Evaluation of driver stress using biomarker in motor-vehicle driving simulator.

Employing the analysis of a biomarker, an oculomotor angle and a subjective evaluation, we have examined the acute, psychological effect human stress of driving using a motor-vehicle driving simulator. Salivary amylase is used as a biomarker, as it is considered to be one of the indicators of sympathetic nervous activity. 20 healthy female subjects in their early twenties were enrolled in this study. The time-course change of their salivary amylase activity (sAMY) is analyzed before and during the driving. At the same time, using a questionnaire, subjective evaluations are conducted with each subject. As for comparison, the effect of operating a car navigation device, which is not directly associated with driving, is also evaluated. Our results indicate that the psychological effect of driving-induced stress, a condition that can not be easily detected or recognized by a subjective evaluation, is quickly quantified using a biomarker in saliva. Moreover, the results suggest that operation of a non-driving-related device may also reduce the capacity to concentrate on driving. These data imply that evaluation of driver stress using a biomarker can be very useful for improvement of safety during driving.

[A case of breast cancer with multiple bone metastases improved by high-dose toremifene].

A 63-year-old woman underwent modified radical mastectomy with 3 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, 5-fluorouracil) and MPA endocrine therapy for breast cancer. Because of nausea and general fatigue, she refused to continue this therapy and did not visit the hospital. When she came our hospital and 16 months later, she had developed multiple bone metastases. At the same time, she was suffering from lung tuberculosis. She was treated with toremifene at a dose of 120 mg/day without any side effects. After 3 months administration of toremifene, pain disappeared and her high serum CA15-3 and BCA225 dropped to within the normal range. On bone scintigrams, abnormal accumulation almost disappeared after 9 months of administration of toremifene. In this case, the patient was suffering from lung tuberculosis and did not desire intensive chemotherapy. Administration of high-dose toremifene was effective for multiple bone metastases without any side effects.

[Interim report of JFMTC study no. 20 on the effectiveness of high dose CDDP plus 5-FU regimen as an adjuvant therapy for far-advanced cancer of the stomach].

This interim analysis of the JFMTC study as of May, 1998 covers 321 gastrectomized patients with far-advanced stomach cancer from 135 institutions between November, 1993 and March, 1996. The intensive therapy group (I-group) received CDDP i.p. administration on resective surgery with 70 mg/m2 followed by CDDP i.v. of 80 mg/m2 (day 1, i.v.), accompanying 5-FU of 350 mg/m2/day (day 1-5, c.v.i.) in the 4th, 8th and 12th weeks. The I-group was randomly compared with the standard therapy group (S-group) of MMC of 6 mg/m2 i.v. in the 4th, 8th and 12th weeks and UFT of 3-4 capsules daily for postoperative one year. The results obtained were that 1. adverse reactions were found more in the I-group than in the S-group, particularly notable in the decrease in blood cells, loss of appetite and nausea/vomiting, and incidence of grade 3 or more being 13% (neutrophile leukocytes), 26% and 21%, respectively; 2. there was no significant difference between I- and S-groups in terms of 3-year survival or disease-free survival rates. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

[Interim report on JFMTC Study no. 21 on the effectiveness of UFT as an adjuvant therapy for semi-advanced cancer of the stomach].

This interim report, for findings as of May, 1998, covers data on 435 gastrectomized patients with semi-advanced stomach cancer collected from 144 institutions between November, 1993 and March, 1996. The active arm of the study involved CDDP i.p. administration of 70 mg/m2 at the time of resective surgery, followed by UFT oral administration for one year at 3-4 capsules daily. A randomized control involved no adjuvant therapy after CDDP i.p. administered as in the active arm. The results obtained indicated no significant difference between the groups in terms of 3 year survival or disease free survival rates. Reports appearing elsewhere have suggested that 3-4 capsules/day of UFT may be insufficient to reach the threshold of the effective tissue level, and that 6 capsules may be necessary to obtain the expected results. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Significance of para-aortic lymph node dissection in advanced gastric cancer.

BACKGROUND/AIMS: Since surgical results in advanced gastric cancer remain poor and para-aortic lymph node dissection may contribute to survival, it is useful to determine the significance of para-aortic lymph node dissection. METHODOLOGY: Para-aortic lymph node dissection was provisionally indicated for patients with invasion depth deeper than the subserosal layer. Clinicopathologic variables were retrospectively analyzed using univariate analysis and multivariate analysis to predict para-aortic lymph node metastasis. Similarly, they were analyzed using univariate analysis and the Cox's proportional hazards regression model to estimate the prognostic factor in 120 patients who underwent para-aortic lymph node dissection. Surgical results and post-operative complications were compared between para-aortic lymph node dissection and D2 dissection. RESULTS: Univariate analysis revealed that the mean diameter, the degree of lymph node metastasis, and the invasion depth were significant predictors of para-aortic lymph node metastasis. Multivariate analysis showed that n2 was the only independent predictive factor as to para-aortic lymph node metastasis. Univariate analysis revealed tumor site, tumor diameter, lymph node metastasis, number of positive lymph nodes, INF, and stage were significantly associated with 5-year survival. The Cox's proportional hazards regression model showed that the number of positive lymph nodes and the number of positive para-aortic lymph nodes were independent prognostic factors. Patients with < or = 10 positive lymph nodes in any stage or < or = 3 positive para-aortic lymph nodes in stage IVb had significantly better surgical results. Surgical results for patients who underwent para-aortic lymph node dissection with n2 or invasion depth deeper than the exposed serosa were significantly higher than those in D2. As to post-operative complications, pancreatic fistula and respiratory complications were significantly frequent after para-aortic lymph node dissection. CONCLUSIONS: n2 is helpful in predicting para-aortic lymph node metastasis. Whereas, post-operative morbidity such as pancreatic fistula and respiratory complications after para-aortic lymph node dissection were significantly higher, they were controllable. Para-aortic lymph node dissection should be indicated in advanced gastric cancer patients in which lymph node metastasis is over n2 or invasion depth is deeper than the exposed serosa. But the number of positive para-aortic lymph nodes must be less than three.

