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1.
Thorax ; 58(9): 757-60, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12947131

ABSTRACT

BACKGROUND: The 72 kDa matrix metalloproteinase 2 (MMP-2) and the 92 kDa matrix metalloproteinase 9 (MMP-9) are type IV collagenases implicated in various aspects of inflammation including accumulation of inflammatory cells, tissue injury, and development of remodelling. The role of these enzymes in the pathogenesis of asthma exacerbations is unknown. METHODS: Circulating levels of MMP-2 and MMP-9 proteins and the expression of their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP-1), were measured in 21 patients experiencing an asthma exacerbation and 21 age matched patients with stable asthma. Circulating gelatinolytic activity was compared during the asthma exacerbation and during subsequent convalescence by gelatin zymography in the same individuals. In addition, MMP-9 specific activity was quantified with a colorimetric assay which uses an artificial proenzyme containing a specific domain recognised by MMP-9 in the same paired samples. RESULTS: A significant increase in the circulating level of MMP-9 was seen in patients with an asthma exacerbation compared with patients with stable asthma (202.9 (22.0) v 107.7 (9.9) ng/ml, p=0.0003). There were no significant differences in the circulating levels of MMP-2 or TIMP-1. Gelatin zymography identified two major circulating gelatinolytic activities corresponding to MMP-2 and MMP-9, and showed that asthma exacerbations are characterised by markedly increased MMP-9 activity with no significant change in MMP-2 activity compared with the activities during convalescence in the same individuals. Direct measurement showed that MMP-9 specific activity is significantly increased during asthma exacerbations compared with subsequent convalescence (269.6 (31.7) v 170.4 (12.6) ng/ml, p=0.0099). CONCLUSIONS: Asthma exacerbations are characterised by increased circulating MMP-9 activity. This increased activity may be related to exaggerated airway inflammation and airway remodelling.


Subject(s)
Asthma/enzymology , Matrix Metalloproteinase 9/metabolism , Adult , Calorimetry , Female , Humans , Male , Matrix Metalloproteinase 2/metabolism , Tissue Inhibitor of Metalloproteinase-1/metabolism
2.
Cancer Chemother Pharmacol ; 52(1): 67-72, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12743738

ABSTRACT

PURPOSE: A phase I study was conducted to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of carboplatin in combination with paclitaxel using a biweekly schedule in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The pharmacokinetics of paclitaxel were determined preliminarily in some patients. The criteria for eligibility for study entry included histologically and/or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable disease. Paclitaxel was given in combination with a fixed dose of carboplatin at an area under the concentration-time curve (AUC) of 3 mg/ml x min, every 2 weeks. The starting dose of paclitaxel was 100 mg/m(2), and the dose was increased in increments of 20 mg/m(2). Three to six patients were allocated to each dose level. RESULTS: A total of 19 patients (11 male and 8 female) with a median age of 61 years (range 43-74 years) and a median ECOG performance status of 0 (range 0-1) were enrolled. The MTD of paclitaxel proved to be 160 mg/m(2), and the DLT was neutropenia, which improved well following treatment with G-CSF. Gastrointestinal toxicity was well tolerated. Of 17 patients who received four cycles or more, 7 (41%; 95% confidence interval 18.4-67.1%) responded to this combination therapy. The pharmacokinetics of paclitaxel did not differ from published data. CONCLUSIONS: The recommended dose for phase II study is paclitaxel 140 mg/m(2) with a carboplatin AUC of 3 mg/ml.min. This biweekly regimen is highly effective and acceptable, and the present data indicate that the regimen may be suitable for use on an outpatient basis.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Area Under Curve , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Drug Administration Schedule , Female , Half-Life , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage
3.
Eur J Cancer ; 38(15): 1998-2004, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12376204

ABSTRACT

We conducted a phase I study of irinotecan (CPT-11) and cisplatin with concurrent split-course radiotherapy in limited-disease small-cell lung cancer (LD-SCLC). This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy. Four chemotherapy cycles of CPT-11 (days 1, 8 and 15) and cisplatin (day 1) were repeated every 28 days. Radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle with 20 Gy administered from the first to the third cycles (a total of 60 Gy). 17 patients were enrolled at three dose levels (CPT-11/cisplatin: 40/60, 50/60 and 60/60 mg/m(2)), and 16 were evaluable for toxicity and outcome. 2 of 4 patients at 60/60 mg/m(2) refused continuation of therapy because of general fatigue, and the relative dose intensity of CPT-11 at 50/60 mg/m(2) was approximately 50%. These levels were considered as the MTD. Tumour responses included four complete responses (CR), 11 partial responses (PR) and one no change (NC), and the overall response rate was 93.8% (95% confidence interval: (CI) 71.7-98.9%). This combined modality is tolerable, and CPT-11/cisplatin of 40/60 mg/m(2) in this modality is recommended for phase II study.


