bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser‐induced shock waves enhance sterilization of infected vascular prosthetic grafts
Authors: Nigri Giuseppe R. , Tsai Sheaumei , Kossodo Sylvie , Waterman Peter , Fungaloi Patrick , Hooper David C. , Doukas Apostolos G. , LaMuraglia Glenn M.
Published: October 2004

Background and Objective

Bacteria that cause infection of vascular prosthetic grafts produce an exopolysaccharide matrix known as biofilm. Growth in biofilms protects the bacteria from leukocytes, antibodies and antimicrobial drugs. Laser‐generated shock waves (SW) can disrupt biofilms and increase drug penetration. This study investigates the possibility of increasing antibiotic delivery and sterilization of vascular prosthetic graft.

Study Design/Materials and Methods

Strains of Staphylococcus epidermidis and S. aureus were isolated from infected prosthetic grafts obtained directly from patients. Dacron grafts were inoculated with the isolated bacteria, which were allowed to form adherent bacterial colonies. The colonized grafts underwent the following treatments: (a) antibiotic (vancomycin) alone; (b) antibiotic and SW (c) saline only; and (d) saline and SW. Six hours after treatment, the grafts were sonicated, the effluent was cultured and the colony forming units (CFU) were counted.

Results

CFU recovered from control grafts colonized by S. epidermidis were comparable: saline, 3.05 × 108 and saline + SW 3.31 × 108. The number of S. epidermidis CFU diminished to 7.61 × 106 after antibiotic treatment but the combined antibiotic + SW treatment synergistically decreased CFU number to 1.27 × 104 (P < 0.001). S. aureus showed a higher susceptibility to the antibiotic: 2.26 × 106 CFU; antibiotic + SW treatment also had an incremental effect: 8.27 × 104 CFU (P < 0.001).

Conclusions

This study demonstrates that laser‐generated shock waves have no effects alone, but can enhance the effectiveness of antibiotics against bacteria associated with prosthetic vascular graft biofilms, suggesting that this treatment may be of value as adjunctive therapy for prosthetic graft infections. Lasers Surg. Med. 29:448–454, 2001. © 2001 Wiley‐Liss, Inc.
Sense making: Trojan horse? Pandora's box?
Authors: Craig‐Lees Margaret
Published: October 2004

This article examines the concept of sense making and its application to management disciplines. The ideas of Karl Weick are discussed in terms of their contribution to these disciplines. Two contributions are identified—the validation of the “agent” and the impact of the adoption of the sense‐making construct on current research paradigms, theory, and methodology. The theme of this article is that sense making, whose origin lies in constructivism, has been interpreted and applied within the social‐constructionist worldview. The consequence of this action is a heightening of epistemological discussion in the social and management sciences. © 2001 John Wiley & Sons, Inc.
The influence of topic involvement on mail‐survey response behavior
Authors: Van Kenhove Patrick , Wijnen Katrien , De Wulf Kristof
Published: October 2004

In this study the influence of topic involvement on mail‐survey response rate and speed was experimentally investigated. The results show that response rates for topics that are generally considered as high involvement were higher than for topics that are generally considered as low involvement. However, the speed of response did not differ between the two levels of topic involvement. Moreover, in terms of response rates an interesting interaction effect was observed: For the high‐involvement topic, the response rate showed a further positive and significant correlation with the within‐topic level of involvement, but this was not the case for the low‐involvement topic. The implications of these findings to nonresponse bias in mail survey research are discussed. © 2002 Wiley Periodicals, Inc.
Response of metabolites with coupled spins to the STEAM sequence
Authors: Thompson Richard B. , Allen Peter S.
Published: October 2004

This article demonstrates that a numerical solution of the full quantum mechanical equations for all metabolites with coupled spins is an efficient and accurate means, first, of predicting the optimum STEAM sequence design for quantifying any target metabolite in brain, and, second, for providing the basis lineshapes and yields of these metabolites to facilitate their accurate quantification. Using as illustrations the weakly coupled AX3 system of lactate, the ABX aspartyl group of N‐acetylaspartate, which has only two strongly coupled spins, and the much larger strongly coupled AMNPQ glutamyl group of glutamate, the numerical solutions for the response to STEAM highlight the principal source of response variability, namely, the evolution of and transfer between zero quantum terms during the mixing time, TM. These highlights include the rapid oscillations of zero quantum terms due to the chemical shift difference of the coupled spins, the proliferation of oscillating zero order terms due to strong coupling, and the serendipitous smoothing of the response as the number of strongly coupled spins increases. The numerical solutions also demonstrate that the design of the selective 90° pulses is a far less critical factor in determining the response than was the case for the selective 180° pulses of the PRESS sequence (Thompson and Allen, Magn Reson Med 1999;41:1162–1169). The veracity of the method is demonstrated both in phantom solutions and in the parietal lobe of a normal human brain. Magn Reson Med 45:955–965, 2001. © 2001 Wiley‐Liss, Inc.
Application of 19F chemical shift imaging in studies of mice with orally administered 5‐fluorouracil
Authors: Kuribayashi Hideto , Doi Yoshihiro , Kanazawa Yoko
Published: October 2004

