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Articles by A Malhotra
Total Records ( 4 ) for A Malhotra
  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  clinicaltrials.gov Identifier: NCT00695214

  C. C Apfel , O. S Cakmakkaya , G Frings , P Kranke , A Malhotra , A Stader , A Turan , A Biedler and K. Kolodzie
  Background

Droperidol is commonly noted to be more effective at preventing postoperative nausea (PON) than vomiting (POV) and it is assumed to have a short duration of action. This may be relevant for clinical decisions, especially for designing multiple-drug antiemetic regimens.

Methods

We conducted a post hoc analysis of a large multicentre trial. Within this trial, 1734 patients underwent inhalation anaesthesia and were randomly stratified to receive several antiemetic interventions according to a factorial design, one of which was droperidol 1.25 mg vs placebo. We considered differences to be significant when: (i) point estimates of one outcome are not within the limits of the confidence interval (CI) of the other outcome; and (ii) differences in risk ratio (also known as relative risks, RR) are at least 20%.

Results

Over 24 h, nausea was reduced from 42.9% in the control to 32.0% in the droperidol group, corresponding to a relative risk (RR) of 0.75 (95% CI from 0.66 to 0.84). Vomiting was reduced from 15.6% to 11.8%, and therefore associated with a similar RR of 0.76 (0.59–0.96). In the early postoperative period (0–2 h), droperidol prevented nausea and vomiting similarly, with an RR of 0.57 (0.46–0.69) for nausea and 0.56 (0.37–0.85) for vomiting. In the late postoperative period (2–24 h), the RR was again similar with 0.83 (0.72–0.96) for nausea compared with 0.89 (0.66–1.18) for vomiting but significantly less compared with the early postoperative period.

Conclusions

We conclude that droperidol prevents PON and POV equally well, yet its duration of action is short-lived.

  Y. S Lee , Y Shibata , A Malhotra and A. Dutta
 

New types of small RNAs distinct from microRNAs (miRNAs) are progressively being discovered in various organisms. In order to discover such novel small RNAs, a library of 17- to 26-base-long RNAs was created from prostate cancer cell lines and sequenced by ultra-high-throughput sequencing. A significant number of the sequences are derived from precise processing at the 5' or 3' end of mature or precursor tRNAs to form three series of tRFs (tRNA-derived RNA fragments): the tRF-5, tRF-3, and tRF-1 series. These sequences constitute a class of short RNAs that are second most abundant to miRNAs. Northern hybridization, quantitative RT–PCR, and splinted ligation assays independently measured the levels of at least 17 tRFs. To demonstrate the biological importance of tRFs, we further investigated tRF-1001, derived from the 3' end of a Ser-TGA tRNA precursor transcript that is not retained in the mature tRNA. tRF-1001 is expressed highly in a wide range of cancer cell lines but much less in tissues, and its expression in cell lines was tightly correlated with cell proliferation. siRNA-mediated knockdown of tRF-1001 impaired cell proliferation with the specific accumulation of cells in G2, phenotypes that were reversed specifically by cointroducing a synthetic 2'-O-methyl tRF-1001 oligoribonucleotide resistant to the siRNA. tRF-1001 is generated in the cytoplasm by tRNA 3'-endonuclease ELAC2, a prostate cancer susceptibility gene. Our data suggest that tRFs are not random by-products of tRNA degradation or biogenesis, but an abundant and novel class of short RNAs with precise sequence structure that have specific expression patterns and specific biological roles.

  M Husain , L. G Meggs , H Vashistha , S Simoes , K. O Griffiths , D Kumar , J Mikulak , P. W Mathieson , M. A Saleem , L Del Valle , S Pina Oviedo , J. Y Wang , S. V Seshan , A Malhotra , K Reiss and P. C. Singhal
 

Glomerular visceral epithelial cells (podocytes) play a critical role in the pathogenesis of human immunodeficiency virus (HIV)-associated nephropathy. A key question concerns the mechanism(s) by which the HIV-1 genome alters the phenotype of the highly specialized, terminally differentiated podocytes. Here, using an in vitro system of conditionally immortalized differentiated human podocytes (CIDHPs), we document a pivotal role for the p66ShcA protein in HIV-1-induced reactive oxygen species generation and CIDHP apoptosis. CIDHP transfected with truncated HIV-1 construct (NL4-3) exhibit increased reactive oxygen species metabolism, DNA strand breaks, and a 5-fold increase in apoptosis, whereas the opposite was true for NL4-3/CIDHP co-transfected with mu-36p66ShcA (mu-36) dominant negative expression vector or isoform-specific p66-small interfering RNA. Phosphorylation at Ser-36 of the wild type p66ShcA protein, required for p66ShcA redox function and inhibition of the potent stress response regulator Foxo3a, was unchanged in mu-36/NL4-3/CIDHP but increased in NL4-3/CIDHP. Acute knockdown of Foxo3a by small interfering RNA induced a 50% increase in mu-36/NL4-3/CIDHP apoptosis, indicating that Foxo3a-dependent responses promote the survival phenotype in mu-36 cells. We conclude that inhibition of p66ShcA redox activity prevents generation of HIV-1 stress signals and activation of the CIDHP apoptosis program.

 
 
 
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