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Biomedical subjects

U K Luthra

Publications and source records attributed to U K Luthra.

At least 37 records · Page 2Linked to original sources

Screening for cervical cancer by direct inspection.

OBJECTIVE: To assess the efficacy of visual screening for cervical cancer in the maternal and child health setting. DESIGN: Clinical and cytological screening. SETTING: Maternal and child health centres, Delhi. SUBJECTS: 44,970 women attending the centres from May 1988 to March 1991. RESULTS: 238 cancers in early stages (0-IIa) were detected cytologically and proved through biopsy. Prevalence of cancer in women defined as high risk through examination by speculum was 29/1000 as compared to 1.53/1000 among women with a normal looking cervix. Though only 11.4% women belonged to the high risk category, 63% had early stage cancer. If all women with bleeding symptoms were included in the high risk category, the yield of cancer would be 71.4% (170/238) by referring only 15.6% of women attending maternal and child health centres for further evaluation through cytology or colposcopy. CONCLUSION: Though visual screening is a suboptimal strategy in comparison to the cytological screening, it may be useful where there is a heavy load of prevalent cancer and where cytological screening may not be available for years to come.

Biopsy↗

Supportive role of image analysis and DNA ploidy pattern in the diagnosis of thyroid tumors.

To evaluate the supportive role of image cytometry and DNA ploidy pattern in the diagnosis of thyroid tumors, a preliminary study was performed on fine needle aspirates of 30 cases. Of these, 10 cases each were of colloid goiter, follicular neoplasm, and papillary carcinoma. The nuclear area and DNA value of 50 cells in each case were measured. The mean nuclear area in colloid goiter (69.50 + 12.62 sq.microns) was significantly lower than the mean nuclear area in a follicular neoplasm (88.71 + 15.51 sq.microns) (P less than 0.05). Similar differences between the mean nuclear area in colloid goiter and papillary carcinoma (124.0 + 12.27 sq microns) was also highly significant (P less than 0.001). The results obtained by image cytometry were compared with estimated DNA ploidy pattern of follicular cells from the same cases. All colloid goiter had mean nuclear area below 100 sq.microns with diploid DNA value. However, papillary carcinoma showed aneuploid DNA pattern in eight cases (80.0%), but mean nuclear area was above 100 sq.microns. A diagnostically useful finding obtained in two of the 10 cases of follicular neoplasm was the association of aneuploid DNA pattern with mean nuclear area of the follicular cells above 100 sq.microns indicating a high probability of carcinoma and thus demanding an urgent open biopsy. These cases were readily distinguished from other cases of the same category showing diploid DNA pattern and mean nuclear area of follicular cells below 100 sq.microns.

Cell Nucleus↗

A high frequency of human papillomavirus DNA sequences in cervical carcinomas of Indian women as revealed by Southern blot hybridization and polymerase chain reaction.

Ninety-six colposcopically directed biopsies from squamous epithelial carcinoma of the uterine cervix and 22 age-matched normal control biopsy specimens were examined by both Southern blot hybridization and polymerase chain reaction (PCR) for the presence of different human papillomavirus (HPV) DNA types. Cancer of the uterine cervix, which is the most common malignant disease in Indian women, showed a high frequency (98%) of HPV as compared to those reported from other parts of the world. HPV type 16 was found to be the dominant (64%) type while the frequency of HPV type 18 was very low (3%). On individual typing of HPV, no biopsy was found to contain any other known HPV types under stringent conditions of hybridization except a single case of HPV type 11. Only one case of double infection with HPV types 16 and 18 was recorded. Under low stringency conditions of hybridization with a mixed probe of HPV types 16 and 18, 29 additional biopsies were found to be positive. Southern blot hybridization alone detected HPV DNA in 92% of the cases but none in the controls. By PCR, six (6.25%) more cases and four (18.18%) healthy women were found to be positive for HPVs. Analysis of the physical state of HPV 16 indicated integration in about 70% of carcinoma cases while 30% of them were in episomal form. The findings suggest that infection with HPV is an important etiologic factor for the development of cervical cancer, that a number of such tumours may arise without HPV infection, and that integration of the viral DNA into host genome is not always essential for malignant progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions.

