bluuebunny/crossref_metadata_2025 huggingface dataset:
Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells
Authors: Thomas Susan N. , Schnaar Ronald L. , Konstantopoulos Konstantinos
Published: January 2009

Selectins facilitate metastasis and tumor cell arrest in the microvasculature by mediating binding of selectin-expressing host cells to ligands on tumor cells. We recently identified CD44 variant isoforms as functional P-, but not E-/L-, selectin ligands on colon carcinoma cells. Furthermore, a ∼180-kDa sialofucosylated glycoprotein(s) mediated selectin binding in CD44-knockdown cells. Using immunoaffinity chromatography and tandem mass spectrometry, we identify podocalyxin-like protein (PCLP) as an alternative selectin ligand. Blot rolling and cell-free flow-based adhesion assays disclose that PCLP on LS174T colon carcinoma cells possesses E-/L-, but not P-, selectin binding activity. The selectin-binding determinants on LS174T PCLP are non-MECA-79-reactive sialofucosylated structures displayed on O-linked glycans, distinct from the MECA-79-reactive O-glycans on PCLP expressed by high endothelial venules, which is an L-selectin ligand. PCLP on CD44-knockdown LS174T cells exhibits higher HECA-452 immunoreactivity than PCLP on wild-type cells, suggesting that PCLP functions as an alternative acceptor for selectin-binding glycans. The enhanced expression of HECA-452 reactivity on PCLP from CD44-knockdown cells correlates with the increased avidity of PCLP for E- but not L-selectin. The novel finding that PCLP is an E-/L-selectin ligand on carcinoma cells offers a unifying perspective on the apparent enhanced metastatic potential associated with tumor cell PCLP overexpression and the role of selectins in metastasis.
Lymphocyte-derived interferon-γ mediates ischemia-reperfusion-induced leukocyte and platelet adhesion in intestinal microcirculation
Authors: Osman Mohammad , Russell Janice , Granger D. Neil
Published: January 2009

Although previous studies have implicated lymphocytes in the gut microvascular and inflammatory responses to ischemia-reperfusion (I/R), the lymphocyte population and lymphocyte-derived products that mediate these responses have not been defined. Platelet and leukocyte adhesion was measured in intestinal postcapillary venules of wild-type (WT) mice and mice genetically deficient in either CD4+ T cells (CD4−/−), CD8+ T cells (CD8−/−), B cells (B cell−/−), or interferon-γ (IFN-γ−/−) subjected to 45 min of ischemia and 4 h of reperfusion. The I/R-induced platelet and leukocyte recruitment responses were also evaluated following adoptive transfer of WT splenocytes into CD4−/−, CD8−/−, B cell−/−, and IFN-γ−/− mice. WT mice exposed to gut I/R exhibited significant increases in the adhesion of both platelets and leukocytes, compared with sham-WT mice. These blood cell adhesion responses to I/R were greatly attenuated in CD4−/−, CD8−/−, B cell−/−, and IFN-γ−/− mice. Adoptive transfer of WT splenocytes restored the WT responses to I/R in all mutants except the B cell−/− mice. These findings implicate both T and B cells and lymphocyte-derived IFN-γ as mediators of the proinflammatory and prothrombogenic phenotype assumed by intestinal microvessels after I/R.
A novel echocardiographic marker of end systole in the ischemic left ventricle: “tug of war” sign
Authors: Lyseggen Erik , Vartdal Trond , Remme Espen W. , Helle-Valle Thomas , Pettersen Eirik , Opdahl Anders , Edvardsen Thor , Smiseth Otto A.
Published: January 2009

The present study introduces a new clinical method to define left ventricular (LV) end systole (ES) during tissue Doppler imaging (TDI). Preliminary experiments showed a sharp inflection point in strain traces (SIP) from ischemic borderzones, which coincided with onset of a postsystolic shortening wave ( VPS) in the velocity trace. In a single-vessel disease model, we investigated whether SIP and VPS may serve as markers of global ES and their mechanism. In six anesthetized dogs we measured LV pressure and myocardial long-axis function by using TDI and sonomicrometry. Ischemia was induced by left anterior descending coronary artery occlusion. ES was defined by the minimum first derivative of LV pressure. TDI and sonomicrometry demonstrated a sharp SIP and VPS at ES in the ischemic borderzone (defined as moderately ischemic myocardium by pressure-dimension loop analysis). Time differences relative to ES ( ± SD) were −0.1 ± 2.3 (intraclass correlation coefficient RIC = 0.996) and 6.8 ± 10.7 ms ( RIC = 0.89) for SIP as shown by sonomicrometry and TDI, respectively. There was a strong inverse relationship between postsystolic shortening in the borderzone and simultaneous lengthening of nonischemic myocardium. In 30 patients with acute myocardial infarction, SIP and VPS evaluated by TDI were compared with ES defined by aortic valve closure. Time differences were −4 ± 14 ( RIC = 0.94) and −2 ± 11 ms ( RIC = 0.96), respectively. In the ischemic borderzone, SIP and VPS identified global ES with high accuracy. The force balance or “tug of war” between borderzone and nonischemic myocardium is a likely underlying mechanism for these markers. The method may be used as an “all in one heart beat” approach for TDI analysis in acute myocardial ischemia.
Gene regulation in the adaptive process to hypoxia in lung epithelial cells
Authors: Clerici Christine , Planès Carole
Published: January 2009

