bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of tibial positioning on the diagnosis of posterolateral rotatory instability in the posterior cruciate ligament-deficient knee
Authors: Strauss Eric J , Ishak Charbel , Inzerillo Christopher , Walsh Michael , Yildirim Gokce , Walker Peter , Jazrawi Laith , Rosen Jeffrey
Published: February 2007

Objective:To determine whether positioning of the tibia affects the degree of tibial external rotation seen during a dial test in the posterior cruciate ligament (PCL)–posterolateral corner (PLC)-deficient knee.

Design:Laboratory investigation.

Setting:Biomechanics laboratory.

Hypothesis:An anterior force applied to the tibia in the combined PCL–PLC-deficient knee will yield increased tibial external rotation during a dial test.

Methods:The degree of tibial external rotation was measured with 5 N⋅m of external rotation torque applied to the tibia at both 30° and 90° of knee flexion. Before the torque was applied, an anterior force, a posterior force, or neutral (normal, reduced control) force was applied to the tibia. External rotation measurements were repeated after sequential sectioning of the PCL, the posterolateral structures and the fibular collateral ligament (FCL).

Results:Baseline testing of the intact specimens demonstrated a mean external rotation of 18.6° with the knee flexed to 30° (range 16.1–21.0°), and a mean external rotation of 17.3° with the knee flexed to 90° (range 13.8–20.0°). Sequential sectioning of the PCL, popliteus and popliteofibular ligament, and the FCL led to a significant increase in tibial external rotation compared with the intact knee for all testing scenarios. After sectioning of the popliteus and popliteofibular ligament, the application of an anterior force during testing led to a mean tibial external rotation that was 5° greater than during testing in the neutral position and 7.5° greater than during testing with a posterior force. In the PCL, popliteus/popliteofibular ligament and FCL-deficient knee, external rotation was 9° and 12° greater with the application of an anterior force during testing compared with neutral positioning and the application of a posterior force, respectively.

Conclusion:An anterior force applied to the tibia during the dial test in a combined PCL–PLC-injured knee increased the overall amount of observed tibial external rotation during the dial test. The anterior force reduced the posterior tibial subluxation associated with PCL injury, which is analogous to what is observed when the dial test is performed with the patient in the prone position. Reducing the tibia with either an anterior force when the patient is supine or performing the dial test with the patient in the prone position increases the ability of an examiner to detect a concomitant PLC injury in the setting of a PCL-deficient knee.
The effect of osseous ankle configuration on chronic ankle instability
Authors: Frigg Arno , Magerkurth Olaf , Valderrabano Victor , Ledermann Hans-Peter , Hintermann Beat
Published: February 2007

Background:Chronic ankle instability (CAI) is a common orthopaedic entity in sport. Although other risk factors have been studied extensively, little is known about how it is influenced by the osseous joint configuration.

Aim:To study the effect of osseous ankle configuration on CAI.

Design:Case–control study, level III.

Setting:Radiological examination with measurement of lateralxrays by an independent radiologist using a digital DICOM/PACS system.

Patients:A group of 52 patients who had had at least three recurrent sprains was compared with an age-matched and sex-matched control group of 52 healthy subjects.

Main outcome measures:The radius of the talar surface, the tibial coverage of the talus (tibiotalar sector) and the height of the talar body were measured.

Results:The talar radius was found to be larger in patients with CAI (21.2 (2.4) mm) than in controls (17.7 (1.9) mm; p<0.001, power >95%). The tibiotalar sector, representing the tibial coverage of the talus, was smaller in patients with CAI (80° (5.1°)) than in controls (88.4° (7.2°); p<0.001, power >95%). No significant difference was observed in the height of the talar body between patients with CAI (28.8 (2.6) mm) and controls (27.5 (4.0) mm; p = 0.055).

Conclusion:CAI is associated with an unstable osseous joint configuration characterised by a larger radius of the talus and a smaller tibiotalar sector. There is evidence that a higher talus might also play some part, particularly in women.
STAT3 mRNA and protein expression in colorectal cancer: effects on STAT3-inducible targets linked to cell survival and proliferation
Authors: Lassmann Silke , Schuster Ingrid , Walch Axel , Göbel Heike , Jütting Uta , Makowiec Frank , Hopt Ulrich , Werner Martin
Published: February 2007

Aims:To evaluate mRNA and protein expression of signal transducers and activators of transcription (STAT)3 in colorectal carcinomas (CRCs) and to define the association of STAT3 activity with the STAT3-inducible targets cyclin D1, survivin, Bcl-xl and Mcl-1.

Materials and methods:Matching serial sections of normal colonic epithelium and invasive CRCs (n = 32) were subjected to quantitative reverse transcriptase polymerase chain reaction specific to STAT3, cyclin D1, survivin, Bcl-xl and Mcl-1, as well as immunohistochemistry. For STAT3 immunohistochemistry, two antibodies, recognising unphosphorylated (UP-) and phosphorylated (tyr705, P-) STAT3 were used. Ki-67 (MIB-1) staining was included as a proliferation marker.

