bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen and Tamoxifen Modulate Cerebrovascular Tone in Ovariectomized Female Rats
Authors: Tsang Suk-Ying , Yao Xiaoqiang , Chan Franky L. , Wong Chi-Ming , Chen Zhen-Yu , Laher Ismail , Huang Yu
Published: May 2004

Postmenopausal estrogen deficiency increases the incidence of cerebrovascular disease. However, hormone replacement therapy is associated with an increased cardiovascular risk. Tamoxifen is a selective estrogen receptor modulator with estrogenic effects on cardiovascular risk factors, but its long-term impacts on cerebral vasculature are unknown. We hypothesized that chronic 17β-estradiol or tamoxifen treatment exerted similar effects in reducing cerebrovascular tension in ovariectomized rats. We therefore determine whether (1) chronic 17β-estradiol treatment could influence vasomotor activities, (2) chronic tamoxifen therapy could exert an estrogen-like or estrogen-antagonistic effect, and (3) acute exposure to estrogen could mimic the effect of 17β-estradiol. Isometric tension was measured in cerebral arteries from female rat groups: control, ovariectomy, ovariectomy plus 17β-estradiol treatment, ovariectomy plus tamoxifen treatment, and ovariectomized rats treated with tamoxifen and 17β-estradiol. Ovariectomy enhanced cerebrovascular contractions to endothelin-1 or CaCl
2
, but not to U46619 or phenylephrine. 17β-Estradiol therapy reversed these effects. Chronic tamoxifen treatment exerted estrogen-like actions by reversing ovariectomy-induced enhancement of vessel tone without antagonizing the effect of chronic 17β-estradiol treatment. Ovariectomy enhanced the relaxing potency of nicardipine, and 17β-estradiol treatment prevented this effect. Acute exposure to 10
−9
mol/L 17β-estradiol or 10
−8
mol/L tamoxifen did not modulate contractions in rings from nonoperated female rats. In conclusion, ovariectomy differentially enhances agonist-induced cerebrovascular tone, an effect that was reversed by estrogen therapy. Tamoxifen does not act as an estrogen antagonist; instead, it functions as an estrogen agonist during estrogen deficiency. Thus, tamoxifen may confer beneficial effects similar to estrogen in cerebrovascular vessels.
Vascular Endothelial Growth Factor Overexpression in Ischemic Skeletal Muscle Enhances Myoglobin Expression In Vivo
Authors: van Weel Vincent , Deckers Martine M.L. , Grimbergen Jos M. , van Leuven Kees J.M. , Lardenoye JanWillem H.P. , Schlingemann Reinier O. , van Nieuw Amerongen Geerten P. , van Bockel J. Hajo , van Hinsbergh Victor W.M. , Quax Paul H.A.
Published: May 2004

Therapeutic angiogenesis using vascular endothelial growth factor (VEGF) is considered a promising new therapy for patients with arterial obstructive disease. Clinical improvements observed consist of improved muscle function and regression of rest pain or angina. However, direct evidence for improved vascularization, as evaluated by angiography, is weak. In this study, we report an angiogenesis-independent effect of VEGF on ischemic skeletal muscle, ie, upregulation of myoglobin after VEGF treatment. Mice received intramuscular injection with adenoviral VEGF-A or either adenoviral LacZ or PBS as control, followed by surgical induction of acute hindlimb ischemia at day 3. At day 6, capillary density was increased in calf muscle of Ad.VEGF-treated versus control mice (
P
<0.01). However, angiographic score of collateral arteries was unchanged between Ad.VEGF-treated and control mice. More interestingly, an increase in myoglobin was observed in Ad.VEGF-treated mice. Active myoglobin was 1.5-fold increased in calf muscle of Ad.VEGF-treated mice (
P
≤0.01). In addition, the number of myoglobin-stained myofibers was 2.6-fold increased in Ad.VEGF-treated mice (
P
=0.001). Furthermore, in ischemic muscle of 15 limb amputation patients, VEGF and myoglobin were coexpressed. Finally, in cultured C2C12 myotubes treated with rhVEGF, myoglobin mRNA was 2.8-fold raised as compared with PBS-treated cells (
P
=0.02). This effect could be blocked with the VEGF receptor tyrosine kinase inhibitor SU5416. In conclusion, we show that VEGF upregulates myoglobin in ischemic muscle both in vitro and in vivo. Increased myoglobin expression in VEGF-treated muscle implies an improved muscle oxygenation, which may, at least partly, explain observed clinical improvements in VEGF-treated patients, in the absence of improved vascularization.
Ischemic Stroke Subtypes
Authors: Schneider Alexander T. , Kissela Brett , Woo Daniel , Kleindorfer Dawn , Alwell Kathleen , Miller Rosemary , Szaflarski Jerzy , Gebel James , Khoury Jane , Shukla Rakesh , Moomaw Charles , Pancioli Arthur , Jauch Edward , Broderick Joseph
Published: May 2004

Background and Purpose—

Blacks have an excess burden of stroke compared with whites; however, data comparing ischemic stroke subtypes among the 2 groups are limited and typically involve relative frequencies. The objective of this study is to compare the incidence rates of ischemic stroke subtypes between blacks and whites within a large, representative, biracial population.

