bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in biology of multiple myeloma: clinical applications
Authors: Hideshima Teru , Bergsagel P. Leif , Kuehl W. Michael , Anderson Kenneth C.
Published: April 2004

There appear to be 2 pathways involved in the early pathogenesis of premalignant monoclonal gammopathy of undetermined significance (MGUS) and malignant multiple myeloma (MM) tumors. Nearly half of these tumors are nonhyperdiploid and mostly have immunoglobulin H (IgH) translocations that involve 5 recurrent chromosomal loci, including 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (fibroblast growth factor receptor 3 [FGFR3] and multiple myeloma SET domain [MMSET]), 16q23 (c-maf), and 20q11 (mafB). The remaining tumors are hyperdiploid and contain multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21, but infrequently have IgH translocations involving the 5 recurrent loci. Dysregulated expression of cyclin D1, D2, or D3 appears to occur as an early event in virtually all of these tumors. This may render the cells more susceptible to proliferative stimuli, resulting in selective expansion as a result of interaction with bone marrow stromal cells that produce interleukin-6 (IL-6) and other cytokines. There are 5 proposed tumor groups, defined by IgH translocations and/or cyclin D expression, that appear to have differences in biologic properties, including interaction with stromal cells, prognosis, and response to specific therapies. Delineation of the mechanisms mediating MM cell proliferation, survival, and migration in the bone marrow (BM) microenvironment may both enhance understanding of pathogenesis and provide the framework for identification and validation of novel molecular targets.
Factors Associated With Breast Cancer Clinical Trials Participation and Enrollment at a Large Academic Medical Center
Authors: Simon Michael S. , Du Wei , Flaherty Lawrence , Philip Philip A. , Lorusso Patricia , Miree Cheryl , Smith Daryn , Brown Diane R
Published: April 2004

Purpose

The practice patterns of medical oncologists at a large National Cancer Institute Comprehensive Cancer Center in Detroit, MI were evaluated to better understand factors associated with accrual to breast cancer clinical trials.

Patients and Methods

From 1996 to 1997, physicians completed surveys on 319 of 344 newly evaluated female breast cancer patients. The 19-item survey included clinical data, whether patients were offered clinical trial (CT) participation and enrollment, and when applicable, reasons why they were not. Multivariate analyses using logistic regression were performed to evaluate predictors of an offer and enrollment.

Results

The patients were 57% white, 32% black, and 11% other/unknown race. One hundred six (33%) were offered participation and 36 (34%) were enrolled. In multivariate analysis, CTs were less likely offered to older women (mean age, 52 years for those offered v 57 years for those not offered; P = .0005) and black women (21% of blacks offered v 42% of whites; P = .0009). Women with stage 1 disease, poor performance status, and those who were previously diagnosed were also less likely to be offered trials. None of these factors were significant predictors of enrollment. Women were not offered trials because of ineligibility (57%), lack of available trials (41%), and noncompliance (2%). Reasons for failed enrollment included patient refusal (88%) and failed eligibility (12%).

Conclusion

It is important for cooperative groups to design studies that will accommodate a broader spectrum of patients. Further work is needed to assess ways to improve communication about breast cancer CT participation to all eligible women.
tRNA slippage at the tmRNA resume codon
Authors: TRIMBLE MICHAEL J. , MINNICUS AMY , WILLIAMS KELLY P.
Published: April 2004

The bacterial ribosome does not initiate translation on the mRNA portion of tmRNA; instead translation that had begun on a separate mRNA molecule resumes at a particular triplet on tmRNA (the resume codon). For at least two tRNAs that could pair with both the resume and −2 triplets on mutant tmRNAs, UAA (stop) as the second codon induced high-frequency −2 slippage on the resume codon in the P site. The frameshift product was not detected when the −2 base was altered. Deficiency for ribosomal L9 protein, which affects other cases of frameshifting, had no significant effect. A special feature of this frameshifting is its dependence on a particular context, that of the tmRNA resume codon; it failed on the same sequence in a regular mRNA, and, more strikingly, at the second tmRNA codon. This focuses attention on the peculiar features expected of the slippage-prone state, such as unusual E-site filling, that might make the P-site resume codon:anticodon interaction especially unstable. Keywords: tmRNA; ribosome; frameshift; E site; translation
Hypolipidemic Agents and Their Role in the Therapy of Diabetes Mellitus
Authors: Taskinen Marja-Riitta
Published: April 2004

Coronary heart disease (CHD) is increasingly recognized as the major complication in people with type 2 diabetes. Recent data from large endpoint trials have provided convincing evidence that lowering of LDL cholesterol reduces cardiovascular disease events in people with type 2 diabetes. Consequently, the main target for therapy has been defined to be LDL cholesterol (goal <2.6 mmol/l). Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are recommended for first‐line therapy. Optimum therapy of diabetic dyslipidemia should specifically attack those lipid abnormalities that are most common for diabetic dyslipidemia: elevated triglycerides and low HDL cholesterol. In this regard, fibrates provide an option that produces greater changes of these abnormalities than do statins. Effective therapy will be crucial to reduce the excess risk of CHD beyond LDL cholesterol in people with type 2 diabetes. Ongoing trials performed specifically in people with diabetes will likely provide the data regarding how to optimize and individualize the management of diabetic dyslipidemia.
Pathogenesis of Diabetic Microvascular Complications
Authors: He Zhiheng , Rask-Madsen Christian , King George L.
Published: April 2004

