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Biomedical subjects

M D Kilby

Publications and source records attributed to M D Kilby.

At least 19 recordsLinked to original sources
PubMed2006

Prognosis for the co-twin following single-twin death: a systematic review.

BACKGROUND: Following single-twin death, the perinatal mortality and morbidity for the surviving co-twin is increased but difficult to quantify. We present data on prognosis from a systematic review. OBJECTIVES: We aimed to determine the incidence of a) co-twin death, b) neurological abnormality and c) preterm delivery for the surviving co-twin following single-twin death after 14 weeks of gestation. SEARCH STRATEGY: Literature was identified by searching two bibliographical databases and specialist journals between 1990 and 2005. SELECTION CRITERIA: The selected studies of > or = 5 cases reported on perinatal death and/or neurodevelopmental delay of the surviving co-twin. DATA COLLECTION AND ANALYSIS: Studies were assessed for quality and data extracted to allow computation of rates. The data were inspected for heterogeneity using a Forrest plot and examined statistically using the chi-square test. Data from individual studies were pooled within subgroups defined by prognosis. MAIN RESULTS: The search strategy yielded 632 potentially relevant citations. Full manuscripts were retrieved for 54 citations and 28 studies were finally included in the review. Following the death of one twin, the risk of monochorionic and dichorionic co-twin demise was 12% (95% CI 7-11) and 4% (95% CI 2-7), respectively. The risk of neurological abnormality in the surviving monochorionic and dichorionic co-twin was 18% (95% CI 11-26) and 1% (95% CI 0-7), respectively. The risk of preterm delivery was 68% (95% CI 56-78) and 57% (95% CI 34-77), respectively. Where there was comparative data within studies, the odds of monochorionic co-twin intrauterine death was six times that of dichorionic twins (OR 6.04 [95% CI 1.84-19.87]). Neurological abnormality was also higher in monochorionic compared with dichorionic pregnancies (OR 4.07 [95% CI 1.32-12.51]). AUTHOR'S CONCLUSIONS: More prospective research is required to inform decision making on this subject, especially with data that allow stratification based upon chorionicity.

Child↗
PubMed2006

A systematic review of the accuracy of first-trimester ultrasound examination for detecting major congenital heart disease.

OBJECTIVE: To evaluate the accuracy of first-trimester ultrasound examination in detecting major congenital heart disease (CHD) using a systematic review of the literature. METHODS: General bibliographic and specialist computerized databases along with manual searching of reference lists of primary and review articles were used to search for relevant citations. Studies were included if a first-trimester ultrasound scan was carried out to detect CHD that was subsequently verified by a reference standard. Data were extracted on study characteristics and quality, and 2 x 2 tables were constructed to calculate sensitivity and specificity. RESULTS: Ten studies (involving 1243 patients) were suitable for inclusion. Of these, four used transabdominal ultrasonography, four used transvaginal and two used a combination. Pooled sensitivity and specificity were 85% (95% CI, 78-90%) and 99% (95% CI, 98-100%), respectively. CONCLUSION: Ultrasound examination of the fetus in the first trimester is feasible for accurately detecting major CHD. It may be offered to women at high risk of having children with CHD.

Echocardiography↗
PubMed2006

In-utero pulmonary drainage in the management of primary hydrothorax and congenital cystic lung lesion: a systematic review.

OBJECTIVE: To determine the effect of in-utero pulmonary drainage on perinatal survival in fetuses with primary hydrothoraces and/or congenital cystic lung lesions. METHODS: Relevant papers were identified by searching MEDLINE (1966-2004), EMBASE (1988-2004) and the Cochrane Library (2004 issue 2). Studies were selected if the effect of prenatal pulmonary drainage (shunt, surgery or drainage) on perinatal survival was compared with no treatment, in fetuses with ultrasonic evidence of lung pathology. Study selection, quality assessment and data abstraction were performed independently and in duplicate. RESULTS: Of a total number of 7958 articles, there were 16 controlled observational studies involving 608 fetuses. Study characteristics and quality were recorded for each study. Data were abstracted to generate 2 x 2 tables to compare the effect of pulmonary drainage vs. no drainage on perinatal survival. Pooled odds ratios (ORs) were used as summary measures of effect and the results were stratified according to predicted fetal prognoses. Pulmonary drainage did not improve perinatal survival in cystic lung lesions compared with no drainage (OR 0.56, 95% CI 0.32-0.97, P = 0.04) overall. However there was a marked improvement with this therapy in a subgroup of fetuses with fetal hydrops fetalis (OR 19.28, 95% CI 3.67-101.27, P = 0.0005) but not in the subgroup uncomplicated by fetal hydrops fetalis (OR 0.04, 95% CI 0.01-0.32, P = 0.002). CONCLUSION: Percutaneous, in-utero pulmonary drainage in fetuses with ultrasonic evidence of congenital pulmonary cystic malformations was associated with improved perinatal survival among fetuses with hydrops fetalis and therefore poor predicted survival.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed2006

