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Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 181 records · Page 10Linked to original sources

Stuck twin syndrome without signs of twin-to-twin transfusion.

Twin-to-twin transfusion syndrome represents a dilemma for both diagnosis and management. It has recently been suggested that a difference in contrast on B-mode ultrasound between the placentas is pathognomonic for the syndrome. We describe a case of monochorionic diamniotic twins with normal growth in one twin, the other showing features of stuck twin syndrome. In this case, although the contrast difference between the placentas was marked, twin-to-twin transfusion syndrome was ruled out, rendering this sign unreliable for diagnosis. Furthermore, evaluation of the stuck twin showed excessive adrenal artery flow, a feature that has been described in connection with poor antenatal and neonatal outcome. In this case, serial Doppler ultrasound evaluation of both fetuses enabled optimal timing of delivery.

Adrenal Glands↗

Objective and subjective assessment of abnormal uterine artery Doppler flow velocity waveforms.

OBJECTIVE: Abnormal uterine artery Doppler waveforms in the second trimester of pregnancy can predict adverse outcome. The presence of a diastolic notch is a better predictor than measurement of impedance indices. A notch has generally been assessed subjectively, which has raised questions as to the reproducibility of the method. The aim of this study was to compare subjective and objective assessments of 50 abnormal waveforms. DESIGN: This was a retrospective study of 50 abnormal uterine artery waveforms collected during a previous screening study. Subjective and objective assessments were compared and related to adverse outcomes. Five impedance indices incorporating a measurement of the diastolic notch were compared. Three indices predictive of adverse outcome were compared to subjective assessment. RESULTS: There was good agreement between experienced operators in their subjective assessment of uterine artery waveforms. Adverse outcome was predicted by only moderately or severely abnormal waveforms. Three impedance indices predictive of adverse outcome were the pulsatility index (PI), A/C and (D - C)/B (where A is the peak systolic, D is the maximum diastolic and B is the end-diastolic frequency, and C is the nadir of the notch). The cut-off values combining the highest sensitivity for the lowest false-positive rate were 1.5 for PI, 3.0 for A/C and 0.15 for (D - C)/B. A PI of 1.5 had the highest sensitivity (100%) and positive predictive value (55%) for adverse outcome in this preselected group. These three indices were compared to subjective assessment using the kappa index and the (D - C)/B ratio had the closest agreement, although all three indices showed at least moderate agreement. The cut-off values of 1.5, 3.0 and 0.15 for PI, A/C and (D - C)/B, respectively appear to differentiate between mildly abnormal waveforms and moderately/severely abnormal waveforms. CONCLUSION: Objective assessment of uterine artery waveforms using cut-off values of PI, A/C and (D - C)/B provides an estimation similar to that provided by subjective assessment by an experienced operator. These ratios will now need to be used prospectively in an unselected population to compare their screening properties.

Arteries↗

The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial.

OBJECTIVES: Pre-eclampsia continues to be a major cause of maternal and perinatal mortality. A disorder of the nitric oxide system is implicated in the pathogenesis of this condition and preliminary studies have suggested a possible therapeutic role for nitric oxide donors in women with established pre-eclampsia. The aim of this study was to determine whether pre-eclampsia and its complications could be prevented by the long-term use of nitric oxide donors in a group of women identified to be at risk on the basis of abnormal uterine artery Doppler measurements. STUDY DESIGN: We enrolled 40 healthy normotensive women at high risk of pre-eclampsia selected on the basis of abnormal uterine artery Doppler waveforms at 24-26 weeks of gestation. Women were randomly allocated to receive transdermal glyceryl trinitrate 5 mg-patches or equivalent placebo patches in a double-blind randomized study. The primary outcome measures were pre-eclampsia, fetal growth restriction, preterm delivery or small for gestational age/fetal growth restriction rates. Patches were worn daily from recruitment for 10 weeks or until delivery. RESULTS: The primary outcomes were not significantly different in the placebo compared to the glyceryl trinitrate group. However, survival analysis of adverse events with gestation in both groups showed a significantly reduced risk of an adverse event in the glyceryl trinitrate group (p = 0.004), equating to a 73% reduction in hazard. There was no difference in maternal systolic and diastolic blood pressure, mean uterine artery resistance index and fetal umbilical and middle cerebral artery pulsatility indices between the groups. CONCLUSIONS: Low-dose prophylactic transdermal glyceryl trinitrate commenced late in the second trimester did not reduce the incidence of pre-eclampsia, preterm delivery or fetal growth restriction, but may increase the likelihood of a complication-free pregnancy. Transdermal glyceryl trinitrate (5 mg/day) did not affect maternal cardiovascular, uterine artery or fetal arterial Doppler parameters.

