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N J Sebire

Publications and source records attributed to N J Sebire.

At least 55 records · Page 3Linked to original sources
PubMed2004

The dynamic placenta: I. Hypothetical model of a placental mechanism matching local fetal blood flow to local intervillus oxygen delivery.

The placenta can be severely infarcted and yet return well oxygenated blood in spite of the potential shunt paths produced. Optimisation of oxygen transport by some form of local flow matching has been suggested, either via a direct action of hypoxia on subchorial vessels, or indirectly by syncytiotrophoblastic metabolic products. Using casts of cotyledonal vessels and software modelling, a mechanism of hypoxic fetoplacental vasoconstriction could be demonstrated. A simple previously described passive placental model was extended to include hypoxic sensitive arteries and dependence of syncytio-trophoblastic metabolism on intervillus (maternal) blood oxygen content. Such a mechanism of placental flow matching could maintain fetal pO2 by reducing flow through inadequately oxygenated cotyledons, therefore optimising pO2 at the expense of flow. A further modification stabilising fetal water transfer was required to avoid changes in intervillus oxygen delivery producing changes in fetal water content via placental capillary pressure alterations. Intervillus/villus flow matching is likely in the human placenta and this study suggests probable biologically plausible mechanisms for such a phenomenon.

Casts, Surgical↗
PubMed2004

Alveolar septal collapse in the transitional infant lung: a possible common mechanism in sudden unexpected death in infancy.

Sudden unexpected death in infancy (SUDI) is a category used to represent the largest single group of infant deaths. Although there are several theories, the cause of SUDI remains unknown and the mechanism of co-sleeping associated deaths are also undetermined. We investigate a possible biomechanical mechanism which may be common in SUDI and may provide an explanation for the association of the known risk factors for SUDI such as co-sleeping, prematurity, prone sleeping position, overwrapping, overheating and maternal smoking. The neonatal lung has few, if any, true septa but from about four weeks of age, a period of rapid alveolarisation commences. The developing alveolar walls (septae) have little fibre support against surface tension forces as they grow but are supported by a double layer of capillaries. Until the elastin/collagen supporting network is laid down these nascent septal walls are vulnerable to collapse against sac or duct walls during this transitional period. We hypothesise that such collapse will prevent one side of the septa, and the wall it overlays, from alveolar gas exchange and a functional left-right shunt is formed which may result in hypoxia. Furthermore, lung stretch receptors in bronchi running through or adjacent to collapsed regions will be activated, falsely signalling lung inflation to the brain stem with resultant respiratory inhibition, so precipitating further collapse. The process will continue until lung volume falls below residual capacity, when normal tidal breathing efforts will no longer result in significant air flow, even if stretch receptor signals have not produced complete apnoea. Large inspiratory efforts are then required to break the surface tension seal, which damages capillaries to produce petechial haemorrhages. Many epidemiological risk factors for SUDI could influence such a mechanism, leading to the proposal that Alveolar Septal Collapse in Infancy (ASCI) is a core mechanism via which these factors act.

Airway Obstruction↗
PubMed2004

Decreased endovascular trophoblast invasion in first trimester pregnancies with high-resistance uterine artery Doppler indices.

BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis of pre- eclampsia. This study investigates the relationship between Doppler assessment of uterine artery resistance and endovascular trophoblastic invasion in the first trimester of pregnancy. METHODS: Patients undergoing termination of pregnancy for non-medical reasons were categorized as having a low- or high-resistance uterine artery blood flow pattern by transabdominal Doppler ultrasound. Products of conception were examined histologically with regard to the extent of decidual endovascular trophoblast invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine artery blood flow pregnancies identified at 10-14 weeks of gestation. Normal intradecidual endovascular trophoblast invasion was identified with a similar frequency in both groups (P=0.79). However, the proportion of decidual vessels with endovascular trophoblast invasion was significantly higher in the low-resistance pregnancies (49%) compared with the high-resistance ones (34%, P=0.02). CONCLUSIONS: The findings of this study support the use of uterine artery Doppler investigation for the non-invasive assessment of trophoblast invasion in early pregnancy. Further studies are necessary to clarify the biological significance of these observations and their potential clinical applications.

Adult↗
PubMed2004

p57(KIP2) immunohistochemical staining of gestational trophoblastic tumours does not identify the type of the causative pregnancy.