Lung alveolar epithelial cells are normally very well oxygenated but may be exposed to hypoxia in many pathological conditions such as pulmonary edema, acute respiratory distress syndrome, chronic obstructive pulmonary diseases, or in some environmental conditions such ascent to high altitude. The ability of alveolar epithelial cells to cope with low oxygen tensions is crucial to maintain the structural and functional integrity of the alveolar epithelium. Alveolar epithelial cells appear to be remarkably tolerant to oxygen deprivation as they are able to maintain adequate cellular ATP content during prolonged hypoxic exposure when mitochondrial oxidative phosphorylation is limited. This property mostly relies on the ability of the cells to rapidly modify their gene expression program, stimulating the expression of genes involved in anaerobic energy supply and repressing expression of genes involved in some ATP-consuming cellular processes. This adaptive strategy of the cells is mostly, but not entirely, dependent on the expression of hypoxia-inducible factors (HIFs), known to be responsible for orchestrating a large number of hypoxia-sensitive genes. This review focuses on the role of HIF isoforms expressed in alveolar epithelial cells exposed to hypoxia and on the specific hypoxic gene regulation that takes place in alveolar epithelial cells either through HIF-dependent or -independent pathways.
Attenuated PGI2synthesis in obese Zucker rats
Authors: Hodnett Benjamin L. , Dearman Jennifer A. , Carter Cory B. , Hester Robert L.
Published: January 2009

In obesity, skeletal muscle blood flow during exercise (functional hyperemia) is impaired. We have indirectly demonstrated that an altered arachidonic acid metabolism is responsible for the impaired functional vasodilation in the obese Zucker rat (OZR), a model of obesity. In this study, we tested the hypothesis that there is an impaired release of PGI2due to a nitration of PGI2synthase (PGIS), which is associated with a decreased prostanoid receptor expression. PGI2, PGE2, and thromboxane A2(TXA2) release were determined in vitro using ELISA under basal conditions and in response to arachidonic acid (AA) administration (50 μM). Immunofluorescence of PGI2and TXA2receptors (IP and TP, respectively) was determined in dispersed vascular smooth muscle cells (VSMCs). Nitration of tyrosine residues of the PGIS enzyme was determined using immunoprecipitation and Western blot analysis. Following AA administration, PGI2and PGE2release were attenuated in OZR compared with lean Zucker rats (LZR; controls). Basal and AA-induced TXA2release were not significantly different between groups. IP and TP immunofluorescence were not significantly different between OZR and LZR groups. OZR exhibited elevated nitration of tyrosine residues of PGIS compared with LZR. These results suggest that alterations in the PGI2pathway (attenuated PGI2synthesis), and not the TXA2pathway (normal TXA2synthesis/no change in TP receptor expression), underlie the attenuated functional hyperemia in the OZR.
Expression of rainbow trout glucose transporters GLUT1 and GLUT4 during in vitro muscle cell differentiation and regulation by insulin and IGF-I
Authors: Díaz Mònica , Vraskou Yoryia , Gutiérrez Joaquim , Planas Josep V.
Published: January 2009

Insulin is an important factor for the maintenance of glucose homeostasis, enhancing glucose uptake in its target tissues in a process that has been conserved between fish and mammals. In fish skeletal muscle cells, like in mammals, insulin promotes GLUT4 translocation to the plasma membrane and, consequently, glucose uptake, but its role regulating the expression of glucose transporters in vitro has not been demonstrated to date. Thus, we investigated the expression of GLUT4 and GLUT1 throughout skeletal muscle cell differentiation and their regulation by insulin and IGF-I using a primary culture of trout muscle cells. GLUT4 expression gradually increased during the muscle cell differentiation process, whereas GLUT1 expression remained fairly constant. Insulin and IGF-I similarly increased the mRNA levels of GLUT4 in myoblasts and myotubes. On the other hand, IGF-I appeared to be more potent than insulin in stimulating GLUT1 expression, particularly at the myoblast stage. Therefore, this work provides the first demonstration in nonmammalian vertebrates that insulin and IGF-I may act directly on trout muscle cells to regulate the expression of GLUT4 and GLUT1.
ATP-induced vasodilation and purinergic receptors in the human leg: roles of nitric oxide, prostaglandins, and adenosine
Authors: Mortensen Stefan P. , González-Alonso José , Bune Laurids T. , Saltin Bengt , Pilegaard Henriette , Hellsten Ylva
Published: January 2009

