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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.

Background: Steroid-induced adverse effects including suppression of humoral immunity should be considered in steroid-dependent severe asthma. Only a few studies have determined the exact steroid dose that could potentially suppress humoral immunity in asthmatics. Methods: Randomly selected 100 adult asthmatics treated with inhaled beclomethasone dipropionate (BDP) were classified into three groups based on the dose of steroid to determine the serum IgG, IgA and IgM levels by radioimmunoassay. Relationships between serum immunoglobulin levels and the daily dose and duration of oral prednisolone (PSL) therapy were examined. Results: None of the patients on inhaled corticosteroid alone had hypogammaglobulinemia. Patients on oral PSL at a dose >12.5 mg/day for at least 1 year had low serum IgG. There was no significant correlation between the duration of oral PSL therapy and serum IgG. Conclusions: Oral PSL can potentially suppress humoral immunity in severe asthma. In asthmatics, hypogammaglobulinemia could develop in those on a daily dose of PSL >12.5 mg, but is independent of the duration of such treatment. No suppression of humoral immunity was noted on inhaled corticosteroid therapy alone, either at low or high dose.

A few studies compared the additional effects of oral controller medicines on pulmonary function in asthmatic patients on a moderate dose of inhaled steroids. The aim of this study was to compare the additional effects of two oral asthma controllers, a leukotriene receptor antagonist and a sustained released theophylline (Theo), with a moderate dose of inhaled steroid on peak expiratory flow (PEF) and asthma-related symptoms. A total of 67 adult asthmatic patients with PEF <80% predicted during a 2-week run-in period with 800 μg/day of beclomethasone dipropionate were randomized to receive either pranlukast, 450 mg/day (n = 33), or sustained released Theo, 200 mg/day (n = 34), for 4 weeks. Pranlukast and Theo did not significantly alter the symptom scores, use of rescue β2-agonist, and daily PEF variability. However, both agents significantly increased both morning and evening PEF compared with the run-in periods. The effects of both medications were comparable. For asthmatic patients even on a moderate dose of inhaled steroids, the addition of either leukotriene receptor antagonist or sustained released Theo does not improve asthma-related symptoms but significantly and equally increases PEF.

Leukotrienes (LTs) are important in asthma, and LT modifiers modulate antigen-induced asthma. Overproduction of LT by suppression of cyclooxygenase activity is involved in patients with aspirin-intolerant asthma (AIA). House dust mite (HDM) inhalation provocation tests were performed in HDM-sensitive asthmatic inpatients without AIA (HDM group; n = 6), and aspirin oral provocation tests were performed in AIA patients (ASA group; n = 7). Tests were repeated using the same regimen after 7 days of treatment with pranlukast, an LT receptor antagonist (LTRA). The effects of pranlukast on changes in sputum LTC4-LTD4, eosinophil cationic protein (ECP), eosinophil count, urinary LTE4/creatinine, 11-dehydrothromboxane B2 (11-dhTXB2)/creatinine, serum LTC4-LTD4, ECP, and peripheral blood eosinophil count, during immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) in the HDM group and during IAR in the ASA group for each test, were compared in each group. In the HDM group, IAR and LAR were observed. Sputum LTC4-LTD4 and urinary LTE4/creatinine increased significantly both during IAR and LAR. Sputum ECP increased during IAR and further increased during LAR. Eosinophil count in the sputum did not increase during IAR but significantly increased during LAR. Pranlukast suppressed the fall in FEV1 both during IAR and LAR (73.8% and 51.9%, respectively) and inhibited the increase in sputum eosinophil count during LAR and sputum ECP during IAR and LAR. In the ASA group, aspirin-induced IAR was associated with a fall in urinary 11-dhTXB2/creatinine, increased the levels of sputum LTC4-LTD4 and ECP and urinary LTE4/creatinine. Pranlukast suppressed IAR and inhibited the increase of the level of sputum ECP, but failed to change aspirin-induced LT production in the sputum and urine. The levels of sputum LTC4-LTD4 and urinary LTE4/creatinine in the stable phase in the ASA group were significantly greater than those in the HDM group. Our results indicated that HDM-provoked asthma is associated with overproduction of LT with an antigen-antibody reaction, while AIA is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade. LTRA may be useful against both types of asthma through inhibition of LT activity and eosinophilic inflammation of the airways.

