| 11. |
- Højgaard, Inge
(author)
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Crystallisation of calcium phosphate and calcium oxalate in solutions simulating the composition at different levels of the nephron
- 1998
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Doctoral thesis (other academic/artistic)abstract
- Calcium oxalate (CaOx) is the most common constituent of urinary calcium stones, but in many such stones calcium phosphate (CaP) is also present and often located in the centre. From these observations it has been assumed that CaP is important in the process that leads to the development of a calcium stone and furthermore that the initial steps in this crystallisation take place in the nephron. The present investigation was undertaken to assess the risk of crystallisation of calcium salts at different nephron levels.Calculation of the ion-activity products of CaOx and different CaP salts Wlder solution conditions corresponding to those at various nephron levels, disclosed that the saturation with CaP was relatively higher than that of CaOx in the proximal tubule (PT), as well as in the proximal (DTp) and distal parts (DTd) of the distal tubule. Supersaturation concentrations necessary for the formation of CaOx crystals were recorded only in solutions with a composition corresponding to that in the collecting duct (CD).With an increased calcium concentration CaP was the crystal phase that most easily formed under solution conditions that corresponded to those at nephron levels above the CD. The relative risk of crystallisation of CaP was greatest in DTd~Urine. In CD-solutions CaOx was the preferred crystal type. Precipitation of CaOx in the lower part of CD and in final urine might be the result either of a primary nucleation of CaOx in the presence of a sufficiently high CaOx supersaturation or of a heterogeneous nucleation induced by CaP crystals formed at higher nephron levels.The nucleation of CaP and CaOx accomplished by reduction of volume of DTd- and CD- urine was apparently promoted by the urinary macromolecules in dialysed urine (dU). These macromolecules also inhibited the aggregation of CaP in solutions with a composition similar to that of urine in the distal tubule (DTd) and might counteract stone formation by inhibiting the growth and aggregation of both CaOx and CaP crystals during their passage through the CD. Furthermore, citrate had a direct inhibitory effect on the aggregation of CaP in DTd-solutions, an inhibitory effect that was additive to that of dU at concentrations of citrate above 0.5 mmol/L.The result~ obtained in these experimental studies support the hypothesis that CaP is the primary nucleus in mixed calcium stones. The process starts with the formation of CaP at a nephron level above the CD, possibly in DTd. A heterogeneous nucleation of CaOx is subsequently induced by dissolution of retained CaP crystals in the acid urine in the CD. The heterogeneous nucleation is probably accomplished by an increased local CaOx supersaturation that occurs at the CaP crystal surface as a result of this dissolution.
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| 12. |
- Johansson, Inger
(author)
-
Quality of care and assessment of health among elderly in actue care.
- 1998
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Doctoral thesis (other academic/artistic)abstract
- This thesis describes nursing staff's opinion of quality of care and work satisfaction and elderly patients' perception of health, functional capacity, quality of life and sense of coherence (SOC) from a prognostic point of view. The research was performed within several surgical and orthopaedic wards, and different instruments were developed and tested for reliability and validity. The study groups consisted of nursing staff (n=66), surgical patients clinically ready for discharge (n=53) and a consecutive sample of patients with hip fracture (n=73). All patients were 60+ years of age and livin in their own homes before their stay in hospital.The nursing staff answered questionnaires concerning work satisfaction and perceived quality of care before and one year after the introduction of modular nursing. Among the respondents considerable differences were noted in one ward one year after the intervention, particularly concerning their relationship with colleagues, identification and connnitment, and quality of care. Key factors for this outcome could be related to the quality of the interpersonal relationships and the leadership of the ward.Significant differences between subgroups were revealed when using a Swedish version of the Health Assessment Form (HAF) and a tool measuring Sense of Coherence (SOC) in personal interviews among elderly patients clinically ready for discharge. The patients who could return home showed less discomfort concerning physical variables such as breathing and elimination of urine and scored higher within emotional status and SOC than those who were referred to an institution or were deceased before the one month follow-up. The result indicated that the HAF as well as SOC had some prognostic value for further care as well as for survival/fatal outcome for patients clinically ready for discharge.The Swedish version of the NEECHAM Confusion Scale was found to be reliable and valid for detecting and following up acute confusional states among patients with hip fracture. The part of the scale measuring vital function was found to have predictive power in relation to the Quality of Life Index (QLI) at the four-month follow-up. The parts reflecting cognitive function and urinary continence predicted significantly for function of daily living activities (I-ADL), measured with the Standardized Practical Equipment (SPE). Patients with a stronger SOC, compared with those with a weaker, were discharged earlier from the hospital, reported a higher score on the QLI and performed I-ADL better four months after discharge from the hospital.The findings highlight the importance of having a broad range of valid and reliable instruments when following up organisational changes among nursing staff as well as for assessing the health and functional needs of elderly patients in acute care in order to predict future developments.
