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Notes: Objectives  To evaluate triple tourniquets in controlled conditions and for the first time to investigate the hypothesis that leaving a semi-permanent tourniquet around the uterine artery reduces post-operative bleeding from the uterine incisions.Design  A randomised controlled trial.Setting  Two University teaching hospitals.Population  Twenty-eight patients with symptomatic fibroids and uterine sizes ranging from 14 to 24 weeks of gestation undergoing open myomectomy.Methods  A number 1 polyglactin suture was tied around the cervix to occlude the uterine arteries, and polythene tourniquets were tied around the infundibulopelvic ligament to obstruct the ovarian vessels. At the end of the procedure, the ovarian ties were released but the uterine artery suture remained in situ.Main outcome measures  Intra-operative blood loss, post-operative blood loss, blood transfusion rates, operative morbidity, uterine blood flow and ovarian function.Results  There was significantly less blood lost in the tourniquet group than in the control group (difference between means 1870 mL, 95% CI 1159–2580 mL, P 〈 0.0001; transfusion rates of 7% and 79%, P= 0.0003). The volume in the pelvic drain 20 min post-operatively and after 48 hours failed to reach statistical significance between the two groups (P= 0.10 and P= 0.165). There were no differences in uterine artery Doppler resistance indices at five days (P= 0.54), six weeks (P= 0.47), three months (P= 0.49) and at six months (P= 0.18). Day two serum FSH concentrations after surgery were unchanged (P= 0.45), compared with baseline values.Conclusions  Triple tourniquets are effective in reducing bleeding and transfusion rates. There appears no obvious adverse effect on uterine perfusion or ovarian function.

Notes: Objective  To assess whether outpatient hysteroscopy using the ‘no-touch’ technique confers any advantages in terms of patient discomfort over the traditional technique.Design  Prospective randomised controlled study.Setting  Outpatient hysteroscopy clinic in a large university undergraduate teaching hospital.Population  All women referred for outpatient hysteroscopy in a 12-month period.Interventions  Women were randomised to undergo either traditional saline hysteroscopy requiring the use of a speculum and tenaculum, or a ‘no-touch’ vaginoscopic hysteroscopy which does not require a speculum or tenaculum. Each group was further subdivided to have hysteroscopy with either a 2.9-mm or 4-mm hysteroscope. Patients were asked to complete pre- and postprocedure questionnaires ranking pain scores.Main outcome measures  The relative success of each of these techniques, requirement for local anaesthetic and pain scores at different times during the hysteroscopy were recorded at the end of the procedure. The time taken to carry out each procedure was also measured.Results  One hundred and twenty women were recruited in this study: 60 were randomised to traditional hysteroscopy and 60 to ‘no-touch’ hysteroscopy. The overall success rate for hysteroscopy was 99%. There was no significant difference in the requirement for local anaesthetic between the two groups, but those who underwent ‘no-touch’ hysteroscopy with a 2.9-mm hysteroscope had the lowest requirement of local anaesthetic (10% compared with 27% in the no-touch hysteroscopy with a 4-mm hysteroscope group). The time taken to perform hysteroscopy and biopsy was significantly shorter with ‘no-touch’ hysteroscopy (5.9 vs 7.8 min; difference 1.9, 95% CI 0.7–3.1). There were no differences in pain scores between the groups at different times during hysteroscopy.Conclusions  ‘No-touch’ or vaginoscopic hysteroscopy is significantly faster to perform than the traditional technique. Although there was no difference in pain scores between the two techniques, local anaesthetic requirements were least in those who underwent ‘no-touch’ hysteroscopy with a narrow bore hysteroscope.

Notes: Motoneuron dependence on target-derived trophic factors during development is well established, with loss of trophic support leading to the death of these cells. A complete understanding of the intracellular signal transduction machinery associated with extracellular survival signals requires the examination of individual pathways in various cellular and environmental contexts. In cells deprived of trophic support, and hence compromised for survival, phosphoinositide-3-kinase (PI3K) is decreased when compared with healthy cells supplied with trophic support. Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling is dramatically decreased in deprived cells. We have examined the role of these two pathways to understand how changes in their activity regulate motoneuron survival and death. Pharmacological inhibition of PI3K attenuated motoneuron survival and was important in the regulation of Bcl-2 serine phosphorylation, limited release of cytochrome c into the cytoplasm and caspase activation. Bax translocation from cytoplasm to mitochondria was not altered when PI3K was inhibited. High levels of ERK1/2 inhibition robustly attenuated motoneuron survival in cells supplied with trophic support, whereas moderate inhibition of ERK1/2 activation had little effect. ERK1/2 inhibition in these cells decreased Bcl-2 phosphorylation and resulted in release of cytochrome c from the mitochondria. Bax translocation and caspase activation were not affected by ERK1/2 inhibition. These data reveal that changes in PI3K and ERK1/2 signaling lead to individual and overlapping effects on the cell-death machinery. Characterizing the role of these pathways is critical for a fundamental understanding of the development and degeneration of specific neuronal populations.

