bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Gentamicin to the Cochlea of the Chicken Embryo
Authors: Fikes James D. , Render James A. , Reed Willie M. , Bursian Steven , Poppenga Robert H. , Sleight Stuart D. , Yoshioka T.
Published: September 2009

Aminoglycoside antibiotics are ototoxic in mammals and birds, including recently hatched chicks, but chicken embryos are insensitive to the ototoxicity of gentamicin, kanamycin, and streptomycin. To determine whether or not the insensitivity is due to a lack of antibiotic distribution to the avian cochlea, the distribution of gentamicin to the cochlea of the White Leghorn chicken embryo was compared to the distribution to the cochlea of the recently hatched White Leghorn chick. Fertile eggs were injected with a maximally tolerated dose of gentamicin sulfate (0.1 mg/egg/day) on incubation days 10–18, and the chicks were injected subcutaneously with either 5 mg (non-ototoxic) or 100 mg (ototoxic) gentamicin sulfate/kg body weight on days 1–9 after hatching. Gentamicin sulfate was histochemically detected within the basilar papilla (the avian equivalent of the organ of Corti) in all treated chicken embryos and chicks by 1 day after the first injection, and the staining was intense after 3 days of treatment. By ultrastructural immunocytochemistry, mild, diffuse labeling for gentamicin sulfate was detected within the endoplasmic reticulum of short and tall hair cells of chicken embryos by incubation day 17. Moderate labeling of gentamicin sulfate was detected in the infracuticular region of lysosomes of hair cells in chicks receiving 5 treatments of gentamicin sulfate at 5.0 mg/ kg body weight and after 1 treatment of gentamicin sulfate at 100 mg/kg body weight. There was labeling of phosphatidylinositol 4,5-bisphosphate (PIP2), believed to be an essential factor in the ototoxicity of gentamicin in the stereocilia, cuticular plate, nucleus, endoplasmic reticulum, cell walls, and tight junctions of hair cells in all control and treated chicken embryos and hatched chicks at each time point with little variation in the amount. In hatched chicks from the high-dose group, short and tall hair cell loss was detected after 3 doses of gentamicin sulfate, and degeneration of dark cells in the tegmentum vasculosum was observed after 5 doses. No hair cell loss and no ultrastructural evidence of degeneration, accumulation of gentamicin sulfate, or an increase in the numbers of lysosomes were detected in hair cells from chicken embryos. Although there was no evidence of drug-induced ototoxicity, PIP2 and gentamicin were detected in the hair cells from chicken embryos. Therefore, the intracellular concentration of gentamicin was either insufficient to induce toxicity or the hair cells were still functionally undeveloped and could not be affected by the gentamicin.
The Role of Transport in Chemical Nephrotoxicity
Authors: Berndt William O.
Published: September 2009

Various physiologic factors play a role in determining the extent of chemical-induced nephrotoxicity. One such factor relates to the transport systems that exist in the kidney. Several examples can be given of organic substances that are nephrotoxic only after being transported into renal tubular cells. Some of the cephalosporin antibiotics have been shown to produce proximal tubular necrosis after transport into those cells. Blockade of transport by competitors eliminates or reduces the nephrotoxic response. Citrinin, a secondary product of fungal metabolism, also produces proximal tubular necrosis, but only after transport into proximal tubular cells. Both the cephalosporins and citrinin utilize the organic anion transporter for entry into the cells, a transporter present in adult animals of all species and probably important physiologically for moving metabolic substrates into cells. Various glutathione conjugates (e.g., S-(1,2-dichlorovinyl) glutathione [DCVG]) also are transported into proximal tubular cells with a resulting nephrotoxicity. DCVG utilizes the sodium-dependent transport process that moves glutathione into proximal tubular cells, a process that is inhibited by probenecid. Finally, certain heavy metals also are transported into renal tubular cells. For example, mercuric ion enters proximal cells both from the luminal and peritubular sides and sulfhydryl compounds modify the transport. Movement of mercury from the peritubular side of the cell may be modified by certain organic anions. The characteristics of these mechanisms are less well understood than the mechanisms for the organic compounds.
Urinary Bladder Carcinogenesis
Authors: Cohen Samuel M.
Published: September 2009

Urinary bladder carcinogenesis in rodents bears numerous similarities to the diseases in humans. In rats, the process progresses through the morphologic stages of simple hyperplasia, papillary and nodular hyperplasia, papilloma, noninvasive, and invasive carcinoma. In mice, the pathogenesis can be similar or can follow a sequence of marked dysplasia with or without hyperplasia, leading to carcinoma in situ and ultimately to high-grade invasive carcinoma. Although the papillary and nonpapillary diseases appear to be related in rodents and in humans, they are distinct morphologically, biologically, and molecularly. Numerous classes of genotoxic chemicals have been identified as bladder carcinogens in rodents, and some of these have also been identified as carcinogenic in humans, most notably, aromatic amines, nitrosamines, and cyclophosphamide. In contrast, nongenotoxic chemicals appear to be highly specific with respect to species, strain, diet, agent, dose, and mechanism. For some, it is unclear whether the results at high doses in rodents can be extrapolated to low doses or to humans, e.g., chemicals that cause bladder cancer only at high doses related to the formation of calculi. Numerous observations in rodents can assist in identifying possible mechanisms involved for these nongenotoxic chemicals and therefore can be important for a rational evaluation of human risk.
Submucosal Mesenchymal Tumors of the Mouse Urinary Bladder
Authors: Halliwell William H.
Published: September 2009