Continuous hyperthermic peritoneal perfusion for peritoneal dissemination of gastric cancer.

BACKGROUND/AIMS: We investigated the histological and clinical effectiveness of continuous hyperthermic peritoneal perfusion (CHPP) for treating peritoneal dissemination (therapeutic CHPP) and for the prevention of peritoneal recurrence (prophylactic CHPP). METHODOLOGY: In 5 patients with gastric cancer and peritoneal dissemination, the apoptosis index of the cancer cells on in situ end-labeling for detection of apoptotic cells was 3.0+/-1.2% before CHPP, and had increased to 52.9+/-8.3% after CHPP. The survival curve of the therapeutic CHPP group was significantly better than that of the control group. The therapeutic CHPP group was classified as miliary type or nodular type. The survival curve in the miliary type was significantly better than that in the nodular type. RESULTS: In prophylactic CHPP, there was no improvement in prognosis, but a prophylactic effect against peritoneal recurrence was demonstrated in the patients who were n4 negative when the mean intraperitoneal temperature during CHPP (MIT) was maintained above 42 degrees C. CONCLUSIONS: These results indicated that an improved prognosis can be expected after therapeutic CHPP in patients with peritoneal spread. The beneficial effects are especially marked in patients with the miliary type. Moreover, prophylactic CHPP exerts a prophylactic effect against peritoneal recurrence in patients with n4 negative, providing that the MIT can be maintained above 42 degrees C.

[MRSA enteritis following severe gastroenteritis of salmonellosis].

A 62-year-old female patient was given cancer chemotherapy for lymph nodes metastases in the left breast cancer. She was admitted to the hospital because of severe watery diarrhea, in hypovolemic shock, and was diagnosed as suffering from not-typhoidal Salmonella by stool culture. After systemic administration of antibiotic agents, she became well in a few days, but on the 16th hospital day, she had severe watery diarrhea, hypovolemic shock and then cardiac arrest. She was resuscitated immediately. The stool culture revealed methicillin-resistant Staphylococcus aureus (MRSA), type II coagulase, producing TSST-1 and type BC staphylococcal enterotoxin. It was thought that in this case, MRSA enteritis was caused by damage of the intestinal mucosal barrier of the defense mechanism against infection due to salmonellosis and administration of multiple antibiotic agents.

Linkage of [Ca2+]i in single isolated D cells to somatostatin secretion induced by cholecystokinin.

The Ca2+/inositol phospholipid signaling cascade has been implicated in the mechanism by which cholecystokinin (CCK) stimulates gastric somatostatin release, but a direct linkage between intracellular events in gastric D cells and somatostatin secretion has not been established. To address this problem we developed a method for correlating somatostatin release with the measurement of intracellular Ca2+ concentration ([Ca2+]i) in isolated D cells. Resting [Ca2+]i in single D cells was 100 +/- 5.7 nM (means +/- SE, n = 41), and CCK induced a rise in [Ca2+]i in a dose-dependent fashion, producing a maximal stimulatory effect (243 +/- 15% of control, n = 12) at a peptide concentration of 2 x 10(-8) M. The CCK-mediated increase in [Ca2+]i was biphasic, with a rapid, initial transient elevation followed by a sustained plateau. The rise in [Ca2+]i was accompanied by a concomitant increase in release of somatostatin-like immunoreactivity (SLI). Removal of extracellular Ca2+ had no effect on the initial transient elevation in [Ca2+]i induced by CCK but abolished both the sustained plateau in [Ca2+]i and the release of SLI. The selective CCK antagonist L-364, 718 (10(-7) M) inhibited the effects of CCK on both [Ca2+]i and SLI release. The nonspecific Ca2+ channel blocker NiCl2 (10(-3) M) and the L-type Ca2+ channel blocker nifedipine inhibited the sustained rise in [Ca2+]i and the release of SLI but left the initial transient increase in [Ca2+]i unaltered. These results indicate that CCK-stimulated release of SLI from D cells in the gastric fundus is linked to influx of extracellular Ca2+ via L-type Ca2+ channels.

