bluuebunny/crossref_metadata_2025 huggingface dataset:
How to protect environment and employees against cytotoxic agents, the UZ Ghent experience
Authors: Vandenbroucke Johan , Robays Hugo
Published: January 2007

Objective. To compare two different systems for the reconstitution and preparation of cytotoxic drug-containing infusion bags. The Classical System (open) uses Luer lock syringes and needles, and the PhaSealA System (closed) uses special devices.

Methods. Both wipe samples of the Biological Safety Cabinet (BSC) plus surroundings and urine analysis of technicians and pharmacists involved in the preparatory activities were used. Analyses were performed using gas chromatography in tandem with mass spectroscopy.

Results. An important difference has been found in the surface contamination rate and in the number, periods and values of contaminated urine samples in favour of the closed PhaSealA System. J Oncol Pharm Practice (2001) 6, 146-152.
Presurgery labelling of breast tumours with a charcoal suspension for intratumour injection
Authors: Mathieu Marie-Christine , Bonhomme-Faivre Laurence , Travagli Jean-Paul , Seiller Monique , Contesso Geneviève
Published: January 2007

Objectives. A main goal of neoadjuvant chemotherapy (CT) in locally advanced breast carcinomas (clinical size >3 cm) is to decrease the tumour volume to permit conservative surgery. In about 10% of the cases, the tumour nodule is not clinically palpable after CT and it is necessary to tattoo the initial site in order to guide the surgeon for the resection of any residual tumour. We have developed a charcoal suspension for injection into human breast tumours. The aim is to enable the pathologist to guide the surgeon during excision of the residual tumour, which is not otherwise visible, after CT. Pharmacological and toxicological studies in animals have indicated that the suspension is well tolerated.

Methods. We investigated the efficacy and tolerability of a charcoal suspension in a group of eight patients with a palpable breast tumour of clinical size 1.5-4 cm, which was removed 24 hours to 4 days after the injection of 1 mL of 4% charcoal suspension into the tumour.

Results. This preliminary clinical study shows that the injection of charcoal is well tolerated by patients and is a good method of tattooing tumour. The charcoal was seen in or at the periphery of the nodule in the surgical specimen. No inflammatory reaction or diffusion was observed.

Conclusions. Based on these results, this suspension appears suitable for tattooing breast carcinomas over a period of 3 months for patients programmed to receive preoperative CT.
Impact of centralization of cytotoxic drug preparations
Authors: Cabelguenne Delphine , Pivot-Dumarest Christine , Vermeulen Eliane
Published: January 2007

Two types of circuits of injectable cytotoxic drugs still exist in our hospital: one with pharmaceutical centralization of the preparation and the other without. Our goal is to evaluate each circuit from two points of view: quality of patient care and protection of persons handling cytotoxics. For this evaluation, an original assessment was performed before and after centralization in the same pilot health care unit (two periods of 6 weeks each). To evaluate the prescription-preparation-administration process, six checklists consisting as a whole of 158 observable criteria have been constructed. These criteria have been weighted according to the risk of compromising the quality of patient care and the safety of persons. A total of 117 processes have been observed before centralization; after centralization, 91 were observed. From a qualitative viewpoint, we show that the cost of drugs stocked in the medicine chest of the health care unit has been reduced by 80%, that the flow of information between the different participants in the circuit varied, and that two types of dysfunctions exist: organizational and relational. From a quantitative viewpoint, we demonstrated that pharmaceutical intervention improves the quality of patient care (x2 test, P < 0.001) and reinforces the protection of manipulators (x2 test, P < 0.001). Pharmaceutical centralization of the preparation of cytotoxic drugs increases the efficiency of the circuit, from the prescription to administration.
The role of the oncology pharmacist in 1999
Authors: Goffredo Franca
Published: January 2007

Oncology pharmacy has become a very important area within hospital pharmacy services. The development of new chemotherapies and the increase of incidence of cancers has increased the use of these drugs not only in specialised hospitals (cancer centres) but also in general hospitals. Often their use is extended to home care, which allows the reduction of costs and a better quality of life for the patients. With the development of oncological therapies, oncology pharmacy has also grown. Cancer is also a disease, perhaps more than any other, that requires a multidisciplinary approach and therefore provides many opportunities for pharmacy involvement.
A retrospective review of gemcitabine use in advanced epithelial ovarian cancer
Authors: Spina Sean , Nakashima Lynne , Swenerton Ken
Published: January 2007

Background. In North America, epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Many drugs are used in the treatment of EOC, with gemcitabine showing recent promise. The objective of this study was to determine whether gemcitabine is a beneficial treatment option for patients with EOC.

Methods. The charts of 20 heavily pretreated women (median: four previous treatment protocols, range: 1-6) with a histological diagnosis of EOC were retrospectively reviewed to determine response. Eligible patients were treated with gemcitabine at a starting dose of 800 mg/m2 as an intravenous infusion on days 1, 8, and 15 of each 28-day cycle. The patients had a median age of 56 years (range 37-81).

Results. Response to treatment was assessed both clinically and serologically (CA-125 tumor marker was monitored). Of the 20 enrollees, 17 were evaluable clinically and 16 were evaluable serologically (2 were not evaluable by either technique).

