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Biomedical subjects

C Wild

Publications and source records attributed to C Wild.

At least 19 recordsLinked to original sources
PubMed2007

A recombinant allergen chimer as novel mucosal vaccine candidate for prevention of multi-sensitivities.

BACKGROUND: As conventional immunotherapy is less efficacious in patients with allergic multi-sensitivities compared with mono-sensitized subjects, new intervention strategies are needed. Therefore, an allergen chimer was genetically engineered for treatment of multi-sensitization with birch and grass pollen on the basis of mucosal tolerance induction. METHODS: The major birch pollen allergen Bet v 1 served as a scaffold for N- and C-terminal linkage of the immunodominant peptides of the grass pollen allergens Phl p 1 and Phl p 5 and this new construct was cloned and expressed in Escherichia coli. After purification, physicochemical and immunological characterization the chimer was used for intranasal tolerance induction prior to poly-sensitization with Bet v 1, Phl p 1 and Phl p 5. RESULTS: The immunological characterization revealed that the conformation of Bet v 1 within the chimer was comparable to that of natural as well as recombinant Bet v 1. The chimer was immunogenic in mice for T and B cell responses to the three allergens. Intranasal application of the chimer prior to poly-sensitization significantly suppressed humoral and cellular allergen-specific Th2 responses and prevented development of airway inflammation upon allergen challenge. Moreover, local allergen-specific IgA antibodies were induced by the chimer. The mechanisms of poly-tolerance induction seemed to be mediated by regulatory cytokines, since TGF-beta and IL-10 mRNA in splenocytes were upregulated and tolerance was transferable with these cells. CONCLUSION: The data indicate that such allergen chimers harboring several unrelated allergens or allergen peptides could serve as mucosal polyvalent vaccines for prevention of multi-sensitivities.

Administration, Intranasal↗
PubMed2006

[Health technology assessment: Critical scientific methods for evaluating the effects of medical interventions].

In all western countries health care budgets are under considerable constraint and therefore a reflection process has started on how to gain the most health benefit for the population within limited resource boundaries. The field of health technology assessment (HTA) has evolved over the last 15 years in order to bring some objectivity and rationality in the discussion and to evaluate health interventions systematically not only under clinical, but also under economic and organisational perspectives. The research area is internationally well established and is being used increasingly more in Austria and Germany. In this article the method of HTA and its general applications as well its explosive nature are presented.

Austria↗
PubMed2006

Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1.

BACKGROUND: Probiotic lactic acid bacteria (LAB) are able to modulate the host immune system and clinical trials have demonstrated that specific strains have the capacity to reduce allergic symptoms. Therefore, we aimed to evaluate the potential of recombinant LAB producing the major birch pollen allergen Bet v 1 for mucosal vaccination against birch pollen allergy. METHODS: Recombinant Bet v 1-producing Lactobacillus plantarum and Lactococcus lactis strains were constructed. Their immunogenicity was compared with purified Bet v 1 by subcutaneous immunization of mice. Intranasal application of the live recombinant strains was performed to test their immunomodulatory potency in a mouse model of birch pollen allergy. RESULTS: Bet v 1 produced by the LAB was recognized by monoclonal anti-Bet v 1 and IgE antibodies from birch pollen-allergic patients. Systemic immunization with the recombinant strains induced significantly lower IgG1/IgG2a ratios compared with purified Bet v 1. Intranasal pretreatment led to reduced allergen-specific IgE vs enhanced IgG2a levels and reduced interleukin (IL)-5 production of splenocytes in vitro, indicating a shift towards non-allergic T-helper-1 (Th1) responses. Airway inflammation, i.e. eosinophils and IL-5 in lung lavages, was reduced using either Bet v 1-producing or control strains. Allergen-specific secretory IgA responses were enhanced in lungs and intestines after pretreatment with only the Bet v 1-producing strains. CONCLUSIONS: Mucosal vaccination with live recombinant LAB, leading to a shift towards non-allergic immune responses along with enhanced allergen-specific mucosal IgA levels offers a promising approach to prevent systemic and local allergic immune responses.