Plasma ATP is thought to contribute to the local regulation of skeletal muscle blood flow. Intravascular ATP infusion can induce profound limb muscle vasodilatation, but the purinergic receptors and downstream signals involved in this response remain unclear. This study investigated: 1) the role of nitric oxide (NO), prostaglandins, and adenosine as mediators of ATP-induced limb vasodilation and 2) the expression and distribution of purinergic P2receptors in human skeletal muscle. Systemic and leg hemodynamics were measured before and during 5–7 min of femoral intra-arterial infusion of ATP [0.45–2.45 μmol/min] in 19 healthy male subjects with and without coinfusion of NG-monomethyl-l-arginine (l-NMMA; NO formation inhibitor; 12.3 ± 0.3 (SE) mg/min), indomethacin (INDO; prostaglandin formation blocker; 613 ± 12 μg/min), and/or theophylline (adenosine receptor blocker; 400 ± 26 mg). During control conditions, ATP infusion increased leg blood flow (LBF) from baseline conditions by 1.82 ± 0.14 l/min. When ATP was coinfused with either l-NMMA, INDO, or l-NMMA + INDO combined, the increase in LBF was reduced by 14 ± 6, 15 ± 9, and 39 ± 8%, respectively (all P < 0.05), and was associated with a parallel lowering in leg vascular conductance and cardiac output and a compensatory increase in leg O2extraction. Infusion of theophylline did not alter the ATP-induced leg hyperemia or systemic variables. Real-time PCR analysis of the mRNA content from the vastus lateralis muscle of eight subjects showed the highest expression of P2Y2receptors of the 10 investigated P2receptor subtypes. Immunohistochemistry showed that P2Y2receptors were located in the endothelium of microvessels and smooth muscle cells, whereas P2X1receptors were located in the endothelium and the sacrolemma. Collectively, these results indicate that NO and prostaglandins, but not adenosine, play a role in ATP-induced vasodilation in human skeletal muscle. The expression and localization of the nucleotide selective P2Y2and P2X1receptors suggest that these receptors may mediate ATP-induced vasodilation in skeletal muscle.
Contribution of Commissural Projections to Bulbospinal Activation of Locomotion in the In Vitro Neonatal Rat Spinal Cord
Authors: Cowley Kristine C. , Zaporozhets Eugene , Joundi Raed A. , Schmidt Brian J.
Published: January 2009

Commissural projections are required for left-right coordination during locomotion. However, their role, if any, in rhythm production is unknown. This study uses the neonatal rat in vitro brain stem–spinal cord model to examine the rostrocaudal distribution of locomotor-related commissural projections and study whether commissural connections are needed for the generation of hindlimb rhythmic activity in response to electrical stimulation of the brain stem. Midsagittal lesions were made at a wide range of rostrocaudal levels. Locomotor-like activity persisted in some preparations despite midsagittal lesions extending from C1 to the mid-L1 level or from the conus medullaris to the T12/13 junction. In some preparations, midsagittal lesions throughout the entire spinal cord had no effect on locomotor-like activity if two or three contiguous segments remained intact. Those bridging segments had to include the T13 and/or L1 levels. These observations suggested that commissural projections in the thoracolumbar junction region were critical. However, locomotor-like activity was also elicited in preparations with limited midsagittal lesions focused on the thoracolumbar junction (T12 through L1 or L2 inclusive). In other experiments, locomotor-like activity was evoked by bath-applied 5-hydroxytryptamine (5-HT) and N-methyl-d-aspartate (NMDA). Appropriate side-to-side coordination was observed, even when only one segment remained bilaterally intact. Commissural projections traversing the thoracolumbar junction region were most effective. In combination, these results suggest that locomotor-related commissural projections are redundantly distributed along a bi-directional gradient that centers on the thoracolumbar junction. This commissural system not only provides a robust left-right coordinating mechanism but also supports locomotor rhythm generation in response to brain stem stimulation.
Physical Activity During Daily Life and Functional Decline in Peripheral Arterial Disease
Authors: Garg Parveen K. , Liu Kiang , Tian Lu , Guralnik Jack M. , Ferrucci Luigi , Criqui Michael H. , Tan Jin , McDermott Mary M.
Published: January 2009

Background—

Few modifiable behaviors have been identified that are associated with slower rates of functional decline in persons with lower-extremity peripheral arterial disease. We determined whether higher levels of physical activity during daily life are associated with less functional decline in persons with peripheral arterial disease.

Methods and Results—

The study population included 203 peripheral arterial disease participants who underwent vertical accelerometer–measured physical activity continuously over 7 days and were followed up annually for up to 4 years (mean, 33.6 months). Outcomes were average annual changes in 6-minute walk performance, usual-paced and fast-paced 4-m walking velocity, and the short performance physical battery. Analyses were adjusted for age, sex, race, comorbidities, body mass index, ankle brachial index, smoking, and walking exercise frequency. Higher baseline physical activity levels measured by a vertical accelerometer were associated with significantly less average annual decline in 6-minute walk performance (
P
for trend=0.010), fast-paced 4-m walking velocity (
P
for trend=0.002), and the short performance physical battery (
P
for trend=0.001). Compared with the lowest baseline quartile, those in the highest baseline quartile of physical activity had less annual decline in 6-minute walk performance (−50.82 versus −107.0 ft/y;
P
=0.019), fast-paced 4-m walking speed (−0.0034 versus −0.111 m · s
−1
· y
−1
;
P
=0.002), and the short performance physical battery (−0.074 versus −0.829;
P
=0.005).