There were two (12%) patients with a clinical partial response, six (35%) patients with clinical stable disease, nine (53%) patients with clinical progressive disease, and three patients that were not evaluable clinically. There were four (25%) patients with sero-logical partial response, six (38%) patients with stable serological disease, six (38%) patients with serological progressive disease, and four patients that were not evaluable serologically. Physician-reported toxicity included fatigue; however, this information was recorded inconsistently.

Conclusion. Gemcitabine showed modest activity in heavily pretreated EOC with a 12% clinical partial response rate and a 25% serological partial response rate. No serious toxicities were encountered.
In Search of East Asian Self-Enhancement
Authors: Heine Steven J. , Hamamura Takeshi
Published: January 2007

A meta-analysis of published cross-cultural studies of self-enhancement reveals pervasive and pronounced differences between East Asians and Westerners. Across 91 comparisons, the average cross-cultural effect was d = .84. The effect emerged in all 30 methods, except for comparisons of implicit self-esteem. Within cultures, Westerners showed a clear self-serving bias (d = .87), whereas East Asians did not (d = -.01), with Asian Americans falling in between (d = .52). East Asians did self-enhance in the methods that involved comparing themselves to average but were self-critical in other methods. It was hypothesized that this inconsistency could be explained in that these methods are compromised by the “everyone is better than their group’s average effect” (EBTA). Supporting this rationale, studies that were implicated by the EBTA reported significantly larger self-enhancement effect for all cultures compared to other studies. Overall, the evidence converges to show that East Asians do not self-enhance.
Social Identity Performance: Extending the Strategic Side of SIDE
Authors: Klein Olivier , Spears Russell , Reicher Stephen
Published: January 2007

This article extends the social identity model of deindividuation effects (SIDE) by considering the various ways in which relations of visibility to an audience can affect the public expression of identity-relevant norms (identity performance). It is suggested that social identity performance can fulfill two general functions: Affirming, conforming, or strengthening individual or group identities (the identity consolidation function) and persuading audiences into adopting specific behaviors (the mobilization function). The authors report evidence supporting these two functions of identity performance both in intragroup and intergroup contexts. They argue that through these functions, social identity performance plays a major role in the elaboration and coordination of social action. Finally, and building on this framework, the authors consider the ways through which social identity performance can be used in the very construction of social identity.
The Epistemic-Teleologic Model of Deliberate Self-Persuasion
Authors: Maio Gregory R. , Thomas Geoff
Published: January 2007

Although past theory and research point to the importance of understanding deliberate self-persuasion (i.e., deliberate self-induced attitude change), there have been no empirical and theoretical efforts to model this process. This article proposes a new model to help understand the process, while comparing the process of deliberate self-persuasion with relevant theory and research. The core feature of this model is a distinction between epistemic processes, which involve attempting to form new valid attitudes, and teleologic processes, which involve self-induced attitude change but with minimal concerns for validity. The epistemic processes employ tactics of reinterpretation, reattribution, reintegration, retesting, changing comparators, and changing dimensions of comparison. The teleologic processes include suppression, preemption, distraction, and concentration. By mapping these processes, this model helps to generate many novel and testable hypotheses about the use of deliberate self-persuasion to cope with ambivalent attitudes.
Back From the Brink: Why Customers Stay
Authors: Colgate Mark , Tong Vicky Thuy-Uyen , Lee Christina Kwai-Choi , Farley John U.
Published: January 2007

Much research has explored the customer’s decision to switch from one service provider to another and the impact of this decision. Less research, however, has explored the other possible decision the customer can make when considering switching—the decision to stay—and the reasons behind this decision. In light of this, the authors research customers who remained with their service provider after a recent “switching dilemma.” The dilemma requires the customer to consider carefully whether they should stay or leave. The authors collect data from 24 in-depth interviews and nearly 700 questionnaires. These are gathered from two divergent cultures and reveal seven categories of “reasons to stay,” which are present across many different service industries. The main discovery is that switching barriers, unearthed in previous research on why customers stay, only tell half the story; the other half is told by what we call the “affirmatory” factors.
When Customers Receive Support From Other Customers: Exploring the Influence of Intercustomer Social Support on Customer Voluntary Performance
Authors: Rosenbaum Mark S. , Massiah Carolyn A.
Published: January 2007

Service establishments would relish the opportunity to have their customers display customer voluntary performance (CVP) behaviors, which refer to helpful, discretionary customer behaviors that support an organization’s service performance and quality. This article draws on resource exchange theory to offer an explanation as to why some customers display CVP in the form of customer citizenship and customer care behaviors. The data reveal that customers who receive social-emotional support and, to a lesser extent, instrumental support from other customers in a service establishment reciprocate by exhibiting CVP toward the establishment and to customers in the establishment. This article demonstrates that socially supportive service environments are beneficial for customers’ health and for organizational profitability.
Evaluation of the Apo-1/Fas promoter Mva I polymorphism in multiple sclerosis
Authors: Huang Q R , Teutsch S M , Buhler M McW , Bennetts B H , Heard R NS , Manolios N , Stewart G J
Published: January 2007

