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Biomedical subjects

R George

Publications and source records attributed to R George.

At least 19 recordsLinked to original sources
PubMed2006

Investigation of patient, tumour and treatment variables affecting residual motion for respiratory-gated radiotherapy.

Respiratory gating can reduce the apparent respiratory motion during imaging and treatment; however, residual motion within the gating window remains. Respiratory training can improve respiratory reproducibility and, therefore, the efficacy of respiratory-gated radiotherapy. This study was conducted to determine whether residual motion during respiratory gating is affected by patient, tumour or treatment characteristics. The specific aims of this study were to: (1) identify significant characteristics affecting residual motion, (2) investigate time trends of residual motion over a period of days (inter-session) and (3) investigate time trends of residual motion within the same day (intra-session). Twenty-four lung cancer patients were enrolled in an Institutional Review Board (IRB)-approved protocol. For approximately five sessions, 331 four-minute, respiratory motion traces were acquired with free breathing, audio instructions and audio-visual biofeedback for each patient. The residual motion was quantified by the standard deviation of the displacement within the gating window. The generalized linear model was used to obtain coefficients for each variable within the model and to evaluate the clinical and statistical significance. The statistical significance was determined by a p-value<0.05, while effect sizes of 0.1 cm (one standard deviation) were considered clinically significant. This data analysis was applied to patient, tumour and treatment variables. Inter- and intra-session variations were also investigated. The only variable that was significant for both inhale- and exhale-based gating was disease type. In addition, visual-training displacement, breathing type and Karnofsky performance status (KPS) values were significant for inhale-based gating, and dose-per-fraction was significant for exhale-based gating. Temporal respiratory variations within and between sessions were observed for individual patients. However inter- and intra-session analyses did not show significant time trends on average for any of the variables considered. The lack of significant time trends within and between sessions indicates that on average (1) there is no significant learning period for breathing training, (2) the patients did not experience training-related fatigue and (3) the margin component to account for residual motion during gated radiotherapy appears to remain constant throughout the treatment.

Computer Simulation↗
PubMed2006

OPTN gene: profile of patients with glaucoma from India.

PURPOSE: Optineurin gene (OPTN) mutations are reported in primary open angle glaucoma patients (POAG) from different populations. The coding and noncoding regions of OPTN were screened for mutations in 100 Indian high tension glaucoma patients (HTG). The frequency of the OPTN M98K mutation in an additional 120 patients (70 HTG and 50 normal tension glaucoma [NTG]) was analyzed by restriction enzyme digestion. METHODS: The HTG patients (about 40 years of age) were characterized by open angles on gonioscopy, with raised intraocular pressure (IOP) more than 21 mmHg (<21 mmHg on office diurnal phasing for NTG), and typical glaucomatous disc changes with corresponding visual field defects in the absence of any secondary cause. One hundred HTG patients and controls were screened for OPTN mutations by direct sequencing using an ABI prism 310/3100 Avant genetic analyzer. The M98K status was analyzed by restriction enzyme digestion with StuI. A genotype/phenotype correlation was also attempted for OPTN sequence alterations with clinical parameters such as age at diagnosis, intraocular pressure, cup:disc ratio, etc. The putative change in the transcription factor binding site for the IVS7 +24G>A polymorphism was attempted with AliBaba software (version 2.1). RESULTS: Six sequence alterations were observed in the 100 POAG patients by direct sequencing. The M98K substitution was observed in a total of 10 patients (7/170 HTG and 3/50 NTG) contributing to 4.1% in HTG and 6% in the NTG group and not in the controls. The IVS7+24G>A nucleotide change showed a significant difference in the HTG group (7/100) when compared to the control group (0/100) and found to be associated with increased IOP at diagnosis (p=0.03). The IVS7+24G>A polymorphism resulted in the creation of binding sites for transcription factors NF-1 and CPE that were not present in the wild type. CONCLUSIONS: The current study suggests a possible role of SNPs rather than mutations in OPTN in POAG pathology in the Indian population.

Adenine↗
PubMed2006

Influence of tobacco use on cataract development.