In vivo quantitative metabolic mapping is an ideal tool for pharmacokinetic studies. Oral 5‐fluorouracil (5‐FU) and its metabolites in mice were imaged simultaneously by the 19F fast spin echo (FSE) sequence using interleaved frequency selection at 9.4T. However, 5‐FU images in the small intestine have never been obtained regardless of concentration. The reason for the discrepancy between image intensity and concentration was T2. At a pH above 6, a dramatic decrease in T2 of a 19F 5‐FU signal in an aqueous solution was found; T2 was shorter in the small intestine (14 ms) than in the stomach (52 ms). The 19F CSI sequence in FID sampling mode was employed for detecting short T2 signals. With a 13‐min resolution time, the detection of the 5‐FU signals in the region of the small intestine (0.6 mmol/kg) was successful with a 5 × 5 mm2 in‐plane resolution. Furthermore, two signals separated by 2 ppm were clearly distinguishable, but failed to be separately detectable with the 19F FSE sequence. For quantitative simultaneous monitoring of 5‐FU and its metabolites of varying T2, the 19F CSI sequence in FID sampling mode was found to be superior to the 19F FSE sequence. Magn Reson Med 46:864–869, 2001. © 2001 Wiley‐Liss, Inc.
Modeling in vivo recovery of intracellular pH in muscle to provide a novel index of proton handling: Application to the diagnosis of mitochondrial myopathy
Authors: Chen J.T. , Taivassalo T. , Argov Z. , Arnold D.L.
Published: October 2004

Post‐exercise recovery of intracellular pH (pHi) assessed using phosphorus magnetic resonance spectroscopy has not been previously evaluated in its entirety due to its complex time‐course and missing data points resulting from a transient loss of inorganic phosphate signal. By considering the transition from exercise to recovery as a step function input, pHi recovery was modeled based on the creatine‐kinase equilibrium, and the entire pHi recovery was characterized by calculating the time required for pHi recovery (tpHrec). Applying this methodology, normal subjects showed a strong linear correlation between phosphocreatine (PCr) half‐time and tpHrec (r = 0.90, P < 0.001). In mitochondrial myopathy (MM) patients with weakness in the limb examined, 9/10 had faster pHi recovery relative to PCr recovery; wide normal ranges from a control group which included deconditioned subjects resulted in 7 of those 10 patients having otherwise normal recovery indices. Therefore, modeling pHi recovery allows characterization of the entire pHi recovery and detects altered proton handling in MM patients, including those with otherwise normal recovery indices. Magn Reson Med 46:870–878, 2001. © 2001 Wiley‐Liss, Inc.
Polyunsaturated fatty acids mapping by 1H MR‐chemical shift imaging
Authors: Lunati Ernesto , Farace Paolo , Nicolato Elena , Righetti Claudia , Marzola Pasquina , Sbarbati Andrea , Osculati Francesco
Published: October 2004

Parametric mapping of polyunsaturated fatty acids (PUFA) distribution in adipose tissues was obtained by 1H chemical shift imaging (CSI). A matrix of spectra, acquired with a CSI sequence having two spatial and one spectroscopic dimension, was processed with ad hoc algorithms. The protocol was applied to phantoms containing different lipids in which the degree of polyunsaturation was determined by high‐resolution nuclear magnetic resonance (NMR). High correlation (R2 = 0.998) between degrees of polyunsaturation given by our protocol and that measured by high‐resolution NMR was found. The thoracic region of rats was also examined. Parametric maps of the polyunsaturation degree were obtained for the brown adipose tissue and the white axillary fat: the first deposit was found more polyunsaturated than the second. Finally, in vivo mapping of the inguinal region of the rat was produced that allowed us to individuate PUFA‐rich areas in adipose tissue. This work demonstrates the feasibility of PUFA imaging in vivo. Magn Reson Med 46:879–883, 2001. © 2001 Wiley‐Liss, Inc.
A qualitative test of the balloon model for BOLD‐based MR signal changes at 3T
Authors: Mildner Toralf , Norris David G. , Schwarzbauer Christian , Wiggins Christopher J.
Published: October 2004

The aim of this study was to adapt the balloon model for BOLD‐based MR signal changes to a magnetic field strength of 3T and to examine its validity. The simultaneous measurement of BOLD and diffusion‐weighted BOLD responses was performed. The amplitude of the BOLD peak was found to be similar for all subjects when a short visual stimulus of 6 sec was used. The rise‐time to the BOLD peak and the shape and depth of the poststimulus undershoot varied significantly. A fit of the experimental BOLD responses was found to be possible by use of parameters within a reasonable physiological range. The relations between these parameters and their influence on the modeled BOLD responses is discussed. A prediction of the balloon model is the occurrence of a BOLD overshoot, i.e., a lag between the changes of the blood volume and the blood flow after the start of the stimulation. Experimental evidence for the existence of a BOLD overshoot is presented. Magn Reson Med 46:891–899, 2001. © 2001 Wiley‐Liss, Inc.
Dual contrast TrueFISP imaging for left ventricular segmentation
Authors: Merrifield Robert , Keegan Jennifer , Firmin David , Yang Guang‐Zhong
Published: October 2004

Based on varying tissue contrasts at different RF flip angles, a new TrueFISP imaging strategy for cardiac function measurement is presented. A single breath‐hold dual RF flip angle cine multi‐slice TrueFISP imaging sequence was implemented which provides a significant increase in signal contrast between blood and myocardium. The increase in image contrast combined with different characteristics in RF response facilitates the delineation of cardiovascular borders. Based on this imaging strategy it is demonstrated how a simple 2D histogram clustering algorithm can be used for the fully automatic segmentation of the left ventricular (LV) blood pool. The method is validated with data acquired from 10 asymptomatic subjects, and the results are shown to be comparable to that of manual delineation by experienced observers. Magn Reson Med 46:939–945, 2001. © 2001 Wiley‐Liss, Inc.
Two‐pedal ergometer for in vivo MRS studies of human calf muscles
Authors: Francescato Maria Pia , Cettolo Valentina
Published: October 2004

