bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and performance evaluation of an hybrid reservation‐polling MAC protocol for power‐line communications
Authors: Bianchi G. , Tinnirello I. , Conigliaro G.
Published: June 2003

This paper presents an hybrid reservation‐polling MAC protocol able to effectively deal with the channel disturbances typical of Power‐line communication systems. Channel access is controlled by a scheduler running on a centralized station. Fast retransmission of corrupted packets is employed to achieve high performance on Power‐line channels characterized by frequent error bursts due to impulsive noise. The performance of our proposed mechanism are evaluated by means of simulation, for the more challenging case of time‐sensitive traffic sources (voice calls). Results show that the system efficiency is virtually not affected by lightly to moderately disturbed PLC channel. Moreover, by slightly reducing the system utilization, a target 1% packet loss ratio can be met even in the presence of severe channel disturbances. Copyright © 2003 John Wiley & Sons, Ltd.
Distributed MAC protocols and priority oriented scheduling for a PLC access network
Authors: Sundaresan S. , Anand S. , Srikanth S. , Krishnan C. N.
Published: June 2003

In this paper, we propose a distributed channel allocation scheme for the uplink data traffic and implement a priority oriented scheduling for the downlink data traffic for a powerline access type network. We study the performance of the uplink and downlink protocols in terms of the buffering probability, mean delay, statistical dropping probability and the number of subscriber stations supported. The distributed channel allocation scheme uses a modified carrier sensing mechanism and a centralized collision resolution scheme. We model the channel occupancy of uplink data calls using a continuous time Markov chain (CTMC). We derive the expressions for mean delay, statistical dropping probability, and utilization by solving the CTMC. We also perform extensive simulations to complement our analytical results. Our results indicate that, the distributed channel allocation approach achieves 10% improvement in spectrum utilization compared to a centralized reservation protocol. We also implement a priority oriented scheduling policy for the downlink data traffic. In the system we consider, the downlink channels are adaptively modulated based on their signal strength. We maximize the instantaneous link utilization by using MaxFlow algorithm. Simulation results for downlink scheduling show that the mean buffering delay for the real‐time variable bit rate traffic is zero and that the system supports 170 access stations. We also show that system with adaptive modulation achieves 26% savings in transmitted power compared to the system without adaptive modulation. Copyright © 2003 John Wiley & Sons, Ltd.
Differential acquired immune responsiveness to bacterial lipoproteins in Lyme disease‐resistant and ‐susceptible mouse strains
Authors: Ganapamo Frédéric , Dennis Vida A. , Philipp Mario T.
Published: June 2003

We investigated the effect of Borrelia burgdorferi lipoproteins (outer surface protein A) and the synthetic lipohexapeptide tripalmitoyl‐S‐glyceryl‐Cys‐Ser‐4(Lys) (Pam3‐Cys) on isolated lymph node (LN) cells from Lyme disease‐susceptible (C3H/HeJ) and ‐resistant (C57BL/6J) mice. Mice were either infected with B. burgdorferi for 1 week or left uninfected. Lipoprotein‐stimulated LN cells from infected C3H/HeJ mice produced significantly higher levels of the inflammatory cytokines IL‐6 and IFN‐γ than did cells from C57BL/6J mice. Cells from uninfected mice did not respond. No TNF‐α or IL‐1β were produced by LN cells from infected mice of either strain in response to lipoprotein or B. burgdorferi spirochetes. Unlike with IL‐6 or IFN‐γ, LN cells from either strain failed to produce IL‐10 in response to lipoproteins. However, the LN cells were able to produce this cytokine in response to B. burgdorferi spirochetes or after incubation with phorbol‐12‐myristate‐13‐acetate/ionomycin, anti‐CD3 antibody alone or anti‐CD3 combined with anti‐CD28 antibodies. Addition of exogenous IL‐10 to lipopeptide‐stimulated cultures significantly reduced IFN‐γ and IL‐6 production in a dose‐dependent fashion. This inhibition was more effective with cells from disease‐resistant C57BL/6J mice than with cells from disease‐susceptible C3H/HeJ mice. The proclivity to disease of the C3H/HeJ mouse could be simultaneously based on the phenomena of enhanced inflammatory responsiveness to lipoproteins and diminished ability to respond to IL‐10. An investigation of the determinants of these two phenomena could be used as a blueprint to elucidate the pathogenesis of Lyme disease in humans.
Caspase‐8 and caspase‐10 activate NF‐κB through RIP, NIK and IKKα kinases
Authors: Shikama Yoshiaki , Yamada Masao , Miyashita Toshiyuki
Published: June 2003

NF‐κB regulates the expression of various genes involved in cell growth and differentiation, immune response and inhibition of apoptosis. Recently, some death effector domain (DED)‐containing proteins, such as FADD and c‐FLIP were reported to activate NF‐κB. We previously reported that the prodomain‐only isoforms of caspase‐8 and ‐10 (PDCasp8/10), containing two DED motifs, could inhibit Fas‐mediated apoptosis. Here, we demonstrate that these isoforms also activate NF‐κB, implying this to be one of the mechanisms by which these polypeptides inhibit apoptosis. The GST pull‐down assay revealed that, among upstream kinases that activate NF‐κB, only NIK and RIP, but not RICK or IKKα/β, could directly bind to PDCasp8/10. In addition, both modules ofDED in PDCasp8/10 were required for these interactions as well as NF‐κB activation. Experiments using a kinase‐dead mutant of IKKα and an RIP mutant lacking a kinase domain, both of whichfunction as dominant‐negative mutants for their wild‐type counterparts, blocked PDCasp8/10‐mediated NF‐κB activation. Using small interfering RNA technology, we further demonstrate that the down‐regulation of IKKα but not IKKβ significantly inhibits PDCasp8‐mediated NF‐κB activation. Taken together, these results suggest that caspase‐8 and ‐10 have roles in a non‐ or anti‐apoptotic signaling pathway leading to NF‐κB activation through RIP, NIK and IKKα.
Practical considerations of recombinant adeno‐associated virus‐mediated gene transfer for treatment of retinal degenerations
Authors: Shen Wei‐Yong , Lai Chooi‐May , Lai Yvonne K. Y. , Zhang Dan , Zaknich Tammy , Sutanto Erika N. , Constable Ian J. , Elizabeth Rakoczy P.
Published: June 2003

