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Biomedical subjects

R Sankaranarayanan

Publications and source records attributed to R Sankaranarayanan.

At least 37 records · Page 2Linked to original sources

Socioeconomic status, lifestyle factors and oral premalignant lesions.

Several studies have suggested that low socioeconomic status (SES) is associated with a higher risk of oral cancer, but the association with oral premalignant lesions has not yet been explored. The aim of this study was to examine the association of education, occupation, income and SES index with oral premalignant lesions. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. There were a total of 927 oral leukoplakia, 170 oral submucous fibrosis, 100 erythroplakia and 115 multiple oral premalignant lesion cases and 47,773 controls. Subjects with high SES index had protective ORs for oral premalignant lesions, ranging from 0.6 to 0.7, after adjustment for age, sex, BMI, tobacco chewing, smoking, drinking and fruit/vegetable intake. Higher education levels were also associated with decreased risk of all four oral premalignant lesions. Protective ORs for income were observed for oral leukoplakia and possibly oral submucous fibrosis and erythroplakia. SES may be associated with oral premalignant lesions because of access to medical care, health related behaviors, living environment or psychosocial factors. Though the mechanism for the association is not clear, higher SES index, education and income were associated with decreased risk of oral premalignant lesions in our study.

Adult↗

Survival from oral cancer in Mumbai (Bombay), India.

OBJECTIVE: Cancer survival information is available for only few populations in developing countries. Data on survival of oral cancer patients registered by the Bombay population-based cancer registry, India, during 1992-1994 is presented in this paper. METHODS: Vital status of the patients was established by matching against death certificates, reply paid postal enquiries, telephone enquiries, scrutiny of hospital records and house visits. Of the 1808 eligible cases for analysis, 1204 (66.6%) were dead; and 604 (33.4%) were alive at last follow-up, of whom 136 were lost to follow-up during the first 5-years after diagnosis. Observed and relative survival rates are presented and hazard ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazard model. RESULTS: The overall 5-year observed and relative survival rates were 30.5% and 39.7%, respectively. Survival steadily declined with advancing age and advanced clinical stages. Five-year observed survival was 59.1% for localised cancer, 15.7% for cancers with regional extension and 1.6% for those with distant metastasis. Those with tongue, buccal mucosa and retromolar trigone cancers had poor survival rates. CONCLUSIONS: Our study shows that detecting oral cancer in early stages, when these are amenable to single modality therapies, offers the best chance of long-term survival. However, primary prevention by tobacco/alcohol control measures is important in the long-term perspective.

Age Distribution↗

Early detection of cervical cancer with visual inspection methods: a summary of completed and on-going studies in India.

India is a high-risk country for cervical cancer which accounts a quarter (126,000 new cases, 71,000 deaths around 2,000) of the world burden. The age-standardized incidence rates range from 16-55 per 100,000 women in different regions with particularly high rates in rural areas. Control of cervical cancer by early detection and treatment is a priority of the National Cancer Control Programme of India. There are no organized cytology screening programmes in the country. The technical and financial constraints to organize cytology screening have encouraged the evaluation of visual inspection approaches as potential alternatives to cervical cytology in India. Four types of visual detection approaches for cervical neoplasia are investigated in India: a) naked eye inspection without acetic acid application, widely known as 'downstaging'; b) naked eye inspection after application of 3-5% acetic acid (VIA); c) VIA using magnification devices (VIAM); d) visual inspection after the application of Lugol's iodine (VILI). Downstaging has been shown to be poorly sensitive and specific to detect cervical neoplasia and is no longer considered as a suitable screening test for cervical cancer. VIA, VIAM and VILI are currently being investigated in multicentre cross-sectional studies (without verification bias), in which cytology and HPV testing are also simultaneously evaluated, and the results of these investigations will be available in 2003. These studies will provide valuable information on the average, comparative test performances in detecting high-grade cervical cancer precursors and cancer. Results from pooled analysis of data from two completed studies indicated an approximate sensitivity of 93.4% and specificity of 85.1% for VIA to detect CIN 2 or worse lesions; the corresponding figures for cytology were 72.1% and 91.6%. The efficacy of VIA in reducing incidence of an mortality from cervical cancer and its cost-effectiveness is currently being investigated in two cluster randomized controlled intervention trials in India. One of these studies is a 4-arm trial addressing the comparative efficacy of VIA, cytology and primary screening with HPV DNA testing. This trial will provide valuable information on comparative detection rates of CIN 2-3 lesions by the middle of 2003. The expected outcomes from the Indian studies will contribute valuable information for guiding the development of public health policies on cervical cancer prevention in countries with different levels of socio-economic and health services development and open up new avenues of research. This paper is available too at: http//www.insp.mx/salud/index.html.

