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Elevated Platelets Enhance Cancer Cell Migration, Promote Hematogenous Metastasis and Associate with a Poor Prognosis in Advanced Non-small Cell Lung Cancer Cases

  • Li, Yan;Miao, Li-Yun;Xiao, Yong-Long;Cai, Hou-Rong;Zhang, De-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.139-143
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    • 2014
  • Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

Evaluation of Health-related Quality of Life for Hypothesized Medical States Associated with Cervical Cancer

  • Murasawa, Hideki;Konno, Ryo;Okubo, Ichiro;Arakawa, Ichiro
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9679-9685
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    • 2014
  • Background: When evaluating health-economics for cervical cancer prevention policies in Japan, it is important to use Japanese value settings. This study aimed to obtain preference-based measures (preference measures) for hypothesized health states among healthy Japanese women, and to examine differences between the EuroQol-5D (EQ-5D) and standard gamble (SG) instruments. Materials and Methods: The investigation was performed among female students at a nursing university. We used written hypothetical scenarios describing three grades of cervical intraepithelial neoplasia (CIN) and eight stages of cervical cancer, both at diagnosis and after medical intervention. Preference measures were evaluated using both EQ-5D and SG. Results: We received responses from 136 women. The mean number of respondents per stage was 24.6 (SD: 2.7). At diagnosis, average EQ-5D scores for CIN1, CIN2, CIN3, IA1, IA2, IB1, IB2, IIA, IIB, III, and IV stages were 0.84 (0.14), 0.78 (0.12), 0.73 (0.10), 0.78 (0.12), 0.72 (0.12), 0.63 (0.13), 0.64 (0.12), 0.68 (0.08), 0.62 (0.13), 0.55 (0.21), and 0.18 (0.24), respectively. Using one-way analysis of variance with the Tukey-Kramer method for multiple comparisons (each stage vs. CIN1), we found significant differences for IB1 and more advanced stages (p<0.05). After medical intervention, corresponding EQ-5D scores were 0.84 (0.12), 0.81 (0.12), 0.84 (0.12), 0.80 (0.15), 0.78 (0.11), 0.64 (0.15), 0.63 (0.15), 0.71 (0.15), 0.50 (0.17), 0.52 (0.17), 0.21 (0.28). The multiple comparisons identified significant differences for IB1 and more advanced stages, excepting IIA (p<0.05). SG evaluations were more variable and relatively higher than EQ-5D evaluations. Conclusions: We obtained preference measures for three grades of CIN1-3 and eight stages of cervical cancer. In combination with appropriate sensitivity analyses, these preference measures will provide a basis for an economic evaluation of cervical cancer prevention in Japan. We suggest that EQ-5D is appropriate for cost-utility analysis of this topic.

Arthroscopic Cannulated Screw Fixation Technique for Avulsion Fracture of the Intercondylar Eminence of the Tibia (삽관 나사못(Cannulated screw)을 사용한 경골 과간 융기부 견열 골절의 관절경적 치료 기법)

  • Lee, Kee-Byoung;Chang, Ho-Guen;Lee, Seok-Beom;Moon, Young-Wan;Kang, Ki-Hoon;Lee, Wook-Hyung
    • Journal of the Korean Arthroscopy Society
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    • v.3 no.2
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    • pp.127-131
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    • 1999
  • Avulsion fractures of the intercondylar eminence of the tibia are not uncommon. In the displaced avulsion fracture, anatomical reduction and firm fixation of fracture fragments are needed but the most of the conventional operative techniques including arthroscopic technique are relatively complex and need. The results were not always satisfactory due to the risk of postoperative complications such as wound infection, premature epiphyseal closure and loss of fixation after early motion etc. So we describe a simple and safe modified method of arthroscopic reduction and fixation for avulsion fractures of the intercondylar eminence of the tibia. In our thirteen cases, we achieved anatomical reduction and secure fixation using cannulated screw through the three arthroscopic portals (anterolateral, medial mid-patellar and central). Postoperatively, immediate limited range of motion of the knee and partial weight bearing were possible. Additional use of the washer afforded safe fixation of comminuted avulsion fracture. The advantage of this technique includes its technical simplicity, easy removal of hardware, ability to treat comminuted type IV fracture with washer, no additional skin incision, no damage to growing plate in growth children and less morbidity.

