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Biomedical subjects

L Regan

Publications and source records attributed to L Regan.

At least 37 records · Page 2Linked to original sources
PubMed2002

Clinical outcomes following percutaneous magnetic resonance image guided laser ablation of symptomatic uterine fibroids.

BACKGROUND: Fibroids are common benign tumours of the uterus. Percutaneous magnetic resonance (MR) image guided laser ablation provides a minimally invasive, day-case alternative to surgery for the treatment of symptomatic fibroids. METHODS: Women with symptomatic fibroids wishing to avoid surgery were treated with laser ablation. MR thermal mapping ensured that maximal safe energy was applied. Fibroid volume was measured at 3 and 12 months, menstrual blood loss was recorded before and after treatment and a menorrhagia outcomes questionnaire (MOQ) was used to assess satisfaction. RESULTS: A total of 66 patients was treated. There was a significant (P < 0.001) reduction in mean fibroid volume of 31%. This was 41% at 1 year follow-up (P < 0.001). Measured menstrual blood loss in eight patients complaining of excessive bleeding was reduced (P = 0.012). The MOQ total outcome score was not as good as that seen in hysterectomy patients (P = 0.02) but the quality of life/satisfaction score was similar (P = 0.06). CONCLUSION: We have used objective and subjective outcome measures to determine the efficacy of MR guided laser ablation for fibroids. Based on this limited study we are encouraged that this procedure may represent a minimally invasive alternative therapy for fibroids.

Female↗
PubMed2002

Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages.

BACKGROUND: The aim of this study was to investigate the changes in circulating levels and the clinical use of inhibin A, activin A and follistatin as endocrine markers of early pregnancy loss. METHODS: Blood samples were collected from women presenting with a sporadic missed miscarriage (n = 10), and controls having pregnancy termination at 8-12 weeks (n = 15) and from women with a history of unexplained recurrent miscarriages (n = 12) at 6-12 weeks gestation. All samples were assayed for inhibin A, inhibin B, activin A, follistatin, hCG, estradiol and progesterone. RESULTS: Serum inhibin A, hCG, estradiol and progesterone levels were significantly ( approximately 2-3 fold) decreased in sporadic miscarriages compared with controls. In the recurrent miscarriage group, time dependent changes in plasma inhibin A and hCG levels were significantly (P < 0.05) altered in the group that had a subsequent miscarriage compared with those who had a live birth. At 6-7 weeks gestation, plasma inhibin A ( approximately 4 fold, P < 0.01), hCG ( approximately 4 fold, P < 0.01) and estradiol ( approximately 2 fold, P < 0.001) levels were significantly lower in women who went on to have another miscarriage than those with a live birth. Inhibin B levels were near the detection limit of the assay. CONCLUSIONS: Our findings suggest that inhibin A is a specific marker of early pregnancy loss before the onset of the clinical symptoms of recurrent miscarriage. There is a high degree of association between levels of inhibin A and hCG in cases of miscarriage, indicating that these two proteins could be used in combination to predict future pregnancy outcome.

Abortion, Habitual↗
PubMed2002

Factor V Leiden and recurrent miscarriage-prospective outcome of untreated pregnancies.

BACKGROUND: Some cases of recurrent miscarriage and later pregnancy complications have a thrombotic basis. Factor V Leiden is a common thrombophilic mutation. METHODS: The prospective outcome of untreated pregnancies amongst 25 women heterozygous for the Factor V Leiden allele who had a history of either recurrent early miscarriages only (three or more miscarriages at <12 weeks gestation; n = 19) or of late miscarriage (>12 weeks gestation; n = 9) was studied. Control groups of women with a similar pregnancy history but who had a normal Factor V genotype were also studied. RESULTS: The live birth rate was significantly lower amongst women with a history of recurrent early miscarriage who carried the Factor V Leiden allele (6/16; 37.5%) compared with that amongst those with a normal Factor V genotype (106/153; 69.3%; odds ratio 3.75, 95% confidence intervals 1.3-10.9). The live birth rate was 11.1% (1/9) amongst those with a history of late miscarriage carrying the Factor V Leiden allele and 48.9% (22/45) amongst those with a normal Factor V genotype. CONCLUSIONS: Attention should be directed at screening women with recurrent miscarriage associated with placental thrombosis for Factor V Leiden and a policy of targeted thromboprophylaxis during future pregnancies should be assessed in the form of a randomized controlled trial.

