Muscle Tension Dysphonia: A Sequeale of Chemoradiotherapy in Patients of Head and Neck Cancer.

It's very important to demarcate that voice is the production of sound by the larynx while speech is articulation of the produced sound by tongue movements, soft palate and the lips. Mucositis, dysphagia, change in speech and voice are the common sequelae of Radiotherapy (RT) alone or in combination with chemotherapy (CRT) which is commonly used in the treatment of head and neck cancer (HNC). The aim of this study was to investigate the patient-reported voice impairment among non laryngeal head and neck cancer survivors who were treated with curative RT/CRT with or without surgery. This tertiary institutional assessor blinded study consists of a study cohort of 128 patients who after of completion of treatment for HNC reported to the laryngology clinic for voice complaints and throat discomfort. The assessment included laryngeal endoscopic and stroboscopic imaging, acoustics assessment and VHI (Vocal handicap index). This study cohort consisted of 89.8% males and 11.2% females. There was hyperadduction and strain of ventricular bands in almost all the cases. There was hyperactivity and compression of both true and false cords in 80.5% of the cases. DSI impairment level showed significant association with gender, VHI, GRBAS score and RT/CRT and it did not show significant association with smoking and surgery, while VHI showed significant association with DSI and RT/CRT and it did not show significant association with gender, smoking and surgery. Muscle tension is a very common effect of RT/RCT and dysphonia can be easily associated with it. Future research needs to focus on specific voice treatment regimens in HNC treated with RT/CRT to improve the quality of life of these patients.

The AGE-RAGE Axis and RAGE Genetics in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of lung diseases limiting the airflow due to narrowing of airways, chronic bronchitis and emphysema that leads to difficulties in breathing. Chronic inflammation is another important characteristic of COPD which leads to immune cell infiltration and helps in the alveolar destruction. Pathology of COPD is driven by various environmental and genetic factors. COPD is mainly associated with the inhalation of toxic agents mainly the cigarette smoke. Receptor for advanced glycation end products (RAGE) has emerged as a pattern recognition receptor and is a multiligand receptor expressed moderately in various cells, tissues and highly in the lungs throughout life. RAGE recognizes various ligands produced by cigarette smoke and its role has been implicated in the pathogenesis of COPD. RAGE ligands have been reported to accumulate in the lungs of patients with COPD. RAGE is a membrane receptor but its truncated form i.e. soluble RAGE (sRAGE) mainly functions as a contender of RAGE and inhibits various RAGE dependent cell signalling. Among the various ligands of RAGE, advanced glycation end products (AGEs) are majorly linked with COPD. Accumulated AGE triggers downstream RAGE-AGE axis in COPD. Moreover, RAGE genetics has long been known to play a vital role in the pathology of various airway diseases including COPD and this gene contains an associated locus. A reliable biomarker is needed for the management of this disease. sRAGE has an inverse correlation with the RAGE showed its importance as a valuable marker in COPD. This review is focused on the role of RAGE, sRAGE, RAGE axis and RAGE genetics in COPD.

P2X7 receptor polymorphisms and susceptibility to tuberculosis in a North Indian Punjabi population.

BACKGROUND: Genetic elements are known to influence susceptibility to tuberculosis (TB). P2X7R is a candidate gene with multiple single-nucleotide polymorphisms (SNPs) that has the potential to influence an individual's ability to kill the intracellular pathogen Mycobacterium tuberculosis. OBJECTIVE: To explore the role of five functional polymorphisms of P2X7R in susceptibility or resistance to TB in a North Indian Punjabi population. DESIGN: A case-control study was conducted among 245 TB patients (145 pulmonary TB [PTB] and 100 extra-pulmonary TB [EPTB]) and 247 healthy controls. DNA extracted from samples of peripheral blood was analysed for five SNPs of P2X7R using amplification refractory mutation system-polymerase chain reaction (PCR) [-762(T/C), +1513(A/C), DNA sequencing +1729(T/A)] and PCR-restriction fragment length polymorphism [+489(G/A), +946(G/A)] methods. RESULTS: Of the three loss-in-function polymorphisms, +1513(A/C) showed a statistically significant association with TB susceptibility, while the other two (+946 and +1729) sites were found to be monomorphic in our population. The only gain-in-function polymorphism (+489), and -762 promoter polymorphisms failed to reveal differences in genotypic or allelic distributions. CONCLUSION: The C allele at the +1513 site was identified as a risk factor for TB in this North Indian Punjabi population; the +1729 site was found to be monomorphic, unlike its polymorphic distribution in a South Indian TB patient population.

Peripheral blood based C-PCR assay for diagnosing extra-pulmonary tuberculosis.

Extra pulmonary tuberculosis (EPTB) constitutes around 20% of all tuberculosis cases in India. Conventional methods are of limited use in diagnosing this form of the disease. Polymerase chain reaction (PCR) has emerged as a sensitive and specific tool for documenting the presence of Mycobacterium tuberculosis in clinical samples but lacks quantitative ability. The present study evaluates peripheral blood as an alternative clinical specimen for diagnosing EPTB. Peripheral blood samples from 38 EPTB and 89 non tuberculous subjects were analyzed for the presence of tubercle bacilli by MPB 64 gene based PCR method. The assay gave an overall sensitivity of 60.53% with negative predictive value of 76.92% which is superior to present gold standard of mycobacterial culture (10.53 and 72.36%). Additionally, 43.82% of non tuberculous subjects gave positive results with the PCR, thus mitigating the clinical utility of this test. An in-house Competitive PCR (C-PCR) assay was used to determine the mycobacterial load in peripheral blood from culture positive, culture negative EPTB patients and non tuberculous controls which ranged from 7498-12498, 602-4797 and 101-800 genome equivalent (ge)/mL, respectively. The data clearly demonstrated that C-PCR assay can furnish insightful information in diagnosing extra pulmonary disease.

