bluuebunny/crossref_metadata_2025 huggingface dataset:
Interplay of Politics and Law to Promote Health
Authors: Bezruchka Stephen , Namekata Tsukasa , Sistrom Maria Gilson
Published: February 2008

The health situation in Japan after World War II was extremely poor. However, in less than 35 years the country’s life expectancy was the highest in the world. Japan’s continuing health gains are linked to policies established at the end of World War II by the Allied occupation force that established a democratic government. The Confucian principles that existed in Japan long before the occupation but were preempted during the war years were reestablished after the war, facilitating subsequent health improvements. Japan’s good health status today is not primarily the result of individual health behaviors or the country’s health care system; rather, it is the result of the continuing economic equality that is the legacy of dismantling the prewar hierarchy.
Physical Education and Academic Achievement in Elementary School: Data From the Early Childhood Longitudinal Study
Authors: Carlson Susan A. , Fulton Janet E. , Lee Sarah M. , Maynard L. Michele , Brown David R. , Kohl Harold W. , Dietz William H.
Published: February 2008

Objectives. We examined the association between time spent in physical education and academic achievement in a longitudinal study of students in kindergarten through fifth grade.

Methods. We used data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998 to 1999, which employed a multistage probability design to select a nationally representative sample of students in kindergarten (analytic sample = 5316). Time spent in physical education (minutes per week) was collected from classroom teachers, and academic achievement (mathematics and reading) was scored on an item response theory scale.

Results. A small but significant benefit for academic achievement in mathematics and reading was observed for girls enrolled in higher amounts (70–300 minutes per week) of physical education (referent: 0–35 minutes per week). Higher amounts of physical education were not positively or negatively associated with academic achievement among boys.

Conclusions. Among girls, higher amounts of physical education may be associated with an academic benefit. Physical education did not appear to negatively affect academic achievement in elementary school students. Concerns about adverse effects on achievement may not be legitimate reasons to limit physical education programs.
Secondhand Smoke Exposure Among Women and Children: Evidence From 31 Countries
Authors: Wipfli Heather , Avila-Tang Erika , Navas-Acien Ana , Kim Sungroul , Onicescu Georgiana , Yuan Jie , Breysse Patrick , Samet Jonathan M.
Published: February 2008

Objectives. We sought to describe the range of exposure to secondhand smoke (SHS) among women and children living with smokers around the world and generate locally relevant data to motivate the development of tobacco control policies and interventions in developing countries.

Methods. In 2006, we conducted a cross-sectional exposure survey to measure air nicotine concentrations in households and hair nicotine concentrations among nonsmoking women and children in convenience samples of 40 households in 31 countries.

Results. Median air nicotine concentration was 17 times higher in households with smokers (0.18 μg/m3) compared with households without smokers (0.01 μg/m3). Air nicotine and hair nicotine concentrations in women and children increased with the number of smokers in the household. The dose–response relationship was steeper among children. Air nicotine concentrations increased an estimated 12.9 times (95% confidence interval=9.4, 17.6) in households allowing smoking inside compared with those prohibiting smoking inside.

Conclusions. Our results indicate that women and children living with smokers are at increased risk of premature death and disease from exposure to SHS. Interventions to protect women and children from household SHS need to be strengthened.
Bacillus licheniformis proteases as high value added products from fermentation of wastewater sludge: pre-treatment of sludge to increase the performance of the process
Authors: Drouin M. , Lai C. K. , Tyagi R. D. , Surampalli R. Y.
Published: February 2008

Wastewater sludge is a complex raw material that can support growth and protease production by Bacillus licheniformis. In this study, sludge was treated by different thermo-alkaline pre-treatment methods and subjected to Bacillus licheniformis fermentation in bench scale fermentors under controlled conditions. Thermo-alkaline treatment was found to be an effective pre-treatment process in order to enhance the proteolytic activity. Among the different pre-treated sludges tested, a mixture of raw and hydrolysed sludge caused an increase of 15% in the protease activity, as compared to the untreated sludge. The benefit of hydrolysis has been attributed to a better oxygen transfer due to decrease in media viscosity and to an increase in nutrient availability. Foam formation was a major concern during fermentation with hydrolysed sludge. The studies showed that addition of a chemical anti-foaming agent (polypropylene glycol) during fermentation to control foam could negatively influence the protease production by increasing the viscosity of sludge.
The role of sludge conditioning and dewatering in the fate of nonylphenol in sludge-amended soils
Authors: Kouloumbos V. N. , Schäffer A. , Corvini P. F.-X.
Published: February 2008

