bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the Molecular Adsorbents Recirculating System (MARS) in the management of liver failure
Authors: Sen Sambit , Jalan Rajiv
Published: August 2006

Albumin-bound toxins accumulate in liver failure, and are believed to contribute to the development of the associated end-organ dysfunctions (kidney, circulation, brain). The scavenging functions of albumin are utilized in albumin dialysis for toxin removal. The Molecular Adsorbents Recirculating System (MARS) is an extracorporeal liver support device based on dialysis across an albumin-impregnated membrane, using 20% albumin as dialysate. Charcoal and anion exchange resin columns in the circuit help cleanse and regenerate the dialysate. Clinical studies over the last decade have demonstrated proven reduction in hyperbilirubinaemia, along with an improvement in hepatic encephalopathy, systemic haemodynamics and renal function in liver failure patients, as well as apparent improvement in survival. However, the specific mechanisms underlying these observed clinical changes are as yet unclear. The results of larger controlled clinical trials, as well as studies investigating the pathophysiological basis of its effect, are awaited.
Does modified ultrafiltration reduce the systemic inflammatory response to cardiac surgery with cardiopulmonary bypass?
Authors: Chew Michelle S
Published: August 2006

Cardiopulmonary bypass (CPB) is associated with an accumulation of total body water and a systemic inflammatory response syndrome (SIRS), which, in turn, is associated with organ dysfunction and postoperative morbidity. It has been suggested that modified ultrafiltration (MUF) may be capable of reducing SIRS and improving clinical outcome by filtering out the inflammatory mediators generated during CPB. This paper reviews the data regarding the use of MUF in paediatric and adult settings. Specifically, three issues will be considered: 1) Does MUF improve clinical outcome? 2) Does MUF reduce the systemic inflammatory response to cardiac surgery with CPB? 3) Is MUF more effective than conventional ultrafiltration in improving clinical outcome?
Bubbles and bypass: an update
Authors: Kurusz Mark , Butler Bruce D
Published: August 2006

Bubbles in the bloodstream are not a normal condition -yet they remain a fact of cardiopulmonary bypass (CPB), having been extensively studied and documented since its inception some 50 years ago. While detectable levels of gaseous microemboli (GME) have decreased significantly in recent years and gross air embolism has been nearly eliminated due to increased awareness of etiologies and technological advances, methods of use of current perfusion systems continue to elicit concerns over how best to totally eliminate GME during open-heart procedures. A few studies have correlated adverse neurocognitive manifestations associated with excessive quantities of GME.

Newer techniques currently in vogue, such as vacuum-assisted venous drainage, low-prime perfusion circuits, and carbon dioxide flooding of the operative field, have, in some instances, exacerbated the problem of gas embolism or engendered secondary complications in the safe conduct of CPB. Doppler monitoring (circuit or transcranial) primarily remains a research tool to detect GME emanating from the circuit or passing into the patients’ cerebral vasculature. Newer developments not yet widely available, such as multiple-frequency harmonics, may finally provide a tool to distinguish particulate microemboli from GME and further delineate the clinical significance of GME.
Pathophysiological Basis of CNS Injury in Cardiac Surgical Patients: Detection and Prevention
Authors: Murkin John M
Published: August 2006

The current understanding of adverse central nervous system (CNS) events following cardiac surgery involves several identifiable, evidence-based mechanisms: athero-sclerotic emboli, microgaseous and microparticulate emboli, and hypoperfusion.1 Secondary factors, including patient co-morbidities and inherent genetic susceptibilities, as well as systemic inflammatory processes and a suboptimal metabolic milieu may interact to potentiate the extent of injury.2 In this review a number of these factors and their potential interactions will be explored with a view towards developing a comprehensive management strategy to minimize CNS injury.
Cardiopulmonary Bypass and Renal Injury
Authors: Abu-Omar Yasir , Ratnatunga Chandana
Published: August 2006

Renal dysfunction following cardiopulmonary bypass (CPB) is well recognized. The extent of perioperative renal impairment ranges from subclinical injury to established renal failure requiring dialysis. Its incidence varies considerably, depending on the definition and criteria used in the different studies. Acute renal failure (ARF) affects 1-5% of patients and remains a major cause of morbidity and mortality. Co-morbidities, including diabetes mellitus, impaired left ventricular function and advanced age, are recognized predisposing factors. The pathophysiology is multifactorial and is thought related to the systemic inflammatory response and renal hypoperfusion secondary to extracorporeal circulation. Non-pulsatile flow during CPB is thought to be an important aetiological factor, resulting in renal vasoconstriction and ischaemic renal injury. A theoretical reduction in the incidence and severity of postoperative renal impairment has been proposed by advocating the use of pulsatile flow during CPB, or eliminating CPB, especially in high-risk patients. The current evidence, however, is conflicting. Several large observational studies, including a large proportion of high-risk patients, have demonstrated a significant reduction in the frequency of renal failure in patients undergoing off-pump surgery. As older, sicker patients increasingly constitute the cardiac surgical population, the incidence of postoperative renal injury is likely to increase. Further studies addressing various renoprotective strategies in higher-risk patients are awaited.
Paediatric CPB: Bypass in a High Risk Group
Authors: Jones TJ , Elliott MJ
Published: August 2006

Children and particularly neonates present unique challenges during CPB. Patient age, size, underlying anatomy and surgical strategy influence the perfusion techniques and the construction of the CPB circuit. The normal changes in physiology in the first weeks of life impact upon surgical technique and outcome of repair.

