bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous and Chemically Induced Proliferative Lesions in Tg.AC Transgenic and p53-Heterozygous Mice
Authors: Mahler Joel F. , Flagler Norris D. , Malarkey David E. , Mann Peter C. , Haseman Joseph K. , Eastin William
Published: September 2009

Recently, the use of selected genetically altered mouse models in the detection of carcinogens after short-term chemical exposures has been evaluated. Studies of several chemicals conducted by the National Toxicology Program in Tg.AC transgenic and heterozygous p53-deficient mice have been completed recently and represent a major contribution to this effort, as well as the largest accumulation to date of toxicologic pathology data in these 2 lines of mice. The purpose of this report is to describe the proliferative target organ effects observed in this set of studies, as well as to present the tumor profile in the control groups of this data set. These findings provide a comprehensive toxicologic assessment of these 2 genetically altered mouse strains, which are of emerging importance in toxicologic pathology.
Morphological Characterization of Spindle Cell Tumors Induced in Transgenic Tg.AC Mouse Skin
Authors: Asano Satoshi , Trempus Carol S. , Spalding Judson W. , Tennant Raymond W. , Battalora Michael StJ.
Published: September 2009

Transgenic Tg.AC mice carry a v-Ha- ras coding region flanked by a ζ-globin promoter and an SV40 polyadenylation signal sequence. These mice respond to carcinogens by developing epidermal papillomas. In some cases, malignancies develop at the sites of these papillomas. Various patterns of squamous cell differentiation were observed in these malignancies. One malignancy that developed at the site of the papillomas was composed of bundles of spindle cells. This lesion is difficult to distinguish from fibrosarcomas by light microscopy. We characterized 16 of these malignancies (tentatively classified as spindle cell tumors) to determine if they were of epithelial or mesenchymal origin. Papillomas were induced in Tg.AC mice by full thickness wounding, 12-O-tetradec-anoyl-13-phorbol acetate treatment, or ultraviolet radiation. With time, some papillomas became broad-based, downwardly invading lesions. These lesions were examined by light microscopy with immunohistochemical analysis for cytokeratins and by electron microscopy. Immunohistochemical examination with a polyclonal anti-cytokeratin antibody demonstrated various degrees of keratin staining in all tumors examined. Attenuated desmosomes were also observed in these lesions by electron microscopy. These results indicate an epithelial origin for these malignancies; therefore, they should be classified as spindle cell carcinomas.
Pathological Features of Spontaneous and Induced Tumors in Transgenic Mice Carrying a Human Prototype c-Ha-ras Gene Used for Six-Month Carcinogenicity Studies
Authors: Mitsumori Kunitoshi , Koizumi Haruko , Nomura Tatsuji , Yamamoto Satoshi
Published: September 2009

To validate the transgenic (Tg) mouse carrying a human prototype c-Ha- ras gene (rasH2 mouse) as a model for short or medium-term carcinogenicity testing, 6-mo carcinogenicity studies using more than 30 chemicals, including carcinogens and noncarcinogens, have been performed. The results obtained so far indicate that rasH2 mice are generally much more susceptible to both mutagenic and nonmutagenic carcinogens than are non-Tg mice, pointing to advantageous application for detection of carcinogenic potential. In this review, histopathological features and diagnostic criteria for spontaneous and induced-tumors observed in our 6-mo carcinogenicity studies are described. Incidences of spontaneous tumors were generally low in rasH2 mice during the 6-mo studies, although values for lung adenomas and splenic hemangiosarcomas were higher than those in the control non-Tg mice. A few forestomach papillomas and skin papillomas were also observed in the control rasH2 mice. The target organs in rasH2 mice treated with known carcinogens were not always identical to those in the treated B6C3F1 mice in 2-yr carcinogenicity bioassays, with forestomach squamous cell tumors, lung alveolar epithelial tumors and/or hemangiosarcomas in the spleen observed in addition to some but not all of the lesions in target organs observed in non-Tg mice in long-term carcinogenicity bioassays. The results of the present histological study suggest that the lung, spleen and/or forestomach, where tumors are induced in rasH2 mice treated with known carcinogens, should be regarded as informative target organs in addition to the target organs reported in previous long-term carcinogenicity bioassays in rats and mice.
An Evaluation of the Hemizygous Transgenic Tg.AC Mouse for Carcinogenicity Testing of Pharmaceuticals. I. Evidence for a Confounding Nonresponder Phenotype
Authors: Weaver James L. , Contrera Joseph F. , Rosenzweig Barry A. , Thompson Karol L. , Faustino Patrick J. , Strong John M. , Ellison Christopher D. , Anderson Lawrence W. , Prasanna Hullahalli R. , Long-Bradley Patricia E. , Lin Karl K. , Zhang Jun , Sistare Frank D.
Published: September 2009