Methods—

The Greater Cincinnati/Northern Kentucky Stroke Study is designed to measure incidence rates and trends of all strokes within a well-defined, large, biracial population. Hospitalized cases were ascertained by
International Classification of Disease
(9th revision; ICD-9) discharge codes. Out-of-hospital events were ascertained by prospective screening of emergency department admission logs, review of coroners’ cases, and monitoring all public health and hospital-based primary care clinics. A sampling scheme was used to ascertain events from nursing homes and all other primary care physician offices. All potential cases underwent detailed chart abstraction and confirmed by physician review. Based on all available clinical, laboratory, and radiographic information, ischemic stroke cases were subtyped into the following categories: cardioembolic, large-vessel, small-vessel, other, and stroke of undetermined cause. Race-specific incidence rates were calculated and compared after adjusting for age and gender, and standardizing to the 1990 US population.

Results—

Between July 1, 1993, and June 30, 1994, 1956 first-ever ischemic strokes occurred among blacks and whites in the study population. Small-vessel strokes and strokes of undetermined cause were nearly twice as common among blacks. Large-vessel strokes were 40% more common among blacks than whites, and there was a trend toward cardioembolic strokes being more common among blacks.

Conclusions—

The excess burden of ischemic strokes among blacks compared with whites is not uniformly spread across the different subtypes. Large-vessel strokes are more common and cardioembolic stroke are as common among blacks, traditionally thought to be more common among whites.
Temperature-Regulated Model of Focal Ischemia in the Mouse
Authors: Barber Philip A. , Hoyte Lisa , Colbourne Frederick , Buchan Alastair M.
Published: May 2004

Background and Purpose—

The importance of mouse stroke models has increased with the development of genetically manipulated animals. We hypothesized that immediate postischemia hypothermia may attenuate ischemic brain injury in the mouse.

Methods—

Intraabdominal radio frequency probes were implanted in animals and core temperature monitored. Groups included: MCAO-45-REG (45 minutes middle cerebral artery occlusion [MCAO]) temperature-controlled in the postischemic period >34°C for 24 hours; MCAO-45 (45 minutes MCAO) were allowed to self-regulate core temperature during recovery; MCAO-30-REG (30 minutes MCAO), with the same temperature protocol as MCAO-45-REG; MCAO-30 (30 minutes MCAO), with temperature protocol the same as MCAO-45. Behavior and histological score was assessed at 7 days. The qualitative histological score assessed for injury in 18 specified regions.

Results—

MCAO-45-REG core temperature (mean 34.94°C±0.8°C) was significantly different than the self-regulating (MCAO-45, mean 33.1°C±2.3°C) for the first 4 hours after anesthesia (
P
<0.01). There was a trend toward similar differences in temperatures for MCAO-30-REG and MCAO-30 (
P
=0.08). At 7 days, a greater improvement in behavior score was observed for MCAO-45 and MCAO-30 compared with MCAO-45-REG and MCAO-30-REG (
P
<0.001). The histological score confirmed reduced injury in unregulated temperature groups (MCAO-45-REG mean 38±10 and MCAO-45 30±5.1,
P
<0.05; MCAO-30-REG 41±10 and MCAO-30 30±9,
P
<0.05).

Conclusions—

Hypothermia is an important confounder of stroke injury in the intraluminal filament mouse model. Future mouse stroke studies must use strict temperature regulation.
Effect of Untreated Hypertension on Hemorrhagic Stroke
Authors: Woo Daniel , Haverbusch Mary , Sekar Padmini , Kissela Brett , Khoury Jane , Schneider Alexander , Kleindorfer Dawn , Szaflarski Jerzy , Pancioli Arthur , Jauch Edward , Moomaw Charles , Sauerbeck Laura , Gebel James , Broderick Joseph
Published: May 2004

Background and Purpose—

Stroke is the third leading cause of death and the leading cause of disability in the United States. Intracerebral hemorrhage and subarachnoid hemorrhage represent ≈20% of all stroke cases and have a mortality rate of 40% to 50%. Hypertension is an important risk factor for these subtypes of stroke. We sought to determine whether untreated hypertension carries a different risk from treated hypertension for hemorrhagic stroke.

Methods—

Cases of hemorrhagic stroke in the greater Cincinnati region were identified by screening all area hospital emergency rooms, radiology reports, and International Classification of Diseases 9 codes. Medical records were reviewed for risk factors and medication use. Cases of hemorrhagic stroke were approached for enrollment into the genetic sampling and interview arm. If subjects agreed, the case was matched by age, race, and gender to population-based controls.

Results—

Between May 1997 and December 2002, we recruited 549 cases of hemorrhagic stroke, of which 322 were intracerebral hemorrhage and 227 were subarachnoid hemorrhage. Untreated hypertension was found to be a significant risk factor for hemorrhagic stroke (odds ratio [OR]=3.5 [2.3 to 5.2];
P
<0.0001) as was treated hypertension (OR=1.4 [1.0 to 1.9];
P
=0.03). Insurance status of “self-pay” or Medicaid was a significant risk factor for untreated hypertension (OR=2.7 [1.6 to 4.4]). We estimate that 17% to 28% of hemorrhagic strokes among hypertensive patients would have been prevented if they had been on hypertension treatment.

Conclusion—

Untreated hypertension is highly prevalent and an important risk factor for hemorrhagic stroke. We estimate that among hypertensive subjects, approximately one fourth of hemorrhagic strokes would be prevented if all hypertensive subjects received treatment.
Monocyte Count, But Not C-Reactive Protein or Interleukin-6, Is an Independent Risk Marker for Subclinical Carotid Atherosclerosis
Authors: Chapman Caroline M. L. , Beilby John P. , McQuillan Brendan M. , Thompson Peter L. , Hung Joseph
Published: May 2004

Background and Purpose—

Systemic inflammatory markers have been shown to predict future cardiovascular events, but whether they are associated with early atherosclerosis is uncertain. We investigated the relationship of inflammatory markers interleukin-6 (IL-6), high-sensitive C-reactive protein (hs-CRP), fibrinogen, monocyte count, and white cell count (WCC) with subclinical carotid atherosclerosis in a healthy community population.