A unique morphologic change has been described in the submucosa of the urinary bladder of mice since the 1950s. These lesions, variously referred to as vegetative changes, reactive lesions, submucosal granulomas, leiomyosarcomas, atypical hemangiosarcomas, or submucosal mesenchymal tumors have been considered rare and of questionable etiology. Although the morphologic criteria are fairly well defined, the pathobiology of the lesion is not well characterized and the previously listed nomenclature reflects this uncertainty. The lesion may not be limited to the urinary bladder, the cell of origin is controversial, the biology is unknown, and whether the lesion is granulomatous, hypertrophy, hyperplasia, metaplasia, or a benign or malignant neoplasm is not well defined. Data compiled from multiple sources are discussed to review the strain of mouse most often affected, sex, age at diagnosis, anatomic location, incidence, descriptive morphology, immunohistochemical staining results, and other features of the submucosal mesenchymal tumor of the mouse urinary bladder. Presented are suggested terminology for the lesion, submucosal mesenchymal tumor of the mouse urinary bladder; the relevance of the tumor for human risk assessment; and discussion of the possible histogenesis of this lesion from primitive mesenchymal cells of the submucosa (lamina propria) of the urinary bladder of mice.
Morphological Changes in the Pituitary Gland of Dogs Chronically Exposed to Exogenous Growth Hormone
Authors: Laroque Philippe , Molon-Noblot Sylvain , Prahalada Srinivasa , Stabinski Lea G. , Hoe Chao-Min , Peter Chennekatu P. , Duprat Pierre , van Zwieten Matthew J.
Published: September 2009

Growth hormone (GH) synthesis and release from the pituitary is regulated by hypothalamic releasing hormone, insulin-like growth factor-1 (IGF-1), and somatostatin. However, the potential effects of pharmacological doses of exogenous GH on the pituitary are not well studied. To determine the potential chronic effects of exogenous GH on pituitary morphology in dogs, porcine GH (pGH) was administered subcutaneously to 3 groups of dogs (4 animals/sex/group) at doses of 0.025, 0.1, and 1.0 IU/kg/day for 14 wk. A group (4/sex) of dogs served as the vehicle control. The pituitaries from all dogs were weighed and fixed in appropriate fixatives for light and electron microscopic examination; in addition, cells of the pars distalis were quantitated by a point counting method following immunostaining to identify cells containing GH, prolactin (PRL), and adrenocorticotrophic (ACTH) hormones. Administration of pGH resulted in a statistically significant (p ≤ 0.05) increased pituitary weight through the high dose. By light microscopy (LM), hypertrophy of pars distalis cells was evident in mid- and high-dose female dogs. The pituitaries of dogs given the lowest dose (0.025 IU/kg/day) of pGH were not remarkable based on weight and LM findings. In addition, transmission electron microscopic (TEM) examination of the pituitary gland of high-dose dogs demonstrated, in both sexes, pituitary cells with variably dilated rough endoplasmic reticulum and decreased numbers of secretory granules; some of these cells reacted positively to GH immunostaining. Quantitative analysis of the pituitary gland of high-dose males and females showed an increase in the absolute volume of all cell populations studied: GH-, PRL-, and ACTH-positive cells. Based on the LM and TEM findings, the increased volume of the cell populations studied is likely related to cellular hypertrophy. The expected elevation in serum GH levels following repeated administration of pGH and an associated elevation in serum IGF-1 levels resulted in morphologic changes in the pituitary gland of dogs given high doses (≥0.1 IU/kg/day) of pGH; these observations differed from the reported findings in pituitaries of transgenic mice secreting large quantities of bovine GH.
Pathology of the Oropharyngeal Cavity in Six Strains of Rats: Predisposition of Fischer 344 Rats for Inflammatory and Degenerative Changes
Authors: Germann Paul-Georg , Ockert Deborah , Heinrichs Martin
Published: September 2009

The sagittolongitudinal histopathological evaluation of the oropharyngeal cavity in 6 strains of rats revealed a clear predisposition of the Fischer 344 strain for degenerative and inflammatory lesions in this region. A degeneration and calcification predominantly of the laryngeal cartilage is evident in 72%, granulomas of the seromucinous glands in 38%, and an inflammation with bacterial colonies or plant material in the basal part of the laryngotracheal junction in 26% of the Fischer 344 rats. The incidences of these types of lesions were negligible in the other rat strains evaluated. The comparison of control Fischer 344 rats from 2 carcinogenicity studies (untreated group; gavaged group with water, pH 10; gavaged group with propylene glycol/methocel) showed an influence of the gavage technique with the solvent on the survival rate in the female Fischer 344 rats. The lower survival rate was accompanied by the occurrence of food impaction in the oropharyngeal cavity. This increased mortality in female Fischer 344 rats was also associated with a degeneration of the laryngeal cartilages, whereas the formation, of granulomas and inflammation seemed to have no direct relationship to the mortality. The gavage technique with the applied solvent was an enhancing factor in the female Fischer 344 rats on mortality, on cartilage degeneration, but not on inflammatory changes. In contrast to the females, male Fischer 344 rats had a higher incidence of granulomas and inflammation, which, however, did not influence the survival rate. In conclusion, Fischer 344 rats, especially the female sex, exposed to chronic daily irritation by gavage, are predisposed to have a high mortality rate in chronic toxicologic tests. An explanation lies in the disposition of the Fischer 344 rat to a high incidence of cartilage degeneration, which presumably leads to a dysfunction of the larynx.
Quantitation of Glandular Gastric Changes in Rats Given a Proton Pump Inhibitor for 3 Months with Emphasis on Sampling Scheme Selection
Authors: White S. L. , Smith W. C. , Fisher L. F. , Gatlin C. L. , Hanasono G. K. , Jordan W. H.
Published: September 2009

