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11.
Vassilios I. Avramis Kenneth K. Chan Michelle M. Solorzano Zhan-liu Chen 《Cancer chemotherapy and pharmacology》1993,33(3):197-202
O-6-methylguanine (O6-mG), a guanine analog recently shown to be a potent inhibitor of alkylguanine-DNA alkyltransferase, has been found to potentiate the antitumor activity of nitrosoureas, in particular, carmustine (BCNU), in resistant cell lines (HT-29 mer+) and is targeted for development as a modulating agent with chloroethyl nitrosoureas. A high-performance liquid chromatography (HPLC) assay of O6-mG in plasma has been developed using a C18 reverse-phase column. O6-mG and the internal standard deoxyguanosine (dGuo) were eluted with a linear gradient of from 15% to 35% methanol in 0.5M ammonium acetate (pH 6.5) at a flow rate of 1 ml/min. The assay was linear over a 4-log concentration range with a detection limit of 0.1 g/ml. The within-run and between-run coefficients of variation (CV) were found to be 8.1% and 9.3%, respectively. The pharmacokinetics (PK) of O6-mG were investigated in healthy CDF1 mice following separate i.v. and i.p. administrations. At 20 mg/kg i.v., plasma O6-mG gave a biexponential profile with a terminal half-life (t1/2) of 24 min and a total clearance (CLT) of 23.7 ml min–1 kg–1. Higher doses (40–80 mg/kg) revealed a fluctuating third phase, probably due to enterohepatic cycling. Dose-dependent kinetics as measured by CLT and area under the plasma-concentration curve (AUC) values were also seen. Following i.p. dosing, O6-mG was completely absorbed and available to the circulation. No acute toxicity was observed in the animals, except for mild sedation, a possible side effect of the 10% ethanol used in the formulation. Studies on the cellular metabolism of highly purified [3H]-O6-mG have shown that the compound is not anabolized by a human lymphoblastoid cell line (CEM). Biochemistry studies have shown that the parent molecule is inactivating the alkylguanine-DNA alkyltransferase (AGT), thus exerting its pharmacological effect.Abbreviations O6-mG
O-6-methylguanine
- HPLC
high-performance liquid chromatography
- PK
pharmacokinetics
- CLT
total clearance
- AUC
area under the plasma concentration curve
- AGT
alkylguanine-DNA alkyltransferase
- dGuo
deoxyguanosine
This work was supported in part by contract NO1-CM-97620 from the National Cancer Institute (NIH) and by the Neil Bogart Memorial Laboratories by the T. J. Martell Foundation for Cancer, Leukemia, and AIDS Research 相似文献
12.
Douglas S Hawkins Julie R Park Blythe G Thomson Judy L Felgenhauer John S Holcenberg Eduard H Panosyan Vassilios I Avramis 《Clinical cancer research》2004,10(16):5335-5341
PURPOSE: Asparaginase therapy is an important component in the treatment of children with acute lymphoblastic leukemia. Polyethylene glycol-conjugated asparaginase (PEG-ASNase) has significant pharmacological advantages over native Escherichia coli asparaginase. We investigated the pharmacokinetics of PEG-ASNase, presence of antibodies to PEG-ASNase, and concentrations of asparagine in serum and cerebrospinal fluid (CSF) in combination chemotherapy for relapsed pediatric acute lymphoblastic leukemia. EXPERIMENTAL DESIGN: Twenty-eight pediatric patients with relapsed medullary (n = 16) and extramedullary (n = 11) acute lymphoblastic leukemia were enrolled at three pediatric institutions and had at least two serum and CSF samples obtained for analysis. Patients received induction therapy (including PEG-ASNase 2500 IU/m2 intramuscularly weekly on days 2, 9, 16, and 23) and intensification therapy (including PEG-ASNase 2500 IU/m2 intramuscularly once on day 7). Serum samples were obtained weekly during induction and intensification. CSF samples were obtained during therapeutic lumbar punctures during induction and intensification. RESULTS: Weekly PEG-ASNase therapy resulted in PEG-ASNase activity of >0.1 IU/ml in 91-100% of patients throughout induction. During intensification, PEG-ASNase on day 7 resulted in PEG-ASNase activity >0.1 IU/ml in 94% and 80% of patients on days 14 and 21, respectively. Serum and CSF asparagine depletion was observed and maintained during induction and intensification in the majority of samples. PEG-ASNase antibody was observed in only 3 patients. CONCLUSIONS: Intensive PEG-ASNase therapy in the treatment of relapsed acute lymphoblastic leukemia reliably results in high-level serum PEG-ASNase activity, and asparagine depletion in serum and CSF is usually achieved. Incorporation of intensive PEG-ASNase in future trials for recurrent acute lymphoblastic leukemia is warranted. 相似文献
13.
