Perinatal stroke in term infants with neonatal encephalopathy.
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Cerebral Infarction↗
Biomedical subjects
F M Cowan
Publications and source records attributed to F M Cowan.
Recent advances in imaging the fetus and newborn.
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Brain↗
Developing complex interventions for rigorous evaluation--a case study from rural Zimbabwe.
Much attention has been placed on the need to develop and evaluate complex interventions targeting public health issues, such as reproductive health. However, and as has been the case in the recent past, even well-designed trials will be flawed unless meticulous attention is paid to ensuring the most appropriate intervention is designed and developed. This requires a well-resourced and carefully planned feasibility study, incorporating both formative and process evaluation, with particular attention being paid to the context of the proposed intervention. In this paper, we describe the way in which a feasibility study helped redesign and shape a complex intervention targeting adolescent sexual health in rural Zimbabwe. By using a mixture of in-depth interviews, focus groups and participant observation with pupils, parents, teachers and education officers, we were able to show that the intervention as originally conceived was unlikely to be deliverable. Process evaluation findings from the feasibility study led to substantial changes to both the content and delivery of the proposed intervention, which is now subject to testing for effectiveness in a large community randomized trial.
Adolescent↗
Brain lactic alkalosis in Aicardi-Goutières syndrome.
Aicardi-Goutières syndrome is a rare progressive encephalopathy characterized by acquired microcephaly, basal ganglia calcification, and chronic CSF lymphocytosis, raised levels of interferon alpha in CSF and plasma and chill-blain type lesions. A possible mechanism of injury is cytokine related microangiopathy. We report brain imaging and proton (1H) and phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) findings during the first year after birth in two patients. In patient 1 the evolution of brain metabolite ratios and intracellular pH obtained from serial 1H (long TE) and 31P MRS studies are described; in patient 2 a single 1H (short TE) MRS study is described. Imaging findings included basal ganglia calcifications, cerebral atrophy, and leukodystrophy. The MRS results demonstrated that Aicardi-Goutières syndrome is associated with reduced NAA/Cr, reflecting decreased neuronal/axonal density or viability, increased myo-inositol/Cr, reflecting gliosis or osmotic stress and a persisting brain lactic alkalosis. A brain lactic alkalosis has also been observed in those infants surviving perinatal hypoxia-ischaemia but with a poor neurodevelopmental outcome. A possible mechanism leading to brain alkalosis is up-regulation of the Na+/H+ transporter by focal areas of ischaemia related to the microangiopathy or by pro-inflammatory cytokines. Such brain alkalosis may be detrimental to cell survival and may increase glycolytic rate in astrocytes leading to an increased production of lactate.
Alkalosis↗
Gastrointestinal manifestations of postnatal cytomegalovirus infection in infants admitted to a neonatal intensive care unit over a five year period.
Sixteen cases of postnatal cytomegalovirus (CMV) infection were identified in a neonatal intensive care unit population over a five year period. Eleven of these infants had gastrointestinal signs at the time of presentation. These ranged from minor and transient (abdominal distension and enteral feed intolerance) to severe and life threatening (protein losing enteropathy, diarrhoea, and hypernatraemic dehydration). An initial diagnosis of necrotising enterocolitis was common, but no infant showed intestinal or hepatic portal pneumatosis. The gestational age of the infants was 24-38 weeks. All had received fresh maternal breast milk. It is suggested that CMV enteritis is added to the spectrum of clinical manifestations of postnatal CMV infection. Signs suggestive of necrotising enterocolitis with atypical features should prompt investigations for CMV infection.
Cytomegalovirus Infections↗
Improving young people's access to reproductive health care in rural Zimbabwe.
The aim of this study was to explore ways to improve the accessibility of clinics for young people with reproductive health problems in rural Zimbabwe. This study, which took place in rural Masvingo, was part of a project to develop a comprehensive adolescent reproductive health intervention for Zimbabwean youth. Six focus group discussions were held with secondary school pupils aged 16-19; four focus group discussions were held with nurses. Additionally, 16 community meetings with parents of adolescents were observed. The data were analyzed using the principles of grounded theory: three main categories and several sub-categories emerged from the data. The accessibility of existing services for young people was poor, partly because nurses were reluctant to provide such services due to lack of clarity in legislation and also through fear of condoning adolescent sexual activity. Although the clinical acumen of staff was recognized as sound, service delivery was perceived to be judgemental and lacking in confidentiality and privacy. This reflects the cultural context in which services are delivered. Culturally, adolescents are deemed to be children and as such to have few rights. There is a widely held belief that teaching young people about sex will promote sexual activity. Our findings suggested that staff training should focus on attitudinal rather than medical issues.
Adolescent↗
Magnetic resonance imaging of preterm brain injury.
