Relationship dimensions of the 'Down syndrome advantage'.

BACKGROUND: Some researchers have proposed an 'advantage' for parents of children with Down syndrome over parents of children with other intellectual disabilities, especially in relation to experiencing less parenting stress. Others have maintained that these differences are an artefact of demographic and related differences. This study extends the investigation of possible differences in dimensions of parenting stress and also examines whether differences exist in maternal and child contingent responsiveness during mother-child interaction in these two groups. METHOD: Mothers of children with Down syndrome (n = 43) and undifferentiated developmental disabilities (n = 54) completed measures of children's adaptive functioning and behaviour problems, parenting stress and maternal social support. Observers rated the contingent interactions between mothers and children using the Nursing Child Assessment Teaching Scale. RESULTS: Once mother's age, education and social support as well as child adaptive functioning and behaviour problems were considered, neither parent nor child related parenting stress demonstrated an advantage for parents of children with Down syndrome. However, a 'Down syndrome advantage' was apparent for both maternal and child contingent responsiveness after accounting for maternal demographic and contextual variables and child attributes. CONCLUSIONS: Children with Down syndrome and their mothers have more positive interactions than children with other developmental disabilities, both in terms of the responsiveness of mothers and of child responses contingent on maternal behaviour. These findings suggest that both children with Down syndrome themselves and their mothers are contributing to a Down syndrome advantage.

Comparative study of flexible nasoendoscopic and rigid endoscopic examination for patients with upper aerodigestive tract symptoms.

INTRODUCTION: The objective of the current study was to compare the outcomes of rigid endoscopic procedures with those of pre-operative flexible nasoendoscopy. METHODS: A total of 253 patients who had undergone rigid endoscopic examination under anaesthesia between 6 January 2010 and 31 August 2011 were identified. Their clinical, surgical and histological records were evaluated. RESULTS: A total of 213 patients had a flexible nasoendoscopic procedure performed and recorded pre-operatively, and 82 in this cohort had a specific lesion or area of concern identified. There were 21 confirmed malignant biopsy results, the majority of which were squamous cell carcinoma. No patient with a negative pre-operative endoscopy had a malignant lesion discovered on endoscopic biopsy. The sensitivity and specificity of pre-operative nasoendoscopy were 100 per cent and 66.3 per cent, respectively. CONCLUSION: Diagnostic rigid endoscopic examination of the upper aerodigestive tract remains an important tool for excluding malignancy in high-risk patients, but is an unnecessary procedure in those low-risk patients with normal pre-operative findings.

Early childhood predictors of mothers' and fathers' relationships with adolescents with developmental disabilities.

BACKGROUND: The importance of positive parent-adolescent relationships is stressed in research on adolescents, although very little is known about this relationship when a teen has developmental disabilities (DD). We investigated the relationships of adolescents with disabilities with their mothers and their fathers in order to answer a number of questions regarding these relationships. In particular, we asked: are there differences in the relationships of mothers and fathers with their adolescent with DD? Are there early childhood predictors of the parent-teen relationship and are those based on variables that are amenable to intervention? Finally, do these predictors differ for mothers and fathers? METHODS: This study focused on the relationships of 72 mothers and 53 fathers with their 15-year-old teens with DD and their predictors from the early childhood years. Data were collected from parents through interviews and self-administered questionnaires, and from their children with disabilities through structured assessment when children were age 3 years and again at age 15 years. RESULTS: Analyses indicated that both mother-teen and father-teen relationships were predicted by earlier parenting stress. The father-teen relationship was also predicted by early behaviour problems, but this relation was mediated by parenting stress. Socio-economic status, type of disability and the child's level of functioning were not predictive of later relationships between parents and teens. Mothers and fathers did not differ significantly in their reports of perceived positive relationships with their teens. CONCLUSIONS: The findings from this study suggest two important points of potential intervention during the early intervention years. First, parenting assistance and support to reduce stress during the early childhood years can benefit both mothers and fathers. Second, helping families and children cope with and diminish problem behaviours is likely to yield multiple advantages for parents and children and deserves emphasis in early intervention and pre-school programmes.