The pathogenesis of multiple sclerosis is under strong genetic control involving several or more genes each of modest effect. Whilst the mechanisms underlying the pathogenesis of MS remain unknown, it has been hypothesised that either decreased apoptosis of autoreactive T cells in the CNS, or increased apoptosis of oligodendrocytes may play an important role. The Apo-1/Fas antigen (CD95), the gene for which is located in a chromosomal region showing linkage in MS genome screens, is a critical inducer of apoptosis and studies have shown aberrant expression of this molecule in MS, correlating with a decrease in T cell apoptosis or increase in CNS tissue damage. This study investigated an Mva I polymorphism in the Apo-1/Fas promoter region in a group of 124 Australian patients with relapsing-remitting MS and in 183 normal controls. Whilst there were increases in the Mva I*2 allele in MS individuals overall (59% vs 52%, P not corrected=0.08), and in HLA-DRB1*1501 negative MS patients (62% vs 55%), these were not significantly different from controls. Interactions were investigated between the Mva I alleles and T cell receptor beta chain variable region (TCRBV) germline polymorphisms, with a trend in MS individuals towards a decrease of the Mva I*1 allele when combined with the TCRBV3S1*2 allele (Relative Risk=0.25, P=0.067), and with the TCRBV8S1*1 allele (Relative Risk=0.44, P=0.12). Overall, the findings of this study indicate a possible effect of the Apo-1/Fas promoter Mva I polymorphism in MS susceptibility, which needs to be confirmed in further studies.
Linomide in the treatment of multiple sclerosis: MRI results from prematurely terminated phase-III trials
Authors: Tan I L , Nijeholt G J Lycklmaà , Polman C H , Adér H J , Barkhof F ,   the 95 Line 146/147 Study Group
Published: January 2007

Due to an unexpected increase in serious cardiovascular event in MS patient treated with Linomide, a synthetic immunomodulator, two phase-III multinational relapsing remitting (RR) and secondary progressive (SP) MS trials had to be discontinued. MRI result of 413 patient who participated for at least 3 months were analysed. Patient received placebo, 2.5 or 5 mg Linomide. Scans were performed at pre-enrolment, month 3 and termination. The number and volume of enhancing lesions (ELV), and the number of active scans were evaluated At month 3, the decrease in the number of enhancing lesions in the placebo group was I I1%, compared with 15% in the 2.5 mg group (P=0.027) and 23% in the 5 mg group (P=0.057). Using the percentage of active scans as outcome parameter, the odds ratio for improvement between placebo and 2.5 mg group was 1.62 (P=0.14); between placebo and 5 mg Linomide group 3.58 (P=0.003). At termination, a rebound effect was noted in the 2.5 mg group (P=0.0 1). Analysis of the ELV showed no significant difference between placebo and treatment groups. Although Linomide has unacceptable side effect, it seems to have a modest effect on MS disease activity, as measured by MRI.
Biopsychosocial correlates of lifetime major depression in a multiple sclerosis population
Authors: Patten Scott B , Metz Luanne M , Reimer Marlene A
Published: January 2007

The objective of this paper was to evaluate the lifetime and point prevalence of major depression in a population-based Multiple Sclerosis (MS) clinic sample, and to describe associations between selected biopsychosocial variables and the prevalence of lifetime major depression in this sample. Subjects who had participated in an earlier study were re-contacted for additional data collection. Eighty-three per cent (n=136) of those eligible consented to participate. Each subject completed the Composite International Diagnostic Interview (CIDI) and an interviewer-administered questionnaire evaluating a series of biopsychosocial variables. The lifetime prevalence of major depression in this sample was 22.8%, somewhat lower than previous estimates in MS clinic populations. Women, those under 35, and those with a family history of major depression had a higher prevalence. Also, subject reporting high levels of stress and heavy ingestion of caffeine (>400 mg) had a higher prevalence of major depression. As this was a cross-sectional analysis, the direction of causal effect for the observed associations could not be determined. By identifying variables that are associated with lifetime major depression, these data generate hypotheses for future prospective studies. Such studies will be needed to further understand the etiology of depressive disorders in MS.
The Danish National Project of interferon-beta treatment in relapsing-remitting multiple sclerosis
Authors: Koch-Henriksen Nils , Sùrensen Per Soelberg ,   The Danish Multiple Sclerosis Group
Published: January 2007