Abortion, Habitual↗
PubMed2002

Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure.

BACKGROUND: Primary antiphospholipid antibody syndrome (PAPS) is an established cause of recurrent pregnancy loss, traditionally presumed to be due to 'intraplacental thromboses'. This study examines products of conception (POC) from early pregnancy failures to investigate the mechanism of pregnancy loss. METHODS: POC from patients attending a recurrent miscarriage clinic and from terminations of pregnancy for non-medical reasons were examined histologically with particular regard to the presence or absence of vascular or intervillous thromboses and decidual endovascular trophoblast invasion. RESULTS: There were 31 PAPS-positive, 50 PAPS-negative, 34 aneuploid and 20 control cases at 6-14 weeks gestation. Villous morphology and frequency of intervillous thrombosis were not different among groups. Normal intradecidual endovascular trophoblast invasion was identified significantly less frequently in PAPS+ cases (24%), compared with controls (75%), aneuploid (53%), or PAPS- cases (61%; Z = -3.0, P < 0.01). In all cases there was apparently normal interstitial extravillous trophoblast invasion. CONCLUSIONS: Defective decidual endovascular trophoblast invasion, rather than excessive intervillous thrombosis, is the most frequent histological abnormality in PAPS+ associated early pregnancy loss. Furthermore, endovascular trophoblast invasion is not significantly reduced in the majority of fetal aneuploidy-associated pregnancy failures.

Abortion, Habitual↗
PubMed2002

Placental massive perivillous fibrin deposition associated with antiphospholipid antibody syndrome.

We present three pregnancies in which massive perivillous fibrous deposition (MPVFD) and maternal floor infarction (MFI) occurred in patients with primary antiphospholipid antibody syndrome (PAPS) attending a recurrent miscarriage clinic, and who were treated with low dose aspirin and heparin. We hypothesise that PAPS may be a predisposing factor to the development of this condition. The increased prevalence of late pregnancy complications in PAPS patients with a history of early miscarriage suggests that aspirin and heparin therapy does not eradicate the underlying pathological process but merely reduces the severity. Therefore, untreated early pregnancy losses may be converted into treated pregnancies with late antenatal complications. Some patients with PAPS may therefore be prone to suffer either the previously reported complications of the uteroplacental vasculature, such as pre-eclampsia, and/or specific complications related to the environment of the intervillus space, such as MPVFD/MFI.

Abortion, Habitual↗
PubMed2002

Biology and pathology of the placenta in relation to antiphospholipid antibody-associated pregnancy failure.

The placenta is a complex organ composed of maternal and foetal components whose anatomy and function is often greatly simplified in order to explain a range of presumed placenta-related pregnancy complications. Since one of the major roles of the placenta is its materno-foetal transfer function, abnormalities at the materno-foetal interface may be responsible for a range of pregnancy complications manifesting from the first through third trimesters according to the severity of the pathological process in each case. This article reviews some aspects of abnormal early placental development and its consequences, with particular regard to recurrent pregnancy failure and obstetric complications in association with primary antiphospholipid antibody syndrome.

Abortion, Spontaneous↗
PubMed2002

Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro.

