A requiem for the cholecystokinin provocation test?
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Cholecystectomy↗
Biomedical subjects
S Campbell
Publications and source records attributed to S Campbell.
In vitro human decidual endothelial cell thromboxane secretion in preeclampsia is not abnormal.
OBJECTIVES: The aims of this study were to describe levels of thromboxane secretion by decidual endothelial cells from normal pregnancies and to determine whether decidual endothelial cell secretion of thromboxane, implicated in the causation of the hypertension and vasoconstriction of preeclampsia, is increased in this disorder. METHODS: We measured thromboxane generation by cultured decidual endothelial cells from 13 normal pregnancies (NDEC) and 13 pregnancies complicated by preeclampsia (PEDEC), compared with a control population of 6 normal human umbilical vein endothelial cells (HUVEC). Responses to stimulation by bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) were examined. MAIN OUTCOME MEASURES: Thromboxane B2 levels in supernatants of cultured endothelial cells. RESULTS: The level of secretion over 24 h in culture by NDEC [14 (7-26) pg/10(6) cells] was approximately 25% that of HUVEC [63 (49-70) pg/10(6) cells]. Levels achieved in response to all stimuli examined were consistently lower in NDEC than in HUVEC (p < 0.01). Proportional stimulation by LPS and TNF-alpha was comparable in HUVEC and NDEC, whereas NDEC displayed a greater increase (25-fold) than HUVEC (10-fold) in response to IL-1 beta (p < 0.01). There were no significant differences between decidual endothelial cells from normotensive and preeclamptic women in basal secretion of thromboxane or in responses to the stimuli examined. CONCLUSIONS: In vitro thromboxane secretion by decidual endothelial cells is lower than that of HUVEC, and responsiveness to specific stimuli may be quantitatively different. These findings emphasize the importance of examining endothelial cells from the involved maternal vascular bed if intrauterine vascular pathophysiological events are to be clarified. No significant differences were noted in decidual endothelial cell thromboxane secretion between normal and preeclamptic subjects.
Cells, Cultured↗
Leukocytes infiltrate the myometrium during human parturition: further evidence that labour is an inflammatory process.
Inflammatory mediators in the cervix, placenta and fetal membranes play a crucial role in human parturition. The aim of this study was to determine whether the upper and lower segments of the myometrium are infiltrated by inflammatory cells during pregnancy and parturition. Myometrial biopsies were obtained from non-pregnant women, and pregnant women at term before and after the onset of spontaneous labour. Subpopulations of inflammatory cells were identified using immunocytochemistry. The intercellular adhesion molecules, 1 and 2, platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and E-selectin were immunolocalized to investigate their involvement in leukocyte accumulation. Histological analysis demonstrated that inflammatory cells, predominantly neutrophils and macrophages, infiltrate human myometrium during spontaneous labour at term. The infiltrate is predominant in the lower uterine segment but is also present in the upper segment. Increased expression of E-selectin was found on the vascular endothelium of biopsies obtained during labour, suggesting a role for this molecule in the accumulation of leukocytes. These results suggest that inflammatory cell infiltration is part of the physiological mechanisms that occur in the myometrium during parturition. Further understanding of this process may suggest new strategies aimed at preventing preterm delivery.
Cell Adhesion Molecules↗
Implementation of a national guideline on prophylaxis of venous thromboembolism: a survey of acute services in Scotland. Thromboembolism Prevention Evaluation Study Group.
BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications for hospital patients in developed countries. In 1995, the Scottish Intercollegiate Guidelines Network (SIGN) published an evidence-based guideline to encourage the appropriate use of prophylaxis for DVT among hospitalised patients at risk. The guideline was widely distributed within the NHS in Scotland; however, it is not clear what actions trusts have taken to implement it. OBJECTIVE: To investigate the type and extent of DVT guideline implementation activities in acute trusts in Scotland. METHOD: A semi-structured telephone interview with senior clinical audit staff in those trusts with acute services in Scotland. RESULTS: Twenty-nine of the 30 trusts approached participated in the survey (97%). A range of responses to the guideline were reported, including development of local protocols (n = 20), audit of DVT prophylaxis (n = 19), patient specific reminders (n = 13) and provision of a specialist DVT adviser (n = 3). Overall, 25 of the trusts had undertaken guideline development and dissemination activities, and 17 were involved in more active guideline implementation strategies. CONCLUSIONS: The majority of acute trusts in Scotland have responded to the SIGN guideline, usually through the development of local protocols. Strategies to implement the guideline or local protocol are less common. Further guidance is needed on this in the next edition of the guideline.
