| 11. |
- Windahl, Torgny, 1948-
(författare)
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Clinical aspect of laser treatment of lichen sclerosus and squamous cell carcinoma of the penis
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of these studies was to investigate the efficacy, complications and the long term results after laser treatment of lichen sclerosus et atrophicus and of squamous cell carcinoma of the penis.Patients and Methods: Paper I: In a prospective study from 1985-1991, 62 men with histologically verified lichen sclerosus et atrophicus were given carbon dioxide (CO2) laser treatment following the failure of local corticosteroid treatment. The study was subsequently updated at a median follow-up time of 14 years.Paper II-IV: Sixty-seven men aged 26 to 87 (mean 60 years) with newly diagnosed penile carcinoma were included in a prospective study. The patients were treated by a new combined laser method (CO2 and Nd:YAG) between 1986 and 2000. The median follow-up time was 42 months (range 12-186 months). All patients could be assessed for local recurrence, progression and survival at the end of 2001. Forty-six patients agreed to participate in face-to-face interviews addressing sexual activity, sexual function/dysfunction, satisfaction and cosmetic results.Results: Paper I: The laser treatment was successful in 47 patients (76%) with no local symptoms at a mean follow-up of 30 months. Fifty-three of the 62 men were alive when the update was carried out in February 2004, and we were able to get in contact with 50 of them. Forty of these patients (80%) had no local symptoms or visible lesion. We found concomitant squamous cell carcinoma of the penis in two patients and two further patients had died from anal cancer.Paper II-IV: Local recurrences appeared in 13 patients (19%) at a median follow up of 42 months, and 10 of these patients were successfully retreated with laser treatment. Two patients died from penile carcinoma. The disease-specific 5-years survival rate was 95%. Concomitant lichen sclerosus was found in 11 patients. All patients younger than 75 years reported that they were sexually active before the treatment, and 80% of them had resumed their sexual activity after the treatment. Ten patients (22%) reported decreased erectile function after the treatment, while 33 patients (72%) reported unaltered erectile function. The cosmetic result was regarded as satisfying or very satisfying in 78% of the patients.Conclusion: Carbon dioxide laser treatment is an efficient treatment for lichen sclerosus et atrophicus with excellent long-term results, and the side effects are few. One disadvantages of the treatment is a slow postoperative healing process. Combined CO2 and Nd:YAG laser treatment is effective for treatment of the primary tumour in patients with localized penile carcinoma. It can be safely carried out with good local tumour control and highly satisfactory results with respect to cosmetic aspects and sexual function.
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| 12. |
- Isaksson, Marléne
(författare)
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Clinical and experimental studies in corticosteroid contact allergy
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Corticosteroids are anti-inflammatory and anti-proliferative substances that also can induce sensitization, mainly through skin contact. In a sensitized individual, it can be hard to disclose the contact allergy at patch testing because the anti-inflammatory effect may mask the allergic contact reaction. This is primarily seen when patch testing to potent corticosteroids is performed and the reading is done early, when the anti-inflammatory effect still prevails. In this thesis I present a hypothetical model, which can explain the different situations that emerge, when the anti-inflammatory effect influences the elicitation depending on the individual degree of hypersensitivity in a sensitized subject. Some patients allergic to the corticosteroid budesonide only reacted to very low concentrations of the sensitizer at early readings. When patch testing the corticosteroid triamcinolone acetonide, concentrations 1000 to 10,000 times lower than internationally recommended resulted in allergic reactions while the recommended concentration gave negative reactions. If testing with a corticosteroid at a high concentration results in a negative patch-test reaction, lowering the concentration may result in a positive patch-test reaction. Introducing another parameter into the model, the time factor, made it possible also to explain why negative patch test reactions are sometimes seen at early readings, while the tests may turn positive on late reading occasions. Therefore, not to miss contact allergy to corticosteroids, a reading after one week in addition to an early reading is advocated. The multi-centre study showed that 25% of