Search

Dysphagia is highly prevalent in patients with amyotrophic lateral sclerosis (ALS). Riluzole is a US Food and Drug Administration-approved treatment for ALS. Riluzole oral film (ROF; Exservan™) contains riluzole in a polymer-based film matrix. The ROF is administered by placing on the tongue, where it dissolves and the drug is ingested with the saliva. Two clinical trials assessed the safety and tolerability of the ROF. Bioavailability and pharmacokinetics (PK) were evaluated in an open-label, randomized, single-dose, replicate crossover study of 50 mg of ROF and riluzole 50-mg tablets in 32 healthy volunteers. The second study was a videofluoroscopic swallowing examination conducted with nine patients with ALS before and after receiving a single dose of 50 mg of ROF. The primary outcome was change on penetration-aspiration scale (PAS) scores from pre- to post-dose. Overall, the PK parameters for ROF and riluzole tablets were comparable between treatments and administrations when administered under fasting conditions. Administration of ROF with food resulted in a 15% reduction in area under the curve and a 45% reduction in maximum serum concentration. A total of 44 treatment-emergent adverse events (AEs) were reported in the study; all were mild in severity. No serious AEs were observed and no subjects discontinued due to AEs. In the swallowing study, very little numerical or categorical change was observed following the dose of ROF. No evidence of deterioration of swallowing function was observed post-dose. The ROF was bioequivalent to riluzole tablets, was well tolerated, and had no detrimental effect on swallowing.

Objective: To determine if patterns of hypoxic-ischemic brain injury on magnetic resonance imaging (MRI) in term newborns predict subsequent childhood epilepsy. Methods: This retrospective cohort study includes term newborns with encephalopathy (n = 181) born between 2004-2012 and admitted to British Columbia Children’s Hospital. MRI was performed between 3 and 5 days of age. The predominant patterns of hypoxic-ischemic injury were classified as Normal, Watershed, Basal Nuclei, Total, and Focal-Multifocal. Lesions in hippocampus, motor and occipital cortex were noted. Results: Of 181 newborns, 166 (92%) survived the neonatal period, and 132 (80%) had follow-up with a median duration of 61 months (IQR: 28–95). Twenty-three children (17%) developed epilepsy. A higher proportion with Watershed, Basal Nuclei, or Total patterns developed epilepsy ( P < .001). Injury to motor cortex, hippocampus, and occipital lobe ( P < .01) were independent risk factors for epilepsy. In the adjusting logistic model, Watershed (odds ratio = 16.0, 95% CI [1.3, 197.2], P = .03) and Basal Nuclei injury (odds ratio = 19.4, 95% CI [1.9, 196.3], P = .01) remained independent risk factors. Therapeutic hypothermia did not alter these associations. Severity of brain injury and recurrent neonatal seizures are other clinical risk factors. Significance: In term newborns with hypoxic-ischemic encephalopathy, the predominant pattern of Watershed and Basal Nuclei injury are valuable predictors for development of epilepsy in later childhood.

Context 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting This was a multicenter retrospective study using information collected from 3 predominant centers. Patients A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder., Canadian Institutes of Health Research [201610PJT-377869, MOP-G2-341146-159133-BRIDG]; Fondation Les Amis d'Elliot; Leuco-Action; Fondation Lueur d'Espoir pour Ayden; Fondation le Tout pour Loo; Reseau de Medecine Genetique Appliquee of the Fonds de Recherche du Quebec-Sante; Compute Canada; Fonds de Recherche du Quebec en Sante (FRQS) Doctoral Scholarship; Fondation du Grand defi Pierre Lavoie Doctoral Scholarship; McGill Faculty of Medicine F. S.B. Miller Fellowship; Research Institute of the McGill University Health Centre Desjardins Studentship in Child Health Research; Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia; CIHR [201603PJT-148695]; BC Children's Hospital Foundation through its intramural Investigator Grant Award Program (IGAP); National Institute for Neurological Disorders and Stroke [R01NS082094]; Jakob Kamens Chair in Translational Neurotherapeutics; Fonds de Recherche du Quebec-Sante (FRQS); Canadian Institutes of Health Research; European Reference Network for Rare Neurological Disorders (ERN-RND) [739510], This study was supported by grants from the Canadian Institutes of Health Research (201610PJT-377869, MOP-G2-341146-159133-BRIDG), Fondation Les Amis d'Elliot, Leuco-Action, Fondation Lueur d'Espoir pour Ayden, Fondation le Tout pour Loo, and Reseau de Medecine Genetique Appliquee of the Fonds de Recherche du Quebec-Sante to G. Bernard. This research was enabled in part by support provided by Compute Canada (www.computecanada.ca).S.Perrier is supported by the Fonds de Recherche du Quebec en Sante (FRQS) Doctoral Scholarship, the Fondation du Grand defi Pierre Lavoie Doctoral Scholarship, the McGill Faculty of Medicine F. S.B. Miller Fellowship, and the Research Institute of the McGill University Health Centre Desjardins Studentship in Child Health Research. F. K.C. is a recipient of the Directorate of Higher Education Overseas Scholarship-Dikti Scholarship, Ministry of National Education, Republic of Indonesia. W.T. G. received funding from the CIHR (201603PJT-148695) and is supported by the BC Children's Hospital Foundation through its intramural Investigator Grant Award Program (IGAP). B.L. F. was supported by the National Institute for Neurological Disorders and Stroke (R01NS082094). A.V. receives funding from the Jakob Kamens Chair in Translational Neurotherapeutics. G. Bernard has received a Research Scholar Junior 1 award from the Fonds de Recherche du Quebec-Sante (FRQS) (2012-2016) and the New Investigator Salary Award from the Canadian Institutes of Health Research (2017-2022). I.K.M., M. Synofzik, D. Tonduti, B.P.v.d.W., M.S. V.d.K., and N.I.W. are members of the European Reference Network for Rare Neurological Disorders (ERN-RND), project ID 739510.

