BACKGROUND: To evaluate the effectiveness of early postoperative adjuvant immunochemotherapy in a stage III (UICC, 1997) primary gastric carcinomas we analyzed cases histories of 140 patients retro spectively who had undergone curative gastrectomy at Wonkwang University Hospital from November 1988 to November 1995. METHODS: For immunotherapy, OK-432 intramuscularly or oral PSK was used for 2 months, and for chemotherapy, FAM (8 week cycle) or oral 5-FU derivatives and MMC were used for 6 months or longer. Immunotherapy was started at the 5th postoperative day and chemotherapy at the 7th to 10th postoperative day. Sixty-eight (68) patients received immunochemotherapy (therapy group; TG) and 72 patients did not (nontherapy group; NTG). Statistical analysis were carried out with Anova, Kaplan-Meier, and Log rank test. RESULTS: One hundred eight (108) patients were male, and 84 patients were younger than 60 years. Eighty-one (81) cases involves the lower stomach and 52 the middle stomach. Lymphatic invasion was seen in 60 cases. Twenty-five (25) cases were T2, 112 T3, 42 N1, 90 N2, 75 stage IIIa, and 65 stage IIIb. The overall 5-year survival rate was 48.6% (stage IIIa 58.7%, stage IIIb 36.9%, p<0.05). The 5-year survival rates for the TG and the NTG were 52.9% and 44.4%, respectively (p=0.10). The 5-year survival rates were 85.7% (n=18) and 85.7% (n=7) in T2, 54.0% (n=50) and 40.3% (n=62) in T3 (p<0.05), 69.6% (n=23) and 50.0% (n=24) in N1, 44.4% (n=45) and 42.2% (n=45) in N2 (p=0.14), 61.0% (n=41) and 55.9% (n=34) in stage IIIa, 40.7% (n=27) and 34.2% (n=38) in stage IIIb (p=0.16), 59.5% (n=37) and 48.8% (n=43) in the non-lymphatic invasion group, and 45.2% (n=31) and 37.9% (n=29) in the lymphatic invasion group (p=0.09). There was no significant difference in the 5-year survival rates of the other parameters, such as age, sex, tumor location, size, gross finding, tumor differentiation, between the TG and the NTG. CONCLUSION: The survival rate in the early postoperative immunochemotherapy group was not signi ficantly increased compared to that in the nontherapy group for stage III gastric cancer, but the immuno chemotherapy group showed a tendency for a higher 5-year survival than the nontherapy group did.
Drug Therapy ; Fluorouracil ; Gastrectomy ; Humans ; Immunotherapy ; Male ; Picibanil ; Stomach ; Stomach Neoplasms* ; Survival Rate

The major reason for the chronic graft loss is chronic rejection. The only predictive factor for chronic rejection is a prior acute rejection episode resulting in a poorer long-term outcome. Also the number of acute rejection episodes is a strong predictor of long-term allograft failure. This study evaluated the impact of a first acute rejection episode and the severity of the rejection and the number of acute rejection episodes on allograft survival. Total of 136 renal transplant were performed between August 1987 to January 1996 at Wonkwang university hospital, and we studied 108 renal transplants that were followed for a minimum of 1.5 years. Acute allograft rejection was mainly diagnosed by clinical evaluation and laboratory data. Transplant patients were divided into three groups according to the time to the first acute rejection; no rejection (group I, n=44); acute rejection during the first 6 months (group II, n=42), acute rejection after 6 months (group III, n=22) and divided into four groups according to the number of acute rejection episodes; no rejection (Group A, n=44), one time (Group B, n=24), two times (Group C, n=23), and more than three times (Group D, n=17). Five-year allograft survival rate for group I-III was 96.4%, 82.7%, 58.5%, respectively (p<0.05 for each comparison to group I). Later acute rejection episodes were associated with worse response to rejection therapy and Group III had higher serum creatinine concentration after rejection therapy than Group II (2.46 1.13 mg/dl vs 1.19 0.7 mg/dl, p<0.05). Five-year allograft survival rate for group A-D was 93.4%, 73.2%, 57.4%, 74.5%, respectively, Group A shows higher graft survival rate, but there was not significant difference in long-term allograft survival among Group B-D. We conclude that late occurrence of a first acute rejection portends a worse prognosis for long-term allograft survival and decreases response to rejection therapy and results in poor graft function. Prevention of later rejection may require a broader focus, with additional efforts directed at improving patient compliance and renal allograft monitoring.
Allografts ; Creatinine ; Graft Survival* ; Humans ; Kidney Transplantation ; Patient Compliance ; Prognosis ; Survival Rate ; Transplants*

