bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Waste Generation from Renal Units: Implications and Solutions
Authors: Hoenich Nicholas A. , Levin Robert , Pearce Catherine
Published: September 2005

The treatment of end‐stage renal disease (ESRD) makes extensive use of presterilized disposable items which, after use, are contaminated by blood. The preferred route of disposal of such items is by incineration. Disposal costs have risen and this increase in costs has not been matched by waste management programs in renal units. Many of the waste items generated also contain polyvinyl chloride (PVC) whose incineration is environmentally sensitive. Furthermore blood tubing sets contain plasticizers such as di(2‐ethylhexyl) phthalate (DEHP), which is known to pose health risks to specific groups of patients. The generation of clinical waste in a dialysis unit is analyzed, issues associated with disposal are discussed, and approaches toward a cost‐effective, environmentally sustainable clinical waste management program are reviewed.
Conversion of Temporary Hemodialysis Catheters to Permanent Hemodialysis Catheters: A Retrospective Study of Catheter Exchange versus Classic de novo Placement
Authors: Falk Abigail , Prabhuram Nagarathna , Parthasarathy Saudhamini
Published: September 2005

Many clinicians believe that de novo access is required when converting temporary hemodialysis (HD) catheters to long‐term or permanent catheters. However, since vascular access sites are at a premium in the dialysis patient, it is important to preserve existing central venous catheters and conserve future access sites. In this retrospective study, data from 94 patients referred to interventional radiology for placement of long‐term, tunneled HD catheters between July 2001 and September 2002 were reviewed. The study group consisted of 42 patients in whom the temporary catheter was exchanged for a peel‐away sheath and a tunneled catheter inserted using the existing venous access site. The control group included 52 patients who received traditional de novo placement of permanent catheters. Based on available follow‐up data, we report a 100% technical success rate, with 72% patency at 30 days in the study group (n = 32; mean age 58 years). By comparison, de novo catheter placement (n = 35; mean age 59 years) yielded a 100% technical success rate, with 83% patency at 30 days. The overall infection rate was 0.30 per 100 catheter‐days (total 3036 catheter‐days) and 0.36 per 100 catheter‐days (total 3295 catheter‐days), respectively (χ2 = 0.64, p ≥ 0.05). There was no incidence of exit site infection, tunnel infection, or florid sepsis in either group. Likewise, no stenosis or bleeding complication was noted. Thus conversion of a temporary HD catheter to a tunneled catheter using the same venous insertion site is safe, does not increase the risk of infection, and allows conservation of other central venous access sites.
Dialysis Rounds A Dialysis Case  Presentation and Discussion Edited by Roger A. Rodby : Long‐Term Intravenous Sodium Thiosulfate in the Treatment of a Patient with Calciphylaxis
Authors: Brucculeri Michael , Cheigh Jhoong , Bauer Gregory , Serur David
Published: September 2005

Calciphylaxis is a disabling and life‐threatening complication that primarily affects patients who are dialysis dependent. This disease entity is characterized by calcification, intimal hypertrophy, and thrombosis of small vessels, which results in necrotizing, nonhealing ulcers. The development of these lesions portends a grim prognosis, as they are often accompanied by severe and sometimes fatal infectious complications. Although several strategies aimed at treating and preventing this affliction have been reported in the literature, the outcome for most patients with calciphylaxis remains quite poor. We describe an anuric hemodialysis patient who developed severe calciphylaxis that proved refractory to conventional treatment. Following extensive debridement of several wounds, intravenous sodium thiosulfate was utilized as an adjunctive therapy four times a week. Within 6 months, excellent wound healing ensued as well as a dramatic improvement in the lesions that were not previously resected. Aside from occasional nausea, these treatments were well tolerated, despite the development of an anion gap metabolic acidosis. After 34 months of continued treatment the patient remains free from disease recurrence and has demonstrated no untoward effect of prolonged therapy. In an effort to delineate the pharmacokinetics of this drug in a hemodialysis patient, serum thiosulfate levels were obtained 15 minutes after infusion as well as before and after subsequent dialysis treatments. Consistent with prior studies in anuric canines, we found measurable quantities of the drug more than 50 hours after treatment, in addition to a markedly elevated half life of 478 minutes. However, given the lack of significant toxicity, as well as a dramatic clinical improvement, we feel that sodium thiosulfate may have an important adjunctive role in the treatment of calciphylaxis in dialysis patients.
Pharmacokinetics of Gabapentin during Delivery, in the Neonatal Period, and Lactation: Does a Fetal Accumulation Occur during Pregnancy?
Authors: Öhman Inger , Vitols Sigurd , Tomson Torbjörn
Published: September 2005

Summary:  Purpose: To study the pharmacokinetics of gabapentin (GBP) during delivery, lactation, and in the neonatal period.

Methods: GBP concentrations in plasma and breast milk were determined with high‐performance liquid chromatography in samples from six women treated with GBP and in their offspring. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions during 2 days after delivery. GBP concentration also was determined in breast milk and in blood collected from five of the mothers and suckling infants 2 weeks to 3 months after birth.

Results: The umbilical cord/maternal plasma concentration ratios ranged from 1.3 to 2.1 (mean, 1.7). GBP plasma concentrations in the neonates declined with an estimated half‐life of 14 h. Mean GBP plasma concentrations in the infants were 27% of the cord plasma levels (range, 12–36%) 24 h postpartum. The mean milk/maternal plasma concentration ratio was 1.0 (range, 0.7–1.3) from 2 weeks to 3 months. The infant dose of GBP was estimated to 0.2–1.3 mg/kg/day, equivalent to 1.3–3.8% of the weight‐normalized dose received by the mother. The plasma concentrations in the breast‐fed infants were ∼12% of the mother's plasma levels, but no adverse effects were observed.

