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N S Murthy

Publications and source records attributed to N S Murthy.

At least 37 records · Page 2Linked to original sources

Survival analysis: caveats and pitfalls.

BACKGROUND: Survival analysis in clinical studies is important to assess the effectiveness of a given treatment and to understand the effect of various disease characteristics. A number of methods exist to estimate the survival rate and its standard error. However, one cannot be certain that these methods have been handled appropriately. The widespread use of computers has made it possible to carry out survival analysis without expert guidance, but using inappropriate methods can give rise to erroneous conclusions. The majority of the biomedical journals now recommend that a statistical review of each manuscript should be carried out by an experienced bio-statistician, in addition to obtaining expert referees' comments on the article. The problem is compounded in papers from third-world countries where bio-statisticians may not be available in all institutions to guide clinicians as to the selection of proper techniques. METHODS: The present paper deals with the various techniques of survival analysis and their interpretation, using a modal data set of malignant upper-aerodigestive tract melanoma patients treated in the Regional Cancer Centre, Trivandrum since 1982. RESULTS: The Kaplan-Meier method was found to be the most suitable for survival analysis. The median survival time is a better method of summarizing data than the mean. Rothman's method of estimation of the confidence limit is better than Peto's method as the confidence limit for survival probability tends to go beyond the range of 0-1.0 when calculated by Peto's method, especially when the sample size is small. CONCLUSION: The results from the present study suggest that survival analysis should be carried out by the Kaplan-Meier method. The median survival time should be provided wherever possible, rather than relying on mean survival. Confidence limits should be calculated as a measure of variability. A suitable rank test should be used to compare two or more survival curves, rather than a Z-test. Stratified analysis and Cox's model, when stratified analysis fails, can be used to define the impact of prognostic factors on survival.

Confidence Intervals↗

The supination effect of tendon transfer of the flexor carpi ulnaris to the extensor carpi radialis brevis or longus: a cadaveric study.

Flexor carpi ulnaris (FCU) transfer to the extensor carpi radialis brevis (ECRB) and/or the extensor carpi radialis longus (ECRL) has been commonly used to provide wrist extension. The ability of this wrist extension transfer to also provide forearm supination has been inferred but not formally investigated. This laboratory study investigated the forearm supination effect of FCU transfer to the ECRB and to the ECRL in a cadaveric model. Two vectors of pull were investigated: freeing either the distal one third or the distal two thirds of the FCU ulnar origin. Five fresh-frozen, above-elbow, non-matched cadaveric specimens placed in a mounting device that allowed the arm to rotate about its ulnar axis starting from a full pronated position were measured for resultant supination after tendon transfer and loading. This study showed that the transfer of the FCU into either the ECRB or the ECRL resulted in no significant difference in maximum supination. The vector of origin, however, did significantly affect the maximum supination obtained. Releasing the distal two thirds of the FCU ulnar origin resulted in a mean supination that was significantly greater than the mean supination achieved with releasing the distal one third of the FCU ulnar origin. We concluded that in the cadaveric model, transfer of the FCU into either the ECRB or ECRL provided similar resultant supination and that freeing the distal two thirds of the FCU ulnar origin provided significantly more supination than freeing only the distal one third. For the hand surgeon treating wrist flexion in combination with forearm pronation deformity, transfer of the FCU into the ECRB and/or the ECRL can be used to concomitantly provide wrist extension and forearm supination.

Cadaver↗

Survival analysis: caveats and pitfalls.

BACKGROUND: Survival analysis in clinical studies is important to assess the effectiveness of a given treatment and to understand the effect of various disease characteristics. A number of methods exist to estimate the survival rate and its standard error. However, one cannot be certain that these methods have been handled appropriately. The widespread use of computers has made it possible to carry out survival analysis without expert guidance, but using inappropriate methods can give rise to erroneous conclusions. The majority of the biomedical journals now recommend that a statistical review of each manuscript should be carried out by an experienced bio-statistician, in addition to obtaining expert referees' comments on the article. The problem is compounded in papers from third-world countries where bio-statisticians may not be available in all institutions to guide clinicians as to the selection of proper techniques. METHODS: The present paper deals with the various techniques of survival analysis and their interpretation, using a modal data set of malignant upper-aerodigestive tract melanoma patients treated in the Regional Cancer Centre, Trivandrum since 1982. RESULTS: The Kaplan-Meier method was found to be the most suitable for survival analysis. The median survival time is a better method of summarizing data than the mean. Rothman's method of estimation of the confidence limit is better than Peto's method as the confidence limit for survival probability tends to go beyond the range of 0-1.0 when calculated by Peto's method, especially when the sample size is small. CONCLUSION: The results from the present study suggest that survival analysis should be carried out by the Kaplan-Meier method. The median survival time should be provided wherever possible, rather than relying on mean survival. Confidence limits should be calculated as a measure of variability. A suitable rank test should be used to compare two or more survival curves, rather than a Z-test. Stratified analysis and Cox's model, when stratified analysis fails, can be used to define the impact of prognostic factors on survival.

