Effect of oral and inhaled cetirizine in allergen induced bronchoconstriction

Cetirizine is a potent, selective H₁ histamine receptor antagonist. The effect of oral and inhaled eetirizine was assessed on the early bronchoconstrictor response to inhaled allergen in 10 mild atopie asthmatic patients in a double-blind, randomized, plaeebo controlled trial. All were sensitive to Dermatophagoides pleronyssinus and this was used as the provoking allergen. The geometric mean PD20 FEV] values obtained at allergen challenge were measured as cumulative breath units (c.b.u.) and following oral cetirizine, inhaled cetirizine and placebo were 124–5, 75–7 and 76–7 c.b.u. respectively. These did not differ significantly. We conclude that neither oral nor inhaled cetirizine significantly attenuates the early response to inhaled allergen in atopie asthmatic subjects. However, the method of repeated allergen challenge is likely to be relatively insensitive. Clinical and Experimental Allergy, [o]. 23, pp. 528–531.     

Action of Mitomycin C on Testicular Steroidogenesis and its Probable Mode of Action in Albino Rats

Einfluß von Mitomycin C auf die Steroidgenese im Hoden und ihr möglicher Modus bei Albino-Ratten
Mit Hilfe des Radioimmunassays (Testosteron im Serum) und dem histochemischen Nachweis von dem Schlüsselenzym Δ⁵ 3β hydroxysteroid-dehydrogenase in den Leydig'schen Zwischenzellen nach einer Behandlung mit Mitomycin C wurde die Steroidgenese im Hoden untersucht. Die in vivo Experimente belegen, daß Mitomycin C einen bemerkenswerten Abfall der Serum-Testosteronwerte verursacht im Zusammenhang mit eine signifikanten Reduzierung des Hodengewichtes und des Gewichtes des akzessorischen Geschlechtsdrüsen. In vitro Studien zeigen eine Verminderung der Aktivität von Δ⁵ 3β hydroxysteroiddehydrogenase und der Glukose-6-phosphatdehydrogenase im Hoden nach Zugabe von Mitomycin C in das Inkubationsmedium. Diese Befunde führen zu der Überlegung, daß Mitomycin C die Steroidgenese des Hodens negativ beeinflußt.     

Integrating sibship data for mapping quantitative trait loci

Sibship methods have been shown to be more powerful than traditional sib-pair methods in mapping quantative trait loci. We propose a statistical procedure which integrates data on sibships into a so-called 'contrast function', a natural extension of the classical squared sib-pair trait difference proposed by Haseman & Elston (1972). We also develop a combined mean and contrast function which provides more information on linkage compared to the contrast function. Our method is extended to multiple, epistatically interacting trait loci. Monte-Carlo simulations are included to compare the efficiencies of the proposed procedures with some currently used methods. An application of our proposed method is presented using data on alcohol dependence.     

Level of purposeful hand function as a marker of clinical severity in Rett syndrome

Aim We investigated relationships between hand function and genotype and aspects of phenotype in Rett syndrome. Method Video assessment in naturalistic settings was supplemented by parent‐reported data in a cross‐sectional study of 144 females with a mean age of 14 years 10 months (SD 7y 10mo; range 2y–31y 10mo), 110 of whom had a mutation of the methyl CpG binding protein 2 (MECP2) gene. Ordinal logistic regression was used to assess relationships between hand function and MECP2 mutation, age, a modified Kerr score, Functional Independence Measure for Children (WeeFIM), ambulation level, and frequency of hand stereotypies. Results Approximately two‐thirds of participants demonstrated purposeful hand function, ranging from simple grasping skills to picking up and manipulating small objects. In participants with a confirmed MECP2 mutation, those with the p.R168X mutation had the poorest hand function on multivariate analysis with C‐terminal deletion as the baseline (odds ratio [OR] 0.19; 95% confidence interval [CI] 0.04–0.95), whereas those with the p.R133C or p.R294X mutation had better hand function. Participants aged 19 years or older had lower hand function than those aged less than 8 years (OR 0.36; 95% CI 0.14–0.92). Factors that were associated with better hand function were lower Kerr scores for a 1‐point increase in score (OR 0.77; 95% CI 0.69–0.86), higher WeeFIM scores for a 1‐point increase in score (OR 1.08; 95% CI 1.04–1.12), and greater ambulation than those completely dependent on carers for mobility (OR 22.64; 95% CI 7.02–73.08). The results for participants with a confirmed pathogenic mutation were similar to results obtained when participants without a mutation were also included. Interpretation Our novel assessment of hand function in Rett syndrome correlated well with known profiles of common MECP2 mutations and overall clinical severity. This promising assessment could measure clinical responses to therapy.     

Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England

Background  Infliximab is used for treatment of Crohn's disease and, following the Active Ulcerative Colitis Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerative colitis (UC).
Aim  To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC.
Methods  A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroenterologists from six English centres.
Results  Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing response (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4–59), with 21 (55.3%) being in remission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an average of 10 months (range 8–13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurred in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-severe adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media.
Conclusion  Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC.