bluuebunny/crossref_metadata_2025 huggingface dataset:
Multitasking in Tumor Progression: Signaling Functions of Cell Adhesion Molecules
Authors: CAVALLARO UGO , CHRISTOFORI GERHARD
Published: May 2004

Abstract: Approximately 90% of all cancer deaths arise from metastasis formation. Hence, understanding the molecular mechanisms underlying tumor progression, local invasion, and the formation of tumor metastases represents one of the great challenges in exploratory cancer research. Recent experimental results indicate that changes in cell adhesion play a critical role in tumor progression. Cell adhesion molecules of varying classes and functions, including cadherins, cell adhesion molecules of the immunoglobulin family (Ig‐CAMs), CD44, and integrins, can interact with and modulate the signaling function of receptor tyrosine kinases (RTKs). Conversely, signaling by RTKs can directly affect the adhesive function of adhesion molecules. Loss of E‐cadherin and gain of mesenchymal cadherin function as well as changes in the expression of Ig‐CAMs during the progression of many cancer types exemplify such functional implicatons: cell adhesion molecules not only define a tumor cell's adhesive repertoire, but also directly influence classic signal transduction pathways, thereby modulating the metastatic behavior of tumor cells.
Molecular Regulation of Lymphangiogenesis
Authors: SAHARINEN PIPSA , PETROVA TATIANA V.
Published: May 2004

Abstract: The lymphatic vascular system is necessary for the return of extravasated interstitial fluid and macromolecules to the blood circulation, for immune defense, and for the uptake of dietary fats. Impaired functioning of lymphatic vessels results in lymphedema, whereas tumor‐associated lymphangiogenesis may contribute to the spread of cancer cells from solid tumors. Recent studies have identified lymphatic molecular markers and growth factors necessary for lymphangiogenesis. In particular, lymphatic endothelial receptor tyrosine kinase VEGFR‐3 and its ligands VEGF‐C and VEGF‐D play crucial roles in promoting lymphatic vascular growth both during development and in pathological conditions. Isolation of pure cultures of lymphatic and blood vascular endothelial cells and systematic characterization of their transcriptomes provide useful cell culture models and novel potential vascular markers and offer further insights into the lymphatic vascular biology. Ectopic expression of the lymphatic endothelial specific homeobox transcription factor Prox1 in blood endothelial cells results in a shift in the gene expression profile towards the lymphatic endothelial phenotype, demonstrating the plasticity of endothelial cells and offering the possibility of transcriptional reprogramming of vascular endothelial cells for future therapeutic applications.
Regulation of Insulin Secretion: Insights from Engineered β‐cell Lines
Authors: EFRAT SHIMON
Published: May 2004

Abstract: Abnormalities in insulin secretion are involved in a number of diseases, including type 1 and type 2 diabetes, persistent hyperinsulinemic hypoglycemia of infancy, and insulinoma. Understanding the mechanisms that regulate insulin secretion may allow the development of new therapies for these diseases as well as contribute to our ability to engineer insulin‐producing cells for cell replacement therapy of type 1 diabetes. Glucose phosphorylation in β‐cells has been viewed as a key regulatory event in coupling insulin secretion to extracellular glucose concentrations. Work with transformed rodent β‐cell lines as well as recent findings from human progenitor cells induced to differentiate into insulin‐producing cells has provided new insights into the role of glucose phosphorylating enzymes in the regulation of insulin secretion.
Ca2+ Channel Properties in Neuroendocrine Tumor Cell Cultures Investigated by Whole‐Cell Patch‐Clamp Technique
Authors: MERGLER STEFAN , DROST ADRIANA , BECHSTEIN WOLF‐OTTO , NEUHAUS PETER , WIEDENMANN BERTRAM
Published: May 2004

Abstract: Neuroendocrine tumor (NET) cells of the gastroenteropancreatic system express a variety of voltage‐operated Ca2+ channels (VOCCs). In addition, NET cells release hormones and biogenic amines in distinct patterns, leading to typical hypersecretion syndromes. Interestingly, these patterns depend on the primary location of the NET. The aim of this study was to investigate a possible link between clinically distinct entities of NETs and specific properties of VOCCs. Using whole‐cell patch‐clamp technique, electrophysiological data were obtained from permanent NET cell cultures as well as from primary cultivated NET cells from foregut and midgut tumors. Definite Ca2+ channel characteristics were analyzed by a color‐coding method. As a result, we could demonstrate specific Ca2+ channel characteristics in NET cells from midgut tumors that were not found in NET cells from a foregut location. This may be important functionally with respect to different cell biological functions of NET cells. In summary, clear differences exist in the VOCC pattern in NET cells from foregut versus midgut. This may be functionally relevant in the hypersecretion syndrome predominantly found in foregut NETs. Therefore, these data on the characteristics of VOCCs could be useful in the development of a novel therapy for NET disease; for example, specific VOCC subtype modulators may help.
Regulators of Neurite Outgrowth: Role of Cell Adhesion Molecules
Authors: KIRYUSHKO DARYA , BEREZIN VLADIMIR , BOCK ELISABETH
Published: May 2004

Abstract: Neuronal differentiation is a fundamental event in the development of the nervous system as well as in the regeneration of damaged nervous tissue. The initiation and guidance of a neurite are accomplished by positive (permissive or attractive), negative (inhibitory or repulsive), or guiding (affecting the advance of the growth cone) signals from the extracellular space. The signals may arise from either the extracellular matrix (ECM) or the surface of other cells, or be diffusible secreted factors. Based on this classification, we briefly describe selected positive, negative, and guiding signaling cues focusing on the role of cell adhesion molecules (CAMs). CAMs not only regulate cell‐cell and cell‐ECM adhesion “mechanically,” they also trigger intracellular signaling cascades launching neurite outgrowth. Here, we describe the structure, function, and signaling of three key CAMs found in the nervous system: N‐cadherin and two Ig‐CAMs, L1 and the neural cell adhesion molecule NCAM.
Serotonin Secretion by Human Carcinoid BON Cells
Authors: SAMUEL TRAN VIET , MARION‐AUDIBERT ANNE‐MARIE , KARATEKIN ERDEM , HUET SEBASTIEN , CRIBIER SOPHIE , GUILLAUMIE KOULM , CHAPUIS CATHERINE , DESNOS CLAIRE , DARCHEN FRANÇOIS , HENRY JEAN‐PIERRE
Published: May 2004

Abstract: BON cells are human carcinoid cells that secrete serotonin (5‐HT) and various peptides. Secretion of [3H]5‐HT by cell cultures was investigated. Acetylcholine (Ach) stimulated secretion through a somatostatin‐sensitive muscarinic pathway, whereas isoproterenol was inefficient. [3H]5‐HT secretion also was induced by Ca2+ in the presence of the ionophore A‐23187 or after digitonin permeabilization. These two processes were insensitive to stomatostatin. Ba2+ induced an efficient somatostatin‐sensitive [3H]5‐HT secretory response. Secretion also was analyzed at the single‐cell level, using carbon fiber amperometry and evanescent‐field fluorescence microscopy, after labeling the secretory vesicles by transfection of the cells with a NPY‐GFP construct. Both techniques revealed slow kinetics of secretory responses, suggesting that ready‐to‐fuse vesicles do not accumulate in these cells. Single secretory vesicles were imaged either in resting conditions or after addition of Ca2+ ions to digitonin‐permeabilized cells. The three‐dimensional movements of the vesicles before exocytosis were analyzed. The mean velocity of vesicles that released their content was lower than that of silent ones. Even in the case of mobile vesicles, exocytosis often was preceded by a period of arrest lasting at least 15 seconds, consistent with a docking/priming step.
Survival and Clinical Outcome of Patients with Neuroendocrine Tumors of the Gastroenteropancreatic Tract in a German Referral Center
Authors: PAPE ULRICH‐FRANK , BÖHMIG MICHAEL , BERNDT UTA , TILING NIKOLAUS , WIEDENMANN BERTRAM , PLÖCKINGER URSULA
Published: May 2004

Abstract: Neuroendocrine tumors (NETs) are rare neoplasms. Approximately 75% of all cases manifest in the gastroenteropancreatic (GEP) system. Because of the low incidence of NETs, limited data about the clinical outcome and prognostic variables are available. In an attempt to identify prognostic parameters, we investigated the distribution of primary tumors, pattern of metastasis formation, clinical presentation, histological classification, and outcome of therapeutic interventions in a large patient cohort cared for in a German referral center. In 254 patients with GEP‐NETs, the primary tumor was of foregut, midgut, or hindgut origin in 44.1% (28.7% pancreas), 43.7% (34.7% jejunoileum), and 4.3%, respectively. No primary tumor was found in 7.9%. Metastases occurred preferentially in lymph nodes and the liver. The overall 5‐year survival rate was 57.1%. In the absence or presence of metastases at initial diagnosis the 5‐year survival rate was 80.0% and 51.7%, respectively. The 5‐year survival rate was related to the localization of the primary and was 75.0% and 42.9% for jejunoileal and pancreatic tumors, respectively. The size of the primary tumor (<2 cm) and histological grading as low‐grade malignant were both associated with a significantly longer survival. Surgery with curative intent was attempted in 141 patients. However, an R0 resection was achieved in only 66.0% of these patients. Five‐year survival rate in the latter group was significantly higher (77.3%) as compared with all surgical patients (55.4%). Long‐term tumor‐free survival was obtained in only 53.7% of successfully resected patients. Palliative medical treatment, either with chemotherapy (i.e., especially for foregut NETs) or biotherapy (especially for midgut NETs), was only moderately effective for both therapeutic regimens.
Somatostatin Receptor Targeting for Tumor Imaging and Therapy
Authors: GRÖTZINGER CARSTEN , WIEDENMANN BERTRAM
Published: May 2004

Abstract: Somatostatin receptors and their ligands constitute the prototype targeting system for contrast‐enhanced detection and radiotherapy of cancer. Radiolabeled synthetic analogs of somatostatin have been successfully used in routine molecular imaging of primary gastroenteropancreatic neuroendocrine tumors and their metastases for more than 15 years. Likewise, analog conjugates for radiation therapy have been developed and have been under clinical trial for several years. The vast amount of knowledge accumulated by both basic and clinical science has made the somatostatin/somatostatin receptor system a popular model for new targeting strategies in imaging and therapy. Among those, the use of near‐infrared fluorescent dye‐peptide conjugates for the detection of tumors by endoscopy, mammography, or intraoperative imaging is one of the most promising. This article reviews recent developments in the field and discusses concepts for receptor‐targeted molecular imaging and therapy.
Importance of Vesicle Proteins in the Diagnosis and Treatment of Neuroendocrine Tumors
Authors: NILSSON OLA , JAKOBSEN ANNE‐MARIE LEVIN , KÖLBY LARS , BERNHARDT PETER , FORSSELL‐ARONSSON EVA , AHLMAN HÅKAN
Published: May 2004

