bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of bronchial inflammation using an automated cell recognition system based on colour analysis
Authors: Berger P , Lavallee J , Rouiller R , Laurent F , Marthan R , Tunon-de-Lara JM
Published: October 2002

The aim of this study was to develop an automated system of cell recognition based upon colour analysis suitable for microscopic examination of bronchial inflammation. Human bronchi obtained from 17 patients undergoing thoracotomy were embedded in glycolmethacrylate to perform immunohistochemistry with antibodies against: neutrophil elastase, tryptase, chymase, eosinophil cationic protein, CD68, CD3 and immunoglobulin E. The image analysis system calculates three independent criteria (optic density, hue density, hue) combined with morphological parameters to specifically recognize a positive staining. This automated analysis was applied to the study of bronchial inflammation in smokers and nonsmokers in terms of the absolute number of cells and the expression of different markers by a single cell. The use of these criteria enabled the characterization of a positive stain on single (intraclass correlation coefficient (ICC) = 0.88 or serial (ICC = 0.84) sections. Cell counts obtained by the automated system were highly reproducible. Regarding bronchial inflammation, it was found that the number of inflammatory cells was significantly higher in smokers than in nonsmokers, the majority of these cells bearing immunoglobulin E. These results demonstrate that such computerized analysis of colours is a valuable method for quantifying inflammatory cells in bronchial tissue and for analysing the expression of different markers by a single cell.
A proposed polarity standard for multicomponent seismic data
Authors: Brown R. James , Stewart Robert R. , Lawton Don C.
Published: October 2002

This paper proposes a multicomponent acquisition and preprocessing polarity standard that will apply generally to the three Cartesian geophone components and the hydrophone or microphone components of a 2‐D or 3‐D multicomponent survey on land, at the sea bottom, acquired as a vertical seismic profile, vertical‐cable, or marine streamer survey. We use a four‐component ocean‐bottom data set for purposes of illustration and example. A primary objective is a consistent system of polarity specifications to facilitate consistent horizon correlation among multicomponent data sets and enable determination of correct reflectivity polarity.

The basis of this standard is the current SEG polarity standard, first enunciated as a field‐recording standard for vertical geophone data and hydrophone streamer data. It is founded on a right‐handed coordinate system: z positive downward; x positive in the forward line direction in a 2‐D survey, or a specified direction in a 3‐D survey, usually that of the receiver‐cable lines; and y positive in the direction 90° clockwise from x. The polarities of these axes determine the polarity of ground motion in any component direction (e.g., downward ground motion recording as positive values on the vertical‐geophone trace). According also to this SEG standard, a pressure decrease is to be recorded as positive output on the hydrophone trace. We also recommend a cyclic indexing convention, [W, X, Y, Z] or [0, 1, 2, 3], to denote hydrophone or microphone (pressure), inline (radial) geophone, crossline (transverse) geophone, and vertical geophone, respectively.

We distinguish among three kinds of polarity standard: acquisition, preprocessing, and final‐display standards. The acquisition standard (summarized in the preceding paragraph) relates instrument output solely to sense of ground motion (geophones) and of pressure change (hydrophones). Polarity considerations beyond this [involving, e.g., source type, wave type (P or S), direction of arrival, anisotropy, tap‐test adjustments, etc.] fall under preprocessing polarity standards. We largely defer any consideration of a display standard.
The potential of fracture imaging using high‐frequency, single‐hole electromagnetic data
Authors: Seol Soon Jee , Suh Jung Hee , Song Yoonho , Kim Hee Joon , Lee Ki Ha
Published: October 2002

This paper presents an inversion scheme for high‐frequency electromagnetic (EM) data from a single borehole for detection and characterization of fluid‐filled fractures. Water in the fracture zone may be characterized by its high electrical permittivity and, if saline, by high electrical conductivity. High electrical conductivity results in increased attenuation of EM fields, whereas high electrical permittivity reduces the phase velocity of propagating EM fields. Taking advantage of these effects, we use high‐frequency EM fields to detect and characterize fluid‐filled fractures. To demonstrate the feasibility of single‐hole EM imaging, we develop a three‐step inversion scheme to map a fluid‐filled fracture near the borehole and to evaluate its electrical conductivity and permittivity.

We assume that a fluid‐filled fracture can be simulated by a conductive thin sheet. To test our inversion scheme, we generated synthetic data using the thin‐sheet integral equation method. A vertical magnetic dipole was used as a source, and the resultant magnetic fields were inverted using a nonlinear least‐squares method. First, the background conductivity and permittivity were obtained using vertical magnetic field data from below and above the transition frequency, at which conduction and displacement current magnitudes are equal. Next, using the phase difference between EM fields at two neighboring frequencies in the wave propagation realm, both the vertical and dipping sheets were successfully mapped using NMO and migration techniques. Electrical properties of the sheet were well resolved by subsequent inversion after having fixed the location of the sheet and host electrical properties.

