bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary Enzyme Evaluation of Nephrotoxicity in the Dog
Authors: Clemo Frances A. S.
Published: September 2009

Over the past 20 yr, increased attention has been directed toward evaluation of urinary enzymes as markers of nephrotoxicity in dogs because the technique is noninvasive and considered to be more sensitive than the more commonly used conventional tests of renal function. Urinary enzymes also have the potential of determining the primary site of renal damage because different sections of the nephron have a characteristic complement of enzymes. In dogs, increases in brush border enzymes, including γ-glutamyl transferase and alkaline phosphatase, have been associated with renal proximal tubular damage, while increases in N-acetyl-β-D-glucosaminidase have been observed in the early stage of renal papillary necrosis. Urinary enzymes have been particularly useful in detection of acute renal damage in dogs, specifically tubular damage; however, their corresponding value in providing information about chronic renal damage remains to be established. Although elevation of certain enzymes appears to be a relatively sensitive measure of nephrotoxicity in the dog, there is no current agreement regarding which enzyme assays are the most appropriate for routine use in safety assessment studies. In addition, elevation of a single enzyme is of limited diagnostic value in detection of renal damage because spurious increases in urinary enzymes sometimes occur in normal dogs. Therefore, if one wishes to conduct special assessment of nephrotoxicity in dogs, evaluation of several enzymes at multiple time points is needed to compensate for normal enzyme variation and to identify potential anatomic site selectivity of the toxin.
Chemically Induced Glomerular Injury: A Review of Basic Mechanisms and Specific Xenobiotics
Authors: Robertson John L.
Published: September 2009

Contact with many drugs and chemicals can produce glomerular injury. A common sign of such injury is proteinuria. Chemicals and drugs act through diverse mechanisms to produce injury, including direct damage to cellular and membranous glomerular components, as well as to renal vasculature. Several basic pathophysiologic mechanisms, including the “intact nephron hypothesis” and the “hyperfiltration hypothesis,” help to explain the mode of toxicity of many chemicals. Furthermore, they provide a means to understand the basis for renal damage and the progression of renal disease once injury has occurred.
Renal Effects of Fumonisin Mycotoxins in Animals
Authors: Bucci Thomas J. , Howard Paul C. , Tolleson William H. , Laborde James B. , Hansen Deborah K.
Published: September 2009

Fumonisins are mycotoxins produced worldwide by Fusarium fungi, principally F. moniliforme. The fungus is present in virtually all harvested com, but the toxins produced are variable. The toxins, especially fumonisin B1, cause mild to fatal diseases in animals, with peculiar species specificity for the dominant signs of toxicity. The mechanism of toxicity is poorly understood, but it appears to be related to interference with sphingolipid biosynthesis in multiple organs. Whereas brain, lung, and liver are well-known target organs, toxic effects on the kidney are also widespread and have only recently begun to be characterized. Increased urine volume and decreased osmolality are early changes associated with the toxin, as are increased excretions of high-and low-molecular-weight proteins. Enzymuria in vivo, reduced ion transport in vitro, and elevation of free sphinganine in renal tissue and in urine are present. An increase in serum creatinine and blood urea nitrogen and histopathologic change in renal tubules occur later and at higher doses. The morphologic change principally affects the junction of cortex and medulla and includes prominent apoptosis of epithelial cells of proximal convoluted tubules. Nephrotoxicity has been reported in several species, and in rats and rabbits, the kidney appears to be the most sensitive target organ.
Ocular Irritation: Microscopic Changes Occurring Over Time in the Rat with Surfactants of Known Irritancy
Authors: Maurer James K. , Parker Ronald D. , Carr Gregory J.
Published: September 2009

The pathology of surfactant-induced ocular irritation, especially in the context of accidental human exposures and animal tests used to assess a surfactant's potential ocular irritation, is not well understood. The purpose of this study was to characterize the microscopic changes in rats at 3 hr and on days 1, 2, 3, 4, 7, 14, and 35 following treatment with anionic, cationic, and nonionic surfactants of differing irritancy. The right eye of each rat was treated by placing 10 μl of a surfactant directly on the cornea. Untreated left eyes served as the controls. At each time point, eyes and eyelids were macroscopically examined and collected for microscopic examination. Macroscopically, the differing levels of irritation were characterized by differences in incidence and magnitude of scores, reflecting involvement of the cornea, conjunctiva, and iris, as well as by the incidence of neovascularization and time to recovery. Microscopically, differences in the area and depth of injury paralleled the differences seen grossly and the relative irritancies of the various surfactants. All surfactants affected the corneal and conjunctival epithelium. All surfactants, except the slightly irritating anionic surfactant, caused corneal stromal changes, with this involvement being proportional to their overall level of irritation. Corneal endothelial cell effects principally occurred with only the severely irritating cationic surfactant. Over time, responses to surfactants of differing irritancy were qualitatively and quantitatively different, and these differences correlated with the extent of initial injury. Qualitative differences in response included presence of keratocyte regeneration, corneal neovascularization, and conjunctivalization of the corneal epithelium with all of the surfactants except the slight irritant. Quantitative differences in response occurred in the extent of epithelial regeneration, edema, and inflammation for surfactants of slight to severe irritancy, and with neovascularization, keratocyte regeneration, and conjunctivalization for surfactants of mild to severe irritancy. These results suggest that by defining initial area and depth of injury associated with an ocular irritant, it may be possible to predict the subsequent response and final outcome. Such an approach would be applicable to the development of mechanistically based in vitro assays.
Retinal Degeneration in Rats Induced by CI-1010, a 2-Nitroimidazole Radiosensitizer
Authors: Breider Mike A. , Pilcher Gary D. , Graziano Michael J. , Gough Alex W.
Published: September 2009