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Treatment Strategies for Primary Central Nervous System Lymphoma (원발성 중추신경계 림프종의 치료전략)

  • Kim, Il-Man;Lee, Chang Young;Son, Eun Ik;Kim, Dong Won;Yim, Man Bin;Kim, Sang Pyo
    • Journal of Korean Neurosurgical Society
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    • v.30 no.3
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    • pp.334-341
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    • 2001
  • Objective : We have currently changed treatment strategies to methotrexate(MTX)-based preirradiation chemotherapy with subsequent planned radiation for the initial therapy of primary central nervous system lymphoma (PCNSL). The aim of this study was to evaluate the results of treating PCNSL with chemotherapy plus radiotherapy (CRT) or radiotherapy(RT) alone. Method and Material : This study involved 10 females and 3 males patients with a mean age of 54.2 years. All patients underwent surgery, open(8 cases) or stereotactic biopsy(5 cases) for histological diagnosis. Eleven tumors were diffuse large B-cell lymphomas. Tumor volume change in the follow-up images and survival time were evaluated in patients treated with CRT and RT alone. In the beginning, two patients received ProMACE-Cytabom chemotherapeutic regimen, but did not complete the course and died of progressive tumor 8 and 9 months after diagnosis, respectively. One patient died at 6 months before chemotherapy. These three were excluded from the survival analysis. Five patients(RT group) completed full courses of cranial irradiation with or without boost. For the current combined modality treatment, high-dose MTXbased chemotherapy(systemic and intrathecal MTX, IV vincristine, and oral procarbazine) followed by whole brain irrdiation to 45Gy to tumor was introduced in 5 patients of CRT group. Result : A complete response was achieved in three of five who received RT only and in all of five who received CRT. All patients in CRT groups are in disease free status at a mean 23 months following therapy. The RT group patients refused any additional salvage therapy at tumor relapse and survived at mean 20 months from diagnosis. The Karnofsky performance status improved in eight of ten patients with treatment. The treatment toxicity included leukoencephalopathy in RT group and severe leukopenia, transient hepatitis, avascular necrosis of femoral head, hearing loss, and amenorrhea in CRT group, respectively. Conclusion : The combined modality therapy of MTX-based chemotherapy plus radiotherapy for PCNSL may enhance tumor response and improve patient survival. The patients who received CRT should be carefully followed up because of the higher risk of treatment-induced late neurotoxicity.

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Cell Fusion of Cellulolytic Fungi, Aspergillus sp. HB1 (섬유소 분해균 Aspergillus sp. HB 1의 세포융합에 관한 연구)

  • Kim, Joo-Ho;Chang, Sung-Yeoul;Choi, Yong-Keel
    • The Korean Journal of Mycology
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    • v.15 no.2
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    • pp.80-86
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    • 1987
  • The author isolated high cellulolytic fungi from natural sources and determined optimal condition of protoplast formation and fusion as fundamental step for improvement of the isolated it's cellulolytic ability. Three different cellulolytic fungi, such as Aspergillus sp., Penicillium sp. and Trichoderma sp., were isolated from soil. Their cellulolytic activities were compared with that of Aspergillus niger which was useful industrially and had cellulase activity. It was Aspergillus sp. that showed the highest activity of all these four fungi. And then it was followed by Penicillium sp., Trichoderma sp., and Aspergillus niger in order. An auxotrophic mutant of Aspergillus sp. was obtained by UV mutagenesis method. Having try to produce protoplast from mycelia, the author found that ${\beta}-glucuronidase$, at pH 6.0, was effective cell-wall lytic enzyme. And the optimal concentration of this enzyme was 5,000 unit/ml. Regeneration rates of wild type, met. auxotroph and arg. auxotroph, in presence of osmotic stabilizer, were 7. 0%, 7. 5% and 5.2%, respectively. PEG with M.W. 6,000 was effective stimulator for protoplast fusion in the concentration of 30% (W IV). In such a condition, we obtained 1.2% cell fusion rate.

