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D Simon

Publications and source records attributed to D Simon.

At least 19 recordsLinked to original sources
PubMed2007

[Anti-interleukin-5 therapy for eosinophilic diseases].

In a number of diseases with eosinophilia, elevated interleukin (IL)-5 levels are detected in the peripheral blood and/or tissues. IL-5 plays an important role in regulating the production, differentiation, recruitment, activation, and survival of eosinophils. Therefore, neutralizing IL-5 by blocking antibodies seems a promising approach in the treatment of eosinophilic diseases. Clinical trials have demonstrated that anti-IL-5 therapy results in a rapid decrease in peripheral blood eosinophil numbers. Moreover, improvement of symptoms in patients with lymphocytic variants of hypereosinophilic syndromes, in eosinophilic esophagitis and chronic rhinitis with nasal polyposis has been observed. In contrast, in patients with bronchial asthma or atopic eczema, anti-IL-5 therapy showed only moderate or no clinical effects. Future studies will have to identify those eosinophilic diseases in which anti-IL-5 antibodies are effective, perhaps with the help of newly developed biomarkers.

Animals↗
PubMed2006

Linear and nonlinear optical response of aromatic amino acids: a time-dependent density functional investigation.

The linear and nonlinear optical responses of the three aromatic amino acids tryptophan, tyrosine, and phenylalanine have been investigated by time-dependent density functional theory. The effect of the peptidic chain on the polarizabilities and the first hyperpolarizabilities is addressed by substituting different groups to the chromophores indole, phenol, and benzene. The optimized structures are in very good agreement with the experimental results. Furthermore, the calculated polarizabilities are found to match well with the empirical results, showing the evolution obtained as the chain is lengthened. A systematic and constant increase of the polarizability is found, for the three chromophores, for the various chain lengths. The first hyperpolarizability is also noticeably modified by the chains, but the evolution of this quantity is found to be more dependent on the system considered. Finally, it is suggested that each of the three aromatic amino acids has a significant contribution to the nonlinear response of proteins.

Amino Acids, Aromatic↗
PubMed2006

Development and first validation of the shared decision-making questionnaire (SDM-Q).

OBJECTIVE: Due to a lack of valid German instruments measuring shared decision-making (SDM), a theory-driven questionnaire (SDM-Q) to measure the process of SDM was developed and validated. METHODS: As a theoretical basis steps of the SDM process were defined in an expert panel. Item formulation was then conducted according to the Delphi method. For the first validation on a mixed sample Rasch analysis was used to eliminate items not fitting the construct thus receiving a unidimensional scale. RESULTS: After eliminating 4 items the remaining 11 form a unidimensional scale with an acceptable reliability for person measures (0.77) and very good reliability for item difficulties (0.95). Analysis of subgroups revealed a different use of items in different conditions. Furthermore the scale showed high ceiling effects. CONCLUSION: A new theory-driven instrument to measure the process of SDM has been developed and validated by use of a rigorous method revealing first promising results. Yet the ceiling effects require the addition of more discriminating items, and the different use of items in different conditions demands an in depth analysis. PRACTICE IMPLICATIONS: While the concept of SDM is constantly receiving more attention in medical practice, its valid and reliable measurement remains challenging.

Decision Making↗
PubMed2006

Intermittent recombinant growth hormone treatment in short children born small for gestational age: four-year results of a randomized trial of two different treatment regimens.

