bluuebunny/crossref_metadata_2025 huggingface dataset:
OPTICAL DOMAIN WALLS IN ATOMIC VAPORS
Authors: HAELTERMAN M. , LOUIS Y.
Published: October 2004

We present a theoretical analysis of the recently discovered optical domain-wall solitons. We discuss the fundamental link which exists between diffractive spatial domain-wall solitons and the instability responsible for the self-filamentation of polarized laser beams in self-defocusing Kerr media. We show that the vector properties of the third-order nonlinear response of atomic vapors satisfy the conditions of occurrence of this instability and are therefore suited to the experimental observation of the spatial polarization domain-wall solitons.
TWO-DIMENSIONAL NONLINEAR OPTICS SPECTROSCOPY: SIMULATIONS AND EXPERIMENTAL DEMONSTRATION
Authors: LEPETIT L. , CHÉRIAUX G. , JOFFRE M.
Published: October 2004

We propose a new technique, using femtosecond Fourier-transform spectral interferometry, to measure the second-order nonlinear response of a material in two dimensions of frequency. We show numerically the specific and unique information obtained from such a two-dimensional measurement. The technique is demonstrated by measuring the second-order phase-matching map of two non-resonant nonlinear crystals.
PROGRESS IN Q-SWITCHING OF Nd:YAG SATURABLE ABSORBER
Authors: SHIMONY Y. , BURSHTEIN Z. , KALISKY Y. , BARANGA A. BEN-AMAR , STRAUSS M.
Published: October 2004

We demonstrate the performances of pulsed and CW pumped Nd:YAG lasers, passively Q-switched with Cr 4+: YAG saturable absorbers. Losses contributed by the active Cr4+ ions relate to their excited state absorption. Repetitive Q-switching of the CW pumped Nd:YAG laser was achieved for the first time, providing pulses 80–300 ns wide (FWHM) with repetition rates between 2 and 29 kHz. This laser is applicable where exact pulse timing is not required.
EXCITON AND BIEXCITON PHENOMENA IN ZINC SULPHIDE EPILAYERS
Authors: VALENTA J. , GUENNANI D. , MANAR A. , GILLIOT P.
Published: October 2004

The detailed characterization of metal organic vapour phase epitaxy grown ZnS layers on GaAs is the first step towards the study of their different non-linear optical properties performed with nanosecond lasers. Biexciton phenomena (with a binding energy of about 10 meV) are observed in photoluminescence-excitation and optical-gain spectra.
ELECTRON-HOLE PLASMA GRATINGS RELATED TO THE URBACH TAIL IN POLAR SEMICONDUCTORS
Authors: GRAC R. , IEHL J.L. , PUGNET M.
Published: October 2004

We have studied the optical index modulation in the Urbach tail of Cd 0.96 Zn 0.04 Te , using the transient grating technique in the subnanosecond domain. We have shown that the screening of the electric field due to LO-phonons by free carriers can explain the main features of picosecond transient grating experiments in the spectral region of the Urbach tail in CdZnTe. We can explain simultaneously the following features: the existence of a break in the kinetics, the saturation of the diffraction efficiency with the pump energy, the possibility of grating erasure and finally the order of magnitude of the experimental diffraction efficiency.
CALCULATION OF THE INTERACTION POTENTIAL FOR BICHROMOPHORIC HETERO-MOLECULAR CLUSTERS
Authors: ROSENBLUM GERSHON , SPEISER SHAMMAI
Published: October 2004

An expression for the interaction potential between two anisotropic molecules is derived. This expression is suitable for describing the van der Waals interaction between two chromophores within a bichromophoric molecular cluster. For the anthracene-naphthalene and for the benzene-biacetyl clusters the calculation predicts the existence of two isomers, in agreement with experimental observations. The model is also successfully applied to other clusters yielding better results than those obtained by alternative methods which do not take into account the anisotropy of molecular polarizability.
QUANTUM IMAGES
Authors: LUGIATO L.A. , BARNETT S.M. , GATTI A. , MARZOLI I. , OPPO G.L. , WIEDEMANN H.
Published: October 2004

We illustrate the spatial quantum features that emerge in a degenerate optical parametric oscillator below threshold, where the signal field is purely generated by quantum fluctuations. We analyze the behaviour of the spatial correlation function of a generic quadrature component of the signal field in both cases of a cavity with plane mirrors and a cavity with spherical mirrors. The correlation length diverges when the semiclassical threshold for signal field generation is approached. We focus on the novel concept of quantum image, which is analyzed both in the near field and in the far field.
SQUEEZING OF THE PUMP BEAM IN OPTICAL PARAMETRIC INTERACTION
Authors: KASAI KATSUYUKI , FABRE CLAUDE
Published: October 2004

We investigate the squeezing of the pump beam in optical parametric interaction. According to our semi-classical calculation, the pump beam reflected back from a Triply Resonant Optical Parametric Oscillator (TROPO) is squeezed.1 In this paper we preliminarily demonstrate the squeezing of the pump beam by using a semimonolithic KTP TROPO pumped by a frequency doubled LD-pumped YAG laser. Noise reduction of 1.2 dB below the shot noise level is observed in the bistable region of the parametric oscillation.
Effects of chronic portal hypertension on small heat-shock proteins in mesenteric arteries
Authors: Chen Xuesong , Zhang Hai-Ying , Pavlish Kristin , Benoit Joseph N.
Published: October 2004

