Development of the European Colposcopy Core Curriculum: use of the Delphi technique.

The objective of this study was to develop a European competence-based colposcopy core curriculum using the Delphi technique. Thirty expert colposcopists from 21 countries participated. A four-round iterative questionnaire was used. Competencies were rated using a five-point Likert scale. Competences rated as 4 or more by at least 90% of the respondents were regarded as necessary for the core curriculum. Eighteen participants took part in all four rounds, and 27 were active in each of the last three rounds. Fifty-one core competences were selected from a list of 76 competences collated by the group as a whole. The majority (n = 44) of the selected core competences received a score of 4 or greater in each round. Overall, there was some evidence of increasing consensus but the individual shift in opinion was slight. The Delphi technique was an effective tool for obtaining an expert consensus and enabled group "ownership" of the identified core curriculum.     

Loss of heterozygosity at chromosome 9q22-31 is a frequent and early event in ovarian tumors

Loss of heterozygosity (LOH) studies in ovarian tumors, have highlighted the chromosomal regions at 9q22-31 and 9q32-34 as being potentially important in tumor development. We have investigated LOH at 9q22-31 in 85 patients with epithelial ovarian cancer, 15 with non-epithelial tumors and 16 with benign disease. Varying patterns of LOH were observed across the markers used between different tumors, the most common (71%) being interstitial discontinuous losses. LOH was frequent, and was detected at equally high levels in malignant (71%) and benign tumors (70%). LOH occurred in epithelial invasive tumors, borderline tumors, fibromas and dermoid tumors. In malignant epithelial tumors LOH at 9q22-31 was not significantly associated with patient clinical and pathological parameters; however, survival was 29 months at the 50th centile survival, in those women whose tumors displayed LOH compared with 60 months in women whose tumors retained heterozygosity. LOH at 9q22-31 was significantly associated with LOH at the p53 locus (p=0.02) and the ovarian suppressor locus at 3p21 (p=0.05). We conclude that the chromosome region at 9q22-31, flanked by the microsatellite markers D9S1796 and D9S53, is a frequent and early event in ovarian tumorigenesis. With the of extent of discontinuous LOH, high density deletion mapping of this region using LOH as a strategy to identify candidate genes may be problematic. However with the completion of the human genome sequencing project several candidate genes are identified.     

Longitudinal course of depression, fatigue, and quality of life in patients with high risk melanoma receiving adjuvant interferon

PURPOSE: Treatment of malignant melanoma with interferon-alpha has been associated with a variety of side effects ranging from fatigue to depression, and a concomitant impact on quality of life (QOL), in a variety of case reports and cross-sectional clinical trials. Few, if any, studies have been conducted with the express purpose of assessing the longitudinal course of depression, fatigue, and QOL before and during interferon therapy. DESCRIPTION OF STUDY: The current study reports on 16 patients who were assessed at 6 points in time: baseline, post high dose, and 1, 2, 3, and 6 months post high dose treatment with interferon-alpha with the Brief Symptom Inventory, Beck Depression Inventory, Revised Piper Fatigue Scale, and Functional Assessment of Cancer Therapy-Biological Response Modifiers. RESULTS: Results revealed consistent changes from baseline through 6 month assessment. Specifically, increased somatic complaints, depression, and fatigue were observed on the BSI, BDI, and RPFS, respectively. Additional reductions in QOL on the FACT-BRM were also identified. CLINICAL IMPLICATIONS: The findings suggest that IFN has a significant effect on QOL, but that it may be the somatic symptoms of fatigue that contribute to changes on measures of mood. Limiting the amount of fatigue and depression would appear to be significant if individuals are to successfully complete IFN therapy.     