The anti-cancer compound CI-1010, designated as (R)-α-([(2-bromoethyl)amino]methyl)-2-nitro-]H-imidazole-l-ethanol monohydrobromide, has a proposed dual mechanism of action due to alkylating and radiosensitizing activities. To assess potential toxicity, adult Wistar rats were treated with a single intravenous injection (0, 50, 100, 150, 225, or 350 mg/kg) and necropsied at 4 or 29 days following treatment. In a repeated dose experiment, rats were injected daily (0, 10, 40, or 80 mg/kg; 5 doses/wk) for 3 wk and necropsied at the end of week 3 or 7. CI-1010 induced retinal degeneration by 4 days after a single injection of ≥225 mg/kg or by 3 wk of repeated injections of ≥40 mg/kg. The locally extensive to diffuse retinal degeneration involved the photoreceptor and outer nuclear layer. The photoreceptor layer was vacuolated and compressed corresponding to ultrastructural evidence of inner segment swelling and outer segment fragmentation. The outer nuclear layer was thinned due to loss of nuclei and contained numerous pyknotic or karyorrhectic nuclei. These nuclear changes were morphologically consistent with apoptosis and many outer nuclear layer nuclei labeled with in situ TdT-mediated dUTP-digoxigenin nick end labeling (Apoptag®). The retinal degeneration was nonreversible, evidenced by increased lesion severity and incidence after CI-1010 was withdrawn for either 25 or 28 days.
Effects of Cholestyramine and Diet on Small Intestinal Histomorphometry in Rats
Authors: Burkhardt John E. , Biehl Michael L. , Kowsz Kim P. , Kadyszewski Edmund , Fisher Douglas O. , Ochoa Ricardo
Published: September 2009

Reports on the effects of cholestyramine on small intestinal structure of rats have produced contradictory data about changes in mucosal histomorphometry, perhaps due to interacting effects of dietary composition. In order to identify effects of cholestyramine and diet on structure of the small intestines, 40 male rats were divided into 4 groups of 10 and fed 1 of each of the following diets for 1 month: standard diet, purified fiber-free diet, standard diet + 2% cholestyramine, or purified fiber-free diet + 2% cholestyramine. Serum concentrations of cholesterol and triglycerides were moderately increased in rats fed the purified fiber-free diet versus the standard diet. Neither total length nor weight of small intestine were affected by either diet or cholestyramine. Mucosal weight was affected by interactions between cholestyramine and diet, indicating that outcome depended upon modulating effects of both variables. Significant interactions were similarly detected among the variables of anatomic site, diet, and cholestyramine for many histomorphometric parameters of intestinal mucosa. Cholestyramine reduced total mucosal thickness in both jejunum and ileum and reduced villus height and villus: crypt ratio in the ileum.
A Communicating Intestinal Duplication in a Sprague-Dawley Rat
Authors: Elangbam Chandikumar S. , Clevidence Kerin J. , Jackson Carney B. , Holson Joseph F.
Published: September 2009

Duplications of the gastrointestinal tract arc exceedingly rare in laboratory animals. We report a case of a communicating intestinal duplication in a 17-wk-old Sprague-Dawley (SD) rat. The duplication was present in the mesenteric border of the ileum, and both proximal and distal ends were communicated with the lumen of ileum. Histologically, the duplicated portion had a thick muscle wall and a mucosa similar to that of the small intestine. This is the first reported case of intestinal duplication in an SD rat.
Case Report: Pineocytoma in a Male Fischer 344 Rat
Authors: Heath James E. , Winokur Thomas S.
Published: September 2009

An enlarged pineal gland was observed in a 112-wk-old male Fischer 344 rat from the low-dose treatment group in a 2-yr bioassay. Formalin-fixed, paraffin-embedded sections of the gland were stained with hematoxylin and eosin along with the immunohistochcmical biomarkers synaptophysin, placental alkaline phosphatase, glial fibrillary acidic protein, and vimentin. Based on its histomorphological features and on positive staining with synaptophysin, the lesion was diagnosed as a malignant pineal gland parenchymal cell tumor or pineocytoma of incidental origin.
Cytokeratin Expression Patterns in the Rat Respiratory Tract as Markers of Epithelial Differentiation in Inhalation Toxicology. II. Changes in Cytokeratin Expression Patterns Following 8-Day Exposure to Room-Aged Cigarette Sidestream Smoke
Authors: Schlage Walter K. , Bülles Heidi , Friedrichs Detlef , Kuhn Maria , Teredesai Ashok , Terpstra Pieter M.
Published: September 2009

