Biomedical subjects
M Wickman
Publications and source records attributed to M Wickman.
Influence of early and current environmental exposure factors on sensitization and outcome of asthma in pre-school children.
BACKGROUND: Exposure to furred pets in early life has been considered to increase the risk of allergic sensitization and consequent development of asthma later in children. However, recently, it has been suggested that early exposure to pets prevents sensitization. The aim of this study was to evaluate the importance of early exposure to pets and other environmental risk factors in asthmatic children. METHODS: This is a follow-up study after 2 years of a previously investigated group of 193 asthmatic children, aged 1-4 years. The study was completed by 181 children, who were clinically examined; serum IgE antibodies were also measured and a questionnaire was answered. RESULTS: Children with reported exposure to cats during the first 2 years of life were more likely to have developed sensitization to cat by 4 years of age than unexposed children. High levels of cat allergen (Fel d 1> or =8 microg/g dust) were associated with an increased risk of sensitization to cat and, in combination with tobacco smoke, also with the development of more severe asthma. CONCLUSION: In young asthmatic children, early exposure to cat and tobacco smoke increased the risk of allergic sensitization and further development of more severe asthma later in childhood.
Dispersion of horse allergen in the ambient air, detected with sandwich ELISA.
BACKGROUND: The objective was to establish an ELISA to detect horse allergen in ambient air and settled dust. METHODS: Monoclonal antibodies (mAbs) were produced against extracts of horse antigen. Two mAbs were selected and used in a sandwich ELISA. By the aid of portable pumps, air samples were collected in one stable and in the ambient air surrounding this stable. Furthermore, settled dust was collected by wiping spots with pieces of fabric, at sites within 500 m of the stable. RESULTS: Extracts of horsehair could be extensively diluted and still be positive. Extracts of cat and dog allergen failed to be detected. Furthermore, the mAbs were shown to detect an IgE-binding component. This was demonstrated by an ELISA using mAbs as capture antibody and sera from horse-allergic subjects as secondary antibody with readout depending on anti-IgE antibody. The sera with the highest RAST class to horse were positive in this ELISA. Airborne levels of horse allergen were over 500-fold higher in the stable than just outside the stable and over 3000-fold higher than at a residential building located only 12 m from the stable. Similarly, an inverse correlation was found between the distance to the stable and levels of "outdoor settled" horse allergen (r=-0.9, P<0.001). CONCLUSION: We have developed a sensitive, horse-allergen-specific, mAb assay allowing detection of low levels of horse allergens. Raised levels of horse allergen were found outdoors only in the close vicinity of the stable.
Worsening of asthma in children allergic to cats, after indirect exposure to cat at school.
Exposure to cat allergen at school might exacerbate symptoms in asthmatic children with cat allergy. To study this, we identified 410 children, 6-12 yr of age, who were being treated for asthma (inhaled steroids and beta-agonists), were allergic to cats, and had no cat at home. Peak expiratory flow (PEF), asthma symptoms, medication, fever and/or sore throat, and contact with furred pets were recorded twice daily during the last week of summer holidays and the second and third weeks of school. The number of cat owners in each class was recorded. Ninety-two children with asthma reported no contact with furred pets. Among these, children who attended classes with > 18% (median value) cat owners reported significantly decreased PEF, more days with asthma symptoms, and increased use of medication after school started. Those in classes with < or = 18% cat owners reported no change. Children in classes with many cat owners ran a 9-fold increased risk of exacerbated asthma after school start compared with children in classes with few cat owners, after adjusting for age, sex, and fever and/or sore throat. Thus, asthma symptoms, PEF, and the use of asthma medication in children with cat allergy may be affected by indirect cat exposure at school.
Fewer allergic respiratory disorders among farmers' children in a closed birth cohort from Sweden.
The aim of this study was to investigate the prevalence of respiratory allergy, eczema and atopic sensitization in a closed birth cohort of Swedish schoolchildren, 7-8 yrs of age (n=707), of farmers and nonfarmers on the island of Gotland, in the Baltic Sea. All children were born and raised on the island. The survey comprised a questionnaire on atopic diseases and lifestyle factors. Atopic sensitization was assessed by the skin-prick test (SPT) with 15 standardized allergens. The risk ratio (RR) for ever having asthma and/or allergic rhinoconjunctivitis was significantly lower among children of farmers compared to children of nonfarmers (RR=0.38, confidence interval (CI) 95% 0.19-0.77). SPTs (test rate 92%) showed that 32% of the children had at least one positive test. Although the number of positive SPTs did not differ between the groups, there was a reduced risk among children of farmers for having both respiratory symptoms and sensitization to any International Study on Asthma and Allergy in Childhood allergen (RR=0.28, CI 95% 0.09-0.88). The present indicate that living in a farming population seems to protect against development of respiratory allergic disorders but not against allergic sensitization.