Administration, Cutaneous↗

The role of color Doppler imaging of the uterine arteries at 20 weeks' gestation in stratifying antenatal care.

OBJECTIVE: To determine the value of one-stop color Doppler imaging of the uterine arteries at the time of the 20-week anomaly scan, to select women at risk of developing pre-eclampsia and intrauterine growth restriction (IUGR). PATIENTS AND METHODS: A total of 1022 unselected women had color Doppler imaging of both uterine arteries at the time of their dating/anomaly scan (19-21 weeks' gestation). The presence or absence of notching of the flow velocity waveform (FVW) was noted, and the resistance index (RI) was measured. The main outcome measures were pre-eclampsia, birth weight, placental abruption and stillbirth. RESULTS: The outcome in 946 women (92.6%) was available for analysis. Of these, 216 (23%) had abnormal uterine artery Doppler studies, 117 (12.4%) with bilateral (right and left FVW) notches; 21 (2.2%) women developed pre-eclampsia, and 57 (6.0%) neonates were small for gestational age (SGA; < 5th centile), at birth. For women with bilateral notches the odds ratio (OR) for developing pre-eclampsia was 12.8 (95% confidence interval (CI) 5.3-30.8), and 52.6 (95% CI 6.4-430.1) for pre-eclampsia requiring delivery before 37 weeks' gestation. If the uterine artery Doppler studies were normal, the odds ratio for developing pre-eclampsia was 0.11 (95% CI 0.04-0.28), and 0.3 (95% CI 0.17-0.51) for the delivery of an SGA baby less than the 5th centile. In women with bilateral notches with mean RI greater than 0.55, the positive predictive value for the main outcome measures was 46%. CONCLUSION: Women with normal uterine artery color/pulsed Doppler studies at 20 weeks' gestation constitute a group that have a low risk of developing obstetric complications related to uteroplacental insufficiency. Women with high resistance in both uterine arteries (bilateral notches) have an increased risk of the subsequent development of such complications, in particular those requiring delivery before term. The addition of color Doppler imaging of the uterine arteries at the time of the routine 20-week dating/anomaly scan may be of use in determining the type and level of antenatal care that is offered to women.

Arteries↗

The significance of choroid plexus cysts in an unselected population: results of a multicenter study.

OBJECTIVES: Choroid plexus cysts are commonly found at the time of a routine second-trimester scan, but there is much debate as to their clinical significance. The aims of this study were to define the incidence of choroid plexus cysts in an unselected population and describe their association with aneuploidy. DESIGN: This was a prospective, observational multicenter study. SUBJECTS: Subjects were all fetuses found to have choroid plexus cysts with a maximum diameter of 3 mm or greater and who were between 14 and 24 weeks' gestation when scanned in the routine ultrasound department at any of the 13 participating hospitals. RESULTS: There were 658 fetuses with choroid plexus cysts in a total of 101,600 births. The overall incidence of aneuploidy was 2.1%, but in fetuses with isolated choroid plexus cysts the incidence of proven aneuploidy was 0.5% (95% confidence interval (CI), 0.1-1.4%). If age is taken into consideration, then the incidence of aneuploidy in fetuses with isolated choroid plexus cysts where the mother is under the age of 36 years was 0.36% (95% CI, 0.04-1.3%), and 2.4% (95% CI, 0.06-12.6%) in older women. CONCLUSIONS: We conclude that the presence of choroid plexus cysts increases the risk for aneuploidy, mainly trisomy 18. In the majority of cases, the final risk will remain small, but will increase as maternal age increases.

Aneuploidy↗

A strategy for reducing the mortality rate from vasa previa using transvaginal sonography with color Doppler.

