bluuebunny/crossref_metadata_2025 huggingface dataset:
Danazol therapy in factor X deficiency
Authors: Mukhopadhyay S. , Saxena R. , Kashyap R. , Choudhry V. P.
Published: March 2003

Factor X (FX) deficiency is a rare coagulation disorder that usually presents with bleeding manifestations and is treated with fresh frozen plasma or prothrombin complex concentrates. We report a case of FX deficiency in which the patient presented with bleeding as well as thrombosis. The patient responded to Danazol and relapsed when the drug was stopped. The occurrence of thrombosis in FX deficiency and the role of Danazol in coagulopathies are reviewed.
The effect of resistance training on the frequency of bleeding in haemophilia patients: a pilot study
Authors: TIKTINSKY R. , FALK B. , HEIM M. , MARTINOVITZ U.
Published: March 2003

The benefits and feasibility of progressive resistance training on muscle strength and bleeding profile were studied prospectively in two patients with severe haemophilia. Additionally, retrospective data were collected from three patients who had been training for 11–21 years (one patient for 21 years and two patients for 11 years). Muscle strength increased, especially in muscle groups surrounding the target joints (elbow and knee). Bleeding frequency decreased from 2–3 times per week to 1–2 times per week. Patients who had been training for > 11 years reported bleeding episodes of 2–4 times per month prior to training, but after > 11 years of progressive training a marked decrease in bleeding occurred, as well as a decrease in severity. These data support the importance of resistance training for haemophilia patients, not only for increasing muscle strength, but also for decreasing the frequency and severity of bleeding episodes and the associated pain. A controlled study, with a greater number of patients, is needed to confirm the suggested benefits of resistance training in haemophilia patients.
Haemophilia A: effects of inhibitory antibodies on factor VIII functional interactions and approaches to prevent their action
Authors: SAENKO E. L. , ANANYEVA N. M. , KOUIAVSKAIA D. V. , KHRENOV A. V. , ANDERSON J. A. M. , SHIMA M. , QIAN J. , SCOTT D.
Published: March 2003

Factor VIII (FVIII) is an essential component of the intrinsic pathway of blood coagulation. Normal functioning of FVIII requires its interactions with other components of the coagulation cascade. In the circulation, it exists as a complex with von Willebrand factor (vWF). Upon activation by thrombin or activated factor X (FXa), activated FVIII (FVIIIa) functions as a cofactor for the serine protease factor IXa. Their complex assembled on the phospholipid surface activates FX to FXa, which consequently participates in formation of thrombin, the key protease of the coagulation cascade. Genetic deficiency in FVIII results in a coagulation disorder haemophilia A, which is treated by infusions of FVIII products. Approximately 25–30% of patients develop antibodies inhibiting FVIII activity (FVIII inhibitors). The major epitopes of inhibitors are located within the A2, C2 and A3 domains of the FVIII molecule. The inhibitory effects of antibodies are manifested at various stages of the FVIII functional pathway, including FVIII binding to vWF, activation of FVIII by thrombin, and FVIIIa incorporation into the Xase complex. We summarize the current knowledge of the FVIII sites involved in interaction with its physiological ligands and different classes of inhibitory antibodies and describe their inhibitory mechanisms. We outline the strategies aimed to overcome the effects of inhibitory antibodies such as development of human/porcine FVIII molecules, resistant to inhibitors. We also discuss approaches to modulate the antibody response, as well as efforts to develop a long‐term immunotolerance to FVIII protein.
Modified magnetic resonance imaging score compared with orthopaedic and radiological scores for the evaluation of haemophilic arthropathy
Authors: FUNK M. B. , SCHMIDT H. , BECKER S. , ESCURIOLA C. , KLARMANN D. , KLINGEBIEL T. , KREUZ W.
Published: March 2003

Twenty‐four joints (10 knees and 14 ankles), with at least one manifestation of bleeding (proven by sonographic assessment), of 15 patients with haemophilia were investigated prospectively. For magnetic resonance imaging (MRI) evaluation, the MRI scale of Nuss et al. was modified to a MRI score (max. 13 points/joint) to allow a comparison with the physical examination score (max. 12 points) and the radiological score (Pettersson score; max. 13 points). The number of joint bleeds correlated well with the degree of arthropathy P < 0.01). In all 16 joints with a maximum of two bleeds, no alterations were found by physical examination, or radiological and MRI assessment. Joints with three bleeds had physical examination scores between 0 and 2, Pettersson scores from 0 to 3 and MRI scores of 2. Joints with four or more bleeds had physical examination scores ranging between 3 and 7, radiological scores between 7 and 12 and MRI scores between 3 and 8. The MRI score describes initial joint alterations more precisely and earlier than other assessments, allowing a discerning estimation of the degree of arthropathy, as well as a follow‐up of haemophilic arthropathy and an improvement after change of treatment. In addition, the modified MRI score seems to differentiate better between early and advanced signs of arthropathy than the MRI scale of Nuss et al.
Becoming a partner in your healthcare
Authors: PAPER R.
Published: March 2003

