Summary
This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in ...patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20.
Background
Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term.
Objective
This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs.
Methods
This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients’ conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors.
Results
The mean observation period was 4.0 years (range 0–7 years). The average age at the time of admission was 82 years (range 60–101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio HR 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82–91), low risk (92–98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (
p
< 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88
p
= 0.004).
Conclusions
We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.
Summary
Background
The role in allergic asthma development of the immune response against fungi with concomitant exposure to other common aeroallergens has yet to be determined. In particular, there ...is little understanding of how inhaled fungi affect the host response to mite allergens.
Objective
To characterize the in vitro and in vivo effects of concurrent exposure of Aspergillus fumigatus (Af) and Dermatophagoides farinae (Derf) on dendritic cells (DCs) in the development of allergic asthma.
Methods
Murine bone marrow‐derived DCs were pulsed with Derf and/or live or heat‐inactivated Af. Cytokine production and the expression of pathogen recognition receptors (PRRs) were determined in vitro. Subsequently, these DCs were inoculated into the airway of naïve mice to assess the development of allergic airway inflammation in vivo. The effect of antibodies against PRRs was also evaluated.
Results
Live Af significantly enhanced IL‐10 production and the expression of Toll‐like receptor (TLR) 2 and Dectin‐1 in Derf‐pulsed DCs. Live Af infection significantly attenuated Derf‐pulsed DC‐induced allergic airway inflammation in vivo. Antibodies against either TLR2 or Dectin‐1 significantly reversed the inhibitory effects of live Af in the development of Derf‐pulsed DC‐induced allergic airway inflammation.
Conclusion
Concurrent exposure of DCs to fungal antigens has profound influences on the subsequent mite allergen‐induced allergic airway inflammation. Live Af could regulate the functions of airway DCs in the development of mite allergen‐induced allergic airway inflammation via regulation of their PRRs.
Our results suggest that concurrent exposure to pathogens such as fungi and mite allergens has profound influences on the subsequent allergen‐induced allergic airway inflammation. Furthermore, modulating PRR signalling could provide a therapeutic regimen for the development of asthma.
Cite this as: S. Fukahori, H. Matsuse, T. Tsuchida, T. Kawano, S. Tomari, C. Fukushima and S. Kohno, Clinical & Experimental Allergy, 2010 (40) 1507–1515.
A fully integrated 40 Gb/s transmitter and receiver chipset with SFI-5 interface is implemented in a 65 nm CMOS technology and mounted in a plastic BGA package. The transmitter chip provides good ...jitter performance with a 40 GHz full-rate clock architecture that alleviates pattern-dependent jitter and eliminates duty cycle dependence. The measured RMS jitter on the output is 570 fs to 900 fs over the range of 39.8 Gb/s to 44.6 Gb/s with a 2 31 -1 PRBS pattern. The receiver chip operates over the range of 37 Gb/s to 41 Gb/s. The measured RMS jitter on the recovered clock is 359 fs to 450 fs. By taking advantage of CMOS technology, each chip achieves low power consumption of 2.8 W and full integration of SFI-5 functions, PRBS generators/error checkers, a DPSK precoder/decoder, and control interfaces in a 4.9 × 5.2 mm 2 die.
Summary
Background
Respiratory syncytial virus (RSV) infection is known to develop and exacerbate asthma in young children. In adult, RSV causes recurrent but asymptomatic infections. However, the ...impact of asymptomatic RSV infection on adult asthma is yet to be determined. The present study is designed to determine the effects of primary and secondary low‐grade RSV infections on allergic airway inflammation in a murine model of allergic asthma.
Methods
A low‐grade RSV (2 × 103 plaque‐forming units/mouse) was inoculated, and this caused neither pulmonary inflammation nor symptoms but induced significant IFN‐γ production in thoracic lymph nodes. To investigate interaction between low‐grade virus and Dermatophagoides farinae (Df), airway hyper‐responsiveness, lung inflammation and cytokine production from thoracic lymph nodes were compared after primary and secondary low‐grade RSV infections in four groups of mice; control, Df allergen‐sensitized, RSV‐infected and Df‐sensitized RSV‐infected mice. A direct comparison between low‐ and high‐grade RSV infections was also performed in primary infection. To investigate the role of IL‐5 during secondary RSV infection, anti‐IL‐5 monoclonal antibody (anti‐IL‐5 mAb) was injected in mice and similar parameters were compared in four groups of mice.
Results
Primary high‐grade RSV infection increased allergen‐induced airway inflammation, while primary low‐grade RSV infection attenuated allergen‐induced airway inflammation concomitant with significant IFN‐γ production in lung‐draining lymph nodes. In marked contrast, secondary low‐grade RSV infection increased both IFN‐γ and IL‐5 production, resulting in exacerbation of allergen‐induced airway inflammation. Anti‐IL‐5 mAb treatment in secondary low‐grade RSV infection and Df allergen‐sensitized mice attenuated virus and allergen‐induced airway inflammation.
Conclusions
Low‐grade RSV infection per se does not cause pulmonary inflammation, whereas it induces a significant immunological response in the allergen‐sensitized host. These results indicate that subclinical and recurrent RSV infection may play an important role in exacerbation and maintenance of asthma in adults, wherein IL‐5 is critically involved.
Summary
Background
Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. β2‐agonists could potentially exacerbate type 2 T helper (Th2) ...cell‐mediated immune response.
