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Biomedical subjects

M Whittle

Publications and source records attributed to M Whittle.

At least 19 recordsLinked to original sources
PubMed2001

Enlarged fetal bladders: aetiology, management and outcome.

Ultrasound routinely identifies the fetal bladder from 10 weeks of gestation. Understanding the normal embryology of the fetal bladder forms the basis of understanding the mechanisms for pathology. Early onset megacystis <12 mm (maximum diameter) frequently regresses spontaneously however when associated with other structural abnormalities 40% are chromosomally abnormal. Survival in this group is rare and the underlying histopathology is of urethral fibrostenosis. Second and third trimester megacystic indicates a heterogenous group where a precise antenatal diagnosis may be impossible. A distended thick wall bladder associated with a dilated posterior urethra and oligohydramnios is pathonemonic of posterior urethral valves; without this combination of ultrasound signs the underlying pathology is less certain. Prediction of other aetiologies for the megacystis is less accurate but includes primary reflux, cloacal plate, urethral duplication and megacystic microcolon in the differential diagnosis. Robust published data is currently unavailable to define appropriate management for individual cases of megacystis. Therefore current best practice for antenatal management will be discussed.

Female↗
PubMed2000

Determination of Interparticle Forces by Colloidal Particle Scattering: A Simulation Study.

Colloidal particle scattering is a recently developed method for the determination of forces between micron-sized particles, which has given promising results. Inversion of the experimental scattering results to retrieve the interaction force requires the development of reliable computer code to match theory and experiment. We review the method used, discuss some operational details, and present some validating results for shear and sedimentation fields that compare favorably with the literature. We have used the simulation to compare particle scattering in a simple shear field for a range of exponential surface forces and discuss the sensitivity of these results to changes in potential parameters. We also discuss the sensitivity in relation to sources of error and their magnitude. In particular, we have incorporated a Brownian dynamics algorithm and compared the level of thermal noise with a simple theoretical formula. We introduce a straightforward means of representing the data and find that order of magnitude changes in the parameters evoke changes in the scattering pattern roughly equivalent to the Brownian noise level for a typical experiment with Pe=120. The results demonstrate the ability of the method, in principle, to distinguish between interaction potentials of different ranges and energy parameters. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Magnetic resonance imaging of the primary site in stage I cervical carcinoma: A comparison of endovaginal coil with external phased array coil techniques at 0.5T.

OBJECTIVE: To compare endovaginal with pelvic phased array coil magnetic resonance imaging (MRI) in detection of Stage I cervical carcinoma by correlating the findings with histopathology. PATIENTS AND METHODS: Forty consecutive patients with Stage I cervical carcinoma confirmed histologically were studied using an endovaginal coil alone immediately followed by a pelvic phased array coil. T1-W transverse and T2-W FSE sagittal images made with each coil were analyzed independently by two radiologists noting the presence and size of a mass within the cervix and any parametrial extension or involvement of adjacent organs. Tumor volumes were measured using the electronic calliper to compute tumor area on each slice and multiplying by the slice thickness. Thirty patients underwent radical hysterectomy, one a trachylectomy, one simple hysterectomy and four extended cone biopsies. Four patients had radiotherapy to the primary tumor. Following surgery, histopathologic findings were recorded and tumor volumes measured. RESULTS: Tumor volumes ranged from 0-106 cm(3)(median 1.4 cm(3), mean 9 +/- 19.4 cm(3)). Thirty-six patients had correlation of the primary site with the surgical specimen. Agreement between observers was excellent for both endovaginal (k = 0.90) and pelvic phased array (k = 0.96) techniques. Combined sensitivity and specificity for both observers of endovaginal MR imaging for detection of tumor was 96% and 70%, respectively; for pelvic phased array imaging sensitivity was substantially less at 54%. Specificity was higher at 83.7%, probably because small abnormalities were seldom visible. In patients treated surgically, early parametrial involvement in four women on endovaginal MRI was confirmed histologically in two. Pelvic phased array imaging showed early parametrial involvement in four women and was confirmed in one. CONCLUSION: Endovaginal MRI adds substantially to information from pelvic phased array images in the preoperative assessment of patients with early cervical cancer. J. Magn. Reson. Imaging 2000;12:1020-1026.

Adult↗
PubMed2000

Apexification of an infected untreated immature tooth.

A case of a traumatized permanent young tooth in which apexification occurred without the benefit of endodontic treatment is reported. It illustrates how a immature incisor that underwent pulp necrosis and periapical inflammation could progress to complete apical formation.

