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Biomedical subjects

C D Kim

Publications and source records attributed to C D Kim.

At least 37 records · Page 2Linked to original sources

Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas.

Adenocarcinomas of the pancreas and biliary tract are highly malignant neoplasms, which are found in the advanced stage. Chemotherapy commonly plays a palliative role in the treatment of pancreatic and biliary tract cancers. 5-Fluorouracil (5-FU) is the most widely studied single agent; the response rate of 5-FU is only 20%. Recently, some reports presented interesting results, in which 5-FU, modulated with levofolinic acid (leucovorin), was active in patients with colorectal cancer. In relation, we performed a phase II study of 5-FU, modulated with leucovorin, in patients affected by advanced pancreatic or biliary tract cancer. Fifty-one patients with nonresectable carcinomas of the pancreas or biliary tract admitted to Korea University Hospital between May 1995 and December 1998 were included in this study. Chemotherapy consisted of leucovorin 25 mg/m2/day by 2-hour intravenous infusion, followed by 5-FU 375 mg/m2/day by bolus intravenous infusion, from day I to day 5. The treatment was repeated every 3 to 4 weeks. A total of 51 eligible patients with advanced adenocarcinoma of the pancreas or biliary tract were enrolled. Of 23 enrolled patients with pancreatic adenocarcinoma, one patient showed complete remission with a survival duration of 13 months (response duration was 9 months). Three patients had partial responses (PRs) with survival times of 6, 12, and 15 months, respectively. The overall response rate was 17.4% (95% confidence interval [CI], 7.2%-36.2%). The median time of overall survival was 6 months (range: 1-15 months). Of 28 enrolled patients with biliary tract cancer, complete responses were observed in 2 patients (7.1%) with survival time of 14 and 16 months, respectively. Seven patients had PRs with a median survival of 8 months. The overall response rate was 32.1% (95% CI, 20.3%-57.5%). The median time of overall survival was 6 months (range: 1-16 months). The most prominent toxicity was mucositis. Hematologic toxicity was less severe. 5-Fluorouracil in modulation with intravenous leucovorin is well tolerated by patients with stage IV pancreatic adenocarcinoma or biliary tract cancer. Although the response rate for patients with pancreatic adenocarcinoma is not better than that achieved using 5-FU monochemotherapy, the 32.1% overall response rate achieved in patients with biliary tract cancer suggests that 5-FU modulation with leucovorin is active in biliary tract cancer.

Adenocarcinoma↗

Evaluation of pancreatic exocrine function using pure pancreatic juice in noninsulin-dependent diabetes mellitus.

To investigate the pancreatic exocrine function in noninsulin-dependent diabetes mellitus (type 2 DM), we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 13 healthy control subjects and 22 patients with type 2 DM who had no evidence of pancreatic disease. Samples of pancreatic juices were collected in six fractions for 30 minutes at 5-minute intervals after an intravenous bolus injection of secretin (0.25 CU/kg) and cholecystokinin-8 (CCK) (40 ng/kg). The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose (50%, 40 mL) were measured. The levels of plasma insulin and C-peptide levels in type 2 DM were the same as in healthy controls in the basal state but did not further increase in response to an intravenous glucose. This suggested that patients with type 2 DM had insulin secretion defect rather than insulin deficiency. Pancreatic secretions including volume, bicarbonate, and protein output in response to stimulation with secretin, and CCK were significantly reduced when compared to the healthy controls. We conclude that patients with type 2 DM exhibit impairment of pancreatic exocrine secretion and that this impairment might not be related to insulin deficiency. Therefore, we recommended that careful evaluation for exocrine pancreatic function in type 2 diabetics who have any clinically suspicious symptoms of pancreatic insufficiency.

Adult↗

Weber-Christian disease presenting with proptosis: a case report.