We have completed 2 26-wk studies to evaluate the hemizygous transgenic Tg.AC mouse, which has been proposed as an alternative short term model for testing carcinogenicity. We attempted to evaluate the response to the known rodent carcinogens cyclophosphamide, phenolphthalein, and tamoxifen and to the noncarcinogen chlorpheniramine following topical application. In the first study, a weak response (2/17 animals) was observed to the positive control 12- O-tetradecanoylphorbol 13-acetate (TPA in ethanol, 1.25 μg), and no response was observed to cyclophosphamide, phenolphthalein, or chlorpheniramine, despite evidence for skin penetration. The second study compared 1.25 μg and 6.25 μg of TPA in ethanol and acetone solutions. Tamoxifen was also evaluated in both solvents and orally. No significant response was observed to tamoxifen by skin paint or oral routes. Over 60% of the high dose TPA-treated animals showed no (0 or 1) papilloma response, and 30% of the animals each developed more than 32 papillomas. The heterogenous response to high dose TPA may be related to variability in the responsiveness of hemizygous animals. In light of these findings, further Tg.AC studies should employ homozygous animals, and the underlying cause for heterogeneity in the tumorigenic response of Tg.AC mice should be identified and eliminated.
An Evaluation of the Hemizygous Transgenic Tg.AC Mouse for Carcinogenicity Testing of Pharmaceuticals. II. A Genotypic Marker that Predicts Tumorigenic Responsiveness
Authors: Thompson Karol L. , Rosenzweig Barry A. , Sistare Frank D.
Published: September 2009

The Tg.AC transgenic mouse skin paint assay is one of the short-term carcinogenesis models that has been proposed as a replacement for 1 species in the conventional 2-yr bioassay required for safety testing of pharmaceuticals. In our initial efforts to evaluate the sensitivity and specificity of this model for human pharmaceuticals, 61% of the hemizygous Tg.AC mice in the positive control groups were refractory to treatment with 12- O-tetradecanoylphorbol 13-acetate (TPA). Tg.AC mice are reported to carry ≤10 copies of a transgcne consisting of a ζ-globin promoter fused to the v-Ha-ras structural gene with a terminal simian virus 40 (SV40) polyaden-ylation signal. Southern blot hybridization of genomic DNA from 66 tail biopsies using a ζ-globin probe revealed that all of the hemizygous Tg.AC mice screened contained approximately 40 copies of the transgene and that mice unresponsive to TPA had lost a 2-kb BamHI fragment containing ζ-gIobin promoter sequence. By systematic screening of Tg.AC breeder mice for this diagnostic marker of phenotypic responsiveness, it should be possible to selectively enrich the Tg.AC mouse colony to consist exclusively of responders and to guard against further genetic instability.
Stand-Alone Ethics, Social Responsibility, and Sustainability Course Requirements
Authors: Rundle-Thiele Sharyn R. , Wymer Walter
Published: September 2009

This article analyzes the extent to which Australian and New Zealand marketing educators use dedicated or stand-alone courses to equip students with alternative views of business. A census of marketing programs in degree-granting universities was conducted. Program brochures were obtained via the Internet and were content analyzed. This study reports a lower proportion of universities requiring students to take a course dedicated to society and environmental issues than previous studies have. Only 27% of universities in Australia required students to take a dedicated ethics, social responsibility, and/or sustainability course. Only 8% of universities offered a dedicated core marketing ethical or social responsibility course. Previous sample estimates may have overstated ethical, social responsibility, and sustainability course requirements. There is considerable room for improvement in Australia and New Zealand if universities are to equip their students with the skills, knowledge, and ideas to benefit themselves, the organizations they choose to work for, and society as a whole.
The Long-Term Outcome of Recurrent Defects after Rotator Cuff Repair
Authors: Dodson Christopher C. , Kitay Alison , Verma Nikhil N. , Adler Ronald S. , Nguyen Joseph , Cordasco Frank A. , Altchek David W.
Published: September 2009

Background

Retears of the rotator cuff are not uncommon after arthroscopic and mini-open rotator cuff repairs. In most studies, the clinical results in patients with persistent defects demonstrated significantly less pain and better function and strength compared with their preoperative state at an early follow-up.

Hypothesis

The clinical and structural outcomes of patients with known rotator cuff defects will remain unchanged after a longer period of follow-up.

Study Design

Case series; Level of evidence, 4.

Methods

This study was performed in 15 patients (18 shoulders) from a previous study who had recurrent rotator cuff defects 3.2 years after repair. Each patient completed the American Shoulder and Elbow Surgeons Scoring Survey, the Simple Shoulder Test, the L'Insalata Scoring Survey, and a visual analog scale for pain. Eleven patients (13 shoulders) were clinically reexamined at an average of 7.9 years for range of motion and strength, with targeted ultrasound.

Results

At the 7.9 year follow-up the average scores were 95 (American Shoulder and Elbow Surgeons), 95 (L'Insalata), 11 (Simple Shoulder Test), and 0 (visual analog for pain), which were not statistically significantly different from the scores at 3.2 years. There was no change in the average range of motion; however, there was a statistically significant reduction in forward flexion strength and external rotation strength, as measured by a dynamometer. The average external rotation strength decreased by a mean of 42% and the mean forward flexion strength decreased by a mean of 45% (P < .001). Furthermore, there was a statistically significant increase in the mean size of the defect, from 273 mm2 to 467 mm2 (P < .001). Finally, the size of the defect increased in all patients, and no defects healed structurally.