Results:Compared with normal colonic epithelium, UP-STAT3 and P-STAT3 (p = 0.023 and 0.006) protein expression and expression of its associated targets cyclin D1, survivin and Bcl-xl were significantly (all p<0.001) increased in carcinoma. In carcinomas, STAT3 (p = 0.019) and Bcl-xl (p = 0.001) mRNAs were correlated with lymph node status. Moreover, nuclear P-STAT3 protein expression (active state) was associated with the expression of its target genes Bcl-xl (p = 0.038) and survivin (p = 0.01) as well as with Ki-67 (p = 0.017). By contrast, cytoplasmic UP-STAT was significantly linked to Bcl-xl mRNA (p = 0.024) and protein (p = 0.001) as well as to cytoplasmic survivin protein expression (p = 0.019).

Conclusion:Both inactive (UP-STAT3) and active (P-STAT3) STAT3 proteins are markedly increased in invasive CRCs. This is associated with Bcl-xl and survivin induction, increased proliferation and lymph node metastasis. This study therefore provides the basis for further examination of the prognostic or predictive value of these molecular markers in CRC.
Gender equality in the work of local research ethics committees in Europe: a study of practice in five countries
Authors: Moerman C J , Haafkens J A , Söderström M , Rásky É , Maguire P , Maschewsky-Schneider U , Norstedt M , Hahn D , Reinerth H , McKevitt N
Published: February 2007

Background:Funding organisations and research ethics committees (RECs) should play a part in strengthening attention to gender equality in clinical research. In the research policy of European Union (EU), funding measures have been taken to realise this, but such measures are lacking in the EU policy regarding RECs.

Objective:To explore how RECs in Austria, Germany, Ireland, The Netherlands and Sweden deal with gender equality issues by asking two questions: (1) Do existing procedures promote representation of women and gender expertise in the committee? (2) How are sex and gender issues dealt with in protocol evaluation?

Methods:Two RECs were selected from each country. Data were obtained through interviews with key informants and content analysis of relevant documents (regulations, guidelines and review tools in use in 2003).

Results:All countries have rules (mostly informal) to ensure the presence of women on RECs; gender expertise is not required. Drug study protocols are carefully evaluated, sometimes on a formal basis, as regards the inclusion of women of childbearing age. The reason for excluding either one of the sexes or including specific groups of women or making a gender-specific risk–benefit analysis are investigated by some RECs. Such measures are, however, neither defined in the regulations nor integrated in review tools.

Conclusions:The RECs investigated in five European member states are found to pay limited attention to gender equality in their working methods and, in particular in protocol evaluation. Policy and regulations of EU are needed to strengthen attention to gender equality in the work of RECs.
Effects of Three Different Stimulations (Acupuncture, Moxibustion, Acupuncture Plus Moxibustion) of BL.67 Acupoint at Small Toe on Fetal Behavior of Breech Presentation
Authors: Neri Isabella , De Pace Viviana , Venturini Paolo , Facchinetti Fabio
Published: February 2007

The aim of the study was to evaluate cardiovascular effects and fetal behavior during moxibustion, acupuncture or acupuncture plus moxibustion applied on the BL.67 acupoint of women (beside the outer corner of the 5th toenail) in fetal breech presentation. During the acupoint stimulation (20 min, two times a week), the women were submitted to computerized non-stress test. Fourteen cases were treated by both acupuncture and moxibustion, 15 cases by moxibustion and 10 cases by acupuncture. In 56% of cases, fetal position was converted from breech position to cephalic one; the success share was 80% for moxibustion, 28% for acupuncture, 57% for acupuncture plus moxibustion; the conversion, on average, was achieved after 3 sessions. Statistical analysis indicated that acupuncture plus moxibustion was able to reduce fetal heart rate during the application of stimuli while acupuncture and moxibustion separately did not affect such parameter. Moreover, moxibustion and acupuncture with moxibustion reduced fetal movements while acupuncture only appears ineffective. The present study suggests that fetal movements were reduced by both acupuncture plus moxibustion and moxibustion and that fetal heart rate was reduced just by acupuncture plus moxibustion. The mechanisms leading the effect on fetal heart rate and fetal movements remain to be clarified. Even though further studies are needed, such preliminar report mainly investigated the impact of different stimula on the BL.67 acupoint. Unfortunately these small series of data do not allow us to draw any conclusion about the effectiveness of the different treatments.
ON THE TOPOLOGICAL ORIGIN OF ENTANGLEMENT IN ISING SPIN GLASSES
Authors: SREEDHAR V. V.
Published: February 2007

The origin of entanglement in a class of three-dimensional spin models, at low momenta, is traced to topological reasons. The establishment of the result is facilitated by the gauge principle which, in conjunction with the duality mapping of the spin models, enables us to recast them as lattice Chern–Simons theories. The entanglement measures are expressed in terms of the correlators of Wilson lines, loops, and their generalisations. For continuous spins, these yield the invariants of knots and links. For Ising-like models, they can be expressed in terms of three-manifold invariants obtained from finite group cohomology — the so-called Dijkgraaf–Witten invariants.
Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication
Authors: Lang Charles H. , Frost Robert A. , Vary Thomas C.
Published: February 2007

