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Biomedical subjects

A H Kwon

Publications and source records attributed to A H Kwon.

At least 37 records · Page 2Linked to original sources

An enhancement of nitric oxide production regulates energy metabolism in rat hepatocytes after a partial hepatectomy.

BACKGROUND/AIMS: Infection after a liver resection often results in hepatic failure. Nitric oxide is one of the candidates which has been suspected to cause cellular dysfunction during infection in the liver. We have previously reported that the inflammatory cytokine interleukin-1beta (IL-1beta) induced the expression of the inducible nitric oxide synthase gene in primary cultured rat hepatocytes. We hypothesized that an enhancement of nitric oxide production after the resection was implicated in a change in liver energy metabolism, thus resulting in liver dysfunction. METHODS: In this study, we performed a 70% hepatectomy or a sham operation in rats, and then isolated hepatocytes from the remnant liver by collagenase perfusion. The cultured hepatocytes were treated with cytokines including IL-1beta. The effects on nitric oxide induction, the ATP content and ketone body ratio (acetoacetate/beta-hydroxybutyrate) were then compared between the partial hepatectomized (PH) and sham-operated (control) rats. RESULTS: IL-1beta augmented the induction of nitric oxide production two-fold in hepatocytes from the PH rats as compared to the control rats. IL-1beta markedly decreased the ATP content in the PH rats, although IL-1beta also decreased the ATP content in the control rats, but to a lesser extent. IL-1beta also decreased the ketone body ratio in both groups. The addition of L-arginine further stimulated the inhibition of the ATP levels and the ketone body ratio concomitantly with increased nitric oxide production in the PH rats. N(G)-monomethyl-L-arginine, an inhibitor of nitric oxide synthase, abolished the effects of IL-1beta on the ATP levels and ketone body ratio, as well as on the nitric oxide production. CONCLUSIONS: These results demonstrate that the decreased ATP content observed in PH rats resulted from an increase in nitric oxide production. The decrease in ketone body ratio indicates that nitric oxide-induced mitochondrial dysfunction contributes significantly to ATP attenuation in hepatocytes. Therefore, the regulation of nitric oxide induction may be crucial for preventing liver failure after a hepatic resection.

Adenosine Diphosphate↗

Different responses to surgical stress between extra domain A+ and plasma fibronectins.

1. Fibronectins (FN) are believed to have a role in haemorheological perturbation associated with tissue damage. Fibronectins exist in two antigenically related forms, plasma (p) and cellular fibronectin, which has the extra domain sequences A (EDA) or B (EDB). The present study was designed to determine changes in plasma p-FN and EDA + FN under different types of surgical stress. 2. Sixty-two patients were divided into three groups: (i) group A, 33 patients undergoing hepato-pancreato-biliary surgery; (ii) group B, 19 patients undergoing laparoscopic cholecystectomy; and (iii) group C, 10 patients with postoperative complications. Plasma FN and EDA + FN levels were measured in these patients undergoing different types of surgical operation and either with or without liver cirrhosis using an enzyme-linked immunosorbent assay. 3. After surgery, a significant decrease in p-FN levels and a significant increase in EDA + FN levels was observed in all patient group compared with pre-operative levels. The duration of increased EDA + FN levels, but not p-FN levels, in group A patients was significantly longer than in group B patients. Although changes in p-FN levels between patients with and without liver cirrhosis were significantly different, there were no significant differences in the EDA + FN levels between these two patient groups. 4. In conclusions, EDA + FN and p-FN levels were found to exhibit opposite responses to surgical stress. Furthermore, with greater surgical stress, greater increases in EDA + FN levels were seen. The presence of liver cirrhosis had no significant effect on EDA + FN levels during the perioperative period; however, p-FN levels were significantly affected. 5. Thus, it is suggested that plasma EDA + FN levels reflect the magnitude of surgical stress more closely than do p-FN levels.

Adult↗

Ex vivo liver perfusion with arterial blood from a pig with ischemic liver failure.

