Volume 48, No. 7/2010(July)
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 Int. Journal of Clinical Pharmacology and Therapeutics
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Original Research
Early immunomodulatory effects of linezolid in a human whole blood endotoxin model
C. Lambers, B. Burian, P. Binder, H.-J. Ankersmit, C. Wagner, M. Müller and M. Zeitlinger
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 7/2010 (419-424)
Early immunomodulatory effects of linezolid in a human whole blood endotoxin model
C. Lambers1,3, B. Burian1, P. Binder1, H.-J. Ankersmit2, C. Wagner3, M. Müller3 and M. Zeitlinger1,3
1Internal Medicine II, Department of Respiratory Medicine, 2Department of Cardio-thoracic Surgery and 3Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria
Gram-negative sepsis resulting in endotoxin triggered septic shock is one of the leading causes of death in critically ill patients. Because treatment options are limited, recent approaches focus on immunomodulatory effects of antimicrobials. Thus, we characterized the immunomodulatory effects of linezolid at mRNA and on cytokine levels in supernatants of an ex vivo model of endotoxemia. Whole blood from 10 healthy volunteers was incubated with 50 pg/ml LPS with or without 13 µg/ml linezolid (concentrations were chosen to reflect in vivo conditions) for 2 and 4 hours (h). Quantitative real-time PCR was performed from messenger RNA (mRNA) of IL-1beta;, IL-6, IL-8 or TNF-alpha;. Cytokine levels in the supernatant were measured by ELISA for IL-6, IL-8 and TNF-alpha;. Incubation of human whole blood with LPS increased mRNA levels of cytokines several thousand fold compared with baseline. The addition of linezolid significantly reduced mRNA levels of IL-1beta, IL-6, IL-8 and TNF-alpha; (p < 0.05) after 2 and 4 h. LPS stimulation also increased levels of IL-6, IL-8 and TNF-alpha between 100 and 1000-fold. However, in contrast to mRNA - except for IL-6 - no significant reduction at protein level was observed. These results indicate that immunosuppressive effects of linezolid on mRNA transcription are only partially reflected by cytokine release.Correspondence to:
Prof. Dr. M. Zeitlinger
Department of Clinical Pharmacology
1090 Vienna, Austria
Email: markus.zeitlinger@meduniwien.ac.at
Original Research
Acute interstitial pneumonitis in a patient receiving a FOLFOX-4 regimen plus cetuximab treated with pulse therapy
J.-I. Lai, W.-S. Wang, Y.-C. Lai, P.-C. Lin and S.-C. Chang
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 7/2010 (425-428)
Acute interstitial pneumonitis in a patient receiving a FOLFOX-4 regimen plus cetuximab treated with pulse therapy
J.-I. Lai1, 2, W.-S. Wang1, 2, Y.-C. Lai1, 2, P.-C. Lin1, 2 and S.-C. Chang1, 2
1National Yang-Ming University School of Medicine and 2Department of Medicine, National Yang-Ming University Hospital, Taiwan, Republic of China
We report a case of acute interstitial pneumonitis and respiratory failure occurring in a 69-year-old, previously healthy patient receiving FOLFOX regimen plus cetuximab for colon cancer. Association between this chemotherapy regimen and interstitial pneumonitis is rarely reported in the literature. We treated the patient with pulse steroid therapy, and improvement in respiratory function and decreased pulmonary infiltrations demonstrated good response to steroids use. However, the patient ultimately expired from respiratory complications after 98 days from admission, possibly due to secondary infection. Both oxaliplatin and cetuximab have rarely been associated with interstitial pneumonitis, and our case may serve as an important reference for physicians notice in patients receiving these chemotherapeutic agents.Correspondence to:
S.-C. Chang, MD
Department of Medicine
