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Biomedical subjects

R Tiwari

Publications and source records attributed to R Tiwari.

At least 37 records · Page 2Linked to original sources
PubMed1998

DNA repair and mutagen sensitivity in patients with triple primary cancers.

The purpose of this study was to measure DNA repair capacity and mutagen sensitivity in patients who have had three or more primary forms of cancer. It was hypothesized that, if abnormalities in DNA repair and mutagen sensitivity were cancer susceptibility factors, such findings would be seen with regularity in individuals with multiple primary cancers. DNA repair capacity was measured by determining repair of UV-irradiated plasmid DNA (pCMVCAT) transfected into peripheral blood lymphocytes. Results from 18 patients and a like number of age- and sex-matched controls demonstrated a significant difference in DNA repair capacity (P < 0.0001; odds ratio = 14). Mutagen sensitivity was measured by determining the mean number of chromatid breaks per cell after in vitro exposure to either bleomycin or 4-nitroquinoline-1-oxide. The difference in mean bleomycin- or 4-nitroquinoline-1-oxide-induced mutagen sensitivity between cases and controls was not statistically significant. Fourteen of the 18 patients had positive family histories of cancer; in 10, the history was compatible with cancer susceptibility syndromes. Although the numbers were small, there was no suggestion in this study that treatment or the presence of cancer was the cause of the DNA repair abnormalities encountered. These findings support the concept of diminished DNA repair capacity as an underlying feature in the development of a mutator phenotype.

4-Nitroquinoline-1-oxide↗
PubMed1997

Role of the estrogen receptor in the action of organochlorine pesticides on estrogen metabolism in human breast cancer cell lines.

As interest in the properties of xenoestrogenic compounds has grown, different in vitro cell culture systems have been proposed as models, against which to gauge relative estrogenic impact. Previous research indicated that some organochlorine-based pesticides elevated the production of 16 alpha-hydroxyestrone relative to 2-hydroxyestrone in ER+ MCF-7 breast cancer cells while phytochemicals like indole-3-carbinol reduced this ratio. That this ratio may be a biological marker of the risk of breast cancer has recently been demonstrated. In this study we have carried out the same paradigm in two ER- cell lines to examine the effect of receptor status. To determine whether the impact of chlorinated pesticides can be modulated by phytochemicals, the ability of indole-3-carbinol or brassinin to reverse the changes in metabolism was examined. Non-persisting phosphorus-based pesticides were also studied and shown not to have an effect on estrogen metabolism. The implications of these findings are examined.

Anticarcinogenic Agents↗
PubMed1997

Self medication--a growing concern.

31% persons practiced self medication. They were more in 31-40 years (26.9%) and 41-50 years (30.8%). Males were more than females in self prescribers. Illiterate (23.1%) and graduates (26%) were more common self medicators, while labourers (26%) and business men (19.3%) were more involved in self medication. Fever (17.4%), cough (22.2%), boils (7.6%) and acidity (6.8%) were the common complaints for self-prescription. Thus analgesics and antipyretics, (30.9%), tonics (16.1) and antibiotics (10.7%) were commonly used drugs by the customers. Most of the information of drugs was from friends or neighbours (30.8%) or chemist (23.1%).

Adolescent↗
PubMed1995

Effects of pesticides on the ratio of 16 alpha/2-hydroxyestrone: a biologic marker of breast cancer risk.