After approval by the European Union in 1996 of interferon-beta for treatment of relapsing-remitting multiple sclerosis (RRMS), 862 patients in Denmark have received treatment (by April 1999), and 304 of those were enrolled into an open labelled randomised trial to compare the efficacy and tolerability of treatment with interferon-beta-1b (Betaferon) 8 MIU subcutaneous every other day and interferon-beta-1a (Rebif) 6 MIU subcutaneous once a week. Primary and secondary end-points included: (1) the relapse rate, (2) tolerability, (3) neutralizing antibody formation using the same specialised laboratory and validated assay, (4) time to first relapse, (5) time to sustained progression, and (6) number of gadolinium-enhancing lesions in T1-weighted MRI and the total lesion load in T2-weighted MRI. All the records are kept in a nationwide clinical database connected with the Danish Multiple Sclerosis Registry. The randomised trial will be completed by the end of 1999, and the results are not yet available. The annual relapse rate in all treated patients until April 1999 was 0.73, the annual rate of steroid treated relapses was 0.21. By 1 April 1999 8.8% of the patients had discontinued treatment and 10.4% had changed to another interferon-beta preparation. It has been planned to extend the follow-up of all patients treated according to the Danish National Protocol for a period of several years. The continuous and nation-wide registration of the course of the disease in interferon-beta treated RRMS patients may provide valuable knowledge of the treatment-modified long-term course of the disease in a cohort of patients, selected on the basis of well-defined criteria.
Fatigue in multiple sclerosis and its relationship to depression and neurologic disability
Authors: Bakshi R , Shaikh Z A , Miletich R S , Czarnecki D , Dmochowski J , Henschel K , Janardhan V , Dubey N , Kinkel P R
Published: January 2007

We studied multiple sclerosis fatigue (MSF) and its relationship to depression and disability. Seventy-one patients [50 relapsing-remitting, 21 secondary progressive] were grouped by Fatigue Severity Scale (FSS) into MS-fatigue (MSF) (FSS55; n=46) or MS-nonfatigue (MSNF) (FSS44; n=20). Forty-one patients were grouped into MS-depression (MSD) (n=15) or MS-nondepression (MSND) (n=26) by interview. Higher expanded disability status scale (EDSS) scores were noted in MSF than MSNF patients (P=0.0003); EDSS scores correlated with FSS scores (rho=0.43, P=0.003). However, fatigue was present in 58% (n=29) of relapsing-remitting patients and in 52% (n=26) of patients with mild physical disability (EDSS53.5). Hamilton/Beck depression severity scores were higher in MSF than MSNF patients and correlated with FSS scores (P50.05). MSD had higher FSS scores than MSND patients (P=0.008). After controlling for EDSS, depression severity continued to correlate with FSS scores (rho=0.37, P=0.02). After controlling for depression, FSS scores no longer correlated with EDSS scores (rho=0.27, P=0.09). Thus, MSF is independent of physical disability, but is associated with depression, suggesting that common mechanisms play a role in MSF and MSD including psychological factors or brain lesions in specific neuroanatomic pathways. Further study is warranted to determine if antidepressant medications improve fatigue in MS.
Gabapentin is effective in treating nocturnal painful spasms in multiple sclerosis
Authors: Solaro C , Uccelli M Messmer , Guglieri P , Uccelli A , Mancardi G L
Published: January 2007

In-patients with MS nocturnal spasms (NPS) occur frequently, primarily during the night and may influence the ability to and/or quality of sleep. We enrolled in an open label trial with GBP (up to 600 mg/day) 24 MS patients with NPS. We obtained patient reports of subjective discomfort at pre-treatment and following 2- (T1) and 8 weeks (T2), utilizing a 3-point analogue scale. Twenty of the 22 patients who completed the study reported resolution or amelioration of discomfort. Clinical improvement occurred 1-5 days following initial treatment. Three patients experienced adverse effects but completed the minimal follow-up period (2 weeks). Two patient dropped out of the study due to no compliance or adverse effects. A very low dose of GBP may be effective treatment for MS patients with NPS who may benefit from rapid improvement of discomfort with minimal risk of adverse effects.
Enhanced T cell responsiveness to citrulline-containing myelin basic protein in multiple sclerosis patients
Authors: Tranquill Laura R , Cao Ligong , Ling Nicholas C , Kalbacher Hubert , Martin Roland M , Whitaker John N
Published: January 2007

Myelin basic protein (MBP), a candidate autoantigen in multiple sclerosis (MS), exists in different isoforms and charge isomers generated by differential splicing of exons and by a combination of posttranslational modifications, respectively. These various isoforms and charge isomers of MBP vary in abundance and most likely serve different functions during myelinogenesis and remyelination. The least cationic among the charge isomers of MBP is citrullinated and is referred to as MBP-C8. MBP-C8 is relatively increased in the population of MBP isomers in more developmentally immature myelin and in MS brain tissue. In a previous study, we found that MBP-C8-reactive T cells could be detected in CD4+ T cell lines (TCL) generated with MBP from both MS patients and normal controls. Here, we examined the frequency and peptide specificity of MBPC8-specific TCL generated with MBP-C8 in MS patients and controls. Ten subjects grouped in five sets, each an MS patient and a control, were studied. In all cases, the MS patient had either a higher overall number of MBP-C8-responding lines, responded with greater sensitivity to the MBPC8 antigen or both. Few lines responded to the MBP-C8 peptides but, if they did, they appeared to be specific to the carboxyl-half of the MBP-C8 molecule. Given the large amounts of citrullinated MBP in MS brain tissue, a preferential T cell response to MBP-C8 may be involved in the induction and perpetuation of this disease.
A quality network model for the daily care of multiple sclerosis
Authors: Blumhardt L D , Vermeij B JD , Amato M , Andersen O , Edan G , Fernandez O , Filippi M , Haas J , Hommes O R , Rieckmann P
Published: January 2007

