Search PubMed⌕ Search

Biomedical subjects

S Campbell

Publications and source records attributed to S Campbell.

At least 145 records · Page 8Linked to original sources
PubMed1999

Serum vascular endothelial growth factor (VEGF) in the normal menstrual cycle: association with changes in ovarian and uterine Doppler blood flow.

OBJECTIVE: To investigate whether changes in circulating serum vascular endothelial growth factor (VEGF) concentrations during the menstrual cycle are associated with changes in blood flow within the ovaries and uterus. PATIENTS AND MEASUREMENTS: Serum VEGF concentrations were measured and pulsed and colour Doppler blood flow waveforms recorded within the ovarian stroma and uterine arteries during the early follicular, the immediate preovulatory and the mid-luteal phases of the menstrual cycle of 14 healthy women. RESULTS: Mean (+/- SD) serum VEGF concentrations rose from 2.44 +/- 0.1 ng/ml in the early follicular phase to 3 +/- 0.8 ng/ml in the pre-ovulatory phase and to 4.4 +/- 0.9 ng/ml in the mid-luteal phase (P < 0.0001) of the menstrual cycle. Mean peak systolic blood flow velocity (PSV) and time-averaged maximum flow velocity (TAMXV) were higher within the ovarian stroma of the ovary bearing the dominant follicle and the uterine arteries in the pre-ovulatory and mid-luteal phase than in the same sites during the early follicular phase of the menstrual cycle. PSV rose significantly from the early follicular phase (11 +/- 6 cm/s) to 14 +/- 4 cm/s in the pre-ovulatory phase and further in the mid-luteal phase (26 +/- 7 cm/s, P = 0.0001). Within the uterine arteries, mean PSV rose significantly from 28 +/- 9 cm/s in the early follicular phase to 31 +/- 8 cm/s in the pre-ovulatory phase and further in the mid-luteal phase (44 +/- 11 cm/s, P < 0.005). Serum VEGF correlated with serum progesterone concentrations in the luteal phase (r = 0.85, P < 0.001), with serum oestradiol concentrations in the early follicular (r = 0.67, P = 0.009), pre-ovulatory (r = 0.57, P = 0.03) and luteal phases (r = 0.68, P < 0.005) and with serum testosterone in the early follicular phase (r = 0.63, P = 0.01). CONCLUSIONS: Cyclical changes in serum vascular endothelial growth factor concentrations are associated with coincident changes in ovarian and uterine blood flow.

Adult↗
PubMed1999

The quality of life of cancer patients participating in phase I clinical trials using SEIQoL-DW.

The nature of phase I clinical trials in cancer patients raises many ethical issues. An area of major importance is the quality of life (QoL) of these patients. However, there is limited information available concerning the impact of phase I clinical trials on the QoL of patients with cancer. The primary aim of this study was to examine the QoL of cancer patients participating in phase I clinical trials. A descriptive triangulation approach was employed. The secondary aim was to determine the acceptability of the Schedule for the Evaluation of Individual Quality of Life - Direct Weighting (SEIQoL-DW) within this group of patients. SEIQoL-DW is a relatively new tool which investigates the areas identified by individual patients as important to their QoL. Cancer patients (n=15) participating in phase I clinical trials were interviewed using the SEIQoL-DW tool. During this interview patients nominated the areas of life important to them and rated their relative weighting and current status. Cues nominated were described and results analysed using non-parametric statistical tests. The results showed that health and family were particularly important to patients in relation to their QoL. The importance of an individualized approach in the measurement of QoL was evident. SEIQoL-DW was found to be acceptable and practical to use in cancer patients participating in phase I clinical trials. Recommendations for practice were drawn and suggestions made for further research.

Aged↗
PubMed1999

The pattern of changes in ovarian stromal and uterine artery blood flow velocities during in vitro fertilization treatment and its relationship with outcome of the cycle.

