bluuebunny/crossref_metadata_2025_split huggingface dataset:
Migrating Partial Seizures in Infancy: Expanding the Phenotype of a Rare Seizure Syndrome
Authors: Marsh Eric , Melamed Susan E. , Barron Todd , Clancy Robert R. 
Published: March 2005

Summary:  Purpose: The constellation of early‐onset, unprovoked, alternating electroclinical seizures and neurodevelopmental devastation was first described by Coppola et al. We report six new patients and the prospect of a more optimistic developmental outcome. Methods: Retrospective chart reviews were performed on six infants evaluated at the Children's Hospital of Philadelphia (five patients) and at Hershey Medical Center (one patient) who had electroclinically alternating seizures before age 6 months of age. Electroclinical characteristics and long‐term follow‐up were recorded. Results: All had unprovoked, early‐onset (range, 1 day to 3 months; mean, 25 days) intractable electroclinical seizures that alternated between the two hemispheres. Each patient underwent comprehensive brain imaging and neurometabolic workups, which were unrevealing. In all patients, subsequently intractable partial seizures developed and often a progressive decline of head circumference percentile occurred with age. Three demonstrated severe developmental delay and hypotonia. All survived, and 7‐year follow‐up on one patient was quite favorable. Conclusions: Our patients satisfied the seven major diagnostic criteria first described by Coppola et al. The prognosis of this rare neonatal‐onset epilepsy syndrome from the original description and subsequent case reports was very poor, with 28% mortality, and the majority of survivors were profoundly retarded and nonambulatory. Our patient data validate the diagnostic criteria of this syndrome and further quantify a previously described observation of progressive decline of head circumference percentiles with age. Our data also suggest that the prognosis of this syndrome, although poor, is not as uniformly grim as the cases reported previously in the literature.
Effects of Status Epilepticus Early in Life on Susceptibility to Ischemic Injury in Adulthood
Authors: Giorgi Filippo S. , Malhotra Samit , Hasson Henry , Velíšková Jana , Rosenbaum Daniel M. , Moshé Solomon L. 
Published: March 2005

Summary:  Purpose: Status epilepticus (SE) commonly occurs in children, whereas ischemic stroke is the most frequent neurologic insult in adults. The purpose of this study was to determine the effect of SE induced in immature (15 days old; PN15) male rats, on susceptibility to subsequent transient focal cerebral ischemia induced in adulthood. Methods: SE was induced by flurothyl ether (FE) or kainic acid (KA). Rats that did not develop seizures after FE or KA served as controls. Five weeks later, the now‐adult rats were subjected to middle cerebral artery occlusion (MCAo) for 1 or 2 h by using the intraluminal filament technique. The extent of the infarct volume was evaluated 24 h later. Results: In rats submitted to 1‐h‐long FE‐SE, the volume of infarction was significantly reduced compared with that in rats exposed to FE without SE. Longer duration of FE‐SE was acutely lethal. KA‐SE induced prolonged behavioral SE (156 ± 17.5 min). In these rats, the volume of infarction was significantly larger compared with that in rats that did not show any electrographic seizures after KA administration. Comparison of FE and KA groups revealed that differences in the size of infarction were confined into cortical areas served by the MCA. Neither type of SE induced any obvious histologic changes in these neocortical regions before stroke induction. Conclusions: Early in life, SE can influence the outcome of a subsequent focal ischemic insult in adulthood. The extent of the infarct is related to the duration and cause of SE. Prolonged SE induced by KA worsens the outcome, whereas FE‐SE has a neuroprotective effect.
A Clinical and EEG Study on Idiopathic Partial Epilepsies with Evolution into ESES Spectrum Disorders
Authors: Saltik Sema , Uluduz Derya , Cokar Ozlem , Demirbilek Veysi , Dervent Aysin 
Published: March 2005