Background

Photoreceptor (PR) and retinal pigment epithelium (RPE) are the principal cell targets in retinal gene therapy. Recombinant adeno‐associated virus (rAAV) has emerged as a very promising vector for gene therapy in hereditary retinal diseases. Gene transfer at different stages of the disease is a practical consideration for future clinical application.

Methods

A rAAV carrying the enhanced green fluorescent protein gene driven by a cytomegalovirus promoter was produced by either co‐infecting the 293 cell line with E1‐defective adenovirus and purified by CsCl2 density gradient (CsCl2‐rAAV), or by transfecting with an adenoviral helper plasmid and purified by iodixanol density gradient followed by heparin column chromatography (heparin‐rAAV). The impact of different virus preparations on the patterns of transgene expression was investigated after subretinal injection. Furthermore, rAAV‐mediated gene transfer was evaluated at both early and advanced stages of retinal degeneration in four disease models including the RCS rat, rd, RPE65−/− and cathepsin D mutant mice that are associated with PR‐ or RPE‐related gene defects.

Results

CsCl2‐rAAV predominantly transduced RPE and with less efficiency in PR. In contrast, heparin‐rAAV predominantly transduced PR but with much less efficiency in RPE. Subretinal injection of either rAAV preparation induced no changes to retinal morphology and retinal‐choroidal vasculature. The product of transgene, however, could be observed in multiple tracts in the brain. In the four disease models, target cells were efficiently transduced not only at the early stage, but also at the late stage of disease as long as the target cells were present.

Conclusions

Different preparations of rAAV have an impact on the patterns of transgene expression after subretinal injection. Patients at advanced stages of retinal degeneration may still benefit from rAAV‐mediated gene therapy. The possible side effects of transgenic products on the central nervous system should be carefully monitored once therapeutic genes are employed. Copyright © 2003 John Wiley & Sons, Ltd.
Sendai virus vectors as an emerging negative‐strand RNA viral vector system
Authors: Bitzer Michael , Armeanu Sorin , Lauer Ulrich M. , Neubert Wolfgang J.
Published: June 2003

The power to manipulate the genome of negative‐strand RNA viruses, including the insertion of additional non‐viral genes, has led to the development of a new class of viral vectors for gene transfer approaches. The murine parainfluenza virus type I, or Sendai virus (SeV), has emerged as a prototype virus of this vector group, being employed in numerous in vitro as well as animal studies over the last few years. Extraordinary features of SeV are the remarkably brief contact time that is necessary for cellular uptake, a strong but adjustable expression of foreign genes, efficient infection in the respiratory tract despite a mucus layer, transduction of target cells being independent of the cell cycle, and an exclusively cytoplasmic replication cycle without any risk of chromosomal integration.

In this review we describe the current knowledge of Sendai virus vector (SeVV) development as well as the results of first‐generation vector applications under both in vitro and in vivo conditions. So far, Sendai virus vectors have been identified to be a highly efficient transduction tool for a broad range of different tissues and applications. Future directions in vector design and development are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
A robust incomplete factorization preconditioner for positive definite matrices
Authors: Benzi Michele , Tůma Miroslav
Published: June 2003

We describe a novel technique for computing a sparse incomplete factorization of a general symmetric positive definite matrix A. The factorization is not based on the Cholesky algorithm (or Gaussian elimination), but on A‐orthogonalization. Thus, the incomplete factorization always exists and can be computed without any diagonal modification. When used in conjunction with the conjugate gradient algorithm, the new preconditioner results in a reliable solver for highly ill‐conditioned linear systems. Comparisons with other incomplete factorization techniques using challenging linear systems from structural analysis and solid mechanics problems are presented. Copyright © 2003 John Wiley & Sons, Ltd.
An unstructured multigrid method based on geometric smoothness
Authors: Chow Edmond
Published: June 2003

For non‐M‐matrices, this paper proposes an unstructured multigrid method that only attempts to interpolate in the directions of geometric smoothness. These directions are determined by analysing samples of algebraically smooth error, e. Neighbouring grid points i and j are called smoothly coupled if ei and ej are consistently nearby in value. In addition, these differences may be used to define interpolation weights. These new ideas may be incorporated into the algebraic multigrid method. Test results show that the new method can have much lower grid and operator complexities compared to AMG, leading to lower solve timings. Published in 2003 by John Wiley & Sons, Ltd.
On a possible melting curve of C60 fullerite
Authors: Zubov V. I. , Rodrigues C. G. , Zubov I. V.
Published: June 2003