Peripheral skin necrosis in the recipient of monochorionic twins complicated by twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates approximately 15% of monochorionic, diamniotic twin pregnancies and if untreated carries a high perinatal loss rate of between 80% and 100%, depending on the stage. The underlying pathology in TTTS appears to be an imbalanced intertwin perfusion difference, secondary to functional unidirectional arteriovenous anastomoses within a monochorionic placenta. We report two cases of monochorionic twin pregnancy complicated by TTTS, in which the pregnancies were treated by serial aggressive amnioreduction. However, the recipient twin in each pregnancy developed 'ischemic damage' to a lower limb.

Adult↗
PubMed2006

Laser ablation of foetal microcystic lung lesion: successful outcome and rationale for its use.

OBJECTIVE: A foetus with an echodense, microcystic lung lesion complicated by non-immune hydrops has a high mortality rate. Because of the limited treatment options available, laser ablation was offered in an attempt to reduce the size of the lesion and reduce hydrops fetalis. METHODS AND RESULTS: A 25-year-old nulliparous woman presented at 21 weeks gestation. Ultrasound revealed a male foetus with a large microcystic right sided lung lesion that completely occupied the right hemithorax causing marked mediastinal deviation. The foetus was hydropic with polyhydramnios. Percutaneous laser ablation of the large microcystic lung lesion was performed under direct ultrasound control. At a power setting of 45 W, and using a 400 microm Nd:YAG laser fibre, the core of the lesion was photocoagulated in pulses lasting 5 s at 5 s intervals. The total target dose was 1683 J. This led to a marked but temporary reduction in amniotic fluid volume. The patient was commenced on sulindac and amniodrainage was performed at 27 weeks as reaccumulation of the polyhydramnios occurred. Pre-eclampsia complicated the pregnancy at 38 weeks gestation and an emergency caesarean section was performed. The baby underwent a thoracotomy and lobectomy at 48 h of age, made a good recovery, and is currently well 8 weeks post-delivery. CONCLUSIONS: In cases of cystic lung lesion complicated by hydrops, laser ablation should be considered as a treatment option.

Adenoma↗
PubMed2006

Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction.

Thyroid hormones (THs) are essential for normal fetal development, with even mild perturbation in maternal thyroid status in early pregnancy being associated with neurodevelopmental delay in children. Transplacental transfer of maternal THs is critical, with increasing evidence suggesting a role for 3,3',5-tri-iodothyronine (T3) in development and function of the placenta itself, as well as in development of the central nervous and other organ systems. Intrauterine growth restriction (IUGR) is associated with fetal hypothyroxinaemia, a factor that may contribute to neurodevelopmental delay. The recent description of monocarboxylate transporter 8 (MCT8) as a powerful and specific TH membrane transporter, and the association of MCT8 mutations with profound neurodevelopmental delay, led us to explore MCT8 expression in placenta. We describe the expression of MCT8 in normal human placenta throughout gestation, and in normal third-trimester placenta compared with that associated with IUGR using quantitative reverse transcriptase PCR. MCT8 mRNA was detected in placenta from early first trimester, with a significant increase with advancing gestation (P=0.007). In the early third trimester, MCT8 mRNA was increased in IUGR placenta compared with normal samples matched for gestational age (P<0.05), but there was no difference between IUGR and normal placenta in the late third trimester. Western immunoblotting findings in IUGR and normal placentae were in accord with mRNA data. MCT8 immunostaining was demonstrated in villous cytotrophoblast and syncytiotrophoblast as well as extravillous trophoblast cells from the first trimester onwards with increasingly widespread immunoreactivity seen with advancing gestation. In conclusion, expression of MCT8 in placenta from early gestation is compatible with an important role in TH transport during fetal development and a specific role in placental development. Altered expression in placenta associated with IUGR may reflect a compensatory mechanism attempting to increase T3 uptake by trophoblast cells.

Adult↗
PubMed2005

Prediction of fetal anemia in pregnancies with red-cell alloimmunization: comparison of middle cerebral artery peak systolic velocity and amniotic fluid OD450.

