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Biomedical subjects

J A Tidy

Publications and source records attributed to J A Tidy.

At least 19 recordsLinked to original sources
PubMed2006

Can we identify the patients who are likely to undergo bowel resection at the time of surgery for ovarian cancer?

Surgery for ovarian cancer carries a risk of bowel resection to either achieve optimal debulking or relieve obstruction. This prospective study assessed the likelihood of bowel resection in 842 women undergoing surgery for ovarian cancer and identified factors associated with increased risk. Bowel resection was performed in 8.6% of women. The likelihood of bowel resection increased significantly (p < 0.0001, chi2 test) with: Secondary surgery (22% vs 5.8% at primary surgery). Symptoms of bowel disturbance (21.9% vs 6.3% if no symptoms). FIGO stage III/IV disease (12.8% vs 2% in stage I/II). CA125 levels >or=2500 (12.9% vs 4.8% if CA125<2500). These women should be selectively offered pre-operative computerised tomography, stoma marking and counselling by stoma nurses. The 5-year survival was 14% in patients following bowel resection compared with 44% in patients not having bowel resection. Bowel resection should be performed only if it will result in optimal debulking or it relieves imminent bowel obstruction.

CA-125 Antigen↗
PubMed2003

Gestational trophoblastic disease in the Asian population of Northern England and North Wales.

OBJECTIVE: To determine the incidence and trends of gestational trophoblastic disease in the Asian population of Northern England and North Wales.A prospective observational study. SETTING: Trophoblastic Screening and Treatment Centre, Weston Park Hospital. POPULATION: A total of 3660 women registered with gestational trophoblastic disease between 1991 and 1999. MAIN OUTCOME MEASURES: 1. The incidence of gestational trophoblastic disease in Asian and non-Asian population. 2. Trend in incidence over study period. RESULTS: Three hundred and twenty-two Asian patients were registered. The incidence of gestational trophoblastic disease in the northern part of England and Wales averaged 1 per 714 live births. The incidence of gestational trophoblastic disease in the Asian population was 1.95 times higher than in the non-Asian population (1 per 387 live births vs 1 per 752 live births). There was an excess of molar pregnancies in the extreme maternal age groups; the incidence in these women was twice as high as in the whole reproductive cohort. The ratio of partial to complete hydatidiform mole increased from 0.9 in the lower age to 2.6 in the older age group. There appeared to be a slowly rising trend in the incidence of gestational trophoblastic disease; the increase was higher in the Asian than in the non-Asian population. The ratio of partial to complete moles increased with age in both populations. CONCLUSION: Asian women are at increased risk of having molar pregnancies. Molar pregnancies are more common at the extremes of reproductive age. The setting up of regional or national registration centres has helped to provide more accurate estimates of the true incidence of the disease.

Adolescent↗
PubMed2002

Analysis of CHK2 in vulval neoplasia.

Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia. We identified the previously described silent polymorphism at codon 84 (A>G at nucleotide 252) in the germ-line of six out of 72, and somatic mutations in two out of 40 cases of vulval squamous cell carcinomas and none of 32 cases of vulval intraepithelial neoplasia. One mutation introduced a premature stop codon in the kinase domain of CHK2, whereas the second resulted in an amino acid substitution in the kinase domain. The two squamous cell carcinomas with mutations in CHK2 also expressed mutant p53. A CpG island was identified close to the putative CHK2 transcriptional start site, but methylation-specific PCR did not detect methylation in any of 40 vulval squamous cell carcinomas, irrespective of human papillomavirus or p53 status. Consistent with this observation, no cancer exhibited loss of CHK2 expression at mRNA or protein level. Taken together, these observations reveal that genetic but not epigenetic changes in CHK2 occur in a small proportion of vulval squamous cell carcinomas.

Adult↗
PubMed2002

E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia.

In common with other E2F1 responsive genes such as p14(ARF) and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Delta2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Delta2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium.