Conclusions: Our limited observations suggest an active transplacental transport of GBP, with accumulation in the fetus as a consequence. We suggest that this could be by the specific L‐type amino acid transporter 1 (LAT‐1), which is expressed in the placenta. Newborns seem to have a slightly lower capacity to eliminate GBP than do adults. Transfer of GBP to breast milk is extensive, but plasma concentrations appear to be low in suckling infants. No adverse effects were observed in the newborn. Although more data are needed, our observations suggest that breastfeeding in conjunction with GBP treatment is safe.
Benign Partial Epilepsy in Childhood: Selective Cognitive Deficits Are Related to the Location of Focal Spikes Determined by Combined EEG/MEG
Authors: Wolff Markus , Weiskopf Nikolaus , Serra Emilio , Preissl Hubert , Birbaumer Niels , Kraegeloh‐Mann Ingeborg
Published: September 2005

Summary:  Purpose: Benign partial epilepsy (BPE) in childhood is characterized by the occurrence of interictal stereotyped focal spikes with variable localization in the EEG. Children with BPE often exhibit neuropsychological deficits. It is unclear whether a correlation exists between these deficits and the localization of spikes, several EEG studies giving inconsistent results. Magnetoencephalography (MEG) improves the accuracy of spike localization. Therefore by using combined MEG/EEG, we investigated the topographic relation between focal spikes and neuropsychological findings in children with BPE.

Methods: Twenty‐seven children diagnosed consecutively with BPE were enrolled in the study. All were examined by combined MEG/EEG and magnetic resonance imaging (MRI). Location of spikes was determined by dipole source estimation. A standardized neuropsychological assessment was conducted, including Kaufman ABC battery, language tests, and motor performance series. All children with sufficient MEG data were included in the correlation analysis (N = 20).

Results: Focal spikes were located in the perisylvian region in 13 children, in the occipital region in seven, and in the frontal region in one. Five children had bilateral or multiple foci. Children with left perisylvian spikes did not differ from the others in global IQ, but performed significantly lower in language tests (p = 0.01). Children with occipital spikes performed significantly lower in simultaneous information processing (p = 0.01), especially in visual transformation tasks.

Conclusions: Combined MEG/EEG investigation is a useful tool to examine interictal focal spikes. Our results show a correlation between the location of spikes and selective cognitive deficits in children with BPE. These findings indicate that focal interictal spikes may interfere with complex cognitive functions.
Reliable Registration of Preoperative MRI with Histopathology after Temporal Lobe Resections
Authors: Eriksson Sofia H. , Free Samantha L. , Thom Maria , Harkness William , Sisodiya Sanjay M. , Duncan John S.
Published: September 2005

Summary:  Purpose: Conventional and novel magnetic resonance imaging (MRI) techniques can detect cerebral abnormalities in patients with refractory focal epilepsies. Correlation of preoperative MRI and histopathology is important to validate MRI findings, but in practice is far from straightforward. Peroperative neuronavigation and placement of markers on tissue is of limited use in temporal lobe resections. MRI scanning of the resected specimen for registration with in vivo MRI is complicated by anisotropic tissue deformation. We have developed a method to facilitate registration of preoperative MRI with the resected specimen and to enable correlation of MRI findings with histopathology.

Methods: Sixteen en bloc temporal lobe resections undertaken for refractory temporal lobe epilepsy were studied. The specimens were fixed in formalin and then cut coronally by using a cradle with parallel blades at 5‐mm intervals to ensure evenly thick tissue slices in the same orientation. Volumetric T1‐weighted preoperative MRIs were reformatted, and consecutive slices (0.94 mm) cut in the same orientation as the resected lobe were visually compared with photographs of tissue slices by two independent observers.

Results: In 15 (94%) of 16 cases, a <2‐mm difference was found between the two observers' matches of MRI slices with tissue slices. In the last case, a 4‐mm difference was noted. In all cases, a consensus was reached by the two observers. The suggested MRI–histology matches were within the resections seen on postoperative scans.

Conclusions: Careful labelling and postoperative handling and slicing ensured histopathologic tissue slices of uniform thickness and slicing angle. This technique can be applied to a range of MRI datasets, enabling exploration of the pathologic basis of abnormalities on conventional and novel MRI acquisitions.
Status Epilepticus and Tiagabine Therapy Revisited
Authors: Koepp Matthias J. , Edwards Mark , Collins Jayne , Farrel Fiona , Smith Shelagh
Published: September 2005

Summary: Purpose:To determine whether antiepileptic treatment with tiagabine (TGB) is associated with an increased frequency of nonconvulsive status epilepticus (NCSE) in patients with refractory epilepsy.

Methods:We reviewed retrospectively the medical and EEG records of all inpatients with refractory localization‐related epilepsy at the National Society for Epilepsy treated with TGB between January 1997 and December 2000. Clinical and electroencephalographic (EEG) data before, during, and after TGB therapy were evaluated in those patients who experienced a deterioration in seizure control suggestive of NCSE. Frequency of NCSE was determined in a comparable, non–TGB‐treated patient population.

Results:Seven (7.8%) of 90 TGB‐treated patients were identified who experienced episodes of electroclinically confirmed NCSE. Serial EEGs showed deterioration during TGB treatment, with resolution of abnormality on discontinuation of TGB in all seven patients. During the same observation period, 32 (2.7%) of 1,165 non–TGB‐treated patients developed electroclinically defined NCSE.

