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91.
The effect of a dopamine receptor antagonist on locomotor activity was examined during withdrawal from either self-administered or experimenter-administered cocaine. In the self-administration experiment, the locomotor response to a challenge injection of cis-flupenthixol was assessed in photocell cages at 4 h after the cessation of a 12-h cocaine self-administration session. Rats which had self-administered cocaine, and were challenged with cis-flupenthixol (0.05 mg/kg), were found to be hypoactive relative to controls. In the experimenter-administered cocaine experiment, animals were given eight IP injections of 15 mg/kg cocaine over a 9.5-h period, for a total of 120 mg/kg. At 4, 8, and 24 h (tested in three separate groups of rats) after cessation of the eight injections, the locomotor response to a challenge injection of saline or cis-flupenthixol was tested. Cocaine-treated animals displayed a dose-dependent, heightened sensitivity to the locomotor depressant effects of 0.05 mg/kg and 0.2 mg/kg cis-flupenthixol 4 h post-cocaine, whereas they did not show increased sensitivity to 0.05 mg/kg cis-flupenthixol 8 or 24 h post-cocaine. However, cocaine-treated animals displayed a mild hypoactivity 8 h post-cocaine. In a separate group of animals, a dose-response experiment was performed which indicated that a dose of cis-flupenthixol as high as 0.2 mg/kg was required to produce locomotor depression in cocaine-naive rats. The results of this study support clinical observations of dopamine antagonist-precipitated motor dysfunction in abstinent cocaine abusers, and lend further support to the hypothesis that alterations in dopaminergic neurotransmission consequent to prolonged cocaine exposure are partly responsible for some of the symptoms of cocaine withdrawal. 相似文献
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GF Fleming JW Kugler PC Hoffman R Ansari JD Bitran A Klepsch D Malone AA Fasanmade MJ Ratain EE Vokes 《Canadian Metallurgical Quarterly》1998,16(6):2032-2037
PURPOSE: This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity. PATIENTS AND METHODS: Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies. RESULTS: Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel. CONCLUSION: This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support. 相似文献
94.
M Meylan DM Rings WP Shulaw JJ Kowalski S Bech-Nielsen GF Hoffsis 《Canadian Metallurgical Quarterly》1996,57(11):1580-1585
OBJECTIVE: To determine whether Mycobacterium paratuberculosis could survive in colostrum after pasteurization. Additionally, this study investigated the effect pasteurization had on IgG concentration in colostrum. ANIMALS: Colostrum samples were collected from cattle (beef and dairy) owned by the state of Ohio. PROCEDURE: Colostrum was divided into aliquots and inoculated with variable concentrations of M paratuberculosis (ATCC No. 19698: 10(4), 10(3), and 10(2) colony-forming units/ml). Half the samples at each concentration were subjected to pasteurization temperatures (63 C) for 30 minutes and the remainder were kept at approximately 20 to 23 C. All samples were incubated (Herrold's egg yolk medium with and without mycobactin J) and observed for growth during the next 16 weeks. Additionally, the IgG concentration of colostrum was determined by radioimmunoassay before and after pasteurization. Samples that coagulated at pasteurization temperatures were mechanically resuspended before measurement of IgG concentration. RESULTS: Growth of M paratuberculosis was retarded but not eliminated by pasteurization. Growth was observed in all unpasteurized samples incubated on Herrold's egg yolk medium with mycobactin J but in only 2 of 18 pasteurized samples similarly cultured. Growth from pasteurized samples appeared 5 to 9 weeks after growth was observed from nonpasteurized samples. Mean colostral IgG concentration was 44.4 g/L in nonpasteurized samples and 37.2 g/L in pasteurized samples, a decrease of 12.3%. High-quality colostrum (> 48 g of IgG/L) had a significantly greater loss of IgG concentration than did colostrum of lesser quality (P = 0.002). CONCLUSIONS: Pasteurization lessened, but did not eliminate, growth of M paratuberculosis from experimentally inoculated colostrum samples. Pasteurization resulted in a significant decrease in colostral IgG concentration but not to an unmanageable level that would preclude the colostrum's use for passive transfer of immunity. CLINICAL RELEVANCE: Colostrum is macrophage rich and may serve as a source of M paratuberculosis infection to calves. Pasteurization of colostrum may lessen the risk of infection, but will not totally eliminate M paratuberculosis. 相似文献
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GP Bernini G Brogi GF Argenio A Moretti A Salvetti 《Canadian Metallurgical Quarterly》1998,21(5):310-317
STUDY OBJECTIVE: To determine if there are significant differences in birth outcomes and survival for infants delivered by certified nurse midwives compared with those delivered by physicians, and whether these differences, if they exist, remain after controlling for sociodemographic and medical risk factors. DESIGN: Logistic regression models were used to examine differences between certified nurse midwife and physician delivered births in infant, neonatal, and postneonatal mortality, and risk of low birthweight after controlling for a variety of social and medical risk factors. Ordinary least squares regression models were used to examine differences in mean birthweight after controlling for the same risk factors. STUDY SETTING: United States. PATIENTS: The study included all singleton, vaginal births at 35-43 weeks gestation delivered either by physicians or certified nurse midwives in the United States in 1991. MAIN RESULTS: After controlling for social and medical risk factors, the risk of experiencing an infant death was 19% lower for certified nurse midwife attended than for physician attended births, the risk of neonatal mortality was 33% lower, and the risk of delivering a low birthweight infant 31% lower. Mean birthweight was 37 grams heavier for the certified nurse midwife attended than for physician attended births. CONCLUSIONS: National data support the findings of previous local studies that certified nurse midwives have excellent birth outcomes. These findings are discussed in light of differences between certified nurse midwives and physicians in prenatal care and labour and delivery care practices. Certified nurse midwives provide a safe and viable alternative to maternity care in the United States, particularly for low to moderate risk women. 相似文献
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Optic atrophy, which is indicative of a CNS disorder, is a rarely described manifestation of familial dysautonomia (Riley-Day syndrome). As these patients are now living longer, the prevalence of optic neuropathy also may be increasing. We present a man with familial dysautonomia and visual loss resulting from optic atrophy and visual field defect suggestive of chiasmal pathology. 相似文献
100.
Previous studies in rodents have reported that clonidine, an alpha 2-adrenergic receptor agonist, attenuated conditioned aversions to naloxone-precipitated opiate withdrawal when administered prior to each withdrawal conditioning episode. The current study was designed to determine whether clonidine could modify the expression of previously established conditioned place aversions and conditioned suppression of operant responding. Dose- and time-dependent effects of clonidine on activity and suppression of operant responding for food identified appropriate treatment parameters for subsequent studies in which rats rendered dependent on opiates through implantation of morphine pellets were tested for: (1) conditioned place aversion; and (2) conditioned suppression of operant responding for food (fixed ratio-15 schedule), in a paradigm wherein rats received four pairings of naloxone with a distinct tone and odor stimulus. Clonidine dose-dependently blocked the acquisition of both conditioned behaviors when administered prior to naloxone on each conditioning trial, but was ineffective in blocking the expression of these conditioned withdrawal signs when administered prior to the test session. 相似文献