Digestive System Neoplasms↗

The efficacy of BAY y 1015 in dextran sulfate model of mouse colitis.

OBJECTIVE AND DESIGN: There is crucial evidence that leukotrienes are significant mediators of inflammation in inflammatory bowel diseases (IBD). Thus, selective inhibition of leukotriene synthesis is believed to provide a novel approach to therapy of IBD. The aim of the study is to study the efficacy of a potent 5-lipoxygenase activating protein inhibitor (FLAP), BAY y 1015 in a dextran sulfate model of mouse colitis. MATERIAL: Outbred female mice weighing approximately 25 grams were used to produce acute or chronic colitis by feeding 5% dextran sulfate in drinking water. TREATMENT: Colitic mice were treated with placebo (3% starch suspension, 0.1 ml. p.o., bid) or BAY y 1015 at 8 or 24 mg/kg, p.o., bid or olsalazine, 150 mg/kg/day, p.o. METHODS: Efficacy was determined by measuring daily disease activity index (DAI), quantitative histological scores, qualitative histology and measurement of tissue myeloperoxidase (MPO) and leukotriene B4 (LTB4) levels. RESULTS: BAY y 1015 was significantly more effective in improving the qualitative histology, inhibiting the DAI, inflammation scores (37-79%), crypt scores (28-71%), MPO (49-57%) and LTB4 levels (56-63%) compared to placebo treatment at all levels of colitis. The two doses of BAY y 1015 were equipotent in decreasing TLB4 levels. BAY y 1015 was significantly better than olsalazine in two of the three protocols used in this study. In the advanced disease level both doses of BAY y 1015 were equipotent in inhibiting crypt and (28-32%) inflammation scores (34-36%), LTB4 (34-56%) and MPO 41-49%) compared to olsalazine. CONCLUSION: This study suggests the possibility of investigating the use of this compound for the treatment of human inflammatory bowel diseases.

Animals↗

Prospective randomized trial of endoscopic sclerotherapy versus variceal band ligation for esophageal varices: influence on gastropathy, gastric varices and variceal recurrence.

BACKGROUND/AIMS: Endoscopic variceal ligation and endoscopic sclerotherapy are both recommended for the prevention of variceal rebleeding. To compare their efficacy, their influence on gastric varices and the development of portal gastropathy, 95 patients with variceal bleeding were studied. METHODS: The patients were randomized to receive weekly endoscopic sclerotherapy using alcohol (n=48) or endoscopic variceal ligation (n=47). The endoscopic sclerotherapy and endoscopic variceal ligation groups were comparable in etiology, severity of liver disease and grade of varices. RESULTS: In the arrest of acute bleed, endoscopic sclerotherapy and endoscopic variceal ligation were comparable (86% vs. 80%, p=ns). Endoscopic variceal ligation as compared to endoscopic sclerotherapy, obliterated esophageal varices in fewer sessions (4.1+/-1.2 vs. 5.2+/-1.8, p<0.01) and a shorter time (4.4+/-1.3 vs. 6.9+/-3.4 wk, p<0.01). Three (6.4%) patients bled after endoscopic variceal ligation and 10 (20.8%) after endoscopic sclerotherapy (p<0.05). The actuarial percentage of variceal recurrence during a follow-up of 8.5+/-4.4 months, was higher after endoscopic variceal ligation than endoscopic sclerotherapy (28.7% vs 7.5%, p<0.05). Esophageal stricture formation after endoscopic sclerotherapy occurred in five (10.4%) patients, but in none after endoscopic variceal ligation. Significantly more patients developed gastropathy after endoscopic sclerotherapy than ligation (20.5% vs. 2.3%; p=0.02). Endoscopic sclerotherapy (52%) and endoscopic variceal ligation (59%) were equally effective in obliterating the lesser curve gastric varices. Six patients died: three in each group. CONCLUSIONS: (i) Endoscopic sclerotherapy and endoscopic variceal ligation were equally effective in controlling acute bleed; (ii) endoscopic ligation achieved variceal obliteration faster and in fewer treatment sessions; (iii) endoscopic variceal ligation had a significantly lower rate of development of portal gastropathy and rebleeding, (iv) while both techniques influenced gastric varices equally, there was significantly higher esophageal variceal recurrence after endoscopic variceal ligation than sclerotherapy.