Complications of diabetes have been the leading cause of mortality and morbidity in both type 1 and type 2 diabetes. Based on the sites of functional and pathological changes, these complications have been characterized as cardiomyopathy, macrovasculopathy, and microvasculopathy. Multiple clinical studies have shown that glycemic control is by far the most effective approach in the prevention of microvascular and neuropathic complications. However, tight glycemic control is still difficult to achieve using current available regimen, and therefore novel pathogenesis‐based interventions that can prevent and reverse the complications even in the presence of hyperglycemia are needed. Over the past decade, advances in molecular and cellular biological techniques have revealed many potential mechanisms utilized by hyperglycemia to induce its adverse effects. Several mechanisms, including vascular oxidative stress; formation of advanced glycation endproducts; activation of protein kinase C; increased flux through hexosamine pathway; inflammation‐induced vascular pathology; altered expression and actions of growth factors, cytokines, and vasomotor mediators; and increased flux through polyol pathway, have been studied in detail. The identification of such mechanisms has lead to the development of novel pharmacological approaches.
Preserving Vision
Authors: Aiello Lloyd M. , Cavallerano Jerry D.
Published: April 2004

Early diagnosis of diabetes, regular retinal examination, and applying the standards of care demonstrated in the Diabetes Control and Complications Trial, the United Kingdom Prospective Diabetes Study, and the Early Treatment Diabetic Retinopathy Study can preserve vision for most persons with diabetes mellitus. Vision loss from diabetes mellitus can be prevented for most persons.
Autonomic Neuropathy
Authors: Edmonds Michael
Published: April 2004

This chapter describes the effects of autonomic denervation in diabetic patients. Autonomic neuropathy as defined by abnormal autonomic tests is common but symptoms are rare. However when present, they can be devastating. Cardiovascular autonomic neuropathy leads to an approximately five fold risk of mortality. Autonomic neuropathy can result in hemodynamic and structural changes in the arterial system. This chapter discusses the epidemiology, etiology, and pathology of autonomic neuropathy. It then describes the effect of autonomic neuropathy on the cardiovascular, gastrointestinal, genitourinary, and respiratory systems. It outlines the effects of autonomic denervation on sweating, pupillary reflexes, the response to hypoglycemia, and erythropoietin production. Finally it discusses the clinical associations of autonomic neuropathy and concludes with a summary of its natural history, mortality, and management. Autonomic neuropathy is an important complication of diabetes, resulting in increased patient morbidity and mortality.
Paternal uniparental isodisomy for chromosome 14 in a patient with a normal 46,XY karyotype
Authors: Chu Cathy , Schwartz Stuart , McPherson Elizabeth
Published: April 2004

Chromosome 14 demonstrates imprinting with differing phenotypes for both maternal and paternal uniparental disomy (UPD). Although only 11 cases of paternal uniparental disomy 14 (patUPD14) have been reported, a distinct clinically recognizable syndrome has emerged. The major features are polyhydramnios, small thorax, mildly short limbs, abdominal wall defects, and characteristic face with short palpebral fissures, broad flat nasal bridge, prominent philtrum, and small ears. Radiographically, the chest is bell‐shaped and the ribs are distinctive with caudal bowing anteriorly and cranial bowing posteriorly. Several affected infants have died from respiratory failure. The survivors have short stature and mental retardation. The initial cases were all recognized because of translocations involving chromosome 14. Subsequently, several patients with a similar phenotype and normal chromosomes have been reported, including two with mixed iso‐ and hetero‐disomy as well as one with segmental UPD14. Our patient is the first with pure paternal isodisomy 14 in the absence of a translocation. We present additional clinical information, review the literature, and discuss mechanisms that may explain paternal isodisomy 14 in our chromosomally normal patient. Paternal UPD14 with normal karyotype may be more common than previously suspected and may be overlooked unless recognition of the clinical phenotype prompts investigation for UPD. © 2003 Wiley‐Liss, Inc.
Association of cholecystokinin‐A receptor gene polymorphisms and panic disorder in Japanese
Authors: Miyasaka Kyoko , Yoshida Yuki , Matsushita Sachio , Higuchi Susumu , Shirakawa Osamu , Shimokata Hiroshi , Funakoshi Akihiro
Published: April 2004

Several lines of evidence have suggested that naturally occurring alterations in cholecystokinin (CCK) systems could contribute to the development of panic disorder (PD). Among recent investigations, polymorphisms of the CCK and CCK‐B receptor (R) genes were investigated, but the results were inconclusive. We recently cloned the genomic structures of human CCK‐AR, and determined the transcriptional start site of the human CCK‐AR gene. Two sequence changes were detected in the promoter region: a G to T change in nucleotide −128 and an A to G change in nucleotide −81 (GenBank database under accession number D85606). The frequencies of the genotypes and haplotypes of these two polymorphisms were compared in 109 Japanese patients with PD and 400 age‐ and gender‐matched normal Japanese control subjects. The frequency of variant genotypes (−81A/G, −128G/T; G/G, G/T, and G/G, T/T) having variant haplotype (−81G/−128T) was significantly higher in PD than in controls (P < 0.0001, OR = 2.81, 95% CI = 1.74–4.39). The statistical differences between the haplotype distributions in the PD and control groups were highly significant: the frequency of variant haplotype (−81G/−128T) was higher in the former group than in the latter (P < 0.0001). This association was not affected by clinical characteristics such as age, gender, and age at onset of PD. In this study, the first to report the positive association of the CCK‐AR polymorphisms and PD, haplotype analyses further strengthened the association based on our comparison of genotype distributions. The CCK‐AR gene polymorphism may be involved in the neurobiology of PD. © 2004 Wiley‐Liss, Inc.
Electrophysiologic response recorded in the first dorsal interosseous muscle with stimulation of the tibial and deep fibular nerves
Authors: Galloway Kathleen M. , Greathouse David G. , Olson Ronald , Tracy Mary
Published: April 2004

