Efficacy, Safety, and Pharmacokinetics of Beroctocog Alfa in Patients Previously Treated for Hemophilia A

PURPOSE: Beroctocog alfa is a second generation recombinant factor VIII manufactured by removing the B-domain from factor VIII. This prospective clinical trial was conducted to evaluate the efficacy, safety, and pharmacokinetics of beroctocog alfa in patients of ages > or =12 years previously treated for severe hemophilia A. MATERIALS AND METHODS: Seventy subjects received beroctocog alfa as an on-demand treatment for acute hemorrhage. RESULTS: The final hemostatic effect was excellent in 35 subjects (50%) and good in 26 subjects (37.1%). The drug showed an overall efficacy rate of 87.1%. The majority of acute hemorrhages was treated by administering the study drug once (86.2%) or twice (10.0%), and the mean dose administered per single infusion was 28.55+/-6.53 IU/kg. Ten subjects underwent 12 surgical procedures, and hemostatic efficacy was excellent in seven cases (58.3%) and good in five cases (41.7%), showing a 100% efficacy rate. A total of 52 of 88 subjects (59.0%) experienced 168 adverse events. There were 18 serious adverse events (10.7%) in 11 subjects, and two (mild dyspnea and facial edema) in one subject were related to the study drug. Only one subject formed a de novo factor VIII inhibitor, for an occurrence rate of 1.4% (one-sided 95% upper confidence limit: 3.85%). The final elimination half-life was 13.3 h and 12.6 h at baseline and 6 months after administration, respectively. CONCLUSION: Our results suggest that beroctocog alfa is safe and efficacious as either an on-demand treatment for acute hemorrhage or a surgical prophylaxis in patients with hemophilia A.

Pharmacokinetics and Tolerability Evaluation of Human Coagulation Recombinant Factor VIII (GreenGene(TM)) in Hemophilia A Patients

BACKGROUND: GreenGene(TM) (Green Cross Corp.) is a recombinant clotting factor VIII which is used for hemophilia A. This study aimed to investigate the pharmacokinetics and safety profiles of 25 IU/kg and 50 IU/kg of GreenGene(TM) in Korean hemophilia A patients. METHODS: A dose-block randomized, single-blind, active drug-controlled, single and multiple dose, parallel-group study was conducted with 16 hemophilia A patients (25 IU/kg: 50 IU/kg = 8:8). They received GreenGene(TM) or GreenMono(TM)(active control) intravenously on day 1 and every other day from day 4 to 10. FVIII:C (Factor VIII procoagulant activity) was measured to determine the pharmacokinetics (PK) at baseline and up to 48 hours for single and multiple administration. PK parameters were determined using noncompartmental methods. RESULTS: The maximum concentration (Cmax) and the area under the concentration-time curve (AUC0-48) of the GreenGene(TM) 25 IU/kg (mean +/- SD) were 59.00 +/- 19.26 % and 774.40 +/- 380.13 %.h respectively, while those of 50 IU/kg were 131.50 +/- 39.81 % and 1462.44 +/- 397.09 %.h after single administration. The Cmax and AUC0-48 in steady state of the GreenGene(TM) 25 IU/kg were 68.17 +/- 22.75 % and 863.30 +/- 334.40 %.h, while those of 50 IU/kg were 147.17 +/- 18.47 % and 1820.08 +/- 704.42 %.h. No serious adverse event was observed. CONCLUSION: The GreenGene(TM) to hemophilia A patients appeared to be well tolerated within range of 25-50 IU/kg. The PK parameters of factor VIII showed dose-independent manner with 25 IU/kg and 50 IU/kg dose ranges.

Pseudoaneurysm of the Medial Superior Genicular Artery after Arthroscopic Partial Meniscectomy

We describe a case of 43-year-old man who had a pseudoaneurysm of the medial superior genicular artery after arthroscopic partial meniscectomy with standard anterolateral and anteromedial portals. Pseudoaneurysm of the medial superior genicular artery has been reported at the previous superomedial portal site after arthroscopy. Described herein is a unique case that involved the medial superior genicular artery at the previous anteromedial portal site after arthroscopy. The pseudoaneurysm was successfully treated with transcatheter embolization.

