bluuebunny/crossref_metadata_2025 huggingface dataset:
An Association Between Migrainous Aura and Hereditary Haemorrhagic Telangiectasia
Authors: Steele J. G. , Nath P. U. , Burn J. , Porteous M.E.M.
Published: June 2005

SYNOPSIS

Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by a variety of abnormalities of the vasculature.

This study investigated by questionnaire an unselected group of 58 patients suffering from HHT to identify and diagnose any headache history. These were compared with a control group comprising 40 patients with an unrelated autosomal dominant disorder, familial adenomatous polyposis.

Fifty percent of the HHT patients reported attacks of headache which fulfilled current diagnostic criteria for migraine with aura. This was over four times the figure for the control group and at least 10 times the expected level for a normal population. The auras described by all the affected patients were classic visual disturbances preceding the headaches. Two patients also described typical visual auras unassociated with headache symptoms.

The reason for such a clear association between migraine with aura and HHT is uncertain but cerebral arteriovenous malformations seem to be the likely link. A greater understanding of the reasons for the relationship may provide an insight into the pathophysiology of both conditions.
Developmental Program of Epileptogenesis in the Brain of EL Mice
Authors: Murashima Yoshiya L. , Suzuki Jiro , Yoshii Mitsunobu
Published: June 2005

Summary:  Purpose: We recently observed inducible nitric oxide synthetase (iNOS) expression and decreased Cu, Zn‐superoxide dismutase (Cu, Zn‐SOD) activities in the hippocampus of epileptic mutant EL mice at the age of 30 weeks. In addition, the immediate early gene (IEG) c‐fos is unusually expressed in the interictal period, suggesting activation of protein cascades associated with the epileptogenesis. Furthermore, DNA fragmentation has been detected preferentially in the hippocampus CA1 and the parietal cortex of EL mouse brain. It remains to be seen, however, how these abnormalities are related to the DNA fragmentation, and whether neuronal cell loss is involved. The present study was designed to address these issues.

Methods: NOS isoenzymes, pro‐ (Bax) and antiapoptotic factors (Bcl‐2, Bcl‐XL), and neurotrophic factors (brain‐derived neurotrophic factor, BDNF; neurotrophin‐3, NT‐3; fibroblast growth factor‐2, FGF‐2) were determined by immunoblotting in the EL mouse brain at various developmental stages. Hematoxylin–eosin staining was applied to the formalin‐fixed brains to examine the cell loss in the tissue. IEG expression in the interictal period was analyzed by in situ hybridization by using the 35S x‐ray emulsion method.

Results: nNOS was the major component of NOS in the hippocampus of either EL or control DDY mice. In EL mice, however, iNOS was detectable at the age of 10 weeks, at which the animals usually experience the first seizures. eNOS, which appears in DDY brain, could scarcely be identified. Even in the interictal period, EL mice expressed c‐fos continuously, preferentially in the parietal cortex and hippocampal CA1. In DDY mice, very low steady‐state levels of Bcl‐2 and Bax remained constant throughout development. In EL mice, these Bcl‐2 and Bax levels were increased even before experiencing frequent seizures. BDNF in EL mice markedly increased temporarily during ictogenesis and epileptogenesis in their early periods. Unexpectedly, no cell loss was found in the hippocampus.

Conclusions: DNA fragmentation without cell loss found in EL mouse brains appears to result from initial activation and later inactivation of the apoptotic process. Neurotrophic factors may play a role in the ictogenesis and the epileptogenesis during the early development. These gene expressions closely related to the periods critical for ictogenesis and epileptogenesis may be of particular importance in the development of antiepileptic drugs (AEDs) with novel mechanisms.
The Acute and Chronic Effect of Vagus Nerve Stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS)
Authors: Dedeurwaerdere Stefanie , Vonck Kristl , Van Hese Peter , Wadman Wytse , Boon Paul
Published: June 2005

Summary:  Purpose: The aim of this study was to evaluate the efficacy of acute and chronic vagus nerve stimulation (VNS) in genetic absence epilepsy rats from Strasbourg (GAERS). This is a validated model for absence epilepsy, characterized by frequent spontaneous absences concomitant with spike and wave discharges (SWD) on the EEG. Although absences are a benign form of seizures, it is conceptually important to investigate the efficacy of VNS in a controlled study by using this chronic epilepsy model.

Methods: Both control and stimulated GAERS were implanted with five epidural EEG electrodes and a stimulation electrode around the left vagus nerve.

In the first experiment, VNS was given when SWD occurred in the EEG; this was repeated the next day. A randomized crossover design (n = 8) was used.

In the chronic experiment, GAERS underwent EEG monitoring during a first baseline week. During the second week, the treated group (n = 18) received VNS; controls (n = 13), on the other hand, only underwent EEG recordings.

Results: On day 1 of the acute VNS experiment, the mean duration of the SWD when VNS was applied was higher than in baseline conditions (p < 0.05). However, on day 2, there was no difference in mean duration of the SWD. In the chronic VNS experiment, no statistically significant differences were found between control and stimulated GAERS.