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| 13. |
- Julge, Kaja
(author)
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Humoral immune responses to allergens in early childhood
- 1998
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Doctoral thesis (other academic/artistic)abstract
- Sensitivity to eight standardized allergen extracts (Solu-Prick SQ, ALK, Hørsholm, Denmark) was assessed in 1580 schoolchildren. The prevalence of atopic sensitization among these 10-12-year-old children was 3--4 times lower in Estonia (8.1-14.3%) than in Sweden (24.2-35.3%). Sensitization among schoolchildren was associated with atopic heredity, gender of the child (boys were more often sensitized) and passive smoking during infancy and inversely related with crowded living.In a prospective study 298 infants were followed from birth to 2 years of age. Clinical examination and skin-prick tests (SPT) were carried out, and venous blood samples were collected at 6, 12 and 24 months. SPT were done with natural food allergens (cow's milk (CM), egg white (EW)), and standardized inhalant allergens (cat, dog, house-dust mite (D. pteronyssinus), birch, timothy, mugwort). Serum IgE and circulating IgE antibodies against allergens were determined by a chemiluminescence method. IgG and IgG4 antibodies to ovalbumin, ~-lactoglobulin, cat allergen and birch (rBet v l) were analyzed with ELISA. Atopic sensitization according to SPT results (7%) among the Estonian children during the first two years of life was not significantly less common than among the Swedish children of the same age. The prevalence of SPT positivity to CM at 6 months of age (2%) was also similar in the Estonian and the Swedish children during the first two years of life, while positive SPT to EW (5%) was three times less common among the Estonian children.The prevalence of circulating IgE antibodies to food allergens increased over the first two years of life in the Estonian children. Sensitization to indoor allergens (18%) seemed to be more prevalent among the Estonian, as compared to the Swedish children, however sensitization to cat allergen ( 12%) was equally common during the first two years of life but not so in schoolchildren. IgG subclass antibodies to food and inhalant allergens generally developed with similar kinetics as in the Swedish children. In contrast to the Swedish children, however, the levels of IgG4 antibodies to the inhalant allergens were higher during the first two years of life. The antibody levels to ß-lactoglobulin in the Estonian children did not peak in infancy and they did not have higher levels of antibodies to ß-lactoglobulin than non-atopic children.When the infants were about 6 weeks old, visits were performed to 197 homes. Questionnaires about living conditions were completed and three dust samples were collected from each home. The levels of Der p I, Der f I, Fe/ d I and Can f I in the dust samples were determined by ELISA, using monoclonal antibodies (ALK, Hørsholm, Denmark) .The levels of dog, cat and house-dust mite allergens were comparable in the homes of Estonia and Sweden and thus the differences in allergy prevalence in Estonia and Sweden cannot be explained by different levels of exposure to indoor allergens.Microbiological investigations of faeces samples of 27 Estonian and 29 Swedish one-year-old infants indicated major differences in the composition of the colonic microflora with high counts of lactobacilli and eubacteria in the Estonian and increased number of clostridia in the Swedish infants. Differences in the indigenous intestinal flora might affect the development and priming of the immune system in early childhood.Whether the increase of IgE antibodies was related to new environmental factors or temporary production of IgE will be revealed by a follow-up of the children. The different kinetics of IgG subclass responses to food and inhalant allergens could support the hypothesis that Th2-like responses during infancy are more transient in the Estonian as compared to the Swedish children. Future follow-up of the children will reveal if this is the case.
