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91.
R. B. Stewart D. L. Kurtz M. Zweifel T. -K. Li J. C. Froehlich 《Psychopharmacology》1992,106(2):169-174
The duration of retention of tolerance to ethanol was tested in the alcohol-preferring (P) and alcohol-nonpreferring (NP)
rats lines, using ethanol-induced hypothermia as a measure of tolerance. Rats received two injections of ethanol (3.5 g/kg)
body wt, IP) and the time between the injections was 1, 2, or 3 days. When one day separated the two injections, tolerance
to the hypothermic effect of a second “test” injection was found in both lines. When 2 or 3 days separated the two injections,
the P line showed a loss of tolerance and the NP line showed sensitization to ethanol. Sensitization in the NP line grew stronger
when the interval between injections was increased from 2 to 3 days. The duration of retention of tolerance to ethanol-induced
hypothermia in the P line was shorter than has previously been reported for motor impairment in this line. It appears that
the duration of tolerance retention in the P line depends on the test used to measure tolerance. Sensitization to ethanol
in the NP line may be associated with low oral ethanol intake.
This research was supported, in part, by grants AA08312, AA03243, and AA07611 from the PHS 相似文献
92.
Dr. Steven A. Curley MD Robert A. Newman PhD Thomas B. Dougherty MD PhD George M. Fuhrman MD Diana L. Stone BS Jeffrey A. Mikolajek CRNA Sal Guercio CCP Ann Guercio CCP C. Humberto Carrasco MD M. Tien Kuo PhD David C. Hohn MD 《Annals of surgical oncology》1994,1(5):389-399
Background: We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in
patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could
be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin.
Methods: Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were
treated with doxorubicin 60 mg/m2, three patients were treated at 90 mg/m2, and five patients received 120 mg/m2. A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to
isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters
before return of the blood to the systemic circulation.
Results: Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p<0.01). Because all catheters
were placed percutaneously and because the chemofiltration markedly limited systemic chemotherapy exposure, patients were
discharged 1 day after 16 of the 17 treatments. The hepatic and systemic MTD of doxorubicin in this treatment protocol was
120 mg/m2.
Conclusions: This novel system of complete hepatic venous isolation and chemofiltration limits systemic chemotherapy toxicity and will
allow use of higher doses of chemotherapeutic agents to treat HCC.
The results of this study were presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles,
California, March 18–21, 1993. 相似文献
93.
M. L. Strong BS RPh L. J. Schaaf PhD M. C. Pankaskie PhD D. H. Robinson PhD 《Journal of clinical pharmacy and therapeutics》1994,19(6):361-369
Published reports regarding the stability of morphine are at variance, especially in syringes used in patient-controlled analgesia (PCA) devices. In addition to the effects of container type and vehicle, reasons for this variation include the effect of excipients temperature and light during storage. Furthermore, the literature varies regarding the mechanisms of decomposition for morphine. To our knowledge, the stability of meperidine (pethidine) stored in plastic syringes has not been reported. The purposes of this study were to investigate the stability of morphine sulphate (1 and 5 mg/ml) and meperidine hydrochloride (5 and 10 mg/ml) in plastic syringes for use in PCA devices for a duration of 12 weeks, and evaluate the influence of light (240 foot-candies), temperature (-20, 4 and 23d?C), diluent (5% dextrose or normal saline), and drug concentration on the stability of these narcotic analgesics. Samples were taken bi-weekly for solutions protected from light and weekly for solutions exposed to light. Morphine sulphate and meperidine hydrochloride concentrations were quantified using independent, stability-indicating, high performance liquid chromatographic assays. The within-day and between-day coefficients of variation for these assays were 4% over each of the concentration ranges studied. Under the conditions of this study, it is proposed that although decomposition of morphine to its main product, pseudomorphine, can be interpreted using first-order kinetics, consecutive (to form the N-oxide) and parallel mechanisms (to form apomorphine) exist. Morphine solutions were more stable in normal saline than in 5% dextrose. SheIf-life data indicate that morphine is stable for at least 6 weeks when protected from light. Exposure to light accelerates morphine decomposition two to six-fold depending on the concentration, and the shelf-life is reduced to about 1 week in some instances. Meperidine solutions in both vehicles under all conditions had shelf-lives of at least 12 weeks. No effects of light were detected and no changes in solution colour were observed. This study illustrates that patients using PCA devices must be advised about shelf-lives as well as correct storage conditions to protect solutions of these drugs from environmental factors that may alter shelf-lives. Pharmacists should also note that other formulation factors such as: antioxidants, preservations, buffers, impurities, and the source and quality of containers, may significantly alter the shelf-lives of these drugs. 相似文献
94.
