Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizoma siccus) for a variety of illnesses during pregnancy.

The present study was designed to investigate if exposure to dried ginger during pregnancy would increase the risk of adverse fetal and neonatal outcomes. Participants consisted of 159 singleton pregnant women who received dried ginger as a herbal medication. We also included a control group of 306 pregnant women who had not been exposed to any herbal medication or any known teratogen. No increased risk of major malformations was detected in exposed women (OR = 4.9; 95% CI 0.9-25.5; p = 0.051). The incidence of stillbirths in the exposed group was marginally higher than in the controls (OR = 7.8; 95% CI 0.9-70.3; p = 0.05). The risk was more evident when the exposed group was compared with the general population in the Republic of Korea (OR = 7.9; 95% CI 2.9-21.4; p < 0.0001). Other fetal and neonatal study outcomes investigated in the exposed group were similar (p > 0.05) to the controls. In conclusion, dried ginger does not appear to be a major teratogen. However, due to the limitations of the study, e.g. the large variability in the dose of dried ginger in the exposed group, as well as the concomitant exposure to other herbal medications, the increased incidence of stillbirths requires confirmation in larger cohort studies.

Effect of complementary and alternative medicine on the survival and health-related quality of life among terminally ill cancer patients: a prospective cohort study.

BACKGROUND: We evaluated whether complementary and alternative medicine (CAM) use influenced outcomes [survival and health-related quality of life (HRQOL)] of cancer patients whose condition had just been judged terminal. PATIENTS AND METHODS: From July 2005 to October 2006, we conducted a prospective cohort study of 481 terminally ill cancer patients at 11 university hospitals and the National Cancer Center in Korea. We assessed how the use of CAM affected HRQOL and survival. RESULTS: In a follow-up of 481 patients and 163.8 person-years, we identified 466 deceased cases. On multivariate analyses, CAM users did not have better survival compared with nonusers [adjusted hazard ratio (aHR), 0.91; 95% confidence interval (CI) 0.74-1.10]. Among mind-body interventions, prayer showed significantly worse survival (aHR, 1.56; 95% CI, 1.00-2.43). Clinically, CAM users reported significantly worse cognitive functioning (-11.6 versus -1.3; P < 0.05) and fatigue (9.9 versus -1.0; P < 0.05) than nonusers. Compared with nonusers in subgroup analysis, users of alternative medical treatments, prayer, vitamin supplements, mushrooms, or rice and cereal reported clinically significant worse changes in some HRQOL subscales. CONCLUSION: While CAM did not provide any definite survival benefit, CAM users reported clinically significant worse HRQOLs.

Effects of licochalcon A on the pharmacokinetics of losartan and its active metabolite, EXP-3174, in rats.

Losartan and licochalcon A interact with cytochrome P-450 (CYP) enzymes and P-glycoprotein (P-gp), and the increase in the use of health supplements may result in licochalcon A being taken concomitantly with losartan to treat or prevent cardiovascular diseases as a combination therapy. The effect of licochalcon A, a natural flavonoid, on the pharmacokinetics of losartan and its active metabolite, EXP-3174, was investigated in rats. Pharmacokinetic parameters of losartan and EXP-3174 were determined after oral administration of losartan (9 mg/kg) to rats in the presence or absence of licochalcon A (0.5, 2.5 and 10 mg/kg). The effect of licochalcon A on P-glycoprotein (P-gp) as well as CYP3A4 and 2C9 activities was also evaluated. Licochalcon A inhibited CYP3A4 and CYP2C9 enzyme activities with 50% inhibition concentrations (IC50) of 2.0 and 0.1 microM, respectively. In addition, licochalcon A significantly enhanced the cellular accumulation of rhodamine-123 in a concentration-dependent manner in MCF-7/ADR cells overexpressing P-gp. The pharmacokinetic parameters of losartan were significantly altered by licochalcon A. Licochalcon A (2.5 mg/kg or 10 mg/kg) increased AUC0-infinity of losartan by 33.4-63.2% and Cmax of losartan by 34.0-62.8%. The total body clearance (CL/F) was significantly decreased (2.5 mg/kg, p < 0.05; 10 mg/kg, p < 0.01) by licochalcon A. Consequently, the absolute bioavailability of losartan in the presence of licochalcon A increased significantly (2.5 mg/kg, p < 0.05; 10 mg/kg, p < 0.01) compared to that in the control group. The relative bioavailability (R.B.) of losartan was 1.15- to 1.63-fold greater than that of the control group. However, there was no significant change in Tmax and t1/2 of losartan in the presence of licochalcon A. Licochalcon A (10 mg/kg) increased the AUC0-infinity of EXP-3174 but this was not significant. Furthermore, concurrent use of licochalcon A (10 mg/kg) significantly decreased the metabolite-parent AUC ratio (M.R.) by 20%, suggesting that licochalcon A inhibited the CYP-mediated metabolism of losartan to its active metabolite, EXP-3174. In conclusion, the enhanced oral bioavailability of losartan in the presence of licochalcon A may mainly result from decreased P-gp-mediated efflux transporter in the small intestine and from the inhibition of CYP 3A- and CYP2C9-mediated metabolism in the small intestine and liver and/or from the reduction of total body clearance of losartan by licochalcon A.

