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S Campbell

Publications and source records attributed to S Campbell.

At least 73 records · Page 4Linked to original sources
PubMed2001

Modulation of HIV-like particle assembly in vitro by inositol phosphates.

HIV-1 Gag protein assembles into 100- to 120-nm diameter particles in mammalian cells. Recombinant HIV-1 Gag protein assembles in a fully defined system in vitro into particles that are only 25-30 nm in diameter and that differ significantly in other respects from authentic particles. However, particles with the size and other properties of authentic virions were obtained in vitro by addition of inositol phosphates or phosphatidylinsitol phosphates to the assembly system. Thus, the interactions between HIV-1 Gag protein molecules are altered by binding of inositol derivatives; this binding is apparently essential for normal HIV-1 particle assembly. This requirement is not seen in a deleted Gag protein lacking residues 16-99 within the matrix domain.

Amino Acid Sequence↗
PubMed2001

Igf2/H19 imprinting control region (ICR): an insulator or a position-dependent silencer?

The imprinting control region (ICR) located far upstream of the H19 gene, in conjunction with enhancers, modulates the transcription of Igf2 and H19 genes in an allele-specific manner. On paternal inheritance, the methylated ICR silences the H19 gene and indirectly facilitates transcription from the distant Igf2 promoter, whereas on the maternal chromosome the unmethylated ICR, together with enhancers, activates transcription of the H19 gene and thereby contributes to the repression of Igf2. This repression of maternal Igf2 has recently been postulated to be due to a chromatin boundary or insulator function of the unmethylated ICR. Central to the insulator model is the site-specific binding of a ubiquitous nuclear factor CTCF which exhibits remarkable flexibility in functioning as transcriptional activator or silencer. We suggest that the ICR positioned close to the enhancers in an episomal context might function as a transcriptional silencer by virtue of interaction of CTCF with its modifiers such as SIN3A and histone deacetylases. Furthermore, a localised folded chromatin structure resulting from juxtaposition of two disparate regulatory sequences (enhancer ICR) could be the mechanistic basis of ICR-mediated position-dependent (ICR-promoter) transcriptional repression in transgenic Drosophila.

Animals↗
PubMed2001

Prenatal findings on ultrasound and X-ray in a case of overgrowth syndrome associated with increased nuchal translucency.

A case of prenatal diagnosis of an overgrowth syndrome at 30 weeks of gestation is reported. The diagnosis was suggested on the basis of increased fetal growth from 16 weeks onwards, advanced bone age, and characteristic facial features such as hypertelorism, broad forehead and small chin. The fetus presented at 12 weeks with a markedly increased nuchal translucency thickness and generalized skin edema, but normal karyotype. Serial ultrasound scans revealed brain abnormalities including mild unilateral ventriculomegaly and a cyst in the cavum septi pellucidi. The pregnancy was terminated at the parents' request at 32 weeks of gestation and postmortem examination confirmed the prenatal findings. This case demonstrates the possibility of prenatal diagnosis of early overgrowth syndromes and highlights the dilemma arising from the prenatal diagnosis of a non-lethal condition associated with an uncertain prognosis and poorly documented in utero.

Abnormalities, Multiple↗
PubMed2001

Evolutionary pattern and prognostic importance of heart rate variability during the early phase of acute myocardial infarction.

AIMS: To investigate the evolution of time domain heart rate variability in the early phase of acute myocardial infarction (MI) and assess its prognostic ability. METHODS: We analysed several measures of heart rate variability (SDNN, SDANN, SDNN index, RMSSD) in 138 patients at days 0, 1 and 5+/-1 after hospital admission for acute MI. Results were correlated with infarct site, clinical variation and clinical outcome (death, MI, PTCA, CABG surgery). RESULTS: Measures of heart rate variability (SDNN, SDANN and SDNN index) declined during the first 24 h after acute MI (P<0.01) and increased to admission levels after about 5 days. SDNN values on day 0, 1 and 5 respectively were: 86+/-35, 75+/-28 and 87+/-27 ms. Patients with anterior infarction had lower heart rate variability than patients with inferior infarction on all test days but similar evolution patterns. After 3 years of follow-up there were 12 cardiac deaths (8.7%) and six resuscitated arrests and 33 (24%) new MIs, or revascularisation procedures. The evolutionary pattern of heart rate variability was similar in survivors to those who died although values were generally lower. Mortality was significantly higher in the group with SDNN<50 ms at day 1 (P<0.01) and 5 (P<0.05), but not at day 0. CONCLUSIONS: Our findings show that autonomic imbalance, already evident on the day of the acute event, progresses further over the next 24 h and recovers over the next few days. Low heart rate variability as early as 24 h after acute MI may be a useful predictor of cardiac mortality and contribute to the early risk stratification and therapeutic management of patients.