BACKGROUND: Treatment of short children born small for gestational age SGA with recombinant human growth hormone r-hGH increases growth velocity during childhood. As in other indications, the growth velocity in these patients is more marked during the first year of treatment and then decreases. This study was undertaken to evaluate the efficacy of different r-hGH treatment schedules (67 microg/kg/day in a discontinuous or continuous regimen) during the second year of r-hGH treatment by comparing height velocity changes and total gain of height over a 4-year period. METHODS: 58 growth-retarded SGA children aged 2-5 years were randomized to a TOTO regimen (4 years alternating treatment (T) and observation (O), n = 30) or a TTOO regimen (2 years' treatment, followed by 2 years' observation, n = 28). Height velocity HV and total height gain were assessed during the 4-year study. RESULTS: In both groups, HV and HV standard deviation score HV-SDSCA increased during treatment and decreased during observation periods. Interruption of treatment in the TOTO group did not result in a better gain in height standard deviation score H-SDSCA when compared with the TTOO group. After 4 years of study, the gain in H-SDSCA was 1.4 + or - 01 in the TOTO group and 1.6 + or - 0.2 in the TTOO group leading to a mean height of -2.0 + or - 1.0 SDS and -2.0 + or - 0.8 SDS, respectively. The rate of bone maturation was similar in the two groups. CONCLUSIONS: In short SGA children, TOTO and TTOO regimens produced significant improvements in growth during r-hGH treatment. However, treatment interruption after 1 year did not influence the overall gain in height SDS when compared with 2 years' continuous treatment.

Body Height↗
PubMed2006

Water solvent effect on the first hyperpolarizability of p-nitrophenol and p-nitrophenylphosphate: a time-dependent density functional study.

The first hyperpolarizabilities of p-nitrophenol and p-nitrophenylphosphate have been investigated in vacuum and in neutral aqueous solution by means of time-dependent density functional theory. The calculated excited states and hyperpolarizabilities obtained for these systems and for the molecules of phenol, nitrobenzene, and p-nitroaniline in vacuum match well with the experimental trends. The water solvent has been described by the conductorlike screening model and has been completed by water molecules interacting by hydrogen bonds with the solute. The results show a significant effect of the solvent on the first hyperpolarizability. In particular, the hyperpolarizability of p-nitrophenylphosphate (6.78 x 10(-30) esu) in vacuum is only 1.2 times larger than p-nitrophenol (5.63 x 10(-30) esu), whereas it is almost twice higher in aqueous environment, 12.6 x 10(-30) and 6.5 x 10(-30) esu, respectively. This difference in the nonlinear response in neutral water makes the p-nitrophenylphosphate substrate a suitable probe for measuring the activity of alkaline phosphatase enzymes.

Journal Article↗
PubMed2006

[Pemphigoid nodularis triggered by hypereosinophilic syndrome?].

Pemphigoid nodularis (PN) is a rare clinical variant of pemphigoid characterized by prurigo-like skin lesions and antibodies against BP180 and BP230 characteristic for bullous pemphigoid. Interestingly, most PN patients never develop blisters. This condition is often resistant to treatment. We describe a female patient who was initially diagnosed with hypereosinophilic dermatitis. Later on, in the presence of eosinophilic infiltrations in the gastrointestinal tract, obstructive ventilation disorder, pericardial and pleural effusions, the diagnosis of idiopathic hypereosinophilic syndrome was made. During the following 3 years she developed recalcitrant PN.

Aged↗
PubMed2006

Glucose intolerance and other cardiovascular risk factors in Haiti. Prevalence of Diabetes and Hypertension in Haiti (PREDIAH).

AIMS: To assess the prevalence of diabetes and other forms of glucose intolerance and to examine their relationship with some cardiovascular risk factors in a population representative of the capital of Haiti. METHODS: This cross-sectional survey was conducted in the metropolitan area of Port-au-Prince, Haiti. A population-based sample of 1620 adults was randomly selected using a two-stage cluster method, stratified in 3 age groups: 20-39, 40-64 and > or =65 years of age. Diagnosis of diabetes and pre-diabetes (IFG and IGT) was based on the 2003 Expert Committee criteria. RESULTS: The total response rate was 69%. The age-standardized prevalence of diabetes was 4.8% in men and 8.9% in women (P=0.0014), with, overall, 70.6% of previously diagnosed cases. Standardized for the Segi world population aged 30-64 years, its prevalence was 7.4% in men and 11.1% in women (NS). The age-standardized prevalence of pre-diabetes was 6.4% in men and 8.0% in women (NS). Hypertension was found in 48.7% in men and 46.5% in women (NS). Its rates in people > or =40 years old were 69.1% in men and 67.2% in women (NS). Abdominal obesity was strongly independently associated with diabetes and pre-diabetes in both genders. Hypertension was shown to be risk factor for pre-diabetes and total glucose intolerance in women. High education was associated with lower risk of diabetes in men. CONCLUSION: Prevalence of diabetes and pre-diabetes is moderately high in Port-au-Prince, Haiti. In people aged > or =40 years, the rate of normal blood pressure is less than 25%. Intervention programs to prevent simultaneously and manage diabetes and hypertension are imperative, and prevention strategies through lifestyle modifications should be cost-effective.