Conclusion

At an average of 7.9 years, patients with recurrent defects after rotator cuff repair still had an improvement in terms of pain, function, and satisfaction. However, the rotator cuff defect significantly increased in size, and there was a progression of strength deficits. These findings suggest that patients with recurrent defects can remain asymptomatic over the long term but will predictably lose strength in the involved extremity. Furthermore, the study demonstrated that defects after rotator cuff repair increase in size but often remain asymptomatic.
The Clock Gene period Plays an Essential Role in Photoperiodic Control of Nymphal Development in the Cricket Modicogryllus siamensis
Authors: Sakamoto Tomoaki , Uryu Outa , Tomioka Kenji
Published: September 2009

Photoperiodic regulation of development is a common strategy for insects in the temperate zone to adapt to the seasonally changing environment. Although the circadian clock is generally thought to be involved, the underlying time measurement mechanism is still elusive. Here, we demonstrate that the circadian clock gene period ( per) plays an essential role in the photoperiodic regulation of nymphal development in the cricket Modicogryllus siamensis. Nymphal development of this cricket depends on photoperiods, being accelerated by long days and slowed down by short days. We examined the role of per in the nymphal photoperiodic response as well as circadian rhythm generation using parental RNA interference (pRNAi). per mRNA levels in nymphal heads showed a rhythmic expression with the pattern dependent on photoperiods, and pRNAi significantly suppressed the per mRNA level with no significant rhythmicity in the early nymphal stage. Irrespective of photoperiods, nymphs treated with per pRNAi showed adult emergence patterns neither of intact nymphs nor of DsRed2 pRNAi nymphs kept under long days or under short days but similar to those kept under constant dark conditions. Most per pRNAi adults showed arrhythmic or aberrant circadian locomotor activity. These results suggest that the photoperiodic time measurement requires the normal circadian clock that is controlled by the per gene.
Circadian Modulation of Melanopsin-Driven Light Response in Rat Ganglion-Cell Photoreceptors
Authors: Weng Shijun , Wong Kwoon Y. , Berson David M.
Published: September 2009

Intrinsically photosensitive retinal ganglion cells (ipRGCs) project to the suprachiasmatic nucleus (SCN) and are essential for normal photic entrainment of global circadian rhythms in physiology and behavior. The effect of light on the central clock is dependent on circadian phase, and the retina itself contains intrinsic circadian oscillators that can alter its sensitivity to light. This raises the possibility that the ipRGCs, and hence the photoentraining signals in the retinohypothalamic tract, are subject to circadian modulation. Although the ipRGC photopigment melanopsin reportedly exhibits circadian variations in expression, there has been no direct test of the hypothesis that ipRGC sensitivity is under circadian control. Here, the authors provide such a test by measuring the sensitivity of intrinsic photoresponses of rat ipRGCs at 4 circadian times (CTs) using multielectrode array recording. There was little if any circadian modulation in the threshold of intrinsic ipRGC photoresponses. However, very bright light evoked significantly more spiking early in the subjective night (CT12-13) than at other circadian phases. Thus, the gain of the melanopsin-driven response is slightly increased in the early night, at roughly the circadian phase when melanopsin synthesis is thought to be elevated. However, this gain change is probably too modest to contribute much to shape the phase response curve (PRC) for behavioral photoentrainment.
Controlled Patterns of Daytime Light Exposure Improve Circadian Adjustment in Simulated Night Work
Authors: Dumont Marie , Blais Hélène , Roy Joanie , Paquet Jean
Published: September 2009

Circadian misalignment between the endogenous circadian signal and the imposed rest-activity cycle is one of the main sources of sleep and health troubles in night shift workers. Timed bright light exposure during night work can reduce circadian misalignment in night workers, but this approach is limited by difficulties in incorporating bright light treatment into most workplaces. Controlled light and dark exposure during the daytime also has a significant impact on circadian phase and could be easier to implement in real-life situations. The authors previously described distinctive light exposure patterns in night nurses with and without circadian adaptation. In the present study, the main features of these patterns were used to design daytime light exposure profiles. Profiles were then tested in a laboratory simulation of night work to evaluate their efficacy in reducing circadian misalignment in night workers. The simulation included 2 day shifts followed by 4 consecutive night shifts (2400-0800 h). Healthy subjects (15 men and 23 women; 20-35 years old) were divided into 3 groups to test 3 daytime light exposure profiles designed to produce respectively a phase delay (delay group, n = 12), a phase advance (advance group, n = 13), or an unchanged circadian phase (stable group, n = 13). In all 3 groups, light intensity was set at 50 lux during the nights of simulated night work. Salivary dim light melatonin onset (DLMO) showed a significant phase advance of 2.3 h (± 1.3 h) in the advance group and a significant phase delay of 4.1 h (± 1.3 h) in the delay group. The stable group showed a smaller but significant phase delay of 1.7 h (± 1.6 h). Urinary 6-sulfatoxymelatonin (aMT6s) acrophases were highly correlated to salivary DLMOs. Urinary aMT6s acrophases were used to track daily phase shifts. They showed that phase shifts occurred rapidly and differed between the 3 groups by the 3rd night of simulated night work. These results show that significant phase shifts can be achieved in night workers by controlling daytime light exposure, with no nighttime intervention.
Analysis of the Drosophila Clock Promoter Reveals Heterogeneity in Expression between Subgroups of Central Oscillator Cells and Identifies a Novel Enhancer Region
Authors: Gummadova Jennet Orazmuradovna , Coutts Graham Andrew , Glossop Nicholas Robert John
Published: September 2009

