Noninvasive, direct visualization of macro-reentrant circuits by using magnetocardiograms: initiation and persistence of atrial flutter.

AIMS: We analysed the cardiac magnetic fields on the body surface to visualize electrical currents noninvasively during reentrant arrhythmias. METHODS AND RESULTS: Seven patients with counterclockwise atrial flutter (AFL) were studied during 17 episodes of AFL using 64-channel magnetocardiograms (MCGs) and electrophysiological study. Eight of the episodes were paroxysmal AFL, in which MCGs were recorded from the time of spontaneous onset to the time of termination. We constructed iso-magnetic field maps of the tangential components and produced MCG animations. With respect to AFL initiation, an atrial premature complex induced AFL. Prior to the initiation of AFL, atrial fibrillation (AF) transiently occurred. The cardiac magnetic fields revealed a single peak during sinus rhythm or with premature complexes but a disorganized pattern during AF. When AF transformed to AFL, the magnetic fields changed from a disorganized pattern to a single peak at first and then evolved to a circular pattern. During persistent AFL, the magnetic source moved in a counterclockwise circuit. CONCLUSION: MCG animation can be used to visualize the sequence in which a premature complex transforms sinus rhythm to AFL via AF. Our findings indicate that MCGs can be used to identify noninvasively the mechanisms responsible for atrial tachyarrhythmias.

Disseminated peritoneal adenomucinosis associated with a panperitonitis-like onset: report of a case.

A 59-year-old man was admitted to our department due to a fever of unknown origin. Abdominal ultrasonography and computed tomography showed a large cystic mass in the lower abdomen and a massive amount of abdominal fluid. A laparotomy was performed under a diagnosis of panperitonitis. Diffuse pyogenic gelatinous ascites and a large cystic mass with a grayish wall, and a hard solid lesion in part were found. The microscopic findings of the hard solid lesion showed calcification, osteogenesis, and focal epithelial proliferation in a tiny area consisting of mucinous cells with no significant cytologic atypia. The remaining part of the cystic wall and small cystic lesions were hyalinized, fibrous, or necrotic tissue. Since a total resection of the masses was not possible, the patient received adjuvant chemotherapy with cisplatin followed by the administration of mitomycin C and 5-fluorouracil. An abdominal fistula with the excretion of pyogenic gelatinous fluid occurred, but the patient is still alive and doing well over 2 years postoperatively. The primary site of this tumor could unfortunately not be identified.

Prophylactic chemolipiodolization for postoperative hepatoma patients.

BACKGROUND/AIMS: The efficacy of prophylactic chemolipiodolization following hepatic resection in patients with hepatocellular carcinoma was studied. METHODOLOGY: Forty-four of 67 consecutive patients with hepatocellular carcinoma who underwent hepatectomy between 1980 and 1997 were divided into two groups: group A (n = 21), in which prophylactic chemolipiodolization was performed during postoperative follow-up (2.4 times on average using a 39 mg mean dose of epirubicin or doxorubicin); and group B (n = 23), without prophylactic chemolipiodolization. The clinicopathological background and patient survival were compared retrospectively. RESULTS: There were no differences in the clinicopathological background between the two groups. Multiple intrahepatic recurrence was frequently observed in group B (P < 0.02). The recurrence-free survival rates in group A (54.4% and 31.1% at 3 and 5 years, respectively) were significantly higher than those in group B (15.7% and 7.9%, respectively). The survival rates of group A (95.2% and 80.4% at 3 and 5 years, respectively) were significantly higher than those in group B (40.1% and 22.9%, respectively). CONCLUSIONS: Our data suggest that postoperative prophylactic chemolipiodolization can be an effective treatment in reducing intrahepatic recurrence and may prolong survival for hepatocellular carcinoma patients following hepatic resection.

Cross-linked hyaluronate hydrogel prevents adhesion formation and reformation in mouse uterine horn model.

