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Biomedical subjects

P Chamberlain

Publications and source records attributed to P Chamberlain.

At least 19 recordsLinked to original sources
PubMed2004

Follow-up of children with isolated fetal echogenic bowel with particular reference to bowel-related symptoms.

OBJECTIVES: To determine whether there was any evidence of long-term bowel pathology in children, apparently healthy at birth, who had a prenatal second-trimester diagnosis of isolated grade 2 fetal echogenic bowel. METHODS: This was a retrospective study using data from the Oxford Congenital Anomaly Register. Fetuses with isolated grade 2 fetal echogenic bowel and date of delivery from 1994 to 2000 inclusive were identified. Information about the health of the children, particularly relating to bowel symptoms, was obtained from hospital records and from a questionnaire sent to the general practitioner. RESULTS: A total of 109 cases were identified, with delivery details available for 108. There was one unexplained intrauterine death, and additional problems were subsequently diagnosed in four cases (cystic fibrosis (2), Down syndrome (1), and VACTERL (1)). Questionnaires were sent to the GPs of the 103 who had no problems identified at the time of discharge from the maternity hospital. Age at follow-up ranged from one to four years. Responses to the questionnaires were received from 83 (81%). Of these, 74 (89%) had not reported bowel symptoms to the GP, 9 (11%) reported symptoms relating to constipation (6), chronic abdominal pain (1), infantile colic with milk intolerance (1) and gastro-oesophageal reflux (1). CONCLUSION: This small study provides some reassurance that there was no evidence of any serious long-term bowel pathology associated with isolated fetal echogenic bowel.

Child, Preschool↗
PubMed2003

An overview of scientific and regulatory issues for the immunogenicity of biological products.

Immunogenicity of biological products can occur pre-clinically and clinically when products elicit immune responses in animals or humans receiving the products. This is a concern for manufacturers, regulatory agencies and clinicians as immune responses can result in effects on product effectiveness and safety. The clinical sequelae of immunogenicity range from no effects to serious, life-threatening syndromes. However, although many biological products are immunogenic to some extent, it is quite rare that immunogenicity leads to serious adverse events. Whilst there are methods to detect immunogenicity, they currently rely on detecting the humoral rather than the cellular response of the immune system. The design and validation of assays such as immuno-assays and bio-assays are critical for a meaningful assessment of immunogenicity. There are a growing number of computational and laboratory-based methods for the prediction of immunogenicity, as well as methods to reduce potential immunogenicity and these may lead to less immunogenic biological products in future.

Animals↗
PubMed2003

The usefulness of ultrasound assessment of amniotic fluid in predicting adverse outcome in prolonged pregnancy: a prospective blinded observational study.

OBJECTIVE: To determine whether a single ultrasound scan at or beyond 40 weeks of gestation to detect a single deepest pool of amniotic fluid <2 cm and amniotic fluid index (AFI) <5 cm is clinically useful in the prediction of subsequent adverse pregnancy outcome. DESIGN: A prospective double blind cohort study. SETTING: A university teaching hospital delivering approximately 6000 women annually. POPULATION: One thousand and five hundred and eighty-four pregnant women at or beyond 40 weeks of gestation. METHODS: Ultrasound assessment of liquor to detect the single deepest pool of amniotic fluid and derive the AFI at or after 40 weeks of gestation. MAIN OUTCOME MEASURES: Perinatal death, meconium aspiration, birth asphyxia, intervention in labour for fetal distress, a cord arterial pH <7 and admission to the neonatal unit. RESULTS: An AFI <5 cm but not a single deepest pool <2 cm was significantly associated with birth asphyxia or meconium aspiration. An AFI <5 cm was also significantly associated with caesarean section for fetal distress in labour, a cord arterial pH <7 at delivery and low Apgar scores. Despite there being a statistically significant association with adverse outcomes the sensitivity of AFI was low at 28.6%, 12% and 11.5% for major adverse outcome, fetal distress in labour or admission to the neonatal unit, respectively. CONCLUSIONS: The AFI is superior to a measure of the single deepest pool as an assessment of the fetus at or after 40 weeks but has a poor sensitivity for adverse pregnancy outcome. Routine use is likely to lead to increased obstetric intervention without improvement in perinatal outcomes.

Adult↗
PubMed2001

Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors.

