bluuebunny/crossref_metadata_2025 huggingface dataset:
High Efficacy of β-Blockers in Long-QT Syndrome Type 1
Authors: Vincent G. Michael , Schwartz Peter J. , Denjoy Isabelle , Swan Heikki , Bithell Candice , Spazzolini Carla , Crotti Lia , Piippo Kirsi , Lupoglazoff Jean-Marc , Villain Elizabeth , Priori Silvia G. , Napolitano Carlo , Zhang Li
Published: January 2009

Background—

β-Blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite β-blocker therapy have not been ascertained.

Methods and Results—

This was a retrospective study of the details surrounding cardiac events in 216 genotyped long-QT syndrome type 1 patients treated with β-blocker and followed up for a median time of 10 years. Before β-blocker, cardiac events occurred in 157 patients (73%) at a median age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%; odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3;
P
<0.001). After β-blocker, 75% were asymptomatic, and cardiac events were significantly reduced (
P
<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1). Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The risk for CA/sudden death in compliant patients not taking QT-prolonging drugs was dramatically less compared with noncompliant patients on QT-prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22;
P
=0.001). None of the 26 patients with CA before β-blocker had CA/sudden death on β-blockers.

Conclusions—

β-Blockers are extremely effective in long-QT syndrome type 1 and should be administered at diagnosis and ideally before the preteen years. β-Blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening “β-blocker failures.” β-Blockers are appropriate therapy for asymptomatic patients and those who have never had a CA or β-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.
Pressure Overload–Induced Alterations in Fibrillar Collagen Content and Myocardial Diastolic Function
Authors: Bradshaw Amy D. , Baicu Catalin F. , Rentz Tyler J. , Van Laer An O. , Boggs Janet , Lacy John M. , Zile Michael R.
Published: January 2009

Background—

Chronic pressure overload causes myocardial hypertrophy, increased fibrillar collagen content, and abnormal diastolic function. We hypothesized that one determinant of these pressure overload–induced changes is the extracellular processing of newly synthesized procollagen into mature collagen fibrils. We further hypothesized that secreted protein acidic and rich in cysteine (SPARC) plays a key role in post–synthetic procollagen processing in normal and pressure-overloaded myocardium.

Methods and Results—

To determine whether pressure overload–induced changes in collagen content and diastolic function are affected by the absence of SPARC, age-matched wild-type (WT) and SPARC-null mice underwent either transverse aortic constriction (TAC) for 4 weeks or served as nonoperated controls. Left ventricular (LV) collagen content was measured histologically by collagen volume fraction, collagen composition was measured by hydroxyproline assay as soluble collagen (1 mol/L NaCl extractable) versus insoluble collagen (mature cross-linked collagen), and collagen morphological structure was examined by scanning electron microscopy. SPARC expression was measured by immunoblot. LV, myocardial, and cardiomyocyte structure and function were assessed by echocardiographic, papillary muscle, and isolated cardiomyocyte studies. In WT mice, TAC increased LV mass, SPARC expression, myocardial diastolic stiffness, fibrillar collagen content, and soluble and insoluble collagen. In SPARC-null mice, TAC increased LV mass to an extent similar to WT mice. In addition, in SPARC-null mice, TAC increased fibrillar collagen content, albeit significantly less than that seen in WT TAC mice. Furthermore, the proportion of LV collagen that was insoluble was less in the SPARC-null TAC mice (86±2%) than in WT TAC mice (99±2%,
P
<0.05), and the proportion of collagen that was soluble was greater in the SPARC-null TAC mice (14±2%) than in WT TAC mice (1±2%,
P
<0.05) As a result, myocardial diastolic stiffness was lower in SPARC-null TAC mice (0.075±0.005) than in WT TAC mice (0.045±0.005,
P
<0.05).

Conclusions—

The absence of SPARC reduced pressure overload–induced alterations in extracellular matrix fibrillar collagen and diastolic function. These data support the hypothesis that SPARC plays a key role in post–synthetic procollagen processing and the development of mature cross-linked collagen fibrils in normal and pressure-overloaded myocardium.
Multipotent Mesenchymal Stem Cells Acquire a Lymphendothelial Phenotype and Enhance Lymphatic Regeneration In Vivo
Authors: Conrad Claudius , Niess Hanno , Huss Ralf , Huber Stephan , von Luettichau Irene , Nelson Peter J. , Ott Harald C. , Jauch Karl-Walter , Bruns Christiane J.
Published: January 2009

Background—

The importance and therapeutic value of stem cells in lymphangiogenesis are poorly understood. We evaluated the potential of human and murine mesenchymal stem cells (MSCs) to acquire a lymphatic phenotype in vitro and to enhance lymphatic regeneration in vivo.

Methods and Results—

We assessed the lymphendothelial differentiation of human and murine MSCs after induction with supernatant derived from human dermal microvascular endothelial cells, isolated lymphatic endothelial cells, and purified vascular endothelial growth factor (VEGF)-C in vitro. We used human or murine progenitor MSC lines and then characterized the lymphatic phenotype by morphology, migratory capacity, and the expression of lymphatic markers such as Prox-1, podoplanin, Lyve-1, VEGF receptor-2, and VEGF receptor-3. Using a murine lymphatic edema model, we assessed the potential of these cells to form a functional lymphatic vasculature in vivo after injection of syngeneic MSCs. Incubation with supernatant from lymphatic endothelial cells induced an endothelium-like morphology and the expression of lymphendothelial markers in both human and murine MSCs in vitro. MSCs showed migratory activity along a VEGF-C gradient, which was enhanced by VEGF-C conditioning. In vivo, the local application of MSCs resulted in a significant decrease in edema formation (−20.1%;
P
<0.01 versus untreated tails) after 3 weekly cell injections and restored the drainage of intradermally injected methylene blue after 7 weekly injections.