Subject(s)
Camptothecin/analogs & derivatives , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy/methods , Dose-Response Relationship, Drug , Female , Hematologic Diseases/chemically induced , Humans , Irinotecan , Male , Maximum Tolerated Dose , Middle Aged , Survival Analysis
4.
Surg Endosc ; 16(9): 1363-4, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12235509

ABSTRACT

Hemostasis of a resected stump of liver is extremely difficult in laparoscopic hepatectomy. Although Pringle's maneuver, which is a total clamping of the hepatoduodenal ligament, is a useful technique, it is often difficult in laparoscopic circumstances. Moreover, total inflow occlusion leads to postoperative liver damage. Therefore, the local bleeding method is ideal. The Endoclose, a device for port site closure, is formed from an outer sheath and an inner needle with a notch to load the suture. The Endoclose is loaded with a suture and passed through the liver. The suture is left under the liver, and the device is removed. Next, the suture carrier is passed through the liver at an appropriate distance, and the suture is regrasped by this suture carrier and brought out of the liver. Herein we report a case in which a new bleeding control method using Endoclose was introduced for laparoscopy-assisted hepatectomy.


Subject(s)
Hepatectomy/instrumentation , Hepatectomy/methods , Laparoscopy/methods , Aged , Hemostasis, Endoscopic/instrumentation , Hemostasis, Endoscopic/methods , Humans , Liver/blood supply , Liver/diagnostic imaging , Liver/pathology , Liver/surgery , Liver Neoplasms/blood supply , Liver Neoplasms/diagnosis , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Male , Suture Techniques , Tomography, X-Ray Computed , Ultrasonography
5.
Surg Endosc ; 16(12): 1806, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12239645

ABSTRACT

Usually intrahepatic cholangiocarcinoma has a poor prognosis, especially when it occurs with lymph node metastasis. As a treatment for intrahepatic cholangiocarcinoma, dissection of lymph nodes alone does not seem to offer any significant advantages. The laparoscopic hepatectomy procedure, however, is a minimally invasive liver surgery. We recently had the case of a patient who underwent successful laparoscopic hepatectomy and dissection of lymph nodes for intrahepatic cholangiocarcinoma in the left lateral segment of the liver. The patient had intrahepatic cholangiocarcinoma with distant lymph node metastasis around the common hepatic artery determined to stage IVb according to TNM classification. The operation time was 335 min, and the total blood loss was only 225 ml. A left lateral hepatectomy and complete lymph node dissection around the hepatoduodenal ligament and celiac trunk was performed. In this case, a laparoscopic procedure enabled the patient to have an early discharge, and there was no recurrence for 14 months. Another advantage for this patient was that the hospital stay lasted only 10 days. As compared with conventional surgery, laparoscopic surgery reduces blood loss and shortens the hospital stay. In conclusion, laparoscopic surgery for intrahepatic cholangiocarcinoma is a good treatment for advanced intrahepatic cholangiocarcinoma because it allows a positive early postoperative outcome and possibly a better result over the long term.


Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/surgery , Hepatectomy/methods , Laparoscopy/methods , Lymph Node Excision/methods , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Blood Loss, Surgical , Cholangiocarcinoma/pathology , Dissection/methods , Hepatectomy/adverse effects , Humans , Laparoscopy/adverse effects , Length of Stay , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Time Factors , Treatment Outcome
6.
Int J Tuberc Lung Dis ; 6(9): 763-70, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12234131

ABSTRACT

OBJECTIVES: The incidence of infections caused by multidrug-resistant strains of Mycobacterium tuberculosis (MDR-TB) has been increasing. Antiseptics are frequently used to prevent mycobacterial infection. The aim of this study was to determine those antiseptics that are useful against MDR-TB. DESIGN: We evaluated bactericidal activity against clinical isolates of MDR-TB in vitro. METHOD: Thirteen strains of MDR-TB were tested against povidone-iodine (PVP-I), cresol, akyldiaminoethyl glycine hydrocloride (AEG), and glutaraldehyde. After bacilli were exposed to the antiseptic solution with 2% human serum, the disinfectant was inactivated by addition of neutraliser. RESULTS: PVP-1 at a final concentration of 0.2% killed all of the strains within 120 seconds, and PVP-I at 0.1% killed 99.9% or more bacilli within 60 seconds. Most strains were killed after exposure to 0.5% cresol at 300 seconds and to 1.0% cresol at 60 seconds; 3.0% cresol killed all bacilli within 120 seconds, while 0.1%, 0.2%, and 0.5% AEG all required 60 minutes to kill 99.9% or more of the bacilli; 2.0% glutaraldehyde required 10 minutes to kill all bacilli. CONCLUSION: The bactericidal activities of antiseptics for MDR-TB were similar to those for drug-sensitive M. tuberculosis strains. PVP-I would be a useful antiseptic against MDR-TB. The bactericidal activities of glutaraldehyde are effective against MDR-TB as an antiseptic for medical equipment.


Subject(s)
Anti-Infective Agents, Local/pharmacology , Disinfectants/pharmacology , Drug Resistance, Multiple, Bacterial , Mycobacterium tuberculosis/drug effects , Cresols/pharmacology , Glutaral/pharmacology , Glycine/pharmacology , Outcome Assessment, Health Care , Povidone-Iodine/pharmacology
7.
Dermatology ; 204 Suppl 1: 15-20, 2002.
Article in English | MEDLINE | ID: mdl-12011515

ABSTRACT

Seventeen clinical isolates of Mycobacterium tuberculosis were selected in order to study the bactericidal activities against drug-resistant M. tuberculosis. The effects of different antiseptics against multidrug-resistant M. tuberculosis (MDR-TB) were examined. Each of the test strains was cultured on the surface of an agar slant containing Löwenstein-Jensen medium. 0.05 ml of the bacillary suspension was poured into a test tube, and 0.45 ml of various antiseptics was added. After the bacilli had been exposed to the antiseptic solution with 2% human serum for various periods of incubation time, the antiseptic was inactivated by addition of 0.45 ml neutralizer, a mixture containing 10% Tween 80, 3% soybean lecithin and 0.5% sodium thiosulfate. As the results, povidone-iodine (PVP-I) at a concentration of 0.2% killed 99.9% or more of all strains tested within 30 s. All of the strains tested with PVP-I were killed almost completely within 60 s. There was no difference in bactericidal activities of PVP-I between standard strain H37Rv and MDR-TB. 99.9% or more of all strains tested were killed after exposure to 1.0% cresol for 60 s. In the case of cresol however, the exposure time of 30 s was not enough to get satisfactory effects. 2.0% glutaraldehyde needed 5 min to kill 99.99% or more of the bacilli tested, and 0.2% alkyldiaminoethylglycine hydrochloride required 60 min to do so. The results of bactericidal activities of common antiseptics against MDR-TB were similar to those against H37Rv. We conclude that the commercially available PVP-I product is a useful antiseptic against MDR-TB similar to other M. tuberculosis.


Subject(s)
Anti-Infective Agents, Local/pharmacology , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/microbiology , Cresols/pharmacology , Disinfectants/pharmacology , Glutaral/pharmacology , Humans , Povidone-Iodine/pharmacology , Time Factors
8.
Surg Endosc ; 15(6): 541-4, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11591936