This article describes an ergometer that enables human subjects to exercise one or both limbs while 31P NMR spectra are obtained. Two independent pedals, equipped with position and force transducers, were mounted on the ergometer in order to calculate mechanical work performance. First, the effect of the magnetic field upon the signal coming from the transducers was investigated. Then the ergometer was tested by performing a series of steady‐state exercises of increasing intensity. Experimental data showed that actual mechanical power ranged from 1.5 ± 0.2 W to 11.0 ± 1.6 W, while the corresponding oxygen consumption increased from 0.28 ± 0.04 l/min at rest to 0.48 ± 0.10 l/min at the highest load, and the PCr/(PCr+Pi) ratio, as calculated from the 31P spectra, decreased from 0.94 ± 0.01 at rest to 0.73 ± 0.04. These results are consistent with the values reported in the literature and show that this ergometer, which is easy to use, is suitable for in vivo spectroscopy research when metabolic steady‐state conditions are required. Magn Reson Med 46:1000–1005, 2001. © 2001 Wiley‐Liss, Inc.
Temperature dosimetry using MR relaxation characteristics of poly(vinyl alcohol) cryogel (PVA‐C)
Authors: Lukas L.A. , Surry K.J.M. , Peters T.M.
Published: October 2004

Hyperthermic therapy is being used for a variety of medical treatments, such as tumor ablation and the enhancement of radiation therapy. Research in this area requires a tool to record the temperature distribution created by a heat source, similar to the dosimetry gels used in radiation therapy to record dose distribution. Poly(vinyl alcohol) cryogel (PVA‐C) is presented as a material capable of recording temperature distributions between 45 and 70°C, with less than a 1°C error. An approximately linear, positive relationship between MR relaxation times and applied temperature is demonstrated, with a maximum of 16.3 ms/°C change in T1 and 10.2 ms/°C in T2 for a typical PVA‐C gel. Applied heat reduces the amount of cross‐linking in PVA‐C, which is responsible for a predictable change in T1 and T2 times. Temperature distributions in PVA‐C volumes may be determined by matching MR relaxation times across the volumes to calibration values produced in samples subjected to known temperatures. Factors such as thermotolerance, perfusion effects, and thermal conductivity of PVA‐C are addressed for potentially extending this method to modeling thermal doses in tissue. Magn Reson Med 46:1006–1013, 2001. © 2001 Wiley‐Liss, Inc.
k‐Space weighted least‐squares algorithm for accurate and fast motion extraction from magnetic resonance navigator echoes
Authors: Nguyen Thanh D. , Wang Yi , Watts Richard , Mitchell Ian
Published: October 2004

Navigator echoes provide an effective method to monitor physiological motion, allowing motion artifacts to be suppressed by modifying the data acquisition accordingly. The displacement can be measured directly from the navigator phase using an algorithm suggested by Ahn and Cho (IEEE Trans Med Imaging 1987;MI‐6:32–36). Although computationally efficient, it is susceptible to noise, particularly contributions from points at the edges of k‐space. A k‐space weighted least‐squares (kLS) algorithm is proposed which fits a straight line to the motion‐induced phase shift. The linear fit is weighted strongly to high SNR points near the k‐space center and only weakly to the poor SNR points at the edges of k‐space. This algorithm was found to be as efficient as Ahn's algorithm but more robust against noise. Magn Reson Med 46:1037–1040, 2001. © 2001 Wiley‐Liss, Inc.
Recasting Intractable Policy Issues: The Wider Implications of The Netherlands Civil Aviation Controversy
Authors: van Eeten Michel J.G.
Published: October 2004

The explosive growth of civil aviation is among the most difficult issues in transportation policy, and nowhere are the fundamental economic and environmental challenges it poses more apparent than in airport expansion. Conventional policy analyses have ineffectively handled these problems, characterized by uncertainty, complexity, and polarization. Increasingly, policy analysts and public managers depend on stakeholder involvement to recast intractable issues into a more tractable format. This article describes a method that supports this recasting process through analysis of stakeholders' policy arguments; and in so doing contributes to the increasing literature on recasting intractable policy issues and to the recent discussion of Q‐methodology in the Journal of Policy Analysis and Management. The method is applied in a policy analysis of the controversy over the expansion of Amsterdam's Schiphol Airport. The analysis, which was under‐taken on behalf of the Dutch government and which has wider implications, leads to a new agenda for transportation policy by uncovering and addressing a fuller range of alternatives that move beyond the current polarization and allow the problem to be redefined more tractably. © 2001 by the Association for Public Policy Analysis and Management.
Packaging Support for Low‐Income Families: Policy Variation across the United States
Authors: Meyers Marcia K. , Gornick Janet C. , Peck Laura R.
Published: October 2004

This paper addresses a gap in state‐level comparative social policy research by analyzing policies that support low‐income families with children. Variation in state policy “packages” is measured by considering three characteristics of 11 social programs. Individual measures of policy are found to be weakly and inconsistently inter‐correlated at the state level, but when cluster analysis is used to analyze multiple dimensions simultaneously, five clusters or regime types are identified that have distinctive policy approaches. These range from the most minimal provisions, to conservative approaches emphasizing private responsibility, to integrated approaches that combine generous direct assistance with employment support and policies that enforce family responsibility. A comparison of a subset of programs at two points in time (1994 and 1998) suggests that states made substantial changes in cash assistance and taxation policies after the 1996 federal welfare reforms. The magnitude and direction of these changes remained consistent with the state clusters identified in 1994. © 2001 by the Association for Public Policy Analysis and Management.
Location‐Efficient Mortgages: Is the Rationale Sound?
Authors: Blackman Allen , Krupnick Alan
Published: October 2004