Summary:  Purpose: Questioning the presence of any possible prognostic predictors, this study includes a long‐term follow‐up of clinical and EEG characteristics of 16 patients with idiopathic partial epilepsy (IPE) who subsequently developed epilepsy with electrical status epilepticus during slow sleep (ESES) spectrum disorders. Methods: Epilepsy, cognitive and behavioral parameters, and waking and non–rapid eye movement (NREM) EEG data were evaluated and scored for initial stage (i.e., IPE stage), preESES, ESES, and ESES remission periods, individually, on a chronologic basis. Data from 25 healthy subjects who had had IPE at the appropriate ages served for comparison with the patients' data during the IPE stage. Results: Results revealed a higher incidence in seizure frequency and variability in the ESES group and a resistance to a single antiepileptic drug (AED), as compared with controls, during the IPE stage. Mean age at onset of epilepsy was younger in the ESES group versus controls (5.5 and 7.3 years, respectively). At least one of the premonitory clinical features for development of ESES [an increase in the seizure frequency and/or addition of new types of seizures (93%), appearance of cognitive and/or behavioural changes (81.2%), or a progression in EEG abnormalities (66%)] was present in all patients. Epilepsy remitted in patients within the ESES spectrum at a similar age as in controls in 81.2%, as ESES findings in the EEG disappeared by age 13 years in 94%. Seizure prognosis proved to be the most favorable among the questioned parameters. Conclusions: An increase in seizure frequency or development of new seizure types, a deviance in behavior or decrease in cognitive performance, or a spreading tendency of the previously focal abnormalities in control EEGs may be premonitory features of a developing ESES and necessitate close follow‐ups with sleep EEGs in children with IPEs.
Atypical Language Representation in Patients with Chronic Seizure Disorder and Achievement Deficits with Magnetoencephalography
Authors: Breier Joshua I. , Castillo Edwardo M. , Simos Panagiotis G. , Billingsley‐Marshall Rebecca L. , Pataraia Ekaterina , Sarkari Shirin , Wheless James W. , Papanicolaou Andrew C. 
Published: March 2005

Summary:  Purpose: To characterize the relation between hemispheric asymmetries in language‐specific brain activity and reading/spelling achievement by using magnetoencephalography (MEG). Methods: Patients (n = 83) with medically intractable complex partial seizures of either left‐ or right‐hemisphere origin were classified as having reading and/or spelling deficits (RS) or as not impaired (NI) by using standard achievement tests. All patients had undergone noninvasive functional mapping of receptive language cortex by using MEG as part of a preoperative seizure surgery evaluation. Results: RS patients with left‐hemisphere seizure onset exhibited relatively greater activation and earlier onset of late, language‐specific MEG activity in posterior temporal and inferior parietal areas of the right as compared with the left hemisphere than did NI patients. These findings also were evident on an individual basis and were independent of global intellectual abilities. Conclusions: Reading and spelling achievement deficits in patients with complex partial seizures of left‐hemisphere origin are associated with atypical language organization, possibly secondary to reorganization of language function to right‐hemisphere areas that are not as efficient as homotopic areas in the left hemisphere in supporting reading and spelling functions.
Can You Predict an Immediate, Complete, and Sustained Response to the Ketogenic Diet?
Authors: Than Khoi D. , Kossoff Eric H. , Rubenstein James E. , Pyzik Paula L. , McGrogan Jane R. , Vining Eileen P. G. 
Published: March 2005

Summary:  Purpose: Although the ketogenic diet has been in use for >80 years, little agreement exists as to which patients are most likely to have dramatic, sudden, and complete seizure control. Methods: A case–control study was performed of children with intractable epilepsy started on the ketogenic diet at our institution since June 2001. Patients with a dramatic response were defined as those becoming seizure free within 2 weeks of diet onset. These children were compared with all other patients treated with the diet over the same time period in terms of patient demographics, epilepsy characteristics, and diet parameters. Results: Eighteen early, dramatic responders over a 3‐year period were identified and compared with 89 patients who were not similarly improved. The absence of complex partial seizures as the predominant seizure type (0 vs. 23%; p = 0.02) correlated with this dramatic success. The presence of infantile spasms (39% vs. 20%; p = 0.09) approached significance, but all other variables did not. Conclusions: An early, dramatic response to the ketogenic diet is more likely in patients with predominant seizure types other than complex partial. It may also be more likely to occur in children who have infantile spasms. In all other patient demographics and diet parameters, an equal likelihood of similar success was found.
Upregulation of MMP‐9/TIMP‐1 enzymatic system in eosinophilic meningitis caused by Angiostrongylus cantonensis
Authors: Chen Ke‐Min , Lee Hsiu‐Hsiung , Chou Hui‐Lin , Liu Jer‐Yuh , Tsai Bo‐Cyuan , Lai Shih‐Chan 
Published: March 2005