The immunology of fetuses and infants.
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Window pane condensation and high indoor vapour contribution - markers of an unhealthy indoor climate?
OBJECTIVE: The aim of this study was to investigate whether window pane condensation and indoor vapour contribution >/= 3 g/m3 could be used as indicators of defective air change rate, high indoor humidity and high mite allergen concentration in mattress dust. METHODS: Actual ventilation rate, indoor temperature, air humidity (AIH/RH) and concentrations of mite allergen were measured in 59 houses and compared with received outdoor temperatures and air humidity. Indoor vapour contribution defined as the difference between the indoor and the outdoor vapour concentration was calculated. Sensitivity, specificity, predictive values and accuracy were calculated for window pane condensation and high vapour contribution (>/= 3 g/m3), as indicators of defective ventilation (< 0.5 ACH), high indoor humidity (>/= 7 g/kg and >/= 45% RH) and high mite allergen concentration in mattress dust (>/= 2 microg/g). RESULTS: All houses with high humidity and high mite allergen concentrations were positive for the two indicators (high sensitivity), but with a specificity of only 50% so that half of the houses with reported condensation and high vapour contribution turned out to be low pollution houses with adequate high ventilation levels. Both indicators had high negative predictive values and absence of the two indicators almost certainly (97-100%) excluded high indoor pollution with high humidity and high mite concentrations. Overall more than 70% of the dwellings were correctly classified by the two indicators. CONCLUSION: Absence of window pane condensation on double-glazed windows and low indoor vapour contribution (< 3 g/m3) during the winter are true markers of a dwelling without high indoor air humidity and without high mite allergen concentrations in mattress dust in houses in a cold temperate climate with subzero outdoor temperatures. The presence of the two indicators is associated with a 18-45% risk of high humidity and mite allergen concentrations so in this latter group further measurements are needed for correct classification.
Initial experiences of women from hereditary breast cancer families after bilateral prophylactic mastectomy: a retrospective study.
BACKGROUND: Women from families with breast and/or ovarian cancers seek advice and counselling for risk assessment, but they also want information about preventive measures that might reduce their risk of developing these neoplasms. PATIENTS AND METHODS: This study was undertaken in order to assess 15 women's experience with the decision-making process prior to undergoing prophylactic bilateral mastectomy (PM) and immediate breast reconstruction (IBR). It was also designed to determine the degree of the women's satisfaction with the information delivered by the different caregivers, and whether the women felt that their need for psychosocial support was appropriately met. An additional goal was to learn about the patients>> satisfaction with the operations. RESULTS: The women found it difficult to translate the genetic information transmitted to them, although they were satisfied by the way it was given. At some stage during the pre-operative and post-operative period nearly all women stated that they lacked psychological support from the different caregivers. No woman regretted her choice to undergo PM and IBR. By far, the most important issue was the actual risk reduction. However, the result exceeded all patients' initial expectations. When performing PM and IBR, a multidisciplinary team approach, including a psychologist, seems mandatory. It will facilitate the overall management of this group of women.
School as a risk environment for children allergic to cats and a site for transfer of cat allergen to homes.
BACKGROUND: Many children are allergic to furred pets and avoid direct pet contact. The school may be a site of indirect exposure to pet allergens, which may induce or maintain symptoms of allergic diseases. OBJECTIVE: We sought to investigate airborne levels of cat allergen (Fel d 1) at schools and in homes with or without cats and to study clothes as a route for dissemination of allergens between homes and school. METHODS: Airborne cat allergen was collected with personal samplers from (1) children attending classes with many (>25%) or few (<10%) cat owners and (2) homes with or without cats. A recently developed amplified ELISA assay, which detects low levels of airborne cat allergen in pet-free environments, was used. Dust samples were collected from clothes and mattresses. RESULTS: There was a 5-fold difference in the median levels of airborne cat allergen between classes with many and few cat owners (2.94 vs 0.59 ng/m3; P <.001). The median airborne cat allergen concentration in classes with many cat owners was significantly higher than that found in the homes of non-cat owners (P <.001) but lower than that found in homes with cats (P <.001). Allergen levels in non-cat owners' clothes increased after a school day (P <.001). Non-cat owners in classes with many cat owners had higher levels of mattress-bound cat allergen (P =.01). CONCLUSION: The results indicate significant exposure to cat allergen at school. Allergen is spread through clothing from homes with cats to classrooms. There the allergen is dispersed in air and contaminates the clothes of children without cats. The allergen levels in non-cat owners' homes correlate with exposure to cat allergen at school.