Aged↗
PubMed2001

Fetal Doppler velocimetry at high altitude.

OBJECTIVES: To determine impedance and velocity characteristics of the fetal circulation using Doppler ultrasound, at extremely high altitude (4300 m) in the Peruvian Andes compared to an ethnically similar population at sea level. METHODS: This was a cross-sectional study of 196 women resident at high altitude (Cerro de Pasco, 4300 m above sea level) and 196 women resident at sea level (Lima) with normal singleton pregnancies. Pulsatility index (PI), maximum velocity (Vmax) and minimum velocity (Vmin) in the umbilical artery, the descending aorta, the middle cerebral artery and the ductus venosus were compared between the two populations using fractional polynomial regression analysis. RESULTS: The PI was higher at high altitude than at sea level in the umbilical artery (regression coefficient = 0.112, P < 0.001), and not significantly different in the descending aorta, middle cerebral artery and ductus venosus. Vmax was lower at high altitude than at sea level in all three arterial vessels assessed; Vmin was lower in two: the umbilical artery and the descending aorta. The high-altitude/sea-level ratios for umbilical artery Vmax and Vmin were 0.93 and 0.82, respectively (P < 0.001 for each), the ratios for descending aorta Vmax and Vmin were 0.93 and 0.89, respectively (P = 0.003 and P < 0.001, respectively), and the regression coefficient for the middle cerebral artery Vmax was -2.844 (P = 0.003). There was no significant difference in the middle cerebral artery Vmin or in the ductus venosus Vmax and Vmin. CONCLUSIONS: Despite the lower ambient oxygen at high altitude and an increase in umbilical artery PI, the fetal circulation does not exhibit a 'brain sparing effect'. This and the overall decrease in blood flow velocities in the fetal circulation at high altitude may be due to the increased fetal hematocrit, which will result in increased blood viscosity.

Adult↗
PubMed2001

Reproducibility and repeatability of transabdominal uterine artery Doppler velocimetry between 10 and 14 weeks of gestation.

OBJECTIVE: To assess the intraobserver repeatability and interobserver reproducibility of Doppler flow velocity measurements of the uterine arteries in pregnant women between 10 and 14 weeks of gestation. METHODS: In this prospective study, Doppler velocimetric indices (maximum peak systolic velocity, end-diastolic velocity, peak systolic velocity/end-diastolic velocity ratio, pulsatility index and resistance index) were measured twice by the same trained observer in each uterine artery of 63 women. In 47 of these women, a second trained observer then repeated the measurements. In addition, both observers classified qualitatively the blood flow with regard to the presence or absence of an early diastolic notch. The coefficient of variation, intraclass correlation coefficients, within observer and between observers repeatability coefficient and Cohen's kappa coefficient were calculated. RESULTS: The best parameter in terms of repeatability and reproducibility in both uterine arteries was the resistance index with a low coefficient of variation and high intraclass correlation coefficient. The other parameters (pulsatility index, peak systolic velocity/end-diastolic velocity ratio, peak systolic velocity and end-diastolic velocity) performed poorly with high coefficients of variation on both sides. Agreement between the repeated observations (inter- and intraobserver) with regard to the presence or absence of an early diastolic notch was good. CONCLUSION: Doppler velocimetry of uterine artery blood flow is technically feasible between 10 and 14 weeks of gestation. This study demonstrates that this technique is prone to measurement errors. Quantitatively, the resistance index appears to be the most repeatable and reproducible measurement at this gestational age. Qualitative assessment of the waveform morphology also shows high levels of intra- and interobserver agreement.

Adult↗
PubMed2001

Maternal uterine artery Doppler studies at high altitude and sea level.

