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.
Anesthesia, General ; Animals ; Ceramics ; Collagen ; Cytoplasm ; Dogs ; Femur ; Foreign-Body Reaction ; Osteoblasts ; Osteoclasts ; Osteocytes ; Osteogenesis ; Pentobarbital ; Porosity ; Transplants

BACKGROUND: Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukemia in children. However, quality of life and even survival may be threatened by infection. Immunosuppression is experted due to disease itself or therapy, and sometimes, immunosuppression itself may lead to reactivation of latent viral infections in these patients. Often the viruses involved in the most severe infections suggest that patients suffer from defect in the cellular immunity. The principal defects that predispose leukemia patients to infection are defects of T cell, B cell, stem cell, complement, and macrophage. These contributing factors interact in a complex manner resulting in spectrum of problems. But these may result from a T cell defect and, in this study, 7 cell responsiveness of patients at diagnosis, remission induction, maintenance chemotherapy and after chemotherapy for leukemia has been investigated. Studies of the immune competence of patients undergoing chemotherapy for leukemia is in progress, but results are different from each other. METHOD: Between July 1994 and May 1996, seventy patients with childhood ALL were enrolled in this study. In order to expect frequency and depth of infection and prognosis, we investigated concentrations of immunoglobulins G, A, M, peripheral total lymphocyte count, 7 cell subsets, phytohemmaglutinin responsiveness, interleukln-2(IL-2), gamma-interferon(gamma-INF), and natural killer cell activity. RESULTS: 1) IgA concentrations were often markedly raised at diagnosis, and IgG, IgM concentrations both were within normal limits. During and after chemotherapy, IgA had fallen significantly but IgG, IgM are within normal limits. 2) Total lymphocyte count had fallen during chemotherapy, and returned to normal levels after chemotherapy. CD4+ T cell were markedly decresed at diagnosis, during chemotherapy and returned to normal levels after chemotherapy. 3) In vitro proliferative response of peripheral blood lymphocytes to the T cell mitogen phytohenagglutinin were impaired at diagnosis, during chemotherapy but did not returned to normal levels. 4) Interlekin-2, gamma interferon were normal levels at diagnosis, and had fallen in the induction of remission and quickly returned to normal levels with the swish to maintenance chemotherapy. But Interleukin-2 had fallen during and after chemotherapy. Natural killer cell activity had fallen at diagnosis, during chemotherapy and returned to normal levels after chemotherapy. CONCLUSION: It is assumed that evidence of impaired T cell responses is somewhat definite. These observations suggest that proliferative responses to phytohemagglutinin, CD4+ T cell, natural killer cell activity defects are due to leukemia itself but others more likely are generalizable defects caused by chemotherapy. Further investigations, however, have suggested a persisting defect in IgA, proliferative reponses to phytohemagglutinin, and interleukln-2. Our observations also show that despite normal immunoglobulin levels, most of these children have nonprotective levels for common childhood bacterial or viral disease. These results support to the praxis to withdraw prophylactic antibiotics after discontinuation of intensive chemotherapy and to start the immunization. It is expect to try to use cytokine on treatment and to improve mortality and morbidity for children of acute leukemia also.
Anti-Bacterial Agents ; Child* ; Complement System Proteins ; Diagnosis ; Drug Therapy* ; Humans ; Immunity, Cellular ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Immunosuppression ; Interferons ; Interleukin-2 ; Killer Cells, Natural ; Leukemia ; Lymphocyte Count ; Lymphocytes ; Macrophages ; Maintenance Chemotherapy ; Mental Competency ; Mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Prognosis ; Quality of Life ; Remission Induction ; Stem Cells ; Virus Diseases