We study the thermodynamic properties of the high‐temperature modification of fullerites on the basis of the Girifalco intermolecular potential. In the present work, using Lindemann's melting criterion, we estimate a possible melting curve Tm(P) of C60 fullerite. To take into account the lattice anharmonicity, which has a strong effect at T > 700 K, we use the correlative method of unsymmetrized self‐consistent field. To check this approach, first we have applied it to solid Ar. In the range between its triple point Tt = 83.807 K and 260 K we obtained the mean square relative deviation from experimental data of about 0.7%. The melting curve for C60 fullerite has been calculated from the melting point at normal pressure estimated at 1500 K up to 15 kbar, which corresponds to Tm = 4000 K, i.e. to the temperature estimated by Kim and Tománek [Phys. Rev. Lett. 72, 2418 (1994)] as that of the decomposition of the C60 molecule itself. The temperature dependence of the melting pressure is approximated very well by the Simon equation (Pm(T)/bar – 1)/b = (T/T0)c with T0 = 1500 K, b = 6643.8, and c = 1.209. The temperature dependence of the molar volume along the melting curve is described by Vs(T) = Vs(T0) – 29.20 ln (T/T0.
Theoretical analysis of disorder effects on electronic and optical properties of the quaternary alloy In1–xGaxAsySb1–y epilayer on GaSb and InAs
Authors: Rabah M. , Sahraoui B. , Bouhafs B. , Abbar B. , Abid H.
Published: June 2003

The effects of structural and chemical disorder on electronic and optical properties of In1–xGaxAsySb1–y quaternary alloy are studied on the basis of a modified virtual crystal approximation calculated within a simple tight‐binding sp3s* theory, which incorporates relaxation parameters and compositional disorder as an effective potential. Using a minimal set of fitting parameters, we show that such an approach provides analytical results for calculating energy gaps and bowing parameters. The electronic structure are studied for In1–xGaxAsySb1–y (x = 0.5, y = 0.5) and In1–xGaxAsySb1–y lattice matched to GaSb and as well as to InAs. In addition, a method for calculating the refractive indices at energies below the direct band gap edge is presented. The photon energy dependence of the refractive index is calculated with the model of dielectric constants of semiconductors based on simplified models of the interband transitions. Also the composition dependence of the refractive index is discussed; the result indicates that the refractive index increases with alloying for an In1–xGaxAsySb1–y lattice matched to InAs and GaSb. The lattice thermal resistivity has been calculated using interpolation schemes. The result indicates that the thermal resistivity of an In1–xGaxAsySb1–y lattice matched to InAs and GaSb for the composition of (0 ≤ x ≤ 1) increases markedly with alloying and exhibits a maximum value of about 41 W–1 deg cm at an alloying composition of x ≅ 0.45 and about 40 W–1 deg cm at an alloying composition of x ≅ 0.50 for InGaAsSb on a substrate of GaSb and InAs, respectively.
Preclinical removable partial dentures curriculum survey
Authors: Rashedi Behnoush , Petropoulos Vicki C.
Published: June 2003

Purpose In 2001, a survey of U.S. dental schools was conducted to determine the curricular structure, teaching philosophies, and techniques used in preclinical removable partial denture (RPD) courses and to also establish what newer educational techniques and materials are currently being used by U.S. dental schools.

Materials and Methods The questionnaire was mailed to the chairpersons of the prosthodontic/restorative departments of 54 U.S. dental schools. Of these, 43 schools returned the completed survey, resulting in a response rate of 80%. The mean, median, and range of responses were computed where applicable.

Results Results from this survey show that the mean student‐to‐faculty ratio in the preclinical RPD course was 12:1, with a median of 10:1 and a range of 6:1 to 27:1. The mean number of laboratory hours was 55, with a median of 50 and a range of 13.5 to 120. The mean number of lecture hours reported was 21, with a median of 20.5 and a range 10 to 60. The mean number of practical examinations was 2, with a median of 3 and a range of 0 to 8. The mean number of written examinations given was 2, with a median of 2 and a range of 1 to 6. Ninety‐five percent of the schools have prosthodontists teaching this course. The mean number of months that this course is taught is 4.4 months, with a median of 4 and a range of 1.5 to 10. Fifty‐five percent of the schools used the Hanau semiadjustable articulator. One hundred percent of the schools teach students to use a surveyor when designing an RPD, and 84% percent of the schools teach the Krol or the Kratochvil RPI design or a combination of the 2 designs.

Conclusions Preclinical RPD educational programs vary from school to school, yet a large percentage of schools agree on certain topics. Only 19% of dental schools are incorporating new technologies, such as the use of the internet, in their preclinical RPD curriculum.
Anomalous transport in heterogeneous media demonstrated by streamline‐based simulation
Authors: Di Donato Ginevra , Obi Eguono‐Oghene , Blunt Martin J.
Published: June 2003

We use fine‐grid streamline simulation to demonstrate that anomalous (non‐Gaussian) transport arises from purely advective movement through heterogeneous systems.The simulation model represents a channeled sandstone North Sea oil field and contains over one million grid blocks. We find the average location and spreading of the plume and the breakthrough curves. These features are consistent with anomalous transport described by an exponent β that characterizes the long‐time tail of the transit time distribution. β depends on the degree of heterogeneity and whether the tracer was injected or originally uniformly distributed across the domain. Incorporating dispersion to account for sub‐grid‐block heterogeneity does not affect the results.
Histological features of renal allograft biopsies in ABO minor‐mismatched kidney transplantation
Authors: Shimizu Tomokazu , Tanabe Kazunari , Tokumoto Tadahiko , Shimmura Hiroaki , Ishikawa Nobuo , Ishida Hideki , Toma Hiroshi , Kawaguchi Hiroshi , Tokiwa Michio , Yamaguchi Yutaka
Published: June 2003

