How to write a Case Report.
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Biomedical subjects
Publications and source records attributed to A B Maclean.
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To develop a new noninvasive technique to measure vulval blood flow changes during sexual arousal; 18 healthy volunteers between the age of 20 and 33 years were studied. Each subject underwent two experimental sessions at least 2 weeks apart to coincide with the proliferative and luteal phases of her menstrual cycle. An initial laser Doppler perfusion imaging (LDPI) scan of the vulva was performed. The subject was then given a chapter of erotic fiction to read and a repeat LDPI scan was performed immediately after. The percentage change in flux were calculated: the clitoral skin blood flow increased by 26.4% (P < 0.05), labial skin blood flow by 24.9% (P < 0.05) and the posterior fourchette skin blood flow by 35.3% (P < 0.05). LDPI can detect changes in vulval perfusion during the sexual arousal response and could be used to compare healthy subjects with female sexual dysfunction patients, as well as for assessing the benefits of any treatment for this condition.
BACKGROUND: Although uterine fibroids are very common, their pathogenesis and clinical behaviour are poorly understood. Since they may be prevalent in some families, we investigated whether such a prevalence was associated with distinctive clinical and molecular features. METHODS: A case-control questionnaire study of 300 multi-ethnic women with uterine fibroids at a London university hospital was undertaken, with review of case notes and immunohistochemical determination of vascular endothelial growth factor (VEGF-A) in fibroids. RESULTS: When compared with families with sporadic fibroids, familial prevalence of fibroids was associated with a higher incidence of abdominal swelling (59.1% versus 41.6%; P=0.037), menorrhagia (84.4% versus 51.9%; P=0.042), dysmenorrhoea (64.4% versus 46.3%; P=0.004), dyspareunia (43.2% versus 27.9%; P=0.012) and family history of cancers (52.3% versus 32.4%; P<0.01). The fibroids were also more multiple (mean +/- SEM: 7 +/- 0.86 versus 3 +/- 0.42; P<0.011) and strong VEGF-A expression in fibroids was more common in the familial group (64% versus 28%). Racial distribution was the same in both groups (blacks 49%, whites 33.4%, others 18.6%). CONCLUSIONS: Familial prevalence of uterine fibroids is associated with distinct clinical and molecular features that differ from those found when fibroids occur sporadically in families.
This pilot study investigated the use of the non-invasive cytospin monolayer technique in the diagnosis and screening of neoplastic and non-neoplastic vulval disease. Twenty-three patients (age range 34-86 years) attending a vulval disease clinic had brush cytology performed. The samples were prepared with a cytospin monolayer technique and the slides Papanicolaou-stained. Subsequent cytological interpretation and diagnosis were performed without knowledge of the clinical history and correlated with follow-up biopsy histopathology from each patient. Twenty-eight cytospin samples were analysed in total, of which 11 (39%) contained dyskaryotic cells which were assessed and a predicted VIN/AIN grade given. Ten of 11 samples (91%) reported as dyskaryotic had VIN/AIN on biopsy histology. One of 11 samples (9%) was reported as containing occasional squamous cells with borderline nuclear features and, although the corresponding biopsy did not show VIN, basal atypia was reported. One patient had features suggesting invasive carcinoma on cytology which was verified on subsequent biopsy. The 15 cases in which no dyskaryotic cells were identified did not show VIN or AIN on subsequent histology. Two cases were acellular and considered inadequate for cytological interpretation. The cytospin monolayer technique allows the diagnosis of neoplastic from non-neoplastic vulval disease. It is a quick, inexpensive and non-invasive method that may have a role in diagnosis, screening and surveillance of patients.
Although uterine leiomyomas constitute the commonest benign tumour in women, the regulation of their growth is poorly understood. It is believed that angiogenesis, the process by which new capillaries develop from pre-existing blood vessels, may be involved. We therefore investigated the expression of vascular endothelial growth factor-A (VEGF-A), a primary regulator of angiogenesis, in leiomyoma tissue and the adjacent myometrium in 36 pre-menopausal women undergoing hysterectomy for leiomyomas, with or without prior treatment with gonadotrophin-releasing hormone analogue (GnRHa). In 5 microm sections prepared from archival paraffin-wax blocks, VEGF-A was demonstrated by standard immunohistochemistry using a monoclonal antibody. VEGF-A was expressed in 14 of 18 (77.8%) leiomyoma sections from women without GnRHa pretreatment, and in 15 of 18 (83%) of those from women with prior treatment. VEGF-A expression in the adjacent myometrium was much lower, being noted in two of 18 (11.1%) sections from women without prior GnRHa treatment and in one of 18 (5.5%) sections from tissue that had been subject to prior down-regulation. Moreover, when VEGF-A expression was present, expression was strong in leiomyomas (> or =20 focal areas/cm(2)), but not in adjacent myometrium. The differential expression of VEGF-A antigen in leiomyomas compared with the adjacent myometrium indicates that local angiogenesis may be important in the development and growth of these tumours. GnRHa therapy does not appear to alter this pattern of VEGF-A expression.
