BACKGROUND: Upper airway diseases, such as vocal cord dysfunction (VCD), masquerade as asthma. Bronchial hyperresponsiveness (BHR) to methacholine (MCh) has been demonstrated in only part of suspected asthma patients. Investigators have shown upper airway hyperresponsi- veness (UHR) in patients with VCD. OBJECTIVE: To determine the clinical importance of UHR and to evaluate the usefulness of UHR test in patients with suspected asthma. METHODS: Thirty-six consecutive patients with suspected asthma underwent a MCh inhalation challenge. BHR was determined with PC20 < 8 mg/ml, UHR with a decrease in MIF50 > 25% from the baseline, and upper airway obstruction (UAO) with MEF50/MIF50 > 1. RESULTS: Only 17 patients (47.2%) showed BHR. Also, the same proportion of subjects showed UHR, and the each combination of BHR/UHR was nearly equal in distribution (9 BHR+/UHR-, 8 BHR+/UHR+, 9 BHR-/UHR+, and 10 BHR-/UHR-). Patients with BHR-/UHR+ had significantly lower serum total IgE level than those with BHR-/UHR-. Eight patients with UHR and UAO showed significantly shorter duration of disease (p < 0.05), smaller numbers of atopy family history (p < 0.05), and lower serum total IgE level than the others (p < 0.05). CONCLUSION: Many patients with suspected asthma showed UHR, and about half of patients with negative MCh-BHR showed UHR that might be related to non-asthmatic diseases including VCD. Therefore, a routine UHR test may be warranted in detecting upper airway diseases in suspected asthma.
Airway Obstruction ; Asthma* ; Humans ; Immunoglobulin E ; Inhalation ; Methacholine Chloride* ; Research Personnel ; Vocal Cord Dysfunction

The objective of this study is to investigate whether BCG infection before, during or after sensitization suppresses allergen-induced airway hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to determine the required dose of BCG to induce such an inhibition. Eighty-seven Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or saline was done at four different times: 3 days before sensitization, at sensitization, 3 days before provocation, or at provocation. The assessment of tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats infected 3 days before sensitization or at sensitization, but not 3 days before provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly inhibited not only the airway eosinophilia of rats infected 3 days before sensitization or at sensitization, but also the TSM sensitivity of rats infected 3 days before provocation or at provocation. In conclusion, BCG infection suppresses the development of sensitivity of airway smooth muscle and airway eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high dose of BCG infection inhibits airway sensitivity, even after allergen sensitization.
Animal ; Asthma/immunology* ; BCG Vaccine/immunology* ; Disease Models, Animal ; Disease Models, Animal ; Eosinophils/immunology ; Leukocyte Count ; Lung/immunology* ; Male ; Muscle, Smooth, Vascular/immunology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Vaccination

The objective of this study is to investigate whether BCG infection before, during or after sensitization suppresses allergen-induced airway hyperresponsiveness and eosinophilic inflammation in allergic asthma rats, and to determine the required dose of BCG to induce such an inhibition. Eighty-seven Sprague-Dawley (SD) rats were sensitized and provoked with ovalbumin (OA). A pretreatment of 6 x 10(4) or 6 x 10(5) colony forming units (CFUs) of BCG or saline was done at four different times: 3 days before sensitization, at sensitization, 3 days before provocation, or at provocation. The assessment of tracheal smooth muscle (TSM) responsiveness to electrical field stimulation or acetylcholine (ACh) and bronchoalveolar lavage (BAL) were performed 1 day after OA provocation. Doses of 6 x 10(4) CFUs inhibited TSM sensitivity of rats infected 3 days before sensitization or at sensitization, but not 3 days before provocation or at provocation. However, doses of 6 x 10(5) CFUs significantly inhibited not only the airway eosinophilia of rats infected 3 days before sensitization or at sensitization, but also the TSM sensitivity of rats infected 3 days before provocation or at provocation. In conclusion, BCG infection suppresses the development of sensitivity of airway smooth muscle and airway eosinophilic inflammation in allergic asthma rats. Furthermore, a relatively high dose of BCG infection inhibits airway sensitivity, even after allergen sensitization.
Animal ; Asthma/immunology* ; BCG Vaccine/immunology* ; Disease Models, Animal ; Disease Models, Animal ; Eosinophils/immunology ; Leukocyte Count ; Lung/immunology* ; Male ; Muscle, Smooth, Vascular/immunology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Vaccination