Conclusions—

MSCs were capable of expressing a lymphatic phenotype when exposed to lymph-inductive media and purified VEGF-C. Migratory activity toward VEGF-C in vitro suggests homing capability in vivo. Restoration of lymphatic drainage after injection of MSCs in a lymphedema model indicates that MSCs play a role in lymphatic regeneration. The potential clinical application of MSC in wound healing and reduction of lymphatic edema warrants further research.
Pulmonary Vascular Reactivity and Prognosis in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Skoro-Sajer Nika , Hack Niklas , Sadushi-Koliçi Roela , Bonderman Diana , Jakowitsch Johannes , Klepetko Walter , Hoda Mir Ali Reza , Kneussl Meinhard P. , Fedullo Peter , Lang Irene M.
Published: January 2009

Background—

Surgical pulmonary endarterectomy is the preferred treatment for chronic thromboembolic pulmonary hypertension. Persistent pulmonary hypertension after pulmonary endarterectomy has been recognized as a major determinant of poor outcome. We tested whether acute vasoreactivity identifies chronic thromboembolic pulmonary hypertension patients prone to develop persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and whether the degree of acute vasoreactivity affects survival or freedom from lung transplantation.

Methods and Results—

Right-sided heart catheterization at baseline and after inhalation of 40 ppm nitric oxide for 20 minutes was performed in 103 patients (56.3±15.3 years old, 53 women). Reductions in mean pulmonary arterial pressure (ΔmPAP; −8.8±12.6%;
P
<0.0001) and pulmonary vascular resistance (−16.1±18.1%;
P
<0.0001) and an increase in mixed venous saturation during inhaled nitric oxide (9.1±11.6%;
P
<0.0001) were observed. Sixty-two patients underwent pulmonary endarterectomy after a median of 49 days (25th and 75th percentiles: 24 and 123 days). Operated patients were followed up for a median of 70.9 months (25th and 75th percentiles: 14 and 97 months). Change in mPAP during inhaled NO was identified as a predictor of persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. Patients experiencing a reduction in mPAP >10.4% with nitric oxide inhalation had a better postoperative outcome. A significant correlation was found between ΔmPAP and immediate postoperative pulmonary vascular resistance (
r
=0.5,
P
<0.0001).

Conclusions—

A total of 80 (77.7%) of 103 patients demonstrated acute pulmonary vascular reactivity of some degree. A decrease in mPAP >10.4% under inhaled nitric oxide is a predictor of long-term survival and freedom from lung transplantation in adult patients with chronic thromboembolic pulmonary hypertension who are undergoing pulmonary endarterectomy.
Derivation and Validation of a Preoperative Prediction Rule for Delirium After Cardiac Surgery
Authors: Rudolph James L. , Jones Richard N. , Levkoff Sue E. , Rockett Christopher , Inouye Sharon K. , Sellke Frank W. , Khuri Shukri F. , Lipsitz Lewis A. , Ramlawi Basel , Levitsky Sidney , Marcantonio Edward R.
Published: January 2009

Background—

Delirium is a common outcome after cardiac surgery. Delirium prediction rules identify patients at risk for delirium who may benefit from targeted prevention strategies, early identification, and treatment of underlying causes. The purpose of the present prospective study was to develop a prediction rule for delirium in a cardiac surgery cohort and to validate it in an independent cohort.

Methods and Results—

Prospectively, cardiac surgery patients ≥60 years of age were enrolled in a derivation sample (n=122) and then a validation sample (n=109). Beginning on the second postoperative day, patients underwent a standardized daily delirium assessment, and delirium was diagnosed according to the confusion assessment method. Delirium occurred in 63 (52%) of the derivation cohort patients. Multivariable analysis identified 4 variables independently associated with delirium: prior stroke or transient ischemic attack, Mini Mental State Examination score, abnormal serum albumin, and the Geriatric Depression Scale. Points were assigned to each variable: Mini Mental State Examination ≤23 received 2 points, and Mini Mental State Examination score of 24 to 27 received 1 point; Geriatric Depression Scale >4, prior stroke/transient ischemic attack, and abnormal albumin received 1 point each. In the derivation sample, the cumulative incidence of delirium for point levels of 0, 1, 2, and ≥3 was 19%, 47%, 63%, and 86%, respectively (C statistic, 0.74). The corresponding incidence of delirium in the validation sample was 18%, 43%, 60%, and 87%, respectively (C statistic, 0.75).

