bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern reversal visual evoked potentials as a measure of visual pathway pathology in multiple sclerosis
Authors: Weinstock-Guttman B , Baier M , Stockton R , Weinstock A , Justinger T , Munschauer F , Brownscheidle C , Williams J , Fisher E , Miller D , Rudick R
Published: November 2003

Background: Pattern reversal visual evoked potentials (PRVEPs) have a well-documented role in diagnosis of multiple sclerosis (MS), but their value as a visual function surrogate remains controversial. Methods: We evaluated PRVEP in 37 patients with MS who were participating in a long-term follow-up study following a phase III trial of interferon b-1a (A vonex®). Patients were examined to determine the Kurtzke Extended Disability Status Score (EDSS), multiple sclerosis functional composite (MSFC), contrast letter acuity (CLA), and had cranial MRI scans to determine whole brain atrophy (BPF). PRVEP was evaluated for P100 latency, amplitude, and waveform morphology. Two summary scores were created: for Score A, abnormal latencies, morphologies, and amplitudes of each individual eye were added; for Score B, abnormal latencies, morphologies, and amplitude ratio between eyes was determined. Sixteen patients in this group also had PRVEP at the time they enrolled in the clinical trial, eight years previously. Results: A t the follow-up exam, over 75% of patients had abnormal PVEP parameters while visual acuity (VA) was abnormal only in 59%. Increased PRVEP latency over the eight-year period correlated with deterioration assessed by EDSS (P = 0.006), BPF (P = 0.0001), and MSFC (P = 0.0041). Score A was significantly correlated with EDSS, BPF, C LA, cognitive function, and quality of life assessed with the Sickness Impact profile. No correlation was seen with the MSFC. Conclusions: The results indicate that PRVEP measures MS-related patho logy, and can provide not only diagnostic but also prognostic information during evaluation of MS patients.
MRI/MRS of corpus callosum in patients with clinically isolated syndrome suggestive of multiple sclerosis
Authors: Ranjeva J P , Pelletier J , Confort-Gouny S , Ibarrola D , Audoin B , Le Fur Y , Viout P , Chérif A Ali , Cozzone P J
Published: November 2003

A trophy of corpus callosum (C C) related to axonal loss has previously been observed in patients at the early stage of clinically definite multiple sclerosis (CDMS). Atrophy increases with the progression of the disease. Nevertheless, no data concerning the onset of atrophy of C C are currently available. The purpose of this study is to determine if damage in callosal tissue was present at the earliest stage of MS, in a subgroup of patients presenting with a clinically isolated syndrome suggestive of MS (C ISSMS), fulfilling the dissemination in space criteria according to McDonald. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) techniques were applied to measure C C volume, magnetization transfer ratio (MTR), mean diffusivity (MD), N-acetyl aspartate/choline-containing compounds (NAA/C ho) ratio, N-acetyl aspartate/total creatine (NA A/C r) ratio and C ho/C r ratio inside the C C of 46 C ISSMS patients and 24 sexand age-matched controls. No atrophy of C C was observed in the C ISSMS group. C C of patients was character ized by decreased MTR and increased MD. No change in the NA A/C r ratio was observed while the NA A/C ho ratio decreased and C ho/C r ratio increased in the splenium and the central anterio r part of C C. These abnormalities were present in patients with, but also without, macroscopic lesions inside the C C. O ur results indicate that diffuse structural and metabolic changes, which may be interpreted as representing predominantly myelin patho logy, occur in the C C at the earliest stage of MS before any atrophy is detected.
Chronic pain in a large community sample of persons with multiple sclerosis
Authors: Ehde Dawn M , Gibbons Laura E , Chwastiak Lydia , Bombardier Charles H , Sullivan Mark D , Kraft George H
Published: November 2003

Introduction: This study examined the prevalence, intensity, interference, and biopsychosocial correlates of pain in a large community-based sample of persons with multiple sclerosis (MS). Methods: Mail surveys were returned by 442 members of the King C ounty (WA) MS Association. Average pain intensity, pain-related activity interference, depressive symptoms and severity of MS were assessed. Results: Forty-four percent reported persistent, bothersome pain in the three months prior to completing the survey. Participants with pain reported an average pain intensity rating of 5.2 (SD =2.3) on the 0 (no pain) to 10 (pain as bad as could be) scale. Twenty-seven percent reported severe pain (score of 7-10), while 51% of those with pain rated the interference of their pain with daily activities as none to minimal. Twenty percent reported severe interference in activities as a result of pain. In multivariate modeling, MS illness severity, marital status, and self-ratings of overall health were significantly associated with pain-related interference with activities. Conclusions: A pproximately a fourth of this sample described having a chronic pain problem characterized by severe pain intensity and significant pain-related interference with activities. Disability due to pain may be more important than previously recognized for the MS population.
Neuromyelitis optica after a spinal anaesthesia with bupivacaine
Authors: Hosseini H , Brugieres P , Degos J D , Cesaro P
Published: November 2003

