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Biomedical subjects

B Mathew

Publications and source records attributed to B Mathew.

At least 37 records · Page 2Linked to original sources
PubMed1999

Synthesis of heptadentate (N4O3) amine-phenol ligands and radiochemical studies with technetium-99m.

Heptadentate amine-phenol ligands with N4O3 donor atoms for coordination were synthesized by condensing tris(2-aminoethyl)amine with salicylaldehyde or acetophenone and reducing the Schiff bases formed with NaBH4. The ligands were characterized by 1H and 13C nuclear magnetic resonance spectroscopy. Radiochemical studies were carried out with no-carrier-added 99mTc and 99mTc spiked with 0.1-100 microM of 99Tc. Complexation yields were estimated from thin layer chromatography, paper electrophoresis, and solvent extraction studies. 99mTc complexes were formed in yields better than 90% with the amine-phenol ligands. The complexes were found to be neutral and lipophilic. Biodistribution studies of the 99mTc complexes showed that clearance was mainly through the hepatobiliary system.

Animals↗
PubMed1999

Third ventriculostomy in normal pressure hydrocephalus.

Improvement in three out of four cases of normal pressure hydrocephalus after third ventriculostomy is reported. Pre- and postoperative ventricular pressure recording suggested that this improvement may be occurring in the absence of an improvement in ventricular pressures. Third ventriculostomy may relieve periventricular tissue stress and thus improve local blood flow, which is a likely mechanism in the syndrome of normal pressure hydrocephalus.

Aged↗
PubMed1999

Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers.

Oral cancer is the most common cancer in males and third most common in females in India, the main causative agent being the use of chewing tobacco with or without betel quid (BQ). However, nothing is known about the role of the host metabolic genes in oral cancer in ethnic Indian population. In this study, the prevalence of GSTM1 and GSTT1 null genotypes (GSTM1*2 and GSTT1*2) in oral premalignant leukoplakia cases and controls was ascertained in genomic DNA by a multiplex PCR technique. Biopsies taken from 98 oral leukoplakia patients and exfoliated cells from 82 healthy controls both of Indian ethnicity were analysed. GSTM1*1 (active) was present in 83% and GSTT1*1 (active) was present in 78% of all control subjects, while prevalence of GSTM1*2 and GSTT1*2 null genotypes was significantly higher among oral leukoplakia cases. The prevalence of GSTM1*2 in leukoplakia cases was 81.6% compared with 17% in controls [odds ratio (OR), 22; 95% confidence interval (CI), 1047] and GSTT1*2 was 75.5% in the cases versus 22% in controls (OR, 11; 95% CI, 5-22). Combined null genotypes of GSTM1 and GSTT1 prevailed in 60.2% of the cases with none detected in controls. Glutathione S-transferase M1 and T1 enzymes are both known to catalyse detoxification of reactive oxygen species, lipid peroxidation products and tobacco-derived carcinogens that have been found in the saliva of BQ/tobacco chewers. Our results, still requiring confirmation by a larger study, demonstrate that the null genotypes of both GSTM1 and GSTT1 increase with high penetrance, separately or in combination, the risk for developing leukoplakia in an Indian ethnic population.

Adult↗
PubMed1998

Giardiasis in the adult population of Dakshina Kannada district of south India.

A 10-year study of Giardia intestinalis infections in adults was conducted in the Dakshina Kannada District of Karnataka State, South India. Coproparasitological investigations were made on 10,000 stool specimens collected from selected patients. The infection rate was 37.1% with a male disease rate of 91.4%. The highest incidence rate was recorded in the age group 15-26 years. A possible reason for this preponderance of giardiasis in these males, is discussed. The optimum time for transmission appeared to be during the warmer months of the year (May to October) which coincided with the greatest amount of rainfall. The most common symptoms were abdominal discomfort, flatulence, diarrhoea, weight loss and anorexia. The predominating symptoms in our series varied with socio-economic level. There appeared to be some correlation between the clinical manifestations and the immune status of the individual.

Adolescent↗
PubMed1997

Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment.