This study shows the potential of imaging the fracture using high‐frequency EM data obtained from single‐hole surveys.
The moments of the impulse response: A new paradigm for the interpretation of transient electromagnetic data
Authors: Smith Richard S. , Lee Terry J.
Published: October 2002

We define the nth moment of the transient electromagnetic impulse response as the definite integral with respect to time of the “quadrature” magnetic‐field impulse response weighted by time to the nth power. In this context, the quadrature response is defined as the full impulse response with the in‐phase component (i.e., the delta function component at zero time) removed. The low‐order moments are equivalent to familiar quantities: the zeroth moment (n = 0) is numerically equal to the frequency‐domain inductive limit, and the first moment is the resistive‐limit response. The higher order moments can be of particular benefit: successively they put greater emphasis on the late‐time data, and hence can bring out features in the data that are more conductive or deeper.

An advantage of calculating moments (and hence the inductive and resistive limit) is that these data are not strongly dependent on any distortion of the waveform from an ideal impulse. Hence, it is not critical to deconvolve the data prior to estimating the moments.

If a conductor has a single exponential decay, the nth moment of the decay is proportional to the nth power of the time constant of the exponential. Thus, it is relatively easy to estimate the time constant from the moments. For a conductive sphere model, the expressions for the moments are more complicated, but are still simpler than the full transient solution or the frequency‐domain solution.

In a field example, the high‐order moments emphasize local highly conductive features, but also show the noise present in the late‐time data. A discrete feature on the profile evident in moments 3 through 10 has been modeled as a spherical conductor with its center at 90 m depth, a radius of 45 m, and a conductivity of 9.4 S/m.
Residual migration‐velocity analysis in the plane‐wave domain
Authors: Jiao Junru , Stoffa Paul L. , Sen Mrinal K. , Seifoullaev Roustam K.
Published: October 2002

Over the last few years, migration‐velocity analysis methods have been developed for 2‐D and 3‐D models by extending the assumptions and approximations used for rms velocity models. Computational requirements for these analyses have increased dramatically because top‐down layer‐stripping migration is needed to derive interval velocities directly instead of using rms velocities and then converting into interval velocities. We establish exact equations for 1‐D and 2‐D residual velocity analysis in the depth‐plane‐wave domain and use these in an iterative and interactive migration velocity analysis program. The new method updates interval velocities directly in a top‐down residual‐difference correction for all layers after prestack depth migration instead of top‐down layer‐stripping migration followed by residual analysis. This makes the new method a suitable tool for migration velocity analysis, especially for 3‐D surveys. We test the method on synthetic and field data. The field data results show that a reasonable velocity model is obtained and most common image gathers are correctly imaged using no more than four iterations.
Finite‐difference calculation of direct‐arrival traveltimes using the eikonal equation
Authors: Mo Le‐Wei , Harris Jerry M.
Published: October 2002

Traveltimes of direct arrivals are obtained by solving the eikonal equation using finite differences. A uniform square grid represents both the velocity model and the traveltime table. Wavefront discontinuities across a velocity interface at postcritical incidence and some insights in direct‐arrival ray tracing are incorporated into the traveltime computation so that the procedure is stable at precritical, critical, and postcritical incidence angles. The traveltimes can be used in Kirchhoff migration, tomography, and NMO corrections that require traveltimes of direct arrivals on a uniform grid.
3‐D tomographic static correction
Authors: Chang Xu , Liu Yike , Wang Hui , Li Fuzhong , Chen Jing
Published: October 2002

A 3‐D tomographic inversion approach based on a surface‐consistent model for static corrections is presented in this paper. Direct, reflected, and refracted waves are used simultaneously to update the near‐surface model. We analyze the characteristics of the first‐break traveltime in complicated low‐velocity layers. To improve the accuracy for the velocity model, the various first‐break times from direct, reflected, and refracted waves are considered for model inversion. A fractal algorithm which overcomes the error caused by wavelet shape differences is applied to pick first breaks. It also overcomes the leg jump of refractions. The method can pick a large number of first breaks automatically. The raypaths and traveltimes are calculated with a 3‐D ray tracer that does not increase computation time for complicated geological models. Our method can determine the raypath associated with minimum traveltimes regardless of wave mode (direct, refracted, or reflected). We use a least‐squares approach in conjunction with a matrix decomposition to reconstruct a 3‐D velocity model from the actual first‐break times obtained from 3‐D data. Finally, long‐ and short‐wavelength static corrections are calculated concurrently, based on the reconstructed velocity profile. The method can be applied to wide‐line profiles, crooked lines, and 2‐D and 3‐D seismic survey geometries. The results applied to a real 3‐D data example indicate that the 3‐D tomographic static corrections are effective for field data.
A high voltage computer controlled experimental system for the investigation of amorphous semiconductors as image sensors
Authors: Vaezi-Nejad S. M. , Jenner R. P.
Published: October 2002