[Characterization of a liver metastatic cell line derived from a human gastric cancer cell line].

This study was carried out to investigate whether there is any difference of biological characteristics between a gastric cancer cell line (KATOIII) and another cell line derived from liver metastasis of the same cell line (KATOIII-H2). The liver metastasis was produced by intrasplenic injection of the fluid containing of KATOIII in nude mouse and new cell line was established using the cells of metastatic site. The results are as follows. 1) Inoculation of KATOIII-H2 into the spleen produced liver metastases in all of the experimental animals, whereas the same procedure with KATOIII produced metastasis only in 30% of the animals. 2) KATOIII-H2 exhibited more prominent platelet-aggregating activity than KATOIII. 3) There is no difference between two cell lines on doubling time, histological findings of the xenografts and chromosomal number. 4) DNA index of KATOIII-H2 is lower than KATOIII and the trisomy in NO. 20 chromosome of KATOIII-H2 was noted. The results indicate that metastatic potential is different between two cell lines and this fact is probably in a part because of the different platelet-aggregating activity of each cell line.

Effect of probucol on macrophages, leading to regression of xanthomas and atheromatous vascular lesions.

To explain the strong effect of probucol on xanthomas, the drug's effect on lipid storage in macrophages in the presence of denatured low-density lipoprotein (LDL) was studied. Two macrophage cell lines, UE-12 and THP-1, were used. Those cells stored lipids and became foam cells when they were incubated with acetylated LDL (acetyl-LDL). When probucol was added into the medium either in ethanolic solution or in the form bound to LDL, the storage of cholesterol and other lipids and the development of macrophages into foam cells were greatly suppressed. Two functions of probucol should be considered: (1) It inhibited the uptake of acetyl-LDL by macrophages; and (2) it enhanced the release of cholesterol from these cells. Cells were first incubated with probucol. After the cells were washed with fresh medium, the radiolabeled acetyl-LDL was added to the medium and the degradation of acetyl-LDL was measured. Increasing the concentration of probucol led to a decrease in degradation of acetyl-LDL by macrophages. Probucol also suppressed the uptake of albumin. Macrophages were incubated with acetyl-LDL, washed once, then incubated with or without probucol and high-density lipoprotein (HDL). Addition of HDL caused a rapid decrease in cholesterol content in the cells, and this phenomenon was enhanced by probucol for both kinds of cells. The secretion of apolipoprotein E was also stimulated by the addition of probucol. These 2 sets of experimental results suggest that probucol prevents lipid storage in macrophages by both suppressing the uptake and stimulating the release of cholesterol and other lipids into or from the macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Action of malotilate on reduced serum cholesterol level in rats with carbon tetrachloride-induced liver damage.

The mode of action of malotilate in normalizing serum cholesterol in hypocholesterolemic rats with fatty liver was examined by determination of biosynthesis, catabolism and excretion of cholesterol. Fatty liver was produced by subcutaneous injection of CCl4 at the dose of 1 ml/kg into male rats (SLC-SD) twice a week for 3 weeks. Daily administration of malotilate (100 mg/kg) in rats with hypocholesterolemia resulted in a rapid normalization of lowered serum cholesterol. Such a recovery of cholesterol level in serum coincided in time with normalization of the decreased cholesterol level of each lipoprotein fraction, VLDL-triglycerides secretion and the decreased apolipoprotein A1 value. Histopathological improvement in liver was also confirmed by a decrease in the size of fat droplets stored within the hepatocytes. The malotilate treatment gave a tendency to facilitate hepatic cholesterol synthesis in rats with fatty liver. Malotilate at a concentration of 0.5-2 micrograms/ml also stimulated cholesterol biosynthesis in cultured normal hepatocytes. The drug had the action to accelerate the catabolic excretion of 3H-labeled cholesterol into feces. These results suggest that the mode of action by which serum cholesterol is normalized in rats with fatty liver is probably due to a stimulative effect of malotilate on hepatic cholesterol synthesis and cholesterol secretion from the liver.

Antagonism of L(-)pantothenic acid on lipid metabolism in animals.

The inhibition rate of L(-)pantothenate as an antagonist of D(+)pantothenate was discussed from the viewpoint of growth and lipid metabolism. The growth rate of mice given pantothenate-deficient diets containing L(-)pantothenate (300 mg per 100g diet) was markedly decreased, and such pantothenate-deficient symptoms as "spectacle eyes" appeared. However, it was recovered by the simultaneous addition of D(+)pantothenate. This result suggets that L(-)pantothenate is an antagonist of D(+)pantothenate. The same phenomenon was observed in a rat experiment. The growth of rats given L(-)pantothenate was extremely poor but recovered by the simultaneous addition of D(+)pantothenate. Its complete recovery was seen when the ratio of L(-)pantothenate to D(+)pantothenate reached 100:1. The same tendencies were observed in the liver levels of total lipid, total cholesterol and triglyceride, and also in the lipoperoxide values. This experiment suggests that the inhibition rate of L(-)pantothenate to D(+)pantothenate in animals is similar to that of DL-omega-methyl pantothenate.