BACKGROUND:CAVI, Cardio Ankle Vascular Index, has been proposed as an independent marker of arterial stiffness regardless of the blood pressure. We measured the CAVI of hemodynamically unstable patients on maintenance hemodialysis and at the same time measured other pulse pressure-related parameters in order to study their correlations with each other. METHODS:We studied 85 patients undergoing maintenance hemodialysis over 3 months. We categorized patients into 4 subgroups: Diabetes+Hypotension (N= 12), Diabetes+Normal blood pressure (N=16), Non- diabetes+Hypotension (N=15), and Non-diabetes+Normal blood pressure (N=42). Using automatic waveform analyzer, we measured CAVI and pulse pressure- related markers twice, before and after the hemodialysis session, and observed the change. RESULTS:After the dialysis, CAVI did not change despite the decreased mean blood pressure. Yet both brachial and ankle pulse pressure dropped significantly (4.34+/-15.22 mmHg, 11.50+/-20.65 mmHg, p<0.01). PEP (Pre-Ejection Period) on the other hand, remarkably increased (12. 13+/-22.18 msec) while ET (Ejection Time) showed considerable decrease (35.86+/-45.68 msec), and PEP/ ET ratio increased as well. Predialysis CAVI was significantly higher in Diabetes group than in Non-diabetes (11.02+/-2.33 vs. 8.20+/-1.87, p<0.001). However, no significant difference of CAVI was observed between Hypotension and Normal blood pressure groups. Diabetes+Hypotension Group displayed reduction in CAVI after dialysis with marginal significance (0.68+/-1.07, p=0.05) whilst PEP, ET and PEP/ET ratio showed no significant change compared to other groups. CONCLUSION:CAVI, a newly developed marker of arterial stiffness, is expected to be useful in prediction of the cardio-vascular risk and prognosis of patients undergoing hemodialysis.
Ankle ; Blood Pressure ; Dialysis ; Hand ; Humans ; Hypotension ; Prognosis ; Renal Dialysis* ; Vascular Stiffness

In order to examine the neurotoxic mechanism of oxygen radicals on cultured bovine oligodendrocytes, cytoxic effect of oxygen radicals was examined when cultures were treated with various concentrations of xanthine oxidase (XO) and hypoxanthine (HX) in culture medium. In addition, the neuroprotective effect of iron-chelators against the neurotoxicity induced by oxygen radicals was evaluated by MTT assay. Cell viability was remarkably decreased in a time-dependent manner after exposure of cultured bovine oligodendrocytes to 20mU/ml XO and 0.1mM HX for 4 hours. In the neuroprotective effect of iron-chelators on oxidant-induced neurotoxicity, tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) blocked the neurotoxicity induced by oxygen radicals, while DFX was not effective in blocking oxidant-induced neurotoxicity in these cultures. These results suggest that oxygen radicals are toxic in cultured bovine oligodendrocytes, and also selective iron-chelators such as TPEN are effective in blocking the neurotoxicity induced by oxygen radicals.
Allopurinol* ; Cell Survival ; Hypoxanthine ; Neuroprotective Agents ; Oligodendroglia ; Reactive Oxygen Species ; Xanthine Oxidase

