European Regulatory Science and Regulatory Science Expert Training Project

Background@#Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts. @*Methods@#Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice. @*Results@#EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities. @*Conclusion@#Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.

The Development of Antibody-Drug Conjugates for Urothelial Carcinoma Treatment

Urothelial cancer is the seventh most common cancer among men worldwide. Bacille de Calmette-Guérin is a type of anticancer immunotherapy that has been used to treat targeted bladder cancer, but the number of patients with treatment-refractory advanced urothelial cancer, patients has been increasing recently. To overcome this, enfortumab vedotin (novel nectin-4 targeting antibody-drug conjugate) known as antibody-drug conjugate (ADC), was approved. We describe the clinical development process of ADC and the potential for future development as a bladder cancer treatment.

Analysis of Trends in Regulatory Science and Regulatory Science Experts Training Projects: US, Japan, Singapore, and Korea

Background@#The need for regulatory science development to evaluate advanced regulatory products is gradually increasing without hindering the technological development. Creating a research environment and fostering experts through the establishment of regulatory agency-led policies are essential for the development of regulatory science. Method: This is a comparative study of the United States, Japan, Singapore, and Korea. The literature and websites of each regulatory agency were reviewed, and the focus was on advantages and comparing advantages based on definition, development trends, and expert training projects. @*Results@#The United States is striving to develop regulatory science in response to changes in the new pharmaceutical industry through the regulatory science report, and to foster expert both inside and outside the Food and Drug Administration (FDA). Japan is promoting regulatory science centered on regulatory science centers, and is focusing on researching work-related regulatory science within the Pharmaceuticals and Medical Devices Agency (PMDA) and improving employees’ ability to make regulatory decisions. Singapore was aiming to improve Southeast Asia’s regulatory capabilities under the leadership of Centre of Regulatory Excellence (CoRE) within Duke-NUS University. In 2021, Korea is in its early stages, starting to run a university's degree program related to regulatory science this year. @*Conclusion@#Regulatory science should be developed with the aim of improving the regulatory ability of the Ministry of Food and Drug Safety with Korea’s independent concept of regulatory science.

European Regulatory Science and Regulatory Science Expert Training Project

Background@#Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts. @*Methods@#Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice. @*Results@#EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities. @*Conclusion@#Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.

Bacillus Calmette-Guérin (BCG)-Cell Wall Skeleton as Immunotherapeutic Option for BCG-Refractory Superficial Bladder Cancer

Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system.

Effect of Poly(Lactide-Co-Glycolide) Nanoparticles on Local Retention of Fluorescent Material: An Experimental Study in Mice

OBJECTIVE: Poly(lactide-co-glycolide) (PLGA) nanoparticles are promising materials for the development of new drug-releasing systems. The purpose of this study was to evaluate the in vivo retention time of materials loaded in nanoparticles as compared with that of the material alone by in vivo imaging in nude mice. MATERIALS AND METHODS: Mice (n = 20) were injected with 0.1 mL fluorescent material 1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide (DiR)-loaded PLGA nanoparticles (200 nm) into the right paraspinal muscle, and the same volume of pure DiR solution was injected into the left paraspinal muscle. Fluorescence images were obtained using an in vivo optical imaging system. Fluorescent images were taken 1 day after the injection, and seven more images were taken at 1-week intervals. Image analysis was done with ImageJ program, and one region of interest was chosen manually, which corresponded to the highest signal-intensity area of fluorescence signal intensity. RESULTS: After 7 weeks, 12 mice showed a right-sided dominant signal, representing the DiR loaded PLGA nanoparticles; 5 mice showed a left-side dominant signal, representing the free DiR solution; and 3 mice showed no signal at all beginning 1 day after the injection. During the 7-week period, the mean signal intensities of the free DiR solution and DiR-loaded PLGA nanoparticles diverged gradually. On day 1, the mean signal intensity of free DiR solution was significantly higher than that of DiR-loaded PLGA (p < 0.001). Finally, by week 7, DiR-loaded PLGA express significantly high signal intensity compared with free DiR solution (p = 0.031). CONCLUSION: The results of the current study suggested that therapeutic agents bound to PLGA nanoparticles may exhibit prolonged retention times.

Poloxamer 407 Hydrogels for Intravesical Instillation to Mouse Bladder: Gel-Forming Capacity and Retention Performance

PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.