Suppression of airway hyperresponsiveness induced by ovalbumin sensitisation and RSV infection with Y-27632, a Rho kinase inhibitor.

BACKGROUND: Smooth muscle contraction is one of the hallmarks of asthma. A recently developed pyridine derivative, Y-27632, a selective Rho kinase inhibitor, has been reported to inhibit the smooth muscle contraction of human and animal trachea in ex vivo systems but its effect in animal models of airway hyperresponsiveness (AHR) has not been examined. The purpose of this study was to evaluate the effect of Y-27632 in a murine model of allergic and virally induced AHR. METHODS: Baseline lung resistance and methacholine induced AHR were measured in mice sensitised to ovalbumin (OVA) and also in mice infected with respiratory syncytial virus (RSV) following ovalbumin sensitisation (OVA/RSV). RESULTS: Time course and dose ranging experiments indicated that 30 mg/kg Y-27632 given by gavage 2 hours before methacholine challenge significantly reduced baseline lung resistance and prevented AHR in OVA sensitised mice. Y-27632 also suppressed AHR induced by the bronchospastic agent serotonin in OVA sensitised mice and prevented methacholine induced AHR in OVA/RSV mice. CONCLUSIONS: These results suggest that the signalling pathway mediated through Rho kinase may have an important role in bronchial smooth muscle tone in allergen induced and virus induced AHR and should be considered as a novel target for asthma treatment.

Immune interaction between respiratory syncytial virus infection and allergen sensitization critically depends on timing of challenges.

Severe respiratory syncytial virus (RSV) infection has been hypothesized to be a risk factor for the development of allergy and asthma, but epidemiologic studies in humans have been inconclusive. By use of a well-characterized murine model of RSV infection and allergic sensitization with ovalbumin, the effect of a preceding severe RSV infection on the development of the pulmonary allergic inflammatory response and airway hyperresponsiveness (AHR) was tested. The impact of prior allergic sensitization on RSV-induced illness, as measured by weight loss, also was evaluated. RSV infection before allergic sensitization decreased allergen-induced AHR, production of interleukin-13 in lung tissue, and lung eosinophilia. In contrast, allergic sensitization before RSV infection increased AHR and decreased RSV-related weight loss and lung levels of interferon-gamma but did not alter viral clearance. These data provide evidence that RSV-associated AHR occurs in hosts with allergic responses and that allergic inflammation is diminished when preceded by RSV infection.

Malakoplakia of the oropharynx.

We present a case of malakoplakia presenting as a lesion in the oropharynx of an elderly smoker. In this case a clinical diagnosis of carcinoma of the pharynx was made, biopsy revealed the nature of the lesion and management was radically altered.

Major complications and consent prior to endoscopic sinus surgery.

The endonasal endoscopic approach to the paranasal sinuses is no longer exclusively practised by a small number of dedicated super-specialists and has gained widespread acceptance in the UK. We have audited the practice of the Consultant members of the BAO-HNS via a confidential postal questionnaire with regards to the consent of their patients prior to surgery, and to the complications they have experienced. The overall rate of complications following endoscopic sinus surgery (ESS) was 0.69%, with the incidence of major complications 0.25% and of minor complications 0.44%. Wide variations in the practice of informed consent were found to exist, and this is discussed with reference to a suggested template for preoperative discussion with the patient.

Bulbar presentations of myasthenia gravis in the elderly patient.

We report on three cases of patients whose primary symptoms of myasthenia gravis were related to the upper aerodigestive tract. Symptoms had been present unrecognized in all patients for up to three years, and one patient subsequently developed a myasthenic crisis. We highlight the clinical features of myasthenia gravis to allow its prompt recognition in patients presenting to the ENT surgeon or physician.

