Search PubMed⌕ Search

Biomedical subjects

N H Shear

Publications and source records attributed to N H Shear.

153 records · Page 9Linked to original sources
PubMedDate not supplied

Systemic gold therapy.

Explore the source record for details and available documents.

Administration, Oral↗
PubMedDate not supplied

A cost-utility analysis of second-line antibiotics in the treatment of acute otitis media in children.

Newer antibiotics have higher acquisition costs than the first-line antibiotics but may offer superior outcomes, including enhanced eradication of resistant organisms, safety, and compliance in the treatment of acute otitis media. A rational choice among differing therapies should systematically address all these factors. We conducted a cost-utility analysis to compare the commonly used second-line antibiotics--cefaclor (CEF), amoxicillin-clavulanate (AMX-CLA), and erythromycin-sulfisoxazole (ERY-SULF). A meta-analysis of comparative clinical trials was performed to derive point estimates with a 95% confidence interval for rates of success and adverse events. Costs for drugs, laboratory tests, and physician visits were obtained from the government formulary and fee schedules. The cost for management of adverse events was estimated from the findings of a survey of pediatricians. Utilities (preferences or ratings of health states) were derived from responses of physicians to a standardized scenario of acute otitis media with combinations of adverse events. These utilities were used to obtain quality-adjusted life-day (QALD) scores over a 30-day horizon as a measure of effectiveness. Overall cost and QALD were calculated using decision analytic modeling. CEF performed significantly better than the two other drug treatments with the lowest expected cost ($108.00) and highest outcome (28.15 QALD); AMX-CLA was second in cost and third in outcome ($119.00, 27.98 QALD); and ERY-SULF was third in cost and second in outcome ($120.00, 28.03 QALD). These rankings were robust to variations in event rates over the 95% confidence interval. In this analysis, CEF was the most cost-effective antibiotic strategy for second-line therapy when differential success rates, adverse-event profiles, and impact on quality-of-life were considered.

Anti-Bacterial Agents↗
PubMedDate not supplied

A double-blind, randomized, placebo-controlled trial of eutectic lidocaine/prilocaine cream 5% (EMLA) for analgesia prior to cryotherapy of warts in children and adults.

Liquid nitrogen cryotherapy is an effective treatment modality for verrucae in children. However, sometimes the pain of the procedure is too much for the young child. In such instances the availability of an effective topical anesthetic would be of tremendous benefit. Warts are usually present on hardened skin, that is, the palms, periungual areas, and soles. In a double-blind, randomized, placebo-controlled, single-center, parallel-group trial with one visit, children (6-18 years old) and adults (>18 years old) had 2.5 g of lidocaine/prilocaine cream 5% applied under an occlusive dressing to the wart and a 1 to 2 mm area surrounding it 1 hour prior to liquid nitrogen cryotherapy. In both age groups the warts were subdivided by location-hardened skin areas versus nonhardened skin sites. The topical anesthetic was then removed and cryotherapy applied for 5 to 10 seconds. The pain of cryotherapy was assessed by the patient on a visual analogue scale (VAS) immediately after the cryotherapy and 4 and 8 hours later. There was no statistically significant difference in the pain of cryotherapy experienced following the application of active cream (n = 64) and placebo (n = 64). Exploratory subgroup analysis by wart location showed promising results for lidocaine/prilocaine cream 5% over placebo in children with warts on hardened skin sites (palms and soles). The topical anesthetic was safe and generally well-tolerated. Lidocaine/prilocaine cream 5% may provide some anesthesia in children receiving cryotherapy when the wart is on the palms or soles. Further studies are needed to better understand the site and age specificity of the anesthetic properties of lidocaine/prilocaine cream 5% when used to reduce the pain experienced during cryotherapy of warts.

Administration, Topical↗
PubMedDate not supplied

Ethanol-modulated cytokine production and expression in skin cells exposed to methotrexate.

Evidence suggests a link between alcohol consumption, psoriasis and the response of psoriatic patients to methotrexate (MTX) therapy. Ethanol (EtOH) may play a role in the pathogenesis of psoriasis by upregulating the expression and inducing the local secretion of proinflammatory cytokines, e.g. interleukins IL-1alpha, IL-6, chemokine IL-8 and tumor necrosis factor alpha (TNF-alpha). We investigated whether EtOH or MTX or their combination influence the secretion of these cytokines using normal human primary skin cells (NHPSC) and epidermoid cell line A431. The objectives of this study were: (1) to quantify the differences in cellular changes induced by MTX, (2) to measure the effect of EtOH on MTX toxicity and (3) to determine the relationship between MTX and EtOH exposure and production of proinflammatory cytokines. NHPSC and A431 were incubated with 0-10 mM MTX or alpha-MEM (control) in the presence or absence of 40 mM EtOH. A formazan 3-(4,5-dimethylthiazole-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay was used as a marker for cell viability (control was 100%). Significance was calculated by ANOVA. Cytokine release into media was quantitated by ELISA. After 24 h of MTX exposure, the release of IL-1alpha was unchanged. IL-6 increased 1.7 times in both cultures, and IL-8 increased 1.7 times in NHPSC and 2.1 times in A431. TNF-alpha release increased twice in A431 but not in NHPSC. Human recombinant IL-1alpha and IL-6 for 24 h had no effect, while TNF-alpha reduced cytoviability by 30% in NHPSC and 22% in A431. Anti-TNF-alpha reversed the effect produced by TNF-alpha in NHPSC and reduced it in A431 (11.8%, p < 0.05). We concluded that in vitro in normal human primary keratinocytes, toxicity and inflammatory responses are enhanced by EtOH.

Antibodies, Monoclonal↗
PubMedDate not supplied

N-chlorination of sulfamethoxazole and dapsone by the myeloperoxidase system.

It is known that activation of neutrophils or monocytes leads to the formation of hydrogen peroxide and the release of myeloperoxidase (MPO). We found that sulfamethoxazole was chlorinated by the combination of MPO, hydrogen peroxide, and chloride. The product, N-chlorosulfamethoxazole, is reasonably stable but reacts rapidly with a variety of compounds. The same product was formed by the reaction between sulfamethoxazole and hypochlorous acid, and dapsone was also N-chlorinated by the MPO system or hypochlorous acid. Although N-chlorination was not observed when sulfamethoxazole or dapsone was incubated with activated neutrophils, this is presumably because the chloramine products react rapidly with the cells. When radiolabeled sulfamethoxazole was incubated with activated neutrophils, covalent binding was observed. When radiolabeled sulfamethoxazole was incubated with MPO and hydrogen peroxide in the presence of albumin, covalent binding to the albumin occurred. Although binding to albumin occurred in the absence of chloride, it was increased by the presence of chloride. This suggests that N-chlorosulfamethoxazole may be one of several reactive metabolites of sulfamethoxazole that covalently bind to neutrophils. We suspect that covalent binding of arylamine drugs, such as sulfamethoxazole, to activated leukocytes is responsible for some of the adverse reactions associated with these drugs, especially adverse reactions that involve leukocytes such as agranulocytosis or drug-induced lupus.

Chlorides↗