This paper describes an ongoing programme of work designed to investigate dark discharge and photoconductivity in amorphous semiconductors with a view to applying these materials to industrial optical process tomography (OPT). Extensive laboratory equipment has been developed to investigate the aforementioned phenomena in amorphous arsenic triselenide (a-As2Se3) and hydrogenated amorphous silicon (a-Si: H). Photoconductivity measurements are performed in both xerographic and electroded modes by the use of a purpose built xenon ‘ash facility which can deliver pulsed light of user defined intensity, duration, and frequency. Control of the laboratory apparatus and the collection of data is fully automated, and the laboratory apparatus conforms to all relevant health and safety regulations concerning working with high voltages. Extensive software has been written for the data handling, data management, data display and numerical analysis of the experimental data. The advantages of amorphous semiconductors for OPT are discussed in section 1. Section 2 contains an overview of the developed experimental apparatus, and finally, section 3 brie‘y describes the amorphous semiconductor material’s ability to produce qualitative and quantitative data for imaging or control signal generation.
The exponential limit to the cooling of buildings by natural ventilation
Authors: Levermore G J
Published: October 2002

In manual heat gain and heat loss calculations the standard linear ventilation and infiltration heat loss formula (/)NV(tai tao), (with a suitable factor to relate to comfort temperature), is used. In the 1986 CIBSE Guide Section A8, Summertime temperatures in buildings, a limiting ventilation heat loss formula is used as the air change rate, N, increases, but, as with older guides, there is no reference or explanation of its derivation,1 although the 1970 Guide offers some explanation. This limiting equation is not used in the 1999 Guide A, Environmental design which is unfortunate. This paper analyses the ventilation heat loss based on a log mean temperature difference heat transfer approach which also shows a limiting heat loss effect like the A8 equation. It is also suggested that an admittance value should be used instead of a constant heat transfer coefficient which gives greater insight into the heat transfer process. Significant reductions in the heat transfer process are found at relatively low air change rates using the more correct formulae, which could have implications for summer natural ventilation, during both day and night.
Subsystem organ function during coronary surgery
Authors: Ascione Raimondo , Al-Ruzzeh Sharif , Amer Khalid , Angelini Gianni D
Published: October 2002

Conventional coronary artery bypass grafting (CABG) carries a mortality rate of 1% to 2% in elective patients. However, despite advances in perfusion, anaesthetic, and surgical techniques cardiopulmonary bypass (CPB) is still associated with subsystem dysfunction. Off-pump coronary artery bypass grafting (OPCAB) has recently gained popularity as a potentially more physiological method to maintain the functional integrity of major organ systems. The review of observational reports, case-matched studies and prospective randomized trials seems to suggest that OPCAB surgery reduces postoperative subsystem organ dysfunction when compared with conventional coronary revascularisation.
Whole-body hyperthermia: a review of theory, design and application
Authors: Vertrees Roger A , Leeth Angela , Girouard Mark , Roach John D , Zwischenberger Joseph B
Published: October 2002

The intentional induction of elevated body temperature to treat malignant lesions has its origins in the 18th century. The mechanism of heat-induced cell death is not clear; however, heat induces a variety of cellular changes. For heat to exert a therapeutic effect, pathogens (bacteria, viruses, or neoplastic tissues) need to be susceptible within temperature ranges that do not exert deleterious effects on normal tissues. Hyperthermia has been used successfully to treat isolated neoplastic lesions of the head and neck, regional tumors such as melanoma of the limb, and is under investigation as either an adjunct to, or therapy for, locally disseminated and systemic diseases. The clinical utility of perfusion hyperthermia has evolved into three approaches -isolated organ or limb, tumorous invasion of a cavity, and systemic or metastatic spread. When whole-body hyperthermic treatment has been tried, it has been induced in the patient by submersion in hot wax or liquid, wrapping in plastic, encasement in a high-flow water perfusion suit, or by extracorporeal perfusion. Our group has developed an extracorporeal method, veno-venous perfusion-induced systemic hyperthermia, that was used first to safely heat swine homogenously to an average body temperature of 43°C for 2 h. More recently, a Phase I clinical trial has been completed in which all patients were safely heated to 42 or 42.5°C for 2 h and survived the 30-day study period. We have been sufficiently encouraged by these results and are continuing to develop this technology.
Challenges in paediatric perfusion
Authors: Brawn W J
Published: October 2002

In the last 50 years cardiopulmonary bypass has evolved dramatically, so that even the most complex heart lesions can be repaired successfully. However, we are aware that whilst survival may be excellent, organ damage, even though minor, particularly to the central nervous system is common. The next challenge in paediatric perfusion is to reduce this damage to a minimum.
Performance of a mail-administered version of a stroke-speci” c outcome measure, the Stroke Impact Scale
Authors: Duncan Pamela W , Reker Dean M , Horner Ronnie D , Samsa Gregory P , Hoenig Helen , LaClair Barbara J , Dudley Tara K
Published: October 2002

Objective: To evaluate the feasibility and concurrent validity of a new, mail-administered, stroke-speci”c outcome measure, the Stroke Impact Scale (SIS).

