隔离饲养及给药时刻对小鼠阿米卡星药物动力学的影响

目的：研究社会环境及给药时刻对小鼠阿米卡星代谢的影响。方法：小鼠按饲养环境；隔离饲养（Ｉ）或集体饲养（Ａ）及给药时间：日中（Ｄ）及午液（Ｎ）随机分为：Ｉ－Ｄ，Ｉ－Ｎ，Ａ－Ｄ，Ａ－Ｎ４组，饲养４周后于Ｄ（１３：００）或Ｎ（０１：００）ｓｃ阿米卡星１５ｍｇ．ｋｇ＾－１测定给药后血浆浓度，以开放一室模型拟合计算有关药代动力学参数，结果：Ａ－Ｎ组阿米卡星清除较率Ａ－Ｄ及Ｉ－Ｎ组增大，血浆半衰期变短，０－１     

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.     

Sparfloxacin pharmacokinetics in healthy volunteers: the influence of acidification and alkalinization

Objective: To investigate the effect of acidification and alkalinization on the pharmacokinetics of sparfloxacin in healthy subjects. Methods: A single 200-mg oral dose of sparfloxacin was given to nine healthy Japanese volunteers on three separate occasions under different conditions of urinary pH. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride and sodium bicarbonate, respectively. The concentrations of sparfloxacin and its metabolite in plasma and urine were determined by high-performance liquid chromatography assays. Results: The difference between treatments for C_max, AUC_∞, and CL · f⁻¹ were found to be significant. The relative bioavailability of sparfloxacin was 84.4% and 122.3% after ammonium chloride and sodium bicarbonate treatments, respectively. The amount of unchanged sparfloxacin in urine samples collected 0–48 h after sparfloxacin administration represented 10.1% of the dose in the control, 14.3% of the dose in urine acidification and 8.4% of the dose with alkalinization of urine. Renal clearance was found to depend on urinary pH. However, the plasma elimination and the metabolism of sparfloxacin were not significantly altered by acidification or alkalinization of the urine. Conclusion: The urinary pH dependence of the renal clearance of sparfloxacin will be of minor clinical importance with regard to the low contribution of renal excretion to the overall elimination of sparfloxacin. On the other hand, the alteration in the environmental pH in the gastrointestinal tract, produced by the concomitant ingestion of ammonium chloride or sodium bicarbonate, influences the absorption and bioavailability of sparfloxacin. This effect is likely to be clinically significant. Received: 18 March 1998 / Accepted in revised form: 1 July 1998     

Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy

To investigate possible effects of implantation on apoptosis, we examined the cleavage of DNA in human chorionic villi and decidua in intrauterine and ectopic pregnancy. Very limited but detectable cleavage of DNA was recognized in the chorionic villi and decidua in normal pregnancy. A ladder pattern, characteristic of the apoptotic breakdown of DNA, was present in the villi in tubal pregnancy. High molecular weight DNA was predominant in the decidua in tubal pregnancy. Quantitative analysis of low molecular weight fragments of DNA revealed a significant increase in the villous tissue, together with a significant decrease in the decidual tissue, in tubal pregnancy as compared to those in normal pregnancy. An analysis in situ revealed that apoptotic cells were predominant in the syncytiotrophoblast in tubal pregnancy. In decidual tissue, labelled cells were occasionally seen in normal pregnancy, and their numbers decreased in tubal pregnancy. The present study demonstrates that apoptosis occurs in the villi, but not in the decidua in tubal pregnancy, unlike the situation in normal pregnancy. Our results suggest that the implantation site might affect the occurrence of apoptotic changes in early pregnancy of humans.      

An autopsy case of deep cerebral venous thrombosis: serial CT, MRI and pathological findings]

A 17-year-old girl developed vomiting of sudden onset, followed by a state of confusion that progressed rapidly to coma within one day. Laboratory tests indicated iron deficiency anemia and reactive thrombocytosis, but there was no evidence of coagulopathy. There was no history of medication including the contraceptive pill, either. Emergency CT scan without contrast enhancement showed increased density along the course of the vein of Galen and internal cerebral veins. A repeated CT scan without contrast enhancement carried out 24 hours after the onset of the illness confirmed extensive bilateral hypodensity of the thalami, basal ganglia and adjacent white matter. There was also a prominent spontaneous increase in the density of the deep cerebral venous system. MRI was performed 3 days after the onset of the illness, which showed absence of a flow void in the region of the internal cerebral veins and septal veins on T1-weighed images. T2-weighted images showed low intensity in these veins. At autopsy, the bilateral internal cerebral veins were occluded by fresh thrombosis and hemorrhagic infarction was seen in the bilateral thalami.     