ABSTRACT

BACKGROUND: No reports exist on the role of laparoscopic hepatectomy in the short- and long-term outcomes of patients with hepatocellular carcinoma (HCC). We present our results from using laparoscopic hepatectomy for HCC and discuss the importance of this procedure. METHODS: To investigate the role of laparoscopic hepatectomy in the short- and long-term outcomes, 17 patients with HCC who underwent laparoscopic hepatectomy (laparoscopic hepatectomy group) were compared with 38 patients who underwent conventional open hepatectomy (open hepatectomy group) during the same period. RESULTS: No differences in operation time, blood loss, rate of blood transfusion, or incidence of postoperative complications were found between the two groups. The postoperative hospital stay for the laparoscopic hepatectomy group was significantly shorter than for the open hepatectomy group. With long-term prognosis, no difference was found in survival rate and disease-free survival rate between the two groups. No recurrence was found in the stump of the remaining liver after laparoscopic hepatectomy. CONCLUSIONS: Laparoscopic hepatectomy has resulted in a better short-term outcome after surgery than conventional open hepatectomy. The long-term prognosis in the laparoscopic hepatectomy group was similar to that in the open hepatectomy group. Therefore, laparoscopic hepatectomy can be a new alternative for treatment of cirrhotic patients with HCC when patients are strictly selected.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Laparoscopy , Liver Neoplasms/surgery , Carcinoma, Hepatocellular/blood , Disease-Free Survival , Esophageal and Gastric Varices/epidemiology , Humans , Incidence , Length of Stay , Liver Neoplasms/blood , Platelet Count , Prognosis
9.
Am J Surg ; 182(2): 177-82, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11574092

ABSTRACT

BACKGROUND: Little has been reported on the role of macroscopic classification of hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification of HCC might have a strong correlation with long-term prognosis after hepatectomy. METHODS: Four hundred and four patients with a macroscopically nodular type of HCC who underwent a hepatectomy were studied. The patients were divided into three groups: single nodular (SN) group (n = 312); single nodular with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN) group (n = 40). Clinicopathological variables were compared among the three groups. The patient survival rate was also compared among the three groups. Finally, a multivariate analysis was performed to clarify the independent significant variables of the long-term prognosis. To confirm the consistency of the results in small-size HCC, the same analyses were made using patients whose tumor size was equal to or less than 3 cm in diameter. RESULTS: The alpha-fetoprotein value, tumor size, and rate of absolute noncurative operation in the SNEG group were higher than in other groups. The positive rate of both portal vein invasion of cancer cells and intrahepatic metastasis in the SN group was lower than those in other groups. The rate of poorly differentiated histology in the SN group was lower than in the other groups. Patient survival in the SNEG group was worst among the three groups. However, patient survival showed no significant difference between the SN and CMN groups. The multivariate analysis showed that the presence of intrahepatic metastasis, the macroscopic classification of SNEG type, and absolute noncurative operation were independent poor prognostic indicators. The results for patients with small HCCs measuring equal to or less than 3 cm in diameter were quite similar to the results for the other patients. CONCLUSIONS: Among the three subtypes of macroscopically nodular type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer cells, intrahepatic metastasis, and poorly differentiated histology. The patient survival rate in the SNEG type was worst, and the SNEG type was an independent poor prognostic indicator. The macroscopic classification of HCC, especially the SNEG type, helps predict the long-term outcome after hepatectomy.


Subject(s)
Carcinoma, Hepatocellular/classification , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/classification , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Male , Middle Aged , Prognosis , Survival Rate , Time Factors
10.
World J Surg ; 25(8): 991-5, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11571981

ABSTRACT

Characteristics of multicentric hepatocellular carcinomas (HCCs) remain obscure. We therefore aimed to clarify them and compare them with HCC with intrahepatic metastases. A series of 118 patients who had definite hepatitis C viral status and multinodular HCC were divided into two groups: a multicentric occurrence (MO) group (n = 38), with multicentric HCCs; and an intrahepatic metastasis (IM) group (n = 80), with HCC having intrahepatic metastases. Clinicopathologic variables, including the patient's survival and disease-free survival rates, were compared between the MO and IM groups. Univariate analysis revealed the presence of esophageal varices, the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, hepaplastin test, gamma-globulin, the histologically active hepatitis, tumor size, des-gamma-carboxy prothrombin > 0.1 AU/ml, positive portal vein invasion, and histologic grade as discriminating factors. The MO score to differentiate multicentric HCCs from intrahepatic metastatic HCCs was determined using the following four independent factors selected by a stepwise regression analysis: the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, tumor size, and histologic grade. The sensitivity and specificity of the MO scores using those factors were 84% and 70%, respectively, when the cutoff value was 0.4. The disease-free survival rate in the MO group was similar to that in the IM group, whereas the survival rate in the MO group was significantly better than that in the IM group. The multivariate analysis revealed the multicentric occurrence of HCC as one of the independent prognostic factors. Clinicopathologic factors differentiating multicentric HCCs from intrahepatic metastatic HCCs were the presence of hepatitis C virus infection, a platelet count of less than 10 x 10(4)/microliter, small tumor size, and low histologic grade.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Female , Humans , Male , Middle Aged
11.
Int J Tuberc Lung Dis ; 5(8): 769-74, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11495269

