bluuebunny/crossref_metadata_2025 huggingface dataset:
Migraine as an Etiology of Stroke in Young Adults
Authors: Spaccavento Leo J. , Solomon Glen D.
Published: June 2005

SYNOPSIS

A retrospective study of strokes due to ischemic cerebrovascular disease in young adults was undertaken, and the incidence of migraine as an etiologic factor was studied. Within the last five years, fifteen patients between the ages of twenty and forty were admitted to the USAF Medical Center Wright‐Patterson with the diagnosis of stroke due to ischemic cerebrovascular disease. These patients underwent extensive evaluations including CT scan and/or cerebral angiography. In four patients (27%), there was a previously documented history of classic migraine. Three patients experienced migraine attacks at the time of their stroke. The fourth had an antecedent history of classic migraine with basilar artery migraine symptoms, and suffered a lateral medullary syndrome. The remaining data are as follows: 3 patients (20%) had valvular heart disease, 1 patient had sickle cell anemia, 1 patient had a dural sinus thrombosis following infection and 6 patients (40%) had no discernible etiology. We conclude that migraine may represent a more common etiology of stroke in young adults than has been previously recognized.
Plasma Cyclic Nucleotide Responses to Methacholine and Epinephrine in Patients With Migraine
Authors: Okada Fumihiko , Miyagishi Tsutomu , Honma Miyuki , Ui Michio
Published: June 2005

SYNOPSIS

The purpose of the present study is to show anomalies of the plasma cyclic nucleotide responses of patients with migraine to intramuscular injections of methacholine (80 μg/kg body wt) and epinephrine (0.4 mg/person). The methacholine‐ or epinephrine‐induced increases in plasma cyclic GMP were much larger in patients with migraine than in controls. In the case of methacholine injection, there was also a small but significant rise of plasma cyclic AMP in patients with migraine, while no change was observed in controls. On the other hand, there was no significant difference in the epinephrine‐induced increase in plasma cyclic AMP between patients with migraine and controls. From these findings it may be assumed that cholinergic or a‐adrenergic receptor responses are enhanced in patients with migraine.
Efficacy of Meclofenamate Sodium versus Placebo in Headache and Craniofacial Pain
Authors: Mongini F. , Bona G. , Garnero M. , Gloria A.
Published: June 2005

SYNOPSIS

Twenty patients were enrolled in a double‐blind, placebo‐controlled crossover study of meclofenomate sodium in headache and craniofacial pain. There were four observation periods of 15 days each: Period I was a wash‐out period. In period 2, subjects were randomly assigned to a 15‐day regimen of taking two capsules a day of 100mg meclofenamate sodium (group 1) or placebo (group 2). In period 3, group I was switched to placebo and group 2 to meclofenamate sodium for the next 15 days. Lastly, the patients took no medication for a further 15 days (period 4). A thermographic record of the craniofacial and neck areas was taken at the end of periods 1 and 4. A record of the pressure threshold and tissue compliance at different sites of the craniofacial, neck and shoulder areas was taken at the end of each period. During the trial, number and duration of painful events were recorded daily by the patients, and the level of pain evaluated on a visual analog scale. Mean data were analyzed for significant difference by ANOVA and paired t‐test. During the meclofenamate sodium period, there was a significant decrease of days with painful events compared to the wash‐out period in group I and compared to the placebo period in group 2. In the majority of patients, the meclofenamate sodium period scored lowest or second‐lowest after the follow‐up period in mean pain intensity. Data for pressure threshold, although not significant, were indicative of a possible increase during and after intake of meclofenamate sodium. An improvement of thermal symmetry was recorded at the second thermogram in a majority of patients. It is concluded that meclofenamate sodium showed a consistent analgesic effect in our patients, compared to the placebo.
Autonomic Function Testing in Patients with Tension‐Type Headache
Authors: Pogacnik Tomaz , Sega Sasa , Mesec Anton , Kiauta Tomaz
Published: June 2005

SYNOPSIS

Autonomic nervous system function was studied in 51 patients with tension‐type headache. The Valsalva manoeuvre, deep breathing test, sustained handgrip test, orthostatic test and spectral analysis of heart rate variability in the supine and standing positions were performed in a group of 51 patients of both sexes aged 21 to 50 years and in an age‐matched control group of 45 healthy volunteers.

Diastolic blood pressure increase and particularly heart rate increase during sustained handgrip were significantly reduced in the headache group, when compared to the control group, while the results of the remaining tests did not significantly differ between the control and headache groups. No significant differences were found between the episodic (19 patients) and chronic (32 patients) tension‐type headache subgroups.

