bluuebunny/crossref_metadata_2025 huggingface dataset:
Interval training as an alternative modality to continuous exercise in patients with COPD
Authors: Vogiatzis I. , Nanas S. , Roussos C.
Published: October 2002

Understanding of what constitutes a training load adequate to induce training effects in patients with chronic obstructive pulmonary disease (COPD) is still evolving. The present study investigated whether interval training (IT) is effective in terms of inducing measurable improvements in physiological response and compared its effects on exercise tolerance (ET) and quality of life to those of continuous training (CT).

Thirty-six COPD patients, with a forced expiratory volume in one second of 45±4% of the predicted value (mean±sem), were randomly assigned to CT (exercise at 50% of baseline peak work-rate) or IT (work for 30 s at 100% of peak work-rate alternating with 30‐s rest intervals) groups that cycled 40 min·day−1and 2 days·week−1for 12 weeks.

After training, both groups showed significantly improved ET (IT, 57±6 to 71±8 W; CT, 57±5 to 70±6 W) and total quality-of-life score of the Chronic Respiratory Disease Questionnaire (IT, 77±3 to 88±2; CT, 78±3 to 93±2). At identical levels of exercise, minute ventilation was significantly reduced (IT, 35.8±2.5 to 31.7±2.5 L·min−1; CT, 36.4±2.7 to 32.5±2.7 L·min−1). The magnitude of improvement in these variables was not significantly different among groups.

The present data expand on the principles of exercise prescription for chronic obstructive pulmonary disease patients by demonstrating that interval training elicits substantial training effects, which are similar in magnitude to those produced by continuous training at half the exercise intensity but double the exercise time.
Screening for α1‐Pi deficiency in patients with lung diseases
Authors: Wencker M. , Marx A. , Konietzko N. , Schaefer B. , Campbell E.J.
Published: October 2002

In patients with pulmonary emphysema, studies have reported 2–3% of individuals with severe α1‐Pi deficiency. The aims of this study were to evaluate the accuracy of a new method for quantifying α1‐Pi through phenotyping from dried blood spots (DBS) and to test the hypothesis that the screening of a population at risk increases the detection rate for severe α1‐Pi deficiency.

The accuracy of phenotyping results from DBS was compared to conventional methods in a total of 555 individuals. In a prospective study 1,060 patients with chronic lung disease were screened for α1‐Pi deficiency using DBS.

The validation of the phenotyping method from DBS showed an accuracy of 100%. Out of 1,060 tested patients, none had a severe PiZ deficiency and only 3 had PiSZ, whilst 36 (3.34%) individuals were identified as heterozygous for PiMS and 39 (3.68%) for PiMZ.

No patients with severe α1‐Pi deficiency could be detected in this population and the frequency of PiMS or PiMZ detected was similar to that of the normal population. Thus, the screening of an unselected population of chronic obstructive pulmonary disease and asthma patients may not detect a large number of individuals with severe α1‐Pi deficiency.
Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone
Authors: Rao R , Gregson RK , Jones AC , Miles EA , Campbell MJ , Warner JO
Published: October 2002

Inhaled steroids are frequently used in childhood asthma, but concerns based on limited objective evidence remain, regarding long-term side-effects. In this study the systemic effects of standard doses of inhaled steroids in childhood asthma were assessed, comparing beclomethasone dipropionate (BDP) with fluticasone propionate (FP). The study was prospective, randomized and double-blind. Twenty-three steroid-naive children with moderately severe asthma, aged 5-10 yrs, were allocated either BDP (400 microg x day(-1) or FP (200 microg x day(-1)) using a metered-dose inhaler with a spacer. Asthma control was assessed at regular intervals over 20 months. Fasting morning blood and overnight urine samples were collected for estimation of serum cortisol, serum 1-carboxyterminal telopeptide (ICTP), serum osteocalcin and urine deoxypyridinoline (DPD). Bone mineral density (BMD) was measured at each visit. None of the markers of bone turnover showed any change during the study period. BMD increased at normal rates with age. Serum cortisol significantly decreased on BDP, but not on FP. A significant difference in growth rates was found between the groups, with a slower rate of growth towards the end of the observation period in the BDP group. In conclusion when taken in a relatively modest dose over a period of time, beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma. These systemic effects were not seen with an equipotent dose of fluticasone propionate.
Effects of tongue electrical stimulation on pharyngeal mechanics in anaesthetized patients with obstructive sleep apnoea
Authors: Isono S , Tanaka A , Nishino T
Published: October 2002