Influence of interaction of environmental risk factors and sensitization in young asthmatic children.
BACKGROUND: The increasing prevalence of asthma and allergy in many countries demands evaluation of potential risk factors to improve the possibility of prevention. OBJECTIVE: We studied the association between exposure to cat and dog allergen and allergic sensitization in young children with asthma and interactions with potential environmental risk factors. METHODS: One hundred eighty-nine young children with asthma were evaluated. IgE antibodies to cat and dog were analyzed. Questionnaires were filled in focusing on exposure to cats and dogs, environmental tobacco smoke (ETS), and signs of home dampness as indicated by window pane condensation (WPC) during the first years of life. House dust was analyzed for content of cat (Fel d 1) and dog (Can f 1) allergen. RESULTS: There was a strong association between the degree of reported exposure to cat and dog and the concentration of the respective allergens in floor dust. A dose-response relationship was found between cat exposure, measured as either reported degree of cat exposure or cat allergen levels in dust, and sensitization both to cat and dog. No such relationship was found between exposure and sensitization to dog. WPC increased the risk for sensitization to cat (odds ratio = 2.6, 95% confidence interval 1.2-5.8), whereas ETS strongly tended to do so both to cat and dog. Interaction was found between exposure to ETS, WPC, and high levels of cat allergen (>8 microg/g dust). The presence of all 3 risk factors revealed a multiplicative interaction with a high risk of sensitization to cat (odds ratio = 42.0, 95% confidence interval 3.7-472.8). CONCLUSIONS: Keeping cats indoors may be a health hazard for infants and young children at risk for development of asthma, particularly when they live in a damp house and their parents smoke.
17Beta-hydroxysteroid dehydrogenases in normal human mammary epithelial cells and breast tissue.
17Beta-hydroxysteroid dehydrogenase activity represents a group of several isoenzymes (17HSDs) that catalyze the interconversion between highly active 17beta-hydroxy- and low activity 17-ketosteroids and thereby regulate the biological activity of sex steroids. The present study was carried out to characterize the expression of 17HSD isoenzymes in human mammary epithelial cells and breast tissue. In normal breast tissues 17HSD types 1 and 2 mRNAs were both evenly expressed in glandular epithelium. In two human mammary epithelial cell lines, mRNAs for 17HSD types 1, 2 and 4 were detected. In enzyme activity measurements only oxidative 17HSD activity, corresponding to either type 2 or type 4 enzyme, was present. The role of 17HSD type 4 in estrogen metabolism was further investigated, using several cell lines originating from various tissues. No correlation between the presence of 17HSD type 4 mRNA and 17HSD activity in different cultured cell lines was detected. Instead, oxidative 17HSD activity appeared in cell lines where 17HSD type 2 was expressed and reductive 17HSD activity was present in cells expressing 17HSD type 1. These data strongly suggest that in mammary epithelial cell lines the oxidative activity is due to type 2 17HSD and that oxidation of 17beta-hydroxysteroids is not the primary activity of the 17HSD type 4 enzyme.
Peanut oil in vitamin A and D preparations: reactions to skin test and manifestation of symptoms.
The aim of this study was to establish whether there is a link between sensitisation to peanut and exposure to peanut oil in vitamin A and D preparations. Forty-one children with a positive in vivo or in vitro test towards peanut were included. Twenty-one children had consumed vitamins A and D in oil solution, 14 in water solution, and 6 both types. Refined and unrefined peanut oils were obtained and skin prick test extracts were prepared. None of the children exhibited a positive SPT in response to the refined peanut extract. In contrast, 15 children exhibited a positive SPT to the unrefined extract. There was no significant difference in the number of children reacting clinically to peanut exposure who had received vitamins A and D in oil-based or water-based formulations. However, children with clinical allergy to peanut and who had exclusively consumed vitamin A and D in peanut oil, exhibited a greater number of different allergic symptoms upon consumption of peanut compared with clinical allergic children who had consumed the vitamins in water solution or both types (p<0.01). This study indicates that sensitisation to peanut during childhood through consumption of vitamins A and D in oil-based solution seems unlikely, but its consumption may contribute to the development of a wider range of clinical symptoms due to peanut exposure.
Fel d 1 and Can f 1 in settled dust and airborne Fel d 1 in allergen avoidance day-care centres for atopic children in relation to number of pet-owners, ventilation and general cleaning.