Conclusions:Treatment with TGB is associated with an increased frequency of NCSE in patients with refractory localization‐related epilepsy.
Tuberous Sclerosis Complex and the Ketogenic Diet
Authors: Kossoff Eric H. , Thiele Elizabeth A. , Pfeifer Heidi H. , McGrogan Jane R. , Freeman John M.
Published: September 2005

Summary:  Purpose: Tuberous sclerosis complex (TSC) is a condition that is frequently associated with intractable, early‐onset epilepsy, and often is first seen as infantile spasms. If medications fail and no clear epileptogenic tuber is identified, nonpharmacologic therapies are often attempted. The use of the ketogenic diet specifically for children with TSC and epilepsy has not been previously described.

Methods: A chart review was performed of patients with TSC treated with the ketogenic diet over a 5‐year period at Johns Hopkins Hospital and Massachusetts General Hospital.

Results: Twelve children, ages 8 months to 18 years, were identified. Eleven (92%) children had a >50% reduction in their seizures at 6 months on the diet, and 8 (67%) had a >90% response. Five children had at least a 5‐month seizure‐free response. Diet duration ranged from 2 months to 5 years (mean, 2 years).

Conclusions: In this limited‐duration case series of 12 patients, the ketogenic diet was a generally effective therapeutic modality for the intractable epilepsy occasionally seen in children with TSC.
Analysis of Chronic Seizure Onsets after Intrahippocampal Kainic Acid Injection in Freely Moving Rats
Authors: Bragin Anatol , Azizyan Avetis , Almajano Joyel , Wilson Charles L. , Engel Jerome
Published: September 2005

Summary:  Purpose: The goal of this study was to analyze the transition period between interictal and ictal activity in freely moving rats with recurrent spontaneous seizures after unilateral intrahippocampal kainic acid (KA) injection.

Methods: Pairs of tungsten electrodes (50 μm O/D) were implanted bilaterally under anesthesia at symmetrical points in the dentate gyrus (DG) and CA1 regions of anterior and posterior hippocampi and entorhinal cortex of adult Wistar rats. Stimulating electrodes were placed in the right angular bundle and KA was injected into the right posterior CA3 area of hippocampus after 1 week of baseline EEG recording. Beginning 24 h after injection, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for 60 days.

Results: Seventy percent of seizures started locally in the DG ipsilateral to injection, with an increase in frequency of interictal EEG spikes (hypersynchronous type, HYP), and 26% of seizures started with a decrease of EEG amplitude with parallel increase in frequency (low‐voltage fast type, LVF). During HYP seizures, a significant increase was observed in amplitude of beta‐gamma range frequencies, ripple frequency, and fast ripple (FR) frequency, whereas during LVF seizure, an increase was noted only in the beta‐gamma range. In all cases but one, an EEG wave preceded ripple and FR oscillations. Before seizure onset, the amplitude of DG‐evoked responses to single pulses decreased, whereas the amplitude of the response to the second pulse delivered at 30‐ms interval increased.

Conclusions: If ripple and FR oscillations indicate the seizure‐generating neuronal substrate, these areas must be small and widespread, so that the probability of recording from them directly is very low. The decreased response to electrical stimulation before seizures could indicate a protective inhibitory mechanism that contains or prevents seizure occurrence. The presence of decreased paired‐pulse suppression could indicate a network predisposition to follow an external input with a certain frequency.
Optimal Tracking and Testing of U.S. and Canadian Herds for BSE: A Value‐of‐Information (VOI) Approach
Authors: Cox Louis Anthony , Popken Douglas A. , VanSickle John J. , Sahu Ranajit
Published: September 2005

The U.S. Department of Agriculture (USDA) tests a subset of cattle slaughtered in the United States for bovine spongiform encephalitis (BSE). Knowing the origin of cattle (U.S. vs. Canadian) at testing could enable new testing or surveillance policies based on the origin of cattle testing positive. For example, if a Canadian cow tests positive for BSE, while no U.S. origin cattle do, the United States could subject Canadian cattle to more stringent testing. This article illustrates the application of a value‐of‐information (VOI) framework to quantify and compare potential economic costs to the United States of implementing tracking cattle origins to the costs of not doing so. The potential economic value of information from a tracking program is estimated to exceed its costs by more than five‐fold if such information can reduce future losses in export and domestic markets and reduce future testing costs required to reassure or win back customers. Sensitivity analyses indicate that this conclusion is somewhat robust to many technical, scientific, and market uncertainties, including the current prevalence of BSE in the United States and/or Canada and the likely reactions of consumers to possible future discoveries of BSE in the United States and/or Canada. Indeed, the potential value of tracking information is great enough to justify locating and tracking Canadian cattle already in the United States when this can be done for a reasonable cost. If aggressive tracking and testing can win back lost exports, then the VOI of a tracking program may increase to over half a billion dollars per year.
A Benefit‐Cost Analysis of Retrofitting Diesel Vehicles with Particulate Filters in the Mexico City Metropolitan Area
Authors: Stevens Gretchen , Wilson Andrew , Hammitt James K.
Published: September 2005

