Urticaria and its subtypes: the role of second-generation antihistamines

Urticaria is a heterogeneous group of debilitating skin disorders characterized by wheals, pruritus, and frequently angioedema. The various forms of urticaria are often chronic and can exact a toll on quality of life. New diagnostic criteria and management guidelines are available to assist primary care physicians in the identification and proper treatment of different subtypes of urticaria. Second-generation antihistamines are recommended as first-line therapy because of their high degree of efficacy and safety. It is important to note, however, that European indications for most agents in this class are limited to specific forms of urticaria. The exception is desloratadine, the only second-generation antihistamine approved for the treatment of all urticaria subtypes in the European Union. Guidelines and best practice suggest that doses of antihistamines up to 4 times higher than those normally recommended for urticaria may benefit patients who do not respond to standard doses of antihistamines. Adjunctive therapy with leukotriene receptor antagonists may be advantageous in certain subgroups of patients who have suboptimal responses to antihistamine monotherapy. In all cases, physicians should work closely with patients to ensure proper adherence to prescribed regimens—a component that is often lacking but holds the key to successful outcomes.     

A cohort cost analysis of lumbar laminectomy—current trends in surgeon and hospital fees distribution

Background contextSpine-related health-care expenditures accounted for $86 billion dollars in 2005, a 65% increase from 1997. However, when adjusting for inflation, surgeons have seen decreased reimbursement rates over the last decade.PurposeTo assess contribution of surgeon fees to overall procedure cost, we reviewed the charges and reimbursements for a noninstrumented lumbar laminectomy and compared the amounts reimbursed to the hospital and to the surgeon at a major academic institution.Study design/settingRetrospective review of costs associated with lumbar laminectomies.Patient sampleSeventy-seven patients undergoing lumbar laminectomy for spinal stenosis throughout an 18-month period at a single academic medical center were included in this study.Outcome measuresCost and number of laminectomy levels.MethodsThe reimbursement schedule of six academic spine surgeons was collected over 18 months for performed noninstrumented lumbar laminectomy procedures. Bills and collections by the hospital and surgeon professional fees were comparatively analyzed and substratified by number of laminectomy levels and patient insurance status. Unpaired two-sample Student t test was used for analysis of significant differences.ResultsDuring an 18-month period, patients underwent a lumbar laminectomy involving on average three levels and stayed in the hospital on average 3.5 days. Complications were uncommon (13%). Average professional fee billing for the surgeon was $6,889±$2,882, and collection was $1,848±$1,433 (28% overall, 30% for private insurance, and 23% for Medicare/Medicaid insurance). Average hospital billing for the inpatient hospital stay minus professional fees from the surgeon was $14,766±$7,729, and average collection on such bills was $13,391±$7,256 (92% overall, 91% for private insurance, and 85% for Medicare/Medicaid insurance).ConclusionBased on this analysis, the proportion of overall costs allocated to professional fees for a noninstrumented lumbar laminectomy is small, whereas those allocated to hospital costs are far greater. These findings suggest that the current focus on decreasing physician reimbursement as the principal cost saving strategy will lead to minimal reimbursement for surgeons without a substantial drop in the overall cost of procedures performed.     

IL-13 induces expression of CD36 in human monocytes through PPARgamma activation

The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)gamma pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARgamma pathway was demonstrated using transfection of a PPARgamma expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARgamma, and in peritoneal macrophages from PPARgamma-conditional null mice. We also show that CD36 induction by IL-13 via PPARgamma is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-Delta12,14-prostaglandin J2, an endogenous PPARgamma ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARgamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARgamma in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARgamma ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.     

Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy

Here, we analyze the complete coding sequences of all recognized tick-borne flavivirus species, including Gadgets Gully, Royal Farm and Karshi virus, seabird-associated flaviviruses, Kadam virus and previously uncharacterized isolates of Kyasanur Forest disease virus and Omsk hemorrhagic fever virus. Significant taxonomic improvements are proposed, e.g. the identification of three major groups (mammalian, seabird and Kadam tick-borne flavivirus groups), the creation of a new species (Karshi virus) and the assignment of Tick-borne encephalitis and Louping ill viruses to a unique species (Tick-borne encephalitis virus) including four viral types (i.e. Western Tick-borne encephalitis virus, Eastern Tick-borne encephalitis virus, Turkish sheep Tick-borne encephalitis virus and Louping ill Tick-borne encephalitis virus). The analyses also suggest a complex relationship between viruses infecting birds and those infecting mammals. Ticks that feed on both categories of vertebrates may constitute the evolutionary bridge between the three distinct identified lineages.     

Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic β3-adrenoceptor deficiency

This study investigated the influence of chronic β₃-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca²⁺-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and β₃-adrenoceptor knockout mice (β₃-KNO, n=7). Morphometric heart analysis showed no difference between WT and β₃-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in β₃-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in β₃-KNO. Alterations in phospholamban phosphorylation were independent of alterations in β₁/β₂-adrenoceptor distribution and protein expression of G proteins in β₃-KNO. Measurement of myofibrillar Ca²⁺ sensitivity showed no difference in the Ca²⁺/force relation for WT and β₃-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and β₃-KNO. The conclusion is that depression of β₃-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca²⁺ uptake. Thus, β₃-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.