Conclusions: Acute VNS applied shortly after the onset of SWD prolonged the mean duration of SWD in GAERS at least during the first day of VNS. Chronic stimulation hardly affected SWD in GAERS.
Modification of Epileptiform Discharges in Neocortical Neurons Following Glutamate Uptake Inhibition
Authors: Campbell Susan , Hablitz John J.
Published: June 2005

Summary:  Sodium‐dependent high‐affinity glutamate transporters regulate synaptic glutamate levels to maintain low ambient levels of glutamate and prevent excitotoxicity. Most studies using pharmacological inhibition of glutamate transport to examine the involvement of glutamate transporters in regulating synaptic activity have examined small synaptic currents. Using in vitro brain slices, we investigated the effects of uptake inhibition on two types of epileptiform activity, bicuculline‐induced paroxysmal activity, and epileptiform responses in the freeze‐lesion epilepsy model. In layer II/III pyramidal cells of the prefrontal cortex, inhibiting uptake with low concentrations of DL‐threo‐ß‐benzyloxyaspartic acid (TBOA) (20 or 30 μM) prolonged bicuculline‐induced epileptiform activity. At higher concentrations, TBOA (150 or 300 μM) caused a transient enhancement of epileptiform discharges that was followed by a decrease. In the freeze‐lesion model, inhibiting uptake also increased the amplitude and response area of evoked activity. The prolongation of epileptiform activity exhibited by the inhibition of glutamate uptake (TBOA 20 or 30 μM) is attributed to an increase in the level of glutamate extracellularly during uptake blockade, resulting in sustained activation of glutamate receptors. The decrease in epileptiform activity at higher TBOA concentration could be due to glutamate receptor desensitization or loss of excitability due to a depolarization block. The present results suggest that decreases in glutamate uptake can be proconvulsant in the two models of epilepsy examined.
Plasticity, Synaptic Strength, and Epilepsy: What Can We Learn from Ultrastructural Data?
Authors: Leite João Pereira , Neder Luciano , Arisi Gabriel Maisonnave , Carlotti Carlos Gilberto , Assirati João Alberto , Moreira Jorge Eduardo
Published: June 2005

Summary:  Central nervous system synapses have an intrinsic plastic capacity to adapt to new conditions with rapid changes in their structure. Such activity‐dependent refinement occurs during development and learning, and shares features with diseases such as epilepsy. Quantitative ultrastructural studies based on serial sectioning and reconstructions have shown various structural changes associated with synaptic strength involving both dendritic spines and postsynaptic densities (PSDs) during long‐term potentiation (LTP). In this review, we focus on experimental studies that have analyzed at the ultrastructural level the consequences of LTP in rodents, and plastic changes in the hippocampus of experimental models of epilepsy and human tissue obtained during surgeries for intractable temporal lobe epilepsy (TLE). Modifications in spine morphology, increases in the proportion of synapses with perforated PSDs, and formation of multiple spine boutons arising from the same dendrite are the possible sequence of events that accompany hippocampal LTP. Structural remodeling of mossy fiber synapses and formation of aberrant synaptic contacts in the dentate gyrus are common features in experimental models of epilepsy and in human TLE. Combined electrophysiological and ultrastructural studies in kindled rats and chronic epileptic animals have indicated the occurrence of seizure‐ and neuron loss‐induced changes in the hippocampal network. In these experiments, the synaptic contacts on granule cells are similar to those described for LTP. Such changes could be associated with enhancement of synaptic efficiency and may be important in epileptogenesis.
Behavioral and Histopathological Analysis of Domoic Acid Administration in Marmosets
Authors: Perez‐Mendes Patricia , Cinini Simone M. , Medeiros Magda A. , Tufik Sergio , Mello Luiz E.
Published: June 2005

Summary:  Purpose: To induce status epilepticus (SE) followed by the subsequent onset of spontaneous recurrent seizures, thus characterizing a new model of temporal lobe epilepsy in a nonhuman primate.

Methods: Male and female marmosets (Callithrix jacchus) (n = 18), ages between 2 and 8 years, were injected with domoic acid (0.5–4 mg/kg, i.p.) or saline, and behaviorally assessed with regard to the presence of acutely induced seizures and for ≤6 months for spontaneous seizures. Injection of doses ranging from 3.5 to 4 mg/kg either did not induce SE or resulted in fatal SE. Even a 5‐min SE duration (SE blockade resulting from diazepam injection) proved lethal to marmosets within 1 h of domoate administration, regardless of intensive care and monitoring of the animals. Animals injected with doses ranging from 0.5 to 3 mg/kg that developed only a few minor convulsive signs were allowed a 6‐month survival period for the assessment of spontaneous epileptic events. At the end of the experiment, 6‐month period, or acute intoxication associated with SE induction, animals were deeply anesthetized and had their brains subjected to histologic processing for Nissl and delta‐FosB.

Results: For the animals injected with domoate that did not develop SE (i.e., those that survived), we could not detect any behavioral signs of spontaneous epileptic seizures in the 6‐month observation period, and only minor indications of neuropathologic changes (i.e., neuronal death) over Nissl‐stained sections, as well as some small changes in the staining for delta‐FosB in a few of the animals.