Vasa previa is a cause of sudden unanticipated fetal death, with a fetal mortality of 33-100%. Transvaginal sonography (TVS) and color Doppler may aid in making the diagnosis antenatally, allowing elective Cesarean delivery, thereby avoiding fetal death from exsanguination which would occur if the membranes were allowed to rupture in labor. Whilst it is not feasible to screen all pregnant women for vasa previa, antenatal examination with TVS and color Doppler of women at risk, specifically those with low-lying placentas, bi-lobed, multi-lobed and succenturiate-lobed placentas, multiple pregnancies and pregnancies resulting from in vitro fertilization may lead to antenatal diagnosis of the condition. We present the last three cases of vasa previa to have occurred in our institution, two of which were diagnosed antenatally using TVS and color Doppler. In all three cases, routine 20-week obstetric sonography revealed low-lying placentas; in only one of these did the placenta remain low at term. A low-lying placenta at 20 weeks may be a risk factor for vasa previa; we suggest that further studies be carried out to ascertain this. Judicious use of TVS and color Doppler in women considered at risk of vasa previa may help to reduce the mortality from this condition.

Cesarean Section↗

Serum vascular endothelial growth factor concentrations and ovarian stromal blood flow are increased in women with polycystic ovaries.

The aim of this study was to determine basal serum vascular endothelial growth factor (VEGF) concentrations and Doppler blood flow changes within the ovarian stroma of women with polycystic ovaries (PCO) and women with normal ovaries. Pulsed and colour Doppler blood flows within the ovarian stroma were recorded, and serum VEGF concentrations measured, in the early follicular phase (days 2-3 of a menstrual cycle) in 60 women undergoing ovarian stimulation for in-vitro fertilization. 36 women had normal ovaries, 14 women had PCO as seen on pelvic ultrasound examination and 10 had polycystic ovarian syndrome (PCOS). Mean+/-SD serum VEGF concentrations were significantly higher (P < 0.001) in women with PCO and PCOS (3.4+/-0.7 and 3.2+/-0.66 ng/ml respectively) compared with women with normal ovaries (2.3+/-0.5 ng/ml). Mean peak systolic blood flow velocity (PSV) and time-averaged maximum flow velocity (TAMXV) were significantly higher (P < 0.001) in women with PCO and PCOS compared with women with normal ovaries. The mean PSV were 15+/-4 and 16+/-4 cm/s in women with PCO and PCOS respectively, compared with 9+/-2 cm/s in women with normal ovaries. The TAMXV were 9+/-3 and 11+/-3 cm/s in women with PCO and PCOS respectively compared with women with normal ovaries (5.8+/-1.5 cm/s). Serum VEGF concentrations were positively correlated with PSV (r=0.44, P=0.001) and TAMXV (r=0.45, P < 0.000) in all three groups of women. Higher serum concentrations of VEGF in women with PCO and PCOS may relate to the increased vascularity that underlies the increased blood flow demonstrated by Doppler blood flow velocity measurements in these women. The results may explain the higher risk of ovarian hyperstimulation syndrome in programmes of ovarian stimulation in patients with PCO compared with those with normal ovaries.

Adult↗

Endothelin receptor expression in human decidua.

The endothelins are signalling peptides that act via two receptors, ET(A) and ET(B). In the human endometrium, endothelin receptors have been demonstrated in glands and stroma and have been shown to vary during the course of the menstrual cycle. The present study was undertaken to determine whether or not expression of endothelin receptors changes during pregnancy or after administration of exogenous progestagens. The expression of the receptors was correlated with the appearance of basement membrane components during decidualization of the endometrial stroma. Decidual specimens (n = 15) were obtained during the first trimester of pregnancy and 10 at term. Sixteen pairs of endometrial biopsies were obtained from women with menorrhagia before and after exposure to exogenous progestagens. A total of 15 hysterectomy specimens were used as controls for the expression of stromal basement membrane proteins in the absence of decidualization. Autoradiography was carried out with selective ligands for ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of ligand binding was then compared with the distribution of laminin alpha2 light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and collagen IV were expressed in stromal decidual cells in the first trimester of pregnancy. ET(B) was also found on endometrial glandular epithelium. Quantitative macro-autoradiography and multiple regression analysis demonstrated a highly significant positive correlation (P < 0.001) between expression of ET(B) and laminin alpha2 light chain. In the third trimester qualitative examination suggested a reduction of ET(A) in the stroma. Progestagen-induced decidua exhibited a similar pattern to that found in first trimester decidua. This study has demonstrated up-regulation of ET(B) during the progesterone-dependent process of decidualization and suggests a paracrine or autocrine role for endothelins in the decidua.

Abortion, Induced↗

Is blood pressure related to kidney size and shape?