OBJECTIVE: To compare the accuracy of Doppler velocimetry (middle cerebral artery peak systolic velocity, MCA-PSV) and amniocentesis (amniotic fluid delta optical density 450 (OD450)) for the detection of fetal anemia against the gold standard of fetal blood sampling (FBS). METHODS: Thirty-eight pregnancies were identified to be at risk of fetal anemia from immune causes between January 2000 and May 2002. In a cross-sectional diagnostic accuracy study, MCA-PSV and amniotic fluid delta OD450 values were plotted on reference charts and compared to an FBS obtained within the subsequent 7 days. Receiver-operating characteristics (ROC) curves were used and the area under the curve (AUC) calculated to compare the overall accuracy of the two tests. Sensitivity, specificity and likelihood ratios for positive (LR+) and negative (LR-) test results were generated for specific thresholds of MCA-PSV and delta OD450. RESULTS: For MCA-PSV (n = 38), the AUC was 0.71 (95% CI 0.57-0.85) and for amniotic fluid delta OD450 (n = 22) it was 0.68 (95% CI 0.49-0.87) compared with FBS within 7 days. Sensitivity, specificity and LR+, LR- for MCA-PSV were 64%, 81%, 3.4 and 0.5, respectively, and 53%, 71%, 1.9 and 0.7 for amniotic fluid OD450, respectively. CONCLUSION: MCA-PSV and OD450 have similar test accuracy in detecting fetal anemia. MCA-PSV is non-invasive and therefore presents no risk of miscarriage or preterm labor and thus is a preferable method of screening for fetal anemia.

Amniocentesis↗
PubMed2005

The use of high resolution magnetic resonance imaging in the prenatal diagnosis of fetal nuchal tumors.

Fetal magnetic resonance imaging (fetal MRI) is an important adjunct to antenatal imaging especially when neonatal surgery is contemplated. We report two cases of fetal nuchal tumors, which were diagnosed incidentally on an ultrasound scan and had fetal MRI to aid diagnosis, prognosis, counseling and management planning. In the first case, fetal MRI aided diagnosis and prenatal multidisciplinary management of a cervical teratoma. Tracheal involvement could not be excluded and an ex-utero intrapartum treatment procedure was planned. Postnatal MRI and angiography provided further information prior to surgery. In the second case, fetal MRI assisted thorough counseling following the finding of a cervical lesion thought to be a cervical teratodermoid, a multicystic hygroma or congenital lymphectasia. The parents opted for termination of the pregnancy. Postmortem findings confirmed the extent of involvement of surrounding structures diagnosed prenatally. The mass was found to be a hamartomatous hemangiolymphangioma.

Adult↗
PubMed2005

Thyroid hormones and fetal brain development.

Thyroid hormones are intricately involved in the developing fetal brain. The fetal central nervous system is sensitive to the maternal thyroid status. Critical amounts of maternal T3 and T4 must be transported across the placenta to the fetus to ensure the correct development of the brain throughout ontogeny. Severe mental retardation of the child can occur due to compromised iodine intake or thyroid disease. This has been reported in areas of the world with iodine insufficiency, New Guinea, and also in mother with thyroid complications such as hypothyroxinaemia and hyperthyroidism. The molecular control of thyroid hormones by deiodinases for the activation of thyroid hormones is critical to ensure the correct amount of active thyroid hormones are temporally supplied to the fetus. These hormones provide timing signals for the induction of programmes for differentiation and maturation at specific stages of development. Understanding these molecular mechanisms further will have profound implications in the clinical management of individuals affected by abnormal maternal of fetal thyroid status.

Animals↗
PubMed2004

The in vitro effects of triiodothyronine on epidermal growth factor-induced trophoblast function.

The development of the human placenta involves a complex process of tightly regulated proliferation and invasion by extravillous trophoblast into the uterine decidua. Inadequate placentation is a feature of intrauterine growth restriction and other gestational pathology. There is some evidence that T(3) plays a role in the regulation of these processes and that T(3) may act synergistically with epidermal growth factor (EGF). The aim of this study was to define the expression of thyroid hormone receptors in extravillous trophoblast, elucidate the effects of T(3) on both proliferation and differentiation of human trophoblast cells of varying origins, and define the potential interaction between EGF and T(3) on these processes. Using immunohistochemistry, specific thyroid hormone receptor isoforms were localized in extravillous trophoblast in first- and second-trimester placental bed biopsies, indicating potential sensitivity to T(3). In studies of human trophoblast-derived cell lines and primary cultures of cytotrophoblast cells in vitro, T(3) and EGF exerted an antiproliferative effect on an extravillous-like cell line (SGHPL-4) but stimulated proliferation in JEG-3 choriocarcinoma cells. EGF enhanced survival of nonproliferative term primary cytotrophoblast cells and significantly enhanced invasion of fibrin gels by SGHPL-4 cells, an effect attenuated by T(3). Both T(3) and EGF also significantly enhanced SGHPL-4 motility. These results suggest that EGF and T(3) may act synergistically to regulate both proliferation and differentiated function of human trophoblast.