OBJECTIVES: To assess the effect of short-term (2-3 weeks) pituitary suppression and controlled ovarian stimulation on ovarian and uterine artery Doppler measurements during the in vitro fertilization (IVF) treatment cycle and to compare the pattern of these changes between conception and non-conception cycles as well as between patients with normal and those with polycystic ovaries. DESIGN: Prospective observational study of women undergoing IVF treatment. SUBJECTS: Women using the long-treatment buserelin protocol who did not have uterine fibroids, ovarian cysts or endometrioma. METHODS: Serial transvaginal color and pulsed Doppler measurements of ovarian stromal and uterine artery blood flow velocity were carried out in the early follicular phase of the menstrual cycle, on the day of pituitary suppression and on the day of administration of human chorionic gonadotropin (hCG). The main outcome measures were the ovarian stromal and uterine artery blood flow peak systolic velocity (PSV) and pulsatility index (PI). RESULTS: A total of 105 patients were recruited but six patients were excluded from the analysis because they had only one stage of the measurements performed. There was a significant decline in mean ovarian stromal artery PSV after 2-3 weeks of gonadotropin releasing hormone (GnRH) agonist therapy but no effect on ovarian stromal artery PI. The mean uterine artery PSV or PI did not change significantly after 2-3 weeks of GnRH agonist therapy. There was a significantly higher mean ovarian stromal artery PSV in conception cycles compared to non-conception cycles in the early follicular phase and on the day of pituitary suppression, but not on the day of hCG administration. There were no differences between conception and non-conception cycles in the mean uterine artery PSV or PI. Women with polycystic ovaries had a higher mean ovarian artery PSV on all the three occasions of measurement. CONCLUSION: These data suggest that assessment of ovarian blood flow before commencement of gonadotropin stimulation may play a role in assessing cycles likely to result in pregnancy.

Adult↗
PubMed1999

The outcome of in-vitro fertilization treatment in women with sonographic evidence of polycystic ovarian morphology.

This study compared the outcome of a course of up to three cycles of in-vitro fertilization (IVF) treatment in 46 women (97 cycles) who had polycystic ovaries (PCO) seen on ultrasound scan, but who had no clinical symptomatology associated with polycystic ovary syndrome, with that of 145 women (332 cycles) who had normal ovarian morphology on ultrasound examination. All 191 women had normal early follicular phase serum follicle stimulating hormone (FSH) concentrations, were less than 40 years of age and used the long protocol of pituitary suppression with gonadotrophin-releasing hormone agonist therapy. On average, the women with PCO produced more follicles, oocytes and embryos than the women with normal ovaries, but the fertilization, cleavage and miscarriage rates were similar. Adjusted for age, the odds of achieving a pregnancy within three cycles of treatment in a woman with PCO were 69% higher than those of a woman with normal ovaries [odds ratio (OR): 1.69, 95% confidence interval (CI) 0.99-2.90, P = 0.05)] and the odds of achieving a live birth were 82% higher (OR: 1.82, 95% CI 1.05-3.16, P = 0.03). There is, therefore, evidence that outcome of IVF treatment for women with PCO seen on ultrasound examination may be better than that for women with normal ovaries.

Abortion, Spontaneous↗
PubMed1999

Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 in human endometrium: regulation by interferon-gamma.

The purpose of this study was to localize intercellular adhesion molecule (ICAM)-1 and ICAM-2 in human endometrium and myometrium throughout the menstrual cycle, and to determine whether the expression of these molecules is regulated by interferon (IFN)-gamma. ICAM-1 and ICAM-2 distribution was examined in endometrial biopsies by immunocytochemistry, and Northern blotting was used to quantify ICAM-1 and ICAM-2 mRNA expression in isolated endometrial glands. Stromal fibroblast cultures were exposed to IFN-gamma and the effect on expression of ICAM-1 and ICAM-2 was determined by immunocytochemistry and Northern blotting. ICAM-1 was localized in vivo to the apical surface of the glandular epithelium, the vascular endothelium and endometrial stromal cells throughout the menstrual cycle. Stromal expression of ICAM-1 was up-regulated in menstrual specimens. Northern blotting confirmed the presence of ICAM-1 mRNA in isolated endometrial glands. The expression of ICAM-1 antigen and message was increased in stromal cell culture after incubation with IFN-gamma in a time-dependent manner, suggesting that this cytokine stimulates the expression of ICAM-1 in the endometrial stroma. ICAM-2 antigen expression was restricted to the vascular endothelium. ICAM-2 mRNA was absent in endometrial glands. The widespread distribution of ICAM-1 in human endometrium suggests that this molecule is involved in the process of menstruation, the functioning of glands, blood vessels and stroma, and in regulating leukocyte trafficking into the tissue. ICAM-2 is restricted to the vascular endothelium where it might modulate leukocyte invasion of the stroma and myometrial connective tissue.