To simplify liver support using an ex vivo perfused liver, an isolated pig liver was perfused with arterial blood from the recipient pig while monitoring the metabolic capacity of the ex vivo perfused liver. It was possible to perfuse the isolated liver for more than 24 h using arterial blood from a pig with ischemic liver failure. The viability of the isolated liver during support from the liver failure pig was well maintained as evidenced by the high adenylate energy charge (0.815) and a constant ketone body ratio (KBR) of over 1.0 sampled from the hepatic vein. Oxygen consumption (mean, 29.0 microl/min/g of liver) and bile production (mean, 24.2 microl/h/g of liver) were significantly higher in the isolated liver connected to the liver failure pig than in the organ connected to the pig without liver failure (15.5 microl/min/g and 7.3 microl/h/g, respectively). These findings suggest that this liver support system has sufficient metabolic capacity to support a failed liver. Further studies may provide the experimental basis necessary for the clinical application of this device in treatment of patients with acute liver failure.

Animals↗

Hepatocyte growth factor stimulates synthesis of lipids and secretion of lipoproteins in rat hepatocytes.

We have reported that infusion of recombinant human hepatocyte growth factor (rhHGF) stimulates liver regeneration after hepatectomy in cirrhotic rats and increases the level of serum lipids and secretion of very-low density lipoprotein (VLDL). Studies were now performed to determine whether rhHGF directly influences lipid synthesis and its secretion in cultured rat hepatocytes. Isolated cells were cultured in the presence or absence of rhHGF (20 ng/mL) for 2 days. During the first 12 hours, rhHGF transiently inhibited the release of lipids (triacylglycerol, total cholesterol, and phospholipids), but stimulated their releases with maximal levels achieved at 36 hours. [3H]-glycerol experiment with the transcriptional and translational inhibitors revealed that rhHGF stimulated de novo synthesis of lipids by affecting activities of lipid metabolic gene. [35S]-Methionine experiment also revealed de novo synthesis of apolipoprotein B by rhHGF. Furthermore, lipid analysis of lipoprotein fractions in the conditioned medium showed that rhHGF enhanced levels of triacylglycerol, total cholesterol, and phospholipids by 50% to 200% in both VLDL and low-density lipoproteins (LDL)/high-density lipoprotein (HDL). Genistein, a tyrosine kinase inhibitor, blocked the secretion of VLDL, as well as synthesis of lipids and apolipoprotein B stimulated by rhHGF. These results indicate that HGF likely stimulates lipid biosynthesis and lipoprotein secretion in hepatocytes through its tyrosine kinase-associated receptor, c-met, and accelerates the progress of cell maturation in liver regeneration.

Androstadienes↗

Managing bile duct injury during and after laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is now the treatment of choice for gallstones, but there has been concern that bile leakage after a laparoscopic cholecystectomy is more frequent than after an open cholecystectomy. We have experienced 16 patients with bile duct injury after a laparoscopic cholecystectomy. Five patients had a circumferential injury to the major bile duct, and we employed a converted open technique for biliary reconstruction. The other 11 patients had partial injury to the major bile duct, and we performed laparoscopic restoration; all 11 of these patients received endoscopic retrograde cholangiography (ERC) on the day after the operation and stenting for biliary decompression and drainage. No complications were identified and the duration of hospitalization in these patients was significantly shorter than in those who had the converted procedure. If intraoperative cholangiography is performed routinely, the presence and form of bile duct injury can be clearly identified, and the decision to restore the site of injury or to convert to the open technique for biliary reconstruction can be made immediately.

Adult↗

A simplified model of hypoxic injury in primary cultured rat hepatocytes.