PURPOSE: Nonoperative management is currently considered a treatment modality in 50 to 80% of patients with blunt liver injury. Nevertheless 10 to 50% of patients need operative management, and the criteria for operative management have not established. The purpose of this study is to find criteria for operative management of patients with blunt liver injury. METHODS: The records of 117 patients who experienced blunt hepatic injury from January 1992 to April 1999 were reviewed retrospectively with respect to hemodynamic stability, transfusion requirement, injury severity score, liver injury grade, amount of blood in the peritoneal cavity, and pooling of contrast material on computerized tomography (CT). RESULTS: Among the 117 patients, 29 patients (25%) were treated operatively (Group 1) and 88 patients (75%) were treated nonoperatively (Group 2). The initial systolic blood pressure in Group 1 was significantly lower than that of Group 2 (74.4+/-30.3 mmHg vs 107.1+/-27.2 mmHg, p<0.001). The amounts of transfusion for hemodynamic stability were 2.1 units in Group 1 and 0.4 units in Group 2 (p<0.001). The injury Severity score of Group 1 was significantly higher than that of Group 2 (20.8 +/- 11.0 vs 10.7+/-6.8, p=0.03). The mean injury grade was 3.7+/-0.1 for Group 1 and 2.4+/-1.0 for Group 2, which was a statistically significant difference was seen (p<0.001). The amount of hemoperitoneum in Group 1 was significantly higher than that of Group 2 (p<0.001). The pooling of contrast material on CT was detected in 3 cases in Group 1. CONCLUSION: We can establish the following criteria for operative management: operative management is necessary for hemodynamic instability during resusci tation, positive peritoneal irritation signs, and presence of pooling of contrast material on CT. In cases above grade IV, above 500 mL of hemoperitoneum on CT, or above 2 units of blood transfusion during resuscitation, close observation in an intensive care unit is necessary. If abnormality develops during observation, prompt operative management is mandatory.
Blood Pressure ; Blood Transfusion ; Hemodynamics ; Hemoperitoneum ; Humans ; Injury Severity Score ; Intensive Care Units ; Liver ; Peritoneal Cavity ; Resuscitation ; Retrospective Studies

BACKGROUND/AIMS: A lymph-node dissection around the abdominal esophagus, vagotomy, and dissection to the phrenoesophageal membrane performed during a radical subtotal gastrectomy result anatomical changes and may result functional changes in the lower esophageal sphincter. We performed this study to define the changes of the esophageal reflux and motility in the development of these complications. METHODS: We performed this study before and after the radical subtotal gastrectomy with the esophageal manometry and 24hour ambulatory esophageal pH monitoring in 16 gastric cancer patients. RESULTS: There were no significant changes of the length, resting pressure of the lower esophageal sphincter, and the velocity of peristalsis in the lower esophageal area after the radical subtotal gastrectomy (3.94+/-0.66 vs. 3,85+/-0.61, 24.93+/-8.68 vs. 24.21+/-9.43, 3.99+/-0.95 vs. 3.79+/-1.01, respectively). There were no significant changes of the number of reflux episodes >or= 5 min (0.56+/-0.96 vs. 0.44+/-1.03), the duration of longest reflux episodes (5.19+/-6.84 vs. 4.25+/-7.22), and the total reflux time of pH below 4 (11.13+/-14.32 vs. 12.19+/-19.11) after the radical subtotal gastrectomy. CONCLUSION: This study suggests that acid reflux and esophageal motility after the radical subtotal gastrectomy might not be affected by anatomical derangement due to the surgical procedure itself.
Esophageal pH Monitoring ; Esophageal Sphincter, Lower ; Esophagus ; Gastrectomy* ; Gastroesophageal Reflux ; Humans ; Hydrogen-Ion Concentration ; Manometry ; Membranes ; Peristalsis ; Stomach Neoplasms ; Vagotomy

Aspergillus funigatus and other pathogenic fungi synthesize a toxic epidithi-odiopiperzine (ETP) metabolite, namely gliotoxin. Gliotoxin commonly react with sulfhydryl groups, and then, forms hydrogen peroxide. These fungal toxins induce apoptotic cell death in various cells. Apoptosis induced by gliotoxin need calcium. Effect of calcium preconditioning was not reported in gliotoxin-induced apoptosis. To examine the effect of protein kinase C (PKC) and calcium which was regulate caspase-3, PKC and calcium preconditioning before gliotoxin treatment, apoptotic agents such as bcl-2 family, caspase-3 and DNA fragmentation in A7r5 cell line from rat smooth muscle cell were studied. These results showed that gliotoxin induces the expression of bad of bcl-2 family, caspase-3 activation and DNA fragmentation in A7r5 cells. Gliotoxin treatment followed by calcium and PKC preconditioning suppress the Bad of bcl-2 family, and inhibited caspase-3 activation, respectively. These results suggest that PKC and calcium preconditioning protect the gliotoxin-induced apoptosis, through the protection of pro-apoptotic bcl-2 family in A7r5 cells.
Animals ; Apoptosis ; Aspergillus ; Calcium ; Caspase 3 ; Cell Death ; Cell Line ; DNA Fragmentation ; Fungi ; Gliotoxin ; Humans ; Hydrogen Peroxide ; Muscle, Smooth* ; Mycotoxins ; Myocytes, Smooth Muscle* ; Protein Kinase C ; Rats*

