bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of vasoactive intestinal peptide-mediated vasodilation in human skin
Authors: Wilkins Brad W. , Chung Linda H. , Tublitz Nathan J. , Wong Brett J. , Minson Christopher T.
Published: May 2004

Vasoactive intestinal peptide (VIP) is known to induce histamine release in human skin and to include a nitric oxide (NO)-dependent dilation in several other vascular beds. However, the relative contribution of histamine and NO to VIP-mediated vasodilation in human skin is unknown. Forty-three subjects volunteered to participate in two studies designed to examine the mechanism of VIP-mediated vasodilation in human skin. Study 1 examined the contribution of NO in the skin blood flow response to eight doses of VIP ranging from 25 to 800 pmol. In addition, study 1 examined a specific role for NO in VIP-mediated dilation. Study 2 examined the relative contribution of NO and histamine to VIP-mediated dilation via H1and H2histamine receptors. Infusions were administered to skin sites via intradermal microdialysis. Red blood cell flux was measured by using laser-Doppler flowmetry (LDF), and cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was calculated and normalized to maximal vasodilation. VIP-mediated vasodilation includes a NO-dependent component at doses above 100 pmol, where NO synthase inhibition significantly attenuates CVC ( P < 0.05). Inhibition of H1receptors attenuates the rise in CVC to exogenous VIP ( P < 0.05); however, combined H1-receptor inhibition and NO synthase inhibition further reduced VIP-mediated vasodilation compared with either H1inhibition or NO synthase inhibition alone ( P < 0.05). In contrast to H1-receptor inhibition, H2-receptor inhibition did not affect vasodilation to exogenous VIP. Thus, in human skin, VIP-mediated vasodilation includes a NO-dependent component that could not be explained by H1- and H2-receptor activation.
Evidence for a rapid vasodilatory contribution to immediate hyperemia in rest-to-mild and mild-to-moderate forearm exercise transitions in humans
Authors: Saunders Natasha R. , Tschakovsky Michael E.
Published: May 2004

Controversy exists regarding the contribution of a rapid vasodilatory mechanism(s) to immediate exercise hyperemia. Previous in vivo investigations have exclusively examined rest-to-exercise (R-E) transitions where both the muscle pump and early vasodilator mechanisms may be activated. To isolate vasodilatory onset, the present study investigated the onset of exercise hyperemia in an exercise-to-exercise (E-E) transition, where no further increase in muscle pump contribution would occur. Eleven subjects lay supine and performed a step increase from rest to 3 min of mild (10% maximal voluntary contraction), rhythmic, dynamic forearm handgrip exercise, followed by a further step to moderate exercise (20% maximal voluntary contraction) in each of arm above ( condition A) or below ( condition B) heart level. Beat-by-beat measures of brachial arterial blood flow (Doppler ultrasound) and blood pressure (arterial tonometry) were performed. We observed an immediate increase in forearm vascular conductance in E-E transitions, and the magnitude of this increase matched that of the R-E transitions within each of the arm positions ( condition A: E-E, 52.8 ± 10.7 vs. R-E, 60.3 ± 11.7 ml·min−1·100 mmHg−1, P = 0.66; condition B: E-E, 43.2 ± 12.8 vs. R-E, 33.9 ± 8.2 ml·min−1·100 mmHg−1, P = 0.52). Furthermore, changes in forearm vascular conductance were identical between R-E and E-E transitions over the first nine contraction-relaxation cycles in condition A. The immediate and identical increase in forearm vascular conductance in R-E and E-E transitions within arm positions provides strong evidence that rapid vasodilation contributes to immediate exercise hyperemia in humans. Specific vasodilatory mechanisms responsible remain to be determined.
Impact of Rearing Conditions and Short-Term Light Exposure on Signaling Performance inDrosophilaPhotoreceptors
Authors: Wolfram Verena , Juusola Mikko
Published: May 2004

The amount of visual information an animal can extract from its environment is ultimately limited by the signaling performance of its photoreceptors. To maximize their performance, photoreceptors must be able to accommodate large changes in input caused by the dynamic properties of the visual environment and the animal's own behavior. This is likely to require a range of adaptation mechanisms operating over multiple time scales. Using intracellular recordings, we investigated the effects of developmental light rearing conditions and the effects of 2 h light or dark exposure prior the experiment on the signaling performance of adult Drosophila melanogaster photoreceptors. We show that light-rearing amplifies photoreceptors' voltage responses to light contrast changes by ≥20% and accelerates them by 3 ms. We argue that these differences mostly reflect changes in the timing of the early phototransduction reactions, some of which are persistent. However, being born and nurtured in certain lighting conditions does not set an ultimate limit for the signaling performance of Drosophila photoreceptors. Two-hour light exposure prior to the experiment can improve the information capacity of dark-reared photoreceptors close to the values of light-reared photoreceptors by reducing voltage noise. This effect may originate from plastic changes in the utilization of phototransduction proteins and ion channels.
Single Pulse Stimulation of the Human Subthalamic Nucleus Facilitates the Motor Cortex at Short Intervals
Authors: Hanajima Ritsuko , Ashby Peter , Lozano Andres M. , Lang Anthony E. , Chen Robert
Published: May 2004