ABSTRACT

OBJECTIVES: Endobronchial tuberculosis (EBTB) is defined as a tuberculous infection of the tracheobronchial tree. It has been reported that aerosolized therapy with streptomycin and steroids is useful for EBTB; however, the effectiveness of this therapy for bronchial stenosis has yet to be clarified. This study was undertaken to determine the effectiveness of aerosol therapy in the treatment of bronchial stenosis due to EBTB. DESIGN: An observational, historical, controlled comparative study. Retrospective analysis of 27 patients treated with conventional therapy, and prospective analysis of 30 patients treated with aerosol therapy. METHOD AND PATIENTS: Flexible bronchoscopy was performed at least twice in 57 patients with ulcerative EBTB, in whom the degree of bronchial stenosis between the first and last bronchoscopic examinations was estimated. Bronchial stenosis was graded as minimal, mild, moderate, severe or obstructive, and the follow-up of bronchial stenosis assessed as aggravation, no change or improvement. RESULTS: Conventional therapies led to aggravation in 13 patients, no change in 13 patients, and improvement in one patient. Aerosol therapy led to no change in 27 patients, and improvement in three patients. No patients developed aggravation. The differences between the therapeutic groups were significant. CONCLUSION: Aerosol therapy helps to prevent progressively severe bronchial stenosis due to EBTB.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibiotics, Antitubercular/therapeutic use , Bronchial Diseases/drug therapy , Bronchial Diseases/etiology , Dexamethasone/therapeutic use , Streptomycin/therapeutic use , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/drug therapy , Ulcer/drug therapy , Ulcer/etiology , Administration, Inhalation , Adolescent , Adult , Aged , Aged, 80 and over , Bronchial Diseases/pathology , Constriction, Pathologic/drug therapy , Constriction, Pathologic/etiology , Constriction, Pathologic/pathology , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Naphazoline/therapeutic use , Nasal Decongestants/therapeutic use , Prospective Studies , Retrospective Studies , Tuberculosis, Pulmonary/pathology , Ulcer/pathology
12.
Eur J Cancer ; 37(11): 1359-65, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11435065

ABSTRACT

We conducted a phase I study of irinotecan (CPT-11) and cisplatin with concurrent split-course radiotherapy in locally advanced stage III non-small cell lung cancer (NSCLC). This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy. Two chemotherapy cycles of CPT-11 (days 1, 8 and 15) and cisplatin (day 1) were repeated with a 28-day interval. Radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle, with 24 Gy and 36 Gy administered for the first and second cycle, respectively. 24 eligible patients were enrolled at five dose levels (CPT-11/cisplatin: 40/60, 50/60, 60/60, 60/70 and 60/80 mg/m(2)), and 23 patients were evaluated for toxicity and clinical outcome. Only 1 patient experienced a DLT with neutropenia and diarrhoea at 60/60 mg/m(2). Dose escalation was limited to 60/80 mg/m(2) which was the recommended dose for CPT-11/cisplatin alone in NSCLC. Tumour responses included one complete response (CR), 15 partial response (PR), and 7 no change (NC), and the overall response rate was 69.6% (95% confidence interval (CI) 47.1-86.8%). This combined modality is tolerable, and CPT-11/cisplatin of 60/80 mg/m(2) in this modality is recommended for phase II study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy/methods , Dose-Response Relationship, Drug , Female , Humans , Irinotecan , Male , Middle Aged , Treatment Outcome
13.
Int J Artif Organs ; 24(1): 34-40, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11266040