It is concluded that sympathetic function is impaired in tension‐type headache patients.
Relation Between Headaches and Neuropsychological Functioning Among Head Injury Patients
Authors: Tsushima William T. , Tsushima Vincent G.
Published: June 2005

SYNOPSIS

The Luria‐Nebraska Neuropsychological Battery (LNNB) and the Minnesota Multiphasic Personality Inventory (MMPI) were administered to 184 head injury patients with varying degrees of headache activity. A multiple regression analysis, controlling for neurological status, compared the 11 LNNB scores ofpatients with Daily Headache, Frequent Headaches, Infrequent Headaches, and No Headaches and foundthat the Arithmetic Scale was the only significant predictor, with the Daily Headache patients performing more poorly than the Infrequent Headache patients. A similar analysis of the 13 MMPI scores indicated that the K, He, and Pt Scales were significant predictors. However, post hoc Tukey tests revealed that K and Pt scores did not vary significantly among the four headache groups and only showed that Daily Headaches and Frequent Headaches patients had significantly higher Hs scores than the No headaches group. Subsequent comparisons of patients with and without headaches at the time of testing revealed no differences between the two groups on the LNNB and MMPI, after controlling for age, duration of symptoms, and neurological status. Overall, the results suggested that the relation between headache symptoms and neuropsychological functioning was insignificant.
Headache Associated With the Chiari Type I Malformation.
Authors: Stovner Lars Jacob
Published: June 2005

SYNOPSIS

The main purpose of the present study was to define and understand more clearly the headache, and in particular the long‐lasting attacks or continuous pain associated with the Chiari type I malformation. Of 34 patients with the malformation, the 20 patients who had or had had headache problems were interviewed according to a standardized questionnaire. Many patients had several headache types. Ten patients had shortlasting “cough headache” attacks lasting less than 5 minutes, 14 patients had relatively long‐lasting attacks lasting from 3 hours to several days, and 8 patients had continuous headache. Unlike the short‐lasting cough headache attacks, long‐lasting attacks were usually not precipitated by Valsalva‐like maneuvers. With discriminant analysis, this headache could rather well be differentiated from that of migraine and cervicogenic headache patients. In many respects, however, this headache resembled cervicogenic headache with occipital and neck pain, pain In the arm, restriction of neck movement, and dizziness often accompanying the headache. Dizziness was the meat distinguishing feature in the Chiari patients. These features, together with a beneficial effect of surgical treatment in some patients, suggest a causal relationship between the malformation and headache. From the histories of a few Illustrative cases, It is suggested that the malformation may cause long‐lasting headache attacks or continuous head pain by compression of the brainstem, central cord degeneration or intracranial hypertension.
Headache in College Students: A Comparison of Four Populations
Authors: Forgays Donald G. , Rzewnicki Randy , Ober Allison J. , Forgays Deborah K.
Published: June 2005

SYNOPSIS

Recent studies have reported a much lower rate of headache prevalence for Australian college students as compared with those for two campuses in the United States. We present such data here for a third U.S. campus and make several comparisons of these data for the four campuses. While the gender difference of higher female over male headache frequency was found for all four campuses, the same measure for combined genders is reliably higher for all three U.S. groups over their Australian counterpart and there are significant differences among the U.S. groups as well. Possible reasons for these campus differences in headache prevalence are outlined and discussed and further research is indicated.
Episodic Paroxysmal Hemicrania: 3 New Cases and a Review of the Literature
Authors: Newman Lawrence C. , Lipton Richard B. , Solomon Seymour
Published: June 2005

SYNOPSIS

Episodic paroxysmal hemicrania (EPH) is a rare, benign disorder characterized by discrete bouts of hemicranial headaches separated by periods of pain‐free remissions. EPH is frequently mistaken for episodic cluster headache because they have similar temporal profiles and clinical features. EPH is differentiated from cluster headaches by an increased frequency and a shorter duration of individual attacks. Establishing the diagnosis of EPH is important because of its unique response to treatment with indomethacin and not standard anti‐cluster headache medications.
Cluster Headache In Identical Twins
Authors: Sjaastad O. , Shen J‐M. , Stovner L.J. , EIsås T.
Published: June 2005

SYNOPSIS

Twin brothers with cluster headache are described. Monozygosity was demonstrated by conventional genetic markers and DNA‐typing. Both had “mini‐bouts” in the early stages. In the one, attacks were always excruciatingly severe; in the other, they started out as “mild”, eventually becoming more severe. Both brothers also suffered from paroxysmal tachycardia. The connection between attacks of tachycardia and cluster headache remains enigmatic.

The observation of cluster headache in monozygotic twins underscores the importance of genetic factors in the etiology. The ratio between cluster headache prevalence in close family members vs. prevalence in the general population may be higher in cluster headache than in migraine.
Changes of Cortical Interhemispheric Responses after Status Epilepticus in Immature Rats
Authors: Mareš Pavel , Tsenov Grygoriy , Aleksakhina Katarina , Druga Rastislav , Kubová Hana
Published: June 2005

Summary: Purpose:To study cortical excitability after status epilepticus induced in two age groups of immature rats.

Methods:Lithium‐pilocarpine status epilepticus was elicited in 12‐ (SE12) or 25‐day‐old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of sensorimotor region of cerebral cortex 3, 6, 9, 13, or 26 days after status. Single biphasic pulses with intensities from 0.2 to 4 mA were used for stimulation; eight responses were always averaged. Amplitude of the first positive and negative waves (i.e., monosynaptic transcallosal responses) was measured and used for construction of input–output (I/O) curves. FluoroJade B was used to visualize degenerating neurons 24 h after status in both age groups.

Results:No significant changes were found at short intervals, but only a tendency to lower amplitudes 3 days after status in SE12 group. Marked changes appeared 26 days after status. The younger group exhibited lower amplitudes than did control rats, whereas SE25 animals generated responses with higher amplitude than did controls (i.e., the I/O curve was steeper. FluoroJade B‐positive neurons were scarce in SE12 rats, whereas a substantial number of positive neurons was found in SE25 animals. The positive neurons exhibited characteristics of interneurons, and their distribution in cortical layers differed in the two groups.