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). The mechanism is poorly understood. High-frequency STN DBS has been reported to affect motor cortex excitability in a complex way, but the timing between STN stimuli and changes in motor cortical (M1) excitability has not been investigated. We examined the time course of changes in motor cortical excitability following single pulse STN DBS. We studied 14 PD patients with implanted DBS electrodes in the STN, 2 patients with electrodes in internal globus pallidus (GPi), and 1 patient with an electrode in the sensory thalamus. Transcranial magnetic stimulation (TMS) was delivered to the M1 ipsilateral to the DBS with induced currents either in the anterior-posterior direction in the brain to evoke indirect (I) waves or in the lateral-medial direction to activate corticospinal axons directly. Single pulse stimulation through the DBS contacts preceded the TMS by 0–10 ms. Surface EMG was recorded from the contralateral first dorsal interosseous muscle. Three milliseconds after STN stimulation, the motor evoked potential (MEP) amplitudes produced by anterior-posterior current were significantly larger than control responses, while the responses to lateral-medial currents were unchanged. Similar facilitation also occurred after GPi stimulation, but not with thalamic stimulation. Single pulse STN stimulation facilitates the M1 at short latencies. The possible mechanisms include antidromic excitation of the cortico-STN fibers or transmission through the basal ganglia-thalamocortical pathway.
Medial Perforant Path Inhibition Mediated by mGluR7 Is Reduced After Status Epilepticus
Authors: Bough Kristopher J. , Mott David D. , Dingledine Raymond J.
Published: May 2004

Metabotropic glutamate receptor (mGluR)-mediated inhibition within the dentate gyrus is altered after epilepsy. Whether these changes occur during the developmental period of the disease (i.e., the latent period) has not yet been investigated. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the lateral (LPP) and medial perforant path (MPP) simultaneously in adult mouse hippocampal slices 3–9 days after pilocarpine (PILO)-induced status epilepticus. Genetically manipulated mice (mGluR8 knockout and mGluR4/8 double knockout) and pharmacologically selective agonists were used to identify specific mGluR subtypes affected after PILO. Pharmacological activation of mGluR7 by L-AP4 in both wild-type and mGluR4/8 double knockout mice selectively reduced fEPSPs in the MPP, but not LPP, and this level of inhibition was significantly reduced 3–9 days after PILO-induced SE. Activation of mGluR2/3 reversibly depressed the fEPSP slopes in both the MPP and LPP, but no alterations were noted after PILO. mGluR8 activation selectively inhibited evoked responses in the LPP, but not in the MPP, and this level of inhibition did not change after PILO treatment. These data suggest that reduced presynaptic inhibition mediated by mGluR7, but not mGluR2/3 or mGluR8, may play a role during the latent period in generating hyperexcitability in the dentate and thereby contribute to epileptogenesis.
Long-Term Outcome of Renal Transplant Recipients in the United States After Coronary Revascularization Procedures
Authors: Herzog Charles A. , Ma Jennie Z. , Collins Allan J.
Published: May 2004

Background—

Retrospective studies in dialysis patients have reported increased survival after coronary artery bypass (CAB) compared with coronary artery stenting and PTCA. The purpose of this study was to compare the long-term outcome of renal transplant recipients after stent, PTCA, or CAB with or without internal mammary grafting (CAB [IMG+] or CAB [IMG−]).

Methods and Results—

Renal transplant recipients hospitalized from 1995 to 1999 for first coronary revascularization procedure were retrospectively identified from the United States Renal Data System database. Event-free survival for the end points of all-cause death, cardiac death, acute myocardial infarction (AMI), and the combined end point of cardiac death or AMI was estimated by the life-table method. The impact of independent predictors on survival was examined in a comorbidity-adjusted Cox model. In-hospital mortality rate was 2.3% for 909 stent patients, 4.3% for 652 PTCA patients, 9.4% for 288 CAB (IMG−) patients, and 5.0% for 812 CAB (IMG+) patients. Two-year all-cause survival (±SE) was: stent, 82.5±2.8%; PTCA, 81.6±3.1%; CAB (IMG−), 74.4±5.4%; and CAB (IMG+), 82.7±2.8%. The relative risks of all-cause and cardiac death were not significantly different among revascularization groups. The relative risk of cardiac death or AMI (versus PTCA) was 0.90 (95% CI, 0.69 to 1.17) for stent, 0.80 (95% CI, 0.55 to 1.17) for CAB (IMG−), and 0.57 (95% CI, 0.42 to 0.76) for CAB (IMG+).

Conclusions—

Renal transplant recipients in the United States have comparable long-term survival after percutaneous and surgical coronary revascularization procedures. The most favorable long-term outcome occurs after surgical coronary revascularization.
Prognostic Assessment of Patients With Acute Myocardial Infarction Treated With Primary Angioplasty
Authors: De Luca Giuseppe , Suryapranata Harry , van’t Hof Arnoud W.J. , de Boer Menko-Jan , Hoorntje Jan C.A. , Dambrink Jan-Henk E. , Gosselink A.T. Marcel , Ottervanger Jan Paul , Zijlstra Felix
Published: May 2004

Background—

The aim of this study was to create a practical score for risk stratification in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary angioplasty and to assess the feasibility of early discharge in low-risk patients.

Methods and Results—

A prognostic score was built according to 30-day mortality rates in 1791 patients undergoing primary angioplasty for STEMI. For the identified low-risk patients without any contraindication to early discharge, we estimated and compared the costs of conventional care (prolonged 24-hour hospitalization) with the costs of shifting the care from inpatient to outpatient setting (early discharge) between 48 and 72 hours. Independent predictors of 30-day mortality included in the score were age, anterior infarction, Killip class, ischemic time, postprocedural Thrombolysis In Myocardial Infarction (TIMI) flow, and multivessel disease. This score was able to identify a large cohort (73.4%) of low-risk (score ≤3) patients, with a good discriminatory capacity (
c
statistic=0.907). The mortality rate was 0.1% at 2 days and 0.2% between 2 and 10 days in patients with a score ≤3. The incremental cost-effectiveness ratio for late discharge in low-risk patients was estimated at

1949.33. Therefore, this policy would save 1 life per 1097 low-risk patients, at additional costs of

194 933.33, in comparison with an early discharge policy.