Administration, Intranasal↗
PubMed2006

Successful treatment of life-threatening bleeding after cesarean section with recombinant activated factor VII.

Hemorrhagic shock developed in a 29-year-old nullipara without coagulopathy after emergency caesarean section. Treatment with uterotonic drugs, prostaglandins, and conservative procedures with transfusion of packed red cells and fresh-frozen plasma failed to control the diffuse vaginal and uterine bleeding. Finally an intravenous bolus injection of 90 microg/kg recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark), was given and showed success within 20 minutes after administration, without any side effects.

Adult↗
PubMed2005

The Barrow-in-Furness legionnaires' outbreak: qualitative study of the hospital response and the role of the major incident plan.

OBJECTIVE: To document the organisational response of Furness General Hospital to the large outbreak of legionnaire's disease in April 2002 and assess the contribution made by the hospital's major incident plan. METHOD: Qualitative analysis of interview transcripts and written comments from some staff involved in the management of the incident. Documentary analysis of major incident plan and other written materials. RESULTS: The incident posed considerable managerial and clinical problems and this paper describes how they were overcome. In particular, strategies for dealing with supply (of staff, beds, and resources) and managing demand (by liaising with primary care and the public) seem to have been successful. Many functions necessary for managing the incident were poorly dealt with in the plan, especially procedures for handling the news media and liaison with agencies outside the hospital. Lack of explicit guidance appeared not to hinder the organisational response. There may have been an unspoken high level decision to allow staff to draw on their skills and experience in improvising a response to the initial challenge and learning adaptively as the incident unfolded. There was also evidence that staff disregarded existing job and role boundaries and focused instead on tasks, working flexibly to ensure that these tasks were completed. CONCLUSIONS: Protracted major incidents pose particular management challenges and may benefit from an approach different from that set out in typical major incident plans. Staff must be able to act flexibly and responsively. Some form of checklist or toolkit may be preferable to a detailed plan for some types of incident.

Attitude of Health Personnel↗
PubMed2004

Three-dimensional hydrogen microscopy in diamond.

A microprobe of protons with an energy of 17 million electron volts is used to quantitatively image three-dimensional hydrogen distributions at a lateral resolution better than 1 micrometer with high sensitivity. Hydrogen images of a <110>-textured undoped polycrystalline diamond film show that most of the hydrogen is located at grain boundaries. The average amount of hydrogen atoms along the grain boundaries is (8.1 +/- 1.5) x 10(14) per square centimeter, corresponding to about a third of a monolayer. The hydrogen content within the grain is below the experimental sensitivity of 1.4 x 10(16) atoms per cubic centimeter (0.08 atomic parts per million). The data prove a low hydrogen content within chemical vapor deposition-grown diamond and the importance of hydrogen at grain boundaries, for example, with respect to electronic properties of polycrystalline diamond.

Journal Article↗
PubMed2004

Analgesia for day-case shoulder surgery.

BACKGROUND: Single-shot nerve blocks provide excellent postoperative analgesia for a limited period and are increasingly used in day-case units. They allow early patient discharge following painful operative procedures that would otherwise require overnight hospitalization. We investigated the adequacy of analgesia at home after the block had worn off. METHODS: A prospective audit by telephone 1 week after surgery of 50 consecutive patients who had had a single-shot interscalene block for day-case shoulder arthroscopic surgery. RESULTS: The mean length of adequate sensory block was 22.5 h (9-48 h) after which 20% of patients had a maximum visual analogue scale (VAS) score of 5/5. Most patients did not take analgesics as prescribed and two patients (5.4%) required additional analgesia from their family doctor or accident and emergency department. CONCLUSIONS: We conclude that analgesia at home is often inadequate after painful day-case surgical procedures if single-shot local anaesthetic blockade is used.