Conclusions: Systemic administration of domoic acid to marmosets is not effective for the generation of a model of chronic temporal lobe epilepsy. Administration of domoic acid at doses that do not lead to SE also did not lead to the development of temporal lobe epilepsy or clear‐cut behavioral changes over a 6‐month period.
Proechimys guyannensis: An Animal Model of Resistance to Epilepsy
Authors: Arida Ricardo Mario , Scorza Fulvio Alexandre , De Amorim Carvalho Reinaldo , Cavalheiro Esper A.
Published: June 2005

Summary:  Purpose: The potential interest of Proechimys guyannensis (PG), a spiny rat species living in the Amazonian region, as an animal model of anticonvulsant mechanisms, prompted the investigation of the susceptibility of this animal species to different epileptogenic treatments.

Methods: Adult male Wistar and PG animals were submitted to amygdala kindling, the pilocarpine model and the intrahippocampal kainic acid (KA) model. Electrographic, behavioral, and neuropathological changes were compared between Wistar and PG animals.

Results: PG animals demonstrated a striking resistance to reaching stage 5 of kindling. Of the 43 PG rats submitted to the kindling process, only three animals reached stage 5. In the pilocarpine and KA models, doses lower than those used in Wistar rats were able to induce status epilepticus (SE) in PG animals. Pilocarpine‐induced SE in PG had a shorter duration, rarely exceeding 2 h, in contrast to the 8‐ to 12‐ h long SE in the Wistar rat. Of the 61 PG animals injected with pilocarpine, 48 presented with SE and only two presented with some spontaneous seizures after silent periods of 60 and 66 days. KA elicited self‐sustained electrographic SE in PG animals, which lasted for 72 h. None of the surviving animals presented with spontaneous seizures in the long‐term observation period (up to 120 days).

Conclusions: These findings indicate that the PG animal may have natural endogenous anticonvulsant mechanisms and also may be an animal model that is resistant to epileptogenic treatments.
The Subiculum: A Potential Site of Ictogenesis in Human Temporal Lobe Epilepsy
Authors: Wozny Christian , Knopp Andreas , Lehmann Thomas‐Nicolas , Heinemann Uwe , Behr Joachim
Published: June 2005

Summary:  Purpose: This study determines synaptic and intrinsic alterations of subicular pyramidal cells that are associated with activity recorded in patients suffering from temporal lobe epilepsy.

Methods: Electroencephalograms with sphenoidal electrodes were correlated with in vitro single cell recordings of subicular pyramidal cells from the corresponding resected epileptic tissue. We determined alterations of synaptic and intrinsic properties of subicular pyramidal cells that accompany spontaneous rhythmic activity in human sclerotic and nonsclerotic epileptic tissue.

Results: We found that in sclerotic, but also in nonsclerotic hippocampal tissue, the subiculum showed cellular and synaptic changes that were associated with spontaneous rhythmic activity correlated to the occurrence and frequency of interictal discharges recorded in the electroencephalograms of the corresponding patients.

Conclusions: Even though Ammon's horn sclerosis (AHS) in resected hippocampi from patients suffering from temporal lobe epilepsy has important prognostic implications for freedom from seizures postoperatively, we report here that both synaptic and intrinsic alterations enhance seizure susceptibility of the subiculum also in the absence of classical AHS.
SEN virus: epidemiology and characteristics of a transfusion‐transmitted virus
Authors: Akiba Jun , Umemura Takeji , Alter Harvey J. , Kojiro Masamichi , Tabor Edward
Published: June 2005

SEN virus (SEN‐V) is a blood‐borne, single‐stranded, nonenveloped DNA virus. Although its prevalence varies by geographic region, it has been detected in as many as 30 percent of postoperative transfusion recipients, compared to 3 percent of postoperative patients who did not receive transfusions. A significant association has been observed between transfusion volume and the occurrence of SEN‐V infection. Transmission by transfusion also has been confirmed by the detection of greater than 99 percent homology between SEN‐V in donor and recipient sera. Concurrent infections with SEN‐V and hepatitis B virus, hepatitis C virus, or human immunodeficiency virus type 1 have been documented, and these observations probably reflect the blood‐borne transmission of these viruses as well as SEN‐V. Although SEN‐V was discovered as part of a search for causes of posttransfusion hepatitis, there is no firm evidence so far that SEN‐V infection either causes hepatitis or worsens the course of coexistent liver disease. Nevertheless, SEN‐V appears to be transmitted by transfusion, and further studies may reveal more about its role in the future.
Use of a pH meter for bacterial screening of whole blood platelets
Authors: Yazer Mark H. , Triulzi Darrell J.
Published: June 2005

BACKGROUND: Bacterial contamination of blood products is a leading cause of transfusion‐related morbidity and mortality. Transfusion services are now compelled to employ methods of detecting bacteria in platelet (PLT) components. The use of pH screening of whole‐blood PLTs (WBPs) was evaluated with a pH meter at the time of issue as a surrogate test for bacterial contamination.

STUDY DESIGN AND METHODS: All WBPs selected for transfusion in May through September 2004 were tested individually for pH at time of issue. Those with a pH value of less than 7.0 were cultured in an automated culture system for 5 days. The white blood cell (WBC) and PLT counts in 56 representative WBP units that failed pH screening were compared to WBP units with acceptable pH values.

