PURPOSE: Bone morphogenetic proteins (BMPs) play an important role in the formation of cartilage and bone, as well as regulating the growth of chondroblasts and osteoblasts. In this study, we investigated whether recombinant human BMP adenoviruses are available for ex vivo gene therapy, using human fibroblasts and human bone marrow stromal cells in an animal spinal fusion model. MATERIALS AND METHODS: Human fibroblasts and human bone marrow stromal cells were transduced with recombinant BMP-2 adenovirus (AdBMP-2) or recombinant BMP-7 adenovirus (AdBMP-7), referred to as AdBMP-7/BMSC, AdBMP-2/BMSC, AdBMP-7/HuFb, and AdBMP-2/HuFb. We showed that each cell secreted active BMPs by alkaline phosphatase staining. Since AdBMP-2 or AdBMP-7 tranducing cells were injected into the paravertebral muscle of athymic nude mice, at 4 weeks and 7 weeks, we confirmed that new bone formation occurred by induction of spinal fusion on radiographs and histochemical staining. RESULTS: In the region where the AdBMP-7/BMSC was injected, new bone formation was observed in all cases and spinal fusion was induced in two of these. AdBMP-2/BMSC induced bone formation and spinal fusion occurred among one of five. However, in the region where AdBMP/HuFb was injected, neither bone formation nor spinal fusion was observed. CONCLUSION: The osteoinductivity of AdBMP-7 was superior to that of AdBMP-2. In addition, the human bone marrow stromal cells were more efficient than the human fibroblasts for bone formation and spinal fusion. Therefore, the results of this study suggest that AdBMP-7/ BMSC would be the most useful approach to ex vivo gene therapy for an animal spinal fusion model.
Adenoviridae* ; Alkaline Phosphatase ; Animals ; Bone Morphogenetic Protein 7 ; Bone Morphogenetic Proteins ; Cartilage ; Chondrocytes ; Fibroblasts ; Genetic Therapy* ; Humans* ; Mesenchymal Stromal Cells ; Mice ; Mice, Nude ; Osteoblasts ; Osteogenesis ; Spinal Fusion* ; Spine

This phase II study aimed to assess the clinical activity and toxicity of ifosfamide based regimen in patients with epithelial ovarian cancer, relapsed or refractory to cisplatin-containing combination chemotherapy. From July 1991 to June 1993, 18 patients with epithelial ovarian cancer, relapsed or refractory to cisplatin were treated as follows. Relapsed cases were treated with IP(ifosfamide 4,0g/m2 intravenously and cisplatin 60mg/m2 intravenously on day 1) regimen every 3-4 weeks. The regimen used in refractory cases was Et-I(etoposide 100mg/m2 intravenously on days 1 to 3 and ifosfamide 1.0g/m2 intravenously on days 1 to 5) regimen every 3 or 4 weeks. The uroprotectant mesna was concomitantly used. Responses and toxicities were evaluated according to the WHO Criteria. The overall response rate was 27.8%(5/18), including 2 complete response and 3 partial response. There were four episodes(22.2%) of grade 3, 4 myelosuppression, but no other grade 3, 4 non-hematologic toxicity. Salvage therapy with ifosfamide based regimen is a useful and well tolerated treatment strategy in selected patients with relapsed ovarian cancer.
Cisplatin ; Drug Therapy, Combination ; Humans ; Ifosfamide ; Mesna ; Ovarian Neoplasms* ; Recurrence ; Salvage Therapy

BACKGROUND: In patients who need sustained endotracheal intubation and mechanical ventilation due to respiratory failure after traumatic cervical spinal cord injury, tracheostomy can be performed to reduce the duration of mechanical ventilation and respiratory complications. The purpose of this study was to determine criteria and timing of tracheostomy in patients with severe traumatic cervical spinal cord injury accompanied by motor weakness. METHODS: We reviewed 22 patients who underwent tracheostomy (study group) and 27 patients who did not (control group) from January 2005 to March 2016. We assessed the American Spinal Injury Association (ASIA) impairment scale score and investigated accompanying thoracic injury, paradoxical respiration, postoperative endotracheal intubation and other clinical parameters. The study group was also subdivided into the early tracheostomy group and late tracheostomy group depending on whether the tracheostomy was performed within or later than 7 days after surgery. RESULTS: Twenty-two patients in the study group had a mean ASIA impairment scale score of 14.1 points, which was lower than the control group's 23.4 points. Paradoxical respiration was observed in 77% of the patients in the study group compared to 18% in the control group. Postoperative intubation was maintained in 68% in the study group; 32% underwent endotracheal intubation due to respiratory failure within 4 days after surgery and had a tracheostomy. In the control group, postoperative intubation was maintained in 22%, and all of them were weaned off intubation within 4 days after surgery. The duration of intensive care unit hospitalization was 11.4 days for the early tracheostomy group, which was shorter than the late tracheostomy group's 19.7 days. CONCLUSIONS: In patients with severe traumatic cervical spinal cord injury, tracheostomy may be needed when the motor grade of the ASIA scale is low, above the C4 segment is injured, or paradoxical respiration occurs after injuries. In addition, if endotracheal extubation is not feasible within 4 days after surgery, an early tracheostomy should be considered.
Airway Extubation ; Asia ; Cervical Cord* ; Hospitalization ; Humans ; Intensive Care Units ; Intubation ; Intubation, Intratracheal ; Respiration ; Respiration, Artificial ; Respiratory Insufficiency ; Spinal Injuries ; Thoracic Injuries ; Tracheostomy*