The CLOCK-CYCLE (CLK-CYC) heterodimer lies at the heart of the circadian oscillator mechanism in Drosophila, yet little is known about the identity of transcription factors that regulate the expression of Clk and/or cyc. Here, the authors have used a transgenic approach to isolate regions of the Clk locus that are necessary for expression in central oscillator neurons in the adult fly brain. This analysis shows that central clock cells can be subdivided into 2 distinct groups based on Clk gene regulation. Expression in the lateral neuron (LN), dorsal neuron 1 anterior (DN1a) and 2 (DN2) clusters requires cis-elements located in a 122 base-pair (bp) region (–206 to –84) of the Clk promoter. Expression in the remaining dorsal neurons, 1 posterior (DN1p) and 3 (DN3) and the lateral posterior neurons (LPN), requires regulatory elements located in the –856 to –206 region. In addition, expression in photoreceptors of the compound eye is enhanced by cis-elements located in a 3rd region of the Clk locus (–1982 to –856). This region also enhances expression in nonoscillator cells in the brain including the Kenyon cells, but expression in these neurons is suppressed by regulatory sites located further upstream of –1982. The authors’ analysis reveals clear heterogeneity in Clk gene expression in the adult brain and provides a necessary focus to isolate novel transcription factors that bind at the Clk locus to regulate expression in different oscillator neuron subgroups. These results also suggest that the DN1a/DN2 neurons may have more molecular commonality with the LNs than they do with the DN1p/DN3/LPN neurons. Finally, this analysis has generated new transgenic lines that will enable genes to be misexpressed in subgroups of central oscillator cells that have previously been resistant to discrete genetic manipulation. Hence, these lines provide important new tools to facilitate a more complete dissection of the neural network that regulates output rhythms in physiology and behavior.
Circannual Phase Response Curves to Short and Long Photoperiod in the European Hamster
Authors: Monecke Stefanie , Saboureau Michel , Malan André , Bonn Daniel , Masson-Pévet Mireille , Pévet Paul
Published: September 2009

This study investigated in male European hamsters ( Cricetus cricetus ) whether entrainment of circannual rhythms follows the principles of the nonparametric entrainment model. In 2 experiments the times of the year when long (LP) or short photoperiod (SP) are able to synchronize the reproductive cycle were determined, by recording phase response curves (PRCs). A total of 28 groups of 10 hamsters were synchronized by SP, before being subjected to 2 converse experiments: a) 14 groups were transferred to constant LP, only interrupted by SP for 1 month (SP-pulse), the pulse being increasingly delayed between groups by 2 weeks or 1 month steps; and b) the remaining 14 groups stayed in constant SP interrupted by LP for 1 month (LP-pulse) at different phases of the cycle. In a 3rd experiment 5 groups of 10 European hamsters were subjected to constant LP interrupted by 1-month SP-pulses in regular non-365-day zeitgeber intervals (circannual T-cycles) differing between groups (c). The reproductive state was checked every 2 or 4 weeks. The PRCs revealed that an SP-pulse had a very strong phase-resetting capability of —180° to at least +81° in subjective summer (a). During subjective winter when the animals hibernate, a SP-pulse had only weak effectiveness (a) whereas an LP-pulse advanced the circannual clock by up to +41° (b). In the latter conditions a further advance of up to +156° was achieved by the decrease in photoperiod at the return to SP conditions, which terminated the reproductive phase already after 4 to 5 weeks. In different circannual T-cycles the animals entrained for at least 2 cycles (c). In conclusion, 1) the circannual rhythm of European hamsters can be entrained by one photoperiodic signal per cycle, 2) the decrease in photoperiod is most important for its synchronization, and 3) as in circadian clocks the resetting of circannual clocks follows the principles of the nonparametric entrainment model.
Basis of Robustness and Resilience in the Suprachiasmatic Nucleus: Individual Neurons Form Nodes in Circuits that Cycle Daily
Authors: Butler Matthew P. , Silver Rae
Published: September 2009

How the cellular elements of the SCN are synchronized to each other is not well understood. We explore circadian oscillations manifest at the level of the cell, the tissue, and the whole animal to better understand intra-SCN synchrony and master clock function of the nucleus. At each level of analysis, responses to variations in operating environment (robustness), and following damage to components of the system (resilience), provide insight into the mechanisms whereby the SCN orchestrates circadian timing. Tissue level rhythmicity reveals circuits associated with an orderly spatiotemporal daily pattern of activity that is not predictable from their cellular elements. Specifically, in stable state, some SCN regions express low amplitude or undetectable rhythms in clock gene expression while others produce high amplitude oscillations. Within the SCN, clock gene expression follows a spatially ordered, repeated pattern of activation and inactivation. This pattern of activation is plastic and subserves responses to changes in external and internal conditions. Just as daily rhythms at the cellular level depend on sequential expression and interaction of clock genes, so too do rhythms at the SCN tissue level depend on sequential activation of local nodes. We hypothesize that individual neurons are organized into nodes that are themselves sequentially activated across the volume of the SCN in a cycle that repeats on a daily basis. We further propose that robustness is expressed in the ability of the SCN to sustain rhythmicity over a wide range of internal and external conditions, and that this reflects plasticity of the underlying nodes and circuits. Resilience is expressed in the ability of SCN cells to oscillate and to sustain activity-related rhythms at the behavioral level. Importantly, other aspects of pacemaker function remain to be examined.
Topical Review: Neuroimaging in Leukodystrophies
Authors: Barker Peter B. , Horská Alena
Published: September 2009