The expression of specific cytokeratin (CK) polypeptide patterns is a sensitive marker of the cytoskeletal differentiation of epithelial cells. We developed an immunohistochemical method to assess CK expression patterns in the rat respiratory tract using serial paraffin-embedded sections from the nasal cavity, trachea, and lung. In the present study, this method was used to detect exposure-related differences in CK expression patterns in adult Wistar rats following inhalation of room-aged sidestream smoke (11 mg total particulate matter/m3 air, 8 days, 12 hr/day, whole body). In the anterior nasal cavity level 1 (NL1), changes in CK expression patterns were observed in the respiratory epithelium of the lateral wall and the maxilloturbinate (CK14, CK15, and CK18) and in the squamous epithelium of the ventral meatus (CK13). At nasal'cavity level 2 (NL2), immediately behind NL1, changes were observed in the olfactory epithelium (CK13, CK14, and CK18) and in the respiratory epithelium of the septum (CK7 and CK19), the lateral wall (CK7 and CK13), and the lateral aspect of the maxilloturbinate (CK14). Changes were also observed in the submucosal glands, nasolacrimal duct, and vomeronasal organ. In the trachea only CK7 expression changed, and in the lung expression of CK7 (bronchioli) and CK8 (bronchus) changed; the expression of other CK polypeptides did not change. The observed changes in CK expression at NL1 correlated with the histomorphological changes, whereas CK expression changes were also seen in the olfactory and respiratory epithelia at NL2 and in the trachea and lung, where no histomorphological changes were seen. These findings indicate that changes in CK expression in respiratory tract epithelial cells are a sensitive marker for cellular stress response.
Exploration of the Transformation Potential of a Unique Male Rat Protein Alpha2u-Globulin Using Hamster Embryonic Cells
Authors: Oshiro Yuki , Balwierz Patrick S. , Eurell Thomas E. , Morris Dale L. , Alden Carl L.
Published: September 2009

Several environmentally and socially important chemicals such as d-limonene and unleaded gasoline have been demonstrated to induce alphas-globulin (a2u) nephropathy in male rats. Substantial progress has been made in characterizing the biological effects of these chemicals on the kidney and in further defining prerequisite events in the pathogenesis of this syndrome. The ot2u increase in the kidney is hypothesized to be the proximal event in the toxicologic and tumorigenic sequelae associated with administration of these xenobiolics over the male rat's lifetime rather than a direct effect of the administered chemical. The administered chemical appears to simply mediate the increase in ot2u concentration in the kidney. To further investigate the properties of a2u, this protein was tested in the pH 6.7 Syrian hamster embryo (SHE) cell transformation assay. The a2u caused morphological transformation in these cells, whereas another protein, bovine serum albumin, did not induce transformation at equimolar concentrations, suggesting a protein-specific phenomenon. Neither rf-limonene nor trimethylpentane (a causarcomponent in unleaded gasoline) induced SHE cell transformation. These results support the hypothesis that a2u increase in proximal convoluted tubules may directly cause renal tumorigenesis in male rats. The SHE cell transformation assay may be a useful tool for mechanistic studies of this syndrome.
Spontaneous Proliferative Lesions in the Nasopharyngeal Meatus of F344 Rats
Authors: Hayashi Shim-Mo , Mori Ikuo , Nonoyama Takashi
Published: September 2009

Spontaneous proliferative lesions in the nasopharyngeal meatus were identified as the cause of death in 12 of 1,600 male and 5 of 1,600 female Fischer 344 (F344) rats used in 2-yr carcinogenicity studies; none of the lesions were considered treatment related. All the rats showed dyspnea, abdominal distension, and clinical deterioration. Gross features were characterized by simultaneous occurrence of conspicuous gaseous distension of the intestinal tract, especially in the ileum and cecum, and focal nodular lesions in the nasopharyngeal meatus. Histopathologically, the nasopharyngeal meatus was partially obstructed by the following proliferative lesions: 3 areas of hyperplasia of the ectopic sebaceous glands in the soft and hard palate, 4 areas of squamous metaplasia (SM) with massive hyperkeratosis, 5 squamous cell papillomas (SCPs), and 5 squamous cell carcinomas (SCCs). No pathological changes were found in the distended portion of the intestinal tract. Formalin-fixed, paraffin-embedded samples of the proliferative lesions from the nasopharyngeal meatus were examined for the presence of mutations in the c-H-ras and c-K-ras genes. In vitro amplification of DNA using a polymerase chain reaction was combined with a nonisotopic method for selective oligonucleotide hybridization. Two of the 4 SM lesions, 3 of the 5 SCPs, and 5 of the 5 SCCs contained 1-3 point mutations in the c-H-ras and/or c-K-ras gene. Immunohistochem-ically, overexpression of p53 protein was found in 1 area of SM with a dysplastic lesion and 2 SCCs. These findings indicate that detailed examination of the upper respiratory system, including the nasopharyngeal meatus, may be particularly helpful for identifying primary occult lesions in F344 rats that show only gut distension at necropsy in long-term toxicity studies. In addition, mutations of the ras genes may be an important step in the early stages of carcinogenesis in the rat nasopharyngeal meatus, whereas p53 mutations could occur relatively late.
The Carcinogenic Risk of Ethene (Ethylene)
Authors: Bolt Hermann M.
Published: September 2009

On occasion of the 25th year of publication of Toxicologic Pathology, the Editor has asked for a report about recent progress in the area addressed by an article entitled “Olefinic Hydrocarbons: A First Risk Estimate,” one of the top 10 most frequently cited papers of the journal (3). Because general issues of risk assessment have very recently been addressed in this journal (6), I will focus on new specific aspects of ethene carcinogenicity.
Dermal Carcinogenicity in Transgenic Mice: Relative Responsiveness of Male and Female Hemizygous and Homozygous Tg.AC Mice to 12-O-Tetradecanoylphorbol 13-Acetate (TPA) and Benzene
Authors: Blanchard K. T. , Ball D. J. , Holden H. E. , Furst S. M. , Stoltz J. H. , Stoll R. E.
Published: September 2009

