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To study the changes of bacterial susceptibility during exposure to antimicrobials, the respective minimal inhibitory concentrations (MICs) of 50 colonies from each of various bacterial test strains were determined in an experimental system using an in vitro urinary bladder model. The MICs of gatifloxacin and meropenem for Pseudomonas aeruginosa strains were not homogeneous before exposure to the drugs. The MICs of the strains examined reflected only that of their dominant population. When starting from 10(7)CFU/ml, the bacterial count was determined serially during exposure to gatifloxacin or meropenem in therapeutic urinary concentrations. The MIC of the less susceptible population of each strain was changed serially to a higher one. The more susceptible strains were eradicated before the change of the MIC. The bacteria originally consisted of strains having heterogeneous susceptibility to drugs, in which major strains had susceptibility expressed by the MIC and minor ones had a higher or lower MIC. This heterogeneity may be responsible for the change of susceptibility in strains after exposure to the drugs.

Recently, the progress in chemotherapy has brought an improvement in the survival rate of patients with non-resectable digestive tract cancer. Simultaneously, maintenance of patients' QOL is regarded as important. In our hospital, we use low-dose FP therapy to maintain QOL and a satisfactory survival rate. To date, we have administered low-dose FP to more than 50 patients with non-resectable digestive cancer. We investigated patients who received home chemotherapy after being evaluated NC, and found no remarkable side effects as a result of this therapy during admission.

The anatomical relationship between motoneuron dendrites and primary afferent fibers innervating the same muscle were examined by using a modified cholera toxin tracing method. The cholera toxin B subunit conjugated with latex beads was injected into the posterior iliotibial muscle (PIT) of chicken. Both motoneuron dendrites and primary afferent fibers were intensely labeled. Labeled primary afferent fibers innervating the PIT were mainly located in laminae I (ventral part), V (lateral part), VI, VII (except ventromedial part) and lateral motor column (LMC, lamina IX) of the lumbar spinal cord. Numerous labeled primary afferent fibers were observed in proximity to the motoneuron pool of the PIT located in the dorsolateral region of the LMC; primary afferent fibers were closely apposed to somatic profiles of the PIT motoneurons.

The synergistic mechanism of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear, despite its substantial antitumor activity, which has been demonstrated clinically. To clarify the mechanism(s), we determined the sensitivity or resistance factors to either drug in seven gastrointestinal cancer cell lines and then analyzed the altered gene expression after different exposures to CDDP and 5-FU. At the basal gene expression level, glutathione S-transferase pi (GSTpi) expression correlated with the observed resistance to CDDP, whereas dihydropyrimidine dehydrogenase (DPD) and multidrug resistance-associated protein (MRP) expression was related to 5-FU resistance. GSTpi, DPD, and MRP expression increased in response to the respective drug, but they also increased in response to the other drug as well. Additionally, 5-FU revealed a drastically increased thymidylate synthase (TS) gene expression in 5-FU-resistant cells. However, the increasing actions of CDDP and 5-FU on GSTpi, DPD, MRP, and TS expression varied according to the exposure time, concentration, and schedule. A low concentration of CDDP (1 microg/ml, 30 min) followed by 5-FU (0.5 microg/ml, 72 h) was found to cause a less increased expression of DPD, MRP, GSTpi, and TS than either drug alone, thus resulting in synergistic cytotoxicity in 5-FU-resistant COLO201 and CDDP-resistant HCC-48 cells. The sequential combination of CDDP and 5-FU inhibited the growth of human normal renal proximal tubule cells by less than 20%. Low concentrations of CDDP followed by continuous exposure to 5-FU can repress increased gene expression related to both drug resistances, thereby being synergistically cytotoxic in human gastrointestinal cancer cells.

Endoscopic therapies for the treatment of cancers of the digestive tract have been improved. Today, some early cancers can be curatively treated by endoscopy (endoscopic polypectomy, endoscopic mucosal resection, heatprobe method, etc.). In addition, endoscopic local injection chemotherapy is performed for some advanced cancers as an adjuvant therapy. Recent progress in endoscopic therapies for cancer is reviewed in this paper, including their historical background. Improvements in these endoscopic treatment methods are expected to provide increased advantages for the treatment of patients with cancer in the near future.

From the stand point of investigators doing clinical trials of anti-cancer drugs, a questionnaire to survey of the current status of clinical trials concerning on the reactions of medical institutions to the new GCP started in April 1997, sent to 75 institutions all over the Japan. 56 institutions (75%) gave answers to the questionnaire, in August 1998. As the results, apparent decrease of Phase IIIII trials were noticed compared the numbers before March 1997. IRB with one or two outside members are well functioned in these institutions. But, training related doctors, nurses (especially CRC) are nowadays most important problems, which are strongly expected to Ministry of Health and Welfare and related medical societies, for instance Japan Society of Clinical Oncology.