Acetic Acid↗

Pseudohypoparathyroidism with systemic lupus erythematosus.

A female patient with short stature, of systemic lupus erythematosis and hypocalcemia presented to us. On examination and investigations she was found to be a case of Type Ia pseudohypoparathyroidism. The patient's quality of life improved after appropriate treatment. The case is a rare combination of two disorders.

Adult↗

Effect of stabilizing additives on the structure and hydration of proteins: a study involving monoclinic lysozyme.

In pursuance of a long-range programme on the hydration, mobility and action of proteins, the structural basis of the stabilizing effect of sugars and polyols is being investigated. With two crystallographically independent molecules with slightly different packing environments in the crystal, monoclinic lysozyme constitutes an ideal system for exploring the problem. The differences in the structure and hydration of the two molecules provide a framework for examining the changes caused by stabilizing additives. Monoclinic crystals were grown under native conditions and also in the presence of 10% sucrose, 15% trehalose, 10% trehalose, 10% sorbitol and 5% glycerol. The crystal structures were refined at resolutions ranging from 1.8 to 2.1 A. The average B values, and hence the mobility of the structure, are lower in the presence of additives than in the native crystals. However, a comparison of the structures indicates that the effect of the additives on the structure and the hydration shell around the protein molecule is considerably less than that caused by differences in packing. It is also less than that caused by the replacement of NaNO(3) by NaCl as the precipitant in the crystallization experiments. This result is not in conformity with the commonly held belief that additives exert their stabilizing effect through the reorganization of the hydration shell, at least as far as the ordered water molecules are concerned.

Animals↗

Assessment of the cervix after acetic acid wash: inter-rater agreement using photographs.

OBJECTIVE: To estimate the inter-rater agreement on the assessment of cervical photographs after acetic acid wash, using visual inspection with acetic acid categories. METHODS: Three raters individually assessed 144 photographs as negative, positive, or suspicious for cancer. The inter-rater agreement was analyzed using the unweighted and weighted kappa coefficient. To explore the reasons for concordancy and discordancy, photographs were compared on histologic evidence of cervical intraepithelial neoplasia and on testing for oncogenic types of human papillomavirus. RESULTS: Overall raw agreement among the three raters was 66.7% (96 of 144) with a kappa of 0.57 (95% confidence interval 0.48, 0.66). Pair-wise agreement using unweighted and weighted kappa was moderate to substantial: 0.54-0.60 and 0.56-0.63, respectively. There was concordance on negative in 25.7% (37 of 144) and on positive or suspicious for cancer in 41.0% (59 of 144). Cervical intraepithelial neoplasia II or III was not present on biopsy if photographs were concordant-negative, and the human papillomavirus test was less likely to be positive (relative risk 0.3; 95% confidence interval 0.2, 0.6) in concordant-negatives compared with concordant-positives, including suspicious for cancer. Cervical intraepithelial neoplasia II or III was more common in photographs that were concordant-positive, including suspicious for cancer, compared with discordants (relative risk 3.4, 95% confidence interval 1.5, 7.6). CONCLUSION: Based on photographs of the cervix taken after acetic acid wash, the level of agreement among raters using visual inspection with acetic acid categories was moderate to substantial, consistent with other commonly used tests.

Acetic Acid↗

Visual inspection in oral cancer screening in Cuba: a case-control study.