Adult↗
PubMed2006

EAACI/GA2LEN/EDF guideline: management of urticaria.

This guideline is the result of a consensus reached during a panel discussion at the second International Consensus Meeting on Urticara, Urticaria 2004, a joint initiative of the EAACI Dermatology Section and GA2LEN. Urticaria has a profound impact on the quality of life, and effective treatment is therefore required. The recommended first line treatment are nonsedating H1 antihistamines. They have proven to be effective in double-blind controlled studies, but dosages increased up to fourfold over the recommended doses may be necessary. However, for different urticaria subtypes and in view of individual variation in the course of the disease and response to treatment, additional or alternative therapies may be required. Immunosuppressive drugs like cyclosporin A and corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and formally approved by the European Union of Medical Specialists (UEMS).

Anti-Allergic Agents↗
PubMed2006

EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis of urticaria.

This guideline is the result of a consensus reached during a panel discussion at the 2nd International Consensus Meeting on Urticaria, Urticaria 2004, a joint initiative of the European Academy of Allergology and Clinical Immunology Dermatology Section and the European Union (EU)-funded network of excellence, GA2LEN. It covers the definition and classification of urticaria, taking into account the recent progress in identifying causes, eliciting factors and pathomechanisms of this disease. We have outlined useful diagnostic approaches for different subtypes of urticaria. This guideline was, in addition, accepted by the European Dermatology Forum (EDF) and was formally approved by the European Union of Medical Specialists (UEMS).

Allergens↗
PubMed2006

Eosinophilic esophagitis in adults--no clinical relevance of wheat and rye sensitizations.

BACKGROUND: Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases. In children with EE in whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. Most adult EE patients are sensitized to aeroallergens, which cross-react with plant-derived food allergens, most commonly to grass pollen and cereals. AIMS OF THE STUDY: To investigate the clinical relevance of the sensitization to wheat and rye, and the efficacy of an allergen-specific elimination diet in adult EE patients. METHODS: Six patients (five men, one women) with permanently active EE sensitized to grass pollen and the cereals wheat and rye underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet avoiding wheat and rye for 6 weeks. RESULTS: The challenge tests with wheat and rye did not provoke any EE symptoms in all patients. The elimination diet failed in reducing disease activity. Although one patient noticed an improvement of symptoms, endoscopic and histopathologic findings remained unchanged. CONCLUSIONS: In adult EE patients, sensitization to wheat and rye does not seem causative for EE. Elimination diet is not a reliable and efficient therapeutic measure in EE patients sensitized to wheat and rye. Low specific immunoglobulin-E levels to wheat and rye may be a consequence of the underlying grass pollen allergy.

Adult↗
PubMed2006

Assessment of diabetes screening by general practitioners in France: the EPIDIA Study.