Conclusions—

Delirium occurs frequently after cardiac surgery. Using 4 preoperative characteristics, clinicians can determine cardiac surgery patients’ risk for delirium. Patients at higher delirium risk could be candidates for close postoperative monitoring and interventions to prevent delirium.
Mechanisms of Aortic and Cardiac Dysfunction in Uremic Mice With Aortic Calcification
Authors: Maizel Julien , Six Isabelle , Slama Michel , Tribouilloy Christophe , Sevestre Henry , Poirot Sabrina , Giummelly Philippe , Atkinson Jeffrey , Choukroun Gabriel , Andrejak Michel , Kamel Said , Mazière Jean Claude , Massy Ziad A.
Published: January 2009

Background—

Chronic renal failure (CRF) is associated with cardiac dysfunction and increased aortic stiffness. The mechanisms involved are not clearly understood. We examined changes over time in cardiac and aortic function in a murine CRF model.

Methods and Results—

Eight-week-old mice were randomly assigned to 1 of 4 groups: wild-type non-CRF, wild-type CRF, apolipoprotein E knockout non-CRF, and apolipoprotein E knockout CRF. Echocardiography was performed and blood samples were taken at baseline and after 6 and 10 weeks of CRF. Vascular reactivity and adhesion molecule expression were studied after 6 and 10 weeks of CRF. Left ventricular hypertrophy, altered left ventricular relaxation, and increased aortic stiffness were observed after 6 weeks of CRF and persisted after 10 weeks. The 4 groups of mice did not significantly differ in terms of arterial blood pressure and aortic structure. The degree of vascular calcification and serum total cholesterol concentration were higher in the CRF groups than in the non-CRF groups. These changes, however, could not explain the cardiac and vascular differences seen in the 2 CRF groups. In contrast, alterations in vascular reactivity, the upregulation of adhesion molecule expression, and CRF status were significantly associated with these changes.

Conclusions—

In a mouse model of CRF, left ventricular hypertrophy, cardiac diastolic dysfunction, and increased aortic stiffness were not related to structural changes in the aorta (including aortic calcification) or high serum cholesterol levels. However, cardiac and aortic abnormalities were associated with the extent of subendothelial dysfunction and the severity of CRF.
Single Versus Combined Blood Pressure Components and Risk for Cardiovascular Disease
Authors: Franklin Stanley S. , Lopez Victor A. , Wong Nathan D. , Mitchell Gary F. , Larson Martin G. , Vasan Ramachandran S. , Levy Daniel
Published: January 2009

Background—

The utility of single versus combined blood pressure (BP) components in predicting cardiovascular disease (CVD) events is not established. We compared systolic BP (SBP) and diastolic BP (DBP) versus pulse pressure (PP) and mean arterial pressure (MAP) combined and each of these 4 BP components alone in predicting CVD events.

Methods and Results—

In participants in the original (n=4760) and offspring (n=4897) Framingham Heart Study who were free of CVD events and BP-lowering therapy, 1439 CVD events occurred over serial 4-year intervals from 1952 to 2001. In pooled logistic regression with the use of BP categories, combining SBP with DBP and PP with MAP improved model fit compared with individual BP components (
P
<0.05 to
P
<0.0001). Significant interactions were noted between SBP and DBP (
P
=0.02) and between PP and MAP (
P
=0.01) in their respective multivariable models. Models with continuous variables for SBP+DBP and PP+MAP proved identical in predicting CVD events (Akaike Information Criteria=10 625 for both). Addition of a quadratic DBP
2
term to DBP and SBP further improved fit (
P
=0.0016).

Conclusions—

Combining PP with MAP and SBP with DBP produced models that were superior to single BP components for predicting CVD, and the extent of CVD risk varied with the level of each BP component. The combination of PP+MAP (unlike SBP+DBP) has a monotonic relation with risk and may provide greater insight into hemodynamics of altered arterial stiffness versus impaired peripheral resistance but is not superior to SBP+DBP in predicting CVD events.
Disruption of Striated Preferentially Expressed Gene Locus Leads to Dilated Cardiomyopathy in Mice
Authors: Liu Xiaoli , Ramjiganesh Tripurasundari , Chen Yen-Hsu , Chung Su Wol , Hall Sean R. , Schissel Scott L. , Padera Robert F. , Liao Ronglih , Ackerman Kate G. , Kajstura Jan , Leri Annarosa , Anversa Piero , Yet Shaw-Fang , Layne Matthew D. , Perrella Mark A.
Published: January 2009

Background—

The striated preferentially expressed gene (Speg) generates 4 different isoforms through alternative promoter use and tissue-specific splicing. Depending on the cell type, Speg isoforms may serve as markers of striated or smooth muscle differentiation.

Methods and Results—

To elucidate function of Speg gene isoforms, we disrupted the Speg gene locus in mice by replacing common exons 8, 9, and 10 with a lacZ gene. β-Galactosidase activity was detected in cardiomyocytes of the developing heart starting at day 11.5 days post coitum (dpc). β-Galactosidase activity in other cell types, including vascular smooth muscle cells, did not begin until 18.5 dpc. In the developing heart, protein expression of only Spegα and Spegβ isoforms was present in cardiomyocytes. Homozygous Speg mutant hearts began to enlarge by 16.5 dpc, and by 18.5 dpc, they demonstrated dilation of right and left atria and ventricles. These cardiac abnormalities in the absence of Speg were associated with a cellular hypertrophic response, myofibril degeneration, and a marked decrease in cardiac function. Moreover, Speg mutant mice exhibited significant neonatal mortality, with increased death occurring by 2 days after birth.