The tongue plays a significant role in the maintenance of a patent airway. The purpose of this study was to examine the effects of tongue musculature contraction on the static mechanical properties of the pharynx in patients with obstructive sleep apnoea (OSA). During hyperventilation-induced apnoea in seven OSA patients anaesthetized with sevoflurane, the static pressure/area relationships of the oropharynx were obtained by means of step changes in airway pressure while endoscopically measuring cross-sectional area. At each airway pressure, the tongue was electrically stimulated via electrodes placed bilaterally. Tongue electrical stimulation (TES) did not further dilate the oropharyngeal area at higher airway pressure (3.2+/-1.9 versus 3.0+/-2.1 cm2), although the narrowed oropharyngeal area at lower airway pressures increased during TES (0.8+/-9.0) versus 1.7+/-1.8 cm2, p<0.05). Accordingly, the slope of the pressure/area relationship decreased during TES (0.24+/-0.20 versus 0.12+/-0.09 cm2 x cm H2O(-1), p<0.05). In conclusion, electrical stimulation of the tongue stiffens the retroglossal airway wall in patients with obstructive sleep apnoea.
Detection of SV40 like viral DNA and viral antigens in malignant pleural mesothelioma
Authors: Ramael M , Nagels J , Heylen H , De Schepper S , Paulussen J , De Maeyer M , Van Haesendonck C
Published: October 2002

This study investigated the presence of simian vacuolating virus 40 (SV40) deoxyribonucleic acid (DNA) in malignant pleural mesothelioma, non-neoplastic mesothelium and pleural carcinoma metastasis and correlated these data with immunohistochemistry for SV40 viral antigens. The novel Primed In Situ (PRINS) method was applied to detect the presence of SV40 DNA in situ in tissue sections of malignant mesothelioma (n = 25), non-neoplastic mesothelium (n = 30) and pleural carcinoma metastasis (n = 30). Immunohistochemistry with an SV40-specific antibody was applied for detection of the SV40 viral antigen in the same material. SV40 DNA and expression of one of the viral proteins (small t-antigen) was found in approximately 60% of the investigated mesothelioma cases in contrast to non-neoplastic mesothelium and carcinoma metastasis that were negative for both SV40 DNA and SV40 viral antigens. These results suggest that simian vacuolating virus 40 deoxyribonucleic acid may be biologically active as there was also immunoreactivity for simian vacuolating virus 40 viral antigen in those cases positive for simian vacuolating virus 40 deoxyribonucleic acid with the primed in situ reaction. Simian vacuolating virus 40 viral deoxyribonucleic acid and antigens may be potential markers for neoplastic mesothelium that may prove useful in the rather difficult histopathological differential diagnosis between malignant mesothelioma and reactive mesothelium or pleural carcinoma.
The distal airways: are they important in asthma?
Authors: Kraft M
Published: October 2002

Although the airways of <2 mm in diameter have been dubbed the "quiet zone", they do not appear to be so in asthma. Physiological and pathological evidence suggests that the small airways and lung parenchyma participate in asthma pathogenesis, and may explain many of the clinical observations noted. This review presents this evidence, beginning with physiological evidence, followed by pathology and last by imaging studies that evaluate the distal lung. Seminal physiological studies date back to the 1960s, with significant progress in the area of airway smooth muscle and its contribution to airways responsiveness noted over the last several years. The use of bronchoscopy in clinical studies has complemented the autopsy studies in advancing knowledge about airway structural changes appreciated in asthma in the small airways and lung parenchyma. These pathological studies have allowed validation of the physiological, and more recently the imaging studies performed to evaluate this compartment of the lung in asthma. Thus, the evidence suggests that the small airways and parenchyma contribute significantly to asthma pathogenesis. The challenge now lies in evaluating this compartment in the context of its value as a therapeutic target in asthma.
Increasing dose of methylprednisolone pulse therapy treats desquamative interstitial pneumonia in a child
Authors: Paul K , Klettke U , Moldenhauer J , Muller KM , Kleinau I , Magdorf K , Wahn U
Published: October 2002

A 10 yr old male with hypoxaemia, progressive infiltration on the chest radiograph and biopsy-proven desquamative interstitial pneumonia was treated with daily oral prednisolone for 6 months. Intravenous methylprednisolone pulses were concomitantly administered in doses averaging 10 mg x kg body weight(-1) on three consecutive days every 4-6 weeks. After 6 months improvement could be noted and oral steroids were stopped, while pulse therapy continued. Three months later, when seven pulses had been administered, a relapse occurred and the clinical status deteriorated. Instead of reinstating daily systemic steroids, the dose of methylprednisolone pulses was increased to 20 mg x kg body weight(-1) i.v. given on three consecutive days and repeat pulses every 4 weeks. This was followed by continuous improvement. After 24 months corticosteroid pulses were terminated. Normal lung function, serum lactate dehydrogenase, blood gases upon exertion and regular development was achieved. During the course of treatment, the child has grown 10 cm. It is concluded that the effect of corticosteroid pulse therapy on interstitial lung disease in childhood is dose-dependent and that the dose can be adjusted to the effect observed.
Cardiac cause of hypoxaemia in a kyphoscoliotic patient
Authors: Herry I , Iung B , Piechaud JY , Saidi F , Mayaud C , Boissonnas A
Published: October 2002