All presidents promise change. Few presidents, however, promised change as radical as Donald Trump has. In the course of the 2016 election campaign Trump declared that NATO, was ‘obsolete’, that Am...

In examining the Trump administration’s foreign policy practice and strategy, it is all too easy to fixate on the constant flow of outrageous comments made by Trump and treat this as the best route...

The numerical solution of transient stability problems is a key element for electrical power system operation. The classical model for multi-machine systems is defined as a set of non-linear differential equations for the rotor speed and the generator angle for each electrical machine, this mathematical model is usually known as the swing equations. This paper presents how to use direct Richardson extrapolation of several orders for the numerical solution of the swing equations and compares it with other commonly used implicit and explicit solvers such as Runge-Kutta, trapezoidal, Shampine and Radau methods. A numerical study on a simple three machine system is used to illustrate the performance and implementation of algebraic Richardson extrapolation coupled to several solution methods. Normally, the order of accuracy of any numerical solution can be increased when Richardson Extrapolation is used. A numerical example is provided for an electrical grid consisting of three machines and nine buses undergoing a disturbance. It is shown that in this case Richardson extrapolation effectively increases the order of accuracy of the explicit methods making them competitive with the implicit methods. La solución numérica de problemas de estabilidad transitoria es un elemento clave para la operacion de sistemas eléctricos. El modelo clásico para sistemas multi-máquina se define como un conjunto de ecuaciones diferenciales no lineales para la velocidad del rotor y el ángulo del generador para cada máquina eléctrica, este modelo matemático se conoce generalmente como las ecuaciones de oscilación. Este artículo presenta la forma de utilizar la extrapolación directa de Richardson de varios órdenes para la solución numérica de las ecuaciones de oscilación y la compara con otros métodos implícitos y explícitos de uso común como los métodos Runge-Kutta, Trapezoidal, Shampine y Radau. Se presenta un estudio numérico sobre un sistema simple de tres máquinas para ilustrar el desempeño y la implementación algebráica de la extrapolación de Richardson. El orden de exactitud de cualquier solución numérica puede aumentarse cuando se utiliza la extrapolación de Richardson. Se proporciona un ejemplo numérico para una red eléctrica que consta de tres máquinas y nueve buses que sufren una perturbación. Se demuestra que en este caso la extrapolación de Richardson aumenta efectivamente el orden de exactitud de los métodos explícitos haciéndolos competitivos con los métodos implícitos.

In cooled newborns with encephalopathy, although late magnetic resonance imaging (MRI) scan (10-14 days of age) is reliable in predicting long-term outcome, it is unknown whether early scan (3-6 days of life) is. We compared the predominant pattern and extent of lesion between early and late MRI in 89 term neonates with neonatal encephalopathy. Forty-three neonates (48%) were cooled. The predominant pattern of lesions and the extent of lesion in the watershed region agreed near perfectly in noncooled (kappa = 0.94; k = 0.88) and cooled (k = 0.89; k = 0.87) infants respectively. There was perfect agreement in the extent of lesion in the basal nuclei in noncooled infants (k = 0.83) and excellent agreement in cooled infants (k = 0.67). Changes in extent of lesions on late MRI occurred in 19 of 89 infants, with higher risk in infants with hypoglycemia and moderate-severe lesions in basal nuclei. In most term neonates with neonatal encephalopathy, early MRI (relative to late scan) robustly predicts the predominant pattern and extent of injury.

