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Biomedical subjects

V Heath

Publications and source records attributed to V Heath.

At least 19 recordsLinked to original sources

Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations.

OBJECTIVES: To assess whether there is a need to correct first-trimester biochemical markers (free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A)) or first-trimester fetal nuchal translucency thickness (NT) in different ethnic groups, when screening for Downs syndrome at 11-14 weeks of gestation. METHODS: Free beta-hCG, PAPP-A and fetal NT were measured at 11-14 weeks of gestation in a group of women presenting for first-trimester screening in two OSCAR centres. The group comprised 61 219 sets of data from Caucasian women (the reference group); 4835 sets of data from South Asian women; 3450 sets of data from Oriental women and 2727 sets of data from Afro-Caribbean women. The Oriental data set was supplemented with a further 480 cases collected in Hong Kong and the Afro-Caribbean data set was supplemented with 216 cases collected from Kings College. The difference in marker values between the reference group and the other ethnic groups was compared before and after weight correction for the biochemical markers using standard statistical techniques. A correction factor for ethnic origin was applied for all three markers and the screen-positive rate before and after correction was assessed for the various groups. RESULTS: After maternal weight correction, in Afro-Caribbean women, the median PAPP-A was increased by 55% and the free beta-hCG increased by 11%. In south Asian women, the PAPP-A was increased by 8% and the free beta-hCG decreased by 7.5%. In Oriental women, the PAPP-A was increased by 9% and the free beta-hCG by 6%. For delta NT in Afro-Caribbean women, the values were 0.064 mm lower on average than in Caucasian women and for south Asian women 0.045 mm lower. The difference of -0.012 for Oriental women was not significant. Before correcting for ethnic origin, these changes resulted in the screen-positive rates being lower in the Afro-Caribbean group (3.7% vs 5.6%), the south Asian group (4.3% vs 5.6%) and Oriental group (4.9% vs 5.6%). After correction, the screen-positive rates were largely similar in the four groups. CONCLUSION: Differences in median PAPP-A, free beta-hCG and, to a lesser extent, in NT exist in Afro-Caribbean, South Asian and Oriental women. In populations where the medians and delta NT reference ranges are established in predominantly Caucasian populations, some correction for ethnicity is appropriate and can redress differences in screen-positive rates between these different groups.

Adult↗

Delta-NT or NT MoM: which is the most appropriate method for calculating accurate patient-specific risks for trisomy 21 in the first trimester?

OBJECTIVE: To assess whether in screening for trisomy 21 by nuchal translucency (NT) the delta or the multiples of the median (MoM) approach is the most appropriate method for calculating accurate individual patient-specific risks. METHODS: Data on fetal NT and crown-rump length from 128,030 unaffected and 428 trisomy 21 pregnancies, measured by sonographers who had obtained The Fetal Medicine Foundation Certificate of Competence in the 11-14-Week Scan, were used. We examined first, if the distribution of NT MoM and log(10)(NT MoM) was Gaussian; second, if the standard deviation of the distributions did not change with gestation; and third, if the median MoM in the affected population was a constant proportion of the median for unaffected pregnancies. All of these features are required to underpin the MoM approach. NT distributions and those of delta-NT were also analyzed. A non-parametric kernel density method was then used to assess the validity of both methods. Errors in the estimation of individual patient-specific risks using the MoM approach were assessed. RESULTS: In the unaffected pregnancies, the distributions of NT MoM and log(10)(NT MoM) were not Gaussian and the standard deviation of log(10)(NT MoM) decreased with gestation. In the trisomy 21 pregnancies, the median NT MoM decreased significantly with gestation, whereas the median delta-NT did not change with gestation. The non-parametric density approach showed that contours of constant likelihood ratio were parallel to the gestational age-dependent median NT values, thus supporting the delta-NT approach. The NT MoM approach resulted in women being given an overestimate of risk for trisomy at 11 weeks and a considerable underestimate of risk at 13 weeks. CONCLUSION: In the calculation of risk for trisomy 21 by NT the NT MoM approach is inaccurate and inappropriate because the underlying assumptions are not valid. In contrast, the delta-NT approach gives accurate estimates of risks.

Adult↗

Transvaginal ultrasound in pregnancy: its acceptability to women and maternal psychological morbidity.

