bluuebunny/crossref_metadata_2025 huggingface dataset:
A Direct Comparison of Whole Cell Patch and Sharp Electrodes by Simultaneous Recording From Single Spinal Neurons in Frog Tadpoles
Authors: Li W.-C. , Soffe S. R. , Roberts Alan
Published: March 2004

High-impedance, sharp intracellular electrodes were compared with whole cell patch electrodes by recording from single spinal neurons in immobilized frog tadpoles. A range of neuron properties were examined using sharp or patch test electrodes while making simultaneous recordings with a second control patch electrode. Overall, test patch electrodes did not significantly alter the activity recorded by the control electrode, and recordings from the two electrodes were essentially identical. In contrast, sharp electrode recordings differed from initial control patch recordings. In some cases, differences were due to real changes in neuron properties: the resting membrane potential became less negative and the neuron input resistance ( Ri) fell; this fall was larger for neurons with a higher Ri. In other cases, the control patch electrode revealed that differences were due to the recording properties of the sharp electrode: tip potentials were larger and more variable; resting potentials appeared to be more negative; and spike amplitude was attenuated. However, sharp electrode penetration did not, in most cases, significantly alter the pattern of neuron firing in response to injected current or the normal pattern of activity following sensory stimulation or during fictive swimming. We conclude that sharp electrodes introduce a significant leak to the membrane of tadpole spinal neurons compared with patch electrodes but that this does not change the fundamental firing characteristics or activity of the neurons.
Mice lacking neuronal nicotinic acetylcholine receptor β4-subunit and mice lacking both α5- and β4-subunits are highly resistant to nicotine-induced seizures
Authors: Kedmi Merav , Beaudet Arthur L. , Orr-Urtreger Avi
Published: March 2004

Nicotine, the main addictive component of tobacco, evokes a wide range of dose-dependent behaviors in rodents, and when administrated in high doses, it can induce clonic-tonic seizures. Nicotine acts through the nicotinic acetylcholine receptors (nAChRs). Mutations in the human α4- and the β2-nAChR subunit genes cause autosomal dominant nocturnal frontal lobe epilepsy. Using transgenic mice with mutations in nAChR subunits, it was demonstrated previously that the α4-, α5-, and α7-subunits are involved in nicotine-induced seizures. To examine the possibility that the β4-subunit is also involved in this phenotype, we tested mice with homozygous β4-subunit deficiency. The β4 null mice were remarkably resistant to nicotine-induced seizures compared with wild-type and α5 null mice. We also generated mice with double deficiency of both α5- and β4-nAChR subunits and demonstrated that they were more resistant to nicotine’s convulsant effect than either the α5 or the β4 single mutant mice. In addition, the single α5 mutants and the double α5β4-deficient mice exhibited a significantly shorter latency time to seizure than that of the wild-type mice. Our results thus show that β4-containing nAChRs have a crucial role in the pathogenesis of nicotine-induced seizures. Furthermore, by comparing multiple mutant mice with single and double subunit deficiency, we suggest that nicotinic receptors containing either α5- or β4-subunits are involved in nicotine-induced seizures and that receptors containing both subunits are likely to contribute to this phenomena as well. However, the α5-subunit, but not the β4-subunit, regulates the rate of response to high doses of nicotine.
Managing Gastro-Oesophageal Reflux Disease in Children
Authors: Cezard Jean Pierre
Published: March 2004

Gastro-oesophageal reflux (GOR) and gastro-oesophageal reflux disease (GORD) have a higher prevalence among infants than among children or adults. This is linked to the immaturity of the oesophagus and stomach and the higher liquid intake of infants. Genetic factors could also be contributory in some families. Clinical symptoms in infants are mainly regurgitation and vomiting, which usually disappear between 1 and 3 years of age. Symptoms in children are similar to those in adults. Treatment in children depends on age and GORD severity. With GOR or mild GORD, particularly in infants, explanation and reassurance together with thickening of formula feed and lifestyle changes are usually effective. Prokinetics either have unproven efficacy (metoclopramide, domperidone) or have been withdrawn (cisapride). Chronic antacid therapy is not recommended. In moderate to severe GORD, histamine-2-receptor antagonists and particularly proton pump inhibitors (PPIs) are effective, especially when oesophagitis is present. PPIs, in particular omeprazole and lansoprazole, have proven efficacy in infants and children. They are well tolerated, with pharmacokinetics similar to those in adults. However, dosages should be adapted in neonates and children under 10 years old. Fundoplication should be avoided before 2 to 3 years of age if possible.
Yeyi Clicks: Acoustic Description and Analysis
Authors: Fulop Sean A. , Ladefoged Peter , Liu Fang , Vossen Rainer
Published: March 2004

Yeyi has the largest known inventory of click sounds in the Bantu language family. It is now entering a moribund state, and this paper documents a variety of acoustic and distributional details of the clicks found in the speech of 13 Yeyi speakers by presenting sound inventories, spectrograms, palatograms, and related acoustic data. The durations of the closure and release phases of the clicks were measured, and an analysis demonstrates that the two duration measures together are statistically able to distinguish the dental, alveolar, palatal, and lateral clicks from one another. A second quantitative study examines the discriminability of the four click places using solely the anterior burst power spectra, as parametrized using the first four spectral moments. The places of articulation are found to be moderately well classified by this means. The patterns of interspeaker variation affecting the clicks are also documented, and these are found to accord rather well with the classification errors made by the optimal classifier using the anterior burst spectra.
Sledding Accidents in Children: Potential for Serious Injury, Risk of Fatality
Authors: Verrees Meg , Robinson Shenandoah , Cohen Alan R.
Published: March 2004