RESULTS: Of the 37,060 WBP units that underwent pH screening, 405 had a pH value of less than 7.0 (1.1%). Four of those units were culture positive (1.0%) for Staphylococcus aureus, Bacillus subtilis, diphtheroids, and coagulase‐negative Staphylococcus. Only one cocomponent red blood cell (RBC) unit was culture‐positive and grew the same bacteria (S. aureus) as the WBP unit. The rate of pH failure increased with WBP storage length with the greatest rate of pH failures occurring in 5‐day‐old WBPs. The units that failed pH screening had significantly more WBCs and PLTs than units with acceptable pH values.

CONCLUSION: pH screening of WBPs at issue prevented transfusion of bacterially contaminated WBPs and RBCs. This method, however, results in significant PLT wastage. Higher WBC and PLT content likely explains pH failures not due to bacterial contamination.
ISBT Code 128 implementation at a regional blood center
Authors: Peck K.B. , Sher L.D. , Parton P.A. , Wright J.F. , Menitove J.E.
Published: June 2005

BACKGROUND: Application specifications for ISBT 128 bar code symbology and the International Council for Commonality in Blood Bank Automation (ICCBBA) were created in 1994. By June 2000, the FDA considered ISBT 128 a standard for uniform labeling of blood and blood components. Our blood center initiated a change process for ISBT 128 implementation and “went live” in 2003.

STUDY DESIGN AND METHODS: The intention to adopt ISBT 128 symbology with hospitals was actively communicated in October 2001. A Codabar‐ISBT label cross‐reference book was developed, FDA approval for the fullface label format in April 2002 was requested, and FDA approval was received in March 2003. In December 2002, donor identification labels and number sets were ordered, and an integration test plan was subsequently developed with departmental process flowcharts for each of the nine affected departments. Each step was tested, the labeling changes were approved in May 2003, training was completed in June 2003, and ISBT bar code symbology was implemented on July 1, 2003. A written survey was sent to hospital transfusion services in April 2004.

RESULTS: Implementation went smoothly except for an unanticipated high rate of “no‐reads” on some analyzers in the testing lab. The hospitals spent an average of 18 hours preparing for changes, 14 hours on validation, 4 hours on documentation and procedure development, and 8 hours on training.

CONCLUSION: ISBT bar code symbology was successfully implemented. Hospital transfusion services made some adjustments and, overall, readily accepted the new bar code symbology.
Amino‐acid substitution in the disordered loop of blood group B‐glycosyltransferase enzyme causes weak B phenotype
Authors: Yazer Mark H. , Denomme Greg A. , Rose Natisha L. , Palcic Monica M.
Published: June 2005

BACKGROUND: Few studies have investigated the reaction kinetics and interactions with nucleotide donor and acceptor substrates of mutant human ABO glycosyltransferases. Previous work identified a Bw allele featuring a 556G>A polymorphism giving rise to a weak B phenotype. This polymorphism is predicted to cause a M186V amino‐acid mutation within a highly conserved series of 16 amino acids present both in both blood group A– and blood group B–synthesizing enzymes. These residues are known as the disordered loop because their location cannot be determined in the crystal structure of the enzyme. Another patient has been identified with a 556G>A Bw allele and the kinetics of the resulting mutant glycosyltransferase were studied.

STUDY DESIGN AND METHODS: Serologic testing with murine and human reagents, amplification of the coding regions of exons 6 and 7, and DNA sequencing were performed with standard protocols. Enzyme kinetic studies utilized a model of human GTB M186V expressed in Escherichia coli with radiolabeled UDP‐galactose and UDP‐N‐acetylgalactosamine as donor substrates and synthetic H‐disaccharide as acceptor following standard protocols.

RESULTS: The patient's red blood cells demonstrated a weak, but not mixed‐field, B phenotype. Kinetic studies on the mutant enzyme revealed diminished activity (kcat = 0.15 per sec with UDP‐galactose compared to 5.1 per sec for wild‐type GTB) and elevated Km values for all substrates.

CONCLUSION: This enzyme with a mutation in the disordered loop produces weak B antigen expression because of greatly decreased enzyme activity and reduced affinity for B‐donor and acceptor substances.
The α4β1 and α5β1 integrins mediate engraftment of granulocyte–colony‐stimulating factor–mobilized human hematopoietic progenitor cells
Authors: Carstanjen Dirk , Gross Anna , Kosova Nevin , Fichtner Iduna , Salama Abdulgabar
Published: June 2005

BACKGROUND: The α4β1 and α5β1 integrins are major adhesion molecules of murine and human hematopoietic progenitor cells. Granulocyte–colony‐stimulating factor (G‐CSF)–mobilized peripheral blood progenitor cells (PBPCs) are the most important source for clinical hematopoietic cell transplantation today. The contribution of α4β1 and α5β1 integrins to homing of PBPCs has not been studied yet.

STUDY DESIGN AND METHODS: The expression of α4β1 and α5β1 integrins on purified human PBPCs was analyzed. Integrin function in adhesion to recombinant fibronectin and migration on fibronectin‐coated transwells was assessed with fragments combining different adhesion domains and function‐blocking antibodies. Finally, the function of those integrins in a transplantation model was investigated with repopulating cells of nonobese diabetic/severe combined immune‐deficient (NOD/SCID) mice.