Cell Division↗
PubMed2004

Congenital malformations of the diaphragm: findings of the West Midlands Congenital Anomaly Register 1995 to 2000.

OBJECTIVES: To describe trends in incidence, associated anomalies, clinical outcomes and sensitivity of prenatal diagnosis for congenital malformations of the diaphragm in the West Midlands Region between 1995 and 2000. METHODS: Information was retrieved from a population-based register of major congenital malformations in a health region of England, the West Midlands Congenital Anomaly Register (WMCAR), between 1995 and 2000. RESULTS: One hundred and sixty-one confirmed cases of congenital malformations of the diaphragm were notified from 396 577 births. This gives an incidence of 4.1 per 10,000 births. After natural losses and terminations, the incidence at birth was 2.9 per 10,000 registered births. For live-born cases, the infant mortality rate was 317 per 1000 births. 47% of the cases had additional structural or chromosomal anomalies; the infant mortality rate for these complex cases was 533 per 1000, an increased relative risk of 2.37 compared with isolated lesions. 66% of the cases were diagnosed prenatally, 51% of isolated lesions and 84% of complex cases. Fourteen prenatally diagnosed cases (12%) were false-positives; however, 11 of these cases had other significant pathology. These 14 cases were not included in the 161 confirmed cases. CONCLUSION: Congenital malformations of the diaphragm remain associated with considerable infant mortality. Most cases are now diagnosed before birth and the prognosis is adversely affected by the presence of other structural or chromosomal anomalies. This presents significant challenges for those involved in counselling the parents of affected fetuses.

Chromosome Aberrations↗
PubMed2003

Providing letters and audiotapes to supplement a prenatal diagnostic consultation: effects on later distress and recall.

OBJECTIVES: Information provided at a mid-trimester fetal scan aims to improve patients' knowledge and minimize anxiety. This randomized controlled trial conducted at the Fetal Medicine Centre at Birmingham Women's Hospital aimed to assess the relative value of providing 1.standard information: a consultation and computer-generated ultrasound report (n = 29); 2.standard information plus a post scan written non-technical letter (n = 29); 3.standard information plus audiotapes of the consultation (n = 29); 4.standard information plus both non-technical letters and audiotapes (n = 30). It also aimed at exploring whether severity of diagnosis (none; mild; moderate-severe) interacted with the type of information provided to affect subsequent anxiety, depression and recall of information. PARTICIPANTS: Women (n = 550) referred with suspected fetal anomalies (without a previous history of anomaly or known psychiatric illness) were sent information regarding this study. One hundred and seventeen women consented and were randomly assigned to one of four information groups. The groups were similar with regard to age, education and marital status. MAIN OUTCOME MEASURES: State anxiety and depression were evaluated with the self-report State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI) prior to consultation and two weeks post-scan. A structured telephone interview assessed recall of information approximately two weeks later. RESULTS: Two weeks after the initial consultation, women who received an audiotaped recording of the consultation reported significantly less anxiety than the control group (mean STAI 41.44 [95% CI 35.63-47.26] versus 44.92 [39.32-50.52]; difference = 10.70 [3.56-17.83], p < 0.01). Women who received a non-technical letter also reported less anxiety than the control group, an effect that approached significance (mean STAI 39.08 [95% CI 32.85-45.30]; difference = 6.48 [0.21-13.16], p = 0.058). There were no differences between the information groups on depression scores or recall of information. Women with a more severe abnormality reported higher anxiety and depression two weeks post-consultation, and had greater free recall but less cued recall of information. CONCLUSIONS: Provision of additional material (particularly an audiotape) following a prenatal scan appears to minimise anxiety compared with standard practice. Provision of audiotapes and non-technical letters do not appear to affect patient recall.

Adult↗
PubMed2003

Characterization of human trophoblast as a mineralocorticoid target tissue.