Objectives: Attention deficit/hyperactivity disorder (ADHD) is a condition characterized by inattention or hyperactivity and impulsivity that hinders function and development. The purpose of this study was twofold, that is, to check the diagnostic rate of ADHD, which is first diagnosed in adulthood as well as in childhood, and to compare drugs prescribed to children and adult patients. Methods: This study utilized Health Insurance Review & Assessment Service data from 1 January 2009 to 31 December 2018. Only first entered International Classification of Diseases diagnostic codes were collected. We set the first year as a clearance period, checked changes in drug prescriptions over the years, and investigated differences found between pediatric and adult patients. Results: The overall diagnostic rate of ADHD decreased from 71.9 to 69.7 per 100000 people between 2009 and 2012. This reducing trend was noticeable from 2012 and decreased to 43.7 by 2015, and then rose again to 65.4 in 2018. Extended-release formulation of the methylphenidate (ER-MPH) was found to be the most frequently used first drug. Conclusion Overall diagnostic rate decreased from 2009 to 2018, and the incidence of adult ADHD showed a steady increase. For children, ER-MPH was the most prescribed drug at all ages, while osmotic-release oral system formulation of the methylphenidate was most prescribed for adults.

Malignant small round cell tumor is very rare, especially in the head and neck area. It is also difficult to make a differential diagnosis due to their undifferentiated or primitive character. Immunohistochemical staining and chromosomal study is useful to categorize these tumors. Since these are rare tumors, treatment protocols are is not well established. While combined treatments (surgery, chemotherapy, radiotherapy) is currently being applied, the tumor still has a poor prognosis. We present a rare case of a rapidly growing temporal bone malignant small round cell tumor which initially showed facial paralysis.
Clinical Protocols ; Diagnosis, Differential ; Facial Paralysis ; Head ; Neck ; Prognosis ; Temporal Bone

Malignant small round cell tumor is very rare, especially in the head and neck area. It is also difficult to make a differential diagnosis due to their undifferentiated or primitive character. Immunohistochemical staining and chromosomal study is useful to categorize these tumors. Since these are rare tumors, treatment protocols are is not well established. While combined treatments (surgery, chemotherapy, radiotherapy) is currently being applied, the tumor still has a poor prognosis. We present a rare case of a rapidly growing temporal bone malignant small round cell tumor which initially showed facial paralysis.
Clinical Protocols ; Diagnosis, Differential ; Facial Paralysis ; Head ; Neck ; Prognosis ; Temporal Bone

Background/Aims: Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the microbiome during gastric carcinogenesis in structural and functional aspects, with a specific focus on the association between oral and gastric microbiomes. Methods: We collected saliva, gastric juice, and gastric tissue samples from 141 patients at different stages of gastric carcinogenesis and processed them for microbiome analysis using 16S rRNA gene profiling. The alpha and beta diversities were analyzed, and the differences in microbiome composition and function profiles were analyzed among the groups, as well as the correlation between changes in the oral and gastric microbiomes during carcinogenesis. Results: We observed significant differences in microbial diversity and composition between the disease and control groups, primarily in the gastric juice. Specific bacterial strains, including Schaalia odontolytica, Streptococcus cristatus, and Peptostreptococcus stomatis, showed a significant increase in abundance in the gastric juice in the low-grade dysplasia and gastric cancer groups. Notably, the correlation between the oral and gastric microbiota compositions, increased as the disease progressed. Predictive analysis of the metagenomic functional profiles revealed changes in functional pathways that may be associated with carcinogenesis (ABC transport and two-component systems). Conclusions During gastric carcinogenesis, the abundance of oral commensals associated with cancer increased in the stomach. The similarity in microbial composition between the stomach and oral cavity also increased, implying a potential role of oral-gastric bacterial interactions in gastric cancer development.