Assessment of the carcinogenic potential of chemical agents continues to rely primarily upon the chronic rodent bioassay, a resource-intensive exercise. Recent advances in transgenic technology offer a potential resource conserving approach to carcinogen detection. Incorporation of oncogenes with known roles in the development of neoplasms into the genomes of laboratory rodents may provide new models with the potential of quickly and accurately separating carcinogenic from noncarcinogenic chemicals. The insertion of the v-Ha- ras oncogene into the genome of FVB/N mice imparts the qualities of genetically initiated skin in the transgenic mouse line designated as Tg.AC. The skin of either hemizygous (animals carrying the transgene on 1 allele) or homozygous (transgene copies on both alleles) Tg.AC mice promptly responds to the application of nongenotoxic carcinogens, such as the classical tumor promoting phorbol esters, with the development of squamous papillomas. Tumor production generally begins after 8-10 applications of 2.5 μg/mouse (3 times/wk) of 12- O-tetradecanoylphorbol 13-acetate (TPA). Maximal tumor response is usually in evidence within 20 wk. If this transgenic mouse line is to be useful in the identification of carcinogenic chemicals, experimental protocols must be systematically optimized. Experiments were conducted to compare the relative responsiveness of male and female hemizygous and homozygous Tg.AC mice to the dermal application of TPA and the known human leukemogen, benzene. Results revealed shipment-related variabilities in the relative responsiveness of hemizygous male and female mice to the application of the proliferative agent. Homozygous mice of both sexes were more reliable and uniform in responsiveness to both TPA and benzene. Therefore, our standard protocol for the conduct of bioassays with the Tg.AC mouse line specifies the use of homozygous males and/or females.
Point Mutations of the c-H-ras Gene in Spontaneous Liver Tumors of Transgenic Mice Carrying the Human c-H-ras Gene
Authors: Hayashi Shim-mo , Mori Ikuo , Nonoyama Takashi , Mitsumori Kunitoshi
Published: September 2009

Spontaneous proliferative liver lesions were found in 15 (13 males and 2 females) of 244 (122 of each sex) transgenic (Tg) mice carrying the human prototype c-H- ras gene (rasH2). The liver lesions included 3 foci of cellular alteration, 1 hepatocellular adenoma, 5 hepatocellular carcinomas, and 4 hepatic hemangiosarcomas in the males and 1 focus of cellular alteration and 1 hepatocellular carcinoma in the females. The mutation patterns of the human and endogenous mouse c-H-ras codon 61 in these proliferative liver lesions were analyzed by DNA amplification using polymerase chain reaction, single-strand conformation polymorphism (PCR-SSCP), and oligonucleotide dot blot hybridization. The hepatocellular carcinomas in 4 males and 1 female contained a point mutation in the mouse c-H- ras gene: 3, 1, and 1 carcinomas had a CAA to AAA transversion at the first base of codon 61, a CAA to CTA transversion, and a CAA to CGA transition at the second base of codon 61, respectively. No point mutations in the human c-H- ras transgene were detected in any hepatocellular carcinoma. All 4 hepatic hemangiosarcomas had a CAG to CTG transversion at codon 61 of the human c-H- ras gene, but no point mutations were detected in codon 61 of the mouse c-H- ras gene. No mutations in human or mouse c-H- ras codon 61 were detected in altered cell foci or hepatocellular adenoma. These results indicate that spontaneous liver tumors in rasH2 Tg mice contain different mutation patterns depending on the histologic type or cell origin of the tumors (i.e., hepatocellular carcinomas or hepatic hemangiosarcomas). The absence of similar mutations in foci of cellular alteration and the hepatocellular adenoma suggests that the occurrence of codon 61 point mutations is a late event in the progression of hepatocellular neoplasia in rasH2 Tg mice.
Twilight and Photoperiod Affect Behavioral Entrainment in the House Mouse (Mus musculus)
Authors: Comas M. , Hut R.A.
Published: September 2009

The effect of twilight transitions on entrainment of C57BL/6JOlaHsd mice ( Mus musculus) was studied using light-dark cycles of different photoperiods (6, 12, and 18 h) and twilight transitions of different durations (0, 1, and 2 h). Phase angle differences of the onset, center of gravity, and offset of activity, activity duration (α), as well as free-running period (τ) in continuous darkness were analyzed. The main finding was that for all conditions the onset of activity was close to dusk or lights-off except for the short photoperiod with 2 h of twilight where activity onset was on average 5.3 (SEM 1.07) h after lights-off. This finding contrasts with the results of Boulos and Macchi for Syrian hamsters where a 5.9-h earlier activity onset was observed when similar photoperiod and twilight conditions are compared with a rectangular LD cycle. The authors suggest the opposite effects of 2 h of twilight in the 2 species may be related to their different free-running periods under DD conditions following entrainment to short photoperiod with 2-h twilight conditions. Since the authors observed larger variation in phase angle of entrainment in longer twilight conditions, twilight does not necessarily form a stronger zeitgeber.
Topical Review: Photosensitivity and Epilepsy
Authors: Verrotti Alberto , Trotta Daniela , Salladini Carmela , di Corcia Giovanna , Chiarelli Francesco
Published: September 2009

Photosensitive epilepsy is a well-known condition characterized by seizures in patients who show photoparoxysmal responses on electroencephalography (EEG) elicited by intermittent photic stimulation. Photoparoxysmal responses can be defined as epileptiform EEG responses to intermittent photic stimulation or to other visual stimuli of everyday life and are frequently found in nonepileptic children. The modern technologic environment has led to a dramatic increase in exposure to potential trigger stimuli; nowadays, television and video games are among the most common triggers in daily life. There is ample evidence for genetic transmission of photoparoxysmal responses; systematic family studies have provided data for an autosomal dominant mode of inheritance with age-dependent penetrance for photosensitivity. The age of maximum penetrance is between 5 and 15 years. The prognosis for control of seizures induced by visual stimulation is generally very good. The large majority of patients do not need anticonvulsant therapy, but, when needed, the drug of choice is valproate. Stimulus avoidance and stimulus modification can be an effective treatment in some patients and can sometimes be combined with antiepileptic drug treatment. (J Child Neurol 2004;19:571-578).
Effect of Topiramate on Seizures and Respiratory Dysrhythmia in Rett Syndrome
Authors: Goyal Monisha , O'Riordan Mary Ann , Wiznitzer Max
Published: September 2009

