Serum Bile Acid Levels in Preoperative and Postoperative Patients with Congenital Biliary Atresia

To elucidate the bile acid metabolism in the preoperative and postoperative stages of congenital biliary atresia (CBA), the unconjugated and conjugated bile acid levels in sera were measured by high performance liquid chromatography (HPLC). The results showed that the mean total serum bile acid (TSBA) level in the preoperative cases of CBA was higher, 122.1±39.0 n?mol/1 (1SD), and was about 12 times higher than the level in the age-matched normal controls (9.9±6.0). Even in the non-icteric patients several years after operation, the mean TSBA level was still much higher (15.2±9.6) than that of normal controls (5.7±3.1). The mean ratio of cholic acid to chenodeoxycholic acid (CA/CDCA) in the preoperative and postoperative cases of CBA was less than 1.0. The mean ratio of glycine-conjugated bile acids to taurine-conjugated bile acids (G/T) in the preoperative cases of CBA was the lowest (1.9±1.1). In the clinically good cases with sufficient bile flow after operation, G/T ratio was the highest (9.3±6.5). In the normal controls and the patients with preoperative and postoperative CBA, the main bile acids were glycocholic acid, taurocholic acid, glycochenodeoxycholic acid and taurochenodeoxycholic acid. These conjugated bile acids comprised more than 85% of the total in amount.     

Alternate-day oral therapy with TS-1 for advanced gastric cancer

Background TS-1 (1M tegafur-0.4M 5-chloro-2,4-dihydroxypyrimidine-1M potassium oxonate) has a high single-agent response rate, of more than 40%, for gastric cancer; however, the recommended regimen of 4 weeks of administration interrupted by 2 weeks of drug withdrawal frequently causes adverse effects. The alternate-day dosage of pyrimidine fluoride anticancer drugs could reduce their adverse effects without compromising their effects. We attempted an alternate-day therapy with TS-1 aiming at the avoidance of adverse effects and significantly longer duration of administration.Methods We observed patients for clinical effects and adverse effects under alternate-day dosage of TS-1, and determined blood 5-fluorouracil (FU) levels. The judgment of clinical effects was based on the New Guidelines to Evaluate the Response to Treatment in Solid Tumors (RECIST), whereas the evaluation of adverse effects was based on the National Cancer Institute NCI-common toxicity criteria (CTC).Results In 72 (78%) of 92 patients, the TS-1 regimen was converted to the alternate-day dosage because of adverse effects. Twenty patients were treated with the alternate-day dosage regimen from the start because of the fear of adverse effects. The alternate-day dosage was clinically effective, as 28 of 34 patients after relatively curative resection remained alive and free from recurrence. The median survival time of 58 patients after noncurative resection or with unresectable or recurrent cancer was 332 days. Fifty-three percent of these 58 patients achieved partial response and stable disease of more than 12 weeks duration. We followed time-dependent changes in blood 5-FU levels in 36 of the patients on alternate-day therapy, in whom TS-1 had been administered daily before being administered every other day. The trough level was significantly lower when TS-1 was administered on alternate days, and blood 5-FU reached a peak at sufficiently effective levels at 2h even after administration on the alternate-day basis.Conclusion This study demonstrated that, compared with daily administration, alternate-day administration of TS-1 reduces adverse effects, and simultaneously ensures effective blood levels and provides sufficient clinical effects.     

Expression and distribution of c-kit receptor and its ligand in human CNS germ cell tumors: A useful histological marker for the diagnosis of germinoma

We previously reported the expression of protooncogenec-kit in CNS germ cell tumors and suggested that the soluble form of c-kit (s-kit) may represent a specific clinical marker for germinoma-containing tumors. Here we investigated the expression of stem cell factor (SCF), a specific ligand of c-kit, in CNS germ cell tumor samples from 16 patients, using immunohistochemical methods to assay the expression of c-kit and SCF protein. The immunostaining patterns of c-kit and SCF were almost identical. In all germinoma-containing tumors, c-kit and SCF were diffusely expressed on the surface of germinoma cells; lymphocytes and interstitial cells were negatively stained. In immature teratomas, only some mature components, e.g., cartilage and gland, were immunoreactive for c-kit and SCF. Syncytiotrophoblastic giant cells (STGCs) were negative for both SCF and c-kit, suggesting that germinoma cells primarily coexpress SCF and c-kit. The coexpression of c-kit and SCF may be an important immunohistochemical marker for the diagnosis of CNS germinoma, and the SCF/c-kit pathway may be an alternative molecular target for the treatment of human CNS germinomas.     

Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression

We used an experimental murine cancer metastasis model in which a colon adenocarcinoma cell line generates lung metastases, whose growth is stimulated in response to injection of bacterial lipopolysaccharide (LPS), to investigate the role of NF-kappaB in inflammation-induced tumor growth. We found that LPS-induced metastatic growth response in this model depends on both TNFalpha production by host hematopoietic cells and NF-kappaB activation in tumor cells. Inhibition of NF-kappaB in both colon and mammary carcinoma cells converts the LPS-induced growth response to LPS-induced tumor regression. The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells.     

Diamond-Blackfan Anemia in Japan: Clinical Outcomes of Prednisolone Therapy and Hematopoietic Stem Cell Transplantation

The epidemiology and treatment outcomes for Diamond-Blackfan anemia (DBA) were surveyed in a cohort of 54 children (M/F = 26:28) registered in Japan from 1988 to 1998. The annual incidence was 4.02 cases per million births, the median age at diagnosis was 60 days, and 59% of the cases presented by 3 months of age. Three patients had a familial occurrence. All patients received prednisolone (PSL), and cyclosporin A (CsA) was added to the therapy in 17 patients. Forty-seven patients received transfusions, and 13 underwent hematopoietic stem cell transplantation (HSCT). The cumulative probabilities of a medication-free or a transfusion-free state prior to HSCT were 36% and 69%, respectively, at more than 5 years after diagnosis. Thirteen patients were weaned from PSL therapy without HSCT, and CsA was not associated with weaning from therapy. Transfusion and medication were stopped at 249 days and 933 days after diagnosis in 34 and 13 patients, respectively, who achieved a state of independence. No initial findings predicted the treatment dependence. More than 20% of patients experienced sustained hemosiderosis and/or adverse effects of PSL. The ages and reticulocyte counts at diagnosis of the patients who underwent HSCT were lower than in the patients who did not. HSCT led to the highest success (85%) of all previous reports, even though 5 alternative donors were included in our study. Two cord blood transplants from unrelated donors failed. These findings suggest the need for developing an integral treatment strategy including selective HSCT for refractory DBA.     

Additional effect of SERM: central nervous system

Raloxifene is a selective estrogen-receptor modulator recently launched in Japan as a new medicine for treatment of postmenopausal osteoporosis. Raloxifene stimulates neurite outgrowth in cultured cells and increases hippocampal cholineacethyl trasferase activity and serotonin receptor in the brain of ovariectomized rats. As a part of the Multiple Outcomes of Raloxifene Evaluation trial, 7,478 postmenopausal women with osteoporosis were studied by using six tests of cognitive function. There was some evidence that Raloxifene may lower the risk of a decline in memory and attention. It is expected that novel SERM, which has more specific efficacy improving cognitive function will be developed.     

Impact of previous multiple portoenterostomies on living donor liver transplantation for biliary atresia

BACKGROUND/AIMS: The present study examined the impact of portoenterostomy on the morbidity and mortality of patients who later underwent living donor liver transplantation for biliary atresia. METHODOLOGY: Sixty-one consecutive patients from January 1996 to May 2001 were analyzed. They were divided into two groups according to the number of previous portoenterostomies: once (group A, n=26) and twice or more (group B, n=35). Preoperative status, mortality, morbidity, hospital duration and survival were examined and compared between the groups. RESULTS: Preoperative parameters regarding liver function and urgency status were comparable between the groups. The operation duration tended to be longer in group B than in group A (p=0.07). The blood loss and transfusion volumes in group B were greater than those in group A (p=0.03 for both comparisons). Vascular complications tended to be more frequent in group B patients. However, this difference was not significant (12% vs. 29%, p=0.06). The duration of hospitalization was longer in group B (p=0.04). Survival rates were comparable between the groups. CONCLUSIONS: Our surgical results suggest that multiple previous portoenterostomies might have negative short-term effects in patients who undergo living donor liver transplantation for biliary atresia.     