Proton pump inhibitors and H2-receptor antagonists suppress gastric acid secretion and secondarily induce hypergastrinemia. Sustained hypergastrinemia has a trophic effect on stomach fundic mucosa, including enterochromaffin-like (ECL) cell hypertrophy and hyperplasia. Histomorphometric quantitation of the pharmacologic gastric effects was conducted on 10 male and 10 female rats treated orally with LY307640 sodium, a proton pump inhibitor, at daily doses of 25, 60, 130, or 300 mg/kg for 3 mo. Histologic sections of glandular stomach, stained for chromogranin A, were evaluated by image analysis to determine stomach mucosal thickness, mucosal and nonmucosal (submucosa and muscularis) area, gastric glandular area, ECL cell number/area and cross-sectional area. Total mucosal and nonmucosal tissue volumes per animal were derived from glandular stomach volumetric and area data. Daily oral doses of compound LY307640 sodium caused slight to moderate dose-related mucosal hypertrophy and ECL cell hypertrophy and hyperplasia in all treatment groups as compared with controls. AU observed effects were prominent in both sexes but were generally greater in females. The morphometric sampling schemes were explored to optimize the data collection efficiency for future studies. A comparison between the sampling schemes used in this study and alternative schemes was conducted by estimating the probability of detecting a specific percentage of change between the male control and high-dose groups based on Tukey's trend test. The sampling scheme analysis indicated that mucosal thickness and mass had been oversampled. ECL cell density quantitation efficiency would have been increased by sampling the basal mucosa only for short-term studies. The ECL cell size sampling scheme was deemed appropriate for this type of study.
Dermatotoxicity of Agricultural Chemicals in the Dorsal Skin of Hairless Dogs
Authors: Klmura Tohru , Kuroki Koji , Doi Kunio
Published: September 2009

Dermatotoxicity of agricultural chemicals (ACs) with or without ultraviolet (UV) irradiation was histologically examined using hairless descendants of Mexican hairless dogs. ACs examined were pentachlorophenol sodium salt, 2,4-dichlorophenoxyacetic acid (DCPAA), Maneb, and Zineb. One day after cessation of the 7-day AC treatment, the skin treated with DCPPA and Maneb indicated only slight histological changes. The UV+AC-treated sites had as much pigmentation as the control sites. Fourteen days after cessation of treatment, dogs treated with Maneb showed marked reactions such as epidermal degeneration, vasodilation, and intradermal infiltration of inflammatory cells. These histological changes were more severe in the UV+AC-treated sites. Zineb induced comedones with well-developed pilosebaceous glands. These results suggest that hairless dogs may be useful laboratory animals for the investigation of dermatotoxicity of ACs in conjunction with UV irradiation.
A Spontaneous Seminal Vesicle Adenocarcinoma in an Aged F344 Rat
Authors: Shoda Toshiyuki , Mitsumori Kunitoshi , Imazawa Takayoshi , Toyoda Kazuhiro , Tamura Toru , Takada Kouichi , Takahashi Michihito
Published: September 2009

A rare seminal vesicle adenocarcinoma was found in a 109-wk-old Fischer 344 (F344) rat. At necropsy, the right seminal vesicle was enlarged, containing a 15- × 18- ×18-mm mass. The neoplasm occupied almost the entire seminal vesicle lumen and consisted of epithelial cells arranged in papillary, glandular, and solid patterns. Tumor cells were larger than their normal counterparts in the seminal vesicles and had round nuclei and abundant cytoplasm. Clusters of macrophagelike cells with less abundant cytoplasm and indented nuclei were apparent in the lumina of the glandular structures formed by the tumor cells. No metastasis to other tissues or organs was observed. Immunohistochemically, tumor cells were positive for keratin and S-100, and the macrophagelike cells bound antibodies against vimentin and ED-1. Ultrastructurally, the tumor cells exhibited many small secretory granules, some microvilli, and intercellular junctions. The macrophagelike cells, in contrast, were characterized by lysosomes and abundant rough endoplasmic reticulum. Therefore, a diagnosis of seminal vesicle adenocarcinoma with intraluminal macrophage infiltration was made. This is the first case report of such a seminal vesicle tumor in an F344 rat.
The National Toxicology Program Evaluation of Genetically Altered Mice as Predictive Models for Identifying Carcinogens
Authors: Eastin William C. , Haseman Joseph K. , Mahler Joel F. , Bucher John R.
Published: September 2009