Conventional barium enema in early pregnancy.

X-ray exposure, especially if directed to the abdominal region, is of major concern for pregnant women and their physicians. In this study, favourable long-term outcomes are reported in a series of babies born to women inadvertently exposed to barium enema, and associated ionising radiation, early in pregnancy. Six singleton babies were vaginally delivered without any evidence of gross malformations. There was one voluntary abortion. Follow-up on five of the babies was performed over the course of at least 4 years. All the children were deemed healthy and had developed milestones according to their age. Our findings support larger studies suggesting barium enema is not a teratogenic agent. Collectively, this research can be used to counsel women undergoing radiological procedures early in pregnancy.

Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking Akt activation and TGF-beta signaling.

Diabetic nephropathy (DN) characterized as nephrotic syndrome and diffuse glomerulosclerosis can cause renal failure and end-stage kidney disease. Expansion of mesangial matrix around capillaries in the kidney glomeruli is a prominent feature of DN. This study investigated whether licorice extracts inhibited mesangial cell (MC) proliferation and matrix accumulation induced by high glucose (HG). Human renal MC were cultured in media containing 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 d in the presence of water or ethanol extracts from raw licorice (LW, LE) or roasted licorice (RLW, RLE). Non-polar components including glycyrrhetic acid were elevated during licorice roasting, whereas polar components soluble in water extracts were diminished. Exposure of cells to HG caused significant increases in collagen IV secretion and connective tissue growth factor (CTGF) expression, which was appeased by RLW and RLE at transcriptional levels. The inhibitory potency was high in the order of RLE > or = RLW > or = LE > > LW. Non-polar glycyrrhetic acid but not glycyrrhizin retarded HG-stimulated mesangial matrix deposition through diminishing CTGF expression. In addition, RLW and RLE but not LW modulated membrane type matrix metalloproteinase-1 (MT-1 MMP) expression, MMP-2 activity and tissue inhibitor of MMP-2 (TIMP-2), which facilitated the degradation of mesangial matrix. Furthermore, the augmented expression of CTGF and TIMP-2 in HG-exposed cells was mediated by Akt activation and TGF-beta/Smad signaling through PKCbeta2-responsive signaling pathways. However, HG-down-regulated MT-1 MMP expression was independent of activation of ERK1/2 and Akt when using their inhibitors of DB98059 (ERK1/2) and LY294002 (Akt) alone or in combination. These results demonstrate that extracts from roasted licorice may be highly potent therapeutic agents for the prevention and treatment of mesangial fibrosis and glomerulosclerosis leading to diabetes nephropathy due to longstanding diabetes mellitus.

Biofeedback therapy for rectal intussusception.

BACKGROUND: Surgery for isolated internal rectal intussusception is controversial due to high morbidity. Therefore, there is interest in other forms of treatment that are safe and effective. The aim of this study was to determine outcome and identify predictors for success of biofeedback therapy in patients with rectal intussusception. METHODS: We retrospectively evaluated the results of electromyography (EMG)-based biofeedback in 34 patients with rectal intussusception without any other major pelvic floor or colonic physiologic disorder. RESULTS: A total of 34 patients (7 men) had undergone at least 2 biofeedback sessions. The patients had a mean age of 68.5 years (SD=11.4 years). In the 27 patients with constipation, the frequency of weekly spontaneous bowel movements (mean+/-SD) was 2.0+/-6.8 before and 4.1+/-4.6 after biofeedback (p<0.05). The frequency of weekly assisted bowel movements decreased from 3.8+/-3.5 before to 1.5+/-2.2 after therapy (p<0.005). The number of patients who experienced incomplete evacuation decreased from 17 (63%) to 9 (33%) (p<0.05). Thirty-three percent of patients had complete resolution of the symptoms, 19% had partial improvement, and 48% had no improvement. Patients with constipation lasting less than nine years had a 78% success rate vs. 13% in patients who were constipated more than 9 years (p<0.01). In seven patients with incontinence, the frequency of daily incontinence episodes decreased from 1.0+/-0.7 before to 0.07+/-0.06 after biofeedback (p<0.05). The fecal incontinence score decreased from 13.1+/-4.2 before to 4.6+/-3.6 after treatment (p<0.005). Two patients (29%) were completely continent following biofeedback, 2 had partial improvement, and 3 (43%) had no significant improvement. There was no mortality in either group. CONCLUSIONS: Biofeedback is a safe and effective treatment option for constipation and fecal incontinence due to rectal intussusception in patients who are willing to complete the course of treatment. Long-standing constipation is less effectively cured by biofeedback.