A case-control study was conducted to evaluate the efficacy of an on-going oral cancer screening programme in Cuba in preventing advanced oral cancer in Cuba. The cases for the study consisted of 200 oral cancer patients with stage III and IV disease. Three apparently healthy subjects per case, matched for sex, age (plus or minus 5 years) and residing within a perimeter of 200 m of the house with the case, and willing to be interviewed, were recruited as the controls. Information on socio-economic indicators, smoking, drinking, diet and screening history in the form of visits to the dentist were collected by personal interview with the subjects. Odds ratio (OR), with 95% confidence intervals (CI), of being diagnosed with an advanced oral cancer, in relation to the screening experience at the date of diagnosis of case, 1, 2, 3, 6, and 12 months prior to the date of diagnosis of case were estimated by conditional logistic regression for matched data. The odds ratio of advanced oral cancer associated with screening in relation to screening experience 3 months prior to the diagnosis of the case was 0.67 (95% CI: 0.46-0.95). The odds ratio was 0.91 (95% CI: 0.60-1.37) for a single screening test and 0.41 (95% CI: 0.24-0.68) for two or more tests. The protection offered by screening persisted up to 3 years since the last test. The results of a descriptive evaluation of the programme also revealed limited evidence towards a shift from advanced to early stages after the introduction of the programme. Nonetheless, the results should be interpreted with caution in view of the several limitations in the study, particularly the fact that screening history was established indirectly by interviews and advanced oral cancers constituted the cases, rather than those who died from the disease.

Case-Control Studies↗

Effective screening programmes for cervical cancer in low- and middle-income developing countries.

Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes--either organized or opportunistic--have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening. This article briefly reviews the experience from existing screening and research initiatives in developing countries. Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programmes for cervical cancer. Owing to their limited health care resources, developing countries cannot afford the models of frequently repeated screening of women over a wide age range that are used in developed countries. Many low-income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening programme. Middle-income developing countries, which currently provide inefficient screening, should reorganize their programmes in the light of experiences from other countries and lessons from their past failures. Middle-income countries intending to organize a new screening programme should start first in a limited geographical area, before considering any expansion. It is also more realistic and effective to target the screening on high-risk women once or twice in their lifetime using a highly sensitive test, with an emphasis on high coverage (>80%) of the targeted population. Efforts to organize an effective screening programme in these developing countries will have to find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and following up the targeted women. The findings from the large body of research on various screening approaches carried out in developing countries and from the available managerial guidelines should be taken into account when reorganizing existing programmes and when considering new screening initiatives.

Adult↗

Quantum chaos of a particle in a square well: competing length scales and dynamical localization.

The classical and quantum dynamics of a particle trapped in a one-dimensional infinite square well with a time-periodic pulsed field is investigated. This is a two-parameter non-KAM (Kolmogorov-Arnold-Moser) generalization of the kicked rotor, which can be seen as the standard map of particles subjected to both smooth and hard potentials. The virtue of the generalization lies in the introduction of an extra parameter R, which is the ratio of two length scales, namely, the well width and the field wavelength. If R is a noninteger the dynamics is discontinuous and non-KAM. We have explored the role of R in controlling the localization properties of the eigenstates. In particular, the connection between classical diffusion and localization is found to generalize reasonably well. In unbounded chaotic systems such as these, while the nearest neighbor spacing distribution of the eigenvalues is less sensitive to the nature of the classical dynamics, the distribution of participation ratios of the eigenstates proves to be a sensitive measure; in the chaotic regimes the latter is log-normal. We find that the tails of the well converged localized states are exponentially localized despite the discontinuous dynamics while the bulk part shows fluctuations that tend to be closer to random matrix theory predictions. Time evolving states show considerable R dependence, and tuning R to enhance classical diffusion can lead to significantly larger quantum diffusion for the same field strengths, an effect that is potentially observable in present day experiments.

Journal Article↗

Population-based cancer survival in Singapore, 1968 to 1992: an overview.