OBJECTIVE: To determine uterine artery impedance using Doppler in the second and third trimesters at sea level and at high altitude. METHODS: Uterine artery resistance and pulsatility indices (RI and PI, respectively) were obtained by Doppler velocimetry from 242 women in Cerro de Pasco (4300 m altitude) and 200 women in Lima (sea level), all with normal singleton pregnancies between 14 and 40 weeks of gestation. Impedance indices at high altitude and sea level were compared using fractional polynomial regression analysis. RESULTS: Impedance to uterine artery blood flow was lower at high altitude than at sea level (for PI ratio Lima/Cerro de Pasco = 1.06; P = 0.011). If gestation bands were compared, the difference was significant up to 25 weeks. CONCLUSION: At high altitude, pregnancy is associated with lower uteroplacental impedance than at sea level. This may reflect a compensatory mechanism of uteroplacental development to lower oxygen tension associated with altitude.

Adult↗
PubMed2001

The anatomy of the umbilical, portal and hepatic venous systems in the human fetus at 14-19 weeks of gestation.

BACKGROUND: Ultrasound imaging of the fetal ductus venosus is becoming increasingly commonplace in clinical practice. The true anatomical relationships of the fetal umbilical and portal venous systems have not been clearly defined due to paucity of published data on the relevant anatomy. This has led to confusing terminology when describing the fetal umbilical, portal and hepatic circulations. The aim of the present study was to examine and document the anatomy of the umbilical, portal and hepatic venous systems and to propose a standardized nomenclature. METHODS: This was a prospective study on 11 fetuses obtained from medical termination of pregnancies between 14 and 19 weeks of gestation. The liver was microdissected to expose the branching pattern and anatomical relations of the umbilical, portal and hepatic venous systems. RESULTS: A wide L-shaped venous confluence at the terminal end of the umbilical vein, termed the portal sinus, was identified. The portal sinus was connected to the right and left hepatic lobes, by the right and left intrahepatic portal veins, respectively. The extrahepatic portal vein drained into the portal sinus just before the origin of the right intrahepatic portal vein. The ductus venosus, a branchless straight vessel, originated from the portal sinus and ascended steeply in the direction of the diaphragm. Numerous small vessels draining the liver converged into three main hepatic veins, which open into the subdiaphragmatic vestibulum. CONCLUSION: Based on detailed sequential anatomical dissection and clear illustrations, the present study documents the anatomy of the umbilical, portal and hepatic venous systems. Taking into account the embryological origin of the vessels, a new anatomically appropriate and simplified nomenclature of these venous systems is proposed. In clinical practice, the consistent use of the suggested terminology would allow collection of comparable data between units and enable operators to be confident of which vessels they are sampling by Doppler ultrasound.

Dissection↗
PubMed2001

Effect of alcohol withdrawal on liver transaminase levels and markers of liver fibrosis.

BACKGROUND AND AIM: Acute alcohol withdrawal causes changes in hepatic blood flow and metabolism that may result in liver damage. This study aims to assess liver function tests and markers of hepatic fibrogenesis following alcohol withdrawal in alcoholics with clinically compensated liver disease. METHODS: Serial liver function tests and clinical assessments were performed on 22 male alcoholics during alcohol withdrawal. Plasma tissue inhibitor of metalloproteinase 1 (TIMP1), an inhibitor of collagen degradation, and plasma amino-terminal procollagen III peptide (PIIINP), a collagen precursor molecule, were measured in these alcoholics and in 11 control subjects. RESULTS: Transaminase levels did not change significantly over 7 days when all subjects were analyzed together. However, 32% of subjects showed a marked transaminase rise. These subjects did not differ from the others in baseline characteristics or short-term outcome, but had a greater benzodiazepine requirement. Only one subject consumed paracetamol (acetaminophen; 1-2 g/day). He had the largest transaminase rise. By comparing PIIINP assays, intact PIIINP concentration appears to increase following alcohol withdrawal. The TIMP1 levels were elevated in alcoholic subjects, but did not change following withdrawal. CONCLUSIONS: Increasing PIIINP suggests that hepatic fibrogenesis increases, or hepatic clearance falls, during acute alcohol withdrawal. The TIMP1 elevation in these alcoholics suggests that the inhibition of collagen degradation occurs while liver disease is still compensated. The period following alcohol withdrawal may be a time of marked increased susceptibility to paracetamol. The biochemical changes we observed were not associated with adverse short-term outcome, but the cumulative effect after repeated episodes of abrupt withdrawal may be of concern.

Adult↗
PubMed2001

Comparison of adipose tissue changes following administration of rosiglitazone in the dog and rat.