Carcinoma, Squamous Cell↗
PubMed2001

p73 is over-expressed in vulval cancer principally as the Delta 2 isoform.

p73 was studied in squamous cancers and precursor lesions of the vulva. Over-expression of p73 occurred commonly in both human papillomavirus (HPV)-positive and -negative squamous cell cancers (SCC) and high-grade premalignant lesions. Whereas expression in normal vulval epithelium was detected only in the basal and supra-basal layers, expression in neoplastic epithelium increased with grade of neoplasia, being maximal at both protein and RNA levels in SCC. p73 Delta 2 was the principal over-expressed isoform in the majority of cases of vulval SCC and often the sole form expressed in SCC. Over-expression of p73 was associated with expression of HPV-encoded E7 or with hypermethylation or mutation of p16(INK4a) in HPV-negative cases. There was a close correlation between expression of p73 and p14(ARF) in cancers with loss of p53 function. The frequent over-expression of p73 Delta 2 in neoplastic but not normal vulval epithelium, and its co-ordinate deregulation with other E2F-1 responsive genes suggests a role in the oncogenic process.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed2001

Over-diagnosis of hydatidiform mole in early tubal ectopic pregnancy.

AIMS: Tubal ectopic hydatidiform moles are rare lesions, and only 40 cases have been reported in the world literature. We investigated the apparently high incidence of tubal ectopic hydatidiform moles in women referred for treatment to a Supraregional Trophoblastic Tumour Screening and Treatment Centre between 1986 and 1996. METHODS AND RESULTS: Of 4261 women referred during the study period, 25 (0.6%) had a suspected tubal ectopic hydatidiform mole and paraffin-embedded tissue was available in 20 (80%) of these. Each case was reviewed by two pathologists and DNA flow cytometric analysis was undertaken when the histological diagnosis was initially deemed equivocal or suggestive of hydatidiform mole. On review, 17 cases (85%) showed no evidence of hydatidiform mole (circumferential trophoblastic proliferation, hydrops, scalloped villi, and stromal karyorrhexis). Of these, 11 cases (65%) showed features of early placentation and six (35%) showed hydropic abortion. DNA flow cytometry was performed in 14 (82%) of these cases and revealed a diploid population in each case. Three cases of molar pregnancy (15%) were identified. Each of these cases had the histological features of an early complete hydatidiform mole. Sufficient tissue was available for DNA flow cytometric analysis in two of these cases and confirmed the presence of diploidy in each. CONCLUSION: Our results show that tubal ectopic hydatidiform mole is a rare entity and demonstrate that it is over-diagnosed. Polar trophoblastic proliferation and hydropic villi are features of early placentation and of hydropic abortion. Sheets of extravillous trophoblast may be particularly prominent in tubal ectopic gestation. In the absence of circumferential trophoblastic proliferation combined with hydropic change a diagnosis of gestational trophoblastic disease should be avoided.

Abortion, Spontaneous↗
PubMed2001

The surgical management of ovarian cancer.

This article aims to cover current concepts and controversies in the surgical management of ovarian cancer. While there have been significant advances in the surgical management of vulval, cervical and even endometrial cancer there have been few developments in the surgical management of ovarian cancer. This situation is likely to continue until we get a clearer understanding of the natural history of this disease and better therapeutic options become available.

Combined Modality Therapy↗
PubMed2000

Preferential retention of codon 72 arginine p53 in squamous cell carcinomas of the vulva occurs in cancers positive and negative for human papillomavirus.

We have sought to determine the basis for preferential loss of the codon 72 proline (72P) rather than the arginine (72R) allele in squamous cell carcinoma of the vulva with loss of heterozygosity (LOH) in p53. The proportion of cases containing human papillomavirus (HPV) 16 was not statistically different among individuals with either 72RR or 72RP in the germ line (P > 0.99), but p53 LOH was significantly more common in individuals heterozygous 72RP than in 72RR individuals (P = 0.04). LOH more commonly involved the 72P allele in both HPV-positive and HPV-negative cancers. Our results imply that preferential loss of the 72P allele in vulval squamous cell carcinoma occurs by HPV-dependent and -independent mechanisms.

Alleles↗
PubMed2000

Relation between tissue structure and imposed electrical current flow in cervical neoplasia.

BACKGROUND: When an electrical potential is applied to human tissue, the pattern of the resulting current flow is determined by the shapes, arrangements, and internal structure of the tissue cells. By measurement of the electrical current patterns over a range of frequencies, and use of an inverse modelling procedure, electrical variables describing the tissue structure can be calculated. We used this method to develop a screening technique for the detection of cervical precancers. METHODS: We used a pencil probe (diameter 5 mm) to measure electrical impedance spectra from eight points on the cervix in 124 women with abnormal cervical smears. Variables that should be sensitive to the expected tissue changes were calculated. These were compared with the colposcopic results. FINDINGS: The measured electrical impedance changes were those predicted on the basis of the expected tissue structures. Measurements made on normal squamous tissues were well separated from those made on precancerous tissues. We constructed receiver-operating-characteristic curves, comparing measurements made on normal tissue and that showing cervical intraepithelial neoplasia grade 2/3; the area under the curve was 0.951. These groups of women could be separated with a sensitivity of 0.92 and a specificity of 0.92. INTERPRETATION: Characteristics of the electrical impedance spectra of tissues can be explained by changes in cell arrangements (layering) and in the size of the nuclei. This relation opens the way to deriving tissue structure from electrical impedance spectral measurements. We show that this approach can be used to give good separation of normal and precancerous cervical tissues.

