Determinants of liquid gastric emptying: comparisons between milk and isocalorically adjusted clear fluids.

BACKGROUND: Although current preoperative fasting guidelines apply restrictions to drinks containing milk because of delayed gastric emptying, the safe volume of milk that can be consumed up to 2 h before surgery on a theoretical basis has not yet been defined. We aimed to determine whether delayed gastric emptying depended mainly on the total amount of calories irrespective of compositional differences between milk and clear fluids. METHODS: We prepared five beverages with a uniform volume (500 ml) and step-wise increments in calories (0, 220, and 330 kcal), comprised mainly of non-human milk, pulpless orange juice, water, and gum syrup. The gastric emptying rate of each beverage was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by eight healthy fasting volunteers. RESULTS: The emptying rates of 500 ml of orange juice and 330 ml of non-human milk with 170 ml of water (both were 220 kcal) from the stomach were similar. Furthermore, 450 ml of orange juice with 50 ml of gum syrup and 500 ml of non-human milk (both were 330 kcal) left the stomach at similar rates. The 220 kcal beverages emptied faster than the 330 kcal beverages. CONCLUSIONS: There were no significant differences in liquid gastric emptying after drinking equal volumes of either orange juice or milk as long as both had the same amount of calories. Liquid gastric emptying depends chiefly on the total caloric content. CLINICAL TRIAL REGISTRATION: UMIN000012537.

Indian hedgehog roles in post-natal TMJ development and organization.

Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation. To determine whether it regulates those processes during post-natal life, we ablated Ihh in cartilage of neonatal mice and assessed the consequences on temporomandibular joint (TMJ) growth and organization over age. Ihh deficiency caused condylar disorganization and growth retardation and reduced polymorphic cell layer proliferation. Expression of Sox9, Runx2, and Osterix was low, as was that of collagen II, collagen I, and aggrecan, thus altering the fibrocartilaginous nature of the condyle. Though a disc formed, it exhibited morphological defects, partial fusion with the glenoid bone surface, reduced synovial cavity space, and, unexpectedly, higher lubricin expression. Analysis of the data shows, for the first time, that continuous Ihh action is required for completion of post-natal TMJ growth and organization. Lubricin overexpression in mutants may represent a compensatory response to sustain TMJ movement and function.

Serum keratan sulfate is a promising marker of early articular cartilage breakdown.

OBJECTIVES: To find serum markers that may serve as indices for an early diagnosis of degeneration or damage of the articular cartilage. METHODS: Twenty-four healthy volunteers, 19 individuals with knee trauma (KT) and 31 with knee osteoarthritis (OA) were evaluated. KT patients were divided into a group (n = 5) with an injury <2 months old (recent KT) and a group (n = 14) with that >2 months old (old KT). Articular cartilage damage was assessed using either arthroscopy or direct observation. Serum concentrations of hyaluronic acid (HA), cartilage proteoglycan aggrecan turnover epitope (CS846) and cartilage oligomeric protein (COMP) were measured using enzyme-linked immunosorbent assay kits and those of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) using high-performance liquid chromatography. RESULTS: Serum KS in the recent KT group (2095 +/- 594 ng/ml) was significantly higher than that in the old KT group (1373 +/- 418 ng/ml; P = 0.021), and serum COMP in the recent KT group (1572 +/- 182 ng/ml) showed a tendency that was higher than that in the old KT group (1350 +/- 250 ng/ml; P = 0.079). Serum KS in OA patients with Kellgren and Lawrence (KL) grades 0 and I (1456 +/- 334 ng/ml) showed a tendency that was higher than that in OA patients with KL grades II, III and IV (1248 +/- 220 ng/ml; P = 0.084). CONCLUSIONS: The serum concentration of KS correlated with the damage of the articular cartilage and it was significantly increased even at an early stage after the injury.

Hard tissue formation in subcutaneously transplanted rat dental pulp.