Chronic disorders such as haemophilia and von Willebrand disease can rob people of a feeling of control over their lives. Added to this is often a feeling of confusion or intimidation when dealing with the healthcare system. People may begin to feel like victims of their disorders and of the healthcare system. The healthcare system defines people who are in receipt of care as patients. The word patient comes from the Latin word patiens, which means to suffer, endure, allow, permit or undergo. Even the term implies a sense of victimization. People who become partners in their care and view the receipt and delivery of healthcare as a service wherein they are the consumer and the doctor or clinician is the provider, will feel more in control and will likely have better outcomes than people who assume the more traditional role of `patient'.
Education and career development
Authors: MÁRQUEZ C. S.
Published: March 2003

The main objective of this paper is to briefly analyse the different factors and circumstances that a person with haemophilia should take into account before undertaking the challenge of going to university and, in turn, choosing a profession or career.

Although education systems in different countries or regions present fundamental differences, some characteristics remain the same, and these will be the focus of our study.

The child with haemophilia will most likely encounter three challenges:

(1) the challenge of choosing a career; (2) the challenge of choosing a college or university; and (3) the challenge of adjusting to college or university life.

The young haemophiliac should be taught to exploit their strengths, and to feel that their only limit is their intellectual development. They should feel that they are only competing against themselves and that any adversities they might face due to haemophilia should not disfavour them; instead they should learn how to live with them and allow these to make them into stronger people.
Bone fractures in the haemophilic patient
Authors: RODRIGUEZ‐MERCHAN E. C.
Published: March 2003

The goal of modern fracture treatment is to obtain an optimal outcome, with the patient's return to full activity as soon as possible. Nowadays, internal stabilization is indicated in most displaced fractures in adults, whereas external fixation remains the best choice for initial stabilization with severe soft‐tissue injuries. If a fracture is correctly treated in a haemophilic patient, it will progress to consolidation in a similar time‐frame to fractures occurring in the general population.
The impact of chronic disease on the family
Authors: Goldstein G. , Kenet G.
Published: March 2003

Summary.  Haemophilia is a chronic disease, affecting patients and their families. The impact of such a disease upon each family is dependent upon family type and characteristics and adjustment to it varies with time, in concordance with the family's lifecycle. In the National Hemophilia Center in Israel we lead a special support system and conduct group therapy from the very early stage of haemophilia diagnosis throughout the lifetime of patients. The general definitions of a family's lifecycle, the effect of the disease and the required adjustment to it are described in this paper. We refer to special difficulties associated with haemophilia as a chronic, genetic disease and describe ways to cope, discussing the support systems that have been established in our centre.
Quality management and quality assurance in haemophilia care: a model at the Bonn haemophilia centre
Authors: Brackmann H‐H. , Effenberger W. , Schwaab R. , Hess L. , Hanfland P. , Oldenburg J.
Published: March 2003

Summary.  The severe clotting defects associated with the diagnosis of severe haemophilia A and B require a quality management and quality assurance system designed to avoid both bleeding sequelae (such as damaged joints) through early on‐demand or prophylactic treatment in a home‐care setting, and side‐effects such as infectious diseases (hepatitis A–G and human immunodeficiency virus), allergic reactions, haemolysis and if possible inhibitor formation, by using highly purified, virus‐inactivated or recombinant products in which the factor VIII and IX proteins are as natural as possible. As the intravenous injection of the required clotting factor is entrusted to the patients in home treatment, the haemophilia centre has to check treatment protocols and, when necessary, joint and muscle status. In addition, it is imperative to ensure the safety of the product, and checks must be carried out to make sure that batch numbers are recalled as soon as possible if side‐effects are observed. These are the reasons for several Acts of Parliament in Germany requiring special treatments and regular checks (the Disabled Act, recommendations by the German Medical Council, the Transfusion Act). Thus, at the haemophilia centre in Bonn we have established a special quality management and quality assurance system taking into account the great number of patients (> 800), the often considerable distance between the centre and the patient, and the aforementioned regulations and laws. Quality management involves dealing with daily practicalities such as 24‐h availability of a physician, medical technologist and nurse, careful instruction of patient and family in home care, genetic counselling, regular laboratory tests (especially recovery time, half‐life, inhibitors and gene defects, clinical chemistry and serology) and clinical investigations (especially joint and muscle status). It also includes co‐operation with family doctors and different departments at our university hospital (e.g. orthopaedic, microbiology), daily conferences with staff, information for nursery schools, schools, training institutions and/or the workplace in case of emergency, and cooperation with German haemophilia foundations. For quality assurance, several self‐controlling systems are in place, such as distribution of concentrate, laboratory data, treatment protocols, joint and muscle status and bleeding tendencies. All these and more are double‐checked and interactive, controlling data and activities with the help of EDP. Exceptional staff motivation and patient compliance are important for this quality system.
Continuous factor VIII infusion therapy in patients with haemophilia A undergoing surgical procedures with plasma‐derived or recombinant factor VIII concentrates
Authors: Dingli D. , Gastineau D. A. , Gilchrist G. S. , Nichols W. L. , Wilke J. L.
Published: March 2003

