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Articles by C. E McCulloch
Total Records ( 3 ) for C. E McCulloch
  E. J Kezirian , D. P White , A Malhotra , W Ma , C. E McCulloch and A. N. Goldberg

Objective  To determine the interrater reliability of drug-induced sleep endoscopy (DISE).

Design  Prospective cohort; blinded comparison.

Setting  Academic referral center.

Participants  Subjects with obstructive sleep apnea unable to tolerate positive airway pressure therapy.

Interventions  Drug-induced sleep endoscopy was performed with intravenous propofol infusion to achieve sedation, and the videoendoscopy recording was evaluated by 2 independent reviewers.

Main Outcome Measures  The following outcomes were measured: a global assessment of obstruction at the palate and/or hypopharynx; the degree of obstruction at the palate and hypopharynx; and the contribution of individual structures (palate, tonsils, tongue, epiglottis, and lateral pharyngeal walls) to obstruction.

Results  A total of 108 subjects underwent DISE examination. Diagnostic sleep studies demonstrated a mean (SD) apnea-hypopnea index of 39.6 (24.0). Three-quarters of the subjects demonstrated multilevel airway obstruction at the palate and hypopharynx, with a diversity of individual structures contributing to obstruction. The interrater reliability for the presence of obstruction at the palate and hypopharynx ( values, 0.76 and 0.79, respectively) was higher than for the degree of obstruction (weighted values, 0.60 and 0.44). The interrater reliability for the assessment of primary structures contributing to obstruction at the palate and hypopharynx (0.70 and 0.86) was higher than for the contributions of individual structures ( values, 0.42-0.71). The interrater reliability for evaluation of the hypopharyngeal structures was higher than for those of the palate region.

Conclusion  The interrater reliability of DISE is moderate to substantial.

Trial Registration Identifier: NCT00695214

  J. Y Tang , M Aszterbaum , M Athar , F Barsanti , C Cappola , N Estevez , J Hebert , J Hwang , Y Khaimskiy , A Kim , Y Lu , P. L So , X Tang , M. A Kohn , C. E McCulloch , L Kopelovich , D. R Bickers and E. H. Epstein

In vitro and epidemiologic studies favor the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) in preventing skin squamous photocarcinogenesis, but there has been relatively little study of their efficacy in preventing the more common skin basal cell carcinoma (BCC) carcinogenesis. We first compared the relative anti-BCC effects of genetic deletion and NSAID pharmacologic inhibition of cyclooxygenase (COX) enzymes in the skin of Ptch1+/– mice. We then assessed the effects of celecoxib on the development of BCCs in a 3-year, double-blinded, randomized clinical trial in 60 (PTCH1+/–) patients with the basal cell nevus syndrome. In Ptch1+/– mice, genetic deletion of COX1 or COX2 robustly decreased (75%; P < 0.05) microscopic BCC tumor burden, but pharmacologic inhibition with celecoxib reduced microscopic BCCs less efficaciously (35%; P < 0.05). In the human trial, we detected a trend for oral celecoxib reducing BCC burden in all subjects (P = 0.069). Considering only the 60% of patients with less severe disease (<15 BCCs at study entry), celecoxib significantly reduced BCC number and burden: subjects receiving placebo had a 50% increase in BCC burden per year, whereas subjects in the celecoxib group had a 20% increase (Pdifference = 0.024). Oral celecoxib treatment inhibited BCC carcinogenesis in PTCH1+/– mice and had a significant anti-BCC effect in humans with less severe disease. Cancer Prev Res; 3(1); OF1–11

  S Weinsheimer , H Kim , L Pawlikowska , Y Chen , M. T Lawton , S Sidney , P. Y Kwok , C. E McCulloch and W. L. Young

Background— Brain arteriovenous malformations (BAVMs) are a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation and an important cause of intracranial hemorrhage (ICH). EphB4 is involved in arterial-venous determination during embryogenesis; altered signaling could lead to vascular instability resulting in ICH. We investigated the association of single-nucleotide polymorphisms (SNPs) and haplotypes in EPHB4 with risk of ICH at clinical presentation in patients with BAVM.

Methods and Results— Eight haplotype-tagging SNPs spanning 29 kb were tested for association with ICH presentation in 146 white patients with BAVM (phase I: 56 ICH, 90 non-ICH) using allelic, haplotypic, and principal components analysis. Associated SNPs were then genotyped in 102 additional cases (phase II: 37 ICH, 65 non-ICH), and data were combined for multivariable logistic regression. Minor alleles of 2 SNPs were associated with reduced risk of ICH presentation (rs314313_C, P=0.005; rs314308_T, P=0.0004). Overall, haplotypes were also significantly associated with ICH presentation (2=17.24, 6 df, P=0.008); 2 haplotypes containing the rs314308 T allele (GCCTGGGT, P=0.003; GTCTGGGC, P=0.036) were associated with reduced risk. In principal components analysis, 2 components explained 91% of the variance and complemented haplotype results by implicating 4 SNPs at the 5' end, including rs314308 and rs314313. These 2 SNPs were replicated in the phase II cohort, and combined data resulted in greater significance (rs314313, P=0.0007; rs314308, P=0.00008). SNP association with ICH presentation persisted after adjusting for age, sex, BAVM size, and deep venous drainage.

Conclusions— EPHB4 polymorphisms are associated with risk of ICH presentation in patients with BAVM, warranting further study.

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