Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptococcus pneumoniae has been recognised as a major cause of pneumonia since the time of Sir William Osler. Drug-resistant S. pneumoniae (DRSP), which have gradually become resistant to penicillins as well as more recently developed macrolides and fluoroquinolones, have emerged as a consequence of indiscriminate use of antibacterials coupled with the ability of the pneumococcus to adapt to a changing antibacterial milieu. Pneumococci use cell wall choline components to bind platelet-activating factor receptors, colonise mucosal surfaces and evade innate immune defenses. Numerous virulence factors that include hyaluronidase, neuraminidase, iron-binding proteins, pneumolysin and autolysin then facilitate cytolysis of host cells and allow tissue invasion and bloodstream dissemination. Changes in pneumococcal cell wall penicillin-binding proteins account for resistance to penicillins, mutations in the ermB gene cause high-level macrolide resistance and mutations in topoisomerase IV genes coupled with GyrA gene mutations alter DNA gyrase and lead to high-level fluoroquinolone resistance. Risk factors for lower respiratory tract infections in the elderly include age-associated changes in oral clearance, mucociliary clearance and immune function. Other risks for developing pneumonia include poor nutrition, hypoalbuminaemia, bedridden status, aspiration, recent viral infection, the presence of chronic organ dysfunction syndromes including parenchymal lung disease and recent antibacterial therapy. Although the incidence of infections caused by DRSP is rising, the effect of an increase in the prevalence of resistant pneumococci on mortality is not clear. When respiratory infections occur, rapid diagnosis and prompt, empirical administration of appropriate antibacterial therapy that ensures adequate coverage of DRSP is likely to increase the probability of a successful outcome when treating community-acquired pneumonia in elderly patients, particularly those with multiple risk factors for DRSP. A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of pneumonia and antibacterial administration. The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs. If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep drug concentrations above the minimal inhibitory concentration that is effective for DRSP. Treatment guidelines and recent studies suggest that combination therapy with a beta-lactam and macrolide may be associated with a better outcome in hospitalised patients, and overuse of fluoroquinolones as a single agent may promote quinolone resistance. The ketolides represent a new class of macrolide-like antibacterials that are highly effective in vitro against macrolide- and azalide-resistant pneumococci. Pneumococcal vaccination with the currently available polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive pneumococcal disease), but more effective vaccines, such as nonconjugate protein vaccines, need to be developed that provide broad protection against pneumococcal infection.
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PMID:Drug treatment of pneumococcal pneumonia in the elderly. 1549 50

Immunoglobulin (Ig) replacement therapy has been the mainstay of primary immunodeficiencies (PID) treatment for more than 30 years and has substantially changed the lives of patients. This review focuses on aspects of Ig use in clinical practice in addition to discussing prioritizing future Ig use. Despite Ig therapy, PID patients continue to be predisposed to recurrent, subclinical respiratory tract infections, which may lead to chronic lung disease. Research has shown that one of the underlying reasons for this deterioration in lung function is the differential distribution and concentration of Ig isotypes in the airway lumen. Further to this, the relationship between Ig dose and infection outcome is explored, expanding on end-of-cycle loss of efficacy (wear-off) particularly with intravenous immunoglobulin (IVIg), how this can confound the determination of optimal IgG dose and how our aim of treatment should be to improve clinical outcome. This review goes on to discuss the safety of Ig replacement therapy, which is generally well tolerated by most patients, compares the rates of systemic adverse reactions between IVIg and SCIg and highlights the advantages of SCIg administration in this respect, including the use of pre-infused subcutaneous recombinant human hyaluronidase to aid subcutaneous infusion volumes. The growing demand for Ig replacement therapy is challenging physicians; here we show the development of prioritization algorithms to assist in identifying those who will benefit most from this clinically valuable therapy.
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PMID:7th International Immunoglobulin Conference: Immunoglobulin in clinical practice. 2554 66

Intravenous and subcutaneous immunoglobulins (IVIg and SCIg, respectively) are increasingly used in clinical practice, not only as replacement therapy but also for immunomodulation. Physicians have learned that primary immunodeficiency (PID) patients are susceptible to recurrent respiratory tract infections even when appropriately treated with immunoglobulin (Ig) therapy. Further investigation will establish whether a combined therapeutic approach including Ig dose optimization will prevent progressive lung disease in PID. The wear-off effects observed with IVIg can be minimized by adjusting the dosing regimen. It is also possible to avoid the cyclic wear-off following transition to SCIg administration. Consideration of benefit versus risk with Ig therapy includes evaluating the potential occurrence of thromboembolic and haemolytic events, which may be more frequent when Ig is administered in high doses and in the presence of pre-existing risk factors. The ability to select an administration method from IVIg, SCIg or hyaluronidase-facilitated SCIg infusions provides patient choice and alternatives if one or other administration route is not suitable for a patient. The evolution in indications, applications, and understanding of Ig therapy described here has reinforced the need for robust methods to prioritize Ig use.
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PMID:7th International Immunoglobulin Conference: Immunoglobulin in clinical practice. 2554 73