Abstract: We have analyzed the expression of synaptic vesicle proteins in human neuroendocrine tumors and the potential use of vesicle proteins in the diagnosis and treatment of neuroendocrine tumors. Biopsies from endocrine and nonendocrine tumors of the gastrointestinal tract, pancreas, and adrenals were examined by immunocytochemistry using antibodies against synaptic vesicle protein 2 (SV2), vesicular monoamine transporter 1 and 2 (VMAT1&2), and neuroendocrine secretory protein 55 (NESP55). SV2 was expressed in all endocrine tumors of the gastrointestinal tract and pancreas as well as in gastrointestinal stromal tumors (GISTs). None of the adenocarcinomas expressed SV2. VMAT1&2 were expressed in amine‐producing tumors of the gastrointestinal tract (ECL cell and EC cell carcinoids) and in a small number of peptide‐producing pancreatic endocrine tumors. NESP55 was expressed in neuroblastomas and adrenal pheochromocytomas as well as in a subgroup of pancreatic endocrine tumors. The importance of VMAT1&2 for the uptake of 123I‐MIBG in tumor cells was demonstrated. It was concluded that neuroendocrine tumors express multiple synaptic vesicle proteins that are useful in the histopathological diagnosis and classification of tumors. Vesicle proteins may prove to be useful for targeting tumor therapy.
An Ejection Chain Approach for the Generalized Assignment Problem
Authors: Yagiura Mutsunori , Ibaraki Toshihide , Glover Fred
Published: May 2004

We propose a tabu search algorithm for the generalized assignment problem, which is one of the representative combinatorial optimization problems known to be NP-hard. The algorithm features an ejection chain approach, which is embedded in a neighborhood construction to create more complex and powerful moves. We also incorporate an adaptive mechanism for adjusting search parameters, to maintain a balance between visits to feasible and infeasible regions. Computational results on benchmark instances of small sizes show that the method obtains solutions that are optimal or that deviate by at most 0.16% from the best known solutions. Comparisons with other approaches from the literature show that, for instances of larger sizes, our method obtains the best solutions among all heuristics tested.
An Algorithm to Compute the Waiting Time Distribution for the M/G/1 Queue
Authors: Shortle John F. , Brill Percy H. , Fischer Martin J. , Gross Donald , Masi Denise M. B.
Published: May 2004

In many modern applications of queueing theory, the classical assumption of exponentially decaying service distributions does not apply. In particular, Internet and insurance risk problems may involve heavy-tailed distributions. A difficulty with heavy-tailed distributions is that they may not have closed-form, analytic Laplace transforms. This makes numerical methods, which use the Laplace transform, challenging. In this paper, we develop a method for approximating Laplace transforms. Using the approximation, we give algorithms to compute the steady state probability distribution of the waiting time of an M/G/1 queue to a desired accuracy. We give several numerical examples, and we validate the approximation with known results where possible or with simulations otherwise. We also give convergence proofs for the methods.
Health Literacy: A Review
Authors: Andrus Miranda R. , Roth Mary T.
Published: May 2004

Illiteracy has become an increasingly important problem, especially as it relates to health care. A national survey found that almost half of the adult population has deficiencies in reading or computation skills. Literacy is defined as the basic ability to read and speak English, whereas functional health literacy is the ability to read, understand, and act on health information. Up to 48% of English‐speaking patients do not have adequate functional health literacy. The consequences of inadequate health literacy include poorer health status, lack of knowledge about medical care and medical conditions, decreased comprehension of medical information, lack of understanding and use of preventive services, poorer self‐reported health, poorer compliance rates, increased hospitalizations, and increased health care costs. The medical community must acknowledge this issue and develop strategies to ensure that patients receive assistance in overcoming the barriers that limit their ability to function adequately in the health care environment.
Effect of a Standardized Meal on the Bioavailability of a Single Oral Dose of Tibolone 2.5 mg in Healthy Postmenopausal Women
Authors: Timmer Cees J. , Huisman Johannes A. M.
Published: May 2004

Study Objective. To assess the effect of food on absorption and pharmaco‐kinetic disposition of tibolone.

Design. Open‐label, randomized, crossover study with a 1‐week washout period.

Setting. Institut für Klinische Pharmakologie, Höhenkirchen‐Siegertsbrunn, Germany.

Subjects. Twenty‐four healthy, early postmenopausal women.

Intervention. Single doses of tibolone 2.5 mg were administered after subjects consumed a high‐fat meal or fasted.

Measurements and Main Results. Plasma concentrations of tibolone and its three primary metabolites, Δ4‐tibolone, 3α‐hydroxytibolone, and 3β‐hydroxytibolone, were assayed by gas chromatography with mass spectrometry. Peak plasma concentration (Cmax), time to Cmax, area under the plasma concentration versus time curve from time zero to infinity (AUC0‐∞), and elimination half‐life were calculated, and food effects were evaluated. Plasma concentrations of tibolone and Δ4‐tibolone were too low to estimate AUC0‐∞ and half‐life. Absorption or formation of 3α‐hydroxytibolone and 3β‐hydroxytibolone was slower in fed participants than in fasting participants, but this was of no clinical relevance because of the long‐term nature of tibolone treatment. Meal consumption did not affect AUC0‐∞ or half‐life for 3α‐hydroxytibolone and 3β‐hydroxytibolone.