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Experimental Studies on Extracorporeal Circulation by Rygg-Kyvsgaard Heart-Lung Machine, Hartman`s Solution Prime,and Moderate Hypothermia: [Part I] (Hartmann`s 용액으로 충진한 혈희석 체외순환에 관한 실험적 연구: (1보: 심폐기 Rygg-Kyvsgaard 의 혈산화와 혈압 및 혈액상에 미치는 영향))

  • 지행옥
    • Journal of Chest Surgery
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    • v.4 no.2
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    • pp.69-80
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    • 1971
  • Total body perfusion using Rygg-Kyvsgaard Heart-Lung-Machine, Mark IV, Polystan was attempted in the dogs by the hemodilution method with total prime of buffered Hartman's solution and under hypothermia. The first of all, the functions of Rygg--Kyvsgaard Heart-Lung-Machine and the effects of the hemodilution perfusion by buffered Hartman's solution was studied. At the same time the changes of blood pressure, oxygen consumption, and influence on the blood pictures were observed before, during, and in 1-3 days after perfusion. Hemodilution rates were the average 74. 22cc/Kg(the ranges of 67 to 81 cc/Kg) and perfusion flow rates were maintained in the mean 62. 6cc/Kg/min., Although it was possible to check up to 87 cc/ Kg/min. The total body perfusion continued for 60-80 minutes. Hypothermia was employed between $36^{\circ}C$ and $32^{\circ}C$ of the rectal temperature. Arterial pressure was ranged approximately between 68mmHg and 149mmHg, but generally, it was maintained over 80mmHg. Venous pressure was measured between 6.5cm $H_2O$and 11.5cm $H_2O$. Optimum oxygenation can be expected when oxygen flow into the disposable bubble oxygenator was maintained approximately at 3.5 L/min .. Inthis way, the oxygen contents were measured in the mean value of 13.11${\pm}$O.56 vol. % of arterial blood and 8.67+1.08 vol.% of venous blood(P${\pm}$0.86 vol.% in arteriovenous oxygen difference and 2. 97${\pm}$0.62cc/Kg in oxygen consumption were calculated. According to these dates, it is as plain as pikestaff that excellent oxygenation and good tissue perfusion was accomplished. Erythrocyte, hemoglobin and hematocrit were decreased about 38% during extracorporeal circulation and these were not recovered until 1-3 days after perfusion. These decrease was resulted from relatively high degree of hemodilution rate and no blood transfusion to compensate during these experimental studies. The platelets were also decreased about 76% during perfusion, but on the contrary, it was increased progressively after perfusion and in 1-3 days after perfusion was returned to the control level. Leucocyte were also decreased during perfusion, but it was increased progessively after perfusion and in 1-3 days after perfusion exceed the control level. This increase was resulted from postoperative infection of the wound, but its analysis were not changed significantly.

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Lung Cancer in Women, a Different Disease: Survival Differences by Sex in Turkey

  • Ulas, Arife;Tokluoglu, Saadet;Kos, Mehmet;Silay, Kamile;Akinci, Sema;Oksuzoglu, Berna;Alkis, Necati
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.815-822
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    • 2015
  • Purpose: In this study, we aimed to evaluate the effects of sex-based non-small cell lung cancer (NSCLC) varieties on survival rates. Materials and Methods: A retrospective study was performed in patients with NSCLC who were diagnosed by histological methods between the years 2000 and 2010. A chi-square test was used to compare variables. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Of the 844 patients, 117 (13.9%) were women and 727 (86.1%) were men. Adenocarcinoma was more common in women than in men (p<0.0001). There were more women non-smokers than men (p<0.0001). There was no statistically significant difference in ECOG PS, weight loss>10%, stage, LDH, albumin and treatment between women and men. Women younger than 65 years (17.0 vs 12.0 months; p=0.03), who had adenocarcinoma histology (15.0 vs 10.0 months; p=0.006) and who had a hemoglobin level ${\geq}12g/dL$ (18.0 vs 12.0 months; p=0.01) were found to have a better median OS rate than men. Median OS rates were found to be 13.0 months in females and 12.0 months in males (p=0.14). Among metastatic patients, the median OS was 11.0 months in females and 8.0 months in males (p=0.005). Among stage IIIB and stage IV patients who had first line platinum-based chemotherapy, the median OS was 17.0 months in women and 11.0 months in men (p=0.002). The response rate of chemotherapy was higher in women than in men (p=0.03). Conclusions: In our study, we found that survival duration is longer and chemotherapy response is better in women with NSCLC who do not have anemia or comorbidities and who are mostly non-smokers with adenocarcinomas. Further studies regarding the causes of these differences may provide clarity on this subject.