SummaryProteolysis depends on the balance between the proteases and their inhibitors. Matrix metalloproteinase‐9 (MMP‐9) and its specific inhibitors, tissue inhibitors of metalloproteinases (TIMP), contribute to eosinophilic inflammatory reaction in the subarachnoid space of the Angiostrongylus cantonensis‐infected mice. The expression of MMP‐9 in cerebrospinal fluid (CSF) was significantly increased in mice with eosinophilic meningitis, compared to that in uninfected ones. However, the TIMP‐1 levels were unchanged and remained at basal levels at all time points, even in uninfected mice. Elevated MMP‐9 mRNA expression coincided with protein levels and proteolytic activity, as demonstrated by means of positive immunoreactivity and gelatin zymography. CSF protein contents correlated significantly with MMP‐9 intensity and CSF eosinophilia. In addition, immunohistochemistry demonstrated MMP‐9 and TIMP‐1 localization in eosinophils and macrophages. When the specific MMP inhibitor, GM6001, was added, MMP‐9 enzyme activity was reduced by 45.4%. The percentage of eosinophil increased significantly upon the establishment of infection, but subsided upon inhibition. These results show that MMP‐9/TIMP‐1 imbalance in angiostrongyliasis may be associated with eosinophilic meningitis.
A transmission electron microscopic study of microglia/macrophages in the hippocampal cortex and neocortex following chronic exposure to valproate
Authors: Sobaniec‐Lotowska Maria E. 
Published: March 2005

SummaryIn chronic administration of sodium valproate to rats, significant disorders of structural integrity of the hippocampal gyrus and the neocortex of the temporal lobe, observed in the last two stages of the experiment (after 9 and 12 months), coexisted with increased number of microglial cells and, especially after 12 months, with intense phagocytic activity within these cells. At the ultrastructural level, phagocyte microglial cells were hypertrophied with several broadened processes. Their cytoplasm contained rich lysosomal apparatus, numerous lipofuscin‐like structures, lipid droplets and multilaminated bodies. The nuclei of these cells were characteristic oval or round and sometimes triangle in shape with dense and highly clumped heterochromatin, distinctly accumulated under nuclear envelope, and sparse euchromatin. Microglia/macrophages were frequently present in a close vicinity of changed neuronal somata and also close to the altered elements of the neuropil pyramidal layer of the cortex. Microglial response may, together with abnormalities in neurones, astroglia and blood–brain barrier, play a significant role in the development of experimental valproate encephalopathy.
Effects of neutrophil depletion in the local pathological alterations and muscle regeneration in mice injected with Bothrops jararaca snake venom
Authors: Teixeira Catarina F. P. , Chaves Fernando , Zamunér Stella R. , Fernandes Cristina M. , Zuliani Juliana P. , Cruz‐Hofling María Alice , Fernandes Irene , Gutiérrez José María 
Published: March 2005

SummaryIn order to study the role of neutrophils in the acute local pathological alterations induced by Bothrops jararaca snake venom, and in the process of skeletal muscle regeneration that follows, an experimental model was developed in mice pretreated with either an anti‐mouse granulocyte rat monoclonal immunoglobulin G, which induces a profound neutropenia, or an isotype‐matched control antibody. B. jararaca venom induced prominent haemorrhage and oedema, but only a moderate myonecrosis. No significant differences were observed in the extent of local haemorrhage, oedema and myonecrosis between neutropenic and control mice, suggesting that neutrophils do not play a determinant role in the acute pathological alterations induced by B. jararaca venom in this experimental model. Moreover, no differences were observed in skeletal muscle regeneration between these two experimental groups. In both the cases, limited areas of myonecrosis were associated with a drastic damage to the microvasculature and a scarce inflammatory infiltrate, with the consequent lack of removal of necrotic debris during the first week, resulting in a poor regenerative response at this time interval. Subsequently, a similar regenerative process occurred in both groups, and by 30 days, necrotic areas were substituted by groups of small regenerating muscle fibres. It is suggested that the drastic effect exerted by B. jararaca venom in the microvasculature precludes an effective access of inflammatory cells to necrotic areas, thereby compromising an effective removal of necrotic debris; this explains the poor regenerative response observed during the first week and the fact that there were no differences between neutropenic and control mice. As neutropenia in this model lasted only 7 days, the successful regenerative process observed at 30 days is associated with revascularization of necrotic regions and with a successful removal by phagocytes of necrotic debris in both groups.
Enhancement of the repair of meniscal wounds in the red–white zone (middle third) by the injection of bone marrow cells in canine animal model
Authors: Abdel‐Hamid Mohammed , Hussein Mahmoud R. , F. Ahmad Ahmad , Elgezawi Ebtisma M. 
Published: March 2005