We report the case of a 53-year old woman who developed a neuromyelitis optica (NMO or Devic’s syndrome) after a spinal anaesthesia with bupivacaine. To our knowledge, the use of bupivacaine in human has not been associated to neurological complications like myelitis or NMO. The patho genesis of this complication will be discussed.
Longitudinal disability curves for predicting the course of relapsing-remitting multiple sclerosis
Authors: Achiron Anat , Barak Yoram , Rotstein Zeev
Published: November 2003

Background: Multiple sclerosis (MS) is a lifelong disease affecting young adults that ultimately can lead to significant neurological disability. Identifying the rate of progression of disability for an individual patient early in the disease process can influence treatment decisions as well as enable monitoring of the disease overtime. Objective: The aims of the present study were to develop longitudinal disability curves to assess disease progression in patients with relapsing -remitting MS. The construction of these disability curves was based on the mean yearly Expanded Disability Status Scale (EDSS) scores, represented as a major percentile group. To determine their predictive ability, validation of the percentile curves was performed. Methods: Using the Multiple Sclerosis C enter computerized database of 1540 patients’ records, we identified 1317 subjects with a definite MS and a relapsing-remitting disease course. Longitudinal disability curves were constructed for a subgroup of relapsing-remitting patients (n=1001) with consecutive (3-6 months) EDSS assessments for a period of up to 10 years since onset. The constructed disability curves were then validated in an additional subgroup of relapsing - remitting MS patients (n=268) with continuous follow-up visits for a period of 10 years. Results: Statistical procedures using parametric and nonparametric regression procedures were applied to the data in two stages. In the first stage, selected major percentiles were generated for up to 10 years from disease onset with a variety of parametric procedures including moving averages. In the second stage, the empirical percentiles were smoothed to obtain the final disability progression curves. The log-rank test for equality demonstrated a significant adjustment between the initial percentile assignment and disability progression (P B-0.001). Life table analysis demonstrated that the probability of deviating from the initially assigned percentile to a higher percentile over time, representing more severe disability than expected, is in the range of 6.5% for the 50th percentile to 10.4% for the 75th percentile. Conclusion: Longitudinal disability curves can be used in MS to assess individual patient disability, can contribute to the overall clinical impression of disease progression and can add to the evaluation of immunomodulating treatment effects overtime.
Cognitive fatigue during a test requiring sustained attention: a pilot study
Authors: Schwid Steven R , Tyler Carolyn M , Scheid Eileen A , Weinstein Amy , Goodman Andrew D , McDermott Michael P
Published: November 2003

Background: Fatigue is common in multiple sclerosis (MS), but difficulty quantifying fatigue severity has impeded studies of its characteristics, mechanisms, and therapeutics. Motor fatigue can be objectively measured as the decline in strength occurring during sustained contractio ns. A nalogous declines in cognitive performance occur during tasks requiring sustained attentio n. Objective: To objectively measure cognitive fatigue as a decline in performance during tests requiring sustained attentio n. Design/Methods: Patients with clinically stable MS (n=20) and healthy controls (n=21) with comparable age, gender, and education completed the Paced A uditory Serial A ddition Test (PA SAT) and the Digit O rdering Test (DOT) at two identical test sessions separated by 4-10 days, within a month after two practice sessions. C ognitive fatigue was quantified with two pre-specified methods for each test. The reliability of cognitive fatigue assessments was evaluated with intraclass correlation coefficients (ICC s) and construct validity was evaluated using correlations with measures of self-reported fatigue, cognition, and overall impairment/disability. Results: MS patients had an average of 18.7 items correct on the first 20 items of the PA SAT and 17.8 correct on the last 20 items, quantified as 5.3-5.8% declines in performance using the different measurement methods (P =0.01, rejecting the null hypothesis of zero mean decline). A lthough MS patients as a group demonstrated a similar decline at both sessions, IC C s were relatively low. C ontrol patients did not demonstrate significant declines in performance during PA SAT administration, but tests comparing declines in MS patients and controls did not demonstrate significant differences. Fatigue was not demonstrated using the DOT, and test-retest reliability was very poor. Conclusions: MS patients have objectively measurable cognitive fatigue during administration of the PASAT.
Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis
Authors: de Seze J , Lebrun C , Stojkovic T , Ferriby D , Chatel M , Vermersch P
Published: November 2003