Though a pastime rarely considered rough or dangerous, sledding is not risk-free. The presentation of several serious injuries to Rainbow Babies and Children’s Hospital in Cleveland, Ohio, led us to examine our emergency department and admitting records to determine the incidence of neurological injury among children involved in sledding accidents. We discovered 24 children who had sustained brain or spine injuries as sequelae to sledding mishaps during a 5-year period. The ages ranged from 3 months to 15 years. Injuries included multiple skull fractures, 2 epidural hematomas, 1 subdural hematoma, 1 odontoid fracture and 1 anoxic brain injury. There was 1 death. Twenty-one of 24 patients incurred their injuries by colliding with fixed objects. Both improvised crafts and models intended for sledding were involved in the injuries. Only 3 sleds possessed steering capability. Eight of the 9 children who sustained a serious neurosurgical injury were supervised by an adult. Only 2 children had received instruction before sledding. The lack of awareness of the potential for injury together with the dearth of instruction and lack of control over a vehicle dashing down a hill studded with obstacles can change a carefree pastime into a hazardous activity.
Frameless Stereotactic Navigation in Transsphenoidal Surgery: Comparison with Fluoroscopy
Authors: McCutcheon Ian E. , Kitagawa Ryan S. , Demasi Paula F. , Law Brian K. , Friend Keith E.
Published: March 2004

Surgical navigation systems (frameless stereotaxy) have been used in addition to or instead of fluoroscopy during transsphenoidal surgery. This study compares the intraoperative localization by an optical tracking system (Elekta Viewscope) with fluoroscopy. Viewscope and fluoroscope sagittal images were compared by the establishment of a Cartesian coordinate system based on anatomical landmarks and by the spatial localization of surgically relevant points for 20 patients. The Viewscope was found to have a total deviation of 3.0 ± 0.6 mm (mean ± SD) compared to fluoroscopy (p < 0.01). Much of the error resulted from the registration process, which according to the Viewscope software had an expected error of 3.1 ± 0.8 mm for this series of patients, and from the probe-to-system correlation (error of 1.0 ± 0.3 mm). Although frameless stereotactic systems give the surgeon useful trajectory data with three-dimensional visualizations, they remain somewhat inaccurate. The multiplanar abilities of the Viewscope provide an additional but not mandatory advantage to the simplicity and accuracy of fluoroscopy during this type of surgery.
The Duration and Amplitude of the Plateau Phase of ATP- and ADP-Evoked Ca2+ Signals Are Modulated by Ectonucleotidases in in situ Endothelial Cells of Rat Aorta
Authors: Berra-Romani Roberto , Rinaldi Chiara , Raqeeb Abdul , Castelli Loretta , Magistretti Jacopo , Taglietti Vanni , Tanzi Franco
Published: March 2004

ATP has a long-lasting vasodilatory effect, possibly due to its capability to induce a prolonged increase in the intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells (EC) and activate constitutive nitric oxide synthase. However, contradictory data have been reported regarding the time course of ATP-evoked Ca2+ signals in in situ EC. In particular, short-duration Ca2+ signals have been reported, which might be thought to be unable to sustain a prolonged, NO-induced vasodilation. The current experiments were therefore performed in in situ EC of rat aorta in order to more fully define the time course of ATP-evoked Ca2+ signals. 20 µM ATP evoked a short-lasting Ca2+ signal. However, medium stirring, high agonist concentrations, inhibition of ectonucleotidases and application of a poorly hydrolyzable agonist evoked long-lasting Ca2+ signals (up to 20 min at 37°C). These studies suggest that ATP is able to sustain a prolonged [Ca2+]i increase, unless ectonucleotidase activity reduces the agonist concentration near the EC surface to subthreshold values, quickly cutting the Ca2+ signal. Furthermore, the amplitude of the long-lasting phase of the Ca2+ signal depended on the balance between agonist degradation by ectonucleotidases and agonist transport, by diffusion and convection, from bulk solution to the EC surface.
Matrix Metalloproteinases of Human Leiomyoma in Various Stages of Tumor Growth
Authors: Wolańska Małgorzata , Sobolewski Krzysztof , Bańkowski Edward , Jaworski Stefan
Published: March 2004

The amounts and activities of matrix metalloproteinases (MMPs) were studied in human myometrium and uterine leiomyomas in various stages of growth. It was found that both myometrium and the investigated tumors contain collagenolytic enzymes. MMP-1, MMP-2, MMP-3 and MMP-9 were found. Gelatinase A (MMP-2) is the most abundant. In control myometrium only 10% of this enzyme exists in an active form, whereas in tumors, especially in large ones, the values reach 30%. It is suggested that the high activity of MMP-2 is responsible for remodelling of extracellular matrix in the growing tumors.
Effect of Rosiglitazone on Common Carotid Intima-Media Thickness Progression in Coronary Artery Disease Patients Without Diabetes Mellitus
Authors: Sidhu Jagdip S. , Kaposzta Zoltan , Markus Hugh S. , Kaski Juan Carlos
Published: March 2004

Objectives—

Thiazolidinediones, such as rosiglitazone, have been shown to retard atherosclerosis disease progression in diabetic subjects. These agents may have anti-atherosclerotic effects through direct inhibition of inflammatory processes in the vessel wall, and so their benefit may extend to patients with atherosclerotic disease, even in the absence of diabetes. In this study, we assessed the effect of rosiglitazone on common carotid intima-media thickness (IMT) progression in nondiabetic coronary artery disease (CAD) patients.