The urgent need to optimise treatment strategies for patients with Multiple Sclerosis (MS) was recognised by the participants at the 1998 European Charcot Foundation (ECF) symposium in Nice. The `Nice Declaration' led to the formation of a Task Force Essentials Group charged with developing measures of the quality of MS care in Europe. Algorithms for nine critical domains (disability, spasticity, ataxia, pain, cognition, mood, fatigue, bladder function and sexual activity) and `educated guesses' have been developed to measure interventions and outcomes which reflect the quality of clinical decision-making processes. A generic model called a `quality network', consisting of a group of clinics connected to a central server, has been successfully applied to the care of diabetes across Europe. This model will now be developed and applied to MS management, to provide clinicians with longitudinal epidemiological data and, to evolve treatment algorithms and further quality measures. The ECF will next validate the system in a 1-year pilot study using a net of 10 clinics. Finally, an extended European network working in a learning environment will continuously assess, update and improve the quality of care of MS patients.
A meta-analysis of methylprednisolone in recovery from multiple sclerosis exacerbations
Authors: Miller Deborah M , Weinstock-Guttman Bianca , Béthoux François , Lee Jar-Chi , Beck Gerald , Block Vicki , Durelli Luca , LaMantia Loredana , Barnes David , Sellebjerg Finn , Rudick Richard A
Published: January 2007

Despite recent advances in multiple sclerosis treatment, patients experience relapses for which standard treatment remains glucocorticosteroids (GCS). However, there is limited information comparing doses or routes of administration for different GCS types or the benefit of GCS compared to natural recovery. Currently, high dose (HD) methylprednisolone (MP) is the preferred therapy. We conducted meta-analyses of published studies assessing MP at different doses and in comparison to other steroid products or no treatment. Relevant studies were identified through predetermined processes and five articles met the inclusion criteria. Three studies compared HD MP to placebo; two studies compared the effect of HD MP and low dose (LD) MP; only one accepted report compared HD MP to another GCS. This report could not be included in a meta-analysis. The meta-analysis of HD MP vs placebo studies indicated a mean treatment difference of 0.76 in Expanded Disability Status Score (EDSS) changes from baseline. The meta-analysis of HD and LD MP demonstrated no difference in EDSS change. Despite these rather obvious findings, these meta-analyses have been valuable in identifying further research questions. We recommend studies to determine optimum benefit related to dosage, timing for starting therapy and the most appropriate GCS type. Given the advances in MS therapeutics, these studies will have to include patients on additional disease modifying therapy.
Neuropsychological impairment in multiple sclerosis patients: the role of (juxta)cortical lesion on FLAIR
Authors: Lazeron R HC , Langdon D W , Filippi M , van Waesberghe J HTM , Stevenson V L , Boringa J BS , Origgi D , Thompson A J , Falautano M , Polman ChH , Barkhof F
Published: January 2007

In this study we evaluated the correlation between neuropsychological impairment (measured with the Brief Repeatable Battery Neuropsychological Tests) and (juxta)cortical lesions detected with FLAIR and the relative sensitivity of the FLAIR sequence compared to spin-echo MRI sequences in detecting (juxta)cortical MS lesions. A total of 39 patients with definite MS were evaluated by MRI with a conventional and fast spin echo sequence and fast FLAIR sequence, and neuropsychological tests of the Brief Repeatable Battery Neuropsychological tests were performed. The Z-score of all subtests were used to calculate a Cognitive Impairment Index. The results show that a high number of (juxta)cortical lesions is detected with thin slice FLAIR (30% of all lesions seen). This percentage was not superior to spin-echo, reflecting the thin slice thickness (3 mm) we used. The lesions detected with FLAIR were to a certain degree different ones than the lesions detected with the other techniques. While the number of non-cortical lesions correlated with the expanded disability status scale (r=0.32, P=0.045), the number of (juxta)cortical lesions detected with the FLAIR showed a correlation (r=0.34, P=0.035) with the Cognitive Impairment Index. Our study underlines the high number of (juxta)cortical lesions in MS and the value of thin slice FLAIR sequence to detect such lesions with MRI. It also stresses the importance of (juxta)cortical lesions on determining neuropsychological impairment.
Kinetic profiles of cerebrospinal fluid anti-MBP in response to intravenous MBP synthetic peptide DENP85VVHFFKNIVTP96RT in multiple sclerosis patients
Authors: Warren K G , Catz Ingrid
Published: January 2007