Conclusions:Status epilepticus resulted in neuronal death in both SE12 and SE25 animals. Changes in transcallosal evoked potentials were opposite in the two age groups. Augmented amplitude of responses in SE25 rats may indicate an increased cortical excitability.
Inflammatory Response and Glia Activation in Developing Rat Hippocampus after Status Epilepticus
Authors: Ravizza Teresa , Rizzi Massimo , Perego Carlo , Richichi Cristina , Velískǒvá Jana , Moshé Solomon L. , De Simoni M. Grazia , Vezzani Annamaria
Published: June 2005

Summary:  Purpose: We investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal damage, 4 and 24 h after kainic acid–induced status epilepticus (SE) in postnatal day (PN) 9, 15, and 21 rats.

Methods: Limbic seizures were induced by systemic injection of kainic acid. Glia activation and neuronal cell loss were studied by using immunocytochemistry and Western blot. Cytokine expression was analyzed by reverse transcriptase–polymerase chain reaction (RT‐PCR) followed by Southern blot quantification.

Results: After SE onset, hippocampal glia activation, cytokine expression, and neuronal damage are all age‐dependent phenomena. In the hippocampus, neuronal injury occurs only when cytokines are induced in glia, and cytokine synthesis precedes the appearance of degenerating neurons. Neuronal injury is more pronounced when interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) are produced in addition to IL‐1β.

Conclusions: This study shows that cytokine induction in rat brain after sustained seizures is age dependent, and it is associated with the appearance of cell injury.
Reduced Serotonin and 3‐Hydroxyanthranilic Acid Levels in Serum of Cystatin B‐Deficient Mice, a Model System for Progressive Myoclonus Epilepsy
Authors: Arbatova Jelena , D'Amato Elena , Vaarmann Annika , Zharkovsky Alex , Reeben Mati
Published: June 2005

Summary:  Purpose: To evaluate the levels of tryptophan and its metabolites along serotonin (5‐HT) and kynurenine (KYN) pathways in serum of progressive myoclonus epilepsy (EPM1) patients and cystatin B (CSTB)‐deficient mice, a model system for EPM1.

Methods: Tryptophan and its metabolites along serotonin (5‐HT) and KYN pathways were determined in serum of EPM1 patients and CSTB‐deficient mice by reverse‐phase high‐pressure liquid chromatography (HPLC) with electrochemical detection.

Results: Reduced levels of 5‐HT and KYN intermediate metabolite 3‐hydroxyanthranilic acid were found in serum of CSTB‐deficient mice. A similar trend was found in EPM1 patients. Although tryptophan concentration was reduced in serum of EPM1 patients, no such decrease was observed in CSTB‐deficient mice.

Conclusions: The present study demonstrates that tryptophan metabolism along 5‐HT and KYN pathways are disrupted in EPM1. Further studies are needed to elucidate the role of KYN pathway in pathogenesis of EPM1.
Alterations in Seizure Susceptibility and in Seizure‐induced Plasticity after Pharmacologic and Genetic Manipulation of the Fibroblast Growth Factor‐2 System
Authors: Zucchini Silvia , Barbieri Mario , Simonato Michele
Published: June 2005

Summary:  Purpose: The adult brain undergoes activity‐dependent plastic modifications during pathologic processes that are reminiscent of those observed during development. For example, seizures induce neuronal loss, neurogenesis, axonal and dendritic sprouting, gliosis, and circuit remodeling. Neurotrophic factors and fibroblast growth factor‐2 (FGF‐2), in particular, are well‐known mediators in each of these cellular events. The aim of this minireview is to summarize and discuss the data supporting the idea that FGF‐2 may be involved in seizure generation and in their sequelae.

Methods: We used epilepsy models of kainate and kindling, with FGF‐2 knockout mice and FGF‐2 overexpressing mice.

Results: Seizures increase FGF‐2 mRNA and protein levels in specific brain areas and upregulate the expression of its receptor FGFR‐1. Short‐term intrahippocampal injection of FGF‐2 cause seizures, whereas long‐term i.c.v. infusion of low‐dose FGF‐2 does not affect kainate seizures but promotes behavioral recovery and reduces hippocampal damage. Kainate seizure severity is not altered in FGF‐2 knockout mice, but is increased in FGF‐2 overexpressing mice.

Conclusions: FGF‐2 is implicated in seizure susceptibility and in seizure‐induced plasticity.
The Role of Extracellular Potassium in the Epileptogenic Transformation of Recurrent GABAergic Inhibition
Authors: Bihi Rachid Id , Jefferys John G. R. , Vreugdenhil Martin
Published: June 2005

Summary:  Purpose: Epileptiform burst‐firing can occur in hippocampal area CA1 where recurrent excitation is relatively weak and recurrent inhibition strong. Recent observations suggest that recurrent inhibition can transform into recurrent excitation because of collapse of the chloride gradient. Here we assess the role of potassium in this epileptogenic transformation.

Methods: Extracellular field potential recordings, combined with either intracellular recordings from pyramidal neurons or extracellular potassium concentration recordings, were made in vitro from isolated CA1 minislices cut from the rat hippocampus and in vivo from area CA1 in urethane‐anesthetized rats. Burst responses were evoked by 5‐Hz alveus stimulation.