BACKGROUND: Special day-care centres for atopic children have been established in Sweden. OBJECTIVE: To study concentrations of cat (Fel d 1) and dog (Can f 1) allergens in settled dust and airborne cat allergen in day-care centres in relation to pet ownership among children and staff, ventilation and general cleaning. METHODS: Twelve allergen avoidance day-care centres and 22 conventional day-care centres were included in the study. Settled dust was collected and analysed with ELISA. Airborne cat allergen levels were measured in eight allergen avoidance and seven conventional centres with a personal air sampler and analysed with an amplified ELISA. Air change rate per hour (ACH) was measured. A questionnaire which focused on keeping of cat and dog among staff and children and frequency of general cleaning was used. RESULTS: In the allergen avoidance day-care centres neither children nor staff reported ownership of cats or dogs, compared with 21/22 of the conventional centres in which children and staff kept furred animals. Fel d 1 and Can f 1 were found in settled dust in all day-care centres. In the allergen avoidance compared with the conventional centres the concentrations of Fel d 1 and Can f 1 were lower, Fel d 1: median 0. 64 microg/g vs 5.45 microg/g and Can f 1: 0.39 microg/g vs 2.51, both P < 0.001, and airborne Fel d 1 was also lower in the allergen avoidance centres compared with the control centres, 1.51 ng/m3 vs 15.8 ng/m3, P = 0.002. A correlation was found between airborne and settled Fel d 1, rs = 0.75, P < 0.001. Furthermore, a correlation was found between increased ACH and decreased levels of Fel d 1 in the air in the day-care centres with no cat-owners, rs = - 0.86, P = 0.007. No relation was found between levels of cat or dog allergen and amount of general cleaning. CONCLUSION: Not keeping pets seems to reduce children's exposure to pet-allergen in their 'working environment'. Additionally, appropriate ventilation seems to reduce Fel d 1 in the air in day-care centres.
Increased mast cell tryptase in sudden infant death - anaphylaxis, hypoxia or artefact?
BACKGROUND: Increased concentrations of mast cell tryptase in post mortem blood have frequently been observed in sudden infant deaths but the cause of this has not yet been clarified. OBJECTIVE: The aim was to evaluate factors (immunological, morphological and anamnestic data) behind the observed increase in mast cell tryptase in sudden infant deaths with elevated tryptase. METHODS: Mast cell tryptase and total immunoglobulin (Ig) E were measured in post mortem sera from 44 infants younger than 1.5 years. Radioallergosorbent tests were performed for possible allergens (mixture for relevant food allergens, Phadiatop and latex). IgG subclasses, IgM, and complement factors (C3, C4 and factor B) were measured with radial immunodiffusion. Mast cells, labelled with antibodies against mast cell tryptase, were counted in the lungs and heart. The circumstances of death and medical history of the deceased infant and family were obtained through police and hospital records. RESULTS: In 40% of the SIDS cases tryptase was elevated (>10 microg/L). Total IgE in serum was increased in 33% compared with clinical reference values but showed no association with mast cell tryptase. RAST tests were positive in three cases. In one of these cases both tryptase and total IgE were elevated. The only variable that was associated with high tryptase values was prone position at death (P < or = 0.05 ). Allergy or asthma in the family were alleged in 50% of the cases, but was not associated with elevated tryptase or IgE. Children with elevated total IgE also displayed high concentrations of IgG1 and IgG2. Infants who died in the spring had significantly higher IgE than the others (P < or = 0.05). CONCLUSION: The results do not support the hypothesis that the elevated tryptase concentrations in sudden infant death are caused by allergy. The association between prone position at death and elevated tryptase could hypothetically be explained by mast cell degranulation due to, for example, a hypoxic stimulus in these infants.
Somatosensory status after pedicled or free TRAM flap surgery: a retrospective study.
The transverse rectus abdominis musculocutaneous (TRAM) flap is widely used in autologous breast reconstructions. In transferring tissue as a pedicled or free flap, alterations in sensibility are unavoidable. This study evaluated somatosensory function in the reconstructed breast at least 2 years after pedicled or free TRAM flap surgery. Thirteen patients who had a pedicled TRAM flap and 13 patients who had a free TRAM flap participated in the study. The patients completed a questionnaire regarding subjective sensibility and their general opinion of the reconstructed breast. Somatosensory examinations to study the sensations of touch, warmth, cold, and pain were performed using nonquantitative and quantitative techniques. An age-matched control group of eight women who had never had breast surgery was also examined because the majority of the women who had breast reconstruction also had a mammaplasty performed on the contralateral breast, which disqualified it as a control. The majority of the patients reported that the reconstructed breast felt like a real breast. However, sensibility to touch, warmth, cold, and pain was decreased in the study groups compared with the control group. No clinically significant differences existed in sensibility between the pedicled and free TRAM flap groups.