Magnetic resonance imaging (MRI) has proved to be a valuable tool for monitoring development and pathology in the preterm brain. This imaging modality is useful for assessing numerous pathologies including periventricular leukomalacia, intraventricular haemorrhage/germinal layer haemorrhage, and periventricular haemorrhagic infarction, and can help to predict outcome in these infants. MRI has also allowed the detection of posterior fossa lesions, which are not easily seen with ultrasound. Additionally, and perhaps most relevant, quantitative MR studies have shown differences between the normal appearing preterm brain at term equivalent age and term born infants, confirming that the brain develops differently in the ex utero environment. Further studies using quantifiable MR techniques will improve our understanding of the effects of the ex utero environment, including aspects of neonatal intensive care on the developing brain.
Brain Injuries↗
Seroepidemiological study of herpes simplex virus types 1 and 2 in Brazil, Estonia, India, Morocco, and Sri Lanka.
BACKGROUND: The association between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) and the development of HSV vaccines have increased interest in the study of HSV epidemiology. OBJECTIVES: To estimate the age and sex specific seroprevalence of HSV-1 and HSV-2 infections in selected populations in Brazil, Estonia, India, Morocco, and Sri Lanka. METHODS: Serum samples were collected from various populations including children, antenatal clinic attenders, blood donors, hospital inpatients, and HIV sentinel surveillance groups. STD clinic attenders were enrolled in Sri Lanka, male military personnel in Morocco. Sera were tested using a common algorithm by type specific HSV-1 and HSV-2 antibody assay. RESULTS: 13,986 samples were tested, 45.0% from adult females, 32.7% from adult males, and 22.3% from children. The prevalence of HSV-1 varied by site ranging from 78.5%-93.6% in adult males and from 75.5%-97.8% in adult females. In all countries HSV-1 seroprevalence increased significantly with age (p<0.001) in both men and women. The prevalence of HSV-2 infection varied between sites. Brazil had the highest age specific rates of infection for both men and women, followed by Sri Lanka for men and Estonia for women, the lowest rates being found in Estonia for men and India for women. In all countries, HSV-2 seroprevalence increased significantly with age (p<0.01) and adult females had higher rates of infection than adult males by age of infection. CONCLUSIONS: HSV-1 and HSV-2 seroprevalence was consistently higher in women than men, particularly for HSV-2. Population based data on HSV-1 and HSV-2 will be useful for designing potential HSV-2 vaccination strategies and for focusing prevention efforts for HSV-1 and HSV-2 infection.
Adolescent↗
Suppression of sulfur mustard-increased IL-8 in human keratinocyte cell cultures by serine protease inhibitors: implications for toxicity and medical countermeasures.
The toxicity of the chemical warfare blistering agent sulfur mustard (2,2'-dichlorodiethyl sulfide; SM) has been investigated for nearly a century; however, the toxicological mechanisms of SM remain obscure and no antidote exists. The similarity of dermal-epidermal separation caused by SM exposure, proteolysis, and certain bullous diseases has fostered the hypothesis that SM vesication involves proteolysis and/or inflammation. Compound screening conducted by the US Army Medical Research Institute of Chemical Defense established that topical application of three tested serine protease inhibitors could reduce SM toxicity in the mouse ear vesicant model. Although most of the drugs with efficacy for SM toxicity in rodent models are anti-inflammatory compounds, no in vitro assay is in current use for screening of potential anti-inflammatory SM antidotes. IL-8 is a potent neutrophil chemotactic cytokine that is increased in human epidermal keratinocyte (HEK) cell cultures following exposure to SM and has been proposed as a marker for SM-induced inflammation. This study was conducted to establish in vitro screening of IL-8 in SM-exposed HEK as a possible model for evaluating candidate compounds prior to in vivo testing. We chose two protease inhibitors, one from those shown as successful in the MEVM (ethyl p-guanidinobenzoate hydrochloride, ICD 1579) and a prototypic inhibitor of trypsin, N-tosyl-L-lysine chloromethyl ketone (TLCK). TLCK (62.5 to 1000 micromol/L) or ICD 1579 (31.25 to 1000 micromol/L) was added to HEK cell cultures 1 h after SM exposure (200 micromol/L) and dose-dependently suppressed SM-increased IL-8. The suppression of SM-increased IL-8 by a class of drug candidate compounds such as protease inhibitors may provide a mechanistic marker that helps predict future medical countermeasures for SM toxicity and reduces the need for testing in animal models.
Animal Testing Alternatives↗
Adolescent reproductive health interventions.
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Adolescent↗
Herpes simplex virus type 1 infection: a sexually transmitted infection of adolescence?
