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Downtown Bicycle, a corporation, was not represented by an attorney as required by Alaska law. AAG Dan Branch represented the defendants in the case. ACPE PREVAILS AGAINST TERMINATED EMPLOYEE AAG Mary Ellen Beardsley successfully represented the Alaska Commission on Postsecondary Education in a superior court appeal brought by a terminated former employee. In September 2001, ACPE's executive director terminated Dennis Watson as director of the division of student financial aid claiming he was still a probationary employee who could be terminated without cause. Watson appealed the decision to the commission and a three-member panel was established to consider his appeal. AAG Sarah Felix represented ACPE during this administrative process. After a two day hearing in November 2000, the hearing panel issued a decision upholding the termination. The panel concluded there were sufficient grounds to consider him a probationary employee and therefore, he could be terminated without cause. They also concluded that there was sufficient evidence to support a termination for cause as well. Watson then filed a separate action in the superior court claiming breach of contract and the covenant of good faith and fair dealing. AAG Beardsley took over the case at that point and filed a motion to have the case converted to an administrative appeal. Judge Weeks granted this motion. Oral argument occurred on December 17, 2002, and on December 20th, Judge Weeks issued an opinion upholding the commission's decision. He ruled that the commission has special expertise in determining whether someone is qualified to serve in upper management. He also ruled that the record supported Watson's termination for cause. A motion for attorney's fees is now pending. RCA HAS HEAVY DOCKET AAG Virginia Rusch has been busy assisting the Regulatory Commission of Alaska with an unusual number of court filings, regulations projects, and numerous orders the RCA is issuing to close old dockets and to comply with the first deadline for commission action under the new statute adopted in the legislature's special session last June. AAG Rusch has filed briefs for the RCA in response to two Petitions for Review of commission orders, and three requests for stays. Aurora Energy LLD petitioned for review of the commission order denying an interim increase after Aurora asked for an increase in the rates for electric power it sells to Golden Valley Electric Association under a wholesale power contract. This case involves a first impression interpretation of AS 42.05.431 b ; . The superior court ordered the commission to hold a hearing and consider giving Aurora Energy an interim increase. Golden Valley has now moved for a stay of the superior court's order, which the commission has opposed. In the Trans-Alaska Pipeline intra-state rate case, the commission ordered refunds of excessive rates paid by shippers in the years 1997 through 2000. The carriers have appealed and have filed a motion which argues that under AS 42.06.480 b ; , the commission may not enforce the refund order because they filed their appeal within 10 days. The commission argued that the carriers misinterpret the statute and the judge ruled in the commission's favor. AAG Rusch has also been working with the RCA and legislation and regulations section on several regulations projects. Amendments to 3 AAC 52.900-940, which set terms for pole attachments between utilities, have now been filed with the lieutenant governor's office. Review is ongoing for amendments or new regulations that address the role of the Public Advocacy Section in RCA proceedings, and that adopt new filing requirements and other criteria for interstate interexchange carrier telephone competition, because .
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Antifungal Agents: In vitro Susceptibility Testing, Pharmacodynamics, and Prospects for Combination Therapy 573 Andreas H. Groll, M.D. and Hedwig Kolve, Pharm.D. Amphotericin B 591 Astrid M.L. Oude Lashof, M.D. and Bart-Jan Kullberg, M.D. Azoles Clotrimazole, Fluconazole, Itraconazole, Ketoconazole, Miconazole, Voriconazole ; 609 Andreas H. Groll, M.D., Hedwig Kolve, Pharm.D. and Thomas J. Walsh, M.D. Echinocandins Caspofungin ; Alexander Imhof, M.D. and Kieren A. Marr, M.D. Flucytosine 651 Richard H. Drew, Pharm.D. and John R. Perfect, M.D. 637.
