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Frances M Cowan

Publications and source records attributed to Frances M Cowan.

18 recordsLinked to original sources
PubMed2006

Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography.

Our aim was to investigate the feasibility of studying white matter tracts and connections between the thalamus and the cortex in 2-year-old infants who were born preterm by probabilistic magnetic resonance (MR) tractography. Using this approach, we were able to visualize and quantify connectivity distributions in a number of white matter tracts, including the corticospinal tracts, optic radiations, fibers of the genu and splenium of the corpus callosum, superior longitudinal fasciculus and inferior fronto-occipital fasciculus, and to map the distribution within thalamus of fibers connecting to specific cortical regions. In eleven infants with no MR evidence of focal cerebral lesions and appropriate neurodevelopment as shown by general quotient (GQ) scores above 100, we mapped cortical connections to the thalamus that appeared similar to those reported in adults. However, in a proof-of-principle experiment, we examined one further child with marked white matter abnormalities and found that the volume and pattern of thalamo-cortical connections were severely disrupted. This technique promises to be a useful tool for assessing connectivity in the developing brain and in infants with lesions.

Cerebral Cortex↗
PubMed2006

Using cerebral ultrasound effectively in the newborn infant.

Cranial ultrasound is the most available and easily repeatable technique for imaging the neonatal brain. Its quality and diagnostic accuracy depend on various factors; the suitability of the ultrasound machine for neonatal cranial work, the use of optimal settings and probes, appropriate scanning protocols, the use of a variety of acoustic windows and, not least, the scanning experience of the examiner. Knowledge of normal anatomy and the echogenicities of different tissues in normal and pathological situations as well as familiarity with the physiological and pathological processes likely to be encountered is vital. This paper assesses the value and appropriate use, safety and diagnostic accuracy of modern, high-quality ultrasound in evaluating the brain of the preterm and term born infant. Issues of concern regarding teaching, supervision and experience of the examiner are also addressed.

Brain↗
PubMed2006

The role of cranial ultrasound and magnetic resonance imaging in the diagnosis of infections of the central nervous system.

Imaging data concerning infection of the central nervous system (CNS) in neonates are usually confined to small groups of infants. We have reviewed the imaging findings in 96 preterm and full-term infants admitted to our neonatal intensive care unit over a 15 year period. Neuro-imaging, especially cranial ultrasound (CUS) and magnetic resonance imaging (MRI) provided useful information; CUS allows the early and later detection of calcification, germinolytic and parenchymal cysts, ventricular dilatation and strands and ependymal abnormality; diffusion weighted imaging (DWI) is especially useful in the acute stage of bacterial and viral infections, while conventional MRI helps in the detection of neocortical dysplasia in CMV infection and defining cerebellar abnormality.

Central Nervous System Infections↗
PubMed2006

The effect of preterm birth on neonatal cerebral vasculature studied with magnetic resonance angiography at 3 Tesla.

Preterm birth is associated with a high incidence of neurodevelopmental deficits. Magnetic resonance imaging (MRI) has proved to be a valuable tool for monitoring development in the preterm brain. We used a dedicated time-of-flight (TOF) magnetic resonance angiography (MRA) protocol at 3 Tesla (3T) optimized to assess morphological characteristics of the neonatal cerebral vessels associated with preterm birth in a sample of 37 infants. We found statistically significant decreased tortuosity in all proximal segments of the cerebral vasculature (anterior, middle and posterior cerebral arteries) in the preterm infants imaged at term equivalent age compared to the term born infants, with no differences in vessel diameter between the two groups. This distinct phenotype of decreased tortuosity was shown to persist until 18 months of age in longitudinal MRA studies in infants born preterm, suggesting that this is not a delay in maturation. Biparietal head diameter measurements were significantly smaller in the preterm at term infants and were inversely correlated with middle cerebral artery tortuosity measurements in both the term born and the preterm at term infants. To our knowledge, this is the first systematic MRA study on the effect of preterm delivery on neonatal cerebral vasculature. Our intention is to build on the findings of this study by combining the data with other measurements of brain growth and vascular haemodynamics to understand more about the interdependence of vessel and brain development and their relationship to prematurity.

Adult↗
PubMed2006

Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus.

Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3' --> 5' DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1(-/-) mouse leads to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response.

Animals↗
PubMed2006

Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age.

OBJECTIVE: Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants. METHODS: Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum. RESULTS: Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied. CONCLUSIONS: These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM.

Brain↗
PubMed2006

Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment.