Weber-Christian disease (WCD) is a rare inflammatory disease of adipose tissue, which is characterized by painful cutaneous nodules and constitutional symptoms. Although any area of the body containing fat can be affected by WCD, the involvement of retrobulbar fat is uncommon and proptosis is a rare presenting manifestation. We report a case who presented with proptosis of the right eye which is accompanied by painful subcutaneous nodules, high fever and myalgia. Biopsies of retrobulbar tissue and suprapubic nodule showed lobular panniculitis with mixed cellular infiltration, mainly composed of histiocytes and lymphocytes. He responded well to high-dose glucocorticoid.

Adult↗

Rebamipide inhibits neutrophil adhesion to hypoxia/reoxygenation-stimulated endothelial cells via nuclear factor-kappaB-dependent pathway.

This study was designed to determine whether rebamipide can inhibit neutrophil adhesion to human umbilical vein endothelial cells (HUVECs) stimulated with 1 h of hypoxia followed by 4 h of reoxygenation (H/R). Furthermore, to define the action mechanisms, we determined the effect of rebamipide on the surface expression of endothelial cell adhesion molecules E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1) on H/R-stimulated HUVECs. Under resting conditions, both E-selectin and P-selectin were not expressed on the surface of HUVECs in contrast to ICAM-1, which was constitutively expressed. After stimulation with H/R, HUVECs showed an enhanced neutrophil adhesivity in association with an increased surface expression of E-selectin and P-selectin with a marginal increase in ICAM-1 expression. In parallel, the increased nuclear translocation of nuclear factor-kappaB in H/R-stimulated HUVECs was monitored by electrophoretic mobility shift assay (adjusted volume units, 11.9 +/- 2.5 x 10(4) counts x mm(2) in unstimulated cells versus 24.2 +/- 3.0 x 10(4) counts x mm(2) in H/R-stimulated cells). Rebamipide suppressed the surface expression of E-selectin and P-selectin with a subsequent inhibition of neutrophil adhesion to H/R-stimulated HUVECs. In line with these results, rebamipide (100, 300, and 1000 microM) inhibited H/R-induced nuclear translocation of nuclear factor-kappaB in a concentration-dependent manner. Taken together, this study demonstrates that rebamipide inhibits neutrophil adhesion to HUVECs by a mechanism involving inhibition of transcription-dependent surface expression of E-selectin and P-selectin in H/R-stimulated endothelial cells.

Alanine↗

Association of pseudoachalasia with advancing cancer of the gastric cardia.

BACKGROUND: Pseudoachalasia is attributable to malignant tumors of the gastric cardia in more than 50% of cases. Study of the progression of esophageal manometric abnormalities with increasing tumorous involvement of the esophagogastric junction may improve our understanding of the pathophysiologic characteristics of pseudoachalasia. METHODS: During a 2-year period, esophageal manometric characteristics were evaluated for 17 of 21 consecutive patients with cancer of the gastric cardia. Manometry was not possible in the other four. Manometric parameters assessed included lower esophageal sphincter pressure, percentage lower esophageal sphincter relaxation, and percentage failed peristalsis. The extent of malignant involvement of the esophagogastric junction was graded as none, less than 50% of the circumference, or 50% or more of the circumference, assessed from surgical specimens in 13 cases and endoscopy in 4 cases. RESULTS: Pseudoachalasia was diagnosed in 3 cases, all with 50% or greater circumferential involvement of the esophagogastric junction. The first manometric indication of evolving pseudoachalasia was impaired lower esophageal sphincter relaxation; loss of peristaltic function was a secondary consequence. CONCLUSIONS: These findings suggest that the primary mechanism of pseudoachalasia with gastric cardia cancer is malignant stenosis of the esophagogastric junction.

Adult↗

Epidemiological study on Korean gallstone disease: a nationwide cooperative study.