Differential association of tumour necrosis factor-alpha single nucleotide polymorphism (-308) with tuberculosis and bronchial asthma.

BACKGROUND: Tumour necrosis factor (TNF)-alpha is a pleiotropic, pro-inflammatory cytokine of 17 kDa, whose gene is localized on the short arm of chromosome 6. It has a G-308A polymorphism in the promoter region, which is known to be associated with its differential production; the A allele being the high producer. The circulating level of TNF-alpha is under genetic control and implicated in the pathophysiology of asthma and tuberculosis. Since raised levels of TNF-alpha have been found in asthma and tuberculosis, we looked for the association of TNF-alpha G-308A polymorphism in patients with these diseases. METHODS: A total of 300 blood samples from patients (155 with asthma, 145 tuberculosis) and 211 normal healthy controls were collected. The G-308A polymorphism was studied using amplification refractory mutation system analysis. RESULTS: The distribution of G/A alleles in the two patient groups when compared with normal controls revealed a statistically significant association with asthma (p = 0.016) but not with tuberculosis (p = 0.178). CONCLUSION: The data support the common variant common disease hypothesis, which emphasizes that common genetic variations may participate as critical players in inciting common diseases.

Genetic diversity in clinical Mycobacterium tuberculosis isolates from Punjab.

SETTING: Two hospitals, Sri Guru Ram Das Institute of Medical Sciences and Research and the TB and Chest Hospital, Amritsar, Punjab. OBJECTIVE: To explore genetic diversity among the clinical Mycobacterium tuberculosis isolates prevalent in Punjab. DESIGN: Fifty-six random clinical isolates of M. tuberculosis were cultured from the sputum specimens of pulmonary tuberculosis patients. DNA was extracted from cultured biomass and analysed using the mycobacterial interspersed repetitive units (MIRU) typing method. RESULTS: MIRU typing of 51 isolates revealed 45 different patterns, with a combined Hunter-Gaston discriminatory index (HGDI) of 0.990. Five clinical isolates failed to amplify for one or more MIRUs and were excluded from the analysis. The remaining isolates were categorised in three groups based on the allelic heterogeneity of individual MIRUs. MIRU 10, 16, 26 and 31 were highly discriminant, with an HGDI value >0.6; MIRU 4, 23, 24, 39 and 40 were designated as moderately discriminant (HGDI value 0.6-0.3) and MIRU 2, 20 and 27 were poorly discriminant (HGDI value <0.3). CONCLUSION: MIRU typing and the HGDI values revealed that M. tuberculosis strains from Punjab are genetically quite heterogeneous.

Tumor necrosis factor--alpha and transforming growth factor--beta1 polymorphisms in bronchial asthma.

BACKGROUND: Bronchial asthma is a complex genetic disorder regulated by the release of cytokines and inflammatory mediators. Tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta1) cytokines play pivotal roles in the inflammatory response of the airways. Differential production of these two cytokines is associated with allelic variations in the transcriptional regulatory region of these genes. AIMS: The objective of the present study was to investigate G-308A TNF-alpha and C-509T TGF- beta1 polymorphisms for their association with Bronchial Asthma. MATERIALS AND METHODS: DNA isolated from 123 asthmatics and 100 normal healthy controls were screened for these polymorphisms using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) methods, developed in our laboratory. RESULTS: Significant allelic association was observed between G-308A TNF-alpha polymorphism and asthma (P = 0.031) while no association was observed with C-509T TGF- beta1 polymorphism (P = 0.207). Further sub-grouping based on either allergic response or family history failed to reveal any statistical significance among the groups or with controls. The interaction between these polymorphisms revealed statistically significant association between the high producer genotype alleles of TNF-alpha and TGF-beta (A/T) and asthma (P = 0.016). CONCLUSIONS: The present study reports, for the first time, the role of two polymorphisms, in concert, for their association with asthma in an Indian population. Our study supports the findings that the G-308A TNF-alpha promoter polymorphism is a risk factor for asthma and furthermore suggests that the patients with high producer alleles for TNF-alpha (-308) and TGF-beta (-509) have the highest risk of getting this disease in the Punjabi population.

Association of G-308A TNF-alpha polymorphism with bronchial asthma in a North Indian population.

Bronchial asthma is an inflammatory disorder in which genetic and environmental factors play an important role. Several susceptible genes have been identified using whole genome scan and candidate gene approaches. Tumor necrosis factor alpha, a pro-inflammatory cytokine, is one such gene that figures prominently in such investigations. The secreted levels of this cytokine are under genetic control and attributed to the presence of single nucleotide polymorphism G-308 A in the promoter region of its gene. However, the association of this polymorphism varies from population to population. As there are no data available on North Indians, the present study aims to fill this void. For this, 366 subjects (155 asthmatic and 211 normal control subject) were genotyped using Amplification Refractory Mutation System Analysis (ARMS-PCR) and agarose gel electrophoresis. The distribution of G/A alleles between the two groups revealed statistically significant differences (p = 0.016). Furthermore, the asthma patients categorized on the basis of pattern (Seasonal versus Perennial) and age of onset of disease (Childhood versus Late Onset) revealed significant association with only seasonal (p = 0.021) and late onset asthmatic groups (p = 0.039). The data from the present study strongly suggest an association between TNF-alpha and asthma in the North Indian population.