AIM: To study the influence of tobacco use on cataract formation in a rural South Indian population. METHODS: 3924 subjects from the Chennai Glaucoma Study conducted in rural south India underwent a comprehensive eye examination, including Lens Opacities Classification System II grading. Information on tobacco use, type of tobacco (smoking and smokeless), duration and quantity of use was collected. RESULTS: 1705 (male:female (M:F) 1106:599) people used tobacco and were significantly older (mean (standard deviation (SD)) age 55.80 (10.64) years) than non-users (52.23 (10.51); p<0.001). 731 (M:F 730:1) people smoked, 900 (M:F 302:598) used smokeless tobacco, and 74 (M:F, 74:0) used tobacco in both forms. The unadjusted and adjusted (age and sex) odds ratio (OR) for a positive history of tobacco use and cataract was 1.72 (95% confidence interval (CI) 1.51 to 1.96) and 1.39 (95% CI 1.15 to 1.68), respectively. The unadjusted OR for smokers and smokeless tobacco users was 1.04 (95% CI 0.88 to 1.23) and 2.74 (95% CI 2.31 to 3.26), respectively. The adjusted OR was 1.19 (95% CI 0.89 to 1.59) and 1.54 (95% CI 1.22 to 1.95), respectively. No significant association was noted between smoking and any particular type of cataract. Smokeless tobacco use was found to be significantly associated with nuclear cataract even after adjusting for age and sex (OR 1.67, p = 0.067, 95% CI 1.16 to 2.39). CONCLUSION: Tobacco use was significantly associated with cataract. Smoking was not found to be significantly associated with cataract formation; however, smokeless tobacco use was more strongly associated with cataract.

Age Distribution↗
PubMed2006

The current burden of pneumococcal disease in England and Wales.

OBJECTIVE: To evaluate the potential impact of various pneumococcal conjugate vaccination strategies, it is critical to ascertain the pre-vaccination epidemiology and to have a detailed evaluation of the current burden of pneumococcal disease. METHOD: A variety of national data sources and GP sentinel surveillance systems were used to estimate the incidence, number of hospital admissions, deaths, and GP consultations due to pneumococcal disease in England and Wales. Clinical outcomes included pneumococcal meningitis, bacteraemia, pneumonia and otitis media. A statistical model was used to attribute GP consultation recorded as pneumonia and acute otitis media to specific aetiological causes when these were not recorded. RESULTS: The burden of pneumococcal disease is considerable, with incidence rates of both invasive and non-invasive disease peaking in children (<5 years) and in the elderly (75+ years). Around 5800 hospitalisations specifically mentioning Streptococcus pneumoniae are estimated to occur annually in England and Wales, almost 40,000 for lobar pneumonia and over 15,000 for otitis media. There may be an additional 70,000 GP consultations for pneumococcal related community acquire pneumonia and over 630,000 for otitis media. A significant proportion of hospitalisations and GP consultations for pneumococcal disease occur among high-risk groups, with over 80% of hospital admissions reporting more than one diagnosis.

Adolescent↗
PubMed2006

A bioinformatics pipeline for high-throughput microbial multilocus sequence typing (MLST) analyses.

Multilocus sequence typing (MLST) analysis for semi-routine applications is hindered by the downstream, manually intensive steps of processing the raw sequence data files. This report describes the development of an MLST pipeline that automates DNA sequence editing and analysis in order to significantly reduce the time required for processing data. Validation using a pneumococcal dataset revealed complete agreement between the results generated by manual and automated workflows. The MLST pipeline was developed for both double-strand and single-strand sequencing.

Bacteria↗
PubMed2006

Prevalence and causes of blindness in the rural population of the Chennai Glaucoma Study.