Abstract:  We examined histological features of allograft biopsies in ABO minor‐mismatched kidney transplantation. Forty‐five patients who underwent ABO minor‐mismatched kidney transplantation between September 1999 and December 2001 at our institute. The mean age was 32.6 years, with 28 males and 17 females. We divided them into five groups based on the donor and recipient ABO blood groups. Group 1, O renal allografts given to A patients (13 patients); Group 2, O to B (9), Group 3, O to AB (2); Group 4, A to AB (9); and Group 5, B to AB (12). From September 1999 to April 2002, we performed 127 allograft biopsies in these 45 ABO minor‐mismatched kidney transplant recipients. Among a total of 127 biopsy specimens, 47 specimens were taken as 0‐ or 1‐h biopsies and 6 were protocol biopsies. Pathological analysis of 74 episode biopsy specimens showed: acute humoral rejection (AHR) in 13 (18%); acute cellular rejection (ACR) in 17 (23%); combined AHR and ACR in eight (11%); borderline change in six (8%); chronic rejection in 10 (12%); cyclosporin or tacrolimus nephrotoxicity in seven (10%) and chronic allograft nephropathy in three (4%). In total, some form of acute rejection (AR) was seen histologically in 38 biopsy specimens (48%) from 19 patients (42%). When we investigated AR in two separate categories, i.e. AHR and ACR, AHR was diagnosed in 21 biopsy specimens (26%) from 15 patients (33%) and ACR was seen in 25 biopsy specimens (31%) from 13 patients (29%). We compared the incidence rate of acute rejection in the cases of ABO minor‐mismatched renal transplantation with ABO‐incompatible and ABO‐compatible cases between January 1989 and December 1999. The incidence rate of AR in ABO minor‐mismatched cases (42%) was statistically lower than that in ABO‐incompatible cases (63%). There was no statistical difference in the incidence rate of AR between ABO minor‐mismatched cases and ABO‐compatible cases (49%). There was statistical difference in the incidence of AR among the donor and recipient ABO blood groups. Group 4 (A allografts given to AB patients) had the statistically highest rate of AR (89%), followed by Group 1 (54%), Group 5 (33%) and Group 2 (11%), and there was no AR case in Group 3 (O to AB). In conclusion, the incidence rate of AR in ABO minor‐mismatched kidney transplantation is statistically lower than ABO‐incompatible cases and is not statistically different from that in ABO‐compatible cases. The incidence cases of AHR are slightly higher than that of ACR in ABO minor‐mismatched kidney transplantation and this finding is similar to findings of ABO incompatible kidney transplantation. Finally, there is a statistical difference in AR incidence among the donor and recipient ABO blood groups.
Sympathetic nerve activity does not reduce proprioceptive acuity in humans
Authors: Matre D. , Knardahl S.
Published: June 2003

Aim:  Proprioception is essential in coordinating body segments and controlling muscles to perform movements. Animal studies have reported reduced muscle spindle sensitivity in jaw muscles during stimulation of sympathetic nerves. A stress‐induced distortion of proprioception has been suggested that could lead to reduced fine control of movement and inefficient muscle use. The present study investigated whether increased muscle sympathetic activation alter human proprioception.

Method:  Movement detection thresholds of the right ankle were determined in eight healthy subjects, before and during two conditions known to increase muscle sympathetic activity (MSA); a cold pressor test (CPT) and oral glucose ingestion (GLUC).

Results:  During a cold pressor test plasma noradrenaline (NA) and mean arterial pressure (MAP) increased significantly, compared with baseline (Ps < 0.01), whereas the movement thresholds were unchanged (Ps >> 0.05). After GLUC plasma NA and MAP increased significantly, compared with baseline (Ps < 0.05). The movement threshold into flexion decreased (P = 0.022), whereas into extension there was no change (P = 0.28). The most prominent increase of plasma NA corresponded with a reduced movement detection threshold, suggesting increased muscle spindle sensitivity.

Conclusion: The present findings contradict previous reports from animal studies and the hypothesis that sympathetic nerve activity reduces proprioceptive acuity.
Remission maintenance by tioguanine in chronic active Crohn's disease
Authors: Herrlinger K. R. , Deibert P. , Schwab M. , Kreisel W. , Fischer C. , Fellermann K. , Stange E. F.
Published: June 2003

Background: Tioguanine may offer an alternative for immunosuppression in chronic active Crohn's disease. Recently, we have shown that tioguanine is effective in inducing rapid remission.

Aim: To evaluate the role of tioguanine in the maintenance of remission in chronic active Crohn's disease.

Methods: A follow‐up study was performed to investigate the long‐term efficacy and safety of and tolerance to tioguanine in chronic active Crohn's disease. Sixteen patients who had successfully received 6‐tioguanine for remission induction were enrolled. The reasons for immunosuppressive therapy were steroid dependence (n = 10), steroid refractoriness (n = 6) and intolerance (n = 6) or refractoriness (n = 1) to azathioprine. After remission induction therapy for 6 months, patients were treated for another 6 months with a daily dose of 20–40 mg tioguanine. Primary outcomes were remission (Crohn's disease activity index < 150) and complete steroid reduction in steroid‐dependent patients at 12 months. Laboratory controls of white blood count and liver enzymes, as well as erythrocyte tioguanine nucleotide levels, were performed regularly.

Results: After 12 months of treatment, 14 of 16 (88%) patients were in remission, and 12 of these were completely free of systemic steroids. Adverse events during maintenance therapy included photosensitivity (one patient), minor viral infections (one), headache (four) and mild alopecia (one). One patient developed elevated liver enzymes, splenomegaly and thrombocytopenia, indicative of nodular regenerative hyperplasia of the liver.

