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Development and psychometric properties of a disease-specific quality of life questionnaire for adult patients with growth hormone deficiency 总被引:2,自引:0,他引:2
Herschbach P Henrich G Strasburger CJ Feldmeier H Marín F Attanasio AM Blum WF 《European journal of endocrinology / European Federation of Endocrine Societies》2001,145(3):255-265
BACKGROUND: Adults with growth hormone (GH) deficiency (GHD) may experience physical and psychological disturbances, which can affect their quality of life (QOL). OBJECTIVES: To develop and validate a disease-specific module from the previously published QOL measure Questions on Life Satisfaction Modules (QLS(M)): the QLS(M)-H that specifically addressed the needs of patients with hypopituitarism. A second aim was for the questionnaire to be applicable across different cultural backgrounds in order to evaluate the efficacy of therapy in large, international clinical trials, thus providing additional clinical endpoints for these studies. DESIGN: A preliminary German language version of the QLS(M)-H was developed from 26 semi-structured interviews of adults with GHD. The questionnaire was then independently translated into five other languages and applied in open, non-controlled, multicentre, longitudinal studies to patient (n=717) and normative populations (n=2700). METHODS: A revised, nine-item version of the questionnaire was developed, based on previously defined criteria, and was evaluated for reliability and validity. Sensitivity to detect changes after GH replacement was also assessed. RESULTS: The 16 items of the preliminary questionnaire were reduced to nine items on the basis of the correlation of items/factors from initial patient interviews. Psychometric analysis revealed the reliability of the nine-item scale. The Cronbach's alpha scores ranged from 0.81 to 0.89 and the test-retest correlations ranged from 0.76 to 0.88, all of which indicate reliability over time. Mean scores increased significantly during GH replacement therapy, with observed changes greater than those seen with the non-specific modules of the QLS(M), indicating the sensitivity of the scale. CONCLUSIONS: The QLS(M)-H questionnaire is concise, easy to complete, and can be effectively applied across different cultural backgrounds. Psychometric evaluation of the questionnaire reveals that it is a valid, reliable and sensitive tool useful for assessing impaired life satisfaction in adult patients with GHD and also for monitoring the efficacy of GH therapy. 相似文献
94.
Anders Juul Katharina Main Werner F. Blum Jorgen Lindholm Michael B. Ranke Niels E. Skakkebaek 《Clinical endocrinology》1994,41(1):85-93
OBJECTIVE Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-l/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated In active acromegaly due to excessive GH secretion. However, the Individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously. METHODS AND MATERIALS We studied this ratio In 198 healthy adults and In 56 acromegalic patients, grouped according to their serum GH levels (group I GH < 2mLU/l II GH 2–10mLU/l; III GH > 10mLU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination. RESULTS In healthy adults serum levels of IGF-I and IGFBP-3 decreased with Increasing age (r =?0.52 and r=?0.34, respectively, P< 0.0001). In addition, the molar IGF-l/IGFBP-3 ratio declined with increasing age (r =?0.44, P – 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7–97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SOS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 ± 240μ/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-l/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001). CONCLUSION We demonstrated a decreasing molar IGF-l/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels In the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and Is dependent on GH levels. 相似文献
95.
Kunie Ando Pierre Dourlen Anne-Véronique Sambo Alexis Bretteville Karim Bélarbi Valérie Vingtdeux Sabiha Eddarkaoui Hervé Drobecq Antoine Ghestem Séverine Bégard Emmanuelle Demey-Thomas Patricia Melnyk Caroline Smet Guy Lippens Claude-Alain Maurage Marie-Laure Caillet-Boudin Yann Verdier Joelle Vinh Isabelle Landrieu Marie-Christine Galas David Blum Malika Hamdane Nicolas Sergeant Luc Buée 《Neurobiology of aging》2013
A prerequisite to dephosphorylation at Ser–Pro or Thr–Pro motifs is the isomerization of the imidic peptide bond preceding the proline. The peptidyl-prolyl cis/trans isomerase named Pin1 catalyzes this mechanism. Through isomerization, Pin1 regulates the function of a growing number of targets including the microtubule-associated tau protein and is supposed to be deregulated Alzheimer's disease (AD). Using proteomics, we showed that Pin1 is posttranslationally modified on more than 5 residues, comprising phosphorylation, N-acetylation, and oxidation. Although Pin1 expression remained constant, Pin1 posttranslational two-dimensional pattern was modified by tau overexpression in a tau-inducible neuroblastoma cell line, in our THY-Tau22 mouse model of tauopathy as well as in AD. Interestingly, in all of these systems, Pin1 modifications were very similar. In AD brain tissue when compared with control, Pin1 is hyperphosphorylated at serine 16 and found in the most insoluble hyperphosphorylated tau fraction of AD brain tissue. Furthermore, in all tau pathology conditions, acetylation of Pin1 may also contribute to the differences observed. In conclusion, Pin1 displays several posttranslational modifications, which are specific in tauopathies and may be useful as biomarker. 相似文献
96.