Foot intrinsic muscle innervation may demonstrate some variability. The first dorsal interosseous muscle (FDI) is innervated by the deep branch of the lateral plantar nerve (LPN) from the main trunk of the tibial nerve. Contribution from the deep fibular nerve (DFN) may also play a role in the supply of the FDI. Thirty healthy adult volunteers were studied to determine the presence and type of response in the FDI with stimulation of the tibial nerve/deep branch of the LPN and DFN. Both nerves were stimulated at the ankle and knee with a surface and needle recording from the FDI. Latency, amplitude, and conduction values were recorded for each nerve. The incidence of DFN supply to the FDI was 16.6% with a mean ankle amplitude of 152 μV. The incidence of tibial nerve/deep branch of the LPN supply to the FDI was 100%, with a mean ankle amplitude of 5.11 mV. The superficial branch of the LPN is most often studied when evaluating for tarsal tunnel syndrome because the standard recording site is the abductor digiti minimi (ADM). Recording from the ADM, however, frequently produces a less than desirable waveform, and the technical challenges encountered with this site make tarsal tunnel syndrome assessment difficult. It is also possible that selective involvement of the deep branch of the LPN may occur, and if so, recording from the FDI may prove valuable. Clin. Anat. 17:312–317, 2004. © 2004 Wiley‐Liss, Inc.
Role of fine‐needle aspiration cytology in breast lymphoma
Authors: Levine Pascale Hummel , Zamuco Ronaldo , Yee Herman T.
Published: April 2004

Lymphomas of the breast are rare and may mimic carcinoma clinically. We investigated the ability of fine‐needle aspiration (FNA) biopsy combined with adjunctive flow cytometry (FC), immunofluorescence microscopy (IFM), and immunocytochemistry (ICH) to diagnose and eventually subclassify lymphomas of the breast according to the Revised European American Lymphoma/World Health Organization classification. We retrieved 21 breast aspirates from 19 patients with a cytologic diagnosis of lymphoma or plasmacytoma over a 10‐year period (1992–2002), excluding 98 benign intramammary lymph nodes and 1 atypical lymphohistiocytic proliferation (Rosai Dorfman disease). FC was performed in 15/21 aspirates, IFM in 1/21, ICH in 3/21. Histologic follow‐up (HF) was obtained for 10 patients, most of them with primary lymphoma. For the remaining nine patients without HF, flow cytometric analysis, comparative morphology, or remission after chemotherapy regimens supported the cytologic diagnosis. Of 19 patients, 11 patients had a secondary lymphoma (SL) and 8 patients had a primary lymphoma (PL). FNA and FC/IFM/ICH classified 7/8 PLs as B‐cell lymphomas and 1/8 PLs as plasmacytoma. However, FNA could only subclassify 3 of 8 PLs. FNA and/or FC subclassified accurately 10/11 SLs. All cases were accurately immunophenotyped as B‐, T‐cell non‐Hodgkin's lymphomas or plasmacytoma. World Health Organization classification was achieved in 3/8 PLs (42%) and 10/11 SLs (91%; P = 0.04). Subclassification (which has an impact on long‐term management and prognosis) was significantly better in SL, when a previous histologic diagnosis had already been made, when compared to PL, of which 5/8 cases (62.5%) could not be accurately classified. Diagn. Cytopathol. 2004;30:332–340. © 2004 Wiley‐Liss, Inc.
Resolving operational and performance problems encountered in the use of a pilot/full‐scale biotrickling filter reactor
Authors: Webster Todd S. , Cox Huub H. J. , Deshusses Marc A.
Published: April 2004

A pilot/full‐scale biotrickling filter reactor experiment was performed at an industrial site to treat styrene laden waste gas. The engineered system consisted of two stainless steel tanks in series, each with filter bed volumes of 4.0 m3, filled with 3.5‐inch plastic spheres. The system treated 340 m3 h−1 of air laden with styrene concentrations ranging up to 0.8g m−3. Over the five‐month study, styrene elimination was demonstrated up to 24g m−3 h−1 (35g m−3 h−1 across the first tank in series) with 70 to 85% removal. Operational and performance problems we re identified that differ from those developed under controlled, laboratory set‐ups. Op e rational problems typically involved equipment malfunctions, with the most prone to failure pieces of equipment being the air sampling system and water level sensors. Performance problems were identified that possibly limited the styrene re m oval. The transient operation of the plant, producing discontinuous, unsteady‐state concentrations, made it difficult to establish a stable biofilm on the packing material. Experiments we reperformed indicating both biological and mass transfer limitations may have occurred.
Continuous flow integrated chemical (ozone)‐activated sludge system treating combined agroindustrial‐domestic wastewater
Authors: Beltrán Fernando J. , García‐Araya Juan F. , Álvarez Pedro M.
Published: April 2004