We evaluated the long-term results of 28 operative survivors who underwent surgical repair for acute type A dissection. Residual dissection of the thoracic aorta was found in 21 patients (75.0%) postoperatively, and 6 of them underwent reoperation with no operative death. There were 2 late death; one died in the third operation for thoracoabdominal aorta and the other died of cancer. Two of 4 patients with Marfan's syndrome required total aortic replacement ultimately. Since the elective reoperation can be performed safely, careful follow-up and management is essential for the improved survival of the patients with residual aortic dissection.

Oxygen-derived free radicals play an important role in myocardial injury associated ischemia and reperfusion. To investigate whether ginsenosides, as an additive agent of cardioplegic solution, can decrease toxicity of oxygen free radicals in myocardial injury, a heterotopic heart transplantation model in Wistar rats was employed. St. Thomas II cold cardioplegia containing ginsenosides 80 mg/l was used in the experimental group. St. Thomas II cold cardioplegia alone was used in the control group. After global ischemia for 60 minutes and reperfusion for 30 minutes of a transplanted heart, SOD activity in the myocardium treated with ginsenosides was significantly higher than that in the control group (N=10, p0.01), whereas the MDA in the myocardium treated with ginsenosides were markedly lower than that of the control group (p0.01). The amounts of oxygen free radicals in the myocardium treated with ginsenosides were significantly lower than that of the control group (p0.001). This study demonstrates that ginsenosides, as a proper additive agent of cardioplegic solution, can decrease toxicity of oxygen free radicals, suggesting one of the mechanisms for its protective effects against myocardial ischemia and reperfusion injury.

Forty-five patients aged 80 years or older at the time of initial permanent pacemaker implantation were followed for 3 to 132 months (mean 40.8). There were 27 males and 18 females. The mean age was 84 years. Acute voltage threshold, lead impedance, R wave amplitude of these patients showed no difference from those of younger patients (80 years). Complications occurred in 5 patients as follows: cerebral infarction, 3: perforation, 1; lead displacement, 1. Ten patients died, and main causes of death were decrepitude and cancer. The five-year cumulative survival rate (75.9%) was superior to the expected survival rate (65.8%) by life-table analysis. In conclusion, pacemaker therapy for elderly patients is safe, and seemed to improve their long-term prognosis.

Carcinosarcoma is a rare lung tumor and accounts for less than 0.3% of primary lung malignancies. Since the first description by Kika in 1908, only 36 cases with this kind of tumor have been appeared in the Japanese literatures by 1993. This report presents our surgical experiences of two cases with carcinosarcoma of the lung confirmed by pathological examination. Case 1: 64-year-old male underwent left lower lobectomy with lymph node resection. The patient has been well 27 months after the operation without tumor recurrence. Case 2: was a 75-year-old male, who underwent left upper lobectomy, partial resection of left lower lobe (S6) with lymph node resection. This patient died of aspiration pneumonia 90 days after successful resection of the tumor. In both patients, resected lung tumors were diagnosed to be true carcinosarcoma by histopathological examinations. True carcinosarcoma is defined to contain both cancelous and sarcomatous elements. Sarcomatous elements may differentiate into rhabdomyosarcoma, osteosarcoma and so on, or they may have non-epithelial elements demonstrated by electron microscopy or immunohistochemical studies. We reviewed the 36 cases with carcinosarcoma of the lung reported in Japanese literatures with special consideration of their histopathological findings. The prognosis of the patients with this rare tumor is also discussed according to the TMN stages.

Between February, 1982, and September, 1994, 24 patients underwent aortic root replacement using a valve-bearing composite graft and coronary perfusion grafts. The indications for surgery were annulo-aortic ectasia in 21 patients, and aortic dissection associated with significant aortic regurgitation in 3 patients. Aortic root was reconstructed employing the techniques described by Cabrol and colleagues (Cabrol operation) in 16, and by Piehler and Pluth (Piehler operation) in 8. Two of 16 patients who underwent Cabrol operation required concomitant procedures. Four patients (25.0%) who underwent Cabrol operation had technical troubles relating to coronary reattachements (kinking and torsion of coronary grafts in 2, obstruction of left limb of coronary graft in 1, and coronary graft compression by aortic wall wrapping in 1), while one patient (12.5%) having Piehler operation had coronary graft compression by partial wrapping of aortic root. The hospital deaths occurred in 4 patients undergone Cabrol operation, with the hospital mortality rate being 16.7%. Three patients including 2 with concomitant procedures died of low cardiac output and one died of rupture of residual dissecting aneurysm of the aortic arch. No pseudoaneurysm nor anastomotic stenosis was observed in any hospital survivors. Late deaths occurred in 5 patients, in whom there was no late complication relating to coronary reconstruction. However, late obstruction of left ostial stenosis developed in one patient who underwent Piehler operation, which required coronary artery bypass. We conclude that aortic root replacement using coronary perfusion grafts provides sound coronary anastomoses without late pseudoanurysm. Coronary reattachments is facilitated by use of Piehler technique, preventing coronary graft kinking or torsion. Late coronary ostial stenosis should be considered as a possible cause of fatal myocardial infarction and sudden death, and careful follow-up is required for patients having these kinds of operation for the prevention of late cardiac events.