Rett syndrome, a neurodevelopmental disorder, manifests in the first few years of life with developmental arrest, stereotyped behaviors, and respiratory abnormalities. Seizures occur in 70 to 80% of patients. Clinical drug trials have not demonstrated the superiority of any specific antiepilepsy drug. We report our experience with topiramate in eight patients with Rett syndrome. Topiramate was initiated as monotherapy in two patients and as adjunctive therapy in six patients. Seven patients had improved seizure control. Respiratory abnormalities improved by 50 to 75% in two patients and by 20 to 50% in two others. In our cohort, seven of eight patients showed improvement in seizure control and/or respiratory abnormalities on topiramate. Topiramate was well tolerated. The effect of topiramate, a broad-spectrum drug, could be due to its γ-aminobutyric acid (GABA)ergic and glutaminergic effects, both systems thought to be disordered in Rett syndrome. (J Child Neurol 2004;19:588-591).
Babkin Reflex and Other Motor Responses to Appendicular Compression Stimulus of the Newborn
Authors: Pedroso Fleming S. , Rotta Newra T.
Published: September 2009

This cross-sectional study evaluated 106 normal newborns with the aim of determining the prevalence of mouth opening, neck rotation, and limb flexion or extension responses triggered by pressure stimuli applied to the hand, forearm, arm, foot, leg, or thigh. Mouth opening, neck rotation, and lower limb flexion responses were found in the three segments of the lower limb, with mouth opening obtained in 100% of newborns, neck rotation in 88.7%, and flexion of lower limbs in 67.9% with stimuli to the hand. Upper limb extension response was obtained by stimulation of the three segments of the lower limb and was found in 86.7% of the infants with stimuli to the foot. The limb segment more effective in eliciting a response was the hand, followed by the foot, forearm, leg, arm, and thigh. When pressure was applied to the three upper segments, the reflex responses of the head, neck, and limb flexion predominated, whereas when pressure was applied to the three lower segments, extension responses of the upper limbs predominated. (J Child Neurol 2004;19:592-596).
Epilepsy and Electroencephalographic Findings in Pericentric Inversion of Chromosome 12
Authors: Grosso Salvatore , Pucci Lucia , Farnetani MariAngela , Di Bartolo Rosanna Maria , Galimberti Daniela , Mostardini Rosa , Anichini Cecilia , Balestri Martina , Morgese Guido , Balestri Paolo
Published: September 2009

Epilepsy, together with mental retardation, represents a common manifestation of chromosomal aberrations. Specific electroencephalographic (EEG) and epileptic patterns have been described in several chromosomal disorders, such as Angelman's syndrome, Miller-Dieker syndrome, Wolf-Hirschhorn syndrome, and ring 20 syndrome. A peculiar electroclinical pattern has also been identified in trisomy 12p syndrome. We report three patients with a pericentric inversion of chromosome 12, with breakpoints localized to p11-q13 and affected by epilepsy or EEG anomalies. Two suffered from epilepsy, which, in the clinical course, was mainly characterized by complex partial seizures with a semiology related to the temporal lobe. In one patient, myoclonic absences, head drop, and massive jerky attacks were also present. In both patients, generalized 3 Hz bursts were registered, together with multifocal and focal paroxysmal activity, which were most prominent in the temporoparietal and temporal areas, respectively. In the other patient, who had no epilepsy, EEG showed bioccipital paroxysmal activity. In all patients, the clinical picture was characterized by the presence of moderate mental retardation and behavioral disorders. The incidence of epilepsy or EEG anomalies among patients with a pericentric inversion of chromosome 12 remains to be ascertained. However, the present study confirms that chromosome 12 anomalies can be associated with epilepsy. Although myoclonic absence-like episodes can occasionally be part of the epileptic phenotype, the electroclinical pattern in pericentric inversion of chromosome 12 seems to be more polymorphic when compared with that observed in trisomy 12p syndrome. (J Child Neurol 2004;19:604-608).
Spectrum of Anticonvulsant Hypersensitivity Syndrome: Controversy of Treatment
Authors: Lee Wing-Cheong , Leung Joy Lok-Sum , Fung Cheuk-Wing , Chung Brian Hon-Yin , Wong Virginia
Published: September 2009

An 18-month-old girl presented with a maculopapular rash 10 days after carbamazepine treatment. Initially, she was suspected of having a viral rash owing to associated fever. She deteriorated rapidly and was suspected of having anticonvulsant hypersensitivity syndrome or Stevens-Johnson syndrome. She developed features compatible with toxic epidermal necrolysis rapidly over 24 to 36 hours. Carbamazepine was then stopped. She responded immediately to high-dose intravenous pulse methylprednisone treatment. We discuss the controversy in the management of anticonvulsant hypersensitivity syndrome, toxic epidermal necrolysis, or Stevens-Johnson syndrome with high-dose corticosteroids, intravenous immunoglobulin, and antibiotics. (J Child Neurol 2004; 19:619-623).
Intravenous Immunoglobulin and Interferon: Successful Treatment of Optic Neuritis in Pediatric Multiple Sclerosis
Authors: Spalice Alberto , Properzi Enrico , Lo Faro Valentina , Acampora Barbara , Iannetti Paola
Published: September 2009