the allergic reactions to corticosteroids would have been missed if a late reading had not been done. The edge reaction, consisting of a blank centre representing the whole area of the test unit and surrounded by an eczematous infiltrate, is seen in some corticosteroid allergic patients when potent corticosteroids are patch-tested. This phenomenon can also be explained by the same model. If an edge reaction appears, a late reading or testing with a lower concentration should be done. I also investigated the cross-reactivity pattern for the two diastereomers of budesonide, the R and S diastereomers, and found that results concurred with the theory that the R diastereomer cross-reacts with other substances from the group to which it belongs, group B, while the S diastereomer cross-reacts not only with other group B substances but also with some esters of group D. No inhibition of the patch test reactions was observed when patch testing the corticosteroid tixocortol pivalate and potentially cross-reacting substances at high concentrations. Aldehydes of corticosteroids are thought to be intermediates in the sensitization process. The aldehyde of hydrocortisone was therefore tested in subjects allergic to hydrocortisone. Patients reacting to hydrocortisone also reacted to the aldehyde, speaking in favour of the aldehyde being an intermediate in the sensitization. When trying to elucidate whether a corticosteroid mix, consisting of the three corticosteroids budesonide, tixocortol pivalate and hydrocortisone-17-butyrate (Hc-17-B) in petrolatum, could disclose corticosteroid allergy I found that 60% of the patients allergic to tixocortol pivalate were missed. Thus, in a corticosteroid mix containing budesonide and Hc-17-B, tixocortol pivalate should not be a part. Of the separate markers that were patch-tested simultaneously in petrolatum, budesonide 0.10% detected most allergic subjects, followed by budesonide 0.002% and tixocortol pivalate, both concentrations (1.0% and 0.10%) detecting the same number of patients. Hc-17-B at 1.0% detected more than 0.10%. Investigations on the stability of budesonide, tixocortol pivalate and Hc-17-B patch-test preparations in petrolatum disclosed that these were stable for at least one year in room temperature, refrigerated and frozen. Budesonide and tixocortol pivalate in ethanol showed the same stability. Hc-17-B 1.0% in ethanol was only stable frozen for one year and at room temperature for three months. In the study on local clinical relevance, the flare-up reactions in the budesonide-allergic individuals consisted not only of a severe deterioration of the Preferid® treated eczema but also toxicoderma-like eruptions with a conspicuous distribution. A correlation was found between contact allergy to budesonide and deterioration of the eczema treated with Preferid® cream containing budesonide. To study flare-up reactions at earlier budesonide test sites a systemic provocation with Pulmicort® Turbuhaler® (budesonide) via inhalation was performed in subjects allergic to budesonide but without asthma or other lung dysfunction. The study clearly showed that flare-up reactions were found after normal doses of budesonide. Therefore, a person hypersensitive to budesonide should not be given the drug as an inhalant. In the same study a new method in humans to test for cross-sensitivity was used. When budesonide was inhaled, a flare-up was noted where triamcinolone acetonide had been tested previously, indicating cross-reactivity between budesonide and triamcinolone acetonide.
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| 13. |
- Pontén, Ann
(författare)
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Contact Allergy to Epoxy Resins of the Bisphenol F-type
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epoxy resins based on bisphenol A are well-known contact allergens and often cause occupational contact allergy. The most important allergen is the monomer diglycidyl ether of bisphenol A (DGEBA). Epoxy resins of the bisphenol F-type contain 3 isomers of the diglycidyl ether of bisphenol F; p,p'-DGEBF, o,p'-DGEBF, and o,o'-DGEBF, whereas epoxy resin(s) based on bisphenol A (DGEBA-R) contain virtually only 1 isomer of DGEBA. The allergenicity of DGEBA has been investigated earlier, but the DGEBF isomers have not previously been investigated as contact allergens. When an epoxy resin based on bisphenol F was inserted in the standard patch test series of our department, it was found that contact allergy to this type of epoxy resin was at least as common as contact allergy to DGEBA-R. A majority of the patients reacted to both types of epoxy resins. Both p,p'-DGEBF and o,p'-DGEBF were shown to be sensitizers in humans, while o,o'-DGEBF elicited surprisingly few reactions. p,p'-DGEBF was found to be a sensitizer and at least as strong as DGEBA. All 3 DGEBF isomers were found to be strong sensitizers in