AIM: To study the prevalence and causes of blindness in a rural south Indian population. METHODS: 3924/4800 enumerated (81.75%) subjects, aged 40 years or more from rural Tamil Nadu, underwent comprehensive ophthalmic examination-visual acuity, refraction, intraocular pressure, gonioscopy, cataract grading (LOCS II), retinal examination, and SITA Standard where indicated. Blindness was defined using WHO criteria as best corrected visual acuity of less than 3/60 and/or visual field of less than 10 degrees in the better eye. The influence of age, sex, literacy, and occupation was assessed using multiple logistic regression. RESULTS: 753 subjects (19.2%; 321 males, 432 females) presented with a visual acuity of <3/60; 132 subjects (3.36%, 95% CI: 2.80 to 3.93) were diagnosed to be blind. Cataract was responsible in 74.62% of eyes; glaucoma, cystoid macular oedema, optic atrophy, and corneal scars accounted for 3.79% each. Bilateral causes of blindness were cataract (78.63%), glaucoma (4.29%), optic atrophy (3.42%), cystoid macular oedema, and corneal scars (2.56% each). In 19 eyes (7.2%) the blindness was probably related to cataract surgery. Blindness was positively associated with increasing age (p<0.0001). CONCLUSION: 3.36% of the studied rural population was bilaterally blind, with cataract being the single most important cause.

Adult↗
PubMed2005

A longitudinal household study of Streptococcus pneumoniae nasopharyngeal carriage in a UK setting.

A 10-month longitudinal household study of pre-school children and their families was undertaken with monthly visits collecting epidemiological data and nasopharyngeal swabs in Hertfordshire, England from 2001 to 2002. Pneumococcal culture was with standard methods. In total, 121 families (489 individuals) took part. Mean prevalence of carriage ranged from 52% for age groups 0-2 years, 45% for 3-4 years, 21% for 5-17 years and 8% for >or=18 years. Carriage occurred more than once in 86% of children aged 0-2 years compared to 36% of those aged >or=18 years. The most prevalent serotypes in the 0-2 years age group were 6B followed by 19F, 23F, 6A and 14. Young children were responsible for the majority of introductions of new serotypes into a household. Erythromycin resistance (alone or in combination) occurred in 10% of samples and penicillin non-susceptibility in 3.7%. Overall the recently licensed 7-valent conjugate vaccine (PCV) would protect against 64% of serotypes with no intra-serogroup cross protection and 82% with such protection. Nasopharyngeal carriage of S. pneumoniae is common in a UK setting in the pre-conjugate vaccine era. PCV would protect against a large proportion of carriage isolates. However, the impact of vaccination on non-vaccine serotypes will need to be monitored.

Adolescent↗
PubMed2005

A prospective analysis of extended endoscopic mucosal resection for large rectal villous adenomas: an alternative technique to transanal endoscopic microsurgery.

INTRODUCTION: Endoscopic mucosal resection is a safe resection tool for selected flat, sessile and lateral spreading tumours of the colon. Transanal microsurgical resection of select rectal neoplastic lesions is another accepted modality. Recent data suggests transanal microsurgery may have high complication rates. We conducted a prospective clinicopathological evaluation of an extended endoscopic mucosal resection technique for highly selected lesions of the rectum and assessed outcome data over a maximal 24-month period. PATIENTS AND METHODS: Eighty-three patients with known rectal neoplastic lesions underwent chromoscopic colonoscopy and on-table staging using a high-frequency (12.5 MHz) mini-probe EUS by a single endoscopist. Patients with T2 or node positive disease were referred for surgery. Following extended endoscopic mucosal resection patients were followed-up at 3, 6, 12 and 24 months post 'index' resection with chromoscopic endoscopy and EUS. Procedural complications, recurrence rates and outcome data were collected. RESULTS: Sixty-two patients fulfilled inclusion criteria. Median procedure time was 48 mins (range 32-126). Lateral spreading tumours (median diameter 30 mm; range 18-42 mm) and sessile lesions (median diameter 38 mm; range 25-86 mm) accounted for 19% and 81% of lesions, respectively. Ninety-seven percent of patients undergoing EMR were discharged within 6-h of procedure. Thirty-day re-admission and death rate was 0%. Bleeding complications occurred in 5/62 (8%) of patients with all achieving complete haemostasis using endo clips. None required transfusion. There were no procedural related complications or perforations. Overall 'cure' rate at a median follow-up of 16 months was 98%. CONCLUSIONS: Extended endoscopic mucosal resection for rectal neoplastic lesions can achieve superior results to those of per-anal excision and trans-anal microsurgery with regard to complications and recurrence rates. Extended endoscopic mucosal resection may be an alternative therapeutic modality in selected patients.