Limited surgical access necessitates alternative cannulation strategies. Deep hypothermia, low flow CPB and circulatory arrest are frequently used. An understanding of the related pathophysiology is therefore required to make the correct choices and to optimise patient outcome.
Would the addition of TENS to exercise training produce better physical performance outcomes in people with knee osteoarthritis than either intervention alone?
Authors: Cheing Gladys LY , Hui-Chan Christina WY
Published: August 2006

Objective: To examine if the addition of transcutaneous electrical nerve stimulation (TENS) to exercise training would produce better physical outcomes than TENS or exercise alone in people with knee osteoarthritis.

Design: Sixty-two subjects were randomly allocated to four groups.

Interventions: Patients received either (1) TENS, (2) placebo stimulation, (3) exercise training, or (4) TENS and exercise training five days a week for four weeks.

Main outcome measures: The isometric peak torque, spatiotemporal gait parameters and range of knee movement were assessed in treatment session1, session10 and session20 and the four-week follow-up.

Results: By session20, the TENS and exercise group demonstrated an average of 26.6% cumulative gain in the knee extensor peak torque for the different knee positions (all p < 0.05). Although the between-group difference was short of being statistically significant, the gain found in the TENS and exercise group was greater than that found in the other three groups. The TENS and exercise group also tended to show greater cumulative increase in stride length (12.6%, p-0.006), walking cadence (9.3%, p-0.098) and gait velocity (22.4%, p-0.034) than the other groups. By session20, it was the only group that produced a significant increase in the range of knee motion during walking (12.0%,p-0.000). The TENS group and the exercise group both demonstrated some improvements in the above physical outcomes, but negligible change was found in the group receiving placebo stimulation (all p > 0.05).

Conclusion: No significant difference was found among the four treatment protocols, but the addition of TENS to exercise training tended to produce the best overall improvement in physical outcomes in people with knee osteoarthritis.
Home training with and without additional group training in physically frail old people living at home: effect on health-related quality of life and ambulation
Authors: Helbostad Jorunn L , Sletvold Olav , Moe-Nilssen Rolf
Published: August 2006

Objective: To test the effect of two exercise regimes on health-related quality of life (HRQoL) and ambulatory capacity.

Design: Randomized controlled trial.

Subjects: Seventy-seven community-dwelling physically frail people over 75 years of age (mean=81, SD=4.5).

Interventions: Home training (HT, N =38) comprised twice daily functional balance and strength exercises and three group meetings. Combined training (CT, N =39) included group training twice weekly and the same home exercises. Interventions lasted 12 weeks. Physiotherapists ran both programmes. Home exercises were recorded daily.

Main measures: HRQoL was assessed by SF-36, and ambulatory capacity by walking speed and frequency and duration of outdoor walks.

Results: Following intervention, CT improved the SF-36 mental health index significantly more than HT (p =0.01). The SF-36 physical health index (p =0.002) and walking speed (p =0.02) demonstrated improvements, but no group differences. Six months after cessation of intervention there was still overall improvements on the mental health index (p =0.032), borderline overall improvements on the physical health index (p =0.057), higher weekly number of outdoor walks for the CT group than for the HT group (p =0.027) and an improved habitual walking speed in the CT group only (p =0.022).

Conclusions: HT improved HRQoL and walking speed, but additional group training gave larger benefits on mental health. Group training away from home may be beneficial for mental health and ambulatory capacity.
A task-orientated intervention enhances walking distance and speed in the first year post stroke: a randomized controlled trial
Authors: Salbach N M , Mayo N E , Wood-Dauphinee S , Hanley J A , Richards C L , Côté R
Published: August 2006

Objective: To evaluate the efficacy of a task-orientated intervention in enhancing competence in walking in people with stroke.

Design: Two-centre observer-blinded stratified block-randomized controlled trial.

Setting: General community.

Subjects: Between May 2000 and February 2003, 91 individuals with a residual walking deficit within one year of a first or recurrent stroke consented to participate.

Interventions: The experimental intervention comprised 10 functional tasks designed to strengthen the lower extremities and enhance walking balance, speed and distance. The control intervention involved the practice of upper extremity activities. Subjects in both groups attended sessions three times a week for six weeks.