Georgios Labiris Zisis Gatzioufas Haris Sideroudi Athanassios Giarmoukakis Vassilios Kozobolis Berthold Seitz 《Acta ophthalmologica. Supplement》2013,91(4):e258-e262
Purpose: To evaluate the diagnostic capacity of the Ocular Response Analyser’s keratoconus match index (KMI) and keratoconus match probability (KMP) classification in a sample of keratoconus (KC) patients. Methods: Keratoconus match index and KMP from 114 KC eyes, randomly selected from 114 patients with bilateral keratoconus (KCG), were compared with the corresponding ones from 109 normal eyes (CG). Keratoconus match index’s predictive accuracy was assessed by receiver operating curves (ROC). Keratoconus match probability level of agreement was evaluated at the different KC stages of the Amsler–Krumeich classification. Correlations were estimated with topographic keratoconus classification (TKC), keratoconus index (KI), index of surface variance (ISV), vertical asymmetry (IVA), height asymmetry (IHA), height decentration (IHD), minimal radius (Rmin), central corneal thickness (CCT), thinnest corneal thickness (TCT) mean keratometry (Km) and intraocular pressure (IOPg). Results: Mean KMI in KCG and CG was 0.20 ± 0.38 and 0.98 ± 0.25, respectively (p < 0.01). Significant KMI differences (p < 0.01) were detected in different KC groups [range: 0.62 ± 0.38 (KC 1), ?0.62 ± 0.04 (KC 4)]. Significant correlation was detected between KC staging and KMI (r = ?0.56, p < 0.0001). Keratoconus match probability identified 22.03% of the CG eyes as suspect. Moreover, KMP identified 7.01% and 23.68% of the KCG eyes as normal and suspect, respectively. Receiver operating curves analysis for KMI parameter indicated a predictive accuracy of 97.7% (cut‐off point: 0.512, sensitivity: 91.18%, specificity: 94.34%). Conclusions: Keratoconus match index seems to be a reliable index in keratoconus diagnosis and staging. Keratoconus match probability identifies a significant percentage of topographically defined KC and CG eyes as suspect. Diagnostic capacity of these novel indexes needs to be further explored. 相似文献
14.
A 60-year-old man with polyarteritis nodosa under treatment presented with syncope. Echocardiography demonstrated hypertrophic obstructive cardiomyopathy; coronary arteriography revealed normal findings, and Holter monitor showed episodes of non-sustained ventricular tachycardia. This is the first report of hypertrophic obstructive cardiomyopathy developing in a patient with polyarteritis nodosa. Further studies should examine whether a true association exists.Abbreviations ESR
Erythrocyte sedimentation rate
- PAN
Polyarteritis nodosa 相似文献
15.