In the Mexico City metropolitan area, poor air quality is a public health concern. Diesel vehicles contribute significantly to the emissions that are most harmful to health. Harmful diesel emissions can be reduced by retrofitting vehicles with one of several technologies, including diesel particulate filters. We quantified the social costs and benefits, including health benefits, of retrofitting diesel vehicles in Mexico City with catalyzed diesel particulate filters, actively regenerating diesel particulate filters, or diesel oxidation catalysts, either immediately or in 2010, when capital costs are expected to be lower. Retrofit with either type of diesel particulate filter or an oxidation catalyst is expected to provide net benefits to society beginning immediately and in 2010. At current prices, retrofit with an oxidation catalyst provides greatest net benefits. However, as capital costs decrease, retrofit with diesel particulate filters is expected to provide greater net benefits. In both scenarios, retrofit of older, dirtier vehicles that circulate only within the city provides greatest benefits, and retrofit with oxidation catalysts provides greater health benefits per dollar spent than retrofit with particulate filters. Uncertainty about the magnitude of net benefits of a retrofit program is significant. Results are most sensitive to values used to calculate benefits, such as the concentration‐response coefficient, intake fraction (a measure of exposure), and the monetary value of health benefits.
Catheter Ablation of Long‐Lasting Persistent Atrial Fibrillation: Clinical Outcome and Mechanisms of Subsequent Arrhythmias
Authors: HAÏSSAGUERRE MICHEL , HOCINI MÉLÈZE , SANDERS PRASHANTHAN , SACHER FREDERIC , ROTTER MARTIN , TAKAHASHI YOSHIHIDE , ROSTOCK THOMAS , HSU LI‐FERN , BORDACHAR PIERRE , REUTER SYLVAIN , ROUDAUT RAYMOND , CLÉMENTY JACQUES , JAÏS PIERRE
Published: September 2005

Background: Catheter ablation of atrial fibrillation (AF) is challenging in patients with long‐standing persistent AF. The clinical outcome and subsequent arrhythmia recurrence after using an ablation method targeting multiple left atrial sites with the aim of achieving acute AF termination has not been characterized.

Methods: Sixty patients (mean age: 53 ± 9 years) with persistent AF (mean duration: 17 ± 27 months) were prospectively followed after catheter ablation. Catheter ablation targeting the following sites was performed in a random sequence: (i) electrical isolation of all pulmonary veins (PV); (ii) disconnection of other thoracic veins; (iii) atrial ablation at sites possessing complex electrical activity, activation gradients, or short cycle lengths. Finally, linear ablation of the LA roof and mitral isthmus was performed if sinus rhythm was not restored following energy delivery to the above sites. At 1, 3, 6, and 12 months after ablation, patients underwent clinical review and 24‐hour ambulatory ECG monitoring to identify asymptomatic arrhythmia. Repeat mapping and catheter ablation was performed in any patient experiencing recurrent atrial tachycardia (AT). Clinical success was defined as the absence of any sustained atrial arrhythmia.

Results: AF terminated during ablation in 52 patients (87%). The fluoroscopy and procedural durations were 84 ± 30 minutes and 264 ± 77 minutes, respectively. Three months after ablation, sustained ATs were documented in 24 patients (associated with AF in 2). Mapping in 23 patients showed a single AT in 7 while multiple ATs were observed in 16. Macroreentry was confirmed to be due to gaps in the ablation lines, while focal ATs originated from discrete sites or isthmuses near the left atrial appendage, coronary sinus, pulmonary veins, or fossa ovalis; these sites were similar to those at which the greatest impact was observed on the fibrillatory process during the initial ablation procedure. After repeat ablation, at 11 ± 6 months of follow‐up, 57 patients (95%) were in sinus rhythm and 3 developed recurrent AF or AT. All patients in sinus rhythm demonstrated improved exercise capacity and all but 2 had evidence of atrial transport as assessed by Doppler echocardiography (mitral A wave velocity 34 ± 17 cm/sec) by 6 months.

Conclusion: Catheter ablation of long‐lasting persistent AF associated with acute AF termination achieves medium to long‐term restoration and maintenance of sinus rhythm in 95% of patients. Arrhythmia recurrence in the majority of patients is AT.
Comparison of Proximal Isovelocity Surface Area Method and Pressure Half Time Method for Evaluation of Mitral Valve Area in Patients Undergoing Balloon Mitral Valvotomy
Authors: Roy Thottuvelil Narayanan Sunil , Krishnan Mangalth Narayanan , Koshy Cherian , Sajeev Chakanalil Govindan , Francis Johnson , Velayudhan Chamapparayil Chandran , Venugopal Krishnannair
Published: September 2005

Background: The pressure half time (PHT) method is unreliable for measurement of mitral valve area (MVA) immediately after valvotomy. The proximal isovelocity surface area (PISA) method has been used to derive mitral valve area in patients with mitral stenosis. The aim of our study was to compare PISA method and PHT method in patients undergoing percutaneous balloon mitral valvotomy (BMV). Methods: The PISA was recorded from the apex and MVA was calculated using continuity equation by the formula 2πr2 Vr/Vm, where 2πr2 is the hemispheric isovelocity area, Vr is the velocity at the radial distance “r” from the orifice, and Vm is the peak velocity. A plain angle correction factor (θ)/180 was used to correct the inlet angle subtended by leaflet tunnel as a result of leaflet doming. Results: MVA calculated using PISA method (r = 0.5217, P < 0.0001, SE = 0.016) and PHT (r = 0.6652, P < 0.0001, SE = 0.017) correlated well with 2D method in patients with mitral stenosis before BMV. After BMV, MVA by PISA method correlated well with 2D planimetry (r = 0.5803, P < 0.0001, SE = 0.053) but PHT showed poor correlation (r = 0.1334, P = 0.199, SE = 0.036). The variability of measurement of MVA was most marked with PHT method in the post‐BMV period. Conclusion: The PISA method correlates well with 2D planimetry in patients with mitral stenosis before and after BMV and is superior to the PHT method in the post‐BMV period where the latter may be unreliable.
Color M‐Mode Regurgitant Flow Propagation Velocity: A New Echocardiographic Method for Grading of Mitral Regurgitation
Authors: Akdemir Ramazan , Ozhan Hakan , Bulur Serkan , Unlu Hakan , Gunduz Huseyin , Arinc Huseyin , Yildiz Ahmet , Uyan Cihangir
Published: September 2005