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| 14. |
- Kjellgren, Karin I.
(author)
-
Antihypertensive medication in clinical practice : Aspects of patient adherence in treatment
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- Adherence to antihypertensive drug regimens is a well-documented determinant of blood pressure control. A review of the literature shows that little attention has been paid to how antihypertensive medication is managed in clinical practice.The aim of the empirical studies was to document and analyse the prerequisites of patient adherence to antihypertensive medication in routine clinical practice. The studies are based on two complementary sets of data, generated through intensive and extensive studies. In the intensive studies, audio-recordings (n=51) of follow-up appointments with hypertensive patients and their physicians were made in order to explore the nature of interaction ih routine clinical practice. Afterwards, patients (n=33) were interviewed to assess their knowledge of high blood pressure and antihypertensive medication. The extensive studies were population-based and carried out at Swedish primary health care centres (n=55) and clinics of internal medicine (n=ll). The intention of these studies was to assess perceived symptoms among hypertensive patients with (n=l 013) and without (n=l35) antihypertensive medication. Furthermore, concordance between the patients' and physicians' (n=212) views regarding risks of hypertension and benefits from antihypertensive medication was analysed.Most patients had a passive role and initiated few topics during the consultations. Little time was invested in discussing risks related to hypertension. The interviewed hypertensive patients had an unsatisfactory understanding of their condition and of the effects of the medication. The prevalence of perceived symptoms did not differ between patients with and without antihypertensive medication. Patients estimated the effects of medication to be more beneficial than did their physicians. Trade-offs between perceived benefits and side-effects of drug treatment showed that patients were generally unwilling to endure side-effects in return for long-term benefits of treatment. In routine clinical praxis, 14% of the antihypertensive medicated patients had reached a blood pressure o:;l40/90 mm Hg. Target values above 140/90 mm Hg were given for 63% of the patients by their physicians. Among patients who where aware of their target blood pressure, we found close agreement between the values given by patients and physicians. This implies that when the target blood pressure is communicated in clinical practice, the patients remember quite accurately.Better control of hypertension and coexisting risk factors is an essential objective in clinical practice. From the studies, two factors stood out as. important to improve adherence: more knowledge-sharing with the aim of increasing self-care competence and more effort to reduce side-effects of treatment.
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| 15. |
- Kristenson, Margareta, 1950-
(author)
-
The LiVcordia Study : Possible causes for the differences in coronary heart disease mortality between Lithuania and Sweden
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- Background: In recent decades coronary heart disease (CHD) mortality has declined in Western Europe and increased in Central and Eastern Europe. A large difference in CHD mortality has developed and the causes are not known. Lithuania and Sweden had similar CHD mortality rates for middle-aged men twenty years ago but in 1994 this mortality was four times higher in Lithuania than in Sweden. Also within countries CHD mortality is higher in low socioeconomic groups.Aim of the study: The LiVicordia (Linköping-Vilnius-coronary-artery-disease-risk-assessment) study aimed at identifying possible explanations for the different CHD mortality rates in the two countries.Method: This cross-sectional study concomitantly compared 150 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden from October 1993 nntil March 1995 using identical, standardised methodology. Investigations included a broad range of traditional and psychosocial risk factors for CHD, measures of oxidative stress, a standardised laboratory stress test and ultrasound measures of Peripheral atherosclerosis.Results: The differences found in traditional risk factors for CHD were small. Systolic blood pressure (SBP) was higher in Vilnius men, smoking was similar and plasma LDL cholesterol levels higher in Linköping men. Lower serum levels of the lipid soluble antioxidant vitamins carotene, lycopene and