The application of techniques based on in vivo magnetic resonance to the study of leukodystrophies is evaluated. Magnetic resonance imaging (MRI), the most important neuroimaging modality for patients with leukodystrophies, has proven invaluable for the detection of the extent and etiology of white-matter involvement, diagnosis, and monitoring of disease progression. Proton magnetic resonance spectroscopy, which can detect several brain metabolites, including those related to axonal function and myelination, can provide additional diagnostic and prognostic information and, in some cases, allows a rare insight into the biochemical pathology of leukodystrophies. The potential of other advanced magnetic resonance techniques, including diffusion tensor imaging, magnetization transfer contrast, and molecular imaging, is also discussed. In the future, anatomic and physiologic magnetic resonance techniques are expected to be integrated into a single examination that will provide a detailed characterization of white-matter diseases in children. (J Child Neurol 2004;19:559-570).
Influence of Neuroendoscopic Third Ventriculostomy on the Size of Ventricles in Chronic Hydrocephalus
Authors: NowosXawska Emilia , Polis Lech , Kaniewska Danuta , MikoXajczyk Wanda , Krawczyk Jacek , Szymański Wojciech , Zakrzewski Krzysztof , Podciechowska Joanna
Published: September 2009

Our intention was to compare the clinical outcome after surgical treatment of chronic hydrocephalus between patients who were subjected to neuroendoscopic third ventriculostomy and patients who underwent shunt implantation. At the Department of Neurosurgery of the Research Institute of Polish Mothers' Memorial Hospital from 1999 to 2001, 29 children, of an average age of 7 years (±7.1 years SD), underwent successful neuroendoscopic procedures, and from 1992 to 1994, 59 children, of an average age of 2 months (±1.9 months SD), underwent shunt implantation. The size of the ventricular system was described by the Frontal Horn Index and its change after operative procedures by the ratio of the final to the primary Frontal Horn Index. Head circumference was measured in percentiles according to the Kurniewicz-Witczakowa chart for Polish children. The reduction in head circumference after a neuroendoscopic procedure was, on average, significantly less than after a shunt implantation (0.39 percentiles ± 29.6 SD vs 17.93 percentiles ± 19.93 SD). Concerning the change in ventricular size after a neuroendoscopic procedure, it was noticed that the average ratio of the final to the primary Frontal Horn Index was 0.9. Meanwhile, the same parameter after a shunt implantation was 0.55. Based on the values of the Frontal Horn Indexes, it was observed that the ventricular system in infants after neuroendoscopic procedures was significantly larger than in other age groups (0.7 vs 0.5). After successful neuroendoscopic operations in a group of children suffering from Chiari II malformation, ventricular systems were slightly enlarged. The ratio of the final Frontal Index to the primary Frontal Horn Index was 1.31. In children suffering from chronic hydrocephalus, the average reduction in the size of the ventricular system and the rate of head circumference growth are lower after neuroendoscopic operations than after shunt implantations. Successful neuroendoscopic procedures are characterized by, on average, a higher rate of head circumference growth in infants than in neonates. In addition, the rate of head circumference growth after successful neuroendoscopic procedures could be higher than before the operation, which is clearly visible in children suffering from Chiari II malformation, but it does not mean a constant increase of that parameter during the postoperative period. (J Child Neurol 2004;19:579-587).
Neonatal Seizures
Authors: Camfield Peter R. , Camfield Carol S.
Published: September 2009

Despite the immaturity of the newborn brain, the neonatal period is reported to have a very high frequency of seizures. This review concludes that many of the neonatal events that are called seizures probably originate from subcortical structures, have little in common with cortical seizures seen in older individuals, and may not benefit from conventional anticonvulsant treatment. Many studies of anticonvulsants in the newborn have important methodologic problems, compounded by the fact that the seizures tend to spontaneously remit with the resolution of the acute hypoxic-ischemic encephalopathy that is most often the cause. Randomized trials of anticonvulsants in this setting have not been carried out. Even if many of these seizures do not originate in the cortex, they still imply profound cortical disturbance and are associated with high mortality and morbidity. It is unknown if the type and duration of treatment influence the long-term, overall outcome. The seizures usually stop in the newborn period, and anticonvulsants beyond hospital discharge seem unwarranted because they are unlikely to prevent subsequent epilepsy. Newer investigations, including video-EEG and nuclear magnetic resonance studies, may clarify the real significance of neonatal seizures. ( J Child Neurol 1987;2:244-51).
Clinical Significance of Childhood Communication Disorders: Perspectives From a Longitudinal Study
Authors: Cantwell Dennis P. , Baker Lorian
Published: September 2009

A group of 202 children who were referred for evaluation of communication disorders were also evaluated for psychiatric and learning disorders at two points in time. High rates of both psychiatric and learning disorders were found at initial evaluation, and even higher rates were found at follow-up 3 to 4 years later. Recovery from communication disorder occurred in approximately one fourth of the cases and varied widely depending on the type of disorder involved. Poor psychiatric outcome could be predicted by the presence and severity of initial disorders of language comprehension and expression, and by certain environmental factors (such as psychosocial stress). The high prevalence of linguistic, psychiatric, and development disorders at follow-up for the children in this study suggests the need for close monitoring of children with early communication impairments. ( J Child Neurol 1987;2:257-264).
Self-Mutilation and Tourette's Disorder
Authors: Eisenhauer Gail L. , Woody Robert C.
Published: September 2009

Tourette's disorder is a stereotyped movement disorder that carries with it the risk of self-mutilation. Two cases are presented in which children with Tourette's disorder mutilated themselves. Possible physiologic mechanisms by which self-mutilation occurs in patients with Tourette's disorder are reviewed and treatment strategies are discussed. ( J Child Neurol 1987;2:265-267).
Hyperdensity on CT After Seizure: A Pitfall
Authors: Hussain Bangash I. , Kandt Raymond S. , D'Souza Bernard J. , Heinz Ralph
Published: September 2009