Conclusions: In responders to tioguanine, the drug appears to be very effective in maintaining remission of chronic active Crohn's disease. Unfortunately, long‐term hepatotoxicity seems to be an unpredictable and potentially severe adverse drug reaction. Therefore, to date, tioguanine cannot be recommended for general use outside clinical trials.
Conscious sedation with propofol in elderly patients: a prospective evaluation
Authors: Heuss L. T. , Schnieper P. , Drewe J. , Pflimlin E. , Beglinger C.
Published: June 2003

Aim: To characterize the safety of endoscopic procedures and propofol use as administered by nurses in a cohort of elderly patients.

Methods: During 19 months all endoscopy patients > 70 years were eligible for this prospective observational study. Patients were assigned to group A (70–85 years) or group B (> 85 years). Records from all patients < 70 years treated during the same period served as controls. Specially trained nurses administered the propofol and monitored for complications (decrease in the peripheral oxygen saturation, mean arterial pressure or heart rate).

Results: There were 1435 endoscopic procedures in group A and 351 in group B. There was no procedure or sedation‐related mortality, nor a significantly greater need for emergency intervention than in the control group. Two patients required short mask ventilation but recovered without sequelae. Compared with younger patients, there was a significant increase in risk for a short oxygen desaturation < 90% and a decrease in oxygen saturation > 5%. Arterial hypotension occurred significantly more often in the control group than among the aged patients.

Conclusions: This present study documents that gastrointestinal endoscopic procedures are safe and well tolerated even in the very elderly. Nurse‐administered propofol is a safe and reasonable sedation method in these patients.
CYP2C19 pharmacogenetics in the clinical use of proton‐pump inhibitors for gastro‐oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms
Authors: Egan L. J. , Myhre G. M. , Mays D. C. , Dierkhising R. A. , Kammer P. P. , Murray J. A.
Published: June 2003

Background:  The rate of metabolic inactivation of proton‐pump inhibitors is determined by polymorphisms of CYP2C19. It is not known if CYP2C19 variant alleles affect responses to proton‐pump inhibitor therapy in gastro‐oesophageal reflux disease (GERD).

Aim:  To determine if the CYP2C19 genotype is associated with clinical effectiveness of proton‐pump inhibitors during GERD therapy.

Methods:  GERD patients undergoing ambulatory gastric and oesophageal pH monitoring were genotyped for CYP2C19 polymorphisms.

Results:  Sixty subjects were enrolled. Forty‐four subjects had two wild‐type alleles, 15 had one variant, and one had two variant CYP2C19 alleles. The presence of a variant allele was significantly associated with a lower odds of gastric acid breakthrough during proton‐pump inhibitor therapy [odds ratio 5.14, 95% confidence interval (CI) 1.17–22.61]. The presence of a variant allele was not associated with a lower odds of significant oesophageal acid exposure (odds ratio 2.50, 95% CI 0.60–10.52), or the occurrence of symptoms (incidence rate ratio 1.06, 95% CI 0.54–2.06).

Conclusions:  These results indicate that factors other than gastric acid secretion are important determinants of reflux in GERD patients. This suggests that CYP2C19 genotype testing will not be useful in proton‐pump inhibitor therapy of GERD, except perhaps in identifying patients at risk for hypochlorhydria and consequent hypergastrinemia.
The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia: the Canadian Adult Dyspepsia Empiric Treatment – Prompt Endoscopy (CADET–PE) study
Authors: Thomson A. B. R. , Barkun A. N. , Armstrong D. , Chiba N. , White R. J. , Daniels S. , Escobedo S. , Chakraborty B. , Sinclair P. , Veldhuyzen Van Zanten S. J. O.
Published: June 2003

Background: Uninvestigated dyspepsia is common in family practice. The prevalence of clinically significant upper gastrointestinal findings (CSFs) in adult uninvestigated dyspepsia patients, and their predictability based on history, is unknown.

Methods: Prompt endoscopy was performed within 10 days of referral, in 1040 adult patients presenting with uninvestigated dyspepsia at 49 Canadian family practitioner centres. Subsequent management strategies during a 6‐month follow‐up period were determined by the individual family practitioners.

Results: CSFs were identified in 58% (603/1040) of patients. Erosive oesophagitis was most common (43%; N = 451); peptic ulcer was uncommon (5.3%; N = 55). Alarm symptoms were uncommon (2.8%; N = 29). Most patients had at least three dyspepsia symptoms, more than 80% had at least six, and approximately half had eight or more. Based on the dominant symptom, 463 (45%) patients had ulcer‐like, 393 (38%) had reflux‐like and 184 (18%) had dysmotility‐like dyspepsia. The patients' dominant symptom was not predictive of endoscopic findings. Oesophagitis was more common in those with dominant reflux‐like symptoms and was the most common finding in all subgroups. The prevalence of gastroduodenal findings was similar in all symptom subgroups. Helicobacter pylori (H. pylori) infection (30%; 301/1013) was associated with gastroduodenal findings.

