The Efficacy of Mitomycin C in the Treatment of Laryngotracheal Stenosis: Results and Experiences with a Difficult Disease Entity.

BACKGROUND/AIMS: Laryngotracheal stenosis (LTS) is a difficult entity to treat, with many patients requiring multiple procedures. Our study assessed the efficacy of mitomycin C (MMC) application as complimentary treatment of LTS. METHODS: We reviewed clinical charts of patients with operative procedures for LTS between January 2005 and May 2013. Patients were grouped according to mitomycin use. Several outcome measures were assessed, including the number of procedures and time between procedures. RESULTS: Seventy-one patients were included in the study (30 MMC, 41 non-MMC). They underwent similar numbers of procedures (2.3 MMC, 2.0 non-MMC, p > 0.05). The average time between procedures was 360 (MMC) and 178 (non-MMC) days (p = 0.015). Multiple treatments with mitomycin increased the duration between procedures (366 vs. 340 days, multiple vs. single application, p > 0.05). Fewer mitomycin patients underwent procedures for respiratory distress than non-MMC patients (6.6 vs. 19.5%, p > 0.05). Mitomycin use increased the duration between procedures in patients treated specifically for subglottic stenosis (375 vs. 186 days, p > 0.05). CONCLUSION: Our results and experiences with mitomycin demonstrate it is an effective agent for adjuvant treatment of LTS. Its use lengthens the symptom-free period, with further improvement demonstrated when patients expected to undergo multiple surgeries receive multiple mitomycin treatments.

Management of Weight Regain Following Bariatric Surgery: Behavioral Intervention and Pharmacotherapy.

INTRODUCTION: Bariatric surgery is the most effective intervention currently available for significant and durable weight loss, but weight regain after surgery is not uncommon. This paper focuses on updates in behavioral interventions and pharmacotherapy to combat weight regain after bariatric surgery. AREAS COVERED: This paper critically reviews both prospective and retrospective studies assessing pharmacotherapy in post-bariatric surgical patients published within the past 5 years. It also evaluates updates in behavioral therapies and delivery of the therapies in this patient population. EXPERT OPINION: Weight regain after bariatric surgery is common. Patients who experience weight regain should be evaluated and treated by a multidisciplinary team. Antiobesity pharmacotherapy should be considered for those who qualify as an adjunct to lifestyle modifications, along with behavioral interventions such as cognitive behavioral therapy.

GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers.

The apolipoprotein E (APOE) epsilon4 allele is the best established genetic risk factor for late-onset Alzheimer's disease (LOAD). We conducted genome-wide surveys of 502,627 single-nucleotide polymorphisms (SNPs) to characterize and confirm other LOAD susceptibility genes. In epsilon4 carriers from neuropathologically verified discovery, neuropathologically verified replication, and clinically characterized replication cohorts of 1411 cases and controls, LOAD was associated with six SNPs from the GRB-associated binding protein 2 (GAB2) gene and a common haplotype encompassing the entire GAB2 gene. SNP rs2373115 (p = 9 x 10(-11)) was associated with an odds ratio of 4.06 (confidence interval 2.81-14.69), which interacts with APOE epsilon4 to further modify risk. GAB2 was overexpressed in pathologically vulnerable neurons; the Gab2 protein was detected in neurons, tangle-bearing neurons, and dystrophic neuritis; and interference with GAB2 gene expression increased tau phosphorylation. Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's neuropathology.

Temporal maps in appetitive Pavlovian conditioning.

Previous research suggests animals may integrate temporal information into mental representations, or temporal maps. We examined the parameters under which animals integrate temporal information in three appetitive conditioning experiments. In Experiment 1 the temporal relationship between 2 auditory cues was established during sensory preconditioning (SPC). Subsequently, rats were given first order conditioning (FOC) with one of the cues. Results showed integration of the order of cues between the SPC and FOC training phases. In subsequent experiments we tested the hypothesis that quantitative temporal information can be integrated across phases. In Experiment 2, SPC of two short auditory cues superimposed on a longer auditory cue was followed by FOC of either one of the short cues, or of the long cue at different times in the cue. Contrary to our predictions we did not find evidence of integration of temporal information across the phases of the experiment and instead responding to the SPC cues in Experiment 2 appeared to be dominated by generalization from the FOC cues. In Experiment 3 shorter auditory cues were superimposed on a longer duration light cue but with asynchronous onset and offset of the superimposed cues. There is some evidence consistent with the hypothesis that quantitative discrimination of whether reward should be expected during the early or later parts of a cue could be integrated across experiences. However, the pattern of responding within cues was not indicative of integration of quantitative temporal information. Generalization of expected times of reward during FOC seems to be the dominant determinant of within-cue response patterns in these experiments. Consequently, while we clearly demonstrated the integration of temporal order in the modulation of this dominant pattern we did not find strong evidence of integration of precise quantitative temporal information. This article is part of a Special Issue entitled: Associative and Temporal Learning.