AIM: To audit Type 2 diabetes screening in general practice in France and to determine the frequency of undiagnosed diabetes in patients at high risk, after systematic screening and diagnosis. METHODS: For this study, 288 general practitioners volunteered to include all consecutive non-diabetic patients aged < 65 years who had at least two risk factors for diabetes, whatever the reason for consultation. If a plasma glucose had not been recorded in the previous 12 months, a fasting plasma glucose (FPG) was performed, with a second test if FPG >or= 7.0 mmol/l. RESULTS: There were 5950 patients included. The most frequent diabetes risk factors were: age >or= 40 years, 92%; overweight [body mass index (BMI) >or= 27 kg/m2], 59%; treated hypertension, 48%; treated dyslipidaemia, 37%; family history of diabetes, 24%. Of these subjects at high risk for diabetes, 88% had a FPG measurement in their medical record (75% measured during the preceding 12 months). In the 1499 patients in whom FPG was measured, diabetes was diagnosed in 40 patients (2.7% 95% CI 1.9-3.5) and 22% had impaired fasting glucose (IFG). Thus, the frequency of undiagnosed diabetes in the 5950 high-risk patients was 0.67% (0.46-0.88). CONCLUSION: Screening for diabetes by general practitioners in France appears to be adequate and undiagnosed diabetes is rare in patients with risk factors for diabetes, at least in those consulting the general practitioners studied.

Blood Glucose↗
PubMed2005

Quasielastic 3He(e,e'p)2H reaction at Q2 = 1.5 GeV2 for recoil momenta up to 1 GeV/c.

We have studied the quasielastic 3He(e,e(')p)2H reaction in perpendicular coplanar kinematics, with the energy and the momentum transferred by the electron fixed at 840 MeV and 1502 MeV/c, respectively. The 3He(e,e(')p)2H cross section was measured for missing momenta up to 1000 MeV/c, while the A(TL) asymmetry was extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150 MeV/c, the cross section is described by variational calculations using modern 3He wave functions. For missing momenta from 150 to 750 MeV/c, strong final-state interaction effects are observed. Near 1000 MeV/c, the experimental cross section is more than an order of magnitude larger than predicted by available theories. The A(TL) asymmetry displays characteristic features of broken factorization with a structure that is similar to that generated by available models.

Journal Article↗
PubMed2005

Measurement of the 3He(e,e'p)pn reaction at high missing energies and momenta.

Results of the Jefferson Lab Hall A quasielastic 3He(e,e'p)pn measurements are presented. These measurements were performed at fixed transferred momentum and energy, q=1502 MeV/c and omega=840 MeV, respectively, for missing momenta p(m) up to 1 GeV/c and missing energies in the continuum region, up to pion threshold; this kinematic coverage is much more extensive than that of any previous experiment. The cross section data are presented along with the effective momentum density distribution and compared to theoretical models.

Journal Article↗
PubMed2005

Efficient and fast targeted production of murine models based on ENU mutagenesis.

Mice with targeted genetic alterations are the most effective tools for deciphering organismal gene function. We generated an ENU-based parallel C3HeB/FeJ sperm and DNA archive characterized by a high probability to identify allelic variants of target genes as well as high efficiencies in allele retrieval and model revitalization. Our archive size of over 17,000 samples contains approximately 340,000 independent alleles (20 functional mutations per individual sample). Based on an estimated number of approximately 30,000 mouse genes, the parallel sperm/DNA archive should permit the identification and recovery of ten or more alleles per average target gene which translates to a calculated 99% success rate in the discovery of five allelic variants for any given average gene. The low rate of unrelated ENU-induced passenger mutations has no practical impact on the analysis of the allele-specific phenotype at the G3 generation because of dilution and free segregation of such unrelated passenger mutations. To date 39 mouse models representing 33 different genes have been recovered from our archive using in vitro fertilization techniques. The generation time for a murine model heterozygous for a mutation in a gene of interest is less than 2 months, i.e., three to four times faster compared with current embryonic stem-cell-based technologies. We conclude that ENU-based targeted mutagenesis is a powerful tool for the fast and high-throughput production of murine gene-specific models for biomedical research.

Alleles↗
PubMed2005

Burden of diabetes in an aging population: prevalence, incidence, mortality, characteristics and quality of care.