OBJECTIVE: To examine the relationship between blood pressure and the size and shape of the kidneys in healthy volunteers from the community. DESIGN: A cross-sectional community-based study of normal volunteers in Portsmouth City, Hampshire, UK. SUBJECTS: Subjects numbered 185 (99 female), aged 19-66 years. RESULTS: Blood pressure was higher in men, and in those with higher body mass index. Both systolic and diastolic blood pressure were correlated with the derived kidney volume. However, when corrected for age, sex and BMI the relationship was not statistically significant. Blood pressure correlated inversely with the width : length ratio of the left kidney. CONCLUSIONS: Blood pressure was not correlated with kidney size in this group of adults.

Adult↗

Screening strategies for ovarian cancer.

Alternative procedures have been proposed for the detection of early ovarian cancer in asymptomatic women. Transvaginal ultrasonography, with or without colour Doppler imaging and intra-tumoural blood flow analysis, is used as the definitive technique in all current screening programmes. Target populations for clinical trials are recruited on the basis of risk factors for the disease (e.g. age or postmenopausal status, family history of ovarian cancer). Whether or not a participant is scanned may depend on results from the immunoassay of tumour antigens in peripheral serum, or from pedigree analysis. New developments include the use of: (i) intra-tumoural blood velocity as an end-point of colour Doppler imaging, (ii) serial measurements of serum tumour antigens to identify women for ultrasonography, and (iii) tests which detect regionally clustered germ-line BRCA1 mutations. More research is required to assess the beneficial and adverse effects of the new strategies.

Antigens, Neoplasm↗

Effect of norepinephrine on proliferation, migration, and adhesion of SV-40 transformed human corneal epithelial cells.

PURPOSE: To determine the ability of norepinephrine to modulate proliferation, adhesion, and migration of SV-40 transformed human corneal epithelial cells. METHODS: Assays were performed using SV-40 transformed human corneal epithelial cells. For proliferation assays, cells were plated in 96-well plates coated with fibronectin and collagen (FNC). A dose-response curve was generated for norepinephrine in concentrations of 100 nM-100 microM. The cell number in each well was evaluated using the fluorochrome Calcein AM (an intracellular esterase cleavage substrate), and fluorescence was determined using an automated fluorescent plate reader. For cell adhesion, 25 x 10(-3) cells were plated onto FNC-coated 96-well plates, incubated in 10 nM-100 microM norepinephrine for 90 min, gently irrigated, and the remaining adherent cells quantitated. Cell migration was measured using blind-well migration chambers with a 10-microm pore size and FNC-coated filters. Cells (250 x 10(3)) were added to the upper chamber, incubated for 18 h in the presence of factors, after which time the cells that had migrated through the filter were quantitated. The toxicity of norepinephrine was evaluated using a standard Live/Dead assay employing the combined fluorochromes of ethidium homodimer (to indicate dead cells) and Calcein AM (to indicate viable cells). Varying concentrations of norepinephrine were added, and the cells incubated for 3 h and the fluorometric assay performed. RESULTS: Norepinephrine stimulated corneal epithelial cell proliferation and migration over a wide range of concentrations. It did not modulate cell adhesion and demonstrated cell toxicity only at the highest (supraphysiologic) concentration tested. CONCLUSIONS: Norepinephrine is normally found in the cornea and may be important in the maintenance of normal corneal homeostasis and in wound-healing processes.

Antigens, Polyomavirus Transforming↗

An analysis of risk assessment tools for falls in the elderly.

The authors entered into a collaborative project with the staff of a visiting nurse service to evaluate the utility of a risk assessment inventory (RAI) in identifying factors that lead to falls in elderly persons receiving home care. Although no clear pattern emerged among personal factors, the majority of patients who experienced a fall used one or more assistive devices for ambulation.

Accidental Falls↗

A novel approach to the management of pregnancies complicated by uteroplacental insufficiency and previous stillbirth.

To our knowledge, this is the first time that a combination of aspirin and glyceryl trinitrate (GTN) has been used in the prophylaxis of preeclampsia and fetal growth retardation, and their use associated with not only Doppler screening of the uterine arteries but also regular Doppler follow-up of the fetal arterial and venous circulation. Whilst future trials are needed to prove whether screening, prophylaxis and Doppler management are individually beneficial, we propose that this combination of management strategies contributed to a good outcome in the cases described. Furthermore, randomized trials are required to determine the safety and efficacy of prophylactic low-dose aspirin combined with GTN treatment in pregnancies affected by an impaired uteroplacental circulation.