Summary. We describe the experience of a single medical centre with continuous factor VIII (FVIII) infusion therapy in a cohort of patients undergoing elective surgery. Twenty‐eight patients had a total of 45 procedures. Intraoperative haemostasis was considered excellent in all 45 cases. FVIII levels were maintained between 46% and 191% of normal (median, 103%) for 2–7 days. Bleeding occurred after five procedures (11%) at times when factor VIII levels were within haemostatic range. No patient required reoperation to control bleeding. There were no cases of sepsis related to continuous infusion of factor VIII. We conclude that continuous infusion: (1) is a safe and effective means of replacement therapy in patients with haemophilia undergoing surgery; (2) provides easier monitoring and more constant coagulation factor levels; and (3) has the potential to decrease the cost of replacement therapy by reducing overall usage of product.
Perioperative substitution therapy with plasma‐derived factor VIII concentrate in patients with von Willebrand disease
Authors: Wolf H‐H , Dorligschaw O , Eberspächer B
Published: March 2003

Von Willebrand (vW) disease is a common hemorrhagic disorder characterized by various clinical manifestations and a variety of bleeding symptoms. By classification 3 types of vW disease are described concerning synthesis and multimeric constitution of vW factor. Especially the type 3 disorder is often complicated by perioperative hemorrhages.

vW factor may be released from endothelial depots due to hormonal regulation or stress. Therefore, patients (pts) with vW disease type 1 or 2 may suffer from haemorrhagic complications after major surgery even if preoperative coagulation tests had found to be normal. Especially in pts with combined plasmatic disorders as coagulation factor (F) V or F XI deficiency bleeding may start once more after initial haemostasis.

Until now, recombinant vW factor is not available. There are no clear dosage regimens of plasma derived FVIII concentrate. Substitution therapy with plasmatic F VIII / vW factor concentrates usually has to be adjusted to plasma concentrations of vW ristocetin cofactor.

We report 5 pts with vW disease type 1 and 1 patient type 2 and history of bleeding disorders who received F VIII / vW factor concentrate (Immunate) meanwhile surgery. In 2 pts there was evidence of additional F XI or F V deficiency. After initial bolus administration (80 – 120 IU / kg body weight) we started continuous infusion (3.4 – 9.8 IU / kg body weight) for 48 h. The initial dose of continuous infusion was reduced to 50% after 24 h and to 25% after 36 h, respectively.

In type 1 pts we saw a 3.4‐fold increase in collagen binding activity and 1.9‐fold increase in plasma concentration of vW ristocetin cofactor, respectively. Clinical effectiveneness of substitution therapy was good.

We conclude that continuous infusion of F VIII/vW Factor concentrate (Immunate) may provide sufficient haemostasis in pts with vW disease. Increase in collagen binding activity has been shown to correspond well to substitution. Further data are necessary to prove whether collagen binding activity rather than plasma concentration of vW ristocetin cofactor could be a more relevant parameter concerning dosage administration.
Complications of central venous access devices in paediatric haemophilia patients
Authors: Domm J. A. , Hudson M. G. , Janco R. L.
Published: March 2003

Summary. We conducted a retrospective survey of our experience with central venous access devices (CVADs) implanted in children with haemophilia seen at the Vanderbilt Hemostasis–Thrombosis Clinic from 1986 to 2000. Following discussion with parents on the merits and risks associated with the use of CVADs for immune tolerance induction or factor prophylaxis, catheters were inserted under sterile technique in the operating room. One nurse provided demonstration and teaching about catheter care and access. Thirty central venous catheters were inserted in 22 children. Our survey revealed that the two most common complications associated with central venous catheters were bacteraemia and thrombosis. We found a sepsis rate of 0.30/1000 catheter‐days or one episode of bacteraemia for every 3346 days of catheter use. The thrombosis rate of our cohort was 0.13/1000 catheter‐days or one episode of thrombosis for every 7529 days of catheter use. Uncomplicated venous access is essential in children with severe haemophilia who require prophylaxis or immune tolerance induction. While infection was the most common complication observed in our series, we experienced a lower overall infection rate than several reported series. Catheter thrombosis and subsequent obstruction may occur as a result of intraluminal fibrin deposits. We conclude that the use of implantable central venous catheters is an effective method for accessing children with haemophilia. We accept that the benefits of CVADs in the treatment of paediatric haemophilia patients outweigh the previously documented risks. Future prospective studies should be designed to define all associated risks and to determine effective strategies to reduce them.
Molecular cloning, expression and characterization of the rat analogue of human membrane cofactor protein (MCP/CD46)
Authors: Mead  , Hinchliffe  , Morgan
Published: March 2003