National Yang-Ming University Hospital
No. 152, Xin-Min Road, Yilan, 26042 Taiwan
Email: dtsurga9@yahoo.com.tw
Original Research
A multicentric, randomized, comparative clinical trial to evaluate the efficacy and safety of S-etodolac in the treatment of osteoarthritis in Indian patients
P. Sancheti, M. Hardikar, N. Karne, J. Panse, S. Singh, A. Maria and I. Basu
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 7/2010 (429-434)
A multicentric, randomized, comparative clinical trial to evaluate the efficacy and safety of S-etodolac in the treatment of osteoarthritis in Indian patients
P. Sancheti1, M. Hardikar2, N. Karne3, J. Panse4, S. Singh5, A. Maria6 and I. Basu7
1Sancheti Institute for Orthopedics and Rehabilitation, 2Orthopedic Surgeon, Hardikar Hospital, 3Orthopedic Surgeon, Pune Institute of Accident and Orthopedics, 4Orthopedic Surgeon, Panse Hospital, Agarkar Colony, Pune, 5Orthopedic Surgeon, Department of Orthopedics, Apex Hosiptal, Varanasi, 6Consultant Orthopedic Surgeon and Traumatologist, Orthocare, New Delhi and 7Consultant Physician, Ramkrishna Mission Hospital, Varanasi, India
Objective: To compare the efficacy and safety of S-etodolac with etodolac in the treatment of osteoarthritis in Indian patients. Materials and methods: This was a double-blind, multicentric, comparative clinical trial conducted in 108 Indian patients with osteoarthritis. All patients received either S-etodolac ER 300 mg or etodolac ER 600 mg tablets once daily. Assessment was done on the basis of WOMAC score and VAS pain score, patient’s and physician’s global assessment of the arthritic condition. All patients were evaluated after every 2 weeks for 4 weeks for efficacy and safety variables. Results and discussion: Total 49 patients in the test group and 52 patients in the reference group completed the study. There was significant improvement (p < 0.0001) in all WOMAC subscales (pain, stiffness and physical function), WOMAC total score and VAS pain score in both the groups. Patient’s and physician’s global assessment of the arthritic condition also improved significantly (p < 0.0001). All patients showed improvement in WOMAC and VAS pain score by ³ 20%. There was no significant difference between the groups for the efficacy parameters. The adverse events reported were few and no serious adverse events were reported. Total 5 patients in S-etodolac group and 2 patients in etodolac group dropped out of the study. Only 1 patient dropped out because of the side effects of burning sensation, palpitations and anxiety in the test group. Conclusion: The present study has established the efficacy, tolerability and safety of S-etodolac extended release tablets in the treatment of osteoarthritis in Indian patients.Correspondence to:
Dr. P. Sancheti, MS (Ortho), Mch (Ortho)
Medical Director
Sancheti Institute for Orthopedics and Rehabilitation
16, Shivaji Nagar
Pune, 411 005, India
Email: parag@sanchetihospital.org
Extended Abstract
10 Years CESAR Anticancer Drug Research – The 7th CESAR Annual Meeting 2009
L. Edler, D. Sehrt and M.E. Scheulen
Abstract
10 Years CESAR Anticancer Drug Research – The 7th CESAR Annual Meeting 2009
L. Edler, D. Sehrt and M.E. Scheulen
Extended Abstract
New insights into nanoparticles – status in therapy
P. Debbage
Abstract
New insights into nanoparticles – status in therapy
P. Debbage
Extended Abstract
Targeted doxorubicin-liposomes as a tool to circumvent P-gp-mediated resistance in ovarian carcinoma cells
M.L. Krieger, A. Konold, M. Wiese, U. Jaehde and G. Bendas
Abstract
Targeted doxorubicin-liposomes as a tool to circumvent P-gp-mediated resistance in ovarian carcinoma cells
M.L. Krieger, A. Konold, M. Wiese, U. Jaehde and G. Bendas
Extended Abstract