Results: The 5‐Hz alveus stimulation in vitro caused a transient period of burst responses that was associated with a transient increase in synaptic input in stratum oriens and a transient shift of the reversal potential of the synaptic potential. These changes were related to the transient increase in extracellular potassium concentration in stratum oriens. Observations in vivo confirmed the relation between bursting and extracellular potassium concentration in stratum oriens.

Conclusions: Use‐dependent increase of extracellular potassium concentration in stratum oriens facilitates the collapse of the chloride gradient in the basal dendrites and transforms γ‐aminobutyric acid (GABA)ergic inhibition into GABAergic excitation, giving rise to burst firing. Improvement of intracellular chloride homeostasis or extracellular potassium homeostasis could reduce epileptogenicity.
Detection of Increased Local Excitatory Circuits in the Hippocampus during Epileptogenesis Using Focal Flash Photolysis of Caged Glutamate
Authors: Shao Li‐Rong , Dudek F. Edward
Published: June 2005

Summary:  Purpose: Local synaptic circuits, particularly recurrent excitation, are hypothesized to contribute to the generation and synchronization of epileptiform activity. The present study tested whether local excitatory circuits in the hippocampus are increased in an animal model of temporal lobe epilepsy, and thus may contribute to epileptic seizures.

Methods: Rats were given hourly injections of kainic acid to induce status epilepticus, which led to chronic epilepsy with spontaneous recurrent seizures. Whole‐cell recording was performed in hippocampal slices, and focal flash photolysis of caged glutamate was used to detect local excitatory circuits.

Results: In the dentate gyrus of rats with kainate‐induced epilepsy and mossy fiber sprouting, focal stimulations with caged glutamate at many different sites in the granule cell layer consistently evoked repetitive excitatory postsynaptic currents (EPSCs) in normal medium and prolonged bursts of action potentials in bicuculline; these responses were not observed in similarly treated slices from control rats. In CA1, focal flash photolysis of caged glutamate in stratum pyramidale revealed significantly more excitatory connections between CA1 pyramidal cells in rats with kainate‐induced epilepsy than saline‐treated control animals.

Conclusion: Focal flash photolysis of caged glutamate revealed that new local excitatory circuits are formed in both the dentate gyrus and CA1 area of rats with kainate‐induced epilepsy, which supports the hypothesis that the progressive formation of new local excitatory circuits occurs in many locations during epileptogenesis.
Autoantibodies and Cell‐mediated Autoimmunity to NMDA‐type GluRɛ2 in Patients with Rasmussen's Encephalitis and Chronic Progressive Epilepsia Partialis Continua
Authors: Takahashi Yukitoshi , Mori Hisashi , Mishina Masayoshi , Watanabe Masahiko , Kondo Naomi , Shimomura Jiro , Kubota Yuko , Matsuda Kazumi , Fukushima Katsuyuki , Shiroma Naohide , Akasaka Noriyuki , Nishida Hiroshi , Imamura Atsushi , Watanabe Hiroo , Sugiyama Nobuyoshi , Ikezawa Makoto , Fujiwara Tateki
Published: June 2005

Summary:  Purpose: To evaluate antibody‐mediated and cytotoxic T cell–mediated pathogenicity that has been implicated as the autoimmune pathophysiological mechanism in Rasmussen's encephalitis.

Methods: We examined autoantibodies against the N‐methyl‐d‐aspartate glutamate receptor (NMDA‐type GluR) ɛ2 subunit and its epitopes in serum and CSF samples from 20 patients [five histologically proven (definitive) Rasmussen's encephalitis with epilepsia partialis continua (EPC), four definitive Rasmussen's encephalitis without EPC, and 11 clinical Rasmussen's encephalitis with EPC]. We examined 3H‐thymidine uptake into lymphocytes after stimulation by GluRs.

Results: All nine definitive patients (five patients with EPC and four without EPC), and 10 of 11 clinical Rasmussen's encephalitis patients had the autoantibodies. In four patients, the autoantibodies were absent in early stage when epileptic seizures had already become frequent, and appeared subsequently. In two patients, the autoantibodies persisted in the serum after frontal lobe resection or functional hemispherectomy, although epileptic seizures were completely controlled. Autoantibodies to the C2 epitope predominated, while autoantibodies to the extracellular N epitope were rare. The mean 3H‐thymidine uptake ratios (stimulation by GluRɛ2‐containing homogenates/stimulation by PHA) were significantly higher in definitive and clinical Rasmussen encephalitis patients than in controls. The mean 3H‐thymidine uptake ratios (relative to PHA) were significantly higher for GluRɛ2‐containing homogenate than for control homogenate or GluRδ2‐containing homogenate.