The aim of this study was to evaluate the efficacy of cross-linked hyaluronate hydrogel (HA gel) as an adjuvant for postoperative adhesion prevention, in a mouse uterine horn model. In experiment 1 uterine horns were abrased with iodine. HA gel was applied to the injured surface before closure in the treatment group. In experiment 2, after injuring the uterine horns, three stitches were placed at equal distances around the uterine horns to appose the injured medial surfaces of the two horns during healing. HA gel was inserted between the uterine horns in the treatment group. In experiment 3 prevention of adhesion reformation was assessed. After lysis of adhesions that were induced as in experiment 2, HA gel was introduced between the serosal surfaces of apposing uterine horns. Untreated animals served as controls in each experiment. Statistical analysis was carried out using Student's t-test. The adhesion score was significantly lower in the HA gel group on the 14th day compared with controls in all the experiments: in experiment 1, 0.3 +/- 0.4 versus 1.7 +/- 1.2; in experiment 2, 0.9 +/- 1.0 versus 2.6 +/- 0.5; and in experiment 3, 1.5 +/- 0.9 versus 2.2 +/- 0.6 respectively. Cross-linked HA gel significantly reduced de-novo adhesions (P< 0.03) and adhesion reformation (P < 0.03).

Non-Hodgkin's lymphoma of the ascending colon in a patient with becker muscular dystrophy: report of a case.

We herein present the findings of a 10-year-old boy with non-Hodgkin's lymphoma of the ascending colon which caused intussusception and intestinal bleeding. He had a history of Becker muscular dystrophy. However, he had neither hypertrophic calves nor cardiomyopathy, and his serum creatine kinase (CK) level always exceeded 2000 IU/l. Preoperatively, a laboratory examination revealed high serum levels of CK (2038IU/l), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and the blood hemoglobin level was 7.0g/dl. A barium enema examination revealed an intussusception in his ascending colon, which was found to be a highly vascular tumor on Doppler ultrasound scans. A right hemicolectomy was performed. Macroscopically, the 5 x 6 x 8-cm solid tumor of the ascending colon resembled a submucosal tumor and had two ulcerous lesions at the tip. The tumor was histologically diagnosed to be a diffuse large B-cell lymphoma of the ascending colon. General examinations revealed no involvement of lymphoma postoperatively. At 13 months after surgery, the CK (37861U/l), AST (110lU/l), ALT (1381U/ l), and LDH (420lU/l) levels are still high, and the patient is doing well without any signs of recurrence.

Synergistic antiproliferative effect of delta 12-prostaglandin J2 (delta 12-PGJ2) and hyperthermia on human esophageal cancer cell lines.

delta 12-PGJ2, one of the cyclopentenone prostaglandins and the ultimate metabolite of prostaglandin D2, has been reported to have potent antiproliferative activity on various tumor cells in vitro and in vivo. In this study, the combined effect of delta 12-PGJ2 and hyperthermia on six established cell lines of human esophageal carcinoma (SGF series) was analyzed by an in vitro assay, and the degree of apoptosis induced by this combination was examined to clarify the mechanism of supra-additive effects. In five SGF cell lines, except SGF-7 cells, combination therapy with delta 12-PGJ2 and hyperthermia showed synergistic antiproliferative effects. The supra-additive combined effect of delta 12-PGJ2 and hyperthermia on esophageal cancer cells is attributed to the synergistic induction of apoptosis. delta 12-PGJ2 induced G1 accumulation and apoptosis was induced by delta 12-PGJ2 from G1 phase. Hyperthermia induced G1 accumulation and apoptosis was induced by hyperthermia during all cell phases. Both augmented G1 arrest followed by G1 phase-selective induction of apoptosis and increased apoptotic induction without cell-cycle specificity are responsible for the synergism of combined treatment with delta 12-PGJ2 and hyperthermia.

The combined effect against colon-26 cells of heat treatment and immunization with heat treated colon-26 tumour cell extract.