Methanolic extract of Pterocarpus santalinus induces apoptosis in HeLa cells.

Ptercarpus santalinus (Fabaceae) has been used as a folk remedy in Korea, and it has been shown to exhibit antiinflammations, antiulcers and anticancer effects. In this study, therefore, we report the cytotoxic activity and the mechanism of cell death exhibited by the methanol extract of Ptercarpus santalinus (MEPS) against human cervical adenocarcinoma cell line, HeLa. Treatment of HeLa cells with various concentrations of MEPS resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as determined by cell viability, chromatin condensation, DNA fragmentation and sub-G1 phase accumulation. In Western blot analysis, apoptosis in the HeLa cells was associated with the release of cytochrome C from mitochondria into the cytosol, activation of caspases-3, -8, -9 and proteolytic cleavage of PARP. These results suggest that MEPS exhibits antiproliferative effect on HeLa cells via apoptosis, and it may be a potential candidate in field of anticancer drug discovery.

Recognition and phagocytosis of multiple periodontopathogenic bacteria by anti-Porphyromonas gingivalis heat-shock protein 60 antisera.

The present study has been performed to evaluate Porphyromonas gingivalis heat shock protein (HSP) 60 as a candidate vaccine to protect against multiple putative periodontopathic bacteria. Mouse anti-P. gingivalis HSP antisera demonstrated the elevated IgG antibody titers against the multiple bacteria tested and cross-reacted with heat-induced bacterial proteins of the target bacteria. The antisera also demonstrated a significantly higher opsonophagocytosis function against all the target bacteria than the control sera (P<0.01). We concluded that P. gingivalis HSP 60 could potentially be developed as a vaccine against multiple periodontopathic bacteria.

A new C-methylated flavonoid glycoside from Pinus densiflora.

A new C-methyl flavonol glycoside, 5,7,8,4'-tetrahydroxy-3-methoxy-6-methylflavone 8-O-beta-D-glucopyranoside (1), has been isolated from the needles of Pinus densiflora, together with kaempferol 3-O-beta-(6"-acetyl)-galactopyranoside.

Effects of (-)-epigallocatechin-3-gallate, the main component of green tea, on the cloned rat brain Kv1.5 potassium channels.

The interaction of (-)-epigallocatechin-3-gallate (EGCG), the main component of green tea (Camellia sinensis), with rat brain Kv1.5 channels (rKv1.5) stably expressed in Chinese hamster ovary (CHO) cells was investigated using the whole-cell patch-clamp technique. EGCG inhibited rKv1.5 currents at +50 mV in a concentration-dependent manner, with an IC50 of 101.2+/-6.2 microM. Pretreatment with protein tyrosine kinase (PTK) inhibitors (10 microM genistein, 100 microM AG1296), a tyrosine phosphatase inhibitor (500 microM sodium orthovanadate), or a protein kinase C (PKC) inhibitor (10 microM chelerythrine) did not block the inhibitory effect of EGCG on rKv1.5. The inhibition of rKv1.5 by EGCG displayed voltage-independence over the full activation voltage range positive to +10 mV. EGCG had no effect on the midpoint potential or the slope factor for steady-state activation and inactivation. EGCG did not affect the ion selectivity of rKv1.5. The activation (at +50 mV) kinetics was significantly slowed by EGCG. During repolarization (at -40 mV), EGCG also slowed the deactivation of the tail currents, resulting in a crossover phenomenon. Reversal of inhibition was detected by the application of repetitive depolarizing pulses and of identical double pulses, especially during the early part of the activating pulse, in the presence of EGCG. EGCG-induced inhibition of rKv1.5 showed identical affinity between EGCG and the multiple closed states of rKv1.5. These results suggest that EGCG interacts directly with rKv1.5 channels. Furthermore, by analyzing the kinetics of the interaction between EGCG and rKv1.5, we conclude that the inhibition of rKv1.5 channels by EGCG includes at least two effects: EGCG preferentially binds to the channel in the closed state, and blocks the channel by pore occlusion while depolarization is maintained.