Adenoma, Villous↗
PubMed2005

Is the diaphragm motion probability density function normally distributed?

During radiotherapy treatment planning, the margins given to the clinical target volume to form the planning target volume accounts for internal motion and set-up error. Most margin formulas assume that the underlying distributions are independent and normal. Clinical data suggests that the set-up error probability density function (pdf) can be considered to have an approximately normal distribution. However, there is evidence that internal motion does not have a normal distribution. Thus, in general, a convolution of the two pdfs should be performed to determine the total geometric error. The goals of this article were to (1) determine if the internal motion pdf due to respiration can be characterized using a normal distribution, and (2) if not, determine if the total geometric uncertainty for combining internal motion and set-up error can be characterized by a normal distribution. Sixty fluoroscopy diaphragm motion data sets were obtained using three breathing training types: free breathing, audio instruction, and visual feedback. Diaphragm motion was used as a surrogate for liver and lung cancer motion. The data were analyzed with normality tests in the following groups: (1) single motion measurements, (2) combined motion measurements for each patient, and (3) combined motion measurements for all patients. Following this analysis, the diaphragm motion pdfs were convolved with a set-up error pdf, and the standard deviation of the set-up error pdf at which the total geometric error pdf became normal was determined. At set-up error standard deviation values of at least 0.27 and 0.1 cm for free breathing, 0.57 and 0.42 cm for audio instruction, and 0.55 and 0 cm for visual feedback, for single motion measurements and combined motion measurements for each patient, respectively, total geometric error pdfs became approximately normal. When the motion measurements for all the patients were combined, diaphragm motion pdfs were approximately normal for all feedback types. Therefore, for treatment planning purposes in the absence of individual patient measurements, the diaphragm motion pdf can be considered an approximately normal distribution. However, care should be taken when determining a margin based on individual patients measurements as the total geometric error will, in general, not be normally distributed.

Artifacts↗
PubMed2005

The application of the sinusoidal model to lung cancer patient respiratory motion.

Accurate modeling of the respiratory cycle is important to account for the effect of organ motion on dose calculation for lung cancer patients. The aim of this study is to evaluate the accuracy of a respiratory model for lung cancer patients. Lujan et al. [Med. Phys. 26(5), 715-720 (1999)] proposed a model, which became widely used, to describe organ motion due to respiration. This model assumes that the parameters do not vary between and within breathing cycles. In this study, first, the correlation of respiratory motion traces with the model f(t) as a function of the parameter n (n = 1, 2, 3) was undertaken for each breathing cycle from 331 four-minute respiratory traces acquired from 24 lung cancer patients using three breathing types: free breathing, audio instruction, and audio-visual biofeedback. Because cos2 and cos4 had similar correlation coefficients, and cos2 and cos1 have a trigonometric relationship, for simplicity, the cos1 value was consequently used for further analysis in which the variations in mean position (z0), amplitude of motion (b) and period (tau) with and without biofeedback or instructions were investigated. For all breathing types, the parameter values, mean position (z0), amplitude of motion (b), and period (tau) exhibited significant cycle-to-cycle variations. Audio-visual biofeedback showed the least variations for all three parameters (z0, b, and tau). It was found that mean position (z0) could be approximated with a normal distribution, and the amplitude of motion (b) and period (tau) could be approximated with log normal distributions. The overall probability density function (pdf) of f(t) for each of the three breathing types was fitted with three models: normal, bimodal, and the pdf of a simple harmonic oscillator. It was found that the normal and the bimodal models represented the overall respiratory motion pdfs with correlation values from 0.95 to 0.99, whereas the range of the simple harmonic oscillator pdf correlation values was 0.71 to 0.81. This study demonstrates that the pdfs of mean position (z0), amplitude of motion (b), and period (tau) can be used for sampling to obtain more realistic respiratory traces. The overall standard deviations of respiratory motion were 0.48, 0.57, and 0.55 cm for free breathing, audio instruction, and audio-visual biofeedback, respectively.