Mutations at either Tyr181 or Tyr188 within HIV-1 reverse transcriptase (RT) give high level resistance to many first generation non-nucleoside inhibitors (NNRTIs) such as the anti-AIDS drug nevirapine. By comparison second generation inhibitors, for instance the drug efavirenz, show much greater resilience to these mutations. In order to understand the structural basis for these differences we have determined a series of seven crystal structures of mutant RTs in complexes with first and second generation NNRTIs as well as one example of an unliganded mutant RT. These are Tyr181Cys RT (TNK-651) to 2.4 A, Tyr181Cys RT (efavirenz) to 2.6 A, Tyr181Cys RT (nevirapine) to 3.0 A, Tyr181Cys RT (PETT-2) to 3.0 A, Tyr188Cys RT (nevirapine) to 2.6 A, Tyr188Cys RT (UC-781) to 2.6 A and Tyr188Cys RT (unliganded) to 2.8 A resolution. In the two previously published structures of HIV-1 reverse transcriptase with mutations at 181 or 188 no side-chain electron density was observed within the p66 subunit (which contains the inhibitor binding pocket) for the mutated residues. In contrast the mutated side-chains can be seen in the NNRTI pocket for all seven structures reported here, eliminating the possibility that disordering contributes to the mechanism of resistance. In the case of the second generation compounds efavirenz with Tyr181Cys RT and UC-781 with Tyr188Cys RT there are only small rearrangements of either inhibitor within the binding site compared to wild-type RT and also for the first generation compounds TNK-651, PETT-2 and nevirapine with Tyr181Cys RT. For nevirapine with the Tyr188Cys RT there is however a more substantial movement of the drug molecule. We conclude that protein conformational changes and rearrangements of drug molecules within the mutated sites are not general features of these particular inhibitor/mutant combinations. The main contribution to drug resistance for Tyr181Cys and Tyr188Cys RT mutations is the loss of aromatic ring stacking interactions for first generation compounds, providing a simple explanation for the resilience of second generation NNRTIs, as such interactions make much less significant contribution to their binding.

Binding Sites↗
PubMed2001

Prenatal diagnosis of an epignathus: a case report and review of the literature.

An epignathus is an extremely rare form of teratoma that arises from the oral cavity, most commonly from the palate. We describe a case identified sonographically at 17 weeks' gestation after a raised maternal serum alpha-fetoprotein was recorded. This pregnancy was terminated but we review the literature over the last 10 years and describe the management options available in such cases.

Adult↗
PubMed2000

Megacystis-microcolon-intestinal hypoperistalsis syndrome: the difficulties with antenatal diagnosis. Case report and review of the literature.

Megacystis on antenatal scan in female fetuses is rare and has serious diagnostic implications. We report two cases of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in female infants in whom antenatal scan abnormalities were identified, but the diagnosis not made until after delivery. MMIHS is a rare autosomal recessive condition which is usually lethal in the first year of life. Prenatal diagnosis is hampered by the lack of specific diagnostic findings on ultrasound and the absence of an identified genetic locus. The prenatal findings in MMIHS are reviewed and contrasted with those of other causes of lower abdominal masses on antenatal ultrasound.

Abnormalities, Multiple↗
PubMed2000

Lipoprotein-associated phospholipase A(2), platelet-activating factor acetylhydrolase: a potential new risk factor for coronary artery disease.

A specific and robust immunoassay for the lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), platelet-activating factor acetylhydrolase, is described for the first time. The immunoassay was used to evaluate possible links between plasma Lp-PLA(2) levels and atherosclerosis risk amongst susceptible individuals. Such an investigation was important because Lp-PLA(2) participates in the oxidative modification of low density lipoprotein by cleaving oxidised phosphatidylcholines, generating lysophosphatidylcholine and oxidised free fatty acids. The majority of Lp-PLA(2) was found associated with LDL (approximately 80%) and, as expected, enzyme levels were significantly positively correlated to LDL cholesterol. Plasma Lp-PLA(2) levels were significantly elevated in patients with angiographically proven coronary artery disease (CAD) when compared with age-matched controls, even though LDL cholesterol levels did not differ significantly. Indeed, when included in a general linear model with LDL cholesterol and other risk factors, Lp-PLA(2) appeared to be an independent predictor of disease status. We propose, therefore, that plasma Lp-PLA(2) mass should be viewed as a potential novel risk factor for CAD that provides information related to but additional to traditional lipoprotein measurements.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Five cases of brain injury following amniocentesis in mid-term pregnancy.