RESULTS: More than 90 percent of all purified peripheral blood CD34+ cells express α4β1 integrins, whereas only 10 to 15 percent express α5β1. The α4β1 integrin alone influences adhesion whereas α4β1 and α5β1 both mediate chemotaxis of clonogenic CD34+ progenitor cells on recombinant fibronectin. Importantly, antibodies against the integrins α4β1 and α5β1 independently reduce the repopulation of NOD/SCID mouse marrow after transplantation of human peripheral blood CD34+ cells.

CONCLUSIONS: Α4β1 and α5β1 integrins are functional and critical adhesion receptors expressed on G‐CSF–mobilized CD34+ hematopoietic blood progenitor cells with repopulating capacity mediating engraftment after transplantation.
Random survey for RHD alleles among D+ European persons
Authors: Chen Qing , Flegel Willy A.
Published: June 2005

BACKGROUND: RHD alleles are considered more variable in African persons than in European persons. A systematic survey, however, was lacking among D+ European persons at the molecular level, precluding any definite frequency estimate.

STUDY DESIGN AND METHODS: A random survey was performed among 500 ccDee, 250 CcDee, and 250 ccDEe blood donors in southwestern Germany. They were tested by polymerase chain reaction with sequence‐specific priming (PCR‐SSP) for up to 12 single‐nucleotide polymorphisms representative for the most frequent RHD alleles among European persons. The RHD exon 5 nucleotide sequence was also tested in all 1000 samples. The nucleotide sequence of the 10 RHD exons was checked in all samples with aberrant exon 5 or positive PCR‐SSP procedures.

RESULTS: By PCR‐SSP, 15 aberrant RHD alleles were found among the 500 ccDee, 2 among the 250 CcDee, and none among the ccDEe samples. One of these was the novel RHD(F223V, E233Q, T379M) allele dubbed DAU‐5. Weak D type 4 was detected more frequently than expected, whereas the population frequencies of the other RHD alleles conformed to published estimates. Nucleotide sequencing of RHD exon 5 further revealed three novel alleles RHD(G212G), RHD(R234W), and RHD(V245L), dubbed DUC‐1, DQC, and DUC‐2.

CONCLUSION: In a limited screen at the molecular level among 1000 random D+ donors in southwestern Germany, 20 donors were found carrying aberrant RHD alleles. Four of these alleles were new and likely sporadic. An estimate was derived of the variety that may be encountered in genotyping approaches, and it was concluded that even within the European population the variety of RHD alleles may be larger than anticipated.
Use of B‐natriuretic peptide as a diagnostic marker in the differential diagnosis of transfusion‐associated circulatory overload
Authors: Zhou Lan , Giacherio Donald , Cooling Laura , Davenport Robertson D.
Published: June 2005

BACKGROUND: Transfusion‐associated circulatory overload (TACO) occurs when the transfusion rate or volume exceeds the capacity of a compromised cardiovascular system. Characteristic symptoms and signs associated with TACO are neither sensitive nor specific. B‐natriuretic peptide (BNP) is a 32‐amino‐acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. This study was performed to explore the usage of BNP in the differential diagnosis of TACO.

STUDY DESIGN AND METHODS: Pre‐ and posttransfusion BNP levels were determined in 21 patients with suspected TACO and 19 control patients. The BNP was considered significant if the posttransfusion‐to‐pretransfusion ratio was at least 1.5 and the posttransfusion BNP level was at least 100 pg per mL.

RESULTS: The BNP test has a sensitivity and specificity of 81 and 89 percent, respectively, in diagnosis of TACO. It has a positive predictive value of 89 percent, a negative predictive value of 81 percent, and an accuracy of 87 percent. In logistic regression analysis, BNP was found to have significant predictive power independent of other clinical variables in models predicting which patients had TACO.

CONCLUSIONS: Our study suggests that in patients who present symptoms suggestive of TACO, BNP can be a useful adjunct marker in confirming volume overload as the cause of acute dyspnea and symptoms related to cardiovascular compromise.
Occurrence of hepatitis A virus genotype III in Germany requires the adaptation of commercially available diagnostic test systems
Authors: Heitmann Alke , Laue Thomas , Schottstedt Volkmar , Dotzauer Andreas , Pichl Lutz
Published: June 2005

BACKGROUND:A blood donation, obtained in 2003 in Germany during the preseroconversion diagnostic window period of a hepatitis A virus (HAV) infection, tested HAV‐negative by commercially available HAV reverse transcription–polymerase chain reaction (RT‐PCR) detection assays.

STUDY DESIGN AND METHODS:The virus responsible for this infection was identified as HAV genotype IIIA by characterization of the nearly complete genome sequence.

RESULTS:Thereby, this HAV variant, which was named strain HMH, was detected in Germany for the first time. Because the commercially available HAV RNA detection systems failed to detect this genotype, a real‐time RT‐PCR kit was developed that allows quantification and detection of all HAV genotypes. The first nearly full‐length nucleotide sequence so far available for HAV genotype IIIA is also provided.