Mixtures of wine‐distillery and domestic wastewater were continuously treated by combined ozonation‐ activated sludge (ASP) and ASP‐ozonation systems. Ozone has been shown to effectively oxidize recalcitrant compounds in wastewater to more readily biodegrade oxidation products that can betreated using a conventional aerobic biological treatment. Main parameters affecting the overall efficiency were the ozone dose required for biodegradability enhancement and food to microorganism ratio (F/M) at the biological step. Preozonation enhances not only COD and TOC disappearance but also nitrogen re m oval in a subsequent biological nitrification step and settling properties of the sludge. Kinetic results of this study reveal that ozonation treatment prior to ASP favors the organic matter removal by an increase in the maximum microbial growth rate, μmax, and a decrease in the inhibitory effect by microorganisms. Biomass oxygen uptake rate tests showed ozonation products to be highly biodegradable. The feasibility of single and combined treatments was examined primarily in terms of organic matter and nitrogen removal efficiency. Best results were attained with the integrated ozonation‐ASP system.
Comparison of biodegradation kinetic parameters for naphthalene in batch and sand column systems by pseudomonas putida
Authors: Park Jeong‐Hun , Zhao Xianda , Voice Thomas C.
Published: April 2004

Kinetic parameters for the degradation of naphthalene by Pseudomonas putida ( ATCC 17484) were estimated in both batch and column assays, in order to evaluate the role of flow and cell attachment on biodegradation rates. Suspended cells and cells attached to Ottawa sand were used under a variety of biomass levels, column flow‐rates, and substrate concentrations. In batch systems, degradation followed zero order kinetics across the entire concentration range, while the columns exhibited decreased rates at concentrations less than 100 (μg/L), describable by Michaelis‐Menten kinetics. This is reflected in elevated values of the half‐saturation constant, Ks, in columns. We offer the explanation that this may have resulted from reactive heterogeneity within the porous media, imposing a distribution of length‐scales for transfer of substrate to the cell surfaces. Well‐mixed batch systems are expected to have both shorter and more uniform transfer distances. When kinetic parameters obtained in batch system are used for prediction of degradation in columns, at least two factors—exposed reduction of exposed cell surface are a and heterogeneity of cell distribution—will likely reduce overall column degradation rates.
Software tool for environmental plant modeling
Authors: Caputo Antonio C. , Pelagagge Pacifico M. , Scacchia Federica
Published: April 2004

Waste disposal and the control of polluting emissions represent a critical operational issue for industrial enterprises. In this paper a software tool for computer‐aided design and economical analysis of environmental plants is presented. The tool has been developed in order to assist process engineers in the proper choice and sizing of the different pieces of pollution control equipment, as well as in the correct planning of waste treatment plants. The model is able to quantitatively characterize the processes involved, while also performing an overall sizing and costing of main equipment, taking into account different process units and a variable mix of incoming waste streams. The software tool is built in the Vis Sim programming environment, enabling ease of use, modularity, and expandibility. After a description of the software architecture and features, an example is presented showing the capability of the developed plant simulator.
Stewardship and U.S. nuclear weapon production wastes—an introduction
Authors: Jarvis Timothy Thomas
Published: April 2004

The article provides new perspectives on the amounts and types of nuclear and toxic waste produced by the United States nuclear weapons production industry. These wastes are spread over 28 of the 50 states at 129 nuclear weapons related properties. The total quantity would fill a line of semi trucks, over 24 miles abreast, parked bumper‐to‐bumper, extending from Chicago, IL, to Laredo, TX.

Much of the waste generated by nuclear weapon production has very long radioactive half‐lives, and exists in uncontrolled or unstabilized forms. This article presents new categories for waste based on their relative accessibility to the environment, in contrast to old waste categories that are tied to nuclear weapon production terminology. Also discussed are potential risks from nuclear weapons waste, such as threats to public safety, cultural threats, and risks to natural resources.

Because these wastes are extremely persistent (i.e., an average radioactive half‐life of 3,000 years), they are managed under a concept new to the industry termed “stewardship.” Management by stewardship is described, along with its organizational and funding framework, decision‐making philosophy, and how one goes about trans‐generational information transfer.
Alternative chromium reduction and heavy metal precipitation methods for industrial wastewater
Authors: Chang Li‐Yang
Published: April 2004

A study of alternative chromium‐reduction and heavy‐metal precipitation methods was performed on wastewater generated by a metal‐cleaning facility. Four existing chromium‐reduction treatment methods were tested on the wastewater samples: treatment with (1) sodium metabisulfite, (2) ferrous sulfate, (3) zero‐valent iron, and (4) dimethyl dithio carbamate, ferrous sulfate, and aluminum/chloride. We found that the first two methods are more effective in chrome reduction, while the last method achieved similar reduction results but produced more sludge than any of the other methods. Our results also indicated that when ferrous sulfate was used as a chrome reduction reagent at a low initial pH (2 to 3), the competitive oxidation reaction of ferrous ions with dissolved oxygen in solution is insignificant.