Adult↗

Reduction in the cumulative incidence rate of cervical cancer by one life time selective screening.

Mass scale cervical cytology which is the most accepted strategy for the control of cervical cancer cannot be undertaken in developing countries in view of paucity of resources, hence a need arises to examine alternate strategy. The present exercise attempts to study the reduction in cumulative incidence rate of cervical cancer by one life time selective screening. The results revealed that cumulative incidence rate (CIR) of cervical cancer per 100,000 in cohort of women during the age of 20 to 64 years was found to be 2555.0 in the absence of screening. One life time selective screening at the age of 40 and 45 years showed the reduction of 11.6 and 17.2% in CIR respectively where as respective estimates in case of complete screening at mentioned age groups were found to be 21.5% and 25%. In order to further conserve the resources the strategy seems to be optimum for developing countries.

Adult↗

Prevalence of serum antibodies to synthetic peptides to HPV16 epitopes among Indian women with cervical neoplasia.

Serum samples from 38 Indian women with cervical intraepithelial neoplasia (CIN) and cancer along with 20 control women were analysed for IgG antibodies against a panel of four synthetic peptides derived from early and late gene open reading frames of HPV16. The cervical tissue samples from these patients were also subjected to PCR in order to detect the presence of human papilloma viruses (HPVs) type 6, 11 and 16 DNA, using a set of primers for the E6 open reading frames in order to establish the acquisition of HPV infection. E2, E6 and L1 peptides of HPV16 were found to be highly reactive with the patients' sera, and a significant prevalence of antibodies to E6, E2 and L1 (P < 0.01) was observed among women with CIN, while antibodies to E6 peptide were only significantly elevated (P < 0.01) among women with cervical invasive carcinoma. Furthermore, there was good agreement between the development of the E6 antibody response and the presence of HPV16 E6 DNA among women with CIN and cervical invasive carcinoma as shown by high values of the kappa coefficient (0.7-1.0). The study clearly revealed a strong agreement between two assay methods defining unambiguous immunogenic B-cell epitopes on synthetic peptides to early and late gene open reading frames of HPV16 which could be used in HPV peptide serology. As such, single or combination of peptides in HPV peptide serology can be used as a screening tool to identify HPV-associated cervical lesions.

Amino Acid Sequence↗

Biological behaviour of moderate dysplasia--a prospective study.

The present communication reports the biological behaviour of women with moderate dysplastic lesions of uterine cervix based on a long term prospective study. Two hundred and thirty nine women with moderate dysplasia by cervical cytology who satisfied the criteria for registration were longitudinally followed up at 3 +/- 1 monthly intervals along with age and parity matched controls for a period ranging from 4 to 132 months. The cumulative rate of progression from moderate dysplasia to malignancy (CIS) was observed to be 23.0% at the end of 72 months of follow up with mean transition interval of 24.2 months. Out of 239 cases, 142 women who had more than 24 months of follow up were considered for studying the biological behaviour of the lesion. It was observed that during a follow up of 132 months, 14(9.9%) and 15(10.6%) women progressed to carcinoma in-situ and severe dysplasia respectively. The persistence of lesion was observed in 21(14.8%) women while 11(7.3%) and 81(57.0%) regressed to mild dysplasia and normalcy respectively.

Carcinoma in Situ↗

Evaluation of a hospital based cytology screening programme for reduction in life time risk of cervical cancer.

Hospital based cytology screening is one of the suggested alternative strategies for the developing countries. The present communication attempts to estimate the reduction in lifetime risk of cervical cancer initiated through a hospital based single lifetime screening programme. The percent reduction in cumulative incidence of cervical cancer during lifetime in different age groups of women was calculated after estimating the number of incident cases in the absence as well as presence of screening. Our analysis revealed that by introducing the single life time cytology screening in the group of hospital attending population, an overall reduction in the cumulative incidence of cervical cancer during lifetime was found to be 10.2%. It was further estimated that the reduction was much less in the early age groups (2.4-10.2% in 20-34 years) as compared to later age groups (11.2-55.6% in 35+ years).