SummaryBone marrow stem cells (BMSCs) can differentiate into several cells that participate in the healing of meniscal wounds. To test this hypothesis, we examined the effects of injected BMSCs on the healing of meniscal wounds. Autologous BMSCs from eight adult dogs were injected into meniscal wounds (knee joints). After 12 weeks, the healing process was clinically and immunomorphologically evaluated using: (i) histochemical stains (haematoxylin and eosin, Masson trichrome and periodic acid–Schiff) and (ii) immunoperoxidase staining methods (CD3, CD79a, CD68, CD31 and alpha smooth‐muscle actin for T, B lymphocytes, macrophages, endothelial cells and smooth‐muscle lineage). Complete (six vs. three), partial (one vs. one) and no healing (one vs. four animals) of the meniscal wounds were observed in the injected and noninjected menisci. As compared with the noninjected menisci, examination of the tissues from the injected ones revealed: (i) marked angiogenesis (microvessel density: 3.22 ± 0.66 vs. 6.50 ± 2.10); (ii) chondrogenesis; (iii) prominent immune cell infiltrate (4.07 ± 0.78 vs. 9.56 ± 1.69, 8.33 ± 0.77 vs. 3.67 ± 1.00 and 4.38 ± 0.62 vs. 11.1 ± 1.43 for the total numbers of immune cells, lymphocytes and macrophages, respectively); and (iv) proliferation of the fibroblasts with marked deposition of collagen fibres (2.0 ± 0.84 vs. 2.66 ± 0.48). These values were statistically significantly higher for the injected menisci as compared with the noninjected ones (P ≥ 0.05). Autologous BMSCs can improve meniscal wound healing. Whether this improvement occurs through BMSC differentiation into cells operational in the repair process, the release of certain mediator or other unknown mechanisms mandates further investigations.
Differences in the effects of age on intestinal proliferation, crypt fission and apoptosis on the small intestine and the colon of the rat
Authors: Mandir Nikki , FitzGerald Anthony J. , Goodlad Robert A. 
Published: March 2005

SummaryThe increase in gastrointestinal epithelial tissue mass and the development of the gut can occur through three main mechanisms, namely elevated cell production from the intestinal crypts, by raised crypt number, which occurs through the process of crypt fission or by altered apoptosis. The small bowel and the colon have various rates of these, which were studied in rats of various ages. Wistar rats were fed ad libitum, and were killed at 3, 4, 6, 9, 12, 18, 26 and 48 weeks of age. Tissue was later stained and microdissected and the number of native mitoses and apoptotic figures per crypt and the percentage of crypts in fission were determined. There was an almost linear increase in body weight from 3 to 9 weeks, followed by a more gradual rise until 18 weeks. The weight of the stomach and the small intestine reached maximum values at 9 weeks, whereas the caecum and the colon approached this at 12 weeks. Mitotic activity per crypt in the small intestine increased from 3.8 ± 0.1 at 3 weeks to 7.8 ± 0.4 mitoses per crypt (P < 0.001) at 9 weeks and then decreased slightly; crypt fission increased from 4.6% ± 0.8 at 3 weeks to 8.4 ± 0.9% at 6 weeks and then decreased gradually reaching a value of 1.5 ± 0.4% at 48 weeks. Apoptosis also peaked at 6 weeks and was then very low. In the colon, the proliferation decreased from 4.2 ± 0.2 mitoses per crypt in the young (3 weeks) rat and reached a plateau by 9 weeks (2.5 ± 0.1 mitoses per crypt, P < 0.001). Crypt fission also declined rapidly in the first 9 weeks (from 67.6 ± 4.2 to 23.1 ± 4.6%, P < 0.01) and then continued to decline, although at a lower rate. The crypt fission index at 48 weeks was 9.8 ± 1.0. Apoptosis in the colon persisted throughout the duration of the study, 0.19 ± 0.06 apoptotic bodies per crypt were seen at week 48. The development of the small intestine is more dependent on cell proliferation, whereas in the colon crypt fission is far more predominant, with the colon having fission indices approximately six times greater than those of the small intestine. Proliferative activity in the colon was approximately half that of the small intestine.
Intramuscular pressure and tissue oxygenation during low‐force static contraction do not underlie muscle fatigue
Authors: Blangsted A. K. , Vedsted P. , Sjøgaard G. , Søgaard K. 
Published: March 2005