Xenobiotic estrogens are external compounds with estrogenic activity that may thereby affect the risk of breast cancer. This paper describes a mechanism by which xeno-estrogens may affect the development of breast cancer. Estradiol metabolism proceeds by hydroxylation at one of two mutually exclusive sites at C-2 and C-16 alpha. The catechol pathway yields the weakly estrogenic 2-hydroxyestrone (2-OHE1), which inhibits breast cell proliferation. In contrast, the alternative pathway yields the genotoxic 16 alpha-hydroxyestrone (16 alpha-OHE1), which enhances breast cell growth, increases unscheduled DNA synthesis, and oncogene and virus expression, and increases anchorage-independent growth. Using a radiometric assay that measures the relative formation of 16 alpha-OHE1 versus 2-OHE1 from specifically tritiated estradiol in (ER+) MCF-7 cells, we compared the ratio of 16 alpha-OHE1/2-OHE1 observed after treatment with the known rodent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) with the ratios after treatment with DDT, atrazine, gamma-benzene hexachloride, kepone, coplanar PCBs, endosulfans I and II, linoleic and eicosapentenoic acids, and indole-3-carbinol (I3C). These pesticides significantly increase the ratio of 16 alpha-OHE1/2-OHE1 metabolites to values comparable to or greater than those observed after DMBA. In contrast, the antitumor agent I3C increased 2-OHE1 formation and yielded ratios that are 1/3 of those found in unexposed control cells and 1/10th of those found in DMBA-treated cells. Thus the ratio of 16 alpha-OHE1/2-OHE1 may provide a marker for the risk of breast cancer. Assays of this ratio, which can be measured in spot urines, may prove useful for a variety of in vitro and in vivo studies bearing on breast cancer risk.

Biomarkers↗
PubMed1994

Recurrence at the primary site in head and neck cancer and the significance of neck lymph node metastases as a prognostic factor.

BACKGROUND: Biologic aggressiveness of head and neck carcinoma is reflected in its capability to metastasize to regional lymph nodes and its propensity to recur after treatment. METHODS: The authors report on 244 patients treated at the Department of Otolaryngology-Head and Neck Surgery of the Free University Hospital, Amsterdam, The Netherlands, with excision of primary tumor with incontinuity neck dissection with or without postoperative radiation therapy between January 1973 and July 1986. All patients had surgical margins free of tumor. RESULTS: The overall recurrence rate was 12.3%. Stages T3-4 and the presence of more than three positive nodes on histopathologic examination were associated with a 16.2% and 26.2% incidence in recurrence at the primary site, respectively. No prognostic influence arose from primary tumor localization, three or fewer positive nodes, extranodal spread, and postoperative radiation therapy. CONCLUSIONS: Patients with T3-4 disease and those with more than three positive lymph nodes may benefit from novel adjuvant treatment modalities.

Adult↗
PubMed1994

Reconstruction of the mandible with conventional bone graft: an evaluation.

Eighteen patients with bony defects of the mandible had the mandible reconstructed using conventional nonvascularized bone grafts from the iliac crest. After surgery they received radiotherapy for cancer in the oropharynx or oral cavity. This study was carried out over a 10-year period. All patients were followed-up both for their tumour growth and the results of their reconstruction. Four to 10 years after surgery 55.5 per cent were alive and well. Full dental rehabilitation was achieved in 33 percent and 12.5 percent were without dental rehabilitation.

Adult↗
PubMed1994

Carcinoma of the soft palate and anterior tonsillar pillar.

The results after treatment of a total of 52 patients between 1974 and 1990 for squamous cell carcinoma of the soft palate and anterior tonsillar pillar by surgery, radiotherapy, or a combination of the two are reported in the present study. Of the 45 patients who were treated for cure, 38 were treated by surgery, followed by radiotherapy in 19 patients (50%). Five patients received definitive radiotherapy only, and 2 were treated by other modalities such as intra-arterial methotrexate and carbon dioxide (CO2) laser. Absolute and determinant 5-year survival rates were 62% and 77%, respectively. Sixty-four percent of patients survived 5 years recurrence-free, and 27% developed multiple primary tumors in the head and neck. Tumor stages III and IV were shown to decrease survival by half compared to stages I and II. A 42% occult nodal metastases rate was observed, and 3 of 11 patients experienced regional relapse in an untreated neck. From this review it appears that surgery, combined with postoperative radiotherapy when indicated, is an effective form of treatment for carcinoma of the soft palate and anterior tonsillar pillar.

Adult↗
PubMed1993

Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma.

