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OBJECTIVE: To monitor the presence and persistence of high risk (HR) human papillomavirus (HPV) in cervical brushings from HIV infected women. METHODS: Prospective observational cohort study of HIV infected women. Women were enrolled from the cohort of 164 HIV infected women who attend the colposcopy clinic at the Edinburgh Regional Infectious Diseases Unit. A single cervical brush scrape was obtained from 39 women and two or more samples from 63 women who attended regularly at approximately 6 monthly intervals. HPV typing was carried out using a commercial hybrid capture assay (HCA). Details of antiretroviral therapy, cytological assessment, and histological evaluation were made available and the interrelation with HR-HPV detection analysed. RESULTS: Abnormal cervical cytology, particularly of low grade, was common in these HIV infected women. HR-HPV types were detected in 25% of the women with normal cytology, while over 80% of those with abnormal cytology of any grade were HR-HPV positive. Persistent HR-HPV, as defined by two or more consecutive HPV positive results, was common and found in 27/63 women from whom multiple samples were obtained. HR-HPV was detected at high levels whether or not patients were receiving antiretroviral therapy. Profound immunosuppression was not necessarily associated with progression of cervical disease and no cases of invasive cervical disease were seen. CONCLUSION: While mild dyskaryosis (low grade squamous intraepithelial lesion (LSIL)) and persistence of HR-HPV are common in HIV infected women in Edinburgh, regular cytological and colposcopic evaluation with appropriate intervention and treatment appears to limit the progression of cervical disease.

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This was an open Phase I study of i.p. matrix metalloproteinase inhibitor BB94 in patients with malignant ascites. The objective of the study was to determine the effect of increasing i.p. doses of BB94 with reference to the tolerance, safety, and pharmacokinetics of the compound. Twenty-three patients with malignant ascites had BB94 instilled into the peritoneal cavity after paracentesis. The compound was well tolerated; no serious adverse events were seen, and no specific toxicities were observed. High plasma concentrations were seen an hour after dosing, and BB94 was still present in the plasma at day 28 after treatment at levels in excess of the IC50 identified in preclinical studies. Five of the 23 patients neither reaccumulated ascites nor died up to 112 days after dosing. Seven patients died without reaccumulating ascites. Although the study was not designed to demonstrate clinical efficacy, the results were encouraging and support the further therapeutic evaluation of matrix metalloproteinase inhibitors in the management of malignant ascites.

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A case report of a woman with a history of breast carcinoma who presented with metastatic infiltration of uterine leiomyoma is described. The previously published literature on the subject is reviewed.

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The clinical and pathological findings of a case of diffuse leiomyomatosis of the uterus are described. The unique feature of this case is the extension of the disease process to the pelvic mesocolon. The diagnostic difficulties encountered in the histological assessment of smooth muscle tumors of the uterus are discussed.

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Foetal breathing movement (FBM) in utero has come to play an important role in foetal diagnosis. FBM may be monitored using real time ultrasound imaging of the foetus in utero. Foetal breathing activities can also be detected by monitoring maternal abdominal wall movement in the frequency range of 0.5-2.5 Hz. This paper presents a transducer which detects FBM non-invasively by monitoring maternal abdominal wall movements. Foetal heart sounds can also be monitored. The transducer presented uses piezo-electric film as the transducing medium. Results from preliminary clinical trials of prototype transducers on 10 patients are discussed.

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We examined the prognostic value of early serum CA125 assay in 58 patients with advanced epithelial ovarian cancer together with residual disease, age, tumour grade, performance status, and the presence of ascites or adhesions at primary surgery. CA125 was a highly significant predictor of both progression free and overall survival after the first cycle and throughout primary chemotherapy. After the first cycle, CA125 was by far the most significant predictor of progression free survival (P < 0.0005). At this time, CA125 was a highly significant predictor of survival (P < 0.005), but did not add to performance status (P < 0.001) in multivariate analysis. We were able to identify three statistically-distinct prognostic groups. Patients in the upper quartile, with CA125 levels greater than 450 U ml-1, had a very poor median survival of 7 months. Patients in the lower quartile, with CA125 levels less than 55 U ml-1 had a good median survival of 23 months. Those in the two interquartile groups, who had CA125 levels ranging from 58-221 U ml-1 and 228-434 U ml-1, had relatively intermediate median survival times of 16 months and 15 months respectively. Although CA125 levels provided significant prognostic information, in the majority of patients CA125 merely confirmed overall clinical impression.

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The association of endometrioid carcinoma of the ovary and primary carcinoma of the endometrium is well recognised. These tumours are often synchronous in occurrence. Oestrogen stimulation is often postulated as a significant factor in the development of the endometrial carcinoma in such cases. We describe the case of a patient who developed a mucinous endometrial carcinoma 18 years after initial bilateral ovariectomy. The aetiology and pathogenesis of the uterine tumour is discussed.

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80 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was assessed by second-look surgery. The objective response rate was 69% with 38% achieving a complete response for up to 55 months. The toxicity of this regimen was acceptable. Statistically, de-bulking or partial de-bulking had a significant beneficial effect on the likelihood of a complete response. The best survival figures were associated with maximum de-bulking. The combination of cisplatinum and prednimustine is a new and active regimen for operable advanced epithelial ovarian carcinoma.

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Fetal breathing movement (FBM) in utero may be an indicator of fetal health. This paper provides a second-by-second estimate of FBM rate. In the absence of a statistical model for the fetal breathing movement, block data structured autoregressive spectral estimation is used. The optimum tapered Burg algorithm provides a minimum variance breathing rate estimate from a short block of data. The data were recorded using a PVDF (PolyVinyliDeneFluoride) transducer which picks up maternal abdominal wall movements. A peak tracking algorithm is used to extract the fetal breathing rate. Results from these signals are presented in graphical form. Further analysis of the fetal breathing rate has revealed periodicities, similar to that observed in the fetal heart rate.

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Unpleasant constitutional side-effects such as fever, rigors and sweating are commonly associated with the administration of interferons [Billiau A, Burke D C, Morris A G (eds): Interferons: from Molecular Biopsy to Clinical Application, p. 225. London & New York, Cambridge University Press (1983)]. We report here on two patients with metastatic renal carcinoma in whom oral diazepam given prior to the administration of gamma interferon ablated sweating and rigors and reduced the fever. Such an observation has not been reported previously.

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Murine lymphoid cell lines and rat thymocytes treated in vitro with glucocorticoid hormones provide a convenient system for studying the nuclear changes in apoptosis. Morphologically the nucleolus disintegrates and chromatin undergoes an unusual generalized condensation. This is associated with excision of most of the nuclear DNA to short but well-organized chains of nucleosomes, apparently by an endogenous non-lysosomal nuclease. The process is dependent upon macromolecular synthesis and probably is mediated, at least remotely, by the classical steroid-receptor-gene activation pathway. A similar process of chromatin condensation and excision can be produced by the calcium-magnesium ionophore A23187. In other circumstances of 'programmed cell death', analogous chromatin condensation, excision and requirements for macromolecular synthesis have been documented.

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