This report presents the case of a 73 yr-old female in whom kyphoscoliosis, osteoporotic vertebra compression fractures and sternal injury resulted in severe respiratory failure and hypoxaemia. Pulmonary function testing showed moderate restrictive pattern and rare mismatches were found on lung ventilation/perfusion scanning. Transoesophageal echocardiography with contrast studies showed abnormal anatomic mediastinal interactions which led to right-to-left interatrial shunt, through patent foremen ovale. First-intention treatment, because of orthopaedic and respiratory surgical restraints, was to close the shunt using transcatheter devices. Follow-up after 6 months demonstrated that these interauricular umbrella devices corrected arterial hypoxaemia. True right-to-left interatrial shunts can be found in kyphoscoliotic patients, as a result of thoracic deformation, and can be safely treated with percutaneous trancatheter closure.
The message from the World Asthma Meeting. The Working Groups of the World Asthma Meeting, held in Barcelona, Spain, December 9-13, 1998
Authors: Sterk PJ , Buist SA , Woolcock AJ , Marks GB , Platts-Mills TA , von Mutius E , Bousquet J , Frew AJ , Pauwels RA , Ait-Khaled N , Hill SL , Partridge MR
Published: October 2002

The 1998 World Asthma Meeting (WAM) has been the first multidisciplinary event aimed to consider asthma as a global public health problem in children and adults. The purpose of the meeting was to present state-of-the-art scientific information and to make recommendations on the research agenda for the coming years. Five Working Groups of invited experts were appointed to pin-point the established knowledge and the important questions in the areas of epidemiology, prevention, pathogenesis, management, and education. Their reports were discussed during the final plenary session, and are forming the current proceedings of the meeting. The message of the World Asthma Meeting provides a research agenda supported by the major international bodies involved in this disease. An integrated approach is considered to be essential in order to improve the prevention and care of asthma in all countries of the world.
Estimating anisotropy parameters and traveltimes in the τ‐pdomain
Authors: van der Baan Mirko , Kendall J. Michael
Published: October 2002

The presence of anisotropy influences many aspects of seismic wave propagation and has therefore implications for conventional processing schemes. To estimate the anisotropy, we need both forward modelling and inversion tools. Exact forward modelling in anisotropic media is generally done by raytracing. However, we present a new and fast method, using the τ‐p transform, to calculate exact P and SV reflection moveout curves in stratified, laterally homogeneous, anisotropic media which requires no ray tracing. Results are exact even if the SV‐waves display cusps. In addition, we show how the same method can be used for parameter estimation.

Since inversion for anisotropic parameters is very nonunique, we develop expressions requiring only a reduced number of parameters. Nevertheless, predictions using these expressions are more accurate than Taylor series expansions and are also able to handle cusps in the SV traveltime curves. In addition, layer stripping is a linear process. Therefore, both effective (average) and local (interval) estimates can be obtained.
Electromagnetic induction in a fully 3‐D anisotropic earth
Authors: Weiss Chester J. , Newman Gregory A.
Published: October 2002

The bulk electrical anisotropy of sedimentary formations is a macroscopic phenomenon which can result from the presence of porosity variations, laminated shaly sands, and water saturation. Accounting for its effect on induction log responses is an ongoing research problem for the well‐logging community since these types of sedimentary structures have long been correlated with productive hydrocarbon reservoirs such as the Jurassic Norphlet Sandstone and Permian Rotliegendes Sandstone. Presented here is a staggered‐grid finite‐difference method for simulating electromagnetic (EM) induction in a fully 3‐D anisotropic medium. The electrical conductivity of the formation is represented as a full 3 × 3 tensor whose elements can vary arbitrarily with position throughout the formation. To demonstrate the validity of this approach, finite‐difference results are compared against analytic and quasi‐analytic solutions for tractable 1‐D and 3‐D model geometries. As a final example, we simulate 2C–40 induction tool responses in a crossbedded aeolian sandstone to illustrate the magnitude of the challenge faced by interpreters when electrical anisotropy is neglected.
Detection of reservoirs from normalized full gradient of gravity anomalies and its application to Shengli oil field, east China
Authors: Zeng Hualin , Meng Xiaohong , Yao Changli , Li Xiaomeng , Lou Hai , Guang Zhining , Li Zhiping
Published: October 2002

We present how to detect reservoirs by the 3‐D normalized full gradient (NFG) of gravity anomalies constrained by seismic and drilling data. The normalized full gradient represents the full gradient of the gravity anomaly at a point divided by the average of the full gradient at the datum. The closed minima on an NFG map indicate the occurrence and horizontal locations of the centers of mass of density anomalies related to oil reservoirs. This information can be used to select well locations in an oil field. On a cross‐section, the closed minima can be used to estimate the depth to centers of mass of possible hydrocarbon reservoirs.