Location efficient mortgage (LEM) programs are an increasingly popular approach to combating urban
sprawl. LEMs allow families who want to live in densely populated, transit‐rich communities to obtain a
larger mortgage with a smaller down payment than traditional underwriting guidelines allow. LEMs are premised on
the proposition that homeowners in such “location‐efficient” areas can safely be allowed to
breach underwriting guidelines designed to prevent mortgage default because they have lower than average
automobile‐related transportation expenses and more income available for mortgage payments. This paper
employs records of more than 8000 FHA‐insured mortgages matched with data on various measures of location
efficiency to test this proposition. The results suggest that it does not hold and that LEMs—like other
low‐down‐payment mortgage programs—will raise mortgage default rates. This cost must be
weighed against any potential anti‐sprawl benefits LEMs may have. © 2001 by the Association for
Public Policy Analysis and Management.
Assessing OSHA Performance: New Evidence from the Construction Industry
Authors: Weil David
Published: October 2004

The determinants of OSHA performance can be examined by breaking the regulatory process into three elements
relating to enforcement, compliance behavior, and the adequacy of standards in addressing safety outcomes. This
paper develops and applies this framework to the U.S. construction industry during the period 1987 to 1993.
Enforcement activity among the firms in the sample was substantial, with firms facing a high probability of
annual inspection. But, despite this significant enforcement effort, inspections have a modest effect on firm
compliance with OSHA standards. Finally, the health and safety standards cited most frequently diverge from the
major sources of fatalities and injuries on construction projects. These results suggest that historic
enforcement policies toward construction make less sense as OSHA moves into its fourth decade of operation. More
generally, the paper illustrates the problem of focusing enforcement resources on large, high‐profile
companies even though they often are not the major source of regulatory problems in an established area of
public policy intervention. © 2001 by the Association for Public Policy Analysis and Management.
Moving Up, Moving Out, or Going Nowhere? A Study of the Employment Patterns of Young Women and the Implications for Welfare Mothers
Authors: Pavetti LaDonna , Acs Gregory
Published: October 2004

Conventional wisdom holds that women on welfare will be better off in the long run if they take a job, even
if it means initially having less money to spend on their and their children's needs. Underlying this
thinking is the belief that women who take low‐paying jobs will eventually move up to higher paying jobs
either with their current employer or by changing employers. This paper examines the employment transitions of
young women focusing on the likelihood that women who turn to the welfare system for support will make the
transition from low‐paying to high‐paying jobs. The data are drawn from the National Longitudinal
Survey of Youth (NLSY). Based on the experiences of women who never received welfare, an estimated
one‐quarter of young women who received welfare could be firmly established in jobs paying more than
$9.50 an hour by ages 26 and 27. An additional 40 percent would work steadily but in low‐paying
jobs, and more than one‐third would work only sporadically. © 2001 by the Association for Public
Policy Analysis and Management.
Novel fixed‐site–carrier polyvinylamine membrane for carbon dioxide capture
Authors: Kim Taek‐Joong , Li Baoan , Hägg May‐Britt
Published: October 2004

Fixed‐site–carrier membranes were prepared for the facilitated transport of CO2 by casting polyvinylamine (PVAm) on various supports, such as poly(ether sulfone) (PES), polyacrylonitrile (PAN), cellulose acetate (CA), and polysulfone (PSO). The cast PVAm on the support was crosslinked by various methods with glutaraldehyde, hydrochloric acid, sulfuric acid, and ammonium fluoride. Among the membranes tested, the PVAm cast on polysulfone and crosslinked by ammonium fluoride showed the highest selectivity of CO2 over CH4 (>1000). The permeance of CO2 was then measured to be 0.014 m3 (STP)/(m2 bar h) for a 20 μm thick membrane. The effect of the molecular weight of PVAm and feed pressure on the permeance was also investigated. The selectivity increased remarkably with increasing molecular weight and decreased slightly with increased pressure in the range of 1 to 4 bar. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4326–4336, 2004
How pediatricians manage asthma in Thailand
Authors: Vichyanond Pakit , Hatchaleelaha Sombat , Jintavorn Viravich , Kerdsomnuig Sirikul
Published: October 2004

Currently, there is no existing information regarding prescribing practices for the management of childhood asthma among pediatricians in Thailand. In order to evaluate the management standards for childhood asthma in Thailand, 400 self‐administered questionnaires were randomly mailed to nonacademic pediatricians throughout Thailand, asking questions about their preferences in the treatment of childhood asthma.

One hundred and seventy‐four of these 400 questionnaires were returned (a response rate of 43.5%). Data were analyzed using the descriptive module of the Epi‐info 6 program. For acute asthma, 17% of the respondents used objective measures such as peak flow meters in assessing asthma severity and severity of acute asthma attacks. The drug of first choice for treating acute attacks was a nebulized beta‐agonist q 20 min (81.8%). Although 93% indicated that they had used theophylline for treating acute attacks, most would reserve the drug for patients with severe symptoms. Corticosteroids were reserved for those with severe attacks (91.7% both for clinic and for in‐hospital settings). Hydrocortisone was the most preferred corticosteroid preparation (59.8%). Ninety‐seven percent used antibiotics in treating acute asthma, but only with appropriate indications. For chronic asthma, a strong preference was observed for oral beta‐agonists as the bronchodilator of choice (88%). For moderately severe asthmatics, theophylline was still preferred by 41% of the responders. Among prophylactic agents, ketotifen was the most favored drug (90.4%), whereas inhaled steroids and cromolyn were chosen by 9.6% and 2.4%, respectively. Eighty‐five percent indicated that they would prescribe prophylactic agents for 1 year or less. Forty‐two percent never considered allergy evaluation as a part of a workup for childhood asthma.