Conclusions: Autoantibodies against GluRɛ2 may be one of the diagnostic markers for Rasmussen's encephalitis with and without EPC. Patients have activated T cells stimulated by GluRɛ2 in peripheral blood circulation. We speculate that cellular autoimmunity and the subsequent humoral autoimmunity against GluRɛ2 may contribute to the pathophysiological processes in Rasmussen's encephalitis.
Long‐term Effect of Convulsive Behavior on the Density of Adenosine A1 and A2A Receptors in the Rat Cerebral Cortex
Authors: Rebola Nelson , Porciúncula Lisiane O. , Lopes Luísa V. , Oliveira Catarina R. , Soares‐da‐Silva Patrício , Cunha Rodrigo A.
Published: June 2005

Summary:  Purpose: Adenosine is a neuromodulator that has been proposed to act as an anticonvulsant mainly via inhibitory A1 receptors, but recent data show that genetic deletion of facilitatory A2A receptors might also attenuate convulsions. Since both A1 and A2A receptors are prone to down‐ and upregulation in different stressful situations, we investigated if convulsive behavior leads to a long‐term change in A1 and A2A receptor density in the rat cerebral cortex.

Methods: Stage 4‐5 convulsions (Racine's scale) were induced in adult Wistar rats either through amygdala stimulation (kindling) or by intraperitoneal injection of kainate (10 mg/ml). Rats were killed after 4 weeks to evaluate adenosine A1 and A2A receptor density in the cerebral cortex using both Western blot and membrane binding assays.

Results: The binding density of the A1 antagonist, 3H‐DPCPX, decreased by 40. ± 4.4% and by 20.7 ± 0.5% after kindling or kainate injection. Likewise, A1 receptor immunoreactivity in cortical membranes from kindled or kainate‐injected rats decreased by 19.1 ± 3.3% and 12.7 ± 5.7%, respectively. In contrast, the binding density of the A2A receptor antagonist 3H‐SCH 58261 increased by 293 ± 34% and by 159 ± 32% in cortical membranes from kindled or kainate‐injected rats, and A2A receptor immunoreactivity also increased by 151 ± 12% and 79.6 ± 7.0%.

Conclusions: This indicates that after convulsive behavior there is a long‐term decrease of A1 receptors accompanied by an increased density of A2A receptors, suggesting that A2A antagonists rather than A1 agonists may be more promising anticonvulsive drugs.
Modulation of Seizures and Synaptic Plasticity by Adenosinergic Receptors in an Experimental Model of Temporal Lobe Epilepsy Induced by Pilocarpine in Rats
Authors: Vianna Eduardo Paulo Morowsky , Ferreira Alice Teixeira , Doná Flávia , Cavalheiro Esper Abrão , Da Silva Fernandes Maria José
Published: June 2005

Summary:  Purpose: Adenosine is a major negative neuromodulator of synaptic activity in the central nervous system and can exert anticonvulsant and neuroprotective effects in many experimental models of epilepsy. Extracellular adenosine can be formed by a membrane‐anchored enzyme ecto‐5′‐nucleotidase. The purposes of this study were to characterize the role of adenosine receptors in modulating status epilepticus (SE) induced by pilocarpine and evaluate its neuroprotective action. Ecto‐5′‐nucleotidase activity was studied during the different phases of pilocarpine‐induced epilepsy in rats.

Methods: Adult rats were pretreated with different adenosinergic agents to evaluate the latency and incidence of SE induced by pilocarpine in rats. The neuroprotective effect also was evaluated.

Results: A proconvulsant effect was observed with DPCPX and DMPX that reduced the latency of SE in almost all rats. Pretreatment with the MRS 1220 did not alter the incidence of SE but reduced the latency to develop SE. An anticonvulsant and neuroprotective effect was detected with R‐PIA. Rats pretreated with R‐PIA had a decreased number of apoptotic cells in the hippocampus, whereas pretreatment with DPCPX did not modify the hippocampal damage. An intensification of neuronal death was observed in the dentate gyrus and CA3 when rats were pretreated with DMPX. MRS‐1220 did not modify the number of apoptotic cells in the hippocampus. An increase in the ecto‐5´‐nucleotidase staining was detected in the hippocampus during silent and chronic phases.

Conclusions: The present data show that adenosine released during pilocarpine‐induced SE via A1‐receptor stimulation can exhibit neuroprotective and anticonvulsant roles. Similar effects could also be inferred with A2a and A3 adenosinergic agents, but further experiments are necessary to confirm their roles. Ecto‐5´‐nucleotidase activity during silent and chronic phases might have a role in blocking spontaneous seizures by production of inhibitory neuromodulator adenosine, besides taking part in the mechanism that controls sprouting.
The RADAR repository: a resource for studies of infectious agents and their transmissibility by transfusion
Authors: Kleinman S.H. , Glynn S.A. , Higgins M.J. , Triulzi D.J. , Smith J.W. , Nass C.C. , Garratty George , Murphy E.L. , LeParc G.F. , Schreiber G.B. , King M.R. , Chamberland M.E. , Nemo G.J.
Published: June 2005

BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor‐recipient repository.

STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow‐up specimens for long‐term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent.

RESULTS: The repository contains pre‐ and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood–derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor‐recipient–linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T‐lymphotropic virus.

CONCLUSIONS: RADAR is a contemporary donor‐recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.
Hemostatic effects of fibrinogen γ‐chain dodecapeptide‐conjugated polymerized albumin particles in vitro and in vivo
Authors: Okamura Yosuke , Takeoka Shinji , Teramura Yuji , Maruyama Hitomi , Tsuchida Eishun , Handa Makoto , Ikeda Yasuo
Published: June 2005

BACKGROUND: Prototypes of platelet (PLT) substitutes have been studied and the focus was on a dodecapeptide, HHLGGAKQAGDV (H12), which is a fibrinogen γ‐chain carboxy‐terminal sequence (γ 400‐411) and exists only in the fibrinogen domain.