No abstract available.
Glutathione* ; Oligodendroglia*

Nitric oxide (NO) elevates intracellular calcium. But the actions of calcium in NO-induced cell death are not well understood. This study was carried out to investigate the signal transduction pathways of calcium and NO-induced cytotoxicity in H9c2 cardiac myoblasts by using NO donor compounds such as sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP). Pretreatment of intracellular calcium chelating agent (BAPTA/AM) or L-type calcium channel blockers (nicardipine, nifedipine, diltiazem and veraparmil) or T-type calcium channel blocker (flunarizine) blocked SNP-induced cytotoxicity respectively only in a three hours. However, thapsigargin (TG), which inhibits endoplasmic reticulum dependent Ca(2+)-ATPase and thereby increases cytosolic Ca(2+), augmented SNP-induced cytotoxicity. The protective effect of BAPTA/AM was inhibited by treatment of protein synthesis inhibitor, cyclohexamide. In addition, pyrrolidine dithiocarbamate (PDTC), NF-kB inhibitor, attenuates the protective effect of BAPTA/AM against SNP-induced cytotoxicity. It is indicated that the protective effect of BAPTA/AM against NO-induced cytotoxicity might be due to the expression of protein related to activation of NFkB. From these results, it is concluded that SNP-induced cytotoxicity is mediated by calcium in a 3 hours via down regulation of protein expression rleated to activation of NFkB.
Calcium Channels, L-Type ; Calcium Channels, T-Type ; Calcium* ; Cell Death ; Cytosol ; Diltiazem ; Down-Regulation ; Endoplasmic Reticulum ; Humans ; Myoblasts, Cardiac* ; NF-kappa B ; Nifedipine ; Nitric Oxide ; Nitroprusside ; S-Nitroso-N-Acetylpenicillamine ; Signal Transduction* ; Thapsigargin ; Tissue Donors

Paclitaxel (taxol) is known as effective drug inhibition of cell cycle encouraging activity in human ovarian and metastatic breast cancers and malignant melanoma. It is an antimicrotubule agent that is believed to mediate its antineoplastic effects by inducing mitotic arrest followed by apoptosis. The relation between phorbol 12 myristate 13 acetate (PMA), protein kinase C (PKC) activator, and taxol-induced apoptosis is not well understood until now. This study was performed to investigate the effects of PMA on the signal transduction pathways of taxol-induced apoptosis in MCF-7 human breast carcinoma cells. Taxol-induced apoptosis is attenuated by curcumine, JNK inhibitor, and pyrrolidine dithiocarbamate (PDTC), inhibitor of NFkB. Pretreatment with PKC activator (PMA) or protein kinase A (PKA) activators (forskolin and dibutyryl cAMP) inhibited taxol-induced apoptosis in MCF-7 cells. In addition, thapsigargin, a specific inhibitor of endoplasmic reticulum(ER) Ca(2+)-ATPase and CaCl2, also blocked the activation of caspases by taxol. From these results suggest that taxol-induced apoptosis may be mediated via JNK or NFkB pathway and PKC activation.
Apoptosis ; Breast ; Breast Neoplasms ; Caspases ; Cell Cycle ; Curcumin ; Cyclic AMP-Dependent Protein Kinases ; Humans ; MCF-7 Cells* ; Melanoma ; Myristic Acid ; Paclitaxel ; Protein Kinase C ; Signal Transduction ; Thapsigargin