Methods—

B-mode carotid ultrasound was performed on 1111 randomly selected male and female subjects aged 27 to 77 years. Serum IL-6, hs-CRP, plasma fibrinogen, monocyte count, and WCC were measured on all subjects, along with conventional cardiovascular risk factors.

Results—

Multivariate analysis showed that IL-6 (
P
<0.0001), fibrinogen (
P
=0.007), and monocyte count (
P
=0.001) were associated with carotid plaque formation in the whole population. Monocyte count remained associated independently with carotid plaque formation when adjusted further for conventional risk factors (odds ratio per SD increase in monocyte count 1.4; 95% CI, 1.13 to 1.73;
P
=0.002). IL-6 (
P
<0.0001), fibrinogen (
P
<0.0001), and monocyte count (
P
=0.04) were also associated with carotid intima-medial thickness (IMT) in the whole population. However, when adjusted further for conventional risk factors, none remained independently predictive of carotid IMT. Further analysis showed an age-monocyte interaction (
P
=0.03), with monocyte count being an independent predictor of carotid IMT in the older age group only (>53 years;
P
=0.003).

Conclusion—

In a healthy community population, monocyte count is a better independent predictor of common carotid IMT and plaque formation than IL-6, hs-CRP, fibrinogen, and WCC. Monocyte count may represent an inexpensive, easy-to-measure risk marker for subclinical carotid atherosclerosis.
Transcranial Infrared Laser Therapy Improves Clinical Rating Scores After Embolic Strokes in Rabbits
Authors: Lapchak Paul A. , Wei Jiandong , Zivin Justin A.
Published: May 2004

Background and Purpose—

Because photon energy delivered using a low-energy infrared laser may be useful to treat stroke, we determined whether transcranial laser therapy would improve behavioral deficits in a rabbit small clot embolic stroke model (RSCEM).

Methods—

In this study, the behavioral and physiological effects of laser treatment were measured. The RSCEM was used to assess whether low-energy laser treatment (7.5 or 25 mW/cm
2
) altered clinical rating scores (behavior) when given to rabbits beginning 1 to 24 hours postembolization. Behavioral analysis was conducted from 24 hours to 21 days after embolization, allowing for the determination of the effective stroke dose (P
50
) or clot amount (mg) that produces neurological deficits in 50% of the rabbits. Using the RSCEM, a treatment is considered beneficial if it significantly increases the P
50
compared with the control group.

Results—

In the present study, the P
50
value for controls were 0.97±0.19 mg to 1.10±0.17 mg; this was increased by 100% to 195% (P
50
=2.02±0.46 to 2.98±0.65 mg) if laser treatment was initiated up to 6 hours, but not 24 hours, postembolization (P
50
=1.23±0.15 mg). Laser treatment also produced a durable effect that was measurable 21 days after embolization. Laser treatment (25 mW/cm
2
) did not affect the physiological variables that were measured.

Conclusions—

This study shows that laser treatment improved behavioral performance if initiated within 6 hours of an embolic stroke and the effect of laser treatment is durable. Therefore, transcranial laser treatment may be useful to treat human stroke patients and should be further developed.
Knee Laxity Does Not Vary with the Menstrual Cycle, before or after Exercise
Authors: Belanger Michael J. , Moore Douglas C. , Crisco Joseph J. , Fadale Paul D. , Hulstyn Michael J. , Ehrlich Michael G.
Published: May 2004

Background

An intriguing explanation for the disproportionately high rate of anterior cruciate ligament injury in female athletes is that the structural properties of the anterior cruciate ligament are affected by the menstrual hormones. Whether this actually occurs, however, is the subject of ongoing debate.

Hypotheses

(1) Anterior cruciate ligament laxity is different in the follicular, ovulatory, and luteal phases of the menstrual cycle, and (2) exercise exacerbates the difference in anterior cruciate ligament laxity in the 3 phases.

Methods

Over the course of 10 weeks, repeated knee laxity measurements were taken on 27 high-level female athletes, before and after exercise. Point in the menstrual cycle was determined with charts of waking temperature and menstruation. The independent effects of menstrual phase and exercise were evaluated using generalized estimating equations.

Results

Data from 18 participants were included in the final analysis. There were no significant differences in anterior cruciate ligament laxity in any of the 3 menstrual phases, before or after exercise.

Conclusions

Anterior cruciate ligament laxity is not significantly different during the follicular, ovulatory, and luteal phases of the menstrual cycle, and bicycling exercise does not exacerbate or create any differences in anterior cruciate ligament laxity.
Ulnar Collateral Ligament Reconstruction in High School Baseball Players
Authors: Petty Damon H. , Andrews James R. , Fleisig Glenn S. , Cain E. Lyle
Published: May 2004

Background

The incidence of ulnar collateral ligament injury has increased in baseball, especially at the high school level.

Hypothesis

Ulnar collateral ligament injury in high school baseball players is associated with overuse, high-velocity throwing, early throwing of breaking pitches, and improper warm-ups.

Study Design

Retrospective cohort study.