Ambulatory Surgical Procedures↗
PubMed2004

[Me-too pharmaceuticals -- marketing-strategies of drug producers and drug purchasers. Example: non-ionic contrast media].

UNLABELLED: In the context of increasing economic pressure upon on hospital budgets, it is inevitable that central and standardized purchasing of pharmaceuticals must be considered. It was the aim of this assessment to analyse the many different non-ionic contrast media/CM products on the actual "clinical relevance of the differences" in order to give advice for a more concerted purchasing of CM. The assessment was commissioned by a large scale Austrian hospital cooperation; it can be regarded as the beginning of a broad strategy against the many new, only rarely innovative, but nevertheless patent-protected pharmaceuticals. Eight different non-ionic contrast media - used in routine care - were compared for their physico-chemical characteristics: osmolality, nephrotoxicity, viscosity, hydrophilicity and electric charge. In a systematic review 193 publications were analysed. RESULT: The examined CM show similar pharmacokinetic and -dynamic attributes, and no differences of clinical relevance. An optimisation of purchasing pharmaceuticals by standardisation of the range of products takes place in the context of common strategies of producers and buying agents in marketing-economies. The strategies of the pharmaceutical industry (patent protection of me-too drugs, high-price-policy, extensive marketing of up to 40 % of revenue) and the counter-strategies of the central hospital purchasers (market concentration, drug commissions, institutional measures to disentangle interests) are presented - exemplified by contrast media - in this article.

Austria↗
PubMed2004

Influence of the route of sensitization on local and systemic immune responses in a murine model of type I allergy.

The pathophysiological and immunological characteristics of allergic immune responses are controlled by a variety of factors. We have studied the extent to which the route of sensitization influences allergen-specific IgE synthesis and local airway inflammation using a mouse model of allergic sensitization to the major birch pollen allergen Bet v 1. Sensitization of BALB/c mice with recombinant (r)Bet v 1 was performed using intraperitoneal (i.p.), subcutaneous (s.c.) or aerosol (a.s.) sensitization protocols. Mice were analysed for allergen-specific serum antibodies by ELISA and IgE-dependent basophil degranulation. Proliferative responses and cytokine production of splenocytes were measured upon Bet v 1 stimulation in vitro. Bronchoalveolar lavages were performed after airway challenge with aerosolized birch pollen extract for assessment of eosinophilic airway inflammation and local cytokine production in vivo. Highest allergen specific IgE levels and IgE-dependent basophil degranulation were achieved using the SC route. High IL-5 production by spleen and lung cells was associated with pronounced eosinophilia in bronchoalveolar lavages. After i.p. sensitization, despite giving the highest IgG levels, only low IgE levels, basophil degranulation and IL-5 production were seen. On the other hand, a.s. sensitization, resulting in the lowest systemic IgE and IL-5 levels, led to a comparably strong airway inflammation as the s.c. route. Our finding that the route of sensitization can result in a dissociation of local and systemic immune responses may contribute to a better understanding of the pathogenesis of allergic diseases and help to develop new treatment strategies.

Aerosols↗
PubMed2003

[To what extent can the publicly sponsored health system afford predictive genetic diagnostics?--first approaches to pinpoint and limit responsibilities, exemplified by hereditary carcinomas].

Present predictive genetic tests for widespread multicausal and chronic conditions such as carcinoma and in the near future heart diseases and neurodegenerative conditions, urge their way into the health care system. In health care a change of the paradigm takes place: from caring for sick individuals to counselling and taking care of healthy persons and families burdened by a hereditary disposition. Essential for health care services is the question of actual advantage of the genetic tests for individuals, families as well as for society, and closely associated with the medical consequences of the tests. Decision makers in the financing of health care services are faced by the challenge to create a generally valid regulatory framework applicable for inclusion or refusal of present and future genetic tests by public health care services. Of relevance for those decisions are the questions whether the genetic tests make a difference in the impediment and primary prevention of disease, and the possibilities for successful early treatment.