Antigens, CD↗
PubMed1999

Violence in America: a public health crisis--domestic violence.

Domestic violence is a major public health problem. It is important that physicians are aware of the extent and pervasiveness of this disease. It is important to identify potential victims of domestic violence when they are encountered in the hospital or office environment. A few, short, carefully asked questions can serve an important surveillance and diagnostic function. Once domestic violence is identified, a well thought out, sensitive, safe plan of action should be discussed with the victim. In this way, not only will the current event be well managed, but also the potential for mitigating further domestic violence events will be initiated. Through this document, EAST hopes to add its voice to that of other physician groups to serve as a catalyst for broad education on the subject of domestic violence as well as activating victim advocacy among physicians and others who come into contact with this problem in their patients.

Adolescent↗
PubMed1999

Vasa previa: an avoidable obstetric tragedy.

UNLABELLED: Vasa previa is a rarely reported condition in which the fetal blood vessels, unsupported by either the umbilical cord or placental tissue, traverse the fetal membranes of the lower segment of the uterus below the presenting part. The condition has a high fetal mortality due to fetal exsanguination resulting from fetal vessels tearing when the membranes rupture. Despite improvements in medical technology, vasa previa often remains unsuspected until this fatal fetal vessel rupture occurs. Significant reduction in the fetal mortality from this condition depends on a high index of suspicion leading to antenatal diagnosis, and elective delivery by cesarean. We believe transvaginal ultrasound in combination with color Doppler is the most effective tool in the antenatal diagnosis of vasa previa and should be utilized in patients at risk, specifically those with bilobed, succenturiate-lobed, and low-lying placentas, pregnancies resulting from in vitro fertilization, and multiple pregnancy. Where there has been antepartum or intrapartum hemorrhage, especially when associated with fetal heart irregularities, we also recommend a test to exclude fetal blood in the vaginal blood. Similarly, amnioscopy before amniotomy may help to diagnose this condition. Cesarean delivery is the method of delivery of choice, and aggressive resuscitation of the affected neonate may be life saving. With a high index of suspicion, antenatal diagnosis using transvaginal sonography in combination with color Doppler, elective delivery by cesarean, and aggressive resuscitation of the neonate where fetal vessel rupture has occurred, the mortality from this complication may be considerably reduced. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to identify the risk factors and associated conditions for vasa previa, to identify the various clinical presentations and management of vasa previa, and to be aware of the diagnostic tools available to make the antepartum diagnosis of vasa previa.

Cesarean Section↗
PubMed1999

Sonographic prediction of malignancy in adnexal masses using an artificial neural network.

OBJECTIVE: To generate a neural network algorithm which computes a probability of malignancy score for pre-operative discrimination between malignant and benign adnexal tumours. DESIGN: A retrospective analysis of previously collected data. Information from 75% of the study group was used to train an artificial neural network and the remainder was used for validation. SETTING: The Gynaecological Ultrasound Research Unit at King's College Hospital, London. POPULATION: Sixty-seven women with known adnexal mass who had been examined using transvaginal B-mode ultrasonography and colour Doppler imaging with pulse spectral analysis immediately before surgery. The excised masses were classified histologically as benign (n = 52) or malignant (n = 15), of which three were borderline. METHODS: The variables that were put into the artificial neural network were: age, menopausal status, maximum tumour diameter, tumour volume, locularity, the presence of papillary projections, the presence of random echogenicity, the presence of analysable blood flow velocity waveforms, the peak systolic velocity, time-averaged maximum velocity, the pulsatility index, and resistance index. Histological classification, categorised as benign or malignant, was the output result. RESULTS: A variant of the back propagation method was selected to train the network. The overall architecture of the network with the best performance contained an input layer with four variables (age, time-averaged maximum velocity, papillary projection score and maximum tumour diameter), a hidden layer with three units and an output layer with one. The sensitivity and specificity at the optimum diagnostic decision value for the artificial neural network output (0.45) were 100% (95% CI 78.2%-100%) and 98.1% (95% CI 89.5%-100%), respectively. These values were significantly better than those obtained from the independent use of the resistance index, pulsatility index, time-averaged maximum velocity or peak systolic velocity at their optimum decision values (P < 0.01). CONCLUSION: Artificial neural networks may be used on clinical and ultrasound derived end-points to accurately predict ovarian malignancy. There is a need for a prospective evaluation of this technique using a larger number of patients.