Cancer vaccines represent a promising new strategy for immunotherapy against cancer, but their effects are insufficiently understood. The effect of heat treatment against mouse colon adenocarcinoma cell line (colon-26), and combined effects of heat treatment and immunizing host animals with heat treated colon-26 cell extracts were investigated. Heat treatment of colon-26 cells induced heat-shock protein 70 (HSP70), but not other HSP. Immunization of BALB/cJ mice with heat treated colon-26 cell extract, which was enriched in HSP70, elicited antitumour immunity against subcutaneously injected colon-26 cells. Furthermore, combination therapy of heat treatment and immunization with heat treated colon-26 cell extract significantly reduced tumour volumes compared with heat treatment alone. Similar immunization enhanced the cytotoxic activity of mouse splenic lymphocytes against untreated and heat treated colon-26 cells in an in vitro assay, as well as against heat treated allogenic mouse lymphoma cell line (YAC-1). These findings suggest possible usefulness of heat treated cancer cell extract as a cancer vaccine, especially if given in combination with hyperthermia.

Tumor regression by inductive hyperthermia combined with hepatic embolization using dextran magnetite-incorporated microspheres in rats.

We formulated a novel preparation of microspheres incorporating dextran magnetite complex (DM-MS), which enable magnetic field-induced heating for the induction of hyperthermia. Using a 500 kHz magnetic field combined with arteriolar embolization of DM-MS, inductive hyperthermia was performed for the treatment of liver tumors in rats. Three days after treatment, the percentage increase of tumor volume in the embolo-hyperthermia, embolization alone, and control groups were 28%, 124%, and 385%, respectively, with the embolo-hyperthermia group differing significantly from the remaining groups. This study demonstrated the feasibility of combining embolization of DM-MS with hyperthermia as an antitumor therapy.

Orally administered ginseng extract reduces serum total cholesterol and triglycerides that induce fatty liver in 66% hepatectomized rats.

The effects of ginseng extract (from the root of Panax ginseng) on factors inducing fatty liver were examined in 66% hepatectomized rats. Oral administration of ginseng extract at 125 or 250 mg/kg/day produced statistically significant reductions in total cholesterol and triglyceride concentrations in the blood 3 days after hepatectomy (P<0.05); the total cholesterol response appeared to be dose-related. Administration of ginseng extract at both doses also reduced total cholesterol and triglyceride concentrations in the liver 3 days after hepatectomy. Food intake and serum chemistry parameters indicating liver and kidney function were unchanged after ginseng administration except for the lipid metabolic parameters. These observations suggest that orally administered ginseng extract can suppress the formation of fatty liver after hepatic resection.

Expression of the anti-metastatic effect induced by Juzen-taiho-to is based on the content of Shimotsu-to constituents.

We investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, and its related formulations on the experimental liver and lung metastasis of tumor cells in vivo. Oral administration of Juzen-taiho-to for 7 d before tumor inoculation significantly reduced the number of liver metastatic colonies of colon 26-L5 carcinoma cells and attenuated the increase of liver weight in a dose-dependent manner ranging from 4 to 40 mg/d. Its oral administration for this same period before tumor inoculation also significantly inhibited lung metastasis of B16-BL6 melanoma cells. Juzen-taiho-to originally consisted of 8 crude drugs derived from Shimotsu-to and Shikunshi-to prescriptions together with two crude drugs (Cinnamomi Cortex and Astragali Radix). Oral administration of Shimotsu-to as well as Juzen-taiho-to for 7 d before tumor inoculation resulted in a significant reduction in the number of metastatic colonies and the liver weight as compared with the control, whereas Shikunshi-to did not exhibit such an inhibitory effect. Unsei-in containing four Shimotsu-to constituents was also active in inhibiting liver metastasis. Toki-shakuyaku-san and Ninjin-yoei-to, which include all Shimotsu-to constituents except Rehmanniae Radix and Cnidii Rhizoma, respectively, did not show a significant anti-metastatic effect. Rikkunshi-to and Ninjin-yoei-to, which contain Shikunshi-to constituents, did not affect the inhibition of liver metastasis. Hochu-ekki-to treatment before tumor inoculation also led to a significant inhibition of liver metastasis, probably through an inhibitory mechanism different from Juzen-taiho-to. These results suggest that the anti-metastatic effect of Juzen-taiho-to is partly associated with its Shimotsu-to-derived constituents.