In humans, host cells are protected from homologous complement by membrane proteins encoded in the regulators of complement activation (RCA) gene cluster. These include complement receptor 1 (CR1), decay‐accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46). In mouse and rat a single membrane inhibitor, Crry, appeared to perform the functions of both DAF and MCP and was proposed to be the functional analogue of both. Recently, however, murine homologues of DAF and MCP have been identified, prompting a search for the rat counterparts. We have described the identification of rat DAF and here describe the cloning of rat MCP from cDNA and genomic libraries, using a probe based on the mouse MCP cDNA sequence. The domain structure for rat MCP was identical to that of mouse MCP with four short consensus repeats (SCRs) followed by a STP domain, transmembrane segment and cytoplasmic tail. Overall identity of rat and mouse MCP was 77% at the amino acid level and 88% at the nucleotide level. Northern blot analysis from a range of tissues indicated that high‐level expression was limited to the testis, although expression in other tissues was detected using reverse transcription–polymerase chain reaction. Rat MCP mRNA localized to Sertoli cells and spermatogonia in seminiferous tubules by in situ hybridization, but was absent in mature sperm. In cofactor assays utilizing human factor I, a recombinant soluble form of rat MCP catalysed cleavage of human C3ma.
Periapical status and quality of root fillings and coronal restorations in a Danish population
Authors: Kirkevang L.‐L. , Ørstavik D. , Hörsted‐Bindslev P. , Wenzel A.
Published: March 2003

Aim

The aim of this study was to investigate the quality of endodontic and coronal restorations and the association with periapical status in a Danish population.

Methodology

A total of 614 randomly selected individuals (20–60+ years of age) from Aarhus County had a full‐mouth radiographic examination. The quality of endodontic and coronal restorations and the periapical status of endodontically treated teeth were assessed by radiographic criteria. Root fillings were categorized as ‘adequate’ or ‘inadequate’ with regard to root filling length and lateral seal. Coronal restorations were categorized into ‘adequate’ and ‘inadequate’, defined by the absence or presence of radiographic signs of overhangs or open margins. Results were analysed statistically using the chi‐squared test.

Results

The total number of endodontically treated teeth was 773, and 52.3% had apical periodontitis (AP). Root‐filled teeth with an adequate lateral seal had a lower incidence of AP than teeth with an inadequate seal (44.3% vs. 57.8%), and teeth with an adequate root filling length were associated with a better periapical status than teeth with inadequate length of the root filling (42.0% vs. 67.6%). Similarly, adequate coronal restorations were associated with better periapical status than inadequate restorations (48.0% vs. 63.9%). When both root filling and coronal restoration quality were assessed, the incidence of AP ranged from 31.2% (optimal quality) to 78.3% (all parameters scored as inadequate).

Conclusions

Inadequate root canal and coronal restorations were associated with an increased incidence of AP.
A study of endodontic treatment carried out in dental practice within the UK
Authors: Jenkins S. M. , Hayes S. J. , Dummer P. M. H.
Published: March 2003

Aim

The purpose of this study was to gather both qualitative and quantitative information on the nature of root canal treatment carried out by a group of dentists working within the United Kingdom.

Methodology

A two‐part questionnaire was posted to 720 dentists who graduated from the Dental School, Cardiff, Wales, UK. The first part requested basic information regarding age, year of qualification, field of practice, etc. The second part consisted of 15 questions on endodontic practice and root canal treatment.

Results

The response rate was 41.5%. Two hundred and ninety‐nine questionnaires contained useful information. The majority of practitioners did not use rubber dam during root canal treatment. The vast majority (89%) exposed a radiograph with an instrument of known length in situ to gauge the ‘working length’, a small number relied upon tactile sensation. Most practitioners used local anaesthetic solution as an irrigant during instrumentation of the root canal. A wide variety of instruments were used for root canal treatment; a stepback technique was preferred by almost half the practitioners. Antiseptic solution was preferred as an interappointment dressing. More than half of the respondents used laterally condensed gutta‐percha to obturate root canals in anterior teeth but only one‐third used the same technique in posterior teeth. Less than half the respondents exposed a radiograph to check the fit of the master point prior to obturation. Two‐thirds of practitioners used a zinc oxide based material as their root canal sealer. Three‐quarters of the practitioners exposed a post obturation radiograph.