Methods and Results—

Consecutive subjects (n=92) with clinically stable, angiographically documented CAD and without diabetes mellitus were randomized in a double-blind manner to receive placebo or rosiglitazone for 48 weeks. They received single-dose placebo and rosiglitazone 4 mg daily for the initial 8 weeks, and the doses were doubled for the remainder of the study. Common carotid IMT together with fasting glucose, insulin, and lipid profile were measured at baseline and repeated after 24 and 48 weeks. Rosiglitazone-treated patients showed reduced IMT progression compared with the placebo group, −0.012 mm/48 weeks versus 0.031 mm/48 weeks (
P
=0.03). Rosiglitazone treatment significantly reduced insulin resistance, estimated by homeostasis model of insulin resistance index, compared with placebo (
P
=0.01).

Conclusions—

Rosiglitazone reduces common carotid IMT progression in nondiabetic CAD patients, and insulin-sensitization may be one contributory mechanism.
Direct Detection and Quantification of Transition Metal Ions in Human Atherosclerotic Plaques: Evidence for the Presence of Elevated Levels of Iron and Copper
Authors: Stadler Nadina , Lindner Robyn A. , Davies Michael J.
Published: March 2004

Objective—The involvement of transition metals in atherosclerosis is controversial. Some epidemiological studies have reported a relationship between iron (Fe) and cardiovascular disease, whereas others have not. Experimental studies have reported elevated levels of iron and copper (Cu) in diseased human arteries but have often used methods that release metal ions from proteins.

Methods and Results—In this study, we have used the minimally invasive technique of electron paramagnetic resonance (EPR) spectroscopy and inductively coupled plasma mass spectroscopy (ICPMS) to quantify iron and copper in ex vivo healthy human arteries and carotid lesions. The EPR spectra detected are characteristic of nonheme Fe(III) complexes. Statistically elevated levels of iron were detected in the intima of lesions compared with healthy controls (0.370 versus 0.022 nmol/mg tissue for EPR, 0.525 versus 0.168 nmol/mg tissue by ICPMS,P<0.05 in each cases). Elevated levels of copper were also detected (7.51 versus 2.01 pmol/mg tissue, lesion versus healthy control, respectively,P<0.05). Iron levels did not correlate with the gender or age of the donor, or tissue protein or calcium levels, but cholesterol levels correlated positively with iron accumulation, as measured by EPR.

Conclusions—These data support the hypothesis that iron accumulates in human lesions and may contribute to disease progression.
Increased Carotid Wall Stress in Vascular Ehlers-Danlos Syndrome
Authors: Boutouyrie Pierre , Germain Dominique P. , Fiessinger Jean-Noël , Laloux Brigitte , Perdu Jérôme , Laurent Stéphane
Published: March 2004

Background—

Vascular Ehlers-Danlos syndrome (vEDS), also known as EDS type IV, an inherited disorder of connective tissue, results from mutations in the gene encoding type III procollagen (
COL3A1
). Affected patients are at risk for arterial dissection or rupture, the main cause of death. To understand the pathogenesis of the vascular lesions, we used a biomechanical approach and determined steady and pulsatile wall stress.

Methods and Results—

Sixteen patients with vEDS and 16 age-, gender-, and blood pressure–matched control subjects were included in this cross-sectional noninvasive study. Circumferential wall stress was determined under steady and pulsatile conditions at the site of an elastic (common carotid) and a muscular (radial) artery from the measurements of intima-media thickness and internal diameter with high-resolution echo-tracking systems and either mean blood pressure or pulse pressure, respectively. At the site of the carotid artery, steady circumferential wall stress was 43% higher in vEDS patients than in control subjects (68.9±14.3 versus 48.2±12.1 kPa,
P
<0.001), and pulsatile circumferential wall stress was 22% higher (28.2±7.7 versus 23.1±5.7 kPa,
P
<0.001). Carotid intima-media thickness was 32% lower (408±56 versus 598±171 μm,
P
<0.001) in vEDS patients, and internal diameter was not different between groups. Radial artery parameters were not significantly different between groups.