STUDY DESIGN AND METHODS: H12 was conjugated to the surface of polymerized albumin particles (polyAlb) as biocompatible and biodegradable particles with a mean diameter of 260 ± 60 nm, and the hemostatic ability of H12‐conjugated polyAlb (H12‐polyAlb) under flow conditions and thrombocytopenic rats have been studied.

RESULTS: H12‐polyAlb enhanced the in vitro thrombus formation of activated PLTs on a collagen‐immobilized plate when exposed to the flowing thrombocytopenic imitation blood. Furthermore, the analysis of the tail bleeding time of rats that were made thrombocytopenic by busulfan injection showed that H12‐polyAlb had a hemostatic effect. Based on the bleeding time and the amount injected, the hemostatic capacity of 20 H12‐polyAlb was estimated to correspond to that of one PLT.

CONCLUSION: These results were important first steps toward the development of PLT substitutes and indicated that H12‐polyAlb may be a suitable candidate for an alternative to human PLT concentrates transfused into thrombocytopenic patients in the future.
Does prevalence of transfusion‐transmissible viral infection reflect corresponding incidence in United States blood donors?
Authors: Wang Baoguang , Schreiber G.B. , Glynn S.A. , Kleinman Steven , Wright D.J. , Murphy E.L. , Busch M.P. ,   Retrovirus Epidemiology Donor Study
Published: June 2005

BACKGROUND:  Calculation of viral residual risk is dependent on estimating incidence, which is not easily obtainable by most blood centers. Prevalence, however, is readily available. Understanding whether prevalence reflects corresponding incidence may help blood centers monitor disease risks.

STUDY DESIGN AND METHODS:  With data on 12 million allogeneic donations, prevalence and incidence of transfusion‐transmitted viral infections (TTVIs) were calculated. Relationships between prevalence (in total, first‐time, and repeat donations) and incidence were analyzed for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) relative to temporal and donor demographic stratifications, respectively.

RESULTS:  Overall prevalence of HIV, HBV, and HCV did not consistently reflect corresponding incidence. The relationship between prevalence and incidence varied with time and donors’ age and was virus‐specific.

CONCLUSION:  Incidence of TTVIs cannot be easily predicted from overall prevalence. Accurate assessment of TTVI risk necessitates knowledge about donation histories and person‐years at risk. Establishing comprehensive frameworks for monitoring blood donations and infectious disease markers remains a key to monitoring blood safety.
Purification of severe acute respiratory syndrome hyperimmune globulins for intravenous injection from convalescent plasma
Authors: Zhang Zhan , Xie Yi‐Wu , Hong Jiling , Zhang Xin , Kwok Sui Yi , Huang Xiaowu , Wong Sai Wah , Wong Bing‐Lou ,   SARSIg Group
Published: June 2005

BACKGROUND:  Severe acute respiratory syndrome (SARS) is a new infectious disease caused by the SARS virus. Current first‐line treatments are experimental, and their effectiveness remains open to question. For more effective treatment and prevention of SARS, human SARS hyperimmune globulins for intravenous (IV) injection were purified in this study.

STUDY DESIGN AND METHODS:  A combination of cold ethanol precipitation and ion‐exchange chromatography was used to process pooled SARS convalescent plasma samples. Virus inactivation and removal approaches were taken to ensure safety.

RESULTS:  The purified hyperimmune globulins were formulated as a 5 percent solution, with an antibody titer specifically against the SARS virus of 1:83, 1:1600, and 1:200, as determined by enzyme‐linked immunosorbent assay, immunofluorescence assay, and neutralizing antibody test, respectively. The purity of the SARS hyperimmune globulins was 99.0 percent, and the monomer and dimer content was 100 percent. Other variables analyzed met the Chinese Requirements of Biologics for IV immune globulin. The  SARS hyperimmune globulins prepared were subsequently approved for clinical evaluation by the Chinese National Institute for the Control of Pharmaceutical & Biological Products.

CONCLUSION:  IV‐injectable, purified, and concentrated human SARS hyperimmune globulins were prepared from pooled convalescent plasma samples, which are ready to be further evaluated.
Toward closed‐system culture of blood origin endothelial cells
Authors: Wagner Stephen J. , Myrup Andrew C.
Published: June 2005

BACKGROUND: Blood outgrowth endothelial cells (BOECs) are thought to arise from very rare progenitors that are present in the mononuclear fraction of marrow or peripheral blood. Recently, BOECs have been expanded from progenitors present in buffy coat into confluent monolayers on fibronectin‐ or collagen‐coated polystyrene surfaces. A method for sterile closed‐system culture of these cells has not been described, however. Here, efforts are described toward developing closed‐system culture of BOECs derived from progenitors present in a mononuclear apheresis unit by use of a cord blood filter, a sterile connection device, and a fibronectin‐coated polycarbonate cassette.

STUDY DESIGN AND METHODS: Strongly adherent cells from a mononuclear apheresis unit were eluted from a cord blood filter and resuspended in EGM‐2 with 10 percent serum. Approximately 2 × 108 eluted cells were introduced into human fibronectin‐coated polycarbonate cassettes. Medium was introduced and removed from cassettes with a sterile connection device and changed every 2 days. After expansion, cells were either cryopreserved or characterized by fluorescence‐activated cell sorting analysis and ability to take up Dil‐Ac‐LDL.