Devic's neuromyelitis optica (NMO) associates optic neuritis and myelopathy without other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS). However, there have been no previous studies comparing these two patho logies and it is still unclear if NMO is a separate entity or a subtype of MS. In the present study, we compared a series of NMO patients with a series of MS patients for whom optic neuritis or myelopathy was the presenting symptom, in order to determine the place of NMO in the spectrum of MS. We retrospectively studied 30 patients diagnosed with NMO and we compared these patients with 50 consecutive MS cases revealed by optic neuritis or acute myelopathy. MS patients were only included if a relapse occurred demonstrating time and space dissemination. We compared the two groups in terms of clinical presentatio n, laboratory findings (MRI and C SF) and clinical outcome. NMO patients were older and more frequently women than MS patients but the difference was not significant. C SF and MRI data were clearly different: oligoclonal bands (O C B) were found in 23% of NMO cases and 88% of MS (P B/0.001), abnormal brain MRI data were observed in 10% of NMO cases and 66% of MS (P B/0.001) and a large spinal cord lesion was observed in 67% of NMO cases and 7.4% of MS cases (P B/0.001). C linical outcome was evaluated as more severe in the NMO group (P B/0.001). O n the basis of clinical data, all NMO patients but three had dissemination in time and space. When we included MRI parameters, only two of the NMO patients met criteria for MS and one of the MS patients met criteria for NMO. O ur study demonstrates that NMO and MS should be considered as two different entities. The respective criteria for NMO and MS were able to distinguish these two patho logies but only when MRI data were applied. This finding could have implications for future therapeutic trials.
Effect of visual information on step-tracking movements in patients with intention tremor due to multiple sclerosis
Authors: Feys P , Helsen W F , Liu X , Lavrysen A , Loontjens V , Nuttin B , Ketelaer P
Published: November 2003

The effect of visual information on step-tracking movements was studied in 18 patients with intention tremor due to multiple sclerosis (MS) and 15 healthy controls. Participants performed a slow wrist step-tracking task with stationary targets under five visual feedback conditions. The display of the target and movement cues was selectively withdrawn to examine the effects of visual information on intention tremor and movement accuracy.

Results showed that intentio n tremor was most pronounced when visual display of both target and movement cues was available. Withdrawing visual information of the limb movement reduced tremor more than withdrawing the visual display of the target cues. Both the patient and control group was less accurate when the display of limb movement was occluded. Patients, however, were more dependent on visual information of the limb movement for accurate motor performance than healthy controls.

When the visual display of the limb movement was partially occluded between or near to the targets, tremor decreased without deterioration of movement accuracy.
Elispot assay detection of cytokine secretion in multiple sclerosis patients treated with interferon-b1a or glatiramer acetate compared with untreated patients
Authors: Jansson A , Ernerudh J , Kvarnström M , Ekerfelt C , Vrethem M
Published: November 2003

The mechanisms behind the beneficial effects of interferon-b1a (IFN-b1a) and glatiramer acetate (GA) in the treatment of multiple sclerosis (MS) are still uncertain. A ltered cytokine patterns have been suggested including inhibition of proinflammatory cytokines like interferon-g (IFN-g) and enhancement of anti-inflammato ry cytokines such as interleukin-4 (IL-4). Twenty-nine patients with MS (10 untreated, nine treated with IFN-b1a and 10 with GA) were investigated with elispot of peripheral blood mononuclear cells. Spontaneous and myelin induced (myelin basic protein (MBP), myelin oligodendro cyte glycoprotein (MO G)-14-39 and MO G 63-87) IFN-g, IL-4, IL-5 and IL-10 secretion was studied. We found a significant reduction of spontaneous IFN-g, IL-4 and IL-5, but no difference in IL-10 secreting cells in both groups of treated patients compared with the untreated patients. Myelin-specific responses showed a significant decrease of IFN-g and an increase of IL-5, but no change in IL-4 and IL-10 secreting cells in treated compared with untreated patients. Both treatment groups revealed similar cytokine secretion patterns except for a more pronounced decrease of both spontaneous and MO G 14-39 induced IL-4 secretion in the IFN-b1a treated group. Thus, immunological effects of IFN-b1a and G A were similar showing that disease promoting Th1 (IFN-g) cells were reduced while the potentially beneficial Th2 response (IL-4) was maintained.
Sick leave and professional assistance for multiple sclerosis individuals in Vä sterbotten C ounty, northern Sweden
Authors: Sundström P , Nyström L , Svenningsson A , Forsgren L
Published: November 2003

The aims of this study of a cross-sectional multiple sclerosis (MS) population in V ä sterbotten C ounty, northern Sweden, were to estimate the prevalence of sick leave, professional assistance and housing; to study risk factors for sick leave; and to estimate the odds for sick leave in comparison with the general population of the county. The consequences of MS-related incapacity on the socioeconomic factors studied were considerable. A lmost half (45%) of prevalent MS cases aged 18-64 years were fully sick listed and only one-third (35%) were not sick listed at all. Every fourth individual in the prevalence population received professional assistance, and 9% were living in care homes or special apartments for the disabled. Multiple logistic regression analysis identified the Expanded Disability Status Scale (EDSS) as the strongest predicto r of sick leave. The time from symptom onset to full sick leave leading to temporary or permanent disability pension was significantly shorter for cases with progressive onset, higher age at onset and in males. The risk of full sick leave due to MS was six times higher than in the general population.
Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities
Authors: Traboulsee A , Dehmeshki J , Peters Kevin R , Griffin C M , Brex P A , Silver N , Ciccarrelli O , Chard D T , Barker G J , Thompson A J , Miller D H
Published: November 2003