Conclusions: Dyspepsia subclassifications, based on dominant symptom, are of limited value in predicting the presence and nature of CSFs. Oesophagitis was by far the most common diagnosis (43% of patients). CSFs were common in uninvestigated dyspepsia patients and their nature suggests patients could be initially treated effectively, without endoscopy, using empirical acid suppressive therapy.
Upregulation of osteoblast apoptosis by malignant plasma cells: a role in myeloma bone disease
Authors: Silvestris Franco , Cafforio Paola , Tucci Marco , Grinello Daniela , Dammacco Franco
Published: June 2003

Summary. Typical features of multiple myeloma (MM) are osteolytic lesions and severely affected bone regeneration. This study of 53 MM patients demonstrates an enhancement of osteoblast cytotoxicity by malignant myeloma cells via the upregulation of apoptogenic receptors, including Fas ligand (Fas‐L) and tumour‐necrosis‐factor‐related apoptosis inducing ligand (TRAIL). Both were significantly increased in the marrow myeloma cells of patients with extensive osteolytic lesions in a fashion similar to the highly malignant human myeloma cell line MCC‐2. Osteoblasts from these subjects over‐expressed Fas and death receptor (DR) 4/5 and underwent dramatic apoptosis when co‐cultured with either MCC‐2 or autologous myeloma cells. In osteoblast and myeloma cell co‐cultures, monocyte chemoattractant protein 1 (MCP‐1) mRNA was upregulated in osteoblasts from patients with severe bone disease in parallel with increased CC‐chemokine receptor R2 (CCR2) expression, the ligand of MCP‐1, in the myeloma cells. This chemokine was shown to activate malignant cell migration in vitro. An upregulation of ICAM‐1 expression occurred in osteoblasts from patients with active skeleton disease. This upregulation appeared to be an effect of malignant plasma cell contact, as MCC‐2 co‐culture greatly enhanced ICAM‐1 production by resting osteoblasts from patients without skeleton involvement. Our results suggest that osteoblasts in active myeloma are functionally exhausted and promptly undergo apoptosis in the presence of myeloma cells from patients with severe bone disease. It is suggested that this cytotoxic effect plays a pivotal role in the pathogenesis of defective bone repair.
The human granulocyte/macrophage colony‐stimulating factor receptor α2 isoform influences haemopoietic lineage commitment and divergence
Authors: Slater Nicholas J. , Yamaguchi Masafumi , Rothwell Dominic G. , Baker Patrick , Heyworth Clare M. , Chopra Rajesh
Published: June 2003

Summary. A number of alternatively spliced isoforms of haemopoietic growth factor receptors (HGFRs) have been described, but their role in human haemopoiesis remains undetermined. We have investigated the relative expression of the α1 and α2 isoforms of human granulocyte/macrophage colony‐stimulating factor receptor (hGM‐CSFR) during haemopoietic cell differentiation, and have shown that both subunits are independently regulated during differentiation of CD34+ human haemopoietic progenitor cells. To further investigate these ex‐vivo observations, we established a series of murine FDCP mix cell lines, which, as a consequence of the ectopic expression of α1 or α2 hGM‐CSFR, demonstrated differential differentiation responses to hGM‐CSF. In this model system, hGM‐CSFR‐α2‐expressing cells showed increased hGM‐CSF‐mediated erythroid/megakaryocytic differentiation compared with hGM‐CSFR‐α1‐expressing cells.
Minimal residual disease prior to stem cell transplant for childhood acute lymphoblastic leukaemia
Authors: Goulden Nick , Bader Peter , Van der Velden Vincent , Moppett John , Schilham Marco , Masden Hans O. , Krejci Ondrej , Kreyenberg Hermann , Lankester Arjan , Révész Tom , Klingebiel Thomas , Van Dongen Jacques
Published: June 2003

Summary.Allogeneic stem cell transplantation (SCT) is a highly effective therapy for childhood acute lymphoblastic leukaemia (ALL). Concerns about unnecessary toxicity and expense mean that SCT is currently largely reserved for children who cannot be cured with chemotherapy. Not surprisingly, many such children also fail SCT. Retrospective studies have shown that a single analysis of minimal residual disease (MRD) pre‐SCT identified those at highest risk of relapse. It is now appropriate to call for the universal incorporation of standardized MRD testing into SCT protocols as the next step to maximize the clinical impact of this technology in ALL.
Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy
Authors: Lachmann Helen J. , Gallimore Ruth , Gillmore Julian D. , Carr‐Smith Hugh D. , Bradwell Arthur R. , Pepys Mark B. , Hawkins Philip N.
Published: June 2003

Summary. Monoclonal immunoglobulin light chains are deposited as amyloid fibrils in systemic AL (primary) amyloidosis, but the underlying plasma cell dyscrasias are often difficult to detect or unquantifiable. The relationships between circulating monoclonal light chains, amyloid load and clinical outcome, and the relative efficacies of chemotherapy regimens aimed at suppressing monoclonal immunoglobulin production, have not been determined. Circulating free immunoglobulin light chain (FLC) concentration was measured with a sensitive nephelometric immunoassay in 262 patients with AL amyloidosis, and followed serially in 137 patients who received either high‐dose chemotherapy or one of two intermediate‐dose cytotoxic regimens. Amyloid load was quantified by serum amyloid P component scintigraphy. A monoclonal excess of FLC was identified at diagnosis in 98% of patients. Among 86 patients whose abnormal FLC concentration fell by more than 50% following chemotherapy, 5‐year survival was 88% compared with only 39% among those whose FLC did not fall by half (P < 0·0001). Amyloid deposits regressed in 58 patients. The magnitude and duration of the FLC responses to intermediate‐ and high‐dose chemotherapy regimens were similar. The FLC assay enabled the circulating fibril precursor protein in AL amyloidosis to be quantified and monitored in most patients. Reduction of the amyloidogenic FLC by more than 50% was associated with substantial survival benefit, regardless of the type of chemotherapy used. Clinical improvement following chemotherapy in AL amyloidosis is delayed, but treatment strategies can be guided by their early effect on serum FLC concentration.
Effect of Er:YAG laser and EDTAC on the adhesiveness to dentine of different sealers containing calcium hydroxide
Authors: Picoli F. , Brugnera‐Junior A. , Saquy P. C. , Guerisoli D. M. Z. , Pecora J. D.
Published: June 2003

Aim  To evaluate the effect of 15% EDTAC solution and Er:YAG laser irradiation on the adhesiveness to dentine of root canal sealers containing calcium hydroxide.