Conclusions—

In vEDS patients, an abnormally low intima-media thickness generates a higher wall stress than in control subjects at the site of an elastic artery, which may increase the risk of arterial dissection and rupture.
Identification of Telmisartan as a Unique Angiotensin II Receptor Antagonist With Selective PPARγ–Modulating Activity
Authors: Benson Stephen C. , Pershadsingh Harrihar A. , Ho Christopher I. , Chittiboyina Amar , Desai Prashant , Pravenec Michal , Qi Nianning , Wang Jiaming , Avery Mitchell A. , Kurtz Theodore W.
Published: March 2004

The metabolic syndrome is a common precursor of cardiovascular disease and type 2 diabetes that is characterized by the clustering of insulin resistance, dyslipidemia, and increased blood pressure. In humans, mutations in the peroxisome proliferator–activated receptor-γ (PPARγ) have been reported to cause the full-blown metabolic syndrome, and drugs that activate PPARγ have proven to be effective agents for the prevention and treatment of insulin resistance and type 2 diabetes. Here we report that telmisartan, a structurally unique angiotensin II receptor antagonist used for the treatment of hypertension, can function as a partial agonist of PPARγ; influence the expression of PPARγ target genes involved in carbohydrate and lipid metabolism; and reduce glucose, insulin, and triglyceride levels in rats fed a high-fat, high-carbohydrate diet. None of the other commercially available angiotensin II receptor antagonists appeared to activate PPARγ when tested at concentrations typically achieved in plasma with conventional oral dosing. In contrast to ordinary antihypertensive and antidiabetic agents, molecules that can simultaneously block the angiotensin II receptor and activate PPARγ have the potential to treat both hemodynamic and biochemical features of the metabolic syndrome and could provide unique opportunities for the prevention and treatment of diabetes and cardiovascular disease in high-risk populations.
Evidence for Mitochondrial K
+
Channels and Their Role in Cardioprotection
Authors: O’Rourke Brian
Published: March 2004

Twenty years after the discovery of sarcolemmal ATP-sensitive K
+
channels and 12 years after the discovery of mitochondrial K
ATP
(mitoK
ATP
) channels, progress has been remarkable, but many questions remain. In the case of the former, detailed structural information is available, and it is well accepted that the channel couples bioenergetics to cellular electrical excitability; however, in the heart, a clear physiological or pathophysiological role has yet to be defined. For mitoK
ATP
, structural information is lacking, but there is abundant evidence linking the opening of the channel to protection against ischemia-reperfusion injury or apoptosis. This review updates recent progress in understanding the physiological role of mitoK
ATP
and highlights outstanding questions and controversies, with the intent of stimulating additional investigation on this topic.
Seeing Within
Authors: Jaffer Farouc A. , Weissleder Ralph
Published: March 2004

Molecular imaging is a rapidly evolving discipline with the goal of developing tools to display and quantify molecular and cellular targets in vivo. The heart of this field is based on the rational design and screening of targeted and activatable imaging reporter agents to sense fundamental processes of biology. Parallel advances in small animal imaging systems and in agent synthesis have allowed molecular imaging applications to extend into the in vivo arena. These advances have permitted, for example, in vivo sensing of inflammation, apoptosis, cell trafficking, and gene expression. In this review, we first review core principles of molecular imaging with an emphasis on smart, activatable agent technology. We then discuss applications of state-of-the-art molecular probes to interrogate important aspects of cardiovascular biology, with a focus on atherosclerosis, thrombosis, and heart failure. In the ensuing years, we anticipate that fundamental aspects of cardiovascular biology will be detectable in vivo, and that promising molecular imaging agents will be translated into the clinical arena to guide diagnosis and therapy of human cardiovascular illness.
Cellular Mechanisms of Contractile Dysfunction in Hibernating Myocardium
Authors: Bito Virginie , Heinzel Frank R. , Weidemann Frank , Dommke Christophe , van der Velden Jolanda , Verbeken Erik , Claus Piet , Bijnens Bart , De Scheerder Ivan , Stienen Ger J.M. , Sutherland George R. , Sipido Karin R.
Published: March 2004

Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (n=13, ISCH), an acquired coronary stenosis >90% (4 to 6 weeks) resulted in the development of hibernating myocardium. Single cardiac myocytes from the ISCH area were compared with cells from the same area obtained from matched normal pigs (n=12, CTRL). Myocytes from ISCH were larger than from CTRL. In field stimulation, unloaded cell shortening was reduced and slower in ISCH; relaxation was not significantly different. The amplitude of the [Ca
2+
]
i
transient was not significantly reduced, but reducing [Ca
2+
]
o
for CTRL cells could mimic the properties of ISCH, inducing a significant reduction of contraction, but not of [Ca
2+
]
i
. Action potentials were longer in ISCH. With square voltage-clamp pulses of equal duration in ISCH and CTRL, the amplitude of the [Ca
2+
]
i
transient was significantly smaller in ISCH, as was the Ca
2+
current. Near-maximal activation of the myofilaments resulted in smaller contractions of ISCH than of CTRL cells. There was no evidence for increased degradation of Troponin I. In conclusion, cellular remodeling is a major factor in the contractile dysfunction of the hibernating myocardium. Myocytes are hypertrophied, action potentials are prolonged, and L-type Ca
2+
currents and Ca
2+
release are decreased. The steep [Ca
2+
]
i
dependence of contraction and possibly a reduction of maximal myofilament responsiveness further enhance the contractile deficit.
Body Mass Index and Ischemic and Hemorrhagic Stroke
Authors: Song Yun-Mi , Sung Joohon , Smith George Davey , Ebrahim Shah
Published: March 2004

Background and Purpose—

The association between obesity and stroke remains controversial, with earlier studies suggesting that differences might stem from heterogeneous stroke subtype compositions. The association between body mass index (BMI) and stroke subtypes was examined prospectively in a large cohort study.