ABSTRACT

Nafamostat mesilate (FUT) is a protease inhibitor of complement activation. The present study investigates whether FUT protects porcine hepatocytes from being injured by human plasma in a multi-capillary polyurethane foam packed-bed culture system (MC-PUF) such as the hybrid-artificial liver (PUF-HAL). Human plasmas with 1 mM of added ammonia were perfused using a small-scale PUF-HAL with porcine hepatocytes. FUT was continuously infused (10 microg/ml, 50 microg/ml). The ammonia detoxification was maintained in human plasma for 24 hours and for 48 hours with FUT which suppressed the rapid increase of asparaginic acid aminotransferase (AST) and alanine aminotransferase (ALT). After 60 hours of perfusion, hepatocyte spheroids completely collapsed in the human plasma, but a small amount of hepatocyte spheroid was maintained by FUT. The effect of FUT was slightly greater at 50 microg/ml than at 10 microg/ml. Our results suggest that FUT has protective effects against porcine hepatocytes in human plasma, and our PUF-HAL using porcine hepatocytes can function in human plasma for about 48 hours with FUT.


Subject(s)
Guanidines/pharmacology , Liver, Artificial , Liver/cytology , Liver/drug effects , Protease Inhibitors/pharmacology , Alanine Transaminase/blood , Ammonia/blood , Animals , Benzamidines , Cell Survival , Female , Humans , Liver/enzymology , Liver Failure/blood , Liver Failure/therapy , Plasma , Polyurethanes , Swine , Transaminases/blood
14.
Arch Surg ; 136(3): 328-33, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11231856

ABSTRACT

HYPOTHESIS: Preoperative administration of methylprednisolone sodium succinate can control surgical stress in patients undergoing hepatic resection. DESIGN: A prospective randomized trial. SETTING: A university hospital department of surgery. PATIENTS: Thirty-three patients who underwent hepatic resection were classified into 2 groups: a control group (n = 16) and a steroid group (n = 17) in which patients were intravenously administered 500 mg of methylprednisolone 2 hours before surgery. MAIN OUTCOME MEASURES: Perioperative levels of interleukin (IL)-6 and IL-10 (serum and peritoneal), immunosuppressive acidic protein, Candida antigen, and other laboratory and clinical variables were measured. RESULTS: Postoperative levels of serum and peritoneal IL-6 and levels of C-reactive protein were significantly lower in the steroid group than in controls. Furthermore, serum and peritoneal IL-10 levels were significantly higher in the steroid group. The total bilirubin value on postoperative day 1 was significantly lower in the steroid group than in controls. Postoperative immunosuppressive acidic protein levels were also significantly lower in the steroid group, as was the positive rate of serum Candida antigen. No differences were found in the incidence of postoperative complications. CONCLUSIONS: Preoperative steroid administration significantly elevated anti-inflammatory cytokine IL-10 levels, suppressed the levels of inflammatory cytokines IL-6 and C-reactive protein, and prevented postoperative elevation of total bilirubin values. Furthermore, postoperative elevation of immunosuppressive acidic protein levels and the positive rate of Candida antigen were suppressed, indicating that the immune response was maintained by preoperative steroid administration.


Subject(s)
Acute-Phase Reaction/prevention & control , Hepatectomy , Methylprednisolone Hemisuccinate/administration & dosage , Postoperative Complications/prevention & control , Premedication , Acute-Phase Proteins , Acute-Phase Reaction/blood , Adult , Aged , Bile Duct Neoplasms/surgery , Bilirubin/blood , C-Reactive Protein/metabolism , Carcinoma, Hepatocellular/surgery , Cholangiocarcinoma/surgery , Female , Humans , Interleukin-10/blood , Interleukin-6/blood , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Male , Methylprednisolone Hemisuccinate/adverse effects , Middle Aged , Postoperative Complications/blood , Prospective Studies
15.
Cancer Res ; 61(3): 1005-12, 2001 Feb 01.
Article in English | MEDLINE | ID: mdl-11221826