animal studies. It was also found that DGEBA, p,p'-DGEBF and o,p'-DGEBF cross-reacted with one another to a high degree, while o,o'-DGEBF did not. o,o'-DGEBF was assumed to be a sensitizer mainly in the absence of the other 3 substances. Humans are then generally not sensitized to o,o'-DGEBF, since it does not occur alone in the epoxy resins of the bisphenol F-type. For the individuals with contact allergy both to DGEBA-R and epoxy resins of the bisphenol F-type, concomitant sensitization as well as cross-sensitization might be the case. When contact allergy to epoxy resins of the bisphenol F-type is suspected, this type of epoxy resin should be patch tested, especially if the DGEBA-R patch test is negative. Depending on the clinical situation, the patch-test concentration recommended is 0.25-0.5%. Consecutive patch testing with epoxy resins of the bisphenol F-type at a concentration of 1.0% is not recommended due to the possibility of patch-test sensitization. It was found that the sensitivity of the thin-layer chromatography method was around 200 times more sensitive for DGEBA than for DGEBF isomers. In patients with contact allergy to DGEBA-R, the cause of allergic contact dermatitis might be an epoxy resin of the bisphenol F-type. The latter resins are most probably not detected by the TLC method developed for DGEBA-R. If the product is analyzed only with the TLC method, the relevance of the contact allergy to DGEBA-R might therefore remain unrecognized. In an industrial investigation among 603 workers exposed to epoxy resins 20.3% of the 325 patch-tested workers had occupational ACD. Approximately 15% of the workers with occupational ACD had contact allergy to DGEBA-R and 36% had contact allergy both to epoxy resins of the bisphenol F-type and DGEBA-R. Around 40% of the patch-tested workers were estimated to have skin disease either caused or aggravated by work. Although a well-known occupational contact allergen, a high frequency of contact allergy to DGEBA-R among exposed workers was found. Thorough instruction concerning protection, most importantly for new employees, as well as the development of production methods that minimize exposure, especially to DGEBA-R, are necessary measures for preventing occupational dermatoses among workers exposed to ERS in the manufacture of rotor blades for wind turbines.
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| 14. |
- Sköldberg, Filip
(författare)
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Studies of Autoantibodies in Systemic and Organ-Specific Autoimmune Disease
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease, whereas autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal disorder characterized by combinations of organ-specific autoimmune manifestations including hypoparathyroidism and intestinal dysfunction, and may serve as a model for organ-specific autoimmunity. Autoantibodies directed against proteins expressed in the affected tissues are found in both diseases. From a chondrocyte cDNA expression library, we identified the protein AHNAK as an autoantigen in SLE. Anti-AHNAK antibodies were found in 29.5% (18/61) of patients with SLE, 4.6% (5/109) of patients with rheumatoid arthritis, and 1.2% (2/172) of blood donors. Using a candidate approach, we analyzed the prevalence in APS1 and other organ-specific autoimmune diseases, of autoantibodies against the pyridoxal phosphate-dependent enzymes histidine decarboxylase (HDC) and cysteine sulfinic acid decarboxylase (CSAD), which are structurally closely related to known autoantigens. Anti-HDC and anti-CSAD reactivity was detected exclusively in APS1 patient sera. Anti-HDC antibodies were detected in 37.1% (36/97) of the APS1 sera, did not cross-react with aromatic L-amino acid decarboxylase, and were associated with intestinal dysfunction and loss of histamine-producing gastric enterochromaffin-like cells. In contrast, anti-CSAD reactivity was detected in 3.6% (3/83) of APS1 sera and cross-reacted with recombinant glutamic acid decarboxylase. From a parathyroid cDNA expression library, novel spliced transcripts of the CLLD4 gene on human chromosome 13q14, encoding 26 and 31 kDa isoforms recognized by autoantibodies in 3.4% (3/87) of APS1 patients, were identified and found to be preferentially expressed in lung and ovary. Both isoforms contain an N-terminal BTB/POZ domain, similarly to the TNF-alpha-regulated protein B12, localize both to the cytoplasm and nucleus in transfected COS cells, and form oligomers in vitro. The CLLD4 gene is located in a region frequently deleted in several forms of cancer, including lung and ovarian tumors. In conclusion, we have identified and partially characterized AHNAK and HDC as two common targets of autoantibodies in SLE and APS1, respectively. We have also identified CSAD and CLLD4 as two minor autoantigens in APS1, one of which is a novel protein with unknown function.