Biopsy↗
PubMed2000

Gestational trophoblastic disease: a study of mode of evacuation and subsequent need for treatment with chemotherapy.

OBJECTIVES: The aim of this study was to assess whether there was a change in the mode of evacuation of GTD over two time periods and to assess whether mode of evacuation influenced the subsequent need for chemotherapy. METHODS: A retrospective case note study of 4257 cases between 1986 and 1996, at a screening and treatment center managing GTD, was performed. RESULTS: Between the time periods 1986-1989 and 1990-1996 there was significant change in the mode of evacuation to suction curettage. The mode of evacuation was significant in determining the need for chemotherapy. The highest rate of chemotherapy was associated with medical methods of evacuation. CONCLUSIONS: Suction curettage is a safe method of uterine evacuation in GTD and its usage has increased with time. Medical methods of uterine evacuation are associated with higher rates of chemotherapy. This is probably due to a higher rate of incomplete evacuation. Medical methods of evacuation should not be used in cases of complete hydatiform mole.

Abortifacient Agents, Steroidal↗
PubMed2000

A common polymorphism acts as an intragenic modifier of mutant p53 behaviour.

The p73 protein, a homologue of the tumour-suppressor protein p53, can activate p53-responsive promoters and induce apoptosis in p53-deficient cells. Here we report that some tumour-derived p53 mutants can bind to and inactivate p73. The binding of such mutants is influenced by whether TP53 (encoding p53) codon 72, by virtue of a common polymorphism in the human population, encodes Arg or Pro. The ability of mutant p53 to bind p73, neutralize p73-induced apoptosis and transform cells in cooperation with EJ-Ras was enhanced when codon 72 encoded Arg. We found that the Arg-containing allele was preferentially mutated and retained in squamous cell tumours arising in Arg/Pro germline heterozygotes. Thus, inactivation of p53 family members may contribute to the biological properties of a subset of p53 mutants, and a polymorphic residue within p53 affects mutant behaviour.

Alleles↗
PubMed1999

CD44 is a marker of endocervical neoplasia.

The expression of CD44s, CD44v4, CD44v5, CD44v7-8, and CD44v10 was investigated immunohistochemically in a variety of neoplastic cervical lesions. Normal endocervical columnar cells exhibited no reactivity for any of the antibodies, whereas the subcolumnar reserve cells were strongly positive for CD44s, CD44v5, and CD44v7-8. In some cases, positive cells were identified in the stroma surrounding the endocervical glands and adjacent to reserve cells. Cervical glandular intraepithelial neoplasia and adenocarcinoma showed consistent immunoreactivity for CD44v5. There was no significant change in CD44 immunoreactivity in squamous cell carcinoma compared with normal epithelia and cervical intraepithelial neoplasia. These findings lend support to the origin of carcinoma of the cervix from a common progenitor reserve cell and suggest the origin of reserve cells from the stroma. CD44v5 may be useful as a diagnostic marker of endocervical neoplasia and could provide a target for therapeutic approaches directed against specific epitopes.

Adenocarcinoma↗
PubMed1998

Are the benefits of errorless learning dependent on implicit memory?

The effectiveness of errorless and errorful learning methods was compared in two experiments in which a group of memory-impaired individuals learned lists of single words. In both experiments, error prevention during learning resulted in higher levels of cued recall performance than trial-and-error learning. Experiment 1 showed that the beneficial effects of the errorless learning method extended over a delay of up to 48 hr and were also observed in free recall. The hypothesis that the benefits of errorless learning rely upon implicit memory was tested in Experiment 2. No evidence was found to support the hypothesis. Implicit memory was observed following both errorless and errorful learning, but there was no indication that enhanced performance in the errorless condition could be accounted for by implicit memory. There was no correlation between performance on a direct test (cued recall) and performance on an indirect test (fragment completion) for the same materials. Furthermore, the extent of priming was no greater for recalled items than non-recalled items in the cued recall test. It is proposed that the benefits of errorless learning in this paradigm stem from the effects of error prevention on residual explicit memory.