Some characteristics of the NFG are calculated for a hypothetical case of an anticline saturated with oil and gas. The relationship of these characteristics to the geometry and physical parameters of the anticline is studied. Modeling studies show that the NFG largely depends on the number of terms in the Fourier series used to calculate it, and it closely related to the length of the gravity profile or the size of the study area.

Applying the NFG method to the Shengli oil field, i.e., using closed minima of NFG alongside drilling data, showed an effectiveness of up to 70%. These results were used to select well locations with the result that some high‐production gas‐bearing strata were discovered by drilling.
Characterization of a coalesced, collapsed paleocave reservoir analog using GPR and well‐core data
Authors: McMechan George A. , Loucks Robert G. , Mescher Paul , Zeng Xiaoxian
Published: October 2002

The three‐dimensional architecture, spatial complexity, and pore‐type distribution are mapped in a near‐surface analog of a coalesced, collapsed paleocave system in the Lower Ordovician Ellenburger Group near the city of Marble Falls in central Texas. The surface area of the site has dimensions of about 350 × 1000 m. The data collected include about 12 km of 50‐MHz ground‐penetrating radar (GPR) data arranged in a grid of orthogonal lines, 29 cores of about 15‐m length, and detailed facies maps of an adjacent quarry face. Electrical property measurements along with detailed core descriptions were the basis of integrated interpretation of the GPR data. Three main GPR facies are defined on the basis of degree of brecciation in the corresponding cores: undisturbed host rock, disturbed host rock, and paleocave breccia. This GPR facies division defined the major paleocave trends and the distribution of porosity types, which correlate with reservoir quality. Highly brecciated zones are separated by disturbed and undisturbed host rock. The breccia bodies that outline the trend of collapsed cave passages are up to 300 m wide; the intervening intact areas between breccias are up to 200 m wide. Understanding the breccia distribution in a reservoir analog will help in defining strategies for efficient development of coalesced, collapsed paleocave reservoirs.
Earth‐surface effects on the temperature distribution in the earth's crust due to magma intrusion
Authors: Aldaz Rafael , Martin Pablo
Published: October 2002

We have carried out a 2‐D analysis for the isotherm evolution resulting from the intrusion of a hot dike in a cold rock, including earth‐surface effects. Our analysis differs from previous analysis in that we include the influence of the earth surface in the isotherm evolution. The analysis in this case is more complex than in the usual 1‐D case. A relatively simple solution has been found despite the additional complexity due to the depth dependence. The analysis carried out leads to analytic solutions for the isothermal evolution in time. A good view of this evolution is given by the curve envelope of the isothermals. One of the aims of this analysis is to determine the location of gold veins in the Callao mines, Venezuela. The 400°C and 500°C isotherms have been studied in detail because of their importance for the determination of the gold‐vein sites. One important difference between our analysis and previous 1‐D treatments is that our analysis shows that the isotherms move further away from the dike with depth—a result borne out by mapping in the Callao mines.
Migration velocity analysis from locally coherent events in 2‐D laterally heterogeneous media, Part II: Applications on synthetic and real data
Authors: Chauris Hervé , Noble Mark S. , Lambaré Gilles , Podvin Pascal
Published: October 2002

We demonstrate a method for estimating 2‐D velocity models from synthetic and real seismic reflection data in the framework of migration velocity analysis (MVA). No assumption is required on the reflector geometry or on the unknown background velocity field, provided that the data only contain primary reflections/diffractions. In the prestack depth‐migrated volume, locations where the reflectivity exhibits local coherency are automatically picked without interpretation in two panels: common image gathers (CIGs) and common offset gathers (COGs). They are characterized by both their positions and two slopes. The velocity is estimated by minimizing all slopes picked in the CIGs.

We test the applicability of the method on a real data set, showing the possibility of an efficient inversion using (1) the migration of selected CIGs and COGs, (2) automatic picking on prior uncorrelated locally coherent events, (3) efficient computation of the gradient of the cost function via paraxial ray tracing from the picked events to the surface, and (4) a gradient‐type optimization algorithm for convergence.
3‐D eikonal solvers: First‐arrival traveltimes
Authors: Kim Seongjai
Published: October 2002

The article is concerned with the development and comparison of three different algorithms for the computation of first‐arrival traveltimes: the fast marching method (FMM), the group marching method (GMM), and a second‐order finite‐difference eikonal solver. GMM is introduced as a variant of FMM. It proceeds the solution by advancing a selected group of grid points at a time, rather than sorting the solution in the narrow band to march forward a single grid point. The second‐order eikonal solver studied in the article is an expanding‐box, essentially nonoscillatory scheme for which the stability is enforced by the introduction of a down ‘n’ out marching and a post‐sweeping iteration.