BACKGROUND: The incidence of distant metastases in head and neck cancer patients is rising because of greater locoregional control of the disease. METHODS: The relative risks for having distant metastases as first site of failure relative to the regional lymph node involvement were determined. RESULTS: The overall incidence was 10.7%, with a clear relationship between the number of involved lymph nodes and extranodal spread on one hand, and distant spread on the other hand. The group with histopathologic presence of disease in the neck had twice as much distant metastases as did those with histopathologic absence (13.6% versus 6.9%). Patients with more than three histologically positive lymph nodes were most at risk for having distant metastases (46.8%). The presence of extranodal spread meant a threefold increase in the incidence of distant metastases, compared with patients without this feature (19.1% versus 6.7%). CONCLUSIONS: Patients with three or more positive nodes and with extranodal spread may benefit from adjuvant systemic therapy.

Adult↗
PubMed1993

Total glossectomy with laryngeal preservation.

OBJECTIVE: To evaluate the results of a planned combined therapy with surgery and postoperative radiotherapy in the management of large (T3 to T4) squamous cell carcinomas of the tongue-tongue base in properly selected patients. PATIENTS AND METHODS: Twenty-one patients underwent this procedure in a 4-year period. The selection criteria were directed to identify those patients in whom laryngeal preservation was feasible and who were motivated. Five categories of patients were included: those with (1) large primary tumors of the tongue-tongue base; (2) recurrence after initial radiotherapy, brachytherapy, chemotherapy, or a combination of these modalities; (3) recurrence after initial surgery and radiotherapy; (4) double primary tumors; and (5) second or third primary tumors arising in the tongue or base of the tongue. Preoperative investigation included examination under anesthetic and magnetic resonance imaging. Depending on the proximity of the primary tumor to the mandible, a mandibular split, a marginal resection, or a segmental resection was carried out. Soft-tissue replacement was achieved by a myocutaneous or a muscle flap of the pectoralis muscle with split skin. Whenever possible tissues of the contralateral floor of the mouth were also used. Laryngeal suspension was performed in all cases. Postoperative radiotherapy consisted of megavolt therapy, 66 Gy in 6 weeks to the primary site and both sides of the neck. RESULTS: Resumption of swallowing and speech was achieved in all patients. External deformity was slight. Patients were able to return to their families. CONCLUSIONS: Total glossectomy with laryngeal preservation in properly selected patients provides local and regional control and preserves quality of life.

Adult↗
PubMed1992

Cowden's disease. A case report with analyses at the molecular level.

Cowden's disease (multiple hamartoma syndrome) is characterized by multiple hamartomas of ectodermal, endodermal, and mesodermal origin, a high incidence of malignant tumors of the breast and/or thyroid gland, and an autosomal dominant pattern of inheritance. Similar to sporadic breast cancer, chromosomal studies have not elucidated the cause of this syndrome. The authors report the case of a patient with this syndrome and analyze the pattern of amplification or rearrangement of three genes: the HER-2/neu oncogene, the ras oncogene, and the estrogen-inducible gene, pS-2. All three of these genes were present in single copies without translocations. It was noteworthy that three of the most important genes currently studied in relation to breast cancer existed in a unamplified unrearranged state in this patient. Those with clinical manifestations of Cowden's disease may be candidates for prophylactic bilateral total mastectomy, and the authors recommend that these patients undergo this procedure by their third decade of life. An alternative to this approach would entail monthly self examinations, breast examinations by the patient's physician every 3 months, bilateral mammograms every 6 to 12 months, and biopsy of any suspicious lesions. It is crucial, however, that these patients be identified by their mucocutaneous lesions and family history before an underlying malignant lesion develops.

Adult↗
PubMed1992

Management of cervical lymph nodes in patients with head and neck cancer.

The status of the cervical lymph nodes is the single most important prognostic factor in head and neck cancer. Unfortunately, clinical assessment of the neck is not very accurate, although newer imaging techniques such as CT, MRI and ultrasound-guided fine needle aspiration cytology can be used to improve upon the results of clinical palpation alone. While diagnostic techniques remain less than 100% accurate, the risk of occult disease in the neck will remain. If this occurrence is judged to be greater than 15-20%, elective treatment to the neck may then be justified. When the neck is treated surgically, histological information can be gained which has both prognostic and therapeutic implications. Indications for the use of surgery and radiotherapy for the elective and therapeutic management of the neck and the results of such treatment are discussed.

Combined Modality Therapy↗
PubMed1992

Temporal bone resections for carcinoma of the middle ear and the external ear canal.