ytocopherol were found in Vilnius men, and also a higher susceptibility of LDL to oxidation in vitro. An unfavourable pattern of psychosocial risk factors for CHD: job strain, social isolation, depression and vital exhaustion characterised Vilnins men, who also showed an attenuated cortisol response to the laboratory stress test. This stress response has earlier been shown in states of chronic stress; loss of dynamic capacity to respond to new demands may be a predisposing factor for disease. Vilnius men had more peripheral atherosclerosis; thicker intima media, more and larger plaques and greater stiffness. Measures of atherosclerosis related to SBP, smoking, LDL cholesterol arrl P-carotene. The same unfavourable profile of risk factors for CHD, which characterised Vilnius men, was also found in underprivileged groups withip the cities. There were few differences in traditional risk factors.Conclusions: Thus, based on our survey on risk factors for CHD, it can be stated that traditional risk factors seem not to explain the different CHD mortality rates between Lithuania and Sweden. Possible alternative explanations are psychosocial strain and oxidative stress. These factors were also found among men in underprivileged groups within the cities. Therfore the influence of the risk factors studied may be relevant also for socioeconomic inequalities in CHD mortality within countries.
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| 16. |
- Lilja, Magnus
(author)
-
Prosthetic fitting : stump-socket interaction in transtibial amputees
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- This thesis is comprised of five different studies, all concerning the interaction between the transtibial amputation stump and the prosthetic socket. The aim was to analyse some of the factors influencing this interaction.CAD CAM (Computer Aided Design Computer Aided Manufacturing) and roentgen were used as measuring instruments. Errors of measurements of one CAD CAM system were evaluated. Volume deterrninations were performed on regular cylinder objects, and on amputation stump models with an irregular shape. For the cylindrical objects there was no statistically significant systematic error, but the volumes of the stump models were significantly overestimated with 2.5%. The random errors were small, with 95% of the random variation within ±1%. A clinical evaluation of a commercial CAD CAM system was performed, primarily from the patient's point of view. The only variable showing a significant difference between CAD CAM made and conventionally made prostheses was the number of terry cloth stockings necessary to compensate for volume differences between the stump and the socket. After operation, amputation stumps may change their volume considerably. For this reason patients should not be provided with expensive definitive prootheses until the post-amputation volume of the stump has stabilized. The volumes of amputation stumps were evaluated with CAD CAM for 160 days after operation in eleven transtibial amputees. The volume changes could be described by a negative power function, (γ = a · x2). From these results, proper time for a definitive prosthesis could be determined - three to four months after amputation. In order to obtain a prosthetic socket with correct volume and shape, an accurate and precise hand cast must be taken. One important question is whether the muscles of the amputation stump should be relaxed or contracted during the casting session. In this thesis is reported a volume difference between a relaxed and contracted amputation stump of approximately 5.8%, and 3.5% when the stump was donned with a silicon liner. During gait the tibia moves inside the amputation stump, and these movements may reflect the success of prosthetic fitting. Tibial displacements in the sagittal plane in a PTB (Patella Tendon Bearing) prosthesis were evaluated with radiographic technique. The average total tibial movement was 7.5 cm, the average movements in the anterio-posterior direction was 2.2 cm, and in the proximo-distal direction 2.8 cm.From the studies of this thesis can be concluded, that there are tibial movements inside a prosthetic socket, large enough to influence the prosthetic fitting; that the examined CAD CAM system had sufficient accuracy and precision for routine clinical practice in prosthetics; that CAD CAM technique had no major advantage compared with traditional technique from the patient's point of view; that the hand cast should be taken on a relaxed amputation stump; and that proper time for definitive prosthetic fitting after transtibial amputation was approximately three to four months after operation.