While dental pulp appears to be able to form mineralized matrices that do not always resemble dentin, the precise characteristics of the hard tissue and the mechanism of its induction remain unknown. Therefore, we evaluated hard tissue induced by transplantation of pulp into subcutaneous tissue. Seven days after transplantation, initial hard tissue was formed at the inner periphery of the pulp. After 14 days, this hard tissue expanded inwardly. Mineralized matrix was immunopositive for osteocalcin, osteopontin, and bone sialoprotein, but negative for dentin sialoprotein. Transplantation of GFP-labeled pulp into wild-type rats showed these formative cells to have been derived from the transplant. TEM observation revealed apatite crystals within necrotic cells and matrix vesicles at the initial stage of calcification. These results indicate that pulp cells possess the ability to form a bone- or cementum-like matrix. Calcification of the matrix may occur in necrotic cells and matrix vesicles, followed by collagenous calcification.

Perioperative real-time monitoring of indocyanine green clearance by pulse spectrophotometry predicts remnant liver functional reserve in resection of hepatocellular carcinoma.

BACKGROUND: There is no standard method for predicting remnant liver functional reserve after hepatectomy or for monitoring it in real time. METHODS: Indocyanine green (ICG) clearance (K) was measured non-invasively and instantaneously using pulse spectrophotometry before surgery, during inflow occlusion and after hepatectomy in 75 patients who underwent anatomical liver resection for hepatocellular carcinoma (HCC). RESULTS: Eight patients (11 per cent) suffered liver failure and one (1 per cent) died in hospital. An estimated remnant K value of 0.090 per min was the cut-off value for liver failure. In a logistic regression model, the estimated remnant K (0.090 per min; P = 0.022) and age (65 years; P = 0.025) were significant predictors of postoperative liver failure. There was a correlation between the estimated and measured post-hepatectomy K, and between the inflow occlusion K and measured post-hepatectomy K (P < 0.001). The cut-off value of less than 0.090 per min for the estimated remnant K resulted in 88 per cent sensitivity and 82 per cent specificity for predicting liver failure. CONCLUSION: Perioperative real-time monitoring of ICG-K is useful for evaluating the remnant liver functional reserve before, during and after liver resection for HCC. The estimated remnant K is a significant predictor of liver failure.

A large inflammatory fibroid polyp of the colon treated by endoclip-assisted endoscopic polypectomy: A case report.

Inflammatory fibroid polyp is a rare benign polypoid lesion of the gastrointestinal tract. Histologically, inflammatory fibroid polyp is characterised by an admixture of numerous small vessels, fibroblasts and oedematous connective tissue, accompanied by marked inflammatory infiltration by eosinophils. A 40-year-old man visited our hospital for the purpose of colorectal screening due to a positive faecal occult blood test. A pedunculated and reddish polyp was found endoscopically in the ascending colon. The polyp was large but was resected endoscopically without any problems. Histologically, the abnormal tissue of the polyp was located in the submucosal and mucosal layer. Proliferation of spindle cells and infiltration of inflammatory cells, such as plasma cells and eosinophils, were observed. Immunohistochemically, the spindle cells were positive for CD34, which was localised in the cytoplasm. These cells were also positive for S100 protein but were negative for c-kit and muscle markers. These findings are compatible with the histological diagnosis of inflammatory fibroid polyp. The surgical margin of the polyp was free of the tumour. Inflammatory fibroid polyp is more commonly found in the stomach or small intestine, and rarely in the colon, and therefore our case is a rare example of large and pedunculated colonic inflammatory fibroid polyp, which was treated successfully by endoscopic polypectomy.

Expression of a CD44 variant and VEGF-C and the implications for lymphatic metastasis and long-term prognosis of human breast cancer.

