Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

Dental management of a patient with takotsubo cardiomyopathy: a case report.

Takotsubo cardiomyopathy (TCM) is a relatively new concept in cardiovascular disease. The clinical symptoms of TCM are similar to those of a myocardial infarction, but both the mechanism and the management of TCM are different from those of myocardial infarction. The cause of TCM is unclear, but it is suggested to occur in conjunction with excessive circulating catecholamines due to stress. Thus, control of the stress reaction and restriction of catecholamine levels are considered important for prevent of TCM onset. We report the dental management of a patient with intellectual disability who had anamnesis of TCM and cardiopulmonary arrest under restraint during a previous dental appointment in another dental clinic. We used intravenous sedation with both midazolam and propofol, by which the excessive hormonal reaction that caused TCM onset and cardiopulmonary arrest was controlled, for dental treatment in our facility. All planned dental treatment was then performed without any problems.     

Combined cisplatin and radiation therapy in patients with invasive bladder cancer

Thirty-five patients with T2–T4 invasive bladder cancer were treated with combined cisplatin and radiation therapy. In 18 patients radical cystectomy was performed after the combined therapy. In the other 17 patients radical cystectomy could not be performed for various reasons. Pathological examination of the cystectomy specimens showed down-staging in 66.7% and no residual tumour in 33.3%. These results suggest a synergistic action of cisplatin and radiation. Side effects were not severe and were well tolerated. This combined therapy of cisplatin and radiation is very effective for invasive bladder cancer.     

Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants

Background: Only few data exist on pharmacokinetics of tacrolimus in children. Patients: In 1995 and 1996, 14 children (mean age 13 years, range 5-23 years) received tacrolimus after renal transplantation; 10 of these after biopsy-proven steroid-resistant rejection (2 with vascular rejection), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one for untreatable gingival hyperplasia on CsA, and one child was treated primarily after transplantation because of severe liver involvement in nephronophthisis. Pharmacokinetic investigations were performed after establishing a stable maintenance dose with trough levels in the desired window of 5-12 ng/ml. Results: Mean follow-up time was 6 months (range 3-25 months). Eleven patients were still on tacrolimus. Two were discontinued because of severe aggravation of chronic persistent hepatitis C (one of them also developed diabetes mellitus),and one patient was subsequently switched to conventional immunosuppression because of tacrolimus-associated nephrotoxicity. All tacrolimus levels were measured by a modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity. At the time of switch, median serum creatinine was 234±82 7mgr;mol;l and 6 months after switch 201±99 &mgr;mol/l. All grafts are still functioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range 0.036-0.30 mg/kg). Mean trough level was 7.1±2.6 ng/ml in the morning and 6.5±2.0 ng/ml in the evening. Median time of maximum concentration (tmax) was 120 min after application, and the mean maximum concentration (Cmax) was 15.2±6.7 ng/ml. Mean area under the curve (AUC) was 104±33 ng * h/ml, with a range from 65 to 169 ng * h/ml. No patient had unsatisfactorily low trough levels during the study. There was only a weak but significant (P<0.05) correlation between dose per kg body weight and AUC and, as expected, an excellent correlation (r²=0.73, P<0.001) between AUC and trough level. Conclusion: Because of interindividual variation between patients, therapeutic drug monitoring of tacrolimus is mandatory. In this study, a daily dose of 0.15 mg/kg was sufficient in most patients. We recommend the performance of at least one pharmacokinetic study after establishing stable FK 506 trough levels to ascertain a safe profile.     

组织多肽特异性抗原在乳腺癌中的临床研究

OBJECTIVE: To investigate the expression of serum tissue polypeptide-specific antigen (TPS) in breast cancer patients and its clinical value in such cases. METHODS: Altogether 160 subjects (90 patients with breast cancer, 40 with benign breast lesions, and 30 healthy subjects) were enrolled in this study. The serum TPS and CA153 levels were measured by ELISA in all the subjects. RESULTS: The levels and positivity rate of serum TPS and CA153 in breast cancer group were significantly higher than those in the normal subjects group and benign lesion group (P<0.01), and became even higher as the malignancy progressed. High serum TPS level was detected in the cancer patients in stage I. Serum TPS level was the most sensitive to bone metastasis of the malignancy, but its highest levels occurred in cases of lymphoid node metastasis (P<0.05). In patients who responded favorably to the treatment, serum TPS and CA153 levels were significantly reduced (P<0.05), but the reduction in TPS levels tended to be more obvious (P<0.05). CONCLUSION: Serum TPS can be used as a very useful and sensitive tumor marker in the diagnosis of breast cancer, especially in case of bone metastasis, and may be of great value in clinical decision-making and assessment of therapeutic effect.     