National Institute of Environmental Health Sciences researchers are exploring the utility of genetically altered mice to study mechanisms of carcinogenesis. Two of these mouse models, the Tg.AC (carrier of an activated mouse H- ras oncogene) and the p53+/- (heterozygous for the wild-type tumor suppressor gene Trp53), have genetic alterations that appear to hasten their expression of chemically induced tumors. These 2 models have been proposed as a basis for new strategies for identifying chemical carcinogens and for assessing risk. The National Toxicology Program (NTP) is conducting a series of studies with these 2 genetically altered strains to further examine their strengths and weaknesses for identification of documented rodent and human carcinogens. In this first evaluation, candidates for study were drawn from the NTP historical database of 2-yr rodent carcinogenicity studies and the open literature (primarily for drugs). Results with this first set of 11 chemicals tested in genetically altered mice, compared with previous findings in the traditional 2-yr rodent assays and literature on human tumor findings, appear to support the premise advanced by Tennant et al that these models have the potential to serve as more rapid and less expensive test systems to identify carcinogens.
TGFα is Dispensable for Skin Tumorigenesis in Tg.AC Mice
Authors: Humble Michael C. , Szczesniak Carl J. , Luetteke Noreen C. , Spalding Judson W. , Cannon Ronald E. , Hansen Laura A. , Lee David C. , Tennant Raymond W.
Published: September 2009

Alterations in growth factor signaling pathways frequently accompany the development and maintenance of epithelial neoplasia. Transforming growth factor a (TGFα) and its epidermal growth factor receptor have been thought to play an especially important role in epithelial neoplasia. In this study, mice were derived genetically deficient (null) in functional TGFα expression and carrying the Tg.AC/v-Ha- ras transgene. The goals were to determine if (a) papillomagenesis was dependent on TGFα and (b) progression to malignancy was dependent on TGFα expression. Groups of male and female mice heterozygous or homozygous for the TGFα null allele and hemizygous for the Tg.AC transgene were treated twice weekly for 10 or 15 wk with doses of 12- O-tetradecanoylphorbol-13-acetate (TPA) known to produce papillomas in Tg.AC mice. Papillomas were readily induced in both male and female TGFα null mice. Malignant progression of papillomas was observed in all TGFα null treatment groups. Additionally, we examined the response of TGFα null mice to full thickness dorsal wounds, a stimulus known to promote papillomagenesis in Tg.AC mice. As in the TPA study, papillomas were induced in both male and female TGFα null mice. These studies indicate that TGFα is not required for the induction and maintenance of papillomas nor is it essential for the malignant conversion of papillomas in Tg.AC mice.
Altered Differentiation of Hepatocytes in a Transgenic Mouse Model of Hepatocarcinogenesis
Authors: Enomoto Akiko , Sandgren Eric P. , Maronpot Robert R.
Published: September 2009

Transgenic mice carrying the SV40 T antigen (TAg) gene, which develop hepatocellular and biliary cell tumors by 4 mo of age, show ductular structures in the neonatal liver. Coexpression of c- myc with TAg increases the extent and persistence of ductular lesions and also accelerates tumor development. To analyze possible links between altered gene expression and cell differentiation and to determine the relationship between the ductular structures and tumor development in these mice, ductular cells in single (TAg) and bitransgenic (TAg X c- myc) mice were characterized for biliary and hepatocellular differentiation, transgene expression, and proliferation activity. The results show that the ductular cells in these transgenic mice have characteristics of biliary cells, including basement membrane formation, positive laminin staining, and bile duct-specific lectin ( Dolichos biflorus agglutinin and peanut agglutinin) binding, and characteristics of hepatocytes, including albumin expression and ultrastructural features such as round nuclei with 1 or 2 nucleoli and well-developed cytoplasmic organelles. However, differences in transgene expression and cell proliferation between the ductular cells and nonductular hepatocytes were not apparent. Thus, the ductular cells could not be defined as tumor progenitor cells in these mouse livers. However, this model suggests that manipulation of gene expression can alter differentiation of hepatic parenchymal cells.
Genetic Analysis of Ectopic Circadian Clock Induction in Drosophila
Authors: Kilman Valerie L. , Allada Ravi
Published: September 2009

Cell-autonomous feedback loops underlie the molecular oscillations that define circadian clocks. In Drosophila the transcription factor Clk activates multiple clock components of feedback loops many of which feed back and regulate Clk expression or activity. Previously the authors evoked similar molecular oscillations in putatively naïve neurons in Drosophila by ectopic expression of a single gene, Clk, suggesting a master regulator function. Using molecular oscillations of the core clock component PERIOD (PER), the authors observed dramatic and widespread molecular oscillations throughout the brain in flies expressing ectopic Clk. Consistent with the master regulator hypothesis, they found that Clk is uniquely capable of inducing ectopic clocks as ectopic induction of other clock components fails to induce circadian rhythms. Clk also induces oscillations even when expression is adult restricted, suggesting that ectopic clocks can even be induced in differentiated cells. However, if transgene expression is discontinued, PER expression disappears, indicating that Clk must be continually active to sustain ectopic clock function. In some cases Clk-mediated PER induction was observed without apparent synchronous cycling, perhaps due to desynchronization of rhythms between clocks or truly cell autonomous arrhythmic PER expression, indicating that additional factors may be necessary for coherent rhythms in cells ectopically expressing Clk. To determine minimal requirements for circadian clock induction by Clk, the authors determined the genetic requirements of ectopic clocks. No ectopic clocks are induced in mutants of Clk’s heterodimeric partner cyc. In addition, noncycling PER is observed when ectopic Clk is induced in a cryb mutant background. While other factors may contribute, these results indicate that persistent Clock induction is uniquely capable of broadly inducing ectopic rhythms even in adults, consistent with a special role at the top of a clock gene hierarchy.
Autism in Several Members of a Family With Generalized Epilepsy With Febrile Seizures Plus
Authors: Dixon-Salazar Tracy J. , Keeler Lesley C. , Trauner Doris A. , Gleeson Joseph G.
Published: September 2009