Methodology  The crowns of 60 maxillary human molars were ground until dentine was exposed. The teeth were divided into three groups of 20 teeth: group I, the dentine surface received no treatment; group II, 15% EDTAC solution was applied to the dentine; group III, the dentine received Er:YAG laser application (11 mm focal distance with perpendicular incidence to dentine surface; 4 Hz frequency; 200 mJ energy; 2.25 W potency; 62 J total energy; 1 min application time). Aluminium cylinders filled with the sealers, Sealer 26, Apexit, Sealapex and CRCS, were then applied to the treated surfaces. Adhesiveness was measured with a universal testing machine, with traction results given in MegaPascals (MPa). These results were submitted to anova tests.

Results  Statistical analysis showed significant differences (P < 0.01) amongst adhesiveness values of the sealers and treatments tested. Thus, sealers could be ranked in decreasing adhesiveness values: Sealer 26, CRCS, Apexit, Sealapex. Er:YAG laser irradiation and EDTAC solution application increased adhesiveness values only for Sealer 26 and Apexit. Laser irradiation was superior to EDTAC application only for Sealer 26 adhesiveness values.

Conclusions  Er:YAG laser is as efficient as EDTAC solution in increasing adhesiveness of root canal sealers containing calcium hydroxide to human dentine.
Investigation of the marginal adaptation of root‐end filling materials in root‐end cavities prepared with ultrasonic tips
Authors: Gondim E. , Zaia A. A. , Gomes B. P. F. A. , Ferraz C. C. R. , Teixeira F. B. , Souza‐Filho F. J.
Published: June 2003

Aim  To compare the surface topography of root apices following ultrasonic root‐end preparation, and again after root‐end fillings submitted to three different finishing techniques.

Methodology  Eighty‐one root‐end cavities prepared ultrasonically in human canines, were divided at random into three test groups of 27 each. The cavities were filled with Super‐EBA, IRM, or ProRoot‐MTA and finished by ball burnishing. Eighteen roots from each group received a final finish with either a 30‐fluted tungsten carbide finishing bur, or a Zekrya carbide 28 mm bur after storage in water at 37 °C for 24 h. The root‐end surface topographies were reproduced by means of polyvinylsiloxane impressions and epoxy resin replicas. Scanning electron micrography (SEM) images of each replica were taken prior to and after root‐end filling. An image analysis system was used to compare the alteration of the marginal chipping areas and to calculate the gaps located in the dentine/root‐end filling interface.

Results  When a bur was used to finish the set materials, a significant (P < 0.05) area of marginal chipping was eliminated. The finishing technique did not significantly (P > 0.05) affect the incidence of gaps in groups root‐end filled with MTA or IRM. Super‐EBA and IRM retrofillings finished with a ball burnisher or a Zekrya bur displayed a significantly (P < 0.05) larger calculated gap area than roots filled with MTA.

Conclusion  Under this in vitro study, the marginal adaptation of MTA was good with or without finishing procedures. Applying a finishing bur over the condensed and set IRM and Super‐EBA created better marginal adaptation.
Values‐led conservation
Authors: Jepson Paul , Canney Susan
Published: June 2003

In international nature conservation policy, value‐arguments based on science and economic rationalism increasingly overshadow the aesthetic and ethical arguments that originally inspired the conservation movement. We argue that this trend risks removing conservation from the public realm, in part because it facilitates the adoption by nongovernment conservation bodies of corporate values and/or their integration with government bureaucracies. By contrast, the explicit recognition of aesthetic and ethical values would complement arguments based on science and economic utility. We subscribe to a reformist view of globalization that accepts the inevitability of a globalizing world but argues that the process needs humanizing by incorporating quality of life values in the policy process. We argue that re‐emphasis of aesthetic and ethical arguments in international conservation policy would contribute to this goal by reasserting links between conservation bodies and the public, thereby leading to more effective action on the ground.
Native and alien plant species richness in relation to spatial heterogeneity on a regional scale in Germany
Authors: Deutschewitz Kirstin , Lausch Angela , Kühn Ingolf , Klotz Stefan
Published: June 2003

Aim The aim of our study was to reveal relationships between richness patterns of native vs. alien plant species and spatial heterogeneity across varying landscape patterns at a regional scale.

Location The study was carried out in the administrative district of Dessau (Germany), covering around 4000 km2.

Methods Data on plant distribution of the German vascular flora available in grid cells covering 5′ longitude and 3′ latitude (c. 32 km2) were divided into three status groups: native plants, archaeophytes (pre 1500 AD aliens) and neophytes (post 1500 AD aliens). Land use and abiotic data layers were intersected with 125 grid cells comprising the selected area. Using novel landscape ecological methods, we calculated 38 indices of landscape composition and configuration for each grid cell. Principal components analysis (PCA) with a set of 29 selected, low correlated landscape indices was followed by multiple linear regression analysis.