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| 15. |
- Zimerson, Erik
(författare)
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Contact allergens in p-tert-butylphenol-formaldehyde resin
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- p-tert-Butylphenol-formaldehyde resin (PTBP-F-R) is used as a binder in many adhesive formulations and it consists of a complex mixture of substances, most of which are unknown. The resin has been reported to cause allergic contact dermatitis since the 1950s. The aim of the study was to investigate allergens in p-tert-butylphenol-formaldehyde resin (PTBP-F-R) and to isolate and identify sensitizers that are important factors for the development of hypersensitivity to PTBP-F-R in man. Chemical separation methods were used to isolate fractions and pure substances from the resin. These were patch tested in patients hypersensitive to PTBP-F-R. The sensitizing capacities and cross-reaction patterns of 11 isolated substances were investigated using the Guinea pig maximization test. In the present investigation 7 new allergens in PTBP-F-R were established and 1 more was strongly indicated. The allergens were found among monomers, dimers and trimers. Patch testing of formaldehyde and 4-tert-butyl-phenol, the raw materials for production of PTBP-F-R, indicated that these substances are not frequent allergens among patients hypersensitive to PTBP-F-R. 5-tert-Butyl-2-hydroxy-3-hydroxymethyl-benzaldehyde was considered to be an important allergen among the monomers. The dimers 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethyl-phenol and 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethyl-phenol were considered main allergens in the resin. The investigated substances were quantitatively determined in 2 PTBP-F-Rs and shown to be present in concentrations varying between 0.01 and 1.7% w/w.
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| 16. |
- Albinsson, Lars, 1944-
(författare)
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A Palliative Approach to Dementia Care : Leadership and organisation, existential issues and family support
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this thesis was to apply the WHO and NHS palliative care approach to dementia care. Thirty-one staff-members in mid-Sweden (studies I and II) and 20 next-of- kin (study IV) were interviewed. In study III, 316 staff-members from dementia care and 121 staff-members from palliative cancer care responded to a questionnaire about family support. The interviews were tape-recorded and analysed with a qualitative phenomenographic (I and II) and a hermeneutic approach (IV). The questionnaires (III) were analysed using qualitative and quantitative content analysis.The staff-members stated almost unanimously that daily leadership was lacking, and consequently clear goal formulations and care planning were rare (I). Proper teamwork between the doctor and the staff who worked on a daily basis with the patients was absent (I). With respect to existential issues, education and staff discussions were lacking (II). The staff were at a loss concerning how to deal with these issues. Nevertheless, these issues are central to family-members who have to deal with an existential crisis (IV). Important questions emerged about obligation and guilt, faithfulness, responsibility, and paying back what you once received. Existential isolation could be identified e.g. in the reversal of roles experienced as "being a parent to your parent" and in the burden of "visiting a living dead person". There were no routines for bereavement visits. The type of support suggested for dementia family members is partly similar to support in palliative cancer care, but it also differs in other respects such as feelings of guilt because the early signs of the disease are misunderstood, the need for respite because of the long trajectory of dementia diseases, and the occurrence of anticipatory grief because in the late phase family members can no longer make any contact at all with the patient (III).A palliative approach can improve the quality of life for the dementia patient and for the family. It can be used as a basis for a clear goal formulation. Some of the suggestions listed in this thesis for improving the quality of care are more a reflection of the need for a change in attitudes rather than the need for substantial budget increases.