We conducted a double-blind placebo-controlled trial to evaluate the chemopreventive potential of either vitamin A alone or beta carotene alone in subjects with oral leukoplakia in Kerala, India. We randomised 160 fishermen and women with oral precancerous lesions to receive oral vitamin A (retinyl acetate 300,000 IU/week x 12 months, n = 50), or beta carotene (360 mg/week x 12 months, n = 55), or placebo (n = 55). Blood, saliva and urine samples were collected at baseline and at exit to study serum micronutrients and mutagenicity assays. Biopsies of the mucosal lesions at entry were performed for histopathological exclusion of malignancy. The subjects were examined once every 2 months to establish clinical response of lesions and toxicity, if any. The results are based on 43 complaint subjects on placebo, 42 on vitamin A and 46 on beta carotene. The complete regression rates were: 10% in the placebo arm, 52% with vitamin A and 33% with beta carotene (P < 0.0001). Homogeneous leukoplakias and smaller lesions responded better than non-homogeneous and larger lesions. No major toxicities were observed. Half of the responders with beta carotene and two thirds with vitamin A relapsed after stopping supplementation. Serum beta carotene concentration increased substantially with beta carotene administration while with vitamin A supplementation there was no change in serum retinol levels. In the vitamin A treated group there was a significant decrease in serum alpha tocopherol. Vitamin A administration resulted in a significant remission of oral leukoplakia without any side effects of prolonged vitamin A supplementation. The results of this study, as well as those from previous studies, appear to provide strong supporting evidence to justify long term trials with vitamin A in subjects with high-risk leukoplakias with oral cancer as an endpoint.

Adult↗
PubMed1997

Reproducibility and validity of oral visual inspection by trained health workers in the detection of oral precancer and cancer.

A randomized intervention trial is in progress in Kerala, India, to evaluate the effectiveness of oral visual inspection by trained health workers (HWs) in the prevention of oral cancer. Fourteen health workers with college graduation as the basic qualification were trained in oral visual inspection to identify oral cancers and precancers among the participants of the screening trial and to refer them for further confirmation and management. The aim of the present study was to evaluate the reproducibility and validity of the screening test provided by the health worker against the reference oral visual findings of three physicians. A total of 2069 subjects who had already been examined were re-examined by the health workers and physicians. The sensitivity and the specificity of the oral visual inspection were 94.3% and 99.3% respectively. There was moderate agreement between the findings of the initial and the repeat mouth examinations carried out by the health workers, which were on average 6 months apart. There was almost perfect agreement (kappa = 0.85) between the findings of the health workers and the physicians in identifying the different types of oral precancerous lesions. The findings of our study indicate that it is possible to train resource persons to perform the oral cancer screening test as accurately as doctors, although experience appears to be a crucial component of health workers' accuracy. The efficacy of such an approach to reduce the incidence of and mortality from oral cancer, however, remains to be proven.

Education↗
PubMed1997

Evaluation of visual inspection as a screening test for cervical cancer.

Visual inspection of the uterine cervix by paramedical personnel has been proposed for the early detection of cervical cancer, as an alternative to routine cytology screening in developing countries. We evaluated the performance of this procedure in detecting precursor lesions and cancer in a study involving 2843 married women in Kerala, India. Two thresholds were used to define a positive test. In the lower one, any abnormality was considered as positive. The cut-off point for the high threshold was one or more of the high-risk findings: bleeding on touch, suspicious growth/ulcer and hard, irregular, oedematous cervix. A Pap smear was performed on all subjects, and a biopsy was done for those with moderate dysplasia and above. A combination of cytology and histology findings was used as the 'gold standard'. Using the low threshold, 1279 (45%) women were positive on visual inspection, and with the higher threshold 179 (6.3%) were positive. There were six moderate dysplasias, nine severe dysplasias, ten carcinomas in situ and 13 invasive carcinomas. With the lower threshold, sensitivity and specificity to detect moderate dysplasia and above were 65.8% and 55.3% respectively; the values for severe dysplasia and above were 71.9% and 55.3% respectively and for invasive cancer were 92.3% and 55.2% respectively. With the higher threshold, the sensitivity decreased considerably (28.9% to detect moderate dysplasia lesions, 31.3% for severe dysplasia and 53.8% for clinical cancer) and the specificity increased to approximately 94%. At a lower threshold, the sensitivity was not satisfactory, and the test was highly non-specific; at a higher threshold sensitivity was even lower. Thus, the test characteristics of visual inspection are not very promising either as a preselection procedure for cytology or as a low-technology measure for cervical cancer screening in developing countries.