CONCLUSION:This case demonstrates that owing to the genetic variability of HAV, constant monitoring and adaptation of the diagnostic nucleic acid assays are required to guarantee the safety of blood and blood products.
In vitro photochemical inactivation of cell‐associated human T‐cell leukemia virus Type I and II in human platelet concentrates and plasma by use of amotosalen
Authors: Jauvin Valérie , Alfonso Ryan D. , Guillemain Bernard , Dupuis Kent , Fleury Hervé J.A.
Published: June 2005

BACKGROUND: Human T‐cell leukemia virus Types I and II (HTLV‐I and HTLV‐II), blood‐borne retroviruses found worldwide, can cause leukemia, immunosuppression, and severe neurologic diseases. In most countries, HTLV‐I and ‐II screening is not performed systematically for blood donations. A new photochemical treatment (PCT) with a synthetic psoralen was developed to inactivate most pathogens in platelet (PLT) concentrates or plasma and to improve the safety of blood donations.

STUDY DESIGN AND METHODS: Cell‐associated HTLV‐I or ‐II (106/mL) was inoculated in full‐size fresh PLT concentrates or fresh frozen plasma and treated with 150 µmol per L amotosalen (S‐59) and different doses of long‐wavelength ultraviolet A (UVA) light. The residual viral titer in the treated samples was assessed by a cocultivation assay on indicator cells.

RESULTS: The inactivation obtained at a 3.0 J per cm2 UVA dose was greater than 5.2 log foci‐forming units (FFUs) per mL for HTLV‐I and 4.6 log FFUs per mL for HTLV‐II in presence of human PLT concentrates and greater than 4.5 log FFUs per mL for HTLV‐I and 5.7 log FFUs per mL for HTLV‐II in the presence of human plasma. The residual infectivity was very low and shown as the limit of detection of the cocultivation assay.

CONCLUSION: In human plasma or PLT concentrates, the retroviruses HTLV‐I and ‐II were strongly sensitive to the PCT with 150 µmol per L amotosalen (S‐59) and a 3.0 J per cm2 UVA dose. This high efficiency for photoinactivation of these retroviruses opens a possibility of improving the safety of PLTs or plasma transfusion in the future.
Beam modeling and verification of a photon beam multisource model
Authors: Ahnesjö Anders , Weber Lars , Murman Anders , Saxner Mikael , Thorslund Ingvar , Traneus Erik
Published: June 2005

Dose calculations for treatment planning of photon beam radiotherapy require a model of the beam to drive the dose calculation models. The beam shaping process involves scattering and filtering that yield radiation components which vary with collimator settings. The necessity to model these components has motivated the development of multisource beam models. We describe and evaluate clinical photon beam modeling based on multisource models, including lateral beam quality variations. The evaluation is based on user data for a pencil kernel algorithm and a point kernel algorithm (collapsed cone) used in the clinical treatment planning systems Helax‐TMS and Nucletron‐Oncentra. The pencil kernel implementations treat the beam spectrum as lateral invariant while the collapsed cone involves off axis softening of the spectrum. Both algorithms include modeling of head scatter components. The parameters of the beam model are derived from measured beam data in a semiautomatic process called RDH (radiation data handling) that, in sequential steps, minimizes the deviations in calculated dose versus the measured data. The RDH procedure is reviewed and the results of processing data from a large number of treatment units are analyzed for the two dose calculation algorithms. The results for both algorithms are similar, with slightly better results for the collapsed cone implementations. For open beams, 87% of the machines have maximum errors less than 2.5%. For wedged beams the errors were found to increase with increasing wedge angle. Internal, motorized wedges did yield slightly larger errors than external wedges. These results reflect the increased complexity, both experimentally and computationally, when wedges are used compared to open beams.
Sensitive and fast mapping based on two inversion recovery images and a reference image
Authors: Jahng Geon‐Ho , Stables Lara , Ebel Andreas , Matson Gerald B. , Meyerhoff Dieter J. , Weiner Michael W. , Schuff Norbert
Published: June 2005

We developed a fast method to obtain relaxation maps in magnetic resonance imaging (MRI) based on two inversion recovery acquisitions and a reference acquisition, while maintaining high sensitivity by utilizing the full dynamic range of the MRI signal. Optimal inversion times for estimating in the human brain were predicted using standard error propagation theory. In vivo measurements on nine healthy volunteers yielded values of in gray matter and in white matter, in reasonable agreement with literature values using conventional approaches. The proposed method should be useful for clinical studies because the maps can be obtained within a few seconds.
Dosimetric impact of geometric errors due to respiratory motion prediction on dynamic multileaf collimator‐based four‐dimensional radiation delivery
Authors: Vedam S. , Docef A. , Fix M. , Murphy M. , Keall P.
Published: June 2005