Amygdalar nmda receptors are critical for the expression of multiple conditioned fear responses.

There is conflicting evidence regarding the issue of whether NMDA receptors in the basolateral amygdalar complex (BLA) are critically involved in the expression of conditioned fear. This matter was addressed by infusing the rat BLA with d,l-2-amino-5-phosphonovaleric acid (APV), a competitive NMDA receptor antagonist. APV infusion into the BLA was reported to block the expression of conditioned fear when measured by freezing but not when measured by fear-potentiated startle response to a loud noise. To examine this issue further, here we used multiple indices of conditioned fear, including analgesia, 22 kHz ultrasonic vocalization (USV), defecation, and freezing. Rats with bilateral BLA cannula implants underwent fear conditioning consisting of 10 tone-footshock pairings. Before context and tone fear-retention tests, animals received intra-BLA infusions with APV (2.5 microg/side) or artificial CSF. Both tone and context tests demonstrated that the expression of conditioned freezing, USV, defecation, and analgesia were significantly impaired by intra-amygdalar infusions of APV. In a second set of experiments, intra-BLA infusions of APV markedly impaired the normal expression of postshock fear responses during training, as measured by freezing, USV, and defecation. Immediate postshock fear expression was predictive of subsequent fear retention to the tone and context when the animals were not infused. These results are consistent with the hypothesis that amygdalar NMDA receptors participate in normal synaptic transmission and therefore the overall functioning of the amygdala.

Outcome and management of patients with large rectoanal intussusception.

OBJECTIVES: Rectoanal intussusception is the funnel-shaped infolding of the rectum, which occurs during evacuation. The aims of this study were to evaluate the risk of full thickness rectal prolapse during follow-up of patients with large rectoanal intussusception, and whether therapy improved functional outcome. METHODS: Between September 1988 and July 1997, patients diagnosed with a large rectoanal intussusception by cinedefecography (intussusception > or = 10 mm, extending into the anal canal) were retrospectively evaluated. Patients with full thickness rectal prolapse on physical examination or cinedefecography were excluded, as were patients with colonic inertia or a history of surgery for rectal prolapse. The patients were divided into three groups according to the treatment received: group I, conservative dietary therapy; group II, biofeedback; and group III, surgery. Outcomes were obtained by postal questionnaires or telephone interviews. Parameters included age, gender, past medical and surgical history, change of bowel habits, fecal incontinence score, and development of full thickness rectal prolapse. RESULTS: Of the 63 patients, 18 were excluded (seven patients had confirmed full thickness rectal prolapse, four had previous surgery for rectal prolapse, three had colonic inertia, and four died). Follow-up data were obtained in 36 (80%) of the remaining 45 patients. The mean follow-up of this group was 45 months (range, 12-118 months). There were 34 women and two men, with a mean age of 72.4 yr (range, 37-91 yr). The mean size of the intussusception was 2.2 cm (range, 1.0-5.0 cm). The patients were classified as follows: group I, 13 patients (36.1%); group II, 13 patients (36.1%); and group III, 10 patients (27.8%). Subjectively, symptoms improved in five (38.5%), four (30.8%), and six (60.0%) patients in the three groups (p > 0.05). Among the patients with constipation, the decrease in numbers of assisted bowel movements per week (time of diagnosis to present) was significantly greater in group II compared to group 1 (8.1+/-2.8 vs 0.8+/-0.5, respectively, p = 0.004). Among the patients with incontinence, incontinence scores improved more in group II as compared to either group I or group III (time of diagnosis to present, 3.7+/-4.2 to 1.1+/-5.4 vs 1.4+/-2.2, respectively, p > 0.05). Six patients (two in group I, three in group II, and one in group III) had the sensation of rectal prolapse on evacuation; however, only one patient in group I developed full thickness rectal prolapse. CONCLUSIONS: This study demonstrated that the risk of full thickness rectal prolapse developing in patients medically treated for large intussusception is very small (1/26, 3.8%). Moreover, biofeedback is beneficial to improve the symptoms of both constipation and incontinence in these patients. Therefore, biofeedback should be considered as the initial therapy of choice for large rectoanal intussusception.