In mineralocorticoid target tissues, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) confers mineralocorticoid receptor selectivity by metabolizing hormonally active cortisol to inactive cortisone, allowing aldosterone access to the receptor. This enzyme is also expressed in high abundance in fetal tissues, particularly in placental trophoblast, where a role has been proposed in regulating fetal growth and development by protecting the fetus from maternal hypercortisolaemia and modulating local glucocorticoid receptor (GR), rather than mineralocorticoid receptor-mediated responses. As such the placenta has not been considered a mineralocorticoid target tissue. We have used conventional RT-PCR and real-time quantitative RT-PCR to demonstrate that primary cultures of term human cytotrophoblast express the mineralocorticoid-responsive genes Na/K-ATPase (alpha1 and beta1 subunits), epithelial sodium channel (ENaC, alpha and gamma subunits) and the serum and glucocorticoid-inducible kinase (SGK). SGK expression was found to be rapidly and strongly induced by corticosteroids (24- and 38-fold by 10(-7) mol/l aldosterone and 10(-7) mol/l dexamethasone respectively after 1 h). Dexamethasone-, but not aldosterone-stimulated SGK induction was inhibited by GR antagonist (RU38486), confirming the presence of a functional mineralocorticoid receptor and suggesting that placental trophoblast expresses a functional mineralocorticoid receptor, which is in part responsible for the corticosteroid regulation of SGK expression. Placental 11beta-HSD2 may protect the MR in a fashion analogous to classical mineralocorticoid tissues to modulate trophoblast sodium transport.

Adult↗
PubMed2003

A potential role for PTTG/securin in the developing human fetal brain.

Human securin, known also as PTTG, has established oncogenic and cell cycle regulatory functions. PTTG/securin transforms cells in vitro, inhibits sister chromatid separation, and regulates secretion of fibroblast growth factor-2. FGF-2 is a key regulator of CNS development and PTTG/securin expression has been reported in murine fetal brain. We examined the expression and function of securin and FGF-2 in the developing human fetal brain and in a fetal neuronal cell line (NT 2). Securin expression was significantly reduced in first and second trimester fetal cerebral cortex compared with adult cerebral cortex, where immunocytochemistry revealed intense securin staining in neuronal cell bodies. FGF-2 protein was concordantly lower in fetal cortex, whereas pretranslational expression of PTTG binding factor (PBF) was not significantly altered in fetal brain compared with adult. PCNA expression demonstrated that high securin levels in adult cortex were associated with absent cell proliferation. In NT-2 cells, securin stimulated FGF-2 expression, which could be abrogated by a carboxyl-terminal mutation. Low transient expression of securin resulted in a significant proliferative effect, whereas high levels of securin expression inhibited cell turnover. We propose a potential role for human PTTG/securin in modulating cell proliferation and FGF-2 expression during human neurogenesis.

Brain↗
PubMed2003

Placental iodothyronine deiodinase expression in normal and growth-restricted human pregnancies.

We have described the expression of specific iodothyronine deiodinase mRNAs (using quantitative RT-PCR) and activities in normal human placentas throughout gestation and compared our findings to those in placentas from pregnancies affected by intrauterine growth restriction (IUGR). The predominant deiodinase expressed in placenta was type III (D3); type II (D2) was also present. In general terms, the activities of the enzymes D2 and D3 (and mRNAs encoding these enzymes) were higher earlier in gestation (<28 wk) than at term and displayed an inverse relationship with the duration of gestation (P < 0.05). Comparison of the relative expressions of mRNAs encoding D2 and D3 as well as their activities in placentas associated with IUGR (early and late gestational groups) with findings from normal placentas of similar gestational ages revealed no significant differences. Immunolocalization of D2 and D3 in syncytiotrophoblast (including syncytial sprouts) and cytotrophoblast of human placentas was demonstrated at both early and late gestation. Treatment of primary cultures of term cytotrophoblast cells in vitro with increasing doses of T(3) (1, 10, and 100 nM) resulted in increased expression of mRNAs encoding both D2 and D3 at 100-nM concentrations (P < 0.01) compared with control. Experiments with JEG-3 choriocarcinoma cells demonstrated a similar effect on D3 mRNA at 10 and 100 nM T(3) (P < 0.01). The demonstrated changes in iodothyronine deiodinase expression in the placenta across pregnancy are likely to contribute to regulation of the thyroid hormone supply to the developing fetus. The lack of difference in deiodinase expression in normal placentas and those found in IUGR argues against placental deiodinases being responsible for the hypothyroxemia in circulating fetal thyroid hormones observed in this condition.

Adult↗