Differentiation of human endometrium during the secretory phase of the menstrual cycle is characterized by expression of a variety of genes implicated in the establishment and maintenance of pregnancy. An increased abundance of signal transducers and activators of transcription (Stats) in the secretory phase suggests Stat5 as a component of the differentiation of endometrium in response to ovarian hormone stimulation in vivo. Decidualization is initiated in a subset of endometrial stromal cells (ESC) in vivo during the secretory phase, but it is unclear whether regulated expression of Stat5 is a feature of these cells. Here, therefore, the abundance and subcellular distribution of Stat5 in ESC after a decidualization stimulus of cAMP plus medroxyprogesterone acetate (MPA) has been investigated in vitro. Western blotting revealed an increase in the apparent abundance of Stat5a and Stat5b, in the cytosolic and nuclear fractions, at 2, 3, and 4 d after stimulation. The potential functional relevance of this increase in Stat5 is suggested by the ability of transiently transfected Stat5a or Stat5b to significantly enhance the response of the decidual PRL promoter to cAMP/MPA and attenuation of the response to cAMP/MPA by dominant negative Stat5. Recent evidence suggests endometrial differentiation, including PRL production, as a possible target of antiphospholipid antibodies (aPL) prevalent in recurrent miscarriage. Monoclonal antibody, ID2, which has similar reactivity as human aPL, significantly decreased the apparent abundance of nuclear Stat5b in response to cAMP/MPA and was associated with decreased decidual PRL promoter activation and PRL secretion. Regulated expression of Stat5 is therefore a component of decidual differentiation of human ESC and contributes significantly to activation of the decidual PRL promoter. Alteration of this process by an aPL component suggests decidual differentiation as a potential clinical target in recurrent early miscarriages.

Antibodies, Antiphospholipid↗
PubMed2002

Psychiatric morbidity among patients with recurrent miscarriage.

In this study 81 women with recurrent miscarriages completed questionnaires designed to assess depression, anxiety and general health. This data was matched with data from their medical notes to ascertain demographic and reproductive variables. The results indicated that 33% of patients could be classified as depressed with 9.9% of women being moderately depressed and 7.4% suffering from severe depression. Twenty-one percent of patients had levels of anxiety that were equal or higher to a typical psychiatric outpatient population. Neither age, cigarette consumption, alcohol intake, previous live birth, number of miscarriages, lateness of miscarriage nor length of time since last miscarriage were found to affect the degree of psychiatric morbidity. These findings add to our understanding of the degree to which recurrent miscarriage can affect mental health.

Abortion, Habitual↗
PubMed2001

Reengineering granulocyte colony-stimulating factor for enhanced stability.

Granulocyte colony-stimulating factor is a long-chain cytokine that has both biological and therapeutic applications. It is involved in the production and maturation of neutrophilic progenitor cells and neutrophils and is administered to stimulate the production of white blood cells to reduce the risk of serious infection in immunocompromised patients. We have reengineered granulocyte colony-stimulating factor to improve the thermodynamic stability of the protein, focusing on enhancing the alpha-helical propensity of residues in the antiparallel 4-helix bundle of the protein. These redesigns resulted in proteins with substantially enhanced stability while retaining wild-type levels of biological activity, measured as the ability of the reengineered proteins to stimulate the proliferation of murine myeloid cells transfected with the granulocyte colony-stimulating factor receptor.

Animals↗
PubMed2001

Dynamic imaging of the pelvic floor using an open-configuration magnetic resonance scanner.

The aims of this study were to develop a noninvasive, erect, gravity-dependent method for assessing movements of the female pelvic floor, to describe the range of movements in pelvic floor ascent and descent in asymptomatic and symptomatic women, and to quantify any differences. A total of 102 women, 28-86 years of age, 35 symptomatic and 67 asymptomatic, were included in the study. They were scanned in a sitting position in an open scanner with good vertical access using fast-gradient echo sequences fast spoiled grass (FSPGR). Measurements of the bladder base, uterocervical junction, and anorectal junction were taken in the sagittal plane. The levator ani (LA) muscle insertion was assessed in the coronal plane with the patients at rest, during maximal strain, and during maximum contraction of the pelvic floor. Premenopausal multiparous women have a significantly lower bladder base (8/0 mm above the baseline; P value = 0.009) and uterocervical junction (15.5/3.5 mm; P value = 0.03) at rest than nulliparous women, and this becomes more apparent on straining. Parity confers a more significant effect on the position and function of the pelvic floor than menopausal status. All pelvic organs are lower at rest and on straining in women with defecation difficulties (0/-24 mm; P value = 0.001). These differences are also seen when comparing women with and without urinary incontinence. Dynamic seated magnetic resonance imaging (MRI) shows that all the pelvic organs are lower at rest and on straining in multiparous women and in those with urinary incontinence than in a group of asymptomatic nulliparous volunteers. This difference is also seen in the position of the bladder base and anorectal junction during pelvic floor contraction. These findings suggest general pelvic floor weakness in women who present with symptoms in one compartment and indicate the need for evaluation of the entire pelvic floor particularly prior to surgery. J. Magn. Reson. Imaging 2001;13:923-929.

