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Biomedical subjects

C H Buckley

Publications and source records attributed to C H Buckley.

At least 37 records · Page 2Linked to original sources
PubMed1996

Angiogenesis in normal, hyperplastic, and neoplastic endometrium.

The purpose of this study was to quantify vascular density in the stroma of normal, hyperplastic, and neoplastic endometria and to explore its relationship to other prognostic features of endometrioid adenocarcinoma. Curettage specimens of proliferative and mid-secretory endometrium; simple, complex, and atypical endometrial hyperplasia; and grade I endometrioid adenocarcinoma were stained with Factor VIII-related antigen. The number of vessels per mm2 of stroma was calculated for each case. The stroma of mid-secretory and hyperplastic endometrium was more vascular than that of proliferative endometrium. The stroma of adenocarcinoma, though reduced in proportion to the epithelium, was significantly more vascular than that of normal or hyperplastic endometrium. Stromal vascular density was not related to the depth of invasion, the presence of lymphovascular space permeation, or the state of the adjacent endometrium, whether atrophic or hyperplastic.

Adenocarcinoma↗
PubMed1996

A randomised trial investigating the dose intensity of primary chemotherapy in patients with ovarian carcinoma: a comparison of chemotherapy given every four weeks with the same chemotherapy given at three week intervals.

BACKGROUND: The dose intensity of chemotherapy for patients with ovarian carcinoma remains a controversial issue. Few randomised trials have been conducted examining dose intensity using the same total dose of chemotherapy. This study was designed to investigate two schedules of chemotherapy using standard and higher dose intensity with both groups receiving the same total dose. PATIENTS AND METHODS: Patients with FIGO stage IC, II, III and IV epithelial ovarian carcinoma were randomised to receive cycles of cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with doxorubicin (50 mg/ m2) and ifosfamide (5 g/m2) at either four-weekly (n = 47) or three-weekly (n = 97) intervals (1:2 randomisation). At randomisation patients were stratified according to histological grade and amount of post operative residual tumour (greater or less than 2 cm). The two arms of the study were well balanced in terms of the major prognostic features. RESULTS: There was no difference in either progression free survival or overall survival between the two arms. The median overall survival was 730 days for the three-weekly treatment and 740 days in the four-weekly arm (progression-free survival was 500 days and 483 days, respectively). The combined overall response rate (complete and partial response) in the 114 assessable patients was 65.7% (66.7% for the three-weekly treatment and 64% for the four-weekly treatment). These differences were not statistically different. CONCLUSIONS: A modest increase in the dose intensity of chemotherapy (1:3 fold) failed to improve the response rate, progression-free survival and overall survival in patients with ovarian carcinoma.

Adult↗
PubMed1996

The effects of post-ovulatory administration of onapristone on the developmnent of a secretory endometrium.

The purpose of this study was to assess the ability of the anti-progestin onapristone administered in the immediate post-ovulatory period to disrupt endometrial differentiation as a potential method of fertility control. In all, 10 healthy female volunteers were given 400 mg onapristone 2 days after the mid-cycle luteinizing hormone (LH) surge in urine (LH+2). An endometrial biopsy was taken 4 or 6 days after the LH surge (i.e. LH+4 or LH+6) in a control cycle and on the corresponding day of the treatment cycle. Biopsies were assessed for histological dating and immunolocalization of oestrogen receptors, progesterone receptors and 15-hydroxyprostaglandin dehydrogenase (PGDH). On day LH+12, blood was taken for the measurement of insulin-like growth factor binding protein-1 (IGFBP-1) and placental protein 14 (PP14). Hormonal measurements in blood and urine were used to monitor the effects on the menstrual cycle. In addition, the concentration of cortisol in plasma was measured to determine if this dose of onapristone exerted significant anti-glucocorticoid activity. Treatment with onapristone retarded the development of secretory changes within the endometrium without affecting the length of the luteal phase. Intense nuclear immunostaining of oestrogen and progesterone receptors was evident in glands and stroma after treatment, suggesting that the progesterone-dependent down-regulation of steroid receptors was inhibited by the anti-progestin. Onapristone also affected the production of luteal phase endometrial proteins, as judged by the pronounced reduction in immunostaining of PGDH within the glands and the significant reduction in plasma concentrations of PP14. However, plasma concentrations of IGFBP-1 did not differ between cycles. Onapristone did not appear to exert significant anti-glucocorticoid activity because concentrations of cortisol were unaffected. These findings suggest that onapristone could potentially be used as a method of postovulatory fertility control.