The aim of the present study was to determine whether expression of the CD44 variant v7-v8 (CD44v7-v8) or vascular endothelial growth factor-C (VEGF-C) is associated with long-term prognosis in breast cancer patients. A 10-year follow-up of 91 patients with primary breast cancer who were previously assessed for CD44 expression was undertaken. Immunohistochemical evaluation of VEGF-C expression was performed in 87 of these patients and their long-term prognosis was assessed. The disease-free and overall survival rates were significantly poorer for the CD44v7-v8-positive patients than for the patients negative for this marker. VEGF-C expression was detected in 38 out of the 87 patients (43.7%) with primary human breast cancer. There were no significant differences in tumor size, histological type, axillary lymph node status, presence of lymphatic or venous invasion, or presence of estrogen receptors and progesterone receptors between the VEGF-C-positive and -negative patients. There were also no significant differences in the disease-free or overall survival rates in these patient groups. In conclusion after the 10-year follow-up, expression of CD44v7-v8 was associated with poor prognosis for breast cancer patients. However, there was no association between VEGF-C expression and the clinicopathological factors or prognosis of breast cancer patients.

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species.

[Effect of G-CSF (nartograstim) on neutropenia (leukopenia) induced by taxane in metastatic breast cancer--time-course changes in neutrophil and leukocyte counts].

Since 1997, we have used docetaxel and paclitaxel as the second-line and third-line chemotherapies against anthracycline-resistant metastatic breast cancer. However, these taxane compounds induced neutropenia and leukopenia, which may be reversed by G-CSF (Nartograstim). We thus examined the therapeutic efficacy of nartograstim for time-course changes in neutrophil and leukocyte counts in these patients. No difference was observed in neutrophil or leukocyte count whether the patient was treated with docetaxel or paclitaxel. Neutrophil and leukocyte counts reached a nadir on days 7 to 8 after administration. With a 5-6 day administration of nartograstim, neutrophil or leukocyte counts recovered by the second or third day after the nadir, indicating that the chemotherapy was given safely with nartograstim. In these same patients receiving a given treatment cycle, the number of days until reaching the nadir were almost identical for neutrophils and leukocytes; however, the duration of the nadir and the time to count recovery was significantly longer for neutrophils than for leukocytes. In the clinical setting, the parameter "leukocyte count" has been occasionally used for evaluation of the severity of myelosuppression, because the data is more readily available. However, at least during the nadir, the "neutrophil count" should be used as the parameter of choice.

Saturated FFAs, palmitic acid and stearic acid, induce apoptosis in human granulosa cells.

Obesity is associated with insulin resistance and some reproductive abnormalities. Circulating FFAs are often elevated in obese subjects and are also closely linked to insulin resistance. In this study, we demonstrated that saturated FFAs, such as palmitic acid and stearic acid, markedly suppressed the granulosa cell survival in a time- and dose-dependent manner. Polyunsaturated FFA, arachidonic acid, had no effect on the cell survival, even at supraphysiological concentrations. The suppressive effect of saturated FFAs on cell survival was caused by apoptosis, as evidenced by DNA ladder formation and annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effects of palmitic acid and stearic acid were unrelated to the increase of ceramide generation or nitric oxide production and were also completely blocked by Triacsin C, an inhibitor of acylcoenzyme A synthetase. In addition, acylcoenzyme A, pamitoylcoenzyme A, and stearylcoenzyme A markedly suppressed granulosa cell survival, whereas arachidonoylcoenzyme A had no such effect, and this finding was consistent with the effect of the respective FFA form. Surprisingly, arachidonic acid instead showed a protective effect on palmitic acid- and stearic acid-induced cell apoptosis. A Western blot analysis showed the apoptosis of the granulosa cells induced by palmitic acid to be accompanied by the down-regulation of an apoptosis inhibitor, Bcl-2, and the up-regulation of an apoptosis effector, Bax. These results indicate that saturated FFAs induce apoptosis in human granulosa cells caused by the metabolism of the respective acylcoenzyme A form, and the actual composition of circulating FFAs may thus play a critical role in the apoptotic events of human granulosa cells. These effects of FFAs on granulosa cell survival may be a possible mechanism for reproductive abnormalities, such as amenorrhea, which is frequently observed in obese women.

Biological activity of alpha-thujaplicin, the minor component of Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO.