Main measures: Six-minute walk test (SMWT), 5-m walk (comfortable and maximum pace), Berg Balance Scale, timed ‘up and go’.

Results: At baseline, subjects in the experimental ( n = 44) and control ( n = 47) groups walked an average distance of 209 m (SD = 126) and 204 m (SD = 131), respectively, on the SMWT. Mean improvements of 40 m (SD = 72), and 5 m (SD = 66) were observed following the experimental and control interventions, respectively. The between-group difference was 35 m (95% confidence interval (CI) 7, 64). Significant between-group effects of 0.21 m/s (95% CI 0.12, 0.30) and of 0.11 m/s (95% CI 0.03, 0.19) in maximum and comfortable walking speed, respectively, were observed. People with a mild, moderate or severe walking deficit at baseline improved an average of 36 (SD = 96), 55 (SD = 56) and 18 m (SD = 23), respectively, in SMWT performance following the experimental intervention.

Conclusions: Study findings support the efficacy of a task-orientated intervention in enhancing walking distance and speed in the first year post stroke, particularly in people with moderate walking deficits.
The long-term outcomes from a randomized controlled trial of an educational–behavioural joint protection programme for people with rheumatoid arthritis
Authors: Hammond A , Freeman K
Published: August 2006

Objective: To evaluate the long-term effects of joint protection on health status of people with early rheumatoid arthritis (RA).

Design: A four-year follow-up of a randomized, controlled, assessor-blinded trial was conducted.

Setting: Two rheumatology outpatient departments.

Participants: People with rheumatoid arthritis less than five years since diagnosis.

Interventions: Two 8-hour interventions were originally compared: a standard arthritis education programme, including 21/2 hours of joint protection based on typical UK occupational therapy practice (plus 51/2 hours on RA, exercise, pain management, diet and foot care); and a joint protection programme, using educational-behavioural training.

Main measures: Adherence to joint protection, pain, hand pain on activity, Arthritis Impact Measurement Scales 2 and Arthritis Self-efficacy were recorded at 0 and 4 years.

Results: Sixty-five people attended the joint protection and 62 the standard programmes. Groups at entry were similar in age (51 years; 49 years), disease duration (21 months: 17.5 months) and use of nonsteroidal anti-inflammatory and disease-modifying drugs. At four years, the joint protection group continued to have significantly better: joint protection adherence (p=0.001); early morning stiffness (p=0.01); AIMS2 activities of daily living (ADL) scores (p=0.04) compared with the standard group. The joint protection group also had significantly fewer hand deformities: metacarpophalangeal (MCP) (p=0.02) and wrist joints (p=0.04).

Conclusion: Attending an educational=behavioural joint protection programme significantly improves joint protection adherence and maintains functional ability long term. This approach is more effective than standard methods of training and should be more widely adopted.
Can augmented physiotherapy input enhance recovery of mobility after stroke? A randomized controlled trial
Authors:   The Glasgow Augmented Physiotherapy Study (GAPS) group
Published: August 2006

Objective: To discover if the provision of additional inpatient physiotherapy after stroke speeds the recovery of mobility.

Design: A multisite single-blind randomized controlled trial (RCT) comparing the effects of augmented physiotherapy input with normal input on the recovery of mobility after stroke.

Setting: Three rehabilitation hospitals in North Glasgow, Scotland.

Subjects: Patients admitted to hospital with a clinical diagnosis of stroke, who were able to tolerate and benefit from mobility rehabilitation.

Intervention: We aimed to provide double the amount of physiotherapy to the augmented group.

Main measures: Primary outcomes were mobility milestones (ability to stand, step and walk), Rivermead Mobility Index (RMI) and walking speed.

Results: Seventy patients were recruited. The augmented therapy group received more direct contact with a physiotherapist (62 versus 35 minutes per weekday) and were more active (8.0% versus 4.8% time standing or walking) than normal therapy controls. The augmented group tended to achieve independent walking earlier (hazard ratio 1.48, 95% confidence interval 0.90–2.43; p=0.12) and had higher Rivermead Mobility Index scores at three months (mean difference 1.6; 0.1 to 3.3; p=0.068) but these differences did not reach statistical significance. There was no significant difference in any other outcome.

Conclusions: A modest augmented physiotherapy programme resulted in patients having more direct physiotherapy time and being more active. The inability to show statistically significant changes in outcome measures could indicate either that this intervention is ineffective or that our study could not detect modest changes.
Does motor imagery training improve hand function in chronic stroke patients? A pilot study
Authors: Dijkerman H C , Ietswaart M , Johnston M , MacWalter R S
Published: August 2006

Objective: To assess the efficacy of motor imagery training for arm function in chronic stroke patients. The relation between mental processes such as attentional and perceived personal control over recovery, and motor imagery was additionally investigated.

