Development of the Qualeffo–31, an osteoporosis-specific quality-of-life questionnaire

Introduction Vertebral deformities are a common consequence of osteoporosis and are known to decrease quality of life. The Qualeffo–41 is a quality-of-life questionnaire especially developed for measuring quality of life in patients with vertebral deformities. It consists of 41 questions arranged in five domains: pain, physical function, social function, general health perception, and mental function. The objectives of this study were: (1) to develop a shorter version of the Qualeffo–41 by removing redundant questions; and (2) to investigate the scale characteristics, reliability, and validity of this shorter version. Methods The study was performed using data from the Qualeffo validation study and the Multiple Outcomes of Raloxifene Evaluation (MORE) study. The analyses were performed in patients with vertebral deformities (n=579). Factor analysis on polychoric correlations and an item response theory (IRT) model, i.e., the generalized partial credit model (GPCM), were used to create a shorter version of Qualeffo–41. Using GPCM, scoring weights were computed for all items. Results Three items were removed from the data set because of too many missing values. Factor analysis identified three instead of five domains: (1) pain, (2) physical function, and (3) mental function. Five items had factor loadings <0.4 and were not included in the GPCM. After excluding several items, the domains pain (four items), physical function (18 items), and mental function (nine items) showed a good, reasonable, and excellent fit, respectively. This indicates that the mental function domain and the pain domain are more unidimensional than the physical function domain. All three domains showed a very high correlation (r ≥0.95) with the corresponding domains of the Qualeffo–41. Conclusions Qualeffo–31 was developed, consisting of three domains with a reasonable to excellent fit to the GPCM. Although the fit to the GPCM supports the construct validity of the Qualeffo–31, validation in a new study should be performed before using it in practice.     

Characterization of T cell epitopes in αs1-casein in cow''s milk allergic, atopic and non-atopic children

BACKGROUND: One to two percent of infants suffer from IgE-mediated allergic reactions against cow's milk proteins. Most children develop clinical tolerance, but approximately 15% are still allergic by the age of 10 years. Little is known about the T cell epitopes in individual cow's milk protein in relation to allergy and tolerance. OBJECTIVE: To identify T cell epitopes in alphas1-casein, the most abundant milk protein, and to investigate T cell responses toward these epitopes in allergic, atopic and non-atopic children. METHODS: Allergen-specific T cell lines (TCLs) were derived from peripheral blood mononuclear cells of 11 cow's milk allergic, nine atopic and nine non-atopic children. T cell responses were measured to alphas1-casein and to overlapping peptides (18-mers), spanning the alphas1-casein molecule. Proliferation was determined by incorporation of (3)H-thymidine, and cytokine production (IL-10, IL-13 and IFN-gamma) was measured by ELISA. RESULTS: Four main regions (amino acid (AA) residues 43-66, 73-96, 91-114 and 127-180) in the alphas1-casein molecule were immunogenic to T cells, among which the AA residues 133-156 spanned the immunodominant part. Only subtle differences were found in peptide recognition between the subject groups. Some of the peptides induced slightly Th1- or Th2-skewed cytokine responses. The increased levels of IL-10 in response to alphas1-casein observed in TCLs from atopic children appeared not to be linked to recognition of specific IL-10-inducing epitopes. CONCLUSIONS: The immunodominant sequence in alphas1-casein is spanned by AA residues 133-156. Tolerance towards alphas1-casein in atopic children may be mediated by an overall induction of IL-10 and not by recognition of certain T cell epitopes. The identified T cell epitopes in children with cow's milk allergy may be useful targets in developing peptide immunotherapy.     

Cortisol moderates the relationship between testosterone and aggression in delinquent male adolescents.

BACKGROUND: In animals, strong evidence exists for an association between testosterone and aggression. In humans, and particularly in children and adolescents, findings have been less consistent. Previous research has suggested that this may partly be due to moderating effects of other factors, e.g., hormones. This study aims to investigate the moderating effect of cortisol on the relationship between testosterone and subtypes of aggression in delinquent male adolescents. METHODS: Participants were 103 boys (mean age 13.7) referred to a delinquency diversion program. Testosterone and cortisol levels were determined from saliva samples collected during resting conditions and related to self-report scores on overt and covert aggression. RESULTS: Linear regression analyses revealed a significant interaction between cortisol and testosterone in relation to overt aggression, with a significant positive relationship between testosterone and overt aggression in subjects with low cortisol levels but not in subjects with high cortisol levels. Using the same model for covert aggression, no significant effects of testosterone, cortisol, or testosterone x cortisol interaction were found. CONCLUSIONS: These results indicate a moderating effect of cortisol on the relationship between testosterone and overt aggression in delinquent male adolescents. Implications and directions for future research are discussed.     

Operative timing and patient survival following distal splenorenal shunt

The importance of "operative timing" in cirrhotic patients with variceal hemorrhage is often underemphasized. To evaluate the effects of immediate versus delayed selective portasystemic decompression on hepatic function, operative mortality, and long-term patient survival, we reviewed the records of 77 patients who underwent distal splenorenal shunts (DSRS) over a 14-year period. A hepatic risk status score was calculated at the time of the index bleed (HRS1) or presentation and again just prior to operation (HRS2). Variables analyzed included age, sex, prior bleeding episodes, time from index bleed to operation, transfusion requirements, and etiology of cirrhosis. Operative mortality rates for immediate versus delayed DSRS were 46.2 per cent and 17 per cent, respectively. HRS improved significantly in elective DSRS patients from 1.46 to 1.30. Predictors of HRS2 included HRS1 and time in days from the index bleed to operation. The most important predictor of early survival for all patients after elective DSRS was the HRS2; however, for patients who underwent elective DSRS and survived, HRS1 was a better predictor of length of survival than HRS2. No other variable analyzed accurately predicted survival. We conclude that HRS can be expected to improve with supportive inhospital therapy; improved HRS at the time of operation is associated with decreased operative mortality; and the extent of liver disease as determined by HRS1 appears to be the chief determinant of long-term patient survival.     

