Mutagenic cervical mucus in women with cervical intraepithelial neoplasia.
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Biomedical subjects
Publications and source records attributed to M M Gupta.
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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).
Three rapid urease tests, i.e., liquid urea broth containing phenol red as indicator, liquid urea broth containing bromothymol blue as indicator and CLO gel were compared in 109 patients of dyspepsia for the diagnosis of Campylobacter pylori (Helicobacter pylori) infection. Mean time taken for positive reaction in liquid broth with phenol was 3 minutes (range 0.6 to 5.3 minutes) with bromothymol blue was 3.5 minutes (range 0.4 to 5.5 minutes) while with CLO gel it was 101 minutes (range 11-261 minutes). There was no difference in results of liquid urea broth containing phenol red and bromothymol blue. The difference in timing of urea broth containing phenol red and bromothymol blue was statistically significant as compared to CLO gel (p less than 0.05). Rapid urease tests employing liquid urea broth are quick, simple and reliable for the diagnosis of Helicobacer pylori infection.
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.
Three-hundred-eighty-four leprosy patients were clinically examined for sexually transmitted diseases (STD) in north and northeastern India, revealing a high incidence (5.2%) of STD among them. Eighteen males, one female, and one eunuch were found to have chancroid ulcer, gonococcal urethritis, lymphogranuloma inguinale, and primary chancre. Of these patients, only 100, selected randomly, could be screened serologically for STD due to Treponema pallidum, herpes simplex (type 1 and 2), Entamoeba histolytica, hepatitis-associated virus, cytomegalovirus, Chlamydia trachomatis and human immunodeficiency virus (HIV); 100 control sera were included for comparison. In addition, sera from another 133 normal subjects and another 176 lepromatous patients were also screened for HIV antibody. Thus, a total of 233 normal sera and 276 leprosy sera were tested for HIV antibody. Although our leprosy patients have shown significantly high incidences of clinical STD and also high seropositivity against T. pallidum, herpes-simplex viruses types 1 and 2, hepatitis-associated virus, and cytomegalovirus, the search for antibody against HIV was negative. Our clinical and serological data suggest promiscuity in our patient population. The absence of HIV antibody in this high-risk population, however, seems to be an enigma.
11 cases of primary hyperparathyroidism were seen during 1975-1988. Follow up has varied from 1-10 years. Renal disease in the form of renal calculi and nephro-calcinosis was observed in nine cases (81.8%). Two presented in chronic renal failure and required dialysis. Bone disease was found radiologically in six patients (54.5%); two had bone cysts in multiple bones while all six had subperiosteal bone erosion. Hypertension was found in three patients (27.3%). Proximal myopathy was observed in two cases (18.1%). One patient each presented with hypercalcaemic crisis, chondrocalcinosis and acute pancreatitis. The calcification of blood vessels and cornea was seen in two cases.
The incidence of adult leukaemias, their response to therapy and the complications of therapy were studied in 121 cases over seven years (1981-1987). All cases were followed up till recovery or death for periods ranging from seven days to seven years. Adult leukaemias accounted for 2.56% of all admissions due to malignancies. There were 21 cases of acute lymphoblastic leukaemia, 61 of acute myelogenous leukaemia, 36 of chronic myelocytic leukaemia and 3 chronic lymphocytic leukaemia. All received aggressive combination chemotherapy. Remission could be achieved in 57% to 60% of cases. Infection (34%), bleeding (34%), and central nervous system involvement (25%) were the complications during therapy. The cause of death was ascertained in 87 of 90 deaths by a detailed postmortem. Haemorrhage (34.5%), infection (31%) and uncontrolled leukaemia (22%) were the leading causes, either singly or in combination. Some of the uncommon causes of death were fulminant hepatic failure, coronary artery disease, gangrene of the colon and disseminated tuberculosis.