OBJECTIVES: The aim was to survey the range of cerebral injury and abnormalities of cerebral development in infants born between 23 and 30 weeks' gestation using serial MRI scans of the brain from birth, and to correlate those findings with neurodevelopmental outcome after 18 months corrected age. METHODS: Between January 1997 and November 2000, consecutive infants born at < 30 weeks' gestational age underwent serial MRI brain scans from birth until term-equivalent age. Infants were monitored after 18 months of age, corrected for prematurity, with the Griffiths Mental Development Scales and neurologic assessment. RESULTS: A total of 327 MRI scans were obtained from 119 surviving infants born at 23 to 30 weeks of gestation. Four infants had major destructive brain lesions, and tissue loss was seen at term for the 2 survivors. Fifty-one infants had early hemorrhage; 50% of infants with term scans after intraventricular hemorrhage had ventricular dilation. Twenty-six infants had punctate white matter lesions on early scans; these persisted for 33% of infants assessed at term. Early scans showed cerebellar hemorrhagic lesions for 8 infants and basal ganglia abnormalities for 17. At term, 53% of infants without previous hemorrhage had ventricular dilation and 80% of infants had diffuse excessive high signal intensity within the white matter on T2-weighted scans. Complete follow-up data were available for 66% of infants. Adverse outcomes were associated with major destructive lesions, diffuse excessive high signal intensity within the white matter, cerebellar hemorrhage, and ventricular dilation after intraventricular hemorrhage but not with punctate white matter lesions, hemorrhage, or ventricular dilation without intraventricular hemorrhage. CONCLUSIONS: Diffuse white matter abnormalities and post-hemorrhagic ventricular dilation are common at term and seem to correlate with reduced developmental quotients. Early lesions, except for cerebellar hemorrhage and major destructive lesions, do not show clear relationships with outcomes.

Basal Ganglia↗
PubMed2005

Is sexual contact with sex workers important in driving the HIV epidemic among men in rural Zimbabwe?

OBJECTIVE: To establish the importance of commercial sex in driving the HIV epidemic in the general population by determining risk factors for HIV infection among male mine and farm workers and estimating the fraction of prevalent HIV infections attributable to sexual contact with sex workers (SWs). SETTING: Five commercial farms and 2 mines in Mashonaland West, Zimbabwe. METHODS: A cross-sectional interviewer-administered questionnaire and urine survey of 1405 male workers. Urine samples were tested for HIV antibodies by a particle agglutination test and enzyme-linked immunosorbent assay and for Chlamydia trachomatis and Neisseria gonorrhoeae using a polymerase chain reaction assay. RESULTS: The overall prevalence of HIV antibodies was 27.3% (95% confidence interval [CI]: 24.8 to 29.5), that of C. trachomatis was 1.5% (95% CI: 1.0 to 2.1), and that of N. gonorrhoeae was 0.5% (95% CI: 0.1 to 0.9). A total of 48.4% (95% CI: 45.8 to 51.0) of men reported ever having had sexual contact with an SW, and 29.3% (95% CI: 26.9 to 31.7) reported contact in the past year. HIV was more common among men who reported SW contact on univariate (1.9% [95% CI: 1.5 to 2.4]) and multivariate (1.4% [95% CI: 1.0 to 1.8]) analysis after adjusting for confounding. HIV was also strongly associated with self-reported genital ulceration in the previous 6 months (adjusted odds ratio [OR] = 3.1, 95% CI: 2.2 to 4.3). Genital ulceration and SW contact were highly correlated. A total of 19.6% of HIV infections in men could be attributed to ever having had sexual contact with an SW (95% CI: 10.8 to 27.6). CONCLUSIONS: An appreciable proportion of HIV infection in men is attributable to sexual contact with SWs. Consideration should be given to developing interventions that target male clients of SWs.

Adult↗
PubMed2005

The appropriateness of core group interventions using presumptive periodic treatment among rural Zimbabwean women who exchange sex for gifts or money.