Alpha-thujaplicin, a minor component of Thujopsis dolabrata SIEB. et ZUCC. var. hondai MAKINO, which was synthesized, showed the antibacterial activity, phytogrowth-inhibitory effect, inhibition of carboxypeptidase A and cytotoxic effect. Antibacterial activity of alpha-thujaplicin on Enterococcus faecalis IFO-12965 [minimum inhibitory concentration (MIC): 1.56 microg/ml] was higher than that of gentamicin (MIC: 6.25 microg/ml) used as a positive control. Inhibitory activity of alpha-thujaplicin on carboxypeptidase A [50% inhibitory concentration (IC50): 3.24 x 10(-5) M] was higher than that of 1,10-phenanthroline used as a positive control. Alpha-thujaplicin showed germination inhibition toward the seed of Echinochloa utilis Ohwi et Yabuno even at the low concentration of 10 ppm and its growth inhibitory effect was stronger than that of sodium 2,4-dichlorophenoxyacetate used as a standard. Alpha-thujaplicin at 1.25 microg/ml inhibited cell growth of human stomach cancer KATO-IIl by 86%, and Ehrlich's ascites carcinoma by 87%, respectively. This compound even at the low concentration of 0.32 microg/ml also inhibited cell growth of the former by 66%, and the latter by 75%, respectively. The acute toxicity of alpha-thujaplicin [50% lethal dose (LD50) value: 256 mg/kg] in mice was as strong as those of beta-dolabrin (LD50 value: 232 mg/kg) and gamma-thujaplicin (LD50 value: 277 mg/kg).

The subnuclear three-dimensional image analysis of androgen receptor fused to green fluorescence protein.

To establish the novel approach in order to distinguish the transcriptionally active androgen receptor (AR) from the transcriptionally inactive AR, we performed the three-dimensional construction of confocal microscopic images of intranuclear AR. This method clearly distinguished the subnuclear localization of transcriptionally active AR tagged with green fluorescent protein (AR-GFP) from the transcriptionally inactive AR-GFP. Transcriptionally active AR-GFP mainly produced 250-400 fluorescence foci in the boundary region between euchromatin and heterochromatin. Although the AR-GFP bound to such antiandrogens as hydroxyflutamide or bicalutamide translocated to the nucleus, they homogeneously spread throughout the nucleus without producing any fluorescence foci. Antiandrogenic environmental disrupting chemicals, such as 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, vinclozolin, or nitrofen, also disrupted the intranuclear fluorescence foci. A point mutation (T877A) resulted in the loss of ligand specificity in AR-GFP. Even in this mutant receptor, agonists, such as dihydrotestosterone, hydroxyflutamide, or progesterone, produced the fluorescence foci in the nucleus, whereas the transcriptionally inactive mutant binding bicalutamide was observed to be spread homogeneously in the nucleus. Taken together, our findings suggest that, after nuclear translocation, AR is possibly located in the specific region in the nucleus while demonstrating clustering tightly depending on the agonist-induced transactivation competence.

Cytotoxicity of the hinokitiol-related compounds, gamma-thujaplicin and beta-dolabrin.

Gamma-thujaplicin and beta-dolabrin, the constituents of the wood of Thujopsis dolabrata Sieb. et Zucc. var. hondai showed strong in vitro cytotoxic effects against the human stomach cancer cell lines KATO-III and Ehrlich's ascites carcinoma. The cytotoxic effects of the two compounds against both tumor cell lines were clear when cell growth was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Gamma-thujaplicin and beta-dolabrin at 0.32 microg/ml inhibited cell growth of human stomach cancer KATO-III by 85 and 67%, and Ehrlich's ascites carcinoma by 91 and 75%, respectively. There is no large difference in cytotoxicity between these compounds, but the activity of gamma-thujaplicin was slightly more potent than that of beta-dolabrin. On the other hand, hinokitiol acetate did not show a cytotoxic effect, suggesting that at least a part of the mechanism of the cytotoxic effect of hinokitiol-related compounds is due to metal chelation between the carbonyl group at C-1 and the hydroxyl group at C-2 in the tropolone skeleton of these molecules. The acute toxicities [50% lethal dose (LD50) value: intraperitoneal injection, Van der Waedem] of gamma-thujaplicin and beta-dolabrin in mice were 277 mg/kg and 232 mg/kg, respectively.