Effect of blood pressure and glycemic control on the plasma cell-free DNA in hemodialysis patients

BACKGROUND: The plasma levels of cell-free DNA (cfDNA) are known to be elevated under inflammatory or apoptotic conditions. Increased cfDNA levels have been reported in hemodialysis (HD) patients. The aim of this study was to investigate the clinical significance of cfDNA in HD patients. METHODS: A total of 95 patients on HD were enrolled. We measured their predialysis cfDNA levels using real-time EIF2C1 gene sequence amplification and analyzed its association with certain clinical parameters. RESULTS: The mean plasma cfDNA level in the HD patients was 3,884 +/- 407 GE/mL, and the mean plasma cfDNA level in the control group was 1,420 +/- 121 GE/mL (P < 0.05). Diabetic patients showed higher plasma cfDNA levels compared with nondiabetic patients (P < 0.01). Patients with cardiovascular complications also showed higher plasma cfDNA levels compared with those without cardiovascular complication (P < 0.05). In univariable analysis, the cfDNA level was associated with 3-month mean systolic blood pressure (SBP), white blood cell, serum albumin, creatinine (Cr), normalized protein catabolic rate in HD patients. In diabetic patients, it was significantly correlated with SBP, hemoglobin A1c, and serum albumin. In multivariate analysis, SBP was the independent determinant for the cfDNA level. In diabetic patients, cfDNA level was independently associated with hemoglobin A1c and SBP. CONCLUSIONS: In patients with HD, cfDNA is elevated in diabetic patients and patients with cardiovascular diseases. Uncontrolled hypertension and poor glycemic control are independent determinants for the elevated cfDNA. Our data suggest that cfDNA might be a marker of vascular injury rather than proinflammatory condition in HD patients.

Computer-aided detection system for masses in automated whole breast ultrasonography: development and evaluation of the effectiveness

PURPOSE: The aim of this study was to evaluate the performance of a proposed computer-aided detection (CAD) system in automated breast ultrasonography (ABUS). METHODS: Eighty-nine two-dimensional images (20 cysts, 42 benign lesions, and 27 malignant lesions) were obtained from 47 patients who underwent ABUS (ACUSON S2000). After boundary detection and removal, we detected mass candidates by using the proposed adjusted Otsu's threshold; the threshold was adaptive to the variations of pixel intensities in an image. Then, the detected candidates were segmented. Features of the segmented objects were extracted and used for training/testing in the classification. In our study, a support vector machine classifier was adopted. Eighteen features were used to determine whether the candidates were true lesions or not. A five-fold cross validation was repeated 20 times for the performance evaluation. The sensitivity and the false positive rate per image were calculated, and the classification accuracy was evaluated for each feature. RESULTS: In the classification step, the sensitivity of the proposed CAD system was 82.67% (SD, 0.02%). The false positive rate was 0.26 per image. In the detection/segmentation step, the sensitivities for benign and malignant mass detection were 90.47% (38/42) and 92.59% (25/27), respectively. In the five-fold cross-validation, the standard deviation of pixel intensities for the mass candidates was the most frequently selected feature, followed by the vertical position of the centroids. In the univariate analysis, each feature had 50% or higher accuracy. CONCLUSION: The proposed CAD system can be used for lesion detection in ABUS and may be useful in improving the screening efficiency.

Taxifolin Glycoside Blocks Human ether-a-go-go Related Gene K+ Channels

Taxifolin glycoside is a new drug candidate for the treatment of atopic dermatitis (AD). Many drugs cause side effects such as long QT syndrome by blocking the human ether-a-go-go related gene (hERG) K+ channels. To determine whether taxifolin glycoside would block hERG K+ channels, we recorded hERG K+ currents using a whole-cell patch clamp technique. We found that taxifolin glycoside directly blocked hERG K+ current in a concentration-dependent manner (EC50=9.6+/-0.7 microM). The activation curve of hERG K+ channels was negatively shifted by taxifolin glycoside. In addition, taxifolin glycoside accelerated the activation time constant and reduced the onset of the inactivation time constant. These results suggest that taxifolin glycoside blocks hERG K+ channels that function by facilitating activation and inactivation process.