OBJECTIVES: To examine the factors associated with antibodies to herpes simplex virus type 1 (HSV-1). DESIGN: Cross sectional study with HSV-1 antibody testing performed by University of Washington western blot assay. SETTING: Central London STD clinic (1990-1) and central London blood donation centre (1992). PARTICIPANTS: Representative sample of 869 new and rebooked GUM clinic attenders and 1494 consecutive blood donors. RESULTS: The prevalence of HSV-1 antibody among clinic attenders was 60.4% (95% CI 57.0 to 63.7) and among donors was 46.1% (95% CI 43.5 to 48.7). HSV-1 antibody was independently associated with increasing age in both populations (p<0.001). Among clinic attenders, HSV-1 was less common among heterosexual men than women and homosexual men (p<0.005), and was more common among black people (p=0.001) and those of lower socioeconomic status (p=0.05). Among blood donors, being single rather than married was independently associated with HSV-1 infection (p=0.03). Early age at first intercourse was strongly associated with presence of HSV-1 in both populations. The adjusted odds of HSV-1 among GUM clinic attenders was 0.37 (95% CI 0.21 to 0.65) for someone aged 20 at first intercourse compared with someone aged <or=15. Among blood donors, those aged 20 had an adjusted odds of 0.64 (95% CI 0.39 to 1.05) compared with someone aged 15. HSV-1 was not associated with increasing number of lifetime partners after adjustment for other factors. CONCLUSIONS: Genital herpes due to HSV-1 antibody is increasing in the United Kingdom, particularly among young people. In this study we found that HSV-1 was strongly associated with early age of first sexual intercourse, which may reflect the sexual practices of people initiating sex in this age group.
Adolescent↗
An evidence based approach to testing for antibody to herpes simplex virus type 2.
OBJECTIVES: To establish whether a simple risk scoring system, based on limited information, can reflect the variation in HSV-2 prevalence in a population, and whether a common system can be used across settings. To establish whether knowledge of a patient's score can aid the interpretation of the result from one of the commercial type specific assays. METHODS: Four previous cross sectional studies are considered, with HSV-2 antibody results by western blot or type specific ELISA tests. The clinical settings were a blood donor centre (1359 participants) and STD clinic (808 participants), London, United Kingdom, an antenatal clinic, Sydney, Australia (2317 participants), and a family medical centre, Seattle, United States (478 participants). We determined the factors associated with HSV-2 prevalence, the similarity of associations across settings, and the variation in HSV-2 prevalence by risk score. RESULTS: A simple scoring captured much variation in HSV-2 prevalence in each population-for example, for London blood donors, scoring based on sex, age, and number of lifetime partners, prevalence varied from 0.7% (95% CI 0.1 to 2.0) to 47.3% (37.9 to 56.6) across five risk groups. For number of lifetime partners, and sex, the association with HSV-2 varied significantly across studies. CONCLUSIONS: A scoring system can aid test interpretation-for example, in London blood donors the post-test probability of infection following a positive result varies from around 25% to 98% across risk groups for a typical type specific assay. Further work could address whether this theoretical benefit can be realised in practice. A common risk scoring probably could not be used across settings.
Adult↗
A cognitive behavioural intervention to reduce sexually transmitted infections among gay men: randomised trial.
OBJECTIVE: To determine the effectiveness of a brief cognitive behavioural intervention in reducing the incidence of sexually transmitted infections among gay men. DESIGN: Randomised controlled trial with 12 months' follow up. SETTING: Sexual health clinic in London. PARTICIPANTS: 343 gay men with an acute sexually transmitted infection or who reported having had unprotected anal intercourse in the past year. MAIN OUTCOME MEASURES: Number of new sexually transmitted infections diagnosed during follow up and self reported incidence of unprotected anal intercourse. RESULTS: 72% (361/499) of men invited to enter the study did so. 90% (308/343) of participants returned at least one follow up questionnaire or re-attended the clinic and requested a check up for sexually transmitted infections during follow up. At baseline, 37% (63/172) of the intervention group and 30% (50/166) of the control group reported having had unprotected anal intercourse in the past month. At 12 months, the proportions were 27% (31/114) and 32% ( 39/124) respectively (P=0.56). However, 31% (38/123) of the intervention group and 21% (35/168) of controls had had at least one new infection diagnosed at the clinic (adjusted odds ratio 1.66, 95% confidence interval 1.00 to 2.74). Considering only men who requested a check up for sexually transmitted infections, the proportion diagnosed with a new infection was 58% (53/91) for men in the intervention group and 43% (35/81) for men in the control group (adjusted odds ratio 1.84, 0.99 to 3.40). Using a regional database that includes information from 23 sexual health clinics in London, we determined that few participants had attended other sexual health clinics. CONCLUSIONS: This behavioural intervention was acceptable and feasible to deliver, but it did not reduce the risk of acquiring a new sexually transmitted infection among these gay men at high risk. Even carefully designed interventions should not be assumed to bring benefit. It is important to evaluate their effects in randomised trials with objective clinical end points.
