Drugs
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Meconium aspiration syndrome (MAS) is an important cause of respiratory distress in the term infant. Therapy for the disease remains problematic, and newer treatments such as high-frequency ventilation and inhaled nitric oxide are being applied with increasing frequency. There is a significant disturbance of the pulmonary surfactant system in MAS, with a wealth of experimental data indicating that inhibition of surfactant function in the alveolar space is an important element of the pathophysiology of the disease. ⋯ Combined animal and human data suggest that lung lavage can remove significant amounts of meconium and alveolar debris, and thereby improve oxygenation and pulmonary mechanics. Arterial oxygen saturation inevitably falls during lavage but has been noted to recover relatively rapidly, even in infants with severe disease. Several randomised controlled trials of surfactant lavage in MAS are underway, and until the results are known, lavage must be considered an unproven and experimental therapy.
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Recombinant factor VIIa (NovoSeven) [also known as recombinant activated factor VII or eptacog alfa] is a vitamin K-dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. It is a recombinant product, manufactured using DNA biotechnology. Intravenous recombinant factor VIIa has been evaluated in the treatment of bleeding episodes and for providing haemostasis cover during surgery in patients with certain bleeding disorders. ⋯ Direct head-to-head comparisons and robust pharmacoeconomic data are required to fully determine the position of recombinant factor VIIa in relation to other therapies. Importantly though, the product appears to be relatively free of antigenicity, thrombogenicity and risk of viral transmission that, in the past, have limited the utility of blood products. Given that these characteristics are important determinants of the place of a treatment in bleeding disorders, recombinant factor VIIa provides a valuable treatment alternative in patients with haemophilia with inhibitors, platelet-refractory Glanzmann's thrombasthenia or congenital factor VII deficiency.
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Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. ⋯ Other agents being investigated for the treatment of Crohn's disease include inhibitors of T-cell activation, peroxisome proliferator-activated receptors, proinflammatory cytokine receptors and T(h)1 polarisation, and growth hormone and growth factors. Agents being investigated for treatment of ulcerative colitis include many of those mentioned for Crohn's disease. More controlled clinical trials are currently being conducted, exploring the safety and efficacy of old and new biologic agents, and the search certainly will open new and exciting perspectives on the development of therapies for IBD.
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Nelfinavir (Viracept) is an orally administered protease inhibitor. In combination with other antiretroviral drugs (usually nucleoside reverse transcriptase inhibitors [NRTIs]), nelfinavir produces substantial and sustained reductions in viral load in patients with HIV infection. Nelfinavir may be used in the treatment of adults, adolescents and children aged >or=2 years with HIV infection. ⋯ Resistance to nelfinavir may develop, but the most common mutation (D30N, appearing mainly in HIV-1 subtype B) does not confer resistance to other protease inhibitors, thereby conserving these agents for later use. Although less effective than lopinavir/ritonavir, the preferred first-line treatment in US guidelines, nelfinavir is positioned as an alternative agent for the treatment of adults and adolescents with HIV infection and is an option for those unable to tolerate other protease inhibitors. Nelfinavir also has a role in the management of pregnant patients as well as paediatric patients with HIV infection.
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Serious urinary tract infections (UTIs) in adults--defined as acute complicated UTIs or pyelonephritis requiring initial intravenous antimicrobials and/or hospitalisation and nosocomial infections--cause significant morbidity and economic burden. In the US, UTIs are responsible for nearly 7 million outpatient physician office visits, 1 million emergency room visits and over 100 000 hospital admissions annually. Complicated UTIs often affect patients with underlying functional, metabolic or anatomical defects of the urinary tract, whereas most nosocomial UTIs (~80%) are related to short- or long-term catheterisation. ⋯ Several pivotal clinical trials support the use of fluoroquinolones for serious UTIs with most experience garnered with ciprofloxacin, including a new once-daily extended-release tablet formulation. Treatment of patients with serious UTIs remains challenging. Physicians should choose empirical therapy based on patient demographics/medical history, presumed aetiology and local resistance patterns until more definitive guidelines become available.