Conclusions—

Higher physical activity levels during daily life are associated with less functional decline among people with peripheral arterial disease. These findings may be particularly important for the large number of peripheral arterial disease persons without access to supervised walking exercise programs.
Cardiovascular Death and Nonfatal Myocardial Infarction in Acute Coronary Syndrome Patients Receiving Coronary Stenting Are Predicted by Residual Platelet Reactivity to ADP Detected by a Point-of-Care Assay
Authors: Marcucci Rossella , Gori Anna Maria , Paniccia Rita , Giusti Betti , Valente Serafina , Giglioli Cristina , Buonamici Piergiovanni , Antoniucci David , Abbate Rosanna , Gensini Gian Franco
Published: January 2009

Background—

The clinical impact of platelet aggregation assessed by point-of-care assays is unknown. We sought to evaluate whether high residual platelet reactivity (RPR) to ADP during clopidogrel therapy, measured by a point-of-care assay, predicts adverse clinical events in acute coronary syndrome patients undergoing percutaneous coronary intervention.

Methods and Results—

We used the VerifyNow P2Y12 assay (Accumetrics Inc, San Diego, Calif) to determine RPR to ADP in 683 patients with acute coronary syndrome undergoing dual-antiplatelet therapy who underwent percutaneous coronary intervention with bare-metal or drug-eluting stent implantation. All patients received a single 600-mg clopidogrel loading dose followed by 75 mg of clopidogrel daily and 100 to 325 mg of aspirin daily. The end points of the study at follow-up of 12 months were cardiovascular death, nonfatal myocardial infarction (MI), and target-vessel revascularization. At a 12-month follow-up, we found 51 ischemic events (24 cardiovascular deaths [3.5%], 27 nonfatal MIs [3.9%]) and 40 target-vessel revascularizations (5.8%). By receiver operating characteristic curve (ROC) analysis, the optimal cutoff value in predicting 12-month cardiovascular death and nonfatal MI was P2Y12 reaction unit values ≥240. RPR, defined in the presence of P2Y12 reaction unit values above this cutoff, was found to be a significant and independent predictor of cardiovascular death and nonfatal MI in a model that adjusted for cardiovascular risk factors, renal failure, reduced left ventricular ejection fraction, multivessel disease, total stent length, bifurcation lesions, number of lesions treated, type of stent, and use of glycoprotein IIb/IIIa inhibitors (cardiovascular death: hazard ratio 2.55, 95% CI 1.08 to 6.07,
P
=0.034; nonfatal MI: hazard ratio 3.36, 95% CI 1.49 to 7.58,
P
=0.004). No significant association was found between high RPR and the risk of target-vessel revascularization.

Conclusions—

RPR to ADP with clopidogrel therapy, measured by the point-of-care assay VerifyNow P2Y12, is able to detect acute coronary syndrome patients at risk of 12-month cardiovascular death and nonfatal MI. The optimal cutoff value was identified as being 240 P2Y12 reaction units.
Impaired Baroreceptor Reflex Sensitivity in Acute Stroke Is Associated With Insular Involvement, But Not With Carotid Atherosclerosis
Authors: Sykora Marek , Diedler Jennifer , Rupp Andre , Turcani Peter , Steiner Thorsten
Published: January 2009

Background and Purpose—

Impaired baroreflex sensitivity (BRS) has been previously shown to be of prognostic value in patients with cardiovascular disease and stroke. Because baroreflex seems to be blunted by both carotid atherosclerosis and by lesions affecting central processing, controversy exists regarding the etiology of stroke-related baroreflex changes. The insula may play a central role in baroreflex modulation. The aim of the study was therefore to examine BRS in patients with acute stroke with regard to carotid atherosclerosis and insular involvement.

Methods—

We evaluated spontaneous BRS in 96 patients with acute stroke within 72 hours of ictus and 41 control subjects using a sequential crosscorrelation method.

Results—

Fifty-two patients with ischemic stroke and 44 patients with intracerebral hemorrhage, mean age 58.4 years, were included. With comparable carotid atherosclerosis profiles, patients with stroke had significantly lower BRS than control subjects (3.3 versus 5.3,
P
<0.001). Carotid atherosclerosis had no influence on variance of the BRS values in the acute stroke group. Patients with insular involvement had significantly lower BRS than patients with no insular involvement (2.55 versus 4.35,
P
=0.001) or control subjects (2.55 versus 5.3,
P
<0.001). Furthermore, patients with left insular involvement had significantly lower BRS than patients with right insular involvement (2.3 versus 3.5,
P
=0.049). There was no significant difference between patients with no insular lesions and control subjects (
P
=0.263).

Conclusions—

We demonstrated that baroreflex impairment in acute stroke is not associated with carotid atherosclerosis but with insular involvement. Both insulae seem to participate in processing the baroreceptor information with the left insula being more dominant.
Involvement of PTEN Promoter Methylation in Cerebral Cavernous Malformations
Authors: Zhu Yuan , Wloch Andreas , Wu Qun , Peters Christian , Pagenstecher Axel , Bertalanffy Helmut , Sure Ulrich
Published: January 2009

Background and Purpose—

Cerebral cavernous malformations (CCMs) are prevalent cerebral vascular lesions involving aberrant angiogenesis. However, the underlying mechanism is poorly understood. Phosphatase and tension homolog deleted on chromosome 10 (PTEN), a tumor suppressor, is frequently deficient in various pathologies due to mutation or epigenetic alterations. PTEN promoter hypermethylation is a major epigenetic silencing mechanism leading to activation of angiogenesis in tumors. The present study aimed to investigate whether PTEN promoter methylation was involved in CCMs.

