bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperbaric oxygen therapy for stroke: a systematic review of the evidence
Authors: Carson Susan , McDonagh Marian , Russman Barry , Helfand Mark
Published: October 2005

Objective: To identify the benefits and harms of using hyperbaric oxygen therapy to treat acute or subacute stroke or the chronic effects of a stroke. We aimed to identify any gaps in the evidence to provide guidance for future research.

Design: A systematic review of the evidence.

Search strategy: We searched MEDLINE, EMBASE, the Cochrane Library, HealthSTAR, CINAHL, MANTIS, bibliographic databases from professional societies and hyperbaric oxygen therapy practitioners, and reference lists. Databases were searched from inception to December 2003.

Inclusion criteria: Studies: Controlled clinical trials and observational studies published in English.

Participants: Patients with ischaemic stroke in any inpatient or outpatient setting.

Outcomes: Mortality, functional health outcomes and adverse events.

Data collection and analysis: Using predetermined criteria, two reviewers assessed each study for inclusion, and abstracted data about study design, population, interventions, and outcomes. We assigned an overall quality rating (good, fair, or poor) based on internal validity.

Results: We identified only four randomized controlled trials and one controlled clinical trial. The best evidence shows no benefit to hyperbaric oxygen therapy in patients with stroke, but because the stage of patients enrolled (acute, subacute, or chronic), the documentation of type and severity of stroke, and the dosage of hyperbaric oxygen therapy given varied considerably, the generalizability of these results is limited. We identified 17 observational studies; all were poor quality.

Conclusions: The overall evidence is insufficient to determine the effectiveness of hyperbaric oxygen therapy in any subgroup of stroke patients. To determine if hyperbaric oxygen therapy for stroke provides any benefit and that these outweigh potential harms, good quality studies are needed.
Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study
Authors: Bottino Cássio MC , Carvalho Isabel AM , Alvarez Ana Maria MA , Avila Renata , Zukauskas Patrícia R , Bustamante Sonia EZ , Andrade Flávia C , Hototian Sérgio R , Saffi Fabiana , Camargo Cãndida HP
Published: October 2005

Objective: To study the efficacy of cognitive rehabilitation combined with acetylcholinesterase inhibitor (AChE-I) treatment in patients with mild Alzheimer's disease and their relatives.

Method: Thirteen patients with mild Alzheimer's disease treated with rivastigmine 6-12 mg/day for more than two months started cognitive rehabilitation training. Before and after the cognitive rehabilitation training patients were assessed through cognitive tests, activities of daily living scale, neuropsychological battery and scales to evaluate caregivers' depressive and anxiety symptoms. Six patients were randomized to a combined treatment group (AChE-I plus cognitive rehabilitation and caregiver support) and seven patients to a control group (AChE-I only) and followed up for five months.

Results: Mini-Mental State Examination (MMSE) scores (p=0.047) and backward digit span scores (p=0.018) were significantly different between the groups on follow-up. The combined treatment group showed a better positive treatment effect on cognitive and neuropsychological tests applied to patients and reduction of psychiatric symptoms was observed in their caregivers (nonsignificant).

Conclusion: Cognitive rehabilitation associated with AChE-I treatment can potentially be useful to stabilize or improve cognitive and functional performance of patients with mild Alzheimer's disease and can reduce caregivers' psychiatric symptoms.
The effect of cardiac rehabilitation on recovery of heart rate over one minute after exercise in patients with coronary artery bypass graft surgery
Authors: Tsai Sen-Wei , Lin Yi-Wen , Wu Shyi-Kuen
Published: October 2005

Objective: To evaluate the effects of cardiac rehabilitation on the recovery of heart rate over 1 min after peak exercise of patients who received coronary artery bypass graft (CABG) surgery.

Design: Thirty subjects who received CABG surgery were randomly assigned to enter or not enter a cardiac rehabilitation exercise programme (cardiac rehabilitation n=15; control group n=15).

Setting: Outpatient cardiac rehabilitation centre in a national medical hospital.

Interventions: Patients assigned to the cardiac rehabilitation group received 36 sessions of the exercise programme, three times a week, with the intensity designed to achieve an individual 60-85% peak heart rate in cardiopulmonary exercise test. Patients assigned to the control group did not get further advice about a specific exercise programme.

Main outcome measures: Resting heart rate and recovery of heart rate over 1 min after a peak exercise test at discharge and three months later were collected. The heart rates were analysed with computer-recorded electrocardiogram.

Results: At follow-up, the 15 patients in the cardiac rehabilitation group had a significantly lower resting heart rate (77.469± 9.49 versus 92.319± 10.18 bpm; p B± 0.001) and a significantly higher recovery of heart rate over 1 min (16.389± 6.32 versus 11.389± 4.81 bpm; p ± 0.03) compared with the control group. There were also significant reductions in resting heart rates (cardiac rehabilitation p ± 0.001; control p=0.05) and improvements in recovery on heart rate over 1 min (cardiac rehabilitation p ± 0.001; control p= 0.001) compared with baseline measurements in both the cardiac rehabilitation and control groups.