Development of transfusion-related acute lung injury (TRALI), a non-cardiogenic pulmonary edema, after blood transfusion, is a rare but potentially leading cause of mortality from blood transfusion. We report on a case of TRALI in a 51-year male with acute calculous cholecystitis and liver cirrhosis. As preoperative treatment, he was given ten units of fresh frozen plasma (FFP) for 3 days before the operation. During the transfusion of the 10th unit of FFP, he experienced a sudden onset of hemoptysis, tachypnea, tachycardia, and cyanosis. Bilateral pulmonary infiltration not observed on the chest X-ray at the visit was newly developed. There was no evidence of volume overload but severe hypoxemia. Blood transfusion was stopped and he recovered fully after 8 days of oxygen therapy through a nasal cannula. Although HLA and HNA antibodies were not detected in the donor's blood, HLA antibodies (A2, B57, B58) were detected in the patient's blood. We reported this meaningful case of TRALI that occurred after transfusion of only fresh frozen plasma which did not contain human leukocyte antibody in a patient with HLA antibody.
Acute Lung Injury* ; Anoxia ; Antibodies ; Blood Transfusion ; Catheters ; Cholecystitis ; Cyanosis ; Hemoptysis ; Humans ; Leukocytes ; Liver Cirrhosis ; Male ; Mortality ; Oxygen ; Plasma* ; Pulmonary Edema ; Tachycardia ; Tachypnea ; Thorax

PURPOSE: Anaplastic large cell lymphoma (ALCL) is a rare aggresive non-Hodgkin lymphoma, of which over 50% of cases have an aberrant nucleophosmin (NPM)‒anaplastic lymphoma kinase (ALK) fusion protein. Both mechanistic target of rapamycin (mTOR) inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines. However, their combined effect has not yet been investigated. MATERIALS AND METHODS: We evaluated the anti-proliferative effects of everolimus and/or crizotinib in ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1, and lung adenocarcinoma cell line, NCI-H2228. RESULTS: We found that individually, both everolimus and crizotinib potently inhibited cell growth in a dose-dependent manner in both Karpas 299 and SU-DHL-1 cells. A combination of these agents synergistically inhibited proliferation in the two cell lines. Crizotinib down-regulated aberrant AKT and ERK phosphorylation induced by everolimus. Combination treatment also significantly increased G0/G1 cell-cycle arrest, DNA damage, and apoptosis compared with everolimus or crizotinib alone in ALK-positive ALCL cells. In the Karpas 299 xenograft model, the combination treatment exerted a stronger antitumor effect than monotherapies, without significant change in body weight. The synergistic effect of everolimus and crizotinib was also reproduced in the ALK-positive lung adenocarcinoma cell line NCI-H2228. The combination treatment abrogated phosphoinositide 3-kinase/AKT and mTOR signaling pathways with little effect on the Ras/ERK pathway in NCI-H2228 cells. CONCLUSION: Crizotinib combinedwith everolimus synergistically inhibits proliferation of ALK-positive ALCL cells. Our results suggest that this novel combination is worthy of further clinical development in patients with ALK-positive ALCL.
Adenocarcinoma ; Apoptosis ; Body Weight ; Cell Line ; DNA Damage ; Everolimus* ; Heterografts ; Humans ; Lung ; Lymphoma* ; Lymphoma, Large-Cell, Anaplastic* ; Lymphoma, Non-Hodgkin ; Phosphorylation ; Phosphotransferases ; Sirolimus ; TOR Serine-Threonine Kinases