Methods—

PTEN promoter methylation was detected in surgical specimens of CCMs (n=69) by methylation-specific polymerase chain reaction. The methylation status was correlated to the clinical manifestations and to PTEN expression, which was analyzed by both Western blot and immunohistochemistry. To investigate the endothelial proliferation and the potential signaling pathways affected by PTEN methylation, proliferating cell nuclear antigen as well as phosphor-Akt and phosphor-Erk1,2 were detected by immunofluorescence and Western blot, respectively, in CCM specimens.

Results—

Methylation-specific polymerase chain reaction revealed PTEN promoter methylation in 15.9% CCMs. Strikingly, 5 of 6 familial CCMs showed PTEN promoter methylation (83.3%), which was significantly higher than in sporadic cases (9.4%;
P
<0.001). In addition, PTEN promoter methylation appeared more frequently in multiple CCMs, including familial cases (46.7%), than that in single-lesioned CCMs (11.8%;
P
<0.05). Immunostaining and Western blot revealed a more significant PTEN downregulation in PTEN-methylated CCMs in comparison to PTEN-unmethylated CCMs. Reduced PTEN expression was inversely correlated to the expression of proliferating cell nuclear antigen and to the activation of Erk1,2, but not of Akt.

Conclusion—

We reported here for the first time the involvement of PTEN promoter methylation in CCMs, particularly in familial CCMs, suggesting this epigenetic alteration as a potential pathomechanism of CCMs. The identification of Erk1,2 as triggered signaling in the lesions may be valuable for the development of effective therapy for this disease.
Interhemispheric Distribution of Alzheimer Disease and Vascular Pathology in Brain Aging
Authors: Giannakopoulos Panteleimon , Kövari Enikö , Herrmann François R. , Hof Patrick R. , Bouras Constantin
Published: January 2009

Background and Purpose—

Most of the neuropathological studies in brain aging were based on the assumption of a symmetrical right–left hemisphere distribution of both Alzheimer disease and vascular pathology. To explore the impact of asymmetrical lesion formation on cognition, we performed a clinicopathological analysis of 153 cases with mixed pathology except macroinfarcts.

Methods—

Cognitive status was assessed prospectively using the Clinical Dementia Rating scale; neuropathological evaluation included assessment of Braak neurofibrillary tangle and Aß deposition staging, microvascular pathology, and lacunes. The right–left hemisphere differences in neuropathological scores were evaluated using the Wilcoxon signed rank test. The relationship between the interhemispheric distribution of lesions and Clinical Dementia Rating scores was assessed using ordered logistic regression.

Results—

Unlike Braak neurofibrillary tangle and Aß deposition staging, vascular scores were significantly higher in the left hemisphere for all Clinical Dementia Rating scores. A negative relationship was found between Braak neurofibrillary tangle, but not Aß staging, and vascular scores in cases with moderate to severe dementia. In both hemispheres, Braak neurofibrillary tangle staging was the main determinant of cognitive decline followed by vascular scores and Aß deposition staging. The concomitant predominance of Alzheimer disease and vascular pathology in the right hemisphere was associated with significantly higher Clinical Dementia Rating scores.

Conclusions—

Our data show that the cognitive impact of Alzheimer disease and vascular lesions in mixed cases may be assessed unilaterally without major information loss. However, interhemispheric differences and, in particular, increased vascular and Alzheimer disease burden in the right hemisphere may increase the risk for dementia in this group.
Lack of Impact of Paramedic Training and Use of the Cincinnati Prehospital Stroke Scale on Stroke Patient Identification and On-Scene Time
Authors: Frendl Daniel M. , Strauss David G. , Underhill B. Kevin , Goldstein Larry B.
Published: January 2009

Background and Purpose—

The Cincinnati Prehospital Stroke Scale (CPSS) is recommended for emergency medical services use in identifying patients with stroke. Data evaluating its performance in the field are limited. We assessed the impact of training and use of the CPSS on the accuracy of paramedics’ stroke patient identification and on-scene time.

Methods—

A 1-hour interactive educational presentation on the use of the CPSS was conducted for paramedics transporting patients to an academic medical center. Patients with stroke/transient ischemic attack (TIA) were identified retrospectively from paramedic records and were compared with the hospital’s prospective stroke registry for the year before and after the training.

Results—

There were 154 patients with suspected stroke/transient ischemic attack identified (56% women, 53% white, 44% black, mean age 67±16 years). There was no difference in paramedics’ use of the CPSS (37.5% versus 23.8%,
P
=0.123) or accuracy of stroke/TIA patient identification (40.5% versus 38.9%,
P
=0.859) before and after training. Of responsive patients identified by paramedics as having a stroke/TIA, 57% had an abnormality in at least one CPSS item with no effect on on-scene time (17±6 minutes with a normal versus 18±6 minutes with an abnormal CPSS,
P
=0.492). Those with a final diagnosis of stroke/TIA (n=61, 40%) more frequently had at least one abnormal CPSS item (70% versus 30%,
P
=0.008, sensitivity 0.71, specificity 0.52) with 49% of patients with an abnormality having a discharge diagnosis of stroke/TIA.