Conclusion: Cardiac rehabilitation had a positive effect on the improvement of recovery on heart rate over 1 min in patients with coronary artery disease who received CABG surgery.
Effects of whole-body vibration in patients with multiple sclerosis: a pilot study
Authors: Schuhfried Othmar , Mittermaier Christian , Jovanovic Tatjana , Pieber Karin , Paternostro-Sluga Tatjana
Published: October 2005

Objective: To examine whether a whole-body vibration (mechanical oscillations) in comparison to a placebo administration leads to better postural control, mobility and balance in patients with multiple sclerosis.

Design: Double-blind, randomized controlled trial.

Setting: Outpatient clinic of a university department of physical medicine and rehabilitation.

Subjects: Twelve multiple sclerosis patients with moderate disability (Kurtzke's Expanded Disability Status Scale 2.5-5) were allocated either to the intervention group or to the placebo group.

Interventions: In the intervention group a whole-body vibration at low frequency (2.0-4.4 Hz oscillations at 3-mm amplitude) in five series of 1 min each with a 1-min break between the series was applied. In the placebo group a Burst-transcutaneous electrical nerve stimulation (TENS) application on the nondominant forearm in five series of 1 min each with a 1-min break between the series was applied as well.

Main outcome measures: Posturographic assessment using the Sensory Organization Test, the Timed Get Up and Go Test and the Functional Reach Test immediately preceding the application, 15 min, one week and two weeks after the application. The statistical analysis was applied to the change score from preapplication values to values 15 min, one week and two weeks post intervention.

Results: Compared with the placebo group the intervention group showed advantages in terms of the Sensory Organization Test and the Timed Get Up and Go Test at each time point of measurement after the application. The effects were strongest one week after the intervention, where significant differences for the change score (p=0.041) were found for the Timed Get Up and Go Test with the mean score reducing from 9.2 s (preapplication) to 8.2 s one week after whole-body vibration and increasing from 9.5 s (preapplication) to 10.2 s one week after placebo application. The mean values of the posturographic assessment increased from 70.5 points (preapplication) to 77.5 points one week after whole body vibration and increased only from 67.2 points (preapplication) to 67.5 points one week after the placebo application. No differences were found for the Functional Reach Test.

Conclusion: The results of this pilot study indicated that whole-body vibration may positively influence the postural control and mobility in multiple sclerosis patients.
A randomized clinical trial of TENS and exercise for patients with chronic neck pain
Authors: Chiu Thomas TW , Hui-Chan Christina WY , Cheing Gladys
Published: October 2005

Objective: To investigate the effect of transcutaneous electrical nerve stimulation (TENS) on acupuncture points and neck exercise in chronic neck pain patients.

Design: A randomized clinical trial.

Setting: Hospital-based practice.

Subjects: Two hundred and eighteen patients with chronic neck pain.

Interventions: Subjects were randomized into three groups, receiving either (1) TENS over the acupuncture points plus infrared irradiation (TENS group); (2) exercise training plus infrared irradiation (exercise group); or (3) infrared irradiation alone (control); twice a week for six weeks.

Outcome measures: The values of verbal numeric pain scale, Northwick Park Neck Pain Questionnaire, and isometric neck muscle strength were assessed before, at the end of the six-week treatment, and at the six-month follow-up.

Results: Results demonstrated that after the six-week treatment, significant improvement in the verbal numerical pain scale was found only in the TENS group (0.60±2.54, p=0.027) and the exercise group (1.57±2.67, p<0.001). Though significant reduction in Northwick Park Neck Pain Questionnaire score was found in all three groups, post-hoc tests showed that both the TENS and the exercise group produced better improvement (0.38±0.60% and 0.39±0.62% respectively) than the control group (0.23±0.63%). Significant improvement (p = <0.001 to 0.03) in neck muscle strength was observed in all three groups, however, the improvement in the control group was not clinically significant and it could not be maintained at the six-month follow-up.

Conclusions: After the six-week treatment, patients in the TENS and exercise group had a better and clinically relevant improvement in disability, isometric neck muscle strength, and pain. All the improvements in the intervention groups were maintained at the six-month follow-up.
Describing rehabilitation interventions
Authors: Wade Derick T
Published: October 2005

Rehabilitation is an effective process for reducing the morbidity and sometimes the mortality associated with many illnesses. This statement is supported by much evidence, but there is less evidence to support most specific actions undertaken in rehabilitation. In part this is inevitable because there are so many interventions. However the lack of an adequate system to classify and describe the complex interventions that constitute rehabilitation is also a great hindrance. This is in marked contrast to the detailed specification used in pharmacological research and reasonable description available for some surgical interventions. This editorial puts forward a classification system that is derived from two models relevant to rehabilitation: the World Health Organization's International Classification of Functioning model of illness and a model of rehabilitation described here. Interventions may be described in terms of the situations where these actions are applied, the immediate goals of any action, the level at which the intervention acts, the actions involved, the knowledge and skills needed to give the treatment, any specific equipment used, and any concomitant actions that may be necessary. In addition the context of the interventions should be described: the underlying theory or principles guiding actions, and the organization of the service internally, and in relation to other related services.
Remote sensing for large-area habitat mapping
Authors: McDermid Gregory J. , Franklin Steven E. , LeDrew Ellsworth F.
Published: October 2005