One of the main concerns associated with the recycling of biosolids to arable land is their contamination by organic pollutants, like endocrine disruptors. Conditioning and dewatering are usually the last steps of the sewage sludge treatment, before its further utilization. The choice of the specific conditioning/dewatering method may have an effect, not only on the amount of residues in the biosolids, but also on the fate of these compounds in amended soils. Anaerobically digested wastewater sludge was conditioned at lab-scale by means of physical and chemical methods and subsequently dewatered by centrifugation. The produced biosolids plus non-conditioned and non-dewatered sludges were amended separately to soil and spiked with 14C radiolabelled single isomer of nonylphenol. The persistence and leaching potential of nonylphenol after an incubation period of three months were correlated to the sludge treatment method. In comparison to non-conditioned sludge, 54% and 72% higher amount of pollutant residues were extractable when freeze-thawed and limed sludge, respectively, were used. Conditioning of sludge with cationic polymer decreased the leaching potential of nonylphenol in sludge-amended soils, while liming increased it. Fractions of the model compound recovered as extractable and bound residues were analyzed in order to interpret nonylphenol fate.
Design criteria for semi-central sanitation with low pressure network and membrane bioreactor–the ENREM project
Authors: Gnirss Regina , Luedicke Carsten , Vocks Martin , Lesjean Boris
Published: February 2008

MBR-technology is able to fulfil similar or even higher standard for nutrients removal than conventional activated sludge processes. This paper presents the optimisation of the membrane bioreactor technology, together with a low pressure sewer, to equip a remote and yet unsewered area of Berlin requiring high quality wastewater treatment. The hydraulic flow pattern of the entire system has to be studied carefully due to the small collection system (no time delay between wastewater discharge and treatment to minimise the daily profile). The pollutant concentrations in the wastewater exhibit also stronger variations. In order to flatten out the hydraulic and load profile, and therefore to reduce the size of the biological reactor and the membrane surface, a buffer tank was installed before the MBR-plant. A full analysis of the influent hydraulic flow and wastewater characterisation is provided for the demonstration MBR-plant.
Optimal sludge retention time for a bench scale MBR treating municipal sewage
Authors: Pollice A. , Laera G. , Saturno D. , Giordano C. , Sandulli R.
Published: February 2008

Membrane bioreactors allow for higher sludge concentrations and improved degradation efficiencies with respect to conventional activated sludge. However, in the current practice these systems are often operated under sub-optimal conditions, since so far no precise indications have yet been issued on the optimal operating conditions of MBR for municipal wastewater treatment. This paper reports some results of four years of operation of a bench scale membrane bioreactor where steady state conditions were investigated under different sludge retention times. The whole experimental campaign was oriented towards the investigation of optimal process conditions in terms of COD removal and nitrification, biomass activity and growth, and sludge characteristics. The membrane bioreactor treated real municipal sewage, and four different sludge ages were tested (20, 40, 60, and 80 days) and compared with previous data on complete sludge retention. The results showed that the the biology of the system, as assessed by the oxygen uptake rate, is less affected than the sludge physical parameters. In particular, although the growth yield was observed to dramatically drop for SRT higher than 80 days, the biological activity was maintained under all the tested conditions. These considerations suggest that high SRT are convenient in terms of limited excess sludge production without losses of the treatment capacity. Physical characteristics such as the viscosity and the filterability appear to be negatively affected by prolonged sludge retention times, but their values remain within the ranges normally reported for conventional activated sludge.
Adding realism to simulated sensors and actuators
Authors: Rosen C. , Rieger L. , Jeppsson U. , Vanrolleghem P. A.
Published: February 2008

In this paper, we propose a statistical theoretical framework for incorporation of sensor and actuator faults in dynamic simulations of wastewater treatment operation. Sensor and actuator faults and failures are often neglected in simulations for control strategy development and testing, although it is well known that they represent a significant obstacle for realising control at full-scale facilities. The framework for incorporating faults and failures is based on Markov chains and displays the appealing property of easy transition of sensor and actuator history into a model for fault generation. The paper briefly describes Markov theory and how this is used together with models for sensor and actuator dynamics to achieve a realistic simulation of measurements and actuators.
Continuous measurement of dissolved sulfide in sewer systems
Authors: Sutherland-Stacey L. , Corrie S. , Neethling A. , Johnson I. , Gutierrez O. , Dexter R. , Yuan Z. , Keller J. , Hamilton G.
Published: February 2008

Sulfides are particularly problematic in the sewage industry. Hydrogen sulfide causes corrosion of concrete infrastructure, is dangerous at high concentrations and is foul smelling at low concentrations. Despite the importance of sulfide monitoring there is no commercially available system to quantify sulfide in waste water. In this article we report on our use of an in situ spectrometer to quantify bisulfide in waste water and additional analysis with a pH probe to calculate total dissolved sulfide. Our results show it is possible to use existing commercially available and field proven sensors to measure sulfide to mg/l levels continuously with little operator intervention and no sample preparation.
Intelligent monitoring system for long-term control of Sequencing Batch Reactors
Authors: Marsili-Libelli S. , Spagni A. , Susini R.
Published: February 2008