Conclusion. Food consumption decreased and delayed Cmax but had no effect on the exposure of tibolone and its metabolites. Tibolone therefore can be administered irrespective of meal timing.
Effect of Milk Thistle on the Pharmacokinetics of Indinavir in Healthy Volunteers
Authors: Piscitelli Stephen C. , Formentini Elizabeth , Burstein Aaron H. , Alfaro Raul , Jagannatha Shyla , Falloon Judith
Published: May 2004

Study Objective. To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition.

Design. Prospective open‐label drug interaction study.

Setting. Outpatient clinic.

Subjects. Ten healthy volunteers.

Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11‐day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction.

Measurements and Main Results. Indinavir concentrations were measured by using a validated high‐performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (Cmax), hour‐0 concentration, hour‐8 concentration (C8), time to reach Cmax, and area under the plasma concentration‐time curve over the 8‐hour dosing interval (AUC8). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC8 after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C8) was significantly decreased by 25%.

Conclusion. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus.
Noninvasive 24‐Hour Ambulatory Blood Pressure Monitoring: Overview of Technology and Clinical Applications
Authors: Ernst Michael E. , Bergus George R.
Published: May 2004

During the last 25 years, 24‐hour noninvasive ambulatory blood pressure monitoring (ABPM) has evolved from a research tool of limited clinical use into an important tool for stratifying cardiovascular risk and guiding therapeutic decisions. Until recently, clinical use of ABPM focused on identifying patients with white‐coat hypertension, but accumulated evidence now points to greater prognostic significance of ABPM in determining risk for target‐organ damage compared with that of office blood pressure measurements. Clinicians involved in the care of patients with hypertension should familiarize themselves with the role of this technology and how to use it in an appropriate and cost‐effective manner.
Low‐Dosage Methotrexate for Treatment and Maintenance of Remission in Patients with Inflammatory Bowel Disease
Authors: Vandell Alexander G. , DiPiro Joseph T.
Published: May 2004

A literature search was conducted to examine the safety and effectiveness of low‐dosage methotrexate for treatment and maintenance of remission in patients with inflammatory bowel disease. Nine published articles indicated that for patients with Crohn's disease, oral or intramuscular methotrexate 20–25 mg/week is safe and effective to induce remission, followed by a lower dosage to maintain remission. In addition, methotrexate allows for corticosteroid dosage reduction. Therapy may be continued until the disease flares or adverse events occur. Evidence is insufficient to support methotrexate as treatment for ulcerative colitis.
Celecoxib‐Induced Erythema Multiforme with Glyburide Cross‐Reactivity
Authors: Ernst Erika J. , Egge Jason A.
Published: May 2004

Erythema multiforme is an acute inflammatory skin reaction that often is caused by drugs, especially sulfonamides and their derivatives. Celecoxib, a cyclooxygenase‐2 inhibitor, is a sulfonamide derivative commonly prescribed to treat arthritis in patients who cannot tolerate or who have a contraindication for taking traditional nonsteroidal antiinflammatory agents. A 57‐year‐old man with a previously undocumented sulfa allergy experienced an allergic skin reaction and had difficulty breathing secondary to throat swelling. His condition was believed to be erythema multiforme associated with the introduction of celecoxib into his drug regimen. His drug therapy was discontinued, but a subsequent reaction occurred when the sulfonamide derivative glyburide was reintroduced. It is important for clinicians to obtain a careful history and perform a thorough medical evaluation in all patients receiving sulfonamides and their derivatives, as a potentially life‐threatening allergic reaction may be prevented.
Effectiveness of Pretreatment in Decreasing Adverse Events Associated with Pamidronate in Children and Adolescents
Authors: Robinson Renee F. , Nahata Milap C. , Hayes John R. , Batisky Donald L. , Bates Carlton M. , Mahan John D.
Published: May 2004

Study Objectives. To assess the effectiveness of pretreatment with ibuprofen or acetaminophen compared with no pretreatment in decreasing adverse events in children and adolescents receiving the first and second series of pamidronate therapy; and to compare the effectiveness of ibuprofen versus acetaminophen for prevention of adverse events associated with pamidronate infusion.

Design. Retrospective case review.

Setting. Children's hospital.

Patients. Twenty‐seven children and adolescents aged 3–21 years receiving pamidronate therapy.

Measurements and Main Results. Data for patient demographics, medical history, genetic history of disease, pamidronate infusion dosage, and concurrent drug therapy were collected. Adverse drug events secondary to pamidronate infusion and subsequent drug therapies received were documented. Data were categorized by presence or absence of pretreatment and analyzed by cross‐tabulation to determine whether the presence of adverse events differed between groups (no pretreatment, acetaminophen pretreatment, and ibuprofen pretreatment). Fewer adverse events were reported in patients receiving ibuprofen (17% of patients) versus acetaminophen (83%). Differences in presence of fever (χ2=10.5, p=0.005) and bone pain (χ2=7.3, p=0.027) among the three pretreatment groups were also statistically significant.