Integration of human papillomavirus (HPV) DNA into the host cell genome is believed to be essential for malignant progression. However unambiguous detection of the physical state of HPV is a difficult and time-consuming procedure. To resolve this issue a simple, rapid and highly sensitive technique of polymerase chain reaction (PCR) has been utilized for detecting the physical state of HPV-16 DNA. Investigations were carried out in 122 cervical specimens comprising the whole spectrum of cervical lesions starting from cervical dysplasia to invasive carcinoma including HPV-16-positive normal controls. A pair of oligonucleotide primers specific to the E2 open reading frame, which is often deleted or disrupted following HPV integration, was used for the study. Distinction between episomal and integrated forms of viral DNA was accomplished by detecting amplification of the E2-specific fragment (1139 bp) in the PCR product. The PCR results were compared with those obtained by the conventional methods of Southern blotting, two-dimensional gel electrophoresis and chromosomal in situ hybridization; a high degree of agreement was observed between the methods. The findings indicate that although integrated forms of HPV-16 DNA were detected in more than 70% of cervical cancer specimens, integration was less frequent (23%) in severe dysplasia and carcinoma in situ. Only 2.5% of cases showed both episomal and integrated forms of HPV-16 DNA. The difference between episomal and integrated forms was statistically significant (P less than 0.01). The absence of integration in about 30% of cancer cases suggests that integration of HPV may not be necessary for malignant progression and alternative mechanism(s) of malignant transformation may occur without HPV integration. The PCR test thus provides an effective complement to Southern blotting and two-dimensional gel electrophoresis for accurate detection of the integration of HPV DNA.

Base Sequence↗

Efficacy of a hospital based cytology screening program.

From 1976 to 1986, a total of 117,471 women attending gynecologic outpatient departments of six hospitals in Delhi, India, were screened cytologically. The cytodiagnosis revealed 30,399 (25.9%) normal finding, 84,889 (72.3%) inflammatory changes, 1910 (1.6%) dysplasia of various grades and 213 (0.2%) malignant lesions. Of the 213 cases detected as malignant, clinical suspicion of cervical cancer was not present in 125 women (58.7%). Histologically malignancy was confirmed in 192 women (90.1%) of the 213 cytologically diagnosed malignant cases. The diagnosis revealed 94 (49.0%) as carcinoma in situ and the rest of the cases were invasive lesions. This was in contrast to only 5.2% (10/194) of cases with carcinoma in situ seen at the cancer clinic during 1983-1986 in one of the major collaborating hospitals of Delhi. The analysis of data according to age revealed that median age at detection of mild/moderate, severe dysplasia, carcinoma in situ (CIS) and invasive cancers was 34.0, 37.9, 38.6, and 47.8 years, respectively, indicating a latency period of one and a half decade from the onset of precursor lesions to invasive disease. Mass population screening in our country is not feasible in the near future and this may be true also for other developing countries. In its absence cytological screening of patients attending hospitals and maternity homes can give a large yield of early cervical cancers, which are curable.

Adult↗

Screening for cervical cancer by direct inspection.

Since cytology-based screening programmes for cervical cancer cannot be provided on a large scale in developing countries, an alternative approach is needed. To find out whether visual inspection of the cervix is an adequate alternative, women with cytological evidence of dysplasia were followed up cytologically and colposcopically until cancer was detected, and the gross appearance of the cervix was recorded at each stage. Although only 40-50% of cancers were accompanied by abnormal-looking cervices, whereas 71% were detectable on cytology and 87% on colposcopy, visual inspection may be useful in areas where cytological screening programmes are not available.

Adult↗

Identification of human papillomaviruses in paraffin embedded cervical pathological tissues from Indian women by polymerase chain reaction.

The polymerase chain reaction (PCR) technology was used to identify human papillomaviruses (HPV) in 52 paraffin embedded cervical tissues from Indian women with chronic cervicitis, different grades of cervical dysplasia and invasive cervical carcinoma. The tissues were screened for amplification of the cellular beta-globin gene as well as of HPVs. Sets of primers designed to amplify a portion of the E6 gene of HPV 6, 11, 16, 18, 31, 33 and 35 were employed. HPV 6, 16 and 31 were identified in 58% of 33 beta-globin positive tissues as compared to 16% of 19 beta-globin negative tissues. HPV 11, 18, 33 and 35 were not identified in any of the specimens. Double infection of HPV 16 and 31 was observed in one case of carcinoma in situ and one case of invasive carcinoma. HPV-16 was the predominant virus in HPV positive cases of higher grades of cervical dysplasia (severe dysplasia and carcinoma in situ) and cervical cancer.