Remote sensing has long been identified as a technology capable of supporting the development of wildlife habitat maps over large areas. However, progress has been constrained by underdeveloped linkages between resource managers with extensive knowledge of ecology and remote sensing scientists with backgrounds in geography. This article attempts to traverse that gap by (i) clarifying the imprecise and commonly misunderstood concept of ‘habitat’, (ii) exploring the recent use of remote sensing in previous habitat-mapping exercises, (iii) reviewing the remote sensing toolset developed for extracting information from optical satellite imagery, and (iv) outlining a framework for linking ecological information needs with remote sensing techniques.
Optical remote sensing techniques in high-mountain environments: application to glacial hazards
Authors: Quincey D. J. , Lucas R. M. , Richardson S. D. , Glasser N. F. , Hambrey M. J. , Reynolds J. M.
Published: October 2005

Remote sensing studies have shown that glaciers and their proximal environments exhibit unique temporal, spatial and spectral characteristics that can be analysed to better quantify glacial hazard potential. In this review, the optical remote sensing data sources available to glacial hazard assessors are considered and the range of information on glacial environments that can be derived is analysed. The review shows that the integration of a variety of data sources can provide geoscientists with information regarding glacial lakes and lake development, glacier dynamics, avalanche sources and ice-marginal fluctuations. Such data can be used to complement and, in many cases, improve field-based glacial hazard assessments. The review concludes that aerial photography still remains the main source of data for measuring a number of glacier characteristics, but that fine to moderate spatial resolution satellite sensors (e.g., ASTER, SPOT 5 HRVIR, Landsat ETM) also provide useful information that can be used to support the assessment of hazards in high-mountain glacierized terrain.
Approaching the physical-biological interface in rivers: a review of methods for ecological evaluation of flow regimes
Authors: Bragg O. M. , Black A. R. , Duck R. W. , Rowan J. S.
Published: October 2005

New European legislation known as the Water Framework Directive (WFD) challenges catchment hydrologists and freshwater biologists to quantify the risk of damage to the organic communities of rivers that arises from anthropogenic distortion of the natural flow regime. Here, we take the first step towards this goal by collecting together relevant information from the two disciplines. An extensive biological literature is examined for insights into the ways in which the species and communities associated with rivers might change when the flow regime is altered. From the hydrological literature, the indicators of flow regime and flow regime change that are pertinent to ecology are described, and consideration is given to means of deriving flow regime data for ungauged river reaches. Attempts to combine hydrology and ecology in classifying rivers and in setting flow objectives to favour biota are then reviewed, together with integrated approaches to river management that aim to promote ecological quality. A significant scale disparity is noted between the disciplines, hydrology being studied at catchment, subcatchment and reach scales, and biology generally at local level. Nonetheless, both yield methods with potential applications in aspects of WFD implementation. The approach with most appeal for general risk assessment is based on the concept of hydrological alteration. This technique employs flow regime variables selected for their importance to aquatic and riparian ecology, and quantifies deviations from the natural values of these variables at reach scale. For WFD purposes, calibration of the scale of hydrological alteration in terms of risk to ecological status is desirable. In this, priority should be given to identification of the level of hydrological alteration that corresponds to the division between good and moderate ecological status.
Methodological approaches to determining the marine radiocarbon reservoir effect
Authors: Ascough Philippa , Cook Gordon , Dugmore Andrew
Published: October 2005

The marine radiocarbon reservoir effect is an offset in 14C age between contemporaneous organisms from the terrestrial environment and organisms that derive their carbon from the marine environment. Quantification of this effect is of crucial importance for correct calibration of the 14C ages of marine-influenced samples to the calendrical timescale. This is fundamental to the construction of archaeological and palaeoenvironmental chronologies when such samples are employed in 14C analysis. Quantitative measurements of temporal variations in regional marine reservoir ages also have the potential to be used as a measure of process changes within Earth surface systems, due to their link with climatic and oceanic changes. The various approaches to quantification of the marine radiocarbon reservoir effect are assessed, focusing particularly on the North Atlantic Ocean. Currently, the global average marine reservoir age of surface waters, R(t), is c. 400 radiocarbon years; however, regional values deviate from this as a function of climate and oceanic circulation systems. These local deviations from R(t) are expressed as +R values. Hence, polar waters exhibit greater reservoir ages (δR = c. +400 to +800 14C y) than equatorial waters (δR = c. 0 14C y). Observed temporal variations in δR appear to reflect climatic and oceanographic changes. We assess three approaches to quantification of marine reservoir effects using known age samples (from museum collections), tephra isochrones (present onshore/offshore) and paired marine/terrestrial samples (from the same context in, for example, archaeological sites). The strengths and limitations of these approaches are evaluated using examples from the North Atlantic region. It is proposed that, with a suitable protocol, accelerator mass spectrometry (AMS) measurements on paired, short-lived, single entity marine and terrestrial samples from archaeological deposits is the most promising approach to constraining changes over at least the last 5 ky BP.
Presettlement land survey records of vegetation: geographic characteristics, quality and modes of analysis
Authors: Wang Yi-Chen
Published: October 2005