Methods—

A total of 234 863 Korean men aged 40 to 64 years without substantial weight loss over 4 years after baseline examination in 1986 were divided into 8 categories of BMI and were followed up between 1991 and 2000 for fatal and nonfatal stroke events.

Results—

There was a positive association across the whole range of BMI and ischemic stroke, with a confounder-adjusted hazard of 11% (95% CI, 1.09 to 1.12) for 1 kg/m
2
higher BMI. A J-shaped association was observed between BMI and hemorrhagic stroke; groups with a higher BMI than the reference category (22 to 23 kg/m
2
) had significantly increased risks. Full adjustment for confounders and variables potentially on the causal pathway (ie, blood pressure, blood glucose, and cholesterol) attenuated the association between BMI and stroke subtypes only for those with BMI greater than the reference category. Exclusion of deaths during the first 8 years or stratified analysis according to smoking habit did not change the relation between BMI and stroke subtypes.

Conclusions—

BMI is a risk factor for both ischemic and hemorrhagic stroke but shows different relationships with each. When the total burden of stroke is considered, there is an urgent need to find better ways of reducing the trend toward growing obesity in both Western and Asian countries.
Cerebral Ischemia Enhances Vascular Angiotensin AT
1
Receptor–Mediated Contraction in Rats
Authors: Stenman Emelie , Edvinsson Lars
Published: March 2004

Background and Purpose—

The aim of the study was to examine how focal cerebral ischemia affects the expression and function of vascular angiotensin II receptors.

Materials and Methods—

We used an intraluminal filament occlusion technique to occlude the right middle cerebral artery (MCA) of the rat. Myographs were used for functional studies of the MCA and real-time polymerase chain reaction, for determination of relative mRNA levels.

Results—

The contractile responses to angiotensin II were stronger in the right occluded MCA compared with the left MCA and the MCA from sham-operated rats 48 hours after MCA occlusion (
P
<0.05). The angiotensin II type 1 (AT
1
) receptor antagonists candesartan and losartan abolished the enhanced responses to angiotensin II (
P
<0.05), whereas the AT
2
receptor antagonist PD123319 had no effect. The amount of AT
1
receptor mRNA was lower in the occluded MCAs compared with nonoccluded MCAs 48 hours after occlusion (
P
<0.05), whereas the mRNA levels of angiotensin converting enzyme (ACE) were higher in the occluded arteries. The mRNA levels of the AT
2
receptor and nuclear factor-κB were unchanged.

Conclusions—

Focal cerebral ischemia in the rat upregulated the contractile responses to angiotensin II in the ipsilateral MCA, and this contraction was mediated by AT
1
receptors. Real-time polymerase chain reaction revealed decreased AT
1
receptor mRNA levels in the occluded MCA, whereas the amount of ACE mRNA was increased, suggesting locally enhanced angiotensin II production. These results support a role for AT
1
receptors in cerebral ischemia, and we think that AT
1
receptors might be a future therapeutic target in ischemic stroke.
Learning Obstacle Avoidance with an Operant Behavior Model
Authors: Gutnisky D. A. , Zanutto B. S.
Published: March 2004

Artificial intelligence researchers have been attracted by the idea of having robots learn how to accomplish a task, rather than being told explicitly. Reinforcement learning has been proposed as an appealing framework to be used in controlling mobile agents. Robot learning research, as well as research in biological systems, face many similar problems in order to display high flexibility in performing a variety of tasks. In this work, the controlling of a vehicle in an avoidance task by a previously developed operant learning model (a form of animal learning) is studied. An environment in which a mobile robot with proximity sensors has to minimize the punishment for colliding against obstacles is simulated. The results were compared with the Q-Learning algorithm, and the proposed model had better performance. In this way a new artificial intelligence agent inspired by neurobiology, psychology, and ethology research is proposed.
Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase–mediated tryptophan degradation
Authors: Meisel Roland , Zibert Andree , Laryea Maurice , Göbel Ulrich , Däubener Walter , Dilloo Dagmar
Published: March 2004

Marrow stromal cells (MSCs) inhibit allogeneic T-cell responses, yet the molecular mechanism mediating this immunosuppressive effect of MSCs remains controversial. Recently, expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-γ (IFN-γ) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in professional antigen-presenting cells. Here we show that human MSCs express IDO protein and exhibit functional IDO activity upon stimulation with IFN-γ. MSCs inhibit allogeneic T-cell responses in mixed lymphocyte reactions (MLRs). Concomitantly, IDO activity resulting in tryptophan depletion and kynurenine production is detected in MSC/MLR coculture supernatants. Addition of tryptophan significantly restores allogeneic T-cell proliferation, thus identifying IDO-mediated tryptophan catabolism as a novel T-cell inhibitory effector mechanism in human MSCs. As IDO-mediated T-cell inhibition depends on MSC activation, modulation of IDO activity might alter the immunosuppressive properties of MSCs in different therapeutic applications. (Blood. 2004;103:4619-4621)
The utility of the Stroke Aphasia Depression Questionnaire (SADQ) in a stroke rehabilitation unit
Authors: Leeds L , Meara R J , Hobson J P
Published: March 2004

Objective: To determine the utility of an observer-based rating scale to detect depression in patients without aphasia.