When iron powder was used to reduce hexavalent chromium to trivalent chromium, we found that (a) when the sample containing low levels of total chromium (⩽ 1.54 × 10− 4 mole/liter) was mixed properly with zero‐valent iron powders at a low pH (4 to 5), the total chromium concentration could be reduced to 1 mg/l in 3 hours; and (b) the chrome absorption‐reduction efficiency is limited by the transport process of Cr(VI) from the bulk of the wastewater to the surface of the iron powder. In a leaching test of used iron powder filtered from the treated wastewater, we also found that most of chromium absorbed on the iron powder was very stable, and only low Cr(VI) was detected in the leachate.
Gender in the boss–subordinate relationship: a Nigerian study
Authors: Adebayo D. O. , Udegbe I. B.
Published: April 2004

The present study examines the interaction effect of gender of both subordinates and supervisors on subordinates' perception of differentiation of boss–subordinate relationship in an African setting. Data was collected from a total of 60 boss–subordinate dyads in four‐sex combinations obtained through a survey of a large five‐star hotel in Abuja, Nigeria. Results revealed that subordinates in opposite‐sex dyads perceived better quality of exchange than those in same‐sex dyads. The strongest quality of exchange was perceived in male boss–female subordinate dyad, while the weakest was perceived in female boss–female subordinate dyad. This emphasizes the importance of gender in the differentiation of boss–subordinate relationships in an African setting. Copyright © 2004 John Wiley & Sons, Ltd.
Long-term immune response after liver transplantation in patients with spontaneous or post-treatment HCV-RNA clearance
Authors: Casanovas-Taltavull Teresa , Ercilla Guadalupe M. , Gonzalez Cecilia P. , Gil Elias , Viñas Odette , Cañas Concha , Casanova Aurora , Figueras Juan , Serrano Teresa , Casais Luis A.
Published: April 2004

Recurrent HCV infection after liver transplantation is universal and sustained clearance of HCV-RNA rarely occurs. The aim of this study was to characterize cell-mediated immunity and cytokine production in HCV-infected patients after liver transplant. The study included 6 pretransplantation patients (PT) and 15 liver transplanted patients, including 5 with spontaneous HCV-RNA clearance (SC group), 5 with sustained virological response after antiviral treatment (SVR group), and 5 no response (NR group). The control group included 5 HCV-RNA negative, anti-HCV negative healthy individuals. This study examines proliferative T-cell response and cytokine production (gamma-interferon and IL-10) after HCV specific and phytohemagglutinin (PHA) stimulation in cultured peripheral blood mononuclear cells (PBMCs) from each group. Multispecific proliferative responses to HCV antigens (mean Stimulation Index; SI) were higher in the SVR group (mean SI 7.4 ± 2) and SC group, as compared with the NR group (P < .05, vs SVR) and PT group (P < .05, vs SVR and SC). After PHA stimulation, gamma-interferon levels were similar to controls (4330 ± 640 pg/ml) in the SC (4474 ± 300 pg/mL) and SVR groups (3647 ± 300 pg/mL), but were significantly lower than controls in the PT (401 ± 331 pg/mL; P < .02) and NR groups (546 ± 360 pg/mL; P < .01). IL-10 production after PHA stimulation was similar in SC, SVR, and controls (647 ± 279 pg/mL, 674 ± 310 pg/mL and 841 ± 294 pg/mL, respectively), but was lower in PT patients (232 ± 94 pg/mL). The NR group showed high basal IL-10 production with little increase after stimulation. In conclusion, liver post-transplantation patients with spontaneous clearance of HCV-RNA and those with sustained viral response after therapy showed an immune response despite immunosuppression that might have contributed to their favorable outcome. (Liver Transpl 2004;10:584-594.)
Achieving adequate cyclosporine exposure in liver transplant recipients: A novel strategy for monitoring and dosing using intravenous therapy
Authors: Lück Rainer , Böger Jan , Kuse Ernst , Klempnauer Jürgen , Nashan Björn
Published: April 2004

It has been demonstrated that achieving therapeutic levels of cyclosporine (CsA) exposure in the first days posttransplant is critical for effective prevention of rejection. In patients receiving oral CsA, it has been shown that C2-monitoring is superior to trough (trough level [C0]) measurement. Intravenous administration may overcome the problem of CsA absorption dysfunction seen in some patients. Currently, little evidence is available concerning CsA exposure after intravenous application. Twenty de novo liver transplant recipients were given twice-daily 4-hour infusions of intravenous CsA, with full pharmacokinetic profiles undertaken during the first postoperative week. The greatest CsA exposure occurred during the period 2 to 4 hours after the start of infusion. The correlation between C0 and area under the curve (AUC0-12) was r

2
= 0.18; the correlation between C2 and AUC0-12 was r

2
= 0.82. The best 2-point predictive model included both C2 and C4 (r

2
= 0.90). There was a poor correlation between CsA dose per kilogram of body weight and AUC0-12 (r

2
= 0.19); total CsA dose also showed a weak relationship to exposure (r

2
= 0.37). When patients were divided according to initial or delayed graft function, there was good correlation between total CsA dose and AUC0-12 (initial function, r

2
= 0.71; delayed function, r

2
= 0.86). In conclusion, previous discouraging results with intravenous CsA in liver transplant patients may have been due to a limited understanding of CsA pharmacokinetics. Our results show that C2-monitoring during 4 hour infusion provides a reliable indication of CsA exposure. Calculation of starting dose based on initial graft function is more precise than use of body weight. Using C2-monitoring to individualize dosing and function-based calculations of starting dose could be expected to improve clinical outcomes in patients receiving intravenous CsA. (Liver Transpl 2004;10:686-691.)
Hepatocellular carcinoma in HCV-infected patients awaiting liver transplantation: Genes involved in tumor progression
Authors: Mas Valeria R. , Maluf Daniel G. , Stravitz Richard , Dumur Catherine I. , Clark Bradly , Rodgers Cheryl , Ferreira-Gonzalez Andrea , Fisher Robert A.
Published: April 2004