Presettlement land survey records (PLSRs) of North America provide insights into the landscape before European disturbance and have been used in various ecological studies. The usefulness of the data, however, varies with their characteristics and qualities. The purpose of this paper is to examine the geographic characteristics of PLSRs, to review PLSR studies in the last five decades and trends in these studies based on the geographic characteristics that have been analysed, and to investigate data quality issues concerning the PLSRs. The framework used in this examination is that of Geographic Information Science (GIScience), including geographic characteristics of space, theme and time, and data quality components of lineage, positional accuracy, attribute accuracy, logical consistency and completeness. The results show that different types of PLSRs have distinct geographic characteristics, especially regarding the spatial characteristics of shape and size/resolution. Prior studies have used PLSRs in six modes of analysis, with presettlement vegetation patterns and compositions analysed most often. Data quality investigations suggest that whether the potential quality issues will influence an analysis depends on the study purpose and the spatial extent of interest. In cases of studying vegetation dynamics of small areas, the positional accuracy of landscape features is essential, while this issue may not impede large area reconstruction. Finally, thoughts concerning future research avenues are presented. This study uses a GIScience framework to provide a more systematic and comprehensive examination of the usefulness and limitations of PLSRs than previous studies, and can assist future research to employ the data most appropriately.
Estimating long-term effects of disease-modifying drug therapy in multiple sclerosis patients
Authors: Rudick R A , Cutter G R , Baier M , Weinstock-Guttman B , Mass M K , Fisher E , Miller D M , Sandrock A W
Published: October 2005

Two methods were used to estimate the long-term impact of disease-modifying drug therapy (DMDT) in patients with relapsing multiple sclerosis (MS) who completed a placebo-controlled, randomized clinical trial of interferon beta-1a (IFNβ-1a). The study cohort consisted of patients with ambulatory relapsing MS who had previously participated in a placebo-controlled clinical trial for two years. At its end, patients were managed in an unstructured fashion by their neurologists and re-evaluated at an average of 6.1 years after the end of the trial. Follow-up evaluation was obtained for 93% of the 172 eligible patients. Because study inclusion criteria required that all patients have an Expanded Disability Status Scale (EDSS) score of ≤3.5 at entry, disability progression at follow-up was defined as EDSS≥6.0. Two methods were used to estimate the expected proportions that reached EDSS≥6.0 at follow-up. Estimates were compared with observed proportions. Method 1 used progression rates observed during the two-year phase III clinical trial and the percentage of time that patients were on DMDT during the follow-up period. Method 2 used progression rates from a natural history comparison group of relapsing-remitting MS patients. At the eight-year follow-up, 42.0% of the original placebo patients and 29.1% of the original IFNβ-1a patients reached an EDSS ≥ 6.0, an observed treatment effect of approximately 30%. Using method 1, it was estimated that 36.3% of the original placebo patients and 27.6% of the original IFNβ-1a patients should have reached an EDSS ≥ 6.0. Use of the natural history control group (method 2) predicted less plausible outcomes. Estimated proportions of patients reaching the endpoint were 63.3% for the original placebo group and 55.8% for the original IFNβ-1a group. Treatment effect sizes of 75-90% would be required to match estimates from method 2 with the observed outcome. The paucity of data on the long-term treatment of patients with MS may be aided by applying these or similar methods to vigorously followed cohorts of patients.
Predictors of dyadic adjustment in multiple sclerosis
Authors: King Kristin E , Arnett Peter A
Published: October 2005

Because multiple sclerosis (MS) is usually diagnosed between the ages of 20 and 50, a time during which most people begin serious relationships, dyadic adjustment for MS patients is a salient issue. However, little is known about factors that might contribute to dyadic adjustment problems in MS. In the present study, we predicted that MS patients showing evidence of three common sequelae of MS-depression symptoms, fatigue and cognitive dysfunction-would be most likely to display problems with dyadic adjustment. Sixty-four MS patients and 49 significant others were assessed. Patient-reported dyadic adjustment was significantly (P at least <0.05) associated with depression (r=-0.48) and fatigue (r=-0.31), but not cognitive functioning. Significant other-reported dyadic adjustment was significantly associated with patients’ depression (r=-0.38), fatigue (r=-0.30) and executive functioning impairments (r=0.37). Stepwise regression analyses revealed that depression was the only significant predictor of dyadic adjustment, regardless of whether significant other (r2 change=0.16) or patient-reported (r2 change=0.22) dyadic adjustment was used as the criterion variable. If depression leads to dyadic problems in MS patients, treatment of depression may result in improved dyadic adjustment. Conversely, if dyadic problems contribute to depression in MS, then treatment of dyadic problems may lead to relief from depression in these patients.
Relapsing-remitting tumefactive multiple sclerosis
Authors: Selkirk Stephen M , Shi Jiong
Published: October 2005

Tumefactive multiple sclerosis (MS) is a rare form of demyelinating disease. The natural course of the disease has been characterized as presenting with a mass-like demyelinating lesion converting to typical relapsing-remitting disease with future exacerbations. Herein we describe a case of a patient whom over a six-year period developed relapsing-remitting tumefactive MS. The natural course, pathophysiology, prognosis and diagnosis are briefly discussed.
Multiple sclerosis management for low-income minorities
Authors: Shabas Debra , Heffner Megan
Published: October 2005

