Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid‐naïve, allergen‐challenged and allergen‐naïve subjects (atopic asthmatics, atopic non‐asthmatics and non‐atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA‐DR⁺ (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4⁺ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC‐dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05–P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c⁻CD123^high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.     

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.     

General practitioners' views on the implementation of community-led maternity care in south Camden, London.

New recommendations suggesting that maternity care should be increasingly community-based have generated concern regarding the interprofessional cooperation between general practitioners and midwives. In Camden, London, this service was expanded in 1993. Although existing joint antenatal care arrangements between GPs and midwives were not expected to alter significantly, the shift of care from hospital to community midwives, and the expansion of community-led care to women with complications, was expected to have implications for the GPs. A questionnaire-based study asked GPs who provide antenatal care about their role and liaison with other professionals. Most were satisfied with the current arrangements; only a minority felt that their workload, clinical practice, or communication with obstetric teams had altered.     

A prospective study of the effectiveness of brief professionally-led support groups for infertility patients.

OBJECTIVE: This study prospectively evaluates the effectiveness and patient acceptability of professionally-led support groups in alleviating psychologic distress in infertility patients. METHOD: Sixty-four consecutive patients in a university hospital infertility program were administered a battery of psychologic tests before and after attendance at an 8 weekly session support group. The comparison group consisted of 35 consecutive infertility referrals to the same unit who were not initially offered the support group and were similarly tested over an 8 week period. RESULTS: Support group patients had significantly greater (p less than or equal to 0.01) entry than exit scores on several measures of psychologic distress and depression (the Beck Depression Inventory, the Hamilton Rating Scale for Depression, and the Global Severity Index, Anxiety, Depression, Hostility and Obsessive Compulsive Subscales of the Brief Symptom Inventory). The Avoidance Coping Style on the Moos Coping Responses Inventory was correlated with a higher Global Severity Index (p less than or equal to 0.01). Comparison group patients had similar psychometric scores to the support group patients at entry but showed no change over 8 weeks. Attenders expressed a high rate of satisfaction with the support group. CONCLUSIONS: Professionally-led support groups are a highly acceptable and effective intervention in self-referred patients in alleviating psychological distress related to infertility.     

Effectiveness of two palliative support teams.

The palliative care of 227 consecutive patients by two support teams was measured according to 17 key indicators in the Support Team Assessment Schedule (STAS), an instrument previously developed and validated for use in these settings. Mean time in care was 71 days (range 1-547); 56 per cent of patients died at home, 26 per cent in hospital, 18 per cent in a hospice. Totalled ratings (sum of 15 items, excluding two items owing to missed ratings) improved in 83 per cent of cases, remained unchanged in 3 per cent and deteriorated in 13 per cent. The main problems which the STAS identified at referral were family anxiety, symptom control, patient anxiety and communication between patient and family. Fifteen of the 17 items showed significant improvements (Wilcoxon Z ranged from -3.18 to -8.20, p less than 0.00005) between referral ratings and ratings for the last week of the patient's life; family anxiety and spiritual needs did not. Patient anxiety and symptom control, although improved, also remained relatively severe at death. These results demonstrate the value of measuring key indicators and indicate areas where improvement in palliative care is needed.     

Predicting drug-resistant patients who respond to add-on therapy with levetiracetam.

INTRODUCTION: Levetiracetam (LEV) is approved for use as add-on therapy in adult patients with partial epilepsy. It is apparent from clinical trials that up to 8% of previously drug-resistant patients may be rendered seizure-free by adding-on levetiracetam. As yet there is no way of predicting these unexpectedly responsive patients. We set out to identify our previously refractory patients who had demonstrated unexpected responsiveness to add-on therapy with levetiracetam, and compared these to patients who had not responded to the drug. We then attempted to characterise any clinical features that differentiated these groups of patients. METHODS: We included all patients with a history of present or previous exposure to levetiracetam who had been unresponsive to at least two other prior anti-epileptic drugs (AEDs) and recorded their demographic and clinical data. We divided response into (a) 'seizure-free' (seizure-free for a minimum of 6 months after commencing LEV); (b) 'partial > 50%' (greater than 50% reduction in seizures for a minimum of 6 months after commencing LEV); (c) 'honeymoon' (seizure-free for less than 6 months after commencing LEV and then returned towards baseline frequency); and (d) 'no-response'. For the purpose of analysis we considered the 'seizure-free' and 'partial > 50%' groups as 'responders', and the 'no response' group as 'non responders'. RESULTS: 344 patients were included in the analysis. Fifty-six patients (16.3%) were rendered seizure-free on levetiracetam. Idiopathic generalised epilepsy and post-traumatic partial epilepsy were more common in the responder than the non-responder group (p = 0.005 and 0.05 respectively). Lamotrigine was used significantly more often in combination with levetiracetam in responders than non-responders (p = 0.003). The mean daily dose of levetiracetam was lower in responders than non-responders. DISCUSSION: A higher than expected number of previously drug resistant patients was rendered seizure-free by add-on therapy with levetiracetam. Those who respond best appear to do so at relatively low doses and our data suggest the possibility of a beneficial pharmacodynamic interaction between levetiracetam and lamotrigine. We were unable to identify any clinical factors that clearly predicted which patients would become seizure-free and we hypothesise that response may be determined by genetic or molecular factors. All drug-resistant patients, including those being assessed for surgery, should be considered for a trial of levetiracetam, regardless of their epilepsy classification.     

A cognitive-behavioral approach to understanding and treating sexual trauma

This paper presents a cognitive-behavioral model for conceptualizing and intervening in the area of sexual trauma. A central theme is understanding and modifying the process of victimization. The survivor of sexual trauma can regain a positive sexual self-esteem and view sexuality as a planful, choiceful activity which can enhance her life.