Design: Observational cohort study.

Setting and patients: Stroke patients who had lived independently in the community prior to their stroke and who were candidates for post-stroke rehabilitation were recruited from nine, high-volume, Department of Veteran Affairs Medical Centers.

Methods: Two hundred and six patients were mailed the SIS after a sixmonth post-stroke telephone interview. Telephone assessments included the Functional Independence Measure, the Lawton IADL and the SF-36.

Results: The response rate for the mailed SIS was 63%, with 45% of the responses from proxies. The average rate of missing item level scores per patient was 1.3 (range 0–20) resulting in an average rate of 0.13 missing domain scores per patient (range 0–3). Nonresponders to the mailed SIS had more severe strokes with lower functional status at the time of the survey than responders. Proxies were more likely to complete the survey if the subjects were older, married, cognitively impaired and more functionally limited. The SIS did not exhibit a high rate of ‘oor and ceiling effects, particularly in physical function domains, as did the FIM and the SF-36.

Conclusions: The mailed SIS is a feasible means of assessing post-stroke function. Missing items and missing domain scores were extremely low, however, there is a trade-off between the low-cost mail SIS survey on the one hand and the resulting nonresponse bias on the other.
Prevalence of spasticity post stroke
Authors: Watkins C L , Leathley M J , Gregson J M , Moore A P , Smith T L , Sharma A K
Published: October 2002

Objectives: To establish the prevalence of spasticity 12 months after stroke and examine its relationship with functional ability.

Design: A cohort study of prevalence of spasticity at 12 months post stroke. Setting: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, UK.

Subjects: One hundred and six consecutively presenting stroke patients surviving to 12 months.

Main outcome measures: Muscle tone measured at the elbow using the Modi”ed Ashworth Scale and at several joints, in the arms and legs, using the Tone Assessment Scale; functional ability using the modi”ed Barthel Index.

Results: Increased muscle tone (spasticity) was present in 29 (27%) and 38 (36%) of the 106 patients when measured using the Modi”ed Ashworth Scale and Tone Assessment Scale respectively. Combining the results from both scales produced a prevalence of 40 (38%). Those with spasticity had signi”cantly lower Barthel scores at 12 months ( p < 0.0001).

Conclusion: When estimating the prevalence of spasticity it is essential to assess both arms and legs, using both scales. Despite measuring tone at several joints, spasticity was demonstrated in only 40 (38%) patients, lower than previous estimates.
The effect of independent practice of motor tasks by stroke patients: a pilot randomized controlled trial
Authors: Pollock Alexandra S , Durward Brian R , Rowe Philip J , Paul John P
Published: October 2002

Objective: To investigate the effect of independent practice of sitting balance as an addition to standard physiotherapy treatment for patients with stroke.

Design: Randomized controlled trial, using blocked randomization procedure with 2:1 ratio.

Subjects: Inpatients with diagnosis of stroke, having achieved one minute of independent sitting balance but not yet achieved 10 independent steps, and with no known previous disabilities, pathology or neurological de”cit affecting mobility prior to stroke.

Intervention: A four-week regime of independent practice aimed at improving aspects of balance, as an addition to standard physiotherapy treatment based on the Bobath Approach.

Main outcome measure: Proportion of patients achieving ‘normal’ symmetry of weight distribution during sitting, standing, rising to stand, sitting down, and reaching.

Results: Nineteen subjects were randomized to the control group; nine to the intervention group. There were no clinically signi”cant differences in measured outcome between the groups.

Conclusions: The regime of independent practice had no measured bene”cial effect on the balance ability of patients with recently acquired stroke.
Modelling spatial choice: a review and synthesis in a migration context
Authors: Pellegrini Pasquale A. , Fotheringham A. Stewart
Published: October 2002

This paper reviews various approaches to the modelling of spatial choice. Spatial choice modelling is viewed as a distinct area of research, within the larger field of discrete choice modelling, with a sound methodological basis and computationally tractable modelling framework. This review draws upon empirical application of spatial choice models to interregional migration and identifies the main research issues, summarizes the progress of research thus far, and suggests some paths for future research. It is argued that some of the widely used models suffer from problems derived from their development in aspatial choice contexts. Acknowledging the increased complexity and, possibly, the different choice process that spatial choice situations present over their aspatial counterparts leads to the development of the socalled competing destinations model and its variants. Evidence from empirical tests of these spatial choice models suggests that analysts engaged in interregional migration modelling risk model misspecification if they ignore the peculiarities of spatial choice.
Effect of organophosphate intoxication on human serum paraoxonase
Authors: Sözmen E Y , Mackness B , Sözmen B , Durrington P , Girgin F K , Aslan L , Mackness M
Published: October 2002