RESULTS: After 2 to 3 weeks of culture, 3 to 28 colonies with cobblestone morphology were observed in cassettes and passed to new cassettes within 3 to 4 weeks. By approximately 5 weeks of culture, 2 × 106 cells were typically obtained. BOECs uniformly took up Dil‐Ac‐LDL and were CD31+, CD105+, CD146+, CD45–, and CD14–. A population of BOECs was HLA‐ABC+ or CD34+.

CONCLUSION: BOEC progenitors can be isolated from mononuclear apheresis units with cord blood filters, expanded with fibronectin‐coated polycarbonate cassettes, and cryopreserved.
A prospective randomized trial of a prophylactic platelet transfusion trigger of 10 × 109 per L versus 30 × 109 per L in allogeneic hematopoietic progenitor cell transplant recipients
Authors: Diedrich Beatrice , Remberger Mats , Shanwell Agneta , Svahn Britt‐Marie , Ringdén Olle
Published: June 2005

BACKGROUND: The impact of lowering the platelet (PLT) count threshold for prophylactic PLT transfusion on bleeding and PLT use in allogeneic hematopoietic progenitor cell (HPC) transplant recipients is a matter of debate.

STUDY DESIGN AND METHODS: In 166 patients, randomly assigned to receive prophylactic PLT transfusion at a trigger level less than 10 × 109 PLTs per L (T10; n = 79) or less than 30 × 109 per L (T30; n = 87), the number of PLT and red blood cell (RBC) transfusions given and the number of hemorrhagic events (WHO Grades 2‐4) were recorded.

RESULTS: No significant differences were found between the two groups regarding the clinical outcome variables (i.e., bacteremia, engraftment, graft‐vs.‐host disease [GVHD], hospital stay, death, and survival) or in the median total number of RBC transfusions given. The incidence, in Group T10 18 percent (14/79) and in Group T30 15 percent (13/87), as well as the type of bleeding were comparable. No deaths were attributed to hemorrhages. The number of PLT units transfused, however, was significantly lower in Group T10 (median, 4; range, 0‐32), than in Group T30 (median, 10; range, 0‐48; p < 0.001). Apart from the trigger level, the day of engraftment, the presence of acute GVHD, or bacteremia also affected the number of PLT transfusions.

CONCLUSION: A prophylactic PLT transfusion trigger level of less than 10 × 109 PLTs per L instead of less than 30 × 109 PLTs per L in allogeneic HPC transplant recipients was found to be safe and resulted in a decreased use of PLTs.
Magnetic bead technology in viral RNA and DNA extraction from plasma minipools
Authors: Pichl Lutz , Heitmann Alke , Herzog Petra , Oster Juergen , Smets Helga , Schottstedt Volkmar
Published: June 2005

BACKGROUND:Nucleic acid testing (NAT) of pooled plasma samples from individual blood donations for viral nucleic acids has become widely established. Full automation of such sample processing can overcome many of the problems associated with methods used so far.

STUDY DESIGN AND METHODS:In this study an automated extraction method for viral nucleic acids (parvovirus [PAV] B19 DNA, hepatitis B virus [HBV] DNA, and hepatitis A virus [HAV] RNA), starting directly from the minipool sample (n = 96, 9.6 mL), was evaluated. A magnetic separation module I (chemagic, Polymer Laboratories) in combination with the chemagic viral DNA and RNA kit special based on the use of magnetic beads was used for this purpose. More than 144 pools spiked with defined concentrations of reference material and an additional 102 pools negative for the analyte were extracted and amplified. The isolated viral nucleic acids were detected by polymerase chain reaction (PCR).

RESULTS:The assays were highly specific and obtained a 95 percent detection limit of 875 IU per mL of pooled single donation for PAV B19, 260 IU per mL for HAV, and 1274 IU per mL for HBV, respectively. The crossing points showed variation coefficients from 1.49 to 2.76 percent. The turnaround time for the whole process was 3 hours. Testing of subpools to determine an infected single donation would be possible with the same general extraction method. A total of 102 unspiked minipools (96 × 100 µL per donation) were analyzed and none tested positive.

CONCLUSION:The automated magnetic bead–based extraction in combination with real‐time PCR detection can be used to routinely screen blood donations for viremic donors to further increase the safety of blood products. Minipools as well as subpools can be directly processed.
Accuracy of the photon and electron physics in GEANT4 for radiotherapy applications
Authors: Poon Emily , Verhaegen Frank
Published: June 2005

This work involves a validation of the photon and electron transport of the GEANT4 particle simulation toolkit for radiotherapy physics applications. We examine the cross sections and sampling algorithms of the three electromagnetic physics models in version 4.6.1 of the toolkit: Standard, Low‐energy, and Penelope. The depth dose distributions in water for incident monoenergetic and clinical beams are compared to the EGSNRC results. In photon beam simulations, all three models agree with EGSNRC to within 2%, except for the buildup region. Larger deviations are found for incident electron beams, and the differences are affected by user‐imposed electron step limitations. Particle distributions through thin layers of clinical target materials, and perturbation effects near high‐ and low‐ interfaces are also investigated. The electron step size artifacts observed in our studies indicate potential problems with the condensed history algorithm. A careful selection of physics processes and transport parameters is needed for optimum efficiency and accuracy.
Improved targeting device and computer navigation for accurate placement of brachytherapy needles
Authors: Pappas Ion P. I. , Ryan Paul , Cossmann Peter , Kowal Jens , Borgeson Blake , Caversaccio Marco
Published: June 2005