Adult↗
PubMed1997

When is bacterial vaginosis not bacterial vaginosis?--a case of cervical carcinoma presenting as recurrent vaginal anaerobic infection.

Vaginal anaerobic infection is the most common cause of vaginal discharge in women. We present a case of recurrent vaginal anaerobic infection and cervical carcinoma and discuss the association of the two conditions. More frequent cytology/colposcopy may be indicated in women who give a history of recurrent or persistent vaginal anaerobic infection.

Adult↗
PubMed1996

Management of lichen sclerosus and intraepithelial neoplasia of the vulva in the UK.

Women with vulval intraepithelial neoplasia (VIN), lichen sclerosus (LS) and Paget's disease are referred either to gynaecologists or to dermatologists. We have ascertained the caseloads, referral patterns and treatment modalities used in the two specialties. A postal questionnaire was sent to 540 consultant gynaecologists and 225 consultant and senior registrar members of the British Association of Dermatologists. 350 gynaecologists and 161 dermatologists returned completed questionnaires. The workload of LS and Paget's disease was evenly distributed, with 54% of dermatologists and 58% of gynaecologists seeing more than six cases of LS per annum and less than 1% seeing more than five cases of Paget's disease. 92% of responding gynaecologists saw at least one case of VIN per year whereas 43% of dermatologists saw no cases. Patients with VIN and Paget's were referred to gynaecologists for treatment by 66% of dermatologists. Both groups are equally prepared to treat LS. Indications for treatment of VIN and LS were suspicion of invasion and symptoms. Local excision of VIN is the treatment of choice by both gynaecologists and dermatologists. LS is predominantly treated with topical steroids but gynaecologists also use topical oestrogen and testosterone. The great majority of responders favoured establishing a national register to study the outcome of vulval lesions.

Carcinoma in Situ↗
PubMed1995

Presentation and management of choriocarcinoma after nonmolar pregnancy.

OBJECTIVE: To ascertain the mode of presentation and treatment outcome for women with choriocarcinoma after a nonmolar pregnancy. DESIGN: Retrospective analysis of case records between 1985 and 1994. SETTING: A referral centre for trophoblastic disease. SUBJECTS: One hundred women with choriocarcinoma: 62 after a live birth, six after a live birth preceded by a molar pregnancy and 32 after a nonmolar abortion. RESULTS: Choriocarcinoma after nonmolar pregnancies represent 17% of the total gestational trophoblastic tumours requiring treatment. Vaginal bleeding was the commonest symptom in all groups, but symptoms from metastatic disease were important in the group presenting after a live birth. Metastatic disease was present in 31% of cases after live birth and 43% post-abortion. The median interval between the antecedent pregnancy and choriocarcinoma was five and six months, respectively. High risk multi-agent chemotherapy was required in 82% and 60% of cases, respectively. The mortality rate was significantly higher after a live birth than a nonmolar abortion (21% vs 6%). CONCLUSIONS: Treatment of choriocarcinoma after a live birth is associated with an unacceptably high mortality rate. Vaginal bleeding is an important early symptom and a pregnancy test should be performed if it persists after usual medical treatment.

Adolescent↗
PubMed1992

Clonal p53 mutation in primary cervical cancer: association with human-papillomavirus-negative tumours.

Analyses of cancer cell lines and of anal cancers suggest an inverse correlation between infection with human papillomavirus (HPV) and somatic mutation of the p53 tumour-suppressor gene. We have investigated this association in primary cervical tumours. Tumour-tissue samples from 28 women with primary cancer of the cervix were analysed for presence of HPV sequences and for somatic mutations of the p53 gene. Southern blot analysis and the polymerase chain reaction (PCR) showed that 25 of the tumours contained HPV sequences; 20 were HPV16 positive and 5 HPV18 positive. 17 tumours subjected to restriction fragment length polymorphism analysis for the short arm of chromosome 17 showed no evidence of allelic deletion. Sequencing of the entire coding region of the p53 gene by asymmetric PCR detected heterozygous point mutations in only 3 HPV-negative tumours. By contrast, in 21 HPV-positive cancers the p53 sequence was wild-type throughout. Our data indicate that loss of wild-type p53 function is important in the pathology of cervical cancer and that in the absence of an HPV-encoded gene product that mediates loss of p53 function, somatic mutation of the gene is required. This pattern of p53 mutation may partly explain the apparently worse prognosis of HPV-negative cervical cancers.

Adenocarcinoma↗