Informed decision making for cancer screening--not all of the ethical issues have been considered...still.
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Decision Making↗
Biomedical subjects
A Y Warren
Publications and source records attributed to A Y Warren.
Vascular endothelial growth factor is a chemoattractant for trophoblast cells.
A role for angiogenic growth factors in trophoblast invasion has been postulated. Directional motility (chemotaxis) is an important function of trophoblast cells. We have previously shown that vascular endothelial growth factor (VEGF) increases the random movement of trophoblast cells although placental growth factor (PlGF) has no effect. Heparin inhibited this effect of VEGF. Motility of trophoblast cells has been proposed to be mediated by a nitric oxide (NO) pathway. We hypothesized that VEGF but not PlGF would be chemotactic for trophoblast cells. Chemotaxis of a first trimester extravillous trophoblast cell line, SGHPL-4, and primary isolates of first trimester and term trophoblast cells was measured using a Boyden chamber. Initial experiments to optimize the time of the experiment and identify a positive control were performed. Subsequent experiments ran for 20 h, used 0.5 per cent FBS or 10 ng/ml PDGF as negative and positive controls and were performed in triplicate. VEGF (1, 10 and 100 ng/ml+/-1 microg/ml heparin or +/-100 microM L-NAME) and PlGF (1, 10, 100 ng/ml) were tested. The chamber was placed in a 5 per cent CO(2) in air, 37 degrees C incubator. The number of cells in the lower chamber were counted. There was a dose dependent increase in chemotactic motility of the SGHPL-4 cell line and term trophoblast cells in response to VEGF. PlGF had no effect on the movement of the first trimester trophoblast cell line but did increase the motility of the term trophoblast cells in a dose dependent manner. Heparin increased the cellular motility of both cell types alone. It also further enhanced the chemoactivity of VEGF on the term trophoblast cells but not the cell line. L-NAME did not affect the VEGF-stimulated motility of the first trimester cell line. However, in the term trophoblast cells L-NAME increased the directional cellular motility in the absence of, or in the presence of low concentrations of VEGF. In conclusion, the first trimester and term trophoblast cells appeared to respond differently to the various factors tested in the present study that may reflect differential cellular function as gestation progresses.
Adult↗
Characterization of small arteries isolated from the human placental chorionic plate.
Despite the essential role of the placenta in pregnancy, the control of the blood flow within the fetoplacental circulation is poorly understood. A handful of myography studies have directly assessed the role of vasoactive agonists in fetoplacental vasculature contractility but have used a range of steady-state conditions. Our aim, therefore, was to determine the optimal vessel diameter and oxygen tension to assess vascular function in small arteries isolated from the chorionic plate of normal term placentae. Biopsies were obtained from term placentae from uncomplicated pregnancies. Small arteries were dissected from the chorionic plate, mounted onto a wire myograph in HCO3(-) -buffered physiological salt solution at 37 degrees C and equilibrated for 20 min. Two methods for normalization of the optimal length/diameter for contractility of chorionic plate small arteries were assessed. Both classical normalization (CN) and length-tension curve (LTC) methods produced similar data. These data were agonist-independent. Data for CN and LTC were unaffected but maximal force generation (for U46619) was decreased in reduced oxygen tensions. Using conditions for optimal tension production in chorionic plate small arteries the thromboxane-mimetic U46619 produced the greatest and most reproducible constrictive effect. Relaxations were only achieved with endothelial-independent agonists (sodium nitroprusside and papaverine).
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Re "ABC2"; several paces forward but a big leap back for cervical cancer audit.
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Female↗
Problems with audit in cervical cytology.
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Cervix Uteri↗
Relationship between myometrial resistance artery behavior and circulating lipid composition.
OBJECTIVES: The study investigated whether an inducible alteration in endothelium-dependent relaxation in myometrial vessels could be correlated with plasma lipid composition. STUDY DESIGN: Myometrial resistance vessels were obtained from 10 women with normal pregnancy undergoing elective cesarean delivery. Paired vessels were incubated with plasma samples from patients with preeclampsia or from women with normal pregnancy and mounted on a wire myograph. After contraction with vasopressin, the degree of relaxation in response to bradykinin was observed. Plasma samples were assayed for cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B. RESULTS: A significant reduction in endothelium-dependent relaxation with respect to control values was observed in vessels incubated in plasma samples from patients with preeclampsia (P =.0001). Although no significant difference was noted between the lipid profiles of the 2 subgroups, a significant correlation was found between the vessel relaxation and the plasma content of apolipoprotein A1 (R2 = 0.36, P = .025). CONCLUSION: Plasma samples from women with pregnancies complicated by preeclampsia are capable of altering endothelium-dependent myometrial vessel relaxation. A significant relationship between the apolipoprotein A1 concentration and endothelial behavior supports the suggestion that aberrant lipid metabolism may be involved in the endothelial dysfunction characteristic of preeclampsia.
Adult↗
Tumoral calcinosis in the premaxillary region.