Nailbed Repair using 2-octyl Cyanoacrylate (Dermabond(R))

PURPOSE: Nailbed repair using fine 6-0 or 7-0 absorbable sutures can be technically demanding and time-consuming. We describe a simpler method of nailbed repair using 2-octyl cyanoacrylate (Dermabond(R)) topical adhesive. MATERIALS AND METHODS: Fifteen consecutive patients with nailbed injuries not involving the germinal matrix were repaired with Dermabond(R). There were 7 simple lacerations, 4 stellate lacerations and 4 severe crush injury according to Zook's classification. The appearance of the nail at twelve months was graded according to ridging, splitting, deformity, and sheen of the nail. RESULTS: Nailbed repairs using Dermabond(R) took on average 3.2 minutes to complete. Six patients had excellent aesthetic results, Eight had good results, and one patient with a crush injury had a fair result. There were no complications. CONCLUSION: Dermabond(R) is a useful tool for rapidly repairing acute nailbed injuries. The outcome of repairing injuries not involving the germinal matrix is similar to that expected for suture repairs of similar injuries.

Renal Epidermal Growth Factor Expression and Regulation by Angiotensin II During Neonatal Ureteral Obstruction in the Rat / 대한비뇨기과학회지

No abstract available.

Natural History of Unilateral Ureteropelvic Junciton Obstructed Kidney : Five Cases of High Grade Hydronephrosis

To evaluate the sensitivity and specificity of transthoracic fine needle aspiration cytology(TFNAC) in the preoperative diagnosis of pulmonary nodules, a retrospective analysis was carried out on a consecutive series of 200 TFNACs. They included 186 primary malignant tumors, 66 squamous cell carcinomas, 65 adenocarcinomas, 36 small cell carcinomas, 7 large cell carcinomas, 4 carcinoids, 8 others, 9 metastatic tumors, and 5 benign tumors. On cytohistologic correlation of malignant pulmonary tumors, the pro- cedure had a sensitivity of 97.3% and a specificity of 100%. A 86.6% correct correlation between the cytologic and histologic diagnoses was achieved. Five out of the 7 undifferentiated large cell carcinomas, 10 out of the 65 adenocarcinomas, 2 out of the 36 small cell carcinomas, and 2 out of the 66 squamous cell carcinomas were turned out to be mistyped in cytologic diagnosis. We concluded that TFNAC is a highly sensitive and specific preoperative diagnostic procedure in the investigation of patients with discrete pulmonary nodules in whom the specific cell type of the malignant neoplasm has important implications in treatment modality and prognosis.

Value of ICAM-1 Expression and the Soluble ICAM-1(sICAM-1) Level as a Marker of Activity in Sarcoidosis: The Relationship Between the ICAM-1 Level and the Clinical Course of the Disease / 결핵

BACKGROUND: The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. So the assessment of disease activity is important but no single parameter was generally accepted as a good marker. Recently several studies suggested that adhesion molecules, especially ICAM-1 can be a marker, but there are some controversies. And only few data are available about the relationship of ICAM-1 with clinical follow-up course. METHOD: We measured the expression of adhesion molecules on BAL cells by flow cytometry and the level of soluble ICAM-1 (sICAM-1) in serum and BALF at the time of diagnosis in 12 patients with active disease and 7 inactive sarcoidosis(5 male, 14 female, mean age : 39.4+/-10.7 years, mean follpw-up 20+/-15 months). Follow-up clinical course were compared with the changes in serum sICAMA-1 level and the adhesion molecule on BAL cells. RESULTS: In the patients with active disease, the ICAM-1 on AM(RMFI 3.68+/-1.71) and sICAM-1 level in serum(582+/-193 ng/ml) and BAL fluid(47.8+/-16.5 ng/ml) were all higher than those of 7 inactive disease(RMFI :1.89+/-0.75, p=0.0298, serum : 294+/-117 ng/ml, p=0.0049, BALF : 20.9+/-8.3ng/ml). In the active sarcoidosis, ICAM-1 on AM(RMFI:1.51+/-0.84) and serum sICAM-1 were decreased after the therapy(250+/-147 ng/ml) but no significant change was noted in inactive disease. Also we found the initial ICAM-1 on AM and serum sICAM-1 had a significant correlation with the degree of improvement in PFT after the therapy. During the follow-up, the disease relapsed in 4 patients after the discontinuation of steroid and the serum sICAM-1 level went-up again at the time of relapse. CONCLUSION: Our data suggest that the serum sICAM-1 level and the JCAM-1 expression on AM can be a good marker of disease activity and also a predictor of outcome in sarcoidosis.