Adult↗
PubMed1997

Telomerase activity in premalignant and malignant lesions of human oral mucosa.

Recent studies have demonstrated a strong association between carcinogenesis and re-activation of telomerase in various human tumors. In the present study, we have analyzed the telomerase activity in 105 oral mucosal samples, including normal mucosa and premalignant and malignant lesions, by using the telomeric repeat amplification protocol assay. The telomerase activity was detected in normal oral squamous epithelium and in 75% of the oral leukoplakias and oral carcinomas. Although the telomerase activity was observed in normal and hyperplastic squamous epithelium, it showed some relationship with certain clinico-pathological factors in malignant lesions. Telomerase activity was found to have a relationship with the grade of tumor differentiation. Of 34 well-differentiated squamous cell carcinomas, only 10 (30%) exhibited high telomerase activity, whereas in moderately or poorly differentiated squamous cell carcinomas, all seven (100%) tumors displayed high activity. In addition, the level of telomerase activity had an inverse correlation with the treatment response in the early-stage tumors, and the activity differed significantly between the tumors in the following intraoral sites: nonkeratinizing mucosa (buccal mucosa, alveolus, and floor of mouth) and tongue. This preliminary result shows that telomerase activity is present in normal oral squamous epithelium, as it is in normal hematopoietic cells and in carcinomas, and that telomerase activity has a relationship with degree of tumor differentiation and treatment response. Thus, assessing the telomerase activity may be a useful prognostic marker in oral squamous cell carcinomas.

Biomarkers, Tumor↗
PubMed1997

Serum levels of copper, zinc, iron and ceruplasmin in oral leukoplakia and squamous cell carcinoma.

Trace elements have been extensively studied in recent years to assess whether they have any modifying effects in the etiology of cancer. In the present study serum levels of copper, zinc, ceruloplasmin, total iron and total protein were estimated in 92 patients with oral leukoplakia and squamous cell carcinoma and 45 age and sex matched controls. Copper was significantly increased in oral leukoplakia and cancer in both sexes. The level of zinc decreased significantly only in male patients with leukoplakia and cancer. Copper zinc ratio was found significantly elevated in oral leukoplakia and cancer. A marked increase in serum ceruloplasmin was seen in oral leukoplakia and cancer in both sexes. A significant decrease of serum total iron and proteins were observed only in carcinomas. These findings suggest that reduction in the serum total iron and total protein may be due to malnutrition caused, on its turn, by tumour burden. Serum ceruloplasmin level and copper-zinc ratio demonstrated significant differences in the patients of both sexes from those of controls, while, comparing leukoplakia with cancer, a significant difference is only observed in male patients. Thus, the present study shows that these factors have diagnostic value only in differentiating malignancies from normal and a little value as biomarkers of disease progression. However, the exact mechanism responsible for the alteration of these factors in oral lesions is still not clear and a detailed study on large sample size is therefore needed.

Adult↗
PubMed1996

Lectin histochemistry of oral premalignant and malignant lesions: correlation of JFL and PNA binding pattern with tumour progression.

The expression of glycoconjugates specific to Jack fruit lectin (JFL) and peanut agglutinin (PNA) in various clinicopathological stages of tumour progression in the oral mucosa were studied. These included various clinical forms of dysplastic and non-dysplastic oral leucoplakias, carcinomas, normal keratinising (gingiva) and non-keratinising (buccal mucosa) epithelia. It was seen that the binding patterns of PNA and JFL in the epithelial cells of various types of oral lesions were more or less similar. Normal non-keratinising epithelium showed mild membrane staining only in the spinal layers, while normal keratinising epithelium showed a moderate membrane staining and mild cytoplasmic staining in all layers. Moderate membrane and mild cytoplasmic staining were observed in leucoplakias, irrespective of various clinical or histological types. In carcinomas, the intensity of lectin binding was high, particularly in the membrane of differentiated cells. Correlation analysis of the binding pattern of PNA and JFL showed significant correlation in the membrane and cytoplasm of all layers with histological stages of tumour progression. The present study thus showed that PNA and JFL may be used as cytochemical probes in differentiating malignancy from benign lesions of the oral mucosa.

