Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Jul 2011
ReviewImmune-modulating interventions in critically ill septic patients: pharmacological options.
Critically ill patients with severe sepsis and septic shock are characterized by a systemic inflammatory response consisting of pro- and anti-inflammatory mediators. Owing to the high mortality of severe sepsis, great efforts have been undertaken within the last 30 years to develop an immune-modulating therapy to improve survival. Relatively few pharmacological immune-modulating interventions have demonstrated a beneficial impact on survival, while other studies have shown a detrimental effect of such interventions. ⋯ However, in later studies, it has been difficult to reproduce these beneficial effects. There appears to be a discrepancy between the promising effects of immune-modulating interventions in animal studies and the effects seen in the clinical setting. In the future, the onset of the proinflammatory versus the anti-inflammatory response must be better defined and the timing of treatment with immune-modulating agents should be better managed.
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Expert Rev Clin Pharmacol · May 2011
ReviewTargeting N-methyl-D-aspartate receptors for treatment of neuropathic pain.
Neuropathic pain remains a major clinical problem and a therapeutic challenge because existing analgesics are often ineffective and can cause serious side effects. Increased N-methyl-d-aspartate receptor (NMDAR) activity contributes to central sensitization in certain types of neuropathic pain. NMDAR antagonists can reduce hyperalgesia and allodynia in animal models of neuropathic pain induced by nerve injury and diabetic neuropathy. ⋯ However, patients with postherpetic neuralgia respond poorly to NMDAR antagonists. Recent studies on identifying NMDAR-interacting proteins and molecular mechanisms of increased NMDAR activity in neuropathic pain could facilitate the development of new drugs to attenuate abnormal NMDAR activity with minimal impairment of the physiological function of NMDARs. Combining NMDAR antagonists with other analgesics could also lead to better management of neuropathic pain without causing serious side effects.
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Expert Rev Clin Pharmacol · Nov 2010
Potential clinical application of KGF-2 (FGF-10) for acute lung injury/acute respiratory distress syndrome.
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an acute life-threatening form of hypoxemic respiratory failure with a high mortality rate, and there is still a great need for more effective therapies for such a severe and lethal disease. Dysfunction of endothelial and epithelial barriers is one of the most important mechanisms in hypoxia-associated ALI/ARDS. ⋯ KGF-2, a potent alveolar epithelial cell mitogen, plays an important role in organ morphogenesis and epithelial differentiation, and modulates a variety of mechanisms recognized to be important in alveolar repair and resolution in ALI/ARDS. Preclinical and clinical studies have suggested that KGF-2 may be the candidate of novel therapies for alveolar epithelial damage during ALI/ARDS.
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Expert Rev Clin Pharmacol · Jul 2010
Combination of arginine and omega-3 fatty acids enteral nutrition in critically ill and surgical patients: a meta-analysis.
Immunonutrients may improve outcomes in critically ill and surgical patients. The objective of this meta-analysis was to determine if the combination of arginine and omega-3 fatty acids impacts infection rate, hospital length of stay and mortality in critically ill or surgical patients. In total, 23 studies met all of the criteria. ⋯ Infection rate and length of stay were significantly lower in patients receiving immunonutrition compared with the control group. In a subgroup analysis, these differences were maintained in the pre- and post-operative populations, but were not significant in the critically ill population. Mortality was not significantly different between the immunonutrition and control groups.
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Expert Rev Clin Pharmacol · Mar 2009
Antibiotic resistance: the challenge from an industry perspective.
Trained in medical microbiology and infectious diseases in the UK, Glenn Tillotson has over 20 years pharmaceutical experience in various areas, including clinical research, marketing, scientific communications, strategic development and global launch programs. Mainly in the field of anti-infectives, Tillotson has been instrumental in the development of ciprofloxacin and moxifloxacin, as well as other drugs in the Bayer portfolio. After leaving Bayer, he worked as a consultant microbiologist and, in 2003, consulted with Genesoft to help with the commercialization and launch of gemifloxacin, leading to the development of Oscient following the merger of Genesoft and Genome Therapeutics. ⋯ Presently, Tillotson is Head of Medical Affairs at ViroPharma Inc., where he oversees educational, publication and other related activities for Vancocin(®), maribavir and Cinryze™. Most recently, Tillotson was a member of the Scientific Steering Committee for the International Society of Chemotherapy's Symposium on Clostridium difficile in Leipzig, Germany. Here, he talks with Expert Review of Clinical Pharmacology about the challenge of antibiotic resistance from an industry perspective.