Low-income minorities with complex chronic diseases and physical disabilities have difficulty accessing appropriate healthcare often resulting in suboptimal care. A survey was performed to determine the impact of cultural and socioeconomic factors on the quality of care for low-income minorities with multiple sclerosis (MS) enrolled in Independence Care System (ICS), a Medicaid long-term managed care plan. All 92 ICS members with a diagnosis of MS were surveyed on three aspects of their care: specialty contact, immunomodulating drug therapy and osteoporosis prevention. Of those surveyed, 32% were never seen by an MS specialist. One third were not taking immunomodulatory medications, primarily due to noncompliance caused by a lack of understanding about these drugs. The prevention of osteoporosis and potential fracture in this high-risk population was largely neglected by providers despite the fact that the majority of those surveyed also reported balance difficulties and a history of falling. The survey revealed several deficiencies in the care of low-income minorities with MS. A major issue was the lack of adequate education, particularly about the immunomodulating drugs. Education about the importance of osteoporosis prevention, falls mitigation programmes and rehabilitation evaluations are critical interventions to decrease the risk of fracture.
Tactile temporal thresholds detect relapse-related changes in multiple sclerosis: a preliminary study
Authors: Brown L N , Metz L M
Published: October 2005

Background: Tactile temporal thresholds, which represent the time separating the onset of two tactile stimuli when they are judged as simultaneous, can differentiate a group of people with multiple sclerosis (MS) from normal controls. Demyelination, axonal injury and loss, and altered information processing all occur in MS and may cause these increased thresholds. Thus, tactile temporal thresholds may be a useful outcome measure in MS. Our objective was to assess whether tactile temporal thresholds reflect change during a MS relapse. Methods: During a study to evaluate the stability of tactile temporal thresholds in people with MS, two participants suffered relapses. Both events were associated with prolonged thresholds (i.e., significantly increased thresholds). Conclusions: Tactile temporal thresholds can detect neurologic worsening and thus warrant further evaluation as a useful method to facilitate in the monitoring of disease change in people with MS.
Upregulation of TRAIL expression on human T lymphocytes by interferon b and glatiramer acetate
Authors: Arbour N , Rastikerdar E , McCrea E , Lapierre Y , Dörr J , Bar-Or A , Antel J P
Published: October 2005

We measured the in vivo and in vitro effects of interferon (IFN)b and glatiramer acetate (GA) on the expression of the regulatory molecule, tumor necrosis factor related apoptosis inducing ligand (TRAIL), in patients with multiple sclerosis (MS). We confirmed the prior observation that TRAIL is enhanced on anti-CD3 activated T cells by the in vitro addition of IFNβ. T cells from IFNβ-treated patients stimulated with anti-CD3 only, had higher levels of TRAIL than untreated patients, suggesting that in vivo IFNβ exposure has an effect on TRAIL expression in association with T cell activation. In vitro IFNβ-induced TRAIL upregulation on anti-CD3 or phytohemagglutinin-activated T cells was comparable for IFNβ-treated and non-treated MS patients and controls, indicating that IFN receptors were neither saturated nor down-regulated by current IFNβ therapy. Although GAin vivo orin vitro did not induce TRAIL, the IFNβ-GA combination in vitro enhanced TRAIL expression to higher levels than IFNβ alone on CD4+ T cells obtained from MS patients, regardless of GA treatment status, and healthy donors, and on GA reactive T cell lines derived from GA-treated patients or controls. Whether any observed therapeutic effects of GA/IFNβ combination therapy will correlate with TRAIL expression and function remains to be determined.
Suppression of acute experimental allergic encephalomyelitis with a small molecule inhibitor of α4 integrin
Authors: Piraino P S , Yednock T A , Freedman S B , Messersmith E K , Pleiss M A , Karlik S J
Published: October 2005

Purpose: To determine the efficacy of a small molecule inhibitor of α4 integrin (CT301) at reversing the clinical, pathological and MR- detectable deficits associated with the acute phase of experimental allergic encephalomyelitis (EAE). Materials and methods: EAE was induced in 36 female Hartley guinea pigs, and the treatment period was from day 11 to day 17 post-immunization. Animals received either saline (n=12), anti-α4 integrin antibody (AN100226m; n=12) or CT301 (n=12). T2-weighted fast spin echo and T1-weighted pre- and post-contrast scans were performed at the beginning (day 11) and end (day 18) of the treatment period, and scored for cerebral inflammation and gadolinium enhancement. T1-weighted images were further analyzed to quantify this enhancement as a measure of blood-brain barrier integrity. Dissected CNS was evaluated for inflammation and demyelination. Results: CT301 successfully reversed two clinical indicators of disease over the course of the treatment period. These animals showed decreased T2-weighted abnormalities, as well as a reduction in gadolinium leakage on T1-weighted images. Meningeal and perivascular inflammation was decreased by anti-α4 integrin treatments. Conclusion: CT301 effectively reverses the clinical, pathological and MR-detectable deficits of acute EAE, and may therefore be a promising therapeutic agent in multiple sclerosis (MS).
Population screening for association of mitochondrial haplogroups BM, J, K and M with multiple sclerosis: interrelation between haplogroup J and MS in Persian patients
Authors: Houshmand M , Sanati M H , Babrzadeh F , Ardalan A , Teimori M , Vakilian M , Akuchekian M , Farhud D , Lotfi J
Published: October 2005