A new cyclic phenyllactamide from Salvia miltiorrhiza.

From the rhizome of Salvia miltiorrhiza, a new cyclic phenyllactamide was isolated and characterized as 2,10,11-trihydroxy-8-methoxy-1,6,7,8-tetrahydro-2H-benzo[e]azecine-3,5-dione (1) from spectroscopic evidence. The new compound was found to be a scavenger of 1,1-diphenyl-2-picrylhydrazyl radical.

Isolation of luteolin 7-O-rutinoside and esculetin with potential antioxidant activity from the aerial parts of Artemisia montana.

The antioxidant activity of Artemisia montana was determined by measuring the radical scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and inhibitory activity against free radical generation of hepatocytes (AC2F). The methanol extract of A. montana showed strong radical scavenging activity at a concentration of 10.1 microg/ml, and thus fractionated by solvent extraction. Esculetin and luteolin 7-O-rutinoside (scolymoside) were isolated as the active principles from the EtOAc and Interphase fractions, respectively. The antioxidant activity of these compounds were comparable to that of L-ascorbic acid.

Influence of 5,10-methylenetetrahydrofolate reductase gene polymorphism on plasma homocysteine concentration in patients with end-stage renal disease.

The purpose of this study is to observe the influence of the methylenetetrahydrofolate reductase (MTHFR) gene (677C-->T substitution) on plasma homocysteine levels in end-stage renal disease (ESRD) patients who received a relatively large amount of folate (2 mg/d) and are undergoing hemodialysis. A cross-sectional study of plasma homocysteine, vitamin B(12), and folate was performed in patients with ESRD. The study population for the MTHFR gene study included 312 healthy subjects and 106 patients with ESRD undergoing hemodialysis. The C677T transition in the MTHFR gene was detected by HinF 1 restriction enzyme analysis and subsequent electrophoresis in a 3% agarose gel. The genotype of the MTHFR gene in 106 patients with ESRD was homozygous C677T mutation (VV) in 17 patients (16.1%) and heterozygous (AV) in 63 patients (58.4%); 26 patients (24.5%) did not carry this mutation (AA). The mean levels of homocysteine, vitamin B(12), and folate in the patients with ESRD were 23.3 +/- 14.0 mmol/L, 620.2 +/- 98.5 pmol/L, and 138.6 +/- 55.6 nmol/L, respectively. There was no significant difference in homocysteine levels among the three genotypes: 28.2 +/- 19.4 mmol/L for VV, 22.7 +/- 14.9 mmol/L for AV, and 23.4 +/- 11.1 mmol/L for AA genotype (P > 0.05). There was no difference in genotype distribution between the patient groups of less than 25th and greater than 75th percentiles, classified according to plasma homocysteine levels (P = 0.47). In conclusion, with high-dose folate supplementation, the hyperhomocysteinemia in patients with ESRD does not seem to be caused by the 677C-->T mutation in the MTHFR gene.

Inhibitory effect of luteolin 4'-O-glucoside from Kummerowia striata and other flavonoids on interleukin-5 bioactivity.

Interleukin (IL)-5 is a chemotactic factor of eosinophils, and promotes the growth and survival of eosinophils, which plays an important role in the eosinophilia-associated allergic inflammation. In this study, luteolin 4'-O-glucopyranoside was identified as the IL-5 inhibitor from Kummerowia striata Thunb. (Leguminosae) by activity-guided fractionation followed by structural analysis compared with reported spectral data. The flavone compound exhibited dose-dependent inhibitory effect on IL-5 bioactivity with 95% inhibition at 30 microM, 79% at 15 microM, 60% at 7.5 microM, 54% at 3.8 microM and 29% at 1.9 microM, where 50% of inhibition (IC50) value was shown at the concentration of 3.7 microM. Furthermore, the inhibitory effect on IL-5 bioactivity by other flavonoid compounds available was estimated. In view of the IC50 values, the inhibitory potency on IL-5 bioactivity was in order of luteolin 4'-O-glucopyranoside > cosmosiin (14.2 microM) approximately equal to apigenin (16.4 microM) approximately equal to luteolin (18.7 microM) > quercimeritrin (27.3 microM) approximately equal to kaempferol (30.0 microM).

Antioxidant flavonoids and chlorogenic acid from the leaves of Eriobotrya japonica.