Multiple sclerosis [MS], a demyelinating disease of the central nervous system associated with inflammation and gliosis, may be an autoimmune disease with T lymphocytes and autoantibodies to myelin protein(s). This study deals exclusively with B cell autoimmunity to myelin basic protein (MBP). T lymphocytes and anti-MBP share a common MBP epitope located between P85 and P96 which contains the essential contact residues H88FFK91 for the trimolecular complex. The purpose of this Phase I open label clinical study was to monitor CSF anti-MBP in patients with chronic progressive MS subsequent to IV administration of synthetic peptide (sp) MBP82-98 namely DEN85VVHFFKNIVTP96RT. Fifty-six patients who participated in this project were assigned to two groups: a `control group' of 15 patients who received IV saline injections every 6 months for the first 2 years of the study and a `peptide group' of 41 patients who received IV spMBP82-98 from the beginning of the study and then infrequently subsequent to a rise of their CSF anti-MBP. In the control group antibody levels remained persistently elevated during the 2 year period. Patients in the `peptide group' segregated into four kinetic profiles: Cohort A (15 patients) illustrated prolonged anti-BMP suppression into the normal range. Cohort B (10 patients) illustrated significant anti-MBP suppression into the normal range for shorter durations. Cohort C (eight patients) showed significant CSF anti-MBP suppression after the initial injection but lost the ability to suppress the autoantibody titer following subsequent injections. Cohort D (eight patients) failed to show significant CSF anti-MBP suppression. In conclusion the B cell tolerizing effect of spMBP82-98 segregated into four kinetic profiles; this molecular variability should be considered in attempts to develop specific `peptide therapies' for the broad range of clinical profiles currently diagnosed as `multiple sclerosis'.
Self-reported visual dysfunction in multiple sclerosis: results from the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25)
Authors: Balcer Laura J , Baier Monika L , Kunkle Amy M , Rudick Richard A , Weinstock-Guttman Bianca , Simonian Nancy , Galetta Steven L , Cutter Gary R , Maguire Maureen G
Published: January 2007

Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported visual dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial of interferon β-1a for relapsing-remitting MS. Mean VFQ-25 composite scores and selected sub-scale scores were significantly lower (worse) among patients in our MS cohort (n=35) compared with a published reference group of patients with no history of chronic eye disease (n=118). These differences were observed despite a relatively younger age and tighter distribution of binocular visual acuities in the MS cohort. Patients with MS in this study thus demonstrated a greater degree of self-reported visual dysfunction, as measured by the VFQ-25, compared with an eye disease-free reference group. The VFQ-25 is a potentially useful measure of vision-specific HRQOL in patients with MS.
Neurological worsening due to infection from renal stones in a multiple sclerosis patient
Authors: Hillman Leslie J , Burns Stephen P , Kraft George H
Published: January 2007

Symptomatic bladder dysfunction occurs in the majority of patients with multiple sclerosis (MS). Although guidelines have been established for diagnosis and management of bladder dysfunction in these patients, they are sometimes overlooked in the primary care setting, leading to severe, life threatening complications. A 64-year-old male with a 31-year history of spastic quadriparetic MS and neurogenic bladder dysfunction managed with an indwelling catheter, presented to the hospital with worsening neurological function. He had developed increased weakness and cognitive impairment several weeks after being treated for a urinary tract infection (UTI). He had become unable to perform any activities of daily living or drive his power wheelchair. After an extensive work-up, he was found to have a large (14618630 cm) retroperitoneal abscess and multiple renal stones, including a large obstructing calculus in the collecting system near the ureteropelvic junction, and he underwent nephrectomy and abscess drainage. Of note, he had been found to have multiple renal stones and hydronephrosis on renal ultrasound 3 years earlier, but he had received no treatment. Following drainage of the abscess, his upper extremity neurological function returned to baseline, his cognitive status improved, and he regained the ability to perform activities of daily living. Patients with paralysis from MS, much like those with traumatic spinal cord injuries, are at grave risk of mortality and morbidity from undiagnosed and under-treated urinary complications. This case demonstrates that evaluation and appropriate treatment for complications of neurogenic bladder should be part of routine care for patients with MS. Current recommendations for evaluation and management of bladder dysfunction in patients with MS will be reviewed.
A meta-analysis of genomic screens in multiple sclerosis
Authors:   The Transatlantic Multiple Sclerosis Genetics Cooperative
Published: January 2007

We combined the raw genotyping data from three large multiple sclerosis genome screens and performed a global meta-analysis in order to compare and summarize the linkage results from the different studies. In alphabetical order, the screens provided data from 442 markers typed in 52 multiplex families with a total of 133 affected individuals (the American screen), 314 markers typed in 128 families with 264 affecteds (the British screen) and 257 markers typed in 61 families with a total of 139 affected subjects (the Canadian screen). Multipoint analysis of these data was performed using the GENEHUNTER program. The highest non-parametric linkage (NPL) score in the meta-analysis was observed on chromosome 17q11 (NPL score 2.58), although this score falls short of genome-wide significance. A total of eight regions had NPL scores greater than 2.0. One of the regions with an NPL score greater than 2.0 was the HLA region on chromosome 6p21 (NPL=2.2). This region is known, from association studies, to be involved in MS susceptibility, but the modest linkage result observed here suggests the encoded susceptibility effect is not large compared with the high familial recurrence in MS (λs≈20). Overall, our linkage results suggest that MS is likely to be multigenic in its genetic susceptibility.
Episodic hyperlibidinism in multiple sclerosis
Authors: de Assis Aquino Gondim Francisco , Thomas Florian P
Published: January 2007

