Dynamics of plasma proteome during leptin-replacement therapy in genetically based leptin deficiency.

The effects of leptin-replacement therapy on the plasma proteome of three unique adults with genetically based leptin deficiency were studied longitudinally during the course of recombinant human leptin-replacement treatment. Quantitative proteomics analysis was performed in plasma samples collected during four stages: before leptin treatment was initiated, after 1.5 and 6 years of leptin-replacement treatment, and after 7 weeks of temporary interruption of leptin-replacement therapy. Of 500 proteins reliably identified and quantitated in those four stages, about 100 were differentially abundant twofold or more in one or more stages. Synchronous dynamics of abundances of about 90 proteins was observed reflecting both short- and long-term effects of leptin-replacement therapy. Pathways and processes enriched with overabundant synchronous proteins were cell adhesion, cytoskeleton remodeling, cell cycle, blood coagulation, glycolysis, and gluconeogenesis. Plausible common regulators of the above synchronous proteins were identified using transcription regulation network analysis. The generated network included two transcription factors (c-Myc and androgen receptor) that are known to activate each other through a double-positive feedback loop, which may represent a potential molecular mechanism for the long-term effects of leptin-replacement therapy. Our findings may help to elucidate the effects of leptin on insulin resistance.

Oral mucositis in head and neck cancer.

This module explores the risk factors, pathogenesis and development of oral mucositis. It considers the early diagnosis and accurate management of oral mucositis in head and cancer patients undergoing treatment.

Future perspectives for health related quality of life (HRQOL) studies in head and neck cancer.

The impact of a head and neck cancer (HNC) diagnosis on a person and the consequences of its treatment across multiple functional domains can profoundly alter quality of life (QOL). By pursuing patient-centered management and considering the entire gamut of physical, psychological and social problems, QOL studies contribute more than just routine mortality and morbidity data. Assessments can now be made using a variety of both specific and generic measures to optimise patient care and to aid the development of informed rehabilitation services. Unfortunately, there exists no 'gold-standard' questionnaire in the literature and the choice is largely based on clinician preference, research objectives and psychometric properties. Future efforts must be made to effectively use modern technological and computational advances to set up item banks and newer theoretical models. Longitudinal studies with pre-determined priori should be encouraged as should the utilisation of minimalist approaches and incisive item response theory. Most importantly, in order to link research to clinical practice, health related QOL (HRQOL) studies should be devised and utilised in a way as to provide clinically meaningful data to the treating physician useful for patient' care.

Prospective evaluation of psychological burden in patients with oral cancer.

The high morbidity and mortality that is associated with oral cancer places a huge psychological burden on patients. The purpose of this prospective study was to evaluate levels of depression, anxiety, and stress, at three time points using DASS-21 (Depression, Anxiety and Stress Scale-21). We also compared DASS-21 with HADS (Hospital Anxiety and Depression Scale). A total of 111 patients were enrolled and 75 of them completed the questionnaires at diagnosis, one month after treatment, and three months after discharge. Scores were high for stress at diagnosis, and for depression at the other time points, but were low for anxiety at all three. The results of Friedman's ANOVA showed that mean ranks for depression and stress were significant (p<0.05). Scores for depression and stress rose significantly between diagnosis and three months after operation, but those for anxiety (which had increased between diagnosis and operation p>0.05), were stable three months postoperatively. The DASS-21 was a useful method of evaluating stress. Correlation of the results from the two questionnaires showed a strongly positive association. We therefore recommend psychological intervention to improve overall outcome.

Systematic review and meta-analysis of the complications of salvage total laryngectomy.

BACKGROUND AND OBJECTIVES: Management paradigms in laryngeal cancer have shifted to "organ preservation" chemoradiotherapy protocols. In the event of treatment failure, salvage total laryngectomy remains the only curative treatment option. However a comprehensive review of the complications of this procedure has not been reported. METHODS: A systematic review of the literature was performed using keywords "salvage laryngectomy" to retrieve relevant publications between January 2000 and August 2015. RESULTS: Of the 407 articles retrieved from the literature search, 50 studies encompassing 3292 patients were included. Forty-nine studies reported pharyngocutaneous fistula which occurred in 859 patients (pooled incidence 28.9%; 95% confidence intervals 25.5-32.5%). Twenty-four studies reported complications in addition to PCF and these included wound complications (infection, dehiscence and necrosis), dysphagia, bleeding, and pharyngeal and stomal stenosis. CONCLUSIONS: Overall complication rate was 67.5%, Pharyngocutaneous fistula was the commonest complication with a pooled incidence of 28.9%.

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

OBJECTIVE: A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. METHOD: A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. RESULTS: Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. CONCLUSION: Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

New qualitative colour reaction for the identification of copper(I) compounds and complexes.