Conclusions—

Paramedic training in the CPSS, or its use, had no impact on the accuracy of their identification of patients with stroke/TIA or on-scene time.
Ketoconazole Increases Fingolimod Blood Levels in a Drug Interaction via CYP4F2 Inhibition
Authors: Kovarik John M. , Dole Kiran , Riviere Gilles‐Jacques , Pommier Francoise , Maton Steve , Jin Yi , Lasseter Kenneth C. , Schmouder Robert L.
Published: January 2009

The sphingosine‐1‐phosphate receptor modulator fingolimod is predominantly hydroxylated by cytochrome CYP4F2. In vitro experiments showed that ketoconazole significantly inhibited the oxidative metabolism of fingolimod by human liver microsomes and by recombinant CYP4F2. The authors used ketoconazole as a putative CYP4F2 inhibitor to quantify its influence on fingolimod pharmacokinetics in healthy subjects. In a 2‐period, single‐sequence, crossover study, 22 healthy subjects received a single 5‐mg dose of fingolimod in period 1. In period 2, subjects received ketoconazole 200 mg twice daily for 9 days and a single 5‐mg dose of fingolimod coadministered on the 4th day of ketoconazole treatment. Ketoconazole did not affect fingolimod tmax or half‐life, but there was a weak average increase in Cmax of 1.22‐fold (90% confidence interval, 1.15–1.30). The AUC over the 5 days of ketoconazole coadministration increased 1.40‐fold (1.31–1.50), and the full AUC to infinity increased 1.71‐fold (1.53–1.91). The AUC of the active metabolite fingolimod‐phosphate was increased to a similar extent by 1.67‐fold (1.50–1.85). Ketoconazole predose plasma levels were not altered by fingolimod. The magnitude of this interaction suggests that a proactive dose reduction of fingolimod is not necessary when adding ketoconazole to a fingolimod regimen. The clinician, however, should be aware of this interaction and bear in mind the possibility of a fingolimod dose reduction based on clinical monitoring.
Structural Damage and Chemical Contaminants on Reprocessed Arthroscopic Shaver Blades
Authors: Kobayashi Masahiko , Nakagawa Yasuaki , Okamoto Yukihiro , Nakamura Shinichiro , Nakamura Takashi
Published: January 2009

Background

In response to socioeconomic pressure to cut budgets in medicine, single-use surgical instruments are often reprocessed despite potential biological hazard.

Purpose

To evaluate the quality and contaminants of reprocessed shaver blades.

Hypothesis

Reprocessed shaver blades have mechanical damage and chemical contamination.

Study Design

Controlled laboratory study.

Methods

Seven blades and 3 abraders were reprocessed 1 time or 3 times and then were assessed. In the first part of the study, structural damage on the blades after 3 reprocessings was compared to that after 1 reprocessing using optical microscopy. In the second part, surface damage was observed using optical microscopy and scanning electron microscopy; elemental and chemical analyses of contaminants found by the microscopy were performed using scanning electron microscopy/energy dispersive x-ray spectroscopy, scanning Auger microscopy, and Fourier transform infrared spectroscopy.

Results

Optical microscopic examination revealed abrasion on the surface of the inner blade and cracks on the inner tube after 1 reprocessing. These changes were more evident after 3 reprocessings. Scanning electron microscopy/energy dispersive x-ray spectroscopy of the inner cutter of the blade reprocessed once showed contaminants containing calcium, carbon, oxygen, and silicon, and Fourier transform infrared spectroscopy demonstrated biological protein consisting mainly of collagen, some type of salts, and polycarbonate used in plastic molding. Scanning electron microscopy/energy dispersive x-ray spectroscopy of the inner cutter of the reprocessed abrader revealed contaminants containing carbon, calcium, phosphorous, and oxygen, and Fourier transform infrared spectroscopy showed H2O, hydroxyapatite, and hydroxyl proteins. Scanning Auger microscopy showed that the tin-nickel plating on the moving blade and abrader was missing in some locations.

Conclusion

This is the first study to evaluate both mechanical damage and chemical contaminants containing collagen, hydroxyapatite, and salts on the reprocessed arthroscopic shaver blades.

Clinical Relevance

Surgeons should keep in mind that mechanical damage and chemical contamination are found on reprocessed arthroscopic blades.
Intramedullary Nailing of Clavicular Midshaft Fractures with the Titanium Elastic Nail
Authors: Frigg Arno , Rillmann Paavo , Perren Thomas , Gerber Martin , Ryf Christian
Published: January 2009

Background

Intramedullary nailing of clavicular midshaft fractures using the titanium elastic nail has been described as a technically easy, minimally invasive operation with few complications and an early return to competitive sports.

Hypothesis

The results reported thus far have been positive. The titanium elastic nail is associated with multiple intraoperative and postoperative problems.

Study Design

Case series; Level of evidence, 4.

Methods

From April 2004 to March 2007, 34 patients at our institution were treated with intramedullary nailing. A standard titanium elastic nail was used in 19 cases and a titanium elastic nail with an end cap in 15 cases. The titanium elastic nail was inserted and advanced under fluoroscopic control. A short incision at the fracture site was made for open reduction if needed. Postoperatively, free range of motion was allowed.