Adult↗
PubMed1996

Effects of daily low dose mifepristone on endometrial maturation and proliferation.

Following an ovulatory control cycle, six women took 2 mg of mifepristone daily for 30 days. Endometrial biopsies were collected in the control cycle between 7 and 11 days after the plasma luteinizing hormone (LH) surge and on the corresponding day of the treatment cycle (days 19-28). In order to investigate the effects of unopposed oestrogen on the endometrium, persistent proliferative endometrium was obtained from six women with anovulatory infertility due to polycystic ovarian syndrome (PCOS) on a similar cycle day (days 21-23) following a progestogen-induced withdrawal bleed. Endometrium was evaluated for histology and immunolocalization of oestrogen receptors (ER), progesterone receptors (PR) and the cell proliferation markers [proliferating cell nuclear antigen (PCNA) and Ki67]. Treatment with mifepristone inhibited ovulation in four of the six subjects. In the two subjects in whom ovulation did occur, secretory transformation was delayed, suggesting that successful implantation of a blastocyst would be unlikely. In subjects who remained anovulatory during treatment, the histology and pattern of steroid receptor expression was similar to proliferative phase endometrium. In women with PCOS, mitoses and intense immunostaining for ER, PR and cell proliferation markers were observed in both glands and stroma. Although PCNA and Ki67 immunostaining were also present in mifepristone-treated endometrium from subjects who did not ovulate, there were no mitoses and significantly less ER immunostaining in spite of exposure to unopposed oestrogen for a similar duration. Since PCNA and Ki67 detect cells throughout all stages of the cell cycle this would suggest that mifepristone might affect the entry of cells into the mitotic phase of the cell cycle and, therefore, might prevent endometrial hyperplasia. These findings add further evidence to support the contraceptive potential and antiproliferative activity of daily low dose mifepristone.

Adult↗
PubMed1996

p53 expression in carcinoma of the cervix.

AIM: To assess overexpression of the proposed tumour suppressor gene product p53 using the mouse monoclonal antibody DO-7 in the three main subtypes of carcinoma of the uterine cervix and to evaluate its value as a prognostic indicator. METHODS: Eighty two cases of FIGO Stage IB/IIA uterine cervical carcinoma were studied retrospectively. The tumours had been previously typed into adenocarcinomas, squamous carcinomas and adenosquamous carcinomas after the tissue had been fixed in formalin and embedded in paraffin wax. p53 protein expression was assessed using a standard immunohistochemical technique and the findings were correlated with tumour type, lymph node status and clinical outcome. RESULTS: In total, the p53 gene product was overexpressed in 17.1% (14/82) of all carcinomas and also in areas of cervical intraepithelial neoplasia grade III adjacent to invasive squamous carcinoma. Where present, the normal epithelium was uniformly negative. No association was found between p53 overexpression and tumour subtype, lymph node status or clinical outcome. CONCLUSIONS: It seems unlikely that p53 analysis will be of value in determining prognosis in carcinoma of the uterine cervix.

Adenocarcinoma↗
PubMed1996

Neuroendocrine differentiation in cervical carcinoma.

