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Biomedical subjects

Rajesh Varma

Publications and source records attributed to Rajesh Varma.

15 recordsLinked to original sources

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer.

Histopathology and epidemiology studies have consistently demonstrated a strong link between endometriosis and endometriosis-associated ovarian cancers (EAOCs)--in particular, the endometrioid and clear cell subtypes. However, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link because similar factors predispose to both diseases. In order to search for evidence of clonal progression, we analyzed 10 EAOCs (endometrioid=4; clear cell=6) with coexisting endometriosis for common molecular genetic alterations in both the carcinoma and corresponding endometriosis. We used 82 microsatellite markers spanning the genome to examine loss of heterozygosity (LOH) in the coexisting carcinoma and endometriosis samples. A total of 63 LOH events were detected in the carcinoma samples; twenty two of these were also detected in the corresponding endometriosis samples. In each case, the same allele was lost in the endometriosis and cancer samples. Interestingly, no marker showed LOH in the endometriosis alone. These data provide evidence that endometriosis is a precursor to EAOCs.

Adenocarcinoma, Clear Cell↗

Do screening-preventative interventions in asymptomatic pregnancies reduce the risk of preterm delivery--a critical appraisal of the literature.

Recent research has suggested that women who experience preterm delivery (PTD) may be identified earlier in pregnancy and before onset of symptoms. Interventions commenced at this earlier asymptomatic stage may offer an opportunity to prevent PTD or lengthen gestation sufficiently to reduce adverse perinatal outcome. Our objective was to examine the evidence that supports or refutes this approach to preventing PTD. We therefore conducted a systematic search and critical appraisal of the identified literature. We found evidence that introducing screening-preventative strategies for asymptomatic pregnancies may reduce the rate of PTD. Evidence for screening and selective treatment exists for: asymptomatic bacteriuria; bacterial vaginosis in low-risk population groups; elective cervical cerclage in high-risk pregnancies; indicated cervical cerclage in women with short cervical length on ultrasound; prophylactic progesterone supplementation in high-risk pregnancies, and smoking cessation. However, for most other strategies, such as increased antenatal attendance, or routine administration of prophylactic micronutrients, the evidence is inconsistent and conflicting. Information on neonatal outcomes apart from PTD (such as serious neonatal morbidity and mortality) was found to be lacking in most studies. It was therefore not possible to establish whether preventing PTD or prolonging gestation would correlate to improved perinatal outcome, and this lessened the potential clinical usefulness of any proposed preventative strategy. No studies were found that evaluated the effectiveness of combining screening-preventative strategies. The review concludes with a suggested an antenatal management plan designed to prevent PTD based on current practice and the evidence presented in this article.

Anti-Infective Agents↗

Non-contraceptive uses of levonorgestrel-releasing hormone system (LNG-IUS)--a systematic enquiry and overview.

Levonorgestrel releasing-intrauterine systems (LNG-IUS) were originally developed as a method of contraception in the mid 1970s. The only LNG-IUS approved for general public use is the Mirena LNG-IUS, which releases 20 mcg of levonorgestrel per day directly in to the uterine cavity. However, new lower dose (10 and 14 mcg per day) and smaller sized LNG-IUS (MLS, FibroPlant-LNG) are currently under clinical development and investigation. Research into the non-contraceptive uses of LNG-IUS is rapidly expanding. In the UK, LNG-IUS is licensed for use in menorrhagia and to provide endometrial protection to perimenopausal and postmenopausal women on estrogen replacement therapy. There is limited evidence to suggest that LNG-IUS may also be beneficial in women with endometriosis, adenomyosis, fibroids, endometrial hyperplasia and early stage endometrial cancer (where the patient is deemed unfit for primary surgical therapy). This systematic enquiry and overview evaluates the quality of evidence relating to the non-contraceptive therapeutic uses of LNG-IUS in gynaecology.

Delayed-Action Preparations↗

Antibiotic treatment of bacterial vaginosis in pregnancy: multiple meta-analyses and dilemmas in interpretation.

There is considerable evidence to show an association between genital tract infections, such as bacterial vaginosis (BV), and preterm delivery (PTD). Meta-analyses to date have shown screening and treating BV in pregnancy does not prevent PTD. This casts doubt on a cause and effect relationship between BV and PTD. However, the meta-analyses reported significant clinical, methodological and statistical heterogeneity of the included studies. We therefore undertook a repeat meta-analysis, included recently published trials, and applied strict criteria on data extraction. We meta-analysed low and high-risk pregnancies separately. We found that screening and treating BV in low-risk pregnancies produced a statistically significant reduction in spontaneous PTD (RR 0.73; 95% CI 0.55-0.98). This beneficial effect was not observed in high-risk or combined risk groups. The differences in antibiotic sensitivity between high and low risk groups may suggest differing causal contributions of the infectious process to PTD. The evidence, along with prior knowledge of differing predisposing factors and prognosis between these risk groups, supports the hypothesis that PTD in high and low risk pregnant women are different entities and not linear extremes of the same syndrome.

Anti-Bacterial Agents↗

Determining the quality of educational climate across multiple undergraduate teaching sites using the DREEM inventory.

BACKGROUND: Our obstetrics and gynaecology undergraduate teaching module allocates 40-50 final year medical students to eight teaching hospital sites in the West Midlands region. Based on student feedback and concerns relating to the impact of new curriculum changes, we wished to objectively assess whether the educational environment perceived by students varied at different teaching hospital centres, and whether the environment was at an acceptable standard. METHODS: A Dundee Ready Education Environment (DREEM) Questionnaire, a measure of educational environment, was administered to 206 students immediately following completion of the teaching module. RESULTS: The overall mean DREEM score was 139/200 (70%). There were no differences in the education climate between the teaching centres. CONCLUSION: Further research on the use of DREEM inventory, with follow up surveys, may be useful for educators to ensure and maintain high quality educational environments despite students being placed at different teaching centres.

Adult↗

Multicystic benign mesothelioma of the peritoneum presenting as postmenopausal bleeding and a solitary pelvic cyst--a case report.

BACKGROUND: All non-invasive diagnostic algorithms suffer from diagnostic uncertainty in discriminating benign from malignant adnexal masses. CASE: We present a case where the identification of a large solitary multiloculated pelvic cyst in a woman with postmenopausal bleeding was shown to be multifocal multicystic benign mesothelioma (MBM) of the peritoneum at laparotomy. CONCLUSION: We wish to alert gynaecologists of this rare association and the unique appearance of mesothelioma lesions, which many would not instantly recognise. There is a lack of consensus on the treatment and follow-up of MBM. Most authorities consider curative treatment of MBM is achievable through complete disease cytoreduction (peritonectomy) as carried out in the case.

Cysts↗

Endometriosis and the neoplastic process.

Endometriosis is a frequent disorder that commonly presents with infertility and pelvic pain. Although the precise aetiology of endometriosis is unclear, it is generally considered to involve multiple genetic, environmental, immunological, angiogenic and endocrine processes. Genetic factors have been implicated in endometriosis but the susceptibility genes remain largely unknown. Although endometriosis is a benign disorder, recent studies of endometriosis suggest endometriosis could be viewed as a neoplastic process. Evidence to support this hypothesis includes the increased susceptibility to develop ovarian clear-cell and endometrioid cancers in the presence of endometriosis, and molecular similarities between endometriosis and cancer. In this article we discuss (i) the evidence suggesting that endometriosis might be viewed as a neoplastic process, and (ii) the implications of this hypothesis for elucidating the pathogenesis of endometriosis and developing novel methods of diagnostic classification and individualised treatments.

Adenocarcinoma, Clear Cell↗