OBJECTIVES: To assess the acceptability to women of antenatal transvaginal ultrasound scans; to compare the characteristics of women who accept the offer of a transvaginal scan with those who decline; to establish the prevalence of any psychological morbidity associated with the scan. METHODS: The study was a cross-sectional questionnaire survey. Women were recruited from two hospitals in South London. The sample consisted of 755 pregnant women who had a transvaginal scan at 23 weeks' gestation to assess the risk of preterm delivery and 167 women who were offered the transvaginal scan but declined. Women completed a questionnaire at home. Those who reported finding the scan a difficult experience were sent a questionnaire 4 weeks post-scan to assess its longer term impact. The main outcomes were acceptability (assessed by individual questionnaire items); anxiety before and during the scan (Spielberger State-trait Anxiety Inventory); pain during the scan (Present Pain Intensity Scale of the McGill Pain Questionnaire); psychological trauma (Impact of Event Scale). RESULTS: Over half (55.2%) of women accepted the offer of a transvaginal scan, according to hospital records. The majority of study participants who had transvaginal ultrasound reported finding the experience acceptable. Women experienced some anxiety before and during the scan and over a third experienced some (usually mild) pain during the procedure. Twelve women (1.6%) reported clinically significant levels of psychological trauma in relation to the scan. CONCLUSIONS: Antenatal transvaginal ultrasound for assessing the risk of preterm delivery is an acceptable procedure for the majority of women. A significant minority decline the scan. The procedure has some psychological sequelae for some women.

Adult↗

One-stop clinic for assessment of risk for trisomy 21 at 11-14 weeks: a prospective study of 15 030 pregnancies.

OBJECTIVE: To evaluate the performance of a one-stop clinic for assessment of risk (OSCAR) for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation. METHOD: Screening for trisomy 21 was carried out by OSCAR in 15 030 singleton pregnancies with live fetuses at 11-14 weeks. The estimated risk for trisomy 21 was calculated, and the women were counseled regarding this risk and the option of invasive testing or expectant management. Follow-up of the outcome of all pregnancies was carried out. The detection and false-positive rates for different risk cut-offs were calculated. RESULTS: Fetal NT and maternal serum free beta-hCG and PAPP-A were successfully measured in all cases. Pregnancy outcome, including karyotype results or the birth of a phenotypically normal baby, was obtained from 14 383 cases. The median maternal age of these cases was 34 (range 15-49) years and in 6768 (47.1%) the age was 35 years or greater. The median gestation at screening was 12 (range 11-14) weeks and the median fetal crown-rump length was 64 (range 45-84) mm. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A was 1 in 300 or greater in 6.8% (967 of 14 240) normal pregnancies, in 91.5% (75 of 82) of those with trisomy 21 and in 88.5% (54 of 61) of those with other chromosomal defects. For a fixed false-positive rate of 5% the respective detection rates of screening for trisomy 21 by maternal age alone, maternal age and serum free beta-hCG and PAPP-A, maternal age and fetal NT, and by maternal age, fetal NT and maternal serum biochemistry were 30.5%, 59.8%, 79.3% and 90.2%, respectively. CONCLUSION: Screening for trisomy 21 by a combination of maternal age, fetal NT and maternal serum biochemistry at 11-14 weeks can be provided in an OSCAR setting and is associated with a detection rate of about 90% for a false-positive rate of 5%.

Adult↗

One-stop clinic for assessment of risk of chromosomal defects at 12 weeks of gestation.

Prenatal diagnosis of trisomy 21 requires an invasive test in women considered to be at high risk after screening. At present, there are four screening tests. For a 5% false-positive rate, the sensitivities are approximately 30% for maternal age alone, 60-70% for maternal age and second-trimester maternal serum biochemical testing, 75% for maternal age and first-trimester fetal nuchal translucency (NT) scanning, and 90% for maternal age with fetal NT and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks. This article examines the methodology of first-trimester screening and summarizes the results from all studies reporting on the implementation of this method.

Adult↗

Relationships and diseases among drug users and nonusers.