Results

In 62% of patients, open reduction was necessary independent of fracture type, flattening of the titanium elastic nail, or transverse fragments. Operating time was 44 minutes (range, 10—105 minutes) and fluoroscopy time 9 minutes (range, 2—25 minutes). In 70% of patients, problems or complications occurred (7 medial perforations, 7 lateral penetrations, 1 titanium elastic nail breakage, 1 titanium elastic nail dislocation, 7 hardware irritations). The reoperation rate was 36%. Medial migration and pain were significantly reduced by using an end cap.

Conclusion

Intramedullary nailing of clavicular midshaft fractures using the titanium elastic nail is a technically demanding operation with various complications in the postoperative phase. This study might explain why the implant has not yet achieved widespread application, despite the fact that other authors have reported good results. Amending the operative technique and postoperative treatment might improve the outcome in the future.
The Influence of Item Response Indecision on the Self-Directed Search
Authors: Sampson James P. , Shy Jonathan D. , Hartley Sarah Lucas , Reardon Robert C. , Peterson Gary W.
Published: January 2009

Students (N = 247) responded to Self-Directed Search (SDS) per the standard response format and were also instructed to record a question mark (?) for items about which they were uncertain (item response indecision [IRI]). The initial responses of the 114 participants with a (?) were then reversed and a second SDS summary code was obtained and compared to the first. SDS codes did not change for 82% of IRI participants, but changes occurred in the first and second letters for 6%, the second and third letters for 4%, and the third letter for 9%. There were significant relationships between the extent of IRI and dysfunctional career thoughts, and IRI was inversely related to interest structure, for example, SDS consistency, congruence, and differentiation.
Mentoring and Protégé Narcissistic Entitlement
Authors: Allen Tammy D. , Johnson Hazel-Anne M. , Xian Xu  , Biga Andrew , Rodopman Ozgun B. , Ottinot Raymond C.
Published: January 2009

The relationship between protégé narcissistic entitlement and protégé mentoring outcomes is examined among a total sample of 132 protégés employed in a variety of settings. Narcissistic entitlement (NE) refers to a dispositional variable that reflects preoccupation with the expectation of special and preferential treatment from others. Results indicate that protégés with greater NE report relationships of shorter duration, less career mentoring support, lower relationship quality, and greater negative mentoring experiences than do protégés with lesser NE. Additionally, protégé NE moderated the relationship between mentor commitment and relationship quality such that the relationship was stronger for protégés higher in NE than for protégés lower in NE. NE was not related to whether participants had experience as a protégé. Implications include the need for expanded education regarding mentoring relationships that take into account the role the individual plays in the relationship.
Diffusely Infiltrating Endometrial Carcinomas With No Stromal Response: Report of a Series, Including Cases With Cervical and Ovarian Involvement and Emphasis on the Potential for Misdiagnosis
Authors: Kalyanasundaram K. , Ganesan R. , Perunovic B. , McCluggage W.G.
Published: January 2009

Endometrial carcinomas, particularly of endometrioid type, can invade the myometrium or cervix without eliciting a stromal desmoplastic or inflammatory response and have been referred to as diffusely infiltrating endometrial carcinomas. This study describes a series of 14 endometrial carcinomas infiltrating as single “naked” glands without a stromal response. The neoplasms consisted of 12 endometrioid carcinomas, 1 mixed endometrioid and clear cell carcinoma, and 1 serous carcinoma. In all cases, there was myometrial invasion without stromal response. Seven cases exhibited cervical stromal involvement and in 2 there was involvement of both ovaries in a similar pattern. Several of the cases were seen in consultation and the pattern of infiltration raised a number of differential diagnoses, both benign and malignant, depending on the site of tumor involvement, including adenomyosis, adenomyoma, primary endocervical glandular lesions, cervical mesonephric remnants, endometriosis or tuboendometrioid metaplasia, and ovarian cortical inclusion cysts. Although this pattern of invasion has been reported previously, it continues to present diagnostic difficulties.
Gastrointestinal Complications After 3 Months of Dual Antiplatelet Therapy for Drug-eluting Stents as Assessed by Wireless Capsule Endoscopy
Authors: Seddighzadeh Ali , Wolf Anne T. , Parasuraman Sudha , Shetty Ranjith , Vallurupalli Neelima , Reddy Sarathchandra , Goldhaber Samuel Z.
Published: January 2009

Little is known about the frequency of symptomatic and asymptomatic gastrointestinal complications of dual antiplatelet therapy. We recruited 30 patients between 18 and 80 years who were started on aspirin and clopidogrel following percutaneous coronary intervention with drug-eluting stents. We hypothesized that the 3 months of dual antiplatelet therapy would be associated with frequent upper gastrointestinal endoscopic abnormalities. Patients were followed with weekly phone calls to inquire about the new gastrointestinal symptoms and after a minimum of 80 days, their upper gastrointestinal mucosa was visualized with PillCam ESO® wireless capsule endoscopy. 18 (90%) of the 20 successful wireless capsule endoscopies revealed at least 1 type of gastrointestinal mucosal lesion. Gastric erosions (n = 14, 70%) were the most common abnormality. We believe this is the first noninvasive endoscopic study of gastrointestinal complications of dual antiplatelet therapy in patients who undergo percutaneous coronary intervention with drug-eluting stents. Future studies should expand on our observations to determine whether prophylaxis with proton pump inhibitors is warranted.
Perinatal HIV transmission and the cost-effectiveness of screening at 14 weeks gestation, at the onset of labour and the rapid testing of infants
Authors: Udeh Belinda , Udeh Chiedozie , Graves Nicholas
Published: January 2009

Background

Preventing HIV transmission is a worldwide public health issue. Vertical transmission of HIV from a mother can be prevented with diagnosis and treatment, but screening incurs cost. The U.S. Virgin Islands follows the mainland policy on antenatal screening for HIV even though HIV prevalence is higher and rates of antenatal care are lower. This leads to many cases of vertically transmitted HIV. A better policy is required for the U.S. Virgin Islands.