The aim of this paper is to present how to implement a control volume approach improved by Hermite radial basis functions (CV-RBF) for geochemical problems. A multi-step strategy based on Richardson extrapolation is proposed as an alternative to the conventional dual step sequential non-iterative approach (SNIA) for coupling the transport equations with the chemical model. Additionally, this paper illustrates how to use PHREEQC to add geochemical reaction capabilities to CV-RBF transport methods. Several problems with different degrees of complexity were solved including cases of cation exchange, dissolution, dissociation, equilibrium and kinetics at different rates for mineral species. The results show that the solution and strategies presented here are effective and in good agreement with other methods presented in the literature for the same cases. HighlightsA control volume Hermite RBF scheme has been implemented for groundwater reactive problems.The standard SNIA approach was improved by a Richardson extrapolation.The PHREEQ modules are coupled with a transport solution by a local RBF method.The solution by CV-RBF is effective and in agreement with other numerical methods.

A model which joins the overall design algorithm of a rotary dryer with the drying kinetics equations derived from experimental data and with a finite segment algorithm is implemented in order to verify the dryer dimensions obtained from a basic sizing procedure. Total energy and mass balances and well-known correlations for the overall heat transfer coefficient are employed to develop it. Moreover, a one-dimensional finite segment model is solved to obtain the length profiles of temperature and water content for the air and solid phases. An experimental correlation for the mass transfer coefficient between solid and air phases is included in the finite segment model. The chosen heat transfer unit number for the basic sizing is verified with the outlet temperature and water content calculated by the finite segment scheme.

Brain injury in term neonatal hypoxic-ischemic encephalopathy (HIE) emerges on magnetic resonance imaging (MRI) by day 3. This study aimed to address the relationship of MRI, diffusion tensor imaging (DTI), and MR spectroscopic imaging (MRSI) findings on days 1 and 3 in a prospective cohort of term newborns with HIE.A total of 24 term newborns with HIE were prospectively studied with MRI on days 1 and 3; 19 were imaged with DTI and MRSI on days 1 and 3. MRI was assessed using validated scores. The relationship between MRI, DTI, and MRSI values on days 1 and 3 was determined using linear regression for repeated measures.Conventional MRI showed a complex variation of findings from day 1 to 3. In gray matter, mean diffusivity (Dav) and metabolite ratios measured on day 1 were predictive of values on day 3 (all P ≤ 0.04). In white matter, Dav, fractional anisotropy (FA), and N-acetylaspartate (NAA)/choline on days 1 and 3 were strongly related (all P ≤ 0.003). Hypothermia appeared to attenuate the severity and progression of brain injury in the six treated newborns.In term newborns with HIE, quantitative MR values on days 1 and 3 are strongly associated, providing an objective measure of injury before qualitative images.

Deficiency caused by mutations in the creatine transporter gene (SLC6A8/CT1) is an X-linked form of intellectual disability. The presence of highly homologous pseudogenes and high GC content of SLC6A8 genomic sequence complicates the molecular diagnosis of this disorder. To minimize the pseudogene interference, exons 2 to 13 of SLC6A8 were amplified as a single PCR product using gene-specific long-range PCR (LR-PCR) primers. The GC-rich exon 1 and its flanking intronic sequences were amplified separately in a short fragment under GC-rich conditions and a touchdown PCR program. Traditional Sanger sequence analysis of all coding exons of SLC6A8 from a 3-year-old boy with creatine transporter deficiency did not detect deleterious mutations. The long-range PCR product was used as template followed by massively parallel sequencing (MPS) on HiSeq2000. We were able to detect a tandem duplication involving part of exons 11 and 12 in the SLC6A8 gene. The deduced c.1592_1639dup133 mutation was confirmed to be a hemizygous insertion by targeted genomic DNA and cDNA Sanger sequencing. Combination of deep sequencing technology with long-range PCR revealed a novel intragenic duplication in the SLC6A8 gene, providing a definitive molecular diagnosis of creatine transporter deficiency in a male patient. (C) 2013 Elsevier Inc. All rights reserved