The Anaeropack system for cell culture, which was originally designed for the growth of anaerobic bacteria, was used to produce a hypoxic atmosphere for cultured hepatocytes. We measured changes in the oxygen and carbon dioxide concentrations and the atmospheric temperature in an airtight jar. We also measured changes in the pH of the medium during hypoxia to assess the accuracy of this system. Moreover, we used three durations (2, 3, and 4 h) of hypoxia and 8 h of reoxygenation in cultured rat hepatocytes, and then measured the lactate dehydrogenase (LDH), ketone body concentration (acetoacetate + beta-hydroxybutyrate), and the ketone body ratio (KBR: acetoacetate/beta-hydroxybutyrate) in the medium in order to assess the suitability of this system as a model for reperfusion following liver ischemia. The oxygen concentration dropped to 1% or less within 1 h. The concentration of carbon dioxide rose to about 5% at 30 min after the induction of the hypoxic conditions, and was maintained at this level for 5 h. No effect of the reaction heat produced by the oxygen absorbent in the jar was recognized. The extent of cell injury produced by changing the hypoxic parameters was satisfactorily reflected by the KBR, the ketone body concentration, and the LDH activity released into the medium. Because this model can duplicate the conditions of the hepatocytes during revascularization following ischemic liver, and the Anaeropack system for cell culture is easy to manipulate, it seems suitable for the experimental study of hypoxic injury and revascularization in vitro.

Animals↗

Prolonged decreases in plasma nitrate levels at early postoperative phase after hepato-pancreato-biliary surgery.

Nitric oxide (.NO) is known to influence circulatory, neural, immunologic, and metabolic alterations. To evaluate the clinical significance of .NO production under surgical stress, serial measurements of plasma nitrite plus nitrate levels were performed in 45 surgical patients. Group A included 19 patients who underwent major surgery with uneventful postoperative courses. Group B included 18 patients who underwent laparoscopic cholecystectomy. Group C included 8 patients whose surgery was complicated by intra-abdominal abscesses. Eight healthy volunteers served as controls. Plasma nitrate levels were determined with a redox chemiluminescence .NO analyzer and coincided with measurements made by high-performance liquid chromatography (r = 0.868, p < 0.0001, 58 samples). During laparotomy, arterial nitrate levels correlated well with peripheral, portal, and hepatic venous nitrate levels (r = 0.966, 0.938, and 0.949, respectively; p < 0.0001). A significant decrease in nitrate from preoperative levels in groups A (postoperative day (POD) 1 and 3; p < 0.0005) and B (POD 1, p < 0.0001) was observed; nitrate levels in group C did not decrease for 14 days after surgery. Plasma nitrate levels in groups A and B were significantly different (POD 1 through 6, p < 0.05) and at POD 3 were significantly lower in group A (p < 0.005). Plasma nitrate levels measured before and after fasting or food intake were not significantly different. These results suggest that surgical stress leads to a decrease in the end product of .NO in the whole body, and that the greater the surgical stress the longer the duration of decreased .NO production.

Adult↗

Preoperative assessment for laparoscopic cholecystectomy: feasibility of using spiral computed tomography.

OBJECTIVE: The authors investigated the preoperative feasibility of using spiral computed tomography (SCT) after intravenous infusion cholangiography (IVC-SCT) for laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: In laparoscopic cholecystectomy, the aberrant or unusual anatomy of the bile duct and severe inflammation or adhesions around the gallbladder sometimes require a conversion to open surgery. METHODS: Laparoscopic cholecystectomies (LC's) were attempted on 440 patients, and preoperative IVC-SCT also was attempted in all of these patients. Using this spiral scanning technique, the bile ducts, cystic duct, and gallbladder were assessed for contour abnormalities, relative position, and filling defects. Forty-seven patients were diagnosed with having stones in their common bile duct or common hepatic duct. RESULTS: Three-hundred eighty-seven patients out of the 440 patients (88.0%) who were subjected to IVC-SCT had the length and course of their cystic duct successfully determined. Anomalous unions of the cystic duct were seen in 59 (15.2%) of 387 patients with respect to the operative findings, and 48 of 440 patients (10.9%) had severe adhesions to Calot's triangle and the surrounding tissues. In these 48 patients, 45 patients (94%) had a nonvisualized cystic duct on IVC-SCT. The preoperative assessment of the feasibility (dense adhesions obscuring Calot's triangle) of using IVC-SCT demonstrated that the sensitivity, specificity, and accuracy were 93%, 98%, and 94%, respectively. Five patients had to be converted to open surgery, and the overall morbidity rates for patients undergoing laparoscopic cholecystectomy was 0.9% (4 of 440). CONCLUSIONS: The most important factor in assessing the feasibility of using laparoscopic cholecystectomy is not the nonvisualized gallbladder, but the nonvisualized cystic duct on IVC-SCT. IVC-SCT may be of benefit to those patients scheduled to undergo laparoscopic cholecystectomy.