The antioxidant activity of Eriobotrya japonica was determined by measuring the radical scavenging effect on DPPH (1,1-diphenyl-2-picrylhydrazyl) radical and lipid peroxidation produced when mouse liver homogenate was exposed to the air at 37 degrees C, using 2-thiobarbituric acid (TBA). The methanol extract and its fractions of Eriobotrya japonica leaves showed strong antioxidant activity. The antioxidant activity of EtOAc and n-BuOH soluble fractions were stronger than the others, and were further purified by repeated silica gel, MCl gel CHP-20P, and Sephadex LH-20 column chromatography. Antioxidant chlorogenic acid, quercetin-3-sambubioside from n-BuOH fraction, and methyl chlorogenate, kaempferol- and quercetin-3-rhamnosides, together with the inactive ursolic acid and 2 alpha-hydroxyursolic acid from EtOAc fraction were isolated. Antioxidant flavonoids and chlorogenic acid also showed prominent inhibitory activity against free radical generation in dichlorofluorescein (DCF) method.

In vitro angiogenic activity of Aloe vera gel on calf pulmonary artery endothelial (CPAE) cells.

Angiogenic activity of Aloe vera gel was investigated by in vitro assay. We obtained the most active fraction from dichloromethane extract of Aloe vera gel by partitioning between hexane and 90% aqueous methanol. The most active fraction (F3) increased the proliferation of calf pulmonary artery endothelial (CPAE) cells. In addition, F3 fraction induced CPAE cells to invade type 1 collagen gel and form capillary-like tube through in vitro angiogenesis assay, and increased the invasion of CPAE cells into matrigel through in vitro invasion assay. Furthermore, the effect on the mRNA expression of proteolytic enzymes which are key participants in the regulation of extracellular matrix degradation was investigated by northern blot analysis. F3 fraction enhanced mRNA expression of urokinase-type plasminogen activator (u-PA), matrix metalloproteinase-2 (MMP-2), and membrane-type MMP (MT-MMP) in CPAE cells whereas the expression of plasminogen activator inhibitor-1 (PAI-1) mRNA was not changed.

A triterpenoid saponin from Patrinia scabiosaefolia.

A new triterpenoid saponin, patrinia saponin H3 (3), was isolated from the aerial parts of Patrinia scabiosaefolia Fisch. and determined to be 3-O-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranosyl hederagenin 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester on the basis of NMR and FAB MS experiments and acid hydrolysis.

A randomized trial comparing cisplatin plus 5-fluorouracil with or without levamisole in operable gastric cancer.

OBJECTIVES: To determine the effectiveness and toxicity when levamisole was added to the adjuvant combination chemotherapy in patients with operable gastric cancer. METHODS: After en bloc resection of gastric cancer without gross or microscopic evidence of residual disease from April 1991 to December 1992, 100 patients were randomized to 6 months of 5-fluorouracil 1,000 mg/m2/day administered as continuous infusion for 5 days, cisplatin 60 mg/m2/day as intravenous infusion for 1 day with or without levamisole (50 mg every eight hours P.O for a period of three days every 2 weeks for 6 months). This chemotherapy treatment was begun within 2 to 4 weeks after the surgery. The chemotherapy consisted of discrete 5-day courses administered at 4-weeks intervals. All 100 patients are assessable. RESULTS: The fifty patients were assigned to each treatment group. There was no statistical difference and no bias in the distribution of characteristics of the 100 evaluable patients between the two groups. A total of 274 courses of treatment were given in the levamisole group and 260 courses of treatment in non-levamisole group. Eleven patients in each group did not finish planned 6 courses of treatment mainly due to non-compliance. At median follow up of 39 months, 32 patients relapsed 19 in the levamisole group and 13 in the non-levamisole group (p = 0.284). Twenty five patients died of relapsed diseases, 15 in the levamisole group and 10 in the non-levamisole group. The levamisole group tended to show more risk of overall death rate and recurrence than the non-levamisole group. However, this result was not statistically significant at 3 years. The treatment was well tolerated in both treatment groups. The grade 2-3 toxicities were nausea/ vomiting (levamisole, non-levamisole group; 31.7%, 29.3% of treatment courses respectively), diarrhea (7.6%, 8.4%), mucositis (11.6%, 12.3%), and leukopenia (9.8%, 9.6%). CONCLUSION: Levamisole had negative effects on disease-free survival and overall survival when added to adjuvant combination chemotherapy of cisplatin and 5-fluorouracil in patients with operable gastric cancer. Both treatment arms were generally well tolerated and the toxicity profile was similar with or without levamisole.