Background: Magnetization transfer ratio (MTR) histogram analysis provides a global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in normal appearing brain tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic resonance imaging (MRI). A ims: 1) To compare the MTR histograms from NABT across a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR) MS (including newly diagnosed and benign subgroups) and secondary progressive (SP) MS. 2) To determine the relationship between clinical disability and NA BT MTR histograms. Methods: 2D spin echo magnetization transfer imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR histograms were acquired for NA BT after extracting lesions and cerebrospinal fluid (C SF). T2W images were used to measure the brain parenchymal fraction (BPF) and T2 lesion load. Results: MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5. There was a significant decrease in NA BT mean MTR (± standard deviation) compared with controls (33.07 pu± 1.06 versus 34.26 pu± 0.47; P < 0.001) with an effect size of 2.56. The reductio n in NA BT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for benign MS, compared with controls. NA BT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r =0.58). EDSS score correlated with NA BT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r =0.59). Multivariate analysis using NA BT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r =0.62; P <0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r =0.72; P <0.001). Conclusions: There is evidence of diffuse abnormalities in NA BT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. A trophy, NA BT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.
Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial
Authors: Johnson K P , Brooks B R , Ford C C , Goodman A D , Lisak R P , Myers L W , Pruitt A A , Rizzo M A , Rose J W , Weiner L P , Wolinsky J S
Published: November 2003

The aim of this study was to assess the long-term safety and efficacy of glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received active treatment versus those on placebo for approximately 30 months (24-35 months) before receiving GA during a six-year organized, prospective open label study. Entry required two relapses in the previous two years and an Expanded Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally randomized to daily subcutaneous G A, 20 mg, or to placebo. A fter approximately 30 months, 208 patients continued in an open label study: 101 continued on G A and 107 switched from placebo to active drug. Groups were well matched at randomization and entry to the open label study. Patients always on G A showed a steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over the entire six years (95% C I=0.34-0.51), a 72% reductio n (P =0.0001). They averaged a relapse every four+ years (yearly rate 0.23 in year six) and 26/101 remain relapse free. Patients did less well if on placebo for 30 months, but relapses then declined, and by year six the rates were similar. O f patients always on GA, 69% showed neurological improvement of > 1 EDSS steps or remained stable compared with 57% if G A treatment was delayed. O f relapse-free patients always on G A over six years, only three of 26 (11%) were worse by]-1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P B-0.03). Disability, measured every six months, showed that the group of patients always on G A was relatively stable over the six years, while the group who received placebo for the first two-and-a-half years did significantly less well. Daily injections of GA were well tolerated. This longest ever organized MS treatment trial shows that delaying therapy with GA increases the risk of neurologic disability, reinforcing the rationale for using G A as a first-line treatment early in the course of relapsing-remitting MS.
Antibodies to glatiramer acetate do not interfere with its biological functions and therapeutic efficacy
Authors: Teitelbaum D , Brenner T , Abramsky O , Aharoni R , Sela M , Arnon R
Published: November 2003

G latiramer acetate (GA) previously known as C opolymer 1 (Cop 1), a synthetic amino acid copolymer, suppresses experimental autoimmune encephalomyelitis (EAE) and shows a beneficial effect in relapsing-remitting type of multiple sclerosis (MS). G A acts as a specific immunomodulator by binding to MHC C lass II molecules, inducing specific T suppressor (Ts) cells and interfering with T cell responses to myelin antigens. MS patients treated with GA developed GA reactive antibodies, which peaked at three months and decreased at six months. In order to find out whether anti-G A antibodies may neutralize the therapeutic effect of GA, we tested both polyclonal (mouse and human) and monoclonal G A specific antibodies for their ability to interfere with the biological activity of GA in several assay systems. None of the antibodies interfered with GA activities either in vitro (binding to MHC molecules and T cell stimulation) or in vivo (blocking of EAE). Furthermore, 53 samples of sera obtained from 34 MS patients that participated in the open label trial in Israel, and all developed G A specific antibodies, were tested for their ability to inhibit the proliferation response of GA specific Ts cell clone and to interfere with G A competitive inhibition of the response to peptide 84-102 of myelin basic protein (MBP). None of the sera inhibited and some even enhanced the in vitro activities of G A. Furthermore, representative MS sera with high titer of G A reactive antibodies did not neutralize the biological activities of G A and did not inhibit Th2 cytokine secretion by human G A specific clone. These results are consistent with the findings that the therapeutic effect of GA is not affected by GA reactive antibodies and is sustained upon long term treatment.
Validity and reliability of the MSQ LI in cognitively impaired patients with multiple sclerosis
Authors: Marrie Ruth Ann , Miller Deborah M , Chelune Gordon J , Cohen Jeffrey A
Published: November 2003