An application of a new planar positron imaging system (PPIS) in a small animal: MPTP-induced Parkinsonism in mouse

OBJECTIVE: Recent animal PET research has led to the development of PET scanners for small animals. A planar positron imaging system (PPIS) was newly developed to study physiological function in small animals and plants in recent years. To examine the usefulness of PPIS for functional study in small animals, we examined dopaminergic images of mouse striata in MPTP-induced parkinsonism. METHODS: Male C57BL/6NCrj mice were treated with MPTP 7 days before the PPIS study. Scans were performed to measure dopamine D1 receptor binding and dopamine transporter availability with [11C]SCH23390 (about 2 MBq) and [11C]beta-CFT (about 2 MBq), respectively. After the PPIS study, dopamine content in the striatum was measured by HPLC. RESULTS: The MPTP treatment significantly reduced dopamine content in the striatum 7 days after treatment. In the MPTP-treated group, [11C]beta-CFT binding in the striatum was significantly decreased compared with the control group, while striatal [11C]SCH23390 binding was not affected. Dopamine content in the striatum was significantly correlated with the striatal binding of [11C]beta-CFT. CONCLUSION: The present results suggest that PPIS is able to determine brain function in a small animal. Using PPIS, high throughput imaging of small animal brain functions could be achieved.     

Effect of flumazenil on hypoglossal and phrenic nerves activities in rabbits

BACKGROUND: Upper airway obstruction and inadequate ventilation often arise during sedation and anesthesia by benzodiazepines (Bz). Flumazenil antagonizes these effects of active benzodiazepines on the central nervous system. To estimate the influence of flumazenil on the endogenous Bz system related respiratory control, we studied the effect of flumazenil and diazepam on the neural activity and the respiratory response caused by a brief (60 sec) respiratory arrest (RA) manifested in the hypoglossal nerve (HG) and the phrenic nerve (PH) activities in rabbits. METHODS: Experiments were performed on adult rabbits which were vagotomized, paralyzed and artificially ventilated with 50% N2O, 50% oxygen and 0.5% sevoflurane. We evaluated and compared the effects of the sequential administrations of flumazenil and diazepam on the peak amplitude (AMP) as well as the root mean square (RMS) of HG and PH, and respiratory cycle (Tc). RESULTS: Flumazenil by itself increased HG activity more than PH activity with no influence on Tc. But it was not dose-related. Previous administration of flumazenil in total dose of 0.25 mg x kg(-1) could not prevent the anticipated respiratory depression caused by diazepam 2.0 mg x kg(-1). These depressions are greater in HG activity than in PH activity. Additional flumazenil 0.15 mg x kg(-1) following the administration of diazepam promptly reversed these inhibitory effects on HG activity beyond the control level. The same dose of flumazenil, however, did not reverse PH activity sufficiently. RA response was characterized by raised AMPs and augmented RMSs (deltaAMPs, deltaRMSs) with marked prolongation in Tc (deltaTc). Flumazenil and diazepam did not seem to have any influence upon these RA responses. There was a significant change in cardiovascular parameters with the tested dosages of flumazenil and diazepam, but the change was in the normal physiological range. CONCLUSIONS: These results suggest the possibility that the endogenous benzodiazepine system is likely to play an inhibitory role in the regulation of respiration, especially in the maintenance of upper airway patency but the system is unrelated to the chemosensitive-respiratory control.     

Hospital no-smoking policy could increase smoking cessation rate among preoperative patients

BACKGROUND: Although it is well known that a no-smoking policy can reduce smoking rate among hospital employees, the effect of this policy on patients' smoking behavior has not been examined. METHODS: Starting on the world no-tobacco day in 2001, the Sakai Municipal Hospital changed partial no-smoking policy into complete no-smoking policy. In this study, we examined the effect of this policy change on patients' smoking status during preoperative period. At preoperative visit, we asked a patient a change of smoking status during preoperative period. The change of patients' smoking status was compared between before and after coming into effect of no-smoking policy. RESULTS: Smoking rates at first visit to out-patient clinic of each surgical department before and after coming into effect of no-smoking policy were 35.6%(36/101) and 41.8%(28/67), respectively (P=0.317). Among these smokers, smoking cessation rates at preoperative visit before and after coming into effect of no-smoking policy were 44.4%(16/36) and 75.0%(21/28), respectively (P=0.014). CONCLUSIONS: The hospital no-smoking policy has a strong effect on improvement of patients' smoking behavior during preoperative period.