AIM: To determine whether immunohistochemical staining for p57(KIP2), the product of the maternally expressed gene CDKN1C, can be used to differentiate between gestational trophoblastic tumours arising from a complete hydatidiform mole and those originating from non-molar pregnancies. METHODS: The immunohistochemical expression of p57(KIP2) was investigated in 23 cases of choriocarcinoma and 17 placental site trophoblastic tumours. Fourteen of the tumours examined were shown by DNA analysis to have arisen from complete hydatidiform moles and 26 from non-molar pregnancies. RESULTS: Five of 11 (45%) post-complete hydatidiform mole choriocarcinomas and two of three (67%) post-complete hydatidiform mole placental site trophoblastic tumours were found to be p57(KIP2)+ and showed similar immunostaining characteristics to tumours that developed from non-molar pregnancies. Although there was a statistically significant reduction in the proportion of cases showing positive p57(KIP2) staining in post-complete hydatidiform mole tumours compared with those originating in non-molar pregnancies [proportion difference 0.35 [95% confidence interval (CI) 0.05, 0.61], P = 0.02], immunostaining did not provide diagnostically useful information to differentiate between these tumours in clinical practice. There was no significant difference between the extent of staining in choriocarcinoma versus placental site trophoblastic tumours [proportion difference 0.17 (95% CI - 12, 42), P = 0.19]. The majority of both types of gestational trophoblastic tumour were positive for the presence of the p57(KIP2) protein irrespective of their genetic origin. CONCLUSION: Immunostaining for p57(KIP2) fails to discriminate between gestational trophoblastic tumours that have arisen from complete hydatidiform moles and those that have originated from other types of pregnancy.

Adult↗
PubMed2004

Pathology of astrovirus associated diarrhoea in a paediatric bone marrow transplant recipient.

Human astrovirus infection often causes outbreaks of self limiting diarrhoea, but may also infect patients who are immunodeficient or immunocompromised. Although there are previous publications relating to various aspects of astroviruses, there is a minimal amount of literature on the histopathological features of gastrointestinal astrovirus infection in humans. We report the histopathological findings, including immunohistochemical and electron microscopic features, of astrovirus infection in a bone marrow transplant recipient aged 4 years with diarrhoea. The appearance of a small intestinal biopsy did not suggest graft versus host disease, but demonstrated villous blunting, irregularity of surface epithelial cells, and an increase in lamina propria inflammatory cell density. Immunohistochemical staining with a murine astrovirus group specific monoclonal antibody demonstrated progressively more extensive staining in the duodenal and jejunal biopsies, predominantly restricted to the luminal surface and cytoplasm of surface epithelial cells, most marked at the villus tips. Electron microscopic examination demonstrated viral particles within the cytoplasm of enterocytes, focally forming paracrystalline arrays.

Astroviridae Infections↗
PubMed2003

Fetal loss following ultrasound diagnosis of a live fetus at 6-10 weeks of gestation.

OBJECTIVE: To examine prospectively the value of demographic characteristics and ultrasound findings in the prediction of subsequent fetal loss in pregnancies with live fetuses at 6-10 weeks of gestation. METHODS: Transvaginal ultrasound examination was performed in 866 pregnancies at 6-10 weeks of gestation. The relation of demographic data and ultrasound findings at the time of the initial assessment to subsequent fetal loss was examined. RESULTS: In the 668 singleton pregnancies with live fetuses and complete follow-up there were 50 (7.5%) fetal losses. The incidence of fetal loss increased significantly with maternal age and decreased with gestation. In the pregnancies resulting in fetal loss, compared to those with live births, the incidence of vaginal bleeding and cigarette smoking was higher, the fetal heart rate was significantly lower and the gestation sac diameter was smaller but the yolk sac diameter was not significantly different. CONCLUSION: In pregnancies with a live fetus at 6-10 weeks' gestation the rate of subsequent fetal loss is related to maternal age, gestation, cigarette smoking, history of vaginal bleeding and the ultrasound findings of small gestation sac diameter and fetal bradycardia, relative to crown-rump length.

Female↗
PubMed2003

Megacystis at 10-14 weeks of gestation: chromosomal defects and outcome according to bladder length.