Epidemiological evidence suggests alcoholic myopathy is more severe in females than males, but comparable animal studies are lacking that make elucidating the biochemical locus for this defect problematic. The present study determined whether skeletal muscle protein synthesis and markers of degradation exhibit a sexual dimorphic response to either chronic alcohol consumption or acute intoxication. Male and female rats were fed an alcohol-containing diet, pair-fed for 26 wk (chronic), or received an intraperitoneal injection of alcohol (acute). In males, chronic alcohol decreased gastrocnemius protein synthesis by 20%. This reduction was associated with a twofold increase in the inactive eukaryotic initiation factor (eIF) 4E·4E-binding protein 1 (4E-BP1) complex and a 60% reduction in the active eIF4E·eIF4G complex. This redistribution of eIF4E was associated with decreased phosphorylation of both 4E-BP1 and eIF4G (50–55%). The phosphorylation of ribosomal protein S6 was also reduced 60% in alcohol-consuming male rats. In contrast, neither rates of protein synthesis nor indexes of translation initiation in muscle were altered in alcohol-fed female rats despite blood alcohol levels comparable to males. Chronic alcohol ingestion did not alter atrogin-1 or muscle RING finger-1 mRNA content (biomarkers of muscle proteolysis) in males but increased their expression in females 50–100%. Acute alcohol intoxication produced a comparable decrease in muscle protein synthesis and translation initiation in both male and female rats. Our data demonstrate a sexual dimorphism for muscle protein synthesis, translation initiation, and proteolysis in response to chronic, but not acute, alcohol intoxication; however, they do not support evidence indicating females are more sensitive toward the development of alcoholic skeletal muscle myopathy.
Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models
Authors: Aigner Bernhard , Rathkolb Birgit , Herbach Nadja , Kemter Elisabeth , Schessl Christina , Klaften Matthias , Klempt Martina , de Angelis Martin Hrabé , Wanke Rüdiger , Wolf Eckhard
Published: February 2007

Kidney diseases lead to the failure of urinary excretion of metabolism products. In the Munich ethylnitrosourea (ENU) mouse mutagenesis project, which is done on a C3H inbred genetic background, blood samples of more than 15,000 G1 offspring and 500 G3 pedigrees were screened for alterations in clinical-chemical parameters. We identified 44 animals consistently exhibiting increased plasma urea concentrations. Transmission analysis of the altered phenotype of 23 mice to subsequent generations led to the establishment of five mutant lines. Both sexes were affected in these lines. Urinary urea levels were decreased in the mutants. In addition, most mutants showed increased plasma and decreased urinary creatinine levels. Pathological investigation of kidneys from the five mutant lines revealed a broad spectrum of alterations, ranging from no macroscopic and light microscopic kidney alterations to decreased kidney weight-to-body weight ratio, dilation of the renal pelvis, and severe glomerular lesions. Thus screening for elevated plasma urea levels in a large-scale ENU mouse mutagenesis project resulted in the successful establishment of mouse strains which are valuable tools for molecular studies of mechanisms involved in urea excretion or which represent interesting models for kidney diseases.
High-salt intake and the renal expression of amino acid transporters in spontaneously hypertensive rats
Authors: Pinho Maria João , Serrão Maria Paula , Soares-da-Silva Patrício
Published: February 2007

This study evaluated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) the response to salt loading of the renal dopaminergic system and transcript abundance of Na+-independent (LAT1 and LAT2) and Na+-dependent (ASCT2 and B0AT1) amino acid transporters potentially involved in renal tubular uptake of l-DOPA. Rats were fed normal (NS)- or high (HS; 1% saline as drinking water)-salt intake for 24 h. Transcript abundance of amino acid transporters was age dependent, differently regulated in WKY and SHR and responded differently to salt intake. HS intake similarly increased urinary dopamine in 4-wk-old SHR and WKY. At 12 wk of age, HS intake increased urinary dopamine in SHR, but not in WKY. Changes in urinary dopamine paralleled changes in the uptake of l-DOPA in isolated renal tubules from 4- and 12-wk-old WKY and SHR on NS and HS intake. At 12 wk of age, HS intake was accompanied by decreases in LAT1 and LAT2 transcript abundance in WKY and SHR. ASCT2 and B0AT1 expression was significantly decreased in both 4- and 12-wk-old WKY and in 4-wk-old SHR on HS intake. By contrast, HS intake increased ASCT2 and B0AT1 expression in 12-wk-old SHR. It is concluded that salt-sensitive mechanisms influence LAT1, LAT2, ASCT2, and B0AT1 gene transcription. Differences in urinary dopamine and tubular uptake of l-DOPA between WKY and SHR during HS intake, namely in 12-wk-old animals, may result from increases in the ASCT2 and B0AT1 mRNA levels and less pronounced decreases in LAT2 expression.
Effects of 5-Hydroxytryptamine and Substance P on Neurons of the Inferior Salivatory Nucleus
Authors: Suwabe Takeshi , Bradley Robert M.
Published: February 2007