95.
Lee L. Eckhardt MD Amanda L. Farley MS Esther Rodriguez MD Karen Ruwaldt BS Daniel Hammill David J. Tester BS Michael J. Ackerman MD PhD Jonathan C. Makielski MD 《Heart rhythm》2007,4(3):323-329
BACKGROUND: Loss-of-function mutations in the KCNJ2 cause approximately 50% of Andersen-Tawil Syndrome (ATS) characterized by a classic triad of periodic paralysis, ventricular arrhythmia, and dysmorphic features. Do KCNJ2 mutations occur in patients lacking this triad and lacking a family history of ATS? OBJECTIVES: The purpose of this study was to identify and characterize mutations in the KCNJ2-encoded inward rectifier potassium channel Kir2.1 from patients referred for genetic arrhythmia testing. METHODS: Mutational analysis of KCNJ2 was performed for 541 unrelated patients. The mutations were made in wild type (WT) and expressed in COS-1 cells and voltage clamped for ion currents. RESULTS: Three novel missense mutations (R67Q, R85W, and T305A) and one known mutation (T75M) were identified in 4/249 (1.6%) patients genotype-negative for other known arrhythmia genes with overall incidence 4/541 (0.74%). They had prominent U-waves, marked ventricular ectopy, and polymorphic ventricular tachycardia but no facial/skeletal abnormalities. Periodic paralysis was present in only one case. Outward current was decreased to less than 5% of WT for all mutants expressed alone. Co-expression with WT (simulating heterozygosity) caused a marked dominant negative effect for T75M and R82W, no dominant negative effect for R67Q, and a novel selective enhancement of inward rectification for T305A. CONCLUSIONS: KCNJ2 loss of function mutations were found in approximately 1% of patients referred for genetic arrhythmia testing that lacked criteria for ATS. Characterization of three new mutations identified a novel dominant negative effect selectively reducing outward current for T305A. These results extend the range of clinical phenotype and molecular phenotype associated with KCNJ2 mutations. 相似文献
96.
97.
Amy K. McNulty PhD ; Marisa Schmidt BS ; Teri Feeley BS ; Kris Kieswetter PhD 《Wound repair and regeneration》2007,15(6):838-846
Vacuum Assisted Closure brand Negative Pressure Wound Therapy (V.A.C. NPWT) has been shown to be an effective therapeutic option for the treatment of recalcitrant wounds; however, the mechanism of action at the cellular level remains to be elucidated. Here, we examined the effects of negative pressure wound therapy, manifolded with two different dressings, on fibroblast viability, chemotactic signaling, and proliferation in a fibrin clot matrix. Fibroblasts were grown in a three-dimensional fibrin matrix and were treated for 48 hours with either V.A.C. NPWT and GranuFoam Dressing, or with gauze under suction, or as static controls without negative pressure or dressings. Cells treated by gauze under suction showed significantly greater cell death and stimulated less migration and proliferation than static and V.A.C. NPWT-treated cells (p<0.05). Apoptosis was also significantly higher in gauze under suction than in static treatments. These results indicate that the dressing material has a significant effect on cell response following negative pressure wound therapy. The ability to support cell growth, stimulate chemotaxis, and proliferation without increasing apoptosis may provide an insight into the mechanisms of action of V.A.C. NPWT. 相似文献
98.
99.
Joaquim Ferreira MD João Maia Silva MD Rita Freire BS João Pignatelli MD Leonor Correia Guedes MD Alexandra Feijó MD Mário Miguel Rosa MD Miguel Coelho MD João Costa MD Ana Noronha BS Russell Hewett MD A. Marques Gomes PhD J.L. Cirne de Castro MD Olivier Rascol PhD Cristina Sampaio PhD 《Movement disorders》2007,22(10):1471-1475
Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies. 相似文献
100.