as the baseline for the implementation of the evidence-based guidelines for asthma published in 2000. DESIGN: A descriptive type-2 evaluation (managerial monitoring of a policy implementation), based on operationalised statements of the Asthma Programme. RESULTS: A co-ordinating doctor for asthma, usually a general practitioner (GP), was interviewed in 248 (91%) health centres; 83% of the health centres have at least one GP nominated as the local asthma co-ordinator and 94% have a nurse. Asthma education for the professionals had been organised in 71% of the health centres in the previous 2 years. First-line treatment consists of an inhaled corticosteroid. Guided self-management is used in 98% of the health centres, but its components were not clear to the doctors. CONCLUSION: The basic structure of equipment and organisation for the diagnosis and treatment of asthma has been set up in the primary health care services.

Sleep apnoea: Finnish National guidelines for prevention and treatment 2002-2012.

(1) After negotiations with the Finnish Ministry of Social Affairs and Health, a national programme to promote prevention, treatment and rehabilitation of sleep apnoea for the years 2002-2012 has been prepared by the Finnish Lung Health Association on the basis of extensive collaboration. The programme needs to be revised as necessary, because of the rapid development in medical knowledge, and in appliance therapy in particular. (2) Sleep apnoea deteriorates slowly. Its typical features are snoring, interruptions of breathing during sleep and daytime tiredness. Sleep apnoea affects roughly 3% of middle-aged men and 2% of women. In Finland, there are approx. 150,000 sleep apnea patients, of which 15,000 patients have a severe disease, 50,000 patients are moderate and 85,000 have a mild form of the disease. Children are also affected by sleep apnea. A typical sleep apnea patient is a middle-aged man or a postmenopausal woman. (3) The obstruction of upper airways is essential in the occurrence of sleep apnoea. The obstruction can be caused by structural and/or functional factors. As for structural factors, there are various methods of intervention, such as to secure children's nasal respiration, to remove redundant soft tissue, as well as to correct malocclusions. It is possible to have an effect on the functional factors by treating well diseases predisposing to sleep apnoea, by reducing smoking, the consumption of alcohol and the use of medicines impairing the central nervous system. The most important single risk factor for sleep apnoea is obesity. (4) Untreated sleep apnoea leads to an increase morbidity and mortality through heart circulatory diseases and through accidents by tiredness. Untreated or undertreated sleep apnoea deteriorates a person's quality of life and working capacity. (5) The goals of the Programme for the prevention and treatment of sleep apnoea are as follows: (1) to decrease the incidence of sleep apnoea, (2) to ensure that as many patients as possible with sleep apnoea recover, (3) to maintain capacity for work and functional capacity of patients with sleep apnoea, (4) to reduce the percentage of patients with severe sleep apnoea, (5) to decrease the number of sleep apnoea patients requiring hospitalisation and (6) to improve cost effectiveness of prevention and treatment of sleep apnoea. (6) The following means are suggested for achieving the goals: (1) to promote prevention of obesity, weight loss and weight control; (2) to promote securing of nasal respiration in child patients and removal of obstructing redundant soft tissues; (3) to promote the correction of children's malocclusions, (4) to enhance knowledge about risk factors and treatment of sleep apnoea in key groups, (5) to promote early diagnosis and active treatment, (6) to commence rehabilitation early and individually as a part of treatment and (7) to encourage scientific research. (7) On the national level, the occurrence of sleep apnoea can be prevented, for example, by encouraging weight control. The programme gives examples of such measures and appeals to various authorities and voluntary organisations to reinforce their collaboration. Preventive measures should be individualised, and based on due consideration. (8) The efficacy of diagnosing sleep apnoea should be increased. Attention should be paid to the symptoms of risk group patients at different units of the primary and occupational health care. Even mild forms of the disease should be treated appropriately. Diagnosis and treatment of the disease involve cooperation between the primary and specialised health-care sectors. Methods of treatment are (1) treatment of obesity, (2) positional therapy, (3) reduction of the use of medicines impairing the central nervous system, (4) reduction of smoking and the consumption of alcohol, (5) devices affecting the position of the tongue and lower jaw, (6) treatment with Continuous Positive Airway Pressure (CPAP-treatment), (7) surgical methods of treatment and (8) rehabilitation. (9) The hierarchy of referrals in the prevention and treatment of sleep apnoea should be revised to accord a greater role to the primary health-care sector. Good exchanges of information and cooperation between the primary health care and specialised medical-care sectors should be developed. Hospitals districts in cooperation with provincial governments and municipalities should ensure that different levels of the health-care system are capable of fulfilling the tasks assigned to them appropriately. (10) Rehabilitation of sleep apnoea should be goal-orientated and cover all forms of rehabilitation: medical, occupational and social. Rehabilitation should prevent the effects caused by the disease. Thus, it is possible to support self-care, increase the patient's resources and improve quality of life. (11) Information and training should be directed primarily towards health-care personnel, patients and their families. Organisations should produce materials for health and patient education as well as organising training events. To support the activities. financing will be needed from organisations such as Finland's Slot Machine Association. The Social Insurance Institution should disseminate information about questions of social security. Regional direction and training will mainly be the responsibilities of hospital districts, provincial governments and local health centres. The media will play an important role in the dissemination in-depth information about prevention and treatment of sleep apnoea.