Results PCA reduced 29 indices to eight principal components (PCs) that explained 80% cumulative variance. Multiple linear regression analysis was highly significant and explained 41% to 60% variance in plant species distribution (adjusted R2) with three significant PCs (tested for spatial autocorrelation) expressing moderate to high disturbance levels and high spatial heterogeneity. Comparing the significance of the PCs for the species groups, native plant species richness is most strongly associated with riverine ecosystems, followed by urban ecosystems, and then small‐scale rural ecosystems. Archaeophyte and neophyte richness are most strongly associated with urban ecosystems, followed by small‐scale rural ecosystems and riverine ecosystems for archaeophytes, and riverine ecosystems and small‐scale rural ecosystems for neophytes.

Main conclusions Our overall results suggest that species richness of native and alien plants increases with moderate levels of natural and/or anthropogenic disturbances, coupled with high levels of habitat and structural heterogeneity in urban, riverine, and small‐scale rural ecosystems. Despite differences in the order of relevance of PCs for the three plant groups, we conclude that at the regional scale species richness patterns of native plants as well as alien plants are promoted by similar factors.
Beyond value: biodiversity and the freedom of the mind
Authors: Collar N. J.
Published: June 2003

Circumstances have conspired to render the conservation movement curiously diffident in the expression of the fundamental beliefs that underpin it. ‘Oppositional’ activists assume their case as proven, while ‘institutional’ tacticians tend to adopt the point of view of those they oppose, deploying utilitarian/economic arguments. The latter arguments represent an unstable long‐term option because they are an inadequate defence against compelling forces of corrosion and corruption. On present evidence, in a few hundred years the planet will be devoid of major natural areas, and the quality of human life will have been utterly compromised. A more honest admission that the natural world is an inalienable component of the human capacity to experience freedom (which is also a mental circumstance) would transform the way we treat the natural environment and hence the prospects for the long‐term survival of biological diversity.
Hemodynamic and Volume Changes during Hemodialysis
Authors: Lindsay Robert M. , Shulman Tanya , Prakash Suma , Nesrallah Gihad , Kiaii Mercedeh
Published: June 2003

Background: Volume overload is a factor in the hypertension of hemodialysis (HD) patients. Fluid removal is therefore integral to the hemodialysis treatment. Fluid removal by hemodialysis ultrafiltration (UF) may cause intradialytic hypotension and leg cramps. Understanding blood pressure (BP) and volume changes during UF may eliminate intradialytic hypotension and cramps. Studies (S1, S2, and S3) were carried out to determine the amount and direction of changes in body fluid compartments following UF and to determine the relationships between BP, changes in blood volume (ΔBV), central blood volume (CBV), cardiac output (CO), peripheral vascular resistance (PVR) plus total body water (TBW), and intra‐ and extracellular fluid volumes (ICF, ECF) in both the whole body and body segments (arms, legs, trunk).

Methods: Indicator dilution technology (Transonic) was used for CBV, CO, and PVR; hematocrit monitoring (Crit‐Line) was used for ΔBV segmental bioimpedance (Xitron) for TBW, ICF, and ECF.

Results: S1 (n = 21) showed UF sufficient to cause ΔBV of −7% and lead to minor changes (same direction) in CBV and CO, and with cessation of UF, vascular refilling was preferential to CBV. S2 (n = 20) showed that predialysis HD patients are ECF‐expanded (ECF/ICF ratio = 0.96, controls = 0.74 [P < 0.0001]) and BP correlates with ECF (r = 0.47, P = 0.35). UF to cause ΔBV of −7% was associated with a decrease in ECF (P < 0.0001) and BP directly (r = 0.46, P = 0.04) plus ΔBV indirectly (r = −0.5, P = 0.024) correlated with PVR, while CBV and CO were maintained. S3 (n = 11) showed that following UF, total‐body ECF changes were correlated with leg ECF (r = 0.94) and arm ECF (r = 0.72) but not trunk ECF. Absolute ECF reduction was greatest from the legs.

Conclusions: Predialysis ECF influences BP and UF reduces ΔBV and ECF, but CBV and BP are conserved by increasing PVR. ECF reduction is mainly from the legs, hence may cause cramps. Intradialytic hypotension is caused by failure of PVR response.
Detection of an early HIV‐1 infection by HIV RNA testing in an Italian blood donor during the preseroconversion window period
Authors: Aprili Giuseppe , Gandini Giorgio , Piccoli Pierluigi , Bressan Fausto , Gironcoli Marzia De , Mazzi Romualdo , Parisi Saverio G. , Gessoni Gianluca , Marchiori Giorgio , Franchini Massimo
Published: June 2003

BACKGROUND: The implementation of NAT technologies for HIV screening has further reduced the diagnostic window in recent HIV infection. There is still a debate regarding the cost effectiveness of genomic screening of blood donations for transfusion‐transmitted viruses (HBV, HCV, HIV).

STUDY DESIGN AND METHODS: Since October 2001, at the Transfusion Service of Verona, single‐donation NAT testing for HCV and HIV‐1 (Procleix TMA HIV‐1/HCV Assay) of all blood donations has been performed.

CASE REPORT: A case of acute HIV‐1 infection detected by HIV NAT in a repeat blood donor who donated during the preseroconversion window period is reported. All blood components donated were discarded, and the donor started antiretroviral therapy 2 weeks after blood donation. HIV‐1 p24 antigen was still negative 10 days after the HIV‐1 RNA‐positive blood donation. Seroconversion was documented by Day 41 after donation.

CONCLUSION: This case report testifies that HIV NAT screening of blood donation is effective in preventing the transmission of HIV infection through blood components.