AIMS: To examine the prevalence of chromosomal defects and outcome of fetuses with megacystis at 10-14 weeks of gestation. METHODS: At the 10-14-week scan fetal megacystis was defined by a longitudinal bladder diameter of 7 mm or more. In 145 such fetuses the fetal karyotype and pregnancy outcome were examined in relation to the longitudinal diameter of the fetal bladder. RESULTS: Chromosomal defects, mainly trisomies 13 and 18, were present in 30 cases. In the group with longitudinal bladder diameter of 7-15 mm the incidence of chromosomal defects was 23.6% (26/110), whereas in those with bladder diameter > 15 mm the incidence was 11.4% (4/35). The fetal nuchal translucency (NT) was above the 95th centile of the normal range for crown-rump length in a higher proportion of cases with abnormal rather than normal karyotype (76.7% compared to 31.3%; Chi-square P < 0.0001). The expected number of cases of trisomy 21, estimated on the basis of maternal age, gestational age and fetal NT, was 6.2 rather than the observed 2 and the corresponding numbers for trisomies 13 or 18 were 4.2 for expected and 24 for observed. In the chromosomally normal group with longitudinal bladder diameter of 7-15 mm follow-up scans demonstrated spontaneous resolution of the megacystis in 90% of the cases and enlargement of the megacystis and/or the development of echogenic kidneys in 10%. In contrast, none of the cases with bladder diameter > 15 mm demonstrated spontaneous resolution of the megacystis. CONCLUSIONS: In fetal megacystis with longitudinal bladder diameter of 7-15 mm there is a risk of about 25% that the fetus will have a chromosomal defect but in the chromosomally normal group there is spontaneous resolution of the megacystis in about 90% of cases. If the bladder diameter is > 15 mm the risk of chromosomal defects is about 10% and in the chromosomally normal group the condition is invariably associated with progressive obstructive uropathy.

Adult↗
PubMed2003

Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients.

OBJECTIVE: To examine whether there are characteristic histological features in placentas from ongoing pregnancies of patients with a history of recurrent miscarriage, with and without primary antiphospholipid antibody syndrome, in relation to clinical pregnancy outcome. METHODS: Patients attending a recurrent miscarriage clinic were investigated and treated according to an established protocol. One hundred twenty-one consecutive patients achieving a potentially viable pregnancy (at least 24 completed weeks' gestation), including 60 primary antiphospholipid antibody syndrome-positive cases and 61 primary antiphospholipid antibody syndrome-negative cases were included. After delivery, placental pathologic examination was carried out by a pathologist unaware of the clinical details. Histological sections were examined by two pathologists independently. Pregnancy outcome and placental findings were reviewed in relation to the maternal antiphospholipid antibody status. RESULTS: Pregnancy outcome was similar in primary antiphospholipid antibody syndrome-positive and primary antiphospholipid antibody syndrome-negative groups regarding gestation at delivery and antepartum obstetric complications. Several histological placental abnormalities were identified in both groups, but most pregnancies were clinically uncomplicated, with no significant placental abnormalities. In cases with pregnancy complications, the placental pathology was primarily that of uteroplacental vasculopathy, such as placental infarction and preeclampsia, but there were no specific placental lesions or patterns of abnormalities characteristic of primary antiphospholipid antibody syndrome-positive patients. A small subgroup of primary antiphospholipid antibody syndrome-positive patients may be at increased risk of development of maternal floor infarction or massive perivillus fibrin deposition. CONCLUSION: There are no specific histopathologic placental abnormalities characteristic of treated patients with antiphospholipid antibody syndrome and poor reproductive history, but complications of uteroplacental disease are more common.

Abortion, Habitual↗
PubMed2003

Myogenin and MyoD1 expression in paediatric rhabdomyosarcomas.

The diagnosis of paediatric solid tumours is often based on small tissue needle biopsies in which many different entities demonstrate a "small round cell tumour" phenotype and in which there may be insufficient tissue to allow the interpretation of diagnostic architectural features, which may be present in larger specimens. Therefore, the extensive use of a panel of immunohistochemical markers is part of the routine handling and investigation of such biopsies to reach a definite diagnosis. However, in some cases the morphological and routine immunohistochemical findings may be insufficient for a precise diagnosis or they may be difficult to interpret in the given clinical context. Although many paediatric tumours exhibit characteristic chromosomal translocations with resultant specific fusion transcripts, these require molecular methods for their detection, usually on fresh tissue samples, which may not always be available. As more immunohistochemical markers become available, more precise diagnosis on such small biopsies may be possible. This review examines the use of the immunohistochemical markers, MyoD1 and myogenin, in the diagnosis of paediatric rhabdomyosarcoma, including its subtypes.