Human immunodeficiency virus (HIV) and syphilis are relationship-based diseases that are typically transmitted by the cooperative activities (sex or drug injection) of two persons. A sample of 215 drug users and 52 sociodemographically matched nonusers was collected to examine the behaviors and relationships related to HIV and syphilis transmission. Results showed that, although drug users had more risk opportunities (more sex partners and, of course, more injection partners) than nonusers, actual sex risk behaviors (never using condoms) did not differ appreciably among drug users and nonusers or with opposite-sex partners and same-sex partners. The similarity of sexual risk was supported by the similar levels of syphilis between drug users and nonusers. The unique risk to drug users was drug injection, although drug users were found to engage in fewer risky injection behaviors (sharing of drug injection equipment) than the risky sexual behaviors in which all participants engaged. Although drug users interacted as frequently with partners as nonusers, nonuser relationships were longer lasting and emotionally closer.

Adolescent↗

Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester.

OBJECTIVES: To study the outcome of chromosomally normal pregnancies with increased nuchal translucency at the 10-14-week scan. DESIGN: Retrospective study of 1320 chromosomally normal singleton pregnancies with nuchal translucency of > or = 3.5 mm. In addition to fetal karyotyping these patients were managed with follow-up scans at 14-16 and 20-22 weeks, specialist fetal echocardiography and in selected cases by infection screening and further genetic testing. RESULTS: In the 1320 pregnancies there were 68 (5.15%) spontaneous abortions or intrauterine deaths, 18 (1.36%) neonatal and infant deaths and 154 (11.67%) terminations of pregnancy. In the 1080 (81.82%) survivors, 60 (5.56%) had abnormalities requiring medical or surgical treatment or leading to mental handicap. The chance of a livebirth with no defects in the group with nuchal translucency of 3.5-4.4 mm was 86%, for those with translucency of 4.5-5.4 mm it was 77%, for those with translucency of 5.5-6.4 mm it was 67%, and for those with translucency of > or = 6.5 mm it was 31%. CONCLUSIONS: Increased fetal nuchal translucency is associated with chromosomal abnormalities, many fetal defects and genetic syndromes. In the majority of cases a series of antenatal investigations, including fetal karyotyping, detailed scans, fetal echocardiography, as well as genetic testing and infection screening, that can be completed by 20 weeks of gestation would distinguish between the pregnancies destined to result in adverse outcome and those leading to the delivery of infants without major defects.

Female↗

Accreditation of Prior (Experiential) Learning: making the difference.

This paper considers the use of Accreditation of Prior (Experiential) Learning (AP[E]L) in pre registration nurse education. AP(E)L has opened up many new prospects in post registration nurse education but opportunities for pre registration have, to date, been few. The time for change, however, is upon us all, most particularly for those institutions which have been selected to develop a new approach to nurse education referred to in Making a Difference, published by the Department of Health in 1999 and Fitness for Practice, published by the UKCC in 1999. As one of the selected sites the Institute of Health Studies at the University of Plymouth, in conjunction with the Cornwall and South Devon and Somerset and North Devon Education Purchasing Consortia, is in the process of implementing those required changes. One of the changes integral to the new curriculum is that of AP(E)L for entry to, and exit from, pre registration nurse education.

Accreditation↗

First-trimester screening for trisomy 21 in singleton pregnancies achieved by assisted reproduction.

BACKGROUND: The possible effect of assisted reproduction on first-trimester screening for trisomy 21 was examined by fetal nuchal translucency thickness (NT), maternal serum free beta-human chorionic gonadotrophin (HCG) and pregnancy-associated plasma protein-A (PAPP-A). METHODS: Parameters were measured at 11-14 weeks in 411 singleton pregnancies achieved by controlled ovarian stimulation, including 220 that had undergone IVF. Results were compared with 1233 singleton pregnancies conceived spontaneously. RESULTS: In the IVF pregnancies, the median fetal NT was not significantly different from that in controls, whilst the median free beta-HCG was significantly increased, and PAPP-A was significantly decreased. In the intracytoplasmic sperm injection group, fetal NT and free beta-HCG values were not significantly different from those in controls, but PAPP-A was significantly decreased. In those pregnancies achieved by ovarian stimulation, neither fetal NT, free beta-HCG nor PAPP-A were significantly different from the control group. CONCLUSIONS: In IVF pregnancies, screening for trisomy 21 by fetal NT, maternal serum free beta-HCG and PAPP-A levels may be associated with a 1.2% higher false-positive rate than in natural conception.