The parasympathetic secretomotor innervation of the salivary glands originates from a longitudinal column of neurons in the medulla called the salivatory nucleus. The neurons innervating the parotid and von Ebner salivary glands are situated in the caudal extremity of the column designated as the inferior salivatory nucleus (ISN). Immunocytochemical investigations have demonstrated the presence of a number of neuropeptides surrounding the ISN neurons. We have examined the neurophysiological effect of two of these neuropeptides on neurons of the ISN identified by retrograde transport of a fluorescent label. Both serotonin (5-HT) and substance P (SP) excited virtually all neurons in the ISN. Application of these neuropeptides resulted in membrane depolarization that was concentration dependent. Although the majority of ISN neurons that were depolarized by SP application exhibited an increase in input resistance, application of 5-HT induced widely varied change in input resistance. Membrane depolarization elicited action potential discharges that increased in frequency with increasing concentration of 5-HT and SP. Blocking action potential conduction from surrounding neurons did not eliminate the depolarizing effects of 5-HT and SP, indicating that both neuropeptides acted directly on the ISN neurons. Finally, the use of 5-HT agonists and antagonists indicates that 5-HT acts via a 5-HT2A receptor, and the use of SP agonists suggests that SP acts via neuokinin-1 and -2 receptors. These data show that 5-HT and SP excite most of the ISN neurons innervating the lingual von Ebner glands possibly modulating the synaptic drive to these neurons derived from afferent gustatory input.
Overexpression of SK2 Channels Enhances Efferent Suppression of Cochlear Responses Without Enhancing Noise Resistance
Authors: Maison Stéphane F. , Parker Lisan L. , Young Lucy , Adelman John P. , Zuo Jian , Liberman M. Charles
Published: February 2007

Cochlear hair cells express SK2, a small-conductance Ca2+-activated K+ channel thought to act in concert with Ca2+-permeable nicotinic acetylcholine receptors (nAChRs) α9 and α10 in mediating suppressive effects of the olivocochlear efferent innervation. To probe the in vivo role of SK2 channels in hearing, we examined gene expression, cochlear function, efferent suppression, and noise vulnerability in mice overexpressing SK2 channels. Cochlear thresholds, as measured by auditory brain stem responses and otoacoustic emissions, were normal in overexpressers as was overall cochlear morphology and the size, number, and distribution of efferent terminals on outer hair cells. Cochlear expression levels of SK2 channels were elevated eightfold without striking changes in other SK channels or in the α9/α10 nAChRs. Shock-evoked efferent suppression of cochlear responses was significantly enhanced in overexpresser mice as seen previously in α9 overexpresser mice; however, in contrast to α9 overexpressers, SK2 overexpressers were not protected from acoustic injury. Results suggest that efferent-mediated cochlear protection is mediated by other downstream effects of ACh-mediated Ca2+ entry different from those involving SK2-mediated hyperpolarization and the associated reduction in outer hair cell electromotility.
Lack of Macrophage Migration Inhibitory Factor Regulation Is Linked to the Increased Chronotropic Action of Angiotensin II in SHR Neurons
Authors: Sun Chengwen , Li Hongwei , Gao Yongxin , Matsuura Tomokazu , Upchurch Patrick A. , Raizada Mohan K. , Sumners Colin
Published: February 2007

Macrophage migration inhibitory factor acts via its intrinsic thiol–protein oxidoreductase activity to negatively regulate the neuronal chronotropic actions of angiotensin II in normotensive rat neurons. Because the chronotropic action of angiotensin II is potentiated in spontaneously hypertensive rat neurons, we investigated whether this negative regulatory mechanism is absent in these rats. Angiotensin II (100 nM) elicited an ≈89% increase in neuronal firing in Wistar–Kyoto rat hypothalamus and brain stem cultured neurons and an increase in intracellular macrophage migration inhibitory factor levels in the same cells. The chronotropic action of angiotensin II was significantly greater (≈212% increase) in spontaneously hypertensive rat neurons, but angiotensin II failed to alter macrophage migration inhibitory factor expression in these cells. Intracellular application of recombinant macrophage migration inhibitory factor (0.8 nM) or its specific neuronal overexpression via Ad5-SYN-MIF (1×10
7
infectious units) significantly attenuated the chronotropic action of angiotensin II in spontaneously hypertensive rat neurons, similar to results from Wistar–Kyoto rat neurons. In contrast, C60S-macrophage migration inhibitory factor (0.8 nM), which lacks thiol–protein oxidoreductase activity, failed to alter the chronotropic action of angiotensin II in neurons from either rat strain. Thus, whereas macrophage migration inhibitory factor has the potential to depress the chronotropic action of angiotensin II in spontaneously hypertensive rat neurons, it is unlikely that this regulatory mechanism occurs, because angiotensin II does not increase the expression of this protein. The lack of this regulatory mechanism may contribute to the increased chronotropic action of angiotensin II in spontaneously hypertensive rat neurons.
Lymphocytes
Authors: Gee J. Michael , Kalil Angela , Shea Connor , Becker Kyra J.
Published: February 2007

Antigen-nonspecific inflammation appears to contribute to postischemic brain injury. Because there is a breach in the integrity of the blood-brain barrier after stroke, the immune system encounters novel central nervous system (CNS) antigens that allow for the development of a CNS antigen-specific autoimmune response. The nature of the immune response generated on antigen encounter is determined by the microenvironment at the site of antigen encounter. For instance, a systemic inflammatory response, such as that which would accompany an infection, could alter the microenvironment in such a way as to promote the initiation of deleterious autoimmunity. If patients who develop an infection in the immediate poststroke period are predisposed toward a CNS autoimmune response, it might help to explain why infection after stroke is associated with increased disability. We present data to support this hypothesis and to show that the breach in the blood-brain barrier can also be capitalized on to modulate the immune response to create a neuroprotective environment after stroke.
Carotid Stenting for Asymptomatic Carotid Stenosis
Authors: Derdeyn Colin P.
Published: February 2007