Recently, interindividual variations in serum paraoxonase (PON1) activity and the differences in its metabolic activity towards different organophosphates (OPs) caused by the coding region polymorphisms L55M and Q192R have been found to be important risk factors in susceptibility to OP poisoning. In this study, we investigated the effect of PON1 on the outcome of acute OP intoxication and the effect of acute OP intoxication on PON1. Twenty-eight OP-poisoned patients and 66 healthy volunteers were studied. Patients were evaluated for the clinical manifestations of OP intoxication as well as PON1 activity, PON1 mass and PON1 polymorphisms. Butyrylcholine-esterase (BChE) activity was 50% lower (2276±738 U/L versus 5037±1553 U/L, P<0.01) while PON1 activity was 30% lower (114.2±67.4 nmol/mL/min versus 152.9±78.9 nmol/mL/ min, P<0.05) in patients than in controls. We observed that the PON1 and BChE activities of eight of the original subjects returned to normal levels when they were reinvestigated six months after exposure. The frequency of the PON192Q allele was significantly higher in patients than controls (85.7% versus 59.7%, χ2=6.745, P=0.034). QQ/MM individuals had the lowest activity towards paraoxon, while RR/LL individuals had the highest activity. Our data indicate that interindividual differences in PON1 activity and the PON1-55 and-192 polymorphisms are important risk factors in susceptibility to acute OP poisoning; therefore, identifying an individual's PON1 alloenzymes may play an important role in the treatment of patients suffering from OP intoxication.
Effects of occupational exposure to styrene on expression of adhesion molecule on leukocytes
Authors: Jahnová E , Tulinská J , Weissová S , Dusinská M , Fuortes L
Published: October 2002

Styrene is an indispensable chemical extensively used in plastic and synthetic rubber industries. Styrene is known to produce various types of hepatotoxic, neurotoxic, and genotoxic effects. Styrene may be immunotoxic by both direct and indirect mechanisms. Measurement of adhesion molecules is a new tool for the investigation of immune system modulation. The aim of this study was to evaluate the association of the expression of the adhesion molecules CD11a, CD11b, CD18, CD54, CD49d, and CD62L in white blood cells and levels of soluble adhesion molecules ICAM-1 and L-selectin in serum with occupational exposure to styrene. Analyses by flow cytometry revealed elevated levels of most of the assessed adhesion molecules on surfaces of lymphocytes, monocytes, and granulocytes. Expression of the adhesion receptor antigens CD11a on lymphocytes, CD11b on monocytes, and CD18 on granulocytes were unaffected. Workers exposed to styrene had decreased concentrations of sICAM-1 and no changes in concentrations of sL-selectin. Styrene exposure appears to increase activation of the immune system and alter leukocyte adherence. This interaction is a critical first step in immune stimulation and leukocyte–endothelial interaction.
Flow cytometric detection of apoptotic bone marrow cells with fractional DNA content after application of WR-2721, cyclophosphamide, cisplatin, and exposure of mice to gamma rays
Authors: Mazur L , Czyzewska A , Bochenek M
Published: October 2002

Little is known about the mechanisms of apoptosis triggered in normal cells of the haemopoietic system by the aminothiol WR-2721 (Amifostine), chemotherapeutic drugs, and ionizing radiation; thus, the present study was undertaken to evaluate the effects of WR-2721, cyclophosphamide (CP), cisplatin (CDDP), and 60Co gamma rays on induction of apoptotic DNA degradation in bone marrow cells. Adult male Swiss mice were treated with WR-2721 (400 mg/kg b.wt.), CP (200 mg/kg b.wt.), and CDDP (10 mg/ kg b.wt.), and exposed to 6 Gy 60Co gamma rays. Alterations in the number of apoptotic cells with fractional DNA content and also the cell cycle position of the non-apoptotic cells were determined in the bone marrow at 7 and 24 hours after treatment of mice with these agents, using flow cytometric assay of the controlled extraction of low-MW DNA from apoptotic cells. The chemotherapeutic drugs CP and CDDP and 60Co gamma rays triggered apoptosis and affected the cell cycle position of the non-apoptotic cells in the mouse bone marrow. The pretreatment of mice with WR-2721 resulted in the modulatory action of the aminothiol on induction of apoptotic cell death and changes in the cell cycle distribution of the non-apoptotic cells caused by the DNA-damaging agents. The patterns of changes in the frequency of apoptotic cells and the cell cycle position of the non-apoptotic cells, observed in the bone marrow, were dependent on the agent(s) applied and the time interval after application of the drug(s) and exposure of mice to gamma rays. Understanding of the mechanisms responsible for triggering of apoptotic cell death and disturbing of the cell cycle by the DNA-damaging agents, and modulation of the apoptotic and cell cycle pathways by the aminothiol WR-2721, can lead to more effective therapy and chemo-and radio-protection of normal cells.
Aseptic meningo-encephalitis related to dexibuprofen use in a patient with systemic lupus erythematosus: a case report with MR findings
Authors: Obermoser G , Bellmann R , Pfausler B , Schmutzhard E , Sepp N
Published: October 2002

We report of a 22-year-old woman with systemic lupus erythematosus (SLE) who was admitted to the intensive care unit (ICU) because of obtundation and a febrile illness. These symptoms had occurred after ingestion of 16 tablets of dexibuprofen.Cerebral magnetic resonance imaging (MRI) disclosed multiple hyperintense white matter abnormalities without gadolinium enhancement. No infectious origin or signs of a lupus flare were found.