The neurobiologic basis for autism is not well understood. In contrast, there have been several recent discoveries into the genetics of generalized epilepsy with febrile seizures plus, a group of epilepsy syndromes characterized by multiple seizure phenotypes. Here we describe a family with generalized epilepsy with febrile seizures plus and variably expressed autism spectrum disorder that does not show linkage to any of the four known generalized epilepsy with febrile seizures plus loci. A relationship between these two disorders has not previously been described. ( J Child Neurol 2004;19:597-603).
A Negative Cranial Computed Tomographic Scan Is Not Adequate to Support a Diagnosis of Pseudotumor Cerebri
Authors: Said Rana R. , Rosman N. Paul
Published: September 2009

A 10-year-old boy with daily headache for 1 month and intermittent diplopia for 1 week was found to have a unilateral partial abducens palsy and bilateral papilledema; otherwise, his neurologic examination showed no abnormalities. A cranial computed tomographic (CT) scan was normal. Lumbar puncture disclosed a markedly elevated opening pressure of > 550 mm of cerebrospinal fluid with normal cerebrospinal fluid. Medical therapy with acetazolamide for presumed pseudotumor cerebri was begun. Magnetic resonance imaging (MRI) of the brain, done several days later because of continuing symptoms, unexpectedly showed multiple hyperintensities of cerebral white matter on T2-weighted and fluid-attenuated inversion recovery images. Despite high-dose intravenous methylprednisolone for possible demyelinating disease, he failed to improve. A left temporal brain biopsy followed and disclosed an anaplastic oligodendroglioma. In a patient with features indicating pseudotumor cerebri, a negative cranial CT scan is not adequate to rule out underlying pathology; thus, MRI of the brain should probably always be performed. A revised definition of pseudotumor cerebri could better include "normal MRI of the brain" rather than "normal neuroimaging." (J Child Neurol 2004;19:609-613).
Vestibulospinal Component of Postural Control (Vestibular Function) in Very Preterm Infants (25 to 27 Weeks) at 3, 6, and 12 Months Corrected Age
Authors: de Graaf Marieke T. , Samsom Janny F. , Pettersen Erik Mulder , Schaaf Veronique A. M. , van Schie Petra E. M. , de Groot Laila
Published: September 2009

Postural control, which is important for the development of all movement, balance, and locomotion, depends a great deal on the vestibulospinal component of vestibular function in early childhood. Vestibulospinal input is important for muscle power regulation, which, in turn, influences postural control. The aim of this study was to focus particularly on this component of vestibular function during the first year of life in 67 infants with a very short gestational age (25-27 weeks), to search for possible neonatal confounders, and to see whether it influences the course of muscle power development in preterm infants. Outcome was described as being optimal, suspect, or abnormal. The infants were categorized into the Neonatal Medical Index according to the severity of neonatal illness and separately into three groups for neonatal brain ultrasonography findings (normal to severe abnormalities). At the age of 3 months, 20 infants performed optimally on all items testing vestibular function, increasing to 40 at 6 months and 48 at 12 months. This significant improvement (also seen in muscle power regulation) was primarily caused by better head control (during the traction response and prone position), whereas less shoulder retraction and hyperextension were found in the sitting position. Vestibular function was significantly related to brain ultrasonography classification but not to gestational age, birthweight, the Neonatal Medical Index, or gender. (J Child Neurol 2004;19:614-618).
Pharyngeal-Cervical-Brachial Variant Guillain-Barre Syndrome in a Child
Authors: MacLennan Suzanna C. , Fahey Michael C. , Lawson John A.
Published: September 2009

The pharyngeal-cervical-brachial variant of Guillain-Barré syndrome is uncommon but well recognized in the adult literature. Patients have weakness in a pharyngeal-cervical-brachial distribution with relative lower limb sparing. We describe a 12-year-old boy with predominantly pharyngeal-cervical-brachial weakness and subsequent respiratory failure. Owing to prominent bulbar symptoms, he was initially misdiagnosed as having epiglottitis. This case illustrates that the clinical spectrum of Guillain-Barré syndrome in children includes the pharyngeal-cervical-brachial variant, which is distinct from Miller-Fisher syndrome. Atypical Guillain-Barré syndrome should be considered in the differential diagnosis of a child presenting with bulbar palsy and/or respiratory failure. (J Child Neurol 2004;19:626-627).
Brain Stem Auditory Evoked Potentials as a Tool in the Clinical Assessment of Children With Posterior Fossa Tumors
Authors: Goldie William D. , van Eyes Jan , Baram Tallie Z.
Published: September 2009

The use of brain stem auditory evoked potentials (BAEP) as a diagnostic modality in children with posterior fossa neoplasms is described. Thirty-one patients were examined; their diagnoses were medulloblastoma (12), brain stem glioma (9), cerebellar astrocytoma (6), and ependymoma (4). Distinct differences in the type and severity of waveform abnormalities were observed among the different tumor types, possibly related to location and invasiveness. Medulloblastomas frequently demonstrate normal waveforms, while brain stem gliomas demonstrate severe disruption of BAEP patterns. Ependymomas may result in a variety of abnormal studies, while cerebellar astrocytomas induce mild abnormalities or result in a normal exam. The use of brain stem auditory evoked potentials in the diagnosis of pediatric brain tumors, as well as the underlying mechanisms of the abnormalities, is discussed. ( J Child Neurol 1987;2:272-275)
Patterns of Cerebral Arterial Injury in Children With Neurological Disabilities
Authors: Baumann Robert J. , Carr W. Allen , Shuman Robert M.
Published: September 2009