Design: Correlation analysis between the Stroke Aphasia Depression Questionnaire, shortened version (SADQ-10) and a validated self-rating measure of depression, the Geriatric Depression Scale (GDS). The sensitivity and specificity of the SADQ-10 were also calculated.

Setting: Stroke rehabilitation unit.

Subjects: Sixty-fivestroke patients without significant aphasia undergoing rehabilitation.

Interventions: All patients were assessed with the GDS-15 and the SADQ-10.

Results: The SADQ-10 at a cut-point of 14 out of 30 had a sensitivity of 70% and a specificity of 77% to detect depression. This measure demonstrated good internal consistency but showed only a modest correlation with the GDS-15 ( r = 0.40, p < 0.001).

Conclusion: In the population under study the SADQ-10 did not appear to be a valid measure of depression compared with the GDS and, therefore, may not be suitable for use in patients without significant aphasia.
Changes in a repetitive head movement task after vestibular rehabilitation
Authors: Cohen Helen S , Kimball Kay T
Published: March 2004

Objective: Many papers describe vestibular rehabilitation programmes to reduce vertigo and disequilibrium caused by peripheral vestibular disorders, but few studies have assessed performance on purposeful activities. This study determined if performance on a purposeful activity improves after vestibular rehabilitation exercises, and if the speed of treatment exercises influences performance.Setting: Medical school practice; tertiary care facility.Subjects: Fifty-three patients with chronic vertigo caused by peripheral vestibular weakness.Interventions: Subjects performed vestibular rehabilitation head movement exercises to habituate vertigo, in either slow or rapid movement groups. Main measures: Time to perform a repetitive head movement task and intensity of vertigo elicited by that task, questionnaires about independence in activities of daily living and reported usual intensity of vertigo.Results: Both groups significantly decreased the time to perform the task and the intensity of elicited vertigo. Results were related to improved independence in activities of daily living and to decreased vertigo. Conclusion: Vertigo decreases and speed of head movement improved after a programme of vestibular rehabilitation, regardless of speed of treatment exercises. A simple purposeful activity can be useful to evaluate improvements after vestibular rehabilitation.
Disability evaluation in chronic fatigue syndrome: associations between exercise capacity and activity limitations/participation restrictions
Authors: Nijs J , De Meirleir K , Wolfs S , Duquet W
Published: March 2004

Objective: In an attempt to examine whether impairments in cardiorespiratory fitness are associated with daily functioning in patients with chronic fatigue syndrome (CFS), this study addresses the correlations between exercise capacity and activity limitations/participation restrictions.

Design: Prospective observational study.

Setting: An outpatient tertiary care, chronic fatigue clinic at the Vrije Universiteit Brussel (VUB), Belgium.

Subjects: Seventy-seven patients fulfilling the 1994 Centers for Disease Control and Prevention (CDC) case definition for CFS.

Interventions: All patients filled in the Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ) and performed a maximal exercise stress test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Metabolic and ventilatory parameters were measured through spirometry.

Results: A statistically significant correlation between the score obtained with the CFS-APQ and the body weight-adjusted peak oxygen uptake (Spearman rho = -0.32; p = 0.005), functional aerobic impairment (rho = 0.33; p = 0.004), workload/body weight (rho = -0.30; p = 0.009), exercise duration (rho = -0.30; p = 0.008), and the percentage of target heart rate achieved (rho = -0.33; p = 0.004) was observed. The correlations between the remaining exercise capacity parameters and the scores obtained with the CFS-APQ all indicated a trend towards association (0.01< p<0.05).

Conclusions: These results suggest a moderate association between exercise capacity and activity limitations/participation restrictions in patients with CFS. The observed correlations lack strength to predict activity limitations/ participation restriction based on exercise capacity parameters. Disability evaluation in CFS should therefore encompass both exercise capacity testing and measurements at the activity/participation dimension.
The impact of somatosensory function on activity performance and length of hospital stay in geriatric patients with stroke
Authors: Sommerfeld Disa Kathryn , von Arbin Magnus H
Published: March 2004

Objective: To investigate in geriatric patients with stroke the relationship between somatosensory function, activity performance and the length of stay (LOS) in either hospital or nursing home.

Design: Survey.

Setting: Stroke unit and geriatric rehabilitation unit.

Subjects: One hundred and fifteen consecutive patients with acute stroke ≥65 years old.

Main outcome measures: Clinically assessed somatosensory function, activity of daily living according to the Barthel Index (BI) (0–100 points), mobility according to the Rivermead Mobility Index (RMI) (0–15 points) and LOS.

Results: Ten days after stroke onset, the patients with normal ( n = 46), impaired ( n = 31) and nonassessable ( n = 38) somatosensory function scored 85, 40 and 0 points respectively on the BI, and 8.5, 2 and 0 points respectively on the RMI. Forty-one of 46 patients (89%) with normal somatosensory function were discharged home within three months, compared with 10 of 31 patients (32%) with impaired somatosensory function and three of 38 patients (8%) who were nonassessable. These between-group differences were statistically significant ( p < 0.001). Multiple regression, to adjust for the impact of age, social situation and bladder function on outcome still proved a statistically significant ( p < 0.001) predictive value of normal somatosensory function.