Certain prescribing practices of childhood asthma management in Thailand were observed among pediatricians, i.e., 1) low frequency of using objective measures in assessing asthma severity among pediatricians; 2) frequent use of theophylline and antibiotics in the treatment of acute asthma; 3) late introduction of corticosteroids in treating acute asthma; 4) preference for oral bronchodilators; and 5) preference of ketotifen as the prophylactic drug of choice. This survey provides baseline data and will aid in the evaluation of management guidelines for childhood asthma in Thailand. Pediatr Pulmonol. 2001; 32:109–114. © 2001 Wiley‐Liss, Inc.
Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: Results of a phase I multi‐center study
Authors: Noone Peadar G. , Hamblett Nicole , Accurso Frank , Aitken Moira L. , Boyle Michael , Dovey Mark , Gibson Ron , Johnson Craig , Kellerman Don , Konstan Michael W. , Milgram Laura , Mundahl Jean , Retsch‐Bogort George , Rodman David , Williams‐Warren Judy , Wilmott Robert W. , Zeitlin Pam , Ramsey Bonnie
Published: October 2004

Cystic fibrosis (CF) is characterized by defective cystic fibrosis transmembrane regulator (CFTR) expression and function, associated with abnormal ion transport and mucociliary clearance, and clinical lung disease. Triphosphate nucleotides such as uridine‐5′‐triphosphate (UTP) and INS 365, may be useful for CF through actions, mediated via P2Y2 extracellular receptors, on chloride and liquid secretion, and ciliary beat frequency. INS 365 may offer chemical stability advantages over UTP. In a randomized, double‐blind, multicenter phase I study, we studied the safety and maximally tolerated dose of escalating, single doses of aerosolized INS 365, in adult and pediatric patients with mild to moderate CF lung disease (FEV1 ≥ 45% predicted). In four successive dose cohorts of adult patients (n = 12 per cohort, age ≥ 18 years) and four successive pediatric dose cohorts (n = 12 per cohort, age 5–12 years), patients were randomized 3:1 active/placebo (0.9% saline) to evaluate doses of 20, 40, 80, and 100 mg INS 365 delivered by nebulizer (Pari Star™). Sputum was collected pre‐ and post‐dosing to obtain preliminary results on clinical efficacy. After each dose cohort, a Data Safety Monitoring Committee (DSMC) reviewed the data.

Forty‐eight adult and 36 pediatric patients completed the protocol (up to 100 mg for adults, 80 mg for pediatric patients). The predominant adverse events were cough, wheezing, chest tightness, and a decrease in FEV1 (occurring in 8/48 adults, and 5/36 pediatric patients), which occurred predominantly in the 80‐mg and 100‐mg dose cohorts. Though a few adult patients had a tendency to increase sputum production, there was little consistent effect noted on sputum production in this acute, single‐dose study.

The data suggest that aerosolized INS 365 is safe when delivered at single doses of up to 40 mg in adults and children with CF, but that higher doses are unlikely to be tolerated. Pediatr Pulmonol. 2001; 32:122–128. © 2001 Wiley‐Liss, Inc.
Canine prostate induces new bone formation in mouse calvaria: A model of osteoinduction by prostate tissue
Authors: LeRoy Bruce E. , Bahnson Robert R. , Rosol Thomas J.
Published: October 2004

BACKGROUND

Osteoblastic metastases are common in patients with advanced prostate cancer. The pathophysiology of the new bone formation at metastatic sites is not currently known, but it is hypothesized that growth factors secreted by the prostate may be involved. Unfortunately, most rodent models of prostate cancer with metastasis to bone are osteolytic and not osteoblastic. Significant osteolysis by tumor cells at metastatic sites may also lead to fractures or bone instability. Misinterpretation of new periosteal bone due to bone instability as tumor‐cell osteoinduction is another disadvantage of the osteolytic models. To circumvent these problems, we have developed a model system of new bone formation in the calvaria of nude mice stimulated by normal canine prostate tissue.

METHODS

Collagenase‐digested normal prostate tissue was implanted adjacent to the calvaria of nude mice. Calvaria were examined at 2 weeks post‐implantation for changes in the bone microenvironment by histology, calcein uptake at sites of bone mineralization, and tartrate‐resistant acid phosphatase staining for osteoclasts.

RESULTS

The prostate tissue remained viable and induced abundant new woven bone formation on the adjacent periosteal surface. In some cases new bone formation also was induced on the distant or concave calvarial periosteum. The new bone stained intensely with calcein, which demonstrated mineralization of the bone matrix. The new bone formation on prostate‐implanted calvaria significantly increased (1.7‐fold) the thickness of the calvaria compared with control calvaria. New bone formation was not induced in calvaria of mice implanted with normal canine kidney, urinary bladder, spleen, or skeletal muscle tissue, or mice with surgically‐induced disruption of the periosteum. Osteoclast numbers in the medullary spaces and periosteum of calvaria were mildly increased (61%) in mice with implanted prostate tissue.

CONCLUSIONS

This animal model will be useful for investigating the roles of prostate‐derived growth factors on new bone formation in vivo. Prostate 50: 104–111, 2002. © 2002 Wiley‐Liss, Inc.
Refined mapping of allele loss at chromosome 10q23‐26 in prostate cancer
Authors: Leube Barbara , Drechsler Matthias , Mühlmann Kristina , Schäfer Reinhold , Schulz Wolfgang A. , Santourlidis Simon , Anastasiadis Aristoteles , Ackermann Rolf , Visakorpi Tapio , Müller Wolfram , Royer‐Pokora Brigitte
Published: October 2004

BACKGROUND

Allele loss of at least two segments in 10q, one mapping to the PTEN gene and one more distal were described in prostate cancer, with loss more frequent in advanced prostate cancer.

METHODS

A 63 cM region from 10q23 to q26 was studied for allele loss (LOH) in 59 prostate cancer samples using a dense map of microsatellite markers.