Contribution of glutathione and MRP-mediated efflux to intracellular oxaliplatin accumulation
C. Mohn, G.V. Kalayda, H.-G. Häcker, M. Gütschow, S. Metzger and U. Jaehde
Abstract
Contribution of glutathione and MRP-mediated efflux to intracellular oxaliplatin accumulation
C. Mohn, G.V. Kalayda, H.-G. Häcker, M. Gütschow, S. Metzger and U. Jaehde
Extended Abstract
Blocking of integrin-mediated human MV3 melanoma cell binding by commercial and modified heparins
M. Schlesinger, A. Naggi, G. Torri, R. Zeisig, M. Alexander, P. Schmitz, B. Casu and G. Bendas
Abstract
Blocking of integrin-mediated human MV3 melanoma cell binding by commercial and modified heparins
M. Schlesinger, A. Naggi, G. Torri, R. Zeisig, M. Alexander, P. Schmitz, B. Casu and G. Bendas
Extended Abstract
Neoadjuvant treatment of adenocarcinomas of the gastroesophageal junction and stomach – a feasibility trial combining cisplatin and docetaxel with either 5-fluorouracil or capecitabine
B. Schultheis, J. Riebeling, M. Allali, U. Bergmann, G. Kummer, U. Sendler, A. Tannapfel, A. Sendler and D. Strumberg
Abstract
Neoadjuvant treatment of adenocarcinomas of the gastroesophageal junction and stomach – a feasibility trial combining cisplatin and docetaxel with either 5-fluorouracil or capecitabine
B. Schultheis, J. Riebeling, M. Allali, U. Bergmann, G. Kummer, U. Sendler, A. Tannapfel, A. Sendler and D. Strumberg
Extended Abstract
Albumin, a versatile carrier in oncology
F. Kratz
Abstract
Albumin, a versatile carrier in oncology
F. Kratz
Extended Abstract
Intracellular ATP depletion leads to reduced platinum accumulation in ovarian cancer cells
V. Schneider, G.V. Kalayda, M.L. Krieger, G. Bendas and U. Jaehde
Abstract
Intracellular ATP depletion leads to reduced platinum accumulation in ovarian cancer cells
V. Schneider, G.V. Kalayda, M.L. Krieger, G. Bendas and U. Jaehde
Extended Abstract
Tumor-selective amphiphilic para-quinones and tetramic acids
R. Schobert, F. Sasse, B. Biersack, K. Effenberger, S. Breyer and R. Diestel
Abstract
Tumor-selective amphiphilic para-quinones and tetramic acids
R. Schobert, F. Sasse, B. Biersack, K. Effenberger, S. Breyer and R. Diestel
Extended Abstract
Rat monoclonal antibodies against bone sialoprotein II inhibit tumor growth and osteolytic lesions in nude rats induced by MDA-MB-231 breast cancer cells
M. Zepp, F.P. Armbruster and M.R. Berger
Abstract
Rat monoclonal antibodies against bone sialoprotein II inhibit tumor growth and osteolytic lesions in nude rats induced by MDA-MB-231 breast cancer cells
M. Zepp, F.P. Armbruster and M.R. Berger
Extended Abstract
Web-based open source application for the randomization process in clinical trials: RANDI2
D. Schrimpf, L. Plotnicki and L.R. Pilz
Abstract
Web-based open source application for the randomization process in clinical trials: RANDI2
D. Schrimpf, L. Plotnicki and L.R. Pilz
Extended Abstract
Successful sequential antiangiogenic therapy for alveolar soft part sarcoma – a case report
B. Schultheis, G. Kummer, A. Tannapfel and D. Strumberg
Abstract
Successful sequential antiangiogenic therapy for alveolar soft part sarcoma – a case report
B. Schultheis, G. Kummer, A. Tannapfel and D. Strumberg
Extended Abstract
First-line treatment of patients with metastatic pancreatic cancer: results of a Phase II trial with S-1 (CESAR-Study group)
D. Strumberg, L. Bergmann, U. Graeven, A. Hanauske, R. Lipp, J. Schuette, B. Schultheis, P. Scigalla, P. Urrea and M.E. Scheulen
Abstract
First-line treatment of patients with metastatic pancreatic cancer: results of a Phase II trial with S-1 (CESAR-Study group)
D. Strumberg, L. Bergmann, U. Graeven, A. Hanauske, R. Lipp, J. Schuette, B. Schultheis, P. Scigalla, P. Urrea and M.E. Scheulen
Extended Abstract
Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer
D. Strumberg, B. Schultheis, M.E. Scheulen, R.A. Hilger, J. Krauss, N. Marschner, F. Lordick, F. Bach, D. Reuter, L. Edler and K. Mross
Abstract
Safety, efficacy and pharmacokinetics of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer
D. Strumberg, B. Schultheis, M.E. Scheulen, R.A. Hilger, J. Krauss, N. Marschner, F. Lordick, F. Bach, D. Reuter, L. Edler and K. Mross
Extended Abstract
Continuous monitoring of toxicity in clinical trials – simulating the risk of stopping prematurely
H. Aamot, B. Gigic, U. Abel and I. Karapanagiotou-Schenkel
Abstract
Continuous monitoring of toxicity in clinical trials – simulating the risk of stopping prematurely
H. Aamot, B. Gigic, U. Abel and I. Karapanagiotou-Schenkel
Extended Abstract
Reduction in human melanoma cell adhesion receptor activity by lysophosphatidylcholine (LPC) treatment – functional characterization and signal pathway analyses
M. Alexander, M. Schlesinger, P. Jantscheff, U. Massing and G. Bendas
Abstract
Reduction in human melanoma cell adhesion receptor activity by lysophosphatidylcholine (LPC) treatment – functional characterization and signal pathway analyses
M. Alexander, M. Schlesinger, P. Jantscheff, U. Massing and G. Bendas
Extended Abstract
Emerging role of thymidylate synthase for the pharmacogenomic selection of patients with thoracic cancer
P. Ceppi, V. Monica, L. Righi, M. Papotti and G.V. Scagliotti
Abstract
Emerging role of thymidylate synthase for the pharmacogenomic selection of patients with thoracic cancer
P. Ceppi, V. Monica, L. Righi, M. Papotti and G.V. Scagliotti
Extended Abstract
Evidence for the conversion of docetaxel into 7’-epidocetaxel in patients receiving Taxotere<sup>®</sup>-based conventional chemotherapy
M. Czejka, R. Greil, E. Ulsperger, H. Schnait, K. Kienesberger, T. Brumnik, A. Farkouh and J. Schierholz
Abstract
Evidence for the conversion of docetaxel into 7’-epidocetaxel in patients receiving Taxotere®-based conventional chemotherapy
M. Czejka, R. Greil, E. Ulsperger, H. Schnait, K. Kienesberger, T. Brumnik, A. Farkouh and J. Schierholz
Extended Abstract
New doxorubicin N-acyl hydrazones with improved efficacy and cell line specificity show modes of action different from the parent drug
K. Effenberger, S. Breyer, M. Ocker and R. Schobert
Abstract
New doxorubicin N-acyl hydrazones with improved efficacy and cell line specificity show modes of action different from the parent drug
K. Effenberger, S. Breyer, M. Ocker and R. Schobert
Extended Abstract
Plasma disposition of capecitabine (CCB) and its metabolites 5’-deoxy-5-fluorocytidine (5’-DFCR) and 5’-deoxy-5-fluorouracil (5’-DFUR) with two different capecitabine/oxaliplatin dosage regimens
A. Farkouh, J. Schueller, W. Scheithauer and M. Czejka
Abstract
Plasma disposition of capecitabine (CCB) and its metabolites 5’-deoxy-5-fluorocytidine (5’-DFCR) and 5’-deoxy-5-fluorouracil (5’-DFUR) with two different capecitabine/oxaliplatin dosage regimens
A. Farkouh, J. Schueller, W. Scheithauer and M. Czejka
Extended Abstract
MYCN/MYC-mediated drug resistance mechanisms in neuroblastoma
S. Gogolin, D. Dreidax, G. Becker, V. Ehemann, M. Schwab and F. Westermann
Abstract
MYCN/MYC-mediated drug resistance mechanisms in neuroblastoma
S. Gogolin, D. Dreidax, G. Becker, V. Ehemann, M. Schwab and F. Westermann
Extended Abstract
Radiation induced stress proteins
M. Gehrmann, D. Schilling, M. Molls and G. Multhoff
Abstract
Radiation induced stress proteins
M. Gehrmann, D. Schilling, M. Molls and G. Multhoff
Extended Abstract
Experiences with bortezomib in multiple myeloma – from Phase II studies to daily practice
S. Schmitt, U. Bertsch and H. Goldschmidt
Abstract
Experiences with bortezomib in multiple myeloma – from Phase II studies to daily practice
S. Schmitt, U. Bertsch and H. Goldschmidt