A COMPARATIVE STUDY ON POST-OPERATIVE ANALGESIC EFFECT FOR PATIENT-CONTROLLED AND INTRAMUSCULAR ANALGESIA IN MANDIBULAR FRACTURE PATIENTS (하악골 골절환자에서 술후 자가통증조절장치와 근주용 진통제의 효과에 관한 비교)

  • Lee, Seok-Jae;Kim, Kyung-Wook;Kim, Chul-Hwan
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.1
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    • pp.42-48
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    • 2006
  • Open reduction and rigid internal fixation is the most popular treatment method for maxillofacial fracture patients, and it is unevitable that postoperative pain can be developed. Many surgeons including oral & maxillofacial surgeons have made constant efforts to decrease postoperative pain. This study is a comparison of postoperative analgesia and intramuscular analgesia in patients with mandibular fractures. In this study, twenty-one patients (Experimental group) were randomly selected and they were injected with IV patient-controlled analgesia (PCA; Walkmed$^{(R)}$, USA). For control group another twenty-one patients were injected with intramusclar non-steroid anti-inflammatory drugs (Rheoma$^{(R)}$, Samsung Pharm. Co.). And then, we measured visual analogue scale (VAS) scores from first postoperative day to second day at regular time interval. The following results were uptained; 1. In patient group who with open reduction and rigid internal fixation, there was significant difference of postoperative analgesic effect during the first postoperative day(p<0.05). 2. In patient group with over 90 minutes surgery time, there was significant difference of postoperative analgesic effect during the first and second postoperative day when compared between experimental group and control group(p<0.05). 3. In patient group with less than 90 minutes surgery time, there was no significant difference of postoperative analgesic effect during the first and second postoperative day when compared between experimental group and control group(p>0.05). 4. In patient group with surgery of open reduction using rigid internal fixation at single fractured site, there was no significant difference of postoperative analgesic effect during the first and second postoperative day when compared between experimental group and control group(p>0.05). 5. In patient group with surgery at two fractured sites, there was significant difference of postoperative analgesic effect during the first postoperative day when compared between experimental group and control group(p<0.05). As mentioned above, it suggest that patient-controlled analgesia is more effective for postoperative pain relief than intramuscular injection in patients with rigid internal fixation by open reduction after mandibular fracture occurred. Especially, it is considered that in patient with more than 90 minutes surgery time or in cases with multiple fractured sites had more effective results with PCA therapy than conventional intramuscular analgesics.

AN EXPERIMENTAL STUDY ON THE HEALING PROCESS AFTER THE IMPLANTATION OF VARIOUS BONE SUBSTITUTES IN THE RATS (백서에서 수종의 골대체재료 매식후 치유과정에 관한 실험적 연구)