To clarify the epidemiological characteristics of gallstone disease in Korea and to evaluate the chronological changes in gallstone disease, the authors performed this first prospective nationwide cooperative study. The subjects were 1263 gallstone patients who were admitted at 19 hospitals in Korea from February to July 1997. Questionnaires were recorded on 1263 patients and gallstones were harvested from 1133 patients. The proportion of patients with gallbladder (GB), common bile duct (CBD), and intrahepatic duct (IHD) stones among total gallstone patients was 64.0%, 21.9%, and 14.1%, respectively. GB stones were categorized as cholesterol (58.1%), black pigment (25.2%), and brown pigment (12.1%) stones. CBD stones were classified as brown pigment (76.1%), cholesterol (18.4%), and black pigment (3.5%) stones. IHD stones were classified as brown pigment (61.4%) and mixed (35.6%) stones. Intrahepatic mixed stones had mean cholesterol and bilirubin contents of 63.4 +/- 20.8% and 23.1 +/- 9.9%, respectively. In contrast, IHD brown pigment stones had mean cholesterol and bilirubin contents of 35.1 +/- 20.5% and 39.6 +/- 17.4%, respectively. Our study showed that the type and composition of gallstones in Korea was somewhat different compared with those in the West. This study also demonstrated that there have been chronological changes in the type and composition of gallstones when compared with previous domestic data. Another nationwide cooperative study may be needed to elucidate and confirm the changing pattern of gallstone disease.

Adolescent↗

Effect of omega-conotoxin GVIA and omega-agatoxin IVA on the capsaicin-sensitive calcitonin gene-related peptide release and autoregulatory vasodilation in rat pial arteries.

This study assesses the effect of neuronal voltage-sensitive Ca2+ channel blockers, omega-conotoxin GVIA (CTX), and omega-agatoxin IVA (AgTX) on the vasodilation and release of calcitonin gene-related peptide (CGRP), both of which were induced by either application of capsaicin or acute stepwise hypotension. Changes in pial arterial diameter were determined directly through a closed cranial window. The vasodilation of pial artery induced by either CGRP (0.1 micromol/L) or capsaicin (0.3 micromol/L) was significantly inhibited by CGRP(8-37) (0.1 micromol/L) (P < 0.05 and P < 0.05, respectively). The autoregulatory vasodilation to acute stepwise hypotension was severely attenuated by pretreatment with either CTX or AgTX. When the hypotension was kept for 2, 4, and 10 minutes, the releasable CGRP-like immunoreactivity (CGRP-LI) level (vehicle, 13.4+/-1.5 fmol/mm2/30 min) by 10 micromol/L capsaicin from the isolated pial arteries was significantly reduced in the 4- and 10-minute hypotension groups (11.3+/-1.2 fmol/mm2/30 min, P < 0.05, and 11.1+/-1.5 fmol/mm2/30 min, P < 0.05, respectively), but not in 2-min group. Moreover, the CGRP-LI level released by 10 micromol/L capsaicin (13.7+/-0.9 fmol/mm2/30 min) also was significantly depressed by pretreatment with 1 micromol/L CTX to 10.4+/-1.0 fmol/mm2/30 min (P < 0.01) and with 0.1 micromol/L AgTX to 8.7(1.7 fmol/mm2/30 min (P < 0.001), as well as by pretreatment with 10 micro-mol/L capsaicin (6.0+/-1.6 fmol/ mm2/30 min, P < 0.001). These results suggest that the neuronal N- and P-type voltage-sensitive Ca2+ channels are implicated in the release of CGRP from capsaicin-sensitive perivascular sensory nerves in response to acute hypotension, and that the released CGRP may contribute to the autoregulatory vasodilation in the cerebral microcirculation.

Animals↗

Biliary papillary hyperplasia with clonorchiasis resembling cholangiocarcinoma.

Infection by the liver fluke Clonorchis sinensis is very common in the Far East. It causes low grade inflammatory changes and proliferation in the biliary tree. Initially there is desquamation of the biliary epithelium, followed by hyperplasia and adenomatous proliferation. Cholangiocarcinomas are potential long term complications. We present a case of biliary papillary hyperplasia with clonorchiasis resembling cholangiocarcinoma in a 69-yr-old Korean man. Early recognition of biliary hyperplasia and treatment of Clonorchis sinensis is important to prevent development of cholangiocarcinoma, especially in the Far East.