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Of PBOX-6 on four human breast cancer cell lines. Our results demonstrate that PBOX-6 was a potent inhibitor of both ER-positive MCF-7, IC50 1.9 M; T-47-D, IC50 2 M ; and ER-negative MDA-MB-231, IC50 2.3 M; SK-BR-3, IC50 1 M ; human breast cancer cells. The sensitivities of the four cell lines to PBOX-6 were similar with only a 2-fold difference in the sensitivity observed between the least sensitive MDA-MB-231 ; and most sensitive SK-BR-3 ; cell line. In contrast to these findings, the sensitivity of MDA-MB-231 cells to taxol was 30-fold to that observed for MCF-7 cells 39 ; . This observed difference in taxol sensitivity may be due to factors other than ER status as numerous reports have demonstrated a lack of correlation between cytotoxic chemotherapy and ER status 9, 40 ; . Furthermore, another study again confirmed the lack of correlation between the clinical response to docetaxel and ER status 12 ; . These findings further highlight the potential of PBOX-6 as a chemotherapeutic agent in the management of both hormone-dependent and -independent breast carcinomas. The mechanism of PBOX-6-induced cell death was by apoptosis, as determined by DNA fragmentation pre-G1 peak ; and PARP cleavage. After 48 h treatment, PBOX-6 induced an accumulation of cells in the pre-G1 peak 82.423.10 ; compared with vehicle-treated SK-BR-3 cells 5.940.25 ; . SK-BR-3 cells overexpress the HER-2 oncogene, which is often associated with a poor chemotherapy response 41 ; . As previously discussed, overexpression of the HER-2 oncogene renders breast cancer cells highly resistant to taxol 15 ; . The underlying molecular mechanism is that HER-2 inhibits p34 Cdc2 ; activation, which is required for taxolinduced apoptosis 42 ; . Another study revealed that HER-2 overexpression was also related to poor responsiveness to chemotherapy with cyclophoshamide methotrexate and 5-fluorouracil 42 ; . Given that there was only a 2-fold difference in response to PBOX-6 between the SK-BR-3 and MDA-MB-231 cells, which express low levels of HER-2, PBOX-6 may prove useful as a single agent in the treatment of breast carcinomas overexpressing the HER-2 oncogene. Combination chemotherapy has frequently, but not always produced greater degrees of clinical benefit than single agent therapy. Therefore, it would be interesting to examine the effect of PBOX-6 in combination with other chemotherapeutic agents or hormonal therapy. For example, the combination of paclitaxel with trastuzumab has been shown to be more effective than either drug alone in the treatment of HER-2 overexpressing breast carcinomas 14, 43 ; . Trastuzumab is a humanised monoclonal antibody against the extracellular domain of the HER-2 receptor. Similiarly, increased tumour regressions were also observed in patients with HER-2 overexpressing carcinomas treated with doxorubicin cyclophosphamide supplemented with trastuzumab compared to patients treated with chemotherapy alone 43 ; . In this study, we also showed that PBOX-6 significantly inhibited both the in vitro and in vivo growth of the highly aggressive 4T1 mammary carcinoma cells. No overt toxicity i.e. weight loss ; was apparent in the mice treated with single intratumoural injections of 7.5mg kg PBOX-6 for 7 days. Therefore, it is not unreasonable to assume that higher doses of PBOX-6 may be tolerable and even prove to be more effective at inhibiting tumour growth. However, we found and lamisil.
Bourne DW. Clinical and medicoeconomic impact of the cyclosporine-diltiazem interaction in renal transplant recipients. Pharmacotherapy 1994; 14: 471-81. Sketris IS, Methot ME, Nicol D, Belitsky P, Knox MG. Effect of calcium-channel blockers on cyclosporine clearance and use in renal transplant patients. Ann Pharmacother 1994; 28: 1227-31. Keogh A, Spratt P, McCosker C, Macdonald P, Mundy J, Kaan A. Ketoconazolw to reduce the need for cyclosporine after cardiac transplantation. N Engl J Med 1995; 333: 628-33. Jones TE. The use of other drugs to allow a lower dosage of cyclosporin to be used. Therapeutic and pharmacoeconomic considerations. Clin Pharmacokinet 1997; 32: 357-67. Wenke K, Meiser B, Thiery J, et al. Simvastatin reduces graft vessel disease and mortality after heart transplantation: A four-year randomized trial. Circulation 1997; 96: 1398-402.