Conclusion. Pretreatment with ibuprofen or acetaminophen appears to decrease the occurrence of adverse events from pamidronate therapy. However, adverse events seem less likely to occur with ibuprofen. Further study is necessary to determine the relationship between occurrence of adverse events, other possible treatment strategies, and patient adherence with pamidronate therapy.
Aripiprazole, a Novel Atypical Antipsychotic Drug
Authors: Argo Tami R. , Carnahan Ryan M. , Perry Paul J.
Published: May 2004

Before the 1990s, treatment of psychoses centered on conventional agents whose tolerability was limited by extrapyramidal side effects (EPS). The past decade has seen the emergence of a newer generation of antipsychotic agents, first with clozapine and followed shortly by risperidone, olanzapine, quetiapine, and ziprasidone. These agents have been touted as providing better negative symptom efficacy, less impaired cognition, and lower risk of extrapyramidal syndromes. However, evolving evidence suggests that several drugs in this class may be associated with significant weight gain and lipid abnormalities. Aripiprazole, a new atypical antipsychotic drug, displayed efficacy similar to that of haloperidol and risperidone and superior to that of placebo in numerous clinical trials. Aripiprazole does not cause significant prolactin elevation and is associated with a low rate of clinically significant weight gain compared with other atypical antipsychotics. Patients receiving aripiprazole experienced EPS at a rate similar to that seen with placebo. Aripiprazole provides a new treatment option with limited adverse effects for patients in need of antipsychotic therapy.
Enteral Administration of Naloxone for Treatment of Opioid‐Associated Intragastric Feeding Intolerance
Authors: Mixides George , Liebl Michael G. , Bloom Kim
Published: May 2004

Intragastric enteral feeding intolerance, common in the intensive care setting, is attributed to many causes. Opioid antagonists such as naloxone may have a role in reversing the intolerance when it is associated with intravenous opioid infusions. A 38‐year‐old woman hospitalized for acute respiratory distress syndrome was supported with low tidal volume mechanical ventilation. She required lorazepam and morphine administered by continuous intravenous infusion to achieve ventilator synchrony and pain control. While receiving these therapies, the patient developed persistent intolerance to intragastric feeding. Intravenous metoclopramide and laxatives did not decrease gastric volume residuals, and insertion of a jejunal tube was deemed unsafe due to worsening of her respiratory status. Total parenteral nutrition was begun to meet her caloric needs, but she experienced repeated catheter‐related bloodstream infections. Naloxone 2 mg by gastric tube every 8 hours for 8 days was started; the dosage then was increased to 4 mg every 8 hours. Tube feeding was restarted, which provided the patient with more than 90% of her daily caloric needs and allowed for discontinuation of parenteral nutrition. With this dosage of naloxone, tolerance to intragastric feeding was maintained until the patient's death due to refractory respiratory failure. Enterally administered naloxone is an effective, noninvasive means of reversing intolerance to intragastric feeding associated with opioids.
Pharmacodynamic Effects of Zidovudine 600 mg Once/Day versus 300 mg Twice/Day in Therapy‐Naïve Patients Infected with Human Immunodeficiency Virus
Authors: Ruane Peter J. , Richmond Gary J. , DeJesus Edwin , Hill‐Zabala Christina E. , Danehower Susan C. , Liao Qiming , Johnson Judy , Shaefer Mark S.
Published: May 2004

Study Objective. To compare the virologic activity of zidovudine monotherapy administered as 600 mg once/day versus 300 mg twice/day.

Design. Phase II, randomized (1:1), open‐label study.

Setting. Thirteen medical centers in the United States.

Patients. Thirty‐two antiretroviral‐naïve patients infected with human immunodeficiency virus (HIV).

Intervention. Patients were administered either zidovudine 600 mg every 24 hours (16 patients) or 300 mg every 12 hours (16 patients) for 13 days.

Measurements and Main Results. Plasma HIV‐1 RNA concentration was measured daily. Study end points were between‐group differences in change from baseline of log10‐transformed HIV‐1 RNA and in rates of viral load decline measured by the slope of HIV‐1 RNA over time. At baseline, mean HIV‐1 RNA was similar in the once/day and twice/day groups (4.33 and 4.40 log10 copies/ml, respectively). At day 14, a trend toward lower mean reduction in HIV‐1 RNA from baseline was observed in the once/day group (−0.585, 95% confidence interval [CI] −0.728 to −0.442 log10 copies/ml) compared with the twice/day group (−0.849, 95% CI −1.067 to −0.630 log10 copies/ml, p=0.056). Viral load reduction also tended to be slower in the once/day group, as indicated by the smaller slope of viral load decline in the once/day group than in the twice/day group during days 1–14 (−0.045 vs −0.065 log10 copies/ml/day, p=0.065). Both zidovudine regimens were similarly well tolerated.