Immunohistochemical study of adenohypophysial gonadotropes in the musk shrew, Suncus murinus L. (Insectivora)

Most gonadotropes in the pituitary of male Suncus murinus L. are immunostained with both LH beta and FSH antisera, whereas only a few gonadotropes are positive only for LH beta. The former gonadotropes consist of polygonal or polyhedral cells of medium size, and can be identified by the presence of two types of secretory granules of low density: smaller ones (about 150-250 nm in diameter) which are spherical in shape, and larger ones of irregular form with a maximum diameter of about 1,500 nm. The endoplasmic reticulum is not prominent, while the Golgi apparatus is distinct. Mitochondria are found throughout the cytoplasm but are often concentrated in and around the region of the Golgi apparatus. These fine structural features are somewhat similar to those of the classical Barnes "FSH cells" and Kurosumi-Oota "FSH cells".     

Clinical significance of reverse redistribution in exercise thallium-201 SPECT after percutaneous transluminal coronary angioplasty

Clinical significance of reverse redistribution on thallium image was evaluated in 54 patients who had undergone PTCA. Thallium SPECT imaging was performed one week and three to six months after PTCA. Reverse redistribution was detected eight of 54 patients one week after PTCA and five of 38 patients three to six months after PTCA. In the segments with reverse redistribution, reduced regional wall motion and lesser degree of coronary stenosis was common features (p less than 0.05) angiography. In conclusion, reverse redistribution had a tendency to appear in the region with mild myocardial injury and relatively high coronary blood flow after PTCA. But in cases with new occurrence and disappearance of reverse redistribution during follow up period, we can not assess the factors to explain these phenomena. In these segments, "coronary flow reserve", "stunned myocardium", "hibernating myocardium" or other factors may be related.     

Differential effects of IL-2 and IL-6 on the development of three distinct precursor T-cell populations in the thymus

Three distinct T-cell precursors: bone marrow cells that express low levels of the Thy-1 antigen but no lineage markers (Thy-1-lo/BM); CD4-, CD8-, and CD3- thymocytes that express low levels of the Thy-1 antigen (Thy-1-lo/Thym); and CD4-, CD8-, and CD3- thymocytes that express high levels of the Thy-1 antigen and the IL-2 R alpha chain (Thy-1+/IL2R+) were isolated by fluorescence-activated cell sorter (FACS). These three populations expanded with different kinetics in the thymus of irradiated recipient mice after intrathymic transfer. When a high dose of human recombinant IL-2 (r-IL-2) or human recombinant IL-6 (r-IL-6) was administered, r-IL-6 accelerated donor Thy-1+/IL2R+ to differentiate, whereas r-IL-2 blocked normal differentiation and expansion of donor Thy-1-lo/Thym, but did not show any significant effect on donor Thy-1+/IL2R+. Neither r-IL-2 nor r-IL-6 worked directly on donor Thy-1-lo/BM in this transfer system.     

Genetic control of delayed-type hypersensitivity in mice to Salmonella antigen

Genetic restriction on the expression of delayed-type hypersensitivity (DTH) to Salmonella typhimurium in mice transferred passively with immune spleen cells was studied. After the intravenous transfer of immune C3H/HeJ (H-2Ik) cells into A.TL (H-2Ik) or A.TH (H-2Is) mice, footpad DTH responses could be evoked in the A.TL recipients, but not in the A.TH mice. When the immune cells of BALB/c or C3H/He mice were intravenously-transferred into F1 hybrids produced by mating BALB/c and C57BL/6 or C3H/He and C57BL/6, respectively, no DTH response could be evoked in these F1 hybrids that received immune parental cells. Local transfer as well as systemic intravenous transfer of immune parental cells to F1 haplotype recipients did not cause any DTH. Previous treatment of the F1 hybrid recipients with cyclophosphamide did not result in the expression of the DTH response. Transfer of immune F1 spleen cells into parental strains also did not induce DTH. When the immune cells of parental strains were transferred into F2 mice and into back-cross mice, examination of the DTH response in these mice showed that some of them did not have any obvious footpad swelling, while others revealed various magnitudes of swelling. The resistance of F1 hybrids to transfer of DTH is discussed.     

An assessment of PKI and networked electronic patient record system: lessons learned from real patient data exchange at the platform of OCHIS (Osaka Community Healthcare Information System)

To enhance medical cooperation between the hospitals and clinics around Osaka local area, the healthcare network system, named Osaka Community Healthcare Information System (OCHIS), was established with support of a supplementary budget from the Japanese government in fiscal year 2002. Although the system has been based on healthcare public key infrastructure (PKI), there remain security issues to be solved technically and operationally. An experimental study was conducted to elucidate the central and the local function in terms of a registration authority and a time stamp authority in contract with the Japanese Medical Information Systems Organization (MEDIS) in 2003. This paper describes the experimental design and the results of the study concerning message security.