No abstract available.
Hemorrhage*

We used retroviral-mediated gene transfer of the human interleukin (IL)-2 gene into murine neuroblastoma cells to investigate whether locally-secreted IL-2 is able to influence the generation of anti-tumor immune responses. Supernatant obtained from cultures of approximately 1 x 10(6) IL-2 gene-transduced, G-418 selected neuro-2a cells was assayed for human IL-2 production by ELISA kit. First, to estimate whether the local secretion of IL-2 from the genetically-modified tumor cells would affect their tumorigenicity in vivo, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice and tumor growth was measured weekly. And to estimate whether IL-2 transfected neuroblastoma cells protect mice from tumor development after wild-type tumor cell challenge, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice. Seven days after IL-2 gene-transfected neuroblastoma cell injection, unmodified neuro-2a cells were s.c. injected into the contralateral site of A/J mice and tumor growth was measured weekly. Finally, to estimate IL-2 effect on pre-established large tumor burdens, IL-2-secreting neuro-2a cells were s.c. injected into A/J mice with established tumor and its growth was measured weekly. The IL-2 gene-transduced neuro-2a clones secreted 120.25-177.3 IU of IL-2 per ml per 10(6) cells during 24 hr. None of the mice injected with IL-2-secreting neuro-2a cells developed tumors within 6 weeks, while all of the mice injected with wild-type neuro-2a cells developed tumors. Immunization of mice with IL-2 gene-transfected, irradiated neuro-2a cells protected these animals against a subsequent challenge with wild-type tumor cells. Finally, the size of large neuroblastomas decreased after IL-2-secreting neuro-2a cell injection into mice. Local secretion of IL-2 gene-transduced tumor cells abrogates their tumorigenicity and induces protective immunity and may inhibit the growth of neuroblastoma.
Animal ; Antibody Formation ; Gene Transfer Techniques* ; Human ; Immunization/methods ; Interleukin-2/therapeutic use ; Interleukin-2/genetics* ; Mice ; Neoplasm Transplantation ; Neuroblastoma/therapy ; Neuroblastoma/prevention & control ; Neuroblastoma/pathology ; Neuroblastoma/genetics* ; Retroviridae/genetics* ; Tumor Cells, Cultured

Cardiovascular disease, including stroke, is one of the major causes of death in diabetes. Numerous studies have long suggested reducing macrovascular complication such as ischemic vascular disease through intensive glycemic control, but none was successful proving the effect of glycemic control. Recently, new possibilities in cardiovascular disease reduction have been proposed through cardiovascular safety trials of newly developed anti-hyperglycemic agents. The purpose of this review is to introduce the traditional and newly developed anti-diabetic medications and review their effects regarding cardiovascular outcomes mainly focusing on stroke.
Cardiovascular Diseases ; Cause of Death ; Diabetes Complications ; Diabetes Mellitus ; Drug Therapy ; Hypoglycemic Agents ; Stroke ; Vascular Diseases

Hypoglycemia is common but can lead to life-threatening consequences. Accurate diagnosis is important to establish the appropriate treatment strategy. Most cases of hypoglycemia are caused by hypoglycemic agents, although it can occur in individuals without diabetes. A systemic and comprehensive diagnostic approach is required to diagnose hypoglycemia in patients without diabetes. It is important to perform appropriate blood testing during an episode of hypoglycemia. This review will focus on the definition, differential diagnosis, causes, and treatment of hypoglycemia, particularly in people without diabetes.

Inappropriate secretion of antidiuretic hormone (ADH) secondary to vincristine therapy has been reported frequently. But there has been five previous reports of vinblastine associated SIADH in the world and in 4 reports, bleomycin and cis-platinum were used along with vinblastine together. Because penetration of vinka alkaloids into CSF of humans is known to be poor, it has been suggested that lowering the osmotic threshold for vasopressin release induces SIADH in humans. In our case, the patient did not receive cis-platinum during chemotherapy. From this we concluded that vinblastine alone can induce SIADH without nephrotoxicity of cis-platinum. We experienced a case of inappropriate ADH secretion secondary to vinblastine therapy in a 5- month-old male infant who has been taking vinblastine due to Langerhans cell histiocytosis. We report this case with a brief review of related literatures.
Alkaloids ; Bleomycin ; Cisplatin ; Drug Therapy ; Histiocytosis, Langerhans-Cell ; Humans ; Inappropriate ADH Syndrome ; Infant ; Male ; Vasopressins ; Vinblastine* ; Vincristine