Conclusions

The results of this study suggest that although some dentists are using the techniques taught during their undergraduate careers, a large percentage now use techniques with no evidence of clinical effectiveness.
Differences in the DNA‐stainability of spermatozoa from fertile and suspected infertile men
Authors: Bito Monika , Czihak Gerhard , Betz Sabine , Wastian Elisabeth , Frick Julian
Published: March 2003

The aim of this work was to determine whether it is possible to distinguish between fertile (control group, already fathers) and infertile men (suspected infertility), by comparing the fluorescence intensity of the sperm‐DNA after incubation with appropriate dyes. First we examined two different DNA‐specific dyes (DAPI and YOYO‐1) using bull spermatozoa. Based on good results in immunohistochemical applications, YOYO‐1 was chosen for further work. The fluorescence‐intensity of 200 single, morphologically normal spermatozoa in each semen sample were measured in a cytophotometer, means + SD determined and histograms delineated. Of 20 samples from the control group, 17 had markedly higher fluorescence‐intensity than did 7/15 of the suspected infertile men. It is concluded that the DNA of the latter seven samples was less accessible to the dye than was the DNA of the control group. There are cases of infertility known in which there is loss of one or more of the DNA‐binding proteins, which in spermatozoa are mainly (85%) protamines. The relationship between the stainability of the sperm‐DNA and the packaging with DNA‐binding proteins is discussed. Two of the histograms showed abnormalities in the distribution of the fluorescence‐intensities, one sample was extremely fragile and most of the sperm lysed during the staining‐procedure. Five samples showed normal histograms in comparison with the control group.
The political role of illness narratives
Authors: Sakalys Jurate A.
Published: March 2003

The political role of illness narratives

Cultural criticism is used to describe the political role of autobiographical illness narratives or pathographies. In expressing the subjective experience of illness, authors of pathographies illuminate ideological differences between patient and health care cultures, reveal the dominance of health care ideologies, and explicate patients’ moral and political claims. The contributions of these literary works to nursing practice provide direction for relational restructuring. Gadow’s concept of the relational narrative is proposed as a way to restore patient subjectivity and agency and establish the dialogue necessary for cultural pluralism in nursing and health care.
Modelling the vegetation of China using the process‐based equilibrium terrestrial biosphere model BIOME3
Authors: Ni Jian , Sykes Martin T. , Prentice I. Colin , Cramer Wolfgang
Published: March 2003

1 We model the potential vegetation and annual net primary production (NPP) of China on a 10′ grid under the present climate using the processed‐based equilibrium terrestrial biosphere model BIOME3. The simulated distribution of the vegetation was in general in good agreement with the potential natural vegetation based on a numerical comparison between the two maps using the ΔV statistic (ΔV = 0.23). Predicted and measured NPP were also similar, especially in terms of biome‐averages.

2 A coupled ocean–atmosphere general circulation model including sulphate aerosols was used to drive a double greenhouse gas scenario for 2070–2099. Simulated vegetation maps from two different CO2 scenarios (340 and 500 p.p.m.v.) were compared to the baseline biome map using ΔV. Climate change alone produced a large reduction in desert, alpine tundra and ice/polar desert, and a general pole‐ward shift of the boreal, temperate deciduous, warm–temperate evergreen and tropical forest belts, a decline in boreal deciduous forest and the appearance of tropical deciduous forest. The inclusion of CO2 physiological effects led to a marked decrease in moist savannas and desert, a general decrease for grasslands and steppe, and disappearance of xeric woodland/scrub. Temperate deciduous broadleaved forest, however, shifted north to occupy nearly half the area of previously temperate mixed forest.

3 The impact of climate change and increasing CO2 is not only on biogeography, but also on potential NPP. The NPP values for most of the biomes in the scenarios with CO2 set at 340 p.p.m.v. and 500 p.p.m.v. are greater than those under the current climate, except for the temperate deciduous forest, temperate evergreen broadleaved forest, tropical rain forest, tropical seasonal forest, and xeric woodland/scrub biomes. Total vegetation and total carbon is simulated to increase significantly in the future climate scenario, both with and without the CO2 direct physiological effect.

4 Our results show that the global process‐based equilibrium terrestrial biosphere model BIOME3 can be used successfully at a regional scale.
Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1
Authors: Jarnicki A. G. , Thomas W. R.
Published: March 2003

Background The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory.

Objective To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H‐2b and H‐2q mice and the sequences which induce tolerance by intranasal administration of peptides.

Methods T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H‐2b epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope.

Results Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H‐2b and H‐2q mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H‐2b epitope. This was found about a core region of 118–126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross‐reactive.

Conclusions The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described.
The use of a feather quilt, childhood asthma and allergic rhinitis: a prospective cohort study
Authors: Nafstad P. , Nystad W. , Jaakkola J. J. K.
Published: March 2003

Background Feather bedding has long been considered as a potential source of allergen exposure and thus a potential risk factor for allergic diseases. However, recent cross‐sectional studies have reported a higher risk of allergic diseases among users of synthetic bedding compared with feather‐bedding users.

Objective To explore associations between early life exposure to feather bedding and the risk of developing asthma allergic rhinitis in childhood.

Methods We assessed the association between early life exposure to feather quilts and the risk of bronchial obstruction during the first 2 years of life and asthma and allergic rhinitis in a prospective 4‐year cohort study of 2531 Norwegian children.