The synchronization of dynamic multileaf collimator (DMLC) response with respiratory motion is critical to ensure the accuracy of DMLC‐based four dimensional (4D) radiation delivery. In practice, however, a finite time delay (response time) between the acquisition of tumor position and multileaf collimator response necessitates predictive models of respiratory tumor motion to synchronize radiation delivery. Predicting a complex process such as respiratory motion introduces geometric errors, which have been reported in several publications. However, the dosimetric effect of such errors on 4D radiation delivery has not yet been investigated. Thus, our aim in this work was to quantify the dosimetric effects of geometric error due to prediction under several different conditions. Conformal and intensity modulated radiation therapy (IMRT) plans for a lung patient were generated for anterior‐posterior/posterior‐anterior (AP/PA) beam arrangements at 6 and 18 MV energies to provide planned dose distributions. Respiratory motion data was obtained from 60 diaphragm‐motion fluoroscopy recordings from five patients. A linear adaptive filter was employed to predict the tumor position. The geometric error of prediction was defined as the absolute difference between predicted and actual positions at each diaphragm position. Distributions of geometric error of prediction were obtained for all of the respiratory motion data. Planned dose distributions were then convolved with distributions for the geometric error of prediction to obtain convolved dose distributions. The dosimetric effect of such geometric errors was determined as a function of several variables: response time (0‐0.6 s), beam energy , treatment delivery , treatment type (conformal/IMRT), beam direction (AP/PA), and breathing training type (free breathing/audio instruction/visual feedback). Dose difference and distance‐to‐agreement analysis was employed to quantify results. Based on our data, the dosimetric impact of prediction (a) increased with response time, (b) was larger for 3D radiation therapy as compared with 4D radiation therapy, (c) was relatively insensitive to change in beam energy and beam direction, (d) was greater for IMRT distributions as compared with conformal distributions, (e) was smaller than the dosimetric impact of latency, and (f) was greatest for respiration motion with audio instructions, followed by visual feedback and free breathing. Geometric errors of prediction that occur during 4D radiation delivery introduce dosimetric errors that are dependent on several factors, such as response time, treatment‐delivery type, and beam energy. Even for relatively small response times of 0.6 s into the future, dosimetric errors due to prediction could approach delivery errors when respiratory motion is not accounted for at all. To reduce the dosimetric impact, better predictive models and/or shorter response times are required.
A practical method for three‐dimensional reconstruction of joints using a C‐arm system and shift‐and‐add algorithm
Authors: Li Senhu , Jiang Huabei
Published: June 2005

Currently, radiography with C‐arm systems is playing a major role in the assessment of arthritis. However, the radiographic two‐dimensional projection images of joints often interfere with physicians' efforts to better understand and measure the structure changes of joints due to the overlap of bone structures at different depths. An accurate, low‐cost, and practical three‐dimensional (3D) reconstruction approach of joints will be beneficial in diagnosing arthritis. Toward this end, a novel method is developed in this paper based on a C‐arm system. The idea is to apply the shift‐and‐add algorithm (commonly used in digital tomosynthesis) on the segmented projection images at multiple angles, which results in accurate reconstruction of the 3D structures of joints. The method provides a new solution to precisely distinguish objects from blurring background. The proposed method has been tested and evaluated on simulated cylinders, a chicken bone phantom with known structure, and an in vivo human index finger. The results are demonstrated and discussed.
Parameterized algorithms for quantitative differentials in spectrally equivalent medical diagnostic x‐ray beams
Authors: Okunade Akintunde Akangbe
Published: June 2005

Qualitative and quantitative equivalence of spectra transmitted by two different elemental filters require a good match in terms of shape and size over the entire energy range of 0–150 keV used in medical diagnostic radiology. However, the photoelectric absorptions and Compton scattering involved in the interaction of x rays with matter at these relatively low photon energies differ in a nonuniform manner with energy and atomic number. By careful choice of thicknesses for filter materials with an atomic number between 12 and 39, when compared with aluminum, it is possible to obtain transmitted beams of the same shape (quality) but not of the same size (quantity). In this paper, calculations have been carried out for the matching of the shapes and sizes of beams transmitted through specified thicknesses of aluminium filter and spectrally equivalent thicknesses of other filter materials (different from aluminium) using FORTRAN source codes traceable to the American Association of Physics in Medicine (AAPM), College Park, MD, USA. Parametrized algorithms for the evaluation of quantitative differentials (deficit or surplus) in radiation output (namely, photon fluence, exposure, kerma, energy imparted, absorbed dose, and effective dose) from these transmitted spectrally equivalent beams were developed. These differentials range between 1%, and 4% at 1 mm Al filtration and between 8%, and 25% for filtration of 6 mm Al for different filter materials in comparison with aluminum. Also developed were models for factors for converting measures of photon fluence, exposure‐area product, (EAP), and kerma‐area product (KAP) to risk related quantities such as energy imparted, absorbed dose, and effective dose from the spectrally equivalent beams. The thicknesses of other filter materials that are spectrally equivalent to given thicknesses of aluminum filter were characterized using polynomial functions. The fact that the use of equivalent spectra in radiological practice can provide means of ranking the differentials in radiographic image quality and stochastic risk is discussed.
Compton‐scattering measurement of diagnostic x‐ray spectrum using high‐resolution Schottky CdTe detector
Authors: Maeda Koji , Matsumoto Masao , Taniguchi Akira
Published: June 2005