Design and subjects: Twenty patients with long-term motor impairments (mean two years post stroke), were assessed before and after four weeks of training. Ten patients mentally rehearsed movements with their affected arm. Their recovery was compared with patients who performed nonmotor imagery (n =5), or who were not engaged in mental rehearsal (n =5).

Setting: Patients were recruited from the stroke database of Ninewells Hospital, Dundee. Assessment and training were performed at the patients' home.

Interventions: The motor imagery group was asked to practise daily imagining moving tokens with their affected arm. The nonmotor imagery group rehearsed visual imagery of previously seen pictures. All patients practised physically moving the tokens.

Main measures: The following variables were assessed before and after training: motor function (training task, pegboard and dynamometer), perceived locus of control, attention control and ADL independence.

Results: All patient groups improved on all motor tasks except the dynamometer. Improvement was greater for the motor imagery group on the training task only (average of 14% versus 6%). No effect of motor imagery training was found on perceived or attentional control.

Conclusions: Motor imagery training without supervision at home may improve performance on the trained task only. The relation between movement imagery, attention and perceived personal control over recovery remained unclear.
The effect of an ankle-foot orthosis on walking ability in chronic stroke patients: a randomized controlled trial
Authors: de Wit D CM , Buurke J H , Nijlant J MM , IJzerman M J , Hermens H J
Published: August 2006

Objective: Regaining walking ability is a major goal during the rehabilitation of stroke patients. To support this process an ankle-foot orthosis (AFO) is often prescribed. The aim of this study is to investigate the effect of an AFO on walking ability in chronic stroke patients.

Design: Cross-over design with randomization for the interventions.

Methods: Twenty chronic stroke patients, wearing an AFO for at least six months, were included. Walking ability was operationalized as comfortable walking speed, scores on the timed up and go (TUG) test and stairs test. Patients were measured with and without their AFO, the sequence of which was randomized. Additionally, subjective impressions of self-confidence and difficulty of the tasks were scored. Clinically relevant differences based on literature were defined for walking speed (20 cm/s), the TUG test (10 s). Gathered data were statistically analysed using a paired t-test.

Results: The mean difference in favour of the AFO in walking speed was 4.8 cm/s (95% CI 0.85–8.7), in the TUG test 3.6 s (95% CI 2.4 4.8) and in the stairs test 8.6 s (95% CI 3.1 –14.1). Sixty-five per cent of the patients experienced less difficulty and 70% of the patients felt more self-confident while wearing the AFO.

Conclusions: The effect of an AFO on walking ability is statistically significant, but compared with the a priori defined differences it is too small to be clinically relevant. The effect on self-confidence suggests that other factors might play an important role in the motivation to use an AFO.
Effects of specific rehabilitation for dizziness among patients in primary health care. A randomized controlled trial
Authors: Hansson Eva Ekvall , Ma°nsson Nils-Ove , Ha°kansson Anders
Published: August 2006

Objective: To investigate whether specific rehabilitation for patients with dizziness has any effect on clinical balance measures and/or the apprehension of dizziness measured with a visual analogue scale (VAS).

Design: Randomized controlled trial.

Subjects: Forty-two patients, 50 years or older with dizziness of central or agerelated origin, identified in primary health care.

Method: The patients were randomized to either an intervention or a control group. The intervention included balance training and vestibular rehabilitation in group sessions twice a week for six weeks. All patients were assessed at baseline, after six weeks and after three months with five different balance measures and visual analogue scale.

Results: Statistically significant differences were found between the two groups comparing results at baseline and after six weeks regarding standing one leg eyes closed (SOLEC) on right foot (p 0.011). Results of SOLEC right foot after three months differed significantly between the groups (p -0.033) as did SOLEC left foot (p -0.035). No difference between the groups were found in the Romberg test, figure of eight, walking heel to toe, ‘stops walking when talking’, standing one leg eyes open or estimating the experience of dizziness measured with visual analogue scale.

Conclusions: Balance training and vestibular rehabilitation improved the ability to stand on one leg with eyes closed in persons with dizziness aged 50 years or over.
Acute stroke unit care combined with early supported discharge. Long-term effects on quality of life. A randomized controlled trial
Authors: Fjærtoft Hild , Indredavik Bent , Johnsen Roar , Lydersen Stian
Published: August 2006

Objectives: The aim of the present trial was to compare the effects of an extended stroke unit service (ESUS) with the effects of an ordinary stroke unit service (OSUS) on long-term quality of life (QoL).

Design: One year follow-up of a randomized controlled trial with 320 acute stroke patients allocated either to OSUS (160 patients) or ESUS (160 patients) with early supported discharge and follow-up by a mobile team. The intervention was a mobile team and close co-operation with the primary health care service. All assessments were blinded.

Main outcome measure: Primary outcome of QoL in this paper was measured by the Nottingham Health Profile (NHP) at 52 weeks. Secondary outcomes measured at 52 weeks were differences between the groups measured by the Frenchay Activity Index, Montgomery-A ° sberg Depression Scale, Mini-Mental State Score and the Caregivers Strain Index.