Methods

Follow-up physical examination and questionnaire data were collected at an average of 35 months after ulnar collateral ligament reconstruction from 27 former high school baseball players. Six potential risk factors were evaluated: year-round throwing, seasonal overuse, event overuse, throwing velocity more than 80 mph, throwing breaking pitches before age 14, and inadequate warm-ups.

Results

Overall, 74% returned to baseball at the same or higher level. Patients averaged 3 potential risk factors, and 85% demonstrated at least one overuse category. Of the pitchers, the average self-reported fastball velocity was 83 mph, and 67% threw breaking pitches before age 14.

Conclusions

The success rate of ulnar collateral ligament reconstruction in high school baseball players is nearly equal to that in more mature groups of throwers. Overuse of the throwing arm and throwing breaking pitches at an early age may be related to their injuries. Special attention should be paid to elite-level teenage pitchers who throw with high velocity.
Reducing the Lateral Force Acting on the Patella Does Not Consistently Decrease Patellofemoral Pressures
Authors: Elias John J. , Cech Jennifer A. , Weinstein David M. , Cosgrea Andrew J.
Published: May 2004

Background

Extensor mechanism procedures that decrease the lateral component of the patellar tendon or quadriceps force acting on the patella do not consistently reduce pain.

Hypothesis

Patellofemoral treatments do not consistently decrease patellofemoral pressures because of variations in the moments acting on the patella.

Study Design

Computer simulation study.

Methods

Computational models of 4 knees were constructed to characterize the patellofemoral pressure distribution during simulated squatting from 40° to 90°. The knees were given an initial Q angle of 25°. Patellofemoral treatments were simulated by increasing the percentage of the quadriceps force applied by the vastus medialis by 50% and by medializing the tibial tuberosity to decrease the Q angle to 15°.

Results

Decreasing the Q angle caused a larger decrease in the lateral component of the force applied by the quadriceps and patellar tendon than did increasing the force applied by the vastus medialis and, therefore, was more effective at decreasing patellofemoral pressures and the force needed to resist lateral subluxation. Both treatments also decreased the moments acting to rotate the distal patella laterally and tilt the patella laterally during flexion. Variations in these moments increased patellofemoral pressures for some knees.

Conclusions

Treatments that reduce patellofemoral subluxation can have an unexpected influence on patellofemoral pressures because of the moments acting on the patella.

Clinical Relevance

Extensor mechanism procedures that restore patellofemoral stability may not provide pain relief.
Sagittal Plane Translation during Level Walking in Poor-Functioning and Well-Functioning Patients with Anterior Cruciate Ligament Deficiency
Authors: Kvist Joanna
Published: May 2004

Background

Some patients with anterior cruciate ligament deficiency can function well and participate in high-level sports, whereas others have functional limitations even during activities of daily living.

Hypothesis

Patients who function well after an anterior cruciate ligament injury can stabilize the knee joint during gait by an anterior positioning of the tibia.

Study Design

Controlled laboratory study.

Methods

Sagittal tibial translation was registered with the CA-4000 electrogoniometer, during the Lachman test and walking, in 20 patients with a unilateral anterior cruciate ligament injury. Eleven patients functioned well (Lysholm score [.greaterequal]84), and 9 patients had poor knee function (Lysholm score <84).

Results

During gait, the well-functioning group had 24% greater anterior translation in the injured leg compared to the noninjured leg. In the poor-functioning group, the anterior translation in the injured leg was 16% smaller compared to the noninjured leg (P = .0003). Tibial translation during the Lachman test was similar in the injured leg in the 2 groups.

Conclusion

Patients who function well position their tibiae near the anterior border of the joint play. This position may encourage functional stability.

Clinical Relevance

Rehabilitation that emphasizes training to stabilize the tibia in an anterior position may improve functional stability of the anterior cruciate ligament-deficient knee.
Matrix Metalloproteinase and Tissue Inhibitor of Matrix Metalloproteinase mRNA Levels are Specifically Altered in Torn Rotator Cuff Tendons
Authors: Lo Ian K. Y. , Marchuk Linda L. , Hollinshead Robert , Hart David A. , Frank Cyril B.
Published: May 2004

Background

Rotator cuff tears are a cause of pain and disability in the shoulder. The molecular changes associated with rotator cuff tearing are unclear. A subset of matrix metalloproteinases and tissue inhibitors of metalloproteinase, which are involved in extracellular matrix remodeling and degradation, were evaluated.

Hypothesis

There would be an increase in the mRNA level of spcific matrix metalloproteinase and a decrease in the mRNA level of specific tissue inhibitors of metalloproteinase in rotator cuff tendon tissue obtained from patients with rotator cuff tears.

Study Design

Controlled laboratory study.

Methods

Tissue was obtained from 10 patients undergoing rotator cuff repair for full-thickness rotator cuff tears. Also, tissue was obtained from cadaveric specimens with no gross evidence of rotator cuff tearing. Reverse transcription polymerase chain reaction was performed for the collagenases (MMP-1, MMP-8, MMP-13), the stromelysins (MMP-3, MMP-10, MMP-11), and the tissue inhibitors of metalloproteinase (TIMP-1, TIMP-2, TIMP-3, TIMP-4). Western blotting was performed to confirm the mRNA changes demonstrated in collagenase-3 (MMP-13).

Results

There was a significant increase in collagenase-3 (MMP-13) mRNA levels, a decrease in stromelysin-1 (MMP-3) mRNA levels, and a decrease in tisue inhibitor of metalloproteinase-2, -3, and -4 mRNA levels. Western blotting demonstrated an increase in the active form of collagenase-3 (MMP-13) in rotator cuff tendon tears.