Background For asthma strategy, to avoid the aggravation of bronchial inflammation and contraction, the long acting beta agonist (LABA) addition on inhaled corticosteroids (ICS) has been recommended. Objectives To know whether there is any clinical difference between the additional efficacies of Formoterol (FOR) and Tulobuterol (TUL) onto Budesonide (BUD) may be useful for the elderly patients’ asthma treatment strategy. Methods Eighteen outpatients with mild to moderate bronchial asthma with FEV1.0% < 80% treated by intermediate ICS dosages visited Respiratory Division of Nagasaki University Hospital or Isahaya General Hospital, Japan Community Health care Organization were subjected, and were randomly assigned (9 cases per group) to either the FBC group (BUD/FOR 160/4.5 µg, 2 inhalations twice daily) or BUD + TUL group (BUD 200 mcg: 2 inhalations twice daily + TUL 2 mg daily) and were compared in parallel with 2 arms for 12 weeks prospectively. Peak expiratory flow, forced expiratory volume in 1 second, impulse oscillometry (IOS), fractional exhaled nitric oxide (FeNO), Asthma Control Questionnaire, mini-Asthma Quality of Life Questionnaire (mini-AQLQ), and occurrence of adverse reactions were compared. Results The “Fres” of IOS was improved in FBC group (p = 0.03). The “emotion” domain of mini-AQLQ was improved in BUD + TUL group (p = 0.03). Conclusion By changing the drug formulation, the patch was superior in terms of satisfaction, but it was thought that the inhaled combination was superior in improving the respiratory function itself. It is necessary to pay attention to the characteristics of the patient when selecting treatment.

It remains controversial whether biological or mechanical prostheses in the tricuspid position give better long-term results. The clinical advantage of mechanical prostheses is evaluated in this article. Our subjects were 25 consecutive patients who underwent tricuspid valve replacement (TVR) from January 1985. Five patients underwent TVR with mechanical prostheses (MP), and 20 patients had bioprostheses (BP). The mean age of the patients was 50.8 ± 15.9 years for those with MP and 50.2 ± 11.5 years old for those with BP. The preoperative New York Heart Association (NYHA) functional classification was 3.5 for those with MP and 3.1 for BP. The mean follow-up period was 5.05 ± 2.05 years for MP, ranging from 3 to 7 years, and 7.2 ± 5.6 years for BP, ranging from 1 to 12 years. No operative mortality occurred, but there was a single hospital death in a patient with BP due to sepsis after acute postoperative cholecystitis. One patient with BP suffered from neurological deficiencies. Long-term temporary cardiac pacing was required in one patient with MP and three with BP. A permanent cardiac pacemaker was implanted in one patient with BP. There was one late death in the MP group and three late deaths in the BP group. The actuarial survival rates at 5 and 7 years after surgery were 80% and 80%, respectively, for MP and 88% and 88% for BP. There was one embolic episode, a minor stroke, in the BP group. Four patients with BP had valvular dysfunction at 3, 8, 9, and 10 years after surgery, and two of these required re-TVR. Among BP patients, 93% were free from prostheses dysfunction at 5 years after surgery, and 78% were free from dysfunction after 10 years; all patients (100%) with MP were free from dysfunction at 7 years. This study suggests that TVR with MP shows no late complications and with careful anticoagulant therapy provides highly satisfactory follow-up results.[PUBLICATION ABSTRACT]

Glomerular crescents are a major determinant of progression in various renal diseases. Some types of growth factors are known to be involved in the evolution of crescents and the subsequent scar formation. Although glomerular parietal epithelial cells (PECs) are the major component of cellular crescents, the influence of growth factors on PECs is unknown. We performed immunohistochemical studies and in situ hybridization to examine alterations in connective tissue growth factor (CTGF) expression and to identify CTGF-synthesizing cells in crescents in the crescentic glomerulonephritis model of Wistar Kyoto rats. In addition, we examined the roles of fibroblast growth factor (FGF)-2, platelet-derived growth factor (PDGF)-BB, transforming growth factor (TGF)-β, and CTGF in cell proliferation and matrix synthesis in an established rat PEC cell line (PEC line). In an acute phase of rat crescentic glomerulonephritis, a major component of the crescents were macrophages, which did not express CTGF mRNA. However, in the advanced phase, crescents strongly expressed CTGF mRNA and the epithelial marker pan-cadherin but did not express the macrophage marker ED1, suggesting that PECs synthesized the CTGF. In the PEC line, FGF-2 predominantly promoted [3H]thymidine incorporation compared with PDGF-BB. Both TGF-β and PDGF-BB strongly stimulated extracellular matrix synthesis in association with up-regulation of endogenous CTGF, but TGF-β showed a predominant role. FGF-2 had a minor effect on it. In addition, blockade of endogenous CTGF using an antisense oligodeoxynucleotide significantly attenuated both TGF-β- and PDGF-BB–induced extracellular matrix synthesis. These results suggest that several growth factors promote cell proliferation and matrix production in PECs. CTGF-mediated matrix production via the TGF-β or PDGF-BB pathway in PECs may, in part, play a role in the progression of scar formation in crescents.