Conclusions—

This score is a practical and useful index for risk stratification after primary angioplasty for STEMI, with a significant impact on clinical decision-making and the related costs. It reliably identifies a large group of patients at very low risk, who may safely be discharged early after primary angioplasty.
Tempol Attenuates Excitatory Actions of Angiotensin II in the Rostral Ventrolateral Medulla During Emotional Stress
Authors: Mayorov Dmitry N. , Head Geoffrey A. , De Matteo Robert
Published: May 2004

Superoxide has been shown to be an important intracellular mediator of actions of angiotensin II. Recently, we found that blockade of angiotensin II type-1 receptors in the rostral ventrolateral medulla (RVLM) abrogated the pressor effect of emotional stress in rabbits. In the present study, we examined the influence of superoxide dismutase mimetics, tempol and tiron, in RVLM on cardiovascular stress response in conscious rabbits. Air-jet stress evoked a sustained increase in blood pressure (+14±2 mm Hg), tachycardia (+52±7 bpm), and renal sympathoactivation (+58±8%). Bilateral microinjections of tempol or tiron (20 nmol) into RVLM did not alter resting cardiovascular parameters, but attenuated the pressor, sympathetic, and tachycardiac response to stress by 40% to 55%. By contrast, 3-carbamoylproxyl, which is structurally close to tempol but has a lower superoxide scavenging activity, did not alter the stress response. Neither tempol nor tiron altered the sympathoexcitatory response to glutamate microinjections into RVLM or to baroreceptor unloading. Microinjections of nitric oxide synthase inhibitor
N
G
-nitro-
l
-arginine methyl ester (
l
-NAME; 10 nmol) into RVLM did not affect the stress response. Coinjections of tempol and
l
-NAME decreased the pressor response to stress by 35±3%. Tempol attenuated the pressor response to microinjection of angiotensin II into RVLM by 59±15%, whereas
l
-NAME did not alter this response. These results suggest that superoxide dismutase mimetics in RVLM attenuate, partially via a nitric oxide-independent mechanism, the pressor effect of emotional stress in rabbits. Together with our previous studies, these results also indicate that superoxide is a key mediator of excitatory actions of angiotensin II in RVLM during acute stress.
Hyperexcitability-Associated Rapid Plasticity After a Focal Cerebral Ischemia
Authors: Fujioka Hiroshi , Kaneko Hidekazu , Suzuki Shinya S. , Mabuchi Kunihiko
Published: May 2004

Background and Purpose—

This article addresses how neuroplastic changes are initiated after an ischemic stroke.

Methods—

A focal cerebral ischemia was photochemically induced on the primary somatosensory cortex of rats, and in vivo electrophysiological recordings were performed on the peri-infarct cortex before and from 1 to 6 hours after the infarction.

Results—

Paired-pulse analysis of evoked field potentials to peripheral electrical stimuli showed statistically significant neuronal hyperexcitability that was associated with rapid expansion of receptive fields (146.1% at 1 hour and 553.6% at 6 hours) as early as 1 hour after the infarction (
P
<0.05). Current source density analysis revealed increased current sinks in cortical layer II/III.

Conclusions—

Our electrophysiological results showed, for the first time to our knowledge, rapid plastic changes in the peri-infarct cortex during the hyperacute stage of an ischemic stroke. Manipulation of this rapid plasticity may affect subsequent plastic changes.
Usefulness of Ambulatory 7-Day ECG Monitoring for the Detection of Atrial Fibrillation and Flutter After Acute Stroke and Transient Ischemic Attack
Authors: Jabaudon Denis , Sztajzel Juan , Sievert Katia , Landis Theodor , Sztajzel Roman
Published: May 2004

Background and Purpose—

Although atrial fibrillation is the most frequent cause of cardioembolic stroke, this arrhythmia remains underdiagnosed, as it is often asymptomatic or intermittent and, thus, may not be detected on standard 12-lead ECG or even 24-hour ECG recording (Holter). In this study, we hypothesized that 7-day ambulatory ECG monitoring using an event-loop recording (ELR) device would detect otherwise occult episodes atrial fibrillation and flutter (AF) after acute stroke or transient ischemic attack (TIA).

Methods—

One hundred forty-nine consecutive patients admitted to our neurology department with an acute stroke or TIA were systematically screened for emboligenic arrhythmias using standard ECG. In the absence of AF on standard ECG, patients underwent 24-hour ECG recording (Holter), which was followed by a 7-day ambulatory ECG monitoring (ELR) in patients with a normal Holter. Patients with previously documented persistent AF, with primary hemorrhagic stroke, or with acute large vessel dissection were not included in the study.

Results—

AF was detected in 22 patients. Standard ECG identified AF in 2.7% of the cases at admission (4/149 patients) and in 4.1% of remaining patients within 5 days (6/145). Holter disclosed AF in 5% of patients with a normal standard ECG (7/139 patients), whereas ELR detected AF in 5.7% of patients with a normal standard ECG and normal Holter (5/88 patients).