The purpose of this work is to review the recent publications on prevalence, incidence, mortality, characteristics and quality of care related to diabetes in the elderly population. In France, the prevalence of drug-treated diabetes peaks at 14% by age 75-79 years, and at least one million people aged over 65 years have diabetes. Incidence rates for Northern Europeans rank between 3 and 7 per 1,000 person-years. The World Health Organization expects prevalent cases to further increase, due to better case ascertainment, better survival of people with diabetes, increase in obesity leading to a true increase in diabetes incidence, and, in developed countries, the important impact of population aging. The burden of diabetes in the elderly population is already high. Even in the oldest age-groups, excess mortality risks associated with diabetes are significant and mostly related to cardiovascular disease, accounting for the loss of 3 to 6 years of life. The cardiovascular risk of elderly people with diabetes is poorly controlled, increasing risks of diabetes complications, loss of cognitive functions and mobility, and dependency. Screening for lipid abnormalities and diabetes complications to prevent further damage is insufficient, and antihypertensive and hypolipidemic treatments are, in this population, underused, as in other countries. Specific adjustments of medical nutrition therapy are lacking. In long-term care facilities where the prevalence of diabetes is especially high (8 to 25%), quality of diabetes care is often poorer. As the burden of diabetes is becoming heavier, specific monitoring of the health, quality of care and needs of elderly people with diabetes is required for adequate public health planning.

Aged↗
PubMed2005

Bullous delayed pressure urticaria: pathogenic role for eosinophilic granulocytes?

Bullous delayed pressure urticaria (DPU) is a rare variant of DPU. Treatment of DPU is difficult and the underlying pathogenic mechanism of DPU remains elusive. We report a 72-year-old man with DPU and associated chronic urticaria as well as delayed urticarial dermographism. Pressure challenge gave rise to a deep weal covered by multiple vesicles and bullae after 24 h. Histological examination of a skin biopsy specimen obtained 24 h after pressure challenge demonstrated intraepidermal bullae filled with eosinophils accompanied by a dense, predominantly eosinophilic infiltrate in the dermis. Whereas the numbers and morphology of mast cells were unaltered, the extracellular deposition of eosinophil cationic protein revealed evidence for eosinophil activation. Concomitantly, both CD4+ and CD8+ T lymphocytes were present in the infiltrate and expressed interleukin 5. As bullous DPU may represent the maximal variant of DPU, the investigation of the cellular infiltrate and the chemokines/cytokines released may reveal potential pathogenic mechanisms. A possible effector role of eosinophilic granulocytes, T-cell subsets and mast cells is discussed.

Aged↗
PubMed2005

Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment.

BACKGROUND: In several clinical trials the topical application of pimecrolimus was shown to be effective in the treatment of atopic dermatitis (AD). By targeting calcineurin-dependent signaling pathways, pimecrolimus controls cytokine gene expression. The purpose of this study was to investigate the effect of pimecrolimus on the inflammatory infiltrate and cytokine expression pattern in AD upon topical therapy. METHODS: From 10 patients with acute AD, skin biopsies as well as immunophenotype and cytokine production of peripheral blood mononuclear cells (PBMC) were examined before and 3 weeks after therapy. RESULTS: The clinical improvement was associated with a marked regression of histopathological features. In particular, the density of the inflammatory infiltrate mostly containing lymphocytes and eosinophils declined. By double immunofluorescent staining, a reduced expression of the T helper (Th) 2 cytokines interleukin (IL)-5, IL-10, and IL-13 in both CD4+ and CD8+ T cells was demonstrated after therapy. Pimecrolimus therapy was also associated with a reduced expression of the Th1 cytokine interferon (IFN)-gamma. Interestingly, the numbers of epidermal CD1a+ dendritic cells increased following treatment. In the peripheral blood, a decrease of lymphocytes and eosinophils was noticed, but the distribution of lymphocyte subpopulations and their capacity of cytokine production did not change. CONCLUSIONS: Topical pimecrolimus exhibits anti-inflammatory effects in AD by reducing the inflammatory cell infiltrate and cytokine expression in the dermis.

Administration, Topical↗