Rosiglitazone (BRL-49653-C), a thiazolidinedione, is a potent agonist for the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma). Thiazolidinediones have been reported to induce adipocyte differentiation in vitro and there is limited data on their effects in vivo. The objective of this study was to compare the effects of rosiglitazone on adipocyte differentiation between dogs and rats. Morphological (light and ultrastructural) and morphometric evaluations were conducted on perirenal adipose tissue from dogs that have been treated for 1 month with 0.4, 5, 60 mg/kg/day and rats treated for the same period with 80 mg/kg/day. There was a dose-related change in the phenotype of white adipose tissue in dogs, reflected by an increase in nuclear numerical density (up to threefold) and cytoplasmic area fraction (up to 2.1-fold). In addition, there was an enlargement of the nuclei and a reduction in the size of the white adipocyte lipid vacuoles. Ultrastructural changes included an increase in the number of mitochondria per adipocyte. In the rat, similar changes were seen in nuclear numerical density (1.5-fold increase) and cytoplasmic area fraction (2.2-fold increase). There were also increased numbers of mitochondria per cell in white adipocytes giving them similar numbers of mitochondria to brown adipocytes. In the brown adipocytes, there was a reduction in cytoplasmic area fraction with a corresponding increase in the size of the lipid filled vacuoles in other words there was a converging of the phenotypes of the white and brown adipose tissues.

Adipose Tissue↗
PubMed2001

Limitations of using first-trimester nuchal translucency measurement in routine screening for major congenital heart defects.

OBJECTIVE: To evaluate the effectiveness of nuchal translucency (NT) measurement in screening for major congenital heart disease (CHD) in chromosomally normal fetuses. DESIGN: A population based cohort study of all women having fetal NT measurement at 10-14 weeks of gestation in an unselected population over a 3-year period. The outcome measure was the identification of major CHD in chromosomally normal pregnancies either antenatally or postnatally. RESULTS: Major defects of the heart and great arteries were identified in 26 out of 7339 pregnancies (prevalence 3.5 per 1000 pregnancies). Out of 26 cases, only four (sensitivity 15.4%, 95% CI 4-35) were in the group of 258 pregnancies (3.5%) with increased NT of > or = 2.5 mm. The prevalence of major CHD increased from 3.1 per 1000 for NT < 2.5 mm to 50 per 1000 for NT > or = 3.5 mm (likelihood ratio of 14.1, 95% CI 4.2-47.9). The positive and negative predictive values for NT > or = 2.5 mm were 1.6% and 99.7%, respectively. CONCLUSIONS: The prevalence of major CHD in this study was 3.5 per 1000, suggesting that ascertainment of CHD in our study population was thorough. Fetuses with NT measurements > or = 3.5 mm have a significantly increased risk of major CHD, and this identifies a subgroup of high-risk patients in whom early fetal echocardiography would be advocated. The low sensitivity of NT for major CHD in the general population, however, indicates that NT cannot be relied on as the sole or major screening tool for this condition as previously reported.

Adult↗
PubMed2001

The association of aneuploidy and mild fetal pyelectasis in an unselected population: the results of a multicenter study.

INTRODUCTION: Mild pyelectasis is a common finding and there is some debate as to its association with aneuploidy. The results of a large, prospective, multicenter study of mild pyelectasis designed to determine the incidence and association with aneuploidy in an unselected population are reported. METHODS: A large multicenter, prospective observational study of unselected fetuses with mild pyelectasis identified between 16 and 26 weeks' gestation in routine ultrasound departments. RESULTS: There were 737 fetuses with mild pyelectasis of which 12 had an abnormal karyotype. Pyelectasis was isolated in three fetuses with Down syndrome, but in one the mother was older (36 years). CONCLUSION: These data confirm the fact that the presence of mild fetal pyelectasis increases the risk for aneuploidy, in particular trisomy 21. However, other risk factors should be considered before embarking on fetal karyotyping, as for most pregnancies complicated by isolated mild pyelectasis, risks of aneuploidy will remain small.

Adult↗
PubMed2001

Prenatal diagnosis of mosaic trisomy 8 in a fetus with normal nuchal translucency thickness and reversed end-diastolic ductus venosus flow.

We report a case of the prenatal diagnosis of trisomy 8 in a fetus presenting with normal nuchal translucency of 0.8 mm and reversed end-diastolic ductus venosus blood flow at a routine first-trimester scan at 11 weeks of gestation. No structural abnormalities were detected by the ultrasound scan. Karyotyping by chorionic villus sampling led to the diagnosis of mosaic trisomy 8, which was confirmed by fluorescent in-situ hybridization on fetal tissue samples.