Conclusion. Zidovudine 600 mg once/day has antiviral activity, although less pronounced and more slowly achieved than that seen with zidovudine 300 mg twice/day. No differences were observed between the two treatment groups with respect to safety profile or tolerability.
Board of Pharmaceutical Specialties—Certified Faculty: A Survey of United States Colleges of Pharmacy
Authors: Romanelli Frank , Ryan Melody , Smith Kelly M.
Published: May 2004

Board certification of pharmacists has been a reality in the United States since 1976, when the Board of Pharmaceutical Specialties (BPS) was founded. Little has been reported about the effects of board certification of pharmacists, particularly pharmacy practice faculty, since 1992, when the BPS administered its first certification examination. We developed and pretested a survey to describe and measure the effect of BPS certification on the realm of academia as perceived by deans of colleges of pharmacy in the United States. Deans or other appropriate officials at all 84 colleges of pharmacy in the United States were asked to complete and submit this 13‐question survey, which was administered through the Web and maintained respondents' anonymity. Officials from 35 of the 84 colleges completed the survey, for a response rate of 42%. No college reported that board certification was a condition for employment. Eight schools (23%) anticipated a certification requirement in the future. The most commonly reimbursed items associated with certification were fees for the American College of Clinical Pharmacy preparatory course and the BPS examination. Twelve schools (34%) provided no reimbursement toward certification. The most common incentive for faculty to obtain certification was consideration in promotion and tenure (66%). We believe that this information will facilitate efforts to gauge the effects of BPS certification on colleges of pharmacy. We also anticipate that it will assist colleges as they attempt to recruit and retain the most qualified faculty members possible, particularly in light of the national pharmacist shortage.
Model‐free recursive LQ controller design (learning LQ control)
Authors: Kawamura Yoshiaki , Nakano Masahiro , Yamamoto Hiroyuki
Published: May 2004

A new data‐based iterative self‐optimizing approach to practical design (learning/adaptive process) of the infinite‐horizon LQ regulator is proposed. Optimality is given by a certain orthogonality condition of response signals, and the global convergence of feedback gain is proved for MIMO systems by an expansion of the Riccati equation. The design is applied to stabilizing control and steady state error‐less control of physical systems. Copyright © 2004 John Wiley & Sons, Ltd.
Crystallographic report: Bis{[diacetyl‐bis(2,6‐isopropylphenylimine)]nickel(I)(µ‐chloro)}
Authors: Shao Qing , Sun Hongmei , Shen Qi , Zhang Yong
Published: May 2004

The first α‐diimine nickel(I) complex having a chloro bridge is reported. The centrosymmetric dinuclear structure of {[ArNC(Me)C(Me)NAr]NiCl}2[Ar2,6−C6H3(i‐Pr)2] features two chelating α‐diimine ligands and two bridged chlorine atoms, so that a distorted tetrahedral N2Cl2 coordination geometry for nickel results. Copyright © 2004 John Wiley & Sons, Ltd.
Metallothionein as a biomarker for mercury in tissues of rat fed orally with cinnabar
Authors: Huang Zhi‐Yong , Shen Jin‐Can , Zhuang Zhi‐Xia , Wang Xiao‐Ru , Lee Frank S. C.
Published: May 2004

Cinnabar, as one of the most widely used mineral drugs in traditional Chinese medicines, has been proven to have prominent curative effects in clinical use for more than 2000 years. But the safety and toxicity of the drug has been under constant debate in clinic usage. Metallothionein (MT) contains about 30% of cysteine in the molecule, and plays an important detoxification role against heavy metals. In this study, it was used as a biomarker to assess mercurial accumulation in rats fed orally with cinnabar. After feeding rats with cinnabar by gastric gavage at different dosages and at different times, the distribution of heavy metals (including mercury, copper and zinc) and MT was investigated among rat tissues, including liver, kidney, heart, brain, testis and blood. Metals and MT determinations were carried out using inductively coupled plasma mass spectrometry (ICP‐MS) and a modified mercury saturation assay technique respectively. The results indicated that mercury was easily accumulated in the tissues of rats exposed to cinnabar, especially in kidney. For example: at a feeding dosage of 5 g kg−1 (bw) for 4 weeks, the mercury concentrations in kidney were 13, 8.7, 21.6 and 26 times those in liver, testis, brain and heart respectively; and at 2.5 g kg−1 (bw) for 2 weeks, the mercury concentrations in kidney were 21, 2.1, 3 and 21 times those in liver, testis, brain and heart respectively. In addition, mercury in kidney and liver of all cinnabar groups was significantly higher than that of the control group (P < 0.01). A high positive correlation observed between MT concentrations and mercury levels in both liver and kidney (R2 = 0.9299, P < 0.02 for liver; R2 = 0.9923, P < 0.0008 for kidney) indicated that MT could be used as a biomarker for mercury in tissues. Copyright © 2004 John Wiley & Sons, Ltd.
Should we be using bilateral carotid distal protection devices during the percutaneous closure of patent foramen ovale in patients with a history of paradoxical embolus?
Authors: Richardson Gail , Keeble Thomas R. , Rothman Martin T.
Published: May 2004

Percutaneous closure of patent foramen ovale (PFO) is becoming standard practice, particularly in patients with a history of embolic phenomena. The acute risk of cerebrovascular accident in patients undergoing this procedure is ∼ 1%. We report the first successful use of bilateral carotid artery distal protection in this situation. Catheter Cardiovasc Interv 2004;62:272–275. © 2004 Wiley‐Liss, Inc.
Intra‐arterial thrombolysis for left middle cerebral artery embolic stroke during percutaneous mitral commissurotomy
Authors: Vijayakumar M. , Rajesh T. , Kumar Prasanna , Haridas K.K.
Published: May 2004

Cerebral thromboembolism is a serious complication. Early recognition and rapid reperfusion can prevent long‐term neurological morbidity. We report a case of successful intra‐arterial thrombolysis for middle cerebral artery embolic stroke during percutaneous mitral commissurotomy, which resulted in complete neurological recovery. Catheter Cardiovasc Interv 2004;62:249–251. © 2004 Wiley‐Liss, Inc.
Early ostial saphenous vein graft stenosis associated with the use of Symmetry sutureless aortic proximal anastomosis device: Successful percutaneous revascularization
Authors: Cline Sharon L. , Guduvalli Anuradha , Kalaria Vijay G.
Published: May 2004