The analysis of x‐ray spectra is important for quality assurance (QA) and quality control (QC) of radiographic systems. The aim of this study is to measure the diagnostic x‐ray spectra under clinical conditions using a high‐resolution Schottky CdTe detector. Under clinical conditions, the direct measurement of a diagnostic spectrum is difficult because of the high photon fluence rates that cause significant detector photon pile‐up. An alternative way of measuring the output spectra from a tube is first to measure the 90 deg Compton scattered photons from a given sample. With this set‐up detector, pile‐up is not a problem. From the scattered spectrum one can then use an energy correction and the Klein–Nishina function to reconstruct the actual spectrum incident upon the scattering sample. The verification of whether our spectra measured by the Compton method are accurate was accomplished by comparing exposure rates calculated from the reconstructed spectra to those measured with an ionization chamber. We used aluminum (Al) filtration ranging in thickness from 0 to 6 mm. The half value layers (HVLs) obtained for a 70 kV beam were 2.78 mm via the ionization chamber measurements and 2.93 mm via the spectral measurements. For a 100 kV beam we obtained 3.98 and 4.32 mm. The small differences in HVLs obtained by both techniques suggest that Compton scatter spectroscopy with a Schottky CdTe detector is suitable for measuring the diagnostic x‐ray spectra and useful for QA and QC of clinical x‐ray equipment.
T1 measurement using a short acquisition period for quantitative cardiac applications
Authors: Higgins David M. , Ridgway John P. , Radjenovic Aleksandra , Sivananthan U. Mohan , Smith Michael A.
Published: June 2005

Myocardial signal intensity curves for myocardial perfusion studies may be made quantitative by the use of T1 measurements made after the first‐pass of contrast agent. A short data acquisition method for T1 mapping is presented in which all data for each T1 map are acquired in a short breath hold, and the slice geometry and timing in the cardiac cycle exactly match that of the dynamic first‐pass perfusion sequence. This allows accurate image registration of the T1 map with the first‐pass series of images. The T1 method is based on varying the preparation‐pulse delay time of a saturation recovery sequence, and in this implementation employs an ECG‐triggered, single‐shot, spoiled gradient echo technique with SENSE reconstruction. The method allows T1 estimates of three slices to be made in fifteen heartbeats. For a range of samples with T1 values equivalent to those found in the myocardium during the first‐pass of contrast agent, T1 estimates were accurate to within 6%, and the variation between slices was 2% or less.
Towards biologically conformal radiation therapy (BCRT): Selective IMRT dose escalation under the guidance of spatial biology distribution
Authors: Yang Yong , Xing Lei
Published: June 2005

It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear‐quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel‐dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT) incorporates patient‐specific biological information and provides an outstanding opportunity for us to truly individualize radiation treatment. The proposed formalism lays a technical foundation for BCRT and allows us to maximally exploit the technical capacity of IMRT to more intelligently escalate the radiation dose.
Curvilinear transurethral ultrasound applicator for selective prostate thermal therapy
Authors: Ross Anthony B. , Diederich Chris J. , Nau William H. , Rieke Viola , Butts R. Kim , Sommer Graham , Gill Harcharan , Bouley Donna M.
Published: June 2005

Thermal therapy offers a minimally invasive option for treating benign prostatic hyperplasia (BPH) and localized prostate cancer. In this study we investigated a transurethral ultrasound applicator design utilizing curvilinear, or slightly focused, transducers to heat prostatic tissue rapidly and controllably. The applicator was constructed with two independently powered transducer segments operating at 6.5 MHz and measuring with a 15 mm radius of curvature across the short axis. The curvilinear applicator was characterized by acoustic efficiency measurements, acoustic beam plots, biothermal simulations of human prostate, ex vivo heating trials in bovine liver, and in vivo heating trials in canine prostate . Each transducer segment was found to emit a narrow acoustic beam , which extended the length of the transducer, with deeper penetration than previously developed planar or sectored tubular transurethral ultrasound applicators. Acoustic and biothermal simulations of human prostate demonstrated three treatment schemes for the curvilinear applicator: single shot (10 W, 60 s) schemes to generate narrow ablation zones (, 52 °C at the lesion boundary), incremental rotation (10 W, ) to generate larger sector‐shaped ablation zones ( sector), and rotation with variable sonication times (10 W, ) to conform the ablation zone to a predefined boundary ( sector, 13 min total treatment time). During in vivo canine prostate experiments, guided by MR temperature imaging, single shot sonications (, 2–3 min) with the curvilinear applicator ablated 20° sections of tissue to the prostate boundary (9–15 mm). Multiple adjacent sonications (“sweeping”) ablated large sections of the prostate (180°) by using the MR temperature imaging to adjust the power and sonication time (30–180 s) at each 10° rotation such that the periphery of the prostate reached 52 °C before the next rotation. The conclusion of this study was that the curvilinear applicator produces a narrow and penetrating ultrasound beam that, when combined with image guidance, can provide a precise technique for ablating target regions with a contoured outer boundary, such as the prostate capsule, by rotating in small steps while dynamically adjusting the net applied electrical power and sonication time at each position.
Synchronized delivery of DMLC intensity modulated radiation therapy for stationary and moving targets
Authors: Rangaraj Dharanipathy , Papiez Lech
Published: June 2005

When delivering intensity modulated treatments the “tongue‐and‐groove” underdosage effect is a concern that should not be ignored. Algorithms aimed at removing the tongue‐and‐groove underdosage have been investigated in the past for irradiation of stationary targets. This paper is devoted to algorithms that remove tongue and grove effect for stationary and moving targets. To this end this paper develops original mid‐time based algorithms for leaf synchronization. These algorithms exhibit a few additional advantageous properties for DMLC IMRT delivery beyond the removal of tongue‐and‐grove underdosage. In particular, they safeguard the minimization of time of delivery (for mid‐time synchronized algorithms). Moreover, they avoid iterative procedures for synchronization of delivery for multiple pairs of leaves.