Endoscopic management and long-term follow-up of Dieulafoy's lesions in the upper GI tract 总被引:15,自引:0,他引:15
Kasapidis P Georgopoulos P Delis V Balatsos V Konstantinidis A Skandalis N 《Gastrointestinal endoscopy》2002,55(4):527-531
BACKGROUND: The aim of this study was to retrospectively evaluate the short-and long-term effectiveness of different methods of endoscopic treatment for bleeding Dieulafoy's lesions. METHODS: Patients were allocated into 2 groups according to the hemostatic method applied: (1) injection group (epinephrine and/or ethanolamine oleate), and (2) thermal coagulation group (heat probe), either alone or combined with epinephrine injection. The combination of epinephrine and ethanolamine oleate was used in 5 patients, epinephrine alone in 3, ethanolamine oleate alone in one, heat probe and epinephrine in 8, and heat probe alone in 1 patient. RESULTS: Dieulafoy's lesions were found in 18 (1%) of 1750 patients with acute nonvariceal upper GI bleeding. Comorbid conditions were present in 5 (28%) patients. Initial hemostasis was achieved endoscopically in 13 patients (72%) and permanent hemostasis in 17 patients (94%). Bleeding recurred in 5 patients (2 with concomitant disease) in the injection group; 3 were successfully retreated by heat probe coagulation and epinephrine injection, 1 with hemoclip application and 1 by surgery. There was no recurrent bleeding in thermal treatment group. Thermal treatment was significantly superior to injection (p = 0.0029). CONCLUSIONS: Endoscopic thermal coagulation with or without epinephrine injection should be the initial treatment of choice for Dieulafoy's lesions. Mortality is lowest in patients with no significant comorbidity and an unremarkable medical history. 相似文献
16.
17.
Kamyar Kalantar-Zadeh Philip Kam-Tao Li Ekamol Tantisattamo Latha Kumaraswami Vassilios Liakopoulos Siu-Fai Lui Ifeoma Ulasi Sharon Andreoli Alessandro Balducci Sophie Dupuis Tess Harris Anne Hradsky Richard Knight Sajay Kumar Maggie Ng Alice Poidevin Gamal Saadi Allison Tong 《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2021,41(2):95-101
Living with chronic kidney disease (CKD) is associated with hardships for patients and their care-partners. Empowering patients and their care-partners, including family members or friends involved in their care, may help minimize the burden and consequences of CKD related symptoms to enable life participation. There is a need to broaden the focus on living well with kidney disease and re-engagement in life, including an emphasis on patients being in control. The World Kidney Day (WKD) Joint Steering Committee has declared 2021 the year of “Living Well with Kidney Disease” in an effort to increase education and awareness on the important goal of patient empowerment and life participation. This calls for the development and implementation of validated patient-reported outcome measures to assess and address areas of life participation in routine care. It could be supported by regulatory agencies as a metric for quality care or to support labelling claims for medicines and devices. Funding agencies could establish targeted calls for research that address the priorities of patients. Patients with kidney disease and their care-partners should feel supported to live well through concerted efforts by kidney care communities including during pandemics. In the overall wellness programme for kidney disease patients, the need for prevention should be reiterated. Early detection with a prolonged course of wellness despite kidney disease, after effective secondary and tertiary prevention programmes, should be promoted. WKD 2021 continues to call for increased awareness of the importance of preventive measures throughout populations, professionals, and policy makers, applicable to both developed and developing countries. 相似文献
18.