A recent advance in technology permits the creation of sutureless proximal aortic anastomosis during coronary artery bypass graft surgery. This new tool has significant potential benefit by minimizing aortic manipulation with subsequent reduction in neuroembolization. Implantation of a nitinol‐based proximal aortic connector (Symmetry) has a potential to elicit intimal hyperplastic reaction analogous to restenosis after coronary stent placement. We report cases of early vein graft stenosis in association with the use of the Symmetry device. Three patients suffered from severe ostial stenosis within 6 months of bypass surgery with symptomatic presentation. Of these three patients, two underwent successful percutaneous revascularization. Fluoroscopic star‐shaped appearance of the metallic Symmetry allows device recognition during angiography. We review current data regarding graft patency with the use of Symmetry device and discuss technical issues to address specific problems during percutaneous revascularization. Catheter Cardiovasc Interv 2004;62:203–208. © 2004 Wiley‐Liss, Inc.
Novel use of a high‐energy excimer laser catheter for calcified and complex coronary artery lesions
Authors: Bilodeau Luc , Fretz Eric B. , Taeymans Yves , Koolen Jacques , Taylor Kevin , Hilton David J.
Published: May 2004

This study was designed to evaluate safety and effectiveness of the 0.9 mm excimer laser coronary catheter with increased laser parameters. We report a prospective trial of 100 calcified and/or balloon‐resistant lesions where a new 0.9 mm excimer laser catheter was used at standard or higher energy level to facilitate angioplasty. Standard in‐hospital clinical and angiographic parameters were collected and measured. Laser technical success was obtained in 87 lesions (92%), procedural success was reached in 88 lesions (93%), and clinical success in 82 lesions (86%). Increased laser parameters were used for 29 resistant lesions. This new 0.9 mm excimer laser coronary catheter using higher energy parameters seems to be safe and effective for management of calcified and nondilatable lesions. Catheter Cardiovasc Interv 2004;62:155–161. © 2004 Wiley‐Liss, Inc.
Aortic aneurysm repair with endovascular grafts: Developing a graft surveillance program
Authors: Slovut David P. , Bacharach J. Michael
Published: May 2004

The objective of this study was to describe the development of a comprehensive surveillance program for monitoring the long‐term follow‐up of endoluminal stent graft (ELG) patients. Despite high procedural success rates, ELG patients remain at ongoing risk for aneurysm sac expansion, rupture, and other adverse events that make long‐term surveillance imperative. As they perform more ELG, practitioners face increased logistical difficulty performing appropriate patient follow‐up. A computer‐based data ELG registry was created using Epi Info, a program developed by the Centers for Disease Control and Prevention that enables users to design a data entry form, enter data, and perform statistical analyses. The database has been used to track 259 patients (214 men and 45 women) who underwent ELG between November 1999 and October 2003. One‐year follow‐up was available for 182 patients, 2‐year follow‐up for 104 patients, and 3‐year surveillance data for 40 patients, which represent follow‐up rates of 89.6%, 78.8%, and 61.5%, respectively. There were 25 late deaths. The Kaplan‐Meier estimate for 1‐year survival was 92.5%. Twenty‐one patients underwent 24 secondary angiographic procedures at a mean 8.6 ± 10.3 months (range, 1–37.6) after stent‐graft repair. No mortality was observed in association with a secondary intervention. There were no late conversions to open aneurysm repair. The Kaplan‐Meier estimate for freedom from secondary intervention for all patients at 1 year was 91.0%. A computer‐based registry facilitates appropriate and timely patient follow‐up and may improve the long‐term outcome from ELG. Catheter Cardiovasc Interv 2004;62:252–261. © 2004 Wiley‐Liss, Inc.
Growth of Ba2Re(Y,Pr)Ru1‐xCuxO single crystals in a high temperature solution drop using an infrared imaging system
Authors: Rao S. M. D. , Lin B. H. , Lu C. Y. , Sutanto N. , Liao Y. C. , Wu M. K.
Published: May 2004

Infrared imaging furnace was used to grow single crystals of Ba2YRu1‐xCuxO6 and Ba2PrRu1‐xCuxO6 using high temperature solutions of PbO‐PbF2 in the form of a bubble attached to the feed rods. Several small crystals were found deposited on the cooler portions of the sintered rod as well as in the drop like portion at the end of the rod. These crystals were collected and the morphology, microstructure and magnetic properties were studied. The details of these investigations are presented. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth of near‐stoichiometric LiNbO3 crystals and Li2O contents determination
Authors: Sun D. L. , Hang Y. , Zhang L. H. , Luo G. Z. , Zhu S. N. , Lim P. K. , Hung W. W.
Published: May 2004