Objective: : Cervical expansive laminoplasty is an effective surgical method to address multilevel cervical spinal stenosis. During surgery, the spinous processes of C2 and C7 are usually preserved to keep the insertion points of the cervical musculature and nuchal ligament intact. In this regard, dome-like laminectomy (undercutting of C7 lamina) instead of laminoplasty is performed on C7 in selected cases. However, resection of the lamina can weaken the C7 lamina, and stress fractures may occur, but this complication has not been characterized in the literature. The objective of the present study was to investigate the incidence and risk factors for C7 laminar fracture after C7 dome-like laminectomy and its impact on clinical and radiological outcomes. Methods: : Patients who underwent cervical open-door laminoplasty combined with C7 dome-like laminectomy (n=123) were classified according to the presence of C7 laminar fracture. Clinical parameters (neck/arm pain score and neck disability index) and radiologic parameters (C2–7 angle, C2–7 sagittal vertical axis, and C7–T1 angle) were compared between the groups preoperatively and at postoperatively at 3, 6, 12, and 24 months. Risk factors for complications were evaluated, and a formula estimating C7 fracture risk was suggested. Results: : C7 lamina fracture occurred in 32/123 (26%) patients and occurred at the bilateral isthmus in 29 patients and at the spinolaminar junction in three patients. All fractures appeared on X-ray within 3 months postoperatively, but patients did not present any neurological deterioration. The fracture spontaneously healed in 27/32 (84%) patients at 1 year and in 29/32 (91%) at 2 years. During follow-up, clinical outcomes were not significantly different between the groups. However, patients with C7 fractures showed a more lordotic C2–7 angle and kyphotic C7–T1 angle than patients without C7 fractures. C7 fracture was significantly associated with the extent of bone removal. By incorporating significant factors, the probability of C7 laminar fracture could be assessed with the formula 'Risk score = 1.08 × depth (%) + 1.03 × length (%, of the posterior height of C7 vertebral body)', and a cut-off value of 167.9% demonstrated a sensitivity of 90.3% and a specificity of 65.1% (area under the curve, 0.81). Conclusion : C7 laminar fracture can occur after C7 dome-like laminectomy when a substantial amount of lamina is resected. Although C7 fractures may not cause deleterious clinical outcomes, they can lead to an unharmonized cervical curvature. The chance of C7 fracture should be discussed in the shared decision-making process.

Objective: : Cervical expansive laminoplasty is an effective surgical method to address multilevel cervical spinal stenosis. During surgery, the spinous processes of C2 and C7 are usually preserved to keep the insertion points of the cervical musculature and nuchal ligament intact. In this regard, dome-like laminectomy (undercutting of C7 lamina) instead of laminoplasty is performed on C7 in selected cases. However, resection of the lamina can weaken the C7 lamina, and stress fractures may occur, but this complication has not been characterized in the literature. The objective of the present study was to investigate the incidence and risk factors for C7 laminar fracture after C7 dome-like laminectomy and its impact on clinical and radiological outcomes. Methods: : Patients who underwent cervical open-door laminoplasty combined with C7 dome-like laminectomy (n=123) were classified according to the presence of C7 laminar fracture. Clinical parameters (neck/arm pain score and neck disability index) and radiologic parameters (C2–7 angle, C2–7 sagittal vertical axis, and C7–T1 angle) were compared between the groups preoperatively and at postoperatively at 3, 6, 12, and 24 months. Risk factors for complications were evaluated, and a formula estimating C7 fracture risk was suggested. Results: : C7 lamina fracture occurred in 32/123 (26%) patients and occurred at the bilateral isthmus in 29 patients and at the spinolaminar junction in three patients. All fractures appeared on X-ray within 3 months postoperatively, but patients did not present any neurological deterioration. The fracture spontaneously healed in 27/32 (84%) patients at 1 year and in 29/32 (91%) at 2 years. During follow-up, clinical outcomes were not significantly different between the groups. However, patients with C7 fractures showed a more lordotic C2–7 angle and kyphotic C7–T1 angle than patients without C7 fractures. C7 fracture was significantly associated with the extent of bone removal. By incorporating significant factors, the probability of C7 laminar fracture could be assessed with the formula 'Risk score = 1.08 × depth (%) + 1.03 × length (%, of the posterior height of C7 vertebral body)', and a cut-off value of 167.9% demonstrated a sensitivity of 90.3% and a specificity of 65.1% (area under the curve, 0.81). Conclusion : C7 laminar fracture can occur after C7 dome-like laminectomy when a substantial amount of lamina is resected. Although C7 fractures may not cause deleterious clinical outcomes, they can lead to an unharmonized cervical curvature. The chance of C7 fracture should be discussed in the shared decision-making process.

