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.

Dosimetric comparison of 3DCRT and IMRT in radical chemoradiotherapy of squamous cell carcinoma esophagus.

BACKGROUND: Radical chemoradiation is the standard of treatment for locally advanced squamous cell carcinoma of esophagus and for patients with operable disease, but who are medically unfit or unwilling for surgery. As the esophagus is a central organ, the planning target volume (PTV) is central, lies close to the spinal cord and heart, and is surrounded by the lung, which is a radiosensitive organ. Irradiation of these critical structures is reduced by the use of three-dimensional conformal radiation therapy (3DCRT). Intensity-modulated radiation therapy (IMRT) has the potential to improve the uniformity of dose distribution to the tumor and reduce the dose received by surrounding normal tissues. AIM AND OBJECTIVES: 1. To compare the dose distribution, conformity, and homogeneity indices in radical radiotherapy of squamous cell carcinoma of esophagus using 3DCRT and IMRT techniques 2. To compare the doses received by critical structures such as heart, lung, spinal cord, and liver. MATERIALS AND METHODS: All cases of squamous cell carcinoma esophagus treated with radical chemoradiation to a dose of 50 Gy in 25 fractions using 3DCRT technique from January 2018 to July 2019 were included. IMRT plans were generated for these cases.The parameters that represent dose distribution to the target volume and the dose received by the organs at risk were obtained from the dose-volume histogram. The difference in the mean values of the parameters between the two techniques was calculated. The statistical significance of the difference was determined using Student's t-test and Wilcoxon signed-rank test. RESULTS: The volume of PTV receiving 105% and 107% of prescribed dose was significantly lower with IMRT (3.540% and 0.008%, respectively) compared to 3DCRT (7.654% and 0.623%). The homogeneity index was better with IMRT (0.088 vs. 0.107) than 3DCRT. Conformity index was found to be better with IMRT (1.149 vs. 1.573). Mean heart dose (18.216 vs. 24.591 Gy) and the volume of heart receiving 30 Gy were reduced with IMRT. The volume of lung receiving 20 Gy and the volume receiving 5 Gy were not significantly different between 3DCRT and IMRT. Maximum dose to spinal cord was similar with 3DCRT and IMRT. CONCLUSIONS: IMRT avoids areas of excessive irradiation within the PTV. IMRT improves dose conformity to the target volume and homogeneity of dose distribution within the PTV. The cardiac dose is significantly reduced with IMRT. The mean lung dose remains similar to 3DCRT. There is no significant increase in the volume of lung receiving low-dose radiation with IMRT.

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.

Validation of PRIMO Monte Carlo Model of Clinac®iX 6MV Photon Beam.

PURPOSE: This study aims to model 6MV photon of Clinac®iX linear accelerator using PRIMO Monte Carlo (MC) code and to assess PRIMO as an independent MC-based dose verification and quality assurance tool. MATERIALS AND METHODS: The modeling of Clinac®iX linear accelerator has been carried out by using PRIMO simulation software (Version 0.3.1.1681). The simulated beam parameters were compared against the measured beam data of the Clinac®iX machine. The PRIMO simulation model of Clinac®iX was also validated against Eclipse® Acuros XB dose calculations in the case of both homogenous and inhomogeneous mediums. The gamma analysis method with the acceptance criteria of 2%, 2 mm was used for the comparison of dose distributions. RESULTS: Gamma analysis shows a minimum pass percentage of 99% for depth dose curves and 95.4% for beam profiles. The beam quality index and output factors and absolute point dose show good agreement with measurements. The validation of PRIMO dose calculations, in both homogeneous and inhomogeneous medium, against Acuros® XB shows a minimum gamma analysis pass rate of 99%. CONCLUSIONS: This study shows that the research software PRIMO can be used as a treatment planning system-independent quality assurance and dose verification tool in daily clinical practice. Further validation will be performed with different energies, complex multileaf collimators fields, and with dynamic treatment fields.

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.

Dosimetric Comparison of Treatment Plans Using Physical Wedge and Enhanced Dynamic Wedge for the Planning of Breast Radiotherapy.

The aim of this study is to compare the physical wedge (PW) with enhanced dynamic wedge (EDW) to determine the difference in the dose distribution affecting the treated breast and the contralateral breast, lungs, heart, esophagus, spine, and surrounding skin in the radiotherapy of breast cancer. Computed tomography (CT) data sets of 30 breast cancer patients were selected from the database for the study. The treatment plans which were executed with PW were re-planned with EDW without changing the beam parameters. Keeping the wedge angles same, the analytic anisotropic algorithm (AAA) with heterogeneity correction was used for dose calculation in all plans. The prescription was 50 Gy in 25 fractions. The dose- volume histogram (DVH) of the planning target volume (PTV) and critical structures of both PW and EDW plans were analyzed. The analysis showed that the maximum dose within the target volume is higher in EDW plan compared to PW plan. However the PTV conformity index (CI) remained the same in both plans. For all the critical structures, the EDW technique offered less dose compared to PW technique. The effect of volume of the contralateral breast on the dose to contralateral breast and the effect of volume of PTV breast for patients with carcinoma left breast on the dose to heart were studied and analyzed for the two wedges. No correlation between volumes and dose parameters was found for the two techniques. The number of monitor units to deliver a particular dose with EDW field is less than that of PW field due to change in wedge factor. As EDW produces less scattered dose to structures outside the treatment field, the risk of a second malignancy can be reduced with this technique.

Association of P2X7 receptor +1513 (A-->C) polymorphism with tuberculosis in a Punjabi population.

BACKGROUND: Development of tuberculosis (TB) disease is an outcome of complex host-pathogen interactions. The purinergic P2X(7) receptors are adenosine triphosphate gated molecules shown to induce killing of intracellular Mycobacterium tuberculosis, followed by apoptosis of the infected macrophage. A single nucleotide polymorphism in exon 13 of the P2X(7) receptors gene at +1513 position has been shown to abolish the function of this receptor and to be associated with increased susceptibility to TB in some ethnic groups. OBJECTIVE: To explore the association of +1513 (A-->C) polymorphism in TB patients in Punjab, North India. DESIGN: A case-control study was conducted by studying peripheral blood samples from 204 TB patients (181 pulmonary, 23 extra-pulmonary) and 177 controls with no history of TB. P2X(7) +1513 (A-->C) polymorphism was studied using amplification refractory mutation system analysis. RESULT: The distribution of +1513 A/C genotypes in the TB patient and the control groups revealed a statistically significant association with TB (P = 0.002). CONCLUSION: The +1513C allele is a risk factor for the development of TB in the North Indian Punjabi 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.

Target foil rupture scenario and provision for handling different models of medical cyclotrons used in India.

Medical cyclotron is a particle accelerator used in producing short lived radiotracers such as (18)F, (11)C, (15)O, (13)N etc. These radiotracers are labeled with suitable pharmaceuticals for use to gather information related to metabolic activity of the cell using Positron Emission Tomography (PET) scan. Target foil rupture is considered one of the major emergency situations during medical cyclotron operations because there is a potential of over exposure to the working personnel. Radiation protection survey of a self-shielded medical cyclotron installation was carried out during normal and emergency conditions. It is found that the induced activity in the target foil increases with its successive usages. As a case study, we have evaluated the emergency handling procedures of GE PETtrace-6 medical cyclotron. Recommendations have also been made to reduce personal exposure while handling the target foil rupture condition such as the use of L-Bench near the target area and participation of experienced personnel.

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.