[The sensitivity and clinical implications of periodical bladder biopsy following transurethral resection of superficial bladder transitional cell carcinoma].

The role of the periodical bladder biopsy after transurethral resection (TUR-Bt) of superficial bladder cancer (sBT) was evaluated. Sixty-four patients (85 TURs) with sBT who underwent TUR-Bt between 1993 and 1998 were divided into 14 (22 TURs) who had carcinoma in situ (CIS) at the first TUR (group A), and 50 (64 TURs) who had papillary tumors without concomitant CIS (group B). Post-TUR intravesical instillation was performed with bacillus Calmette-Guerin for the majority of group A, and mitomycin C for the majority of group B. The first biopsy was performed at 3 months postoperatively, and the second biopsy was done at 8 to 12 months postoperatively. The mean observation time was 4 years and 6 months. Residual cancer was detected in 7 out of 34 biopsies (20.6%) in group A, and 19 out of 94 (20.2%) in group B. Every residual lesion in group A was CIS with negative cytology. In group B, with exclusion of 11 recurrent papillary tumors, the detection rate was only 8/83 (9.6%). In both groups, even in the cases with no sign of disease in biopsies, the recurrence immediately after the termination of the biopsy protocol was common. The progression of the cancer was more frequent in group A (4 patients), than in group B (2 patients) (p < 0.01, log-rank test), and no case in group B showed local progression. The periodical biopsy may have a certain, but limited advantage over conventional examinations. A less invasive and more sensitive method in awaited.

Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.

We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17alpha-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)(2)cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.

Regulation of aromatase by nuclear receptors.

We investigated the effects of a nuclear receptor system constituted by retinoid X receptor (RXR) and its heterodimer partner on the aromatase activity in a cultured MCF-7 human breast cancer cell line and also in human ovarian granulosa cells, using each selective ligand for retinoic acid receptor, RAR (TTNPB), retinoid X receptor, RXR (LG100268), PPARgamma (troglitazone), and vitamin D3 receptor (cholecalciferol). In MCF-7 cells, the combined treatment with TTNPB and LG100268 caused a dramatic stimulation of the aromatase activity. The combined treatment with other ligand and LG100268 had little or no effect on the aromatase activity. The increase in the aromatase activity by TTNPB plus LG100268 was accompanied by an increase in the P450arom mRNA levels, which was also found to be related to the specific usage of promoter 1a of the CYP19 gene. These results suggest that a nuclear receptor system constituted by a RAR:RXR heterodimer is involved in the regulation of aromatase activity in MCF-7 breast cancer cells. In cultured human ovarian granulosa cells obtained from patients who underwent in vitro fertilization, troglitazone or LG100268 alone decreased the aromatase activity, while the combined treatment caused an even greater reduction in this activity. Little effect of other specific ligands for RXR heterodimer partners may support the notion that the effects of troglitazone and/or LG100268 in human granulosa cells may be mediated through the specific activation of PPARgamma:RXR heterodimer system. Since similar manners of effects of several PPARgamma ligands and/or LG100268 on the aromatase activity were observed in a newly established human ovarian granulosa cancer cell line, KGN, we performed the detailed analysis of the mechanisms of these effects using this cell line. As a result, the inhibitory effect of aromatase activity by troglitazone plus LG100268 was accompanied by the decrease of P450arom mRNA level. Furthermore, the loss of P450arom expression was considered to be due to both the decreased transcription and rapid degradation of its RNA based on the studies of nuclear run-on assay and RNA stability assay. In conclusion, RAR:RXR and PPARgamma:RXR heterodimer nuclear receptor systems may be other important modulators of estrogen production in human breast cancer cells and ovarian granulosa cells, respectively.