Conclusions—

These findings demonstrate that mutation of the Speg locus leads to cardiac dysfunction and a phenotype consistent with a dilated cardiomyopathy.
The Swan-Ganz Catheters: Past, Present, and Future
Authors: Chatterjee Kanu
Published: January 2009

The Swan-Ganz balloon flotation catheter was introduced in 1970. It can be placed at the bedside within a few minutes even in critically ill patients. Although placement of these catheters is not difficult, some training and experience are required to avoid complications and for proper interpretation of the hemodynamic data that can be obtained by pulmonary artery catheterization. Because of the many advantages of balloon flotation catheters compared with conventional catheters, they have been used without a proper indication and frequently overused in critical care units, resulting in many complications, including mortality. The prospective randomized trials have reported that in the majority of clinical circumstances, the routine use of balloon flotation catheters is not indicated. These results are not surprising because balloon flotation catheters are diagnostic and not therapeutic tools. That we have learned a great deal about hemodynamics in critically ill patients with the use of balloon flotation catheters should not be ignored or forgotten. Furthermore, our clinical knowledge of hemodynamics has been made possible because of extensive experience gained from directly determined hemodynamics with the use of balloon flotation catheters. It should also be realized that despite the introduction and refinement of newer noninvasive imaging modalities, a number of clinical circumstances exist in which determination of hemodynamics with the use of a balloon flotation catheter is necessary and should be considered, but only by experienced physicians. With the proper use of Swan-Ganz catheters, our knowledge of hemodynamics has been enhanced considerably. Its abuse, particularly by relatively inexperienced operators, has resulted in serious complications, including death. Prospective randomized clinical trials have demonstrated that the routine use of Swan-Ganz catheters does not provide any benefit. However, use of the Swan-Ganz catheter is still indicated in many situations.
Isolated Lateral Sinus Thrombosis
Authors: Damak Mariem , Crassard Isabelle , Wolff Valérie , Bousser Marie-Germaine
Published: January 2009

Background and Purpose—

Isolated lateral sinus thrombosis was long considered a complication of middle ear disease. Little attention has been recently paid to this variety of thrombosis. We therefore reviewed all cases of isolated lateral sinus thrombosis prospectively collected in our center (1997 to 2006).

Methods—

Among 195 patients with cerebral venous thrombosis (CVT), we identified 157 patients with lateral sinus thrombosis, including 62 patients with isolated lateral sinus thrombosis. Clinical, etiologic, and prognostic features were compared with those of other 133 CVT cases.

Result—

Sixty-two patients (32%) had isolated lateral sinus thrombosis. Headaches were present in 95% of patients. The main clinical presentation was isolated headache in 28 patients (45%), whereas 15 (24%) had isolated intracranial hypertension. Nineteen patients (31%) had at least one focal sign (deficit and/or focal seizure). Dysphasia was the most common one (8 patients). Compared with the other 133 CVT cases, presentation with isolated headaches was the most frequent one (
P
<0.001). Parenchymal lesions were found in 19 cases and were less frequent than in other CVT cases (
P
=0.007). Numerous causes or predisposing factors were identified without a difference in repartition with other patients with CVT, particularly for local or infectious causes. Treatment consisted of anticoagulation in all patients. Clinical outcome was good with complete recovery in 57 patients (92%). One patient died after the occurrence of massive pulmonary emboli despite adequate anticoagulation. Three patients had sequelae (no difference with the other CVT).

Conclusion—

Isolated lateral sinus thrombosis is a frequent variety of CVT, accounting for one third of all CVT. It presents in more than two thirds of cases with headache as the only symptom either isolated or less frequently associated with papilledema. This stresses the need for CVT workup in a patient with a recent unexplained headache.
Autopsy Prevalence of Proximal Extracranial Atherosclerosis in Patients With Fatal Stroke
Authors: Mazighi Mikael , Labreuche Julien , Gongora-Rivera Fernando , Duyckaerts Charles , Hauw Jean-Jacques , Amarenco Pierre
Published: January 2009

Background and Purpose—

Extracranial atherosclerosis, proximal to the carotid bifurcation and V3 segment of the vertebral artery, is considered to be an infrequent condition with a benign prognosis. However, its prevalence may be underestimated due to lack of data. We aimed to determine the prevalence of proximal extracranial plaques and stenosis in the common carotid artery, innominate and subclavian arteries, and proximal vertebral artery.

Methods—

We performed a systematic analysis of intra- and extracranial arteries, the aortic arch, and the heart in 339 consecutive autopsies of patients with stroke; 259 patients had brain infarction; 80 patients had brain hemorrhage and were used as control subjects. Clinical history, risk factors, imaging data, and general autopsy reports were analyzed.

Results—

Proximal extracranial plaques and stenosis were present in the arteries of 46.9% and 19.8% of patients, respectively, without a significant difference between brain infarction and brain hemorrhage groups. Proximal extracranial atherosclerosis occurred more frequently in the proximal vertebral artery than in other arteries (stenosis prevalence 12.7% versus 5.3% in the common carotid artery) and in patients with posterior circulation brain infarction (except for the posterior cerebral artery territory). More specifically, atherosclerosis in the proximal vertebral artery was significantly associated with posterior circulation brain infarction (age- and sex-adjusted OR, 2.31; 95% CI, 1.28 to 4.17 for plaques and 2.10; 95% CI, 1.01 to 4.38 for stenosis) using patients with isolated anterior circulation infarctions as control subjects.