AIMS: To examine neuroendocrine differentiation, as shown by chromogranin A (CGA) expression, in cervical carcinomas. METHODS: Sixty seven cervical carcinomas were studied and were classified as adenocarcinomas, adenosquamous carcinomas or squamous cell carcinomas based on the assessment of haematoxylin and eosin staining and stains for mucin. Where features of glandular differentiation were identified, sections were also stained for evidence of intestinal type mucin. CGA immunostaining was done and the results were graded on a three point scale: 0, + (1-5% of cells positive) and ++ (> 5% of cells positive). These findings were then analysed with respect to lymph node status, tumour differentiation and clinical outcome. RESULTS: There were 32 adenocarcinomas, 18 adenosquamous carcinomas and 17 squamous cell carcinomas. Positive staining was seen in 14 (20.9%) cases, of which four were strongly positive. All but one case were either adenocarcinomas or adenosquamous carcinomas. There was a trend for CGA positivity to be related to intestinal differentiation but this failed to reach statistical significance. No correlation could be demonstrated between CGA staining and lymph node status, tumour differentiation and clinical outcome. CONCLUSIONS: Neuroendocrine differentiation is common in cervical carcinomas where there is evidence of glandular differentiation. Whilst the numbers in this study are relatively small, the presence of neuroendocrine cells in otherwise typical carcinomas does not seem to have any association with clinical behaviour.

Adenocarcinoma↗
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↗
PubMed1994

The pathology of intra-uterine contraceptive devices.

The IUCD is a simple and effective way of producing contraception without the need for patient compliance. It is not rendered ineffective by other drugs, as may be steroid contraceptives, and its side-effects, for carefully selected patients, are considered by most practitioners to be acceptably low (Van Kets et al. 1989).

Cervix Uteri↗
PubMed1994

Staging, volume estimation and assessment of nodal status in carcinoma of the cervix: comparison of magnetic resonance imaging with surgical findings.

Pre-operative magnetic resonance imaging (MRI) was carried out in 50 women scheduled for operative treatment of invasive carcinoma of the cervix. The extent of the primary tumour (stage), its dimensions and the presence of lymph node enlargement were assessed and compared with findings at surgery and/or histopathological examination of the resected uterus. In 45 patients undergoing radical hysterectomy, accuracy of MRI staging of the primary tumour was 84.4%. In the group as a whole, including four patients with inoperable disease, staging accuracy was 84%. Most errors were due to difficulty in identifying early vaginal or parametrial invasion by tumour. There was close correlation between the volume of tumour measured from pre-operative MRI scans and measurements made on the hysterectomy specimen (r = 0.95). MRI had a sensitivity of 75% and a specificity of 88% in predicting metastatic lymphadenopathy, based solely on the criterion of enlargement of any pelvic or para-aortic nodes to 1.5 cm or greater. However, retrospective analysis of the presence or absence of metastases by site in 49 patients undergoing lymphadenectomy or lymph node sampling at laparotomy showed that true sensitivity to be 57.1% and the specificity 96.8%. Differentiation between malignant and reactive lymphadenopathy was not reliably achieved on MRI, and in several patients, metastases were present in normal-sized lymph nodes.

Adolescent↗
PubMed1994

Endometrial structure after superovulation: a prospective controlled study.

OBJECTIVE: To demonstrate the effect of superovulation using a GnRH agonist (GnRH-a) and hMG and hCG on endometrial structure. DESIGN: Prospective, case-controlled study. SETTING: Tertiary referral assisted reproduction unit in an academic department. PATIENTS: Eleven women undergoing GIFT or IVF, without ET. INTERVENTIONS: All women were treated with a long stimulation regimen using the depot GnRH-a Goserelin (ICI, Macclesfield, United Kingdom) and hMG and hCG. MAIN OUTCOME MEASURES: Comparison of endometrial biopsy specimens taken 4 days after ovulation in an unstimulated cycle with specimens taken 4 days after oocyte recovery, using standard dating criteria and morphometric analysis. RESULTS: There was no difference in endometrial glandular development as assessed by either standard criteria or morphometric analysis. CONCLUSIONS: Superovulation preceded by pituitary down regulation is not associated with abnormal endometrial glandular development, even though supraphysiological levels of E2 and P are induced.

Adult↗
PubMed1993

Cathepsin-D expression in cervical carcinoma and its prognostic significance.

