Are there immunologically mediated abortions? If so, which mechanisms?
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Biomedical subjects
Publications and source records attributed to C W Redman.
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Flow cytometry has enabled the objective assessment of cellular morphology and activity, which can also be biochemically evaluated by measuring products of cellular metabolism, such as cyclic 3'5' guanosine monophosphate (cGMP). Using paraffin-embedded formalin-fixed material obtained from the primary operation, an analysis of the correlation between nuclear ploidy and the proliferative index (PI) as quantified by flow cytometry with pre-treatment urinary cGMP was performed in 40 epithelial ovarian cancer (EOC) patients. The majority of the study group had advanced disease (28 FIGO III/IV) and residual disease (31). All but three (stage I) patients received single agent high dose cisplatinum as first-line therapy (100 mg m-2 x 5); in patients with evaluable disease there was a response rate of 64%. Thirty-one patients have died; the median survival of the study population being 27 months. There was a significant association between cGMP and PI. Significantly more aneuploid tumours had elevated PI values (P = 0.02). No variable predicted response. An initial univariate log rank analysis identified stage, the amount of residual disease, cGMP and PI as prognostic factors. Because of the interrelation between these and other factors and because PI did not conform to the proportional hazards model, a multivariate stepwise discriminant analysis was performed using survival at 36 months (the minimum follow-up for surviving patients) as the end-point. On the basis of this analysis, stage and residual disease were the most important prognostic factors, but cyclic GMP continued to have prognostic value even when these other factors were entered into the predictive model. However, the additional information gained has little clinical relevance.
Stenosis of the residual cervix is not an infrequent complication of cone biopsy which may result in subfertility, problems with adequate follow-up and dysmenorrhoea. In an attempt to minimize this complication a temporary indwelling cervical support stent has been developed. This is sutured into the exposed cone bed immediately after cutting the cone specimen and removed 2 weeks later. A pilot study using this device in 33 cold knife conizations has been performed. There were no primary or secondary haemorrhages and no post-conization pelvic infections. At follow-up, 6 months after cone biopsy two patients (6%) had clinical cervical stenosis, and one patient (3%) complained of dysmenorrhoea (although the cervix was not stenosed). The cervical transformation zone was fully visible in 21/33 patients (64%) (95% CI 48 to 80) and follow-up smears contained endocervical cells in 20/33 patients (61%) (95% CI 44 to 78). These results compare very favourably with historical controls from the same unit and suggest that cone biopsy support stents should now be assessed in a prospective randomized trial.
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Large granular lymphocytes (LGL) have been shown previously to be the most abundant cell type in the first trimester human decidua. Purified populations of decidual LGL were prepared by flow cytometry of cell dispersions labelled with NKH1 (CD56), an antibody specific for peripheral blood LGL, and the functional properties of CD56-positive cells, CD56-negative and unsorted decidual cells compared. Both CD56-positive cells and unsorted decidual cells have cytotoxic activity against the natural killer (NK) cell target K562 which was weak compared with that of peripheral blood mononuclear cells (PBMC). The CD56-negative cells had no cytotoxic activity against K562. All three decidual cell populations proliferated in response to recombinant human interleukin-2 (rIL-2), but none produced detectable levels of IL-2 in culture. When unsorted decidual cells were cultured for 7 days in rIL-2 the proportion of CD56-positive cells increased and NK activity against K562 was augmented. The NK activity of purified CD56-positive decidual cells was also augmented by culturing in rIL-2. The potential role of decidual LGL in regulating the development of the semi-allogeneic placenta is discussed.
The presence and amount of residual disease after primary surgery is a major adverse prognostic factor in epithelial ovarian cancer [EOC]. Rapid initial cytoreduction employing second surgery early in the primary chemotherapeutic management of patients with gross residual disease has been advocated as a means of improving outcome. To evaluate the prognostic value of such an approach we have reviewed the outcome of 24 patients with gross residual disease, who were debulked to less than 2 cm residuum at a second operation, performed after three cycles of cis-platinum-based chemotherapy (a median of 14 weeks from the initial laparotomy), and compared this with an historical series of 195 patients with residual disease (70 patients with less than 2 cm residuum) who received cis-platinum but no early secondary surgery. In the control series, stage and residual disease status were important prognostic factors. There was no significant difference in patient or disease characteristics between those patients in the early second surgery group and control patients with greater than 2 cm disease (n = 125). Initially the survival curve for the early second surgery group was similar to the less than 2 cm disease group, but at about 18 months, there was a rapid deterioration until the survival parallels that of the patients with bulky disease at presentation. Early secondary surgery did not significantly prolong survival in patients with greater than 2 cm of residual disease.
Pelvic examination of women patients under general anaesthesia has long been practised by gynaecologists in order to teach clinical findings to medical students. Although this practice may spare patients discomfort and embarrassment, a recent survey has shown that it should not be carried out without patient consent. Consent, however, is rarely withheld.