The Effects of Acer ginnala Leaves Extraction on the Atopic Dermatitis-like Skin Lesions in NC/Nga Mice / 대한피부과학회지

BACKGROUND: Atopic Dermatitis (AD) is a chronic relapsing inflammatory skin disease that is usually observed in patients with an individual or familial history of atopic diseases, and AD is precipitated by environmental factors, including mite antigens. AD is known to be generated by an imbalance of both Th1 and Th2 cytokines. However, the exact etiology of AD is unclear. The leaves of Acer ginnala (AGL) have been demonstrated to have an anti-oxidant effect. OBJECTIVE: We wanted to investigate the effect of AGL on AD-like skin lesions and the other factors related to an immune response. METHODS: The AGL was applied to the AD-like skin lesions on the backs of NC/Nga mice. The efficacy of AGL in the NC/Nga mice was evaluated by the changes of severity of the skin lesions (a modified SCORAD). Blood was collected from the retro-orbital area and the abdominal vena cava. The levels of eosinophils, immunoglobulin (Ig) E and Th2-related cytokines in the blood were measured. RESULTS: The topical application of AGL suppressed the development of AD-like skin lesions. The percent of blood eosinophils was decreased after treatment with AGL. The serum IgE and Th2-related cytokine levels were decreased after treatment with AGL compared with those treated with base cream (the vehicle treated AD group). The IL-4, IL-5 and IL-13 levels were lower than those of the vehicle treated AD group. CONCLUSION: The findings suggest that AGL may exert an inhibitory effect on atopic dermatitis.

Anticancer Efficacy and Toxicity of Oral GMO-paclitaxel in a Hormone Refractory Prostate Cancer Model / 대한비뇨기과학회지

PURPOSE: We wanted to evaluate the efficacy and toxicity of the newly developed oral glyceryl monooleate (GMO)-paclitaxel in a hormone refractory prostate cancer model. MATERIALS AND METHODS: A paclitaxel formulation was prepared from GMO, tricaprylin, Tween(R) 80 and paclitaxel. The tumor cells of prostate cancer (DU-145 cells) were incubated and then put into different paclitaxel concentrations. The tumoricidal activity was measured by using an indirect methylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay. Cells of the DU-145 cell line were subcutaneously heterotransplanted into 18 nude mice, and they developed prostate cancer. The 18 mice were divided into 3 groups; the control group was injected with the DU-145 cell line (n=6), the GMO group was injected with GMO after the DU-145 cells were injected (n=6), and the oral GMO-paclitaxel group was injected with oral GMO-paclitaxel after the DU-145 cells were injected (n=6). The tumor volume was measured every week and the main organs were evaluated pathologically to determine the toxicity. RESULTS: On the MTT assay, the control group and the GMO group did not display cytotoxicity. However, treatment with the various GMO-paclitaxel formulations (0.1 microgram/ml, 1 microgram/ml, 10 microgram/ml) for treating the DU-145 cell line cancer induced cytotoxicity in a dose dependent fashion. The tumor volumes were not significantly changed in the group that was administered oral GMO-paclitaxel. However, there were significantly increased tumor volumes in the control group and the GMO group (p<0.05). Toxic changes were not detected in liver and kidney, and there was normal cellularity with a normal myeloid:erythroid ratio in the mice after the administration of oral GMO-paclitaxel. CONCLUSIONS: The newly developed oral GMO-paclitaxel has a remarkable cytotoxic effect against DU-145 cells without systemic toxicity. Therefore, oral GMO-paclitaxel therapy promises to be a safe and effective modality for treating hormone refractory prostate cancer, and it can possibly replace IV paclitaxel.

The Anticancer Efficacy and Toxicity of Oral Paclitaxel- Loaded Lipid Nanoparticle in a C3H2 Bladder Cancer Mice / 대한비뇨기과학회지