This paper describes the neuroimaging and neuropathological findings in five cases of severe brain damage after traumatic mid-trimester amniocentesis, all performed between 1986 and 1994. Although fetal injury after amniocentesis has been reported, reports of brain injury are infrequent. Continuous ultrasound monitoring may reduce the risk of fetal injury but follow-up ultrasound scans can be falsely reassuring. Withdrawal of blood-stained fluid, particularly if it contains tissue fragments, should alert the operator to the possibility of fetal damage. Histological examination of such tissue fragments may confirm the nature of the fetal damage. The consequences of fetal brain injury are severe, all five of our cases showed evidence of disruption of brain development compatible with mid-term injury. Obstetricians and their patients should be aware of the small but significant risk of brain damage after mid-term amniocentesis.

Adult↗
PubMed2000

Preventive intervention for maltreated preschool children: impact on children's behavior, neuroendocrine activity, and foster parent functioning.

OBJECTIVE: This article describes the results of a pilot study that evaluated the effectiveness of the Early Intervention Foster Care (EIFC) program in the period immediately following a child's placement in a new foster home. METHOD: Data were collected from an EIFC group, a regular foster care group, and a community comparison group-each with 10 participants-via questionnaires for children and their caretakers and salivary cortisol sampling. RESULTS: EIFC foster parents adopted and maintained positive parenting strategies, EIFC children's behavioral adjustment improved, and changes occurred in several salivary cortisol measures. Moreover, regular foster care children exhibited decrements in functioning in several areas over the same time period. CONCLUSIONS: Results are discussed with regard to how such research fits into a larger program of prevention research for high-risk preschool children.

Black or African American↗
PubMed1999

Congenital diaphragmatic hernia: prenatal diagnosis, outcome and continuing morbidity in survivors.

OBJECTIVE: To improve counselling by investigating the prenatal diagnosis, outcome and morbidity in survivors of congenital diaphragmatic hernia. SETTING: Prenatal Diagnosis Unit, Oxford Radcliffe Women's Centre, Oxford. DESIGN: Cohort study. SAMPLE: Babies with congenital diaphragmatic hernia diagnosed postnatally and born to women scanned prenatally identified between January 1991 and December 1996. METHODS: Associated anomalies, outcome of pregnancy and final diagnoses were determined from hospital records. A report from the general practitioner and paediatrician recorded health and development information. MAIN OUTCOME MEASURES: Accuracy of prenatal diagnosis, survival of cases of congenital diaphragmatic hernia and presence of ongoing morbidity in survivors. RESULTS: There were 35 pregnancies with congenital diaphragmatic hernia, nine of which were not diagnosed prenatally. In 22 pregnancies with isolated congenital diaphragmatic hernia, four were terminated, there were six perinatal deaths and two later deaths. Thirteen of 35 cases (37%) with congenital diaphragmatic hernia were associated with other abnormalities: four with abnormal karyotype and nine with other structural anomalies. Five of these women continued with their pregnancy; there were two neonatal deaths and three survivors. Thirteen of 35 infants (37%) survived, eight with chronic disorders requiring specialist intervention including respiratory problems (n = 6); developmental delay (n = 4); poor growth (n = 5); artificial feeding (n = 3); gastro-oesophageal reflux (n = 3); recurrent hospital admissions (n = 6); and further surgery (n = 4). CONCLUSIONS: The survival for infants born alive with congenital diaphragmatic hernia was 56% (13/23), 61% of whom have persistent disorders. Despite advances in neonatology there is a high mortality and morbidity with congenital diaphragmatic hernia. Prenatal counselling should reflect this.

Cohort Studies↗
PubMed1999

Amniotic fluid concentrations of dimeric inhibins, activin A and follistatin in pregnancy.