This paper discusses the application of artificial intelligence (AI) concepts to the monitoring of a lab-scale Sequencing Batch Reactor (SBR) treating nitrogen-rich wastewater (sanitary landfill leachate). The paper describes the implementation of a fuzzy inferential system to identify the correct switching sequence of the process and discusses the results obtained with six months of uninterrupted operation, during which the process conditions varied widely. The monitoring system proved capable of adjusting the process operation, in terms of phase length and external COD addition, to the varying environmental and loading conditions, with a percentage of correct phase recognition in excess of 95%. In addition, the monitoring system could be remotely operated through the internet via TCP/IP protocol.
Reliability and Transparency of Non-GAAP Disclosures by Real Estate Investment Trusts (REITs)
Authors: Baik Bok , Billings Bruce K. , Morton Richard M.
Published: February 2008

This paper examines whether industry efforts to decrease managerial discretion, increase uniformity, and improve transparency of a non-GAAP performance measure change voluntary disclosure and market perceptions. We find that the frequency of REITs meeting or beating analysts' expectations of funds from operations (FFO) decreases following explicit industry initiatives to discourage manipulation. Concurrent with this shift, we find that the information content of FFO to investors increased, particularly for firms reporting a reconciliation of FFO with GAAP earnings. We also examine firms in other industries to assess alternative explanations for these results, such as SEC intervention. Collectively, our findings suggest that industry guidance about non-GAAP performance curtailed managers' opportunistic reporting. Furthermore, the market response to FFO is consistent with investors perceiving less manipulation and greater reliability. Our evidence also supports the SEC's subsequent requirement that all non-GAAP disclosures be reconciled to the nearest GAAP measures.
Earnings Surprises that Motivate Analysts to Reduce Average Forecast Error
Authors: Barron Orie E. , Byard Donal , Yu Yong
Published: February 2008

Large earnings surprises and negative earnings surprises represent more egregious errors in analysts' earnings forecasts. We find evidence consistent with our expectation that egregious forecast errors motivate analysts to work harder to develop or acquire relatively more private information in an effort to avoid future forecasting failures. Specifically, we find that after large or negative earnings surprises there is a greater reduction in the error in individual analysts' forecasts of future earnings, and these individual forecasts are based more heavily on individual analysts' private information. This increased reliance on private information reduces the error in the mean forecast of upcoming earnings (even after controlling for the effect of reduced error in individual forecasts). As reliance on private information increases, more of each individual forecast error is idiosyncratic, and thus averaged out in the computation of the mean forecast.
Audit Quality and Properties of Analyst Earnings Forecasts
Authors: Behn Bruce K. , Choi Jong-Hag , Kang Tony
Published: February 2008

Under the assumption that audit quality relates positively to unobservable financial reporting quality, we investigate whether audit quality is associated with the predictability of accounting earnings by focusing on analyst earnings forecast properties. The evidence shows that analysts' earnings forecast accuracy is higher and the forecast dispersion is smaller for firms audited by a Big 5 auditor. We further find that auditor industry specialization is associated with higher forecast accuracy and less forecast dispersion in the non-Big 5 auditor sample but not in the Big 5 auditor sample. Overall, our results suggest that high-quality audit provided by Big 5 auditors and industry specialist non-Big 5 auditors is associated with better forecasting performance by analysts.
The Information Role of Conservatism
Authors: LaFond Ryan , Watts Ross L.
Published: February 2008

In this paper we argue that information asymmetry between firm insiders and outside equity investors generates conservatism in financial statements. Conservatism reduces the manager's incentives and ability to manipulate accounting numbers and so reduces information asymmetry and the deadweight losses that information asymmetry generates. This increases firm and equity values.

Our empirical tests are consistent with our proposition that information asymmetry is significantly positively related to conservatism after controlling for other demands for conservatism. Further, our tests are more consistent with our prediction that changes in information asymmetry between equity investors lead to changes in conservatism than the FASB's proposition that conservatism produces information asymmetry among equity investors. An important implication is that, if the FASB was successful in meeting its stated goal of eliminating conservatism, then it would increase information asymmetry between investors, not reduce it. This outcome is inconsistent with the objectives of the Securities Acts.
An Empirical Analysis of the Decline in the Information Content of Earnings Following Restatements
Authors: Wilson Wendy M.
Published: February 2008

Regulatory officials and market analysts have speculated that the loss of credibility in subsequently reported financial information is a long-lasting consequence of earnings restatements. I measure the information content of earnings using a standard earnings-returns framework over several years surrounding restatements to examine characteristics of the decline in the information content of earnings. Results indicate that although the information content of earnings declines following restatements, the loss is temporary. In particular, the earnings response coefficients for earnings announcements surrounding restatements exhibit a U-shaped pattern in which they are no longer significantly lower in the post-restatement period over an average of four quarters. The extent to which the earnings of restatement firms suffer a loss of information content varies across several dimensions. First, the duration of the loss is greater for firms that restate earnings to correct revenue recognition errors and for restatements that result in a large decline in the stock price at the announcement date. Second, there is not a loss in the information content of earnings for firms that make changes to their financial reporting governance structures following restatements. Overall, the evidence in this paper is consistent with a short-term decline in investor confidence regarding financial reporting following restatements, but shows that suspicion regarding the information loss of post-restatement earnings in the long-term is unwarranted.
The Effect of Occlusal Loading on the Microleakage of Class V Restorations
Authors: Arisu H. D. , Üçtasli M. B. , Eligüzeloglu E. , Özcan S. , Ömürlü H.
Published: February 2008