[Evaluation of "Helicobacter-Selective-Medium (Nissui Seiyaku)" for rapid detection of Helicobacter pylori].

We evaluated Helicobacter Selective Agar (HSA) medium (Nissui Pharmaceuticals Co., Ltd., Tokyo, Japan), which has been newly developed and has been commercially available since June in 1998. HSA medium strongly inhibited the growth of possible contaminants from gastric biopsy-specimens, such as alpha-streptococci, Neisseria species, Enterococcus gallinarum, Pseudomonas aeruginosa, Corynebacterium species, Capnocytophaga species, and Candida albicans. Cultures run in parallel with Helicobacter Pylori Agar (HPA) medium (Eiken Chemical Co., Ltd., Tokyo, Japan) disclosed no discordance in the detective rates of H. pylori strains between the media examined. Inaddition, the numbers of the colonies and the colony-sizes grown on the plates were also in good agreement with each other. However, it would be strikingly favorable that the appearing colonies on the HSA medium turned purple. This coloration enabled us to detect the emergence of the colonies much earlier and easier when compared with the conventional other media including HPA medium (Eiken). These findings led us to conclude that HSA medium (Nissui) was superior to HPA medium (Eiken) in the prompt detection and the rapid identification of H. pylori in routine clinical microbiology.

Repeat intervention for in-stent restenosis: re-expansion of the initial stent is a predictor of recurrence of restenosis.

BACKGROUND: In-stent restenosis has become a significant clinical problem as use of stents has increased. The optimal strategy for dealing with in-stent restenosis needs to be evaluated. OBJECTIVE: To compare the acute and late results of interventions for in-stent restenosis according to the device used, and to analyze the clinical and procedural variables of the lesions treated and identify the determinants of recurrence of restenosis and target lesion revascularization (TLR). METHODS: Procedural and late outcomes for 58 lesions in 50 patients who underwent repeat intervention for in-stent restenosis were analyzed. The results of interventions according to the device employed were compared. The predictors of recurrence of restenosis and TLR within 6 months were analyzed. The ratio of balloon diameter in repeat intervention to minimal lumen diameter after initial stenting (MLD0) was used as an index of re-expansion of stents. Serial intravascular ultrasound imaging was performed before and after repeat intervention for 33 lesions, and re-expansion of the initial stent was evaluated. RESULTS: Repeat intervention was successful in treating all lesions. Angiographic follow-up was possible for 49 lesions (84%). The overall incidences of recurrence of restenosis and TLR were 40.1 and 27.6%, respectively. Despite the immediate results having been good, the late results of stenting for in-stent restenosis were not favorable. Diffuse-type in-stent restenosis, early in-stent restenosis, and balloon diameter:MLD0 ratio > 1.25 are independent predictors of poor late results. Intravascular ultrasound findings have shown that expansion of the initial stent leads to recurrence of restenosis and TLR. CONCLUSIONS: Re-expansion of the initial stent can cause further vascular injury and there is a risk of recurrence of restenosis. Alternative therapeutic strategies that work without dilating the initial stent may be necessary for treating lesions with high risk of recurrence of restenosis.

[The effect of combination chemotherapy to adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in patients with gastric or colorectal cancer].

We performed combination chemotherapy adapted to chronotherapy with 5-fluorouracil, leucovorin, mitomycin C and cisplatin in 11 patients with gastric cancer and 7 with colorectal cancer. Treatment consisted of a 5-day course of continuous arterial or intravenous infusion of 5-FU (500 mg/body/day), arterial or intravenous infusion of leucovorin (20 mg/body/day) at 6:00 p.m. on days 1-5, arterial or intravenous infusion of mitomycin C (2 mg/body) at 9:00 a. m. on day 5, and arterial or intravenous infusion of cisplatin (20-80 mg/body) at 6:00 p.m. on day 5. The effective rate against gastric cancer was 73%; however, the effective rate against colorectal cancer was 29%. During and after this therapy, there was only a little appetite loss, nausea and stomatitis.