Techniques such as the maximum angle condition, the average normal velocity, and cache‐based implementation are introduced for the algorithms to improve the numerical accuracy and efficiency. The algorithms are implemented for solving the eikonal equation in 3‐D isotropic media, and their performances are compared. GMM is numerically verified to be faster than FMM. However, the second‐order algorithm turns out to be superior to these first‐order level‐set methods in both accuracy and efficiency; the incorporation of average normal velocity improves accuracy dramatically for the second‐order scheme.
Seismic trace interpolation in the f‐x‐y domain
Authors: Wang Yanghua
Published: October 2002

Seismic trace interpolation is implemented as a 2‐D (x, y) spatial prediction, performed separately on each frequency (f) slice. This so‐called f‐x‐y domain trace interpolation method is based on the relation that the linear prediction (LP) operator estimated at a given frequency may be used to predict data at a higher frequency but a smaller trace spacing. The relationship originally given for thef‐x domain trace interpolation is successfully extended to the f‐x‐y domain. The extension is achieved by masking the data samples selectively from the input frequency slice to design the LP operators. Two interpolation algorithms using the full‐step and the fractional‐step predictions, respectively, are developed. Both methods use an all‐azimuth prediction in the x‐y domain, but the fractional‐step prediction method is computationally more efficient. While the interpolation method can be applied to a common‐offset cube of 3‐D seismic, it can also be applied to 2‐D seismic traces for prestack data processing. Synthetic and real data examples demonstrate the capability of the interpolation method.
Seismic modeling
Authors: Carcione José M. , Herman Gérard C. , ten Kroode A. P. E.
Published: October 2002

Seismic modeling is one of the cornerstones of geophysical data processing. We give an overview of the most common modeling methods in use today: direct methods, integral‐equation methods, and asymptotic methods. We also discuss numerical implementation aspects and present a few representative modeling examples for the different methods.
Thought and Language Index: an instrument for assessing thought and language in schizophrenia
Authors: Liddle Peter F. , Ngan Elton T. C. , Caissie Stephanie L. , Anderson Cameron M. , Bates Alan T. , Quested Digby J. , White Richard , Weg Rowena
Published: October 2002

Background

Subtle formal thought disorders are difficult to quantify. Their relationship to florid thought disorder is unknown.

Aims

To assess the interrater reliability, sensitivity and factor structure of a new assessment instrument, the Thought and Language Index (TLI), and to determine if minor aberrations detectable in the speech of healthy individuals are related to the more severe formal thought disorders characteristic of schizophrenia.

Method

Interrater reliability was evaluated by determining the intraclass correlation for the ratings by five assessors. Factor analysis of the TLI scores of 87 patients was performed, and TLI scores in matched patients and controls were compared.

Results

The intraclass correlation was good for individual TLI items, and excellent for sub-scale scores. Factor analysis identified three groups of approximately orthogonal disorders. Mild speech aberrations were observed in healthy participants and in patients with schizophrenia. The prevalence of mild aberrations was correlated with the prevalence of definite formal thought disorders.

Conclusions

The TLI is reliable and capable of detecting subtle disorders. Some mild aberrations occurring in the speech of healthy individuals appear to be attenuated forms of the florid disorders characteristic of schizophrenia.
Dropping out of care: inappropriate terminations of contact with community-based psychiatric services
Authors: Rossi Alberto , Amaddeo Francesco , Bisoffi Giulia , Ruggeri Mirella , Thornicroft Graham , Tansella Michele
Published: October 2002

Background

Few studies have investigated factors which predict inappropriate terminations (drop-out) of clinical contact with mental health services.

Aims

To identify patient and treatment characteristics associated with dropping out of contact with community-based psychiatric services (CPS).

Method

A 3-month cohort of patients attending the CPS was followed up for 2 years, to identify drop-outs.

Results

We identified 495 patients who had had at least one psychiatric contact of whom 261 had complete ratings for the Global Assessment of Functioning and the Verona Service Satisfaction Scale. In the year after the index contact, 70 terminated contact with the CPS; of these, 44 were rated as having inappropriate terminations (the ‘drop-out’ group) and 26 had appropriate terminations of contact. Drop-outs were younger, less likely to be married and their previous length of contact with services was shorter. No drop-outs had a diagnosis of schizophrenia. Multivariate analysis revealed predictors of dropping out.