Pharmacokinetics of clarithromycin granule and tablet in children

It has been known that clarithromycin (TE-031, A-56268), a new macrolide antibiotic (ML), achieves higher concentrations in blood, is better excreted into urine and is better distributed into various tissues than conventional MLs. We investigated the pharmacokinetics of TE-031 in children upon oral administration of the drug in the following method. TE-031 granular preparation with a potency of 100 mg/g was given to 6 boys (5 years 4 months-14 years 0 month) with dose levels of 5 mg/kg and 10 mg/kg for each 3 boys. A tablet preparation with each tablet containing 50 mg of TE-031 was administered to 4 boys and 2 girls (8 years 5 months-11 years 6 months) with dose level of 2 tablets (i.e., 100 mg) and 3 tablets (i.e., 150 mg) for each 3 children. All administrations were done at 30 minutes before meal. Then, to conduct a cross-over test, the granule preparation was given orally to the 3 children mentioned above who was given 2 tablets and the 1 of 3 cases that were given 3 tablets at the same dose levels (100 mg and 150 mg) respectively. A bioassay was used to determine concentrations in blood of active antibiotic compounds and an high performance liquid chromatography (HPLC) was used to determine unchanged TE-031 and its main metabolite, M-5. Urinary concentrations of active antibiotic compounds were also determined by the bioassay and the HPLC was used to determine concentrations and proportions of unchanged TE-031 and its metabolites, M-1, M-4, M-5, M-6 and M-7 to figure out the urinary recovery rate in the first 6 hours. The results of these experiments are summarized as follows. 1. As was mentioned above, TE-031 was administered orally to 2 groups of children at dose levels of 5 mg/kg and 10 mg/kg, respectively. Mean serum levels of total active antibiotic compounds reached their maximum in 1 and 2 hours for the 5 mg/kg and the 10 mg/kg dosage groups, respectively, at 1.28 and 3.62 micrograms/ml, respectively. Mean half lives of serum concentrations in the 2 groups were quite similar, with values of at 2.1 and 2.0 hours, respectively. Mean serum concentrations of unchanged TE-031 determined by the HPLC method reached their peaks in 1 hour after administration in either of the 5 and 10 mg/kg dosage groups at peak levels of 0.65 micrograms/ml and 2.67 micrograms/ml, respectively. Thus, dose-response relationships were observed with TE-031 and M-5.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pharmacokinetics of amikacin in children and neonates

To evaluate pharmacokinetics of amikacin (AMK), one of the aminoglycoside antibiotics, children with ages from 2 days to 11 years were treated with various doses by various administration routes, and both plasma and urinary levels of AMK were determined. The following is a summary of the results obtained: 1. Of 6 children, three were treated with 2.0 mg/kg of AMK by a 30-minute intravenous drip infusion, and the other 3 with 4.0 mg/kg by a 60-minute. Peaks of average plasma levels were observed at the ends of the infusions in both cases, and their levels were 9.23 and 13.67 micrograms/ml, respectively, showing a dose-dependency. Both half-lives and areas under plasma concentration-time curves (AUCs) were similar to those of adults. However, the volume of distribution (Vd) showed a lower value than that of adults. Peaks of average urine levels were 149.3 micrograms/ml with 2.0 mg/kg in 0-2 hours after the start of the infusion and 223.3 micrograms/ml with 4.0 mg/kg in 2-4 hours. Average urinary recovery rates within 6 hours after the start of the infusion were 95.4% with 2.0 mg/kg and 85.7% with 4.0 mg/kg. These recoveries were equal to or higher than that of adults. 2. When 3.0, 4.0 and 6.0 mg/kg of AMK were administered to 3 groups of mature or premature babies by intramuscular injection, average peak levels of AMK in plasma were 6.26, 8.61 and 12.60 micrograms/ml, respectively, at 30 minutes after the injection, showing dose-dependency. In these groups, the younger the day age after birth was, the longer the half-life became. The AUCs were larger as the half-life became longer. The Vd was larger than that in the intravenous drip infusion group, but, any particular was not observed. Average peak levels of AMK in urine were 78.83 micrograms/ml at 4-6 hours with a dose level of 3.0 mg/kg, 99.17 micrograms/ml at 2-4 hours with 4.0 mg/kg and 139.20 micrograms/ml at 0-2 hours with 6.0 mg/kg. Average urinary recovery rates within 6 hours were 36.57% with 3.0 mg/kg, 34.67% with 4.0 mg/kg and 43.77% with 6.0 mg/kg. These recovery rates were markedly lower than those observed in adults and children. One of the causes of this low recovery is that mature and premature babies have immature renal functions. 3. When 3.0 mg/kg of AMK was administered to three premature babies by a 30-minute intravenous drip infusion, the average peak plasma levels was 7.61 micrograms/ml at the end of the drip infusion.(ABSTRACT TRUNCATED AT 400 WORDS)     

爱母分娩工程初探——产程系列服务模式

爱母分娩工程的核心是产时分娩的管理，除医疗技术水平为重要因素外，改善产科系列服务模式，加强孕妇夫妇有关培训与健康教育，加强保健与临床的结合，对爱母分娩工程的作用亦是举足轻重的。广东省妇幼保健院试运行产时分娩管理新模式、产科系列服务新模式，提高了产科质量和社会效益及经济效益。     

Treatment strategies for hepatic metastasis from colorectal cancer

Hepatic micrometastases of the parenchyma adjacent to a macroscopic lesion were detected in 17 of 31 resected liver metastases. Fifty-nine micrometastatic lesions were detected in total; 26 lesions were situated in the portal vein (PV), 22 in the central vein (CV), 5 in the bile duct (BD), and 6 in the sinusoid (SS). A histological study confirmed the direct invasion of the macrometastatic cancer cells into the adjacent PV, CV, BD, and SS. According to the tumor doubling time, the mean diameter of the macrometastases in 19 remnant livers was calculated to have been 0.57±0.87 cm at the time of the primary resection. The calculated diameter of 3 of these 19 macrometastases was found to be less than 0.01 cm, the minimum implantable size, indicating that the cancer recurrence in these specimens may have developed from macroscopic metastatic lesions as a satellite, and not from the primary tumor. In 13 patients who received doses of 5250 mg or more of 5 fluorouracil (FU) via the hepatic artery, the cumulative disease-free rate 2 years postoperatively was 100%; this value was 47.6% in 11 patients who received less than 5250 mg of 5 FU via the hepatic artery, and 0% in 39 patients who received no chemotherapy (P<0.005). These results suggest that anatomical hepatic resection for satellite lesions, combined with prophylactic hepatic arterial chemotherapy for micrometastases, decreases the recurrence rate of hepatic metastases in the remnant liver.