Background/Aims: The objective of this study was to evaluate the efficacy and feasibility of the pediatric-inspired regimen of the adult acute lymphoblastic leukemia (ALL) Working Party, the Korean Society of Hematology. Methods: Data of 99 patients with newly diagnosed ALL, who were treated with the KALLA 1406/1407 protocol, were retrospectively analyzed. All patients equally received age-adjusted daunorubicin, vincristine, and prednisolone. L-asparaginase was additionally administered to Philadelphia (Ph)-negative patients according to age, whereas Ph-positive patients received 600 mg/day of imatinib. Results: A total of 99 patients were enrolled in this study, of whom 62 (62.6%) were diagnosed with Ph-negative ALL and 37 (37.3%) were diagnosed with Ph-positive ALL. The median age of patients in the Ph-negative ALL group was 46 years, and that of patients in the Ph-positive ALL group was 49 years. In patients with Ph-negative ALL, 57 (92%) patients achieved complete remission (CR) and CR with incomplete hematologic recovery (CRi). Disease-free survival (DFS) and overall survival (OS) rates at 2 years were estimated to be 42% and 63%, respectively. In patients with Ph-positive ALL, 32 (86%) patients achieved CR/CRi, and 2-year DFS and OS were 31.2% and 49.1%, respectively. Patients who were able to proceed to the allogeneic hematopoietic cell transplantation and younger patients showed significantly superior survival in both Ph-negative ALL and Ph-positive ALL. Neutropenic fever and bacterial infection were the most common and severe adverse events. Conclusions The KALLA 1406/1407 protocol showed tolerable toxicities in adult ALL patients. Especially, younger patients had more survival benefits with KALLA 1406/1407 protocol.

The authors describe the case of a 71-year-old patient with acute megakaryocytic leukemia (AML-M7) who was successfully treated with low-dose cytarabine induction followed by intermediate-dose cytarabine consolidation therapy. The patient presented with infection and rapidly increasing blood blasts. The diagnosis was consistent with AML-M7 with a normal karyotype. Peripheral blood blasts decreased rapidly upon low-dose cytarabine administration, and the patient achieved complete remission after two courses of low-dose cytarabine (10 mg/m2 bid for 12 days). Consolidation therapy with intermediate-dose cytarabine (1.0 g/m2 bid on day 1, 3 and 5) was then instituted without serious complication. He remained in complete remission at the time of writing 47 month after diagnosis. In spite of multiple poor prognostic factors, this patient showed excellent treatment outcome through low-dose cytarabine induction and intermediate- dose cytarabine consolidation. It needs to be validated whether acute leukemia with a megakaryocytic morphology is exceptionally sensitive to cytarabine.
Aged ; Cytarabine ; Humans ; Karyotype ; Leukemia ; Leukemia, Megakaryoblastic, Acute ; Leukemia, Myeloid, Acute ; Treatment Outcome ; Writing

Background: The purpose of this study was to identify the prevalence of posttraumatic embitterment disorder (PTED) among soldiers, and examine its relation to stress, depression, self-esteem, impulsiveness, and suicidal ideation. Methods: The subjects of this study were 200 soldiers and 197 control subjects, a total of 397 persons. Measurement tools used included the PTED self-rating scale, Stress Response Inventory, Beck Depression Inventory, Rosenberg Self-Esteem Inventory, Barratt Impulsiveness Scale, and Beck Scale of Suicide Ideation.Result: The major findings of the analysis are as follows: first, 11.5% of the soldiers were in the risk group for PTED, and 4% of them had PTED. Second, PTED in the soldiers was significantly associated with a number of variables such as their educational background, stress, depression, self-esteem, impulsiveness, and suicidal ideation, while it was not significantly associated with age. Third, through the hierarchical multiple regression analysis, it was found that academic background, stress, and depression had a statistically significant positive effect on the incidence of PTED in the soldiers. Conclusion In order to prevent and effectively intervene in PTED in soldiers, there is a need for interventional efforts focused on depression and stress related to negative life events.