Background: Changes in sexual function are commonly associated with MS and occur in many forms. Hypersexual thought or behavior are rare, but can present on the background of persistent cognitive impairment or psychiatric conditions such as mania, whereas isolated hypersexuality is still rarer. Case Report: We describe the clinical neuropsychological electrodiagnostic neuroimaging and endocrine findings in a MS patient with episodes of greatly increased libido. Imaging and neuropsychological studies indicated frontal lobe dysfunction; hormone studies showed no significant changes. Conclusion: Episodic hypersexuality can be a recurrent transient manifestation of MS.
Additive effect of the HLA-DR15 haplotype on susceptibility to multiple sclerosis
Authors: Rasmussen H B , Kelly M A , Clausen J
Published: January 2007

Multiple sclerosis (MS) has been associated with the human leukocyte antigen DR15 allele in Caucasians of North and Central European origin. However, the relative effect of the DR15 homozygous and the DR15 heterozygous genotypes on the disease susceptibility is unclear. Based upon results from three North European studies we have examined this by meta-analysis. Our results suggested that the effect of the DRB1*1501, DQA1*0102, DQB1*0602 haplotype on the susceptibility to MS is additive, perhaps reflecting that development of the disease is facilitated by a high density surface expression of the antigen presenting molecules encoded by this haplotype. Possible implications of our finding to future studies of the genetic background of MS is discussed.
Disease specific quality of life instruments in multiple sclerosis: Validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS)
Authors: Gold S M , Heesen C , Schulz H , Guder U , Mönch A , Gbadamosi J , Buhmann C , Schulz K H
Published: January 2007

Quality of life (QoL) is discussed as an additional outcome measure in multiple sclerosis (MS). However, few questionnaires assessing disease specific QoL in MS have been published. On the basis of the literature and interviews with clinicians and MS patients, we have developed a disease specific QoL instrument and validated it in a broad range of patients with MS. In this study, a heterogeneous sample of n=237 MS patients completed the newly developed Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS, in German language) and a battery of already validated questionnaires. They further underwent neurological scoring and objective tests. By these means, we investigated its validity, appropriateness, internal consistency, and retest reliability. Internal consistency and retest coefficients were high and satisfied psychometric standards. Convergent and discriminant validity was supported by direction, magnitude and pattern of correlations with other health measures. HAQUAMS subscales and its total score distinguished between patient groups of varied disease severity, cognitive impairment, and affective symptomatology. No floor or ceiling effects were found in either of the HAQUAMS subscales. The HAQUAMS is a reliable, valid and appropriate instrument for QoL assessment in multiple sclerosis. Data of responsiveness are currently being obtained.
The relation between objective and subjective impairment in cognitive function among multiple sclerosis patients - the role of depression
Authors: Maor Yasmin , Olmer Liraz , Mozes Benjamin
Published: January 2007

Objective: To evaluate the relations between perceived cognitive function and objective cognitive deficit and to assess variables affecting perceived cognitive function among multiple sclerosis (MS) patients. Methods: A cross sectional study of patients with MS. All patients were interviewed and the Expanded Disability Status Scale (EDSS) score was determined. The dependent variables were four items assessing perceived concentration and thinking, attention, memory, and whether others have noticed memory or concentration problems. The explanatory variables were age, sex, duration of disease, number of relapses in the last 2 years, EDSS score, depressive symptoms score (CES-D) and the domains of the Neurobehavioral Cognitive Status Examination (NCSE) assessing cognitive performance. Bivariate and then multivariate analysis were performed. Results: One hundred and sixty-one MS patients were included. Mean age was 44.2 years (s.d. 11.3 years), mean EDSS score was 4.86 (s.d. 1.93). Seventy-two per cent of the patients had objective cognitive impairment and 51% reported decreased perceived cognitive function. In all models assessing perceived cognitive function we could explain only a small part of the variance (R2 ranged between 18-26%). In all these models depressive symptoms explained the highest portion of the variance (partial R2 ranging between 13-26%). The only domain of the NCSE that entered some of the models was calculation (partial R2 ranging between 3-7%). Conclusions: These findings emphasize the gap between objective and subjective assessment of cognitive function and the high correlation between perceived cognitive deficit and depressive symptoms.
Intracellular cytokine profile in T-cell subsets of multiple sclerosis patients: different features in primary progressive disease
Authors: Killestein J , Den Drijver B F , Van der Graaff W L , Uitdehaag B MJ , Polman C H , Van Lier R AW
Published: January 2007

Objective: To evaluate the expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients with either relapsing-remitting (RR), secondary progressive (SP) or primary progressive (PP) MS and healthy controls (HC). Background: MS is an immune-mediated disease and cytokines have been hypothesized to contribute significantly to disease progression. Compared to the relapse-onset (RR, SP) form of the disease, PPMS patients have different clinical, immunological and pathological features. Surprisingly, the ability of their circulating T cells to produce immunoregulatory cytokines has not been extensively studied so far. Methods: Seventy-two MS patients (24 RR, 26 SP, 22 PP) and 34 HC were studied. Stimulated peripheral blood derived CD4+ and CD8+ T cells were analyzed for IFN-g, IL-2, TNF-a, IL-4, IL-10 and IL-13 production. Results: MS patients express significantly more CD4+ and CD8+ T cells producing IFN-g compared to HC. Compared to the other forms of the disease, PPMS patients display a significant decrease in CD4+ T cells producing IL-2, IL-13 and TNF-a and a significant increase in CD8+ T cells producing IL-4 and IL-10. Conclusions: The data presented here demonstrate that patients with PPMS express less pro- and more anti-inflammatory cytokine producing T cells compared to the relapse-onset form of the disease, confirming the view on PPMS as a distinct disease entity.
Similar pro- and anti-inflammatory cytokine production in the different clinical forms of multiple sclerosis
Authors: Durán I , Martínez-Cáceres E M , Brieva L , Tintoré M , Montalban X
Published: January 2007

