Introduction into fetal rat brain cells of a replication-defective retroviral vector harboring v-Ha-ras and v-gag-myc rapidly causes the induction of highly malignant undifferentiated neuroectodermal tumors following transplantation into the brains of syngeneic hosts [Wiestler, et al. (1992) Cancer Res. 52: 3760–3767]. In the present study, we have investigated the modulating effect of the developmental stage of neural target cells and of the dose of the retroviral vector used in the grafting experiments. Exposure of fetal cells from embryonic day (E)12 or E14 produced a 100% incidence of malignant neuroectodermal tumors which led to the death of recipient animals after a median latency period of 32 days. A 100-fold reduction of the virus dose from 2.062×106 to 2.062×104 focus-forming units/ml resulted in a lower tumor incidence of 25%. Of six neural grafts exposed to v-Ha-ras and v-myc at E16, only one showed evidence of tumorigenesis (low-grade astrocytoma and hemangioma). All other transplants were morphologically normal for observation periods of 26 weeks, indicating a marked loss of transforming activity of ras and myc in more advanced stages of brain development. In retrovirus-exposed donor cells which caused the development of neural tumors in recipient rats, malignant transformation was also evident during culture in vitro, usually after 9–12 days. Oncogene complementation was also studied in the newborn rat brain. After microinjection of the retroviral vector into the brain at postnatal day (P)0, P1 and P3, 5 out of 20 animals (25%) developed a total of seven brain tumors. Histopathologically, three of these neoplasms were malignant neuroectodermal tumors which, in contrast to those induced in fetal brain transplants showed evidence of focal glial and/or neuronal differentiation. In addition, we observed one oligodendroglioma, two hemangiomas and a malignant hemangioendothelioma. These data indicate that neural precursor cells and endothelia of the rat brain represent the major target cells for the complementary action of ras and myc and that the use of target cells from later developmental stages (E16 and postnatal) leads to the induction of both primitive and more differentiated neoplasms.These studies were supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich (Erwin Schrödinger fellowship, JO501-MED), by the Swiss National Science Foundation and by the Cancer League of the Kanton of Zürich 相似文献
Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.
Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.
Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04). 相似文献
OBJECTIVE: To establish the effectiveness and patient acceptability of initiating peritoneal dialysis (PD) according to published guidelines. SETTING: A university teaching hospital and a neighboring district general hospital. DESIGN: Nonrandomized prospective pilot study. PATIENTS: 39 patients with a Kt/V > 2.0 attending predialysis clinics at both hospitals agreed to participate in this study. METHODS: Patients were started on a single exchange of dialysate overnight. Dialysis adequacy was monitored at least every 2 months and incremental increases in dialysis were used to maintain combined urinary and dialysis Kt/V above 2.0. Routine laboratory parameters and complications of dialysis were monitored during the follow-up period. RESULTS: The mean weekly Kt/V at initiation of dialysis was 2.09. Median actuarial survival on a single exchange before requiring incremental dialysis was 297 days. At the end of the study period, all patients were still alive: 8 remained on 1 exchange, 18 were on more than 1 exchange, 8 had switched to hemodialysis, and 5 had received renal transplants. During the 12,665 patient-days on single-exchange dialysis, there were 14 hospital admissions of 12 patients. This resulted in a mean of 1.64 hospital days per patient-year for the whole group. During the follow-up period there were 2 episodes of bacterial peritonitis, 3 pleural leaks, 1 patent processus vaginalis, and 1 inguinal hernia that required surgical intervention. The use single daily icodextrin exchanges was associated with a 46% incidence of culture-negative peritonitis. CONCLUSIONS: This pilot study has shown that a timely start of dialysis with a single overnight PD exchange is acceptable to patients. Incremental dialysis as residual renal function falls is easily managed and patients also find this acceptable. Complication and hospitalization rates were low. The presence of residual renal function often allows complications to be managed without the need for hemodialysis. The use of icodextrin as a single-exchange dialysate is associated with sterile peritonitis in a significant proportion of cases. 相似文献
Background: Lumbar facet nerve (medial branch) blocks are often used to diagnose facet joint-mediated pain. The authors recently described a new ultrasound-guided methodology. The current study determines its accuracy using computed tomography scan controls.
Methods: Fifty bilateral ultrasound-guided approaches to the lumbar facet nerves were performed in five embalmed cadavers. The target point was the groove at the cephalad margin of the transverse (or costal) process L1-L5 (medial branch T12-L4) adjacent to the superior articular process. Axial transverse computed tomography scans, with and without 1 ml contrast dye, followed to evaluate needle positions and spread of contrast medium.