Notes: Background The T-helper type 1 (Th1) trophic properties of bacterial cytosine–phosphate–guanine (CpG) motifs have made them logical adjuvants both for the suppression of Th2-mediated allergic disease in early life and for promoting vaccine responses in neonates who have relatively immature Th1 function. However, little is known about their effects on immature immune responses in this period.Objectives To compare the effects of CpG on adult and neonatal cellular immune responses to various stimuli.Methods The immune responses of mononuclear cells (MC) derived from neonates (n=25) and their mothers (n=25) were compared in vitro. These were stimulated with house dust mite (HDM), CpG B, CpG C, non-CpG oligodeoxynucleotides (ODN) or diphtheria toxoid (DT) in optimized conditions. In parallel cultures, CpGs were combined with HDM or DT antigens to assess the effect of the various ODN on these antigen-specific responses. Lymphoproliferation and cytokine responses IL-13, IFN-γ, IL-6, IL-10, TNF-α) were measured for all of the cultures described above.Results Although neonates showed attenuated lymphoproliferation to CpG, the production of antigen-presenting cell-derived cytokines such as IL-6 and IL-10 and the up-regulation of major histocompatibility complex class II (HLA-DR) were detected at adult levels. T cell-derived cytokines (IL-13 and IFN-γ) were not detectable in response to CpG alone. Most neonates also failed to produce detectable IFN-γ to HDM or DT (unlike adults), but readily produced IL-13 to these stimuli. The addition of CpG resulted in an increase in neonatal IFN-γ production in response to HDM (P=0.011) and a similar but non-significant trend with DT. However, rather than inhibiting Th2 IL-13 responses, the addition of CpGs was associated with a significant increase in the IL-13 responses to HDM (P=0.016) and DT (P=0.03), effects not seen in adults.Conclusions This study provides further evidence that neonatal MC responses to CpG are functionally different from adults, and do not show clear Th1 polarization. The CpG associated increase in Th2 responses may reflect a potentiation of the normal neonatal Th2 propensity, or non-specific activation of neonatal MC.

Notes: Background Through its powerful immunoregulatory effects, infection with atypical mycobacteria may exert a protective effect on the development of childhood allergic disease.Objective To examine the relationship between childhood atopy or allergic disease and previous infection with four species of atypical mycobacteria.Methods Eight hundred and six children aged 8–18 years and living in rural Crete – most of whom had had previous BCG immunization – underwent skin prick testing with 10 aeroallergens; their parents completed a standardized questionnaire relating to allergic disease. No less than 8 weeks later each child underwent intradermal skin tests with 0.1 mL solutions of four selected mycobacterial reagents (Aviumin C, Gordonin, Chelonin and Ranin I).Results Twenty-three percent of children were atopic on skin prick testing; far fewer had symptoms of asthma (5%) or hayfever in conjunction with a positive prick test to pollens (2%). Eighty percent of children had positive skin responses to one or more mycobacterial species. Among all children – and those with a BCG scar – there was no association between atopy or allergic symptoms and mycobacterial skin responses; among the few children without a BCG scar however those with positive mycobacterial responses were less likely to be atopic or to report allergic symptoms; these differences were not statistically significant.Conclusions Our findings, in a population of BCG-immunized children, do not lend support to the suggestion that infection with atypical mycobacteria is protective against childhood allergic disease.

Notes: Background Maternal allergy confers stronger allergy risk (than paternal allergy) suggesting that maternal patterns of immune response can directly influence immune development in offspring. Women prone to allergic immune responses to allergens may also have altered immune responses to other antigens including fetal antigens.Objective This exploratory study examines relationships between maternal immune responses to fetal antigens and the subsequent risk of allergy.Methods Mononuclear cells (MNC) were collected from 36 mother–infant pairs to compare maternal (and fetal) cellular immune responses to alloantigens (fetal, maternal or unrelated donor [URD]), and allergens in allergic (18 pairs) and non-allergic (18 pairs) mothers. Thirty children had documented allergic outcomes at 6 years of age.Results In this population, allergic outcomes in the offspring were associated more strongly with materno-fetal immune interactions than with a maternal family history of allergy. Specifically, allergic disease at 6 years of age was associated with significantly higher maternal responses to fetal alloantigens (lymphoproliferation, P=0.008; IL-13, P=0.02 and IFN-γ, P=0.015), whereas associations with maternal allergy did not reach significance (P=0.07). Fetal IFN-γ alloantigen responses were significantly correlated with the degree of human lymphocyte antigen (HLA) mismatch (maternal HLA class II antibodies) (τ=0.3, P=0.03). The capacity of the fetus to produce IL-13 (τ=0.4, P=0.001) and IL-10 (τ=0.3, P=0.029) was directly related to the level of these cytokines produced by the mother in response to fetal antigens. Allergic mothers showed a non-significant trend for stronger lymphoproliferation to fetal alloantigens. The number of previous pregnancies (gravidity) was associated with stronger maternal responses to fetal alloantigens, as shown by lymphoproliferation (Kendall τ=0.3, P=0.04) and IFN-γ (τ=0.3, P=0.04) synthesis, but did not affect fetal responses to the various stimuli.Conclusions Maternal responses to fetal antigens were related to fetal immune responses and subsequent allergy. This novel observation suggests that events at the materno-fetal interface have an important influence on early immune development and should be investigated further.

Notes: A 7-year-old girl underwent laser ablation of tonsillar remnants. Following the procedure, which was surgically uncomplicated, the laser resistant tracheal tube used could not be removed; it was firmly lodged in the larynx, immediately below the glottic opening. This case highlights the importance of careful selection of laser resistant tracheal tubes for use in paediatric patients and challenges traditional concepts of paediatric upper airway anatomy.