Tumoral calcinosis, an uncommon pathologic condition that manifests itself in many forms, has rarely been described in the craniofacial region. This report describes a case of tumoral calcinosis affecting the premaxillary region.
Aged↗
Mechanisms of endothelium-dependent relaxation in myometrial resistance vessels and their alteration in preeclampsia.
OBJECTIVE: To investigate the importance of prostacyclin and nitric oxide synthesis in endothelium-dependent relaxation in myometrial resistance vessels, and to test the hypothesis that a deficiency in nitric oxide synthesis contributes to the known alterations in endothelial function in preeclampsia. METHODS: Thirty-six women with normal pregnancies and 14 with preeclampsia had the myometrium biopsied at cesarean section. Resistance arteries were dissected and mounted on a wire myograph. After preconstriction with vasopressin, vessels were treated cumulatively with bradykinin. The process was repeated in the presence of indomethacin and then indomethacin and NG-monomethyl-L-arginine (L-NMMA). RESULTS: The vessels from women with normal pregnancies showed endothelium-dependent relaxation to bradykinin which was not significantly altered by the presence of indomethacin. The addition of L-NMMA significantly, but only partially, reduced the relaxation to bradykinin in the presence of indomethacin (p = 0.03). The vessels from women with preeclampsia showed markedly reduced relaxation to bradykinin (p < 0.0001), as compared to vessels from normal pregnant women. Relaxation of vessels from women with preeclampsia was increased by the addition of indomethacin (p = 0.03) but was virtually eradicated by the presence of L-NMMA. CONCLUSIONS: Eicosanoid synthesis plays little part in the relaxation of normal pregnant myometrial vessels to bradykinin. Nitric oxide synthesis mediates part but not all of the endothelium-dependent relaxation. In preeclampsia, relaxation to bradykinin is reduced; inhibition of eicosanoid synthesis allows increased relaxation, and nitric oxide synthesis appears to mediate a greater proportion of the relaxation than in normal pregnant women.
Adult↗
Achievable laboratory standards; a review of cytology of 99 women with cervical cancer.
The Working Party guidelines are a significant advance in the audit of the National Health Service Cervical Screening Programme (NHSCSP), the priority of which is to reduce mortality and morbidity from cervical cancer. This study was undertaken to apply the guidance on review of screening history to a series of 99 women with invasive cervical cancer diagnosed in one centre during a 9 year period. The majority (approx. 64%) of these women had not been screened within the 5 years preceding diagnosis, 25% had negative, inadequate or abnormal smears and 6% had previous treatment for cervical intraepithelial neoplasia (CIN). In four patients diagnosis was delayed. No standards are yet available to test the results of this series of women. Cervical cancer is relatively uncommon, and for data to be aggregated and compared across the UK, it is important that strict criteria are developed and applied to ensure that recruitment to the Working Party categories is uniform and not open to local interpretation. Full review and documentation of screening history should be mandatory for all women who develop cervical cancer.
Adenocarcinoma↗
Plasma from pre-eclamptic women and functional change in myometrial resistance arteries.
This study assesses the ability of plasma from women with pre-eclampsia to induce altered endothelial function in myometrial resistance vessels from normotensive women. Vessels from normotensive pregnant women (n = 7) were incubated with plasma from other pregnant women who were normotensive (n = 6) or had pre-eclampsia (n = 7). A wire myograph was used to test the endothelium-dependent relaxatory response to bradykinin of preconstricted vessels. The relaxation in vessels incubated with plasma from women with pre-eclampsia was markedly less than in vessels incubated with plasma from normotensive pregnant women (P = 0.039). This supports the theory that a plasma-borne factor contributes to the endothelial changes seen in pre-eclampsia.
Arteries↗
Loss of endothelium-dependent relaxation in myometrial resistance arteries in pre-eclampsia.
OBJECTIVE: To measure endothelium-dependent relaxation in myometrial resistance arteries and to compare this parameter in nonpregnant and normotensive pregnant women and those with pregnancies complicated by pre-eclampsia. DESIGN: A prospective study. SETTING: Nottingham City Hospital. SAMPLE: Thirty-seven nonpregnant women undergoing hysterectomy and 51 pregnant women undergoing caesarean section, of whom there were 39 normotensive and 12 with pre-eclampsia. METHODS: Resistance arteries, dissected from myometrial biopsies, were mounted on a wire myograph and preconstricted with vasopressin then subjected to incremental doses of bradykinin. RESULTS: Endothelium-dependent relaxation to bradykinin was seen in the vessels of nonpregnant and normotensive pregnant women. Markedly reduced endothelium-dependent relaxation was found in the myometrial arteries from women with pre-eclampsia when compared with both nonpregnant (P < 0.0001) and normotensive pregnant (P < 0.0001) women. CONCLUSION: A significant loss of endothelium-dependent relaxation in myometrial resistance arteries in pre-eclampsia may contribute to the altered vasoreactivity seen in pre-eclampsia, and particularly to the decreased placental perfusion and fetal growth retardation commonly associated with this condition.