No abstract available.
Carcinoid Tumor* ; Lymph Nodes* ; Neoplasm Metastasis*

BACKGROUND: Chronic idiopathic thrombocytopenic purpura is an autoimmune disorder caused by sequestration of antibody-sensitized platelets in the reticuloendothelial system. However, uncertainty as to the specificity, frequency and clinical significance of such antibodies still remains. So, we tried to further clarify the above uncertainty in childhood chronic idiopathic thrombocytopenic purpura. METHODS: We analyzed sera from 29 patients. Twenty six patients were chronic ITP who were admitted or followed up to the Department of Pediatrics, Severance Hospital, Yonsei University Medical College from August 1996 to March 1997 by employing a modified antigen-capture ELISA(MACE), flow cytometry and electrophoresis(SDS-PAGE) and immuno-blotting(IB) assays. Three patients with ITP less than 6 months after onset of ITP were included to know the possibility to differrentiate between acute ITP and chronic ITP in this study. RESULTS: 1) Glycoprotein(GP)-specific antibodies were found in 28% (8/29) of patients, with 2 patients having antibodies directed solely to Gp II b/III a, no patients holding antibodies specific only for GPI b/I X and 6 possessing antibodies against both anti-GP I b/I X and Gp II b/III a antigen. 2) The detection rate of GP-specific antibodies of flow cytometry was about 10%. The positivity of anti-GPI b/I X antibodies by MACE and immunoblotting was 14% (4/29), respectively, the positivity of anti-Gp II b/III a antibodies by MACE and immunoblotting was, 21 % (6/29) respectively. The concordance rate between two assays(MACE and IB) was 79% (23/29). None of the three methods was good enough to stand alone. 3) Serum antibodies were not more frequently detected in active(p=1.0) or non-splenectomized(p=.54) chronic ITP patients. 4) No association was found between antibody specificity(anti-GPI b/I X, anti-Gp II b/ III a) and platelet counts(p : .87). CONCLUSION: We conclude that in korean childhood chronic ITP, antibodies against both anti-GPI b/I X and Gp II b/III a antigen were predominant antibody. But, the longterm follow-up in more cases is needed to further clarify the clinical significance of antral-platelet antibody in chronic ITP should be assessed.
Antibodies* ; Blood Platelets* ; Flow Cytometry ; Follow-Up Studies ; Humans ; Immunoblotting ; Mononuclear Phagocyte System ; Pediatrics ; Purpura, Thrombocytopenic, Idiopathic* ; Sensitivity and Specificity ; Uncertainty

BACKGROUND: Replication of defective adenoviral vectors can be used for gene transfer into a wide spectrum of replicating and nonreplicating cells. Accordingly, selective introduction of genes encoding for susceptibility to nontoxic drugs into proliferating tumor may be used to treat cancer. We investigated the efficacy of in vitro transduction of neuroblastoma cell with the herpes simplex virus thymidine kinase gene followed by administration of the antiviral drug ganciclovir. METHODS: The recombinant adenoviral vector ADV/TK carrying the HSV-TK gene, under the control of the promoter from Rous sarcoma virus long term terminal repeat was constructed. And 1 x 10(4) Neuro 2a cells were plated in 96 well cultured plates and infected with ADV/TK at multiplicity of infection of 0, 1, 10, and 100. Twenty-four hours later, the infected cells were treated with PBS or ganciclovir at a concentration of 10 g/ml. After 48hr, the surviving cells in 96 well plates were determined by MTT assay. RESULTS: After infection in vitro with ADV/TK at moi of 0, 1, 10, 100 and subsequent ganciclovir treatment, the percent survival rate of 1 x 10(4) Neuro 2a cells were 105%, 32%, 25%, and 15%. But the survival rate of 1 x 10(4) Neuro 2a cells with PBS treatment were 100%, 92%, 105%, 103%. CONCLUSION: We concluded that in vitro transduction of neuroblastoma cell with the herpes simplex-thymidine kinase gene followed by administration of the antiviral drug ganciclovir is very effective.
Cell Line* ; Ganciclovir* ; Neuroblastoma* ; Phosphotransferases ; Rous sarcoma virus ; Simplexvirus ; Survival Rate ; Terminal Repeat Sequences ; Thymidine Kinase