Respiratory syncytial virus infection does not increase allergen-induced type 2 cytokine production, yet increases airway hyperresponsiveness in mice.

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined murine models of allergen-sensitization and RSV infection to explore the interaction of allergic and virus-induced airway inflammation and its impact on airway hyperresponsiveness (AHR). We found that RSV infection during ova-sensitization (OVA/RSV) increased and prolonged AHR compared to mice only RSV-infected (RSV) or ova-sensitized (OVA). AHR is known to be associated with an increase in Type 2 cytokines (IL-4, IL-5, and IL-13) in allergen-sensitized mice. Therefore, we hypothesized that RSV-induced enhancement of AHR was a result of potentiating the Type 2 cytokine profile promoted by ova-sensitization. Surprisingly, we found that Type 2 cytokines induced by ova-sensitization were not increased by RSV infection despite the increase in AHR, and in some cases were diminished. RNAse protection assay revealed no difference in IL-4 and IL-5 mRNA levels between the OVA and OVA/RSV groups, and IL-13 mRNA was significantly decreased in the OVA/RSV mice compared to the OVA group. Flow cytometric analysis of Type 2 cytokines demonstrated the same frequency of IL-4 and IL-5 production in lung-derived T lymphocytes from the OVA/RSV and OVA groups. Direct cytokine ELISA measurements of lung supernatant showed the level of IL-13 was significantly decreased in the OVA/RSV group compared to OVA mice, while there was no difference in either IL-4 or IL-5 between these two groups. These data indicate that the enhanced and prolonged AHR caused by the interaction of allergic airway inflammation and virus-induced immune responses is a complex process that can not be explained simply by augmented production of Type 2 cytokines.

Long-term results of laser-assisted uvulopalatoplasty for snoring.

We present the ongoing results of the series of 53 consecutive patients who underwent laser-assisted uvulopalatoplasty (LAUP) for snoring at the Kent and Canterbury Hospital. Twenty-nine patients (55 per cent) were completely satisfied with their surgery 18 to 24 months following LAUP when previously questioned via telephone questionnaire. We have followed up the 29 patients with a previously successful result at between 70 and 79 months following surgery. They underwent an average of 1.6 procedures. Twelve patients (22 per cent) continue to be completely satisfied at this late stage, and a further 12 (22 per cent) have some ongoing improvement in their snoring. Only three patients have indicated that a previously successful result has failed since the previous survey. The failure rate of LAUP in the treatment of snoring is seen predominantly in the first two years following surgery, but some long-term subjective recurrence of snoring does occur.

Pectoralis major muscle and tendon tears: diagnosis and grading using magnetic resonance imaging.

OBJECTIVE: To assess the accuracy and utility of magnetic resonance (MR) imaging in the detection and grading of pectoralis major muscle and tendon tears. DESIGN AND PATIENTS: A retrospective review was carried out of 10 patients referred for MR imaging for suspected pectoralis muscle injury and possible operative therapy. The pectoralis muscle and tendon were imaged using thin (3-4 mm) axial sections with a variety of sequences combined for anatomical delineation (T1-weighted SE or PD SE) and fluid detection (T2-weighted SE, T2-weighted FSE with fat suppression, or STIR). Surgical correlation was available in six patients. Clinical follow-up was available in four patients treated by nonoperative therapy. RESULTS: MR imaging identified five complete tears, four partial tears and one normal tendon. One complete and one partial tear were at the myotendinous junction. The remaining seven injuries were at the enthesis. Surgical correlation consisted of five complete tears and one partial tear. One complete and one partial tear were at the myotendinous junction with the remaining four complete tears at the enthesis. The MR interpretation and surgical findings were in agreement in all six cases. All four patients treated with nonoperative therapy demonstrated improvement at a clinical follow-up examination, with restoration of function and strength consistent with a healed prior partial injury. CONCLUSION: MR imaging is accurate and useful in detecting and grading tears involving the pectoralis major muscle and tendon, facilitating the identification of patients with complete tears who are candidates for operative therapy.