Petrosectomy has been used in the management of carcinoma of the external ear canal and the middle ear for the last 45 years. In recent years, there have been conflicting reports; some authors advocate a conservative approach, whereas others support an ultraradical approach. Most retrospective studies report patients who have been treated with radiotherapy or surgery as having undergone the primary modality depending on where the patient first presented. No selection criteria seem to have been employed. Although radiotherapy was used postoperatively, the problems of wound healing were not addressed. This study presents our experience with temporal bone resection as described by Lewis and shows that, in combination with patient selection and proper choice of incision, reconstruction and timely postoperative radiotherapy can achieve better results, and the patient's quality of life can be preserved.

Combined Modality Therapy↗
PubMed1992

Squamous cell carcinoma of the nasal vestibule.

We reviewed 30 patients with squamous cell carcinoma of the nasal vestibule to present our experience of their management and to evaluate the prognostic factors that may influence their outcome. For T1 lesions radiotherapy remains the treatment of choice, because of the superior cosmetic result. Fifteen (68 per cent) out of 22 patients with T2 lesions were treated with primary radiotherapy. Surgery however, was eventually required in 16 (72 per cent) out of 22 patients, either as a primary treatment (seven patients) or as salvage surgery (nine patients). For the larger T3 lesions the treatment of choice is surgery followed by post-operative radiotherapy where appropriate. Regional nodal metastases at the time of presentation were a significant indicator of local and regional recurrence and of prognosis. The cause specific five-year survival for patients with an uninvolved neck (22 patients) was 100 per cent compared with 38 per cent for patients with nodal metastases at presentation (eight patients). Elective treatment for uninvolved regional nodes is not considered necessary.

Adult↗
PubMed1991

Discontinuous vs in-continuity neck dissection in carcinoma of the oral cavity.

We compared the results of transoral excision of the primary tumor with discontinuous neck dissection with the results of in-continuity dissection of primary tumor and neck nodes in anteriorly localized squamous cell carcinoma of the oral cavity. We analyzed 27 patients who underwent 28 discontinuous dissections and 34 patients who underwent 40 in-continuity dissections for T2 anterior tongue or floor-of-mouth carcinoma. The overall ipsilateral neck recurrence rate was 11%. The discontinuous dissection group did significantly worse than the in-continuity dissection group, with a neck recurrence rate of 19%. Consequently, the actuarial 5-year survival of patients who underwent a discontinuous dissection was substantially decreased (63%) compared with patients who were treated by an in-continuity dissection (80%). Discontinuous neck dissection, thus, is not to be recommended in oral cancer.

Adult↗
PubMed1990

Experiences with the sternocleidomastoid muscle and myocutaneous flaps.

The use of the sternocleidomastoid muscle and musculocutaneous flaps in the reconstruction of defects arising after surgery for cancer of the head and neck has been a subject of some discussion. Experience with these flaps over a ten year period from 1980 until 1989 is presented. Attention is drawn to the various types of flaps in vogue, their indications to date, benefits and drawbacks. A new reliable compound musculocutaneous flap developed by the author for use in defects of the skull base after total temporal bone excision is presented.

Adult↗
PubMed1990

The efficacy of comprehensive neck dissection with or without postoperative radiotherapy in nodal metastases of squamous cell carcinoma of the upper respiratory and digestive tracts.

Neck recurrence-free curves corrected for local recurrence were compared for 494 patients who underwent 565 comprehensive neck dissections. In 42 dissections, no radicality could be obtained. Of the 523 histologically radical dissections, examination revealed tumor in 352 cases. Patients in whom three or more positive nodes or extranodal spread in one or more nodes were found received postoperative radiotherapy. In the histologically N0 group, the incidence of neck recurrence after 5 years was 3%; in the N+ group as a whole, it was 10%. Analysis of the influence of extranodal spread and the number of positive nodes showed that the group with one or two positive nodes without extranodal spread (that did not receive postoperative radiotherapy) did not statistically differ from the other groups. This suggests that the results of the group with one or two positive nodes without extranodal spread can be improved by postoperative radiotherapy.

Adult↗