We reviewed the data from 215 consecutively imaged children who were referred because of neurologic disease. We specifically looked for evidence of cerebral arterial infarction in the form of focal brain damage in an arterial vascular distribution. Twenty-eight showed an arterial infarction pattern. All the major cerebral arteries were involved: middle cerebral artery, 17/28; posterior cerebral artery, 7/28; anterior cerebral artery, 2/28; carotid, 2/28; and vertebro-basilar, 1/28. Six of the 28 subjects had disorders reported to be associated with cerebrovascular damage. Another 13 subjects had other associated disorders, including perinatal distress and presumed anoxia, closed head trauma, hydrocephalus, and dehydration with electrolyte imbalance. Despite a careful search of medical records, we were unable to find any evidence of an adverse event or associated illness for more than one third of the children. These data suggest that cerebral arterial infarction is a more common lesion in the static neurologic disabilities of childhood than previously thought. ( J Child Neurol 1987;2:298-306).
Cardiac Hypertrophy Associated With ACTH Therapy for Childhood Seizure Disorder
Authors: Young Richard S.K. , Fripp Raymond R. , Stern Diane R. , Darowish Charles
Published: September 2009

Hypertrophic cardiomyopathy is a newly recognized, potentially fatal complication of ACTH therapy. We report the clinical, echocardiographic, and pathologic findings of an infant who was treated with ACTH for seizure disorder and subsequently developed severe systemic hypertension. Echocardiography revealed marked cardiac hypertrophy with disproportionate septal hypertrophy. Decreasing the dose of ACTH reduced the systemic blood pressure, but the cardiac hypertrophy progressed and the child subsequently died. Children who develop hypertension during ACTH therapy should be considered at risk for hypertrophic cardiomyopathy and should undergo routine echocardiographic evaluation. ( J Child Neurol 1987;2:311-312).
The Multiple Causes of Multiple Sclerosis: The Importance of Age of Infections in Childhood
Authors: Alvord Ellsworth C. , Jahnke Ulrike , Fischer Edmond H. , Kies Marian W. , Driscoll Bernard F. , Compston D. Alastair S.
Published: September 2009

The geographic distribution of multiple sclerosis (MS) may relate to the age of inital exposure and degree of sensitization to common viruses or bacteria which have proteins with epitopes (antigenic determinants) which are homologous with potentially encephalitogenic peptides in central myelin proteins, such as basic protein and proteolipid protein. Comparable homologies may exist for the as-yet-undefined nonencephalitogenic myelin antigen(s) which evoke demyelinating factors (probably complement-fixing antibodies). Many of these homologous epitopes occur in microorganisms that also possess adjuvant activity for evoking not only the sensitized T-cells but also the antibodies that cross-react with the target antigens in central myelin. If sufficient sensitization to myelin basic protein or proteolipid protein occurs, especially in infections of young adults, the individual develops acute disseminated encephalomyelitis, exactly comparable to ordinary acute experimental allergic encephalomyelitis (EAE). If very young children are infected, however, practically complete resistance develops, and neither acute disseminated encephalomyelitis nor MS follows. In between these two extremes, especially in slightly older children in whom insufficient sensitization occurs to induce acute disseminated encephalomyelitis, the individual may become resistant to acute disseminated encephalomyelitis, but susceptible to chronic relapsing or progressive disseminated encephalomyelitis, otherwise generally recognized as MS. This is exactly comparable to a recently described variant of chronic EAE in which demyelinating antibodies and large subpial plaques of demyelination occur. The similarity of this form of chronic EAE or chronic disseminated encephalomyelitis to one form of MS is emphasized. ( J Child Neurol 1987;2:313-321).
Scoliosis in Spinal Muscular Atrophy: Review of 63 Cases
Authors: Rodillo E. , Marini M.L. , Heckmatt J.Z. , Dubowitz V.
Published: September 2009

We reviewed the incidence and severity of scoliosis in 37 patients with the intermediate type and 26 with the mild type of spinal muscular atrophy. In the intermediate type, scoliosis has an early onset and rapid progression before puberty, and a spinal fusion will be needed in virtually all cases. This rapid progression occurred despite routine use of a spinal brace. Hip dislocation was frequently present but, in most cases, was secondary to the pelvic tilt and did not contribute to the scoliosis. In the mild type, the scoliosis was more variable. In the 30% of patients who had scoliosis, progression was rapid during puberty but only in those who had lost ambulation. Of the four children with the intermediate type and the seven with the mild type who walked in light-weight orthoses, progression of scoliosis was slow, except in those who had lost ambulation. The ultimate effect of walking in orthoses is difficult to assess because of small numbers, but it seems to slow or at least delay progressive scoliosis. ( J Child Neurol 1989;4:118-123).
Vertebrobasilar Occlusion Complicating Nonpenetrating Craniocervical Trauma in a Child
Authors: Pitter Jean H. , French Joseph H. , PeBenito Rhandy , Hotson Gwendolyn C.
Published: September 2009

We report a juvenile patient who developed vertebrobasilar occlusion following nonpenetrating head and neck trauma, with complete recovery. The patient presented with transient signs of brain-stem dysfunction that were secondary to embolization and/or extension of a thrombus. He was treated with anticoagulants. We have found no other reports of such treatment in juvenile vertebrobasilar occlusion that complicated nonpenetrating head and neck trauma. ( J Child Neurol 1990;5:219-223).
Computed Tomography and Magnetic Resonance Imaging of the Brain in Hurler's Disease
Authors: Afifi Adel K. , Sato Yutaka , Waziri Mary H. , Bell William E.
Published: September 2009