Clinical Relevance

The occlusal stress generated in the cervical region during normal function and parafunction may increase microleakage or detoriate the margins of Class V restorations. This study suggests that self-etch adhesives achieve marginal sealing equal to total-etch adhesives under occlusal loading.
Fluorescence Intensity of Resin Composites and Dental Tissues Before and After Accelerated Aging: A Comparative Study
Authors: Takahashi M. K. , Vieira S. , Rached R. N. , Almeida J. B. , Aguiar M. , Souza E. M.
Published: February 2008

Clinical Relevance

Fluorescence is one of the optical properties of resin composites and dental tissues that is of great interest today. The fluorescence intensity of restorative materials should be as close as possible to that of human enamel and dentin to ensure an acceptable reproduction of these qualities in esthetic restorations.
Interspecies Differences in the Removal of DNA Adducts
Authors: Hart Ronald W. , Chang Ming J.W.
Published: February 2008

Numerous physical and chemical agents damage cellular DNA in vivo. Such damage has been associated with various biochemical, physiological, and pathological dysfunctions including: alterations in gene expression, cell death, mutation, birth defects, cancer, and aging. Cells and organisms unable to prevent the induction of DNA damage or to repair such damage once it is induced, are predisposed to one or more of these pathologies. Over the course of evolution, living systems have developed various mechanisms to cope with such damage including enzymatic repair, information redundancy and, in extreme situations, cellular replacement. Enzymatic repair can be divided into two general categories: prereplication and post-replication repair. Each of these categories includes many “repair” systems which differ with the size of the repaired region, the nature of the enzymes involved in the repair process, the type of agent inducing the repair process or form of lesion removed. Over the last decade, numerous methods have been developed to measure DNA damage, both directly as well as indirectly, but few studies exist comparing the results of these methods with one another. Little is known as to whether these methods are measuring the same or different endpoints. Interspecies, intertissue, and interorgan comparisons can only be made when comparable techniques have been utilized. From such studies, it is now apparent that significant differences in DNA repair exist among species, within species, and between organs. Further, it is now a reasonable speculation that such differences may, in part, account for differences in organ susceptibility and risk per cell per unit time for spontaneous malignant transformation observed between species.
Risk Assessment, Environmental Factors, and Coronary Heart Disease
Authors: Feinleib Manning
Published: February 2008

Since 1965, there has been a steady decline in the age-adjusted death rates for ischemic heart disease in both sexes, all races and at all ages in the United States. The U.S. decline has been particularly striking during the last five years, yet it has not been similarly observed in most other countries in the world. A variety of explanations have been given for this recent decline including improved methods of diagnosing and treating the coronary patient and changes in lifestyle and diet. Several prospective epidemiologic studies such as the 30 year Framingham Heart Study have developed techniques for identifying those individuals at particularly high risk of developing coronary heart disease using the “standard” risk factors (systolic blood pressure, serum cholesterol level, cigarette smoking and glucose intolerance). Further elucidation of these standard risk factors which explain some, but not all, of the risk for developing CHD, as well as investigation of other endogenous and exogenous variables such as genetic or ethnic differences, geographic differences (altitude and weather), water hardness and fluoridation, industrial exposures and chemical factors such as carbon monoxide and hydrocarbons, and behavioral factors such as coronary-prone (Type A) behavior, will provide a more complete risk profile for CHD. Determination of how these latter variables interact with the standard risk factors and the degree to which they further explain risk for CHD is important to understanding the decline in mortality.
A Model for Selecting Short-Term Tests of Carcinogenicity
Authors: Lave Lester B. , Omenn Gilbert S. , Heffernan Kathleen D. , Dranoff Glen
Published: February 2008

A theoretical model is presented that selects among available short term tests of carcinogenicity and then classifies chemicals on the basis of the results. The model is simplified in ignoring the potency of various carcinogens but does take account of the social cost of falsely classifying a chemical as a carcinogen as well as the social cost of falsely classifying a chemical as a noncarcinogen. If some of the currently available short-term tests, separately or in sets, are capable of classifying chemicals with even moderate accuracy, this framework would serve to improve the regulation of suspect carcinogens.
Cardiotoxic Effects in Rats and Rabbits Treated with Terbutaline Alone and in Combination with Aminophylline
Authors: Whitehurst Virgil E. , Joseph Xavier , Hohmann John R. , Pledger Gordon , Balazs Tibor
Published: February 2008