Results: The ESUS group had a significantly better QoL (mean score 78.9) assessed by global NHP after one year than the OSUS group (mean score 75.2) (p -0.048). There were no significant differences between the groups in the secondary outcomes, but a trend in favour of ESUS. Caregivers Strain Index showed a mean score of 23.3 in the ESUS group and 22.6 in the OSUS group (p -0.089).

Conclusion: It seems that stroke unit treatment combined with early supported discharge in addition to reducing the length of hospital stay can improve long-term QoL. However, similar trials are necessary to confirm the benefit of this type of service.
Building Trust in Economic Space
Authors: Murphy James T.
Published: August 2006

While there is widespread recognition of the importance and role of trust in facilitating regional development, technology transfer, and agglomeration economies, the concept remains rather undertheorized within economic geography and regional science. This paper reviews and assesses the literature on the role and constitution of trust for economic and industrial development and presents a conceptualization of the trust building process that accounts for the influences of agency, institutions, materials, and interpersonal expression. In doing so, geographic concerns about the role of space and context are linked to economic and sociological conceptualizations of trust and to scholarship from actor-network theory (ANT) and social psychology regarding the influence of power, non-human intermediaries, and performance on social outcomes and network configurations. The result is a heuristic framework for analyzing trust-building processes as temporally and spatially situated social phenomena shaped by context-specific subjective, intersubjective, and structural factors. The conceptualization’s broader significance lies not in detailing the many factors that influence trust but in its contextualization of the micro-social processes that can strengthen business relationships. In doing so, the framework can facilitate a move beyond solely instrumental conceptualizations of trust and toward a relational understanding of how the means for establishing and sustaining trust influence the development and potential of such ‘ends’ as clusters and production networks.
Governmentality, Geography, and the Geo-Coded World
Authors: Rose-Redwood Reuben S.
Published: August 2006

A growing number of geographers are beginning to explore Foucault’s later work on ‘governmentality’, which examines the relations between the production of governmental rationalities and the technologies of modern power. The current paper traces this critical engagement between geographical scholarship and governmentality studies. Many geographical accounts consider governmentality in terms of the mechanisms of knowledge production that states have used to constitute their subjects and territories as ‘governable’. While this line of inquiry has produced considerable insights, I argue that analyses of governmentality should also explore how various non-state actors have utilized technologies of government in myriad ways. I further suggest that geo-coding was one of the main spatial prerequisites for the larger biopolitical projects of census-taking and mapping at least since the eighteenth century. A critical spatial history of the ‘geo-coded world’, therefore, is required if we are to understand the geographical underpinnings of governmental knowledge production.
Effect of Riluzole on Ca2+ Movement and Cytotoxicity in Madin-Darby Canine Kidney Cells
Authors: Chen W-C , Cheng H-H , Huang C-J , Chou C-T , Liu S-I , Chen I-S , Hsu S-S , Chang H-T , Huang J-K , Jan C-R
Published: August 2006

Riluzole is a drug used in the treatment of amyotrophic lateral sclerosis; however, its in vitro action is unclear. In this study, the effect of riluzole on intracellular Ca2-concentration ([Ca2-]i) in Madin-Darby canine kidney (MDCK) cells was investigated using the Ca2--sensitive fluorescent dye, fura-2. Riluzole (100 -500 mM) caused a rapid and sustained increase of [Ca2-]iin a concentration-dependent manner (EC50= 150 mM). Some 40 and 50% of this [Ca2-]iincrease was prevented by the removal of extracellular Ca2-and the addition of La3-, respectively, but was unchanged by dihydropyridines, verapamil and diltiazem. In Ca2--free medium, thapsigargin -an inhibitor of the endoplasmic reticulum (ER) Ca2--ATPase -caused a monophasic [Ca2-]iincrease, after which the increasing effect of riluzole on [Ca2-]iwas attenuated by 70%; in addition, pre-treatment with riluzole abolished thapsigargin-induced [Ca2-]iincreases. U73122, an inhibitor of phospholipase C (PLC), abolished ATP (but not riluzole)-induced [Ca2-]iincreases. At concentrations of 250 and 500 mM, riluzole killed 40 and 95% cells, respectively. The cytotoxic effect of riluzole (250 mM) was unaltered by pre-chelating cytosolic Ca2-with BAPTA. Collectively, in MDCK cells, riluzole rapidly increased [Ca2-]iby stimulating extra-cellular Ca2-influx via an La3--sensitive pathway and intracellular Ca2-release from the ER via, as yet, unidentified mechanisms. Furthermore, riluzole caused Ca2--unrelated cytotoxicity in a concentration-depen-dent manner.
The Evaluation of Myocardial Damage in 83 Young Adults with Carbon Monoxide Poisoning in the East Anatolia Region in Turkey
Authors: Aslan Sahin , Uzkeser Mustafa , Seven Bedri , Gundogdu Fuat , Acemoglu Hamit , Aksakal Enbiya , Varoglu Erhan
Published: August 2006

