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31.
Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days. 总被引:4,自引:0,他引:4
Jame Abraham Manish Agrawal Susan Bakke Ann Rutt Maureen Edgerly Frank M Balis Brigitte Widemann Louis Davis Bharat Damle Daryl Sonnichsen David Lebwohl Susan Bates Herb Kotz Tito Fojo 《Journal of clinical oncology》2003,21(9):1866-1873
PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. 相似文献
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M Ghosh H Kamma T Kawamoto N Koike M Miwa V K Kapoor N Krishnani S Agrawal N Ohkohchi T Todoroki 《European journal of surgical oncology》2005,31(8):891-896
AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer. 相似文献
34.
Background:The normative data set in authomated perimetry is predominantly of non-Indian origin and hence may not be an accurate basis for visual field analysis in Indian population. This video describes an attempt to create a native normative dataset for automated perimetry, which can then be fed in our machines and be used as the normative database.Purpose:To formulate normative data and to increase domain knowledge of normative values for automated perimetry in Indian population of different age groups.Synopsis:Cross-sectional study conducted on patients receiving outpatient care in a span of 3 years, which included 6586 healthy normal patients (13172 eyes) with vision 6/6 unaided or after refractive correction. The patients were tested with 30-2 SITA FAST threshold algorithm on Humphrey Field Analyzer Model no: 745i. Normative data was calculated on basis of age group ranging from 19-75 years categorized to every decade. Normal values were formulated on basis of perimetry performed on normal patients.Highlights:Our work on creating a native normative dataset may add value as well as increase the accuracy of perimetry analysis in Indian eyes.Online Video Link: https://youtu.be/jqgC2Tn7HIg 相似文献
35.
Agrawal CS Sehgal R Singh RK Gupta AK 《Indian journal of physiology and pharmacology》1999,43(4):501-504
A prospective, randomised and double blind study was undertaken to compare the prophylactic efficacy of ciprofloxacin and cefuroxime in 155 patients undergoing elective cholecystectomy. Patients with past history of jaundice or presence of jaundice, diabetes mellitus, common bile duct stones and previous biliary tract surgery were excluded. Patients were allocated to the following groups: group A-no antibiotic (n = 30); group B-ciprofloxacin (200 mg i/v before surgical incision and a second dose after 12 hrs) (n + 45); group C-ciprofloxacin given only post operatively (200 mg i/v, 12 hourly X 2 days followed by oral 500 mg twice daily X 3 days) (n = 35); group D-cefuroxime (750 mg i/v before surgical incision and a second dose after 12 hrs) (n = 45). Efficacy of the antibiotic was defined as a patient being free of post operative wound infection. Maximum numbers of infection occurred in group A (26.67%) and group C (25.71%). The incidence of wound infection was significantly lower when ciprofloxacin was used as prophylaxis (group B) than when used post operatively (group C) only (P < 0.05). Patients who received ciprofloxacin (group B) and cefuroxime (group D) as prophylaxis had significantly reduced incidence of infection (4.44% and 6/67% respectively); no statistically significant difference was found between these groups. Ciprofloxacin could be used as prophylactic antimicrobial in elective cholecystectomy in developing countries because of its effectiveness, economy and ready availability. 相似文献
36.