Adult↗
PubMed2001

Anti-AIDS agents. Part 47: Synthesis and anti-HIV activity of 3-substituted 3',4'-Di-O-(S)-camphanoyl-(3'R,4'R)-(+)-cis-khellactone derivatives.

Six 3-substituted 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone derivatives (3-8) were synthesized from 3-methyl DCK (2). 3-Hydroxymethyl DCK (6) exhibited potent anti-HIV activity in H9 lymphocytes with EC(50) and TI values of 1.87 x 10(-4) microM and 1.89 x 10(5), respectively. These values are similar to those of DCK and better than those of AZT in the same assay.

Anti-HIV Agents↗
PubMed2001

Screening in Austria: the cases of mammography, PSA testing, and routine use of ultrasound in pregnancy.

OBJECTIVE: To study cases of screening in Austria to learn about national strategies to handle the health policy challenge of early detection of widespread diseases and about the outcome of those strategies. The article describes three healthcare interventions (mammography, PSA testing, and routine use of ultrasound in pregnancy) and the instruments of Austrian health policy that are used-with or without explicit intention-to enforce or to control the widespread use of (early) diagnoses. METHODS: Data and information collection on healthcare services, their accessibility, rate of use, expert consensus, and official regulations. For all three case studies, expert interviews were carried out with main actors. RESULTS: Risk-group screening is not a priority in Austrian federal health policy. Although health promotion and prevention is a national task, examinations for early detection of specific diseases (i.e., carcinoma) are left to the health insurance funds, which delegate the decision to offer early diagnoses to their contracted physicians. In this opportunistic screening, general practitioners or specialists are encouraged by their health insurance funds or motivated by professional guidelines to offer certain examinations. CONCLUSIONS: Screening is a coordinated effort to acquire a grasp of a common disease at an early stage in a specified population. To achieve this objective, a culture of coordination and centralization has to be implemented. The collection of data is an essential element in coordination of decentralized medical interventions as much as quality control is an essential task in looking at and comparing the outcome of interventions. In the three case studies, neither of these two essential criteria were met. Evaluations and scientific evidence on the effectiveness of interventions were not used.

Adult↗
PubMed2001

[Health policy decisions between rationing and rationalization--exemplified by erythropoietin in tumor anemia].

The debate on rationalisation vs. rationing of health care interventions is of great importance for the shaping of social and health care policies. Nevertheless, concrete evaluations mostly deal with health interventions in the grey zone between rationing--withholding effective measures--and rationalisation--avoiding ineffective interventions. The assessment of erythropoietin in tumour anaemia is presented as an example: the results of the treatment of tumour-induced anaemia with EPO are partly unsatisfactory. Only 50-60% of anemic tumor-patients respond to EPO; of these responders 20-30% still require transfusions. The assessment presents the evidence for an "appropriate" application of erythropoietin in tumour anaemia and proposes standard values for a limited access and use of EPO. Additionally the assessment reveals what is known as the benefit of this treatment, and what is questionable. Applying the results of the assessment to clinical practice can be considered as "explicit rationing" according to effectiveness criteria.

Anemia↗
PubMed2001

Induction of potent immune responses by cationic microparticles with adsorbed human immunodeficiency virus DNA vaccines.