The colour reaction of copper(I) salts and complexes, in sulphuric acid medium, with ferricyanide and ammonia, has been used for the general identification of cuprous compounds. A sulphuric acid solution of Cu(I) compound, when treated with a dilute ferricyanide solution in the presence of ammonia, gives a salmon-pink, red-pink, pink-purple or purple colour or precipitate, characteristic of copper(I). Copper(II) compounds fail to give a positive response. The reaction also forms the basis of a test for ammonium ion and differentiation between ferrocyanide and ferricyanide. The preparation of the copper(I) complex of 1-allyl-2-tetrazoline-5-thione is described.

Antithrombin III activity in cerebrovascular accidents.

UNLABELLED: Cerebrovascular accidents are commonly due to occlusive or haemorrhagic lesions. The present prospective study was planned to find out role of antithrombin in possible etiopathological process, which might predispose an individual for stroke. METHOD: Biological activity of antithrombin III was done by the method as described by Innerfield et al (1976). Immunological estimation of an antithrombin III was done by single radial immunodiffusion by the technique of Mancini et al modified by Fahey and Mckelvey. RESULTS: The biological and immunological activity of antithrombin III was measured in 98 patient of occlusive and 56 patients of haemorrhagic strokes. Significant depression in biological as well as immunological activity (p<0.001) was observed in occlusive stroke. In haemorrhagic stroke both, biological and immunological activity was increased. In follow up study, there was progressive normalization of both, biological as well as of immunological activity in both group. CONCLUSION: Decrease of antithrombin III in occlusive and increase in haemorrhagic stroke indicates that these changes have at least an additive role in the pathogenesis of stroke.

Lichen planus of the larynx.

OBJECTIVE: We report an extremely rare case of laryngeal lichen planus. METHOD: A case report and literature review of the aetiopathogenesis, clinical features and management of laryngeal lichen planus are presented. RESULTS: A male patient presented with hoarseness and a history suggestive of squamous cell carcinoma of the larynx. However, characteristic histopathological findings demonstrated lichen planus. The patient responded very well to oral steroids, and at the time of writing had remained symptom-free for two years. CONCLUSION: This is the first English language report of laryngeal lichen planus. Lichen planus is a diagnosis of exclusion and responds well to steroids. However, patients should be followed up regularly as malignant change is known to occur.

Acoustic analysis of tracheo-oesophageal voice in male total laryngectomy patients.

INTRODUCTION: The aim of this study was to test the null hypothesis that voice parameters of post-laryngectomy patients using tracheo-oesophageal (TO) prosthetic valves are similar to those of normal laryngeal subjects. METHODS: Thirty total laryngectomy patients and thirty normal controls were subjected to acoustic analysis of single voice recordings using a sustained vowel. Acoustic parameters including fundamental frequency, jitter, shimmer, harmonics-to-noise ratio and maximum phonation time were analysed. RESULTS: Poorer values were found as well as larger variability for all the voice parameters for the total laryngectomy patients using TO voice compared with those of normal subjects. There were statistically significant differences (p<0.05) for all studied parameters between the TO and normal speech. CONCLUSIONS: Alaryngeal speech with TO voice prosthesis is not yet comparable to laryngeal speech.

Surgical voice restoration after total laryngectomy: an overview.

Total laryngectomy is potentially a debilitative surgery resulting in compromise of some of the most basic functions of life including speech and swallowing. This may have a profound adverse effect on the patient's physical, functional, and emotional health, and may result in a decreased quality of life (QOL). Until the 1980s, total laryngectomy was regarded as a dreadful, but often, life-saving procedure for which there was little alternative, and was used as a last resort. At that time survival at any cost in terms of QOL was paramount and many laryngectomies were forced into an isolated life as a mute and dysphasic recluse. Most attempts at voice restoration produced inconsistent results and often techniques were laborious, expensive, and ineffective, particularly when carried out as a salvage procedure after failed radiotherapy. Progress in voice rehabilitation, following total laryngectomy, over the last 30 years, has made an enormous difference in the whole concept of the management of laryngeal cancers. Currently there are several options available for these patients, namely, esophageal speech, artificial larynx, and tracheoesophageal speech. The choice of speech rehabilitation varies from patient to patient, but tracheoesophageal voice has become the preferred method. This article provides a brief account of surgical voice restoration after total laryngectomy. Special emphasis has been given to the surgical technique, special considerations, complications, and the prevention / treatment of tracheoesophageal voice restoration.

The current role of tissue engineering in head and neck reconstruction.

Tissue engineering is an emerging field that has the potential to revolutionize the field of reconstructive surgery by providing off-the-shelf replacement products. The literature has become replete with tissue engineering studies, and the aim of this article is to review the contemporary application of tissue-engineered products. The use of tissue-engineered cartilage, bone and nerve in head and neck reconstruction is discussed.