Methods

The objective of this research was to estimate the cost-effectiveness of relevant HIV screening strategies for the antenatal population in the U.S. Virgin Islands. An economic model was used to evaluate the incremental costs and incremental health benefits of nine different combinations of perinatal HIV screening strategies as compared to existing practice from a societal perspective. Three opportunities for screening were considered in isolation and in combination: by 14 weeks gestation, at the onset of labor, or of the infant after birth. The main outcome measure was the cost per life year gained (LYG).

Results

Results indicate that all strategies would produce benefits and save costs. Universal screening by 14 weeks gestation and screening the infant after birth is the recommended strategy, with cost savings of $1,122,787 and health benefits of 310 LYG. Limitations include the limited research on the variations in screening acceptance of screening based on specimen sample, race and economic status. The benefits of screening after 14 weeks gestation but before the onset of labor were also not addressed.

Conclusion

This study highlights the benefits of offering screening at different opportunities and repeat screening and raises the question of generalizing these results to other countries with similar characteristics.
"There's nothing I can't do – I just put my mind to anything and I can do it": a qualitative analysis of how children with chronic disease and their parents account for and manage physical activity
Authors: Fereday Jennifer , MacDougall Colin , Spizzo Marianne , Darbyshire Philip , Schiller Wendy
Published: January 2009

Background

This paper reports the findings of a South Australian qualitative, exploratory study of children and young people living with a chronic disease, and their perceptions and experiences of physical activity. The perceptions and experiences of their parents were also explored. The chronic diseases were type 1 diabetes, asthma and cystic fibrosis.

Methods

Multiple qualitative data collection techniques were used to elicit the children and young people's perspectives and experiences of physical activity, including focus groups, maps, photos and 'traffic light posters'. The children's parents were interviewed separately to ascertain their views of their child's participation in physical activities.

Results

Children and young people described their active participation in a wide variety of physical activities including organised sports and play, but made very little mention of any negative influence or impact due to their disease. Their parents' stories described the diligent background planning and management undertaken to enable their child to participate in a wide range of physical activities.

Conclusion

The results of this study suggest that for these children and young people, having a chronic disease was not perceived as a barrier to participation in organised sport and recreational activities. They were physically active and perceived themselves to be no different from their peers. Their positive beliefs were shared by their parents and the level of participation described was enabled by the high level of parental support and background planning involved in managing their child's health care needs.
Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients
Authors: Levandovsky Mark , Harvey Danielle , Lara Primo , Wun Ted
Published: January 2009

Background

Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures.

Results

Overall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions.

Conclusion

Plasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder.
A forensic aspect of age characteristics of dentine using transversal microradiography: a case report
Authors: Vasiliadis Leonidas , Stavrianos Christos , Kafas Panagiotis
Published: January 2009

Background

Translucency of dentine is the result of occlusion of the corresponding dentinal tubules by a mineral substance which has a refractive index similar to that of the rest of the dentine.

Case presentation

This case report describes the microradiographic features of an upper cadaveric canine. Transverse microradiograph is one of the methods assessing apical dentine translucency for various dental and medical reasons.

Conclusion

Estimation of age using teeth structures may be of primary value in forensic dentistry, especially when soft tissues are severely destructed.
Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells
Authors: Attanasio Catia , Reymond Alexandre , Humbert Richard , Lyle Robert , Kuehn Michael S , Neph Shane , Sabo Peter J , Goldy Jeff , Weaver Molly , Haydock Andrew , Lee Kristin , Dorschner Michael , Dermitzakis Emmanouil T , Antonarakis Stylianos E , Stamatoyannopoulos John A
Published: January 2009

Background

Conserved non-coding sequences in the human genome are approximately tenfold more abundant than known genes, and have been hypothesized to mark the locations of cis-regulatory elements. However, the global contribution of conserved non-coding sequences to the transcriptional regulation of human genes is currently unknown. Deeply conserved elements shared between humans and teleost fish predominantly flank genes active during morphogenesis and are enriched for positive transcriptional regulatory elements. However, such deeply conserved elements account for <1% of the conserved non-coding sequences in the human genome, which are predominantly mammalian.

Results

We explored the regulatory potential of a large sample of these 'common' conserved non-coding sequences using a variety of classic assays, including chromatin remodeling, and enhancer/repressor and promoter activity. When tested across diverse human model cell types, we find that the fraction of experimentally active conserved non-coding sequences within any given cell type is low (approximately 5%), and that this proportion increases only modestly when considered collectively across cell types.

Conclusions

The results suggest that classic assays of cis-regulatory potential are unlikely to expose the functional potential of the substantial majority of mammalian conserved non-coding sequences in the human genome.