Carcinoma, Squamous Cell↗
PubMed1996

Cytokine expression in human anterior pituitary adenomas.

OBJECTIVE: There is increasing evidence for the role of cytokines in pituitary differentiated function and tumorigenesis, but the spectrum of cytokines found in the pituitary is unknown. Therefore profiles of cytokine expression were determined in different human anterior pituitary adenoma sub-types. DESIGN: The reverse transcriptase-linked polymerase chain reaction (PCR) was used to identify the presence of cytokine mRNA within human pituitary adenomas. PATIENTS: Seventeen pituitary adenoma biopsies removed at transsphenoidal surgery were examined: 4 somatotrophinomas, 7 non-functional adenomas, 4 prolactinomas, one case of Cushing's disease and one case of Nelson's syndrome. MEASUREMENTS: RNA was extracted from each adenoma biopsy and reverse transcribed into cDNA. This was specifically amplified in a PCR using oligonucleotide primers complementary to each cytokine. The cytokines investigated were interleukin (IL)-I alpha, IL-I beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, tumour necrosis factor (TNF)-alpha, TNF-beta and transforming growth factor (TGF)-beta 1, beta 2 and beta 3. The products of each PCR were visualized using agarose gel electrophoresis. RESULTS: All 17 adenomas expressed IL-8 transcripts, but no expression of IL-2, IL-5 or IL-7 was found. IL-6 was expressed in all 4 somatotrophinomas, 3 of 7 non-functional tumours, 2 of 4 prolactinomas and in the single case of Nelson's syndrome. At least one of the 3 isoforms of TGF-beta was found in all but 2 tumours; one prolactinoma and one non-functional adenoma. IL-1 alpha, IL-beta, IL-4, TNF-alpha and TNF-beta were expressed sporadically by individual adenomas. CONCLUSION: These data suggest that whilst IL-8 may be important, the local expression of the cytokines IL-2, IL-5 and IL-7 is not important in human anterior pituitary tumorigenesis.

Adenoma↗
PubMed1996

Expression of p53 in leukoplakia and squamous cell carcinoma of the oral mucosa: correlation with expression of Ki67.

Aim-To study p53 expression in relation to proliferative status in normal and nondysplastic, dysplastic and malignant lesions of the oral mucosa.Method-The standard avidin-biotin complex (ABC) immunohistochemical staining method was used to study the expression of p53 and Ki67 on frozen sections of oral leukoplakias and carcinomas.Results-Of the leukoplakia and carcinoma samples, 70% expressed p53 in over 5% of cells. In normal mucosa less than 5% of cells expressed p53. The proliferation index, as assessed by expression of Ki67, was highest in the malignant lesions (43%) and lowest in normal mucosa (11%). Statistical analysis revealed that expression of both p53 and Ki67 was correlated significantly with the histopathological stage of the tumour. However, expression of p53 was not correlated with that of Ki67. In leukoplakia lesions with proliferative features p53 immunostaining was less intense than in non-proliferative lesions; this difference was statistically significant.Conclusions-These results emphasise the potential of Ki67 and p53 as biomarkers of carcinogenesis in oral cancer and may also serve as intermediate points for cancer prevention programmes, such as the oral chemopreventive trials. Factors other than p53 may have a more important role in the deregulation of proliferation in pre-malignant oral lesions.

Journal Article↗
PubMed1996

Hyponatraemia secondary to cerebral salt wasting syndrome following routine pituitary surgery.

A female aged 53 years was found to have a suprasellar lesion, which was shown to be a Rathke's cyst after removal by transsphenoidal surgery. She presented 16 days postoperatively, and following two grand mal seizures was found to be profoundly hyponatraemic (sodium 101 nmol/l). She was initially thought to have the syndrome of inappropriate antidiuretic hormone and was treated accordingly, but central venous pressure measurement revealed the hypovolaemia of cerebral salt wasting syndrome. The patient subsequently developed severe neurological sequelae after the correction of her hyponatraemia, following the development of extrapontine myelinolysis. Cerebral salt wasting syndrome is a rare cause of hyponatraemia following pituitary transsphenoidal surgery, which may mimic the syndrome of inappropriate antidiuretic hormone secretion. This case emphasizes the poor prognosis that may result from the rapid correction of profound hyponatraemia.