Adult↗
PubMed2001

Uterine artery Doppler in predicting pregnancy outcome in women with antiphospholipid syndrome.

OBJECTIVE: To assess midtrimester uterine artery Doppler in the prediction of preeclampsia and small for gestational age (SGA) infants in women with primary antiphospholipid syndrome. METHODS: One hundred seventy pregnant women with histories of recurrent miscarriage in association with antiphospholipid antibodies (32 lupus anticoagulant positive, 47 IgG anticardiolipin positive, 78 IgM anticardiolipin positive, and 13 lupus anticoagulant and anticardiolipin antibodies positive) treated with low-dose aspirin and heparin were recruited prospectively. Doppler assessment of the uterine arteries (presence or absence of notches and pulsatility index) were performed at 16-18 and 22-24 weeks. The main outcome measures were the delivery of a SGA infant and the development of preeclampsia. RESULTS: There were 164 live births and six midtrimester losses. The prevalence of preeclampsia and SGA was similar at 10%. In predicting preeclampsia or SGA, uterine artery pulsatility index at either interval was of no value, and the diagnostic accuracy of the Doppler was limited to bilateral uterine artery notches at 22-24 weeks in the subgroup of women with positive lupus anticoagulant. In this subgroup, bilateral uterine artery notches at 22-24 weeks in predicting preeclampsia generated a high likelihood ratio for positive test (12.8, 95% confidence interval 2.2, 75), sensitivity (75%), specificity (94%), positive (75%) and negative (94%) predictive value. In predicting SGA, the corresponding figures were respectively 13.6 (95% confidence interval 1.9, 96), 80%, 94%, 80%, 94%. Uterine artery Doppler was of limited value in pregnancies associated with anticardiolipin antibodies in isolation. CONCLUSION: In pregnancies associated with lupus anticoagulant, uterine artery Doppler at 22-24 weeks is a useful screening test in predicting preeclampsia and SGA infants.

Abortion, Habitual↗
PubMed2001

Reproductive outcomes in women with congenital uterine anomalies detected by three-dimensional ultrasound screening.

OBJECTIVE: To determine reproductive outcomes in women with congenital uterine anomalies detected incidentally by three-dimensional ultrasound. METHODS: We studied 1089 women with no history of infertility or recurrent miscarriage who were seen for a transvaginal ultrasound scan. They were screened for uterine abnormalities using three-dimensional ultrasound. We determined prevalence of miscarriage and preterm labor in women with normal and abnormal uterine morphology. RESULTS: We found that 983 women had a normally shaped uterine cavity, 72 an arcuate, 29 a subseptate, and five a bicornuate uterus. Women with a subseptate uterus had a significantly higher proportion of first-trimester loss (Zeta = 4.68, P <.01) compared with women with a normal uterus. Women with an arcuate uterus had a significantly greater proportion of second-trimester loss (Zeta = 5.76, P <.01) and preterm labor (Zeta = 4.1, P <.01). There were no other significant differences in pregnancy outcomes between women with normal and abnormal uterine morphology. CONCLUSION: This study shows the potential value of three-dimensional ultrasound and confirmed that women with congenital uterine anomalies were more likely to have adverse pregnancy outcomes than women with a normal uterus.