Twenty five cases with systemic lupus erythematosus admitted to a referral service hospital over a period of 6 years have been studied to analyse the pattern of multisystem involvement. Febrile polyarthritis, renal involvement and skin changes dominated the clinical picture. Important serological abnormalities included the presence of antinuclear antibody and anti ds DNA. Renal biopsy carried out in all cases helped to reveal lupus nephritis in subclinical cases. The pattern of renal involvement varied, with diffuse proliferative glomerulonephritis being the commonest. Oral steroids was given to all cases and cyclophosphamide was given to severe and resistant cases. The severity of system involvement, especially renal, influenced the response to treatment. Changes in presentation between Indian and Western patients are highlighted.
Medical emergencies due to severe hypercalcaemia and hypocalcaemia are relatively rare in clinical practice. 89 cases of hypercalcaemia were seen during 1975-1987 and 16 presented as medical emergencies; renal colic (7) acute renal failure (3), spontaneous fractures (3), acute pancreatitis (1), cardiac arrhythmia (1) and acute hypercalcaemic crisis resulting in death (1). 81 cases of severe hypocalcaemia were seen during the same period. 22 presented initially as epileptic seizures with one ending fatally due to status epilepticus. The other emergencies were severe laryngeal stridor and inability to speak (7), papilloedema (3) and acute behavioural disorder (4). A few illustrative cases have been briefly described.
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Cancer of the uterine cervix is the most common malignancy among Indian women. Evidence has shown that cervical cancer is preceded by dysplastic, or precancerous, lesions. HSV-II has been associated with this process of cervical carcinogenesis. We collected 167 cervical smears that had been diagnosed as normal, dysplastic, or carcinoma-in-situ and found a significantly high positivity of HSV-II antigen in women with cervical dysplasia (38.8%) and carcinoma-in-situ (33.3%) versus women with normal cytology (17.02%). Latent HSV-II infection of cervical epithelium may be considered of prognostic value to identify a population at high risk for cervical cancer.
Genital warts are a fairly common sexually transmitted disease and often affect young, illiterate subjects of poor socioeconomic status in India. The mean incubation period was 2.4 months, and the duration varied from 10 days to 4 years. Hyperplastic sessile, verruca vulgaris-like, and flat variants of warts were seen in that sequence, with distinct clinical features. The epidermal and the dermal changes were largely identical; however, the flat type in the epidermal changes were inconspicuous. Koilocytosis was a pathognomonic feature in 28, whereas human papilloma virus (HPV) antigens were detected through peroxidase-antiperoxidase technique in 18 patients.
Paraffin sections of 50 cervical condyloma biopsies from patients with precancerous and early cancerous lesions of the uterine cervix were screened for human papillomavirus (HPV) antigen by peroxidase-antiperoxidase (PAP) staining using genus specific anti-bovine papillomavirus serum (rabbit). The intra-nuclear HPV positivity was observed in 20 percent (10/50) of biopsies studied. Further, proportionately larger number of cases with moderate dysplasia (CIN II) associated with koilocytotic changes were found to be positive for HPV antigen (40%). No HPV positivity was detected from inflammation and mild dysplasia (CIN I) cases. The study strongly supports the association of HPV infection in the process of neoplastic transformation of the uterine cervix.
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Tannic acid is converted to four metabolites on incubation with isolated rat liver microsomes. Bis-(3,4,5-trihydroxyphenyl)methanone (I); 3,4,6,7,9,10-hexahydroxy-2,11-epoxy-1,12-(epoxy-methano)-14H , 16H-benzo[b](1,4)benzodioxepino [3,2-g](1,4)benzodioxepin-14,16,17-trione (II) and 1,1,2-trimethyl-1-ethanyl-2-ylidene tris(3,4,5-trihydroxybenzoate) (III) were isolated from the post-microsomal supernatant of the incubate while 6,12,18,26,27,29,31,33-octahydroxy-22,22-dimethyl-2,8,14,20-tet raoxapentacyclo (22.2.2.2(4,7).2(10,13).2(16,19) tetratriaconta-4,6,10,12,16,18,24,26,27,29,31,33-dodecene-3, 9,15,21,23-pentone (IV) was found attached with the microsomal fraction. Metabolite (III) was found to be a potential carcinogen on the basis of microsomal degranulation technique.
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