The Singapore Cancer Registry has provided comprehensive population-based incidence data since 1968. This paper describes the population-based survival analysis of the registry data. All invasive primary cancers diagnosed from January 1, 1968 to December 31, 1992 were passively followed up until December 31, 1997. Only 5.8% were lost to follow-up. Cumulative and observed survival rates were calculated using Hakulinen's method. Overall 5-year relative survival rates have increased dramatically over the 25-year period in both genders. Significant increases are seen with nasopharynx, stomach and colo-rectum cancers, non-Hodgkin's lymphoma, leukemias and cancers of the testis, cervix, ovaries and breast. When compared with the Surveillance, Epidemiology and End Results (SEER) rates in the United States, the 5-year relative survival rates in Singapore are generally lower. However, the rate of change between the two countries is fairly similar. On the average, the rates are 10 to 15 years behind the SEER rates and 5 to 10 years behind Finland, Switzerland and Japan, but they are close to the UK rates. The age-standardized 5-year survival rate for Singapore is higher for most sites compared with other developing countries like Qidong (China), Madras (India), Bombay (India) and Chiang Mai (Thailand). The 25-year trend in cancer survival in Singapore showed two extreme groups: those showing no change and those showing significant improvements. Reducing the incidence of cancers belonging to the first group remains the only viable mode of cancer control. For cancers in the second group, improvement in survival is due to a combination of successful early detection measures and effective treatment services in Singapore.

Age Factors↗

5-amino-4-(4-diethylaminophenyl)-2-(4-hydroxyphenyl)-7-(pyrrolidin-1-yl)-1,6-naphthyridine-8-carbonitrile.

In the title compound, C29H30N6O, the naphthyridine moiety is planar with a dihedral angle between the fused rings of 1.9 (1) degrees. The phenol ring is nearly coplanar, while the diethylaminophenyl substituent is orthogonal to the central naphthyridine ring and the pyrrolidine ring makes an angle of 11.2 (1) degrees with it. The O atom of the hydroxy substituent is coplanar with the phenyl ring to which it is attached. The molecular structure is stabilized by a C-H...N-type intramolecular hydrogen bond and the packing is stabilized by intermolecular C-H...pi, O-H...N and N-H...O hydrogen bonds.

Crystallography, X-Ray↗

N-Methyl-N-(1-phenylsulfonylindol-2-ylmethyl)aniline.

In the title compound, 2-[(methylphenylamino)methyl]-1-(phenylsulfonyl)indole, C22H20N2O2S, the indole system is not strictly planar and the dihedral angle between the fused rings is 2.7 (1) degrees. The angles around the S atom of the sulfonyl substituent deviate significantly from the ideal value for tetrahedral geometry. The pyramidalization at the indole N atom is very small. Of the two C-H...O interactions, one influences the orientation of indole with respect to the sulfonyl group and the other determines the orientation of the phenyl bound to sulfonyl. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 89.6 (1) degrees with the best plane of the indole. The molecular packing is stabilized by C-H...pi and C-H...O hydrogen bonds.

Aniline Compounds↗

Population-based survival from colorectal cancer in Mumbai, (Bombay) India.

Survival estimates of patients registered by population-based cancer registries reflect the average prognosis from a given cancer as they are based on unselected patients with a wide range of natural histories and treatment patterns. In this paper, we report the survival experience of colorectal cancer patients in Mumbai (Bombay), India. Follow-up information on 1642 colorectal cancer patients registered by the Bombay Population-based Cancer Registry for the period 1987-1991 was obtained by matching with death certificates from the Bombay vital statistics registration system, postal/telephone enquiries, home visits and scrutiny of medical records. Cumulative observed and relative survival proportions were calculated by Hakulinen's method. For comparison of results with other populations, age-standardised relative survival (ASRS) was calculated by directly standardising age-specific relative survival to the specific age distributions of the world standard cancer patient population in 1985. The log-rank test was used to identify the potential prognostic variables which were introduced step-wise into a Cox regression model to identify the independent predictors of survival. The 5-year relative survival was 36.6% for colon and 42.2% for rectal cancer. Age, site of cancer and clinical stage of disease emerged as independent predictors of survival. Age-specific 5-year relative survival declined with advancing age. Survival at 5 years was 61.2% for localised colon cancer; 31.9% for regional and 9.0% for distant metastatic disease. These were 65.7, 25.6 and 4.3%, respectively for rectal cancers. Comparison of the results with other populations revealed significant variations, which seem to be related to differences in detection and treatment. The prognosis from colorectal cancer in Mumbai and developing countries, may be further improved through early detection linked with treatment.