Purpose: The aim of this study was to evaluate the reliability of mitral regurgitation color M‐mode regurgitant flow propagation velocity (RFPV) in grading mitral regurgitation (MR).
Methods: We prospectively examined 52 consecutive patients with grades of MR mild in 10 patients, moderate in 19 patients, and severe in 23 patients with quantitative pulse Doppler echocardiography. MR was evaluated by vena contracta diameter (VCD), regurgitant jet area (RJA), and RFPV. These qualitative and quantitative methods were compared with the pulsed Doppler quantitative flow measurements and concordance of these three methods was determined.
Results: The mean RFPV for mild, moderate, and severe MR were 26.4 ± 7 cm/sec, 43.3 ± 7 cm/sec, and 60.3 ± 7.3 respectively (P < 0.001). RFPV is highly sensitive and moderately specific in differentiating mild and severe MR from other subgroups. Sensitivity and specificity were 92.1%–64.3% for mild and 100%–68.5% for severe MR, respectively. Significant correlation was observed between pulse Doppler quantitative grades, RFPV, VC, and RJA (P < 0.0001, r = 0.87; P < 0.0001, r =−0.84; P < 0.0001, r = 0.76, respectively).
Conclusion: This results show that RFPV is a reliable and simple semiquantitative new method that can be used for determining severity of MR.
Local Intense Mosaic Pattern at Site of Flail Mitral Leaflet: Report of a New Color Doppler Sign
Authors: Khouzam Rami N. , D'Cruz Ivan A. , Minderman Daniel , Kaiser Jacqueline
Published: September 2005

Color flow Doppler has been useful in diagnosing the presence and severity of mitral regurgitation (MR). We noted a hitherto unreported sign of MR due to flail mitral leaflet: intense local mosaic pattern at the site of the flail leaflet. This sign was seen well in 11 of 14 patients (79%) with the two‐dimensional echocardiographic features of flail mitral leaflet, all with moderate or severe MR. In 3 other patients, the sign was absent; two of those had flail mitral leaflet with severe MR. No local mosaic pattern was seen on color Doppler in 20 other patients with MR but no flail mitral leaflet. We speculate that the focal intense mosaic color Doppler morphology may have been caused by intrusion of the flail leaflet into the MR stream, or to a Coanda‐like effect of the MR jet “adhering” to the flail leaflet.
Thermodynamic Assessment of the CaO–Al2O3–SiO2 System
Authors: Mao Huahai , Hillert Mats , Selleby Malin , Sundman Bo
Published: September 2005

The CaO–Al2O3–SiO2 system has been assessed with the CALPHAD technique, based on recent assessments of its binary systems. A new species AlO2−1 was introduced for modeling liquid Al2O3. The ternary liquid phase was described using the ionic two‐sublattice model as
. The available experimental data were critically examined, and a self‐consistent set of thermodynamic descriptions was obtained. Various phase diagrams and property diagrams, including isothermal sections, isoactivity lines, and a projection of the liquidus surface, are presented. Information on viscosity seems to support the use of the AlO2−1 species.
Thermochemical Analysis and Modeling of the Al2O3–Cr2O3, Cr2O3–SiO2, and Al2O3–Cr2O3–SiO2 Systems Relevant to Refractories
Authors: Besmann T. M. , Kulkarni N. S. , Spear K. E.
Published: September 2005

Phase diagram and chemical activity data, where available, for the Al2O3–Cr2O3, Cr2O3–SiO2, and Al2O3–Cr2O3–SiO2 systems were evaluated and used in the development of models for their thermochemical behavior. Ideal, regular, and subregular solution models were used for the various solid and liquid phases in the Al2O3–Cr2O3 and Cr2O3–SiO2 systems, the Al2O3–SiO2 having been previously modeled using the modified associate species approach. It was possible to model the Al2O3–Cr2O3 liquid as an ideal solution, and compute a phase diagram and activities that resolve previous conflicts. The binary oxide systems were combined into a single set of stoichiometric phases, a corundum solid solution, and a liquid solution to represent the Al2O3–Cr2O3–SiO2 system.
Conical Boron Nitride Nanorods Synthesized Via the Ball‐Milling and Annealing Method
Authors: Zhang Hongzhou , Yu Jun , Chen Ying , Fitz Gerald John
Published: September 2005

A boron nitride (BN) nanostructure, conical BN nanorod, has been synthesized in a large quantity on Si substrates for the first time via the ball‐milling and annealing method. Nitridation of milled boron carbide (B4C) powders was performed in nitrogen gas at 1300°C on the surface of the substrates to form the BN nanorods. The highly crystallized nanorods consist of conical BN basal layers stacked along the nanorod axis. Ball milling of the B4C powders can significantly enhance the nitridation of the powders and thus facilitate the formation of nanorods during the annealing process.
Fabrication of Textured Bi3NbTiO9 Ceramics
Authors: Xiang Ping‐Hua , Kinemuchi Yoshiaki , Watari Koji , Cao Fei , Dong Xian‐Lin
Published: September 2005

Highly textured Bi3NbTiO9 ceramics are fabricated by normal sintering from molten salt‐synthesized plate‐like crystallites. Fine Bi3NbTiO9 plate‐like crystallites (∼1 μm) not only facilitate the densification, but also enhance texture in Bi3NbTiO9 ceramics. Weak‐agglomerated platelets exhibit higher sinterability and can be densified at a temperature as low as 1000°C, which is about 100°C lower than that of equiaxed powders prepared by directly calcining Bi3NbTiO9 precursor. Meanwhile, the orientation degree of textured Bi3NbTiO9 ceramics increases with sintering temperature. Highly oriented Bi3NbTiO9 (orientation degree of ∼0.91) ceramic with a relative density of ∼92% is obtained at 1150°C. Because of the oriented grain microstructure, textured Bi3NbTiO9 ceramic exhibits anisotropic electrical properties.
Two‐Step Sintering of Ceramics with Constant Grain‐Size, II: BaTiO3 and Ni–Cu–Zn Ferrite
Authors: Wang X.‐H. , Deng X.‐Y. , Bai Hai‐Lin , Zhou H. , Qu Wei‐Guo , Li L.‐T. , Chen I.‐W.
Published: September 2005