Aged↗

Neuronal NOS provides nitrergic inhibitory neurotransmitter in mouse lower esophageal sphincter.

To identify the enzymatic source of nitric oxide (NO) in the lower esophageal sphincter (LES), studies were performed in wild-type and genetically engineered endothelial nitric oxide synthase [eNOS(-)] and neuronal NOS [nNOS(-)] mice. Under nonadrenergic noncholinergic (NANC) conditions, LES ring preparations developed spontaneous tone in all animals. In the wild-type mice, electrical field stimulation produced frequency-dependent intrastimulus relaxation and a poststimulus rebound contraction. NOS inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM) abolished intrastimulus relaxation and rebound contraction. In nNOS(-) mice, both the intrastimulus relaxation and rebound contraction were absent. However, in eNOS(-) mice there was no significant difference in either the relaxation or rebound contraction from the wild-type animal. Both nNOS(-) and eNOS(-) tissues showed concentration-dependent relaxation to NO donor diethylenetriamine-NO and there was no difference in the sensitivity to the NO donor in nNOS(-), eNOS(-), or wild-type animals. These results indicate that in mouse LES, nNOS rather than eNOS is the enzymatic source of the NO that mediates NANC relaxation and rebound contraction.

Animals↗

Metastasis-induced acute pancreatitis in a patient with small cell carcinoma of the lung.

Acute pancreatitis in cancer patients can be secondary to the malignant process itself or a complication of antineoplastic agent administration. However, acute pancreatitis caused by metastatic carcinoma of the pancreas is an uncommon condition with a poor prognosis. We report a case of a 63-year-old man with small cell carcinoma of the lung, who developed acute pancreatitis lately. Thirteen months earlier, he developed small cell carcinoma of the lung and received 6 cycles of chemotherapy. Abdominal CT scan showed swelling of the pancreas with multiple masses. The patient was managed conservatively and pancreatitis subsided. This case indicates that metastasis induced acute pancreatitis can be a manifestation of lung cancer, especially in small cell carcinoma.

Carcinoma, Small Cell↗

Exogenous cysteamine increases basal pancreatic exocrine secretion in the rat.

To determine whether exocrine pancreatic secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced by cysteamine. Rats were subcutaneously administered a single dose of cysteamine (30 mg/100 g body weight) 12 hr before experiment. Anesthetized rats were prepared with cannulation into bile duct, pancreatic duct, duodenum, and jugular vein and pancreatic juice was collected. For in vitro study, isolated pancreata of rats, pretreated with cysteamine, were perfused with an intraarterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 mL/min, and pancreatic juice was collected in 15-min samples. In vivo experiment of the rat, the mean basal pancreatic secretions, including volume, bicarbonate, and protein output were significantly increased from 18.4+/-0.5 microL/30 min, 0.58+/-0.05 microEq/30 min, and 214.0+/-26.1 microg/30 min to 51.6+/-3.7 microL/30 min, 1.52+/-0.11 microEq/30 min, and 569.8+/-128.9 microg/30 min, respectively (p<0.05). In the isolated perfused pancreas, cysteamine also resulted in a significant increase in basal pancreatic secretion (p<0.05). Simultaneous intraarterial infusion of octreotide (10 pmol/hr) to isolated pancreata partially reversed the effect of cysteamine on basal pancreatic secretion. These findings suggest that endogenous somatostatin play an important role on the regulation of basal pancreatic exocrine secretion.

Animals↗

Bilateral ovarian carcinoma metastatic from the ampulla of Vater: a rare Krukenberg tumor.

Carcinoma of the ampulla of Vater is a relatively rare neoplasm and its longterm survival rate is considerably high. However, because of differences in tumor pathologic features and local invasiveness, a 5-year survival rate differ widely. We present a case of metastatic carcinoma of the ampulla of Vater presenting as a Krukenberg tumor in a 59-year-old woman. Eight months earlier, she had been diagnosed as well-differentiated adenocarcinoma of the ampulla of Vater. Abdominal examination revealed a hard mass with mild tenderness in the RLQ area. The laboratory findings were unremarkable except for mild anemia. CT scan of the abdomen revealed enlargement of both ovaries. An exploratory laparotomy disclosed bilateral ovarian masses, 18 x 12 x 8 cm and 8 x 5.5 x 4 cm in size, respectively. Histologic findings of the both ovarian masses were consistent with metastatic adenocarcinoma from the ampulla of Vater.