Our report is the first description of MR findings in dexibuprofen-induced aseptic meningitis, which here is actually a case of meningo-encephalitis. Patients suffering from SLE show increased susceptibility to non steroidal anti-inflammatory drug (NSAID)-induced aseptic meningitis/encephalitis, an important differential diagnosis to be considered at the work-up of altered mental status.
Physical and chemical stability of methotrexate, cytarabine, and hydrocortisone in Elliott’s B Solution for intrathecal use
Authors: Trissel Lawrence A , King Krista M , Zhang Yanping , Wood Amy M
Published: October 2002

Intrathecal administration of methotrexate sodium and cytarabine with or without hydrocortisone sodium succinate is commonly used to treat metastatic spread of malignancies to the leptomeninges. The existing stability information on these drug combinations is inadequate due to the clinical use of increased doses of the drugs, as well as a change in the formulation of Elliott’s B Solution. The purpose of this study was to evaluate the physical and chemical stability of simulated high intrathecal doses of the subject drugs in the current formulation of Elliott’s B Solution.

Methotrexate sodium 6, 12, and 15 mg was combined with cytarabine 100 mg with and without hydrocortisone sodium succinate 100 mg using Elliott’s B Solution as the intrathecal vehicle. Samples were stored at 4 and 23°C and evaluated for physical and chemical stability over 48 h.

No precipitation or other evidence of physical instability was observed in any sample. Measured pH was 7.2- 7.5 in the samples and was sufficient to prevent methotrexate precipitation. High-performance liquid chromatography analysis found little or no loss of methotrexate and cytarabine in any sample and hydrocortisone at 4°C. At room temperature, hydrocortisone losses of 6-8% occurred in 48 h.

The high doses of methotrexate sodium and cytarabine with or without hydrocortisone sodium succinate evaluated in this study are physically and chemically stable for 48 h at 4 and 23°C in Elliott’s B Solution.
Compatibility screening of oxaliplatin during simulated Y-site administration with other drugs
Authors: Trissel Lawrence A , Saenz Christopher A , Ingram Delshalonda S , Ogundele Abayomi B
Published: October 2002

The physical compatibility of oxaliplatin (Eloxatin, Sanofi-Synthelabo, Malvern, PA) with 58 selected other drugs during simulated Y-site injection was evaluated by visual observation, turbidity measurement, and electronic particle content assessment when appropriate.

Five-milliliter samples of oxaliplatin 0.5 mg/mL in 5% dextrose injection were combined with 5 mL of 58 other drugs. The other test drugs included antineoplastics, analgesics, antihistamines, diuretics, steroids, and other supportive care drugs undiluted or diluted in 5% dextrose injection. Visual examinations were performed with the unaided eye in normal diffuse fluorescent light and using a Tyndall beam (high-intensity monodirectional light beam) to enhance visualization of small particles and low-level turbidity. The turbidity of each sample was measured as well. For samples with no visible incompatibility, the particle content was measured. Evaluation of the samples was performed initially and at 1 and 4 h after preparation.

Fifty-seven of the 58 test drugs were compatible with the oxaliplatin dilution during the 4 h observation period. However, diazepam resulted in precipitation. Oxaliplatin should not be administered simultaneously with diazepam.
The subjective response to linear fluorescent direct/indirect lighting systems
Authors: Houser KW , Tiller DK , Bernecker CA , Mistrick RG
Published: October 2002

This paper characterizes human subjective response to spatial distributions of light resulting from different uplight/downlight photometric distributions. An array of pendant-mounted linear fluorescent luminaires illuminated a 12.7×7.2 m room. Eleven light settings were established at constant horizontal illuminance, which differed in the percentage horizontal illuminance contribution from the uplight and downlight components. Two studies are reported where subjects evaluated the light settings using psychophysical assessments; the first study utilized paired comparisons and the second utilized semantic differential scaling. Findings include: 1) the walls and the ceiling contributed to the perception of overall brightness when the work plane illuminance was held constant, 2) the room appeared more spacious when more light was supplied indirectly, and 3) light settings where the indirect component had a horizontal illuminance contribution of 60% or more were favoured.
User attitudes toward occupant controlled office lighting
Authors: Moore T , Carter DJ , Slater AI
Published: October 2002

The use of locally addressable dimmable lighting systems has been examined in 14 open-plan office buildings. This paper discusses user attitudes toward control systems and the luminous conditions they produce. The majority of users are satisfied with both the quantity and quality of light on their workstations and are generally positive towards systems. This is despite large numbers of them working in illuminances significantly below current CIBSE recommendations. This indicates a significant potential for energy saving, since increased personal control leads to the use of lower lighting levels without detriment to occupants’ perceived lighting quality and visual comfort.
A Study of Bedside Ocular Ultrasonography in the Emergency Department
Authors: Blaivas Michael , Theodoro Daniel , Sierzenski Paul R.
Published: October 2002