Clinical Protocols↗
Risks of brain tumour following treatment for cancer in childhood: modification by genetic factors, radiotherapy and chemotherapy.
A cohort of 4,400 persons treated for various cancers of childhood in France and the UK was followed up over an extended period to assess risks of subsequent brain tumour in relation to the radiotherapy and chemotherapy that the children received for their first cancer. Elevated risks of subsequent brain tumours were associated with first central nervous system (CNS) tumour (two-sided p = 0.0002) and neurofibromatosis (two-sided p = 0.001). There was also elevated brain tumour risk (two-sided p = 0.003) associated with ionising radiation exposure, the risk being concentrated among benign and unspecified brain tumours. The radiation-related risk of benign and unspecified brain tumours was significantly higher than that of malignant brain tumours (two-sided p< or =0.05); there was no significant change of malignant brain tumour risk with ionising radiation dose (two-sided p > 0.2). In general, there were no strong associations between alkylating agent dose and brain tumour risk. The only significant association between brain tumour risk and alkylating agent dose was in relation to compounds used (bleomycin, chloraminophen) that are thought not to deliver substantial doses to the brain; the statistical significance of the trend with dose depended on a single case, and thus must be considered a weak result.
Adolescent↗
Identification of residues in the cysteine-rich domain of Raf-1 that control Ras binding and Raf-1 activity.
We have identified mutations in Raf-1 that increase binding to Ras. The mutations were identified making use of three mutant forms of Ras that have reduced Raf-1 binding (Winkler, D. G., Johnson, J. C., Cooper, J. A., and Vojtek, A. B. (1997) J. Biol. Chem. 272, 24402-24409). One mutation in Raf-1, N64L, suppresses the Ras mutant R41Q but not other Ras mutants, suggesting that this mutation structurally complements the Ras R41Q mutation. Missense substitutions of residues 143 and 144 in the Raf-1 cysteine-rich domain were isolated multiple times. These Raf-1 mutants, R143Q, R143W, and K144E, were general suppressors of three different Ras mutants and had increased interaction with non-mutant Ras. Each was slightly activated relative to wild-type Raf-1 in a transformation assay. In addition, two mutants, R143W and K144E, were active when tested for induction of germinal vesicle breakdown in Xenopus oocytes. Interestingly, all three cysteine-rich domain mutations reduced the ability of the Raf-1 N-terminal regulatory region to inhibit Xenopus oocyte germinal vesicle breakdown induced by the C-terminal catalytic region of Raf-1. We propose that a direct or indirect regulatory interaction between the N- and C-terminal regions of Raf-1 is reduced by the R143W, R143Q, and K144E mutations, thereby increasing access to the Ras-binding regions of Raf-1 and increasing Raf-1 activity.
14-3-3 Proteins↗
Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood.
Osteosarcoma is the most frequent second primary cancer occurring during the first 20 years following treatment for a solid cancer in childhood. Using a cohort study of children treated for a solid cancer, we investigated the incidence and etiology of osteosarcoma as a second malignant neoplasm after childhood cancer in a cohort and a case-control study. We analysed the relationship between the local dose of radiation and the risk of osteosarcoma, taking into account chemotherapy received. A cohort study of 4,400 3-year survivors of a first solid cancer during childhood diagnosed in France or the United Kingdom, between 1942 and 1986, revealed 32 subsequent osteosarcomas. In a nested case-control study, we matched 32 cases and 160 controls for sex, type of first cancer, age at first cancer and the duration of follow-up. Parameters studied were the incidence of osteosarcoma, the cumulative local dose of irradiation and the cumulative dose of chemotherapy received by cases and controls. The risk of a osteosarcoma was found to be a linear function of the local dose of radiation (excess relative risk per gray=1.8), and was found to increase with the number of moles of electrophilic agents per square meter but not with other drugs. No interaction was noted between radiotherapy and chemotherapy. Bilateral retinoblastoma, Ewing's sarcoma and soft tissue sarcoma were found to render patients susceptible to a higher risk of developing an osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance of patients who were treated during childhood for bilateral retinoblastoma, Ewing's sarcoma, soft tissue sarcoma, as well as other first cancer treated with radiotherapy plus high doses of chemotherapy, without focusing exclusively on the radiation field.