Multiple sclerosis (MS) has important effects on quality of life but it is unknown how cognitive impairment affects the ability to assess or report this. O ur objective was to determine whether cognitive impairment negatively affects the construct validity and the reliability of the Multiple Sclerosis Q uality of Life Inventory (MSQLI). A neuropsychological test batter y and the Multiple Sclerosis Functional C omposite (MSFC) were administered to a sample of 136 patients referred for cognitive testing by their neurologists. A ge, sex, educatio n and ethnicity-adjusted T scores were calculated for each cognitive variable. C ognitive impairment was defined as any T score less than the fifth percentile. The MSQ LI was administered prior to neuropsychological testing and readministered one to four weeks later. C orrelations between the MSFC and the SF-36 were determined and compared between the cognitively impaired and unimpaired groups as the main test of construct validity. Test -retest and internal consistency reliability of each of the scales were compared for the impaired and unimpaired groups. Seventy-six (56%) patients were cognitively impaired. C onstruct validity and internal consistency reliability did not differ between the cognitively impaired and unimpaired groups. Test -retest reliability was lower for the bladder and vision scales in the impaired group, but remained acceptable for the bladder scale (r >0.7). C ognitive impairment, a common MS manifestation, does not appear to reduce the reliability or validity of the MSQ LI as a patient self-report measure of health status and quality of life.
The interleukin-1 gene family in multiple sclerosis susceptibility and disease course
Authors: Hooper-van Veen Tineke , Schrijver Hans M , Zwiers Antoon , Crusius J Bart A , Knol Dirk L , Kalkers Nynke F , Laine Marja L , Barkhof Frederik , Peña A Salvador , Polman Chris H , Uitdehaag Bernard MJ
Published: November 2003

Multiple sclerosis (MS) is a chronic disease of presumed autoimmune origin with a considerable polygenic influence. We have previously observed that a specific allele combination in genes of the interleukin-1 (IL-1) family influenced the progression rate in MS. We have considerably expanded our patient population (492 MS patients and 228 controls). In the present study, we investigated the role of the IL- 1A - 889, IL-1B - 511, IL-1B+3953 and IL-1RN VNTR gene polymorphisms in MS. In addition, we performed preliminary analyses on longitudinal magnetic resonance imaging (MRI) data. We found no associations between the polymorphisms and susceptibility to MS or clinical features. In addition, we observed no significant effect of the polymorphisms on brain or lesion volumes, Based on our data and those from the literature, one can conclude that there is currently no evidence to support a role for the IL-1 genes in MS.
Flavonoid treatment in patients with healed venous ulcer: flow cytometry analysis suggests increased CD11b expression on neutrophil granulocytes in the circulation
Authors: Danielsson Gudmundur , Norgren Lars , Truedsson Lennart , Andreasson Annica , Danielsson Peter , Nilsson Anna , Swartbol Paul
Published: November 2003

The objective was to determine the activation of white blood cells (WBCs) and endothelial cells in patients with healed venous ulcer and the influence of the standing position and of treatment with flavonoids. Ten patients with a healed venous ulcer were treated with flavonoid substance (90% diosmin), 1000 mg three times daily for 30 days. Blood samples were taken from arm and dorsal foot veins before and after standing for 30 minutes. Blood sampling was performed before treatment, after three days, one month and three months. The activation of WBCs was determined by measuring adhesion molecule CD11b and CD18 expression on the surface of granulocytes and monocytes. In addition, interleukin 6 (IL-6), IL-8, soluble E-selectin (sE-selectin), sL-selectin and sICAM-1 levels in serum were quantified. The results showed that standing did not influence any of the measured parameters significantly. Expression of CD11b adhesion molecules on granulocytes was significantly up-regulated (p = 0.044) after treatment with flavonoids for one month, but this increase was not significant (p = 0.056) two months after the treatment period compared with the baseline level. The expression of CD18 remained unchanged. Baseline expression of CD11b or CD18 on monocytes did not change significantly during the study period. Neither was any significant change observed in the levels of IL-6, IL- 8 or the soluble adhesion molecules. It was concluded that flavonoid treatment for 30 days increased the expression of CD11b adhesion molecules on circulating granulocytes. No general effect on the inflammatory process could be observed as assessed by levels of cytokines and soluble adhesion molecules. Possible explanations for these findings could be that a decreased number of primed granulocytes leave the circulation due to a changed WBC/endothelial cell interaction or that flavonoids have a direct effect on granulocytes. Further studies are needed to clarify the mode of action of flavonoids in chronic venous disease.
Oral L-arginine improves endothelial function in healthy individuals older than 70 years
Authors: Bode-Böger Stefanie M , Muke Jochen , Surdacki Andrzej , Brabant Georg , Böger Rainer H , Frölich Jürgen C
Published: November 2003

Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects (age 73.8 6 2.7 years) took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia. Baseline artery diameter was 3.88 6 0.18 mm. l-Arginine signifi cantly improved FMD (to 5.7 6 1.2%, p, 0.0001), whereas placebo had no effect (-0.25 6 0.7%; n.s.). After L-arginine, plasma levels of L-arginine increased signifi cantly (114.9 6 11.6 versus 57.4 6 5.0 mmol/l), but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals (3.9 6 0.2 versus 1.0 6 0.1 mmol/l; p, 0.0001). ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio (p, 0.05). We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio.
Early-onset peripheral arterial occlusive disease: clinical features and determinants of disease severity and location
Authors: Barretto Simone , Ballman Karla V , Rooke Thom W , Kullo Iftikhar J
Published: November 2003

Early-onset peripheral lower extremity arterial occlusive disease (PAD) is an uncommon, poorly characterized manifestation of atherosclerotic vascular disease. We studied the clinical presentation and correlates of disease severity and location in patients with early-onset PAD identifi ed at non-invasive arterial evaluation. We identifi ed a series of 159 patients who were younger than 50 years and had an abnormal resting or postexercise ankle brachial index (ABI) (<0.9) or, if arteries were noncompressible, monophasic arterial Doppler signals. Disease severity and location were determined based on results of noninvasive vascular laboratory testing. Presence of coexisting atherosclerosis in other arterial beds was ascertained by review of patient records. Multivariable logistic regression analyses were used to identify risk factors associated with disease severity and location. Mean age of the patients was 42.7 6 4.2 years and 55% were women. Prevalence of risk factors was 76% for current or past smoking; 71%, dyslipidemia; 53%, hypertension; 35%, diabetes; and 53%, family history. Claudication was present in 50%, rest pain in 3%, ulceration in 31% and the remaining 16% did not have symptoms from PAD. Low high-density lipoprotein (HDL)-cholesterol and female sex were associated with severity. Of 102 patients in whom disease location could be determined noninvasively, 65% had aortoiliac disease. Female sex, low HDL-cholesterol, and absence of diabetes were associated with aortoiliac disease. Atherosclerosis in other arterial beds was identifi ed in 53% of the patients. Conclusion: In this study population of early-onset atherosclerotic PAD, men and women were equally represented. The disease involved predominantly the aortoiliac location. Low HDL-cholesterol and female sex were associated with disease severity. An aggressive approach to diagnosis and treatment may be warranted as atherosclerosis in other arterial beds was prevalent in half of the patients.
The challenges of treating peripheral arterial disease
Authors: Kügler Christian FA , Rudofsky Gottfried
Published: November 2003

Today, peripheral arterial disease (PAD) patients need effective medical care for an extended period of their lifetime. Therefore, different treatment modalities have to be tied sequentially into an effective therapeutic chain. First, preventive measures have to be reinforced and risk factors tightly controlled. Furthermore, antiplatelet agents have to be applied in every PAD patient to reduce the risk of cardiac and cerebral ischemic events, restenosis or reocclusion after revascularization, and possibly also progression of the PAD itself. Angiotensin-converting enzyme (ACE) inhibitors should be entertained in high-risk groups such as PAD patients with diabetes. In the claudicant, exercise therapy should be strongly encouraged and vasoactive drugs considered for those who are not good candidates for either exercise training or revascularization. In patients with disabling claudication or critical limb ischemia, revascularization procedures are highly effective. Especially for high-grade stenoses or short arterial occlusions, percutaneous transluminal angioplasty (PTA) should be the method of fi rst choice followed by the best surgical procedure later on. To achieve good long-term effi cacy, a close follow-up including objective tests of both the arterial lesion and hemodynamic status, surveillance of secondary preventive measures and risk factor control is mandatory.
Gender differences in perception of PAD: a pilot study
Authors: Oka Roberta K , Szuba Andrzej , Giacomini John C , Cooke John P
Published: November 2003

Patients with peripheral arterial disease (PAD) report profound limitations in all domains of quality of life that are worse than those for patients with chronic pulmonary disease and moderate to severe heart failure. While claudication has detrimental effects on quality of life, little is understood about the factors that influence quality of life and whether these determinants are similar for men and women with PAD and claudication. The purpose of the present investigation was to evaluate the effect of claudication on quality of life in 71 men and 26 women (mean age 72 and 73 years respectively) with PAD. Disease severity as assessed by ankle brachial index (ABI) and community-based walking was similar for men and women, although men reported greater comorbid conditions than women. Despite the similarity in disease severity, women reported decreased physical functioning (p = 0.01), more bodily pain (p = 0.04) and greater mood disturbance (p = 0.012) than men. Claudication and PAD had a greater impact on women than on men and may result from the higher prevalence of mood disturbance and bodily pain reported by women.
Functional outcomes and quality of life in peripheral arterial disease: current status
Authors: Nehler Mark R , McDermott Mary M , Treat-Jacobson Diane , Chetter Ian , Regensteiner Judith G
Published: November 2003