To map the characteristics of rural based sex workers in Zimbabwe with regard to demographics, mobility, behavior, HIV and sexually transmitted infection (STI) prevalence, to explore the appropriateness and feasibility of presumptive periodic treatment (PPT) for bacterial STIs as an HIV prevention intervention among these women, and to compare tolerability of 2 PPT regimens (1 g of azithromycin and 2 g of metronidazole+/-500 mg of ciprofloxacin). Five commercial farms and 2 mines in Mashonaland West, Zimbabwe. Three hundred sixty-three sex workers were recruited and completed a structured interviewer-administered questionnaire. Each participant had blood tested for antibody to HIV, herpes simplex virus 2 (HSV-2), and syphilis; urine tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and a vaginal swab tested for Trichomonas vaginalis (TV). Women were randomly assigned to receive a single dose of 1 of 2 PPT regimens and then followed to assess rates of side effects and reinfection. The overall prevalence of antibody to HIV was 55.7% (95% confidence interval [CI]: 50.6-60.9) and that of HSV-2 was 80.8% (95% CI: 76.7-84.9). The prevalence of CT and NG was low (CT=1.7%, 95% CI: 0.3-3.0); (NG=1.9%, 95% CI: 0.5-3.4), with a much higher prevalence of TV (TV=19.3%, 95% CI: 15.2-23.4). Prevalence of CT, NG, and TV was appreciably reduced 1 month after PPT but rose to pretreatment levels at the 2- and 3-month visits. The rate of moderate or severe side effects after PPT was low, but it was higher in the women who received ciprofloxacin in addition to azithromycin and metronidazole (P=0.007). It was feasible to access women who reported exchanging money or gifts for sex in rural communities, although many of these women engaged in sex work only infrequently. The prevalence of bacterial STIs was low, suggesting that PPT may not be an appropriate intervention in this setting. Rapid reinfection after PPT suggests that this needs to be given at monthly intervals to reduce prevalence of STIs.

Adult↗
PubMed2005

The internal capsule in neonatal imaging.

The internal capsule is highly visible on conventional magnetic resonance imaging (MRI). It is myelinating rapidly at term, and the time course of its maturation is well known. It carries the major motor and sensory pathways to and from the cortex and the spinal cord. Additionally, fibres from the thalamus pass through it connecting to most regions of the cortex. It is therefore of vital importance, and damage to it has severe consequences. Its abnormal appearance on conventional MRI is a good predictor of an abnormal motor outcome in different clinical situations encountered in perinatal medicine. Its normal appearance on conventional MR images at term age is usually associated with a relatively normal motor outcome. More recently, diffusion-weighted and diffusion tensor imaging have allowed a much more sophisticated assessment of its maturation and connectivity; this has already led to a better understanding of how its development is affected by preterm birth and by hypoxic-ischaemic brain injury. Future studies will assess the relevance of these findings not only for motor outcome but also for cognitive, visual and sensory abilities.

Cerebral Infarction↗
PubMed2004

The value of autopsy in determining the cause of failure to respond to resuscitation at birth.

Autopsy is invaluable in identifying the causes of severe depression and very low Apgar score after birth and in assessing contributory conditions. Brain scans are increasingly used in the care of neonates who fail to respond to resuscitation at birth but their interpretation depends on the information gained from sound neuropathological studies. Asphyxia, both acute intrapartum asphyxia and chronic asphyxia, is an important cause of low Apgar scores. The gestational age and the nature of the asphyxial insult both have a profound influence on the ultimate pattern of injury. Asphyxia in the preterm brain tends to damage preferentially the white matter but some white matter damage is also seen in many infants who have an hypoxia-ischaemic insult at term though the predominant site of injury is to the central grey matter. The nature of the cellular damage and reactive change seen at autopsy is described. There is an association between low Apgar scores and intrauterine exposure to infection and maternal pyrexia. Detailed autopsy examination should include the search for infection. The placenta, cord and membranes should be examined in view of the mounting evidence of the association between intrauterine infection of the placenta and fetal membranes and prenatal brain damage. Additionally, the presence of placental thrombosis and infarction should be sought in relation to focal and global injury in the full term infant. Acquired prepartum lesions rarely cause the infant to present with a low Apgar score. The exception to this is severe damage to the brainstem and basal ganglia. Traumatic injury to the brain is now much less common than in previous decades. Subdural haemorrhage occurs more frequently than intraventricular or subarachnoid haemorrhage. Instrumental and assisted deliveries are associated with an increased incidence of subdural haemorrhage though these rarely cause significant long term damage. Careful autopsy, particularly of the neck and paravertebral tissues, spinal cord, brainstem and nerve roots is important where trauma is suspected. Tearing of nerve roots or fibre bundles in the spinal cord is readily demonstrated under the microscope using immunocytochemistry to beta-amyloid precursor protein. Disorders of the spinal cord, peripheral nerve and muscle as well as some metabolic diseases may cause a baby to be both floppy and weak. Metabolic disease, including peroxisomal disorders, non-ketotic hyperglycinaemia, lipid and glycogen storage disorders and mitochondrial diseases may cause profound hypotonia and respiratory failure at birth or shortly afterwards.

