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Articles by S Khalil
Total Records ( 2 ) for S Khalil
  C. R Butler , S. A. R Nouraei , A. D Mace , S Khalil , S. K Sandhu and G. S. Sandhu

Objective  To report the results of treating laryngeal sarcoidosis with intralesional steroids and minimally invasive laser surgery. Sarcoidosis is a rare multisystem inflammatory disorder of unknown cause. Laryngeal involvement is extremely rare, and its optimal management remains controversial.

Design  Retrospective medical chart review.

Settings  Tertiary care center/national referral airway reconstruction center.

Patients  Ten consecutive patients treated for laryngeal sarcoidosis between 2004 and 2008.

Main Outcome Measures  Demographic and clinical information including extralaryngeal manifestations obtained from patient records, laryngeal anatomic subsite manifestation of disease, intraoperative findings, and scores from the Medical Research Council (MRC) dyspnea outcome assessment instrument (which was administered preoperatively, at the first postoperative outpatient visit 4-6 weeks later, and at last follow-up).

Results  The patients included 9 women and 1 man, a total of 2.8% of the unit's adult surgical airway case mix (10 of 353). Mean (SD) age at presentation was 37 (17) years. All patients presented with dyspnea and dysphonia; 2 required emergency tracheostomy prior to treatment. Six patients presented with isolated laryngeal sarcoid. Supraglottis and arytenoids were affected in all patients. The median number of endoscopic treatments was 2 (range, 1-4). Significant improvement in MRC dyspnea grading was found postoperatively (P < .05), and patients with tracheostomy were successfully decannulated. The mean (SD) follow-up time was 24 (18) months. There were no adverse effects of surgery. Nine patients had a substantial dose reduction or discontinuation of their systemic corticosteroid therapy following endoscopic treatment.

Conclusions  Minimally invasive endoscopic surgery with intralesional corticosteroid injection and laser reduction is an effective method of controlling laryngeal sarcoid. It improves symptoms immediately with minimal morbidity and, most importantly, reduces the need for systemic steroid administration in most patients. This study supports early recognition and endoscopic intervention in the management of laryngeal sarcoidosis.

  O Zabirnyk , W Liu , S Khalil , A Sharma and J. M. Phang

Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy.

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