  • Kim, Young-Kyun;Kim, Su-Gwan;Lee, Jun-Gil;Lee, Mi-Hyang;Cho, Jae-O
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.1
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    • pp.15-24
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    • 2001
  • The purpose of this study is to evaluate the tissue response in applying of various bone substitutes included toothash-plaster mixture, resorbable hydroxylapatite (HA) and demineralized freeze-dried bone and to show the clinical usefulness of toothash-plaster mixture for the repair of craniomaxillofacial bone defect. For this experiment, 100 Sprague-Dawley rats weighing 200gm or more were used. There were four experimental groups: group I, toothash-plaster mixture; group II, demineralized freeze-dried bone; group III, resorbable HA; and group IV, control group. A full thickness, round bone defect measuring 10mm in diameter was created in the midcranium, and the substitutes cited above were embedded in the experimental rats based on their group assignment. Blood clot was filled in the rats assigned to the control group. Experimental rats were sacrificed on the 1st, 3rd, 5th, 8th, 12th and 24th week after implantation and stained with the hematoxylineosin, Masson's Trichrome, using Van Gieson's stain method, and were examined under light microscope. The results were as follows: 1. In all the groups, prominent inflammatory reaction and the infiltration of multinucleated giant cells were noted during the early stage. Gradual healing decreased this reaction. 2. Among the rats in the experimental group II, which were given demineralized freeze-dried bone implants, active formation of new bone traveculae manifested. Chondroid tissues appeared, and it was suggested that the defect was filled with newly formed bone by virtue of osteoinductive activity. On the 12th week after the experiments, most of the defect was filled with newly formed bone trabeculae. 3. In experimental groups I and III, it was noted that HA manifested a healing process similar to that characterized by the toothash-plaster mixture, but inflammatory reaction was more prominent in experimental group I. Active osteoblasts were observed along the periphery of osteoid tissues, while newly formed bone trabeculae appeared adjacent to the implanted materials three weeks later. Formation increased to the extent that newly formed bone trabeculae fused directly with the host bone. Increase in new bone ingrowth into the filling materials was revealed by both experimental groups. 4. In the control group, new bone formation adjacent to the host bone was observed, but most of the defect was filled with mature connective tissue 24 weeks after the experiments.

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Effect of Short-Term Pharmacotherapy on Anxiety Sensitivity, Quality of Life and Functional Disability in Panic Disorder Patients (공황장애에서 단기약물치료가 불안민감도와 삶의 질 및 기능장애에 미치는 영향)

  • Oh, Yun-Hye;Choi, Kwan-Woo;Kim, Bora;Heo, Jung-Yoon;Yu, Bum-Hee
    • Anxiety and mood
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    • v.9 no.1
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    • pp.25-30
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    • 2013
  • Objective : Panic disorder is a chroni, debilitating illness, and has been known to be affected by high anxiety sensitivity and a poor quality of life. We examined if 12 weeks of pharmacotherapy with escitalopram could affect anxiety sensitivity, quality of life, and general disability in patients with panic disorder. Method : We enrolled 27 patients who met the DSM-IV-TR criteria for panic disorder, with or without agoraphobia, and completed 12 weeks of escitalopram treatment. We enrolled 29 normal control subjects who were matched for age and sex compared with the panic patients. All subjects were assessed using the Hamilton Rating Scale for depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index-Revised (ASI-R), WHO quality of life assessment (WHO-QOL) and Sheehan Disability Scale (SDS) before and after 12 weeks of treatment. Result : Panic disorder patients had a higher Anxiety sensitivity, a poorer Quality of life, and significant disability than normal control subjects at baseline. After the treatment, Panic disorder patients showed significant improvement in the severity of panic symptoms in terms of the HAM-A p<0.001), HAM-D (p<0.001) in addition, the reached a remission state in terms of the PDSS score. They also showed significant improvement in the ASI-R (p<0.001), WHO-QOL (p<0.001) and SDS (p<0.001), but mean scores of the ASI-R, WHO-QOL and SDS in panic disorder patients were did not reach normal levels. Conclusion : This study suggests that 12 weeks of pharmacotherapy with escitalopram could improve anxiety sensitivity, quality of life, and disability in panic disorder patients, although their anxiety sensitivity, quality of life and disability were not yet normalized after short-term pharmacotherapy. Thus, long-term pharmacotherapy may be necessary for panic disorder patients in order to get an optimal clinical response in terms of anxiety sensitivity, quality of life, and general disability.