RESULTS

LOH of at least one marker in 10q was observed in 13/59 tumors. LOH increased with grade and stage. Detailed deletion mapping identified three regions of allele loss. The first region mapped to the site of the PTEN gene, the second is defined by loss of one marker, D10S1692, in one tumor, and the third is defined between markers D10S1757 and D10S587, including DMBT, with a subregion of approximately 1.2 Mb mapping between markers D10S209 and D10S1679, lost in one tumor.

CONCLUSIONS

LOH at the PTEN gene is frequent but mutations in the remaining allele were not detected by SSCP‐screening. There may be more than two tumor suppressor (TS) genes mapping more distal of PTEN. The site for these putative TS genes can now be mapped with a dense set of precisely localized markers in a larger series of advanced tumors. Prostate 50: 135–144, 2002. © 2002 Wiley‐Liss, Inc.
Human prostatic carcinoma cells produce an increase in the synthesis of interleukin‐6 by human osteoblasts
Authors: García‐Moreno Carmen , Méndez‐Dávila Cioly , de la Piedra Concepción , Castro‐Errecaborde Nilda Adriana , Traba Maria Luisa
Published: October 2004

BACKGROUND

The aim of this work was to evaluate the effect produced by conditioned medium from human prostatic carcinoma cell (PC‐3) culture on human osteoblast (HOB) interleukin 6 (IL‐6) synthesis.

METHODS

PC‐3 cells were cultured in Ham's F12K medium with 10% fetal calf serum (FCS) up to confluence. Medium was changed by Dulbecco modified Eagle medium (DMEM)/F12K (1:1) with 0.1% bovine serum albumin. Cells were cultured for 24 hr, and medium (PC‐3‐CM) was collected. HOBs were cultured up to confluence, and after 48 hr without FCS, medium was removed and PC‐3‐CM was added to the wells. After 24 hr, supernatant was collected for the determination of IL‐6. In another experiment, HOBs were cultured up to confluence in Petri dishes, and after 48 hr without FCS, PC‐3‐CM or DMEM/F12K (1:1) was added. After different periods of time, medium was removed, and total RNA was extracted. IL‐6 mRNA was quantified using reverse transcription polymerase chain reaction.

RESULTS

PC‐3‐CM significantly enhanced IL‐6 secretion into HOB culture supernatants (between 1,812% and 372%, depending on the osteoblastic line) with respect to HOBs cultured in DMEM/F12K. PC‐3‐CM also produced an increase in IL‐6 mRNA levels in HOBs.

CONCLUSIONS

Prostate carcinoma cells (PC‐3) produce a factor or factors that enhance the synthesis and release of IL‐6, a known activator of bone resorption. Prostate 50: 241–246, 2002. © Wiley‐Liss, Inc.
Establishment and characterization of androgen‐independent human prostate cancer LNCaP cell model
Authors: Igawa Tsukasa , Lin Fen‐Fen , Lee Ming‐Shyue , Karan Dev , Batra Surinder K. , Lin Ming‐Fong
Published: October 2004

BACKGROUND

The acquisition of an androgen‐independent phenotype is the most serious issue of prostate cancer treatment. Although several experimental cell models have been reported for studying androgen independence, they have limited applications related to hormone‐refractory prostate cancer. To investigate the molecular mechanism of androgen‐independent growth of prostate cancer, we established a useful LNCaP cell model that resembles the clinical scenario of hormone‐refractory prostate cancer.

METHODS

Androgen‐sensitive LNCaP parental cells were continuously maintained in a regular cell‐culture medium, that is, phenol red–positive RPMI 1640 medium supplemented with 5% fetal bovine serum and 1% glutamine. Upon passage, the androgen responsiveness of those cells decreased, to a level lower than that of parental cells. We examined the growth properties and androgen responsiveness of these different LNCaP cells in vitro and in vivo. Cytogenetic characteristics and expression of androgen receptors (ARs) and prostate‐specific antigen (PSA) were determined.

RESULTS

Upon continuous passage, the biological behavior of parental C‐33 cells (passage number less than 33) was altered. C‐81 cells (passage number higher than 81) clearly exhibited more aggressive growth and lower androgen responsiveness than C‐33 and C‐51 cells (passage number between 35 and 80) in vitro and in vivo. Nevertheless, all these cells expressed a similar level of functional AR protein as well as a similar genetic profile. Moreover, in a steroid‐reduced culture condition, C‐81 cells secreted a higher level of PSA than C‐33 cells.

CONCLUSIONS

Our LNCaP cell model closely recapitulates the progression of human prostate cancer from the androgen‐responsive to the hormone‐refractory state under the androgen nondeprived condition. This cell model may provide the opportunity to understand the molecular mechanisms associated with the acquisition of androgen independence during human prostate cancer progression. Prostate 50: 222–235, 2002. © 2002 Wiley‐Liss, Inc.
Clinical stage T1c prostate cancer: Pathologic outcomes following radical prostatectomy in black and white men
Authors: Eastham James A. , Carver Brett , Katz Jared , Kattan Michael W.
Published: October 2004

BACKGROUND

The incidence of prostate cancer in black men is 50% to 70% higher than among age‐matched white men. Black men have a twofold higher mortality rate and overall tend to have higher serum prostate‐specific antigen (PSA) levels than white men. To determine whether racial differences exist in men whose prostate cancer was diagnosed based solely on an elevated serum PSA level, we compared clinical and pathologic features in black and white men undergoing radical prostatectomy (RP) for clinical stage T1c prostate cancer.

METHODS

We used a prospectively collected database to identify all men undergoing RP for clinical T1c prostate cancer between July 1995 and October 2000. A total of 129 consecutive men (56 black men and 73 white men) were compared for age at diagnosis, serum PSA level, biopsy Gleason score, pathologic stage, RP specimen Gleason score, incidence of lymph node metastasis, and incidence of positive surgical margins.