Proliferative Properties and Cytokine Secretion of Lung Fibroblast Cell Lines of the Patients with Idiopathic Pulmonary Fibrosis / 결핵

BACKGROUND: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. SUBJECTS AND METHOD: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen RESULT: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212+/- 0.107 vs 0.319+/-0.143, p= 0.0922), also there was no signifrcant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower(33.0+/-13.1%) in IFB than control(46.7+/-10.0%, p= 0.0429). The IFB secreted significantly higher amount of MCP-1(1574+/-1283 pg/ml) spontaneously than NFB(243+/-100 pg/ml) and also after the stimulation with TGF-beta (3.23+/-1.31 ng/ml vs 0.552+/-0.236 ng/ml, p= 0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-beta stimulation. But after the maximal stimulation with IL-1beta, no significant difference in cytokine secretion was found between IFB and NFB. CONCLUSION: Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

Chemokine Secretion From Alveolar Macrophages in Patientswith Diffuse Interstitial Lung Diseases(DILD) / 결핵

BACKGROUND: The type of the infiltrating cells in alveolitis may be determined by the chemokines in the lesion. MIP-1alpha, a C-C type chemokine, stimulates proliferation and cytokine secretion from macrophages and induces early neutrophilic and later monocytic inflammation in vivo. IL-8, a C-X-C type chemokine is known to attract neutrophils and T-lymphocytes. This study is performed to find out the relative role of two different chemokines in diffuse interstitial lung disease. SUBJECT AND METHOD: We measured the secretion of MIP-1alpha and IL-8 from alveolar macrophages(AM), and their level in BAL fluid of 26 patients with DILD (10 IPF, 4 collagen disease, 10 sarcoidosis, and 2 hypersensitivity pneumonitis) and 7 normal control. RESULT: IL-8 secretion was significantly increased in patients with DILD (8.15+/-4.58 ng/ml) than in normal (1.10+/-0.93 ng/ml, p=0.0003). Significant correlation was found between IL-8 secretion and total cell number in BAL fluid (r=0.484, p=0.0068), %(r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte, and % of AM (r=-0.505, 0.0032). MIP-1alpha secretion was also increased in DILD (2.41+/-1.45 ng/ml) compared to control (0.63+/-0.30 ng/ml, p=0.0031), and showed a tendency of correlation with total cell number (r=0.368, p=0.0456) and No. of alveolar macrophages (r=0.356, p=0.0579) in BAL fluid. The concentration of IL-8 in BAL fluid was significantly increased in the patients with DILD (40.4+/-34.5 pg/ml) compared to control (3.90 +/- 2.47 pg/ml, p=0.0094) and it showed a significant correlation with the total cell number(r=0.484, p=0.0068), %(r=-0.505, p=0.0032) of AM, and % (r=0.592, p=0.0004) and No. (r=0.516, p=0.0042) of lymphocyte in BAL fluid. But there was a no significant difference in MIP-1alpha concentration in BAL fluid between normal control group and the patients with DILD. Conclusion: From the above results, we concluded that AM of DILD releases increased amount of both IL-8 and MIP-1alpha but IL-8 has better correlation with the type of alveolitis.

The Expression of Adhesion Molecules on BAL Cells and Serum Soluble ICAM-1Level after the Radiotherapy for the Lung Cancer and Its Relationship to theDevelopment of of Radiation Pneumonitis and Fibrosis / 결핵

BACKGROUND: Lung cancer is the second most frequent malignacy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1 (sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. SUBJECTS: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. RESULT: Clinically significant radiation pneumonitis deveoped in 7 patients. After RT, total cell count in BAL was significantly increased from (20.2+/-10.2)X106 cells/ml to (35.3+/-21.6)X106 cells/ml (p=0.0344) and % lymphocyte was also increased from 5.3 +/- 4.2% to 39.6 +/- 23.4% (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: 378 +/-148, 411 +/-150 ng/ml, BALF: 20.2 +/- 12.2, 45.1 +/-34.8 ng/ml,respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: 505 +/- 164 vs 345 +/- 102 ng/ml, p=0.0253, BALF: 67.9+/-36.3 vs 25.2+/-17.9ng/ml,p= 0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from 1.28 +/-0.479 to 1.63 +/-0.539, p=0.0605), but it was significantly high in patients with pneumonitis (2.10+/-0.390) compared to the patinets without pneumonitis (1.28+/-0.31,p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (beta2-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. CONCLUSION: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.