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death in the world. The present study aimed to investigate the genes involved in viral carcinogenesis and tumor progression in liver transplant recipients with hepatitis C virus (HCV) and HCC. To accomplish this, we performed the analysis of hepatic gene expression in HCV-infected liver recipient patients with stages of disease ranging from early cirrhosis with preserved volume and function to late cirrhosis with diminished volume and function with and without HCC. We found consistent differences between the gene expression patterns in HCV-HCC and those of early HCV-cirrhosis, late HCV cirrhosis, and normal control livers. The expression patterns in HCC were also readily distinguished between early and advanced HCC tumor stages. Moreover, we found different gene expression patterns between early cirrhosis and late cirrhosis. In conclusion, these findings confirm the presence of multiple molecular alterations during HCV-HCC hepatocarcinogenesis and, clinically, indicate the possibility for identifying prognostic factors associated with HCC progression in liver transplant patients waiting for a donor and/or posttransplantation recurrence. (Liver Transpl 2004;10:607-620.)
Human S15a expression is upregulated by hepatitis B virus X protein
Authors: Lian Zhaorui , Liu Jie , Li Li , Li Xianxing , Tufan N. Lale Satiroglu , Wu Meng‐Chao , Wang Hong‐Yang , Arbuthnot Patrick , Kew Michael , Feitelson Mark A.
Published: April 2004

The hepatitis B virus (HBV)–encoded X antigen (HBxAg) may contribute to the development of hepatocellular carcinoma (HCC) through the upregulated expression of selected cellular genes. To identify these genes, RNAs isolated from HBxAg‐positive and ‐negative HepG2 cells were compared by PCR select cDNA subtraction. One gene overexpressed in HBxAg‐positive cells by Northern and Western blotting is the ribosomal protein S15a. The S15a mRNA is 535 base pairs, encoding a protein 130 amino acids long with a molecular weight of 14.3 kDa. S15a expression was upregulated in HBV‐infected livers, where it costained with HBxAg. Overexpression of S15a stimulated cell growth, colony formation in soft agar, and tumor formation in SCID mice. Hence, HBxAg upregulated the expression of S15a, the latter of which participates in the development of HCC, perhaps by altering the integrity of translation. © 2004 Wiley‐Liss, Inc.
P#: a concurrent Prolog for the .NET framework
Authors: Cook Jonathan J.
Published: April 2004

We discuss P#, our implementation of a tool that allows interoperation between a concurrent superset of the Prolog programming language and C#. This enables Prolog to be used as a native implementation language for Microsoft's .NET platform. P# compiles a linear logic extension of Prolog to C# source code. We can thus create C# objects from Prolog and use C#'s graphical, networking and other libraries. We add language constructs on the Prolog side that allow concurrent Prolog code to be written. A primitive predicate is provided that evaluates a Prolog structure on a newly forked thread. Communication between threads is based on the unification of variables contained in such a structure. It is also possible for threads to communicate through a globally accessible table. All of the new features are available to the programmer through new built‐in Prolog predicates. We discuss two software engineering tools implemented using P#. Copyright © 2004 John Wiley & Sons, Ltd.
Supramolecular Assembling of Complex Tellurium Salts: Synthesis and Crystal Structures of {Cs[PhTeCl4]·CH3OH} and Cs[PhTeBr4]
Authors: Schulz Lang Ernesto , de Oliveira Gelson Manzoni , Fernandes Jr. Ramão Marceli , Vázquez–López Ezequiel M.
Published: April 2004

The direct reaction between PhTeCl3 and CsCl in methanol affords {Cs[PhTeCl4]·CH3OH}. Cs[PhTeBr4] was prepared by refluxing [2‐Br‐C5NH5][PhTeBr4] and CsCl in ethanol in the presence of an excess of HBr. In {Cs[PhTeCl4]·CH3OH} the [PhTeCl4]— units form dimers by secondary Te···Cl bonds with methanol molecules bridging adjacent Cs+ cations. In both compounds, the alkali metal cation interacts secondarily with the chlorine and bromine Te‐ligands, achieving singular coordination polyhedrons and holding the lattices in supramolecular tridimensional assemblies. The new complexes, {Cs[PhTeCl4]·CH3OH} and Cs[PhTeBr4], crystallize in the space groups P21/c and P21/n, respectively. Only one such structure has been reported before.
Meshing Glenberg's embodied memories with negative priming research on suppression
Authors: Neumann Ewald
Published: April 2004

This commentary examines Glenberg's characterization of “suppression” in light of negative priming and related phenomena. After offering a radically different slant on suppression, an attempt is made to weave this alternative version into Glenberg's provocative discussion of embodied memories.
Think globally, ask functionally
Authors: Altmann Erik M.
Published: April 2004

The notion of functionality is appropriately central to the Newell Test but is also critical at a lower level, in development of cognitive sub-theories. I illustrate, on one hand, how far this principle is from general acceptance among verbal theoreticians, and, on the other hand, how simulation models (here implemented within ACT-R) seem to drive the functional question automatically.
Race, brain size, and IQ: The case for consilience
Authors: Rushton J. Philippe
Published: April 2004

Data from magnetic resonance imaging (MRI), autopsy, endocranial measurements, and other techniques show that: (1) brain size correlates 0.40 with cognitive ability; (2) average brain size varies by race; and (3) average cognitive ability varies by race. These results are as replicable as one will find in the social and behavioral sciences. They pose serious problems for Rose's claim that reductionistic science is inadequate, inefficient, and/or unproductive.
On the encompassing of the behaviour of man
Authors: Overgaard Morten , Willert Soeren
Published: April 2004