Purpose: Paclitaxel is an anticancer drug that blocks cell division by stabilizing microtubules. Even though paclitaxel has been shown to be effective in killing bladder cancer cell lines in vitro, the in vivo absorption was extremely low. A paclitaxel formulation was prepared in solution only, which was bioadhesive, and its effects evaluated in the MBT-2 cell line and in C3H2 bladder cancer mice. In addition, the toxicity of the paclitaxel formulation was also evaluated. Materials and Methods: A muco-adhesive oily paclitaxel formulation was made by the combining of monoolein, tricaprylin, Tween 80 and paclitaxel. MBT-2 cells were cultivated in different concentration of taxol, and the tumoricidal activity measured by the indirect methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay. In an in vivo study, the treatment regimen for the s.c. C3H2 mice was five consecutive once daily administrations, beginning on day 4 post tumor implant. The length and width of the tumors were measured twice a week, and the tumor volume calculated. On day 21, the tumor volume change and toxicity were evaluated. Results: The average particle size of paclitaxel-loaded lipid nanoparticle was about 600nm, with a polydispersity of 1,000. Only 2.6% of the MBT-2 cells were viable after 24 hour of treatment with the formulation at a paclitaxel concentration of 10mug/ml, while showing minimal toxicity of the formulation without paclitaxel. Paclitaxel-loaded lipid nanoparticles, administered orally, allowed significant antitumor activity in C3H2 mice (p<0.05). Conclusions: Paclitaxel-loaded lipid nanoparticles have a remarkable cytotoxic effect against MBT-2 cells, in a dose dependent manner, and the oral paclitaxel-loaded lipid nanoparticle therapy had an inhibitory effect on bladder tumors in a MBT-2 model, but without systemic toxicity. Therefore, oral paclitaxel-loaded lipid nanoparticles may be used for advanced bladder cancer patients.

Surgical Treatment of Tardy Ulnar Nerve Palsy / 대한정형외과학회잡지

The report on compression neuropathy of the ulnar nerve at the elbow was first submitted by Panas in 1878. Therafter many authors have reported on etiology, pathoanatomy, method of treatment and prognosis of tardy ulnar nerve palsy. But there are some controversies about method of treatment and prognosis. We reviewed 15 patients of tardy ulnar nerve palsy resulted from the fracture of the lateral condyle of the humerus during the growing period. The result obtained are as follows. 1. All 15 patients with tardy ulnar nerve palsy were resulted from non-union of lateral condyle and cubitus valgus deformity. 2. Average carrying angle was 28 degrees. 3. Intial symptoms were pain and paresthesia of the hand in all 15 patients. Eight of them also had atrophy of intrinsic muscle and seven patients had clawing deformity of fingers. 4. Preoperative severity of ulnar neuritis according to Osborne's classification was Grade I; 1 case, Grade lI; 6 case, Grade III; 8 cases. 5. Submuscular transposition of ulnar nerve was performed in 11 and subcutaneous in the other 4 patients. 6. In all patient, pain was markedly improved within a few months after transposition of nerve. Improvement of hypothenar atrophy was obtained in 5 out of 8 and interosseous atropy in 3 out of 7 cases. Clawing was improved in 5 out of 8 cases. 7. Postoperative status of ulnar neuritis by Osborne's criteria was Normal; 1, Grade I; 4, Grade II; 7, Grade III; 3 cases. 8. Postoperative complications were decreased sensation in the medial aspect of forearm in 3 cases and recurrence of nerve compression symptom in 1 csse. 9. Internal neurolysis with anterior transposition of nerve would be recommandable in Grade III severe ulnar neuritis and in case of firm consistency of nerve at the operative field.

A clinical Study of the Fractures of the Femoral Neck in Children / 대한정형외과학회잡지

Fractures of the femoral neck in children are uncommon and usually occur as a result of severe trauma due to their anatomical and physiologic characteristics. There are many difficulties during the treatment period and high incidence of complications such as avascular necrosis, coxa vara and premature epiphyseal closure. Twenty-three cases of fractures of the femoral neck in children which were treated at Kyung-Pook National University Hospital from Aug., 1980 to May, 1989 were analyzed both clinically and radiologically. The results were as follws: l. Among the 23 cases, higher incidence was in girls(13 cases, 56.5%) and the highest incidence was between the age of 11 and 13 years(8 cases, 34.8%). 2. The main cause of fracture was traffic accident(16 cases, 69.6%). 3. The most common type of fracture was the transcervical type(9 cases, 39.1%) and 17 cases (73.9%) were displaced fractures. 4. Associated injuries occurred in 13 cases(56.5%), and the common associated injuries were extremity fractures, head injuries and pelvic bone fractures. 5. Minimally displaced 7 cases(30.4%) were treated by closed reduction & internal fixation, and neglected, irreducible 15 cases(65.2%) by open reduction & internal fixation and undisplaced intertrochanteric fracture(1 case) by closed reduction & hip spica cast. 6. Twenty-three cases were followed from 8 months to 9 years and average period of follow-up studies was 28 months. The results were good in 5 cases(71.4%), fair in 2 cases (28.6%) in closed reduction & internal fixation, and good in 9 cases(60%), fair in 2 case(13.3%), poor in 4 cases(26.7%) in open reduction & internal fixation. 7. Complications were developed in 11 cases(47.8%), and premature epiphyseal closure were in 7 cases(30.4%), and avascular necrosis were in 6 cases(26.1%), and coxa vara were in 3 cases (13%), and delayed union was in 1 case and infection was in 1 case. 8. As a result, we recommend early closed reduction & internal fixation as the favorable method of treatment for the fracture of the femoral neck in children better than open reduction & internal fixation or conservative methods.