Biomarkers, Tumor↗
PubMed2003

Isolated EBV lymphoproliferative disease in a child with Wiskott-Aldrich syndrome manifesting as cutaneous lymphomatoid granulomatosis and responsive to anti-CD20 immunotherapy.

Patients with primary immunodeficiencies such as the Wiskott-Aldrich syndrome (WAS) are prone to develop Epstein-Barr virus (EBV) related lymphoproliferative disorders (LPDs). EBV LPD is most frequently seen in patients receiving immunosuppressive treatment after organ transplantation (post-transplant lymphoproliferative disorder), but can also arise in the primary immunodeficiencies. Typically, EBV LPD presents as a diffuse systemic disease with lymphadenopathy and organ involvement. A rare angiocentric and angiodestructive form of EBV associated B cell LPD, lymphomatoid granulomatosis (LyG), has also been reported in association with WAS. LyG most commonly involves the lung, but can also be seen in brain, kidney, liver, and skin. This report describes the case of a 16 year old boy with WAS who presented with an isolated non-healing ulcerating skin lesion. Biopsy revealed an EBV related LPD with the histological features of LyG. This cutaneous lesion responded dramatically to treatment with specific anti-CD20 immunotherapy and the patient remains clinically free of LPD at 18 months.

Adolescent↗
PubMed2003

Risk of recurrent hydatidiform mole and subsequent pregnancy outcome following complete or partial hydatidiform molar pregnancy.

OBJECTIVE: To determine pregnancy outcome, including the rate of repeat molar pregnancy, following histologically confirmed complete or partial hydatidiform mole. DESIGN: Retrospective review of a large supraregional database of registrations for gestational trophoblastic disease. SETTING: Supraregional Trophoblastic Disease Unit, London. SAMPLE: Women with pregnancies affected by complete or partial hydatidiform mole registered between 1992 and 1998. METHODS: All patients with a diagnosis of histologically confirmed complete or partial hydatidiform mole were identified and data on subsequent pregnancies compared between groups using comparison of proportion test. MAIN OUTCOME MEASURES: Pregnancy outcome by partial or complete mole subtype, with particular regard to risk of subsequent molar pregnancy. RESULTS: Of 2578 complete moles, the subsequent pregnancy was affected by hydatidiform mole in 27 (1.9%) cases, including 22 (81%) complete moles and 5 (19%) partial moles. Of 2627 partial moles, the subsequent pregnancy was also molar in 25 (1.7%) cases, including 17 (68%) partial moles and 8 (32%) complete moles. Overall recurrence risk for molar pregnancy was 1.8% (1 in 55), or a 20-fold increase compared with the background risk. Of 27 cases with repeat complete moles, three had further complete moles, suggesting the recurrence risk following two previous complete moles is approximately 10%. There were no other significant differences in pregnancy outcome between cases with previous complete or partial hydatidiform mole and that expected in an unselected obstetric population. CONCLUSIONS: Women having a pregnancy affected by a histologically confirmed complete or partial hydatidiform mole may be counselled that the risk of repeat mole in a subsequent pregnancy is about 1 in 60 and if this were to occur, the majority of cases will be of the same type of mole as the preceding pregnancy. However, >98% of women who become pregnant following a molar conception will not have a further hydatidiform mole and these pregnancies are at no increased risk of other obstetric complications.

Adolescent↗
PubMed2002

The role of intraplacental vascular smooth muscle in the dynamic placenta: a conceptual framework for understanding uteroplacental disease.

Although non-innervated, the placenta must continually accommodate changes in uteroplacental pressure (due to spiral artery failure, maternal position, maternal emotional state, etc.), which might otherwise be expected to result in rapid feto-maternal water fluxes in the highly water-permeable human hemochorial placenta. Uteroplacental flow must also be under the same influences, producing temporary, or permanent, regions of poor intervillous flow, yet the reduction of umbilical vein oxygen content that would be expected to be produced by such shunts of feto-placental blood do not occur in the normal fetus. We suggest that there is a local villus tree mechanism matching intravillus flow of fetal blood to local uteroplacental oxygen content. By analogy to ventilation/perfusion (V/Q) matching in the postnatal lung we suggest the term U/Q matching for this mechanism in the placenta. We further suggest that such disturbances in flow matching are compensated for by the fetus, via complementary adjustment of umbilico-chorionic artery and umbilical venous flow resistances, utilizing the differing sensitivities of vascular smooth muscle tissues of embryonic and extra-embryonic origin to vasoactive agents.

Adaptation, Physiological↗