Single-cell analysis of Ets-1 transcription factor expression during lymphocyte activation and apoptosis.

The Ets-1 proto-oncogene is a prototype member of Ets family of transcription factors. It is preferentially expressed in lymphoid cells, where it is essential for the maintenance of the normal pool of resting T and B cells. We have investigated the protein expression of the Ets-1 transcription factor during the activation and apoptosis of T and B cells by flow cytometry and confocal microscopy. Cells of the thymus, spleen and bursa expressed high levels of Ets-1 protein, while resting peripheral blood mononuclear cells had lower Ets-1 expression. Activation and proliferation of T cells induced the upregulation of Ets-1. alphabeta-T cells were found to upregulate Ets-1 expression more than gammadelta-T cells. Increased Ets-1 protein expression was located predominantly in the perinuclear area. In contrast, during apoptosis, Ets-1 expression was downregulated. Collectively, our results indicate that Ets-1 expression can be accurately determined by flow cytometry and confocal microscopy. Ets-1 expression level and distribution are differentially controlled in resting, activated and apoptotic lymphocytes.

Implementation of the DOTS strategy for tuberculosis in the Leningrad Region, Russian Federation (1998-1999).

SETTING: The DOTS pilot project for tuberculosis control in the Leningrad Region of the Russian Federation, supported by the Finnish Lung Health Association and the World Health Organization (WHO). OBJECTIVE: To assess the efficacy of WHO-recommended standard short-course chemotherapy in newly detected pulmonary tuberculosis cases positive by smear or with extensive lung lesions suggestive of culture positivity, under project conditions. METHODS: Analysis of data on case detection, sputum smear conversion and treatment outcome based on standardised (WHO) registers from districts and a central computerised database. RESULTS: Of 859 adult pulmonary tuberculosis cases (292 smear-positive) notified in the Leningrad Region in the study period, 312 new cases were included in the project. The sputum conversion rate at the end of the second month was 82.8% and 91.1% at the end of the third month. Of bacteriologically confirmed cases, 71.3% were successfully treated, 4.9% died, 11.7% defaulted and 8.1% failed. CONCLUSION: In the first year of the pilot project in the Leningrad Region, the DOTS strategy revealed feasibility and moderate efficacy among new pulmonary tuberculosis cases who were either smear-positive or showed extensive lung lesions on chest X-ray, and who were therefore of high epidemiological and medical priority.

Prethymic progenitors from the avian para-aortic mesoderm express GATA-3 and distinct chTcf isoforms but still lack T-cell receptor-gamma rearrangements.