Carbon monoxide (CO) poisoning is the leading cause of death from intoxication. In CO poisoning, it is important to know if there are any symptoms regarding myocardial damage, which are usually unobserved as a result of hypoxia. This study was planned to assess myocardial damage in young healthy patients with CO poisoning. Eighty-three young healthy cases who had been exposed to CO were included in this study. The demographic and clinical characteristics, the origin of CO gas and smoking habits of the patients were recorded. The evaluation of ECG, peripheral ABG, complete blood count and serial cardiac biomarkers (creatine kinase, creatine kinasemyocardial band and troponin I) measurements were performed in all cases. Additionally, echocardiogram (ECHO) and myocardial perfusion single-photon emission computed tomography (SPECT) were performed at the appropriate times in all cases. The mean age of the patients was 27.39 /10.9 years. The main complaint of the patients was loss of consciousness with a 62.7% rate. The average carboxyhaemoglobin level of the patients was 34.49 /15.9%. Sinus tachycardia was present in 26.5% of patients. Diagnostic ischaemic ECG changes were present in 14.4% of patients. In myocardial SPECT, myocardial ischaemic damage was observed in 9 cases, in 6 of whom ECHO findings were also confirmed. Myocar-dial damage due to CO poisoning should not be ignored. If patients are at risk in terms of myocardial damage, further studies, such as ECHO and scintigraphy are needed to determine myocardial damage resulting from CO poisoning. However, in the young adults of the risk group, if the baseline ECG and serial cardiac biomarkers are normal, further studies such as ECHO and scintigraphy, considering the length of exposure and the severity of poisoning, may not be necessary for the evaluation of myocardial damage due to CO poisoning.
Toxic Side Effects of Drugs Used to Treat Chagas’ Disease (American Trypanosomiasis)
Authors: Castro José A , deMecca María Montalto , Bartel Laura C
Published: August 2006

Chagas’ disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: 1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; 2) via blood transfusion or congenital transmission, accounting for0.5-8% of transmission; 3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild non-specific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas’ disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas’ disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (eg, hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.
Pharmacology and Toxicology of Bupleurum Root-Containing Kampo Medicines in Clinical Use
Authors: Ikegami F , Sumino M , Fujii Y , Akiba T , Satoh T
Published: August 2006

Kampo (Japanese traditional herbal) medicines have been produced by combining multiple crude drugs, almost all of plant origin but with some of animal or mineral origin, and contain a great many substances. Their effect is a combination of the various interactions of the constituent substances, whether they are enhancing, synergistic or suppressive. Kampo medicine has an overall effect that is different from the combined effects of individual crude drugs, and several side effects such as anorexia, slight fever and nausea have been reported in the treatment of certain disorders and disease states with Kampo medicines. Among 210 medical formulations used in Japan, some relevant information on the clinical uses, pharmacology and toxicology of six manufactured Kampo medical formulations, Shosaikoto, Daisaikoto, Saikokeishito, Hochuekkito, Saibokuto and Saireito, containing Bupleurum root are reviewed. Studies of some potential interactions between Kampo medicine and western drugs are also considered.
‘Concealing the Evidence’: The Importance of Appearance Concerns for Patients with Systemic Lupus Erythematosus
Authors: Hale ED , Treharne GJ , Norton Y , Lyons AC , Douglas KMJ , Erb N , Kitas GD
Published: August 2006

Outwardly visible signs associated with systemic lupus erythematosus (SLE) can include facial rashes, alopecia and weight gain. We sought to understand the concerns of SLE patients about their appearance and the recognition of this by healthcare professionals. Semi-structured interviews were carried out with 10 women aged 26-68 years diagnosed with SLE for one to 12 years. Data were analysed with Interpretative Phenomenological Analysis (IPA); this seeks to describe and provide understanding of people’s experience of a phenomenon by studying in-depth a small number from a relatively homogeneous group (women with SLE in the present study). Analysis revealed three themes concerning appearance issues. Participants described public self-consciousness after the onset of SLE. Cosmetics and clothing were used skilfully to appear ‘normal’, hide the ‘self’ and assert control but could increase feelings of difference and isolation. Self-imposed isolation was also described and may relate to depression. The understanding of family, friends, colleagues and healthcare providers was also important. Awareness of the psychosocial concerns of SLE patients with life-changing skin disease may enable multidisciplinary healthcare teams to offer a more sensitive, practical service. The physical and emotional needs of SLE patients need to be ascertained and appropriate educational and psychological services are required.
Endocrinologic Manifestations of the Antiphospholipid Syndrome
Authors: Uthman I , Salti I , Khamashta M
Published: August 2006

