Effects of total laryngectomy on olfactory function, health-related quality of life, and communication: a 3-year follow-up study

<p>Abstract</p> <p>Background</p> <p>As total laryngectomy results in loss of airflow through the nose, one of the adverse effects for a majority of patients is the reduced or complete loss of olfactory function. However, with the introduction of a new method, the Nasal Airflow-Inducing Maneuver (NAIM), an important technique is available for laryngectomized patients to regain the ability to smell. The purpose of the present study was to assess changes in olfaction, health-related quality of life (HRQL) and communication 3 years after NAIM rehabilitation.</p> <p>Methods</p> <p>18 patients (15 men and 3 women; mean age, 71 years) who had undergone laryngectomy and NAIM rehabilitation were followed longitudinally for 3 years. For comparison an age and gender matched control group with laryngeal cancer treated with radical radiotherapy was included. Olfactory function was assessed using the Questionnaire on Odor, Taste and Appetite and the Scandinavian Odor Identification Test. HRQL was assessed by: 1) the European Organization for Research and Treatment for cancer quality of life questionnaires; and 2) the Hospital Anxiety and Depression Scale. Communication was assessed by the Swedish Self-Evaluation of Communication Experiences after Laryngeal Cancer. Descriptive statistics with 95% confidence interval were calculated according to standard procedure. Changes over time as well as tests between pairs of study patients and control patients were analyzed with the Fisher nonparametric permutation test for matched pairs.</p> <p>Results</p> <p>Thirty-six months after rehabilitation 14 of 18 laryngectomized patients (78%) were smellers. There were, with one exception (sleep disturbances), no clinically or statistically significant differences between the study and the control group considering HRQL and mental distress. However, statistical differences (p < 0.001) were found between the study and the control group concerning changes in communication.</p> <p>Conclusion</p> <p>Olfactory training with NAIM should be integrated into the multidisciplinary rehabilitation program after total laryngectomy. Our study shows that patients who were successfully rehabilitated concerning olfaction and communication had an overall good HRQL and no mental distress. Moreover, the EORTC questionnaires should be complemented with more specific questionnaires when evaluating olfaction and communication in laryngectomized patients.</p

Preparation and Characterization of a Lovastatin-Loaded Protein-Free Nanostructured Lipid Carrier Resembling High-Density Lipoprotein and Evaluation of its Targeting to Foam Cells

This study was designed to investigate whether a non-protein nanostructured lipid carrier (NLC) resembling high-density lipoprotein (HDL) could deliver a hydrophobic anti-atherogenic drug, lovastatin, to foam cells. Lovastatin-loaded NLC (LT-NLC) was prepared by a nanoprecipitation/solvent diffusion method. The LT-NLC-apoprotein (LT-NLC-apo) was prepared by incubating LT-NLC with native HDL. The physicochemical parameters of LT-NLC were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and crystallization behavior. Targeting behavior and mechanism were demonstrated by the incubation of LT-NLC-apo with a RAW 264.7 macrophage-derived foam cell model in the presence or absence of very-low-density lipoprotein (VLDL) and lipase. The results showed that LT-NLC was solid spherical or oval in shape with an average diameter of 13.8 ± 2.2 nm, zeta potential of −29.3 ± 0.2 mV and entrapment efficiency of 96.2 ± 1.3%. Phagocytosis studies showed that uptake of LT-NLC-apo by macrophages was significantly lower than LT-NLC (p < 0.01), suggesting that LT-NLC-apo could possibly escape recognition from macrophages in vivo. The uptake was increased twofold when LT-NLC-apo was incubated with transfected foam cells containing VLDL and lipase. These results indicated that non-protein NLC resembling HDL could be a useful tool to deliver lipophilic anti-atherogenic drugs to foam cells, and that uptake could be enhanced by the VLDL receptor pathway

Sympathetic Activation and Baroreflex Function during Intradialytic Hypertensive Episodes

BACKGROUND: The mechanisms of intradialytic increases in blood pressure are not well defined. The present study was undertaken to assess the role of autonomic nervous system activation during intradialytic hypertensive episodes. METHODOLOGY/PRINCIPAL FINDINGS: Continuous interbeat intervals (IBI) and systolic blood pressure (SBP) were monitored during hemodialysis in 108 chronic patients. Intradialytic hypertensive episodes defined as a period of at least 10 mmHg increase in SBP between the beginning and the end of a dialysis session or hypertension resistant to ultrafiltration occurring during or immediately after the dialysis procedure, were detected in 62 out of 113 hemodialysis sessions. SBP variability, IBI variability and baroreceptor sensitivity (BRS) in the low (LF) and high (HF) frequency ranges were assessed using the complex demodulation technique (CDM). Intradialytic hypertensive episodes were associated with an increased (n = 45) or decreased (n = 17) heart rate. The maximal blood pressure was similar in both groups. In patients with increased heart rate the increase in blood pressure was associated with marked increases in SBP and IBI variability, with suppressed BRS indices and enhanced sympatho-vagal balance. In contrast, in those with decreased heart rate, there were no significant changes in the above parameters. End-of-dialysis blood pressure in all sessions associated with hypertensive episode was significantly higher than in those without such episodes. In logistic regression analysis, predialysis BRS in the low frequency range was found to be the main predictor of intradialytic hypertension. CONCLUSION/SIGNIFICANCE: Our data point to sympathetic overactivity with feed-forward blood pressure enhancement as an important mechanism of intradialytic hypertension in a significant proportion of patients. The triggers of increased sympathetic activity during hemodialysis remain to be determined. Intradialytic hypertensive episodes are associated with higher end-of-dialysis blood pressure, suggesting that intradialytic hypertension may play a role in generation of interdialytic hypertension

A Systems Genetics Approach Implicates USF1, FADS3, and Other Causal Candidate Genes for Familial Combined Hyperlipidemia

We hypothesized that a common SNP in the 3' untranslated region of the upstream transcription factor 1 (USF1), rs3737787, may affect lipid traits by influencing gene expression levels, and we investigated this possibility utilizing the Mexican population, which has a high predisposition to dyslipidemia. We first associated rs3737787 genotypes in Mexican Familial Combined Hyperlipidemia (FCHL) case/control fat biopsies, with global expression patterns. To identify sets of co-expressed genes co-regulated by similar factors such as transcription factors, genetic variants, or environmental effects, we utilized weighted gene co-expression network analysis (WGCNA). Through WGCNA in the Mexican FCHL fat biopsies we identified two significant Triglyceride (TG)-associated co-expression modules. One of these modules was also associated with FCHL, the other FCHL component traits, and rs3737787 genotypes. This USF1-regulated FCHL-associated (URFA) module was enriched for genes involved in lipid metabolic processes. Using systems genetics procedures we identified 18 causal candidate genes in the URFA module. The FCHL causal candidate gene fatty acid desaturase 3 (FADS3) was associated with TGs in a recent Caucasian genome-wide significant association study and we replicated this association in Mexican FCHL families. Based on a USF1-regulated FCHL-associated co-expression module and SNP rs3737787, we identify a set of causal candidate genes for FCHL-related traits. We then provide evidence from two independent datasets supporting FADS3 as a causal gene for FCHL and elevated TGs in Mexicans