OBJECTIVE: This study was undertaken to determine whether preoperative radioimmunoscintigraphy of complex ovarian masses with technetium Tc 99m MAb-170 (Tru-Scint AD; Biomira Inc, Edmonton, Alberta, Canada), a murine whole immunoglobulin G monoclonal antibody that has been found to have panadenocarcinoma affinity, would predict surgical findings. STUDY DESIGN: The age range of studied patients was 42 to 83 years (mean, 60.3 years). Planar computed tomographic imaging and single-photon emission computed tomographic imaging were performed at 15 minutes, 6 to 8 hours, and 18 to 24 hours after injection of 1000 MBq technetium Tc 99m MAb-170. Laparotomy was performed within 10 days. RESULTS: Eighteen patients had borderline or invasive ovarian cancers verified by histologic examination. All primary malignancies or deposits (including intrahepatic deposits) yielded positive results on radioimmunoscintigraphic imaging. Radioimmunoscintigraphy was able to identify serosal deposits not seen on computed tomographic or ultrasonographic scans. False-positive localization of the antibody was noted in 6 of the 9 patients with benign pathologic processes. CONCLUSION: It is possible to detect with technetium Tc 99m MAb-170 all patients who have cancer (including sites not seen on computed tomographic or ultrasonographic scan); however, the low specificity (33%) means that patients still require surgical verification of disease.
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Six patients with severe pre-eclampsia were found to have low central venous pressures. This was considered to be an indication that hypovolaemia was present, depsite concurrent generalized oedema. Treatment with sufficient intravenous saline and albumin, to restore the central venous pressure to normal, resulted in improved renal function and avoidance of permanent renal impairment in all cases. These observations support the view that diuretics should not be administered to patients with pre-eclampsia.
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Pregnancy-associated plasma protein-A was assayed in the blood of 347 women during pregnancy, using a new primary standard of PAPP-A as reference. The protein was assayed by antibody-antigen crossed electrophoresis with the lower limit of confident assay being 9.5 micrograms PAPP-A/ml (13 pmol/ml). PAPP-A was first detected at 14 weeks of gestation; by term it had risen to within the range 20 to 320 micrograms/ml. There was an indication that pregnancies involving a male baby had higher PAPP-A levels in blood than did those involving female babies. In 51 blood samples from 30 patients with gestational diabetes (taken between 28 weeks of pregnancy and term) there was no significant alteration in PAPP-A values compared with controls. In 35 blood samples from 15 patients with insulin-dependent diabetes, levels of PAPP-A were significantly lower than in controls or in gestational diabetes. In 43 blood samples from 35 patients with babies affected with intrauterine growth retardation (between 28 weeks and term), there was no significant difference in PAPP-A levels compared with controls. The effect of insulin on the blood levels of PAPP-A suggests that the concentration of PAPP-A is capable of altering significantly in response to certain physiological changes associated with the control of carbohydrate metabolism.
Abnormalities in the cell cycle are associated with tumorigenesis but have not yet been identified in squamous cell carcinoma (SCC) of the vulva or in adjacent vulvar lesions. The purpose of this study was to identify cell cycle protein expression (cyclin D1 and retinoblastoma protein [pRb]) in vulvar SCC and in adjacent potentially premalignant lesions: lichen sclerosis (LS), squamous cell hyperplasia (SH), and vulvar intraepithelial neoplasia (VIN). Using immunohistochemical techniques, 57 SCCs were analyzed with 19 adjacent areas showing LS, 13 showing SH, 11 VIN, and six normal epithelium. Fifty-one percent of SCCs showed abnormal cyclin D1 expression and 37% showed abnormal pRb. Abnormal cyclin D1 expression in the adjacent areas was as follows: 53% in LS, 31% in SH, 18% in VIN, and 0% in normal. Abnormal pRb expression was as follows: 42% in LS, 62% in SH, 46% in VIN, and 33% in normal. Only 10 lesions showed abnormal expression of both proteins. Abnormal expression of cyclin D1 in SCC was statistically significant compared with adjacent normal epithelium. In SCC lesions, abnormal cyclin D1 expression was associated with greater depth of invasion. Abnormal pRb in SCC was associated with poor tumor grade. Cyclin D1 and pRb are separately involved in the progression of vulvar cancer, and changes in the expression of these proteins may represent an early stage of malignant transformation in vulvar disease.
Microvessel density (MVD) in 92 paraffin sections of ovarian samples of different histologic subtypes was correlated with microvessel counts from 58 corresponding frozen sections. Anti-human von Willebrand factor antibody was used as an endothelial marker. MVD was performed in neovascular hotspots using a Quantimet 500+ Image Analyzer. The highest vessel density (HVD) and average vessel density (AVD) of three fields at the x 200 and x 400 magnification were recorded. There was a strong correlation between the HVD and AVD at the x 200 and x 400 magnifications when comparing fixed with frozen sections (correlation coefficients at x 200 for the HVD was 0.37, P = 0.005 and AVD was 0.30, P = 0.02; correlation coefficients at x 400 for the HVD was 0.38, P = 0.003 and AVD was 0.37, P = 0.004). In the fixed tissue, the HVD and AVD at both these magnifications were significantly greater in the group containing functional cysts; this was also the case for the frozen sections. These findings are consistent with the development of a microcirculation necessary for the growth and maturation of such cysts, and this appears to be greater than that in tumors. The good correlation between MVD in fixed and frozen sections suggests that such observations represent a true reflection of ovarian angiogenesis in both physiologic and pathologic states.
The location of the vulva has had limited technologic progress in the assessment of the skin microcirculation and its application to clinical practice. Our group previously demonstrated increased perfusion in vulvar cancer compared to adjacent uninvolved skin with the laser Doppler flowmetry (LDF). The LDF is severely limited by its low spatial resolution ( approximately 1 mm(2)) and pressure involved in positioning of the probe, which may affect value of the underlying tissue perfusion. Topographic perfusion mapping of the whole vulvar skin using LDF is also time consuming and is not clinically practical. We describe for the first time the application of the novel laser Doppler perfusion imager (LDPI) to map vulvar skin blood flow and give example in two cases with well-defined vulvar pathology-psoriasis and lichen sclerosus with invasive neoplasia-and discuss the potential of LDPI to study vulvar skin blood flow.