Adolescent↗

Preoperative determination of the surgical procedure for hepatectomy using technetium-99m-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy.

Technetium-99m-diethylenetriaminepentaacetic acidgalactosyl human serum albumin (Tc-GSA) is a new liver scintigraphy agent which binds to the asialoglycoprotein receptors. We evaluated the preoperative assessment for hepatectomy using Tc-GSA liver scintigraphy. Ninety patients with hepatocellular carcinoma were admitted for elective hepatectomy. Tc-GSA scintigraphy was conducted after the intravenous injection of Tc-GSA, and maximal removal rate of Tc-GSA (GSA-Rmax) was calculated using a radiopharmacokinetic model. Measurement of GSA-Rmax, conventional liver function, and 15-minute retention rate of indocyanine green (ICGR15) was carried out preoperatively. The relationships between liver functions, histological activity index (HAI), ICGR15, and GSA-Rmax values were estimated. A significant correlation was obtained between GSA-Rmax and ICGR15 (r = .534, P < .0001). Preoperative discrepancies between GSA-Rmax and ICGR15 values were seen in 15 patients. In these cases, the GSA-Rmax values correlated well with the total HAI scores (r = .595, P < .02), but no significant correlation was seen between the ICGR15 and HAI scores. Two patients died of postoperative liver failure within 2 months of the operation. These two patients were found to have severe discrepancies between their preoperative GSA-Rmax and ICGR15 values. We concluded that GSA-Rmax might be useful for selecting candidates for hepatectomy and that extended hepatectomies (di- and tri-segmentectomy) are high-risk surgical procedures in the case of low GSA-Rmax scores (below 0.35).

Adult↗

Clinical evaluation of closed suction drainage following hepatectomy.

A prospective randomized study on 186 patients was conducted to determine the influence of closed suction drainage (n = 102) versus open drainage (n = 84) on the incidence of postoperative complications after elective hepatic resection. The patients were randomly allocated between the two groups. A total of 60 complications occurred in 31 of the 84 patients (36.9%) given open drainage, while 24 complications occurred in 15 of the 102 patients (14.7%) given closed suction drainage. The incidence of pleural effusion, postoperative ascites, and infected subphrenic collections was significantly lower in the closed suction drainage group than in the open drainage group, at 31% vs 16% (P < 0.05), 19% vs 3% (P < 0.01), and 17% vs 5% (P < 0.05) respectively. However, both groups showed similar rates of subphrenic hematoma and bile collection. These findings indicate that closed suction drainage significantly reduces the incidence of postoperative complications after elective hepatic resection.

Adult↗

Assessing the eligibility for liver transplantation of patients with fulminant hepatitis.

The spleen to liver volume (S/L) ratio of 13 patients with fulminant hepatitis was determined using X-ray computed tomography (CT), and the correlation between S/L ratio and prognosis was evaluated. The S/L ratio of 6 patients who died was greater than 0.16, whereas that of the remaining 7 patients who survived was less than 0.15. These findings suggest that determining the S/L ratio using CT may be useful for assessing the eligibility of patients with fulminant hepatitis for liver transplantation.

Adolescent↗

Stimulation of liver regeneration and function after partial hepatectomy in cirrhotic rats by continuous infusion of recombinant human hepatocyte growth factor.