The role of generalized hypoxia-ischemia in the genesis of perinatal focal arterial stroke remains puzzling. Animal studies have demonstrated that hypoxia-ischemia may alter blood flow through the ductus venosus, thereby increasing the risk for placental emboli entering the cerebral circulation. A retrospective review was performed of clinical records of all term newborns admitted to a tertiary perinatal center between January 1995 and May 2007 with acute arterial stroke on neuroimaging during the first week of life. Newborns were classified into 2 groups on the basis of neuroimaging abnormalities: stroke alone, or stroke and nonfocal hypoxic-ischemic brain injury. A total of 62 newborns had focal or multifocal stroke, 36 with stroke alone and 26 with stroke with nonfocal hypoxia-ischemia. Multiple risk factors for hypoxia-ischemia occurred in most newborns in both groups. These data indicate that hypoxia-ischemia may play a role in the genesis of stroke in the term newborn with or without evidence of nonfocal hypoxic-ischemic brain injury on neuroimaging.

Externally driven state-building is a complicated task that rarely fulfils the declared objectives of the international actors or the local state and society. This paper critiques the international dimension to state-building by examining USAID in Afghanistan and identifying the theoretical and practical explanations for its failure to aid democratic consolidation. Arguing that the Bush administration’s democratisation efforts have had a negative impact on consolidating democracy, this paper identifies the democratic product of Afghanistan as characterised, at most, by having the formal institutions, routines and procedures of a democracy. I suggest that this merely ‘formal’ democratic product is too short-term and fails to take fully into account the need to develop a political and social culture capable of supporting democratic institutions. In terms of the future of democracy promotion in US foreign policy, I suggest that a change of emphasis may be occurring in the Obama administration.

For asphyxiated term infants, prediction of neurological outcome based on clinical criteria alone is not always reliable. We have used changes in tissue density on CT scan (known to represent hypoxic-ischaemic injury) as an adjunct to clinical examination to assess the severity of cerebral injury. The study population comprised 56 term newborns with hypoxic-ischaemic encephalopathy. Scans were performed with a General Electric 8800 scanner and classified as Normal, Patchy, Diffuse or Global according to the extent of areas of decreased density (DD). These were correlated with neurological outcome (i.e. Normal, Minor handicap, Major handicap, Indefinite or Death). Death or major handicap occurred in only two of 14 infants in the combined Normal or Patchy DD groups but in 26 of 29 in the combined Diffuse or Global groups. This correlation was highly significant (p less than 0.0005). 13 classified as Indefinite were normal at age three to 10 months but were excluded from analysis because of the short follow-up. The data demonstrate that CT scanning is a valuable adjunct to neurological examination for assessment of cerebral injury in the asphyxiated term infant.

SUMMARY The pathophysiology of pseudotumor cerebri is unclear, but may relate to an abnormality in water transport in the brain. The authors performed MR imaging in seven children with pseudotumor cerebri; the signal intensity in the white matter was normal in all patients. These data suggest that periventricular brain water content is not increased markedly in children with pseudotumor cerebri. The authors speculate that this may relate to the establishment of an equilibrium between increased resistance to cerebrospinal fluid outflow and increased brain stiffness, occurring as a consequence of increased cerebral blood-volume and/or interstitial pressure. RESUME Imagerie par resonance magnetique dans la pseudotumeur cerebrale La physiopathologie de la pseudotumeur cerebrale n'est pas claire mais pourrait etre reliee a une anomalie due au transport hydrique dans le cerveau. Les auteurs ont pratique des IRM chez sept enfants avec pseudotumeur cerebrale; l'intensite du signal dans la substance blanche etait normale chez tous les patients. Les donnees suggerent que ce contenu hydrique cerebral peri-ventriculaire n'est pas accru de facon marquee chez les enfants porteurs de pseudotumeur cerebrale. Les auteurs se demandent si cela ne pourrait s'expliquer par un equilibre entre une resistance accrue a la circulation du liquide cephalo-rachidien et un accroissement de la raideur cerebrale, apparaissant comme une consequence de l'accroissement du volume sanguin cerebral et/ou de la pression interstitielle. ZUSAMMENFASSUNG Magnet-Resonanz-Tomographie beim Peudolumor cerebri Die Pathophysiologic des Pseudotumor cerebri ist unklar, hangt aber vielleicht mit einer Unregelmasigkeit des Wassertransports im Gehirn zusammen. Die Autoren haben bei sieben Kindern mit Pseudotumor cerebri Kernspintomogramme gemacht; bei alien Patienten war die Intensitat in der weisen Substanz normal. Diese Daten lassen vermuten, das der periventrikulare Wassergehalt bei Kindern mit Pseudotumor cerebri nicht stark erhoht ist. Die Autoren sind der Meinung, das dies mit der Herstellung eines Gleichgewichtes zwischen erhohtem Widerstand gegen Liquorausflus und erhohter Hirnverhartung zusammenhangt, was als Folge eines erhohten cerebralen Blutvolumens und/oder Interstitiellen Druckes auftritt. RESUMEN Imagen por Resonancia Magnetica en el pseudotumor cerebral La fisiopatologia del pseudotumor cerebral no esta clara, pero puede relacionarse con una anomalia en el transporte del agua en el cerebro. Los autores practicaron RM en siete ninos con pseudotumor cerebral; en todos los pacientes la densidad de la substantia blanca era normal. Estos hallazgos sugieren que el contenido de agua periventricular no esta muy aumentado en ninos con pseudotumor cerebral. Los autores especulan que puede estar en relacion con el establecimiento de un equilibrio entre un aumento de la resistencia del curso del LCR y un aumento de la rigidez cerebral, como consecuencia de un aumento del volumen de sangre cerebral y/o de la presion intersticial.