Results At the age of 6 months, 24% of the children had a quilt with feathers, decreasing to 20% at the age of 2 years. The adjusted odds ratio for bronchial obstruction 0 to 2 years by exposure to a feather quilt at the age of 6 months was 0.59, 95% confidence interval 0.41 to 0.86, for asthma at the age of 4 years 0.38, 0.23 to 0.64 and for allergic rhinitis at the age of 4 years 0.73, 0.43 to 1.18.

Conclusion The use of a feather quilt in early life does not seem to increase the risk of asthma and allergic rhinitis later in childhood.
Ethanol as a cause of hypersensitivity reactions to alcoholic beverages
Authors: Ehlers I. , Hipler U.‐C. , Zuberbier T. , Worm M.
Published: March 2003

Background Adverse reactions after ingestion of alcoholic beverages are common. Metabolic differences in individuals and also the histamine content in alcoholic beverages have been implicated. By contrast pure ethanol has rarely been reported as a cause of hypersensitivity reactions and its mechanism has not been clarified yet.

Objective To determine whether ethanol itself accounts for alcohol hypersensitivity in patients with anaphylactic reactions after alcohol intake. In search of possible pathomechanisms all patients were analysed by skin prick testing and sulfidoleukotriene production of peripheral leucocytes using ethanol and its metabolites.

Methods Double‐blind, placebo‐controlled food challenges with a cumulated amount of 30 mL ethanol were performed in 12 adult patients with a positive history of adverse reactions after consumption of different alcoholic beverages. Skin prick tests and measurement of sulfidoleukotriene production were performed using different concentrations of ethanol and acetaldehyde from 50 to 1000 mm.

Results Oral challenges with pure ethanol were positive in six out of eleven patients. All challenge‐positive patients, but also four out of five challenge‐negative patients, showed an increased sulfidoleukotriene production in‐vitro compared with healthy controls. Skin prick tests using alcoholic beverages, ethanol, acetaldehyde and acetic acid were negative in all patients (12/12).

Conclusion Our study shows that ethanol itself is a common causative factor in hypersensitivity reactions to alcoholic beverages. These reactions occur dose‐dependent and a non‐IgE‐mediated pathomechanism is likely, because skin prick tests were negative in all cases. Increased sulfidoleukotriene production was determined in some patients, but is no reliable predictor. Therefore oral provocation tests remain indispensable in making the diagnosis of ethanol hypersensitivity.
The impact of climate and traffic‐related NO2 on the prevalence of asthma and allergic rhinitis in Italy
Authors: De Marco R. , Poli A. , Ferrari M. , Accordini S. , Giammanco G. , Bugiani M. , Villani S. , Ponzio M. , Bono R. , Carrozzi L. , Cavallini R. , Cazzoletti L. , Dallari R. , Ginesu F. , Lauriola P. , Mandrioli P. , Perfetti L. , Pignato S. , Pirina P. , Struzzo P.
Published: March 2003

Background Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies.

Aim To evaluate to what extent climate and outdoor NO2 pollution can explain the geographical variation in the prevalence of asthma and allergic rhinitis, and to estimate the relative risk for exposure to different levels of these two factors.

Methods The impact of climate and long‐term exposure to nitrogen dioxide (NO2) pollution on asthma and allergic rhinitis was assessed in a cross‐sectional study, carried out during 1998 to 2000 on young adults aged 20 to 44 years (n = 18 873), living in 13 areas from two different Italian climatic regions (subcontinental and Mediterranean).

Results Mediterranean areas had a significantly higher prevalence of asthma‐like symptoms (P < 0.001), higher annual mean temperature (16.2 °C vs. 12.9 °C), lower temperature range (16.0 C° vs. 22.1 C°) and lower NO2 levels (31.46 µg/m3 vs. 57.99 µg/m3) than subcontinental ones. Mediterranean climate was associated with an increased risk of wheeze (OR = 1.23; 95% CI 1.13 to 1.35), tightness in the chest (OR = 1.21; 95% CI 1.11 to 1.33), shortness of breath (OR = 1.21; 95% CI 1.08 to 1.36) and asthma attacks (OR = 1.19; 95% CI 1.07 to 1.31). After adjusting for climate, an increase of 18.3 µg/m3 in NO2 levels moderately increased the risk of asthma attacks (OR = 1.13; 95% CI 0.98 to 1.32), tightness in the chest (OR = 1.11; 95% CI 0.98 to 1.26) and wheeze (OR = 1.11; 95% CI 0.96 to 1.28). When the levels of outdoor NO2 exposure rose, the prevalence of allergic rhinitis increased significantly in the Mediterranean region (OR = 1.38; 95% CI 1.12 to 1.69), but not in the subcontinental one (OR = 1.03; 95% CI 0.83 to 1.28).