AbstractAim:  To test the hypothesis that time‐wise increase in intramuscular pressure (IMP) and subsequent decrease in muscle tissue oxygenation (TO2) results in muscle fatigue development during a non‐exhaustive, low‐force contraction evidenced by changes in electromyogram (EMG) and particular mechanomyogram (MMG).Methods:  Seven subjects performed static elbow flexion at 10% maximal voluntary contraction (MVC) for 10 min (10% MVC10 min). Surface EMG, MMG, IMP and TO2 measured by near‐infrared spectroscopy was recorded from m. biceps brachii during 10% MVC10 min and during 5% MVC test contractions of 1 min duration performed before 10% MVC10 min, 10 and 30 min post‐exercise. EMG and MMG were analysed for root mean square (rms) and mean power frequency (mpf).Results:  During 10% MVC10 min MMGrms increased from initial level of 0.04 ± 0.01 to 0.11 ± 0.07 m s−2 in the last minute and MMGmpf and EMGmpf decreased from 34.9 ± 8.2 to 21.3 ± 3.8 Hz and from 71.7 ± 10.9 to 61.7 ± 10.0 Hz respectively. Similar changes were present in 5% MVC test contractions 30 min post‐exercise. Initially, TO2 decreased by 6.9 ± 6.5% of resting level but returned to rest within 1 min. IMP remained constant during the contraction after an initial fourfold increase from resting level of 12.2 ± 10.4 mmHg.Conclusions:  IMP was anticipated to increase with time of contraction due to e.g. increased muscle water content; but this was not confirmed. Consequently, muscle blood flow was unlikely to be impeded with contraction time, which may account for the maintenance of TO2. Thus, decreased TO2 did not underlie either acute or long‐term muscle fatigue development evidenced by changes in EMG and particular MMG variables.
Measuring bronchodilation in COPD clinical trials
Authors: Borrill Z. L. , Houghton C. M. , Woodcock A. A. , Vestbo J. , Singh D. 
Published: March 2005

AimsThe aim of this study was to compare the variability and sensitivity of impulse oscillometry (R5, X5 and RF), plethysmography (Raw and sGaw) and spirometry (FEV1, FVC and MMEF) in order to determine the most powerful technique for assessing bronchodilation in COPD clinical trials.MethodsTwenty‐four patients with COPD had impulse oscillometry, plethysmography and spirometry measured twice 30 mins apart, to determine variability. Then ascending doses of salbutamol (20, 50, 100, 200, 400 and 800 µg) were given and the same measurements made after each dose. Significant changes greater than variability were determined for each performed measurement (expressed as mean percentage improvement with 95% CI).ResultsSignificant effects (P < 0.05) were detected after 20 µg by X5 (18.5% CI 9.8–27.2) RF (11.1% CI 7.2–15.0) and sGaw (21.5% CI 10.1–32.9), and after 50 µg by R5 (16.7% CI 10.8–22.5) and Raw (19.7% CI 13.0–26.4). FEV1 was less sensitive, detecting significant bronchodilation at 100 µg (10.2% CI 7.4–12.9).ConclusionsWe conclude that impulse oscillometry and plethysmography should be considered the preferred techniques for measuring bronchodilation in COPD clinical trials.
Pharmacogenetic profiling across the irinotecan pathway in Asian patients with cancer
Authors: Zhou Qingyu , Sparreboom Alex , Tan Eng‐Huat , Cheung Yin‐Bun , Lee Ann , Poon Donald , Lee Edmund J. D. , Chowbay Balram 
Published: March 2005

AimsThe aim of this exploratory study was to investigate associations between irinotecan pharmacokinetic parameters and allelic variants in genes encoding for drug transporters and drug metabolizing enzymes that are involved in irinotecan disposition in Asian patients with cancer.MethodsIrinotecan was administered at 100 mg m−2 over 90 min on a weekly schedule to 29 nasopharyngeal carcinoma patients and pharmacokinetic analysis was performed during the first cycle. All patients were genotyped for allelic variants in genes encoding drug metabolizing enzymes (CYP3A4, CYP3A5, UGT1A1) and drug transporters (ABCB1, ABCC2 and ABCG2) that are involved in irinotecan disposition.ResultsOf the six candidate genes that were analyzed, 11 genetic variants were found. Significant genotypic–phenotypic associations were apparent only for transporter genes. The Cmax of irinotecan was significantly lower in patients carrying the CC genotype at exon 26 of the ABCB1 gene compared with those harbouring at least one variant allele (P = 0.047). Patients harbouring the wild type ABCG2 CTCA genotype were associated with significantly higher values for relative extent of conversion (REC) of irinotecan to SN‐38 compared with patients carrying at least one deletion CTCA allele (P = 0.019).ConclusionsThe present exploratory study shows that genetic polymorphisms in drug transporter genes, particularly in ABCB1 and ABCG2 genes, may be important in influencing the pharmacokinetics of irinotecan and its metabolites. The predictive value of the identified allelic variants in the ABCG2 and ABCB1 genes on irinotecan disposition should be further investigated in a larger patient population as well as in other ethnic populations.