Respiratory syncytial virus (RSV)-induced airway hyperresponsiveness in allergically sensitized mice is inhibited by live RSV and exacerbated by formalin-inactivated RSV.

Respiratory syncytial virus (RSV)-induced disease is associated with recurrent episodes of wheezing in children, and an effective vaccine currently is not available. The use of 2 immunizations (a formalin-inactivated, alum-precipitated RSV vaccine [FI-RSV] given intramuscularly and live RSV given intranasally [LVIN]), with a control immunization, were compared in a well-characterized model of RSV challenge, with or without concomitant allergic sensitization with ovalbumin. FI-RSV caused a significant increase in airway hyperresponsiveness in mice after RSV infection during allergic sensitization, and this was associated with an increase in type 2 cytokine production. In contrast, immunization with LVIN did not change type 2 cytokine production and protected against RSV-induced airway hyperresponsiveness in the setting of allergic sensitization. This study suggests that immune modulation with RSV vaccination can have profound effects on RSV-induced airway disease and that prevention of airway hyperresponsiveness is an important end point in vaccine development.

Cyclooxygenase inhibition increases interleukin 5 and interleukin 13 production and airway hyperresponsiveness in allergic mice.

The immunomodulatory role of arachidonic acid metabolites in allergic sensitization is undefined. Prostaglandin E(2) (PGE(2)), a product of arachidonic acid metabolism through the cyclooxygenase pathway, has been reported to favor Type 2-like cytokine secretion profiles in murine and human CD4(+) T cells by inhibiting the production of Type 1-associated cytokines. On the basis of these in vitro data, we hypothesized that indomethacin, a nonselective cyclooxygenase inhibitor, would diminish allergen-induced production of Type 2 cytokines in mice, and protect against airway hyperresponsiveness (AHR) to methacholine. We found that ovalbumin-sensitized mice that were treated with indomethacin (OVA-indomethacin mice) had significantly greater AHR (p < 0.05) and higher levels of IL-5 (176 +/- 52 versus 66 +/- 4 pg/ml) and IL-13 (1,226 +/- 279 versus 475 +/- 65 pg/ml) in lung supernatants than mice sensitized with ovalbumin alone (OVA mice), while levels of IL-4 and serum IgE were not different. Lung mRNA expression of the C-C chemokine MCP-1 was increased in OVA-indomethacin mice, while there was no difference between the two groups in lung mRNA expression of eotaxin, MIP-1alpha, MIP-1beta, or MIP-2. Histologic examination revealed greater pulmonary interstitial eosinophilia in OVA-indomethacin mice as well. Contrary to our expectations, we conclude that in the BALB/c mouse, cyclooxygenase inhibition during allergen sensitization increases AHR, production of IL-5 and IL-13, and interstitial eosinophilia.

Preferential role for NF-kappa B/Rel signaling in the type 1 but not type 2 T cell-dependent immune response in vivo.

T cell function is a critical determinant of immune responses as well as susceptibility to allergic diseases. Activated T cells can differentiate into effectors whose cytokine profile is limited to type 1 (IFN-gamma-dominant) or type 2 (IL-4-, IL-5-dominant) patterns. To investigate mechanisms that connect extracellular stimuli with the regulation of effector T cell function, we have measured immune responses of transgenic mice whose NF-kappa B/Rel signaling pathway is inhibited in T cells. Surprisingly, these mice developed type 2 T cell-dependent responses (IgE and eosinophil recruitment) in a model of allergic pulmonary inflammation. In contrast, type 1 T cell responses were severely impaired, as evidenced by markedly diminished delayed-type hypersensitivity responses, IFN-gamma production, and Ag-specific IgG2a levels. Taken together, these data indicate that inhibition of NF-kappa B can lead to preferential impairment of type 1 as compared with type 2 T cell-dependent responses.