BACKGROUND/AIMS: Radical resection is accepted as one of the most curative treatments for hepatocellular carcinoma. However, most patients have coexisting cirrhosis and their liver function is usually impaired. It is therefore important to stimulate the regeneration and function of the remnant cirrhotic liver after hepatectomy. Hepatocyte growth factor is a potent mitogen that has been suggested to play a crucial role in liver regeneration. METHODS: In this study, we performed 45% hepatectomy in rats with cirrhosis induced by thioacetamide, and administered recombinant human hepatocyte growth factor (rhHGF) with dextran sulfate by continuous infusion into the jugular vein with an infusion pump. RESULTS: rhHGF stimulated an increase in the wet weight of the remnant liver compared with untreated control rats. The proliferating cell nuclear antigen labeling index showed that this increase resulted from the stimulation of DNA synthesis. Serum levels of liver enzymes increased after hepatectomy, but returned to the prehepatectomy level more rapidly in rhHGF-treated rats than in controls. rhHGF increased hepatic protein synthesis above prehepatectomy levels and also markedly increased the serum levels of hepatic lipid metabolites. CONCLUSIONS: These results demonstrate that continuous intravenous infusion of rhHGF enhances the growth and function of the remnant liver in rats with cirrhosis after partial hepatectomy. Therefore, rhHGF may be useful after hepatic resection in patients with cirrhosis.

Animals↗

Prophylactic laparoscopic ovarian ablation for premenopausal breast cancer: medical and economic efficacy.

Worldwide analysis showed a highly significant reduction in the annual rates both of recurrence and of death produced by ovarian ablation. We examined the safety, efficacy, and cost-effectiveness of prophylactic laparoscopic oophorectomy for premenopausal breast cancer. Prophylactic laparoscopic oophorectomy was attempted in 15 selected premenopausal patients with breast cancer. After mastectomy, these patients had laparoscopic ovarian ablation as treatment for breast carcinoma with positive estrogen receptors. To evaluate the economic impact of laparoscopic oophorectomy, comparisons were made between patients treated laparoscopically and those treated with conventional surgery, chemotherapy, and hormonal therapy. The average time required for laparoscopic bilateral oophorectomy was 44 min. Oral intake was resumed the next morning, and the patients were discharged 3 days after surgery. No limitation on physical activity and no complications were required during postoperative days. There was no reduction in the overall costs of laparoscopic surgery and conventional surgery in Japan. The cost of one year's supply of tamoxifen was equivalent to the overall cost of surgical oophorectomy. From medical and economic viewpoints, we conclude that laparoscopic ovarian ablation should be considered an alternative to adjuvant chemotherapy in premenopausal women.

Activities of Daily Living↗

Spiral computed tomography scanning after intravenous infusion cholangiography for biliary duct anomalies.

BACKGROUND: Iatrogenic injury of the bile duct during cholecystectomy represents a failure of surgical technique, especially for laparoscopic surgery. Knowledge of the patient's individual ductal anatomy and anomalies preoperatively would be helpful in avoiding such injuries. Therefore, we investigated the anatomy of the biliary duct and any anomalies using spiral computed tomography (SCT) scanning following intravenous infusion cholangiography (IVC-SCT). MATERIALS: Laparoscopic cholecystectomies (LC) were attempted on 437 patients at the Kansai Medical University. Preoperative IVC-SCT and laparoscopic cholangiography were attempted in all of the patients. RESULTS: An overall anomalous union of the cystic duct was seen in 71 (16.2%) out of the 437 patients subjected to IVC-SCT. The following anomalies were observed: right hepatic duct entry in 7 cases (1.6%), parallel low entry in 17 cases (3.9%), posterior spiral entry in 35 cases (8.0%), anterior spiral entry in 7 cases (1.6%), and accessory duct entry in 5 cases (1.1%). The success rate for the LC was 99.5% (435/437). Three patients were switched to open surgery owing to advanced gallbladder cancer and severe adhesions. The success rate for the laparoscopic cholangiography was 97.2% (423 of 435). Intraoperative right hepatic duct injury occurred in only 1 patient with a bile duct anomaly, and it was repaired with laparoscopic T-tube drainage. CONCLUSIONS: The preoperative examination of the biliary tract by IVC-SCT was technically simple, less invasive, and may helpful in avoiding damage to the bile duct, especially in patients with biliary duct anomalies.