Variable selection under multiple imputation using the bootstrap in a prognostic study

Background  

Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection.     

Maintenance of tolerance to cow''s milk in atopic individuals is characterized by high levels of specific immunoglobulin G4

BACKGROUND: The central role of specific IgE in cow's milk allergy (CMA) is well documented. However, less is known about the function of other immunoglobulin isotypes in allergy and tolerance to cow's milk proteins (CMPs). OBJECTIVE: To determine differences in the antibody responses that are associated with allergy and tolerance to cow's milk in allergic, atopic and non-atopic individuals of different age groups. METHODS: Nineteen infants (<1 year), 18 children (6-14 years) and 41 adults (21-68 years) were included. Each age group was comprised of subjects with CMA, atopic individuals without a history of CMA and non-atopic subjects. Levels of specific IgE, IgG4, IgG1 and IgA to whole cow's milk and the six most abundant individual CMPs were determined in plasma by ELISA. For comparison, specific IgE and IgG4 were measured to ovomucoid and house dust mite (HDM) in individuals allergic for the respective allergens, and in atopic and non-atopic subjects without allergy. RESULTS: In infants and children with CMA, alphas1-casein and beta-lactoglobulin induced the highest specific IgE response, whereas alphas1-casein was the most allergenic CMP in adult patients. Specific IgG4 and IgG1 responses were the highest to alphas1-casein and beta-lactoglobulin in all age groups, while kappa-casein and alpha-lactalbumin induced the highest levels of IgA. CMP-specific IgG4 was higher in atopic children and adults without CMA, as compared with non-atopic individuals. A similar difference between tolerant atopic and non-atopic subjects was observed for IgG4 specific to ovomucoid, whereas HDM-specific IgG4 was not detectable in these subjects. CONCLUSION: Maintenance of tolerance to cow's milk in atopic children and adults without CMA is associated with elevated levels of specific IgG4, in combination with low specific IgE. The up-regulation of specific IgG4 in tolerant atopic individuals may be related to the type of allergen and its regular dose of exposure.     

Nocturnal asthma,histamine and vagal activity

In a study of two groups of nine allergic asthmatic children, consisting of one group with (group I) and one group without (group II) increased nocturnal airflow obstruction, we determined whether an increase in vagal activity, or inflammatory mediators like histamine are responsible for the nocturnal increase in airflow obstruction. The results of investigations in the two groups of asthmatics were compared to the results of an age matched control group. Forced expiratory volume in one second (FEV₁) and electrocardiogram recordings of one minute were obtained every 4 hours during 24 hours. Heart rate and sinus arrhythmia gap were used to express vagal activity indirectly. N-methylhistamine was determined in urine samples collected in periods of 4 hours between the measurements. In group I, overall N-methylhistamine excretion was on a higher level than in both other groups, and was significantly higher overnight. Parasympathetic stimulation did not seem of importance to the increase of airflow obstruction at night.This study was supported by a grant from the Nederlands Astma Fonds.     

A sequential study of intravenous and oral Fleroxacin for 7 or 14 days in the treatment of complicated urinary tract infections

Objective: To compare 1 and 2-weeks of sequential intravenous and oral treatment for complicated urinary tract infection. Design: Randomized, clinical trial. Setting: 2 secondary and 1 tertiary care hospital in the Netherlands. Patients: Patients (54) were randomly assigned, after 3 days Fleroxacin 400 mg iv once daily, to receive oral fleroxacin (400 mg OD,) either during 4 (total 7) days (n = 26), or during 11 (total 14) days (n = 28). Thirty-four patients were evaluable for efficacy. Complicated urinary tract infection was defined as the presence of an anatomical or functional abnormality of the urinary tract, urinary tract instrumentation, patients presenting with clinical signs and symptoms of pyelonephritis or a serious illness such as diabetes mellitus, immunosuppression or renal failure. Complicated urinary tract infection was defined as the presence of an anatomical or functional abnormality of the urinary tract, urinary tract instrumentation, patients presenting with clinical signs and symptoms of pyelonephritis or a serious illness such as diabetes mellitus, immunosuppression or renal failure. Results: A bacteriological cure was seen in 22 of 34 (65%) patients at 4-6 weeks after therapy. Overall, a favorable bacteriological response was obtained in 26 of 34 (76%) patients. No significant difference could be found among the two dosage groups (7 days: 14 18 = 78 %; 14 days: 12 16 = 75 %). Conclusions: Sequential iv and oral treatment with fleroxacin in complicated UTI is a satisfactory treatment modality. Larger trials should be done in a more homogeneous population, studying shorter treatment durations in complicated UTI.     

白癜风患者合并Sézary综合征的发病机制

皮肤T细胞淋巴瘤（CTCL）合并白癜风的患者罕见，是否CTCL中的某些T细胞亚群能识别黑色素细胞的特异性表位从而引起白癜风，目前尚不清楚。本研究旨在确定在Sézary综合征（SS）患者色素减退皮肤的肿瘤浸润淋巴细胞中，是否可检测到针对黑色素细胞分化抗原的T细胞。1例71岁女性SS患者，在病程中发生白癜风。免疫组织化学检查发现，色素性皮肤活检标本HMB45和MelanA抗体染色阳性，而在色素减退性皮肤活检标本末观察到阳性染色。