Clinical analysis of Carpal Scaphoid Fracture / 대한정형외과학회잡지

Scaphoid fracture is the most common carpal bone fracture and its treatment is frequently delayed due to difficulties of diagnosis. Nonunions and avascular necrosis are commonly developed due to peculiar blood supply. Though most of the undisplaced fracture, diagnosed early, can be managed easily by plaster of Paris immobilization, many cases of delayed diagnosis, displaced fractures and nonunions are difficult to treat and its outcome is not uniform. Ruse reported good results by iliac bone graft via volar approach and several internal fixation methods are reported such as K-wire, compression screw, Herbert screws etc. Recently, many suthors advocated accurate anatomical reduction in fear of volar and dorsal intercalary segmental instability. We reviewed 30 cases of scaphoid fracture at the department of orthopedic surgery, Kyungpook national university hospital, from June, 1986 to April, 1989 and obtained the following results. l. Among 30 cases of scaphoid fractures, 27 cases(90 %) were males. 2. Twenty one cases(70%) were between second decade and third decade. 3. The fracture mechanism is hyperdorsiflexion of the wrist during slip down or fall down in 21 cases(70%). 4. Right side is 17 cases(57%) and left 13 cases. Middle 1/3 fracture occupies 24 cases(80%) in anatomical location. 5. Among 15 cases of the fresh fracture, 11 cases(93%) attained bone union by plaster pf Paris immobilization. 6. Among 18 cases of operation, 3 cases were acute transscaphoid perilunar dislocation(TSPD), 1 case was delayed TSPD, 5 were delayed unions and 9 were monunions. Operative methods were Herbert screw fixations in 8, Herbert screw fication with iliac bone graft in 4, Russe's bone grafts in 6 cases. 7. The results of the treatment were classified according to the bone union status and range of motion of the wrist. In operative treatment, excellent and good results were obtained in 6 and 11 cases respectively, poor result in 1 case. In conservative treatment, excellent and good results in 6 and 5 cases respectively, fair in 1 case.

The Carpal Tunnel Syndrome / 대한정형외과학회잡지

The carpal tunnel syndroms is the most common peripheral nerve entrapment syndrome. The typical symptom is pain, numbness and paresthesia in the median nerve territory of the hand and progressive thenar atrophy. When the symptom is mild and its duration is short, conservative treatment such as splinting or local steroid injection is considered, but when neurological deficit is promiment and conservative treatment is not effective, surgical decompression is indicated.Authors reviewed 15 patients (23 cases) of carpal tunnel syndrome treated with surgical decomression at the Department of Orthopedic Surgery, Kyung-pook National University Hospital from March 1983 to October 1988. The follow up results are as follows; 1. Preoperatively, Tinel sign was present in 17 cases. Phalen test was positive in 17 cases. Sensory disturbance was present in 8 cases. Thenar muscle atrophy was present in 19 cases. Motor weakness was present in 13 cases. 2. Preoperatively, delay of motor conduction velocity of median nerve was noted in 15 cases (65.2%) and sensory nerve conduction velocity in 20 cases (86.9%). Denervation findings such as fibrillation or sharp waves were seen in 15 cases (65.2%). 3. The operative findings were as follows; Synovial hypertrophy in 12 cases, hypertrophy of transcarpal ligament in 4 cases, pseudoneuroma in 3 cases, ganglion in 2 cases, neurilemmoma in 1 case, gout in 1 case. 4. As the operative findings, median nerve had evidence of compression beneath the transcarpal ligament, consisting of flattening. narrowing and decreased epineurial vascularity. 5. External neurolysis was performed in all cases. 6. In case of long duration and severe thenar atrophy, internal neurolysis would be recommendable. 7. Fllow up period was ranged from 7 months to 6 years. 8. 19 cases (82.6%) were excellent or good results.

