Spatiotemporal modeling of cerebral evoked magnetic fields to median nerve stimulation.

We measured somatosensory evoked magnetic fields during median nerve stimulation in 6 normal subjects. We applied multiple dipole models to study the spatiotemporal structure of early somatosensory evoked magnetic fields (SEFs), as well as the number, 3-dimensional location and time activity of their underlying neuronal sources. Two dipole sources were necessary to model the first 40 msec of SEFs explaining 85% of the data variance. Source 1 was located deeper than source 2, showed primarily a tangential orientation, and accounted for a larger part of the variance; source 2 showed no consistent orientation across subjects. Both sources showed biphasic time activities corresponding to the previously described N20-P30 and P25-N35 components. Spatiotemporal modeling could identify sources which could not be modeled consistently above noise by single moving dipoles (P25 component), revealed small latency differences of the two sources in some subjects suggesting parallel activation of these sources, and allowed separation of sources overlapping considerably both in space and time. We conclude that spatiotemporal modeling of SEFs may be useful to study functional anatomy of human sensorimotor cortex non-invasively.     

针刺结合脑超声对脑梗死恢复期疗效观察

目的：探讨针刺结合脑超声治疗仪治疗脑梗死恢复期的疗效。方法：选择经CT或MRI证实的脑梗死患者60例，随机分为治疗1组和治疗2组，治疗1组在治疗2组的基础上接受脑超声治疗，集声、电同步治疗技术，每次治疗30min，每日1次，10次为1疗程，治疗2个疗程。结果：治疗1组总有效率为90．0％，治疗2组为73．3％，差异有统计学意义（P〈0．05）。结论：针刺结合脑超声治疗仪治疗脑梗死恢复期有明显疗效。     

Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.     

BJ-48, a novel thrombin-like enzyme from the Bothrops jararacussu venom with high selectivity for Arg over Lys in P1: Role of N-glycosylation in thermostability and active site accessibility.

BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da by electron spray mass spectrometry. The enzyme was shown to be highly glycosylated with 42% of N-linked carbohydrates composed of Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6-aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective. The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin-like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1muM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like protein C, protease-activated receptor-1 or inhibitors such as hirudin and antithrombin. A non-denaturing procedure using PNGase F and neuraminidase followed by hydrophobic interaction chromatography was employed to obtain active BJ-48 forms with variable carbohydrate content. Compared to the native enzyme, total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in their specific activities upon heating at 55/65 degrees C or treatment with SBTI. These results point out a role for BJ-48 glycosylation in thermostability and controlling the access of some canonical protein inhibitors to the active site.     

Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with Type 2 diabetes.

AIMS: To compare long-term (1 year) efficacy and safety of pioglitazone and gliclazide in patients with Type 2 diabetes. METHODS: This was a double-blind, multicentre, comparative, parallel group trial in 283 patients with Type 2 diabetes, who were randomized to receive 1-year treatment with pioglitazone 30-45 mg/day or gliclazide 80-320 mg/day. Drug dose was titrated on the basis of self-monitored blood glucose (SMBG) measurements and HbA1c values. The 1-year changes in HbA1c, fasting blood glucose (FBG), insulin, HOMA-S (HOmeostatic Model Assessment) and SMBG were compared. In a subgroup of patients (n = 10), systemic glucose production and utilization were determined by a combination of isotopic (deuterated glucose) and clamp techniques. RESULTS: In both groups, there were similar decreases in HbA1c (pioglitazone: -0.79%; gliclazide: -0.79%) and FBG (pioglitazone: -1.0 mmol/l; gliclazide: -0.7 mmol/l), whereas the slope of the reduction of fasting blood glucose was different between groups (P = 0.004). Insulin levels as well as insulin resistance assessed using HOMA-S decreased significantly only after pioglitazone treatment (-11.94 pmol/l and -1.03, respectively, both P = 0.002 vs. baseline). A significantly greater reduction in systemic glucose production was observed in the pioglitazone group (-2.48 micromol/kg/min, P = 0.042) than in the gliclazide group (-1.02 micromol/kg/min). A few, mild adverse events occurred in both groups. CONCLUSIONS: A comparable decrease in HbA1c and FBG was observed with pioglitazone and gliclazide. However, with pioglitazone there was a continuous decrease in FBG over 1 year, whereas gliclazide failed to maintain a similar trend. This favourable effect of pioglitazone was due to its insulin-sensitizing effect and ability to decrease systemic glucose production.     

自体表皮细胞培养与异体真皮组合应用研究

严重烧伤病人皮肤修复中主要未解决的问题是真皮的替代。动物实验结果表明，异体皮移植后５天，用自体培养表皮细胞膜片覆盖真皮床，１４天后复合皮成活率是８４．６％±２．４％。组织学检查证实表皮已形成了复层结构，可见基底层、颗粒层和角质层。临床应用中，异体皮移植后１０天，去除异体表皮覆盖病人的自体培养表皮，３５天后未见排斥征象，异体真皮促进了培养表皮的分层、成熟和完整，组织学检查证实表皮细胞的边缘清楚，已分化形成颗粒层和角质层，真皮多细胞，已血管化，但表皮嵴缺乏。     

Effect of hepatitis C antibody screening in blood donors on post-transfusion hepatitis in Taiwan

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.     

Incidental prostatic carcinoma: four-year follow-up after treatment with cyproterone acetate

This report is a retrospective clinical randomized study carried out on 114 cases of incidental prostatic carcinoma aged 55-87 years, 58 untreated and 56 treated with cyproterone acetate (CPA 200 mg/day) for 6 months, immediately after surgery. 78 cases were staged A1 and the remaining 36 A2. In stage A1, 75 cases were histologically graded G1, and 3 G2, whereas in stage A2, 7 cases were G1, 19 G2 and 10 G3. Moreover, flow cytometric DNA analysis showed in A1 20 G1 carcinomas with nuclear diploidy and 3 G2 with nuclear aneuploidy, in stage A2, 4 G3 tumors with nuclear aneuploidy. During the 4-year follow-up, 25/28 patients of the untreated group and 15/56 of the CPA-treated group were found in progression. In A1, progression was found in 6/37 untreated patients and 5/41 CPA-treated, whilst in A2 progression was observed in 19/21 untreated patients and in 10/15 treated with CPA. The critical period for progression was between the 2nd and 3rd year of follow-up. In A1, therefore, 6 months of therapy with CPA does not modify the progression rate, which is significantly improved in A2 (66% in the treated and 90% in the untreated group) during the first 30 months of follow-up. The prognosis may probably be further improved by continuing endocrine therapy.     

浅谈对传染科护士素质的要求与体会

根据笔者在传染科病房工作中的体会,从六个方面针对传染科工作的特殊性和存在的共性分别阐述了传染科护士在工作中如何高标准、严要求自己,如何对病人做到到位的护理,旨在提高传染科病房的整体护理质量,从而把更多的实惠让利于患者。