Oral administration of a Kampo (Japanese herbal) medicine Juzen-taiho-to inhibits liver metastasis of colon 26-L5 carcinoma cells.

We have investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, on liver metastasis by the inoculation of a liver-metastatic variant (L5) of murine colon 26 carcinoma cells into the portal vein. Oral administration of Juzen-taiho-to for 7 days before tumor inoculation resulted in dose-dependent inhibition of liver tumor colonies and significant enhancement of survival rate as compared with the untreated control, without side effects. We also found that liver metastasis of L5 cells was enhanced in BALB/c mice pretreated with anti-asialo GM1 serum or 2-chloroadenosine, and in BALB/c nu/nu mice, compared to normal mice. This indicates that NK cells, macrophages, and T-cells play important roles in the prevention of metastasis of tumor cells. Juzen-taiho-to significantly inhibited the experimental liver metastasis of colon 26-L5 cells in mice pretreated with anti-asialo GM1 serum and untreated normal mice, whereas it did not inhibit metastasis in 2-chloroadenosine-pretreated mice or T-cell-deficient nude mice. Oral administration of Juzen-taiho-to activated peritoneal exudate macrophages (PEM) to become cytostatic against the tumor cells. These results show that oral administration of Juzen-taiho-to inhibited liver metastasis of colon 26-L5 cells, possibly through a mechanism mediated by the activation of macrophages and/or T-cells in the host immune system. Thus, Juzen-taiho-to may be efficacious for the prevention of cancer metastasis.

Molecular cloning of rat p38 mitogen-activated protein kinase and it's osmotic regulation in rat kidney.

Rat p38 mitogen-activated protein (MAP) kinase cDNA was isolated from rat kidney cDNA library using a PCR cloning strategy. The deduced amino acid sequence consists of 360 amino acids and shares 95.3% similarity with human p38 MAP kinase. The message for rat p38 MAP kinase was about 3.4 kilobases and was highly expressed in the kidney. In water-deprived rat kidneys, the steady-state levels of p38 MAP kinase mRNA increased about 2.7-fold as compared with those of control rats. This result suggests that p38 MAP kinase may play an important role in the osmoregulation in the kidney.

[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.

Amino acids and control of nucleolar size, the activity of RNA polymerase I, and DNA synthesis in liver.

The volume of nucleolar material per nucleus and the activity of RNA polymerase I (RNA nucleotidyltransferase I) become doubled in the liver cells of rats that are fed for several days a diet that lacks essential amino acids. Omission of methionine from a fully supplemented diet is equivalent to leaving out all the amino acids, and the responses to a deficiency of tryptophan are about 40% as great. Deprivation of one of the remaining essential amino acids gives either small responses or none at all. Supplementation of the methionine-free diet with cystine blocks the nucleolar enlargement and the enhancement of the polymerase activity that would otherwise take place, but the dispensable amino acid does not affect the responses to a deprivation of one of the other essential amino acids. After deprivation of all the essential amino acids or only methionine, hepatocytes make DNA when the rat is fed a meal with protein. A preparatory diet lacking in tryptophan is much less effective; a deficiency in any of the other indispensable compounds tested fails to prepare the liver for DNA synthesis. The results give hope that elucidation of the means by which methionine deprivation affects the nucleolus will also provide information on the regulation of nuclear DNA replication in liver. One attractive possibility is that the amino acid deficiency acts by producing some imbalance in protein metabolism.