Haematopoietic precursors first colonizing the avian embryonic thymus are derived from the intraembryonic sites located around the dorsal aortae. These intraembryonic precursors have previously been demonstrated to include cells that harbour T-cell progenitor capacity and express the Ikaros transcription factor, known to be a prerequisite for lymphocyte development. In this study, we further evaluated the properties of these prethymic cells. We show that early intraembryonic cells and prethymic progenitors already express the GATA-3 transcription factor. The chicken homologue of T-cell factor-1, chTcf, is also detected in cells isolated from the avian para-aortic region. However, these intraembryonic cells retain their T-cell receptor gamma loci in germline configuration. Interestingly, chTcf was found to express different alternatively spliced isoforms during early ontogeny and thymic T-cell development, which indicates developmentally regulated expression of chTcf variants. Taken together, these results demonstrate that, although the avian prethymic progenitor cells express T-lineage-associated transcription factors, they have not yet undergone TCR rearrangements. It is therefore suggested that activation of lineage-associated genes is an early event in the generation of haematopoietic progenitor cells during ontogeny.

Gender differences in associations between religious attendance and mental health in Finland.

We investigated in a nationwide sample of the Finnish general population (869 women and 773 men) whether there were gender-differences in associations between religious attendance and mental well-being. Respondents were asked during telephone interviews about sociodemographic variables, frequency of religious attendance and social contacts, and perceived social and family support. Mental health was screened by means of the 12-item General Health Questionnaire (GHQ-12). More women than men (62% vs. 50%) attended religious events, and there was a corresponding difference in percentages relating to regular religious attendance (17% vs. 10%). Regular religious attendance was most common among those over 65 years of age. In women, minor mental disorder (GHQ-12 score > or = 3) was more common among those who never attended religious events than among the others (25% vs. 16%). In men there was no difference. In women, religious attendance associated positively with social contacts, in men with happy family life. In multivariate analyses an independent positive association between religious attendance and absence of minor mental disorder was found in women (adjusted OR 1.58, 95% CI 1.12 to 2.24) but not in men. These results suggest that there may be gender-differences in associations between religious attendance, social and family life, and mental health.

Serum oncostatin M in multiple myeloma: impact on disease severity and prognosis.

Since high levels of serum IL-6 predict a poor prognosis of patients with multiple myeloma (MM), we investigated if a related cytokine, oncostatin M (OSM), correlates with clinical or biochemical findings or has prognostic significance in patients with MM. Among 82 newly diagnosed MM patients, OSM was detected in the sera in 45 (55%). Serum OSM had a borderline statistical correlation with serum IL-6 (r = 0.198, p = 0.074) and C-reactive protein (r = 0.199, p = 0.074) concentrations. However, OSM did not have prognostic significance alone or in combination with other factors. The median survival of patients with detectable serum OSM concentration was 41 months (range 2-124 months) and of OSM negative patients 35 months (1-75 months). Serum OSM concentration was not associated with clinical factors or severity of bone disease at diagnosis. We conclude that serum OSM concentration is not a prognostic factor in MM patients.

Men, women and friends--are there differences in relation to mental well-being?

This is a study on associations between the number of close friends and mental well-being in a nationwide sample of the Finnish general population (n = 1,603). Mental well-being was assessed by means of the 12-item General Health Questionnaire. A total of 3% of the sample had no close friends and another 3% had only one. Over half of the sample (52%) reported having five or more friends. The overall prevalence of mental distress was 15% in men and 21% in women. According to multivariate analyses the risk of mental distress was increased in men among those with no friends (odds ratio [OR]: 2.70) and among those who had one (OR: 4.32) or two to four friends (OR: 1.75), as compared with those who had more friends. In women, having only one friend (OR: 2.30), insufficient family support (OR: 1.63) and insufficient support from relatives (OR: 1.77) associated with the risk of mental distress. These results suggest that mental well-being might be promoted if mentally distressed men seeking professional help were supported in building up and maintaining social networks and mentally distressed women were supported in harmonizing their family life.

Chronic bronchitis and chronic obstructive pulmonary disease: Finnish National Guidelines for Prevention and Treatment 1998-2007.