Conclusions: Normal somatosensory function is related to high activity levels and short LOS more often than somatosensory impairment is related to activity limitations and long LOS.
Young adults with acquired brain injury in nursing homes in Glasgow
Authors: McMillan T M , Laurie M
Published: March 2004

Objective:Tosurvey the characteristics, level of disability and services received by young adults with acquired brain injury(ABI)resident in nursing home sin Greater Glasgow.

Design:Telephone survey of 75nursinghomesfollowedby a questionnaire survey and review of medication cardexes. Included were all peopleunder65 years with ABI resident in nursing home sin Greater Glasgow between 1February2000and31January 2001.

Setting: Twenty-eight nursing home sin Greater Glasgow, Scotland(population 0.9million).

Subjects: Young adults (16–64)withABI.

Main out come measures: Structured questionnaire, Barthel Index, Office of Population Census Survey (OPCS)Disability Form, review of medication cardexe.

Results: Information was obtainedon all cases identified in 75 nursing homes. There were92peoplewith ABIin 28nursinghomes;43/92werein threehomes. Only 42 had inpatient rehabilitation preadmission. Severe disability (OPCS categories 7–10)was foundin54cases andminimal/minor disability (OPCS categories 1–2)in 18.Thirty-two exhibited challenging behaviour, nine of these were physically violent. Homes were staffed by unqualifiedassistants, supervised by nurses. No home itself offered rehabilitation, but some had accessed an NHS physical disability community team (28/92cases) orothercommunityteams (5/92). Proactive medical review was uncommon. Medication had been reviewed since admission in a minority (21/92). Most had regular visits from relatives.

Conclusions: There is awide range of disability in nursing home residents in Greater Glasgow. Proactive, routine review of medical, rehabilitation and medication needs is rare, as is rehabilitation preand post discharge. This is serious given the likely hood of reduced intellectual and/or physical capacity in
Outreach nurse support after stroke: a descriptive study on patients' and carers' needs, and applied nursing interventions
Authors: Boter Han , Rinkel Gabriël JE , de Haan Rob J
Published: March 2004

Objective: To describe the number and types of problems mentioned by successfully contacted home-dwelling stroke patients and their carers, and nursing interventions applied.

Design: In this multicentre quantitative study in the Netherlands, stroke patients and carers received outreach nurse support consisting of three telephone contacts and one home visit within six months after discharge. Standardized checklists describing a wide range of potential problems were used to record problems and interventions.

Subjects: A sample of 173 patients admitted for a stroke and discharged home, and 148 carers.

Results: Of 173 patients, 166 (96%) were contacted and 162 mentioned in total 1419 problems. Physical problems were mentioned most frequently (92%; 153/166), followed by emotional problems (60%; 99/166). The proportion of patients with problems decreased from 94% (142/151) at the first contact to 74% (108/145) at the last contact. Of 148 carers, 118 (80%) were contacted and 84 mentioned 266 problems. ‘Psychosocial burden’ was mentioned most frequently (45%; 53/118). Proportions of carers with problems were 56% (54/96) at the first contact and 37% (26/70) at the last contact. Of 864 interventions to patients, stroke nurses most frequently applied ‘supportive listening’ (55%; 471/864) and ‘reassuring or encouraging’ (12%; 107/864), and of 258 interventions to carers 45% (115/258) were ‘supportive listening’ and 17% (43/258) ‘informing’.

Conclusions: Almost all patients and most carers were contacted. Though the number of needs decreased during the consecutive contacts, many patients and carers still raised problems during the last contact. Nurses most frequently applied the intervention ‘supportive listening’.
Perceived causes of change in function and quality of life for people with long duration spinal cord injury
Authors: Price Glenda L , Kendall Melissa , Amsters Delena I , Pershouse Kiley J
Published: March 2004

Objective: To determine those factors perceived to change or threaten function and quality of life among individuals with long duration spinal cord injury.

Design: Retrospective self-report using telephone-administered questionnaire.

Setting: Queensland, Australia.

Subjects: Eighty-four community-resident persons with spinal cord injury.

Main outcome measures: Functional Independence Measure, Delighted-Terrible Scale, Perceived Causes of Change Inventory.

Results: Pain and loss of strength were perceived to have caused change in function in 11.9% and 14.3% of participants respectively while these same factors were perceived to have caused change in quality of life in 19.0% and 17.9% of participants respectively. Even when measurable change had not occurred, pain and loss of strength were perceived threats to function in 45.2% and 44.0% of participants respectively, while these same factors were perceived threats to quality of life in 10.7% and 11.9% of individuals respectively. Emotional issues such as stress, depression, family functioning, financial status and employment were also perceived causes of change in quality of life.

Conclusions: The ability of participants to identify the perceived causes of change in function and quality of life may have implications for preventative health care if these individuals are encouraged to seek assistance when these factors first become apparent.
Functional outcome of patients with proximal upper limb deficiency–acquired and congenital
Authors: Datta Dipak , Selvarajah Kanther , Davey Nicola
Published: March 2004

Objective: To investigate the functional outcome of patients with proximal upper limb deficiency – acquired and congenital (elbow disarticulation, transhumeral, shoulder disarticulation and forequarter level).