We studied the gamma/delta T cells, which are thought to be one of the local immune-defense system, in an experimental ascending urinary tract infection model in mouse. The experimental infection was induced in the BALB/c mouse by transurethral instillation of Escherichia coli. gamma/delta T cells were stained immunohistochemically with ABC method and the localization in the uninfected and infected murine urinary tract was determined. Then, to determine the CD4 or CD8 phenotype of gamma/delta T cells in the infected site, a two-color immunohistological study was done. In the uninfected state, gamma/delta T cells were observed in the bladder epithelium and submucosa, not in the kidney. It is thought that the difference of gamma/delta T cell distribution between kidney and bladder is affected by the bacteriological milieu, because the chance for foreign antigen exposure of bladder may be greater than that of the kidney. Six hours after inoculation of E. coli, the gamma/delta T cells infiltrated in to the bladder and kidney, following a gradual increase in number. Especially at 105 days after inoculation, severe accumulation of gamma/delta T cells in the renal scarring lesion was observed. Two-color immunohistological study revealed that the phenotypes of gamma/delta T cells in the renal scarring lesion were both CD4-CD8- double negative and CD4-CD8+ single positive. The CD4-CD8+ gamma/delta T cells were probably activated by the bacterial antigen.

Gastric scirrhous cancer was classified from the radiological findings into three phases (typical, latent and early phases) by cancerous involvement in the gastric wall. Radiological findings in the typical phase were divided into a giant-fold type and a no giant-fold type. We made a differential diagnosis for scirrhous cancer and other diseases. Radiological findings in the typical phase of scirrhous cancer were characteristic stiffness and rigidity of the gastric wall; in the latent phase, they were swelling and winding of mucosal folds in appropriate distended stomach; and in the early phase, interrupted folds around barium fleck. The effect of chemotherapy against a gastric scirrhous cancer is decided by distensibility of the gastric wall in radiological findings.

In order to integrate quality of life as the end point in the cancer drug therapy, a questionnaire form has been developed over the past four years by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan. Fifty-one items generated by questionnaires were forwarded to oncologists, nurses, psychologists and 121 patients. Then questionnaires were scaled down to 36 items based upon factor analysis considering correlation to State-Trait Anxiety Inventory (STAI) and Self-rating Depression Scale (SDS). These 36 items were administered to 536 patients. Finally, a 22-item questionnaire was completed by rechecking correlations with PS, STAI, SDS and Cronbach's alpha. It includes such components as physical activities (6 items), psychological (5 items) and social variables (5 items), symptoms (5 items) and global well-being (1 item: face scale). In our treatment of G. I. cancer by chemotherapy, NC patients showed improvement (+1.56 score), especially in physical functions (+2.43 score), but with slight deterioration (-0.25 score).

A device type catalyst with controllable functions is desinged by employing a ferroelectric LiTaO 3 substrate which generates a shear-horizontal leaky surface acoustic wave (SH-LSAW). The propagation of the SH-LSAW on a deposited Pd film caused an increase in the catalytic activity for ethanol oxidation. The effects of the SH-LSAW are accounted for in terms of a high electric field produced by the displacement of the substrate lattice.

In the “Criteria for Evaluating Efficacy of Chemotherapy/Radiation Therapy in the Treatment of Gastric Cancer with Primary Foci” described in the 11th Revised Edition of the General Rules for Gastric Cancer Study, the primary foci of inoperative gastric cancer are classified into three subtypes by X-ray or endoscopic findings, i.e., measurable lesion (a-lesion), not measurable but evaluable lesion (b-lesion), and diffusely infiltrated lesion (c-lesion). PR (partial response) defined for c-lesion required a minimum of 100% enlargement of the affected area in X-ray films for a minimum for 4 weeks. With respect to this requirement for a minimum of 100% of enlargement of the affected area, we have analyzed the results of inoperative cancer study by the Gastric Cancer Study Subgroup under a Grand-in- Aid for Cancer Research from the Ministry of Health and Welfare, and reached the conclusion that it is appropriate to redefine the said cPR requirement as a minimum of 50% enlargement of the affected area for a minimum of 4 weeks.