We investigated the preparation of bulk dense nanocrystalline BaTiO3 and Ni–Cu–Zn ferrite ceramics using an unconventional two‐step sintering strategy, which offers the advantage of not having grain growth while increasing density from about 75% to above 96%. Using nanosized powders, dense ferrite ceramics with a grain size of 200 nm and BaTiO3 with a grain size of 35 nm were obtained by two‐step sintering. Like the previous studies on Y2O3, the different kinetics between densification diffusion and grain boundary network mobility leaves a kinetic window that can be utilized in the second‐step sintering. Evidence indicates that low symmetry, ferroelectric structures still exist in nanograin BaTiO3 ceramics, and that saturation magnetization is the same in nanograin and coarse grain ferrite ceramics.
Zero Thermal Expansion in (Al2x(HfMg)1−x)(WO4)3
Authors: Suzuki Tomoko , Omote Atsushi
Published: September 2005

Low‐thermal‐expansion materials in a wide temperature range are expected to be used in electronic devices, optical devices, and nanoscale devices. The authors have tried to fabricate a single‐phase zero‐thermal‐expansion material. A new single‐phase ceramic material, (Al2x(HfMg)1−x)(WO4)3, could be produced from a mixture of a negative‐thermal‐expansion material, (HfMg)(WO4)3, and a positive‐thermal‐expansion material, Al2(WO4)3. At x=0.15 this material shows nearly zero thermal expansion from room temperature to 800°C.
Budd‐Chiari syndrome as the first manifestation of polycythemia vera in young women with inherited thrombophilic state: an aggressive form of myeloproliferative disorder requiring multidisciplinary management
Authors: Breccia Massimo , Morano Salvatore Giacomo , D'Andrea Mariella , Russo Eleonora , D'Elia Gianna Maria , Alimena Giuliana
Published: September 2005

Abstract:  The Budd‐Chiari syndrome (BCS), characterized by the obstruction and occlusion of the suprahepatic veins, is a rare but typical complication occurring in patients with polycythemia vera (PV). We describe three young women who developed BCS as first manifestation of PV, in association with an inherited thrombophilic state and in the absence of concomitant use of oral contraceptives. Our report illustrates the existence of an aggressive form of myeloproliferative disorder, which requires prompt recognition and immediate therapeutic intervention including cytostatic drugs and anticoagulant treatment. Furthermore, we suggest the need of routine screening for thrombophilic state in young women affected by PV.
Could intensified treatment in childhood acute lymphoblastic leukemia improve outcome independently of risk factors?
Authors: Tzortzatou‐Stathopoulou Fotini , Moschovi Maria A. , Papadopoulou Athina L. , Barbounaki Ioanna G. , Lambrou George I. , Balafouta Myrsini , Syriopoulou Vassiliki
Published: September 2005

Abstract:  Purpose: Many risk‐directed therapeutic protocols have been proposed in acute lymphoblastic leukemia (ALL). However, the relapse rates remain high. The effectiveness of each protocol depends on how quickly the clearance of blast cells is achieved. In an attempt to improve survival, by minimizing treatment toxicity and relapse rate, different therapeutic protocols were used every 3 yr in our Unit. Patients and Methods: During 1991–2000, 132 children with ALL were diagnosed in our Unit. Modified and intensified NY II and BFM protocols, in three consecutive periods [(Hematology/Oncology Pediatric Department of the University of Athens) HOPDA‐91, HOPDA‐94, HOPDA‐97] were used. Results: At a median follow‐up time of 96 months, the 8‐year overall survival (OS) was 88% ± 3%, whereas the event‐free survival (EFS) was 85% ± 3%. There was a significant increase of the 5‐year EFS of the high‐risk (HR) group through time (65% in HOPDA‐91 vs. 80% in HOPDA‐97), whereas EFS of the low risk (LR) group in HOPDA‐97 was 96%. Five cases relapsed (3.8%), four of which underwent successful bone marrow transplantation. Fifteen children died (13 diagnosed by 1996, two in the last 4 yr). Conclusion: Modification of the protocols significantly improved survival in both HR and LR groups. The intensified regimen in the LR group did not increase the adverse toxic events, but on the contrary was extremely effective.
Plasmacytoma relapses in the absence of systemic progression post‐high‐dose therapy for multiple myeloma
Authors: Terpos Evangelos , Rezvani Katayoun , Basu Supratik , Milne Alison E. , Rose Peter E. , Scott Geoffrey L. , Rahemtulla Amin , Samson Diana , Apperley Jane F.
Published: September 2005