Computed tomographic (CT) and magnetic resonance imaging (MRI) scans of the brain in five patients with Hurler's disease are described and compared to the few available reports in the literature. Computed tomographic scans revealed low attenuation areas in the centrum semiovale and peritrigonal white matter. Ventriculomegaly was not a prominent feature in our patients, compared to those previously reported. In two patients, CT scans were normal. The most prominent magnetic resonance imaging abnormalities were the presence of radially oriented cystic areas in the centrum semiovale, peritrigonal white matter, corpus callosum, and pericallosal region. Magnetic resonance imaging abnormalities were present in all patients, even when CT scans were normal. Abnormalities on CT and MRI scans tended to be more prevalent in the posterior regions. Magnetic resonance imaging proved to be a more reliable imaging method in Hurler's disease. T 1-weighted images delineated the cystic areas more clearly, whereas T2-weighted images were more sensitive in detecting small white-matter abnormalities. Magnetic resonance imaging abnormalities correlated well with known neuropathologic alteration in this disease. It is suggested that the cystic areas seen on MRI correspond to perivascular lacunae seen in histopathologic material. ( J Child Neurol 1990;5:235-241).
Effect of Long-Term Vigabatrin Therapy on Selected Neurotransmitter Concentrations in Cerebrospinal Fluid
Authors: Ben-Menachem Elinor , Mumford John , Haegele Klaus D. , Huebert Norman
Published: September 2009

Ten patients, suffering from drug-resistant complex partial seizures were treated for a period of up to 3 years with vigabatrin (Sabril). Vigabatrin is a novel antiepileptic agent, whose action is based on the inhibition of γ-aminobutyric acid (GABA) aminotransferase, the enzyme responsible for the catabolism of the neurotransmitter GABA. Samples of lumbar cerebrospinal fluid were obtained from the patients prior to commencing vigabatrin therapy, and thereafter at 6 months, 1 year, 2 years, and up to 3 years following the initiation of vigabatrin treatment. The influence of vigabatrin on the cerebrospinal fluid concentrations of free and total GABA, homocarnosine, homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol, as well as of the drug itself, was assessed. All patients demonstrated a clinical response to vigabatrin, and the drug was well tolerated over the entire observation period. Mean (±SD) reduction of seizure frequency was 65% ± 23% (range, 26% to 100%) when comparing the end of the treatment period to the previgabatrin baseline. The cerebrospinal fluid concentrations of both free and total GABA and of the dipeptide homocarnosine showed approximately 2- to 5-fold increases over baseline values, with free GABA and homocarnosine being the more sensitive variables. Cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were not altered in a significant manner over the observation period. These findings support the concept that the effects of vigabatrin are restricted to an effect on GABA catabolism and do not extend to the neurotransmitters dopamine and norepinephrine. Clinical efficacy and elevation of GABA and homocarnosine concentration were sustained over the period of observation. (J Child Neurol 1991;6(Suppl):2S11-2S16).
Therapeutic Trial of Vigabatrin in Refractory Infantile Spasms
Authors: Chiron Catherine , Dulac Olivier , Beaumont Daniel , Palacios Leonardo , Pajot Nicole , Mumford John
Published: September 2009

Infantile spasms usually start during the first year of life and constitute one of the most difficult types of epilepsy to treat. They carry a very poor prognosis for both epilepsy and mental development. Seventy children, including 47 infants, with intractable infantile spasms were entered into an open study with vigabatrin as add-on therapy to the usual anticonvulsant treatment. All were resistant to previous treatments, including corticosteroids (43 patients), carbamazepine, benzodiazepines, and sodium valproate. Two children withdrew from the study because of intolerance to vigabatrin (hypotonia or hypertonia) before evaluation of efficacy could be made. Of the remaining 68 children, 29 (43%) showed complete suppression of spasms. Forty-six children had a greater than 50% reduction in spasms. The best response was observed in those with tuberous sclerosis (12/14 compared with 12/18 with symptomatic infantile spasms of other origin and 22/36 with cryptogenic infantile spasms). Following the initial response to treatment of these patients (n = 68), a long-term response was confirmed in 75% of children with symptomatic infantile spasms and 36% of children with cryptogenic infantile spasms. In eight children, all other anticonvulsant medication could be definitively withdrawn. Tolerability appeared excellent, with 52 of 70 patients reporting no side effects. Somnolence, hypotonia, weight gain, excitation, and insomnia were the most common problems at the beginning of the study and were usually transient. Given the poor prognosis of this type of childhood epilepsy, vigabatrin appears to be a very interesting advance in the management of drug-resistant infantile spasms. (J Child Neurol 1991;6(Suppl):2S52-2S59).
Saudi Variant of Multiple Sulfatase Deficiency
Authors: Al Aqeel A. , Ozand P.T. , Brismar J. , Gascon G.G. , Brismar G. , Nester M. , Sakati N.
Published: September 2009