Carcinoma↗

Quantitative analysis of nuclear area variation in benign and malignant breast fine needle aspirates.

The measurement of nuclear area was carried out in 30 benign and 32 malignant breast lumps using Omnicon Alpha 500 Image Analyzer. The mean nuclear area of duct cells in malignant group was greater (157.6 +/- 58.64 sq.microns with a peak around 140 sq.microns) and more heterogenous within and amongst cases than observed in duct cells from most of the cases of fibroadenoma (85.05 ae 14.2 sq.microns with a peak around 80 sq.microns). Taking into consideration 110 sq.microns as a differentiating limit, a significant difference was observed between benign and malignant conditions (p). Similarly taking 118 sq.microns as differentiating limit duct cell carcinomas could be divided into two groups i.e. 9(28.1%) cases of small nuclear type with a range of 80-118 sq.microns and 23(71.9%) cases of large nuclear type with a range of 118-320 sq microns .6(18.8%) cases with small nuclei had an overlap with fibroadenoma. Although 13(72.2%) cases of large nuclear type carcinomas had lymph node metastasis as against 4(44.4%) in small nuclear group, the difference was not statistically significant.

Adenofibroma↗

Peripheral blood lymphocyte subpopulations in Indian women with cervical intraepithelial neoplasia and invasive cancer--an immunocytochemical study using monoclonal antibodies.

The peripheral blood lymphocyte subpopulations in Indian women with various grades of cervical intraepithelial neoplasia [33], invasive cancer [22] and matched controls [30] were studied using specific monoclonal antibodies and biotin avidin immunofluorescence technique. Our results showed a significant fall in peripheral T (CD2) B(CD22) cells in patients with CIN III and invasive cervical cancer lesions compared to controls (P less than 0.001). Similarly the quantum of T helper cells (CD4) decreased according to the severity of cervical lesions (P less than 0.01 - P less than 0.001), whereas the T suppressor cells (CD8) depicted an increasing trend in patients with higher grade of cervical lesions (CIN III and invasive cancer, P less than 0.001) as compared to controls. Further, the CD4/CD8 ratio showed a significant downfall with the severity of cervical lesions (P less than 0.01 - P less than 0.001), indicating a perturbance in the homeostasis of host cellular immunity.

Adult↗

Risk factors related to biological behaviour of precancerous lesions of the uterine cervix.

In a study of factors related to cervical carcinogenesis, a cohort of 1,107 cervical dysplasia along with 1,077 controls matched for age and parity were followed up prospectively. During the follow up 75 dysplasia cases progressed to carcinoma in situ. The overall rate of progression of dysplasia to malignancy was observed to be 15.7% at the end of 108 months of follow-up. The analysis of progression rates in relation to various factors revealed significantly higher progression rates for initially higher grade of dysplastic lesions, and early age at consummation of marriage (ACM). The other factors, such as religion, literacy status of the patient, number of pregnancies, presence of cervical erosion, history of fetal loss and positivity to HSV-II antibodies, did not reveal statistical significance. The case-control comparison for detection of HPV 16/18 by in situ hybridisation revealed the presence of HPV 16/18 sequences in 67.3% of the dysplasia subjects progressed to carcinoma in situ while 27.3% of precancerous cases regressed to normalcy. The difference was found to be statistically significant (P less than 0.001).

Adult↗

Microphotometric DNA analysis in moderate dysplasia of the uterine cervix. Correlation to the progression and regression of the lesion.

Nuclear DNA content was determined by microphotometry in 27 cases of moderate dysplasia of the uterine cervix. All these cases were followed from one to ten years to study the biological behavior of moderate dysplasia in relation to cervical carcinogenesis. Ten of them showed progression to carcinoma in situ during a period of one to six years (median 34.8 months) and 17 cases showed regression to inflammation and normalcy during a period of one to ten years (median 44.2 months). DNA analysis was performed both on initial cervical smear and on representative smears collected during follow-up. Amongst ten cases which progressed to malignancy, nine had aneuploid DNA pattern and one had polyploid DNA pattern throughout the follow-up period. Amongst 17 cases which regressed to inflammation, 11 had euploid and six polyploid DNA pattern. The observation that moderate dysplasia with aneuploid DNA value often develops into carcinoma in situ in contrast to dysplasia with euploid or polyploid DNA value strengthens the conception that DNA aneuploidy may be considered as 'high risk indicator' for cervical precancerous lesions.