Conclusions

In a CPS targeted to patients with severe mental illnesses, those who drop out of care are younger patients without psychoses who are generally satisfied with their treatment.
Small‐volume Resuscitation with HBOC‐201: Effects on Cardiovascular Parameters and Brain Tissue Oxygen Tension in an Out‐of‐hospital Model of Hemorrhage in Swine
Authors: Morabito Diane , Hemphill J. Claude , Erickson Vanessa , Holcroft John J. , Derugin Nikita , Knudson M. Margaret , Manley Geoffrey T. , Lee Seong K.
Published: October 2002

Objective: Hemoglobin‐based oxygen carriers, such as HBOC‐201, offer several potential advantages over conventional resuscitation solutions or banked blood in the acute treatment of hemorrhagic shock. While previous studies with some hemoglobin solutions revealed vasoactive effects resulting in decreased oxygen delivery, these investigations were performed without directly measuring vital tissue oxygenation. The authors tested the hypothesis that a small‐volume bolus of HBOC‐201 would improve and sustain brain tissue oxygen tension (PbrO 2) without adverse effects on cardiovascular end‐points, when used in an acute out‐of‐hospital hemorrhage model. Methods: Male Yorkshire swine (n = 7) were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg while monitoring standard hemodynamic parameters. In addition, Clark‐type polarographic probes were directly inserted into brain tissue to measure PbrO2. Following institution of high‐flow oxygen (FiO2= 1.0), resuscitation was performed with a bolus infusion of HBOC‐201 (6 mL/kg). Swine were observed for two hours. Results: Cardiac output (CO), MAP, pulmonary artery diastolic pressure (PAD), and PbrO2 all decreased significantly with hemorrhage (p < 0.05). Immediately following resuscitation with HBOC‐201 (mean volume = 239 mL), MAP and CO were restored to 83% and 84% of baseline levels, respectively. PbrO2 increased significantly after treatment with HBOC‐201, surpassing baseline levels by 66%. PAD rose above baseline levels during observation, but this increase was not significantly different from baseline levels (24.0 mm ± 4.1 vs. 22.7 mm ± 7.4). Conclusions: Small‐volume resuscitation with HBOC‐201 rapidly restored hemodynamic parameters and PbrO2 following severe hemorrhage without detrimental vasoactive effects and without compromise to directly monitored brain tissue oxygenation. The results of this preliminary study demonstrate that HBOC‐201 could potentially improve current resuscitation measures and that further investigations with HBOC‐201 are warranted.
The Effects of a High‐potency Topical Steroid on Cutaneous Healing of Burns in Pigs
Authors: Singer Adam J. , McClain Steve A.
Published: October 2002

Objective: Burns are dynamic injuries that tend to progress over the course of several days. Steroids inhibit the formation of vasoconstrictive prostanoids that may contribute to this progression of injury. The authors hypothesized that adding topical steroids to a standard antimicrobial agent would reduce the progression of burns and accelerate reepithelialization without increasing infection rates. Methods: This was a prospective, blinded, controlled, experimental trial. Forty‐eight standardized second‐degree burns were created by applying an aluminum bar preheated to 80°C to the flanks of isoflurane‐anesthetized young pigs for 20 seconds. Three equal sets of 16 burns were randomly treated with silver sulfadiazine cream (SSD), clobetasol propionate 0.05% (CP), or both (SSD+CP). Daily dressing changes were performed for 14 days. Full‐thickness biopsies were taken after injury and at one, two, seven, ten, and 14 days for blinded histopathological evaluation using hematoxylin and eosin (H&E) staining. The primary outcome was the % reepithelialization (REP) calculated by dividing the length of the neoepidermis by the section's total length (interobserver correlation = 0.99). Depth of injury was measured for each dermal element (collagen; epithelial, mesenchymal, and vascular cells; and vessel thrombosis). Comparisons across groups were performed using oneway analysis of variance (ANOVA). A repeated‐measures ANOVA was used to compare injury depths over time. This study had 80% power to detect a 33‐percentage point difference in REP across groups (two‐tailed alpha = 0.05). Results: Pretreatment burn depths were similar across groups. While burn depth changed over time, there was no difference between the groups in burn injury progression. There was no difference across the groups in REP or infection rates at all times. Conclusions: Addition of a potent topical steroid to standard antimicrobial topical agents does not reduce burn depth or accelerate reepithelialization after burns.
Evolution of Academic Emergency Medicine over a Decade (1991‐2001)
Authors: Gallagher E. John
Published: October 2002

Objective: To test the hypothesis that emergency medicine (EM) has made significant, quantifiable progress within U.S. academic medicine over the past ten years, 1991‐2001. Methods: Baseline (7/1/1991) and comparison (7/1/2001) data sets contained all Liaison Committee on Medical Education (LCME)‐accredited schools, Association of Academic Chairs of Emergency Medicine (AACEM)‐recognized academic departments of EM, Residency Review Committee (RRC)‐accredited EM residencies, and Association of American Medical Colleges (AAMC)‐designated academic medical centers. The increase over ten years in the two primary variables of academic departmental status, and EM residencies located at academic medical centers, was examined in the aggregate, then stratified by medical schools grouped by academic rank. Differences over time are expressed as simple proportions, bounded by 95% confidence intervals (95% CIs). Results: Between 1991 and 2001, the proportion of academic departments of EM at medical schools increased from 18% to 48% (95% CI for difference of 30%= 19% to 41%). The proportion of EM residencies at academic medical centers increased from 42% to 66% (95% CI for a difference of 24%= 11% to 36%). The largest increment of 37% (95% CI = 22% to 52%) in academic departments of EM, and of 36% (95% CI = 20% to 52%) in EM residencies located at academic medical centers, occurred within medical schools whose academic rank was above the median. Conclusions: A quantitatively and statistically significant increase in academic departments of EM within medical schools and EM residency programs at academic medical centers has occurred over the past decade. Half of all medical schools now have academic departments of EM, and two‐thirds of academic medical centers house EM residency programs. This has taken place largely within institutions whose academic ranking places them among the top half of all U.S. medical schools.
Comparison of the Efficacy of Local Therapies for Localized Prostate Cancer in the Prostate-Specific Antigen Era: A Large Single-Institution Experience With Radical Prostatectomy and External-Beam Radiotherapy
Authors: Kupelian Patrick A. , Elshaikh Mohamed , Reddy Chandana A. , Zippe Craig , Klein Eric A.
Published: October 2002