Adnexal Diseases↗
PubMed1999

Screening for fetal aneuploidies and fetal cardiac abnormalities by nuchal translucency thickness measurement at 10-14 weeks of gestation as part of routine antenatal care in an unselected population.

OBJECTIVES: To evaluate first trimester pregnancy screening for fetal aneuploidy and congenital heart defects by maternal age and nuchal translucency measurement and screening for fetal aneuploidies and congenital heart defects by ultrasound in an unselected population. DESIGN: A prospective study. SETTING: Fetal medicine unit, St George's Hospital, London. SAMPLE: 4523 consecutive viable fetuses at 10-14 weeks with a crown-rump length between 38 and 80 mm were scanned transabdominally (93%) or transvaginally (7%). METHODS: Screening was performed by calculating the background risk from maternal age, gestational age and obstetric history, which was then adjusted with the nuchal translucency measurement in relation to crown-rump length (adjusted risk). MAIN OUTCOME MEASURES: Measurements of crown-rump length and nuchal translucency thickness. An adjusted risk of > 1:270 was considered as a positive screening test. Pregnancy outcome was obtained through karyotyping, outcome questionnaires and examination of the newborn infants. RESULTS: Mean maternal age was 29-4 years and mean gestational age 12.2 weeks. Screening was positive in 230/4523 fetuses (5.1%), when the adjusted risk (mean 1:2649) was > 1:270. Fetal karyotype was abnormal in 23 (0.51%) cases, including twelve with trisomy 21, five trisomy 18, one trisomy 13, one trisomy 10, one monosomy X and two triploidies. For a false positive rate of 4.7%, the sensitivity of this test was 78% in detecting any fetal aneuploidy. Only one out of nine major congenital heart defects in this population was found within the 110 euploid fetuses with increased nuchal translucency thickness (> 2.5 mm). CONCLUSION: Screening for fetal aneuploidy by maternal age and nuchal translucency measurement can be effective in an unselected population. However, our results do not support its effectiveness in the detection of cardiac abnormalities.

Adolescent↗
PubMed1999

Doppler fetal circulation in pregnancies complicated by pre-eclampsia or delivery of a small for gestational age baby: 2. Longitudinal analysis.

OBJECTIVE: To observe the longitudinal changes in growth, and associated Doppler measurements, of the fetal circulation in pregnancies with a normal outcome and those complicated by pre-eclampsia, birth of a small for gestational age baby, or a combination of these complications. METHODS: Two hundred and ninety-two women had serial ultrasound scans performed from the 24th week of pregnancy. Measurements obtained included: the abdominal circumference, umbilical artery pulsatility index, the middle cerebral artery pulsatility index and time-averaged velocity, and the thoracic aorta pulsatility index and time-averaged velocity. Outcome measures included the birth of a small for gestational age infant, pre-eclampsia or a combination of these complications. RESULTS: One hundred and sixty-seven pregnancies ended in the normal birth of an appropriately grown infant at term, while 105 had a complicated outcome. They were divided into three categories: preeclampsia only (i.e. with the birth of an appropriately grown fetus, n = 13); small for gestational age only with no evidence of pre-eclampsia, n = 55; and pre-eclampsia complicated by the birth of a small for gestational age infant, n = 37. The group with pre-eclampsia complicated by small for gestational age was closest in characteristics to true clinical intrauterine growth restriction. A reduction in the abdominal circumference mirrored a rise in the umbilical artery pulsatility index and preceded changes in the middle cerebral artery and thoracic aorta. The greatest degree of change in the fetal circulation was observed during the three weeks preceding delivery. Ratios of the values obtained from the fetal and umbilical circulation demonstrated the greatest deviation from normal. CONCLUSIONS: A reduction in fetal growth velocity preceded changes observed in the fetal circulation. Ratios of the fetal Doppler parameters provided the clearest evidence of deterioration in the fetal condition. The information provided may be of use in the diagnosis and management of the growth-restricted fetus.

Female↗
PubMed1999

In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain.