ABSTRACT

Applications of nonviral vectors for gene transfer into tumors in vivo have been limited by the relatively low expression levels of the transferred gene. The aim of this study is to evaluate the efficacy of electroporation-mediated interleukin-12 (IL-12) gene therapy for hepatocellular carcinoma (HCC). First, we investigated the optimal conditions of electric pulses (voltage, pulsing duration, numbers of shocks) of in vivo electroporation for gene transfer into HCC established by s.c. implantation of MH134 cells to C3H mice. This process made use of plasmid DNA that express the luciferase gene. We concluded that the optimal conditions for the electric pulses are as follows: voltage at 150 V; pulsing duration at 50 ms; nonpulsing duration at 950 ms; and the number of shocks at 10. Second, we tried to treat s.c. HCC by electroporation using plasmid DNA that expresses the murine interleukin-12 (mlL-12) gene. Intratumoral administration of the mIL-12 vector elevated serum IL-12 and IFN-gamma and significantly inhibited the growth not only of HCC into which the mIL-12 vector had been directly transferred, but also of the distant HCC. In addition, intratumoral administration of the mIL-12 vector inhibited spontaneous lung metastasis and delayed establishment of HCC injected 3 days after mIL-12 gene therapy. The IL-12 gene therapy induced more lymphocyte infiltration by NK cells, CD3+ cells, and Mac-1 positive cells into the tumor and reduced the number of microvessels. Therefore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive tumor cells were found. These results demonstrate that gene therapy for HCC by electroporation in vivo using IL-12 is very efficient and is thus promising for further clinical trial.


Subject(s)
Genetic Therapy/methods , Interleukin-12/genetics , Liver Neoplasms, Experimental/therapy , Animals , Cell Division/genetics , Disease Models, Animal , Electroporation/methods , Female , Flow Cytometry , Interferon-gamma/blood , Interleukin-12/blood , Liver Neoplasms, Experimental/genetics , Liver Neoplasms, Experimental/pathology , Luciferases/genetics , Luciferases/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/prevention & control , Lung Neoplasms/secondary , Lymphocyte Activation , Lymphocytes, Tumor-Infiltrating/immunology , Mice , Mice, Inbred C3H , T-Lymphocytes, Cytotoxic/immunology , Tumor Cells, Cultured
16.
Ann Surg ; 233(1): 45-50, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11141224

ABSTRACT

OBJECTIVE: To identify the perioperative risk factors for postoperative bile leakage after hepatic resection, to evaluate the intraoperative bile leakage test as a preventive measure, and to propose a treatment strategy for postoperative bile leakage according to the outcome of these patients. SUMMARY BACKGROUND DATA: Bile leakage remains a common cause of major complications after hepatic resection. METHODS: Between January 1985 and June 1999, 781 hepatic resections without bilioenteric anastomosis were performed at the authors' institution. Perioperative risk factors related to postoperative bile leakage were identified using univariate and multivariate analysis. The characteristics of patients with intractable bile leakage and the effect of intraoperative bile leakage test were also examined. Management was evaluated in relation to the outcomes and the clinical characteristics of the patients with bile leakage. RESULTS: Bile leakage developed in 31 (4.0%) of 781 hepatic resections. This complication carried high risks for surgical death (two patients [6.5%] died). The stepwise logistic regression analysis identified high-risk surgical procedure, in which the cut surface exposed the major Glisson's sheath and included the hepatic hilum (i.e., anterior segmentectomy, central bisegmentectomy, or total caudate lobectomy), as the independent predictor of the development of postoperative bile leakage. None of the 102 cases in which an intraoperative bile leakage test was performed were subsequently complicated by postoperative bile leakage, and the preventive effect of the test was statistically significant. Patients with fisterographically demonstrable leakage from the hepatic hilum and with postoperative uncontrollable ascites had poor outcomes. CONCLUSION: Patients with bile leakage from the hepatic hilum and postoperative uncontrollable ascites tend to have a poor prognosis. Therefore, especially when a high-risk surgical procedure is performed in patients with liver cirrhosis, more careful surgical procedures and use of an intraoperative bile leakage test are recommended.