Ampulla of Vater↗

Endoscopic retrograde pancreatographic findings of pancreatic lipomatosis.

Pancreatic lipomatosis is characterized by fatty infiltration or replacement of the pancreas, and has been associated with many conditions. We recently experienced two cases of pancreatic lipomatosis in patients with pancreatic pseudocyst and a case of lipomatosis in diabetes mellitus. In these patients, abrupt obstruction of the main pancreatic duct with smooth tapering is a typical endoscopic retrograde pancreatography (ERP) finding of pancreatic lipomatosis and must be differentiated with pancreatic carcinoma.

Adult↗

Effects of peritoneal rest on peritoneal transport and peritoneal membrane thickening in continuous ambulatory peritoneal dialysis rats.

OBJECTIVE: To evaluate the effects of peritoneal rest on peritoneal transport and morphology in a rat model of peritoneal dialysis. DESIGN: Twenty-four rats (Sprague-Dawley, male, 250-300 g) were divided into three groups: group 1 (control, n = 6) without dialysis, group 2 (n = 9) sacrificed immediately after 3 weeks of dialysis, and group 3 (n = 9) sacrificed after 4 weeks of peritoneal rest after 3 weeks of dialysis. Both dialysis groups were dialyzed twice daily with an intraperitoneal instillation volume of 25 mL of 3.86% dextrose solution for 3 weeks. Peritonitis was induced by supplementing the dialysis fluid with lipopolysaccharide (5 microg/mL) on days 8, 10, and 12 in both dialysis groups. Peritoneal equilibration tests were performed on each animal at baseline. The equilibration tests were repeated at the 4th and the 8th week of dialysis. Morphometric analyses of the peritoneal membrane were carried out in tissue specimens obtained at the time of sacrifice. RESULTS: The D/D0 ratio for glucose at two hours in groups 2 and 3 at the beginning of week 4 was significantly lower than at baseline, indicating an increase in peritoneal permeability to glucose after 3 weeks of dialysis. D/D0 in group 3 at the beginning of week 8, after 4 weeks of peritoneal rest, was significantly higher than at week 4. The drain volume in groups 2 and 3 at week 4 was significantly lower than at baseline; however, the drain volume in group 3 at week 8 was significantly higher than at week 4. The thickness of the parietal peritoneal membrane in group 3 was significantly greater than in group 1 and less than in group 2 (group 1, 11.4+/-7.6 microm; group 2, 37.5+/-18.4 microm; group 3, 21.4+/-12.1 microm). CONCLUSIONS: Peritoneal rest improves ultrafiltration in rats by decreasing the hyperpermeability of glucose and also reduces the degree of peritoneal thickening. These data suggest that dialysis-induced changes in peritoneal transport and morphology are reversible under the conditions of peritoneal rest in this experimental model.

Animals↗

Inhibitory effect of rebamipide on the neutrophil adherence stimulated by conditioned media from Helicobacter pylori-infected gastric epithelial cells.