OBJECTIVE: The feto-placental unit is the major source of circulating concentrations of inhibin A and activin A in human pregnancy. The aim of this study was to measure the amniotic fluid concentrations of inhibin A, inhibin B, activin A and follistatin in pregnancies bearing male and female fetuses. DESIGN AND METHOD: Amniotic fluid samples collected by amniocentesis were stored at -20 degrees C. Dimeric inhibins, 'total' activin A and 'total' follistatin were measured using specific two-site enzyme immunoassays. Samples were assayed blindly and the information on fetal sex was obtained from the cytogenetics laboratory. RESULTS: Data show that amniotic fluid concentrations of inhibin A, inhibin B and activin A gradually increase with gestation whilst concentrations of follistatin are similar between weeks 15 and 20 of pregnancy. Mean amniotic fluid levels of inhibin A and inhibin B at 16 and 17 weeks gestation and mean activin A levels at 15 and 16 weeks gestation are considerably lower in pregnancies with male (n=24) compared with female (n=28) fetuses. Levels of follistatin are not different in the male and female fetal pregnancies at any studied gestation. CONCLUSIONS: The results indicate that amniotic fluid contains high concentrations of inhibins (A and B), activin A and follistatin in early pregnancy suggesting that these hormones are produced by the fetal membranes and may be involved in the development of the fetus.

Activins↗
PubMed1998

6-year experience of prenatal diagnosis in an unselected population in Oxford, UK.

BACKGROUND: The benefits and harm associated with prenatal diagnosis are open to debate. We give a 6-year overview of the experience of one prenatal-diagnosis unit using a defined, unselected population. METHODS: All congenital malformations suspected prenatally and all congenital malformations, including chromosome anomalies, confirmed at birth were identified from the local Congenital Malformation Register. All fetuses or infants of women booked for delivery at the Oxford Women's Centre who had an OX postcode and date of delivery between 1991 and 1996 were eligible for the study. FINDINGS: 725 (2%) of 33,376 babies, were judged abnormal at delivery. 396 (55%) malformed fetuses and infants had been correctly identified prenatally. 174 fetuses had a suspected abnormality identified on scan and subsequently proved to be normal. 160 (92%) of these false-positive results were attributable to the reporting of so called ultrasound soft markers. Accuracy of ultrasound diagnosis was good for structural malformations. Ultrasound soft markers were responsible for a 4% increase in detection of malformations (from 51% to 55%) and a 12-fold increase in false-positive rate (one in 2332 to one in 188). 171 pregnancies (43% of prenatally diagnosed malformed babies) were terminated because of suspected abnormality. Suspicion of abnormality in these cases was first aroused after ultrasound scan in 136 (79%); chromosome analysis because of advanced maternal age, family history, or higher risk in biochemical screening test in 25 (15%); and molecular analysis of single gene defect because of family history in ten (6%). There was a 20% reduction in prevalence of conditions compatible with survival beyond the neonatal period because of termination of such pregnancies. INTERPRETATION: More than half of all malformed fetuses can be identified prenatally in routine practice, mostly following initial suspicion from ultrasound examination. Ultrasound soft markers lead to a small increase in detection of malformations but a large increase in false positives. Further research on the impact, including psychological, and value of markers is required to determine whether the benefits of reporting them exceeds the harm. Because methods and techniques continually change, ongoing surveillance of prenatal diagnostic services is vital.

Adult↗
PubMed1998

Comparison of two community alternatives to incarceration for chronic juvenile offenders.

The relative effectiveness of group care (GC) and multidimensional treatment foster care (MTFC) was compared in terms of their impact on criminal offending, incarceration rates, and program completion outcomes for 79 male adolescents who had histories of chronic and serious juvenile delinquency. Results show that boys who participated in MTFC had significantly fewer criminal referrals and returned to live with relatives more often. Multiple regression analyses showed that assignment to a treatment condition (i.e., GC or MTFC) predicted official and self-reported criminality in follow-up beyond other well-known predictors of chronic juvenile offending (i.e., age at 1st offense, number of previous offenses, age at referral).

Adolescent↗
PubMed1998

Outcome of prenatally diagnosed anterior abdominal wall defects.