Cytokines play an important role in the initiation and maintenance of the inflammatory reaction in multiple sclerosis, a chronic inflammatory demyelinating disease of the central nervous system. Magnetic resonance imaging evidence supports clinical divergence between forms of multiple sclerosis with relapses and the primary progressive form without relapses, which shows fewer and smaller inflammatory lesions. With the aim of understanding better the relative role of pro-inflammatory and/or anti-inflammatory cytokines in primary progressive multiple sclerosis in comparison to relapsing forms, we analysed in 65 patients (24 primary progressive, 20 relapsing-remitting and 21 secondary progressive) and 29 healthy controls, the production of cytokines (IFN-g, TNF-a, IL-6, IL-10 and IL-12) by peripheral blood mononuclear cells after in vitro stimulation. We found a similar percentage of cytokines producing cells between healthy controls and the different clinical forms of multiple sclerosis patients. Multiple Sclerosis (2001) 7, 151-156
A new test of memory for multiple sclerosis 1: Format development and stimuli design
Authors: Camp S J , Thompson A J , Langdon D W
Published: January 2007

Memory tests were often developed for healthy populations. The accuracy of these measures is reduced when administered to patients with neurological diseases, who may experience physical and/or cognitive symptoms. Also, methodological factors, for example, spanning the ability spectrum, and content/format artefacts, may contribute to a decline in test precision. The aim of this study was to develop a new test of memory, which addresses these issues. The new memory test comprises assessments of recall, paired association, and recognition, at a Task Familiarisation stage and two difficulty levels, for both the verbal and spatial modalities. It was administered to 85 healthy individuals and 100 patients with multiple sclerosis (MS). All patients were able to attempt each task of the new assessment, and there was no influence of visual integrity or manual dexterity on memory test performance, supporting the applicability of the tasks to patients with multiple sclerosis. Both the standardisation and validation samples demonstrated a wide range of scores on each section of the new test, suggesting that the measure spanned an acceptably broad range of abilities. It seems probable, therefore, that the new assessment offers a more exact measure of verbal and spatial recall, paired association, and recognition memory.
Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis
Authors: Egg R , Reindl M , Deisenhammer F , Linington C , Berger T
Published: January 2007

In a subset of multiple sclerosis (MS) patients antibodies against myelin antigens seem to be important in the demyelinating process. In this study we investigated IgM, IgA and IgG serum antibodies against the myelin oligodendrocyte glycoprotein (MOG) and the myelin basic protein (MBP) in 261 MS patients. Seventy-two per cent had anti-MOG antibodies, 59% were anti-MBP seropositive. The dominating antibody was anti-MOG IgM. A significant relationship between IgA and a progressive disease course was found. The predominance of IgG1 together with the significantly associated occurrence of IgG3 against MOG corresponds to the prevailing IgG1 and IgG3 isotypes in other autoimmune diseases. Patients who actually suffered from a relapse were significant more often anti-MOG and anti-MBP IgG3 seropositive than those in remission. However, patients treated either with intravenous immunoglobulins or interferon-b showed a significant reduction of anti-MOG IgG3 antibodies.
Pirfenidone for chronic progressive multiple sclerosis
Authors: Walker Jonathan E , Margolin Solomon B
Published: January 2007

Current treatment of secondary progressive multiple sclerosis is unsatisfactory in stabilizing or reversing the disabilities associated with the disease. Pirfenidone is a new non-peptide drug which has been shown in vitro and in vivo to decrease synthesis of Tumor Necrosis Factor-alpha (TNF-a) and block receptors for TNF-a. Since TNF-a seems to be a key cytokine in demyelination, a pilot study of oral pirfenidone was undertaken in an open-label baseline vs treatment protocol over a 2-year period in 20 patients. Fourteen (14/20) patients (70%) remained in the study for 2 years. Three (3/20) patients dropped out early because of gastrointestinal adverse reactions, and another three patients dropped out for personal reasons after 1 year (not because of adverse reactions). The remaining patients did not manifest any other drug-related adverse reactions and complications. Improvement or stabilization occurred in most patients at about 3 months, and it was sustained at 6, 12 and 24 months as evaluated by both primary and secondary outcome measures. Magnetic resonance imaging failed to reveal any new lesions. Thus, pirfenidone appears to offer protection against the usual slow progression of the disease. Most patients experienced a distinct decrease in their neurological disability. These findings indicate that an extensive multi-center double blind and placebo controlled trial is warranted.