Conclusion Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long‐term role for the effect of traffic pollution on asthma is also suggested.
Are Ca2+‐binding motifs involved in the immunoglobin E‐binding of allergens? Olive pollen allergens as model of study
Authors: Ledesma A. , González E. , Pascual C. Y. , Quiralte J. , Villalba M. , Rodríguez R.
Published: March 2003

Background Several Ca2+‐binding proteins, which possess EF‐hand sites with a high sequence similarity, have been found to be able to induce Type‐I allergy.

Objective To study whether the common EF‐hand sequential motifs can be involved in the IgE‐reactivity of these proteins, thus being responsible of a degree of cross‐reactivity among different Ca2+‐binding proteins.

Methods Two olive pollen allergens, Ole e 3 and Ole e 8, have been used in the study. Parvalbumin and calmodulin were included in immunological analyses. Sera from patients allergic to olive pollen, as well as Ole e 3‐ and Ole e 8‐specific rabbit antisera were used in indirect enzyme‐linked immunosorbent assay (ELISA), ELISA inhibition assays and immunobloting. Conformational analyses (circular dichroism spectra and thermal stability) and specific immunodetection assays were performed in the presence and the absence of Ca2+. Chemical breakdown and high‐performance liquid chromatography (HPLC) was used to obtain fragments from Ole e 3 containing a single EF‐hand motif.

Results Thirty‐four (17%) and 16 (8.2%) out of 195 sera from patients allergic to olive pollen contained specific IgE against Ole e 3 and Ole e 8, respectively. The IgE‐binding of 12 allergic sera diminished up to 22% for Ole e 3 and to 82% for Ole e 8, when depleted Ca2+. A pool of these sera recognized the two olive allergens and parvalbumin, but at very different extent. Inhibition of the IgE‐binding was only achieved between two olive allergens. No structural relationships between Ole e 3 and Ole e 8 were established when specific polyclonal antisera against both proteins were used.

Conclusion EF‐hand Ca2+‐binding sites can not be considered as general allergenic motifs responsible for the cross‐reactivity between Ca2+‐binding allergens. Different families of Ca2+‐binding allergens have specific epitopes that could be involved in the cross‐reactivity among members of the same family.
Household characteristics and mite allergen levels in Manchester,UK
Authors: Simpson A. , Simpson B. , Custovic A. , Cain G. , Craven M. , Woodcock A.
Published: March 2003

Background Mite allergen levels vary enormously between different homes in the same geographical area. No large scale studies of mite levels in Manchester homes has been conducted to identify factors associated with higher levels.

Objectives To quantify exposure to mite allergens and to identify characteristics associated with higher Der p 1 levels in a large sample of homes in Manchester, UK.

Methods Der p 1 was measured in dust from the living room floor, sofa, bedroom floor and mattress in 564 homes. Data on household characteristics were collected by administering a questionnaire. Univariate and multivariate analyses were performed to identify household characteristics associated with higher mite allergen levels.

Results Der p 1 levels were highest in the mattress (GM 1.19 µg/g, 95% CI 0.98–1.45, P < 0.001). Two‐thirds of homes contained Der p 1 levels > 2 µg/g in at least one dust reservoir, and 40.3% contained Der p 1 greater than 10 µg/g. There was a large range in Der p 1 levels between homes (> 103‐fold). Damp and condensation were common findings in homes. In the multivariate analyses, factors associated with higher Der p 1 levels in more than one dust reservoir were older homes, older living room carpets, damp, condensation and mixed glazing. Older mattresses were associated with higher mite allergen levels in the mattress where the age of the mattress was recorded. Twenty‐four homes contained no detectable mite allergen, six of which reported damp.

Conclusions Mite allergen levels are high enough in two of every three homes to be associated with an increase in the risk of sensitization to mite. Factors such as older homes, carpets and mattresses, damp and condensation are associated with higher mite allergen. However, mite allergen levels are occasionally unpredictably very low in homes with risk factors for high levels.
The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin‐12: allergen‐induced Th2 bias determined at the dendritic cell level
Authors: Ghaemmaghami A. M. , Gough L. , Sewell H. F. , Shakib F.
Published: March 2003

Background The proteolytic activity of the house dust mite allergen Der p 1 has recently been shown to bias Th cell subset development in favour of Th2. Apart from its direct effect on T cells, it is conceivable that the proteolytic activity of Der p 1 may induce the generation of dendritic cells (DCs) that favour a Th2 response.

Objective To study the effect of the proteolytic activity of Der p 1 on DC functions; namely cell surface phenotype, IL‐12 production and ability to favour a Th2 response.

Methods We have generated immature DCs from peripheral blood monocytes, matured them with LPS in the presence of either proteolytically active or inactive Der p 1 and compared their functions using flow cytometric analysis.