NA Hanchard DR Murdock PL Magoulas M Bainbridge D Muzny YQ Wu M Wang AL McGuire JR Lupski RA Gibbs CW Brown 《Clinical genetics》2013,83(5):457-461
The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future. 相似文献
97.
Cornelia Speth Gerhard Blum Magdalena Hagleitner Caroline Hörtnagl Kristian Pfaller Beate Posch Helmut Werner Ott Reinhard Würzner Cornelia Lass-Flörl Günter Rambach 《Medical microbiology and immunology》2013,202(5):379-389
Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS). The modifications that result in enhanced AmB sensitivity of isolates are not associated with reduced virulence in vivo; instead, the ATS-infected mice died even faster than the ATR-infected animals. Since A. terreus enters the blood stream in most patients and frequently induces thrombosis, we studied a putative correlation between virulence of the two A. terreus isolates and their effect on thrombocytes. Those mice infected with the more virulent ATS isolate had lower thrombocyte numbers and more phosphatidylserine exposure on platelets than ATR-infected mice. In vitro experiments confirmed that ATS and ATR differ in their effect on thrombocytes. Conidia, aleurioconidia and hyphae of ATS were more potent than ATR to trigger thrombocyte stimulation, and thrombocytes adhered better to ATS than to ATR fungal structures. Furthermore, ATS secreted more soluble factors that triggered platelet stimulation than ATR. Thus, it might be suggested that the capacity of a fungal isolate to modulate thrombocyte parameters contributes to its virulence in vivo. 相似文献
98.
Janneke AL van Kempen Henk J Schers Anne Jacobs Sytse U Zuidema Franca Ruikes Sarah HM Robben René JF Melis Marcel GM Olde Rikkert 《The British journal of general practice》2013,63(608):e225-e231
Background
Primary care is increasingly interested in the identification of frailty, as it selects the target population for integrated care. However, instruments for the identification of frailty specifically validated for use in primary care are scarce. This study developed the Easycare Two-step Older persons Screening (Easycare-TOS), which provides a valid, efficient, and pragmatic screening procedure to identify frail older people.Aim
This paper aims to describe the development of the Easycare-TOS and the data from the pilot studies.Design and setting
Observational pilot study in seven academic GP practices in and around Nijmegen, The Netherlands.Method
The Easycare-TOS was developed in a cyclic process with the input of stakeholders. In every cycle, the requirements were first defined, then translated into a prototype that was tested in a pilot study. The Easycare-TOS makes optimal use of prior knowledge of the GP, and the professionals’ appraisal is decisive in the frailty decision, instead of a cut-off score. Further, it considers aspects of frailty, as well as aspects of the care context of the patient.Results
The pilot data have shown that after step 1, two-thirds of the patients do not need further assessment, because they are judged as not frail, based on prior knowledge of the GP. The overall prevalence of frailty in this pilot study is 24%. Most professionals who participated in the pilot studies considered the time investment acceptable and the method to be of added value.Conclusion
The Easycare-TOS instrument meets the predefined efficiency, flexibility, and acceptability requirements for use as an identification instrument for frailty in primary care. 相似文献99.
Koop Barbara Elisabeth Mayer Felix Gündüz Tanju Blum Jacqueline Becker Julia Schaffrath Judith Wagner Wolfgang Han Yang Boehme Petra Ritz-Timme Stefanie 《International journal of legal medicine》2021,135(1):167-173
International Journal of Legal Medicine - Age estimation based on the analysis of DNA methylation patterns has become a focus of forensic research within the past few years. However, there is... 相似文献
100.