Conclusions—

Following acute stroke or TIA, ELR identified patients with AF, which remained undetected with standard ECG and with Holter. ELR should, therefore, be considered in every patient in whom a cardioembolic mechanism is suspected.
A Two-Year Clinical Follow-Up Study in 80 CADASIL Subjects
Authors: Peters Nils , Herzog Jürgen , Opherk Christian , Dichgans Martin
Published: May 2004

Background and Purpose—

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and dementia. The aim of this study was to explore the patterns of clinical progression in CADASIL, to check for prognostic variables, and to provide sample size estimates for future therapeutic trials.

Methods—

Eighty CADASIL subjects (aged 45.7±9.9 years [mean+SD]) were followed prospectively during a mean period of 26.3±1.1 months. Standardized scales on disability (Rankin), activities of daily living (Barthel index), neurological outcome (National Institutes of Health Stroke Scale [NIHSS]), and cognition (structural interview for diagnosis of Alzheimer dementia and multi-infarct dementia [SIDAM] and Mattis dementia rating scale [MDRS]) were assessed at baseline and at follow-up.

Results—

All but 1 individual completed the protocol. At follow-up, the cohort had deteriorated with respect to all clinical scales: Rankin scores (0.3±0.7 [mean change±SD];
P
=0.001), Barthel index (−5.4±15.9;
P
<0.001), NIHSS scores (1.0±2.6;
P
=0.001), SIDAM scores (−2.1±6.4;
P
=0.004), and MDRS scores (−4.3+18.5;
P
=0.09). The spectrum ranged from marked worsening to some degree of improvement. Seventeen patients experienced a new stroke. Overall, there were 18 strokes within 173 person-years, giving an average incidence rate of stroke of 10.4 per 100 person-years (95% CI, 5.6 to 15.2). Age at baseline was found to be a predictor of clinical progression. Sample size estimates show that the number of individuals needed to include in an interventional trial (assumed duration 2 years, assumed treatment effect 40%) is 602 when using stroke occurrence as an outcome measure.

Conclusions—

The clinical course of CADASIL includes periods of acute worsening, chronic progression, stabilization, and improvement. Sample size calculations emphasize the need for surrogate markers of disease progression for future interventional trials.
Chondral Resurfacing and High Tibial Osteotomy in the Varus Knee
Authors: Sterett William I. , Steadman J. Richard
Published: May 2004

Background

Treatment of patients with degenerative knees and varus malalignment presents a difficult clinical problem.

Hypothesis

Combining a medial opening wedge high tibial osteotomy with the microfracture chondral resurfacing procedure is a viable treatment option.

Study Design

Retrospective review of prospectively collected data.

Methods

A group of 38 consecutive patients (mean age, 51.3 years; range, 34 to 72 years; 29 men and 10 women) with varus malalignment and chondral lesions who were treated with chondral resurfacing (an abrasion and microfracture technique) combined with a medial opening wedge high tibial osteotomy. All patients had >5° of varus malalignment. Patients were evaluated preoperatively with the Lysholm and Western Ontario & McMasters Universities Osteoarthritis Index scoring systems and at a minimum of 2 years follow-up.

Results

Thirty-three of 38 patients (87%) were available for 2-year follow-up (average, 45 months; range, 24 to 80 months). Lysholm scores improved from a preoperative score of 43.5 to 78.0 at follow-up; Western Ontario & McMasters Universities Osteoarthritis Index scores improved from 45.8 to 16.2. The average Tegner score was 5.0.

Conclusions

Combining a medial opening wedge high tibial osteotomy with the microfracture chondral resurfacing procedure in the varus knee is an effective method of decreasing pain and increasing function at a minimum of 2 years follow-up.
Semitendinosus Regrowth
Authors: Gill Sanjitpal S. , Turner Maria A. , Battaglia Todd C. , Leis Henry T. , Balian Gary , Miller Mark D.
Published: May 2004

Background

Previous studies have suggested that hamstring tendons can regenerate following harvesting for anterior cruciate ligament reconstruction.

Hypothesis

This “neo-tendon” is a true, functional tendon, not scar tissue.

Study Design

Controlled laboratory study.

Methods

Semitendinosus tendons were harvested from 35 New Zealand white rabbits using a standard tendon stripper. The rabbits were sacrificed 9 to 12 months following the index procedure and thoroughly evaluated.

Results

Thirty-one rabbits were available at the time of sacrifice. The neo-tendon was present in 26 rabbits but was highly variable in size and location of its tibial insertion. Histologic and immunohistochemical staining confirmed that the regenerate tissue was indeed tendon with normal cellularity, organization, and immunolocalization of type I collagen. Electron microscopy showed regeneration of organized collagen tissue that simulated native tendon but with a smaller cross-sectional diameter. Functionally, the neo-tendon was able to transmit force across the musculotendinous junction but at a significantly slower rate than the opposite, control leg. Biomechanical properties of the neo-tendon were significantly less than the control side. Biochemical analysis revealed that the neo-tendons contained glycosaminoglycans and collagen, but levels were significantly lower than normal tendons.

Conclusions

Semitendinosus tendons regenerate with biologically reactive tendinous tissues in an animal model. This tissue has many of the characteristics of a normal tendon but appears to be inferior to the original musculotendinous unit at 9- to 12-month evaluation. Further characterization of the “lizard tail phenomenon” is still needed.

Clinical Relevance

Hamstring tendon regrowth may have a dramatic impact on postoperative function of patients who undergo anterior cruciate ligament reconstruction with these tendons. Further modulation of this regeneration may further reduce graft harvesting morbidity.
Catastrophic Injuries in High School and College Baseball Players
Authors: Boden Barry P. , Tacchetti Robin , Mueller Fred O.
Published: May 2004

Background

There are few epidemiologic studies of catastrophic baseball injuries.