Background: Multiple sclerosis (MS) is an immunological inflammatory disease of the central nervous system (CNS) which is chronically observed in young adults. On the basis of earlier studies, potential relatedness between MS and mitochondrial DNA (mtDNA) mutations was postulated. Materials and methods: 246 individuals were screened using the PCR-RFLP method, including 70 MS patients examined for mitochondrial haplogroups BM, J, K and M and 176, 149 and 70 normal controls examined for haplogroups BM and M, J and K, respectively. Results and discussion: Our analysis revealed a relatively high proportion of haplogroup BM in MS patients (∼26%) compared to normal controls (∼13%). In addition, a slightly significant increase of MS patients of haplogroup J (20% in MS patients versus 9.39% in normal controls at P-0.049), while haplogroups M and K did not show contribution to MS contingency (2.85 and 2.27%, respectively at P-1.000 in haplogroup M and 12.85 and 7.14% respectively at P-0.399 in haplogroup K).
Interferon-beta-1b effects on re-enhancing lesions in patients with multiple sclerosis
Authors: Gupta S , Solomon J M , Tasciyan T A , Cao M M , Stone R D , Ostuni J L , Ohayon J M , Muraro P A , Frank J A , Richert N D , McFarland H F , Bagnato F
Published: October 2005

Interferon-beta (IFNβ) reduces the number and load of new contrast-enhancing lesions (CELs) in patients with multiple sclerosis (MS). However, the ability of IFNβ to reduce lesion sizes and re-enhancements of pre-existing CELs has not been examined extensively. Activity of contrast re-enhancing lesions (Re-CELs) and contrast single-enhancing lesions (S-CELs) were monitored in ten patients with relapsingremitting (RR) MS. These patients underwent monthly post-contrast magnetic resonance imaging (MRIs) for an 18-month natural history phase and an 18-month therapy phase with subcutaneous IFNβ-1b, totaling 37 images per patient. The activity was analysed using the first image as a baseline and registering subsequent active monthly images to the baseline. There was a 76.4% reduction in the number of CELs with IFNβ therapy. The decrease was greater (P=0.003) for S-CELs (82.3%) than for Re-CELs (57.4%). S-CELs showed no changes in durations of enhancement and maximal lesion sizes with treatment. Exclusively for Re-CELs, IFNβ-1b significantly decreased maximal lesion sizes, total number of enhancement periods and total months of enhancement. Thus, IFNβ appears to be effective in reducing the degree of severity of inflammation among Re-CELs, as reflected by their reduced maximal lesion sizes and durations of enhancement.
The future of multiple sclerosis therapies: redesigning multiple sclerosis clinical trials in a new therapeutic eraa
Authors: McFarland H F , Reingold S C
Published: October 2005

Due to past success in testing and gaining regulatory approval for a variety of therapies in multiple sclerosis (MS), the conduct of future clinical trials has become increasingly problematic. An international workshop has met to discuss the issues facing the MS clinical trial community and to examine possible new strategies for the design of trials. Particular focus has been placed on trials that either avoid the use of a placebo because of ethical considerations or on designs that allow new therapies to be studied more rapidly or with fewer patients than needed in a conventional placebo-controlled trial. The discussions resulting from the workshop should provide a basis for the examination and implementation of innovative clinical trial designs in MS.
Axonal metabolic recovery and potential neuroprotective effect of glatiramer acetate in relapsing-remitting multiple sclerosis
Authors: Khan Omar , Shen Yimin , Caon Christina , Bao F en , Ching Wendy , Reznar Melissa , Buccheister Alyssa , Hu Jiani , Latif Zahid , Tselis Alexandros , Lisak Robert
Published: October 2005

Glatiramer acetate (GA) is a disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) with several putative mechanisms of action. Currently, there is paucity ofin vivo human data linking the well-established peripheral immunologic effects of therapy with GA to its potential effects inside the central nervous system (CNS). Brain proton magnetic resonance spectroscopy (MRS) allows in vivo examination of axonal integrity by quantifying the resonance intensity of the neuronal marker N-acetylaspartate (NAA). In a pilot study to investigate the effect of GA on axonal injury, we performed combined brain magnetic resonance imaging (MRI) and MRS studies in 18 treatment naïve RRMS patients initiating therapy with GA at baseline and annually for two years on therapy. A small group of four treatment naïve RRMS patients, electing to remain untreated, served as controls. NAA/Cr was measured in a large central brain volume of interest (VOI) as well as the normal appearing white matter (NAWM) within the VOI. After two years, NAA/Cr in the GA-treated group increased significantly by 10.7% in the VOI (2.179±0.26 versus 1.969±0.24, P=0.03) and by 7.1% in the NAWM (2.239±0.26 versus 2.089±0.31, P=0.04). In the untreated group, NAA/Cr decreased by 8.9% at two years in the VOI (2.019±0.16 versus 1.839±0.21, P=0.03) and 8.2% in the NAWM (2.079±0.24 versus 1.909±0.29, P=0.03). Our data shows that treatment with GA leads to axonal metabolic recovery and protection from sub-lethal axonal injury. These results support an in situ effect of GA therapy inside the CNS and suggest potential neuroprotective effects of GA.
The initial course of daily functioning in multiple sclerosis: a three-year follow-up study
Authors: de Groot V , Beckerman H , Lankhorst G J , Polman C H , Bouter L M
Published: October 2005