Angioplasty and stenting should not be performed for patients with asymptomatic atherosclerotic carotid bifurcation stenosis, except in the context of randomized clinical trials. Surgical carotid endarterectomy (CEA) has been proven effective over medical therapy in select asymptomatic patient populations. The benefit in these patients is small and easily overcome by procedural complication rates over 3%, owing to the relatively low risk for stroke on medical therapy. Until a randomized controlled clinical trial demonstrates reasonable equivalence of carotid angioplasty and stenting (CAS) to CEA for stroke risk reduction in asymptomatic low-surgical risk patients, there is no rationale for its use in this setting. Furthermore, there is no evidence that revascularization by either CEA or CAS is superior to medical therapy for patients that are not good surgical candidates owing to medical comorbidities or anatomic factors. Randomized trials in this high surgical risk patient population must include a medical treatment arm. In this article, we will review the existing data for CAS in patients with asymptomatic atherosclerotic carotid artery stenosis.
A Model of Cerebral Palsy From Fetal Hypoxia-Ischemia
Authors: Derrick Matthew , Drobyshevsky Alexander , Ji Xinhai , Tan Sidhartha
Published: February 2007

Disorders of the maternal-placental-fetal unit often results in fetal brain injury, which in turn results in one of the highest burdens of disease, because of the lifelong consequences and cost to society. Investigating hypoxia-ischemia in the perinatal period requires the factoring of timing of the insult, determination of end-points, taking into account the innate development, plasticity, and enhanced recovery. Prenatal hypoxia-ischemia is believed to account for a majority of cerebral palsy cases. We have modeled sustained and repetitive hypoxia-ischemia in the pregnant rabbit in utero to mimic the insults of abruptio placenta and labor, respectively. Rabbits have many advantages over other animal species; principally, their motor development is in the perinatal period, akin to humans. Sustained hypoxia-ischemia at 70% (E22) and 79% (E25) caused stillbirths and multiple deficits in the postnatal survivors. The deficits included impairment in multiple tests of spontaneous locomotion, reflex motor activity, motor responses to olfactory stimuli, and the coordination of suck and swallow. Hypertonia was observed in the E22 and E25 survivors and persisted for at least 11 days. Noninvasive imaging using MRI suggests that white matter injury in the internal capsule could explain some of the hypertonia. Further investigation is underway in other vulnerable regions such as the basal ganglia, thalamus and brain stem, and development of other noninvasive determinants of motor deficits. For the first time critical mechanistic pathways can be tested in a clinically relevant animal model of cerebral palsy.
Key Note Lecture
Authors: Bredesen Dale E.
Published: February 2007

Background and Purpose—

Programmed cell death (pcd) plays a critical role in the development of the nervous system, as well as in its response to insult. Both anti-pcd and pro-pcd modulators play prominent roles in development and disease, including ischemic cerebrovascular disease. The purpose of this article is therefore to review the basics of programmed cell death.

Methods—

There have been over 100 000 scientific and clinical publications on the topic of programmed cell death and its most well known form, apoptosis. The principles emerging from these studies are reviewed here.

Results—

Programmed cell death is a form of cell death in which the cell plays an active role in its own demise. Apoptosis is the most well-defined form of pcd, but recent studies have begun to characterize an alternative program, autophagic cell death. In addition, there appear to be programmatic cell deaths that do not fit the criteria for either apoptosis or autophagic cell death, arguing that additional programs may also be available to cells.

Conclusion—

Constructing a mechanistic taxonomy of all forms of pcd—based on inhibitors, activators, and identified biochemical pathways involved in each form of pcd—should offer new insight into cell deaths associated with cerebrovascular disease and other diseases, and ultimately offer new therapeutic approaches.
Tumor Necrosis Factor-α Receptor p75 Is Required in Ischemia-Induced Neovascularization
Authors: Goukassian David A. , Qin Gangjian , Dolan Christine , Murayama Toshinori , Silver Marcy , Curry Cynthia , Eaton Elizabeth , Luedemann Corinne , Ma Hong , Asahara Takayuki , Zak Victor , Mehta Shanu , Burg Aaron , Thorne Tina , Kishore Raj , Losordo Douglas W.
Published: February 2007

Background—

Aging is a risk factor for coronary and peripheral artery disease. Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, is expressed in ischemic tissue and is known to modulate angiogenesis. Little is known about the role of TNF-α receptors (TNFR1/p55 and TNFR2/p75) in angiogenic signaling.

Methods and Results—

We studied neovascularization in the hindlimb ischemia model in young and old TNFR2/p75 knockout (p75KO) and wild-type age-matched controls. Between days 7 to 10 after hindlimb surgery, 100% of old p75KOs experienced autoamputation of the operated limbs, whereas none of the age-matched wild-type mice exhibited hindlimb necrosis. Poor blood flow recovery in p75KO mice was associated with increased endothelial cell apoptosis, decreased capillary density, and significant reductions in the expression of vascular endothelial growth factor and basic fibroblast growth factor-2 mRNA transcripts in ischemic tissue and in circulating endothelial progenitor cells. The number of circulating bone marrow–derived endothelial progenitor cells was significantly reduced in p75KO mice. Transplantation of wild-type bone marrow mononuclear cells into irradiated old p75KO mice 1 month before hindlimb surgery prevented limb loss.