Adolescent↗
Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death.
To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co-twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct < 30%) to raise the fetal Hct to > or = 40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2-5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co-twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound.
Acidosis↗
Diffusion-weighted imaging in neonates.
Diffusion-weighted imaging (DWI) can readily be performed in the neonate, although currently studies remain a few years behind-those carried out on adults. DWI relies on the random diffusion of water molecules. As for the adult population, a pulsed gradient spin echo sequence (PGSE) with cardiac gating can be used to exploit the effect of diffusion on image contrast and to determine the apparent diffusion coefficient (D*) for tissues or fluids. Anisotropic properties caused by the restriction of the movement of water molecules may be demonstrated. In the neonatal brain restricted motion can be detected in both myelinated and unmyelinated white matter tracts. DWI has been used to study changes in global and focal ischaemic injury to the neonatal brain. A decreased D* may be documented after an ischaemic insult followed by a gradual increase. These changes are consistent with animal data but show a slower time course. Intervention following perinatal ischaemic injury must be started within hours. DWI detects early ischaemic injury and may therefore be a useful tool for identifying those infants who could benefit from intervention.
Brain↗
Commentary: developing preventive strategies in Europe.
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Antibodies, Viral↗
Neonatal cranial ultrasound interpretation: a clinical audit.
OBJECTIVE: To assess the abilities of doctors to interpret neonatal cranial ultrasound scans. DESIGN AND SETTING: High resolution scanned images of six important neonatal cranial ultrasound abnormalities were posted as a questionnaire to the 59 neonatal units in the North and South Thames regions. RESULTS: Forty two questionnaires were returned (71%). Currently 56% of those interpreting cranial ultrasound scans are neonatal registrars, 27% are consultant paediatricians or neonatologists, and 17% are radiologists. The response rate from registrars was excellent (97%), but it was poor from consultant paediatric (38%) and radiological (40%) staff. The mean accurate identification of cerebral abnormalities was only 59% (range 45-71%). Only 44% of the neonatal registrars, compared with nearly all the consultant staff, have had any formal training in cranial ultrasonography. CONCLUSIONS: The data highlight the current accuracy of neonatal cranial ultrasound scan reporting in the Greater London region and have important implications for clinical services and research studies. Doctors who are responsible for interpreting neonatal cranial ultrasound scans should have formal training and supervision, and more formal reporting would improve and maintain standards. The findings raise significant doubts about the accuracy of local interpretation of cranial ultrasound scans in multicentre research studies.
Brain Diseases↗
Early increases in brain myo-inositol measured by proton magnetic resonance spectroscopy in term infants with neonatal encephalopathy.
Our aim was to assess brain myo-inositol/creatine plus phosphocreatine (Cr) in the first week in term infants with neonatal encephalopathy using localized short echo time proton magnetic resonance spectroscopy and to relate this to measures of brain injury, specifically lactate/Cr in the first week, basal ganglia changes on magnetic resonance imaging (MRI), and neurodevelopmental outcome at 1 y. Fourteen term infants with neonatal encephalopathy of gestational age (mean +/- SD) 39.6 +/- 1.6 wk, birth weight 3270 +/- 490 g, underwent MRI and magnetic resonance spectroscopy at 3.5 +/- 2.1 d. Five infants were entered in a pilot study of treatment with moderate whole-body hypothermia for neonatal encephalopathy; two were being cooled at the time of the scan. T(1)- and T(2)-weighted transverse magnetic resonance images were graded as normal or abnormal according to the presence or absence of the normal signal intensity of the posterior limb of the internal capsule and signal intensity changes in the basal ganglia. Localized proton magnetic resonance spectroscopy data were obtained from an 8-cm(3) voxel in the basal ganglia using echo times of 40 and 270 ms, and the peak area ratios of myo-inositol/Cr and lactate/Cr were measured. Outcome was scored using Griffith's development scales and neurodevelopmental examination at 1 y. MRI and outcome were normal in six infants and abnormal in eight. myo-Inositol/Cr and lactate/Cr were higher in infants with abnormal MRI and outcome (p < 0.01, p < 0.01, respectively). myo-Inositol/Cr and lactate/Cr were correlated (p < 0.01) and were both correlated to the Griffith's developmental scales (p < 0.01, p < 0.01, respectively). In conclusion, these preliminary data suggest that early increases in brain basal ganglia myo-inositol/Cr in infants with neonatal encephalopathy are associated with increased lactate/Cr, MRI changes of severe injury, and a poor neurodevelopmental outcome at 1 y.
Apgar Score↗