Results Here we demonstrate for the first time that DCs that have been matured in the presence of proteolytically active Der p 1 produce significantly less IL‐12, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. The suppression of IL‐12 production was due to the cleavage of CD40 by the proteolytic activity of Der p 1, hence rendering the DCs less responsive to stimulation through the CD40L‐CD40 pathway. Furthermore, we demonstrate that DCs that have been matured in the presence of proteolytically active Der p 1 induce the production of significantly less IFN‐γ and more IL‐4 by CD4 T cells, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1.

Conclusions Collectively, our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in directing DCs to induce Th2 subset development.
Clinical and immunologic parameters during thalidomide treatment of lupus erythematosus
Authors: Walchner Monika ,   md, Meurer Michael ,   md, Plewig Gerd ,   md, Messer Gerald ,   md
Published: March 2003

Background Thalidomide is used as an experimental drug for the treatment of chronic inflammatory diseases with an autoimmune or infectious background. The pharmacologic action involves the downregulation of the pro‐inflammatory cytokine tumor necrosis factor‐α (TNF‐α) and inhibition of basic fibroblast growth factor (bFGF)‐induced angiogenesis; however, not much is known about thalidomide's effect on immunologic parameters in lupus erythematosus (LE).

Method This is an open study of a group of five consecutive systemic lupus erythematosus (SLE) patients treated with thalidomide (100 mg/day) and five consecutive cutaneous LE patients not responsive to conventional therapy. The clinical and immunologic parameters (C‐reactive protein, immunoglobulin, and complement serum levels, lymphocyte counts) were investigated during thalidomide treatment for up to 2 years in both patient groups.

Results An increase in the absolute peripheral lymphocyte count was observed beginning after 2 weeks of systemic thalidomide treatment in nine out of 10 LE patients, and remained stable throughout thalidomide treatment. Elevated serum levels of C‐reactive protein and titers of autoantibodies to double‐stranded (ds) DNA decreased in SLE patients. No significant changes were detected in the serum levels of the complement components C3 and C4 and immunoglobulins in all LE patients. Regression of inflammatory skin lesions and regrowth of hair were recorded. As a side‐effect, polyneuropathy was observed in four out of 10 patients, with the earliest onset at 3 weeks of thalidomide treatment.

Conclusions Thalidomide is a potent anti‐inflammatory drug in patients with SLE and cutaneous LE, possibly interacting with the recruitment of lymphocytes. It leads to the regrowth of hair in LE‐related alopecia and effluvium. Early symptoms of polyneuropathy should be registered and the drug should be withdrawn. Thalidomide should be restricted to patients who show no response to standard therapeutic regimens and should only be used under strict precautions with regard to its known teratogenic risk.
Do we need to devalue Amazonia and other large tropical forests?
Authors: Bates John M. , Demos Terrence C.
Published: March 2003

Attempts to determine global priorities for conservation and studies aimed at highlighting the conservation value of one continental region over another often devalue specific regions. Amazonia has been a particular recipient of this treatment in a number of recent studies. We suggest that this type of approach is not necessary at this scale, and we argue that the consequences could be devastating for the largest forests of the world. Among our concerns about the treatment of these forests (Amazonia, the Congo Basin and New Guinea) is that there seems to be a lack of appreciation for, or sufficient study of, important biogeographic subdivisions within these regions. In Amazonia, the south‐eastern portion of the basin (the Belém/Pará region) has not been considered a global conservation priority, despite the fact that it is experiencing by far the highest deforestation rates. Parsimony Analyses of Endemicity and genetic data suggest that many Amazonian forest taxa are comprised of numerous regionally distinct units, and this may also be true in other large tropical forests. Such patterns need to be documented for adequate conservation of tropical biodiversity, but this might not happen if these regions are not recognized as priorities for conservation at a global scale.
Quality of care from the patients' perspective: from theoretical concept to a new measuring instrument
Authors: Sixma Herman J. , Kerssens Jan J. , Campen Crétien van , Peters Loe
Published: March 2003

Introduction

Patient views on quality of care are of paramount importance with respect to the implementation of quality assurance (QA) and improvement (QI) programmes. However, the relevance of patient satisfaction studies is often questioned because of conceptual and methodological problems. Here, it is our belief that a different strategy is necessary.

Objective

To develop a conceptual framework for measuring quality of care seen through the patients' eyes, based on the existing literature on consumer satisfaction in health care and business research.

Results

Patient or consumer satisfaction is regarded as a multidimensional concept, based on a relationship between experiences and expectations. However, where most health care researchers tend to concentrate on the result, patient (dis)satisfaction, a more fruitful approach is to look at the basic components of the concept: expectations (or `needs') and experiences. A conceptual framework – based on the sequence performance, importance, impact – and quality judgements of different categories of patients derived from importance and performance scores of different health care aspects, is elaborated upon and illustrated with empirical evidence.

Conclusions

The new conceptual model, with quality of care indices derived from importance and performance scores, can serve as a framework for QA and QI programmes from the patients' perspective. For selecting quality of care aspects, a category‐specific approach is recommended including the use of focus group discussions.