Algorithms↗
PubMed2005

Glaucoma in aphakia and pseudophakia in the Chennai Glaucoma Study.

AIM: To determine the prevalence of glaucoma among aphakes and pseudophakes in a rural population of southern India. METHODS: 3924 subjects aged 40 years or above underwent complete ophthalmic examination. Glaucoma in aphakia/pseudophakia was diagnosed using International Society of Geographical and Epidemiological Ophthalmology criteria in aphakic/pseudophakic people. RESULTS: 54 subjects (37 aphakes, 17 pseudophakes) (1.38% of 3924 subjects, 11.2% of 482 aphakes/pseudophakes) had glaucoma in aphakia/pseudophakia. Aphakia, age, intraocular pressure (IOP), pseudoexfoliation, and peripheral anterior synechiae greater than or equal to 180 degrees of the angle were risk factors for glaucoma on univariate analysis. On multivariate analysis, IOP and aphakia were independent risk factors for glaucoma. 39 people (72.22%) with glaucoma had normal IOP at presentation. None of the people with glaucoma were aware of the disease. Blindness in one or both eyes was seen in 12 subjects (10 unilateral and two bilateral)-that is, 22.22% of people with glaucoma in aphakia/pseudophakia. CONCLUSIONS: Glaucoma is an important cause of ocular morbidity among aphakes and pseudophakes in this rural population of south India. This glaucoma, responsible for unilateral or bilateral blindness in 22.2% of those affected, was entirely undetected in this study population.

Adult↗
PubMed2004

Acquiring 4D thoracic CT scans using a multislice helical method.

Respiratory motion degrades anatomic position reproducibility during imaging, necessitates larger margins during radiotherapy planning and causes errors during radiation delivery. Computed tomography (CT) scans acquired synchronously with the respiratory signal can be used to reconstruct 4D CT scans, which can be employed for 4D treatment planning to explicitly account for respiratory motion. The aim of this research was to develop, test and clinically implement a method to acquire 4D thoracic CT scans using a multislice helical method. A commercial position-monitoring system used for respiratory-gated radiotherapy was interfaced with a third generation multislice scanner. 4D cardiac reconstruction methods were modified to allow 4D thoracic CT acquisition. The technique was tested on a phantom under different conditions: stationary, periodic motion and non-periodic motion. 4D CT was also implemented for a lung cancer patient with audio-visual breathing coaching. For all cases, 4D CT images were successfully acquired from eight discrete breathing phases, however, some limitations of the system in terms of respiration reproducibility and breathing period relative to scanner settings were evident. Lung mass for the 4D CT patient scan was reproducible to within 2.1% over the eight phases, though the lung volume changed by 20% between end inspiration and end expiration (870 cm3). 4D CT can be used for 4D radiotherapy, respiration-gated radiotherapy, 'slow' CT acquisition and tumour motion studies.

Humans↗
PubMed2004

Genital syndromes and syndromic management of vaginal discharge in a community setting.

The objective of the study was to determine the community prevalence of genital syndromes in women and evaluate the syndromic management of vaginal discharge in this setting. A representative sample for the state of Tamilnadu was chosen using probability proportional to size cluster technique. Thirty clusters were selected from three districts. Demographic, sexual behaviour, risk factors, clinical and laboratory data were collected from the selected population using a structured questionnaire. Direct smear examination for Trichomonas vaginalis, culture for Neisseria gonorrhoeae and Haemophilus ducreyi, serological tests for syphilis (RPR and TPHA), hepatitis B (Hbs Ag ELISA), IgM and IgG antibodies to HSV2 (Novum diagnostics, Germany) and PCR test for detection of C. trachomatis from urine were done. There were 1157 women in the selected population. On examination, vaginal discharge was the most common genital syndrome (38.4%). The sensitivity, specificity, positive and negative predictive value of vaginal discharge as a marker for STD in women was found to be 43.3%, 61.6%, 10.7% and 91.1%, respectively. We concluded that treatment on the basis of syndromic management would result in over-treatment of 90% of women with vaginal discharge.

Adult↗
PubMed2003

Palliative care in adolescents.