Adult↗
PubMed2001

Isolated echogenic foci in the fetal heart: do they increase the risk of trisomy 21 in a population previously screened by nuchal translucency?

OBJECTIVES: To confirm the hypothesis that isolated cardiac echogenic foci at the second-trimester anomaly scan do not influence our current calculation of risk of trisomy 21 in individual pregnancies, which is based on maternal age and nuchal translucency thickness at 11-14 weeks. DESIGN: Observational study in a fetal medicine unit. METHODS: In a general pregnant population undergoing first-trimester nuchal translucency screening, data from 239 singleton pregnancies with isolated cardiac echogenic foci at the second-trimester anomaly scan were compared with those of a control group of 7449 pregnancies with normal anomaly scans. Prevalence of trisomy 21 was determined in both groups. Following the anomaly scan, the individual risks of trisomy 21 were calculated by adjusting the previous risk based on maternal age and first-trimester nuchal translucency. We assumed that echogenic foci did not alter each individual risk calculation. The expected number of cases of Down syndrome in both groups was then calculated from the sum of probabilities of each individual affected fetus. The observed number of cases was compared with the expected number in both study and control populations. RESULTS: There was no statistically significant difference between the prevalence of trisomy 21 in the study group (no cases) and in the control population (three cases). From individual risk calculations, observing no cases of trisomy 21 in the study group was the most likely event if echogenic foci did not increase the risk of this chromosomal abnormality (P = 0.62). CONCLUSION: The finding of isolated echogenic foci at the time of the 20 week-scan does not significantly change the risks of trisomy 21 if background risk and previous nuchal translucency measurements are taken into account in the individual risk calculation. We suggest that no further adjustments to risk should be used.

Adult↗
PubMed2001

Investigation of the infertile couple: a one-stop ultrasound-based approach.

The appropriateness of many investigations for subfertility will continue to be of debate for some time yet. Of most benefit to the concerned couple would be a process that is diagnostically accurate, expeditious and reliable. It should be performed with a minimum of invasion and provide both patient and clinician with useful prognostic information regarding possible future treatment. This article is intended to illustrate the advantages of an ultrasound-based process of subfertility investigation. Discussed is the role of ultrasound compared with more invasive investigative methods such as laparoscopy and hysteroscopy. In addition, the potential capacity of newer advanced ultrasound technologies is reviewed.

Fallopian Tubes↗
PubMed2001

Cumulative conception and live birth rates in natural (unstimulated) IVF cycles.

IVF treatment, which involves ovarian stimulation, poses significant health problems such as ovarian hyperstimulation and is associated with a high incidence of multiple pregnancy and premature birth. In this paper, we demonstrate how natural cycle IVF is an effective and potentially cost-effective alternative treatment option for certain groups of infertile couples. The study was conducted in the Assisted Conception Unit at King's College School of Medicine, London. Fifty-two women with regular menstrual cycles whose partners had normal semen parameters were offered a total of 181 cycles of treatment (average 3.49 per couple). Life table analysis was used to calculate cumulative success rates after successive cycles of treatment. After four cycles, the cumulative probability of pregnancy was 46% with an associated live birth rate of 32%. To achieve maximal effectiveness, natural cycle IVF should be offered as a series of treatment cycles, for it is safer, less stressful and can be offered over consecutive cycles. Moreover, the avoidance of expensive drugs and reduced intensity of monitoring make natural cycle IVF less expensive than conventional treatment involving stimulation. We calculate that this treatment can be offered at approximately 23% of the cost of a stimulated cycle, suggesting that it may be a cost-effective alternative to conventional assisted conception techniques.

Adult↗
PubMed2001

Infliximab therapy for Crohn's disease in the presence of chronic hepatitis C infection.

Treatment of Crohn's disease with infliximab is an important drug therapy for patients with refractory and fistulating disease. There are concerns over its use in a proportion of Crohn's patients with concurrent hepatitis C infection, since there are theoretical risks of accelerated hepatic decompensation due to the immunomodulatory impact of infliximab. We report a patient with both Crohn's disease and ongoing active hepatitis C infection who underwent infliximab therapy, with no worsening of his liver function or PCR status.

Adult↗