Chorionic Gonadotropin, beta Subunit, Human↗

First trimester maternal serum AFP and total hCG in aneuploidies other than trisomy 21.

Total human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) were measured in maternal serum at 10-14 weeks of gestation from 53 pregnancies affected by trisomy 18, 42 cases with trisomy 13, 46 with Turner's syndrome and 13 with other sex aneuploides. The only significant association was the finding of reduced levels of total hCG in cases of trisomy 18 and 13. The association of increased levels of AFP in cases of trisomy 18 with ventral wall defects and the slight increase in AFP in cases of sex chromosomal anomalies other than Turner's syndrome was found. AFP and total hCG are not likely to replace the markers free beta-hCG and PAPP-A in first trimester screening for chromosomal anomalies.

Adult↗

The 11-14 week scan.

Fetal nuchal translucency thickness (NT) at the 11-14 week scan has been combined with maternal age to provide an effective method of screening for trisomy 21; for an invasive testing rate of 5%, about 75% of trisomic pregnancies can be identified. When maternal serum free-beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-14 weeks are also taken into account, the detection rate of chromosomal defects is about 90%. Increased NT can also identify a high proportion of other chromosomal abnormalities and is associated with major defects of the heart and great arteries, and a wide range of skeletal dysplasias and genetic syndromes. Other benefits of the 11-14 week scan include early diagnosis of major fetal defects and the detection of multiple pregnancies, as well as reliable identification of chorionicity. As with the introduction of any new technology into routine clinical practice, it is essential that those undertaking the 11-14 week scan are adequately trained and that their results are subjected to rigorous audit.

Chromosome Aberrations↗

Should tissue from pregnancy termination and uterine evacuation routinely be examined histologically?

OBJECTIVE: To assess the value of routine histological examination of tissue samples collected at termination of pregnancy in the first trimester and emergency surgical uterine evacuation. SETTING: The gynaecological department of a teaching hospital. DESIGN: Prospective study of women attending the gynaecological department in a 12-month period. PARTICIPANTS: All women undergoing a therapeutic first trimester medical or surgical abortion or an emergency surgical evacuation of a failed pregnancy, suspected incomplete spontaneous miscarriage or incomplete induced abortion. MAIN OUTCOME: Association of pre-operative clinical diagnosis and the post-operative histological result. RESULTS: Of 1,576 women studied, the histological report confirmed that products of conception were obtained in 1,465 (93%); in two women (0.13%) molar changes were reported confirming the preoperative diagnosis by ultrasound. Products of conception were not confirmed in the tissue specimens in 0.5% medical terminations, 5% surgical terminations, 10% evacuations following a previous evacuation, 12% evacuations for a failed pregnancy, and 19% evacuations for an incomplete miscarriage. In 87 women (6%), decidua was reported; two of these women had undergone an evacuation for an ultrasound diagnosis of spontaneous miscarriage, but in both a tubal ectopic pregnancy was subsequently diagnosed. CONCLUSION: There did not appear to be any obvious benefit from routine histological examination of tissue removed at termination of pregnancy or emergency uterine evacuation. The histological result was sometimes not consistent with the pre-operative diagnosis and may result in unnecessary further investigation and treatment unless due consideration is given to the clinical presentation.

Abortion, Induced↗

Sustained activation of the raf-MEK-ERK pathway elicits cytokine unresponsiveness in T cells.

Activation of T cells via the TCR and other costimulatory receptors triggers a number of signaling cascades. Among them, the Ras-activated Raf-mitogen-activated protein/extracellular signal-related kinase (ERK) kinase (MEK)-ERK signaling cascade has been demonstrated to be crucial for both T cell development and activation. It has previously been demonstrated that high doses of Ag or anti-CD3 mAb are able to induce in T cells a nonresponsive state to subsequent treatment with cytokines such as IL-2. The precise biochemical mechanisms underlying this effect are not fully characterized. In this study, we demonstrate that cytokine nonresponsiveness is accompanied by the induction of the cyclin-dependent kinase inhibitor p21Cip1 that is mediated, at least in part, by the activation of the Raf-MEK-ERK pathway. Furthermore, we demonstrate that selective activation of the Raf-MEK-ERK signaling pathway in T cells is sufficient to induce cytokine nonresponsiveness in both a T cell clone and naive primary T cells. In this case, nonresponsiveness is accompanied by the induction of p21Cip1 and the prevention of p27Kip1 down-regulation, leading to inhibition of cyclin E/cyclin-dependent kinase 2 activity. These data suggest that anti-CD3 mAb-induced cytokine nonresponsiveness may be a consequence of hyperactivation of the Raf-MEK-ERK pathway, leading to alterations in the expression of key cell cycle regulators. These observations may provide a novel insight into the mechanisms of induction of peripheral tolerance.