Conclusions—

Our present study suggests that ischemia-induced endothelial progenitor cell–mediated neovascularization is dependent, at least in part, on p75 TNF receptor expressed in bone marrow–derived cells. Specifically, endothelial cell/endothelial progenitor cell survival, vascular endothelial growth factor expression, endothelial progenitor cell mobilization from bone marrow, endothelial progenitor cell differentiation, and ultimately ischemia-induced collateral vessel development are dependent on signaling through TNFR2/p75. Furthermore, because TNFR2/p75 becomes an age-related limiting factor in postischemic recovery, it may be a potential gene target for therapeutic interventions in adult vascular diseases.
Direct Inhibition of Cardiac Hyperpolarization-Activated Cyclic Nucleotide–Gated Pacemaker Channels by Clonidine
Authors: Knaus Anne , Zong Xiangang , Beetz Nadine , Jahns Roland , Lohse Martin J. , Biel Martin , Hein Lutz
Published: February 2007

Background—

Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic α
2
-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine.

Methods and Results—

To test whether clonidine elicits pharmacological effects independent of α
2
-adrenoceptors, we have generated mice with a targeted deletion of all 3 α
2
-adrenoceptor subtypes (α
2ABC
−/−
). α
2ABC
−/−
mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in α
2ABC
−/−
mice by up to 150 bpm. Clonidine-induced bradycardia in conscious α
2ABC
−/−
mice was 32.3% (10 μg/kg) and 26.6% (100 μg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from α
2ABC
-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (
I
f
) in isolated sinoatrial node pacemaker cells and the
I
f
-generating hyperpolarization-activated cyclic nucleotide–gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking
I
f
, clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and α
2ABC
-knockout mice.

Conclusions—

Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.
Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease
Authors: Angiolillo Dominick J. , Shoemaker Steven B. , Desai Bhaloo , Yuan Hang , Charlton Ronald K. , Bernardo Esther , Zenni Martin M. , Guzman Luis A. , Bass Theodore A. , Costa Marco A.
Published: February 2007

Background—

After treatment with clopidogrel, patients with type 2 diabetes mellitus (T2DM) have reduced platelet inhibition compared with patients who are not diabetic. Whether platelet inhibition can be enhanced by increasing clopidogrel maintenance dosage in T2DM patients is unknown. The aim of this pilot study was to assess the functional impact of a high maintenance dose in T2DM patients with suboptimal clopidogrel-induced antiplatelet effects.

Methods and Results—

T2DM patients on chronic dual antiplatelet therapy were screened to identify suboptimal clopidogrel responders. The latter were randomized to 30-day treatment with a standard (75 mg; n=20) or high (150 mg; n=20) daily maintenance dose. Platelet function was assessed at 3 time points: baseline, 30 days after randomization, and 30 days after resuming standard dosing. Platelet function parameters included adenosine diphosphate–induced (20 and 5 μmol/L) maximal and late platelet aggregation, inhibition of platelet aggregation, platelet disaggregation, and P2Y
12
reactivity index. A total of 64 T2DM patients were screened to identify 40 suboptimal responders. After randomization, maximal adenosine diphosphate–induced (20 μmol/L) platelet aggregation was significantly reduced in the 150-mg group compared with the 75-mg group (
P
=0.002; primary end point). However, suboptimal clopidogrel response was still present in 60% of patients on the 150-mg regimen. All other platelet function parameters showed enhanced clopidogrel-induced antiplatelet effects with 150 mg, which returned to baseline values after resumption of standard dosing.

Conclusions—

A 150-mg maintenance dose of clopidogrel is associated with enhanced antiplatelet effects compared with 75 mg in high-risk T2DM patients. However, enhanced ex vivo platelet reactivity continues to persist, the clinical implications of which are unknown and need to be evaluated in large-scale clinical trials.
Curiosity as the Thief of Wonder An Essay on Heidegger's Critique of the Ordinary Conception of Time
Authors: Stone Brad Elliott
Published: February 2007

What is the connection between curiosity and the ordinary conception of time? This essay offers a reading of Heidegger's account of wonder and curiosity found in Basic Questions of Philosophy (1937-8) and attempts to show its continuity with the discussion of the now-centered ordinary conception of time in Being and Time (1927). Heidegger refutes the claim that one can still say that philosophy begins in wonder in an age that no longer understands what wonder means due to modern Da-sein's obsession with the new (curiosity). Since wonder is no longer a viable philosophical attunement, Heidegger outlines in Contributions to Philosophy (1936) a new attunement, a new key for philosophy: terror.
Effect of additional functional exercises on balance in elderly people
Authors: de Bruin Eling D , Murer Kurt
Published: February 2007

Objective: To evaluate the additional effect of functional exercises on balance and lower extremity function among hostel-dwelling elderly people partaking in strength,training.

Design: A randomized two-group parallel controlled trial.

Setting: A senior resident’s hostel in Switzerland.

Participants: Thirty-two individuals randomized to either strength or strength and functional exercise groups.

Interventions: Both groups received machine-driven strength training for 45 min, twice weekly, for 12 weeks. The strength and functional exercises group received an additional 30 min of functional exercise training, once weekly.

Main outcome measures: Tinetti test, balance tests and a physical performance test. Assessments were performed before and after the intervention.