One supposition underlying the Anderson & Lebiere (A&L) target article is that the maximally broad “encompassing of its subject matter – the behavior of man” (cf. sect. 6, last para.) is regarded as an unquestioned quality criterion for guiding cognitive research. One might argue for an explicit specification of the limitations of a given paradigm, rather than extending it to apply to as many domains as possible.
Connectionism, ACT-R, and the principle of self-organization
Authors: Prudkov Pavel N.
Published: April 2004

The target article is based upon the principle that complex mental phenomena result from the interactions among some elementary entities. Connectionist nodes and ACT-R's production rules can be considered as such entities. However, before testing against Newell's macro-criteria, self-organizing models must be tested against criteria relating to the properties of their elementary entities. When such micro-criteria are considered, they separate connectionism from ACT-R and the comparison of these theories against Newell's Tests is hardly correct.
An interdisciplinary approach to brain evolution: A long due debate
Authors: Aboitiz Francisco , Morales Daniver , Montiel Juan
Published: April 2004

A dorsalization mechanism is a good candidate for the evolutionary origin of the isocortex, producing a radial and tangential expansion of the dorsal pallium (and perhaps other structures that acquired a cortical phenotype). Evidence suggests that a large part of the dorsal ventricular ridge (DVR) of reptiles and birds derives from the embryonic ventral pallium, whereas the isocortex possibly derives mostly from the dorsal pallium. In early mammals, the development of olfactory-hippocampal associative networks may have been pivotal in facilitating the selection of a larger and more complex dorsal pallium which received both collothalamic and lemnothalamic sensory information. Finally, although it is not clear exactly when mammalian brain expansion began, fossil evidence indicates that this was a late event in mammaliaform evolution.
Scavenging by megabenthos and demersal fish on the South Georgia slope
Authors: Yau Cynthia , Collins Martin A. , Bagley Phil M. , Everson Inigo , Priede Imants G.
Published: April 2004

The scavenging megafauna of the South Georgia and Shag Rocks slope in the south-west Atlantic (625–1519 m) were investigated using autonomous baited camera systems. Two surveys were conducted: the first in 1997 (13 deployments) used a conventional 35 mm stills camera with a 200 J flash, whilst the second in 2000 (15 deployments) used low-light digital video cameras. The scavenging community responded rapidly to the arrival of bait on the sea floor and was dominated by stone crabs (Lithodidae) and toothfish (Dissostichus eleginoides). Stone crabs took up residence around the bait until it was consumed, with a maximum number of 108 in the field of view after four hours. The most frequently observed crab species was Paralomis formosa. Paralomis spinosissima, Neolithodes diomedea and Lithodes sp., were also observed. Toothfish were the most frequently observed scavenging fish and were seen during all but one deployment, typically making brief visits (1–2 min) to the bait, but appeared startled by the flash in the 1997 survey. Labriform swimming (sculling with the pectoral fins) was the principal form of locomotion in toothfish (0.22 body lengths (BL) sec−1), but they were capable of more rapid sub-carangiform (using caudal trunk and fin) motion (3 BL sec−1) when startled. Other scavenging fish observed included the blue-hake Antimora rostrata, grenadiers (Macrourus spp.), skates, liparids and zoarcids.
Some dynamics of water outflow from beneath the Ross Ice Shelf during 1995 and 1996
Authors: Bergamasco A. , Defendi V. , Meloni R.
Published: April 2004

The paper presents two years of observations (1995 and 1996) for water velocity and temperature near the Ross Ice Shelf edge, where a mooring, composed of three current meters, five temperature and three conductivity sensors, one turbidimeter, two sediment traps and one Acoustic Doppler Current Profiler, was deployed. The mooring site was chosen to study the behaviour of the Ice Shelf Water, within the framework of the Project on the Climatic Long-term Interaction for the Mass balance in Antarctica of the Italian National Programme for Antarctic Research. The Ice Shelf Water outflow from below the Ross Ice Shelf is a persistent phenomenon in this area, but it is characterized by impulsive injections often associated with recirculation processes. Two years of data records of physical variables are investigated here in order to analyse the Ice Shelf Water outflow behaviour and to give an estimate of this feature. Our results show that the Ice Shelf Water events have variable duration (from one to seven days) and present an interannual variability in their timing. In spite of this, the mean Ice Shelf Water outflow during the overlapping period of the two time series is quite similar: 0.15 Sv for 1995 and 0.28 Sv for 1996.
Complementary and alternative medicine in breast cancer patients
Authors: NAHLEH ZEINA , TABBARA IMAD A.
Published: April 2004

Objective: Complementary and Alternative Medicine (CAM) is becoming increasingly popular among cancer patients, in particular those with breast cancer. It represents one of the fastest growing treatment modalities in the United States. Therefore, knowledge of CAM therapies is becoming necessary for physicians and other health care providers. CAM encompasses a wide range of modalities including special diet and nutrition, mind–body approaches, and traditional Chinese medicine.

Methods:We reviewed the biomedical literature on CAM use in breast cancer patients, using Medline search from 1975 until 2002. In addition, consensus reports and books on CAM and breast cancer were included in the review. We evaluated the prevalence of CAM use in breast cancer patients, the reasons cited for its use, the different available modalities, and the reported outcomes.