Adolescent↗
Diabetics on Metformin.
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Acidosis, Lactic↗
Serum vascular endothelial growth factor and Doppler blood flow velocities in in vitro fertilization: relevance to ovarian hyperstimulation syndrome and polycystic ovaries.
OBJECTIVE: To relate changes in serum and follicular fluid vascular endothelial growth factor (VEGF) concentrations to Doppler blood flow velocities within ovarian and uterine blood vessels during IVF cycles and to assess their relation to ovarian hyperstimulation syndrome (OHSS) and polycystic ovaries (PCO)/polycystic ovary syndrome (PCOS). DESIGN: Prospective descriptive study. SETTING: The London Women's Clinic. PATIENT(S): One hundred seven patients receiving a "long" stimulation protocol of IVF. INTERVENTION(S): Doppler blood flows were recorded in ovarian stromal and uterine arteries; serum VEGF was measured in the early follicular phase, after pituitary desensitization, on the day of hCG administration, on the day of oocyte retrieval, and on the day of ET. MAIN OUTCOME MEASURE(S): Serum and follicular fluid VEGF concentrations and Doppler blood flow measurements. RESULT(S): Serum VEGF concentrations rose after hCG administration. The rise was higher in women in whom OHSS developed. Women with PCO/PCOS had higher serum VEGF concentrations throughout the IVF cycle irrespective of whether OHSS developed. Follicular fluid VEGF concentrations were higher in women in whom OHSS developed and in women with PCO/PCOS. Doppler blood flow velocities in the ovarian blood vessels were higher in women in whom OHSS developed. Within ovarian and uterine blood vessels, blood flow velocities were higher in the early follicular phase and on the day of hCG administration in women with PCO/PCOS. A positive correlation was observed between the serum VEGF and E2 concentrations on the days of hCG administration and oocyte retrieval and between the serum VEGF concentration and Doppler blood flow velocities throughout the IVF cycle. CONCLUSION(S): Our results support the role of VEGF as a mediator of OHSS and establish a possible link between VEGF, OHSS, and PCO.
Adult↗
Comparison of transvaginal color Doppler imaging and color Doppler energy for assessment of intraovarian blood flow.
OBJECTIVE: To investigate any systematic differences in the analysis of blood flow velocity waveforms derived by color Doppler imaging and color Doppler energy examination of corpora lutea and adnexal tumors, to test whether the accuracy for diagnosing ovarian malignancy differs between end points derived by color Doppler imaging and color Doppler energy, and to compare the reproducibility of flow velocity waveform analysis obtained by both methods. METHODS: Fifty-six asymptomatic women with presumed corpora lutea and 67 women with known adnexal masses were included in the study. They all were examined using transvaginal sonography with color Doppler imaging and color Doppler energy. Pulsed Doppler sonography was used to obtain flow velocity waveforms to determine the pulsatility index (PI), resistance index (RI), peak systolic velocity, and time-averaged maximum velocity. The tumors were classified retrospectively according to histologic criteria. RESULTS: There were 52 women with benign, three with borderline, and 12 with malignant ovarian tumors. Repeated-measures analysis of variance revealed no systematic differences in the values of all four measurements performed under color Doppler imaging and color Doppler energy for all cases of corpora lutea and adnexal tumors (PI: P=.153, RI: P=.197, peak systolic velocity: P=.355, time-averaged maximum velocity: P=.159). All cases of borderline and malignant tumors had detectable pulsatile blood flow with color Doppler imaging and color Doppler energy. Forty-two (80.8%) of the benign tumors had flow detectable with color Doppler imaging, compared with 40 (76.9%) with color Doppler energy (P=.480). Analysis of receiver operating characteristic curves showed a marginal but nonsignificant improvement in diagnostic performance with color Doppler energy compared with color Doppler imaging for all four measurements (PI: P=.182, RI: P=.178, peak systolic velocity: P=.254, time-averaged maximum velocity: P=.238). The intraclass correlation coefficients for all four measurements were superior with color Doppler imaging compared with color Doppler energy. CONCLUSION: Flow velocity waveform analysis and diagnostic accuracy for ovarian malignancy are not significantly different between color Doppler imaging and color Doppler energy. Examinations with color Doppler imaging appear to be more reproducible than those with color Doppler energy.