Child↗
PubMed1999

Hypoxia down-regulates placenta growth factor, whereas fetal growth restriction up-regulates placenta growth factor expression: molecular evidence for "placental hyperoxia" in intrauterine growth restriction.

Early placental development occurs in an environment of relative hypoxia. Hypoxia promotes angiogenesis and up-regulates vascular endothelial growth factor (VEGF) expression while it down-regulates placenta growth factor (PIGF) that possess 53% homology with VEGF. Morphological studies show poor placental vascular development and an increase in the mitotic index of cytotrophoblasts in intrauterine growth restriction (IUGR). We hypothesized that the reported relatively high oxygen level in the intervillous space in contact with IUGR placental villi will limit angiogenesis by changes in VEGF and PIGF expression and function. Western immunoblot analysis demonstrates a diametric expression of PIGF and VEGF proteins throughout pregnancy with PIGF levels increasing and VEGF levels decreasing, consistent with placental oxygenation. In IUGR placentae, the ratio of PIGF/GAPDH mRNA was increased by 2.3-fold (p < 0.03) and PIGF protein levels were also increased, (p < 0.05) as compared with gestationally-matched normal placentae. PIGF mRNA and protein were localized to the trophoblast bilayer and villous mesenchyme of the human placenta throughout gestation. In vitro studies demonstrated that increasing oxygen tension (hyperoxia) up-regulated PIGF protein in term placental villous explants, whereas hypoxic culture of a term trophoblast choriocarcinoma cell line (BeWo) down-regulated PIGF mRNA and protein and VEGFR-1 (Flt-1) autophosphorylation. The addition of PIGF-1 to a spontaneously transformed first trimester cytotrophoblast cell line stimulated DNA synthesis while PIGF-2 had little effect. VEGF and PIGF exert their biological actions by means of a common receptor VEGFR-1. In the first trimester trophoblast cells, PIGF-1 increased the association of phosphorylated extracellular signal-related kinase (ERK) with VEGFR-1 immunoprecipitates while both PIGF-1 and PIGF-2 also potentiated endogenous VEGF mediated association of phosphorylated extracellular related kinase (ERK) with VEGFR-2 (KDR). More importantly, the addition of PIGF-1 had little effect while PIGF-2 inhibited cell growth in cultured endothelial cells derived from human umbilical vein. Nitric oxide (NO) is reported to promote angiogenesis and PIGF-2 inhibited the basal release of NO from the first trimester trophoblast. The tissue expression and functional studies support the hypothesis of "placental hyperoxia" in early-onset IUGR because hypoxia down-regulates trophoblast PIGF levels, PIGF expression is increased in IUGR, and PIGF-2 inhibits endothelial cell growth. Taken together, these changes provide a cellular explanation for the observed poor angiogenesis in the pathogenesis of IUGR and show that the two PIGF isoforms may modulate trophoblast and endothelial cell function differently, possibly through potentiation of VEGF mediated activation of VEGF-2.

Cell Line↗
PubMed1998

Cellular localization of AT1 receptor mRNA and protein in normal placenta and its reduced expression in intrauterine growth restriction. Angiotensin II stimulates the release of vasorelaxants.

Angiotensin II (ANG II) is a potent vasoconstrictor and growth promoter. Quantitative receptor autoradiography using the nonselective radioligand [125I]ANG II and subtype-selective competing compounds demonstrated the presence of both ANG II receptor (AT)1 and AT2 receptor recognition sites. In addition, a relatively small population of apparently non-AT1/non-AT2 sites was identified that may represent a novel high affinity ANG II recognition site in human placenta. Using placental membrane preparations, the AT2 receptor antagonist PD123177 failed to compete for [3H]ANG II binding at relevant concentrations, whereas the AT1 receptor antagonist losartan competed in a monophasic manner for all the specific binding, suggesting that the non-AT1/non-AT2 recognition site identified using autoradiography may be a cytosolic binding site. AT1 receptor binding was significantly reduced (P < 0. 02) in intraeuterine growth restriction (IUGR) pregnancies. Western blot analysis confirmed this showing a reduction in AT1 receptor protein. In situ hybridization and immunocytochemistry revealed that AT1 receptor mRNA and protein were localized throughout pregnancy in the cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast, as well as in or around the blood vessels of placental villi. The intensity of the hybridization signal for AT1 receptor mRNA over the syncytium was reduced in IUGR. ANG II evoked a rapid and concentration-dependent release of NO in first trimester cytotrophoblast-like cells that was abolished by the inclusion of the competitive NOS inhibitor NG-monomethyl-L-arginine. Neither losartan nor PD123177 alone significantly inhibited ANG II-evoked NO release, and when cells were stimulated with ANG II in the presence of losartan (10 microM) and PD123177 (10 microM) in combination, NO release was significantly inhibited (P < 0.05). These observations also suggest, for the first time, the existence of a cross-talk between AT1 or AT2 receptors in trophoblast and that the reduction in placental AT1 receptors in IUGR may, in part, account for poor placental function in this disorder.