Apgar Score↗
PubMed2004

The burden of infection with herpes simplex virus type 1 and type 2: seroprevalence study in Estonia.

Information on age- and gender-specific prevalence of herpes simplex virus (HSV) types 1 and 2 infections is crucial to guide genital herpes control strategies. Such data are not available from the newly independent Eastern European countries. We present of study of the age- and gender-specific prevalence of HSV-1 and HSV-2 in low risk populations in Estonia. Serum samples from 1016 children, 794 first trimester antenatal women, and 1036 blood donors (462M, 574F) were tested for HSV IgG antibodies by type-specific HSV-1 and HSV-2 assays. High seroprevalence rates of HSV-1 among children, pregnant women and (non-paid) blood donors were found. HSV-2 infection was not detected among boys. Gender differences in HSV-2 seroprevalence rates among people of reproductive age were observed: higher rates were recorded among pregnant women (23%) and female blood donors (21%), compared to 11% among male blood donors. HSV-1 seroprevalence was high in adults. HSV-2 seroprevalence was higher among females than males and increased substantially with age. HSV-2 prevalence in these non-high risk populations was relatively high, and may indicate a risk for an impending sexually- and STI- driven HIV epidemic.

Adolescent↗
PubMed2004

MR imaging quantification of cerebellar growth following hypoxic-ischemic injury to the neonatal brain.

BACKGROUND AND PURPOSE: Cerebellar atrophy may occur as a result of a primary injury, such as infarction or hemorrhage. Impaired growth of a non-injured cerebellum may be seen as a secondary effect related to damage in other remote but connected areas of the brain, or so-called diaschisis. We sought to determine whether perinatal hypoxic-ischemic injury leads to poor cerebellar growth and whether such impairment occurs asymmetrically in infants with predominantly unilateral brain injury. METHODS: We used a computerized quantification program to measure cerebellar size by using serial MR images. Term-born infants presenting with encephalopathy and/or seizures presumed due to a hypoxic-ischemic insult within 48 hours of delivery were included if they had two or more volume acquisition images obtained at least 3 months apart but within the first 15 months of delivery. RESULTS: When data were grouped by MR appearances, significant differences in total cerebellum growth were seen between infants with focal infarction and those with basal ganglia and thalamic injury (P <.001). Unilateral forebrain lesions shown on MR imaging were not predictive of asymmetric cerebellar growth. CONCLUSION: Infants with focal infarction of the cerebral hemisphere had an apparently normal pattern of growth in both cerebellar hemispheres. However, in infants with severe basal ganglia and thalamic lesions, cerebellar growth was reduced, and the vermis showed little or no growth during the first year after birth.

Asphyxia Neonatorum↗
PubMed2003

Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality.

OBJECTIVE: The most common finding on magnetic resonance imaging (MRI) of the brain in preterm infants at term-equivalent age is diffuse excessive high signal intensity (DEHSI) in the white matter. It is unclear whether DEHSI represents a biological abnormality. This study used diffusion-weighted imaging (DWI) to compare apparent diffusion coefficient (ADC) values in DEHSI with infants with normal imaging and those with overt brain damage to determine whether DEHSI shows the diffusion characteristics of normal or abnormal tissue. METHODS: MRI, using conventional and diffusion-weighted imaging (DWI), was performed in 50 preterm infants at term-equivalent age using a 1.5 Tesla MR scanner. The infants were divided into 3 groups on the basis of their MRI results: 1) normal white matter, 2) DEHSI, or 3) overt white matter pathology. ADC values were measured in the frontal, central, and posterior white matter at the level of the centrum semiovale. ADC values in the 3 groups of preterm infants were compared using a 1-way analysis of variance with a Bonferroni test for multiple comparisons. RESULTS: ADC values were significantly higher in infants with DEHSI and infants with overt white matter pathology than in infants with normal white matter. There was no significant difference between ADC values in infants with DEHSI and those with overt white matter pathology. CONCLUSIONS: This study provides objective evidence that DEHSI represents diffuse white matter abnormality.

Body Water↗
PubMed2003

T2 relaxation values in the developing preterm brain.