Our objective was to study the endocrinologic manifestations of the antiphospholipid syndrome (APS). We reviewed the medical literature from 1968 until 2005 using MEDLINE and the key words: APS, anticardiolipin antibodies, lupus anticoagulant, antiphospholipid antibodies, adrenal, thyroid, parathyroid, pituitary, diabetes, ovaries and testes. Adrenal insufficiency is the most common endocrinologic manifestation and can be the presenting symptom of APS. In patients with autoimmune thyroid disease circulating aPL have been detected. However, no clinical manifestations of APS have been described. A few cases of hypopituitarism have been reported, including a case of Sheehan’s syndrome. aPL has been detected in the sera of diabetic patients, probably associated with some macroangiopathic complications. Finally only very few cases of ovarian and testicular involvement have been reported. The adrenals are the most commonly involved glands in the APS. Clinicians should keep a high index of suspicion for adrenal insufficiency in patients with APS.
The Prevalence of Systemic Lupus Erythematosus in Lithuania: The Lowest Rate in Northern Europe
Authors: Dadoniene J , Adomaviciute D , Rugiene R , Luksiene A , Venalis A
Published: August 2006

The aim of this study was to explore the prevalence of systemic lupus erythematosus (SLE) in Lithuania (Vilnius). Two different studies were designed for SLE cases identification: registry-based SLE study and population-based SLE study. For the registry-based study patients were enrolled during the period of 1999-2004 and from two sources, including out-patient clinics of Vilnius and tertiary rheumatology center with interview during the year 2004. Only Vilnius residents who fulfilled the ACR 1982 revised criteria for the classification of SLE were counted in this study. Seventy-six living adult patients with SLE were interviewed and accounted for the prevalence of 16.2/100 000 (0.016%) using the Vilnius adult population in January 2004 (a population of 470 451). The population study of randomly selected 10 000 Vilnius inhabitants with beforehand validation of the survey was performed in the same year. The population-based study revealed two cases for 4017 respondents, but the low response rate may be important. Extrapolating the results to population of 10 000 inhabitants, the point prevalence of SLE in the entire sample was at least 0.02%. Therefore, the prevalence of SLE in Lithuania is the lowest if compared to Northern European countries.
European Attempts to Set Guidelines for Improving Diagnostics of Autoimmune Rheumatic Disorders
Authors: Wiik A , Cervera R , Haass M , Khamashta M , Meroni PL , Piette J-C , Schmitt R , Shoenfeld Y
Published: August 2006

The rational way to set a diagnosis and estimate a prognosis in rheumatology is to start by setting a tentative diagnosis and then follow a fixed scheme for laboratory testing, eg, by using an agreed algorithm. The use of order algorithms can be extended to post-test algorithms that will assist clinicians in approaching the right diagnosis and prognosis. New methods used in autoimmune serology do not deliver results that can be directly compared to those of older methods, and thus the new methods need to be thoroughly tested with sera from differential diagnostically relevant disease controls to set a clinically meaningful cut-off for positivity. Borderline positive results need to be treated with special care to avoid misuse. Early diagnosis is of great importance, and serological results can be very useful if used the right way. European efforts to secure rational diagnostic work-up in autoimmune rheumatic disease have led to a better dialogue between clinicians and laboratory scientists in several countries.
Quantitation of Autoantibodies in Systemic Autoimmune Diseases: Clinically Useful?
Authors: Kallenberg CGM , Stegeman CA , Bootsma H , Bijl M , Limburg PC
Published: August 2006

Serial assessment of levels of autoantibodies has been proposed as being clinically useful in certain systemic autoimmune diseases. In particular, attention has been given to anti-dsDNA antibodies in systemic lupus erythematosus (SLE) and ANCA in the ANCA-associated vasculitides (AAV). Much controversy exists, however, concerning the value of serial testing in these diseases. We here review the various tests available for quantitation of anti-dsDNA and ANCA, and their capacity to detect changes in autoantibody levels that are associated with changes in clinical disease activity of the respective diseases. It is concluded that changes in anti-dsDNA as measured by the Farr assay and changes in ANCA as assessed by ELISA have predictive value for the occurrence of disease relapses, although this relationship is far from absolute. Consequently, treatment based on changes in levels of the respective autoantibodies only seems at present not justified, in view of the toxicity of currently available immunosuppressive regimens.
Detection of Antibodies to dsDNA: An Overview of Laboratory Assays
Authors: Rouquette AM , Desgruelles C
Published: August 2006

This brief review is focused on different methodologies available for detection of anti-dsDNA antibodies with respect to the best adequacy between biological results of laboratory and clinical significance. A large array of assays has been developed for the measurement of anti-dsDNA. New assays continually introduced have reflected not only technical innovations to avoid difficulties of some assays, but even more with hope to correlate better with systemic lupus erythematosus (SLE), particularly with its clinical course and exacerbations. Finally, with the development of micro arrays technology new insights into the pathophysiology of autoimmune disease processes should be revealed.
Anti-Chromatin (Anti-Nucleosome) Antibodies
Authors: Gómez-Puerta JA , Burlingame RW , Cervera R
Published: August 2006