Respiratory syncytial virus infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin-sensitized mice.

Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined models of allergen sensitization and RSV infection to begin exploring the immunologic interactions between allergic and virus-induced airway inflammation and its impact on airway hypersensitivity. Airway resistance was measured after methacholine challenge in tracheally intubated mice by whole body plethysmography. Lung inflammation was assessed by bronchoalveolar lavage (BAL) and histopathology. RSV infection alone did not cause significant airway hyperresponsiveness (AHR) to methacholine. Ovalbumin (OVA)-induced AHR lasted only a few days past the discontinuance of OVA aerosol in mice that were ovalbumin sensitized and mock infected. In contrast, OVA-sensitized mice infected with RSV during the OVA aerosol treatments (OVA/RSV) had AHR for more than 2 weeks after infection. However, 2 weeks after either RSV or mock infection, OVA/RSV mice had significantly more lymphocytes found during BAL than OVA mice, whereas the OVA and OVA/RSV groups had the same number of eosinophils. Histopathologic analysis confirmed an increased inflammation in the lungs of OVA/RSV mice compared with OVA mice. In addition, OVA/RSV mice had a more widespread distribution of mucus in their airways with increased amounts of intraluminal mucus pools compared with the other groups. Thus, prolonged AHR in RSV-infected mice during ovalbumin-sensitization correlates with increased numbers of lymphocytes in BAL fluid, increased lung inflammation, and mucus deposition in the airways, but not with airway eosinophilia. A further understanding of the immunologic consequences of combined allergic and virus-induced airway inflammation will impact the management of diseases associated with airway hyperreactivity.

Laser assisted uvulopalatoplasty: six and eighteen month results.

Our ongoing evaluation of the results of laser assisted uvulopalatoplasty (LAUP) for snoring is presented. Follow-up between 18 and 24 months post-treatment completion, of patients with a successful result at six months, reveals that 22 per cent of these patients suffer failure of snoring control between these two evaluation points. This equates to an overall success rate at this time of 55 per cent. LAUP, like other surgical remedies for snoring, has a continued relapse rate. This must be considered when counselling patients.

Adult age differences in long-term semantic priming.

Young and older adults were first asked to decide if a list of individually presented words were "living" (e.g., "tree") or "nonliving" (e.g., "store"). This was termed the "orienting task." Next, subjects performed a pronunciation task. Semantic priming for young and older adults was indexed by determining if semantic congruence between words in the orienting task and words in the pronunciation task improved performance on the pronunciation task relative to pronounced words from semantic categories not primed in the orienting task. The present data, from two different experiments, revealed that subjects pronounced high-dominance exemplars of the "living" words primed in the orienting task faster than words not primed in the orienting task. These data indicated that semantic priming for relatively long prime-target stimulus onset asynchronies can occur, and that such priming is at least as robust for older adults as for young adults. The results are discussed in terms of four current models of semantic priming.

Cloning of the phytases from Emericella nidulans and the thermophilic fungus Talaromyces thermophilus.

Phytases (EC 3.1.3.8) belong to the family of histidine acid phosphatases. We have cloned the phytases of the fungi Emericella nidulans and Talaromyces thermophilus. The putative enzyme encoded by the E. nidulans sequence consists of 463 amino acids and has a Mr of 51785. The protein deduced from the T. thermophilus sequence consists of 466 amino acids corresponding to a Mr of 51450. Both predicted amino acid sequences exhibited high identity (48% to 67%) to known phytases. This high level of identity allowed the modelling of all available fungal phytases based on the three-dimensional structure coordinates of the Aspergillus niger phytase. By this approach we identified 21 amino acids which are conserved in fungal phyA phytases and are part of the residues forming the substrate pocket. Furthermore, potential glycosylation sites were identified and compared between the aforementioned phytases and the A. niger phytase.