Recently, hydrokinetic turbines arise as a suitable technology for renewable energy production in isolated zones where solar, wind and tidal energy are limited. Hydrokinetic turbines convert kinetic energy of free water flow in rotational kinetic energy. This energy is finally converted to electrical energy by an integrated generator. Regarding the fact that power output is proportional to the cube of river average velocity, knowing velocity distribution in the installation zone is a crucial aspect for an optimum turbine operation. In this study, two-dimensional Shallow Water equations (SWEs) are solved by the meshless method of local collocation with Radial Basis Function in order to obtain the depth velocity average distribution and water height in open channel flow. Firstly, power output is estimated for a conventional turbine located in the centre of a straight channel. Afterwards, SWEs are solved in a channel with elements to increase local velocity with the aim of estimating power output increment. Electricity production can be increased by adding geometrical elements which modify flow pattern keeping an adequate depth for turbine operation.

SUMMARY A chronic form of tyrositiosis was diagnosed in a mentally retarded girl, aged 13. Concomitant findings were skin lesions of localized epidermolytic hyperkeratosis existing without remission from infancy. A diet low in phenylalanine and tyrosine was started to reduce the patient's blood tyrosine to a normal level. After 6 months of successful dietary control of blood tyrosine, an unexpected result was a complete remission of the skin lesions. The diet was abandoned after a total period of 14 months and the abnormality of tyrosine metabolism became immediately prominent again. Some 4 months later, the skin lesions have recurred. A possible relationship between the congenital skin disorder and the abnormal tyrosine metabolism in this case is considered. It is well known that some inborn errors of amino acid metabolism may be associated with skin lesions. The most cotmnon of the amitio-acidaemias, phenylketonuria (PKU) is characteristically associated with decreased pigmentation. Infantile eczema, dry skin and non-specific rashes are also frequent occurrences and sensitivity to sunlight may be a problem. In some adult phcnylketonuric subjects, eczema may persist in spite of topical treatment and, in our experience, such cases occasionally respond to a modified PKU diet and the lesions may heal in 4-5 weeks. In Hartnup disease, a pellagra-like skin rash aggravated by sunlight is typically associated with periods of ataxia, mental retardation and characteristic amino-aciduria. Skin signs in homocystinuria are mild, consisting of livcdo reticularis, a malar flush and light-coloured hair and skin. In some cases of tyrosinosis, mild hyperpigmentation has been noted. We wish to report an unusual skin lesion occurring concomitantly with elevated blood tyrosine and excretion of tyrosine and its derivatives in urine (tyrosyluria) in a mentally retarded girl diagnosed as a chronic form of tyrosinosis (Zaieski & Hill, 1973).

Energy resource management and energy auditing are two effective methodologies which lead to a rational energy use in the different processes or systems in the industrial sector. This article introduces a methodology focused on energy management through the monitoring of variables as well as the results obtained from its application in “Industrias Alimenticias NOEL S.A., ZENU” plant in Medellin, Colombia. The aim of this methodology is to identify the main sources of energy waste, the way energy is used, and the possibilities for better energy exploitation. The analysis consisted of the periodical measurement of electricity, fuel, water, and propane gas consumption, as well as steam generation, which are then compared to production output (consumption vs. production). Through lineal regression techniques, fixed (baseline) and variable consumption are determined for the comparison. This way, unnecessary consumption and system efficiency data are obtained respectively. By implementing this techniqu...