Results: Forty-five of 50 needle tips were located at the exact target point. The remaining 5 were within 5 mm of the target. In 47 of 50 cases, the applied contrast dye reached the groove where the nerve is located, corresponding to a simulated block success rate of 94% (95% confidence interval, 84-98%). Seven of 50 cases showed paraforaminal spread, 5 of 50 showed epidural spread, and 2 of 50 showed intravascular spread. Despite the aberrant distribution, all of these approaches were successful, as indicated by contrast dye at the target point. Abnormal contrast spread was equally distributed among all lumbar levels. Contrast traces along the needle channels were frequently observed. 相似文献
Gender differences after acute cocaine administration have received little attention in spite of the fact that males and females respond differently to many drugs. Seven male and seven female occasional cocaine users received both an intranasal dose of cocaine hydrochloride (0.9 mg/kg) and placebo powder in a randomized order and reported subjective effects via an instrumental joystick device and various questionnaires. Blood samples were withdrawn at 5-min intervals to assess pharmacokinetic differences. Male subjects achieved the highest peak plasma cocaine levels (144.4 ± 17.5 ng/ml), detected cocaine effects significantly faster than females and also experienced a greater number of episodes of intense good and bad effects. Women studied during the follicular phase of their menstrual cycle had peak plasma cocaine levels of 73.2 ± 9.9 ng/ml, which was significantly higher than when they were studied during their luteal phase (54.7 ± 8.7 ng/ml), but there were no differences in their subjective reports of cocaine effects. In spite of the different cocaine blood levels and subjective effects, peak heart rate increases did not differ between males and females suggesting that women may be more sensitive than males to the cardiovascular effects of cocaine. These data suggest that there are significant gender and menstrual cycle differences in the response to acute intranasal cocaine administration and these differences may have implications for the differential abuse of this drug.This paper is dedicated to Xavier Lamas, MD, PhD, who lost his life while ascending Mt. Everest, August 1995 相似文献
The purpose of this study was to determine if amrinone or milrinone after the electrophysiological responses of canine ventricular tissues to "ischemia" or reperfusion. Isolated canine Purkinje tissue-papillary muscle preparations were studied using standard microelectrode techniques. Tissues were superfused for 10 min with a solution that mimicked ischemia (hypoxia, acidosis, elevated lactate levels and zero substrate). Reperfusion with normal Tyrode's solution was then instituted for 60 min. Next, tissues were equilibrated with amrinone (5.3 X 10(-4) M) or milrinone (2.5 X 10(-4) M) for 15 min and the protocol was repeated with drug in all solutions. Without drug, ischemic conditions resulted in moderate depolarization of Purkinje and muscle tissues. Reperfusion caused a rapid hyperpolarization in Purkinje tissue. This was followed by a phase of mild depolarization associated with enhanced pacemaker activity. All preparations recovered by 45 min of reperfusion. With amrinone or milrinone present, the changes in membrane potential induced by conditions of ischemia and reperfusion were not different from control. However, an early phase of very rapid ectopic activity was seen during reperfusion with amrinone or milrinone. This ectopic activity had a constant cycle length during the pauses in stimulation. However, irregular patterns of spontaneous and driven beats were observed when electrical stimulation was superimposed on the ectopic activity. Amrinone and milrinone also increased pacemaker activity in Purkinje tissue but this occurred later in reperfusion. This study demonstrates that amrinone and milrinone sensitize isolated canine ventricular tissues to the arrhythmogenic effects of reperfusion. The mechanism underlying the arrhythmic activity elicited by the bipyridines is not clear, but may involve re-entry or abnormal automaticity. 相似文献
Summary The spontaneous contractions of segments of rat portal veins have been examined in vitro under isotonic and isometric conditions. The power density spectra of recorded time series lasting 10–60 min were calculated. The spectra usually consist of harmonic frequency components. Only during shorter periods of analysis (10 min time series) we sometimes found additional non-harmonic components. All frequency components are proportionally shifted by changes of the bath temperature according to an average Q10 of 2.0. Increase of the load decreases the frequency of the contractions.The results of the spectral analysis, indicating a preponderance of a single source of periodicity, were supported by direct evidence of a pacemaker region. By recording contractions after systematic dissections of the portal vein segment, we found that spontaneous activity is generated at the central end of the segment.This work was supported by the Austrian Research Fund 相似文献