Background and Objectives: Ototoxic sensorineural hearing loss causes permanent hearing loss in most cases. Recently there have been many reports describing cell base therapy with stem cells that has some effect on hearing recovery. We evaluated the efficacy of clinical grade, pre-made, human bone marrow derived mesenchymal stem cells (BM-MSCs) in ototoxic deaf animal model.Materials and Method BM-MSCs were cultured in a clinical grade laboratory. The animals were divided into 2 groups as follows: a saline injected control group and a stem cell injected group (MSC-group). Cultured MSCs were transplanted into the brachial vein of the deaf mice model. We recorded auditory brainstem response (ABR) and conducted immunohistochemistry at 1, 3, and 5 weeks. Results: After the transplantation of MSC, a significant improvement in the hearing threshold of ABR was observed in the MSC transplanted group. Five weeks after transplantation of MSCs, hair cell regeneration was confirmed from the basal to the apex of the cochlea in fluorescent dyed image under the microscope compared to the control group. Conclusion BM-MSCs were effective in an acute ototoxic deaf animal model. These results show that stem cell transplantation mediate inner ear regeneration.

PURPOSE: Cervical neoplasias are known to be preventable. But the outcome of our efforts for early detection in Korea is disappointing. This study was undertaken to determine the level of screening participation in Korean women with cervical cancer and how the early detection of cervical cancer might be improved. MATERIALS AND METHODS: Two hundred and forty-nine women with cervical cancer diag- nosed and treated at Seoul National University Hospital from September 1996 to February 1998 were subjected to this study. Self-reported cervical cancer screening histories, med- ical records obtainable were reviewed and analysed. RESULTS: One hundred forty-seven women (147/249; 59.0%) hadn't got through the screen- ing at proper intervals. Ninety-nine women (39.9%) had never been screened and remain- ing 48 (19.3%) hadn't had their last Pap test 3 years before their diagnosis of nvasive cancer. Of the 150 women (60.1%) who had ever had a Pap test, only 47 (18.9%) had had annual Pap test during recent 5 years and 55 (22.1%) had had routine Pap test with interval between 1-3 years. Among 102 women who had at least one Pap test during recent 3 year, 73 (71.6%) had had a normal Pap report within three years of diagnosis, including 36 (35.3%) whose last normal Pap report was within a year of diagnosis. This results suggest the possibilities of smear-taking and/or reading errors. Women who had had routine Pap with interval less than 3 years had significantfy less chance of advanced tumor (FIGO stage Ib < ) than unscreened population. There was a statistically significant trend for the more younger and educated groups to be participated at the screening program with more shortened interval. All the other factors had failed to show significant correlation with adequacy or regularity of screening interval. CONCLUSIONS: Despite widespread chance of opportunistic cervical cancer screening, non-participants form the main reason for the failure of cervical cancer screening in Korea. So, far much efforts should be aimed at participating more women in cervical cytologic screening program, especially in the old-aged and less-educated groups.
Diagnosis ; Female ; Humans ; Korea ; Mass Screening* ; Nose ; Seoul ; Uterine Cervical Neoplasms*

OBJECTIVE: To evaluate the prevalence and genotype of high risk HPV infection with oligonucleotide microarray based DNA chip in cervical cancer. METHODS: The presence of HPV and its type were tested with oligonucleotide microarray based DNA chip in 84 specimen from cervical cancer (squamous cell carcinoma; 58, adenocarcinoma; 22, adenosquamous carcinoma and small cell carcinoma; 4). RESULTS: The overall detection rate of high risk HPV infection was 84.5% (71/84). In squamous cell carcinoma and adenocarcinoma, the detection rate were 79.3% (46/58) and 100% (22/22) respectively. The distribution of HPV types in squamous cell carcinoma and adenocarcinoma was as follows; HPV 16 (60.3%, 59.1%), HPV 18 (1.7%, 27.3%). CONCLUSION: The most common type of high risk HPV detected in squamous cell carcinoma and adenocarcinoma of cervix was HPV 16 followed by HPV 18. In contrast with squamous cell carcinoma, HPV 18 was more frequently detected than HPV 16 in adenocarcinoma. HPV DNA chip seems to be effective in the detection and typing of HPV in tissues from cervical cancer.
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Cervix Uteri ; Female ; Genotype ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; Oligonucleotide Array Sequence Analysis ; Prevalence* ; Uterine Cervical Neoplasms*