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| 17. |
- Lindström, Eva G., 1961-
(author)
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Regulation of experimentally induced airway obstruction
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- Asthma is one of the commonest diseases in industrialized countries. The cause and mechanisms of !he disorder are still not fully unden;tood, al!hough it is known that inflammation in !he airways plays an important role. Inflammatory mediators, e.g. leukotrienes, prostaglandins, histamine and bradykinin, are all possible acton; in !he asthmatic condition. Moreover, disturbance in !he neurogenic system has been discussed: the cholinergic, adrenergic, and nonadrenergic noncholinergic systems may influence the airway tone. Structural changes in !he airways of as!hmatics, e.g. epithelial damage, have also been observed. The consequence of epithelial damage is not fully understood, but it is clear that the epithelial layer can act as a physical and metabolic barrier.In the present research, we developed an in vitro model for detenninadon of airway smooth muscle tension and concomitant mediator release in guinea pig airways. This method also allows manipulation of the airway epithelium. We found !he condition of !he airway epithelium to be of great significance for smooth muscle response and mediator release. An intact epithelium acted as a powerful barrier; removal of the epithelium resulted in increased responses to histamine, acetylcholine and potassium ions. An intact epithelial layer was also important for leukotriene and prostaglandin production, whereas in !he absence of epithelium, antigen-induced contractions were almost completely dependent on histamine.Sensory nerve activation provoked by electrical field stimulation (EFS), capsaicin (CAP) and antigen-induced mediators was investigated by analyzing !he amount of neurokinin A-like immunoreactivity (NKA-Ll). Multiple agents were shown to regulate this release. EFSinduced outflow of NKA-LI was powerfully decreased by morphine, and !his reduction was not reversed by naloxone. In contrast, the inhibition obtained upon CAP-challenge was reven;ible. These results may imply !hat EFS also activates endugenous inhibitory systems.Antigen challenge of epithelial-denuded bronchial tube preparations resulted in contractions and concomitant release of histamine and tachykinins. Exposure to pyrilamine (a histamine H 1 receptor antagonist) and icatibant (a bradykinin B2 receptor antagonist) markedly depressed !he NKA-LI outflow. Furthermore, pyrilamine significantly reduced !he basal outflow of NKA-LI and antigen-induced contractions, while icatibant did not. These results show that, among !he mediators released in response to antigen-challenge, histamine and bradykinin are able to modulate both the outflow of tachykinins and contractile responses.The long-acting 132 receptor agonist formoterol was characterized with regard to relaxing properties and effects on tachykinin and histamine release. The RR enantiomer was most potent in relaxing tracheal preparations, followed by racemic and SS-formoterol. Formoterol also reduced the antigen-induced outflow of NKA-LI. RR-formoterol also lowered both CAPand EFS-induced NKA-LI outflow but not histamine release. These results indicate that, in addition to its ability to directly relax smooth muscle, formoterol may decrease the responses of airway tissue to antigen by inhibiting mediator release from sensory neurons, probably through direct interaction with sensory neurones.In summary, we have developed a method for determination of epithelial inlluence, mediator release and smooth muscle contraction in guinea pig airways. We have shown that antigen-challenge release inflammatory mediators and activates sensory neurons. Both histamine and bradykinin are involved in the regulation of the tackykinin release. It was also shown that formoterol reduoed NKA-LI outflow.