We investigated the mechanism or mechanisms by which rebamipide protects against the gastric mucosal inflammation associated with Helicobacter pylori. The production of interleukin (IL)-8 in association with expression of IL-8 mRNA was greatly increased in the H. pylori-infected Kato III cells in a concentration- and time-dependent manner, whereas the secretion of IL-6 and tumor necrosis factor-alpha was not detectable. The increased production of IL-8 and expression of IL-8 mRNA were significantly inhibited by rebamipide (100-1000 microM) in a concentration-dependent manner. Formyl-methionyl-leucyl-phenylalanine (1 nM), as well as conditioned medium (CM) that was produced from H. pylori-infected Kato III cells, caused an increase in surface expression of CD11b on human neutrophils and an increase in neutrophil adhesion to the human umbilical vein endothelial cells. Rebamipide also suppressed the adherence of neutrophils to endothelial cells as well as the expression of CD11b on neutrophils induced by formyl-methionyl-leucyl-phenylalanine and CM. Furthermore, CM-induced neutrophil adhesion to the endothelial cells was significantly inhibited by IL-8-neutralizing antibody, suggesting that IL-8 is implicated in the CM-induced neutrophil adhesion to the cultured human umbilical vein endothelial cells. It is concluded that rebamipide exerts its preventive effect against H. pylori-evoked gastric mucosal cell inflammation by inhibition of the neutrophil adherence to the endothelial cells as well as by suppressing the surface expression of CD11b on neutrophils and the production of proinflammatory cytokine such as IL-8 from gastric epithelial cells.

Alanine↗

Synergistic anti-tumor effects with co-expression of GM-CSF and IFN-gamma in murine tumors.

We explored the potential therapeutic benefit of introducing GM-CSF, IFN-gamma or a combination of both factors into CT26 tumor cells. CT26 cells secreting either GM-CSF or IFN-gamma exhibited delayed tumorigenicity; however, cells expressing both GM-CSF and IFN-gamma did not form tumors. Even when wild type CT26 cells were introduced into a distant site of mice that had been inoculated with CT26/GM-CSF/IFN-gamma cells, no tumors were generated. Furthermore, when we injected GM-CSF + IFN-gamma cells into animals bearing established tumors, the tumors were either rejected or their development was delayed, suggesting that synergistic effects were induced against these tumors via a systemic immune response. Histopathological examination of the tumors injected with cells expressing GM-CSF and IFN-gamma combined showed necrosis and few signs of malignancy. The growth of tumors from mice treated with CT26/GM-CSF/IFN-gamma cells exhibited a delay in tumor formation and no effects were seen in athymic nude mice, which are deficient in T lymphocytes, or in splenectomized nude mice, which are deficient in natural killer (NK) cells, respectively. Our data indicate a dual role for T and NK cells in mediating the anti-tumor activity of this therapy. Our results suggest that transduction of tumor cells with both GM-CSF + IFN-gamma results in a powerful synergistic effect of the 2 cytokines that is of greater therapeutic benefit than transduction with either cytokine alone.

Adenocarcinoma↗

Pharmacological profiles of SKP-450 and its family, a K+ channel opener, in comparison with levcromakalim.

This study was carried out to characterise the vasodepressor and vasorelaxant actions of a benzopyran derivative, SKP-450 and its family, (+/-)-racemate SKP-411, (+)-enantiomer SKP-451, and the metabolites of SKP-450 (SKP-818 and SKP-310) in comparison with levcromakalim (LCRK) in the canine coronary, rabbit basilar and vertebral arterial segments. SKP-450, its family (SKP-411 and SKP-451) and the metabolite of SKP-450 (SKP-818) caused concentration-dependent relaxations as well as LCRK in the canine coronary artery and rabbit basilar and vertebral arteries. The relaxant potency of SKP-450 was significantly higher than that of LCRK in the three arteries in terms of EC50 values. SKP-450- and LCRK-induced vasorelaxations were competitively antagonised by glibenclamide with pA2 values of 7.60 (slope 1.22) and 7.99 (slope, 1.00), respectively. SKP-450 (0.1 and 1.0 microM) caused a significant stimulation of the 86Rb efflux from canine coronary arteries in a concentration-dependent manner as well as LCRK (1 and 10 microM), and their effects were antagonised by glibenclamide (10 microM). SKP-450 as well as LCRK produced long-lasting decreases in mean arterial pressure in the spontaneously hypertensive rats (SHR). These results suggest that SKP-450 has a significantly higher potency than LCRK in in vitro vasorelaxation, and it exerts potent and long-lasting vasodepressor effects with its active metabolite (SKP-818).

Animals↗