The use of ocular ultrasonography for the evaluation of emergency patients has recently been described in the emergency medicine (EM) literature. There are a number of potential uses that may greatly aid the emergency physician (EP) and avoid lengthy consultation or other diagnostic tests. Objective: To examine the accuracy of bedside ultrasonography as performed by EPs for the evaluation of ocular pathology. Methods: This prospective, observational study took place in a high‐volume, suburban community hospital with an EM residency program. All patients arriving with a history of eye trauma or acute change in vision were eligible to participate in the study. A 10‐MHz linear‐array transducer was used for imaging. All imaging was performed through a closed eyelid, using water‐soluble ultrasound gel. Investigators filled out standardized data sheets and all examinations were taped for review. All ultrasound examinations were followed by orbital computed tomography or complete ophthalmologic evaluation from the ophthalmology service. Statistical analysis included sensitivity, specificity, and positive and negative predictive values. Results: Sixty‐one patients were enrolled in the study; 26 were found to have intraocular pathology on ultrasound. Of these, three had penetrating globe injuries, nine had retinal detachments, one had central retinal artery occlusion, and two had lens dislocations. The remaining pathology included vitreous hemorrhage and vitreous detachment. Emergency sonologists were in agreement with the criterion standard examination in 60 out of 61 cases. Conclusions: Emergency bedside ultrasound is highly accurate for ruling out and diagnosing ocular pathology in patients presenting to the emergency department. Further, it accurately differentiates between pathology that needs immediate ophthalmologic consultation and that which can be followed up on an outpatient basis.
American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors as Adjuvant Therapy for Women With Hormone Receptor–Positive Breast Cancer: Status Report 2002
Authors: Winer Eric P. , Hudis Clifford , Burstein Harold J. , Chlebowski Rowan T. , Ingle James N. , Edge Stephen B. , Mamounas Eleftherios P. , Gralow Julie , Goldstein Lori J. , Pritchard Kathleen I. , Braun Susan , Cobleigh Melody A. , Langer Amy S. , Perotti Judy , Powles Trevor J. , Whelan Timothy J. , Browman George P.
Published: October 2002

OBJECTIVE: To conduct an evidence-based technology assessment to determine whether the routine use of anastrozole or any of the aromatase inhibitors in the adjuvant breast cancer setting is appropriate for broad-based conventional use in clinical practice.

POTENTIAL INTERVENTIONS: Anastrozole, letrozole, and exemestane.

OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit.

EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics and is detailed in the text. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO)–prescribed technology assessment procedure was followed.

BENEFITS/HARMS: The ASCO panel recognizes that a woman and her physician’s decision regarding adjuvant hormonal therapy is complex and will depend on the importance and weight attributed to information regarding both cancer and non–cancer-related risks and benefits.

CONCLUSION: The panel was influenced by the compelling, extensive, and long-term data available on tamoxifen. Overall, the panel considers the results of the Arimidex (anastrozole) or Tamoxifen Alone or in Combination (ATAC) trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time (May 2002). A 5-year course of adjuvant tamoxifen remains the standard therapy for women with hormone receptor–positive breast cancer. The panel recommends that physicians discuss the available information with patients, and, in making a decision, acknowledge that treatment approaches can change over time. Individual health care providers and their patients will need to come to their own conclusions, with careful consideration of all of the available data. (Specific questions addressed by the panel are summarized in Appendix 3.)

VALIDATION: The conclusions of the panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

SPONSOR: American Society of Clinical Oncology.
Lead-In Phase to Randomized Trial of Motexafin Gadolinium and Whole-Brain Radiation for Patients With Brain Metastases: Centralized Assessment of Magnetic Resonance Imaging, Neurocognitive, and Neurologic End Points
Authors: Mehta Minesh P. , Shapiro William R. , Glantz Michael J. , Patchell Roy A. , Weitzner Michael A. , Meyers Christina A. , Schultz Christopher J. , Roa Wilson H. , Leibenhaut Mark , Ford Judith , Curran Walter , Phan See , Smith Jennifer A. , Miller Richard A. , Renschler Markus F.
Published: October 2002

PURPOSE: Motexafin gadolinium is a redox mediator that selectively targets tumor cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect of radiation therapy. This lead-in phase to a randomized trial served to evaluate radiologic, neurocognitive, and neurologic progression end points and to evaluate the safety and radiologic response of motexafin gadolinium administered concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the treatment of brain metastases.

PATIENTS AND METHODS: Motexafin gadolinium (5.0 mg/kg/d for 10 days) was administered before each radiation treatment in this prospective international trial. Patients were evaluated by MRI, neurologic examinations, and neurocognitive tests. Prospective criteria and centralized review procedures were established for radiologic, neurocognitive, and neurologic progression end points.