A two-dimensional mathematical model, in stationary state was developed for the separation of species in a thermal diffusion column working with total reflux. The model was applied to a gas mixture of CO2 and N2. The existence of convective currents along the column was verified, the separation of species due to the temperature gradient was predicted and the effect of the thermal gradient and of the operation pressures on the composition profiles was analyzed.

A methodology has been developed to simplify the complex reaction mechanism for the methane and the ethane combustion processes. The methodology is based on the mass balances, the chemical kinetics...

Human bartonellosis in North America is mainly associated with Bartonella henselae, and the availability of laboratory diagnostic tools has significantly heightened awareness of the spectrum of human disease that is caused by this bacterium. We detail herein examples of illness in a pediatric population which serve to confirm that B. henselae-associated disease exists in British Columbia. Seroprevalence studies among asymptomatic adults and among children with symptomatic respiratory illness of other causation demonstrated that 36.8% and 18.5% of sera, respectively, had IFA-IgG titres [Formula: see text] 1:256. IFA-IgG titres did not vary significantly whether B. henselae ATCC 49793 or a local wild-type B. henselae isolate were used as substrate. An assessment of IgM response was consistent with the proposal that endemic seroprevalence is a function of past rather than recent exposure. Both clinical and serological studies are concordant in providing evidence that B. henselae is endemic in British Columbia.Key words: Bartonella henselae, cat scratch disease, serodiagnosis, seroprevalence.

Germinal matrix/intraventricular hemorrhage is a common type of cerebral injury in premature newborns. Based on the improved understanding of underlying pathogenetic mechanisms, numerous interventional strategies for prevention have been proposed. This article summarizes and evaluates the efficacy and safety of major interventions that are currently under consideration for the prevention of germinal matrix/intraventricular hemorrhage.

Enhanced survival of very premature infants may be regarded as the most striking demonstration of the major improvements in perinatal medicine during the last two decades. This article discusses recent perinatal interventions in the context of the pathogenesis and known risk factors for intraventricular hemorrhage (IVH). In addition, controversies related to the evolution and management of posthemorragic hyrdocephalus (PHH) are examined, and current concepts concerning potential brain injury to PHH are reviewed.

Recent epidemiologic data demonstrate that prenatal factors play a major role in the genesis of brain injury in childhood, e.g., cerebral palsy and mental retardation. Nevertheless, there is extensive experimental, clinical, and neuroimaging data that show that acute, intrapartum hypoxic-ischemic insult is an important factor in the genesis of irreversible brain injury, especially in term newborns. The precise timing of onset of hypoxic-ischemic cerebral injury in premature newborns may be more difficult to establish, and postnatal complications (e.g., intraventricular hemorrhage, posthemorrhagic hydrocephalus) undoubtedly play a major role. When the potential deleterious consequences of severe, intrapartum asphyxia are minimized, there is a risk that important opportunities for prevention of newborn cerebral injury may be missed. In this context, new techniques may permit rapid, in vivo delineation of the critical processes involved in newborn hypoxic-ischemic brain injury that are key factors for the development of effective preventive and interventional strategies. MRDD Research Reviews 3:22–27, 1997. © 1997 Wiley-Liss, Inc.

BACKGROUND AND PURPOSE: Low glucose values are often seen in term infants with NE, including HIE, yet the contribution of hypoglycemia to the pattern of neurologic injury remains unclear. We hypothesized that MR features of neonatal hypoglycemia could be detected, superimposed on the predominant HIE injury pattern. MATERIALS AND METHODS: Term neonates (n = 179) with NE were prospectively imaged with day-3 MR studies and had glucose data available for review. The predominant imaging pattern of HIE was recorded as watershed, basal ganglia, total, focal-multifocal, or no injury. Radiologic hypoglycemia was diagnosed on the basis of selective edema in the posterior white matter, pulvinar, and anterior medial thalamic nuclei. Clinical charts were reviewed for evidence of NE, HIE, and hypoglycemia (

ROB SHAPIRO: You might find it odd that we have a panel entitled, “The Needs of the Buy-side: How Well Are They Being Met?” Why? Because we have only one buy-side person on the panel! We did the pre-conference call and wondered aloud, Oh, poor Matt Lyons, the little lamb on the buy-side, will be surrounded by all these lions! I reminded them, however, that this is an 800-pound lamb. So, I am not quite sure he is at risk.