Adult↗
Placental nitric oxide production and umbilical artery vascular impedance in early pregnancy.
OBJECTIVE: To evaluate whether the vasorelaxant molecule nitric oxide (NO) and its second messenger cyclic guanosine monophosphate (cGMP) modulate the reduction in resistance within the fetoplacental circulation that occurs during the first trimester of pregnancy. METHODS: We studied 27 women undergoing termination of pregnancy for psychosocial indications between 9 and 15 weeks' gestation. Each had ultrasound dating of the fetus and Doppler umbilical artery (UA) flow investigation immediately before the operation. Placental tissue was assayed for nitric oxide synthase (NOS) activity and cGMP content. RESULTS: Both UA pulsatility index (PI) and placental endothelial NOS activity decreased significantly with advancing gestation (r = -.52 and -.41, respectively). Umbilical PI correlated positively with endothelial NOS activity and cGMP level. Multiple linear regression analysis indicated that cGMP contributed most strongly to UA PI (P < .001). CONCLUSION: Our findings suggest somewhat paradoxically that NOS activity and cGMP levels are highest in the early gestations, when umbilical PI is also high, and decrease as umbilical PI decreases. Further studies are required to determine whether the predominant effect of NO is that of a vascular relaxant or a modulator of new villous vessel formation.
Blood Flow Velocity↗
Increasing complexity of Ras signal transduction: involvement of Rho family proteins.
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Amino Acid Sequence↗
Communication patterns between caregivers and their spouses with Alzheimer's disease: a case study.
The purpose of this study was to examine the style of communication that takes place between couples in their home environment in relationship to the abilities to the spouse with Alzheimer's disease (AD) and the amount of stress and burden experienced by the caregiver. Three styles of communication emerged: parallel, questioning, and direct. Caregivers engaging in parallel communications reported greater stress and time burden than any other caregivers. Nurses need to be observant of the communication patterns that exist between caregivers and their spouses with AD and help caregivers develop successful communicative strategies that enhance interactions with their spouses.
Adaptation, Psychological↗
Canadian-French, German and UK versions of the Child Health Questionnaire: methodology and preliminary item scaling results.
Using emerging international guidelines, stringent procedures were used to develop and evaluate Canadian-French, German and UK translations/adaptions of the 50 item, parent-completed Child Health Questionnaire (CHQ-PF50). Multitrait analysis was used to evaluate the convergent and discriminant validity of the hypothesized item sets across countries relative to the results obtained for a representative sample of children in the US. Cronbach's alpha coefficient was used to estimate the internal consistency reliability for each of the health scales. Floor and ceiling effects were also examined. Seventy-nine percent of all the item-scale correlations achieved acceptable internal consistency (0.40 or higher). The tests of the item convergent and discriminant validity were successful at least 87% of the time across all scales and countries. Equal item variance was observed 90% of the time across all countries. The reliability coefficients ranged from a low of 0.43 (parental time impact, Canadian English) to a high of 0.97 (physical functioning index, Canadian French) across all scales (median 0.80). Negligible floor effects were observed across countries. Noteworthy ceiling effects were observed, as expected, for the hypothesized physical scales (mean effect 73%). Conversely, fewer ceiling effects were observed for the psychosocial scales (range 3-17% behaviour-parental emotional impact). The item-scaling results obtained in these pilot studies support the psychometric properties of the American-English CHQ-PF50 and its respective translations.
Adolescent↗
Unexpected effect of a nitric oxide donor on uterine artery Doppler velocimetry in oligomenorrheic women with polycystic ovaries.