Brain↗
PubMed1996

Retinoids as cancer-preventive agents.

Vitamin A and its metabolites play a crucial role in regulating the differentiation and proliferation of epithelial cells, and are potent inducers of apoptosis. The effects of retinoids are thought to be mediated through the metabolite retinoic acid, which binds to nuclear retinoic acid receptors that then interact with specific retinoic acid response elements. The development of cancers involves alterations in growth and differentiation of cells as a result of carcinogen-induced damage to DNA of regulatory genes. Most of the results from experimental animal studies indicate that retinoids are effective in preventing or suppressing cancers. Although the relationship between preformed vitamin A in the diet and epithelial cancers remains to be further clarified, a high intake of vegetables and fruits has been consistently associated with a lower risk of these cancers. This interesting biological activity profile of retinoids has prompted investigators to study them in the chemoprevention of epithelial cancers and in the treatment of advanced cancers. Although the therapeutic response of retinoids against advanced cancers is disappointing, they have emerged as promising chemopreventive agents, particularly in head and neck sites. Both natural and synthetic analogues of vitamin A have been shown to be effective in suppressing micronucleated cells, reversing oral leukoplakia, and preventing new and recurrent lesions in subjects with oral leukoplakia, as well as in reducing the occurrence of second primaries in treated head and neck cancer patients. They have not been consistently effective in suppressing either bronchial atypia or metaplasia, nor have they been proven effective in reducing the occurrence of recurrent lesions in treated skin cancer patients, although some activity has been demonstrated in reducing lesion counts in actinic keratoses. Vitamin A in combination with other micronutrients has not reduced incidence and mortality from oesophageal and stomach cancers. A synthetic retinoid, fenretinide, is currently being evaluated in preventing contralateral breast cancer in treated breast cancer patients. Toxicity has been a major concern with retinoids, as prolonged administration is required in chemoprevention studies. Available evidence indicates that natural analogues of retinoids are less toxic than synthetic compounds such as isotretinoin. Large studies are currently evaluating retinoids in the prevention of head and neck cancers and lung cancers. The outcome of these studies will be important in directing future research initiatives and in forming policies regarding the use of vitamin A compounds in the prevention of cancers.

Anticarcinogenic Agents↗
PubMed1996

Cancer screening by local volunteers.

In a tribal village in Kerala, India, local volunteers were trained to work in a programme for the primary prevention of tobacco-related cancers and the secondary prevention of common cancers. They gathered data on the use of tobacco and alcohol in a population of some 19,000 people, and identified one or more warning signals of cancer in 430 persons, who were subsequently examined by physicians. Confirmation was obtained of 10 new cancers, 7 recurrent cancers, 46 oral precancerous conditions, and 58 precancers at other sites. The community's awareness of cancer problems increased and the people learnt about the importance of self-examination in the detection of breast cancer and oral cancer.

Adult↗
PubMed1995

Evaluation of utilisation of health workers for secondary prevention of oral cancer in Kerala, India.

The utilisation of primary health workers (HWs) for cancer control in developing countries has often been suggested, based on the experience of feasibility studies in India and Sri Lanka. We initiated a project in 1988 to evaluate the long-term feasibility of using trained HWs in secondary prevention of oral cancer, to bring about earlier detection of oral cancer in the communities served by them. Two hundred and eighty-two HWs attached to 14 primary health centres (PHCs), serving approximately 0.92 million rural population in the northern half of Trivandrum district in Kerala, India, were trained in oral visual inspection to detect precancerous, malignant and other suspicious lesions of the oral cavity and refer them for confirmation and treatment. They were asked to examine subjects aged 35 years and above and to give person to person health education on tobacco in their target population. The HWs belonging to the PHCs serving approximately 1 million rural population in the southern half of Trivandrum district were not trained, and this region served as the control area. In addition to several process measures, stage distribution of oral cancer in subjects reporting from the intervention and control areas, as well as oral cancers referred by the HWs, as a proportion of total oral cancers from the intervention area, were the outcome measures evaluated. Only 9/282 (3.2%) trained HWs were motivated and they examined 17,812 eligible subjects in 3 years and referred 408 subjects with lesions; 258/408 (63.2%) referred subjects reported for further examination and ten oral cancers were detected among them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