Adult↗

Interobserver agreement in the diagnosis of cervical smears.

The present study was carried out to reveal the magnitude of individual variation in the diagnosis of Pap smears between two cytoscreeners and their compatability with cytopathologists and subsequent final diagnostic comparison with biopsy in 1,17411 cervical smears collected from different hospitals of Delhi during ten-year period. Smears diagnosed as dysplasia at initial level by any one of the cytoscreeners were screened by cytopathologists for confirmation of diagnosis. An overall agreement of 94.9 percent was observed between two screens. 79.5 percent was agreement between screeners and cytopathologists. An agreement between cytology and histology in the diagnosis of dysplasia and malignancy were found to be 61.9 percent and dysplasia and malignancy were found to be 61.9 percent and 40.1 percent respectively. From the above study, it was observed that consistency among the two screeners was fairly acceptable. Keeping this observation in view, we can possibly practice two tier screening in place of three.

Female↗

S-(N-aryl-N-hydroxycarbamoyl)glutathione derivatives are tight-binding inhibitors of glyoxalase I and slow substrates for glyoxalase II.

S-(N-Aryl-N-hydroxycarbamoyl)glutathione derivatives are powerful competitive inhibitors of the anticancer target enzyme glyoxalase I. Indeed, the N-p-bromophenyl derivative is the strongest inhibitor of the enzyme from human erythrocytes yet reported (Ki = 1.4 x 10(-8) M). Structure-activity correlations indicate that the high affinities of the derivatives for both human and yeast glyoxalase I are due to the fact that the derivatives are hydrophobic analogs of the enediol(ate) intermediate associated with the glyoxalase I reaction. The derivatives also proved to be slow substrates for the thioester hydrolase glyoxalase II (bovine liver). Compounds of this type are of interest as potential tumor-selective anticancer agents, based on the abnormally low levels of glyoxalase II activity in some types of cancer cells.

Animals↗

Urinary calcium creatinine ratio and hypercalciuria.

Random urine samples of 352 children in the age group of 5-12 yrs were studied for urinary calcium-creatinine ratio (Uca/Ucr mg/mg). None had any predisposing factor for secondary hypercalciuria. Calcium and creatinine both were estimated by colorimetric method. We observed that Uca/Ucr in the general pediatric population was skewed, the pattern was similar to that described in western children and it was independent of age and sex. The mean and standard deviation (SD) of Uca/Ucr was 0.10 +/- 0.094. Considering mean +2SD as the upper limit of normal, which was 0.29 in this series, the prevalence of hypercalciuria was 6.5%.

Calcium↗

Estimation of reduction of life-time risk of cervical cancer through one life-time screening.

The purpose of screening for cervical cancer is to prevent the appearance of invasive disease by the detection and treatment of precancerous lesions. Based on data from the developed countries, recommendations have been made regarding the age at which cytology screening should begin and the interval with which rescreening should be performed. However, these recommendations may not be applicable for a developing country like India due to human and financial resource constraints. WHO has recommended that for countries where resources are limited the aim should be to screen every woman at least once in her life-time at an appropriate age. Hence, it is essential to determine the age at which screening may be offered to derive maximum gains. With this in background, based on the data of national cancer registries, an attempt has been made for Indian population to estimate the reduction in the cumulative incidence rate of cervical carcinoma which can be achieved in a cohort of women aged 20-64 years by screening once in her life-time at an appropriate age. Our findings revealed that the first screening offered at 45 years of age could produce gains to the extent of 20-27%, while the screening offered at 50 or 55 years produced the maximum gains to the extent of 25-29%. However, keeping in view the produce years of lives lost in younger women, it may be reasonable to offer once in life-time screening to women aged 45 years.

Adult↗

Selective cervical cytology screening: discriminant analysis approach.