Electrophysiological markers predicting impeding AV‐block during ablation of atrioventricular nodal reentry tachycardia 下载免费PDF全文
Nikolaos Fragakis MD PhD Lydia Krexi MD Panagiota Kyriakou MD PhD Melani Sotiriadou MD Charalambos Lazaridis MD Athanasios Karamanolis MD Panagiotis Dalampyras MD Stelios Tsakiroglou Vassilios Skeberis MD PhD Dimitrios Tsalikakis PhD Vassilios Vassilikos MD PhD 《Pacing and clinical electrophysiology : PACE》2018,41(1):7-13
1 Background
Radiofrequency (RF) ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated with atrioventricular block (AVB) often predicted by junctional beats (JB) with loss of ventriculo‐atrial (VA) conduction.2 Methods
We analyzed retrospectively 153 patients undergoing ablation of SP for typical AVNRT. Patients were divided into two age groups: 127 ≤ 70 years and 26 > 70 years. We analyzed the interval between the atrial electrogram in the His‐bundle position and the distal ablation catheter [A(H)‐A(RFd)] and between the distal ablation catheter and the proximal coronary sinus catheter [A(RFd)‐A(CS)] before RF applications with and without JB. We evaluated if these intervals can be used as predictors of JB incidence and also of JB with loss of VA conduction. We also assessed if age influences the risk of loss of VA conduction.3 Results
The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals were significantly shorter in RF applications causing JB than those without JB (33 ± 11 ms vs 39 ± 9 ms, P < 0.001, 14 ± 9 ms vs 20 ± 7 ms, P < 0.001, respectively). The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals were also significantly shorter in RFs causing JB with VA block than those with VA conduction (29 ± 11 ms vs 35 ± 11 ms, P < 0.001, 8 ± 8 ms vs 17 ± 8 ms, P < 0.001, respectively). Patients > 70 years had shorter intervals (36 ± 11 ms vs 29 ± 8 ms, P = 0.012, 17 ± 8 ms vs 13 ± 7 ms, P = 0.027, respectively), while VA block was more common in this age group.4 Conclusions
The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals can be used as markers for predicting JB occurrence as well as impending AVB. JB with loss of VA conduction occur more often in older patients possibly due to a higher position of SP. 相似文献19.
Neuromuscular diseases and their cardiac manifestations under the spectrum of cardiovascular imaging
Alexandridis Georgios M. Pagourelias Efstathios D. Fragakis Nikolaos Kyriazi Maria Vargiami Efthymia Zafeiriou Dimitrios Vassilikos Vassilios P. 《Heart failure reviews》2022,27(6):2045-2058
Heart Failure Reviews - Neuromuscular diseases (NMDs) include a broad spectrum of disorders that affect motor unit in every possible site, extending from the cell body of peripheral nerves to the... 相似文献
20.
Course of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease 总被引:26,自引:0,他引:26
Papatheodoridis GV Dimou E Laras A Papadimitropoulos V Hadziyannis SJ 《Hepatology (Baltimore, Md.)》2002,36(1):219-226
We studied the course of virologic breakthroughs detected by a quantitative polymerase chain reaction (PCR) assay in 32 of 78 patients with hepatitis B e antigen (HBeAg)-negative precore mutant hepatitis B virus (HBV) chronic liver disease under long-term lamivudine monotherapy. Serum HBV DNA levels were measured every 3 months and on every biochemical breakthrough. YMDD mutants were detected in 30 of the 32 patients with virologic breakthroughs. Among these 32 patients, biochemical remission rate was 44% at 6 months, 21% at 12 months, and 0% at 24 months after the onset of virologic breakthrough. Development of biochemical breakthroughs was associated with a significant increase of serum HBV DNA levels, which exceeded 100,000 copies/mL in 19 of 20 patients (95%) with biochemical breakthroughs and in only 1 of 8 patients (12.5%) remaining in biochemical remission for at least 6 months after the onset of virologic breakthrough (P <.001). Alanine aminotransferase (ALT) level peaked within 0 to 3 months after the onset of biochemical breakthrough and decreased at 6 months but remained abnormal in all but 2 patients. Follow-up liver histologic lesions in patients with biochemical breakthroughs did not differ from baseline findings, although they were significantly improved in patients remaining in virologic and biochemical remission. In conclusion, the frequent emergence of viral resistance under long-term lamivudine monotherapy in HBeAg-negative precore mutant HBV chronic liver disease is followed by increasing viremia levels culminating in the development of biochemical breakthroughs in most cases. ALT activity peaks close to the onset of biochemical breakthrough, decreasing thereafter but remaining persistently abnormal with fluctuating levels. 相似文献