This review examines current evidence for baseline functional impairment and changes with therapy in patients with peripheral arterial disease (PAD) - ranging from patients without claudication or critical limb ischemia (CLI) but other exertional leg symptoms (erroneously referred to as asymptomatic in the Fontaine classifi cation system), to patients with claudication and those with CLI. The review points out that the status of functional outcomes research is markedly different in focus and development in the different levels of disease severity - paradoxically less studied in the more severe CLI population than in patients with claudication, for example.
Diagnosis and management of thoracic and abdominal vascular injuries
Authors: Bif‘ WL , Moore EE , Burch JM
Published: November 2003

Thoracic and abdominal vascular injuries present a formidable challenge to the most experienced surgeon. As prehospital care improves, more patients with these injuries are reaching the hospital alive. Thus, the trauma surgeon must be prepared to deal with them rapidly and precisely. Hemodynamically unstable patients should be transferred directly to the operating room. In stable patients with penetrating thoracic wounds, chest X-ray and arteriography are typically employed to exclude vascular injury. Patients sustaining blunt chest trauma can be screened effectively with CT scanning. Incisions are chosen based on the injured vessel. Hemorrhagic shock is the usual presentation for abdominal vascular trauma. A high index of suspicion is critical in diagnosing occult injuries. This presentation reviews the etiology, diagnosis, and treatment of major thoracic and abdominal vascular injuries.
The Glasgow Coma Scale: History and current practice
Authors: Jennett Bryan
Published: November 2003

The Glasgow Coma Scale (GCS) was devised to assess injury severity in a multi-centre study of outcome after severe brain damage. It uses unambiguous terms that are readily understood by a wide range of observers. Giving numbers to responses makes communication and display of responsiveness easy and the overall score allows classifi cation of overall severity of brain injury for triage and for epidemiological studies. The total score involves some loss of predictive information. Outcome correlates well with the early GCS both in head injuries and other intensive care patients. When early sedation and ventilation after head injury makes GCS assessment difficult, the motor score is often available and is a useful index of injury severity. The GCS also facilitates monitoring in the early stages after injury, allowing rapid detection of complications. Even among mild injuries (GCS 13- 15) the scale can discriminate between those more or less likely to have detectable brain damage and to be at risk of complications.
Use of the internet to improve trauma care
Authors: Brohi Karim
Published: November 2003

The Internet has changed the way much of the world communicates. Near-instantaneous global interaction and a planet-sized information database have allowed the Internet to penetrate areas where textbooks, journals and conferences cannot. This essay describes the genesis and evolution of trauma on the Internet, discusses how the Internet may impact on global trauma care and identifies some future applications of the medium.
Thoracic trauma: principles of early management
Authors: Tai Nigel RM , Boffard Kenneth D
Published: November 2003

Thoracic trauma remains an important cause of early and late mortality in the injured patient. This review provides an overview of the emergency room management of thoracic trauma, amplifying the approach and principles of Advanced Trauma Life Support. The presentation, pathophysiology, diagnosis and treatment of the 12 most significant thoracic injuries are described. Focusing on emergency room management, and using the concept of the ‘lethal six’ and ‘hidden six,’ appropriate management strategies are detailed.
Examination of the injured shoulder
Authors: Carmichael Ian W
Published: November 2003

Examination of the shoulder joint should be relatively straightforward, given that it is a very superficial joint. Examination starts with a detailed history, including activities of daily living, and progresses in a logical manner through Apley’s ‘look, feel, move’. ‘Move’ is further split into active, passive and special tests. These are designed to look at various specific aspects of shoulder pathology. Not every test needs to be done in every patient. You should then have a clear idea of the underlying pathology before embarking on radiological examination.
Pretibial wounds: a review of current practice
Authors: Batchelor JS , Alagappan D
Published: November 2003

Pretibial wounds are often associated with prolonged wound healing, particularly in the elderly female population. The wounds characteristically have either a proximally or distally based flap. Delayed wound healing has been attributed to flap necrosis and poor blood supply to this area. The aim of this review article is to examine the vascular anatomy, pathology and management options of patients with pretibial wounds.
Interpolation of nonstationary air pollution processes: a spatial spectral approach
Authors: Fuentes Montserrat
Published: November 2003

Spatial processes are important models for many environmental problems. Classical geostatistics and Fourier spectral methods are powerful tools for stuyding the spatial structure of stationary processes. However, it is widely recognized that in real applications spatial processes are rarely stationary and isotropic. Consequently, it is important to extend these spectral methods to processes that are nonstationary. In this work, we present some new spectral approaches and tools to estimate the spatial structure of a nonstationary process. More specifically, we propose an approach for the spectral analysis of nonstationary spatial processes that is based on the concept of spatial spectra, i.e., spectral functions that are space-dependent. This notion of spatial spectra generalizes the definition of spectra for stationary processes, and under certain conditions, the spatial spectrum at each Location can be estimated from a single realization of the spatial process.