Ketoconazole reactionsDAVID S. GOLDSTEIN et al. second blood sample was drawn and simultaneous heart rate, blood pressure, stroke volume, and cardiac output was recorded. After the operation, the patient recovered in a semisupine position in the same room that had been used for the baseline observation. Three hours after the operation--sooner if the anesthesia had worn off and the patient complained of moderate to severe pain--the patient underwent a third phlebotomy, filled out the questionnaires, and had vital signs measured manually. The postoperative data collection allowed assessment of biochemical and circulatory interrelationships during pain after the anesthetic effect had worn off. evacuated, heparinized tubes containing no additives. The tubes were spun in a refrigerated centrifuge within 30 min of phlebotomy, and the plasma was transferred into plastic sample tubes, frozen in dry ice, and stored in a tank containing liquid nitrogen. The assay technique used high pressure liquid chromatography with electrochemical detection, the validity and reliability of which have been previously documented in our laboratory 3 ; . Minimum detectable norepinephrine and epinephrine levels were about 15 pg cc. Plasma cortisol, lipids, and lipoproteins were measured using standard laboratory techniques. The total amount of blood drawn per patient, including baseline and both operative sets of samples, was less than 450 ml over a period of at least 2 weeks. Drug sensitivity of yeast strains was tested by applying serial dilutions start suspension: 1 107 cells mL ; of cell suspensions from overnight cultures, with an applicator, on to solid YPD medium containing different drugs.The plates were incubated for 13 days at 30 C.The drugs, solubilized in adequate solvents sterile water, DMSO, ethanol, or methanol ; were added after the sterilized medium equilibrated at 55 C. A23187 was acquired from Acros Organics; anisomycin, berberine chloride, cerulenin, clotrimazole, daunomycin, dodecyl aldehyde, dodecyl amine, dodecyl arachidate, fluphenazine, ketoconazole, n-lauroyl sarcosine, monensin, nigericin, nystatin, 1, 10-phenantroline, quercetin, rhodamine B, rhodamine 6G, rhodamine 123, SDS, 2, 3, 5-triphenyl tetrazolium chloride tetrazolium red ; , thiazolyl blue tetrazolium bromide tetrazolium blue ; , trifluoperazine, triton X-15, valinomycin, zwittergents 310 and 314, from Sigma; brij 35 from INC Biomedicals Inc.; imazalil, nuarimol from Dr Ehrenstorfer GmbH; cycloheximide and triton X-114 from Nakalai Tesque; curvularol and tautomycin were gifts from H. Osada RIKEN ; . Staurosporine was obtained from Kyowa Hakkou Co. Ltd. For rhodamine B and tautomycin, the pH of the YPD medium was adjusted to 4.5 with hydrochloric acid; for all the other drugs, it was left unchanged. For quantitative assay in liquid culture, cells from overnight cultures were inoculated to the density of 1 105 cells mL in fresh YPD medium containing drugs in two-fold serial dilutions, and grown for 24 h at OD600 was measured for 50-fold dilutions of the cultures and plotted against drug concentration. Minimal inhibitory concentration MIC ; was determined as the lowest drug concentration at which cell growth is nearly completely inhibited Egner et al. 1998 and levofloxacin. Further, we demonstrate that econazole has a MIC of 4 g and a MBC of 4 g while ketoconazole has a MIC of 8 g and a MBC of 16 g ml. Itraconazole, voriconazole, and fluconazole did not inhibit MAC growth to any significant extent. Our studies suggest that inhibition of CYP51 function in MAC may be of therapeutic benefit for patients with this infection. The cytochrome P450 CYP450 ; enzyme system is responsible for the oxidative-reductive metabolism of medications. These enzymes are primarily concentrated in the liver and small intestines. More than 30 human CYP450 enzymes have been identified; however, only four isoenzymes CYP3A4, CYP2C9, CYP1A2, and CYP2D6 ; are responsible for the majority of drug metabolism. 5 CYP3A4 metabolizes the greatest number of medications and endogenous substances in the body, accounting for most CYP450 enzymes in the liver and small intestines 60 and 70%, respectively ; .6 Many substrates, inhibitors, and inducers of CYP450 isoenzymes have been identified. A substrate is the medication being metabolized by the enzyme system. Warfarin, statins e.g. lovastatin [Mevacor] and simvastatin [Zocor] ; , and theophylline are examples of substrates. An inhibitor is a medication that decreases enzyme activity and leads to increased concentrations of the substrate. Some macrolide antibiotics e.g., erythromycin and clarithromycin [Biaxin] ; , cimetidine Tagamet ; , and azole antifungals e.g., fluconazole [Diflucan], itraconazole [Sporanox], and ketocconazole [Nizoral] ; are known inhibitors of CYP450. An inducer is a medication that increases the number of enzymes and leads to decreased concentrations of the substrate. Notorious enzyme inducers are rifampin Rifadin, Rimactane ; , carbamazepine Tegretol ; , phenytoin Dilantin ; , and phenobarbital. Thus, enzyme inhibitors can predispose to drug toxicity, whereas enzyme inducers have the potential to decrease the effectiveness of a medication. Of the two processes, an interaction that leads to inhibition has a more rapid onset. The optimal management of a drug interaction involves recognition of the interaction; decision regarding whether to prescribe, dispense, or administer the interacting combination; follow-up monitoring; and appropriate patient counseling. Once the interaction is recognized, one must consider the possible outcome before deciding whether to prescribe, dispense, or administer the interacting drugs. If the outcome were possible death, the risk would likely outweigh the benefit. If the outcome were increased drowsiness, the benefit would appear to outweigh the risk and lexapro. Ketoconazole otc products
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