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We report a phase II study of bleomycin, ifosfamide, and cisplatin (BIP) in cervical cancer. Our aims were to assess response rate, toxicity, and survival in women treated with this combination. Among 49 patients, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxic effects were assessed in 186 treatment cycles. All patients had alopecia and nausea and vomiting. Other effects included myelosuppression, infection, reduction in renal function, and disturbance of consciousness. These data indicate that BIP is highly active against advanced and recurrent cervical cancer.
A total of 154 peritoneal lavages was attempted through either a permanent (17) or a temporary percutaneous cannula (137) in 59 ovarian cancer patients undergoing intraperitoneal treatment or monitoring. Seven of the eight permanent catheters were removed because of complications; intraperitoneal adhesions were a major problem in this group. Overall, 137 temporary catheters were inserted (14G Venflon i.v. cannula in 119, Verres needle in 15, and a Trocath peritoneal dialysis catheter in 3 instances) but it was not possible to perform a peritoneal lavage in 42 (30%). Access to the peritoneal cavity was unsatisfactory on 29 (34%) occasions when a Venflon cannula was used, either because there was inadequate flow of lavage fluid into the peritoneal cavity or this was limited by pain. Perforation of the bowel occurred in 12 (9%) cases but there was no significant morbidity. Problems with achieving reliable peritoneal access using either permanent or temporary catheters may limit the potential advantages of the intraperitoneal route for treatment and monitoring.
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Forty-six patients with a primary diagnosis of vulval intraepithelial neoplasia (VIN) have been managed over a 10-year period. The prevalence of VIN has increased and the age at presentation has decreased over the last decade; 59% of our patients had histological evidence of human papillomavirus infection. Pruritus was the commonest symptom at presentation (59%). Of the 46 patients 44 were treated by laser skinning vulvectomy, local excision or simple vulvectomy. Symptomatic relief was best achieved by local excision. Clinical and definitive relapse occurred more often in the laser-treated group. The median time to relapse was 38 months in the laser-treated group and 74 months in the surgically treated group (excision and simple vulvectomy). Two patients have not been treated and their disease has not progressed. The carbon dioxide laser almost certainly has a role in conservative management and although our data possibly do not reflect its full potential they demonstrate a need for a controlled prospective study.
The staining reactions of the monoclonal antibodies anti-EMA, AGF 4:48 and the lectin UEA-1 from Ulex europaeus were investigated in formalin-fixed, paraffin-embedded sections of 36 primary ovarian carcinomas. The staining patterns were graded and related to tumour type, differentiation, FIGO stage and patient survival. Both antibodies and UEA-1 showed variations in their staining between and within tumours. The staining of mucinous tumours using anti-EMA was significantly less than in non-mucinous tumours. No other significant associations were found between staining grade and the different variables under study. The variations in staining were not demonstrated to have any prognostic significance.
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Thirty-six patients with epithelial ovarian cancer, incompletely resected at primary laparotomy, were treated with one of two intensive cis-platinum-based combination chemotherapy regimens. The intention was to perform further surgical debulking (intervention debulking surgery) after three cycles in patients responding to treatment. Intervention debulking surgery was carried out in 28 of 36 patients (78%) at a median interval of 12.7 weeks from primary diagnosis. Omentectomy and total abdominal hysterectomy were the most commonly performed procedures at intervention debulking. As a result of such surgery, 16 of the 28 women (57%) were left with no macroscopic residual disease, five (18%) had less than 1 cm, four (14%) less than 2 cm residuum, and three (11%) remained with more extensive disease. Post-intervention debulking surgical complications were few, with a median postoperative hospital stay of 10 days and a median interval of 21 days from debulking surgery to resumption of chemotherapy. Neoadjuvant (cytoreductive) chemotherapy combined with early secondary surgical debulking is feasible, with little severe morbidity, and can leave a high proportion of patients free of macroscopic disease. The effect of such a program on patient survival is now being tested in a randomized study.
Human fetal macrophages expressing class II major histocompatibility complex (MHC) antigens have been isolated from the stroma of the chorionic plate of term placentas, using enzymatic digestion procedures, and enriched by Percoll density centrifugation. These cells are adherent, phagocytic and express Fc receptors for IgG. By rosetting with bovine erythrocytes coated with IgG, they can be enriched to 77-95% purity. Placental macrophages isolated in this way stimulate the proliferation of lymphocytes from unrelated donors in mixed-cell cultures, and act as accessory cells in oxidative mitogenesis. In a family study, placental macrophages stimulated proliferation of maternal and paternal lymphocytes but there was no evidence for either priming to, or suppression by, the fetal cells when the responses of lymphocytes from the mother and her HLA identical twin were compared. The possibility that these cells can protect the fetus from infection and/or stimulate the production of maternal anti-fetal HLA-antibodies is discussed.