The motivation for this work is the modeling and prediction of ozone concentrations over different geopolitical boundaries for assessment of compliance with ambient air quality standards.
Calibrated spatial moving average simulations
Authors: Cressie Noel , Pavlicová Martina
Published: November 2003

The spatial moving average (SMA) is a very natural type of spatial process that involves integrals or sums of independent and identically distributed random variables. Consequently, the mean and covariance function of the SMAs can be written down immediately in terms of their integrand or summand. Moreover, simulation from them is straightforward, and it does not require any large-matrix inversions. Although the SMAs generate a large class of spatial covariance functions, can we find easy-to-use SMAs, calibrated to be ‘like’ some of the usual covariance functions used in geostatistics? For example, is there an SMA that is straightforward to simulate from, whose covariance function is like the spherical covariance function? This article will derive such an SMA.
Multiresolution models for nonstationary spatial covariance functions
Authors: Nychka Douglas , Wikle Christopher , Royle J Andrew
Published: November 2003

Many geophysical and environmental problems depend on estimating a spatial process that has nonstationary structure. A nonstationary model is proposed based on the spatial field being a linear combination of multiresolution (wavelet) basis functions and random coefficients. The key is to allow for a limited number of correlations among coefficients and also to use a wavelet basis that is smooth. When approximately 6% nonzero correlations are enforced, this representation gives a good approximation to a family of Matern covariance functions. This sparseness is important not only for model parsimony but also has implications for the efficient analysis of large spatial data sets. The covariance model is successfully applied to ozone model output and results in a nonstationary but smooth estimate.
Flexible smoothing with P-splines: a unified approach
Authors: Currie I D , Durban M
Published: November 2003

We consider the application of P-splines (Eilers and Marx, 1996) to three classes of models with smooth components: semiparametric models, models with serially correlated errors, and models with heteroscedastic errors. We show that P-splines provide a common approach to these problems. We set out a simple nonparametric strategy for the choice of the P-spline parameters (the number of knots, the degree of the P-spline, and the order of the penalty) and use mixed model (REML) methods for smoothing parameter selection. We give an example of a model in each of the three classes and analyse appropriate data sets.
Regression analysis of variates observed on (0, 1): percentages, proportions and fractions
Authors: Kieschnick Robert , McCullough B D
Published: November 2003

Many types of studies examine the influence of selected variables on the conditional expectation of a proportion or vector of proportions, for example, market shares, rock composition, and so on. We identify four distributional categories into which such data can be put, and focus on regression models for the first category, for proportions observed on the open interval (0, 1). For these data, we identify different specifications used in prior research and compare these specifications using two common samples and specifications of the regressors. Based upon our analysis, we recommend that researchers use either a parametric regression model based upon the beta distribution or a quasi-likelihood regression model developed by Papke and Wooldridge (1997) for these data. Concerning the choice between these two regression models, we recommend that researchers use the parametric regression model unless their sample size is large enough to justify the asymptotic arguments underlying the quasi-likelihood approach.
Correcting for covariate measurement error in logistic regression using nonparametric maximum likelihood estimation
Authors: Rabe-Hesketh Sophia , Pickles Andrew , Skrondal Anders
Published: November 2003

When covariates are measured with error, inference based on conventional generalized linear models can yield biased estimates of regression parameters. This problem can potentially be rectified by using generalized linear latent and mixed models (GLLAMM), including a measurement model for the relationship between observed and true covariates. However, the models are typically estimated under the assumption that both the true covariates and the measurement errors are normally distributed, although skewed covariate distributions are often observed in practice. In this article we relax the normality assumption for the true covariates by developing nonparametric maximum likelihood estimation (NPMLE) for GLLAMMs. The methodology is applied to estimating the effect of dietary fibre intake on coronary heart disease. We also assess the performance of estimation of regression parameters and empirical Bayes prediction of the true covariate. Normal as well as skewed covariate distributions are simulated and inference is performed based on both maximum likelihood assuming normality and NPMLE. Both estimators are unbiased and have similar root mean square errors when the true covariate is normal. With a skewed covariate, the conventional estimator is biased but has a smaller mean square error than the NPMLE. NPMLE produces substantially improved empirical Bayes predictions of the true covariate when its distribution is skewed.