Two kinds of near‐stoichiometric LiNbO3 crystals (SLN11 and SLN19) were grown by a flux pulling method from stoichiometric melt with addition of 11mol%K2O and 19mol%K2O, respectively. Compared with the congruent melting LiNbO3, the ultraviolet absorption edges of two crystals shift towards shorter wavelengths, and the locations of the OH‐ infrared absorption band have obvious change and the bandwidths become greatly narrower. From these experimental results, the Li2O contents are determined indirectly to be about 49.6mol% for SLN11 and 49.9mol% for SLN19, respectively. The Li2O content in SLN19 is very close to the ideal value of 50mol%. The coercive fields of two crystals were measured by the poling method at room temperature. A linear relationship between the Li2O content and the coercive field was fitted. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thermal conductivity of ZnSe by molecular dynamics simulation
Authors: Balasubramanian A. K. , Sankar N. , Ramakrishnan S. K. , Ramachandran K.
Published: May 2004

Molecular dynamics simulation using the new fit of the empirical Tersoff Potential is applied to study the thermal properties of ZnSe at and below the room temperature. The resulting diffusivity and thermal conductivity are compared with the photoacoustic measurements on the grown ZnSe crystal. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Beamforming array antenna with heterogeneous signal distribution for UWB pulse transmission
Authors: Sato Tadatomo , Abreu Giuseppe , Kohno Ryuji
Published: May 2004

As ultra‐wideband (UWB) is a technology primarily aimed at short‐range communications, it is expected that in many UWB networks transmitters and receivers are concentrated in close proximity. Mutual interference among UWB devices is therefore a key problem to be overcome. One effective method to achieve this goal is the application of spatial division techniques using array antennas, which can have modified radiation patterns modified adaptively. UWB impulse radio systems, however, employ the transmission of baseband (carrierless) signals. This peculiarity of UWB‐IR systems makes the straightforward application of conventional beamforming methods, which are based on the control of amplitudes and phases of the signals transmitted from each element in the array, a rather difficult problem. In this paper a new beamforming method is proposed, which is based on the control of the power intensity profile of the frequency components shared by signals transmitted simultaneously from several antenna elements. In order to demonstrate the effectiveness of the method, computer simulations are shown which demonstrate that if a monocycle waveform is divided into several signals representing overlapping frequency subband components of the original, each transmitted from a different antenna element, a radiation pattern without sidelobes can be synthesized over the UWB. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(11): 1–10, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20074
Comparative study of electron density profiles in compact torus plasma merging experiments
Authors: Hayashiya Hitoshi , Asaka Takeo , Katsurai Makoto
Published: May 2004

Following two previous papers on comparative studies of the electron density distributions for a single compact torus (CT) and a spherical tokamak (ST), and for a single ST and a merged ST, a comparative study on the dynamics of the electron density profile during and after the CT and ST plasma merging process was performed. The sharpness of the peak in the electron density profile around the midplane just after the merging of CT with a low safety factor (q value) such as RFP or spheromak is found to be related to the speed of the magnetic axis during the plasma merging process. It is also found that the electron density gradient near the plasma edge in a high‐q ST is larger than that of a low‐q CT. High‐q ST is found to have a magnetic structure which is able to sustain a large thermal pressure by a strong j × B force. Despite these differences in the electron density profile between CT and ST during merging, the confinement characteristics evaluated from the number of electrons confined within the magnetic separatrix after the completion of the merging are almost similar between the merging CT and the merging ST. For all configurations, the electron density profiles after the completion of the merging are analogous to those of the corresponding single configuration produced without the merging process. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 148(2): 14–21, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10312
Numerical simulation of blow‐down closed‐cycle disk MHD generator
Authors: Inui Yoshitaka , Ito Hideyuki , Ishida Taichi
Published: May 2004

Numerical simulations of the closed‐cycle disk MHD generation experiment with Tokyo Institute of Technology's Fuji‐1 blow‐down facility are performed. In the calculations, the r–z two‐dimensional time‐dependent simulation code developed by the authors that can take the effect of water contamination into account is used, and the experimental conditions of Run A4109 operated by Disk‐F4 generator are selected as the numerical conditions. When the water contamination is the lowest level realized in the experiments, the simulation results coincide with the experimental results reasonably well, though there exist some discrepancies caused by inaccuracy of used basic plasma parameters, limitations of the two‐dimensional approximation, and so on. The voltage–current curve is almost linear, indicating that the MHD interaction is relatively weak and the flow field is mainly determined by the back‐pressure. The increase of the water contamination level results in decreased seed ionization rate at the generator channel inlet, leading to the steep deterioration of the generator performance. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 148(2): 46–54, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10335
Magnetostriction and motor vibration
Authors: Kamimoto Katsumi , Ishibashi Fuminori , Noda Shinichi , Yanase Shunji , Sasaki Tadashi
Published: May 2004

A quiet induction motor is strongly demanded today. Electromagnetic factors are a main cause of vibration and acoustic noise in a small induction motor. Electromagnetic forces and magnetostrictive forces are considered as the origin of electromagnetic vibration and noise. In this paper, magnetostrictive vibration of a ring of electrical steel sheets was simulated by the mechanical finite element method. Magnetostriction was assumed as external forces and they were added at each node of the meshed ring. Resonant frequency and the mode of the ring were calculated. In the steel sheet ring excited by a PWM voltage source inverter, the frequency spectrum of vibration of ring was measured and compared with the calculated results. It was confirmed that these procedures simulated magnetostriction behavior of electrical steel sheets. Furthermore, the electromagnetic forces of a small induction motor were calculated and compared with the magnetostriction data. It became clear that electromagnetic vibration was affected by the magnetostriction of steel. These results will be useful in the reduction of acoustic noise and the development of quiet motors. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 148(2): 8–13, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10338