Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells.

Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell. Stem cells located further from the base are lost and the pool of competing stem cells is reduced. We tested whether this loss of stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis. Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation.

The effects of Mycobacteria vaccae derivative on allergen-specific responses in children with atopic dermatitis.

The capacity of microbial products to inhibit allergic inflammation make them logical candidates for novel therapies in allergic diseases such as atopic dermatitis. To assess the effects of intradermal Mycobacterium vaccae derivative on allergen-specific immune responses in children with moderate to severe atopic dermatitis. Peripheral blood mononuclear cells were isolated from children aged 5-16 years who received intradermal injections of M. vaccae derivative AVAC(TM) (n = 26) or placebo (n = 34) three times at 2-weekly intervals, weeks 0, 2 and 4. Cytokine [interleukin (IL)-13, interferon (IFN)-γ and IL-10] responses to allergen [house dust mite (HDM)], mitogen [phytohaemagglutinin (PHA)], Staphylococcal enterotoxin B (SEB) and Toll-like receptor (TLR) ligands were assessed. At week 8 (1 month after all injections given) children in the AVAC group showed a significant increase in IL-10 (P = 0·009), T helper type 1 (Th1) IFN-γ (P = 0·017) and Th2 IL-13 (P = 0·004) responses to HDM compared with baseline (week 0). There were no significant changes in any cytokine production in the placebo. HDM-specific IL-10 responses remained significantly higher (P = 0·014) than at baseline in the AVAC group by week 12; however, the HDM-specific IL-13 and IFN-γ responses were no longer significantly different from baseline. IL-13 (r = 0·46, P < 0·001) and IL-10 (r = 0·27, P = 0·044) responses to HDM were correlated with total immunoglobulin E but not with disease severity. There were no effects of AVAC on mitogen, SEB, TLR-2- or TLR-4-mediated responses. This M. vaccae derivative appeared to modulate responses to HDM selectively, suggesting the capacity for in vivo effects on allergen-specific immune responses.

Early experience with the TriMed fragment-specific fracture fixation system in intraarticular distal radius fractures.

This paper reports the results of fixation of intraarticular fractures of the distal radius using the TriMed fragment-specific fixation system by surgeons early in their experience with the system. A consecutive series of 22 AO types C2 and C3 fractures in 21 patients were internally fixed with the system. Restoration of articular congruity to less than 2 mm was possible in 20 fractures. At a minimum of 6 months follow-up, mean volar and radial inclination were 8 degrees and 25 degrees , respectively, with no loss of reduction. The patients had a mean of 50 degrees flexion, 63 degrees extension and a pronation-supination arc of 149 degrees . The mean subjective Patient Rated Wrist Score was 20. Our complication rate was comparable to other published series despite long operating times. Therefore, we commend the system as a powerful tool to treat these difficult fractures but acknowledge the significant learning curve.

Induction of class II major histocompatibility antigens on thyroid, adult pancreatic islet, and fetal proislet allografts.

Cultured BALB/c (H-2d) thyroid, adult pancreatic islet and fetal proislet tissues can be accepted permanently in CBA/H (H-2k) recipients until rejection is triggered by the transfer of antidonor strain activated immune T cells. Class II MHC antigens are not expressed on the accepted grafts and are induced following immune cell transfer, but expression is quantitatively and qualitatively different for the different tissues. Thyroid allografts show intense class II MHC antigen expression early after immune cell transfer and before extensive tissue destruction has occurred. In contrast, adult islet and fetal proislet allografts show patchy and cytoplasmic staining usually associated with areas of tissue destruction. Gamma-interferon treatment of tissues in vitro showed that proislet tissue has a greater capacity for class II MHC antigen induction than adult islet tissue. The differences in the capacity for class II MHC induction by fetal and adult islet tissue may be important in relation to the pathogenesis of autoimmune disease.

Two doses of triprolidine for treatment of allergic rhinitis.

Two doses of triprolidine (2.5 mg t.i.d. and 1.25 mg t.i.d.) were compared with placebo in 32 patients suffering from allergic rhinitis. Triprolidine 2.5 mg t.i.d. was statistically significantly better than placebo (p less than 0.05) in reducing the symptoms of sneezing and eye irritation. Neither dose of triprolidine produced significant drowsiness during the second week of treatment.

[Double blind crossover study of pseudoephedrine and triprolidine alone and in combination in the treatment of allergic rhinitis (author's transl)]. / Estudio doble ciego cruzado de seudoefedrina y triprolidina solas y en combinación, en el tratamiento de la rinitis alérgica

In a double-blind crossover trial of pseudoephedrine 60 mg. and triprolidine 2.5 mg. alone and in combination, on 40 volunteers suffering from allergic rhinitis, both drugs were found superior to placebo in reducing the effects of allergic rhinitis and were of equal efficacy. The combination tablet was consistently better than either drug in several of the assessments and was the treatment which the subjects, as a whole, preferred. Side effects were not a problem with any of the medications.

A Double-blind crossover trial of pseudoephedrine and triprolidine, alone and in combination, for the treatment of allergenic rhinitis.

In a double-blind crossover trial of pseudoephedrine 60 mg and triprolidine 2.5 mg, alone and in combination, on 40 volunteers suffering from allergic rhinitis, both drugs were found superior to placebo in reducing the effects of allergic rhinitis and were of equal efficacy. The combination tablet was consistently better than either drug in several of the assessments and was the treatment which the subjects, as a whole, preferred. Side effects were not a problem with any of the medications.