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| 18. |
- Magnusson, Per, 1962-
(author)
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Human Bone Alkaline Phosphatase Isoforms
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- Determination of serum total alkaline phosphatase (ALP) is frequently requested in clinical routine, mostly to estimate skeletal and hepatobiliary status. In this respect, clarification of the various ALP isoenzymes and isoforms contributing to the total ALP activity could be valuable in daily medical decision making. The general aim of this thesis was to investigate methodological, metabolic, and clinical aspects of bone ALP (BALP) isoforms in human bone and mineral metabolism. BALP is a glycoprotein and functions as an ectoenzyme attached to the osteoblast cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. The precise function of BALP is not known, however, there is evidence that BALP is necessary for initiating bone mineralization.A weak anion-exchange high-performance liquid chromatography (HPLC) assay was developed for the determination of BALP and liver ALP (LALP) isoforms. Six peaks with ALP activity were separated and quantified in serum from healthy individuals: B/I, a minor fraction composed of bone (70%) and intestinal (30%) ALP, and two major BALP isoforms B 1 and B2, and three LALP isoforms. Reference intervals were reported for healthy children, adolescents, and adults (range 7-65 years). In healthy adults the BALP isoforms, B/I, Bl, and B2, contributed to 4, 16, and 37%, respectively, of the total ALP activity. Bone samples were prepared from human femora in order to characterize and investigate the origin of these BALP isoforms found in serum. Cortical bone had about 2-fold higher activities of Bl compared with B2, and trabecular bone had about 2-fold higher activities of B2 compared with Bl. Treatment with GPI -specific phospholipase C did not influence the activities or retention times of Bland B2. Thus, the biochemical differences between Bland B2 are likely to be due to different glycosylation patterns, rather than the presence of GPI cell membrane anchor fragments.Decreased B I activity was observed after I week of IGF-I administration, and after I month of GH therapy, followed by an increase after 3 months. B2 was not influenced by IGF-I administration, but was similarly increased after 3 months of GH therapy. It was proposed that the initial decrease of B 1 could be an effect of endocrine IGF-I action mediated by GH. Different responses of B 1 and B2 during IGF-I and during GH therapy suggest different regulations of these BALP isoforms in vivo. Differences of BALP isoforms in metastatic bone disease were found, as well as discrepant effects of clodronate on different skeletal sites indicated by the location of bone pain. Patients with skeletal metastases and healthy males had B2 activities corresponding to 75% and 35% of the total ALP activity, respectively.Taken together, the BALP isoforms B I and B2 can be used as early indicators of pharmacological efficacy and, possibly provide information relating to specific bone compartments. Future investigations have to elucidate if they also reflect different stages in osteoblast differentiation during osteogenesis where one isoform is presented before the other during extracellular matrix maturation.
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| 19. |
- Mårtensson, Lena G. E.
(author)
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New pharmacological aspects of melatonin
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- Melatonin is a hormone that takes part in the regulation of biological rhythms. It is produced in the pineal gland and is stimulated by darkness and inhibited by exposure to light. The increased amouot of melatonin during the hours of darkness sends a chronobiological message throughout the body, and translates it into a chemical message that can be read by target cells. This process requires that a receiving protein, a receptor, is present on the cell surface, and that it can recognize melatonin and transfer the signal from outside of the cell to the inside, where it can be transformed into a cellular response. The present investigation was focused on receptor recognition, receptor activation and receptor-mediated signaling.The scales of the cuckoo wrasse (Labrus ossifagus L.), a teleost fish, bear melanophores that contain pigment granules that can be transported to the center of the cell (pigment aggregation) or distributed throughout the melanophore (pigment dispersion). Pigment aggregation is governed by sympathetic nerve endings that stimulate an α2-adrenoceptor, and also by circulating hormones, for example melatonin. To answer questions regarding receptor interactions, melatonin was used in the melanophore bioassay.The results show that melatonin did not induce pigment aggregation when administrated alone. The hormone did, however, reinforce aggregation induced by noradrenaline, which reveals a melatonin-noradrenaline synergism. Pharmacological studies were performed to elucidate this synergism. Data obtained using α2-adrenoceptor and melatonin receptor ligands, and by investigating intracellular mediators, indicate that, hypothetically, the noradrenaline-melatonin synergism may be due to the existence of an α2-adrenergic receptor with two functional sites: one site for catecholamines, such as noradrenaline, and a second "modulatory" site for melatonin.It is known that smooth muscle cells from pregnant human myometrium express adrenoceptors and that labor tends to begin during the dark hours. The effect of melatonin on myometrial contractility was examined in order to investigate if the same synergism appeares in the myometrium as in the melanophores. The contractility of biopsied myometrial samples taken from women undergoing cesarean sections was measured in vitro. The results show that melatonin alone did not increased myometrial contractility, but it did reinforce noradrenaline-induced contraction, i.e. a melatonin-noradrenaline synergism. Consequently, it is possible that the greater production of melatonin at night induces increased myometrial contractility that leads to the beginning of labor.
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| 20. |
- Nilsson, Lennart, 1954-
(author)
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Risk factors for atopic disease in childhood
- 1998
-
Doctoral thesis (other academic/artistic)abstract
- Background: It is important to assess risk factors for the development of allergic diseases, primarily because these diseases are so common and affect one third of all children in the western world, sometimes with serious manifestations, and also because these diseases have continued to increase over the last few decades.Aims: To study the difference between the cumulative incidence of allergic diseases in 7-ycarold children in 1974 and 1994. To ascertain whether a/ urban as opposed to rural living, b/ maternal allergy, cl season of birth, and particularly, dl pertussis vaccination influence the development of allergic diseases.Material & methods: Two cross-sectional and two prospective studies were evaluated in regard to allergic diseases and their relation to various risk factors. Diagnoses of allergic diseases were obtained from questionnaires and intensive prospective clinical evaluations. Skin prick tests and analyses of IgE to common allergens and pertussis toxin were performed.Results: Allergic diseases increased from 15.1% to 26.1% with a relative risk of 1.7 (95% C.!. 1.4-2.1). The increase was attributed to the children having a heredity of allergic disease. Today, it is more common to have a family member with an allergic disease than not to have allergy in the immediate family. Bronchial asthma and allergic rhinoconjunctivitis in 7-year-old girls increased more than fourfold between 1974 and 1994 but the increase in 7-year-old boys was only 50%.Urban as opposed to rural living during the first two years of life was a moderate risk factor for allergic disease up to 13-14 years of age. The risk was particularly high for bronchial asthma with a relative risk of 2.1 (95% C.!. 1.2-3.7) associated with urban living during the first year of life and 2.1 (1.2-3.6) with urban living the second year. The increase in risk remained after adjustment for family history of allergy, gender, environmental tobacco smoking, smoking during pregnancy, pets indoors, damp indoors and living area. Smoking during pregnancy was an independent risk factor for asthma in the child. The two crosssectional studies both showed significant increase (I 0%) in children if the mother had an allergic disease. Allergic diseases were associated with birth during the winter and negatively associated with birth during spring time. The acellular pertussis vaccines did not influence the development of allergy significantly more than the whole cell pertussis vaccines, or placebo (with diphtheria and tetanus only).Discussion/Conclusions: The increased risk of allergic disease over the last few decades cannot be explained by genetic factors. The most plausible explanation is that there is some factor or factors that influence children with a genetic pre-disposition to allergy. Differences in microbial exposure and infections are conceivable reasons for the increase and may contribute to the difference seen between urban and rural areas. Other possible causes may be exposure to different adjuvants, e.g. nitrogen dioxide and diesel exhausts.The increase in family size in families with an allergic mother, would be a survival advantage of being atopic. This could explain a long-term accumulation but not the dramatic increase during the second half of the 20th century.The seasonal effect is moderate. One plausible explanation of the effect in relation to pollen allergy may be that the levels of maternal IgG to inhalants are dependent on the pollen season. However, the seasonal effects of IgE to egg in infancy may be attributable to the indoor environment.In spite of the fact that acellular vaccines induced more IgE to pertussis toxin and that the Th2-type cytokines increased more than Thl-type cytokines after acellular pertussis vaccines, these vaccines did not significantly increase the risk of allergic disease in the children. Acellular vaccines are therefore recommended owing to their documented safety as well as effectiveness. All in all, several risk factors for allergic diseases have been found but none of them is strong enough to explain the increase over the last few decades.
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