PURPOSE: To review biochemical relapse-free survival (bRFS) rates after either external-beam radiotherapy (RT) or radical prostatectomy (RP) for localized prostate cancer.

PATIENTS AND METHODS: All 1,682 patients had pretreatment prostate-specific antigen (PSA) levels and biopsy Gleason scores (bGS) assigned. No adjuvant therapy was administered after local treatment. RP was the treatment in 1,054 patients (63%) and RT in 628 patients (37%). Median follow-up was 51 months (range, 1 to 134). The median follow-up for RP versus RT patients was 50.5 v 51.0 months. Biochemical relapse was considered detectable PSA levels (> 0.2 ng/mL) in RP patients and three consecutive rising PSA levels in RT patients. The analysis was repeated with a more stringent definition of biochemical control after either RP or RT—namely, reaching and maintaining a PSA level ≤ 0.5 ng/mL—and excluding patients receiving any androgen deprivation (AD).

RESULTS: Eight-year bRFS rates for RP versus RT were 72% and 70%, respectively (P = .010). Multivariate analysis indicated T stage (P < .001), pretreatment PSA (P < .001), bGS (P < .001), year of therapy (P < .001), and neoadjuvant AD (P = .019) to be the only independent predictors of relapse. Age (P = .78), race (P = .29), prior transurethral resection of prostate (P = .81), and treatment modality (P = .96) were not independent predictors of treatment failure. Fifty-one percent of RP patients had favorable tumors (T1 to T2A, pretreatment PSA ≤ 10 ng/mL, bGS ≤ 7), compared with only 34% of RT patients (P < .001). Repeat analysis with a stringent definition of biochemical failure and excluding patients receiving AD indicated no impact of treatment modality on outcome.

CONCLUSION: Eight-year biochemical failure rates were identical between RT and RP in any subgroup. Outcome is determined mainly by pretreatment PSA levels, bGS, clinical T stage, and, for RT patients, radiation dose.
Nutrition and Survival After the Diagnosis of Breast Cancer: A Review of the Evidence
Authors: Rock Cheryl L. , Demark-Wahnefried Wendy
Published: October 2002

PURPOSE: To review and summarize evidence from clinical and epidemiologic studies that have examined the relationship between nutritional factors, survival, and recurrence after the diagnosis of breast cancer.

MATERIALS AND METHODS: Relevant clinical and epidemiologic studies were identified through a MEDLINE search. References of identified reports also were used to identify additional published articles for critical review.

RESULTS: Several nutritional factors modify the progression of disease and prognosis after the diagnosis of breast cancer. Overweight or obesity is associated with poorer prognosis in the majority of the studies that have examined this relationship. Treatment-related weight gain also may influence disease-free survival, reduce quality of life, and increase risk for comorbid conditions. Five of 12 studies that examined the relationship between dietary fat and survival found an inverse association, which was not evident on energy adjustment in most of these studies. The majority of the studies that examined intakes of vegetables or nutrients provided by vegetables and fruit found an inverse relationship with survival. Alcohol intake was not associated with survival in the majority of the studies that examined this relationship.

CONCLUSION: Much remains to be learned about the role of nutritional factors in survival after the diagnosis of breast cancer. Healthy weight control with an emphasis on exercise to preserve or increase lean muscle mass and a diet that includes nutrient-rich vegetables can be recommended. Diets that have adequate vegetables, fruit, whole grains, and low-fat dairy foods and that are low in saturated fat may help to lower overall disease risk in this population.
Clinical Features and Outcome of Initially Unresected Nonmetastatic Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma
Authors: Spunt Sheri L. , Hill D. Ashley , Motosue Alison M. , Billups Catherine A. , Cain Alvida M. , Rao Bhaskar N. , Pratt Charles B. , Merchant Thomas E. , Pappo Alberto S.
Published: October 2002

PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS).

PATIENTS AND METHODS: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival.

RESULTS: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% ± 9% and 56% ± 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% ± 10%).