BACKGROUND AND PURPOSE: MR imaging is increasingly used to assess maturation and disease in the preterm brain. Knowledge of the changes in T2 values with increasing postmenstrual age (PMA) will aid image interpretation and help in the objective assessment of maturation and disease of the brain in infants. The aim of this study was to obtain T2 values in the preterm brain from 25 weeks' gestational age (GA) until term-equivalent age in infants who had normal neurodevelopmental findings at a minimum corrected age of 1 year. METHODS: The study group consisted of 18 preterm infants, born at 33 weeks' GA or sooner. The median GA of the infants at birth was 27 weeks (range, 23-33 weeks), and the median PMA at imaging was 31 weeks (range, 25-41 weeks). T2 measurements were obtained using a 1.0-T MR system and a four-echo pulse sequence (TR/TE, 2500/ 30, 60, 110, and 600). T2 values were measured in the thalami, lentiform nuclei, frontal white matter, occipital white matter, and central white matter at the level of the centrum semiovale. RESULTS: A significant negative linear correlation between T2 values and PMA was demonstrated in the lentiform nuclei (P =.003), frontal white matter (P <.0001), occipital white matter (P <.0001), and central white matter at the level of the centrum semiovale (P <.0001). T2 values were not significantly reduced with increasing PMA in the thalami (P =.06). CONCLUSION: T2 values decrease with increasing PMA in the preterm brain.

Birth Weight↗
PubMed2002

School based HIV prevention in Zimbabwe: feasibility and acceptability of evaluation trials using biological outcomes.

OBJECTIVE: To determine the feasibility and acceptability of conducting a community randomized trial (CRT) of an adolescent reproductive health intervention (ARHI) using biological measures of effectiveness. SETTING: Four secondary schools and surrounding communities in rural Zimbabwe. METHODS: Discussions were held with pupils, parents, teachers and community leaders to determine acceptability. A questionnaire and urine sampling survey was undertaken among Form 1 and 2 pupils. Studies were undertaken to inform likely participation and follow up in a future CRT. A community survey of 16-19-year-olds was conducted to determine levels of secondary school attendance and likely HIV prevalence at final follow up in the event of a trial. RESULTS: Form 1 and 2 pupils aged 12-18 years (n = 723; median age, 15 years) participated in the research. Prevalences of HIV, Chlamydia and gonorrhoea were 3.6% [95% confidence interval (CI), 2.3-5.3%], 0.4% (95% CI, 0.1-1.3%) and 1.9% (95% CI, 1.0-3.3%) respectively. There was poor correlation between biological evidence of sexual experience and questionnaire responses, due to concerns about confidentiality. Only 13% (95% CI, 4-27%) of those infected with HIV and/or a sexually transmitted disease admitted to having had sex. In the community survey of 573 adolescents aged 16-19 years, 6.6% (95% CI, 3.9-10.3%) of females and 5.1% (95% CI, 2.9-8.2%) of males were HIV positive. High participation and retention rates are achievable within a trial in this setting. CONCLUSIONS: It is acceptable and feasible to conduct randomized trials to establish the effectiveness of ARHIs. However, self-reported behavioural outcomes will probably be biased, emphasizing the importance of using externally validated biological outcome measures to determine effectiveness.

Adolescent↗
PubMed2002

Brain alkaline intracellular pH after neonatal encephalopathy.

Experimental studies demonstrate an alkaline shift in brain intracellular pH (pH(i)) after hypoxia-ischemia (HI). In infants with neonatal encephalopathy after HI, our aims were to assess (1) brain pH(i) during the first 2 weeks after birth in infants categorized according to magnetic resonance imaging (MRI) during the first 2 weeks after birth and at more than 3 months of age, and neurodevelopmental outcome at 1 year; (2) the relationship between brain pH(i) and lactate/creatine; and (3) duration of alkaline brain pH(i). Seventy-eight term infants with neonatal encephalopathy were studied using MR techniques. One hundred and fifty-one studies were performed throughout the first year including 56 studies of 50 infants during the first 2 weeks after birth. pH(i) was calculated using phosphorus-31 MR spectroscopy and lactate/creatine was measured using proton MRS. The mean (standard deviation [SD]) brain pH(i) during the first 2 weeks after birth in infants with severely abnormal versus normal MRI was 7.24 (SD, 0.17) versus 7.04 (SD, 0.05; p < 0.001); in infants who subsequently developed cerebral atrophy versus those who did not: 7.23 (SD, 0.17) versus 7.06 (SD, 0.06; p < 0.05); in infants who died or had a severe neurodevelopmental impairment versus normal outcome: 7.28 (SD, 0.15) versus 7.11 (SD, 0.09; p < 0.05). Brain alkalosis was associated with increased brain lactate/creatine (p < 0.001). pH(i) remained more alkaline in the severe outcome group up to 20 weeks after birth (p < 0.05).

Alkalosis↗