Studies were conducted to determine the myocardial effects of a selective beta-adrenoceptor agonist, terbutaline, administered alone and in combination with aminophylline in the 4-to 5-month-old, 500-600 g (heavy) rat and the rabbit, using electrocardiographic and histopathological methods. Terbutaline given at high (5.0 mg/kg) and low (0.1 mg/kg) doses was not arrhythmogenic in the heavy rat; however, dose-dependent myocardial lesions were observed. Terbutaline given at the same doses to heavy rats pretreated with aminophylline was arrhythmogenic and produced severe cardiac lesions. Rats administered aminophylline at a dose of 18.75 mg/kg had plasma theophylline levels of 15-22 μg/ml; these concentrations are similar to the recommended human therapeutic levels, i.e., 10-20 μg/ml. The administration of terbutaline in conjunction with aminophylline did not seem to affect the plasma levels of theophylline. No arrythmias were detected in rabbits given terbutaline alone or in combination with aminophylline and no deaths occurred.
The Response of the Adrenergic System in the Cadmium-Induced Hypertensive Rat
Authors: Revis N. W. , Major T. C. , Horton C. Y.
Published: February 2008

Previous investigators, using an in vitro system, have shown that cadmium inhibits neuronal uptake of norepinephrine (NE). The current studies were performed to determine if the adrenergic system is altered in the cadmium-induced hypertensive rat. The results show that the Fischer and Sprague-Dawley rats develop hypertension, whereas the Wistar normotensive and Wistar hypertensive rats develop hypotension when exposed to 5 ppm of cadmium via drinking water. Results from these studies also show that in the cadmium-induced hypertensive rat, plasma NE is significantly elevated and that plasma clearance of [3H]NE is significantly reduced. However, the changes in NE metabolism observed in the hypertensive rats were also observed in hypotensive rats. Furthermore in the Wistar strain, renal artery cadmium levels were significantly higher than observed in the other two strains. We thus, suggest that the direction of change in blood following cadmium treatment is associated with both the plasma level of norepinephrine and the arterial level of cadmium.
Adsorption of Macromolecules on Mineral Fibers
Authors: Chang Ming J.W. , Joseph Laurie B. , Stephens Ralph E. , Hart Ronald W.
Published: February 2008

Several mineral fibers were shown to adsorb differentially to three classes of biologically significant macromolecules (i.e., DNA, RNA, and protein). The cytotoxicity exerted by the particulates on a normal human fibroblast cell line, with the exception of attapulgite, correlated positively with the degree of macromolecular adsorption exhibited by these substances, namely: short chrysotile > attapulgite = intermediate chrysotile > amosite > glass fiber. Correspondingly, the ability to interfere with the enzymatic hydrolysis of deoxyribonucleic acid by bovine pancreatic deoxyribonuclease I followed a similar pattern, i.e., chrysotile > amosite = glass fiber. The results suggest that adsorption by mineral fibers may induce changes in enzyme-substrate interactions and therefore could interfere with normal biological processes.
Drug-Induced Mesovarial Leiomyomas in the Rat—A Review and Additional Data
Authors: Kelly W. A. , Marler R. J. , Weikel J. H.
Published: February 2008

Leiomyomas developed in the ovarian suspensory ligament (costo-uterine muscle) of rats after long-term treatment with several beta2-adrenoceptor stimulant drugs. The response was evidently related to excessive adrenergic stimulation of a tissue with a high density of β2-receptors; was inhibited by β blockade; and was directly related to in vitro pharmacologic potency. Tumor development was dependent on continuous administration of adequate dosages to a susceptible strain of rat. Histologically, all tumors were benign and none were malignant. After many years of clinical experience, there are no known reports of this response in human patients receiving β2-adrenoceptor-stimulant drugs.
Subacute Intramuscular Toxicity of the Acetylcholinesterase Reactivating Agent HI-6 in Rats and Dogs
Authors: Levine Barry S. , Tomlinson Michael J.
Published: February 2008

Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture, and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters were unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.
Vaginal and Rectal Administration
Authors: Auletta Carol S.
Published: February 2008

Vaginal and rectal routes of administration of test substances are not often used in animal testing procedures. However, these routes are almost obligatory when therapeutic agents intended for vaginal or rectal use in humans have to be evaluated for safety in animals. Applicable study designs and experiences with these routes are described in this report.
Continuous Infusion Animal Model for the Immunoconjugate Xomazyme-CD5 Plus, in the Rat
Authors: Kung Ada H. C. , Kong Kellie N. , Achilles Kirsten A. , Mohler Virginia L. , White Mark L.
Published: February 2008