Results: Improvements for the balance test depended on the type of training (significant interaction effects [F(1,20)= 6.7; P = 0.018]). This test improved from 11.3 ∓ 11.7 to 17 ∓ 11.2 (P = 0.009) in the combined training group (n = 12) and remained from 7.3 ∓ 9.5 to 6.9 ∓ 9.2 unchanged (P = 0.821) in the strength training group (n = 13). A significant difference between groups following training was observed (P = 0.031). The Tinetti balance score and the chair stand test of the physical performance assessment improved from 14.3 ∓ 1.9 to 15.3 ∓ 1.1 (P = 0.026) and 1.8 ∓ 1.2 to 2.8 ∓ 1.1 (P = 0.012) respectively in the combined training group only.

Conclusions: Our findings suggest that twice-weekly lower extremity strength training of 12 weeks’ duration in hostel-dwelling elderly people only improves task-specific balance performance and lower extremity physical function when additional functional exercises are added.
Comparative Accuracy of Magnetic Resonance Imaging and Ultrasonography in Confirming Clinically Diagnosed Patellar Tendinopathy
Authors: Warden Stuart J. , Kiss Zoltan S. , Malara Frank A. , Ooi Alistair B. T. , Cook Jill L. , Crossley Kay M.
Published: February 2007

Background

Diagnosis of patellar tendinopathy is based primarily on clinical examination; however, it is commonplace to image the patellar tendon for diagnosis confirmation, with the imaging modalities of choice being magnetic resonance imaging (MRI) and ultrasonography (US). The comparative accuracy of these modalities has not been established.

Hypothesis

Magnetic resonance imaging and US have good (>80%) accuracy and show substantial agreement in confirming clinically diagnosed patellar tendinopathy.

Study Design

Cohort study (diagnosis); Level of evidence, 2.

Methods

Magnetic resonance imaging and US (gray scale [GS-US] and color Doppler [CD-US]) features of 30 participants with clinically diagnosed patellar tendinopathy and 33 activity-matched, asymptomatic participants were prospectively compared. Accuracy, sensitivity, specificity, positive and negative predictive values, and the likelihood of positive and negative test results were determined for each technique.

Results

The accuracy of MRI, GS-US, and CD-US was 70%, 83%, and 83%, respectively (P = .04; MRI vs GS-US). The likelihood of positive MRI, GS-US, and CD-US was 3.1, 4.8, and 11.6, respectively. The MRI and GS-US had equivalent specificity (82% vs 82%; P = 1.00); however, the sensitivity of GS-US was greater than MRI (87% vs 57%; P = .01). Sensitivity (70% vs 87%; P = .06) and specificity (94% vs 82%; P = .10) did not differ between CD-US and GS-US.

Conclusions

Ultrasonography was more accurate than MRI in confirming clinically diagnosed patellar tendinopathy. GS-US and CD-US may represent the best combination for confirming clinically diagnosed patellar tendinopathy because GS-US had the greatest sensitivity, while a positive CD-US test result indicated a strong likelihood an individual was symptomatic.
A 10-Year Comparison of Anterior Cruciate Ligament Reconstructions with Hamstring Tendon and Patellar Tendon Autograft
Authors: Pinczewski Leo A. , Lyman Jeffrey , Salmon Lucy J. , Russell Vivianne J. , Roe Justin , Linklater James
Published: February 2007

Background

There are no controlled, prospective studies comparing the 10-year outcomes of anterior cruciate ligament (ACL) reconstruction using patellar tendon (PT) and 4-strand hamstring tendon (HT) autografts.

Hypothesis

Comparable results are possible with HT and PT autografts.

Study Design

Cohort study; Level of evidence, 2.

Methods

One hundred eighty ACL-deficient knees that met inclusion criteria underwent ACL reconstruction (90 HT autograft, 90 PT autograft) by one surgeon and were treated with an accelerated rehabilitation program. All knees were observed in a prospective fashion with subjective, objective, and radiographic evaluation at 2, 5, 7, and 10-year intervals.

Results

At 10 years, there were no differences in graft rupture rates (7/90 PT vs. 12/90 HT, P = .24). There were 20 contralateral ACL ruptures in the PT group, compared with 9 in the HT group (P = .02). In all patients, graft rupture was associated with instrumented laxity >2 mm at 2 years (P = .001). Normal or near-normal function of the knee was reported in 97% of patients in both groups. In the PT group, harvest-site symptoms (P = .001) and kneeling pain (P = .01) were more common than in the HT group. More patients reported pain with strenuous activities in PT knees than in HT knees (P = .05). Radiographic osteoarthritis was more common in PT knees than the HT-reconstructed knees (P = .04). The difference, however, was composed of patients with mild osteoarthritis. Other predictors of radiographic osteoarthritis were <90% single-legged hop test at 1 year and the need for further knee surgery. An “ideal” outcome, defined as an overall International Knee Documentation Committee grade of A or B and a radiographic grade of A at 10 years after ACL reconstruction, was associated with <3 mm of instrumented laxity at 2 years, the absence of additional surgery in the knee, and HT grafts.