Decreased tryptophan catabolism by placental indoleamine 2,3-dioxygenase in preeclampsia

OBJECTIVE: Tryptophan degradation and depletion resulting from activation of indoleamine 2,3-dioxygenase is characteristic of inflammatory reactions and may control their intensity. Normal third-trimester pregnancy is characterized by a maternal systemic inflammatory response, which is more intense in preeclampsia. Therefore, we studied tryptophan metabolism in pregnant women, with or without preeclampsia, as well as expression and function of placental indoleamine 2,3-dioxygenase. STUDY DESIGN: Plasma concentrations of tryptophan and kynurenine in women with preeclampsia, appropriately matched women with normal pregnancy, and healthy nonpregnant women were measured. Placental enzymatic activity and messenger RNA (mRNA) expression level of indoleamine 2,3-dioxygenase were determined from the same placental material. Peripheral blood mononuclear cell proliferation was determined in medium conditioned by prior culture with villous tissue. RESULTS: The plasma ratio of kynurenine to tryptophan, an in vivo index of enzyme activity, was significantly increased compared with nonpregnant controls in normal pregnancy but not in preeclampsia. The activity and mRNA expression level of indoleamine 2,3-dioxygenase in term placentas were significantly lower in preeclampsia. Medium conditioned by culture of villous tissue explants of preeclampsia was less effective in inhibiting peripheral blood mononuclear cell proliferation compared with that of normal pregnancy. CONCLUSION: These observations suggest that in preeclampsia, reduced placental indoleamine 2,3-dioxygenase activity (and relatively elevated plasma tryptophan) could cause dysregulation of the inflammatory response that is intrinsic to normal pregnancy. This may contribute to the pathogenesis of the maternal syndrome of preeclampsia.     

Abnormal iron parameters in the pregnancy syndrome preeclampsia

OBJECTIVE: Our purpose was to investigate iron status parameters in preeclampsia with a view to exploring their possible contribution to the etiology. STUDY DESIGN: In prepared serum samples from 40 preeclamptic women and matched pregnant control subjects at the John Radcliffe Hospital, Oxford, a number of iron status parameters were measured. Statistical analysis was by the Wilcoxon signed rank test and linear regression. RESULTS: Serum iron concentration, ferritin, and percent saturation of transferrin were significantly higher in the preeclamptic patients than in control subjects, whereas unsaturated iron-binding capacity and apotransferrin levels were significantly lower. No difference was found in hemopexin concentrations in the two groups. Gestational age at the time of sampling was correlated (positively) with only two parameters, total and unsaturated iron-binding capacity, but only in the preeclampsia group. Eighteen percent of preeclamptic subjects had percent transferrin saturation levels in the region associated with iron overload. CONCLUSION: Released iron species in preeclampsia may contribute to the etiology and will exacerbate lipid peroxidation and endothelial cell injury. Given the high prevalence of heterozygosity for hemochromatosis with the associated reduced ability to exclude ingested iron, it would seem inadvisable, in the absence of evidence of iron deficiency, to give iron supplements to pregnant women at high risk for preeclampsia.     

Endothelial cells and peripheral blood mononuclear cells are a potential source of extraplacental activin a in preeclampsia

An excessive systemic inflammatory response, involving endothelial cells and leukocytes, underlies the maternal symptoms of preeclampsia. Activin A is raised in preeclampsia, suggesting a possible involvement in its pathophysiology. The placenta is the main source of activin A in normal pregnancy. We investigated whether peripheral blood mononuclear cells (PBMCs) and endothelium, activated by proinflammatory stimuli, were a potential source of activin A in preeclampsia. Both endotoxin and TNFalpha stimulated activin A secretion by PBMCs from nonpregnant, preeclamptic, and matched normal pregnant women (P < 0.05). Pregnancy increased the responsiveness of PBMCs to endotoxin (P < 0.05), whereas only the preeclamptic group were significantly more responsive to TNFalpha (P < 0.05). Human umbilical vein endothelial cells secreted activin A spontaneously and in response to TNFalpha (P < 0.05), but recombinant IL-1beta and IL-6 had no significant effect over the 72-h culture period. Inhibin A and follistatin were undetectable (<2 pg/ml and < 20 pg/ml, respectively) in PBMCs and human umbilical vein endothelial cell culture media. These data suggest that PBMCs and endothelium, activated by TNFalpha, could be extraplacental sources of activin A in preeclampsia. The pathological significance of increased activin A in preeclampsia is unknown, although it may have a role in the mechanisms underlying endothelium dysfunction.