The effectiveness of cationic microparticles with adsorbed DNA at inducing immune responses was investigated in mice, guinea pigs, and rhesus macaques. Plasmid DNA vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto the surface of cationic poly(lactide-coglycolide) (PLG) microparticles were shown to be substantially more potent than corresponding naked DNA vaccines. In mice immunized with HIV gag DNA, adsorption onto PLG increased CD8(+) T-cell and antibody responses by approximately 100- and approximately 1,000-fold, respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG, antibody responses showed a more rapid onset and achieved markedly higher enzyme-linked immunosorbent assay and neutralizing titers than in animals immunized with naked DNA. Further enhancement of antibody responses was observed in animals vaccinated with PLG/DNA microparticles formulated with aluminum phosphate. The magnitude of anti-Env antibody responses induced by PLG/DNA particles was equivalent to that induced by recombinant gp120 protein formulated with a strong adjuvant, MF-59. In guinea pigs immunized with a combination vaccine containing HIV env and HIV gag DNA plasmids on PLG microparticles, substantially superior antibody responses were induced against both components, as measured by onset, duration, and titer. Furthermore, PLG formulation overcame an apparent hyporesponsiveness of the env DNA component in the combination vaccine. Finally, preliminary data in rhesus macaques demonstrated a substantial enhancement of immune responses afforded by PLG/DNA. Therefore, formulation of DNA vaccines by adsorption onto PLG microparticles is a powerful means of increasing vaccine potency.

AIDS Vaccines↗
PubMed2001

Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140.

The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015-3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication.

AIDS Vaccines↗
PubMed2000

Health technology assessment in Austria.

The Austrian healthcare system relies mainly on physicians in private practice and on various services provided by hospitals. The social health insurance scheme is compulsory, covering 99% of the population. The system is very decentralized. While the federal state provides the framework, the nine autonomous provinces are responsible for administering health and social services. There is ongoing public discussion about centralizing the healthcare system to make it more efficient and to enforce structural reforms. Because of concerns about healthcare expenditures, in 1997 the Performance-Related Hospital Financing System (LKF), a system similar to the diagnosis-related group system, was introduced for hospitals, including a plan for large medical devices. It is too early to evaluate the success of this new system, although some effects of the LKF system that could have been anticipated, such as shortened lengths of stay and more hospitalizations, have been seen. Previously, health technologies have been almost uncontrolled in Austria. The evaluation of health technologies as an instrument to support or to control their dissemination and use or to help define policies is not institutionalized or systematically used. It seems clear that structural reforms of the Austrian healthcare system are needed. Health technology assessment should be part of such reforms.

Austria↗
PubMed2000

Extracorporeal shock wave therapy in orthopedics. Assessment of an emerging health technology.

OBJECTIVE: Extracorporeal shock wave therapy (ESWT) as an emerging technology in orthopedics has been assessed in Austria with the objective to establish a scientific basis for pending and pressing health policy decisions. Despite encouraging results within some indications and the promising prospect of a noninvasive treatment for some orthopedic diseases, it seemed crucial to assess this new field of application in the light of evidence-based standards, without forgetting the reality of healthcare decisions. This article presents the results of the above mentioned assessment in the context of the policy-making process in Germany, Austria, and Switzerland. METHODS: The study is based on an overview of the already existing reviews on the effectiveness of ESWT as carried out by different actors (health insurances and orthopedists), and on an overview of additional literature covering all relevant aspects (mode of action, recommendations, economic estimates). Orthopedic societies, several institutions involved in health technology assessment, and health insurance agencies were contacted in search of further relevant literature, ongoing studies, and assessments. RESULTS: Until now, clear evidence has not been available on the effectiveness of ESWT in four currently recommended indications (tendinosis calcarea of the shoulder, epicondylopathia humeri radialis, calcaneal spur, and pseudarthrosis), although a substantial body of literature has been produced. Despite encouraging results in some indications, the lack of coherent therapy schemes and the poor quality in the design of clinical studies has been serious enough to hinder the drawing of reasonable conclusions. CONCLUSIONS: Due to the rapid diffusion of ESWT and the pressure on reimbursement agencies to prove the ineffectiveness of ESWT, the policy option of a pragmatic approach is recommended to control the diffusion of an uncertain health technology, alongside active research that would allow a more comprehensive appraisal of this potentially interesting treatment strategy in orthopedics.

Austria↗