The immunoconjugate, XomaZyme-CD5 Plus, consists of a murine immunoglobulin IgGl monoclonal antibody directed against the CD5 antigen present on mature human T lymphocytes and ricin A chain (RTA), a potent ribosomal inhibitory protein. XomaZyme-CD5 Plus, administered as an 1-hour infusion, has shown efficacy in patients with steroid-resistant acute graft versus host disease. An animal model was developed to study the toxicity profile of XomaZyme-CD5 Plus when administered by continuous intravenous infusion in the rat and to support the delivery of the drug by this method in human clinical trials. This animal model involved the continuous i.v. infusion of XomaZyme-CD5 Plus in conscious rats for 10 consecutive days via catheterization of the external jugular vein and surgical attachment of the animals to a tether/swivel system leading to a syringe pump. In addition, a comparison study was conducted with XomaZyme-CD5 Plus administered to rats at the same daily dose by bolus i.v. injection for 10 days. Qualitatively similar toxicity profiles were observed for XomaZyme-CD5 Plus given by bolus injection and by continuous infusion in rats. Comparing equivalent dose levels, 0.5 mg/kg/day, XomaZyme-CD5 Plus given by continuous i.v. infusion was similar in toxicity as given by bolus injection. The anti-immunoconjugate (XomaZyme-CD5 Plus) antibody response occurred later and titers were lower after infusion in comparison to bolus injection. We have demonstrated that the rat continuous i.v. infusion model can be successfully used to deliver protein therapeutics at accurate dosages to study standard acute to subchronic toxicity profiles.
European Regulatory Compliance Issues: Good Research Practices
Authors: Dent N.J.
Published: February 2008

Since the inception of the 1976 Food and Drug Administration (FDA) regulations governing preclinical toxicology, the world has seen an explosion of guidelines, principles, and regulations. The objective of this report is to clarify the situation in Europe as to the status of Good Laboratory Practices (GLPs). An overview of the harmonisation currently underway in Europe is given, although this changes frequently with new countries applying to join the European Community (EC) or undertaking aspects of GLP compliance. Where interactions have occurred between the GLPs and Good Clinical Practices (GCPs) (for example, clinical trials in analyses and bioequivalent studies), the status of clinical pathology and ancillary laboratories is discussed. Finally, particular auditing problems experienced within the EC are addressed. The general concept of GLP has changed very little since the inception of the 1976 FDA regulations governing preclinical toxicology; however, over the past 17 years, several other “good practices” have come into play and, most certainly, the original concept of toxicology and GLP has now been extended into many other scientific areas. Although this text deals primarily with GLP and GCP, the interaction between these two good practices and Good Manufacturing Practice cannot be divorced. The impact of toxicology as a precursor to clinical trials has been seen with the introduction of guidelines for the conduct of such studies. These, with other guidelines for the production of clinical trial materials, mean, in essence, that now the production of a new chemical entity from conception to marketing is completely covered by a series of guidelines and regulations-known colloquially as “the good practices.”
Intraarterial abciximab for treatment of thromboembolism during coil embolization of intracranial aneurysms: outcome and fatal hemorrhagic complications
Authors: Park Jae Hyo , Kim Jeong Eun , Sheen Seung Hun , Jung Cheol Kyu , Kwon Bae Ju , Kwon O-Ki , Oh Chang Wan , Han Moon Hee , Han Dae Hee
Published: February 2008

Object

Experience with intraarterial abciximab for the treatment of thromboembolism during endovascular coil embolization is limited. The authors report the outcome of intraarterial abciximab use, with an emphasis on fatal hemorrhagic complications.

Methods

Between March 2003 and May 2006, the authors treated 606 aneurysms by using endovascular coil embolization, and in 32 (5.3%) of these aneurysms (31 patients) an intraarterial thrombus developed. Sixteen of these aneurysms were ruptured and the other 16 were unruptured. Arterial thrombi were totally occlusive in 3 and partially occlusive in the remaining 29 cases. Intraarterial abciximab was administered at a concentration of 0.2 mg/ml as a bolus of 4–15 mg over a period of 15–30 minutes.

Results

Complete thrombolysis was achieved in 17 (53%) and partial thrombolysis in 15 (47%) of 32 lesions. Twenty-eight patients (90.3%) were asymptomatic after abciximab thrombolysis, but 3 had postprocedural rebleeding that occurred after abciximab treatment; all of these patients had recently experienced an aneurysm rupture. Of these patients, 1 displayed severe thrombocytopenia and the other 2 showed a > 25% reduction in platelet count after abciximab treatment.

Conclusions

Intraarterial abciximab is effective for the treatment of thromboembolic complications that occur during intracranial aneurysm coil insertion. Nevertheless, attention should be paid to prevent potentially fatal complications such as thrombocytopenia and hemorrhage, especially in patients with a ruptured aneurysm.
Whole-hand sensorimotor area: cortical stimulation localization and correlation with functional magnetic resonance imaging
Authors: Boling Warren , Parsons Michael , Kraszpulski Michal , Cantrell Carrie , Puce Aina
Published: February 2008

Object

The pli de passage moyen (PPM) is an omega-shaped cortical landmark bulging into the central sulcus. There has been considerable interest in the PPM given that hand motor and sensory tasks have been found on functional magnetic resonance (fMR) imaging to activate the structure. Note, however, that the cortical function subserved by the PPM is not completely understood. Finger and thumb function are somatotopically organized over the central area and encompass a larger cortical surface than the anatomical PPM. Therefore, a sensory or motor hand area within the PPM would be redundant with the somatotopically organized digit function in the primary sensorimotor cortex. In this study the authors aimed to clarify the function subserved by the PPM and further evaluate hand area function in the primary sensorimotor cortex.