Bile Ducts↗

Inflammatory pseudotumor of the liver: report of a case and review of the literature.

Only 56 cases of inflammatory pseudotumor of the liver have been reported in the world literature since its first documentation in 1953. We report herein the case of a 68-year-old man incidentally found to have a lesion in the right lobe of the liver which closely resembled a neoplasm on imaging studies. Thus, partial hepatic resection was performed and histological examination of the resected specimen revealed a diagnosis of inflammatory pseudotumor. Surgical resection is the preferred treatment for inflammatory pseudotumor of the liver, especially in patients for whom a definite histologic diagnosis cannot be made preoperatively or by intraoperative frozen sections. In fact, most of the patients reported in the literature recovered uneventfully after local resection without any postoperative complications, as did our patient.

Aged↗

Gallbladder cancer with a low junction of the cystic duct or an anomalous pancreaticobiliary junction.

OBJECTIVE: To evaluate conditions similar to those of carcinogenesis of the gallbladder between the gallbladder with a low junction of the cystic duct (LJCD) and an anomalous pancreaticobiliary junction (APBJ). DESIGN: Retrospective and clinicopathological analysis of patients with gallbladder carcinoma. SETTING: First Department of Surgery, Kansai Medical University. PATIENTS: Examination of 47 patients (7 men and 40 women; average age: 67.8 years) with gallbladder carcinoma revealed 7 patients (14.9%; 1 man and 6 women; average age: 67.8 years) with LJCD and 6 patients (12.8%; 6 women; average age: 60.3 years) with APBJ. METHODS: Clinical findings in both groups were compared with those of the 34 patients who remained after exclusion of the data of the above 7 patients with LJCD and 6 patients with APBJ. The data of the three groups were examined by the chi 2 test at the 5% level of significance. RESULTS: Most of the gallbladder cancer patients with LJCD or APBJ had gallstones. The biliary amylase levels determined in the gallbladder of patients with LJCD or APBJ were remarkably high. CONCLUSION: The results indicate that patients with LJCD or APBJ are more likely to develop carcinoma of the gallbladder. The factors responsible for carcinogenesis may be alteration of the bile content due to reflux of pancreatic enzymes through the LJCD or APBJ, and mechanical irritation due to gallstones. Therefore, these pathological conditions in patients with LJCD are similar to those experienced in patients with APBJ.

Aged↗

Hepatocyte volume as an indicator of hepatic functional reserve in cirrhotic patients with liver tumours.

Using computed tomography (CT), measurements of whole liver volume have been used for the assessment of pre-operative functional reserve in cirrhotics. However, measurements of hepatocyte volume, which exclude stromal fibrous tissue, are considered to more directly reflect hepatic functional reserve. We investigated the relationship between total hepatocyte volume and each of the parameters of conventional liver function. Indocyanine green (ICG) tests and blood analyses for the assessment of liver function were performed prior to surgery in cirrhotic patients with liver tumours. Pre-operative liver volume was determined by integrating images of each liver area obtained by CT. Liver area was measured by an image processing program that traced the profile of the liver image while excluding the tumorous area. Sections of normal tissue stained by the haematoxylin-eosin method, were obtained from the resected liver. Using these sections, a hepatocyte area: whole tissue area ratio was calculated using the image processing program, by tracing the profiles of the hepatocyte nodules. The total volume of hepatocytes was then calculated by multiplying the liver volume by this ratio. The hepatocyte volume per unit bodyweight was significantly correlated with ICG tests and with many other parameters of normal liver function. However, the liver volume per unit bodyweight was correlated only with the plasma ICG disappearance rate and with the blood platelet count. These observations suggest that the functional reserve of the cirrhotic liver is assessed more precisely by hepatocyte volume than by liver volume.

Adult↗