Conclusions—

Proximal extracranial atherosclerosis was frequent and was significantly associated with brainstem infarcts. These findings support the importance of a systematic workup, including the evaluation of proximal extracranial atherosclerotic lesions.
Sex Differences in Stroke Care and Outcome in the Swedish National Quality Register for Stroke Care
Authors: Eriksson Marie , Glader Eva-Lotta , Norrving Bo , Terént Andreas , Stegmayr Birgitta
Published: January 2009

Background and Purpose—

Previous reports concerning sex-related differences in stroke management and outcome are inconsistent and are sometimes difficult to interpret. We used data from a national stroke register to further explore possible differences between men and women in baseline characteristics, stroke treatment, and outcome.

Methods—

This study included 24633 stroke events registered in Riks-Stroke, the Swedish national quality register for stroke care, during 2006. Information on background variables and treatment was collected during the hospital stay. After 3 months, the patients’ living situation and outcome were assessed.

Results—

Women were older than men when they had their stroke (mean age, 78.4 versus 73.6 years;
P
<0.001). On admission to the hospital, women were more often unconscious. Among conscious patients, there was no sex-related difference in the use of stroke unit care. Men and women had equal probability to receive thrombolysis and oral anticoagulants. Women were more likely to develop deep venous thromboses and fractures, whereas men were more likely to develop pneumonia during their hospital stay. Women had a lower 3-month survival, a difference that was associated with higher age and impaired level of consciousness on admission. Women were less often living at home at the 3-month follow-up. However, the difference in residency was not present in patients <85 years who were living at home without community support before the stroke.

Conclusions—

Reported sex differences in stroke care and outcome were mainly explained by the women’s higher age and lower level of consciousness on admission.
High-Dose B Vitamin Supplementation and Progression of Subclinical Atherosclerosis
Authors: Hodis Howard N. , Mack Wendy J. , Dustin Laurie , Mahrer Peter R. , Azen Stanley P. , Detrano Robert , Selhub Jacob , Alaupovic Petar , Liu Chao-ran , Liu Ci-hua , Hwang Juliana , Wilcox Alison G. , Selzer Robert H.
Published: January 2009

Background and Purpose—

Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression.

Methods—

In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 μmol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B
12
+50 mg vitamin B
6
) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome).

Results—

Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (
P
=0.31). However, among subjects with baseline tHcy ≥9.1 μmol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (
P
=0.02); among subjects with a baseline tHcy <9.1 μmol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups.

Conclusion—

High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin “replete” individuals at low risk for cardiovascular disease with a fasting tHcy ≥9.1 μmol/L.
Thrombolysis in Childhood Stroke
Authors: Arnold Marcel , Steinlin Maja , Baumann Andreas , Nedeltchev Krassen , Remonda Luca , Moser Sonya Jourdan , Mono Marie-Luise , Schroth Gerhard , Mattle Heinrich P. , Baumgartner Ralf W.
Published: January 2009

Background and Purpose—

No controlled, randomized trial has investigated whether intravenous, intra-arterial (IAT), or mechanical thrombolysis is beneficial in children with ischemic stroke. We report 2 children who underwent IAT for acute ischemic stroke and include them in a review about intravenous thrombolysis, IAT, and mechanical thrombolysis for childhood stroke.

Methods—

We searched in MEDLINE and EMBASE for studies that reported on treatment of childhood stroke with intravenous thrombolysis, IAT, or mechanical thrombolysis in the presence of occlusion of the basilar artery, sphenoidal, or insular middle cerebral artery. To be included in this review, the following findings had to be reported: (1) stroke severity at presentation; (2) cerebral imaging findings before thrombolysis; (3) time to treatment; (4) dose of the thrombolytic agent; (5) pre- and postinterventional angiographic findings in IAT; and (6) outcome assessed at hospital discharge or within 12 months after thrombolysis.

Results—

Adequate data were available in 17 children (including our 2 own cases) who underwent intravenous thrombolysis (n=6), IAT (n=10), or mechanical thrombolysis (n=1). No symptomatic intracranial hemorrhage occurred, but 2 asymptomatic intracranial hemorrhages were present. Sixteen children (94%) survived, and 12 (71%) had a good outcome (modified Rankin Scale score 0 or 1).

Conclusions—

The available data about thrombolysis in pediatric stroke are limited. They suggest that this treatment may be beneficial in children with ischemic stroke. Controlled, randomized trials are needed to determine whether thrombolysis is useful in childhood stroke.
Comparison of Overlap Methods for Quantitatively Synthesizing Single-Subject Data
Authors: Wolery Mark , Busick Matthew , Reichow Brian , Barton Erin E.
Published: January 2009

Four overlap methods for quantitatively synthesizing single-subject data were compared to visual analysts’ judgments. The overlap methods were percentage of nonoverlapping data, pairwise data overlap squared, percentage of data exceeding the median, and percentage of data exceeding a median trend. Visual analysts made judgments about 160 A-B data sets selected randomly from the Journal of Applied Behavior Analysis . The four overlap methods were compared for data sets in which all visual analysts agreed a change in data occurred or a change did not occur across conditions. Each overlap method had unacceptably high levels of errors. Given the findings and weaknesses of the overlap methods, their use should be abandoned. The desirable characteristics of a quantitative synthesis method are described.
Backing-Up Maneuvers of Autonomous Tractor-Trailer Vehicles using the Qualitative Theory of Nonlinear Dynamical Systems
Authors: González-Cantos A. , Ollero A.
Published: January 2009