Conclusions

The mRNA levels of specific matrix metalloproteinases and tissue inhibitors of metalloproteinase are altered in torn rotator cuff tendons.

Clinical Relevance

With the known action of the matrix metalloproteinases and tissue inhibitors of metalloproteinase in extra-cellular matrix remodeling, these findings suggest that their roles in remodeling of rotator cuff tears should be further investigated.
Glenohumeral Arthrosis in Anterior Instability before and after Surgical Treatment
Authors: Buscayret Florent , Edwards Thomas Bradley , Szabo Istvan , Adeleine Patrice , Coudane Henri , Walch Gilles
Published: May 2004

Background

Few large series of arthropathy related to anterior glenohumeral instability are available in the orthopaedic literature, preventing analysis of the incidence and the risk factors of preoperative and postoperative glenohumeral arthritis.

Hypothesis

Anterior stabilization surgery influences the risk factors of glenohumeral arthritis.

Study Design

Retrospective review.

Methods

There were 570 patients who underwent an instability procedure. Clinical and radiographic preoperative data were collected for these patients. Arthritis was evaluated preoperatively and postoperatively with the Samilson classification. The mean age at surgery was 31.9 years. Follow-up averaged 6.5 years.

Results

The preoperative incidence of arthritis was 9.2%. Arthritic risk factors were older age at the initial dislocation and at surgery, increased length of time from the initial dislocation until surgery, and the presence of osseous glenoid rim lesions. Postoperative arthritis in patients without any preoperative arthritis occurred in 19.7% and was correlated with older age at the initial dislocation and at surgery, increased number of dislocations, and longer follow-up. Decreased external rotation at latest follow-up correlated with arthritis, although whether this was the cause or the effect was unclear.

Conclusions

Similar factors contribute to preoperative and postoperative arthritis in patients with anterior glenohumeral instability, suggesting that surgery does not influence the risk factors of arthritis. Although decreased external rotation with the arm at side statistically correlated with arthritis in this study, the authors were unable to establish this as an effectual relationship because nearly all patients with glenohumeral osteoarthritis, whether instability related or not, have decreased external rotation.
Eccentric Training of the Gastrocnemius-Soleus Complex in Chronic Achilles Tendinopathy Results in Decreased Tendon Volume and Intratendinous Signal as Evaluated by MRI
Authors: Shalabi Adel , Kristoffersen-Wilberg Maria , Svensson Leif , Aspelin Peter , Movin Tomas
Published: May 2004

Background

Satisfactory treatment results have been reported after eccentric calf muscle strength training in patients with chronic Achilles tendinopathy.

Hypothesis

Magnetic resonance imaging may be a useful adjunct in the evaluation of the effect of 3 months of eccentric calf muscle strength training.

Study Design

Prospective cohort study.

Methods

Using magnetic resonance imaging, the Achilles tendons were investigated in 25 patients (16 men and 9 women) ranging in age from 28 to 70 years (median, 51 years) before and after training. Five different magnetic resonance imaging sequences were used. Tendon volume and mean intratendinous signal were calculated using a new seed-growing technique showing 99.3% and 96.6% intraobserver reliability, respectively. The clinical outcome was categorized according to pain level and performance using a questionnaire completed by the patient.

Results

The eccentric training resulted in a 14% (mean) decrease of tendon volume measured on T1-weighted images, from 6.6 ± 3.1 cm3 to 5.8 ± 2.3 cm3 (P < .05). The intratendinous signal in the symptomatic Achilles tendon measured on proton density-weighted images decreased 23% (mean), from 227 ± 77 signal units to 170 ± 83 signal units (P < .05). The gadolinium contrast agent-enhanced images did not add further value compared with other sequences.

Clinical Outcome

The clinical outcome was categorized as excellent in 10, good in 3, fair in 5, and poor in 8 patients. The [. Delta]signal correlated significantly with the pain level (P < .05).

Conclusions

Eccentric training resulted in decreased tendon volume and intratendinous signal and was correlated with an improved clinical outcome. Magnetic resonance imaging techniques can be used as an adjunct to clinical evaluation by monitoring morphologic effects in clinical treatment studies of Achilles tendinopathy.
A dose effect of IL-7 on thymocyte development
Authors: El Kassar Nahed , Lucas Philip J. , Klug David B. , Zamisch Monica , Merchant Melinda , Bare Catherine V. , Choudhury Baishakhi , Sharrow Susan O. , Richie Ellen , Mackall Crystal L. , Gress Ronald E.
Published: May 2004

To study interleukin-7 (IL-7) in early thymocyte development, we generated mice transgenic (Tg) for the IL-7 gene under control of the lck proximal promoter. Founder line TgA, with the lowest level of IL-7 overexpression, showed enhanced αβ T-cell development. In contrast, in the highest overexpressing founder line, TgB, αβ T-cell development was disturbed with a block at the earliest intrathymic precursor stage. This was due to decreased progenitor proliferation as assessed by Ki-67 staining and in vivo bromodeoxyuridine (BrdU) incorporation. Bcl-2 was up-regulated in T-cell–committed progenitors in all Tg lines, and accounted for greater numbers of double positive (DP), CD4 single positive (SP), and CD8SP thymocytes in TgA mice where, in contrast to TgB mice, thymocyte progenitor proliferation was normal. Mixed marrow chimeras using TgB+ and congenic mice as donors, and experiments using anti–IL-7 monoclonal antibody (MAb) in vivo, confirmed the role of IL-7 protein in the observed TgB phenotype. In conclusion, at low Tg overexpression, IL-7 enhanced αβ T-cell development by increasing thymocyte progenitor survival, while at high overexpression IL-7 reduces their proliferation, inducing a dramatic block in DP production. These results show for the first time in vivo a dose effect of IL-7 on αβ T-cell development and have implications for IL-7 in the clinical setting.
CP-64131, an aminobenzazepine with cytokine-like properties, stimulates human neutrophil functions through the p38-MAPK pathway
Authors: Anderson Marsha S , Knall Cindy , Thurman Gail , Mann Don , Cusack Nancy , Johnson Gary L , Ambruso Daniel R
Published: May 2004