CONCLUSION: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.
Phase I and Pharmacokinetic Study of E7070, a Novel Chloroindolyl Sulfonamide Cell-Cycle Inhibitor, Administered as a One-Hour Infusion Every Three Weeks in Patients With Advanced Cancer
Authors: Raymond E. , ten Bokkel Huinink W.W. , Taïeb J. , Beijnen J.H. , Faivre S. , Wanders J. , Ravic M. , Fumoleau P. , Armand J.P. , Schellens J.H.M.
Published: October 2002

PURPOSE: The objectives were to determine the maximum-tolerated dose, the recommended dose, the dose-limiting toxicity, the pharmacokinetics, and the activity of E7070, a novel cell-cycle inhibitor.

PATIENTS AND METHODS: E7070 was given as a 1-hour intravenous infusion every 3 weeks in two groups of patients with advanced solid tumors who met prespecified eligibility criteria (group A) or who met the same eligibility criteria but in addition were less heavily pretreated and had more favorable liver functions (group B).

RESULTS: Forty patients (31 patients in group A and nine patients in group B) were entered. Dose escalation proceeded through eight levels (range, 50 to 1,000 mg/m2). In group A, neutropenia and thrombocytopenia were dose-limiting toxicities occurring during the first cycle in two of seven patients treated at the doses of 700 mg/m2 and two of four patients treated at 800 mg/m2. Identical dose-limiting toxicities were observed in zero of six and two of three patients from group B at doses of 800 and 1,000 mg/m2, respectively. Other toxicities included acne-like skin eruption, mucositis, conjunctivitis, nausea, fatigue, and alopecia. At doses greater than 400 mg/m2, the area under the concentration-time curve increased disproportionately to the administered dose. Tumor stabilization lasting ≥ 6 months was observed in six assessable patients.

CONCLUSION: The recommended doses of E7070 in this schedule were 700 mg/m2 (group A) and 800 mg/m2 in patients who were less heavily pretreated (group B) with a moderate tumor burden. Prolonged disease stabilization observed in this study might warrant further investigation of E7070 in selected tumor types.
Randomized Study of Three Different Doses of Suramin Administered With a Fixed Dosing Schedule in Patients With Advanced Prostate Cancer: Results of Intergroup 0159, Cancer and Leukemia Group B 9480
Authors: Small Eric J. , Halabi Susan , Ratain Mark J. , Rosner Gary , Stadler Walter , Palchak David , Marshall Ernest , Rago Randall , Hars Vera , Wilding George , Petrylak Daniel , Vogelzang Nicholas J.
Published: October 2002

PURPOSE: To test the hypothesis that the efficacy and toxicity of suramin in the treatment of patients with hormone-refractory prostate cancer was dose dependent.

PATIENTS AND METHODS: Patients were randomized with equal probability to receive low-, intermediate-, or high-dose suramin (total doses 3.192, 5.320, and 7.661 g/m2, respectively). Overall survival, time to progression, and response rate (prostate-specific antigen [PSA] and objective) for each treatment arm were compared. Relationships between plasma suramin concentrations and response, toxicity, and survival were also evaluated.

RESULTS: Three hundred ninety patients were randomized. For the low-, intermediate-, and high-dose arms, the median survival time was 16, 14, and 13 months, respectively (P = .49). The objective response rate was 9%, 7%, and 15%, respectively (P = .10). PSA response rates were 24%, 28%, and 34%, respectively (P = .082). Landmark analyses of a 50% decline in PSA at 20 weeks showed a significant correlation with survival. There was a dose-response relationship between dose and toxicity. After adjusting for treatment arm, the measured suramin concentration was not associated with clinical response, PSA response, survival, or toxicity.

CONCLUSION: Although high-dose suramin was associated with higher objective and PSA response rates, these were not statistically significant. Overall, no dose-response relationship was observed for survival or progression-free survival, but toxicity was increased with the higher dose. Patients treated with the low-dose level experienced modest toxicity, making it the preferred arm on this study. The lack of a dose-response relationship and the toxicity profile observed raise questions regarding the utility of suramin, particularly high-dose suramin, as administered on this schedule.
Preoperative Combined Nested Reverse Transcriptase Polymerase Chain Reaction for Prostate-Specific Antigen and Prostate-Specific Membrane Antigen Does Not Correlate With Pathologic Stage or Biochemical Failure in Patients With Localized Prostate Cancer Undergoing Radical Prostatectomy
Authors: Thomas John , Gupta Manjula , Grasso Ying , Reddy Chandana A. , Heston Warren D. , Zippe Craig , Dreicer Robert , Kupelian Patrick A. , Brainard Jennifer , Levin Howard S. , Klein Eric A.
Published: October 2002

PURPOSE: We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy.

PATIENTS AND METHODS: One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure.

RESULTS: Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P = .026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P = .009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P = .004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P = .009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results.

CONCLUSION: Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.