We compared uterine artery vascular responses following administration of the nitric oxide donor glyceryl trinitrate to ten women with oligomenorrhea and ultrasound evidence of polycystic ovaries with those of nine women with a normal menstrual cycle and ultrasonically normal ovaries. Mean arterial blood pressure, pulse rate and uterine artery flow velocity waveforms were recorded before and 60-75 min after glyceryl trinitrate patch application. The pulsatility index and resistance index were calculated to describe changes in impedance to flow in the uterine artery. Peak systolic and time-averaged velocities were also measured. Pretreatment median arterial pressure was higher in women with polycystic ovaries (90 mmHg) compared to those with regular cycles (80 mmHg) (p < 0.05). No differences were found in pulse rate and uterine artery blood flow indices between the two groups. After glyceryl trinitrate patch administration, there was no change in blood pressure or pulse rate in either group. In women with polycystic ovaries, there was an increase in uterine artery resistance index (0.93 to 1.00; p < 0.05) and pulsatility index (3.77 to 4.99; p < 0.05) and a decrease in peak systolic (36.8 to 32.3 cm/s; p < 0.05) and time-averaged maximum (8.5 to 5.0 cm/s; p < 0.05) velocities. Uterine artery Doppler parameters remained unchanged in women with normal cycles. Uterine artery vascular responses to the nitric oxide donor glyceryl trinitrate are different in women with normal cycles compared to oligomenorrheic women with polycystic ovaries. This may be relevant to an understanding of the pathophysiology underlying the higher risk of cardiovascular morbidity and mortality associated with polycystic ovarian syndrome.
Adult↗
Presentation of the Ian Donald Gold Medal to Lindsey Allan.
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Awards and Prizes↗
Blood flow changes in the ovarian and uterine arteries in women with polycystic ovary syndrome who respond to clomiphene citrate: correlation with serum hormone concentrations.
OBJECTIVE: Our purpose was to study the hemodynamic changes in the uterine and intraovarian vessels in women with polycystic ovary syndrome (PCOS) and to relate the vascular changes to hormonal indices. METHODS: Six women with a history of previous anovulatory cycles and/or oligomenorrhea and/or elevated serum luteinizing hormone concentrations in addition to polycystic ovaries underwent induction of ovulation with clomiphene citrate. Serial transvaginal ultrasonography was performed on menstrual cycle day 2, daily from the estimated day of ovulation minus 6, 6-hourly from the estimated day of ovulation minus 2 or when the mean follicular diameter was greater than 16 mm (whichever was earlier) until 6 h after follicular rupture, and once 7 days after follicular rupture. At each scan, uterine and intraovarian blood flow was assessed by transvaginal color Doppler ultrasound, and serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone were assessed by fluoroimmunoassay. RESULTS: All six women demonstrated ultrasonographic features of ovulation. Follicular peak systolic blood flow velocity (Vmax) and ovarian stromal Vmax in the dominant ovary increased during the follicular phase of the menstrual cycle and reached a peak at 36 and 42 h after the onset of the LH surge of 30.7 +/- 4.6 cm/s and 37.0 +/- 3.9 cm/s, respectively. There was no significant change in the ovarian stromal Vmax of the non-dominant ovary. There was no significant change in the pulsatility index (PI) in either the follicular or the ovarian stromal vessels during the menstrual cycle. The changes in follicular Vmax correlated significantly with changes in serum concentrations of FSH, LH and progesterone. Uterine artery time-averaged maximum velocity (TAMX) declined to its lowest levels at LH surge minus 6 days, and thereafter increased. In contrast, the PI increased during the follicular phase of the cycle, reaching a peak at LH surge minus 4 days, and thereafter declined. The changes in uterine artery PI correlated inversely with serum estradiol and serum progesterone concentrations. CONCLUSIONS: Women with PCOS have significant differences in intraovarian and uterine artery hemodynamics, both at the baseline ultrasound scan and during the clomiphene-induced menstrual cycle, compared with women with normal ovaries. The intraovarian and uterine artery vascular differences are likely to be due to a primary disorder within the polycystic ovary and their different hormonal status. Clomiphene citrate may have an effect on uterine artery blood flow.
Adult↗