Urinary tract infection in pregnancy.
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Biomedical subjects
Publications and source records attributed to A B MacLean.
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Estimation of tumour proliferation may allow the design of individualised radiotherapy schedules to optimise response. This prospective study correlates the tumour proliferation rate of cervical carcinoma with response to conventional radiotherapy. The potential tumour cell doubling rate (Tpot) was estimated following flash labelling of the tumours in vivo using the DNA precursor, bromodeoxyuridine (BrdUrd); samples were analysed by flow cytometry. Tumour ploidy, DNA index and mitotic count were also assessed as was histological grade and type. Multiple biopsies from each tumour were obtained from 121 women. The median Tpot was 4.0 days, median S-phase duration 12.8 h and median adjusted labelling index 9.8%. Higher BrdUrd labelling was seen in patients who developed pelvic tumour recurrence following radiotherapy. This was the only biological/histological parameter with univariate and multivariate significance in relation to locoregional recurrence (P = 0.006 and P = 0.034 respectively). This study represents the first assessment of Tpot in relation to long-term response of cervical tumours treated by radiotherapy treatment. The association of high BrdUrd labelling and poor pelvic disease-free survival indicates the need for further research into the potential of radiotherapy schedule alteration to reflect tumour proliferation. The predictive value may be enhanced by combination with other biological parameters.
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.
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A set of polypeptides has previously been described as being immunoprecipitated from tumor cell lysates by the sera of tumor-bearing animals (TBS) or by antisera raised to herpes simplex virus type 2 (HSV-2)-infected cells. These polypeptides were not immunoprecipitated from control cells. The principal polypeptides detected of MW 200, 90 (U90 and L90), 40, and 32 kDa were increased by HSV-2 infection. This communication describes the purification of the 40-kDa protein and its identification by amino acid sequence analysis as being homologous to the mature form of mitochondrial aspartate amino transaminase (mAAT). Two different forms of mAAT were purified and sequenced. One form, of low abundance, was immunoprecipitated by TBS and corresponded to the 40-kDa protein immunoprecipitated from tumor, but not control, cell lysates. Western blotting of the 40-kDa protein immunoprecipitated by TBS showed that it was a form of mAAT found only in tumor cells. The other abundant form reacted in Western blots with antibody to mAAT and was clearly the constitutive enzyme, present in all cells. In general, mAAT was increased up to fourfold after infection with HSV-2, HSV-2 infection also increased mAAT enzyme activity. Northern blotting and quantitative PCR showed that mAAT was induced by HSV-2 at the level of transcription. The specific form of mAAT immunoprecipitated from tumor, but not control, cell lysates could have a role in tumorigenesis, could be a putative tumor cell marker, or could be a target for antitumor drugs. HSV-2 probably induces enzymes of glutamine metabolism because HSV-2 requires glutamine for growth, thus revealing potential new antiviral targets.
Over the last decade, laser-Doppler flowmetry has been used to measure perfusion in the skin. To date it has not been used on the lower genital tract, and we describe preliminary results of measurements taken on the vulva. We include results from a control population and describe two cases with premalignant or malignant changes in the vulva.
Pelvic pain syndrome, without an apparent organic cause, is a common gynaecological complaint. Investigations, including laparoscopy are frequently negative but ovarian venography has demonstrated that pelvic varices are a consistent finding in these patients. The aetiology of pelvic varices has been the subject of debate, but it has recently been suggested that the primary problem is venous reflux in dilated, incompetent ovarian veins. Surgical ligation of the ovarian veins has been used effectively in small series of patients with this condition. We report a patient with the clinical and radiological features of this syndrome in which treatment by bilateral ovarian venous embolization produced prolonged symptomatic relief.
The pre-treatment cell kinetics of 120 cervical tumours were assessed following the in vivo labelling with the thymidine analogue Bromodeoxyuridine (BrdUrd). In 89% both static and temporal kinetic parameters could be measured. Through the analysis of multiple biopsies from each tumour marked intra tumour heterogeneity was demonstrated. The median values for the most highly labelled sample analysed for each tumour were; S-phase duration (Ts) 12.1 h, BrdUrd labelling index (CLI) 9.5% and potential tumour doubling time 4.4 days. There was a significant elevation in CLI, but no difference in Ts, between tumour and non-neoplastic cervical tissue. There was a significant elevation in CLI, advanced stage and large size tumours. Although a significant elevation in CLI was found in aneuploid tumours this is likely to represent the systemic bias of the calculation methods, with no difference being seen between aneuploid and diploid tumours when BrdUrd labelling was measured with-out reference to the nuclei DNA content. The majority of these patients were treated with radiotherapy and cell kinetic data will be correlated with treatment response when adequate follow up has been achieved.