RESULTS: Twenty-five patients with brain metastases from lung (52%) and breast (24%) cancer, recursive partitioning analysis class 2 (96%), and an average of 11 brain metastases were enrolled. Neurocognitive function was highly impaired at presentation. Motexafin gadolinium was well tolerated. Freedom from neurologic progression was 77% at 1 year. Median survival was 5.0 months. In 29% of patients, the cause of death was brain metastasis progression. The radiologic response rate was 68%. Motexafin gadolinium’s tumor selectivity was established with MRI.

CONCLUSION: (1) Centralized neurologic progression scoring that incorporated neurocognitive tests was implemented successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control, measured by radiologic response rate, neurologic progression, and death caused by progression of brain metastasis, seemed to be improved compared with historical results. A randomized phase III trial using these methods for evaluation of efficacy has just been completed.
Second Malignant Neoplasms Among Long-Term Survivors of Hodgkin’s Disease: A Population-Based Evaluation Over 25 Years
Authors: Dores Graça M. , Metayer Catherine , Curtis Rochelle E. , Lynch Charles F. , Clarke E. Aileen , Glimelius Bengt , Storm Hans , Pukkala Eero , van Leeuwen Flora E. , Holowaty Eric J. , Andersson Michael , Wiklund Tom , Joensuu Timo , van’t Veer Mars B. , Stovall Marilyn , Gospodarowicz Mary , Travis Lois B.
Published: October 2002

PURPOSE: To quantify the relative and absolute excess risks (AER) of site-specific second cancers, in particular solid tumors, among long-term survivors of Hodgkin’s disease (HD) and to assess risks according to age at HD diagnosis, attained age, and time since initial treatment.

PATIENTS AND METHODS: Data from 32,591 HD patients (1,111 25-year survivors) reported to 16 population-based cancer registries in North America and Europe (1935 to 1994) were analyzed.

RESULTS: Two thousand one hundred fifty-three second cancers (observed-to-expected ratio [O/E] = 2.3; 95% confidence interval [CI] = 2.2 to 2.4), including 1,726 solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) were reported. Cancers of the lung (observed [Obs] = 377; O/E = 2.9), digestive tract (Obs = 376; O/E = 1.7), and female breast (Obs = 234; O/E = 2.0) accounted for the largest number of subsequent malignancies. Twenty-five years after HD diagnosis, the actuarial risk of developing a solid tumor was 21.9%. The relative risk of solid neoplasms decreased with increasing age at HD diagnosis, however, patients aged 51 to 60 years at HD diagnosis sustained the highest cancer burden (AER = 79.2/10,000 patients/year). After a progressive rise in relative risk and AER of all solid tumors over time, there was an apparent downturn in risk at 25 years. Temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, female breast, bladder, thyroid, and bone/connective tissue were suggestive of a radiogenic effect.

CONCLUSION: Significantly increased risks of second cancers were observed in all HD age groups. Although significantly elevated risks of stomach, female breast, and uterine cervix cancers persisted for 25 years, an apparent decrease in relative risk and AER of solid tumors at other sites is suggested.
International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy
Authors: Graefen Markus , Karakiewicz Pierre I. , Cagiannos Ilias , Quinn David I. , Henshall Susan M. , Grygiel John J. , Sutherland Robert L. , Stricker Phillip D. , Klein Eric , Kupelian Patrick , Skinner Donald G. , Lieskovsky Gary , Bochner Bernard , Huland Hartwig , Hammerer Peter G. , Haese Alexander , Erbersdobler Andreas , Eastham James A. , de Kernion Jean , Cangiano Thomas , Schröder Fritz H. , Wildhagen Mark F. , van der Kwast Theo H. , Scardino Peter T. , Kattan Michael W.
Published: October 2002

PURPOSE: We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents.

METHODS: Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification–based risk quadrants were compared with actual Kaplan-Meier plots.

RESULTS: The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low–risk group), 39% (intermediate-high–risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram.

CONCLUSION: The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.
Do Biocides Select for Antibiotic Resistance?
Authors: Russell A D
Published: October 2002

Some similarities exist between bacterial resistance to antibiotics and to biocides, and gram-negative bacteria that have developed resistance to cationic biocides may also be insusceptible to some antibiotics. Outer membrane changes are believed to be responsible for this non-specific increase in resistance. Efflux, another important resistance mechanism, is associated with the qacA/B gene system in staphylococci that confers low-level resistance to cationic agents including chlorhexidine salts and quaternary ammonium compounds. It has been proposed that the introduction into clinical practice of Chlorhexidine and quaternary ammonium compounds has resulted in the selection of staphylococci containing qacA genes on multiresistance plasmids. A linkage between low-level resistance to triclosan and to antibiotics has recently been claimed to occur in Escherichia coli, with the bisphenol selecting for chromosomally-mediated antibiotic resistance. A key issue in many studies has been the use of biocides at concentrations significantly below those used clinically. It remains to be determined how an increase to low-level resistance to cationic biocides can be held responsible for the selection of antibiotic-resistant bacteria.