Objectives
To determine the effects of various anti‐asthmatic agents on DCs function both in vitro and in vivo.
Methods
Murine bone marrow‐derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo.
Results
Pranlukast reduced IL‐10 and increased IL‐12, while fluticasone reduced both IL‐10 and IL‐12 production by mite allergen‐pulsed DCs. Allergic airway inflammation in pranlukast‐ and fluticasone‐treated and mite allergen pulsed DCs‐harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL‐12 production by mite allergen‐pulsed DCs. Lung pathology in β2‐agonist‐harbouring mice was comparable with those of mite allergen‐pulsed DCs‐harbouring mice.
Conclusions
Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs‐induced Th2 skewed immune response, and that short‐ and long‐acting β2‐agonists do not modify DCs‐induced allergic airway inflammation.
Summary
Background The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1 antagonists on inhibition of ...inflammatory cytokine production is yet to be determined.
Objective The present study was designed to determine the effect of pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by allergen‐stimulated peripheral blood monocytes (PBM) from atopic asthmatics.
Methods PBM were obtained from normal control (n = 10) and Dermatophagoides farinae (Der f) allergen‐sensitized atopic asthmatics (n = 12), and were cultured in the presence of Der f allergen. The production of TNF‐α and nuclear‐translocation of nuclear factor kappa B (NF‐κB) was determined. In atopic asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation by Der f. The additive effect of pranlukast and dexamethasone was also determined.
Results PBM from atopic asthmatics cultured with Der f exhibited a significant increase in TNF‐α production and nuclear translocation of NF‐κB compared with normal control (P < 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF‐α and nuclear‐translocation of NF‐κB in PBM of atopic asthmatics (P < 0.01). An additive effect of pranlukast on low‐dose dexamethasone was also demonstrated. However, LTD4 did not induce TNF‐α production or NF‐κB nuclear translocation.
Conclusion Our results suggest that pranlukast may inhibit TNF‐α production via suppression of NF‐κB activation through pathways distinct from cysLTR1 antagonism.
The exact mechanism of aspirin-induced asthma is not clear. It has been postulated that precipitation of asthma attacks by aspirin is linked to inhibition of COX activity and massive release of ...cysteinyl leukotriene into the airway. Tacrolimus, a macrolide-derived immunosuppressant, is used for immunosuppression in organ transplantation and also for allergic diseases such as atopic dermatitis.
We evaluated the effects of tacrolimus in aspirin-induced asthma by using a double-blind, crossover study design.
Twelve patients with aspirin-induced asthma (male:female, 3:9; mean age ± SD, 36.7 ± 7.2 years) received either tacrolimus (0.1 mg/kg) or placebo 2 hours before the threshold dose of oral aspirin.
In the placebo arm, oral aspirin significantly decreased FEV1 concomitant with significant increases in sputum eosinophilic cationic protein and urinary leukotriene E4 levels. Tacrolimus significantly inhibited bronchoconstriction and abrogated aspirin-induced increase in both sputum eosinophilic cationic protein and urinary leukotriene E4 levels.
The current study suggested that tacrolimus inhibited bronchoconstriction to a threshold dose of aspirin by inhibition of cysteinyl leukotriene excretion.
Background: About 70% of childhood asthmatics become free of asthma‐related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young ...adults with “outgrown” childhood asthma.
Methods: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma‐related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte‐macrophage colony stimulating factor (GM‐CSF), and tumor necrosis factor‐α (TNF‐α).
Results: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF‐α and GM‐CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF‐α in sputum correlated significantly with BHR.
Conclusions: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.
Background: We have previously reported that alcohol-induced asthma in Japanese patients is caused by increased blood acetaldehyde concentration resulting from abnormalities of acetaldehyde ...dehydrogenase 2 (ALDH2) enzyme activity on the basis of ALDH2 genotype differences. Objectives: The purpose of the present study was to determine whether the ethanol patch test could predict the ALDH2 genotype in Japanese asthmatic subjects. Methods: An ethanol patch test on the upper arm and a questionnaire survey addressing the past history of alcohol-induced asthma were administered to 148 adult Japanese asthmatic subjects. The ALDH2 genotypes in these 148 subjects were also determined by means of PCR. Results: The genotype distribution of ALDH2 determined by PCR in 68 subjects with positive ethanol patch test results was 4 (5.9%), 56 (82.4%), and 8 (11.8%) for genotypes NN (normal homozygote), NM (mutant heterozygote), and MM (mutant homozygote). The ALDH2 genotype in 80 subjects with a negative test result was only NN. The distribution of ALDH2 genotype in 78 (52.7%) subjects who had experienced alcohol-induced asthma symptoms on the basis of the questionnaire was 27 (34.6%), 44 (56.4%), and 7 (9.0%) for genotypes NN, NM, and MM, respectively. On the other hand, 70 subjects had never experienced alcohol-induced asthma symptoms. In these subjects the ALDH2 genotype was NN in 51 (72.9%), NM in 18 (25.7%), and MM in 1 (1.4%). Conclusions: Our results indicate that the results of ethanol patch testing correlate well with ALDH2 genotype, as determined by means of PCR, suggesting that the ethanol patch test is useful for the screening of alcohol-induced asthma. (J Allergy Clin Immunol 2001;108:715-9.)