Results:Use of CAM in breast cancer patients ranges between 48% and 70% in the United States. The most commonly used CAM modalities include dietary supplements, mind–body approaches, and acupuncture. The reasons cited for using CAM were to boost the immune system, improve the quality of life, prevent recurrence of cancer, provide control over life, and treat breast cancer and the side effects of treatment. Several studies reported favorable results including improved survival, better pain control, reduced anxiety, improvement in coping strategies and significant efficacy in treating nausea and vomiting. Other less well-organized trials have reported either no benefit or negative effect of CAM and potential toxicity of some commercial products.

Significance of results: CAM is a growing field in health care and particularly among breast cancer patients. Knowledge of CAM by physicians, especially oncologists, is necessary. Oncologists should be willing to discuss the role of CAM with their patients and encourage patients to participate in well-organized research about CAM.
Oregon hospice nurses and social workers' assessment of
physician progress in palliative care over the past 5 years
Authors: GOY ELIZABETH R. , JACKSON ANN , HARVATH THERESA A. , MILLER LOIS L. , DELORIT MOLLY A. , GANZINI LINDA
Published: April 2004

Background: The 1997 enactment of the Oregon Death with
Dignity Act intensified interest in improving physician education and
skills in caring for patients at the end of life.

Objective: To obtain hospice nurse and social workers'
collateral ratings of efforts made by Oregon physicians to improve
their palliative care skills over the previous 5 years.

Design: A descriptive survey of nurses and social workers
from all 50 Oregon outpatient hospice agencies.

Measurement and Results: Oregon hospice nurse (N =
185) and social worker (N = 52) respondents, who had worked in
hospice for at least 5 years, rated changes they observed over the past
5 years in physicians' approach to caring for their hospice
clients. Six characteristics, including willingness to refer patients
to hospice, willingness to prescribe sufficient pain medications,
knowledge about using pain medications in hospice patients, interest in
caring for hospice patients, competence in caring for hospice patients,
and fearfulness of prescribing sufficient opioid medications were
evaluated. Positive changes were endorsed by the majority of
respondents on all but the scale measuring fearfulness of prescribing
opioid medications; on the latter, 47% of nurses rated doctors as less
fearful, whereas 53% rated them as about the same or more fearful than
they were 5 years earlier.

Conclusions: Most respondents rated Oregon physicians as
showing improvements in knowledge and willingness to refer and care for
hospice patients.
Zur Diskussion: Kritische Anmerkungen zur Anwendung des Mini-Mental-Status-Tests
Authors: Wegener Bernhard
Published: April 2004

Zusammenfassung: Es werden die testmethodischen Kriterien des Verfahrens untersucht und diskutiert. Neben den bekannten Einwänden bestehen auch Zweifel an der Objektivität. Wenn diese Skala nur für mittlere Grade einer Demenz anwendbar ist, unterliegt die Anwendung einem Zirkelschluss. Eine Anwendung als Test und zur Gewinnung von Entscheidungskriterien im Procedere mit Patienten stellt einen Missbrauch des Verfahrens dar.
Ist der Negative Priming Effekt tatsächlich altersinvariant?
Authors: Titz Cora , Behrendt Jörg , Hasselhorn Marcus
Published: April 2004

Zusammenfassung: Verzögerte Reaktionen auf zuvor ignorierte Reize bezeichnet man als Negative Priming (NP). Eine Metaanalyse zur Altersabhängigkeit dieses experimentellen Markers selektiver Aufmerksamkeit spricht für invariante Reaktionsverzögerungen ( Gamboz, Russo & Fox, 2002 ), obgleich selektive Aufmerksamkeitsveränderungen als Ursache kognitiver Leistungseinbußen im höheren Alter diskutiert werden. Auch in der vorliegenden Studie mit einem Bild-Identifikationsverfahren resultieren für Stichproben von jeweils 60 jüngeren (18-35 Jahre) und älteren Personen (58-84 Jahre) insgesamt gleich große NP-Effekte. Differenziertere Analysen geben aber Hinweise auf Altersunterschiede in Hinblick auf die Anzahl der Objektwiederholungen, zusätzliche Primebedingungen oder optimale Testzeiten. Dies wirft Zweifel bezüglich einer Prozessäquivalenz zugrunde liegender Mechanismen jüngerer und älterer Erwachsener auf, denen in Folgestudien, auch unter Nutzung bildgebender Techniken, nachgegangen werden soll.
Psychometrische Beurteilung der anterograden Gedächtnisstörungen beim amnestischen Syndrom
Authors: Metzler P. , Rösler P. , Siebenstädt A.
Published: April 2004

Zusammenfassung: In die klinische Studie sind N = 118 Patienten mit amnestischem Syndrom aus 5 Diagnosegruppen (Korsakow-Syndrom, Hypoxie, SHT, vaskuläre Demenz und M. Alzheimer im Frühstadium) eingegangen. Bei der psychometrischen Untersuchung mit dem Berliner Amnesie Test (BAT) finden wir ein charakteristisches Testprofil, das durch schwer gestörtes recall, signifikant geringere Defizite beim recognition, extrem schnelles Vergessen, auffallende Enkodierungsdefizite, mnestische Interferenzen und weitgehend erhaltene Kurzzeitgedächtnisspanne gekennzeichnet ist. Bei ca. 80% der Fälle liegen sowohl verbale als auch figural-räumliche mnestische Störungen vor. Bezüglich der Mittelwertprofile der Patientengruppen können keine klinisch wesentlichen statistischen Unterschiede nachgewiesen werden. Es werden Verteilungsparameter zum amnestischen Syndrom angegeben, die zur Schätzung des Schweregrades und zur Abgrenzung von anderen Gedächtnisstörungen geeignet sind.