This paper presents an approach, based on the qualitative theory of nonlinear dynamical systems, for the analysis and design of control systems for autonomous articulated vehicles. In particular, backing-up maneuvers are considered. These maneuvers are dangerous because the vehicles tend to `jackknife' when the angle between the tractor and the trailer is greater than a certain value. This danger is increased when the actuators are saturated because they can cause a lack of controllability in the state space and control becomes complicated. The paper proposes a two-level control system with an orientation controller in the lower level and a look-ahead controller in the higher. In the paper, a general orientation feedback controller is presented. This control strategy represents a wide family of different nonlinear controllers and can be applied with different particular control laws. The paper applies the qualitative theory of nonlinear dynamical systems to study the stability of the control system. Thus, the stability of the system under some constraints is demonstrated. The paper includes both simulation and experimental results of the implementation on the Romeo 4R autonomous vehicle, which is a full-size autonomous electrical golf cart with a trailer.
Tension Level during Preconditioning Influences Hamstring Tendon Graft Properties
Authors: Elias John J. , Kilambi Srianjana , Ciccone William J.
Published: January 2009

Background

Hamstring tendon grafts used for anterior cruciate ligament reconstruction are preconditioned to reduce the influence of viscoelasticity on the stiffness and tension.

Hypothesis

Increasing the tension applied during preconditioning will decrease the loss of tension and stiffness due to viscoelasticity.

Study Design

Controlled laboratory study.

Methods

Six quadruple-strand hamstring tendon grafts were tested twice in vitro with 2 tension levels applied during preconditioning. The grafts were preconditioned at 80 N or 160 N, followed by 15 minutes of relaxation, and subsequently loaded to 80 N to represent application of initial tension. After 5 minutes of relaxation, the tension was recorded and the stiffness was measured over 0.06 mm of displacement. The tension and stiffness measurements were repeated 3 hours later. The data were compared between the 2 preconditioning levels with a 2-way repeated-measures analysis of variance.

Results

Graft tension and stiffness were significantly larger (P <. 05) for 160 N during preconditioning. For 80 N, the average tension at 5 minutes and 3 hours was 40 N and 21 N, respectively, compared with 50 N and 30 N, respectively, for 160 N. For 80 N, the average stiffness at 5 minutes and 3 hours was 152 N/mm and 124 N/mm, respectively, compared with 173 N/mm and 146 N/mm, respectively, for 160 N.

Conclusion

Increasing the tension applied to hamstring tendon grafts during preconditioning can decrease the postoperative loss of tension and stiffness due to viscoelasticity.

Clinical Relevance

The increased graft tension and stiffness could reduce postoperative knee laxity.
The Career Institute
Authors: Rivera Lourdes M. , Schaefer Mary Beth
Published: January 2009

Career development is integral to students' academic and social—personal development, and addressing students' needs in this area is recognized as an important responsibility of the professional school counselor. However, efforts to address students' career development tend to be lacking or services are provided in a disconnected manner. This article provides a brief overview of the literature on career development in schools and presents a schoolwide career development program that is integrated into the school curriculum, collaboratively implemented with teachers, and begins in the sixth grade. The value of this programmatic effort is discussed, and recommendations for program development are offered.
Male Hierarchies and Gender-balanced Boards
Authors: Åhmansson Gabriella , Öhlund Lennart S.
Published: January 2009

The aim of the present study is to examine whether the established fact that men by far outnumber women in leading positions is an inherent unintentional characteristic of a hierarchy where appointments happen one by one on an individual basis, as opposed to boards where the members are appointed as a group. The sample consists of those appointed to the hierarchies as well as the boards of 36 state universities in Sweden. The main finding is that significantly more men are appointed in hierarchies than to group-composed boards. When the gendered distribution of those in leading positions becomes fully apparent, the last and final position in the hierarchy is significantly more often given to a woman. However, these women are much older than their male counterparts, a fact that makes it harder for them to reach the final step of the ladder. The article concludes with a discussion of whether the higher probability of appointing a woman as vice-president when both chair and president are men is a fair acknowledgement of an unfair gender distribution, or if there are other possible explanations.
Simultaneous Occurrence of IgG4-Related Chronic Sclerosing Dacryoadenitis and Chronic Sclerosing Sialadenitis Associated with Lymph Node Involvement and Warthin’s Tumor
Authors: Lee Li-Yu , Chen Tse-Ching , Kuo Tseng-tong
Published: January 2009

Chronic sclerosing dacryoadenitis and chronic sclerosing sialadenitis have been shown to belong to the group of diseases referred to as IgG4-related sclerosing disease. The authors report a case of the simultaneous occurrence of IgG4-related sclerosing disease in both lacrimal and submandibular glands, clinically simulating malignant lymphoma. A cervical lymph node and a Warthin’s tumor were also involved. This unique case of multiple organ involvement in IgG4-related sclerosing disease is documented.
Hepatic Rosai-Dorfman Disease With Coincidental Lymphoma: Report of a Case
Authors: Di Tommaso Luca , Rahal Daoud , Bossi Paola , Roncalli Massimo
Published: January 2009