Optic neuritis is a common clinical condition that causes loss of vision. It can be clinically isolated or can occur as one of the manifestations of multiple sclerosis. Multiple sclerosis is a severe disabling demyelinating disease of the central nervous system, which is rare among children. The treatment of optic neuritis has been investigated in several trials, the results of which have shown that corticosteroids speed up the recovery of vision without affecting the final visual outcome. Treatment of neurologic disorders with intravenous immunoglobulin is an increasing feature of our practice for an expanding range of indications, including multiple sclerosis. Owing to its anti-inflammatory properties, intravenous immunoglobulin can be beneficial in the treatment of acute relapses and in the prevention of new relapses of multiple sclerosis. To our knowledge, there is only one experience of treatment of optic neuritis with intravenous immunoglobulin in multiple sclerosis, even if therapeutic trials are used in the therapy of multiple sclerosis. We report on a girl with optic neuritis and multiple sclerosis in whom treatment with intravenous immunoglobulin at first alone and subsequently associated with interferon achieved great improvement in visual acuity. (J Child Neurol 2004;19:623-626).
Pseudotumor Cerebri Secondary to Subacute Sclerosing Panencephalitis
Authors: Tan Hüseyin , Orhan Asuman , Büyükavcl Mustafa , Koçer Ibrahim
Published: September 2009

Pseudotumor cerebri is characterized by signs of raised intracranial pressure occurring in the absence of obvious brain pathology. We present an 8-year-old boy with pseudotumor cerebri secondary to subacute sclerosing panencephalitis. The reported patient suggests a possible association between subacute sclerosing panencephalitis and pseudotumor cerebri and that subacute sclerosing panencephalitis should be added to the list of disorders known to be associated with pseudotumor cerebri. Patients with subacute sclerosing panencephalitis might benefit from treatment aimed at increased intracranial pressure. (J Child Neurol 2004;19:627-629).
Multiple Sclerosis Beginning in Infancy
Authors: Shaw Cheng-Mei , Alvord Ellsworth C.
Published: September 2009

The clinical and autopsy findings on a 6-year-old child presenting with 11 episodes of relapsing neurological symptoms since age 10 months are reported. The brain showed multiple and irregular demyelinative lesions in the cerebral and cerebellar white matter as well as in the tegmentum and base of the brain stem. This case reconfirms the existence of typical multiple sclerosis (MS) in childhood, beginning even in infancy. In addition, elevated Epstein-Barr virus antibody titers during the clinical course of this patient raise an interesting but still speculative etiological possibility for MS. ( J Child Neurol 1987;2:252-256).
High Prevalence of Infantile Autism in Kurume City, Japan
Authors: Matsuishi Toyojiro , Shiotsuki Yuko , Yoshimura Kohko , Shoji Haruko , Imuta Fusae , Yamashita Fumio
Published: September 2009

We surveyed the prevalence of infantile autism in Kurume City. Children born between 1971 and 1979 ranged in age from 4 to 12 years at the time of the survey. We found 51 cases of infantile autism. In each year group, we determined the ratio of the number of cases of infantile autism to the total number of children. The prevalence ranged from 10.4/10,000 to 17.5/10,000, with a mean prevalence of 15.5/10,000. The sex distribution was 42 males (prevalence of 24.8/10,000) and nine females (prevalence of 5.7/10,000). The results showed a significant sex difference, with a male: female ratio of 4:1 ( p < 0.0005). High prevalence rates of infantile autism in Kurume City were confirmed. ( J Child Neurol 1987;2;268-271).
Encephalomyelitis Associated With Leukemia in a Child
Authors: Gregorios Jocelyn B. , Roldan Eneida , Davis Joanna , Curless Richard
Published: September 2009

A case of an encephalomyelitis in a child with acute lymphoblastic leukemia is reported. The patient was a 5-year-old boy who developed seizures, progressive confusion, and coma after radiation and intrathecal methotrexate therapy. Computed tomography (CT) of the brain showed bilateral hypodensities in the posterior parietal and temporal regions. At autopsy, perivascular inflammation, microglial nodules without intranuclear viral inclusions, and bilateral necrosis of the temporoparietal and hippocampal regions were seen in the brain and spinal cord. Paraneoplastic encephalomyelitis is generally recognized in adult patients with underlying malignancy but, to our knowledge, has not been reported in children with leukemia. This report should alert the clinicians to an entity that must be included in the differential diagnosis of leukemic children with progressive neurologic disorder. ( J Child Neurol 1987;2:293-297).
Zebra Body Myopathy: A Second Case of Ultrastructurally Distinct Congenital Myopathy
Authors: Reyes Marc G. , Goldbarg Hilda , Fresco Kimi , Bouffard Alan
Published: September 2009

Biopsy of the deltoid muscle of a 4-day-old baby boy with congenital hypotonia and weakness showed zebra bodies and other myopathic changes. Our patient and an other patient reported in the literature establish zebra body myopathy as an ultrastructurally distinct benign congenital myopathy. (J Child Neurol 1987;2:307-310).
Congenital Myasthenic Syndromes
Authors: Engel Andrew G.
Published: September 2009