CP-64131 (CP), an aminobenzazepine with cytokine-like, physiologic effects similar to granulocyte-colony stimulating factor (G-CSF) and granulocyte macrophage (GM)-CSF, increases the number of neutrophils and stimulates marrow recovery after doxirubicin ablation. CP can also function as a neutrophil agonist, like formyl-Met-leu-Phe (fMLP). In these studies, we show that CP is unique in that it stimulates the p38-mitogen-activated protein kinase (MAPK) pathway but not extracellular signal-regulated kinase (ERK)1/2 or c-jun N-terminal kinase MAPKs in human neutrophils from peripheral blood. This is in contrast to other neutrophil agonists such as fMLP, interleukin (IL)-8, or GM-CSF, which stimulate multiple MAPK pathways. Like fMLP and IL-8, CP is capable of stimulating superoxide (O2−) production, CD11b expression, and cell polarization in human neutrophils. CP-stimulated O2− production is completely dependent on p38-MAPK activation, as determined by sensitivity to the p38-MAPK inhibitor SB203580. In contrast, SB203580 only partially inhibits expression of CD11b and has no effect on cell polarization stimulated by CP. Therefore, CP treatment of neutrophils activates p38-MAPK but has effects independent of p38-MAPK activation. In human embryonic kidney 293 cells, a human kidney epithelial cell line CP stimulates p38-MAPK and modestly activates ERK1/2. The findings define CP as a novel, small molecule, which has little cellular toxicity in vitro. CP has the ability to activate specific MAPK pathways in different cell types and should prove to be an effective agonist in combination with inhibitors to study biological responses regulated by MAPKs.
P-selectin inhibition suppresses muscle regeneration following injury
Authors: Baker Wallace , Schneider Barbara A St Pierre , Kulkarni Anhurunda , Sloan Gloria , Schaub Robert , Sypek Joseph , Cannon Joseph G
Published: May 2004

This investigation sought to determine if P-selectin-mediated mechanisms contributed to macrophage localization in damaged muscle, an essential process for muscle regeneration. Mice were injected intravenously (i.v.) with soluble P-selectin glycoprotein ligand-1 (sPSGL-1) at 5, 50, or 200 μg/mouse or with 100 μl vehicle alone, and then, lengthening contractions were induced in hindlimb plantar-flexor muscles. The contractions caused fiber damage in soleus muscles, with maximal invasion by CD11b+ mononuclear cells at 24 h post-injury and substantial accumulation of CD11b+ mononuclear cells in the extracellular matrix up to 7 days post-injury. sPSGL-1 treatment caused a dose-dependent decrease in the number of regenerating fibers (P=0.021), as determined by developmental myosin heavy chain (dMHC) expression. This expression was reduced 93% at 7 days post-injury by the highest dose of sPSGL-1, which had no significant influence on intrafiber or extracellular accumulation of cells expressing CD11b, a general marker for phagocytic cells. Additional mice were injected i.v. with 20 μg anti-P-selectin or isotype-control immunoglobulin G and were then subjected to lengthening contractions as before. At 7 days post-injury, soleus muscles from anti-P-selectin-treated mice contained 48% fewer mononuclear cells that bound ER-BMDM1 (P=0.019), a marker for mature macrophages and dendritic cells, and 84% fewer fibers expressing dMHC (P = 0.006), compared with muscles from isotype-injected, control mice. The number of CD11b+ cells was not significantly different between groups. The results are consistent with the concept that P-selectin is involved in the recruitment, maturation, and/or activation of cells that are critical for muscle fiber regeneration.
Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination
Authors: López-Giral Sonia , Quintana Nuria E , Cabrerizo María , Alfonso-Pérez Manuel , Sala-Valdés Mónica , de Soria Valle Gómez Garcia , Fernández-Rañada José María , Fernández-Ruiz Elena , Muñoz Cecilia
Published: May 2004

B cell neoplasms present heterogeneous patterns of lymphoid organ involvement, which may be a result of the differential expression of chemokine receptors. We found that chemokine receptor (CCR)7, CXC chemokine receptor (CXCR)4, or CXCR5, the main chemokine receptors that mediate B cell entry into secondary lymphoid tissues and their homing to T cell and B cell zones therein, were highly expressed in B malignancies with widespread involvement of lymph nodes. Conversely, those pathologies with little or no nodular dissemination showed no expression to very low levels of CCR7 and CXCR5 and low to moderate levels of CXCR4. These findings provide evidence for the role of CCR7, CXCR4, and CXCR5 in determining the pattern of lymphoid organ involvement of B tumors. Functional studies were performed on B malignancies expressing different levels of CCR7, CXCR5, and CXCR4. Multiple myeloma (MM) cells did not express CCR7 nor CXCR5 and did not migrate in response to their ligands; a moderate expression of CXCR4 on MM cells was accompanied by a migratory response to its ligand, CXCL12. By contrast, cells from B cell chronic lymphocytic leukemia (B-CLL) expressed the highest levels of these chemokine receptors and efficiently migrated in response to all ligands of CCR7, CXCR4, and CXCR5. In addition, the migration index of B-CLL cells in response to both of the CCR7 ligands correlated with the presence of clinical lymphadenopathy, thus indicating that the high expression of functional chemokine receptors justifies the widespread character of B-CLL, representing a clinical target for the control of tumor cell dissemination.
On the maximum drawdown of a Brownian motion
Authors: Magdon-Ismail Malik , Atiya Amir F. , Pratap Amrit , Abu-Mostafa Yaser S.
Published: May 2004