Conclusions

It is possible to obtain excellent results with both HT and PT autografts. We recommend HT reconstructions to our patients because of decreased harvest-site symptoms and radiographic osteoarthritis.
Women’s Ways of Organizing
Authors: Mizrahi Terry
Published: February 2007

This article presents a longitudinal qualitative study of the strengths and struggles of a diverse group of 27 women organizers in 1989 and 2003. It highlights the resilience of their core biography, as well as individual and collective differences based on changing context, careers, and aging over 13 years. On the basis of these women’s perspectives, the article examines an analytic document, A Framework for Feminist Organizing, that was produced by a women organizers’ collective and reinforces and modifies its practice principles. The study builds on the growing literature on feminist theory and practice applied to the field of community organizing, activism, and progressive social change.
“Money in the Private Chamber”
Authors: Ho Petula Sik Ying
Published: February 2007

This article reexamines the assumptions of the feminization-of-poverty thesis by investigating the perceptions of Hong Kong Chinese women regarding old age and the women’s strategies for dealing with old age and retirement. It challenges the assumptions of a male-centered model of retirement planning and highlights the significance of women’s definitions of wealth and poverty. It shows that retirement planning cannot be separated from women’s practices of self in the multiple and interrelated domains of their lives by examining how women manage their personal savings or “money in the private chamber.”
A personal BELMAS history
Authors: Ribbins Peter
Published: February 2007

The editorial team thought that the MiE readership might be interested in gaining an insight into the role of the Chair of BELMAS. We therefore invited three chairs to contribute to a mini series of ‘Accounts of BELMAS Chairs’ to appear in concurrent issues of MiE. Professor Peter Ribbins starts this mini series by taking us on a fascinating journey of his amazing work for BELMAS that spans some 35 years, including his work as Chair of BELMAS. The account is striking in its humility and moving in its elegiacal recognition of dear friends and colleagues of BELMAS.
Building trust among educational stakeholders through Participatory School Administration, Leadership and Management
Authors: Antonio Diosdado M. San , Gamage David T.
Published: February 2007

This paper examines the impact of implementing Participatory School Administration, Leadership and Management (PSALM) on the levels of trust among the educational stakeholders in Philippine public secondary schools. After an introductory section, the research context is provided by briefly reviewing relevant literature on PSALM and on trust and by describing the Philippine school system. The next section describes the research methods, which included an experiment with empirical surveys (first survey - 735 respondents; second survey - 603 respondents), documentary analysis and interviews. Research results are then discussed. Finally, based on the data, the paper concludes by suggesting that the Philippines should expedite the process of establishing school councils in its public schools.
Outsourcing in Australian Hotels: A Transaction Cost Economics Perspective
Authors: Lamminmaki Dawne
Published: February 2007

A triangulated field study and questionnaire survey methodology was applied to investigate antecedents of outsourcing activity in Australian hotels. The field study involved the conduct of semistructured interviews with 15 managers in large hotels. Subsequent to this, a survey questionnaire was mailed to 356 general managers in Australian hotels with 100 or more rooms. The survey yielded a return of 111 completed questionnaires. The study represents an examination of transaction cost economics (TCE), a partial investigation of agency theory, and other organizational factors that may influence hotel outsourcing. The study’s findings provide some support for TCE and provide insight into other factors that appear to be affecting Australian hotels’ propensity to outsource.
Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo-controlled, dose-ranging study
Authors: Goodman A.D. , Cohen J.A. , Cross A. , Vollmer T. , Rizzo M. , Cohen R. , Marinucci L. , Blight A.R.
Published: February 2007

Objective To determine the safety of sustained-release 4-aminopyridine in subjects with mutiple sclerosis (MS) and to examine dose-related efficacy up to 40 mg twice daily.

Method Multicenter, randomized, double-blind, placebo-controlled, study. Following a 4-week baseline peroid, subjects were randomly assigned to receive Fampridine-SR (n=25, doses from 10 to 40 mg twice daily, increasing in 5 mg increments weekly) or placebo (n=11). A battery of assessments was performed weekly, including the MS Functional Composite (MSFC), fatigue questionnaires, and lower extremity manual muscle testing.

Results The most common adverse events were dizziness, insomnia, paresthesia, asthenia, nausea, headache, and tremor. Five subjects were discontinued from Fampridine-SR because of adverse events at doses greater than 25 mg, and these included convulsions in two subjects at doses of 30 and 35 mg twice daily. Improvement were seen in lower extremity muscle strength (prospective analysis) and walking speed (post-hoc analysis) in the Fampridine-SR group compared to placebo (unadjusted p-values of 0.01 and 0.03, respectively). There were no significant differences in other MSFC measure or fatigue scores.

Conclusions Future studies should employ doses up to 20 mg twice daily with lower extremity strength and walking speed as potential outcome measures. Multiple Sclerosis 2007; 13: 357-368. http://msj.sagepub.com
Advanced lightweight cooling-garment technology: functional improvements in thermosensitive patients with multiple sclerosis
Authors: Meyer-Heim A , Rothmaier M , Weder M , Kool J , Schenk P , Kesselring J
Published: February 2007

Cooling of thermosensitive patients with multiple sclerosis (MS) can improve clinical symptoms. In order to study the effectiveness of an advanced lightweight cooling-garment technology based on aquatic evaporation, a single-blinded balanced crossover study was performed on 20 patients with an Expanded Disability Status Scale score ≤6.5. The results using a tight-cuff cooling-garment prototype for peripheral cooling suggest improvement of a timed-walking test, leg-strength, fine-motor skills and subjective benefits. Preliminary data of the heart rate variability (HRV) including six patients suggest that the MS patients show an abnormal HRV after sham condition, which is normalized after cooling. Technical information was gained about the cooling activity and the practicability and handling of the device. These encouraging findings promote further adaptations of the prototype to increase its cooling properties and ameliorate the practicability of the cooling garment. Multiple Sclerosis 2007; 13: 232–237. http://msj.sagepub.com