Adolescent↗

Evaluation of surgical excision of non-homogeneous oral leukoplakia in a screening intervention trial, Kerala, India.

It is well established that most invasive oral cancers arise from precancerous lesions such as leukoplakia, erythroplakia and oral submucous fibrosis. One of the approaches for control of oral cancer is to detect oral precancerous lesions early in their development and prevent their malignant transformation to invasive cancer either by chemoprevention or by surgical excision of the lesions, with concurrent control of tobacco and alcohol use and other specific aetiological factors. However, the value of specific approaches such surgery in long-term control of lesions and prevention of malignant transformation is not known. We describe our experience with cold knife surgical excision of 59 cases of non-homogeneous leukoplakia of the oral cavity diagnosed in the context of a community-based oral cancer cluster randomised oral cancer screening trial in Kerala, India. Two-thirds of these revealed dysplasia on histology. After a minimum follow-up of 12 months (range 12-37 months) after surgical excision, 44 (74.8%) were remaining disease free with no evidence of recurrent/new lesions; during follow-up, three (5%) developed new luekoplakic lesions, and six (10.1%) developed recurrent lesions, while six (10.1%) could not be traced after treatment. There was no event of malignant change during follow-up. The proportion of subjects remaining with no evidence of disease at 3 years by Kaplan-Meier method of analysis was 62.1% (95% CI: 0.36-0.87). Accrual and long-term follow-up of large number of surgically treated cases may provide valuable leads to management policies of oral leukoplakia, since, as of now, the added value of specific treatments over and above primary prevention by tobacco and alcohol control remains to be established.

Adult↗

The fidelity of the translation of the genetic code.

Aminoacyl-tRNA synthetases play a central role in maintaining accuracy during the translation of the genetic code. To achieve this challenging task they have to discriminate against amino acids that are very closely related not only in structure but also in chemical nature. A 'double-sieve' editing model was proposed in the late seventies to explain how two closely related amino acids may be discriminated. However, a clear understanding of this mechanism required structural information on synthetases that are faced with such a problem of amino acid discrimination. The first structural basis for the editing model came recently from the crystal structure of isoleucyl-tRNA synthetase, a class I synthetase, which has to discriminate against valine. The structure showed the presence of two catalytic sites in the same enzyme, one for activation, a coarse sieve which binds both isoleucine and valine, and another for editing, a fine sieve which binds only valine and rejects isoleucine. Another structure of the enzyme in complex with tRNA showed that the tRNA is responsible for the translocation of the misactivated amino-acid substrate from the catalytic site to the editing site. These studies were mainly focused on class I synthetases and the situation was not clear about how class II enzymes discriminate against similar amino acids. The recent structural and enzymatic studies on threonyl-tRNA synthetase, a class II enzyme, reveal how this challenging task is achieved by using a unique zinc ion in the active site as well as by employing a separate domain for specific editing activity. These studies led us to propose a model which emphasizes the mirror symmetrical approach of the two classes of enzymes and highlights that tRNA is the key player in the evolution of these class of enzymes.

Amino Acids↗

Transfer RNA-mediated editing in threonyl-tRNA synthetase. The class II solution to the double discrimination problem.

Threonyl-tRNA synthetase, a class II synthetase, uses a unique zinc ion to discriminate against the isosteric valine at the activation step. The crystal structure of the enzyme with an analog of seryl adenylate shows that the noncognate serine cannot be fully discriminated at that step. We show that hydrolysis of the incorrectly formed ser-tRNA(Thr) is performed at a specific site in the N-terminal domain of the enzyme. The present study suggests that both classes of synthetases use effectively the ability of the CCA end of tRNA to switch between a hairpin and a helical conformation for aminoacylation and editing. As a consequence, the editing mechanism of both classes of synthetases can be described as mirror images, as already seen for tRNA binding and amino acid activation.

Acylation↗

Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population.

Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case-control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1. 3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population.

Aged↗