Chromatin is the native complex of histones and DNA found in the cell nucleus of eukaryotes. The fundamental subunit of chromatin is the nucleosome, which is composed of a core particle in which 146 bp of helical DNA are wrapped around an octamer made up of two H2A-H2B dimers that surround an H3-H4 tetramer. The prevalence of anti-chromatin (nucleosome) antibodies in systemic lupus erythematosus (SLE) varies from 50% to 90%, being similar to that of the classical positive LE cell. The presence of these antibodies can be used, in conjunction with clinical findings and other laboratory tests, to help in the diagnosis of SLE and drug induced lupus. The presence of anti-chromatin antibodies has also been linked to glomerulonephritis in SLE patients.
Autoantibody Detection Using Multiplex Technologies
Authors: Binder SR
Published: August 2006

Measurement of multiple antibodies has been possible for years using labor-intensive methods such as counterimmunoelectrophoresis and radioimmunoprecipitation. Recently, simpler methods that are more practical for routine analysis, often described as multiplex technologies, have been introduced. One common technique, the line assay, uses nitrocellulose strips that are precoated at different locations with more than a dozen recombinant proteins or peptides. Detection of results may be performed visually or with scanning instrumentation. A second technique uses families of polystyrene beads that are dyed to establish a unique identity; each bead type is then coated with a specific affinity-purified or recombinant protein. Detection is performed by flow cytometry. There have been multiple descriptions of the use of these techniques for measuring antibodies associated with the antinuclear antibody screen. More recent reports describe applications to antibodies associated with hypothyroidism, ANCA, anti-phospholipid syndrome, and celiac disease. This review summarizes the work that has been performed to date and examines the potential benefits of multiplexing to both the laboratory and the physician.
Advances and Applications of Multiplexed Diagnostic Technologies in Autoimmune Diseases
Authors: Fritzler MJ
Published: August 2006

There is a rapid proliferation of new technologies to identify an ever increasing spectrum of autoantibodies in diverse medical conditions that range from organ-specific autoimmune diseases to systemic rheumatic diseases. Although many laboratories have adopted diagnostic platforms, such as enzyme linked immunoassays (ELISAs), to improve turn around times and meet budget constraints, the prevailing evidence is that the rapid adoption of new technologies is not attended by an appropriate balance of assay sensitivity and specificity. Emerging diagnostic technologies include addressable laser bead immunoassays, microarrays in microfluidics platforms and nanobarcode particles. Although these technologies provide advantages of high-throughput, multiplexed autoantibody assays that can be coupled to other disease specific biomarkers (ie, cytokines, single nucleotide polymorphisms) there is a clear need for standardization and internal validation before they are adopted into the clinical diagnostic laboratory.
Antigen-Chip Technology for Accessing Global Information about the State of the Body
Authors: Quintana FJ , Merbl Y , Sahar E , Domany E , Cohen IR
Published: August 2006

Traditionally, immunologic diagnosis has been based on an attempt to correlate each disease with a specific immune reactivity, such as an antibody or a T-cell response to a single antigen specific for the disease entity. The state of the body, however, appears to be encoded by the immune system in collectives of reactivities and not by single reactivities. Here we describe our use of microarray technology and informatics to develop an antigen chip capable of detecting global patterns of antibodies binding to hundreds of antigens simultaneously. The patterns fashion diagnostic signatures.
Application of a Static Fluorescence-Based Cytometer: The Cellscan in Clinical Immunology
Authors: Szyper-Kravitz M , Harel M , Gilburd B , Trubniykov E , Schiffenbauer YS , Shoenfeld Y
Published: August 2006

The CellScan system is a laser scanning cytometer which enables repetitive fluorescence intensity (FI) and polarization (FP) measurements in living cells, as a means of monitoring lymphocyte activation. By monitoring FP changes in peripheral blood lymphocytes (PBL) following exposure to antigenic stimuli, the CellScan may have a role in the diagnosis of autoimmune diseases. Monitoring changes in FI and FP in PBLs from patients with atherosclerosis following exposure to various stimuli, has illustrated the role of the immune system in the atherosclerotic process. The CellScan has also been evaluated as a diagnostic tool for drug-induced allergy, based on FP reduction in PBLs following incubation with the suspected drugs. FI and FP changes in cancer cells have been found to correlate with the cytotoxic effect of different anti-neoplastic drugs, illustrating the potential role of the CellScan system in clinical oncology. In conclusion, the CellScan is a promising new tool with a variety of applications in cell biology, immunology, cancer research and clinical pharmacology.