Adult↗
A comparison of endothelium-dependent relaxation in omental and myometrial resistance arteries in pregnant and nonpregnant women.
OBJECTIVES: The study aimed to compare endothelium-dependent relaxation in the resistance arteries of the uterine vascular bed by use of a systemic comparison and to investigate the role of the endothelium in adaptation to pregnancy in these vascular beds. STUDY DESIGN: Myometrial and omental resistance arteries were collected from 22 normotensive pregnant women and 27 nonpregnant women of reproductive age. On a wire myograph and preconstricted with vasopressin, the arteries were relaxed with the endothelium-dependent vasodilator bradykinin. RESULTS: The omental arteries showed a consistently greater endothelium-dependent relaxation than the myometrial arteries, both in the nonpregnant state (p < 0.0001) and in pregnancy (p = 0.008); pregnancy did not significantly alter this relaxation in arteries from either the myometrial (p = 0.2075) or omental (p = 0.372) vascular beds. CONCLUSIONS: The endothelium-dependent relaxation to bradykinin is less in myometrial resistance arteries than in omental resistance arteries. There appears to be no intrinsic difference between vessels from nonpregnant and pregnant women in endothelium-dependent response to bradykinin.
Adolescent↗
Effect of the vascular endothelium on norepinephrine-induced contractions in uterine radial arteries from the nonpregnant and pregnant human uterus.
OBJECTIVE: Our purpose was to investigate the role of the endothelium in the human uterine arterial response to norepinephrine in the nonpregnant and pregnant states. STUDY DESIGN: Tissue was obtained from six pregnant and six nonpregnant women undergoing cesarean section or hysterectomy. Uterine radial arteries were isolated and subjected to norepinephrine dose-response curves with and without intact endothelium. RESULTS: Responses were obtained over a dose range of 10(-8) to 10(-4) norepinephrine. Initially there was no difference between vessels from pregnant and nonpregnant patients, but removal of the endothelium significantly increased the response in vessels from pregnant women. Addition of nitro-L-arginine methyl ester when the endothelium was intact did not alter the dose-response curves. CONCLUSIONS: In pregnancy human uterine radial arteries are more sensitive to norepinephrine than during the nonpregnant state. This increase is countered by an endothelium-derived relaxing factor. The factor is unlikely to be nitric oxide.
Arginine↗
Mast cell numbers in melanocytic naevi and cutaneous neurofibromas.
This study aimed to determine the diagnostic utility of mast cell densities in distinguishing neurotised ("neural") melanocytic naevi from neurofibromas. Three groups of lesions were studied: neurofibromas, neural naevi, and naevi showing no neural change (control naevi). A Giemsa stain was used to demonstrate mast cells. The median mast cell density in the neurotised naevus group was significantly higher (p < 0.005) than that of both the neurofibroma and control naevus groups, but the distributions of the individual density counts overlapped considerably. The sensitivity and specificity of the mast cell density as a potential discriminator between neurotised naevi and neurofibromas, determined in relation to the optimal discrimination value obtained using Bayes' minimum cost decision rule, were low. It is concluded that mast cell density on its own is of little use as a classification tool but could be of value in the context of a multivariate decision rule.
Adolescent↗
Production of active and acid-activated renin by cultured explants of human fetal tissues.
Various fetal tissues with gestational ages that ranged from 6 to 22 weeks were cultured as explants, and the culture media were examined for the production of both active and acid-activated renin. Media from cultures of fetal kidney, both the male and female genital tracts, and umbilical cord vessels were found to contain large quantities of active and acid-activated renin. Consistent differences in the production patterns of renin were found between the tissues, which may reflect the different potentials of the tissues to produce renin in vivo.
Culture Media↗
Generation of angiotensin I by human chorion-decidua in vitro.
An angiotensin I-like substance has been detected in media after incubation of human chorion-decidua in vitro. The substance was identified as angiotensin I by gel filtration, ion exchange chromatography, and a specific antiserum to angiotensin I. The presence of angiotensin I in these incubates indicates that renin substrate may be either stored or synthesized by the tissue. The levels of angiotensin I produced during incubation were greater than could be explained by the action of renin on plasma substrate since the major part of the chorion-decidua is avascular. Previously chorion-decidua has been shown to contain large amounts of renin and to be capable of synthesizing both active and inactive forms of the enzyme in vitro; however, renin substrate has not been described in this tissue.
Angiotensin I↗
Generation of angiotensin I by tissues of the human female genital tract.
Tissues from the fetoplacental unit were incubated in medium E 199 at 0 degrees C and following removal of the tissue were incubated at 37 degrees C. Compared to control tissues held at 0 degrees C, large quantities of angiotensin I, measured by means of specific radioimmunoassay, were detected in the media from both amnion and chorion-decidua while only small amounts were found in the media from placenta and umbilical cord. Following prior incubation with antirenin, the generation of angiotensin I was abolished in all tissues. These results indicate that both renin and its substrate are released into the media during incubation at 0 degrees C and suggest the existence of a locally functioning renin-angiotensin system in certain tissues of the human female genital tract.
Amnion↗