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| 17. |
- Engvall, Karin, 1949-
(författare)
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A Sociological Approach to Indoor Environment in Dwellings : Risk factors for Sick Building Syndrome (SBS) and Discomfort
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The principal aim was to study selected aspects of indoor environment in dwellings and their association with symptoms compatible with the sick building syndrome (SBS). A validated questionnaire was developed specifically for residential indoor investigations, using sociological principles and test procedures. The questionnaire was mailed to 14,243 multi-family dwellings in Stockholm, selected by stratified random sampling. Females, subjects with a history of atopy, those above 65 y, and those in new buildings reported more symptoms. Subjects owning their own dwelling had less symptoms. A multiple regression model was developed, to identify residential buildings with a higher than expected occurrence of SBS. In total, 28.5% reported at least one sign of building dampness in their home (condensation on windows, humidity in the bathroom, mouldy odour, water leakage). All indicators of dampness were related to symptoms, even when adjusting for demographic data, and other building characteristics (OR=2.9-6.0). Associations between symptoms and other building data was evaluated in older houses, built before 1961. Subjects in older buildings with a mechanical ventilation system had fewer symptoms. Heating by electric radiators, and wood heating was associated with an increase of most types of symptoms (OR=1.2-5.0). Multiple sealing measures (OR=1.3), and major reconstruction (OR=1.1-1.9), was associated with an increase of symptoms. The effect of seasonal adapted ventilation (SAV) was studied in a small experimental study. A 20% reduction of ventilation flow from 0.5-0.8 ac/h to 0.4-0.5 ACH during the heating season increased the perception of poor indoor air quality in the dwelling in general, and in the bedroom. In conclusion, low building age, and building dampness in the dwelling are associated with SBS. In older houses, mechanical ventilation is beneficial. The thesis did not support the view that energy saving measures in general is an important risk factor for SBS, but major reconstruction and multiple sealing measures can be risk factor for symptoms. Reducing the outdoor ventilation flow below the current Swedish ventilation standard (0.5 ACH) may increase the perception of impaired air quality.
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| 18. |
- Lindgren, Torsten
(författare)
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Cabin Air Quality in Commercial Aircraft : Exposure, Symptoms and Signs
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of the dissertation was to study the cabin environment, and identify personal and environmental risk factors, associated with symptoms, and perception of cabin air quality. Another objective was to study if ban of smoking, and increased relative air humidity on intercontinental flights, could have a beneficial health effect. The studies were performed among Scandinavian cabin crew in one Airline Company. Office workers from the same company served as controls. Exposure differed between cruise and non-cruise conditions. Air humidity was very low during intercontinental flights (3-8%). Concentration of moulds, bacteria, formaldehyde, and ozone was low. Tobacco smoking increased respirable particles in the cabin air, from 3 to 49 mg/m3, and increased cotinine in urine. The ETS-exposure was highest in the aft part of the cabin. Symptoms and environmental complaints were more common among flight crew than office workers. We could identify personal factors of importance, and certain conditions that could be improved, to achieve a better cabin environment. There was an association between symptoms and environmental perceptions and work stress, lack of influence on working condition, and a history of atopy. After ban on smoking in aircraft, there was a decrease of ocular and general symptoms, and increased tear-film stability in aircrew. Air humidification reduced headache and ocular, nasal, and dermal dryness symptoms, increased tear-film stability, and increased nasal patency. Our result indicates that ETS and low air humidity are important environmental factors in aircraft, and that atopy, and work stress could be significant risk factors for symptoms and environmental perceptions.
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| 19. |
- André, Malin, et al.
(författare)
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The Use of CRP Tests in Patients with Respiratory Tract Infections in Primary Care in Sweden Can Be Questioned
- 2004
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 36:3, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1 week in November in 2000 and 2002 respectively. As a part of the study, the use and results of C-reactive protein (CRP) tests in relation to duration of symptoms and antibiotic prescribing in 6778 patients assigned a diagnosis of respiratory tract infections were analysed. In almost half (42%) of the patients, a CRP test was performed. The majority of CRP tests (69%) were performed in patients assigned diagnosis upper respiratory tract infection, where the test is not recommended. Overall, there was a minor decrease in antibiotic prescribing when CRP was used (41%), in comparison to 44% of the patients where no CRP was performed (p<0.01). Patients assigned diagnoses implying a bacterial aetiology were prescribed antibiotics irrespective of result of CRP or length of symptoms before consultation. For patients assigned viral diagnoses, antibiotic prescribing increased with increasing duration of symptoms and increasing value of CRP. The use of CRP decreased antibiotic prescribing in patients assigned to viral diagnoses and with longstanding symptoms (p<0.001). However, 59% of the patients assigned viral diagnoses with CRP≥25 received antibiotics, which seems to indicate a misinterpretation of CRP and a non-optimal use of antibiotics.
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| 20. |
- André, Malin, et al.
(författare)
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Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests
- 2002
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 0036-5548 .- 1651-1980. ; 34, s. 880-
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Tidskriftsartikel (refereegranskat)abstract
- A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment.
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