Animals↗

GATA-3 significantly downregulates IFN-gamma production from developing Th1 cells in addition to inducing IL-4 and IL-5 levels.

IL-12 and IL-4 are dominant factors driving the development of Th1 and Th2 cells, respectively, by their activation of Stat-4 and Stat-6 signaling molecules. Activation of Stat factors, although specific, is a rapid event; however, differentiation of Th cells takes place over several days. Thus, it is unlikely that the expression of effector cytokines is mediated solely by Stat factors. Recently there have been indications that link other molecular factors to Th subset development. The transcription factor GATA-3 is selectively expressed in Th2 cells and has been shown to induce the expression of Th2 cytokines in developing Th1 cells. Using retroviral infection of naive T cells to introduce GATA-3 cDNA, we measured its direct effects on the development of Th1 cytokine production. We now show that ectopic expression of GATA-3 in developing Th1 cells significantly inhibits IFN-gamma, as well as enhancing IL-4 and IL-5 production. Furthermore, GATA-3 inhibits production of IFN-gamma by developing Th1 cells in the complete absence of IL-4. Thus, antagonism of Th1 development by GATA-3 may facilitate rapid divergence of Th subsets toward a Th2 phenotype in concert with other factors.

Animals↗

Cervical length at 23 weeks in twins in predicting spontaneous preterm delivery.

OBJECTIVE: To establish the relationship between cervical length at 23 weeks' gestation in twin pregnancies and risk of spontaneous preterm delivery. METHODS: Cervical length was measured during routine antenatal care by transvaginal sonography at 23 (range 22-24) weeks' gestation in 215 twin pregnancies. Distribution of cervical length was determined, and sensitivity and false-positive rate for spontaneous preterm delivery at or before 28, 30, 32, and 34 weeks for cutoff cervical lengths of 15, 25, 35, and 45 mm were calculated. RESULTS: Cervical length distribution was skewed toward shorter length and the median value was 38 mm. In 11.2% and 4.2% of cases, length was up to 25 mm and up to 15 mm, respectively. The spontaneous delivery rates at or before 28, 30, 32, and 34 weeks were 3.8%, 4.7%, 8.0%, and 17.5%, respectively, and were not statistically significantly related to any demographic characteristics, obstetric history, or chorionicity. Sensitivity to predict spontaneous preterm delivery was 100%, 80%, 47%, and 35% for 28, 30, 32, and 34 weeks, respectively, for cervical length up to 25 mm. The corresponding sensitivity values for cervical lengths up to 15 mm were 50%, 40%, 24%, and 11%. The rate of spontaneous delivery at or before 32 weeks increased exponentially with decreasing cervical length at 23 weeks, from 2.9% at or greater than 46 mm, to 4.3% at 36-45 mm, 6.7% at 26-35 mm, 31% at 16-25 mm, and 66% at 15 mm or less. CONCLUSION: Measurement of cervical length in twin pregnancies predicted risk of spontaneous early preterm delivery.

Adult↗

Homeostatic mechanisms in the control of autoimmunity.

The data in this article challenge the current paradigm that self tolerance among T cells can be fully accounted for in terms of intrathymic clonal deletion, anergy and T-cell 'indifference'. We show that autoreactive T cells are under the control of a dominant T-cell-mediated control mechanism and that the thymus is a particularly potent source of these protective cells. We further show that 'peripheral' self antigens implicated in autoimmune diseases are expressed intrathmically and we consider possible consequences of such expression. Finally we show that autoantigen-specific peripheral T cells can be programmed to prevent autoimmunity.

Adrenal Glands↗