By the mid-1970s the autoimmune origin of myasthenia gravis had been well established. Once this feat had been accomplished, it also became apparent that myasthenic disorders occurring in a genetic or congenital setting had a different etiology. As a result, a number of distinct myasthenic syndromes have been recognized and investigated by electrophysiological and ultrastructural methods. The newly recognized disorders are conditioned by divergent causes, such as a failure of acetylcholine resynthesis or packaging, absence of acetylcholinesterase from the neuromuscular junction, abnormal gating properties of the acetylcholine receptor-associated ion channel, or an abnormality in the regulation of the density of acetylcholine receptor molecules in the postsynaptic membrane. These genetic defects either impair neuromuscular transmission directly or result in secondary derangements that eventually compromise the safety margin of neuromuscular transmission. ( J Child Neurol 1988;3:233-246).
Joubert Syndrome: Early Diagnosis by Recognition of the Behavioral Phenotype and Confirmation by Cranial Sonography
Authors: Edwards Buford O. , Fischer Asma Q. , Flannery David B.
Published: September 2009

Our experience with two children with Joubert syndrome demonstrates how the diagnosis, if suspected by recognition of the behavioral phenotype, can rapidly be made by employing cranial sonography. This technique also may afford prenatal diagnosis of the syndrome in future siblings of confirmed cases. We have produced an educational videotape demonstrating the dynamic behavior of these patients. It is our hope that increased familiarity with the behavior phenotype through this report and through distribution of the videotape will lead to early and accurate diagnosis of further cases of this syndrome. ( J Child Neurol 1988;3:247-249).
Abnormal 13C-Fatty Acid Breath Tests in Patients Treated With Valproic Acid
Authors: Arimoto Kiyoshi , Sakuragawa Norio , Suehiro Makiko , Watanabe Hiroyuki
Published: September 2009

Breath tests using fatty acids labeled with a stable isotope (carbon 13) were carried out on epileptic patients treated with valproic acid in order to detect abnormal fatty acid metabolism. The patients were given 13C-octanoic acid or 13C-palmitic acid orally, and expired air was collected at appropriate intervals for the analysis of 13CO2 content by a mass spectrometer. Eight patients were tested in the palmitic acid breath test and nine patients in the octanoic acid breath test. Controls for these tests were patients treated with antiepileptic drugs other than valproic acid and unmedicated cerebral palsy patients. In the valproic acid-treated group, 13C recovery was reduced by 56% in seven hours on the 13C-palmitic acid breath test, while the octanoic acid breath test showed a 52% reduction in one hour. This suppression of fatty acid oxidation was significantly correlated with dose of valproic acid in both tests. No influence of other drugs was detected, and the effect of administered carnitine was not conclusive. This study demonstrates the usefulness of 13C-labeled fatty acid breath tests in clinical practice. ( J Child Neurol 1988;3:250-257).
Rett Syndrome: Review and Discussion of Current Diagnostic Criteria
Authors: Burd Larry , Gascon Generoso G.
Published: September 2009

Rett syndrome is a mental retardation syndrome that occurs only in females and consists of normal pre-, peri-, and neonatal growth and development. It is followed by rapid neurobehavioral deterioration in late infancy or early childhood, a developmental arrest, plateauing, and then either a course of retarded development or continued deterioration. The period of rapid neuro-behavioral deterioration manifests as a partial autistic syndrome, with loss of production and comprehension of language, hyperactivity, hyperventilation, hand-wringing, and ataxic gait. Current diagnostic criteria are discussed and suggestions for further research are presented. ( J Child Neurol 1988;3:263-268).
Review Article: Sleep, Epilepsy, and the EEG in Infancy and Childhood
Authors: Donat Jane F. , Wright Francis S.
Published: September 2009

Each of the major epileptic syndromes that occur in infants and children demonstrates relationships to sleep and wakefulness that are particular to that syndrome. These relationships include activation or suppression of clinical seizures during certain portions of the sleep-wake cycle, differences in symptomatology of the seizures or in seizure type, alterations in distribution or morphology of epileptiform waveforms, and changes in duration and composition of sleep stages. Knowledge of the interactions between sleep and seizures helps to increase understanding of the physiological mechanisms underlying epilepsy, as well as to improve clinical diagnosis. ( J Child Neurol 1989;4:84-94).
Hydranencephaly and Maximal Hydrocephalus: Usefulness of Electrophysiological Studies for Their Differentiation
Authors: linuma Kazuie , Handa Ikuko , Kojima Akira , Hayamizu Shunzo , Karahashi Minoru
Published: September 2009

The EEG was evaluated in three cases of hydranencephaly and two cases of maximal hydrocephalus, and the visual evoked potential was studied in one case each of hydranencephaly and maximal hydrocephalus. The EEG tracing of hydranencephaly typically showed a flat pattern in most bipolar derivations because of the differential amplification of the same activity from remote generators. However, the EEG of maximal hydrocephalus did not demonstrate a flat pattern in bipolar as well as referential derivation, and the activities were different from various electrodes in referential derivation. The visual evoked potential of maximal hydrocephalus showed a normal pattern, while that of hydranencephaly showed no response. Electrophysiological examinations (such as EEG and visual evoked potential) are useful for differentiation of hydranencephaly and maximal hydrocephalus in cases whose computed tomographic scans do not provide clear differentiation. ( J Child Neurol 1989;4:114-117).
Congenital Choroid Plexus Papilloma of the Fourth Ventricle
Authors: Lippa C. , Abroms I.F. , Davidson R. , DeGirolami U.
Published: September 2009