The maximum drawdown at time T of a random process on [0,T] can be defined informally as the largest drop from a peak to a trough. In this paper, we investigate the behaviour of this statistic for a Brownian motion with drift. In particular, we give an infinite series representation of its distribution and consider its expected value. When the drift is zero, we give an analytic expression for the expected value, and for nonzero drift, we give an infinite series representation. For all cases, we compute the limiting (T → ∞) behaviour, which can be logarithmic (for positive drift), square root (for zero drift) or linear (for negative drift).
On a time deformation reducing nonstationary stochastic processes to local stationarity
Authors: Genton Marc G. , Perrin Olivier
Published: May 2004

A stochastic process is locally stationary if its covariance function can be expressed as the product of a positive function multiplied by a stationary covariance. In this paper, we characterize nonstationary stochastic processes that can be reduced to local stationarity via a bijective deformation of the time index, and we give the form of this deformation under smoothness assumptions. This is an extension of the notion of stationary reducibility. We present several examples of nonstationary covariances that can be reduced to local stationarity. We also investigate the particular situation of exponentially convex reducibility, which can always be achieved for a certain class of separable nonstationary covariances.
A note on the upper bound for the optimal work size
Authors: Cha Ji Hwan
Published: May 2004

Mi (2002) recently considered a two-dimensional optimization problem for the optimal age-replacement policy and the optimal work size. In order to find (y∗,T∗), Mi (2002) found the optimal age-replacement policy T∗(y) for each fixed work size y, and then searched for the optimal work size y∗. When applying this approach, for each fixed work size y, Mi (2002) obtained the bounds for T∗(y). However, no bound for the optimal work size y∗ was derived. In this note, the results on the upper bound for the optimal work size y∗ are given.
On the foundations of multivariate heavy-tail analysis
Authors: Resnick Sidney
Published: May 2004

Univariate heavy-tailed analysis rests on the analytic notion of regularly varying functions. For multivariate heavy-tailed analysis, reliance on functions is awkward because multivariate distribution functions are not natural objects for many purposes and are difficult to manipulate. An approach based on vague convergence of measures makes the differences between univariate and multivariate analysis evaporate. We survey the foundations of the subject and discuss statistical attempts to assess dependence of large values. An exploratory technique is applied to exchange rate return data and shows clear differences in the dependence structure of large values for the Japanese Yen versus German Mark compared with the French Franc versus the German Mark.
Transforming a random variable to a prescribed distribution: an application to school-based assessment
Authors: Brown Timothy C.
Published: May 2004

When can one find a smooth transformation of a random variable so that the transformed random variable has a specified distribution? If the random variable is continuous, the solution is elementary; if it is discrete, it may be impossible. In this paper, a simple method is given of transforming a random variable in a smooth way to match a specified number of quantiles of an arbitrary distribution. The problem arose from a request for a simple way of transforming marks given in school assessment so that the distribution of transformed marks matches the distribution of external assessment.
Some effects of trimming on the law of the iterated logarithm
Authors: Kesten Harry , Maller Ross
Published: May 2004

We investigate some effects that the ‘light' trimming of a sum Sn = X1 + X2 + · ·· + Xn of independent and identically distributed random variables has on behaviour of iterated logarithm type. Light trimming is defined as removing a constant number of summands from Sn. We consider two versions: (r)Sn, which is obtained by deleting the r largest Xi from Sn, and , which is obtained by deleting the r variables Xi which are largest in absolute value from Sn. We summarise some relevant results from Rogozin (1968), Heyde (1969), and later writers concerning the untrimmed sum, and add some new results concerning trimmed sums. Among other things we show that a general form of the law of the iterated logarithm holds for but not (completely) for .
Stieltjes classes for moment-indeterminate probability distributions
Authors: Stoyanov Jordan
Published: May 2004

LetFbe a probability distribution function with densityf. We assume that (a) F has finite moments of any integer positive order and (b) the classical problem of moments forFhas a nonunique solution (Fis M-indeterminate). Our goal is to describe a, wherehis a ‘small' perturbation function. Such a classSconsists of different distributionsFε(fεis the density ofFε) all sharing the same moments as those ofF, thus illustrating the nonuniqueness ofF, and of anyFε,in terms of the moments. Power transformations of distributions such as the normal, log-normal and exponential are considered and for them Stieltjes classes written explicitly. We define a characteristic ofScalled anindex of dissimilarityand calculate its value in some cases. A new Stieltjes class involving a power of the normal distribution is presented. An open question about the inverse Gaussian distribution is formulated. Related topics are briefly discussed.
Random-allocation and urn models
Authors: Gani J.
Published: May 2004

We review some urn and random-allocation models, mostly using probability generating function (PGF) methods. We begin by formulating a basic problem which can be thought of as either an urn or a random-allocation model; a PGF solution to it is outlined. When the compartments in the latter model are no longer homogeneous, the multivariate PGF can still be derived, though the algebra becomes cumbersome. Some results are given for the case where there are two types of compartment and for the case where there are two types of ball. Some comments are offered on the Frobenius–Harper property of PGFs.
Optimal couplings are totally positive and more
Authors: Glasserman Paul , Yao David D.
Published: May 2004