Subject(s)
Bile , Hepatectomy , Intraoperative Care , Postoperative Complications/prevention & control , Female , Humans , Incidence , Logistic Models , Male , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors , Treatment Outcome
17.
Nutr Cancer ; 40(2): 140-8, 2001.
Article in English | MEDLINE | ID: mdl-11962249

ABSTRACT

We examined the effect of dietary conjugated linoleic acid (CLA) on the growth of injected hepatoma dRLh-84 in Donryu rats. After experimental diets containing 0% or 2% CLA were given to male Donryu rats for 3 wk, dRLh-84 cells were injected into the left lobe of the hepatic capsule, and the experimental diet was continued. The cells formed a solid tumor > or = 1 wk after the injection, and thereafter the tumor grew with feeding duration. In a morphological study, this tumor appeared to be a low-differentiated hepatoma, and there was no remarkable difference in the morphology of the tumor between 0% and 2% CLA groups. Tumor weight was significantly higher in the 2% CLA group than in the 0% CLA group throughout the feeding period after the injection. Serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities were significantly higher in 2% CLA-injected rats than in 0% CLA-injected rats at 3 wk after the injection. CLA upregulated acyl-CoA oxidase activity, especially 1 wk after the injection. However, dietary CLA did not activate carnitine palmitoyl transferase II, which is a rate-limiting enzyme in the mitochondrial beta-oxidation pathway. Natural killer cell activity in the spleen tended to be higher in injected rats, but a significant effect of dietary CLA was not recognized. Serum interferon-gamma and tumor necrosis factor-alpha levels were higher in injected than in sham rats. Moreover, these levels were higher in 2% CLA groups than in the respective 0% CLA groups.


Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Linoleic Acid/administration & dosage , Liver Neoplasms, Experimental/pathology , Adipose Tissue/pathology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Cell Division , Interferon-gamma/blood , Killer Cells, Natural/immunology , Liver/metabolism , Liver Neoplasms, Experimental/immunology , Liver Neoplasms, Experimental/metabolism , Male , Organ Size , Oxidation-Reduction , Rats , Safflower Oil/administration & dosage , Tumor Necrosis Factor-alpha/analysis
18.
Int Surg ; 86(3): 141-3, 2001.
Article in English | MEDLINE | ID: mdl-11996069

ABSTRACT

Tumor thrombi of hepatocellular carcinoma occasionally invade into the inferior vena cava (IVC) through the hepatic vein. Once the tumor thrombus is dislodged, severe and lethal complications, such as pulmonary infarction, can develop. We successfully operated on a hepatocellular carcinoma (HCC) patient with a tumor thrombus extending to the IVC through the right hepatic vein. To avoid dislodging the thrombus during surgery, a thrombectomy using selective hepatic vascular exclusion was performed before a hepatic resection, which is the most dangerous procedure to dislodge the thrombus.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatic Veins/diagnostic imaging , Liver Neoplasms/surgery , Vena Cava, Inferior/diagnostic imaging , Venous Thrombosis/therapy , Carcinoma, Hepatocellular/diagnostic imaging , Echocardiography, Transesophageal , Hepatectomy/methods , Humans , Liver Neoplasms/diagnostic imaging , Male , Middle Aged , Neoplasm Invasiveness , Radiography , Thrombectomy/methods , Venous Thrombosis/complications
20.
Kurume Med J ; 48(4): 273-9, 2001.
Article in English | MEDLINE | ID: mdl-11830927

ABSTRACT

The mortality of the influenza virus pneumonia is on the increase caused by the decline of the vaccination for the influenza virus in Japan. The purpose of our research is to study the clinical feature of severe influenza virus pneumonia that caused acute respiratory failure. This study included 68 patients with adult influenza virus infection who consulted our hospital between October 1997 and May 1999. Six (8.8%) of 68 were diagnosed as having influenza virus pneumonia that caused acute respiratory failure. All patients with influenza virus pneumonia showed severe conditions with respiratory failure and a high-risk group. Two super high age patients had emergency status with unconsciousness. A super high age patient with influenza virus pneumonia died of aspiration pneumonia 118 days after admission. All patients with influenza virus pneumonia were received antibiotics. Although 4 of 6 patients did not respond to antibiotics, adrenocorticosteroids were administered. As the result, 3 of 4 patients, healing was achieved. We concluded that adrenocorticosteroids might be useful for treating severe influenza virus pneumonia under the administration of appropriate antibiotics.


Subject(s)
Influenza, Human/complications , Pneumonia, Viral/complications , Respiratory Insufficiency/etiology , Acute Disease , Adult , Aged , Aged, 80 and over , Female , Humans , Influenza, Human/drug therapy , Male , Pneumonia, Viral/drug therapy , Prognosis
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