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OBJECTIVE: To determine the ability of a sensitive one step urine test to detect human chorionic gonadotrophin in women with suspected complications of early pregnancy. DESIGN: Test on women presenting to accident and emergency department with gynaecological problems over six months. Results were validated using a quantitative assay for human chorionic gonadotrophin in serum and urine. SETTING: Accident and emergency department and gynaecology wards of a university teaching hospital. SUBJECTS: 130 unselected women. MAIN OUTCOME MEASURES: Detection of human chorionic gonadotrophin by one step test, presence of ectopic pregnancy, and results of quantitative analysis of chorionic gonadotrophin in serum and urine. RESULTS: 79 women had a positive urine test result and 51 a negative result. All 12 women with ectopic pregnancy had a positive test result, although urinary concentration varied from 191 IU/l to 47,800 IU/l. Only one woman, who had a faintly positive result, was found not to be pregnant on subsequent examination. The sensitivity and negative predictive values of the urine test were 100% respectively. 33 women were sent home from the accident and emergency department with normal clinical findings after a negative urine test result. All these women had undetectable concentrations of chorionic gonadotrophin in matched samples of urine and serum. CONCLUSIONS: A simple, rapid one step test for chorionic gonadotrophin should be available for the initial evaluation of emergency gynaecological problems. The additional cost of the test is offset by not admitting those patients whose clinical findings are normal and who have a negative urine test result and by reducing the number of women requiring quantitative assays of chorionic gonadotrophin.
Expression of the oncogenes Ha-RAS, c-MYC, and ERB-2 was investigated with an automated image analysis system in 12 specimens of normal cervix, 10 of cervical intraepithelial neoplasia (CIN) grade 1, 24 of CIN 3, and 10 of invasive cancer of the cervix. There was amplification of all three oncogenes in CIN 3 and invasive cancer compared with normal cervix and CIN 1. The difference was most pronounced with an antibody to the RAS p21 protein, with no overlap between CIN 3 and the normal range. This method might be useful in screening for cervical neoplasia, and for the determination of which CIN lesions require treatment.
A total of 15 patients with residual ovarian cancer confined to the peritoneal cavity after first-line systemic chemotherapy were treated with triethylene-thiophosphoramide (thioTEPA) in a phase I study. A total of 50 courses of thioTEPA were given intraperitoneally in doses ranging from 30 to 80 mg/m2. The dose limiting toxicity was myelosuppression, which occurred at 80 mg/m2 and was frequently prolonged. Short-lived nausea and vomiting was easily controlled, and there was no local toxicity. Three patients remain free of disease progression at 6, 6 and 12 months. ThioTEPA concentrations were measured by gas chromatography. Peritoneal fluid concentrations declined rapidly in a first-order fashion, with a half-life of 0.96 +/- 0.1 h. A mean of 93% of the drug was absorbed during the 4-h dwell time. Peak plasma levels were achieved 30-60 min after drug instillation and were substantially lower than corresponding peritoneal levels. A pharmacokinetic advantage for intraperitoneal delivery was detected for peak drug concentration (24.9 +/- 8.5) and AUC (9.2 +/- 4.8). Based on this study, the recommended dose for intraperitoneal thioTEPA is 60 mg/m2 every 3-4 weeks. However, the rapid absorption of this drug from the peritoneum, secondary to thioTEPA's small molecular weight and lipophilic nature, suggests that it has only a limited role in intraperitoneal therapy.
A prospective observational study of postoperative infection after gynecologic surgery assessed the need for antibiotic prophylaxis with special reference to the urinary tract. Catheterization requirements in the postoperative period were compared with the development of urinary tract infection after excluding both preoperative and postoperative bacteriuria. Forty-six of 115 patients (40%) developed a urinary tract infection in the postoperative period. Furthermore, this was not clearly related to the need for postoperative catheterization. Significant wound and vaginal vault infections were uncommon, indicating that antibiotic prophylaxis should be directed specifically at the urinary tract.
A rat monoclonal antibody against human estrogen receptor (ER) was used to localize nuclear ER in frozen tissue sections with the peroxidase-antiperoxidase technique. Premenopausal and postmenopausal vaginal, vulvar and nongenital skin was examined. ER was demonstrated in some but not all of the nuclei of basal and suprabasal differentiated epithelial cells of the vagina. ER was seen in the fibroblasts and smooth muscle, but not in the vessel endothelium, of the underlying stroma. ER was demonstrated in epidermal keratinocytes and dermal fibroblasts of the vulva and perineum, hair and non-hair bearing, but at a much lower frequency than in the vagina. Specific ER staining was not detected in the majority of skin specimens for extragenital sites. These findings have implications for the hormonal regulation of the vulva and for the use of estrogen cream in managing vulvar conditions.
There is strong circumstantial evidence that human papillomavirus is a cofactor in the development of cervical neoplasia. Systemic immunosuppression has also been implicated. A study was therefore carried out examining the relation between subtypes of human papillomavirus and local immunocompetent cells in the cervix. Colposcopically directed punch biopsy specimens were taken from normal cervix and from histologically proved cervical intraepithelial neoplasia for immunohistochemical studies. Human papillomavirus genome probing was performed on the abnormal specimens. A relation was apparent between decreased Langerhans' cells and moderate to high copy numbers of human papillomavirus type 16. The reduction in Langerhans' cells was significant for human papillomavirus type 18 even at low copy numbers. Conversely, the absence of human papillomavirus was associated with increased numbers of Langerhans' cells in cervical intraepithelial neoplasia. These findings suggest that the proposed oncogenic potential of human papillomavirus type 16 and human papillomavirus type 18 in particular may be mediated by a specific effect on the afferent limb of the immune response.
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Some patients with histologically proven residual cervical intraepithelial neoplasia after laser ablation have false negative cytology. The explanation for this is not known, but there was no evidence of buried lesions. Follow-up of all patients treated by selective ablation is necessary. Cytology alone is inadequate and careful, accurate pre- and posttherapy colposcopy is essential.