An Experimental Study of Tricalcium Phosphate (TCP) as a Bone Graft Substitutes of Bone Defects in Canine Femur / 대한정형외과학회잡지

The search for useful bone graft substitutes historically has focused on biologic alternatives. TCP has a 36% porosity and variable pores ranging from 100 to 300µm in diameter. They are biocompatible, easy fabricated into any size or shape, and offer a chemical environment and surface conductive to new bone formation. The porous scaffolding of the TCP permits rapid bone ingrowth. Gradual replacement of the ceramic with mature remodelling bone is noted as bioresorption of the TCP proceeds. The author investigated with TCP to evaluate the effect on the healing process of canine femoral bone defect as a bone graft substitutes. Five mongrel dogs(12Kg) were used in this study. Two holes(3.5mm) were created artificially with drill on the lateral surface of both right and left distal femora metaphyseal area in each dog under general anesthesia with nembutal. After creating artificial bone defects, 1 bone defect hole was filled with biodegradable TCP ceramic and adjacent other one was used as a control site wthout filling any implant material. The interval of each observation was 4, 6, 8, 10, 12 weeks after implantation and examined by means of radiology, histology with light and electron microscope. The results obtained were as follows; 1. Lamellar bone was formed around TCP 8 weeks after implantation. 2. In peripheral areas of TCP, collagen fibers, cytoplasm of osteoclasts & osteoblasts present in micropores of TCP. Osteocytes appeared around TCP with time. 3. In central areas of TCP, amorphous matrix was deposited in micropores in the early phase(4 weeks), but later collagen fibers & cytoplasmic processes appeared. 4. Osteoclasts were collected around TCP granules. Size of TCP granules in the periphery was gradually decreased. 5. Foreign body reaction within tissue was not shown during a whole experimental period. 6. Radiologically, opacity of implanted TCP was gradually decreased, and spillage on soft tissue of TCP was resorbed rapidly.

A Clinical Study of congenital Clubfoot / 대한정형외과학회잡지

The treatment, etiology, and even pathological anatomy of congenital clubfoot unfortunately are still controversial. A universially accepted method of classification of the severity of the deformity is lacking, and no standardized method of evaluating the result of treatment has been developed yet. 66 patients with 94 congenital clubfeet treated in orthopedic department of Kyungpook National University Hospital from 1981 to 1986 with nonoperative and operative method were analyzed. The results were as follows :1. Among 66 clubfeet patients, the sex ratio between male & female was 1.9: 1, bilateral involvement was in 28 and unilateral in 38 patients. 2. 10 patients(15%) were associated with other congenital anomalies. 3. Of 94 clubfeet, flexible type were 73(78%), rigid type were 21 feet. 4. Among 74 feet who were treated conservatively with serial cast, good result was obtained in 57 feet(77%). In patients who had conservative treatment within 3 weeks of life, good result was obtained as 84%, but in patients after 3 weeks, good result was obtained as 69%. 5. The average period of serial cast correction was 7.5 weeks. 6. In conservatively treated patients the talocalcaneal index was 25±7 before treatment and 61±8 after treatment. 7. Of 20 feet who were treated with surgical correction, good and fair result was obtained in 17 feet (85%). Key Words : Congenital clubfoot.

Muscle Transpositon in the Treatment of Soft Tissue Defect of the Leg / 대한정형외과학회잡지

The management of chronic osteomelitis of the tibial diaphysis and certain post-traumatic defects of the lower extremity is extremely difficult. the diverse methods of treatment signify current dissatisfaction with any single method. Recently, the muscle transposition technique has gained an accepted place in treating wide soft tissue defect with bone exposure. Popularized by Ger, Vasconez, Pers, Mc Hugh and others, this technique is generally simple, safe, and reliable, The 21 patients who treated by muscle transposition at the Kyungpook National University Hospital between 1980 and 1987 were reported. The results were as follows :l. 19 patients were males and 2 were females. 2. The cause of lesion were 8 cases of open fracture, 10 cases of chronic osteomyelitis, chronic ulcer 1 case, malignent melanoma 1 case, burn scar contracture 1 case. 3. The muscles used for transposition according to lesion site of leg were as follows. Medial head of gastrocnemius was transposed in 2 case of knee and 4 cases of proximal 1/3 lesion, 11 cases of middle l/3 lesion was used soleus, 1 cases were gastrocnemius after soleus, 1 case was tibialis anterior, 2 cases of distal 1/3 were used each 1 case of solus, 1 case of F.H.L. 4. All cases were healed within 2 to 3 weeks after muscle transposition, and this technique seemd to afford favorable influence upon the healing of fracture and the eradication of infection.