Rosai—Dorfman disease (RDD; sinus histiocytosis with massive lymphoadenopathy) is a rare, usually nodal self-limited disease. Sometimes nodal disease is coupled with extranodal localizations, in which case the disease can follow a protracted clinical course characterized by remissions and relapses and, exceptionally, a fatal outcome. Exclusive extranodal localizations are rare and their prognosis variable. This study reports a case of RDD apparently limited to the liver coexisting with a diffuse (stage IV) relapsing follicular lymphoma. The patient is alive and well 24 months after the diagnosis of the lymphoma. It is conceivable that the lymphoma has induced RDD via an immunological disorder, possibly involving interleukin expression. The favorable outcome supports the belief that the prognosis of RDD is largely dependent on the number of extranodal sites involved, rather than on the specific sites themselves.
The Histological Features of Intestinal Spirochetosis in a Series of 113 Patients
Authors: Carr Norman J. , Mahajan Hema , Tan King L. , Sharma Raghwa
Published: January 2009

A multicenter retrospective review of cases diagnosed as spirochetosis was performed to determine the presenting symptoms and histological changes. A total of 113 cases were retrieved from the archives, consisting of 97 colorectal specimens and 16 appendices. In only 25 cases was the presenting symptom recorded as diarrhea. Of the colorectal specimens, 87 (90%) showed no mucosal abnormality (apart from the spirochetes); the other 10 showed mucosal inflammation but 6 of them had a diagnosis of another inflammatory disease process accounting for the inflammatory changes. Five appendices showed acute appendicitis; the other 11 were unremarkable. It is concluded that spirochetosis in an unselected general population is unlikely to be of pathological significance. Furthermore, if spirochetosis is observed in an inflamed biopsy, it is most likely to be an incidental finding.
Assessment of Fibrinolytic Activity by Measuring the Lysis Time of a Tissue Factor-induced Clot: A Feasibility Evaluation
Authors: Cellai Anna Paola , Lami Donatella , Magi Alberto , Liotta Agatina Alessandrello , Rogolino Angela , Antonucci Emilia , Bandinelli Brunella , Abbate Rosanna , Prisco Domenico
Published: January 2009

A clot lysis time assay in which a tissue factor—induced fibrin clot is lysed by exogenously added tissue plasminogen activator has been recently reported. We evaluated the feasibility of clot lysis time in a routine hemostasis laboratory, and its correlation with thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels and changes with aging in 185 healthy participants. Clot lysis time was assessed by monitoring changes in turbidity during clot formation and subsequent lysis using a computerized kinetic spectrophotometric microtiter plate. After preliminary experiments, 100 and 160 ng/mL tissue plasminogen activator concentrations were chosen for the study. Clot lysis time was calculated by a new mathematical analysis of the lysis curve based on discrete derivative. Clot lysis time, thrombin activatable fibrinolysis inhibitor, and plasminogen activator inhibitor-1 plasma levels showed a normal distribution. For both concentrations of tissue plasminogen activator, clot lysis time progressively increased with increase in age (P < .0001) and was significantly correlated with thrombin activatable fibrinolysis inhibitor antigen, thrombin activatable fibrinolysis inhibitor activity, and plasminogen activator inhibitor-1 antigen (at least P < .01). During linear regression analysis, thrombin activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 antigen were found to significantly influence clot lysis time (at least P < .01). Clot lysis time determination has a good laboratory performance. Our new method of calculation is independent of the time of reading and allows a more accurate and consistent detection of both short and prolonged lysis times. Our data suggest the feasibility of the use of this test in the work of routine hemostasis laboratory.
Venous Thromboembolism in Young Female While on Oral Contraceptives: High Frequency of Inherited Thrombophilia and Analysis of Thrombotic Events in 400 Czech Women
Authors: Dulíček Petr , Malý Jaroslav , Pecka Miroslav , Beránek Martin , Čermáková Eva , Malý Radovan
Published: January 2009

Oral contraceptive use is a common risk factor for venous thromboembolism in women of reproductive age. The presence of inherited thrombophilia further increases this risk. Methods: We analyzed a large group of 400 Czech women with venous thromboembolism in association with oral contraceptive with regard to duration of use at the time of manifestation of venous thromboembolism, the frequency of inherited and acquired thrombophilia, the frequency of eliciting risk factor for thrombosis including immobilization, surgery, administration of plaster cast, long travel, and so on, and the type of thrombosis. The mean age of the women was 26 years, and the average duration of use was 45 months at the onset of thrombosis. Results: Venous thrombosis solely due to the pill occurred in 57% of the women, and in the other 43%, an additional transient eliciting factor was recognized. Among the clinical manifestation, distal thrombosis prevailed (N = 231, 58%) followed by proximal deep vein thrombosis (N = 65, 16%), pulmonary embolism (N = 21, 5%), and thrombosis in unusual sites (N = 20, 5%). Inherited or acquired thrombophilia was diagnosed in 195 (49%) women: factor V Leiden mutation in 35%, congenital deficiency of antithrombin in 1.8%, protein C in 0.8%, protein S in 1%, F IIG20210A in 5%, and antiphospholipid syndrome (APS) in 5.3%. Among the most common risk factors were immobilization of lower limb, minor and major surgery, and trauma. Conclusion: The results confirm that venous thromboembolism is a multifactorial disease in which thrombophilia screening is needed in young symptomatic women on the pill with thrombosis. The results also emphasize the value of proper thromboprophylaxis in women while on oral contraceptive in situations of increased risk for venous thromboembolism.
Effect of Sulodexide on Plasma Transforming Growth Factor-β1 in Healthy Volunteers
Authors: Borawski Jacek , Dubowski Miroslaw , Pawlak Krystyna , Mysliwiec Michal
Published: January 2009