Purpose

To develop a profile of catastrophic injuries in baseball players and to describe relevant risk factors.

Study Design

Retrospective cohort study.

Methods

The authors reviewed 41 incidents of baseball injuries reported to the National Center for Catastrophic Sports Injury Research from 1982 until 2002.

Results

There were an estimated 1.95 direct catastrophic injuries per year, or 0.43 injuries per 100,000 participants. The most common mechanisms of injury were a collision of fielders (9) or of a base runner and a fielder (8), a pitcher hit by a batted ball (14), and an athlete hit by a thrown ball (4). Catastrophic injuries included 23 severe head injuries, 8 cervical injuries, 3 cases of commotio cordis, and 2 cases each of a collapsed trachea and facial fractures. Three athletes sustained a severe head injury and facial fractures. Ten of the 41 injuries were fatalities.

Conclusions

Suggestions for reducing catastrophic injuries in baseball include teaching proper techniques to avoid fielding and base running collisions, protecting the pitcher via a combination of screens and/or helmets with faceguards, continued surveillance and modifications of the bat and ball, eliminating headfirst slides, and continued analysis of chest protectors and automatic external defibrillators for commotio cordis.
Excessive Humeral External Rotation Results in Increased Shoulder Laxity
Authors: Mihata Teruhisa , Lee YeonSoo , McGarry Michelle H. , Abe Muneaki , Lee Thay Q.
Published: May 2004

Background

The quantitative relationship between increased anterior shoulder laxity and increased humeral external rotation observed in throwers remains unclear.

Hypothesis

An elongated anterior capsule, especially the anterior band of the inferior glenohumeral ligament, produced by excessive humeral external rotation will result in increased anterior shoulder laxity and increased humeral external rotation.

Study Design

Controlled laboratory study.

Methods

Seven cadaveric shoulders were tested to measure the humeral rotational range of motion, glenohumeral translations, and length of the anterior band of the inferior glenohumeral ligament. Data were collected for the intact shoulders and after nondestructive stretching of 10%, 20%, and 30% beyond maximum humeral external rotation.

Results

Nondestructive excessive external rotational stretching resulted in a significant increase in superior (30%, 3.3 mm) and inferior (30%, 2.3 mm) length of the anterior band of the inferior glenohumeral ligament, external rotation (30%, 35°), and anterior (30%, 2.4 mm), inferior (30%, 2.2 mm), and anterior-posterior (30%, 5.1 mm) translations. There were significant positive linear correlations between the length of the anterior band of the inferior glenohumeral ligament, external rotation, and anterior translation.

Conclusions

Excessive humeral external rotation results in an elongation of the anterior band of the inferior glenohumeral ligament and an increase in anterior and inferior glenohumeral translations and humeral external rotation.

Clinical Relevance

Repetitive excessive humeral external rotation observed in throwers may be one of the biomechanical causes for increased shoulder laxity and increased humeral external rotation.
Shoulder Outcome Measures
Authors: Placzek Jeff D. , Lukens Steven C. , Badalanmenti Sabrina , Roubal Paul J. , Freeman D. Carl , Walleman Kim M. , Parrot Amy , Wiater J. Michael
Published: May 2004

Background

Several shoulder function scores are used in research, with no universally adopted standard. This study compares 6 shoulder outcome scales.

Hypothesis

Correlations exist between shoulder outcome scales, allowing conversion between scales. Shoulder scales are correlated with age.

Study Design

Regression and correlation study.

Methods

Seventy subjects with shoulder pain completed 6 shoulder outcome scales. Pearson correlations were calculated between the total scores of the 6 instruments, between the components of the scales, and with age. Regression equations were calculated between scales.

Results

The range of r values for total scores was 0.495 [.lessequal] r [.lessequal] 0.770, P [.lessequal] .01. In general, a scale's components were themselves highly correlated and added little new information to the scale (0.260 [.lessequal] r [.lessequal] 0.705, P [.lessequal] .05). Most of the scale scores were highly correlated with age (0.291 [.lessequal] r [.lessequal] 0.582, P [.lessequal] .05). Constant's reported corrections for age reduced (from r = -0.582 to r = -0.250, P < .05) but did not eliminate age as a confounding variable.

Conclusions

Correlations exist between shoulder outcome scales, but existing shoulder scales are not equivalent in their assessments of function; they contain redundant information and, in some cases, may reflect a patient's age better than his/her shoulder function. The utility of conversion equations is minimized as a result of low to moderate correlations between scales.
Effect of Increased Excursion of the Ankle on the Severity of Acute Eccentric Contraction-Induced Strain Injury in the Gastrocnemius
Authors: Song Hongsun , Nakazato Koichi , Nakajima Hiroyuki
Published: May 2004

Background

Although muscle strain injury models are frequently employed, highly invasive procedures, including surgical intervention, are typically used to produce these models. In this study, a minimally invasive model of acute strain injury was produced with a single eccentric contraction.

Hypothesis

The authors tested whether the severity of strain injury in the in vivo gastrocnemius depends on the excursion of the ankle.

Study Design

Controlled laboratory study.

Methods

Animals were randomly assigned to 2 groups: a small range of motion group (90°-105°, n = 10) and a large range of motion group (90°-125°, n = 10). Tetanically activated gastrocnemius muscles with percutaneous electrical stimulation were simultaneously elongated by forced dorsiflexion of the ankle joint.

Results

Isometric tetanic force of the large range of motion group was significantly lower than the pretreatment control 1, 2, and 3 days after treatment. Such reduction was not observed in the small range of motion group. Apparent pathologic damage was observed in the large range of motion group throughout the study period of 10 days.