Successful treatment of skull base tumors with interstitial brachytherapy requires high targeting accuracy for the brachytherapy needles to avoid harming vital anatomical structures. To enable safe placement of the needles in this area, we developed an image‐based planning and navigation system for brachytherapy, which includes a custom‐made mechanical positioning arm that allows rough and fine adjustment of the needle position. The fine‐adjustment mechanism consists of an XYZ microstage at the base of the arm and a needle holder with two fine‐adjustable inclinations. The rotation axes of the inclinations cross at the tip of the needle so that the inclinational adjustments do not interfere with the translational adjustments. A vacuum cushion and a noninvasive fixation frame are used for the head immobilization. To avoid mechanical bending of the needles due to the weight of attached tracking markers, which would be detrimental for targeting accuracy, only a single LED marker on the tail of the needle is used. An experimental phantom‐based targeting study with this setup demonstrated that a positioning accuracy of 1.4 mm (rms) can be achieved. The study showed that the proposed setup allows brachytherapy needles to be easily aligned and inserted with high targeting accuracy according to a preliminary plan. The achievable accuracy is higher than if the needles are inserted manually. The proposed system can be linked to a standard afterloader and standard dosimetry planning module. The associated additional effort is reasonable for the clinical practice and therefore the proposed procedure provides a promising tool for the safe treatment of tumors in the skull base area.
Assessment of different computational models for generation of x‐ray spectra in diagnostic radiology and mammography
Authors: Ay M. R. , Sarkar S. , Shahriari M. , Sardari D. , Zaidi H.
Published: June 2005

Different computational methods based on empirical or semi‐empirical models and sophisticated Monte Carlo calculations have been proposed for prediction of x‐ray spectra both in diagnostic radiology and mammography. In this work, the x‐ray spectra predicted by various computational models used in the diagnostic radiology and mammography energy range have been assessed by comparison with measured spectra and their effect on the calculation of absorbed dose and effective dose (ED) imparted to the adult ORNL hermaphroditic phantom quantified. This includes empirical models (TASMIP and MASMIP), semi‐empirical models (X‐rayb&m, X‐raytbc, XCOMP, IPEM, Tuckeret al., and Bloughet al.), and Monte Carlo modeling (EGS4, ITS3.0, and MCNP4C). As part of the comparative assessment, the K x‐ray yield, transmission curves, and half value layers (HVLs) have been calculated for the spectra generated with all computational models at different tube voltages. The measured x‐ray spectra agreed well with the generated spectra when using X‐raytbc and IPEM in diagnostic radiology and mammography energy ranges, respectively. Despite the systematic differences between the simulated and reference spectra for some models, the student's‐test statistical analysis showed there is no statistically significant difference between measured and generated spectra for all computational models investigated in this study. The MCNP4C‐based Monte Carlo calculations showed there is no discernable discrepancy in the calculation of absorbed dose and ED in the adult ORNL hermaphroditic phantom when using different computational models for generating the x‐ray spectra. Nevertheless, given the limited flexibility of the empirical and semi‐empirical models, the spectra obtained through Monte Carlo modeling offer several advantages by providing detailed information about the interactions in the target and filters, which is relevant for the design of new target and filter combinations and optimization of radiological imaging protocols.
A novel method to correct for pitch and yaw patient setup errors in helical tomotherapy
Authors: Boswell Sarah A. , Jeraj Robert , Ruchala Kenneth J. , Olivera Gustavo H. , Jaradat Hazim A. , James Joshua A. , Gutierrez Alonso , Pearson Dave , Frank Gary , Mackie T. Rock
Published: June 2005

An accurate means of determining and correcting for daily patient setup errors is important to the cancer outcome in radiotherapy. While many tools have been developed to detect setup errors, difficulty may arise in accurately adjusting the patient to account for the rotational error components. A novel, automated method to correct for rotational patient setup errors in helical tomotherapy is proposed for a treatment couch that is restricted to motion along translational axes. In tomotherapy, only a narrow superior/inferior section of the target receives a dose at any instant, thus rotations in the sagittal and coronal planes may be approximately corrected for by very slow continuous couch motion in a direction perpendicular to the scanning direction. Results from proof‐of‐principle tests indicate that the method improves the accuracy of treatment delivery, especially for long and narrow targets. Rotational corrections about an axis perpendicular to the transverse plane continue to be implemented easily in tomotherapy by adjustment of the initial gantry angle.
Extracting data from a DICOM file
Authors: Riddle William R. , Pickens David R.
Published: June 2005

DICOM v3.0 is a vendor‐independent standard for digital medical images that describes a file format and network protocol for the exchange of images between computer systems. When simply viewing a DICOM file, it is not necessary for the user to understand the details of the entire DICOM standard. However, understanding parts of the standard is essential when DICOM files are read and processed by a user‐generated program. This paper offers an overview of information a user needs to write a program for extracting the image and acquisition parameters from a DICOM file.