We studied the initial course of daily functioning in multiple sclerosis (MS). A cohort of 156 recently diagnosed patients was prospectively followed for three years (five measurements). Domains of interest were neurological deficits, physical functioning, mental health, social functioning and general health. An a priori distinction was made between a relapse onset group (n=128) and a non-relapse onset group (n=28). At baseline, neurological deficits are relatively minor for most patients, 26.3% have aberrant physical functioning scores, 38.5% have aberrant social functioning scores, 9% have aberrant mental health scores and 25% have aberrant general health scores. The neurological deficits and physical functioning deteriorated significantly over time. This deterioration was more pronounced and clinically relevant in the non-relapse onset group only. Mental health showed a significant, but not clinically relevant deterioration over time. Social functioning and general health showed non-significant effects for time. It is concluded that in the initial stage of MS, when neurological deficits are relatively minor and mental health is relatively unaffected, patients in both groups experience limitations in daily functioning. Patients in the non-relapse onset group have progressive neurological symptoms that are accompanied by progressive limitations in physical functioning, but not by progressive limitations in the other domains.
Autoimmune hepatitis and multiple sclerosis: a coincidental association?
Authors: de Seze J , Canva-Delcambre V , Fajardy I , Delalande S , Stojkovic T , Godet E , Vermersch P
Published: October 2005

In the present study we report, as part of a large multiple sclerosis (MS) cohort (1800 patients), three cases of untreated patients who developed autoimmune hepatitis (AIH). The prevalence of AIH in the general population is about 0.0169% and seems to be higher in our MS cohort (0.17%). We suggest that a liver biopsy should systematically be performed in untreated MS patients with a sustained increase of liver enzyme.
Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity
Authors: Ferretti G , Bacchetti T , Principi F , Di Ludovico F , Viti B , Angeleri V A , Danni M , Provinciali L
Published: October 2005

Paraoxonase, an enzyme associated with high density lipoproteins (HDL), plays an important role in the anti-oxidant and anti-inflammatory properties exerted by HDL. Increasing evidence supports a role of free radicals and oxidative stress in the inflammatory processes and in the pathogenesis of multiple sclerosis (MS). The aim of this study was to further investigate the relationship between oxidative damage and MS; therefore we compared the paraoxonase activity and levels of cholesteryl ester hydroperoxides (CE-OOH), as marker of lipid peroxidation, in plasma isolated from healthy subjects (n=89) and from MS patients (n=24) in the early stage disability (EDSSB<3.5). Our results demonstrated for the first time that the activity of paraoxonase in the plasma of MS subjects was significantly lower with respect to controls (p<0.001). Moreover, our results showed a significant increase in the levels of CE-OOH in plasma from MS subjects (p<0.001). CE-OOH are biologically active substances derived from the oxidation of cholesteryl ester localized in the hydrophobic core of plasma lipoproteins (HDL, LDL). Therefore, our study demonstrates alterations of lipoprotein peroxidation in MS and provides further evidence that oxidative stress and impairment of the anti-oxidant system may play a role in MS.
Response of Retinoblastoma With Vitreous Tumor Seeding to Adenovirus-Mediated Delivery of Thymidine Kinase Followed by Ganciclovir
Authors: Chévez-Barrios Patricia , Chintagumpala Murali , Mieler William , Paysse Evelyn , Boniuk Milton , Kozinetz Claudia , Hurwitz Mary Y. , Hurwitz Richard L.
Published: October 2005

Purpose

To evaluate the feasibility and safety of adenovirus-mediated gene therapy as a treatment for tumor seeds in the vitreous of children with retinoblastoma.

Patients and Methods

An Institutional Biosafety Committee–, Institutional Review Board–, Recombinant DNA Advisory Committee–, and US Food and Drug Administration–approved phase I study used intrapatient dose escalation of adenoviral vector containing a herpes simplex thymidine kinase gene (AdV-TK) followed by systemic administration of ganciclovir to treat bilateral retinoblastoma with vitreous tumor seeding refractory to standard therapies. Vitreous tumor seeds were treated by intravitreous injection of AdV-TK adjacent to disease sites. Each injection was followed by ganciclovir delivered intravenously every 12 hours for 7 days.

Results

Eight patients with vitreous tumor seeds were enrolled. One patient who was treated with 108 viral particles (vp) had resolution of the tumor seeds around the injection site. The seven patients who were treated with doses ≥ 1010 vp had resolution of their vitreous tumor seeds documented by fundoscopy. Toxicity included mild inflammation at 1010 vp and moderate inflammation, corneal edema, and increased intraocular pressure at 1011 vp. One patient was free of active vitreous tumor seeds 38 months after therapy. There has been no evidence of extraocular spread of tumor along the needle tract in any patient.