Impact of 13-valent pneumococcal conjugate vaccine on otitis media bacteriology.

OBJECTIVES: To determine the microbiology of otitis media (OM) since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in February 2010. METHODS: Middle ear effusion from a pediatric Otolaryngology population undergoing pressure equalization tube (PET) placement was obtained and sent for aerobic culture and antibiotic susceptibility testing between August 2012 and April 2013. Vaccination records were obtained and statistical analysis was completed. RESULTS: During the 8-month period, 236 ears were evaluated, and of those 39 ears were found to have positive cultures. The single nonvaccine Streptococcus pneumoniae (serotype 16) isolate was obtained from a PCV7-only vaccinated patient and was penicillin susceptible. The three most common isolates were Staphylococcus coagulase negative (57%), Haemophilus influenzae (17%), and Moraxella catarrhalis (7%). CONCLUSIONS: This study is the first to assess the bacteriology of OM in a pediatric population undergoing PET placement in the immediate post-PCV13 era. Our study is limited by sample size; however, the lack of S. pneumoniae cultures indicates that PCV13 has had a significant impact on pneumococcal infections during these initial years following licensure.

Laser treatment for ethnic skin.

With the growth of new technology and products over the last 10 years, there has been an increased ability to improve a patient's appearance with procedures that can be performed in an office setting, including laser procedures. Demand for these procedures has grown among all ethnic groups. Patients with ethnic skin can have varying response to lasers. This factor should be considered when planning their treatment. After laser treatment, Patients with ethnic skin are at greater risk for laser energy absorption by melanin, postinflammatory hyperpigmentation, and loss of pigment due to laser effects on melanin production leading to hypopigmentation. Therefore, any laser therapy should be planned carefully, especially in the treatment of patients with darker skin types.

Whole genome association analysis shows that ACE is a risk factor for Alzheimer's disease and fails to replicate most candidates from Meta-analysis.

For late onset Alzheimer's disease (LOAD), the only confirmed, genetic association is with the apolipoprotein E (APOE) locus on chromosome 19. Meta-analysis is often employed to sort the true associations from the false positives. LOAD research has the advantage of a continuously updated meta-analysis of candidate gene association studies in the web-based AlzGene database. The top 30 AlzGene loci on May 1(st), 2007 were investigated in our whole genome association data set consisting of 1411 LOAD cases and neuropathoiogicaiiy verified controls genotyped at 312,316 SNPs using the Affymetrix 500K Mapping Platform. Of the 30 "top AlzGenes", 32 SNPs in 24 genes had odds ratios (OR) whose 95% confidence intervals that did not include 1. Of these 32 SNPs, six were part of the Affymetrix 500K Mapping panel and another ten had proxies on the Affymetrix array that had >80% power to detect an association with α=0.001. Two of these 16 SNPs showed significant association with LOAD in our sample series. One was rs4420638 at the APOE locus (uncorrected p-value=4.58E-37) and the other was rs4293, located in the angiotensin converting enzyme (ACE) locus (uncorrected p-value=0.014). Since this result was nominally significant, but did not survive multiple testing correction for 16 independent tests, this association at rs4293 was verified in a geographically distinct German cohort (p-value=0.03). We present the results of our ACE replication aiongwith a discussion of the statistical limitations of multiple test corrections in whole genome studies.

The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts.

Previously we have shown that the H1c haplotype on the background of the H1 clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD). Here we replicated the association with AD in an additional autopsy confirmed series. We show that this haplotype increases both the expression of total MAPT transcript as well as specifically increasing the proportion of 4 microtubule binding repeat containing transcripts. We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.