We describe eight patients with multiple sulfatase deficiency (MSD, or Austin's disease) who differ phenotypically from classic neonatal-, childhood-, or juvenile-onset MSD. The age of onset was in childhood. The patients presented with somatic and facial features of mucopolysaccharidosis reminiscent of Maroteaux-Lamy and Morquio syndromes. They differed from classic MSD by the presence of corneal cloudiness, macrocephaly, severe dysostosis multiplex, and gibbus and the absence of ichthyosis, retinal degeneration, severe deafness, severe mental retardation, and dementia. The main neurologic presentation was cervical cord compression due to axis abnormalities. Despite neuroradiologic evidence of white-matter changes, neurologic presentation was not like metachromatic leukodystrophy. The sulfatase deficiencies were more marked than in the classic juvenile form of MSD, but less marked than in the classic childhood-onset form of MSD. Steroid sulfatase activity was spared except in one patient. This Saudi variant of MSD accounts for 5% of all lysosomal storage diseases in the Cell Repository Registry of our Inborn Errors of Metabolism Laboratory. (J Child Neurol 1992;7(Suppl):S12-S21.)
Unknown Dysmorphic Syndromes and Developmental Delay in Saudi Arabia
Authors: Nester Michael J. , Sakati Nadia , Greer William
Published: September 2009

Forty-four Saudi Arabian patients with unknown dysmorphic syndromes were studied with respect to their level of cognitive delay. The relationship between such delay and particular patterns of dysmorphic features, as well as various demographic and historical data, were also investigated. Prognostication and genetic counseling are difficult for this group because little is known about morbidity or other factors. These concerns, along with broader issues, stimulated this study. Significant associations were found between level of cognitive function and consanguinity, abnormal motor and language milestones, and abnormal electroencephalograms. No significant relationship was found between various dysmorphic feature clusters and measured cognition. Concerns were expressed about demands on family and community for these children, as well as possible larger issues in this heavily consanguineous society. Further research, including epidemiologic studies, was recommended. (J Child Neurol 1992;7(Suppl):S64-S68.)
A Patient With Propionic Acidemia Managed With Continuous Insulin Infusion and Total Parenteral Nutrition
Authors: Kalloghlian Avedis , Gleispach Helmut , Ozand P.T.
Published: September 2009

An infant newly diagnosed with propionic acidemic coma was managed successfully with total parenteral nutrition (TPN) and continuous infusion of insulin. The urinary excretion of 3-hydroxypropionic acid was reduced to 3% of the admission value in 4 days, gradually decreasing to 1.5% in 16 days. The treatment did not prevent a prolonged episode of thrombocytopenia. The infant tolerated TPN well, except for continued hyper-lactic acidemia (2 to 4 times normal). Metabolic acidosis and mild hyperammonemia recurred only when the patient had sepsis secondary to Candida albicans and Staphylococcus aureus infection. ( J Child Neurol 1992;7(Suppl):S88-S91.)
New Antiepileptic Drugs for Children: Felbamate, Gabapentin, Lamotrigine, and Vigabatrin
Authors: Devinsky Orrin , Vazquez Blanca , Luciano Daniel
Published: September 2009

After a 15-year hiatus, several new antiepileptic drugs have been approved or are under Food and Drug Administration investigation for use in the United States. This article reviews four of these new drugs—felbamate, gabapentin, lamotrigine, and vigabatrin. Although these drugs have been primarily developed for use in adults with partial seizures, they will also likely be used in children with partial epilepsy. Pediatric experience with several of these drugs has demonstrated safety and efficacy in other seizure types and epilepsy syndromes. These drugs will be an important addition to the therapeutic armamentarium for pediatric epilepsy. Additional studies are needed to fully explore the safety and efficacy of these drugs in a variety of pediatric epilepsies and to compare them to existing antiepileptic drugs. (J Child Neurol 1994;9(Suppl):S33-S45).
Electroencephalographic-Video Monitoring in Neonates, Infants, and Children
Authors: Mizrahi Eli M.
Published: September 2009

Electroencephalographic (EEG)-video monitoring is a valuable tool in the evaluation and management of neonates, infants, and children suspected of having seizures or those with confirmed epilepsy. Monitoring may provide the basis for detection, characterization, and quantification of seizures in each of these age groups. The basic functional components of monitoring include: EEG, polygraphic measures, video, and synchronization devices that assure that all recorded modalities can be precisely correlated in time. Monitoring techniques may vary depending on patient age, clinical condition, and clinical questions to be addressed. Specially designed instrumentation is required to perform monitoring; however, the role of the technologist is central in conducting a study with maximum clinical yield in the most efficient manner. The clinical neurophysiologist must recognize the specific objectives of each monitoring study and appreciate the age-dependent features of the EEG and the types of clinical paroxysmal events that may occur at different ages. Neonates, infants, and older children all demonstrate special features to be considered in the conduct and analysis of EEG-video monitoring. (J Child Neurol 1994;9(Suppl):S46-S56).
Long-Term Monitoring With Digital Technology for Epilepsy
Authors: Lesser Ronald P. , Kaplan Peter W.
Published: September 2009

The use of video-electroencephalography for the evaluation of children is reserved for inpatients with intractable "seizures." Prolonged video-electroencephalographic monitoring is used to ascertain whether the events are epileptic in nature, or to evaluate the medically intractable patient with epilepsy for surgical management of seizures. The increasing interest in the evaluation of patients with intractable epilepsy and recent technologic advances have led to a greater sophistication and versatility in patient evaluation. This paper reviews currently available technologies and newer digital acquisition and playback systems, and discusses ways of optimizing the evaluation of patients with intractable seizures. (J Child Neurol 1994;9(Suppl):S64-S70).