Abstract:  Autologous (ASCT) and allogeneic stem cell transplantations (alloBMT) are well‐established therapies for multiple myeloma. However, patients continue to relapse at a constant rate. We present here 15 out of 163 patients who underwent SCT and relapsed with plasmacytomas only without evidence of bone marrow disease progression (14/147 post‐ASCT and 1/16 post‐alloBMT). The median time from SCT to plasmacytoma relapse was 24 months. The sites of plasmacytoma included bone, skin, rectum, and testicles. Five patients were treated with local radiotherapy, while seven patients received a combination of radiotherapy and chemotherapy or thalidomide, and two patients received chemotherapy alone with or without thalidomide. The recipient of alloBMT was initially treated with VAD‐chemotherapy and local radiotherapy followed by a mini‐allograft from the original donor. Eleven patients died at a median of 10 months following diagnosis of the plasmacytoma. Four are still alive, 12–20 months post‐plasmacytoma diagnosis. These cases of unconventional disease recurrence are likely to be seen due to sub‐clinical seeding of tumour cells suggestive of the presence of an extramedullary (EM) clone of plasma cells with a high degree of chemoresistance. We also review all the available data in the literature for the optimal therapy for patients with isolated EM relapse.
Multiple myeloma in elderly patients: prognostic factors and outcome
Authors: Anagnostopoulos Athanasios , Gika Dimitra , Symeonidis Argyris , Zervas Konstantinos , Pouli Anastasia , Repoussis Panagiostis , Grigoraki Vassiliki , Anagnostopoulos Nikolaos , Economopoulos Theophanis , Maniatis Alice , Dimopoulos Meletios‐Athanasios
Published: September 2005

Abstract: Objectives: Purpose of this study was to compare prognostic factors and outcome of patients with multiple myeloma (MM) aged >70 yr at diagnosis with those of younger patients. We also applied the recently proposed International Staging System (ISS) for MM in these patients.Patients and methods: Among 1,162 newly diagnosed, symptomatic MM patients included in our database, 357 (31%) were >70 yr of age. Clinical and laboratory variables were evaluated in patients >70 yr and in younger patients and were assessed for possible correlation with survival in patients >70 yr of age.Results: Most clinical and laboratory features were similar in the two groups of patients but older patients presented more frequently with advanced ISS (P = 0.02). Despite similar response rates to primary treatment, younger patients survived longer than patients >70 yr of age (40 vs. 28 months,P = 0.001). There was a longer survival of younger patients than that of older patients diagnosed with ISS stage 1 (median 71 vs. 54 months,P = 0.007) and ISS stage‐2 patients (median: 38 vs. 26 months,P = 0.0008) but for patients with ISS stage 3 median survival was similarly poor in the younger and older age group (21 and 20 months,P = 0.283). Other variables associated with impaired prognosis were severe anemia, extensive bone marrow plasmacytosis and elevated serum LDH.Conclusions: Older patients with MM present more often with advanced ISS and have significantly shorter survival than younger patients. The ISS retained its prognostic significance within the group of elderly patients.
Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome
Authors: Tomizawa Daisuke , Aoki Yuki , Nagasawa Masayuki , Morio Tomohiro , Kajiwara Michiko , Sekine Teruaki , Shimizu Norio , Kato Masahiko , Yachie Akihiro , Mizutani Shuki
Published: September 2005

Abstract:  Omenn syndrome is a variant form of severe combined immunodeficiency. It is fatal unless treated by allogeneic stem cell transplantation (SCT), which is the only curative approach. However, both treatment‐related complications and graft rejection are major obstacles to treatment success. This report describes a case with Omenn syndrome who developed mixed chimerism after unrelated cord blood transplantation (UCBT). This case was successfully treated by altering the patient's immunosuppression and donor lymphocyte infusion (DLI) with donor cord blood‐derived activated CD4+ T cells ex vivo expanded from the cord blood cell residues in an infused bag. This novel development to expand CD4+ T‐lymphocytes from the donor cord blood unit for the use of DLI would serve as a useful method to overcome the risk of graft rejection in SCT for primary immunodeficiency disorders with residual cell‐mediated immunity without compounding graft‐vs.‐host disease, especially in the UCBT setting.
Sustained and stable hematopoietic donor‐recipient mixed chimerism after unrelated cord blood transplantation for adult patients with severe aplastic anemia
Authors: Mao P. , Zhu Z. , Wang H. , Wang S. , Mo W. , Ying Y. , Li Q. , Xu Y.
Published: September 2005

Abstract:  We evaluated the engraftment of donor cells from unrelated cord blood into adult patients with severe aplastic anemia (SAA) and the outcome of allo‐CBSCT (cord blood stem cell transplantation). Nine patients were conditioned with decreased dosage of immunosuppressive agents of CTX (60 mg/kg) and ALG (120 mg/kg). The prophylaxis of GVHD consisted of standard CsA and MTX. Patients have a media age of 25.3 yr (range: 15–37), and a median weight of 57.2 kg (range: 52.5–60) at the time of transplantation. Cord blood searches were all conducted at Guangzhou Cord Blood Bank. The engraftment state of the donor cells into recipients was confirmed by microsatellite DNA fingerprinting and fluorescent quantitative PCR analysis. Engrafted evidence has been found in seven patients involved by biomolecular analyses showing donor‐recipient mixed chimerism post‐transplant which was stable and persistent. After a median follow up of 32.2 months (range: 4–69), seven patients were alive and disease free. This study shows that durable donor‐recipient stable mixed chimerism can be achieved by unrelated CBSCT in patients with SAA. Umbilical cord blood could be employed as a source of hematopoietic stem cell for adult transplantation.
Melatonin counteracts inducible mitochondrial nitric oxide synthase‐dependent mitochondrial dysfunction in skeletal muscle of septic mice
Authors: Escames Germaine , López Luis C. , Tapias Víctor , Utrilla Pilar , Reiter Russel J. , Hitos Ana B. , León Josefa , Rodríguez María I. , Acuña‐Castroviejo Darío
Published: September 2005