Design: Cohort observational study.

Subjects: All proximal upper limb amputees and patients with congenital upper limb absence currently registered with the Sheffeld Mobility and Specialised Rehabilitation Centre.

Methods: A self-administered postal questionnaire and medical records were used to collect data. The questionnaire obtained information about demographic details, dominancy of the amputated arm and independence and participation in activities of daily living (ADL), domestic and recreational activities. The prevalence of pain in the phantom limb and stump, and information regarding the remaining arm was also obtained. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the psychological state of the subjects.

Results: Trauma was the commonest cause of proximal upper limb loss (71.25%). Transhumeral amputation was the predominant level (78.75%). Although 73.2% returned to work following amputation, 66.6% had to change job. Overall rejection rate of prosthesis was 33.75%. Twenty-five per cent of patients found the prosthesis beneficial for driving and a small proportion used the prosthesis for employment and recreational activities, but the vast majority used the prosthesis primarily for cosmesis. Pain in the phantom limb was reported in 60% of our patients but there was no significant correlation between this and depression. Symptoms of overuse injury in the nonamputated limb were higher than expected in the normal population.

Conclusion: As many as 33.75% of patients with proximal upper limb deficiency rejected their prostheses and many who continue to wear them do not find them useful in ADL and employment, etc. It is vital that rehabilitation programmes should focus on both prosthetic and nonprosthetic training to achieve maximal independence.
Spina bifida at the sacral level: more than minor gait disturbances
Authors: Schoenmakers M AGC , Gulmans V AM , Gooskens R HJM , Helders P JM
Published: March 2004

Objective: To investigate functional outcome in two groups of children with sacral level paralysis: myelomeningocele (MMC) versus lipomyelomeningocele (LMMC). Additionally both groups were compared with each other and when possible with reference values.

Design: Cross-sectional study by means of (1) clinical assessment, and (2) disability measurement.

Setting: Spina bifida outpatient clinic at a university hospital in the Netherlands.

Subjects: Sample of 30 children with MMC and 14 with LMMC. Mean age (SD) 6.0 (4.9) and 8.4 (4.9) years respectively.

Main measures: Muscle strength, ambulation level, motor performance (Bayley Scales of Infant Development (BSID) and Movement Assessment Battery for Children), and the Pediatric Evaluation of Disability Inventory (PEDI).

Results: The majority of patients in both groups were normal ambulant, 14/21 (67%) in MMC and 9/14 (64%) in LMMC. Ambulation was strongly associated with muscle strength of hip abductors (odds ratio (OR): 13.5, 95% condfidence interval (CI) 2.5–73.7), and ankle dorsal-flexor muscles (OR: 110, 95% CI 8.9–135.9). No significant differences were found in lesion and ambulation level. Muscle strength and motor performance were significantly lower in the MMC group than in the LMMC group ( p <0.05). PEDI scores were comparable in both groups. Most problems were noted in mobility skills and caregiver assistance in self-care, especially regarding bladder and bowel management.

Conclusions: Gross motor and functional problems were seen in both groups. The MMC group showed more muscle weakness and motor problems. However, in both groups caregiver assistance was needed for a prolonged period, especially regarding bladder and bowel management. These dindings need special attention, particularly in children who attend regular schools.
Avoiding pitfalls of correlation coefficients in the assessment of measurement instruments in rehabilitation research
Authors: Weatherall Mark , McPherson Kathryn , Taylor William , Simpson Russell
Published: March 2004

Objective: To provide a practical guide on how to avoid the pitfalls of correlated correlation coefficients when comparing multiple instruments in rehabilitation research.

Design: An observational study comparing a number of instruments measuring quality of life (QoL) compared with an external criterion.

Subjects: Sixty-eight patients admitted to a rheumatology ward for intensive treatment of rheumatoid arthritis.

Methods: Patients completed three new (QoL) instruments and an established instrument before and after intensive treatment for rheumatoid arthritis.

Main outcome measures: Correlation coefficients together with their confidence intervals and a test for the difference between a set of correlated correlation coefficients for the change in the EuroQoL Quality of Life scale (EuroQoL), the World Health Organization Quality Of Life-Abbreviated version (WHOQoL-BREF) and the Quality of Life Profile (QLP) against the Stanford Health Assessment Questionnaire (HAQ).

Results: Although the range of correlation between the new instruments and the external criterion was between -0.37 and -0.59 and suggested that one new instrument was far more responsive than the others,; an omnibus test for an overall difference could find no difference in responsiveness.

Conclusions: It is conceptually simple to use correlation coefficients to assess the properties of multiple instruments measured on the same subjects to find a ‘best’ instrument. However, proper interpretation of results when correlated correlation coefficients are calculated is complex. We recommend analysis includes: (a) that simple plots of the pairs of analysed variables are shown, (b) that simple linear model-fitting statistics, e.g., the R-squared statistic, accompany the plots, (c) that confidence intervals are presented for correlation coefficients, (d) that an omnibus statistical test for the difference between correlated correlation coefficients is presented, and (e) that normal model assumptions are tested.