Early cancer of the colon and rectum is currently treated by endoscopic or surgical resection. We studied the indications for endoscopic treatment of early colorectal cancers (80 lesions) in relation to the size and macroscopic findings. The endoscopic treatment consists of polypectomy for a pedunculated or a sessile polyp and strip biopsy for a plaque-like or a depressive lesion. Microscopic or most small cancers were completely treated endoscopically. From macroscopic findings of the early cancers, type Ip (less than 2cm and 2cm in diameter) was completely treated by polypectomy, type I s and type II a (less than 1cm and 1cm in diameter) by polypectomy or strip biopsy, and type II c (less than 0.5cm and 0.5cm in diameter) by strip biopsy.

A multicenter cooperative study was conducted to compare the clinical efficacy of UFT-M (UFT, Mitomycin C (MMC)) and UFT-D (UFT, Doxorubicin (DXR)). A total of 62 cases with adenocarcinoma were enrolled in this study. Eligible cases included 25 patients with gastric cancer, 22 with pancreas or biliary tract cancer and 10 with other cancers. They were divided into two groups; 30 in UFT-M and 27 in UFT-D. The treatment schedules were as follows: UFT 400-600 mg/day orally every day, MMC 4-6 mg/m2, IV, every week (UFT-M); UFT 400-600 mg/day orally every day, DXR 20 mg/m2, IV, every 3 weeks (UFT-D). For gastric cancer, 3 of 17 cases treated by UFT-M showed PR, whereas no case showed PR in UFT-D. As for toxicity, bone marrow suppression was more commonly observed in UFT-M than in UFT-D. There was no statistical difference in survival between the two treatment regimens. These results suggested that UFT-D was not effective but UFT-M was a more promising combination therapy against advanced gastric cancer.

We report the first observation of room-temperature persistent spectral hole-burning in glass. The holes were burned in the 7F0→5D0 line of Sm2+ ions in fluorohafnate glass.

A phase II clinical trial of SM-5887, a new totally synthesized anthracycline derivative, was carried out in 13 patients with inoperable or recurrent gastric cancer. No patient had been given anthracycline previously. SM-5887 was administered by I.V. bolus with a dose of 100 mg/m2 every three weeks. Twelve of 13 cases were eligible and evaluable for the response. Of the 12 evaluated cases, 6 showed no change (NC), including one minor response (MR). The remaining 6 cases showed progressive disease (PD). Adverse effects were relatively mild in most cases and included anemia, leukocytopenia, thrombocytopenia, nausea/vomiting, phlebitis, hair loss and fever. Among them, leukocytopenia was observed most frequently.

Resection of bilateral pheochromocytomas of a 33-year-old man with Sipple syndrome was scheduled. Oral prazosin was started twenty days before the operation and increased to a maintenance dose of 6 mg per day. Oral lavetalol 300 mg per day was added for five days before the operation because prazosin alone was insufficient. Intravascular volume was expanded with two units of stored whole blood per day for four days before the operation for preoperative preparation. Anesthesia was induced with thiamylal 250 mg and vecuronium bromide 9 mg, and maintained with enflurane, nitrous oxide and oxygen. Phentolamine, labetalol and nitroglycerin were used for treatment of hypertensive crises during operation and anesthesia. To combat hypotension which follows the resection of the tumor, continuous infusion of norepinephrine was used for four hours after the operation. There were no hypotensive periods and no complications. After removing bilateral pheochromocytomas of the adrenals, treatment of full adrenocortical replacement therapy was performed. Concurrent use of alpha-and beta-adrenergic blocking agents was important for successful anesthetic management for the resection of pheochromocytoma.

The a-b plane thermal conductivity κ for a QMG-YBa 2 Cu 3 O x has been investigated in the temperature range 20 K T K under magnetic fields up to 14 T applied parallel to the c-axis. In zero field, κ strikingly increases below T c and takes a maximum near T c /2. The magnitude of this increase is about 45% of the value at T c . Above T c , κ exhibits slow decrease with increasing temperature, which suggests the importance of the phonon-phonon scattering. By applying magnetic fields, κ is remarkably reduced. The temperature dependence of κ can be explained in terms of the relaxation time approximation including Umklapp processes. The degradation of κ due to a magnetic field is discussed as a function of a scaling parameter to BCS energy gap.

G1383 SEQUENTIAL CHANGE OF ESOPHAGEAL NITRIC OXIDE LEVEL IN EXPERIMENTAL ESOPHAGITIS IN RATS. S. Yamato, K. Matsueda, M. Uchida*, R. Shoda, A. Muraoka, M. Matsukawa, K. Sekigawa, J. Akiyama, S. Fukushima, H. Ohara, A, Niihata, N. Masaki, S. Hayashi, E. Shimojo, and N. Umeda. Division of Gastroenterology, International Medical Center of Japan, Tokyo, Japan, and *Laboratory of Pharmacology, Meiji Institute of Health Science, Kanagawa, Japan.