Methods

To further elucidate the function subserved by the PPM, patients underwent cortical stimulation in the region of the PPM as well as fMR imaging–demonstrated activation of the hand area. Two separate analytical methods were used to correlate hand area functional imaging with whole-hand sensory and motor responses induced by cortical stimulation.

Results

A relationship of the anatomical PPM with cortical stimulation responses as well as hand fMR imaging activation was observed.

Conclusions

A strong relationship was identified between the PPM, whole-hand sensory and motor stimulation responses, and fMR imaging hand activation. Whole-hand motor and whole-hand sensory cortical regions were identified in the primary sensorimotor cortex. It was localized to the PPM and exists in addition to the somatotopically organized finger and thumb sensory and motor areas.
Automated end-to-side anastomosis to the middle cerebral artery: a feasibility study
Authors: Bregy Amadé , Alfieri Alex , Demertzis Stefanos , Mordasini Pasquale , Jetzer Anna Katharina , Kuhlen Dominique , Schaffner Thomas , Dacey Ralph , Steiger Hans-Jakob , Reinert Michael
Published: February 2008

Object

The treatment of complex cerebrovascular or skull base pathological conditions necessitates a microsurgical blood flow preservation or augmentative revascularization procedure as either an adjunctive safety measure or a definitive treatment. The brain is susceptible to ischemia, and procedure-related risks can be minimized by the reduction of occlusion time or the use of a nonocclusive technique. The authors therefore analyzed the feasibility of an automatic device (C-Port xA, Cardica) designed for constructing an end-to-side anastomosis with or without flow interruption for a middle cerebral artery (MCA) bypass in a human cadaveric model and in an in vivo craniotomy simulation model.

Methods

Four Thiel-fixated human head specimens were prepared using 8 standard pterional craniotomies. The sylvian fissure was opened to access the anterior circulation and in particular the MCA. The length of the individual vessel segments was measured. The C-Port xA was tested on each of the 8 exposures. In addition the C-Port xA was deployed in an in vivo craniotomy simulator model in 10 New Zealand rabbits (a total of 20 anastomoses) by using the abdominal aorta jump graft model.

Results

Short-term patency was assessed by angiography and histological findings. In all 8 sylvian exposures, construction of an MCA anastomosis with the aid of the C-Port xA was feasible. All 20 jump graft anastomoses performed in the in vivo craniotomy simulator were found to be patent.

Conclusions

The anatomical studies as well as the in vivo craniotomy simulation studies demonstrated that the dimensions of the automated end-to-side anastomosis device are suitable for an extracranial–intracranial high-flow bypass on the MCA. Further miniaturization and special adaptation of this device would allow bypass procedures to more proximal intracranial vessels.
William P. van Wagenen and the first corpus callosotomies for epilepsy
Authors: Mathews Marlon S. , Linskey Mark E. , Binder Devin K.
Published: February 2008

✓ As a trainee of Dr. Harvey Cushing, cofounder and first president of the American Association of Neurological Surgeons, and founder of a prestigious international academic fellowship, Dr. William P. van Wagenen is an important figure in the history of neurological surgery. Perhaps less well known or appreciated is his seminal role as the first neurosurgeon to attempt, study, and publish results of the corpus callosotomy procedure for patients with epilepsy, and his collaboration with Andrew J. Akelaitis, which led to the description of some features of “split-brain” patients 2 decades before similar work in the 1960s eventually resulted in a Nobel Prize for Roger W. Sperry in 1981. These contributions firmly establish William P. van Wagenen as one of the founding pioneers in the surgical treatment of patients with epilepsy.
Honoring the 75th anniversary of the American Association of Neurological Surgeons
Authors: Laws Edward R.
Published: February 2008

Ever since the Journal of Neurosurgery (JNS) published its first volume in 1944, the journal has reflected the scientific, technical, and clinical evolution of our specialty and parent organization, first called the Harvey Cushing Society and later the American Association of Neurological Surgeons. The JNS has been an uncompromising arbiter of progress in our specialty, and its superb editorial stewardship has led to its recognition as the premier journal in the field. The impact rating of JNS and its wide circulation among neurosurgeons worldwide are two of the many reasons why most of the truly innovative and paradigm-shifting advances in neurosurgery have been published in its pages.