Conclusion

AdV-TK followed by ganciclovir can be administered safely to children with retinoblastoma. Suicide gene therapy may contribute to the treatment of children with retinoblastoma tumor seeds in the vitreous, a resistant complication of retinoblastoma.
Recruiting African American Women to Participate in Hereditary Breast Cancer Research
Authors: Halbert Chanita Hughes , Brewster Kiyona , Collier Aliya , Smith ChaChira , Kessler Lisa , Weathers Benita , Stopfer Jill E. , Domchek Susan , Wileyto E. Paul
Published: October 2005

Purpose

This study evaluated the process of recruiting African American women to participate in genetic counseling research for BRCA1 and BRCA2 (BRCA1/2) mutations with respect to referral, study enrollment, and participation in genetic counseling.

Patients and Methods

African American women (n = 783) were referred for study enrollment.

Results

Of 783 referrals, 164 (21%) women were eligible for enrollment. Eligible women were most likely to be referred from oncology clinics (44%) and were least likely to be referred from general medical practices (11%; χ2= 96.80; P = .0001). Overall, 62% of eligible women enrolled onto the study and 50% of enrollees completed genetic counseling. Women with a stronger family history of cancer (odds ratio [OR] = 3.18; 95% CI, 1.36 to 7.44; P = .01) and those referred from oncology clinics and community oncology resources (OR = 2.97; 95% CI, 1.34 to 6.58; P = .01) were most likely to enroll onto the study. Referral from oncology clinics was associated significantly with participation in genetic counseling (OR = 5.46; 95% CI, 1.44 to 20.60; P = .01).

Conclusion

Despite receiving a large number of referrals, only a small subset of women were eligible for enrollment. Oncology settings were the most effective at identifying eligible African American women and general medical practices were the least effective. Factors associated with enrollment included having a stronger family history of cancer and being referred from oncology clinics and community oncology resources. Referral from oncology clinics was the only factor associated significantly with participation in genetic counseling. Education about hereditary breast cancer may be needed among primary care providers to enhance appropriate referral of African American women to genetic counseling for BRCA1/2 mutations.
Breast Cancer Trends Among Black and White Women in the United States
Authors: Jatoi Ismail , Anderson William F. , Rao Sowmya R. , Devesa Susan S.
Published: October 2005

Purpose

Overall US breast cancer mortality rates are higher among black women than white women, and the disparity is widening. To investigate this disparity, we examined incidence data and changes in mortality trends according to age, year of death (calendar period), and date of birth (birth cohort). Calendar period mortality trends reflect the effects of new medical interventions, whereas birth cohort mortality trends reflect alterations in risk factors.

Patients and Methods

Incidence data were obtained from the Connecticut and National Cancer Institute Surveillance, Epidemiology, and End Results registries and mortality data were obtained from the National Center for Health Statistics. Changes in age, period, and cohort mortality trends were analyzed with Poisson regression.

Results

For both races, breast cancer incidence rates for localized and regional disease diverged in the late 1970s. Almost concurrently, overall mortality rates diverged among blacks and whites. For both races, mortality increases with age, but blacks have higher mortality at age younger than 57. The calendar period curves revealed declining mortality for whites over the entire study period. For blacks, calendar period mortality declined until the late 1970s, and then sharply increased. After 1994, calendar period mortality declined for both. For women born between 1872 and 1950, trends in mortality were similar for blacks and whites. For women born after 1950, mortality decreased more rapidly for blacks.

Conclusion

The widening racial disparity in breast cancer mortality seems attributable to calendar period rather than birth cohort effects. Thus, differences in response or access to newer medical interventions may largely account for these trends.
Reversibility of Trastuzumab-Related Cardiotoxicity: New Insights Based on Clinical Course and Response to Medical Treatment
Authors: Ewer Michael S. , Vooletich Mary T. , Durand Jean-Bernard , Woods Myrshia L. , Davis Joseph R. , Valero Vicente , Lenihan Daniel J.
Published: October 2005

Purpose

Trastuzumab is an important biologic agent with significant activity in breast cancers that overexpress the HER2/neu marker. However, trastuzumab is associated with cardiotoxicity that has not yet been fully explored. We present our experience with patients who developed trastuzumab-related cardiotoxicity.

Patients and Methods

Over a 4-year period, 38 patients with HER2/neu–positive breast cancer were referred for suspected trastuzumab-related cardiotoxicity. All patients had previously received anthracycline-based chemotherapy.

Results

After doxorubicin but before trastuzumab, the mean (± standard deviation) left ventricular ejection fraction (LVEF) was 0.61 ± 0.13, and the LVEF decreased to 0.43 ± 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, the LVEF increased to 0.56 ± 0.11. Mean time to recovery of LVEF was 1.5 months and was temporally associated with medical treatment in 32 (84%) of the 38 patients but occurred without treatment in six patients (16%). Increases in LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were re-treated with trastuzumab; three patients had recurrent left ventricular dysfunction, but 22 patients (88%) did not. All re-treatment patients continued on their therapeutic regimen for heart failure when rechallenged with trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural changes were not seen.

Conclusion

Patients who develop cardiotoxicity while receiving trastuzumab therapy generally improve on removal of the agent. The mechanism of trastuzumab-related cardiac dysfunction is different from that of anthracycline cardiotoxicity, in part, demonstrated by the absence of anthracycline-like ultrastructural changes. Reintroducing trastuzumab may be appropriate for some individuals who previously have experienced trastuzumab-related cardiac dysfunction.