Conclusions

A larger range of motion causes more damage in eccentric contraction by using the in vivo model.

Clinical Relevance

This in vivo model is useful to elucidate mechanisms of prevention and recovery of strain injury.
Immediate Effects of a Knee Brace with a Constraint to Knee Extension on Knee Kinematics and Ground Reaction Forces in a Stop-Jump Task
Authors: Yu Bing , Herman Daniel , Preston Jennifer , Lu William , Kirkendall Donald T. , Garrett William E.
Published: May 2004

Background

A small knee flexion angle in landing tasks was identified as a possible risk factor for noncontact anterior cruciate ligament injuries that are common in sports.

Hypothesis

A specially designed knee brace with a constraint to knee extension would significantly increase the knee flexion angle at the landing of athletic tasks preceded with horizontal movement components, such as stop-jump tasks.

Study Design

Repeated measure design for brace effects.

Methods

Three-dimensional videographic and force plate data were collected for 10 male and 10 female recreational athletes performing a stop-jump task with and without the specially designed brace. Knee flexion angle at landing, maximum knee flexion angle, and peak ground reaction forces during the stance phase of the stop-jump task were determined for each subject with and without the knee brace.

Results

The knee brace decreased the knee flexion angle at the landing by 5° for both genders but did not significantly affect the peak ground reaction forces during the landing.

Conclusions

The specially designed knee brace may be a useful device in the prevention and rehabilitation of noncontact anterior cruciate ligament injuries in sports.
Differences in the Ultimate Strength of the Biceps Anchor and the Generation of Type II Superior Labral Anterior Posterior Lesions in a Cadaveric Model
Authors: Shepard Michael F. , Dugas Jeff R. , Zeng Nigel , Andrews James R.
Published: May 2004

Background

The pathogenesis of superior labral anterior posterior lesions remains controversial.

Hypothesis

The biceps anchor is more vulnerable to loading with a posterior vector as opposed to an in-line pull.

Study Design

Controlled laboratory study.

Methods

Eight pairs of cadaveric shoulders were dissected, and the biceps tendon was loaded to failure in 1 of 2 loading patterns. Loading pattern A was meant to simulate the eccentric load of the biceps in the deceleration phase of throwing; loading pattern B was meant to simulate the posterior biceps load of the late cocking phase.

Results

The biceps anchor demonstrated significantly increased ultimate strength with in-line loading (group A, 508 N) as opposed to posterior loading (group B, 262 N, P < .001). All group B specimens failed at the biceps anchor, resulting in a type II superior labral anterior posterior lesion. Specimens in group A did not create a superior labral anterior posterior lesion.

Conclusions

Direction of biceps loading resulted in significant differences in the ultimate strength of the biceps anchor and the generation of superior labral anterior posterior lesions. The biceps anchor was significantly weaker when loaded with a posterior vector.

Relevance

The superior labrum may be most vulnerable to injury in late cocking. The reproducible generation of type II superior labral anterior posteriorlesions may have applications as a biomechanical model.
Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid
Authors: Kuendgen Andrea , Strupp Corinna , Aivado Manuel , Bernhardt Alf , Hildebrandt Barbara , Haas Rainer , Germing Ulrich , Gattermann Norbert
Published: May 2004

Valproic acid (VPA) has been shown to inhibit histone deacetylase activity and to synergize with all-trans retinoic acid (ATRA) in the differentiation induction of acute myelogenous leukemia (AML) blasts in vitro. We treated 18 patients with myelodysplastic syndromes (MDS) and AML secondary to MDS (sAML/MDS) with VPA monotherapy (serum concentrations 346-693 μM [50-100 μg/mL]). Five patients received VPA and ATRA (80 mg/m2/d, days 1-7, every other week). Response according to international working group (IWG) criteria was observed in 8 patients (44%) on VPA monotherapy, including 1 partial remission. Median response duration was 4 months (range, 3-9 months). Four of 5 patients relapsing were treated with VPA + ATRA, 2 of them responding again. Among 5 patients receiving VPA + ATRA from the start, none responded according to IWG criteria, but 1 patient with sAML/MDS achieved a marked reduction in peripheral and marrow blasts. Thus, VPA is of therapeutic benefit for patients with MDS, and ATRA may be effective when added later.
Chromosomal localization, hematologic characterization, and iron metabolism of the hereditary erythroblastic anemia (hea) mutant mouse
Authors: White Robert A. , McNulty Steven G. , Roman Shelly , Garg Uttam , Wirtz Eric , Kohlbrecher Deanna , Nsumu Ndona N. , Pinson David , Gaedigk Roger , Blackmore Krista , Copple Angela , Rasul Sidrah , Watanabe Masayo , Shimizu Koji
Published: May 2004

Understanding iron metabolism has been enhanced by identification of genes for iron deficiency mouse mutants. We characterized the genetics and iron metabolism of the severe anemia mutant hea (hereditary erythroblastic anemia), which is lethal at 5 to 7 days. The hea mutation results in reduced red blood cell number, hematocrit, and hemoglobin. The hea mice also have elevated Zn protoporphyrin and serum iron. Blood smears from hea mice are abnormal with elevated numbers of smudge cells. Aspects of the hea anemia can be transferred by hematopoietic stem cell transplantation. Neonatal hea mice show a similar hematologic phenotype to the flaky skin (fsn) mutant. We mapped the hea gene near the fsn locus on mouse chromosome 17 and show that the mutants are allelic. Both tissue iron overloading and elevated serum iron are also found in hea and fsn neonates. There is a shift from iron overloading to iron deficiency as fsn mice age. The fsn anemia is cured by an iron-supplemented diet, suggesting an iron utilization defect. When this diet is removed there is reversion to anemia with concomitant loss of overloaded iron stores. We speculate that the hea/fsn gene is required for iron uptake into erythropoietic cells and for kidney iron reabsorption.
Recipient CD4+ T cells that survive irradiation regulate chronic graft-versus-host disease
Authors: Anderson Britt E. , McNiff Jennifer M. , Matte Catherine , Athanasiadis Ionna , Shlomchik Warren D. , Shlomchik Mark J.
Published: May 2004