Cervical cancer is one of the leading malignancies seen in Indian women. It has been well established that organized cervical cytology screening program is the mainstay for control of cervical cancer. It is not possible to carry out cervical cytology screening for masses in India due to paucity of human and financial resources. Hence there is a need for development of an alternate strategy to concentrate on women with high risk. In the present communication attempt was made to define a high risk group based on sociodemographic factors, viz. age, parity, education and clinical features. A total of 67,000 women were screened of which in 250 malignancy was detected. The rate of malignancy was observed to be high in women above 40 years (10.5/1000) with more than two children (6.1/1000) and in illiterate group (4.9/1000) as compared to women below 40 years, more than 3 children and illiterate group. Similarly, the rates were higher in women with clinical diagnosis of cervical erosion which bled on touch, unhealthy cervix and suspicious looking cervix, malignancy rates were 17.1, 24.7, 263.2 (per 1000), respectively. An attempt was made to study the combined effect of all the six factors (sociodemographic and clinical) by employing the technique of linear discriminant analysis to find out the discrimination power between the normal and malignant women. Discriminant score thus obtained would help to classify the case for subjecting to cervical cytology. It was observed that the model containing sociodemographic and clinical variables was able to classify 69% of malignant cases correctly. When the clinical variables were dropped from the model, the sensitivity dropped to 65%. The above exercise indicated that based on the discriminant score even in the absence of facilities for clinical examination of women, it may be possible to identify women of high risk group for subjecting them to cervical cytology screening.

Adult↗

Superficial and deep-seated tuberculous lesions: fine-needle aspiration cytology diagnosis of 574 cases.

Over a period of 2 yr (1987-1988), FNA smears in 574 cases were found to have cytologic features suggestive of or consistent with tuberculous lesions. The age of the patients ranged from 6 mo to 75 ye, with a median of 24 yr. The male to female ratio was 273:301. Sites of FNA were superficial lymph nodes (SLN) in 440 (76.7 percent) cases, superficial extranodal sites (SENS) in 50 (8.7 percent), both SLN and SENS in 7 (1.2%), the thoracic cavity in 16 (2.8%), and the abdominal cavity in 61 (10.6%). Cytologic features were described under 3 major cytologic patterns, i.e., type I: epithelioid granuloma without necrosis, type II: epithelioid granuloma with necrosis, type III: necrosis without epithelioid granuloma. Type I, II, and III reactions were observed in 181 (31.5%), 183 (31.9%), and 210 (36.6%) cases, respectively. The overall AFB positivity was 30.8%. The AFB positivities for type I, II, and III cytologic reactions were 5.4%, 32.0%, and 48.5%, respectively. The AFB positivity was low (less than 30.0%) in swellings of the body surface (23.8%) and abdominal organs (18.9%). High positivity (greater than 60.0%) was observed in lesions of the thorax (63.6%) and thyroid (62.5%).

Adolescent↗

Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.

To determine the prevalence and natural history of gastric varices, we prospectively studied 568 patients (393 bleeders and 175 nonbleeders) with portal hypertension (cirrhosis in 301 patients, noncirrhotic portal fibrosis in 115 patients, extrahepatic portal vein obstruction in 117 patients and hepatic venous outflow obstruction in 35 patients). Primary (present at initial examination) gastric varices were seen in 114 (20%) patients; more were present in bleeders than in non-bleeders (27% vs. 4%, respectively; p < 0.001). Secondary (occurring after obliteration of esophageal varices) gastric varices developed in 33 (9%) patients during follow-up of 24.6 +/- 5.3 mo. Gastric varices (compared with esophageal varices) bled in significantly fewer patients (25% vs. 64%, respectively). Gastric varices had a lower bleeding risk factor than did esophageal varices (2.0 +/- 0.5 vs. 4.3 +/- 0.4, respectively) but bled more severely (4.8 +/- 0.6 vs. 2.9 +/- 0.3 transfusion units per patient, respectively). Once a varix bled, mortality was more likely (45%) in gastric varix patients. Gastric varices were classified as gastroesophageal or isolated gastric varices. Type 1 gastroesophageal varices (lesser curve varices) were the most common (75%). After obliteration of esophageal varices, type 1 gastroesophageal varices disappeared in 59% of patients and persisted in the remainder; bleeding from persistent gastroesophageal varices was more common than it was from gastroesophageal varices that were obliterated (28% vs. 2%, respectively; p < 0.001). Type 2 gastroesophageal varices, which extend to greater curvature, bled often (55%) and were associated with high mortality. Type 1 isolated gastric varices patients had only fundal varices, with a high (78%) incidence of bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