A 12-year-old boy had a hyperdense area corresponding to a gyral pattern on an enhanced CT brain scan within 12 hours of his last seizure. The hyperdense area disappeared on a subsequent enhanced CT scan after he was seizure free for about 48 hours. The hyperdense area was in a location (mesial frontal lobe) predicted by the interictal physical exam findings and the seizure type recorded on video-EEG monitoring. We postulate that the CT abnormality was due to transitory increase of regional cerebral blood flow and vascular permeability. ( J Child Neurol 1987;2:276-278).
Congenital Granuloprival Hypoplasia of Cerebellar and Hippocampal Cortex
Authors: Chou Samuel M. , Mizuno Yoshihiko , Rothner A. David
Published: September 2009

Two siblings with congenital granule cell hypoplasia of the cerebellum and hippocampus are reported. The patients, both male, showed severe psychomotor retardation, microcephaly, hypotonia, athetosis, and seizures; they died at the ages of 37/12 years and 510/12 years, respectively. Postmortem examinations in both cases revealed nearly complete absence of the granule cells of the cerebellum with relative preservation of the Purkinje cells. Also absent were the granule cells of the fascia dentata of the Ammon's horns of the hippocampus, without any detectable gliosis; this has not previously been reported. Twenty-three autopsy cases of granuloprival cerebellar hypoplasia are reviewed. The present cases illustrate a singularly unique disease process, comparable to the classical cerebellar hypoplasia experimentally induced by parvoviruses, and suggest a granule cell specific insult to the brain during the late second trimester. ( J Child Neurol 1987;2:279-286).
Prognostic Significance of the Electrically Elicited Blink Reflex in Neonates
Authors: Tanaka Tomoko , Tomita Yutaka , Nishimura Satoko
Published: September 2009

The electrically elicited blink reflex was examined in ten normal neonates, 11 postasphyxial neonates, and 3 congenital hydrocephalus cases. The blink reflex was elicited in all cases. In normal neonates, the latencies and amplitudes were 10.9 ± 0.7 msec and 159 ± 62 μV at R1, 34.3 ± 1.4 msec and 123 ± 30 μV at R2, and 40.7 ± 2.3 msec and 84 ± 25 μV at R'2 respectively. Ischemic-hypoxic brain damage during the neonatal period mainly influenced the late components of the blink reflex. The blink reflex of the postasphyxial neonates showed significantly prolonged latencies of R 2 and R'2. The amplitudes were increased in cases with a fair prognosis and decreased in cases with a poor prognosis. A case of congenital hydrocephalus with mental retardation also showed the prolonged latencies of R2 and R'2 in neonatal period. The blink reflex in neonates appears to be useful in predicting the outcome in cases of neonatal asphyxia and congenital hydrocephalus. ( J Child Neurol 1987;2:287-292).
Massive Brain Stem Necrosis in the Human Neonate: Presentation of Three Cases With Review of the Literature
Authors: Leech Richard W. , Brumback Roger A.
Published: September 2009

In neonates suffering hypotensive or asphyxial episodes, the brain stem is particularly vulnerable to selective neuronal necrosis. Typically, the pattern is one of generalized neuronal necrosis within well-defined brain stem cranial nerve nuclei, or random neuronal degeneration within the reticular formation. More recently, isolated cases of severe partial or total cystic necrosis of the brain stem reticular formation have been recorded. The pathogenesis is poorly understood at this time, but may be similar to the less severe (but more often recognized) nuclear or focal neuronal loss. Three infants are presented in which severe necrosis of the brain stem occurred. In each, the clinical setting was one of sudden and abrupt worsening of the patient's cardiovascular status. ( J Child Neurol 1988;3:258-262).
Prevention of Rapidly Progressive Scoliosis in Duchenne Muscular Dystrophy by Prolongation of Walking with Orthoses
Authors: Rodillo Eliana B. , Fernandez-Bermejo Esther , Heckmatt John Z. , Dubowitz Victor
Published: September 2009

We reviewed the incidence and severity of scoliosis in 93 boys with Duchenne muscular dystrophy who had been rehabilitated in light-weight knee-ankle-foot orthoses at the point of loss of ambulation, between the ages of 6 and 12 years. There was an inverse relationship between the severity of the scoliosis and the age walking was lost in the orthoses. The scoliosis was less severe in the 20 boys (22%) who walked in their orthoses beyond 13 years of age than in those who stopped walking in their orthoses before 13 years. There was also a rapid deterioration in the scoliosis between the ages of 13 and 15 years in boys who had stopped walking in their orthoses before the age of 13 years, while in comparison, boys of the same age who were ambulant in their orthoses beyond 13 years showed a much slower rate of deterioration. These results strongly suggest that walking in orthoses beyond the age of 13 years prevented rapid progression of scoliosis between 13 and 15 years of age, ie, during the pubertal growth spurt. (J Child Neurol 1988;3:269-274).
Dysmaturation Neuromyopathy: Correlation with Minimal Neuropathy in Sural Nerve Biopsies
Authors: Verity M. Anthony , Gao Yung-Hua
Published: September 2009