Chronic graft-versus-host disease (cGVHD) is an increasingly common cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Relative to acute GVHD (aGVHD), much less is understood about cGVHD. Using the B10.D2 → BALB/c murine cGVHD model, which shares critical pathologic features with human cGVHD, we find that radiation-resistant host T cells regulate cGVHD. We initially observed that recipients lacking all lymphocytes developed accelerated and more severe cGVHD. Using genetically deficient recipients, we determined that αβ+CD4+ T cells were required to regulate cGVHD. Increased cGVHD severity was not due to the absence of T cells per se. Rather, the potency of regulation was proportional to host T-cell receptor (TCR) diversity. Only CD4+CD25+, and not CD4+CD25-, host T cells ameliorated cGVHD when added back, indicating that host T cells acted not via host-versus-graft activity or by reducing homeostatic proliferation but by an undefined regulatory mechanism. Thus, preparative regimens that spare host CD4+CD25+ T cells may reduce cGVHD. Donor CD4+CD25+ T cells also reduced cGVHD. Depletion of CD4+CD25+ cells from the inoculum exacerbated disease, whereas transplantation of additional CD4+CD25+ cells protected against severe cGVHD. Additional CD4+CD25+ cells also promoted healing of established lesions, suggesting that their effects persist during the evolution of cGVHD.
Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded β-thalassemia/HbE patients treated with an oral chelator
Authors: Pootrakul Pensri , Breuer William , Sametband Matias , Sirankapracha Pornpan , Hershko Chaim , Cabantchik Z. Ioav
Published: May 2004

Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated with tissue iron overload and toxicity. We characterized NTBI's susceptibility to deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment of patients with hemoglobin E disease and β-thalassemia (n = 17). In 97% of serum samples (n = 267), the LPI levels were more than 0.4 μM (mean ± SEM, 3.1 ± 0.2 μM) and the percent transferrin (Tf) saturation more than 85 (111 ± 6), whereas only in 4% of sera were the LPI levels more than 0.4 μM for Tf saturation less than 85%. Daily administration of L1 (50 mg/kg) for 13 to 17 months caused both LPI and DCI to decrease from respective initial 5.1 ± 0.5 and 5.4 ± 0.6 μM to steady mean levels of 2.18 ± 0.24 and 2.81 ± 0.14 μM. The steady lowest levels of LPI and DCI were attained after 6 to 8 months, with a half time (t1/2) of 2 to 3 months. Serum ferritin and red cell membrane–associated iron followed a similar course but attained steady basal levels only after 10 to 12 months of continuous treatment, with a t1/2 of 5 to 7 months. These studies indicate that LPI and DCI can serve as early indicators of iron overload and as measures for the effectiveness of iron chelation in reducing potentially toxic iron in the plasma.
Molecular and cellular mechanisms underlying iron transport deficiency in microcytic anemia
Authors: Touret Nicolas , Martin-Orozco Natalia , Paroutis Paul , Furuya Wendy , Lam-Yuk-Tseung Steven , Forbes John , Gros Philippe , Grinstein Sergio
Published: May 2004

A mutation of the iron transporter Nramp2 (DMT1, Slc11a2) causes microcytic anemia in mk mice and in Belgrade rats by impairing iron absorption in the duodenum and in erythroid cells, causing severe iron deficiency. Both mk and Belgrade animals display a glycine-to-arginine substitution at position 185 (G185R) in the fourth predicted transmembrane domain of Nramp2. To study the molecular basis for the loss of function of Nramp2G185R, we established cell lines stably expressing extracellularly tagged versions of wild-type (WT) or mutated transporters. Like WT Nramp2, the G185R mutant was able to reach the plasmalemma and endosomal compartments, but with reduced efficiency. Instead, a large fraction of Nramp2G185R was detected in the endoplasmic reticulum, where it was unstable and was rapidly degraded by a proteasome-dependent mechanism. Moreover, the stability of the mutant protein that reached the plasma membrane was greatly reduced, further diminishing its surface density at steady state. Last, the specific metal transport activity of plasmalemmal Nramp2G185R was found to be significantly depressed, compared with its WT counterpart. Thus, a singlepoint mutation results in multiple biosynthetic and functional defects that combine to produce the impaired iron deficiency that results in microcytic anemia.
Novel di-2-pyridyl–derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment
Authors: Yuan Jun , Lovejoy David B. , Richardson Des R.
Published: May 2004