Abstract:  Mitochondrial nitric oxide synthase (mtNOS) produces nitric oxide (NO) to modulate mitochondrial respiration. Besides a constitutive mtNOS isoform it was recently suggested that mitochondria express an inducible isoform of the enzyme during sepsis. Thus, the mitochondrial respiratory inhibition and energy failure underlying skeletal muscle contractility failure observed in sepsis may reflect the high levels of NO produced by inducible mtNOS. The fact that mtNOS is induced during sepsis suggests its relation to inducible nitric oxide synthase (iNOS). Thus, we examined the changes in mtNOS activity and mitochondrial function in skeletal muscle of wild‐type (iNOS+/+) and iNOS knockout (iNOS−/−) mice after sepsis. We also studied the effects of melatonin administration on mitochondrial damage in this experimental paradigm. After sepsis, iNOS+/+ but no iNOS−/− mice showed an increase in mtNOS activity and NO production and a reduction in electron transport chain activity. These changes were accompanied by a pronounced oxidative stress reflected in changes in lipid peroxidation levels, oxidized glutathione/reduced glutathione ratio, and glutathione peroxidase and reductase activities. Melatonin treatment counteracted both the changes in mtNOS activity and rises in oxidative stress; the indole also restored mitochondrial respiratory chain in septic iNOS+/+ mice. Mitochondria from iNOS−/− mice were unaffected by either sepsis or melatonin treatment. The data suggest that inducible mtNOS, which is coded by the same gene as that for iNOS, is responsible for mitochondrial dysfunction during sepsis. The results also suggest the use of melatonin for the protection against mtNOS‐mediated mitochondrial failure.
A Protein Kinase CK2 Site Flanking the Nuclear Targeting Signal Enhances Nuclear Transport of Human Cytomegalovirus ppUL44
Authors: Alvisi Gualtiero , Jans David A. , Guo Jinjin , Pinna Lorenzo A. , Ripalti Alessandro
Published: September 2005

The processivity factor of the human cytomegalovirus (HCMV) DNA polymerase phosphoprotein ppUL44 plays an essential role in viral replication, showing nuclear localization in infected cells. The present study examines ppUL44's nuclear import pathway for the first time, ectopic expression of ppUL44 revealing a strong nuclear localization in transfected COS‐7 and other cell types, implying that no other HCMV proteins are required for nuclear transportation and retention. We show that of the two potential nuclear localization signals (NLSs) located at amino acids 162–168 (NLS1) and 425–431 (NLS2), NLS2 is necessary and sufficient to confer nuclear localization. Moreover, using enzyme‐linked immunosorbent assays and gel mobility shift assays, we show that NLS2 is recognized with high affinity by the importin (IMP) α/β heterodimer. Using gel mobility shift and transient transfection assays, we find that flanking sequences containing a cluster of potential phosphorylation sites, including a consensus site for protein kinase CK2 (CK2) at Ser413 upstream of the NLS, increase NLS2‐dependent IMP binding and nuclear localization, suggesting a role for these sites in enhancing UL44 nuclear transport. Results from site‐directed mutagenic analysis and live‐cell imaging of green fluorescent protein (GFP)‐UL44 fusion protein‐expressing cells treated with the CK2‐specific inhibitor 4,5,6,7‐tetrabromobenzotriazole are consistent with phosphorylation of Ser413 enhancing ppUL44 nuclear transport.
Multiple Roles for Cyclin G‐Associated Kinase in Clathrin‐Mediated Sorting Events
Authors: Zhang Claire X. , Engqvist‐Goldstein Åsa E. Y. , Carreno Sebastien , Owen David J. , Smythe Elizabeth , Drubin David G.
Published: September 2005

Cyclin G‐associated kinase (GAK), also known as auxilin 2, is a potential regulator of clathrin‐mediated membrane trafficking. It possesses a kinase domain at its N‐terminus that can phosphorylate the clathrin adaptors AP‐1 and AP‐2 in vitro. The GAK C‐terminus can act as a cochaperaone in vitro for Hsc70, a heat‐shock protein required for clathrin uncoating. Here we show that the specificity of GAK is very similar to that of adaptor‐associated kinase 1, another mammalian adaptor kinase. We used siRNA to investigate GAK's in vivo function. We discovered that early stages of clathrin‐mediated endocytosis (CME) were partially inhibited when GAK expression was knocked down. This defect was specifically caused by GAK knockdown because it could be rescued by expressing a rat GAK gene that could not be silenced by one of the siRNAs. To identify the GAK activity required during CME, we mutated the kinase domain and the J domain of the rat gene. Only GAK with a functional J domain could rescue the defect, suggesting that GAK is important for clathrin uncoating. Furthermore, we demonstrated that GAK plays a role in the clathrin‐dependent trafficking from the trans Golgi network.
Plasma Dependent Reduction in Red Blood Cell Aggregation After Dextran Sulfate Low‐density Lipoprotein Apheresis—Implications for Rheological Studies
Authors: Schechner Vered , Ben‐Ami Ronen , Hershcovici Tiberiu , Yedgar Shaul , Beigel Ytzhak , Shapira Itzhak , Berliner Shlomo , Barsthein Gershon
Published: September 2005

Abstract:  Red blood cell (RBC) aggregation is increased in familial hypercholesterolemia, and is reduced significantly after low density lipoprotein (LDL) apheresis. The purpose of the present study was to clarify whether this reduction depends on changes in plasma composition, RBC membrane properties, or both. RBC aggregation was determined in a computerized cell flow‐properties analyzer, before and after LDL apheresis. We compared RBC aggregation in autologous plasma with aggregation in a plasma‐free standard solution (0.5% of dextran 500 kDa) to define the separate contributions of plasma and cellular properties to the observed RBC aggregation. RBC aggregation in autologous plasma was reduced by 35.5% after LDL apheresis (P = 0.01) but was not significantly affected when measured in dextran 500. This suggests that LDL apheresis attenuated RBC aggregation by altering plasma composition rather than RBC membrane properties. These results are relevant to the understanding of hemorheological changes which follow therapeutic apheresis in hypercholesterolemic patients.