Dysmaturation (neuro)myopathy without specific histochemical or cytoarchitectural characteristics accounts for many cases of hypotonia in infancy. We obtained a maturation profile for type I and type II fibers from birth to 6 years of age, from which a classification of fiber dysmaturation based on fiber-type hypotrophy and coefficient of fiber variation is presented. We analyzed the morphometric, ultrastructural, and single fiber teasing findings in the sural nerve of ten infants with hypotonia and dysmaturation myopathy based on the above classification. Data on endoneurial area, myelinated fiber density, proportion of large (> 6 μm) myelinated fibers, unmyelinated fiber density, regression analyses of myelin area:axon area, and mean myelin thickness were developed. Abnormalities in large myelinated fiber density (3 cases), disturbances in myelination index (5), and single fiber teasing abnormalities in internode length (1) were found. Ultrastructural abnormalities were observed and classified as group 0 changes similar to the five control nerves; group 1, in which rare fibers showed degeneration or basement membrane duplication; and group 2, which was characterized by multiple abnormalities including degenerate nuclei, amyelinate fibers, degeneration/regeneration, excessive basal lamina reduplication, and hypomyelination. This study provides evidence that minimal neuropathic abnormalities are present in the sural nerve of infants carrying a diagnosis of dysmaturation neuromyopathy. ( J Child Neurol 1988;3:276-291).
Recurrent Myoglobinuria in a Child With Mental Retardation: Phosphoglycerate Kinase Deficiency
Authors: Sugie Hideo , Sugie Yoko , Nishida Mitsuhiro , Ito Masataka , Tsurui Satoshi , Suzuki Makoto , Miyamoto Reiko , Igarashi Yoshio
Published: September 2009

We report the case of an 11-year-old mentally retarded boy with recurrent myoglobinuria precipitated after a generalized tonic-clonic convulsion. No hemolysis was noted. Ischemic forearm test revealed no rise of venous lactate, suggesting a metabolic defect in an anaerobic glycolytic pathway. Histochemistry studies of the quadriceps muscle showed a normal appearance, but electron microsopy confirmed a moderate increase of the glycogen content in muscle. Direct measurement of glycolytic enzymes demonstrated a marked decrease of phosphoglycerate kinase (PGK) activity in muscle (4.4% of control mean) and hemolysate (8% of control mean). Enzyme characteristics of PGK from our patient (PGK Hamamatsu) using hemolysate demonstrated that it had normal Michaelis constants (Km), normal thermal stability, and a normal pH curve. The reason that hemolytic anemia was absent is uncertain. We concluded that a systematic enzyme analysis of the glycolytic pathway, especially of PGK, should be performed on myoglobinuric patients who are males, or who have an X-linked inheritance as suggested by the family history. ( J Child Neurol 1989;4:95-99).
Childhood Developmental Changes in the Auditory P300
Authors: Pearce James W. , Crowell David H. , Tokioka Abe , Pacheco Gail P.
Published: September 2009

In this study we investigated developmental changes in the auditory P3 latency from childhood to adolescence. Event-related potentials evoked by improbable auditory stimuli were recorded from 35 normal children between the ages of 5 and 13 years. Regression analyses showed significant age trends in the auditory P3 latency. Latencies decreased at a rapid rate (Cz: 20.34 msec/yr; Pz: 19.27 msec/yr) from childhood to adolescence, suggesting an increased efficiency in processing information as children mature. This rate was linear or constant in nature as evidenced by the failure of the quadratic and cubic components to significantly increase predictability of the regression equation. The slope of the P3 latency/age regression line was also shown to be influenced by the interactive effects of task difficulty and maturation. It was hypothesized that neurodevelopmental processes (increased myelination and dendritic arborization) may underlie the maturational changes observed in the P3 latency during childhood. ( J Child Neurol 1989;4:100-106).
Neurological Complications of Hemolytic-Uremic Syndrome
Authors: Hahn Jin S. , Havens Peter L. , Higgins Joseph J. , O'Rourke P. Pearl , Estroff Judy A. , Strand Roy
Published: September 2009

Of 78 children identified with hemolytic-uremic syndrome at the Children's Hospital, Boston, from 1976 to 1986, 16 patients (20.5%) had neurological manifestations during their hospitalization. The most common manifestations were significant alterations in consciousness (coma, stupor) in 12 patients, and either generalized or partial seizures in ten patients. Others included hemiplegia (4 patients), decerebrate posturing (3), cortical blindness (2), hallucinations (1), and dystonic posturing (1). Cranial computed tomographic scans were abnormal in eight of 11 patients scanned. The abnormalities included diffuse cerebral edema (4 patients), large vessel infarctions (3), diffuse multiple small infarcts (4), and multiple hemorrhages (1). Five patients died as a result of their central nervous system complications, and six had neurological sequelae at discharge. Five patients recovered and at discharge had no evidence of neurological dysfunction. ( J Child Neurol 1989;4:108-113).
Home Use of Rectal Diazepam to Prevent Status Epilepticus in Children With Convulsive Disorders
Authors: Camfield Carol S. , Camfield Peter R. , Smith Edythe , Dooley Joseph M.
Published: September 2009

Thirty families were taught to administer rectal liquid diazepam to their children to stop a seizure at home. Twelve children had previous prolonged afebrile seizures, and 18 had either prolonged or repeated febrile seizures. During follow-up, 17 of the 30 families administered the rectal diazepam an average of three times per child with no complications. Fifteen of 17 families reported prompt cessation of the seizure, while in two the rectal diazepam was unsuccessful and hospital treatment was needed. We conclude that rectal diazepam is a useful adjunctive home treatment for children at risk for prolonged seizures. Hospitalization is decreased and parental confidence increased. Without our knowledge, twelve families taught others how to give the rectal diazepam, a practice that might be hazardous and should be anticipated. ( J Child Neurol 1989;4:125-126).
Acute Pseudobulbar Palsy Due to Bilateral Focal Cortical Damage: The Opercular Syndrome of Foix-Chavany- Marie
Authors: Grattan-Smith Padraic J. , Hopkins Ian J. , Shield Lloyd K. , Boldt David W.
Published: September 2009