Abortion, Habitual↗
PubMed2001

'Morphs' (MRFs): metal-reversible folding domains for differential IgG binding.

BACKGROUND: Selective recognition and binding of IgG molecules is the basis for a host of immunological and affinity purification techniques. Capture of an IgG in these procedures relies chiefly on its interaction with one of a variety of reengineered bacterial receptors which bind to the Fc region of IgG molecules with very high affinity. While this interaction is extremely efficient in trapping IgG molecules, the tight interaction between the binding partners often requires denaturing conditions for disruption of the complex, which can adversely affect the yield of purified IgG and also limit the lifetime of the receptor matrix. An effective receptor/IgG binding system which could be modulated by less extreme conditions is of considerable general interest. RESULTS: We describe the properties of a series of modified Fc receptor domains which are competent to bind IgG with high affinity but which can be reversibly unfolded upon addition of modest amounts of transition metal ions. Data are presented demonstrating loss of the secondary structural content of the domains as a function of increasing metal concentration, with a concomitant decrease in IgG binding affinity. Variants of the Fc receptor differing at a single amino acid position display increased sensitivity to metal-induced unfolding, while retaining comparable IgG binding ability in the absence of metal. CONCLUSIONS: The interaction of this series of Fc receptors with metal ions abolishes IgG binding, but removal of metal ions allows refolding of the domains with restoration of the IgG binding function. Examples of the utility and potential applications of these metal-modulated IgG binding domains are discussed.

Binding, Competitive↗
PubMed2001

Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London.

OBJECTIVE: To examine the maternal and foetal risks of adverse pregnancy outcome in relation to maternal obesity, expressed as body mass index (BMI, kg/m(2)) in a large unselected geographical population. DESIGN: Retrospective analysis of data from a validated maternity database system which includes all but one of the maternity units in the North West Thames Region. A comparison of pregnancy outcomes was made on the basis of maternal BMI at booking. SUBJECTS: A total of 287,213 completed singleton pregnancies were studied including 176,923 (61.6%) normal weight (BMI 20--24.9), 79 014 (27.5%) moderately obese (BMI 25--29.9) and 31,276 (10.9%) very obese (BMI> or =30) women. MEASUREMENTS: Ante-natal complications, intervention in labour, maternal morbidity and neonatal outcome were examined and data presented as raw frequencies and adjusted odds ratios with 99% confidence intervals following logistic regression analysis to account for confounding variables. RESULTS: Compared to women with normal BMI, the following outcomes were significantly more common in obese pregnant women (odds ratio (99% confidence interval) for BMI 25--30 and BMI> or =30 respectively): gestational diabetes mellitus (1.68 (1.53--1.84), 3.6 (3.25--3.98)); proteinuric pre-eclampsia (1.44 (1.28--1.62), 2.14 (1.85--2.47)); induction of labour (2.14 (1.85--2.47), 1.70 (1.64--1.76)); delivery by emergency caesarian section (1.30 (1.25--1.34), 1.83 (1.74--1.93)); postpartum haemorrhage (1.16 (1.12--1.21), 1.39 (1.32--1.46)); genital tract infection (1.24 (1.09--1.41), 1.30 (1.07--1.56)); urinary tract infection (1.17 (1.04-1.33), 1.39 (1.18--1.63)); wound infection (1.27 (1.09--1.48), 2.24 (1.91--2.64)); birthweight above the 90th centile (1.57 (1.50--1.64), 2.36 (2.23--2.50)), and intrauterine death (1.10 (0.94--1.28), 1.40 (1.14--1.71)). However, delivery before 32 weeks' gestation (0.73 (0.65--0.82), 0.81 (0.69--0.95)) and breastfeeding at discharge (0.86 (0.84--0.88), 0.58 (0.56--0.60)) were significantly less likely in the overweight groups. In all cases, increasing maternal BMI was associated with increased magnitude of risk. CONCLUSION: Maternal obesity carries significant risks for the mother and foetus. The risk increases with the degree of obesity and persists after accounting for other confounding demographic factors. The basis of many of the complications is likely to be related to the altered metabolic state associated with morbid obesity.