Angiotensin II↗
PubMed1996

Fibula and its ligaments in load transmission and ankle joint stability.

A study was made of the role of the fibula in weightbearing and its contribution to ankle joint stability in 10 anatomic specimen lower limbs. On axial loading of the lower limb, the fibula was found to take an average of 17% of a 1500 N axial load. The proportion of the load carried by the fibula increased with the total loading. It also increased when the line of load was displaced laterally and when the ankle joint was in dorsiflexion and decreased when the line of loading shifted medially or the joint was plantar flexed. With loading, the lateral malleolus migrated distally relative to the medial malleolus, except after fibular osteotomy, when it migrated proximally. There was an approximately inverse relationship between proportional fibular loading and distal fibular migration. Cutting the inferior tibiofibular ligament reduced the proportional load in the fibula and increased its distal migration. The interosseous membrane modified the load distribution between the tibia and the fibula, with the distal fibula carrying a higher proportion of the axial load than did the proximal. Surgical repair of a ruptured inferior tibiofibular ligament, using either 1 or 2 screws, was associated with an abnormal pattern of load distribution and fibular displacement.

Ankle Joint↗
PubMed1995

[Unexplained increase in maternal plasma in alpha-fetoproteins in the second trimester of pregnancy: perinatal results].

To determine the relation between adverse perinatal events and an unexplained mid-trimester elevation in maternal serum alpha-fetoprotein (MSAFP) in an unselected population, 16,093 women with a singleton pregnancy delivered between January 1985 and November 1991, at the Queen Mother's Hospital, Glasgow, Scotland, were studied. The elevated MSAFP group (n = 606) was associated with an increased risk of preterm delivery (odds ratios/95% confidence intervals) (3.7/2.6-5.2), small or gestational age (4.5/3.3-6.1), intrauterine death (3.9/1.7-9.4), and placental abruption (3.2/1.5-6.7). The risks increased with MSAP concentration. An unexplained mid-trimester elevation of MSAFP is associated with increased risk of adverse perinatal events, thus acting as a non-specific marker o a "high risk pregnancy". Alterations to current antenatal management in this group may improve prognosis.

Female↗
PubMed1993

Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: results of a controlled trial.

PROBLEM: It remains unclear whether maternal immunization with paternal lymphocytes prior to conception improves the reproductive outcome in women with recurrent abortion in whom all secondary causes have been excluded. METHOD: A double-blind placebo controlled trial was instituted in women with unexplained recurrent spontaneous abortion, comparing immunization with 400 million paternal to 400 million maternal (autologous) lymphocytes. The groups were compared in a paired sequential trials chart, by logistic regression, and, in addition, a meta-analysis of this and other published trials was carried out. RESULTS: The live birth rate among pregnancies in paired couples with paternal lymphocyte immunization was 68% compared to 47% in the women who received their own cells. The results bordered on, but did not achieve, statistical significance. The women in each group were thoroughly investigated to exclude known causes of recurrent pregnancy loss and appeared to have been well matched in all variables. Women with lymphocytotoxic antibodies against paternal lymphocytes were excluded. Unlike our previous study there was not association between the time to conception and the chance of a successful outcome. Indeed, the time to conception was relatively short, 12 wk in all groups. The meta-analysis supported an overall modest favorable experience with paternal cells. CONCLUSION: The study is consistent with a general trend favoring paternal over maternal lymphocyte immunization but reinforces the need for larger multicenter controlled trials as well as more detailed biological study in humans to understand the nature of the maternal-fetal interface and its breakdown.

Abortion, Habitual↗
PubMed1992

Spontaneous cessation of umbilical blood flow in the acardiac fetus of a twin pregnancy.

The acardiac fetus is a rare entity found only in monozygotic multiple pregnancy. Although the acardiac fetus is non-viable, the perinatal mortality rate for the normal fetus may be as high as 50 per cent, and is usually associated with fetal heart failure and hydrops fetalis, or as the result of prematurity. In this communication, we describe a case of spontaneous cessation of blood flow to an acardiac fetus and discuss the management of this condition with special reference to optimizing the outcome for the normal fetus.

Abnormalities, Severe Teratoid↗