Adult↗

Cancer projection by the turn of century-Indian science.

This is an attempt to understand the magnitude of cancer problem in India. The incidence data generated by the three population based cancer registries at Bangalore, Bombay and Madras and the population projections of country have been utilised for estimating the present and future load of new cancer cases. It is estimated that the total number of incident cases in males increased from 0.29 million to 0.43 million by the turn of the century as a result of change in size and composition of population and when adjusted for tobacco habits the estimates increased to 0.49 million. In females the incident cases of cancer for three registries increased from 0.32 to 0.42 million by 2001, with cancer of uterine cervix and breast being the major problems. The above results show an urgent need for strengthening and augmenting the existing diagnostic/treatment facilities which are vow fully inadequate to tackle even the present load.

Female↗

Risk for development of cancer in three urban areas of India.

The probability of developing cancer by using life table approach has been computed for the population of three metropolitan cities of India based on data of population based cancer registries located at Bangalore, Bombay and Madras. It was observed that the risk for development of malignancy of all sites from 20 to 64 years ranged from 4.73% to 5.28% in males, whereas it was 6.76% to 9.18% in females. The increased risk in females was mainly due to the high risk of development of cancer of the uterine cervix and breast. The available morbidity indices such as cumulative incidence rate and cumulative risk do not account for the mortality experiences of population. The present exercise will be useful in evaluating the changes in the disease spectrum as a result of change in the mortality experiences and population structure.

Adult↗

Microphotometric nuclear DNA analysis in cervical dysplasia of the uterine cervix: its relation to the progression to malignancy and regression to normalcy.

The present study was attempted to reveal the predictive value of DNA ploidy pattern of uterine cervical dysplasia cases in relation to cervical carcinogenesis. Microphotometric nuclear DNA analysis using Feulgen stain was carried out in 310 cervical smears of 80 dysplasia cases consisting of 53 cases which progressed to malignancy and 27 cases which regressed to inflammation or normalcy during their follow-up periods. Aneuploid DNA pattern was observed in initial as well as follow-up smears in 69.8% of cases of the progressive group, and in 7.4% of cases of the regressive group. This difference is statistically highly significant (chi 2 27.88, p less than 0.001). In the progressive group, an aneuploid DNA value was observed in 40.0% of mild dysplasia, 71.9% of moderate dysplasia and 90.9% of severe dysplasia. In the regressive group, DNA aneuploidy was observed in only 9.1% of moderate dysplasia. This difference is statistically significant. These findings indicate that an aneuploid DNA value is a risk indicator for malignant potential of dysplasia cases.

Adult↗

Detection of mutagenicity in cervico-vaginal secretions--a plausible risk factor for cervical cancer.

The cervico-vaginal secretions from 51 women with various grades of dysplastic lesions of uterine cervix were assessed for mutagenic potential by Ames test using histidine deficient mutant strain of Salmonella typhimurium TA-98: with S-9 mix. Twenty three per cent of samples from women with cervical dysplasia were found significantly positive (P less than 0.001) for mutagenic activity compared to 3% positive from control. The frequency of mutagenic secretions detected were almost uniform, irrespective of the severity of cervical lesions. None of cervico-vaginal secretions, positive for mutagenicity could revert the tester strain when tested in absence of S-9 mix (liver microsomal enzymes). This indicates that mutagens in cervico-vaginal secretions are effective only when activated enzymatically.

Animals↗

Microphotometric DNA analysis in mild and moderate dysplasia of the uterine cervix: a retrospective study.

Twenty six cases of mild and moderate dysplasia of uterine cervix were retrospectively subjected to microphotometric study for nuclear DNA estimation in order to correlate their ploidy pattern with biological behaviour at initial presentation and during follow up intervals ranging from six months to six years (median-30.8 months). Of these, fourteen cases had progressed to malignancy, five persisted as dysplasia and seven had regressed to normalcy or inflammation. DNA value of these cases revealed aneuploidy in ten cases whereas polyploid and euploid DNA pattern were observed in eight cases each. Of the ten aneuploid cases eight (80.0 per cent) progressed to malignancy while two persisted as dysplasia. Of the sixteen polyploid and euploid cases, only six (37.8%) progressed to malignancy. However, five of these six cases developed aneuploidy during follow up or at the point of progression to malignancy. The findings indicate that aneuploidy in mild and moderate dysplasia cases is a reliable "high risk indicator".

Adult↗