Specialist Palliative Care's involvement in adolescent cancer is relatively new. The challenges are not so much to do with the technicalities of symptom control, but in walking the fine line with patients and families as they wrestle with transitions into an adulthood that will not happen and attempts to pack a lost future into a few months or years whilst coping with arduous and often futile treatments that attempt to buy some more time. The article explores some underlying principles and the model of care that has emerged at this specialist centre for adolescent care.

Adolescent↗
PubMed2003

Quantifying the effect of intrafraction motion during breast IMRT planning and dose delivery.

Respiratory motion during intensity modulated radiation therapy (IMRT) causes two types of problems. First, the clinical target volume (CTV) to planning target volume (PTV) margin needed to account for respiratory motion means that the lung and heart dose is higher than would occur in the absence of such motion. Second, because respiratory motion is not synchronized with multileaf collimator (MLC) motion, the delivered dose is not the same as the planned dose. The aims of this work were to evaluate these problems to determine (a) the effects of respiratory motion and setup error during breast IMRT treatment planning, (b) the effects of the interplay between respiratory motion and multileaf collimator (MLC) motion during breast IMRT delivery, and (c) the potential benefits of breast IMRT using breath-hold, respiratory gated, and 4D techniques. Seven early stage breast cancer patient data sets were planned for IMRT delivered with a dynamic MLC (DMLC). For each patient case, eight IMRT plans with varying respiratory motion magnitudes and setup errors (and hence CTV to PTV margins) were created. The effects of respiratory motion and setup error on the treatment plan were determined by comparing the eight dose distributions. For each fraction of these plans, the effect of the interplay between respiratory motion and MLC motion during IMRT delivery was simulated by superimposing the respiratory trace on the planned DMLC leaf motion, facilitating comparisons between the planned and expected dose distributions. When considering respiratory motion in the CTV-PTV expansion during breast IMRT planning, our results show that PTV dose heterogeneity increases with respiratory motion. Lung and heart doses also increase with respiratory motion. Due to the interplay between respiratory motion and MLC motion during IMRT delivery, the planned and expected dose distributions differ. This difference increases with respiratory motion. The expected dose varies from fraction to fraction. However, for the seven patients studied and respiratory trace used, for no breathing, shallow breathing, and normal breathing, there were no statistically significant differences between the planned and expected dose distributions. Thus, for breast IMRT, intrafraction motion degrades treatment plans predominantly by the necessary addition of a larger CTV to PTV margin than would be required in the absence of such motion. This motion can be limited by breath-hold, respiratory gated, or 4D techniques.

Algorithms↗
PubMed2003

Severe and unrecognised: pertussis in UK infants.

AIMS: To diagnose pertussis using culture, polymerase chain reaction, and serology, in children admitted to intensive care units (PICUs) and some paediatric wards in London, and in their household contacts to determine the source of infection. METHODS: Infants <5 months old admitted to London PICUs between 1998 and 2000 with respiratory failure, apnoea and/or bradycardia, or acute life threatening episodes (ALTE), and children <15 years admitted to paediatric wards at St Mary's and St George's Hospitals between 1999 and 2000 with lower respiratory tract infection, apnoea, or ALTE were studied. RESULTS: Sixty seven per cent of eligible children (142/212) were recruited; 23% (33/142) had pertussis, 19.8% (25/126) on the PICU and 50% (8/16) on wards. Two died. Only 4% (6/142) were culture positive. Pertussis was clinically suspected on admission in 28% of infants (7/25) on the PICU and 75% (6/8) on the wards. Infants on PICU with pertussis coughed for longer, had apnoeas and whooped more often, and a higher lymphocyte count than infants without pertussis. Pertussis and respiratory syncytial virus (RSV) co-infection was frequent (11/33, 33%). Pertussis was confirmed in 22/33 (67%) of those who were first to become ill in the family. For 14/33 children the source of infection was a parent; for 9/33 the source of pertussis was an older fully vaccinated child in the household. CONCLUSIONS: Severe pertussis is under diagnosed. An RSV diagnosis does not exclude pertussis. Future changes to the UK vaccination programme should aim to reduce pertussis transmission to young infants by their parents and older siblings.

Anti-Bacterial Agents↗