Human immunodeficiency virus type 1 (HIV-1) normally assembles into particles of 100 to 120 nm in diameter by budding through the plasma membrane of the cell. The Gag polyprotein is the only viral protein that is required for the formation of these particles. We have used an in vitro assembly system to examine the assembly properties of purified, recombinant HIV-1 Gag protein and of Gag missing the C-terminal p6 domain (Gag Deltap6). This system was used previously to show that the CA-NC fragment of HIV-1 Gag assembled into cylindrical particles. We now report that both HIV-1 Gag and Gag Deltap6 assemble into small, 25- to 30-nm-diameter spherical particles in vitro. The multimerization of Gag Deltap6 into units larger than dimers and the formation of spherical particles required nucleic acid. Removal of the nucleic acid with NaCl or nucleases resulted in the disruption of the multimerized complexes. We conclude from these results that (i) N-terminal extension of HIV-1 CA-NC to include the MA domain results in the formation of spherical, rather than cylindrical, particles; (ii) nucleic acid is required for the assembly and maintenance of HIV-1 Gag Deltap6 virus-like particles in vitro and possibly in vivo; (iii) a wide variety of RNAs or even short DNA oligonucleotides will support assembly; (iv) protein-protein interactions within the particle must be relatively weak; and (v) recombinant HIV-1 Gag Deltap6 and nucleic acid are not sufficient for the formation of normal-sized particles.

Escherichia coli↗
PubMed1999

The human immunodeficiency virus type 1 Gag polyprotein has nucleic acid chaperone activity: possible role in dimerization of genomic RNA and placement of tRNA on the primer binding site.

The formation of an infectious retrovirus particle requires several RNA-RNA interaction events. In particular, the genomic RNA molecules form a dimeric structure, and a cellular tRNA molecule is annealed to an 18-base complementary region (the primer binding site, or PBS) on the genomic RNA, where it will serve as primer for reverse transcription. tRNAs normally possess a highly stable secondary and tertiary structure; it seems unlikely that annealing of a tRNA molecule to the PBS, which involves unwinding of this structure, could occur efficiently at physiological temperatures without the assistance of a cofactor. Many prior studies have shown that the viral nucleocapsid (NC) protein can act as a nucleic acid chaperone (i.e., facilitate annealing events between nucleic acids), and the assays used to demonstrate this activity include its ability to catalyze dimerization of transcripts representing retroviral genomes and the annealing of tRNA to the PBS in vitro. However, mature NC is not required for these events in vivo, since protease-deficient viral mutants, in which NC is not cleaved from the parental Gag polyprotein, are known to contain dimeric RNAs with tRNA annealed to the PBS. In the present experiments, we have tested recombinant human immunodeficiency virus type 1 Gag polyprotein for nucleic acid chaperone activity. The protein was positive by all of our assays, including the ability to stimulate dimerization and to anneal tRNA to the PBS in vitro. In quantitative experiments, its activity was approximately equivalent on a molar basis to that of NC. Based on these results, we suggest that the Gag polyprotein (presumably by its NC domain) catalyzes the annealing of tRNA to the PBS during (or before) retrovirus assembly in vivo.

Animals↗
PubMed1999

A human TATA binding protein-related protein with altered DNA binding specificity inhibits transcription from multiple promoters and activators.

The TATA binding protein (TBP) plays a central role in eukaryotic and archael transcription initiation. We describe the isolation of a novel 23-kDa human protein that displays 41% identity to TBP and is expressed in most human tissue. Recombinant TBP-related protein (TRP) displayed barely detectable binding to consensus TATA box sequences but bound with slightly higher affinities to nonconsensus TATA sequences. TRP did not substitute for TBP in transcription reactions in vitro. However, addition of TRP potently inhibited basal and activated transcription from multiple promoters in vitro and in vivo. General transcription factors TFIIA and TFIIB bound glutathione S-transferase-TRP in solution but failed to stimulate TRP binding to DNA. Preincubation of TRP with TFIIA inhibited TBP-TFIIA-DNA complex formation and addition of TFIIA overcame TRP-mediated transcription repression. TRP transcriptional repression activity was specifically reduced by mutations in TRP that disrupt the TFIIA binding surface but not by mutations that disrupt the TFIIB or DNA binding surface of TRP. These results suggest that TFIIA is a primary target of TRP transcription inhibition and that TRP may modulate transcription by a novel mechanism involving the partial mimicry of TBP functions.

Amino Acid Sequence↗