It is unknown whether the glycosaminoglycan drug sulodexide interferes with transforming growth factorβ1—a member of heparin-binding family and a potent regulator of human biology and diseases. Hence, a 2-week pilot study was performed in 11 healthy men. Sulodexide was initially administered intravenously in a single dose, then—orally for 12 days and—again intravenously on study completion. Initial injection had no effect on activated form of the growth factor measured in plasma after 10 and 120 min; no change was also observed after 120 min from drug ingestion on day 7. On final intravenous administration, the growth factor levels increased by almost 60% after 10 min and remained elevated; the 120-min levels directly correlated with sulodexide dosage. Baseline cytokine levels decreased during the 2-week trial by more than 50%. In conclusion, transforming growth factor-β1 release and likely downregulation of its expression may constitute novel pharmacological effects of sulodexide.
Comparison of Immunogenic Potentials of Bovine Thrombin Preparations
Authors: He Zhu  , Hoppensteadt Debra , Adiguzel Cafer , Bick Rodger L. , Fareed Jawed
Published: January 2009

Using a membrane filtration step, bovine crude thrombin was purified into thrombin 4A and 4B preparations. The purpose of this study was to determine whether the improved purity of a bovine thrombin preparation can reduce its overall immunogenic potential and lower the risk of development of factor V antibodies. Bovine crude thrombin and its purified versions, thrombin 4A and 4B, were administered to individual groups of rabbits on days 0, 21, 42, 91, 123, and 151 using standard immunologic methods. Blood was drawn from each rabbit on days 30, 50, 105, 137, and 165, and the pooled antisera from individual groups were purified to obtain the Ig Gs using protein G affinity columns. Using Western blotting, the specificity of each immunoglobulin G collected at the first time point (day 30) and last time point (day 165) was determined. The results of Western blotting using the Ig Gs collected on days 30 and 165 were consistent; both demonstrating that thrombin 4B has the least immunogenic potential among the 3 thrombin preparations tested. Compared with the immunoglobulin Gs collected on day 30, the Ig Gs from day 165 did not show obvious difference regarding their ability to detect antigens in bovine thrombin samples. Neither showed cross-reactivity with human coagulation factors nor the recognition of bovine factor Va antigens. These results suggest that despite the presence of a trace amount of bovine factor Va antigen in bovine thrombin preparations, these contaminants failed to elicit the generation of antibodies against factor Va light chain in rabbit
In Vivo Hemostatic Effect of the Medicinal Plant Extract Ankaferd Blood Stopper in Rats Pretreated With Warfarin
Authors: Cipil Handan S. , Kosar Ali , Kaya Arif , Uz Burak , Haznedaroglu Ibrahim C. , Goker Hakan , Ozdemir Oktay , Koroglu Mustafa , Kirazli Serafettin , Firat Huseyin Cahit
Published: January 2009

Aim: Ankaferd comprises a mixture of Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) has been approved in the management of bleedings. This study aimed to evaluate in vivo hemostatic effect of ABS in rats pretreated with warfarin. Materials and methods: Wistar rats (210-270 g) were treated either with warfarin (2 mg/kg) or vehicle (0.9% NaCl) orally before bilateral hind leg amputation. ABS was administered topically to one of the amputed legs. The duration of bleeding and the amount of bleeding were measured to evaluate the hemostatic effect of ABS. Results: Topical ABS administration to amputed leg shortened the duration of bleeding markedly in both untreated and warfarin-treated rats by 31.9% [1.42 min (95% CI: 0.35-2.49)] and 43.5% [5.12 min (95% CI: 2.16-8.07)] respectively. The amount of bleeding in ABS-administered amputed leg showed a decrease by 53.8% in warfarin-treated group. Conclusions: ABS has in vivo hemostatic actions that may provide a therapeutic potential for the management of patients with deficient primary hemostasis in clinical medicine.
Optimal Dosing of Intravenous Unfractionated Heparin Bolus in Transient Ischemic Attack or Stroke
Authors: Kang Kyusik , Dong Wook Kim  , Park Hee-Kwon , Yoon Byung-Woo
Published: January 2009

Early initiation of heparin therapy for treatment of stroke is not only associated with an improved outcome, but also with the risk of hemorrhagic transformation. We compared the efficacy of three unfractionated heparin bolus regimens (0 U/kg, 30 U/kg, or 80 U/kg) in achieving a therapeutic activated partial thromboplastin time over the first 6-hour period in a cohort of 54 patients admitted with transient ischemic attack or stroke. Patients treated with the low bolus dose (30 U/kg) were more often within the therapeutic range for activated partial thromboplastin time at two hours after the initial bolus than patients treated with the other regimens. The percentage of therapeutic activated partial thromboplastin time results within the first six hours of treatment was greater in the group treated with the low bolus dose. Using the low bolus dose may reduce complication rates and improve clinical outcomes in the future clinical trials.