Neelam Pushker Sujeeth Modaboyina Rachna Meel Sahil Agrawal 《Indian journal of ophthalmology》2022,70(4):1404
Full-thickness deficiency of eyelid tissues can result in coloboma or retraction or both. Here we report our initial experience on the use of auricular skin-cartilage sandwich graft technique for full-thickness eyelid deformities. Five patients (4–32 years) underwent the procedure. Patients with full-thickness eyelid deformity were included. Three patients were operated for large-sized coloboma and two for eyelid retraction. One patient had congenital, and four patients had acquired etiology. The following parameters were specifically assessed: correction of deformity, ocular surface problems, graft status, and epithelization of skin-cartilage graft. All the patients had a good correction of eyelid position, except one patient who had severe eyelid retraction (8 mm) at presentation. None of our patients had corneal erosion/defect, persistent ocular surface redness, or graft loss. The auricular skin-cartilage sandwich graft technique produces optimal results with no graft loss. Advancement of orbicularis muscle in between the auricular skin and cartilage grafts (sandwich technique) is an imperative step that leads to the survival of both grafts. 相似文献
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Rice JP Hartz SM Agrawal A Almasy L Bennett S Breslau N Bucholz KK Doheny KF Edenberg HJ Goate AM Hesselbrock V Howells WB Johnson EO Kramer J Krueger RF Kuperman S Laurie C Manolio TA Neuman RJ Nurnberger JI Porjesz B Pugh E Ramos EM Saccone N Saccone S Schuckit M Bierut LJ;the GENEVA Consortium 《Addiction (Abingdon, England)》2012,107(11):2019-2028
AIMS: Nicotine dependence is a highly heritable disorder associated with severe medical morbidity and mortality. Recent meta-analyses have found novel genetic loci associated with cigarettes per day (CPD), a proxy for nicotine dependence. The aim of this paper is to evaluate the importance of phenotype definition (i.e. CPD versus Fagerstr?m Test for Cigarette Dependence (FTCD) score as a measure of nicotine dependence) on genome-wide association studies of nicotine dependence. DESIGN: Genome-wide association study. SETTING: Community sample. PARTICIPANTS: A total of 3365 subjects who had smoked at least one cigarette were selected from the Study of Addiction: Genetics and Environment (SAGE). Of the participants, 2267 were European Americans, 999 were African Americans. MEASUREMENTS: Nicotine dependence defined by FTCD score ≥4, CPD. FINDINGS: The genetic locus most strongly associated with nicotine dependence was rs1451240 on chromosome 8 in the region of CHRNB3 [odds ratio (OR)?=?0.65, P?=?2.4?×?10(-8) ]. This association was further strengthened in a meta-analysis with a previously published data set (combined P?=?6.7?×?10(-16) , total n?=?4200). When CPD was used as an alternate phenotype, the association no longer reached genome-wide significance (β?=?-0.08, P?=?0.0004). CONCLUSIONS: Daily cigarette consumption and the Fagerstrom Test for Cigarette Dependence show different associations with polymorphisms in genetic loci. 相似文献
39.
Asma Dilawari Christopher Gallagher Princess Alintah Ami Chitalia Shruti Tiwari Richard Paxman Lucile Adams-Campbell Chiranjeev Dash 《The oncologist》2021,26(4):292-e548
Lessons Learned
- Despite U.S. Food and Drug Administration approval to reduce alopecia, data on efficacy of scalp cooling in Black patients with cancer are limited by lack of minority representation in prior clinical trials.
- Scalp cooling devices may have less efficacy in Black patients; additional studies are required to explore the possible causes for this, including hair texture and cap design.
40.
BackgroundSelf-retaining brain retractors are commonly used during intracranial surgery, and they are indispensable during microneurosurgery. There is a common severe complication due to the use of self-held retractors, that is, formation of a hemorrhagic infarct area in the brain region exposed to traction. All the more, present retractor systems are fixed and rigid and obstruct surgeons during surgery. Sometimes these retractors create glare in the microscope that distracts the surgeon. We hereby propose a simple and easy method of retraction of brain especially the temporal lobe using the transsylvian approach and vermis using the transvermian approach.MethodsThis is retrospective analysis of 47 patients in 4 years in which we have used our stitch retractor. We have analyzed their outcome, postoperative scan, and ease of performing surgery.ResultsIn 47 patients, there was only 1 postoperative contusion, and the longest period it was kept for is 6 hours. The other advantage was that it does not obstruct in any way while doing dissections and surgery. There was no glare while operating under a microscope.ConclusionWe hereby propose a simple and easy method of retraction of brain especially the temporal lobe using the transsylvian approach and vermis using the transvermian approach. It is minimally traumatic, reducing insult to the brain. It allows the surgeon to dissect without any obstruction and glare in the way. The biggest advantage of the present stitch retractor is that it is very cheap and simple to use. 相似文献