Adult↗

Genetic determinants of Rous sarcoma virus particle size.

The Gag proteins of retroviruses are the only viral products required for the release of membrane-enclosed particles by budding from the host cell. Particles released when these proteins are expressed alone are identical to authentic virions in their rates of budding, proteolytic processing, and core morphology, as well as density and size. We have previously mapped three very small, modular regions of the Rous sarcoma virus (RSV) Gag protein that are necessary for budding. These assembly domains constitute only 20% of RSV Gag, and alterations within them block or severely impair particle formation. Regions outside of these domains can be deleted without any effect on the density of the particles that are released. However, since density and size are independent parameters for retroviral particles, we employed rate-zonal gradients and electron microscopy in an exhaustive study of mutants lacking the various dispensable segments of Gag to determine which regions would be required to constrain or define the particle dimensions. The only sequence found to be absolutely critical for determining particle size was that of the initial capsid cleavage product, CA-SP, which contains all of the CA sequence plus the spacer peptides located between CA and NC. Some regions of CA-SP appear to be more important than others. In particular, the major homology region does not contribute to defining particle size. Further evidence for interactions among CA-SP domains was obtained from genetic complementation experiments using mutant deltaNC, which lacks the RNA interaction domains in the NC sequence but retains a complete CA-SP sequence. This mutant produces low-density particles heterogeneous in size. It was rescued into particles of normal size and density, but only when the complementing Gag molecules contained the complete CA-SP sequence. We conclude that CA-SP functions during budding in a manner that is independent of the other assembly domains.

Animals↗

Measles virus infection and replication in undifferentiated and differentiated human neuronal cells in culture.

Measles virus (MV) infection of the human central nervous system (CNS) typically involves widespread infection of neurons. However, little is known about how they become infected, how defective virus arises and accumulates, or how virus spreads among the cells of the CNS. In vitro studies of viral interactions with human neuronal cells may contribute to the resolution of such issues. In mixed cultures containing differentiated human neuronal (hNT2) cells and neuroepithelial cells, immunofluorescence studies show that the neurons, unlike both their NT2 progenitors and the neuroepithelial cells, are not initially susceptible to MV infection. This is possibly due to their lack of expression of CD46, a known cell surface receptor for MV. Later in the course of infection, however, both MV proteins and genomic RNA become detectable in their processes, where they contact infected, fully permissive neuroepithelial cells. Such a mechanism of virus transfer may be involved in the initiation and spread of persistent MV infection in diseases such as subacute sclerosing panencephalitis. Furthermore, mutated defective virus may readily accumulate and spread without the need, at any stage, for viral maturation and budding.

Cell Differentiation↗

Obstetric outcome in women who present with a reduction in fetal movements in the third trimester of pregnancy.

A complaint of decreased fetal movements is a common indication for the assessment of fetal well being. The aim of this study was to review the outcome of a group of women whose primary indication for referral was decreased fetal movements. Over a 20 month period, 435 patients were seen in the fetal assessment unit of an inner London teaching hospital, following a primary complaint of reduced fetal movements. Investigations included: the fetal abdominal circumference (AC), amniotic fluid volume (AFV), the umbilical artery pulsatility index (UAPI) derived from Doppler ultrasound waveforms and a computerised analysis of fetal heart rate (FHR) recordings or cardiotocograph (CTG). Outcome measures were: gestational age at delivery, Apgar score < 7 at 5 minutes, admission to the Special Care Baby Unit (SCBU), the need for delivery by an emergency cesarean section for fetal compromise (CSFC), and any perinatal deaths. A comparison of actual versus expected outcome for women with decreased fetal movement revealed the following relative risks, with the 95% confidence intervals (CI) in brackets; low 5 minute Apgar score 0.03 vs. 0.05 expected (CI = 0.01, 0.05), SCBU admission, 0.06 vs. 0.07 (0.04, 0.08), and preterm delivery, 0.08 vs. 0.11 (0.05, 0.10). Cesarean sections for fetal compromise, 0.07 vs. 0.053 (0.050-0.096). The addition of FHR monitoring to standard ultrasound assessment of well being did not appear to confer any added benefit. There were no fetal deaths. The outcome for pregnancies where the mother presents with decreased fetal movements in the third trimester is comparable with the outcome for the general population.

Apgar Score↗