Management, morbidity, and oncologic aspects in 100 consecutive patients with immediate breast reconstruction.
BACKGROUND: Immediate breast reconstruction (IBR) is indicated when breast-conserving surgery is inappropriate and the patient refuses mastectomy as the sole procedure. METHODS: Management, morbidity, and oncologic aspects were studied in 100 consecutive patients treated between 1990 and 1994 with a minimum follow-up time of 2 years. Indications for mastectomy and IBR always were discussed within a multidisciplinary group. Eighty-four patients had primary breast cancer, 12 patients underwent salvage mastectomy for an ipsilateral breast tumor recurrence, two patients had benign breast disease, and two patients underwent prophylactic mastectomy because of familial breast cancer. RESULTS: Saline and silicone gel-filled implants were used predominantly (88%), but free and pedicled TRAM flaps were performed in 12 patients (12%). The overall complication rate was 16%. Seven patients lost their implants, three of whom had been irradiated to the chest wall. Sixty-five patients completed breast reconstruction (nipple and areola) within a median time of 418 days (range 40 to 1471 days). At follow-up, eight patients had locoregional recurrences after a median time of 7.2 months (range 1 to 23 months), and nine patients had died from disseminated breast cancer. CONCLUSION: IBR is time-consuming, but it is well tolerated and does not interfere with oncologic adjuvant treatment. IBR can be performed with low morbidity by a dedicated multidisciplinary team.
Mechanical ventilation protects one-storey single-dwelling houses against increased air humidity, domestic mite allergens and indoor pollutants in a cold climatic region.
BACKGROUND: Poor ventilation in modern, highly insulated housing is an important factor in promoting indoor humidity levels to exceed 7 g/kg in cold climatic regions. OBJECTIVE: To investigate the ventilation rate in houses with different ventilation systems in relation to indoor air humidity, domestic mite allergen levels and volatile organic compounds (VOC). METHODS: Measurements were performed regarding ventilation rate, indoor temperature, air humidity, mattress mite allergen concentrations using enzyme-linked immunosorbent assay and total indoor VOC in 59 similarly constructed one-storey single-dwelling houses. In 22 of the houses, a mechanical supply and exhaust ventilation were installed after construction. RESULTS: In only five of the houses with mechanical supply and exhaust ventilation the air exchange rate per hour (ACH) was below 0. 5 compared with 24 of the 29 houses with natural ventilation (OR = 0. 06, CI 95% 0.01-0.2). None of the 23 houses with an ACH >/= 0.5 had an absolute indoor humidity (AIH) of 7 g/kg air or more, compared with 10 of the 36 houses with an ACH < 0.5 (P = 0.01 ). In none of the 23 houses with an ACH >/= 0.5 were concentrations of mite allergen exceeding 2 microg/g of dust found, compared with six of the 36 houses (17%) with an ACH below 0.5 (P = 0.04). Further, 10 of the 34 houses with a total VOC exceeding 200 microg/m3 had mite allergen in mattress dust exceeding 0.5 microg/g, compared with one of the 22 houses with VOC < 200 microg/m3 (P = 0.04). CONCLUSION: The study shows that in modern, highly insulated, one-storey single-dwelling houses in cold temperate regions, mechanical ventilation increases the possibility of reaching an ACH of >/= 5 which protects against indoor humidity levels contributing to mite survival as well as high levels of indoor air pollutants in winter.
Technical aspects of immediate breast reconstruction--two year follow-up of 100 patients treated consecutively.
We report the technical aspects of immediate breast reconstruction of the first 100 consecutive patients done at the Karolinska Hospital. Two patients had bilateral cancer. Preoperative chemotherapy had been given to five patients and postoperative chemotherapy to 13 patients. In 96 patients the indication was breast carcinoma. Mean tumour size was 13.1 mm and always less than 100.0 mm. Radiotherapy had been given preoperatively in nine patients and postoperatively in 10 patients. Mean operation time was 127 minutes, and median operating time 100 minutes. Hospital stay was five days. Breast reconstructions were performed with permanent prostheses in 22, expanders in 66, pedicled TRAM flaps in eight, and free TRAM flaps in four patients. To complete the breast reconstruction one major and 1.4 minor operations were needed. Total time to reconstruction was 461 days. The overall complication rate was 16%, with 13 local complications. Three developed haematomas, seven lost their implants, two developed partial necroses of pedicled TRAM flaps, and one developed abdominal bulging after a free TRAM flap. Patients were followed up after 2.0-5.7 years. The capsular contracture rate in the implant group was 24%.