RESULTS

Statistically significant differences were not found by race in patients' ages, serum PSA levels, biopsy Gleason score, pathologic stage, incidence of lymph node metastases, or incidence of positive surgical margins. The RP specimen Gleason score was more heterogeneous in black men than white men (P = 0.02).

CONCLUSIONS

Racial differences in the incidence and mortality rate of prostate cancer are well known, but differences in the clinical and pathologic features between black and white men with prostate cancer identified solely based on an elevated serum PSA level with negative results on digital rectal examination (clinical stage T1c ) have been poorly studied. Our results suggest that men with clinical stage T1c prostate cancer have similar clinical and pathologic findings regardless of race. These results suggest that early‐detection programs using serum PSA testing for prostate cancer in black men potentially can result in improvements in prostate cancer outcomes in this high‐risk group. Prostate 50: 236–240, 2002. © 2002 Wiley‐Liss, Inc.
Similar rates of exponential decrease in serum concentrations of free prostate‐specific antigen (PSA), PSA complexed to alpha‐1‐antichymotrypsin, and human glandular kallikrein 2 (hK2) in prostate cancer patients treated with GnRH‐analogues
Authors: Björk Thomas , Schalken Jack , Wittjes Wim , Ljungberg Bengt , Lilja Hans
Published: October 2004

BACKGROUND

Our recently reported finding of rapid bi‐exponential elimination of free prostate‐specific antigen (PSA) after radical retropubic prostatectomy in patients with moderately elevated PSA levels, which contrasted a very slow, linear elimination of PSA complexed to alpha‐1‐antichymotrypsin (ACT), prompted us to study whether these elimination rates were applicable for patients selected for castration treatment with very high pretreatment concentrations of PSA in serum. In addition, serum concentrations of hK2, the activator of proPSA, were measured.

METHODS

Pretreatment serum was obtained from 21 previously untreated prostate cancer patients due for hormonal treatment with a GnRH‐analog. Samples were also collected during treatment up to a minimum of 24 weeks at 2‐week intervals and analyzed with immunofluorometric assays for free PSA (PSA‐F), PSA complexed to alpha‐1‐antichymotrypsin (PSA‐ACT), total PSA (PSA‐T), and human kallikrein 2 (hK2). For pharmaco‐kinetic analysis the serum concentrations of hK2 and PSA forms for each patient were plotted against time both before and after logarithmic transformation and the half‐lives were calculated as ln2/k.

RESULTS

Median pretreatment serum concentrations were 322 ng/ml (range, 1.9‐2210) for PSA‐T, 27.8 ng/ml (range, 1.14–259) for PSA‐F, and 207 ng/ml (range, 0.8–2080) for PSA‐ACT. All patients had castrate levels of serum testosterone (<2.5 nmol/l) in less than 21 days after initiation of GnRH‐analog treatment. It was possible to evaluate data from 19/21 patients which showed an exponential decrease of all PSA concentrations in serum, with mean half‐lives of 12.9 days (range, 7.3–30) for PSA‐T, 15.5 days (range, 7.7–37.5) for PSA‐F, and 12.3 days (range, 6.6–30) for PSA‐ACT. Median pretreatment percent free PSA (PSA‐F/PSA‐T) was 12% compared to 18% at nadir. The median pretreatment level of hK2 was 3.5 ng/ml (range, 0.29–30.3). There was an exponential decrease in hK2 concentrations in serum after initiation of hormonal treatment with a mean half‐life of 18.7 days (range, 7.5–37.5).

CONCLUSIONS

For the majority of patients with hormonally treated prostate cancer the serum concentrations of PSA‐T, PSA‐F, PSA‐ACT, and hK2 decreased slowly in parallel and mono‐exponentially after initiation of treatment. Mean half‐lives were between 12 and 19 days. Prostate 47:14–20, 2001. © 2001 Wiley‐Liss, Inc.
Widely used prostate carcinoma cell lines share common origins
Authors: van Bokhoven Adrie , Varella‐Garcia Marileila , Korch Christopher , Hessels Daphne , Miller Gary J.
Published: October 2004

BACKGROUND

Cross‐contamination is a persistent problem in the establishment and maintenance of mammalian cell lines. The observation that the cell lines PC‐3, ALVA‐31, and PPC‐1 all have a homozygous deletion of the α‐catenin gene prompted us to investigate the uniqueness of these and several other widely used prostate carcinoma cell lines.

METHODS

The genetic backgrounds of the putative human prostate cell lines (ALVA‐31, ALVA‐41, BPH‐1, DU 145, JCA‐1, LAPC‐4, LNCaP, NCI‐H660, ND‐1, PC‐3, PC‐3MM2, PC‐346C, PPC‐1, and TSU‐Pr1) were analyzed by cytogenetics, mutation analysis, and DNA profiling.

RESULTS

Similarities between several groups of cell lines were found. ALVA‐31, ALVA‐41, PC‐3, PC‐3MM2, and PPC‐1 all have a deletion of a C in codon 138 of the p53 gene and show almost identical DNA profiles. The ND‐1 cell line has two p53 mutations that are identical to the mutations found in DU 145. These two cell lines also share a high number of structural chromosomal abnormalities and nearly identical DNA profiles. The cell lines TSU‐Pr1 and JCA‐1 share an identical p53 mutation in exon 5 and identical DNA profiles.