An optimal coupling is a bivariate distribution with specified marginals achieving maximal correlation. We show that optimal couplings are totally positive and, in fact, satisfy a strictly stronger condition we call the nonintersection property. For discrete distributions we illustrate the equivalence between optimal coupling and a certain transportation problem. Specifically, the optimal solutions of greedily-solvable transportation problems are totally positive, and even nonintersecting, through a rearrangement of matrix entries that results in a Monge sequence. In coupling continuous random variables or random vectors, we exploit a characterization of optimal couplings in terms of subgradients of a closed convex function to establish a generalization of the nonintersection property. We argue that nonintersection is not only stronger than total positivity, it is the more natural concept for the singular distributions that arise in coupling continuous random variables.
Russian options with a finite time horizon
Authors: Ekström Erik
Published: May 2004

We investigate the Russian option with a finite time horizon in the standard Black–Scholes model. The value of the option is shown to be a solution of a certain parabolic free boundary problem, and the optimal stopping boundary is shown to be continuous. Moreover, the asymptotic behavior of the optimal stopping boundary near expiration is studied.
The spectral representation of Bessel processes with constant drift: applications in queueing and finance
Authors: Linetsky Vadim
Published: May 2004

Bessel processes with constant negative drift have recently appeared as heavy-traffic limits in queueing theory. We derive a closed-form expression for the spectral representation of the transition density of the Bessel process of orderν> −1 with constant driftμ≠ 0. Whenν> -½ andμ< 0, the first term of the spectral expansion is the steady-state gamma density corresponding to the zero principal eigenvalueλ0= 0, followed by an infinite series of terms corresponding to the higher eigenvaluesλn,n= 1,2,…, as well as an integral over the continuous spectrum aboveμ2/2. When −1 <ν< -½ andμ< 0, there is only one eigenvalueλ0= 0 in addition to the continuous spectrum. As well as applications in queueing, Bessel processes with constant negative drift naturally lead to two new nonaffine analytically tractable specifications for short-term interest rates, credit spreads, and stochastic volatility in finance. The two processes serve as alternatives to the CIR process for modelling mean-reverting positive economic variables and have nonlinear infinitesimal drift and variance. On a historical note, the Sturm–Liouville equation associated with Bessel processes with constant negative drift is closely related to the celebrated Schrödinger equation with Coulomb potential used to describe the hydrogen atom in quantum mechanics. Another connection is with D. G. Kendall's pole-seeking Brownian motion.
Convolution equivalence and infinite divisibility
Authors: Pakes Anthony G.
Published: May 2004

Known results relating the tail behaviour of a compound Poisson distribution function to that of its Lévy measure when one of them is convolution equivalent are extended to general infinitely divisible distributions. A tail equivalence result is obtained for random sum distributions in which the summands have a two-sided distribution.
Limit theorems for iterated random functions
Authors: Wu Wei Biao , Shao Xiaofeng
Published: May 2004

We study geometric moment contracting properties of nonlinear time series that are expressed in terms of iterated random functions. Under a Dini-continuity condition, a central limit theorem for additive functionals of such systems is established. The empirical processes of sample paths are shown to converge to Gaussian processes in the Skorokhod space. An exponential inequality is established. We present a bound for joint cumulants, which ensures the applicability of several asymptotic results in spectral analysis of time series. Our results provide a vehicle for statistical inferences for fractals and many nonlinear time series models.
Optimal admission control for a single-server loss queue
Authors: Lin Kyle Y. , Ross Sheldon M.
Published: May 2004

This paper presents a single-server loss queueing system where customers arrive according to a Poisson process. Upon arrival, the customer presents itself to a gatekeeper who has to decide whether to admit the customer into the system without knowing the busy–idle status of the server. There is a cost if the gatekeeper blocks a customer, and a larger cost if an admitted customer finds the server busy and therefore has to leave the system. The goal of the gatekeeper is to minimize the total expected discounted cost on an infinite time horizon. In the case of an exponential service distribution, we show that a threshold-type policy—block for a time period following each admission and then admit the next customer—is optimal. For general service distributions, we show that a threshold-type policy need not be optimal; we then present a sufficient condition for the existence of an optimal threshold-type policy.
An inducing construction of quantum codes from classical error correcting codes
Authors: Parthasarathy K. R.
Published: May 2004

The aim of the present paper is to construct error correcting quantum codes from classical error correcting group codes by using the Schur orthogonality relations for characters of a finite abelian group and the Knill–Laflamme criterion for a quantum code to correct a pre-assigned family of errors. This is an abstraction and generalization of Shor's example of a nine qubit single error correcting quantum code.
An innovation approach to non-Gaussian time series analysis
Authors: Ozaki Tohru , Iino Mitsunori
Published: May 2004

The paper shows that the use of both types of random noise, white noise and Poisson noise, can be justified when using an innovations approach. The historical background for this is sketched, and then several methods of whitening dependent time series are outlined, including a mixture of Gaussian white noise and a compound Poisson process: this appears as a natural extension of the Gaussian white noise model for the prediction errors of a non-Gaussian time series. A statistical method for the identification of non-linear time series models with noise made up of a mixture of Gaussian white noise and a compound Poisson noise is presented. The method is applied to financial time series data (dollar-yen exchange rate data), and illustrated via six models.