An immunohistochemical study was made of cathepsin-D protein expression in each of the three main types of uterine cervical carcinoma (squamous carcinoma, adenosquamous carcinoma and adenocarcinoma) with particular reference to lymph node status and prognosis. Of the 61 cases, 54.1% showed cytoplasmic staining in more than 2.5% of tumour cells counted. Cathepsin-D expression was significantly higher in adenocarcinoma (mean -3.128) than in squamous carcinoma and adenosquamous carcinoma (mean -3.709, p = 0.047 using logit transformation). Cathepsin-D had no prognostic value in any of the three tumour types. No relationship was found between cathepsin-D staining and lymph node status and there was no advantage in adding cathepsin-D values to lymph node status. These results suggest that immunostaining for cathepsin-D protein expression is unlikely to be of use as a prognostic marker.

Adenocarcinoma↗
PubMed1993

HLA expression in pre-invasive cervical neoplasia in relation to human papilloma virus infection.

A significant proportion of cervical carcinomas show loss of major histocompatibility complex human leucocyte antigen (HLA) class I expression while upregulating HLA class II expression. These changes may have direct consequences for immune surveillance of the human papilloma virus (HPV) infection which is strongly associated with cervical malignancy. A relationship between changes in HLA expression and HPV infection may be evident in the evolution of premalignant disease. This immunohistological study of 104 colposcopic biopsies establishes that HLA class II expression occurs in a significant proportion of squamous epithelia showing histological evidence of wart virus infection and cervical intraepithelial neoplasia (CIN) I to III. In comparison, alteration of HLA class I expression in cervical premalignant lesions is rare. There is no correlation between the detection of high risk HPV DNA (types 16, 18, 31 and 33) by polymerase chain reaction (PCR) and the MHC class II phenotype of the lesion. This suggests that altered HLA class II expression is neither a consequence nor a prerequisite for HPV infection.

DNA, Viral↗
PubMed1993

A randomised dose intensity study in ovarian carcinoma comparing chemotherapy given at four week intervals for six cycles with half dose chemotherapy given for twelve cycles.

BACKGROUND: The importance of dose intensity has not been clearly defined in ovarian cancer and we present a prospectively randomised trial of dose intensity in patients with ovarian cancer. PATIENTS AND METHODS: Ninety-nine patients with FIGO stage Ic, II, III and IV epithelial ovarian cancer were randomised to receive cycles of standard dose cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with adriamycin (50 mg/m2) and ifosfamide (5 G/m2) for 6 cycles at monthly intervals (49 patients) or cycles of half dose cyclophosphamide (300 mg/m2) and carboplatin (150 mg/m2) alternating with adriamycin (25 mg/m2) and ifosfamide (2.5 G/m2) for 12 cycles at monthly intervals (50 patients). Patients in each arm were well balanced for major prognostic factors. RESULTS: The combined clinical response rate (complete response and partial response) on the 6 month arm was 76% compared with 48% on the low dose intensity arm (p = 0.009). With a median follow up of 25.7 months the median survival on the low dose intensity arm is 20.9 months. The median survival point on the 6 month arm has not yet been reached. The median progression free interval on the 12 month arm was 19.8 months, the median value has not yet been reached on the standard arm. The amount of residual tumour following initial laparotomy was the only significant independent variable affecting survival (p = 0.0001). The mean received dose intensity of each drug was greater than 80% of the planned dose intensity. More patients had clinical disease progression during treatment on the low dose intensity arm (42%) when compared to the standard dose intensity arm (8%) (p = 0.0003). Fifteen patients on the standard dose arm experienced a total of 18 delays and 5 patients on the low dose arm experienced 17 delays. Nausea, vomiting and diarrhoea were similar for both standard and low dose cycles of chemotherapy with a consequent benefit for patients receiving fewer cycles even though these were of higher dose. CONCLUSIONS: The combination studied was more effective when given at the higher dose intensity and the improved response and survival was not accompanied by a significant increase in toxicity.

Adenocarcinoma↗