One hundred consecutive cases of confirmed anterior abdominal wall defect, identified prenatally in the Oxford Prenatal Diagnosis Unit over 11 years, were studied. Fifty nine per cent of cases were suspected omphaloceles and 41% suspected gastroschisis. Fifty four per cent of omphaloceles were accompanied by other defects compared with 5% of those with gastroschisis. Overall, 29% of fetuses with omphalocele had an abnormal karyotype, and of those with another abnormality identified on scan (excluding four cases with no karyotype performed), 54% had an abnormal karyotype. Of the 27 cases with suspected isolated omphalocele, 14 were live born, all of whom have survived. If the 11 whose parents opted for termination of pregnancy are excluded, survival to birth was 88%. Six of the suspected isolated omphaloceles have Beckwith Wiedemann syndrome (BWS). Eight (57%) of the live born babies with omphaloceles had major problems up to the age of 2, but only one (7%) has long term major problems. This child has BWS and is deaf. Of the 39 cases of suspected isolated gastroschisis, 33 (85%) pregnancies resulted in live birth and one in neonatal death after surgery. Survival rate (excluding terminated pregnancies) was 97%. Gastroschisis was associated with a younger maternal age than omphalocele (p < 0.001) and lower birthweight centile (p < 0.01). Fifteen per cent of the gastroschisis babies had major problems up to the age of 2 years and 12% long term developmental problems. Ninety three per cent of the omphalocele babies and 88% of those who had gastroschisis have no long term problems. Over the study period there have been major changes in scanning equipment and expertise. Since 1991 no woman with a suspected isolated lesion has opted for termination of pregnancy.

Abnormalities, Multiple↗
PubMed1998

Prenatal sonographic diagnosis of skeletal dysplasias--a report of the diagnostic and prognostic accuracy in 35 cases.

Sonographic assessment of the skeleton is a routine part of fetal anomaly scanning. We report a series of 35 cases seen during a 7-year interval in which a skeletal dysplasia was suspected prenatally. In seven (20 per cent) of the 35 cases, a specific diagnosis could not be made either pre- or postnatally. Follow-up was incomplete in one case. In 32 (91 per cent) of the 35 cases, prenatal sonographic examination correctly predicted the prognosis, although in only 11 (31 per cent) of the 35 cases was the suggested prenatal diagnosis proven to be correct. The difficulty of making an accurate prenatal sonographic diagnosis in fetuses with suspected skeletal dysplasias throughout gestation, especially in the third trimester, and the importance of comprehensive multidisciplinary postnatal assessment in these cases are emphasized.

Abortion, Induced↗
PubMed1997

Conducting ecologically valid prevention research: recruiting and retaining a "whole village" in multimethod, multiagent studies.

Many prevention studies are now designed with complementary interventions in different settings. Evaluations of these interventions require assessing the child's behavior in each of these settings. Conducting these studies, therefore, may involve recruiting school districts, principals, classroom teachers, peers, parents, siblings, and in later years, employers and intimate partners. These participants may be considered natural raters or satellite subjects, depending on their degree of involvement. Issues of recruitment and retention thus are magnified in multimethod, multiagent studies. To illustrate these issues, findings are presented for three studies conducted with risk populations in the past decade at the Oregon Social Learning Center: a passive longitudinal study, a selected prevention study, and an indicated prevention study. Findings indicate that achieving high recruitment and retention rates for at-risk and high-risk subjects in multisetting studies is possible, and that a developmental approach should be taken to recruiting risk populations.

Adolescent↗
PubMed1997

Uterine cavity assessment prior to in vitro fertilization: comparison of transvaginal scanning, saline contrast hysterosonography and hysteroscopy.

A total of 44 patients undergoing in vitro fertilization (IVF) and requiring uterine cavity assessment agreed to have both saline contrast hysterosonography (SCHS) and hysteroscopy. SCHS was performed following a baseline transvaginal scan by injection of saline into the uterine cavity during continuous scanning. Hysteroscopy was performed with a flexible fiberscope with a 3.6-mm outer diameter; 38 of 44 women (86%) underwent both procedures. Hysteroscopy diagnosed intrauterine abnormalities in 16 women. SCHS was in complete agreement in 13 of 16 cases. As a screening test for any cavity abnormality, SCHS had a 87.5% sensitivity, 100% specificity, 100% positive predictive value and 91.6% negative predictive value. In 14 women, an abnormal uterine cavity was apparent on transvaginal scanning (TVS). However, TVS, unlike SCHS, could not (1) confidently diagnose submucosal fibroids in the presence of a uterus with multiple fibroids; (2) distinguish between a hyperplastic endometrium and a large polyp; or (3) differentiate between an arcuate and a septate uterus. In addition, ovarian pathology was diagnosed on TVS in five women: endometrioma (n = 1), complex cysts (n = 2) and polycystic ovaries (n = 2). SCHS is a simple, accurate, well-tolerated procedure that can be performed within a fertility unit, avoiding invasive and expensive diagnostic hysteroscopy. Significant findings can be treated by operative hysteroscopy prior to commencing an IVF treatment cycle.

Adult↗