As part of the 75th anniversary of the American Association of Neurological Surgeons celebration, the JNS Publishing Group has initiated a project of reviewing papers published over the years that have had the highest impact factor and greatest scientific interest: papers that have heralded new knowledge, new concepts, and new techniques that have been at the heart of modern neurosurgery and its continuing excitement and progress. We hope you will enjoy these articles and the accompanying commentaries. In this issue we present the next paper in this series.
Craniospinal Langerhans cell histiocytosis in children: 30 years' experience at a single institution
Authors: Davidson Laurence , McComb J. Gordon , Bowen Ira , Krieger Mark D.
Published: February 2008

Object

The goal of this study was to review a large series of patients with Langerhans cell histiocytosis (LCH) who had craniospinal lesions to assess the long-term course, outcome, and efficacy of treatment of the disease.

Methods

Forty-four patients with LCH who presented to a single pediatric neurosurgical department between 1976 and 2006 were retrospectively reviewed.

Results

This series included 29 boys and 15 girls, ranging in age from 2 months to 13 years, with a mean follow-up duration of 4.5 years. Twenty-seven patients (61%) had unifocal bone lesions, 12 (27%) had multifocal bone disease, 2 (5%) had solitary hypothalamic–pituitary axis lesions, and 3 (7%) had multiple organ involvement at presentation. Five (19%) of the 27 patients with unifocal bone disease and 4 (33%) of the 12 patients with multifocal bone disease had delayed development of new bone lesions during the follow-up period. The time to development of new bone lesions ranged from 1 month to 1 year. Two of the 3 patients with multiple-organ LCH died. Patient age ≤ 2 years at the time of initial presentation was a risk factor for both initial multifocality and eventual dissemination. In all patients with initial multifocal bone involvement or later dissemination of unifocal bone disease, LCH was controlled by chemotherapy, except for 2 who were treated by surgery alone. Three patients had histological evidence of spontaneous resolution of their lesions.

Conclusions

Patients with unifocal LCH can be effectively treated with surgery alone. Very young patients are more likely to have multifocal disease and disseminations, and will usually require chemotherapy to control their disease. Spontaneously regressing lesions need not be resected; however, a biopsy procedure can be performed for diagnostic purposes.
Endoscopic cyst fenestration in the treatment of multiloculated hydrocephalus in children
Authors: El-Ghandour Nasser M. F.
Published: February 2008

Object

The treatment of multiloculated hydrocephalus is a difficult problem in pediatric neurosurgery. Definitive treatment is surgical, yet the approach remains controversial. The author has therefore reviewed his results with endoscopic cyst fenestration (ECF) in the management of this disease.

Methods

The author presents the largest series to date of 24 patients with multiloculated hydrocephalus who were treated endoscopically. The group included 10 boys and 14 girls with a mean age of 12.5 months. Uniloculated hydrocephalus was not included in this study because it is a different entity that would be better studied separately.

Results

Neonatal meningitis was the most common cause (in 9 patients), followed by intraventricular hemorrhage (in 6 patients), postoperative gliosis (in 6 patients), and multiple neuroepithelial cysts (in 3 patients). Multiplanar magnetic resonance images made early diagnosis possible and are indicated if the computed tomography scan shows disproportionate hydrocephalus. Surgical treatment included ECF (in 24 patients), endoscopic revision of a malfunctioning preexisting shunt (in 6 patients), placement of a new shunt (in 15 patients), and third ventriculostomy (in 3 patients). The ECF was easily performed in all cases through devascularization of the cyst wall by coagulation to prevent recurrence. The results are encouraging with improvement of hydrocephalus in 18 patients (75%). The need for shunt insertion was avoided in 3 patients (12.5%). Endoscopy reduced shunt revision rate from 2.9 per year before fenestration to 0.2 per year after fenestration. During the overall mean follow-up period (30 months), repeated ECF was necessary in 8 patients (33%). Six (75%) of these 8 patients had already undergone shunt treatment before endoscopy. Endoscopic complications were minimal (2 cerebrospinal fluid leaks and 2 minor arterial hemorrhages), and there were no deaths (0%).

Conclusions

An ECF procedure is recommended in the treatment of multiloculated hydrocephalus because it is effective, simple, minimally invasive, and associated with low morbidity and mortality rates.
Pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage
Authors: Hamada Hideo , Kurimoto Masanori , Hayashi Nakamasa , Nagai Shoichi , Kurosaki Kunikazu , Nomoto Kazuhiro , Kanegane Hirokazu , Nomura Keiko , Endo Shunro
Published: February 2008

✓The authors report on a rare case of pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. This 5-year-old boy presented to the outpatient clinic with headache and vomiting. Computed tomography and magnetic resonance imaging studies revealed a mass lesion with partial hemorrhage in the suprasellar region extending into the third ventricle. Partial resection via a transcallosal approach was performed. Because the pathological diagnosis was pilomyxoid astrocytoma, chemotherapy was administered. However, 4 months after the first operation, during chemotherapy, the boy presented with massive intratumoral and intraventricular hemorrhage with hydrocephalus. Although emergent external ventricular drainage was performed, the patient died. In this report, the authors review the literature and discuss the clinical features and treatment of pilomyxoid astrocytoma.