Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.     

Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death

Human chorionic gonadotropin (hCG) inhibits the progression of 7,12- dimethylbenz[a]anthracene (DMBA) induced mammary carcinomas. In order to determine whether this phenomenon was mediated by induction of programmed cell death or apoptosis, 45-day-old virgin Sprague-Dawley rats received 8 mg DMBA/100 g body weight; 20 days later they were injected daily with 100 IU hCG for 40 days (DMBA + hCG group). Age- matched untreated, hCG- and DMBA + saline treated rats were used as controls. Tissues were collected at the time of DMBA administration and at 5, 10, 20 and 40 days of hCG injection. RNA from mammary glands, adenocarcinomas and ovaries was probed for transforming growth factors (TGF) alpha and beta, and the apoptotic genes TRPM2, ICE, bcl2, bcl-XL, bcl-XS, p53 and c-myc. The mammary glands of hCG-treated animals with or without DMBA exhibited elevated expression of TRPM2, ICE, bcl-XS, c- myc and p53; and elevation in the apoptotic index. Mammary adenocarcinomas developed in those animals treated with hCG showed an elevation in the expression of p53, c-myc and ICE genes in comparison with the levels detected in the adenocarcinomas developed by the animals treated with DMBA alone. No significant alterations in the expression of any of the genes tested was observed in ovarian RNAs. These results led us to conclude that hCG induces programmed cell death in the mammary gland initiated in the carcinogenic process, that this process is p53 dependent, and is modulated by c-myc expression. Our data also indicate the possibility that a cell death program dependent on the bcl2 family exists, because of the potential involvement of p53, bcl-XS and Bax in apoptosis. This additional mechanism of tumor inhibition makes hCG treatment a useful approach for the prevention and therapy of breast cancer.      

Cloning and characterization of DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1

In several families with non-specific X-linked mental retardation (XLMR) linkage analyses have assigned the underlying gene defect to the pericentromeric region of the X chromosome, but none of these genes have been isolated so far. Here, we report on the cloning and characterization of a novel gene, DXS6673E, that maps to Xq13.1, is subject to X-inactivation and is disrupted in the 5' untranslated region by a balanced X;13 translocation in a mentally retarded female. The DXS6673E gene is highly conserved among vertebrates and its expression is most abundant in brain. It encodes a hydrophilic protein of 1358 amino acids (aa) that does not show sequence homology to other known proteins. A segment of this protein consisting of neutral and hydrophobic aa with a proline residue in every second position may represent a transmembrane domain. Almost complete sequence identity was found between the 3' end of the DXS6673E gene and two expressed sequence tags (ESTs) and between the 5' end of the DXS6673E gene and a third EST. Moreover, weaker sequence similarity was observed between coding regions and two other ESTs.      

Late recurrence of liposarcoma simulating adenoma of the duodenum.

A large pedunculated, polypoid mass in the duodenum of a patient with asymptomatic anaemia, with mucosal biopsies indicating a villous adenoma, turned out to be a liposarcoma during laparotomy. The patient had had a completely resected retroperitoneal liposarcoma 8 years before. Liposarcoma recurrence should be highly suspected even in case of atypical presentation and long disease free interval.     

Transmission of a Panton-Valentine leucocidin-positive, methicillin-resistant Staphylococcus aureus strain between humans and a dog

Panton-Valentine leucocidin-positive methicillin-resistant Staphylococcus aureus (MRSA) strains with identical resistance patterns were cultured from recurrent infections of a 51-year-old patient, her healthy husband, son, and dog, and pulsed-field gel electrophoresis showed that all MRSA strains were indistinguishable.     

Development and validation of a questionnaire to identify learning-oriented group interactions in PBL

Collaborative learning attracts attention because of its potential as a powerful learning strategy. This also holds for PBL. However, group work in PBL sometimes encounters problems and the quality of interaction is not always at the desired level. The aim of the present study was to develop and validate a questionnaire to assess the quality of learning-oriented group interactions in PBL in an uncomplicated way. The questionnaire, to be completed by students involved in PBL, contained items on three group-interaction dimensions: exploratory questions, cumulative reasoning and handling conflicts. It was validated by means of confirmatory factor analysis and regression analysis, the latter to investigate the relation between the three-dimension model and the tutorial group's productivity. The factors underlying the questionnaire were confirmed by the data in a linear structural analysis of the data. The regression analysis showed that the 'exploratory questions' and 'cumulative reasoning' factors explained together 26% of the variance of the tutorial group's productivity. This study provided evidence for the validity of the questionnaire. The instrument contains tips for students and tutors to stimulate deep processing interactions in the tutorial group. Nevertheless, it seems useful to investigate the external validity of the questionnaire.     

有机磷解毒剂的研究2.吡啶甲醛肟碘甲烷盐(简称2-PAM)的药理作用

2-吡啶甲醛肟碘甲烷盐(2-PAM)为有效的有机磷解毒剂,本文对其药理作用作了初步的观察.证明对乌拉坦麻醉猫在接近临床用量时已能产生拟肾上腺素作用.连续应用多次后出现快速耐受现象.在应用抗肾上腺素药、利血平或切除两侧肾上腺后,2-PAM作用即减弱.C₆即使用至50毫克/公斤,亦不能阻断其作用,而5毫克/公斤的阿托品几能完全取消之.对离体及在位蟾蜍心脏也表现兴奋,此作用可部分地被C₆所阻断.2-PAM对离体豚鼠肠的兴奋作用,亦可被阿托品所取消.文内对其作用机制作了初步分析.     

Solving problems with group work in problem-based learning: hold on to the philosophy

INTRODUCTION: Problem-based learning (PBL) has gained a foothold within many schools in higher education as a response to the problems faced within traditional education. DISCUSSION: Working with PBL tutorial groups is assumed to have positive effects on student learning. Several studies provide empirical evidence that PBL stimulates cognitive effects and leads to restructuring of knowledge and enhanced intrinsic interest in the subject matter. However, staff members do not always experience the positive effects of group work which they had hoped for. When confronted with problems in group work, such as students who only maintain an appearance of being actively involved and students who let others do the work, teachers all too often implement solutions which can be characterized as teacher- directed rather than student-directed. Teachers tend to choose solutions which are familiar from their own experience during professional training, i.e. using the teacher-directed model. These solutions are not effective in improving group work and the negative experiences persist. CONCLUSION: It is argued that teachers should hold on to the underlying educational philosophy when solving problems arising from group work in PBL, by choosing actions which are consistent with the student-directed view of education in PBL.     

A case of well-differentiated minute hepatocellular carcinoma with extrahepatic metastasis

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) metastasizing to distant sites in a 77-year-old man with hepatitis C virus (HCV)-related cirrhosis is presented. Ultrasonography (US) disclosed a 9 mm hypoechoic lesion in segment seven (S₇) of the liver, although computed tomography (CT), magnetic resonance imaging (MRI) and angiography did not reveal any space-occupying lesion. Ultrasound-guided biopsy showed the histological features of well-differentiated HCC. A plain film of the abdomen and CT revealed osteolytic changes in the sacrum and the lumbar vertebra. Ultrasound-guided biopsy of the sacrum revealed well-to-moderately differentiated HCC metastasizing from the liver. Percutaneous ethanol injection therapy (PEIT) effected complete response and completely eliminated the abnormal findings on US. Three months after PEIT, metastasis to the thoracic vertebra was revealed by CT, despite negative α-fetoprotein-mRNA in serum. This is the first report describing a well-differentiated HCC with metastatic potential. Further studies may provide insights into metastasis of well-differentiated HCC.