Two children are described who suddenly developed an encephalitic illness with intractable bilateral facial seizures. The seizures subsided over several days, but the children were left with the signs of pseudobulbar palsy and are unable to speak or swallow effectively. Bilateral destructive lesions in the opercular regions evolved on computed tomographic scans. Both children were treated with acyclovir relatively early in the illness, and cerebrospinal fluid and serum antibodies support the diagnosis of herpes simplex virus encephalitis. ( J Child Neurol 1989;4.-131-136).
Meconium-Induced Vasocontraction: A Potential Cause of Cerebral and Other Fetal Hypoperfusion and of Poor Pregnancy Outcome
Authors: Altshuler Geoffrey , Hyde Scott
Published: September 2009

Chronically meconium-stained fetuses may ultimately suffer cerebral palsy and other devastation. The mechanism is unknown. Innocuous pregnancy complications may cause some fetuses to discharge meconium, which may become hazardous, independently of aspiration. We herein report previously undescribed, meconium-induced umbilical and placental vascular necrosis. To investigate whether meconium causes vasocontraction, we tested umbilical vein tissue with an isometric transducer connected to a polygraph. The specimens were suspended in a 30-mL organ bath with Krebs solution (pH, 7.4; temperature, 37°C; under aeration with 95% O2 and 5% CO 2). We exposed the tissue to meconium and compared meconium-induced vasocontraction with that induced by Krebs solution and 10-5 molar serotonin. Meconium maximally produced 62.9% of serotonin-induced vasocontraction. Krebs solution and boiled meconium did not produce vasocontraction. We hypothesize that meconium may cause placental and umbilical cord vasocontraction, cerebral and other fetal hypoperfusion, and major poor outcome. ( J Child Neurol 1989;4:137-142).
Spasticity in Cerebral Palsy and the Selective Posterior Rhizotomy Procedure
Authors: Peacock Warwick J. , Staudt Loretta A.
Published: September 2009

A review of the selective posterior rhizotomy procedure for reduction of spasticity in cerebral palsy is presented. The history of the procedure, selection of patients, operative technique, and results are described. The neurophysiologic basis for spasticity is considered, as well as the role of spasticity in the complex motor disorder of cerebral palsy. Cerebral palsy is a multifaceted disorder of which spasticity is only one aspect. Reduction of spasticity can be effectively achieved using the current technique of selective posterior rhizotomy, but careful patient selection and establishment of realistic goals are vital to successful outcome. Postoperative physical and occupational therapy are felt to be essential for regaining strength and improving motor function following the rhizotomy procedure. Further study in the areas of spasticity, cerebral palsy, and the effects of rhizotomy is expected to advance our treatment of spastic children. ( J Child Neurol 1990;5:179-185).
Juvenile Pearson Syndrome
Authors: Blaw Michael E. , Mize Charles E.
Published: September 2009

The clinical and magnetic resonance imaging findings of a 14-year-old boy with Pearson syndrome are presented. The patient represents the oldest living survivor of the original four patients described by Pearson and associates. This syndrome has recently been found to be associated with an mtDNA deletion. The patient reported here has a deletion similar but not identical to that reported in the literature. Several mitochondrial myopathies have been associated with mtDNA deletions, with considerable overlap between and among the phenotypes and underlying mtDNA deletions. The same may well prove to be true for Pearson syndrome. ( J Child Neurol 1990;5:186-190).
Reaction Time, Impulsivity, and Attention in Hyperactive Children and Controls: A Video Game Technique
Authors: Mitchell Wendy G. , Chavez John M. , Baker Sherryl A. , Guzman Bianca L. , Azen Stanley P.
Published: September 2009

Maturation of sustained attention was studied in a group of 52 hyperactive elementary school children and 152 controls using a microcomputer-based test formatted to resemble a video game. In nonhyperactive children, both simple and complex reaction time decreased with age, as did variability of response time. Omission errors were extremely infrequent on simple reaction time and decreased with age on the more complex tasks. Commission errors had an inconsistent relationship with age. Hyperactive children were slower, more variable, and made more errors on all segments of the game than did controls. Both motor speed and calculated mental speed were slower in hyperactive children, with greater discrepancy for responses directed to the nondominant hand, suggesting that a selective right hemisphere deficit may be present in hyperactives. A summary score (number of individual game scores above the 95th percentile) of 4 or more detected 60% of hyperactive subjects with a false positive rate of 5%. Agreement with the Matching Familiar Figures Test was 75% in the hyperactive group. ( J Child Neurol 1990;5:195-204).
Neuropathologic Observations in Congenital Phrenic Nerve Palsy
Authors: Alvord Ellsworth C. , Austin Everett J. , Larson Charles P.
Published: September 2009

A right phrenic nerve palsy with severe respiratory and feeding difficulties throughout the patient's 2½ years of survival was found at autopsy to relate to grossly complete atrophy of the muscle of the right diaphragm. An oblique fibrotic scar transected the right phrenic nerve at the level of the brachial plexus. There was marked reduction of the number of anterior motor neurons in the right central portion of cervical segments 2, 3, and 4. The lesion in the phrenic nerve is what would be expected following stretching during delivery. ( J Child Neurol 1990;5:205-209).