Aroylhydrazone and thiosemicarbazone iron (Fe) chelators have potent antitumor activity. The aim of the current study was to examine the antitumor effects and mechanisms of action of a novel series of Fe chelators, the di-2-pyridyl thiosemicarbazones. Of 7 new chelators synthesized, 4 showed pronounced antiproliferative effects. The most active chelator was Dp44mT, which had marked and selective antitumor activity—for example, an IC50 of 0.03 μM in neuroepithelioma cells compared with more than 25 μM in mortal fibroblasts. Indeed, this antiproliferative activity was the greatest yet observed for an Fe chelator. Efficacy was greater than it was for the cytotoxic ligand 311 and comparable to that of the antitumor agent doxorubicin. Strikingly, Dp44mT significantly (P < .01) decreased tumor weight in mice to 47% of the weight in the control after only 5 days, whereas there was no marked change in animal weight or hematologic indices. Terminal deoxyribonucleotidyl transferase (TdT)–mediated dUTP nick end-labeling (TUNEL) staining demonstrated apoptosis in tumors taken from mice treated with Dp44mT. This chelator caused a marked increase of caspase-3 activity in murine Madison-109 (M109) cells. Caspase activation was at least partially mediated by the release of mitochondrial holo-cytochrome c (h-cytc) after incubation with Dp44mT. In conclusion, Dp44mT is a novel, highly effective antitumor agent in vitro and in vivo that induces apoptosis.
Specific CXC but not CC chemokines cause elevated monocyte migration in COPD: a role for CXCR2
Authors: Traves Suzanne L , Smith Susan J , Barnes Peter J , Donnelly Louise E
Published: May 2004

Leukocyte migration is critical to maintaining host defense, but uncontrolled cellular infiltration into tissues can lead to chronic inflammation. In the lung, such diseases include chronic obstructive pulmonary disease (COPD), a debilitating, respiratory condition characterized by progressive and largely irreversible airflow limitation for which cigarette smoking is the major risk factor. COPD is associated with an increased inflammatory cell influx including increased macrophage numbers in the airways and tissue. Alveolar macrophages develop from immigrating blood monocytes and have the capacity to cause the pathological changes associated with COPD. This study addressed the hypothesis that increased macrophage numbers in COPD are a result of increased recruitment of monocytes from the circulation. Chemotaxis assays of peripheral blood mononuclear cells (PBMC)/monocytes from nonsmokers, smokers, and COPD patients demonstrated increased chemotactic responses for cells from COPD patients when compared with controls toward growth-related oncogene (GRO)α and neutrophil-activating peptide (NAP)-2 but not toward monocyte chemoattractant protein, interleukin-8, or epithelial-derived NAP(ENA)-78. The enhanced chemotactic response toward GROα and NAP-2 was not mediated by differences in expression of their cellular receptors, CXCR1 or CXCR2. Receptor expression studies using flow cytometry indicated that in COPD, monocyte expression of CXCR2 is regulated differently from nonsmokers and smokers, which may account for the enhanced migration toward GROα and NAP-2. The results highlight the potential of CXCR2 antagonists as therapy for COPD and demonstrate that an enhanced PBMC/monocyte response to specific CXC chemokines in these patients may contribute to increased recruitment and activation of macrophages in the lungs.
Fludarabine Plus Mitoxantrone With and Without Rituximab Versus CHOP With and Without Rituximab As Front-Line Treatment for Patients With Follicular Lymphoma
Authors: Zinzani Pier Luigi , Pulsoni Alessandro , Perrotti Alessio , Soverini Simona , Zaja Francesco , De Renzo Amalia , Storti Sergio , Lauta Vito Michele , Guardigni Luciano , Gentilini Patrizia , Tucci Alessandra , Molinari Anna Lia , Gobbi Marco , Falini Brunangelo , Fattori Pier Paolo , Ciccone Fabrizio , Alinari Lapo , Martelli Maurizio , Pileri Stefano , Tura Sante , Baccarani Michele
Published: May 2004

Purpose

Promising new therapeutic options for follicular lymphoma (FL) include fludarabine plus mitoxantrone (FM) and the mouse/human anti-CD20 antibody, rituximab. We performed a randomized comparative trial of FM with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) front-line chemotherapy with and without sequential rituximab.

Patients and Methods

All previously untreated CD20+FL patients presenting in 15 Italian cooperative institutions from October 1999 were randomly allocated to FM or CHOP. Following clinical or molecular restaging, patients in complete remission (CR) with bcl-2/IgH negativity (CR−) received no further treatment; those in CR with bcl-2/IgH positivity (CR+) received rituximab, as did those in partial remission (PR) with bcl-2/IgH negativity (PR−) or positivity (PR+); nonresponders (NR subgroup) were off study.

Results

After chemotherapy, the FM arm achieved higher rates of CR (68% [49 of 72 patients] v 42% [29 of 68 patients]; P = .003) and CR−(39% [28 of 72 patients] v 13 of 68 patients [19%]; P = .001). Rituximab elicited CR−in 55 of 95 treated patients (58%). The final CR−rate was higher in the FM arm (71% [51 of 72 patients] v 51% [35 of 68 patients]; P = .01). However, with a median follow-up of 19 months (range, 9 to 37 months), no statistically significant difference was found among the various study arms in terms of both progression-free (PFS) and overall survival (OS).

Conclusion

These results indicate that FM is superior to CHOP for front-line treatment of FL and that rituximab is an effective sequential treatment option. However, they also confirm that this superiority is unlikely to translate into either better PFS or OS.
On the optimal allocation of service to impatient tasks
Authors: Glazebrook K. D. , Ansell P. S. , Dunn R. T. , Lumley R. R.
Published: May 2004

Service is often provided in contexts where tasks or customers are impatient or perishable in that they have natural lifetimes of availability for useful service. Moreover, these lifetimes are usually unknown to the service provider. The question of how service might best be allocated to the currently waiting tasks or customers in such a context has been neglected and we propose three simple models. For each model, an index heuristic is developed and is assessed numerically. In all cases studied the heuristic comes close to optimality.