Adult↗
PubMed2001

Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage.

While it has been established that anti-phospholipid antibodies (aPL) are associated with recurrent miscarriage (RM), the importance of anti-beta2 glycoprotein 1 (GP1) IgG and anti-annexin V IgG antibodies as risk factors for RM is undefined. We have investigated the prevalence of anti-beta2 GP1 IgG and anti-annexin V IgG antibodies in 54 aPL-positive and 48 aPL-negative women with RM. The prevalence of IgG anti-beta2 GP1 antibodies was not significantly different in persistently aPL-positive women with RM (7%), aPL-negative women with RM (6%) and the normal parous control group (3%). Anti-annexin V IgG antibody prevalence was significantly increased in aPL-positive women with RM compared with aPL-negative women with RM (P = 0.01). The elevations were found in 35%, 19% and 16% of aPL-positive women with RM, aPL-negative women with RM and the control group respectively. No women showed positivity for both anti-beta2 GP1 IgG and anti-annexin V antibodies. Anti-beta2 GP1 IgG antibodies do not appear to be contributory to the investigation of women with RM. Anti-annexin V antibody positivity, although associated with aPL positivity in women with RM, is not an independent risk marker.

Abortion, Habitual↗
PubMed2001

Recurrent miscarriage and variant alleles of mannose binding lectin, tumour necrosis factor and lymphotoxin alpha genes.

Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA) are associated with increased severity of infection. Studies have associated recurrent miscarriage with low serum mannose binding lectin concentrations and premature membrane rupture and preterm delivery with elevated maternal and fetal levels of TNF and the TNF (- 308) polymorphism. In this study the frequencies of variant MBL, TNF and LTA alleles in 76 Caucasian couples with idiopathic recurrent miscarriage were compared with those in 69 Caucasian control couples with no history of miscarriage and at least one previous live birth. A new assay based on hybridization to immobilized sequence-specific oligonucleotides (SSO) was used to rapidly detect nine MBL, two TNF and two LTA sequence variants. The assay genotyped all the structural and promoter MBL variants known to influence serum MBL concentrations. This assay was more reliable than restriction digestion or nested allele-specific PCR for the structural variants at codon 54 or 52, respectively. Reliability for codon 57 alleles was not assessed because of the low frequency in this population. The MBL haplotype frequencies in antenatal controls were similar to those reported in other control populations. The frequencies of structural variant MBL genes and of low, medium and high MBL level haplotypes were similar in the recurrent miscarriage and control couples. The TNF and LTA haplotype frequencies were similar in the recurrent miscarriage and control couples. In this carefully defined population no association has been found between recurrent miscarriage and variant alleles of the MBL, TNF or LTA genes.

Abortion, Habitual↗
PubMed2001

Histological chorioamnionitis in relation to clinical presentation at 14-40 weeks of gestation.

This study examines the prevalence of histological inflammation of the fetal membranes according to gestational age and mode of clinical presentation in a series of 179 consecutive placentas evaluated in a single centre. The frequency of histological inflammation between clinical groups was compared and relation between the prevalence of inflammation and gestational age examined using regression analysis. One hundred and seventy-nine placentas were examined. Histological inflammation was present in 65 (38%) cases including 37/52 (71%) pregnancies presenting with spontaneous preterm labour and delivery (PTL), 23/36 (64%) with preterm prelabour rupture of membranes (PPROM), 1/20 (5%) with vaginal bleeding but no contractions (PVB), 1/13 (8%) with intrauterine death but no labour (IUD), 1/28 (4%) with iatrogenic delivery, 0/4 with termination of pregnancy and 2/20 (10%) delivering spontaneously at term. The prevalence of histological inflammation was significantly higher in those with PTL or PPROM compared to the other groups (P<0.0001). The frequency of histological inflammation was associated with gestational age (F=57.2, P<0.0001, R=0.91), with a peak prevalence (>90%) at 20-24 weeks' gestation.

Journal Article↗