CONCLUSIONS

Several widely used prostate carcinoma cell lines apparently have identities in common. The knowledge that some of these cell lines are derivatives of one another prompts re‐evaluation of previously obtained results. Prostate 47:36–51, 2001. © 2001 Wiley‐Liss, Inc.
High‐grade prostate cancer is associated with low serum testosterone levels
Authors: Schatzl Georg , Madersbacher Stephan , Thurridl Thomas , Waldmüller Julia , Kramer Gero , Haitel Andrea , Marberger Michael
Published: October 2004

BACKGROUND

The aim of this study was to assess whether low serum testosterone levels in men with newly diagnosed prostate cancer have an association to the endocrine status, prostate‐specific antigen (PSA) levels, Gleason score, and androgen receptor expression.

METHODS

Besides a full clinical work‐up, the following hormones were quantified in men with newly diagnosed prostate cancer by serum analysis: total testosterone, human luteinising hormone (hLH), human follicle stimulating hormone (hFSH), estradiol, and dehydroepiandrostendione (DHEA). In a subgroup of men, androgen receptor expression was determined immunohistochemically.

RESULTS

One hundred and fifty six patients (65.7 ± 8.5 yrs) with a mean PSA of 29.8 ng/ml (median: 7.4 ng/ml) were analysed. Fifty‐two patients (33%) had a partial androgen deficiency (serum testosterone <3.0 ng/ml). These men had lower hLH (3.3 vs. 5.9 mIU/ml), hFSH (6.2 vs. 8.4 mIU/ml), and estradiol (18.8 vs. 29.1 pg/ml) serum levels. Mean Gleason score was higher (7.4 vs. 6.2) in men with a low serum testosterone, PSA‐levels were lower (25.3 vs. 31.9 ng/ml). Mean testosterone levels decreased from 4.1 ± 1.7 ng/ml in patients with Gleason scores ≤ 5 to 2.8 ± 2.7 ng/ml with Gleason scores ≥ 8. Androgen receptor expression was higher in patients with low serum testosterone.

CONCLUSIONS

Patients with high Gleason score prostate cancer have lower testosterone and estradiol serum levels. The fact that gonadotropins were lower in parallel suggests a tumor‐mediated suppression of the hypothalamic‐pituitary‐gonadal hormone axis particularly in men with high Gleason score tumours. Prostate 47:52–58, 2001. © 2001 Wiley‐Liss, Inc.
Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences*
Authors: Collette Laurence , Studer Urs E. , Schröder Fritz H. , Denis Louis J. , Sylvester Richard J.
Published: October 2004

BACKGROUND

The meta‐analysis of maximal androgen blockade (MAB) concluded that there is no survival advantage of MAB over castration alone. However, the results from the largest trials yield conflicting results.

METHODS

The design and results of three trials were examined.

RESULTS

Most studies were planned to detect an over‐optimistic difference in survival and immature data were published. The survival curves show that statistical assumptions are not fulfilled. Excluding from the meta‐analysis all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castration.

CONCLUSIONS

Trials of MAB should be planned to detect differences of no more than 5–10% in median survival. The analyses should only be carried out on mature data and should take into account the possibility of a negative impact on survival due to disease flare if no anti‐androgen has been given initially with an LH‐RH agonist. Prostate 48:29–39, 2001. © 2001 Wiley‐Liss, Inc.
Endogenous nitric oxide‐mediated relaxation and nitrinergic innervation in the rabbit prostate: The changes with aging
Authors: Aikawa Ken , Yokota Takashi , Okamura Hiro‐oki , Yamaguchi Osamu
Published: October 2004

BACKGROUND

Nitric oxide (NO) plays the key role in the non‐adrenergic non‐cholinergic (NANC) nerve‐mediated relaxation of prostate. We tried to determine whether nitrinergic innervation of the prostate is reduced with aging, and whether a reduction of this innervation alters the relaxant properties of prostatic tissue.

METHODS

The prostate isolated from young rabbits at the age of 3 months and aged rabbits at the age of 24 months was used. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of prostate. Nitrinergic nerves were identified histochemically by the presence of NADPH diaphorase reactivity.

RESULTS

The prostate weighed 0.34 ± 0.06 g in the young and 0.78 ± 0.13 g in the aged (P < 0.01). Electrical stimulation caused frequency‐dependent relaxation that was inhibited by N‐nitro‐L‐arginine and increased by L‐arginine. Maximum relaxant rates of noradrenaline‐induced tone were 41.3 ± 1.8% and 22.7 ± 0.6% in the young and the aged (P < 0.01), respectively. Exogenous NO caused concentration‐dependent relaxation of the prostate. Both relaxation induced by electrical stimulation and exogenous NO were inhibited by LY83583 (a guanylate cyclase inhibitor). In all specimens, NADPH diaphorase activity was observed in the smooth muscle layer of the prostatic stroma and capsule. However, NADPH diaphorase positive nerves were significantly less in the aged than in the young (P < 0.01).

CONCLUSIONS

As a result of these findings, it is suggested that both NO‐mediated relaxation and nitrinergic innervation are reduced with aging in this animal model. Prostate 48:40–46, 2001. © 2001 Wiley‐Liss, Inc.
Brief communication: Uniform ultimate boundedness of a fuzzy logic controlled industrial robot
Authors: Chen Wuwei , Mills James K. , Chu Jiaxin , Sun Dong
Published: October 2004

This article addresses the proof of uniform ultimate boundedness of a fuzzy logic controller plus a computed torque control scheme applied to trajectory tracking control of robotic manipulators. Further improvement of the performance of this fuzzy logic control scheme is achieved through automatic tuning of a weight parameter α leading to a self‐tuning fuzzy logic compensator. Experimental results demonstrate the effectiveness of the computed torque and fuzzy compensation scheme, as well as the self‐tuning fuzzy logic controller, applied to an industrial CRS Robotics Corporation A460 robot during a trajectory tracking task. © 2001 John Wiley & Sons, Inc.