A newborn infant with marked hydrocephalus had a large papilloma of the choroid plexus originating in the fourth ventricle and infiltrating the brain stem. The computed tomographic (CT) scan appearance was distinctive, showing vascularity and marked enhancement with contrast medium. Histological confirmation was made from several surgical sites. Total removal of the tumor was not possible. Review of congenital choroid plexus brain tumors reveals the location of this child's tumor in the fourth ventricle to be uncommon. ( J Child Neurol 1989;4:127-130).
Photo-Evoked Eyelid Microvibration in Neonates With Hyperosmolality
Authors: Yasuhara Akihiro , Hori Aiko , Sugimoto Tateo , Kobayashi Yohnosuke
Published: September 2009

We studied neonates with hyperosmolar syndrome using photo-evoked eyelid microvibration, a blink reflex elicited by photic stimuli. Patients with hyperosmolality showed disturbance of consciousness, convulsive seizures, hyperexcitability, and tachypnea. The latency of photo-evoked eyelid microvibration tended to be prolonged with an elevation of the plasma osmolality. Photo-evoked eyelid microvibration is believed to be a suitable method for monitoring brain disturbance due to hyperosmolality. ( J Child Neurol 1990;5:191-194).
Rhythmic Coma in Children
Authors: Horton E.J. , Goldie William D. , Baram Tallie Z.
Published: September 2009

We describe a syndrome of rhythmic coma in children that consists of an invariant, nonreactive, diffuse cortical activity of a specific frequency, such as alpha, beta, spindle, or theta, recorded from a comatose child.We report 11 cases of children who were found to be in rhythmic coma during their acute illnesses. Their ages ranged from 2 to 15 years, and their diagnoses included encephalitis, head trauma, seizures, near drowning, brain tumors, stroke, and metabolic derangements. The specific frequency of the electroencephalographic pattern, ie, alpha, beta, spindle, or theta, did not influence the outcome. The clinical outcome appeared to depend on the primary disease process rather than the electroencephalographic finding. The prognosis of alpha-frequency rhythmic coma as well as of rhythmic coma in general was better in children than in adults. The pathophysiology in children may be similar, ie, the interruption of reticulothalamocortical pathways by metabolic or structural abnormalities, but the expression of this deafferentation may be more varied in the developing brain. Thus, we propose the term rhythmic coma as a unified concept for alpha, beta, spindle, and theta coma in children. (J Child Neurol 1990;5;242-247).
Comparative Neuroimaging With Pathologic Correlates in Alexander's Disease
Authors: Hess David C. , Fischer Asma Q. , Yaghmai Farivar , Figueroa Ramon , Akamatsu Yuki
Published: September 2009

We describe a case of pathologically confirmed Alexander's disease in which serial cranial ultrasound studies demonstrated unique findings of enlarging subependymal cysts with evolving periventricular hyperechogenicity. Computed tomographic scan of the head showed low attenuation of the periventricular white matter and centrum semiovale. Magnetic resonance imaging (MRI) demonstrated diffuse, confluent high signal predominantly in frontal white matter. These imaging modalities, particularly cranial ultrasound and MRI, may be useful tools in the diagnostic evaluation of children with degenerative neurologic disease, megalencephaly, and suspected Alexander's disease. ( J Child Neurol 1990;5:248-252).
Pharmacology and Clinical Pharmacology of Vigabatrin
Authors: Richens Alan
Published: September 2009

Vigabatrin is an enzyme-activated, irreversible inhibitor of γ-aminobutyric acid (GABA) aminotransferase, which causes a marked increase in cerebral GABA concentration and a resulting anticonvulsant action. Recovery from its effects requires the synthesis of new enzyme, and this may take several days following a single dose. The pharmacokinetics of vigabatrin are not a good guide to its duration of action. It is cleared rapidly by renal elimination (giving a plasma half-life of approximately 7 to 9 hours), and therefore the effect of the drug long outlasts its presence in the body. Plasma drug level monitoring is therefore of little value in regulating vigabatrin therapy. The drug is not bound to plasma proteins. Interactions with other drugs would not be expected because of its predominant renal elimination and its lack of protein binding. Also, vigabatrin does not induce liver enzymes, as do many of the standard antiepileptic drugs. In several trials, however, a small but significant reduction in phenytoin levels has been seen following the addition of vigabatrin to the antiepileptic medication. The mechanism for this reduction in phenytoin levels has not yet been elucidated, though it does not appear to be of clinical significance. (J Child Neurol 1991;6(Suppl):2S7-2S10).
Neuropathologic Findings in Patients Receiving Long-Term Vigabatrin Therapy for Chronic Intractable Epilepsy
Authors: Cannon D.J. , Butler W.H. , Mumford J.P. , Lewis P.J.
Published: September 2009

Vigabatrin is a new antiepileptic drug that acts by the irreversible inhibition of γ-aminobutyric acid (GABA) aminotransferase. During animal safety testing, vigabatrin was found to cause reversible intramyelinic edema in the brains of rodents and dogs but not in primates. In humans, the drug is well tolerated, and extensive clinical, neurophysiologic, neurochemical, and psychometric testing has failed to demonstrate any evidence of neurotoxicity. Neuropathologic examination has now been carried out on 62 patients with refractory epilepsy, who were on vigabatrin therapy either prior to undergoing neurosurgery for their epilepsy or before death. A further ten similar cases have been included in the study from age-matched patients with refractory epilepsy who had not been treated with vigabatrin prior to surgery or death. None of the neuropathologic changes seen in the preclinical animal studies have been observed in the human cases. In no case was there considered to be any evidence of myelin microvacuolation or myelin sheath splitting that could be attributed to vigabatrin treatment. Demyelination has never been observed in either the animal or human material. These findings support the clinical tolerability seen in long-term treatment. (J Child Neurol 1991;6(Suppl):2517-2524).