Backgrounds: Approximately half of the Japanese asthmatics experience exacerbation of asthma after alcohol consumption. We previously reported that this phenomenon is probably caused by histamine release from mast cells by acetaldehyde stimulation. However, no reports have described the effects of acetaldehyde on human airway mast cells. The purpose of the present study was to demonstrate acetaldehyde-induced histamine release from human airway mast cells with subsequent airway smooth muscle contraction and to investigate the ensuing mechanisms. Methods: Human tissue samples were prepared from the lungs resected from patients with lung cancer. The effect of acetaldehyde on airway muscle tone and the concentration of chemical mediators released in the organ bath were measured before and after acetaldehyde stimulation. Mast cells were prepared from lung parenchyma by the immunomagnetic method and then stimulated with acetaldehyde to determine the chemical mediators released. Results: Acetaldehyde (>3 × 10 –4 M) increased airway muscle tone, which was associated with a significant increase in the release of histamine, but not thromboxane B 2 or cysteinyl-leukotrienes. A histamine (H 1 receptor) antagonist completely inhibited acetaldehyde-induced bronchial smooth muscle contraction. Acetaldehyde also induced a significant histamine release from human lung mast cells and degranulation of mast cells. Conclusions: The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine, which may be involved in bronchial smooth muscle contraction following alcohol consumption.

Abstract Dendritic cells (DCs) are the only antigen-presenting cells that determine T-cell differentiation and play an important role in both allergy and viral infection. Respiratory syncytial virus (RSV) can infect DCs and affect their functions. The aim of this study was to determine the interaction between RSV infection and Dermatophagoides farinae allergen (D. farinae) sensitization on the development of allergy at the DC level. Murine bone marrow–derived DCs were prepared and treated as: control; D. farinae–pulsed DCs (D. farinae–DCs); ultraviolet-inactivated RSV challenged; RSV-infected, D. farinae–pulsed plus ultraviolet-inactivated RSV-challenged; and D. farinae–pulsed plus RSV-infected. In in vitro experiments, we compared the expression of costimulatory molecules and cytokine production between the six groups of DCs. Another group of naive mice were then intranasally inoculated with these DCs, after which intranasal challenge with D. farinae was performed to develop allergic airway inflammation in vivo. In comparison with D. farinae–DCs, D. farinae–pulsed plus RSV-infected DCs showed helper T cell (Th) 1–favored expression of costimulatory molecules and cytokine production. Allergic airway inflammation induced by intranasal instillation of D. farinae–DCs was abrogated when infected with RSV, which was associated with a concomitant suppression of Th2 response in the lung. Our results indicated that RSV suppresses D. farinae–DCs to induce Th2 response both in vitro and in vivo through regulation of expression of surface markers and production of immunoregulatory cytokines.

Background: Pranlukast, a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation. The aim of this study was to determine the mechanism of pranlukast-induced interleukin-5 (IL-5) inhibition in allergic inflammation. Methods: Surgically resected human lung tissue was passively sensitized in vitro with mite-allergen-sensitized sera, followed by stimulation with mite allergen after pretreatment of the tissue with pranlukast, dexamethasone, or both. The IL-5 protein level in the culture medium was measured, and in situ hybridization of IL-5 and CysLTR1 mRNA was performed using lung tissues. Results: Pretreatment of lung tissues with pranlukast alone significantly decreased the amount of IL-5 protein in the culture medium by 40%. The combination of pranlukast and dexamethasone synergistically enhanced this effect. Quantitative in situ hybridization with image analysis revealed abundant expression of IL-5 mRNA in eosinophils, lymphocytes, and mast cells in sensitized and allergen-stimulated lung tissues. CysLTR1 mRNA was detected in macrophages, smooth muscle cells, eosinophils, and mast cells, but was less expressed in lymphocytes. Pranlukast-induced inhibition of IL-5 mRNA expression was noted in various cells, irrespective of their CysLTR1 mRNA expression status. In addition, cysteinyl leukotrienes per se failed to upregulate the IL-5 production. Conclusion: Our results indicate that pranlukast inhibits IL-5 synthesis via a mechanism distinct from CysLTR1 antagonism.