1. A national recommendation for the promotion of prevention, treatment and rehabilitation in relation to chronic bronchitis and COPD from 1998 to 2007 has been prepared on the basis of extensive collaboration by order of the Ministry of Social Affairs and Health. The Programme needs to be revised as necessary, because of rapid developments in medical knowledge, and in drug therapy in particular. 2. COPD is a disease characterized by slowly progressing, irreversible airways obstruction. Over 5% of the population suffer from symptomatic forms of the disease. It is estimated that a further 5% of the population may suffer from latent COPD. Most patients (75%) suffer from mild forms of the disease. The disease is often preceded by chronic bronchitis. A total of 400,000 Finns suffer from chronic bronchitis or COPD. Occurrence of these diseases in future will be particularly affected by decreased smoking by men, increased smoking by the young and by women, and aging of the population. 3. In 1997, the annual treatment costs of chronic bronchitis and COPD were estimated to be FIM 1.5 thousand million, total costs FIM 5 thousand million. Without intensification of measures to prevent and treat the diseases, costs will rise significantly. Costs arising from severe COPD (5% of patients with COPD) account for roughly 65% of costs overall and are primarily related to hospitalizations. 4. The goals of the Programme for the Prevention and Treatment of Chronic Bronchitis and COPD are as follows: (a) to decrease the incidence of chronic bronchitis; (b) to ensure that as many patients as possible with chronic bronchitis recover; (c) to maintain capacity for work and functional capacity of patients with COPD; (d) to reduce the percentage of patients with moderate to severe COPD; (e) to decrease the number of hospitalization days of COPD patients by 25% overall; and (f) to decrease annual costs per patient. 5. The following means are suggested for achieving the goals: (a) reduction in smoking; (b) reduction in work-related and outdoor air pollutants and improvement of quality of indoor air; (c) enhancement of knowledge about risk factors and treatment of the diseases is in key groups; (d) promotion of early diagnosis and active treatment, in smokers in particular; (e) improvement of guided self-care; (f) early commencement of rehabilitation, individual planning and implementation, primarily as an element in treatment; and (g) encouragement of scientific research. 6. COPD and exacerbation of its symptoms can be prevented through choices relating to life habits, such as not smoking, maintaining good general condition, and protection against exposure to dusts. The Programme gives examples of such measures and appeals to various authorities and voluntary organizations to increase their cooperation. Preventive methods should be individualized, and based on due consideration. 7. Chronic bronchitis and COPD should be diagnosed at early stages, and treated appropriately from the outset. Treatment consists of: (a) treatment according to causes, such as stopping smoking and work hygiene; (b) early rehabilitation such as patient education and guided self-care: (c) drug therapy; (d) hospital treatment; and (e) rehabilitation. 8. The hierarchy of referrals in the treatment of COPD should be revised to accord a greater role to the primary health care sector. Good exchanges of information and cooperation between the primary health care and specialized medical care sectors will all be necessary if this hierarchial model is to have the desired effect. 9. Hospital districts and health centres should ensure that different levels of the health-care system are capable of fulfilling the tasks assigned to them appropriately. One specialist in each hospital district should be given charge of prevention and assembly of know-how relating to treatment, and of quality of treatment at regional level. (ABSTRACT TRUNCATED)

Use of alternative drugs in Finland.

OBJECTIVES: The purpose of this study was to assess the use of alternative drugs among the adult population in Finland, especially to find out how the health status, health behaviour and use of licensed drugs and health care services are related to the use of alternative drugs. DESIGN: A telephone interview was conducted in March 1992 with a response rate of 85%. SUBJECTS: A random, representative sample of 2134 Finns aged between 15 and 74 years. RESULTS: A total of 39% of the respondents had used one or more types of alternative drugs during the last year. Most common was the use of health food products. Women used all types of alternative drugs more often than men. The use of alternative drugs was more common among educated and urban respondents. Perceived health or existence of a long-standing illness was not related to alternative drugs use whereas reporting of psychosomatic symptoms was. Non-smoking was positively related to the use of alternative drugs and also active exercise among men. The use of non-prescription drugs, official and unofficial health services were positively related to alternative drugs use. CONCLUSIONS: The use of alternative drugs is popular and it may increase in the future. The use of alternative drugs can be considered a form of medicalization. More information on products used and people using alternative drugs is needed.