Previous studies have shown that impaired vasoconstrictor function in chronic portal hypertension is mediated via cAMP-dependent events. Recent data have implicated two small heat-shock proteins (HSP), namely HSP20 and HSP27, in the regulation of vascular tone. Phosphorylation of HSP20 is associated with vasorelaxation, whereas phosphorylation of HSP27 is associated with vasoconstriction. We hypothesized that alterations in the expression and/or phosphorylation of small HSPs may play a role in impaired vasoconstriction in portal hypertension. A rat model of prehepatic chronic portal hypertension was used. Studies were conducted in small mesenteric arteries isolated from normal and portal hypertensive rats. Protein levels of HSP20 and HSP27 were detected by Western blot analysis. Protein phosphorylation was analyzed by isoelectric focusing. HSP20 mRNA expression was determined by RT-PCR. To examine the role of cAMP in the regulation of small HSP phosphorylation and expression, we treated both normal and portal hypertensive vessels with a PKA inhibitor Rp-cAMPS. We found both an increased HSP20 phosphorylation and a decreased HPS20 protein level in portal hypertension, both of which were restored to normal by PKA inhibition. However, PKA did not change HSP20 mRNA expression. We conclude that decreased HSP20 protein level is mediated by cAMP-dependent pathway and that impaired vasoconstrictor function in portal hypertension may be partially explained by decreased expression of HSP20. We also suggest that the phosphorylation of HSP20 by PKA may alter HSP20 turnover.
Meal-related increases in vascular reactivity are impaired in older and diabetic adults: insights into roles of aging and insulin in vascular flow
Authors: Skilton Michael R. , Lai Nicole T. , Griffiths Kaye A. , Molyneaux Lynda M. , Yue Dennis K. , Sullivan David R. , Celermajer David S.
Published: October 2004

A fatty meal induces vasodilatation (of both resting and stimulated forearm flow) in healthy young adults, an effect most likely mediated by the vasodilator actions of insulin. We therefore hypothesized that an impaired meal-related vascular response might be an in vivo marker of vascular insulin resistance, related to the presence of diabetes and/or higher age. Postprandial vascular responses were assessed in three groups of subjects: 15 Type 2 diabetic subjects (age 58 ± 8 yr), 15 age-, gender-, and body mass index (BMI)-matched older control subjects (age 57 ± 9 yr), and 15 healthy young control subjects (age 33 ± 7 yr). Studies were carried out before and 3 and 6 h after a standardized high-fat meal (1,030 kcal, 61 g fat). Forearm microvascular flows were measured by strain gauge plethysmography and large-artery function by ultrasound. Resting blood flow and hyperemic area under curve (AUC) flow were not significantly different in diabetic subjects (resting 117 ± 42% and AUC 134 ± 46% of premeal values) compared with age-matched controls (resting 131 ± 39% and AUC 134 ± 47%); however, the response in diabetic subjects was blunted compared with young controls (resting 171 ± 67% and AUC 173 ± 99% of premeal values; P = 0.02 and P = 0.18, respectively). On multiple regression analysis, we found that increasing age (but not BMI or diabetes) was significantly associated with impaired postprandial vascular responses (resting: r = −0.4, P = 0.002; AUC: r = −0.4, P = 0.006). Therefore, meal ingestion results in impaired vasodilator responses in older nondiabetic and diabetic adults, related to aging rather than insulin resistance.
Maternal protein restriction leads to hyperinsulinemia and reduced insulin-signaling protein expression in 21-mo-old female rat offspring
Authors: Fernandez-Twinn D. S. , Wayman A. , Ekizoglou S. , Martin M. S. , Hales C. N. , Ozanne S. E.
Published: October 2004

Human adult diseases such as cardiovascular disease, hypertension, and type 2 diabetes have been epidemiologically linked to poor fetal growth and development. Male offspring of rat dams fed a low-protein (LP) diet during pregnancy and lactation develop diabetes with concomitant alterations in their insulin-signaling mechanisms. Such associations have not been studied in female offspring. The aim of this study was to determine whether female LP offspring develop diabetes in later life. Control and LP female offspring groups were obtained from rat dams fed a control (20% protein) or an isocaloric (8% protein) diet, respectively, throughout pregnancy and lactation. Both groups were weaned and maintained on 20% normal laboratory chow until 21 mo of age when they underwent intravenous glucose tolerance testing (IVGTT). Fasting glucose was comparable between the two groups; however, LP fasting insulin was approximately twofold that of controls ( P < 0.02). Glucose tolerance during IVGTT was comparable between the two groups; however, LP peak plasma insulin at 4 min was approximately threefold higher than in controls ( P < 0.001). LP plasma insulin area under the curve was 1.9-fold higher than controls ( P < 0.02). In Western blots, both muscle protein kinase C-ζ expression and p110β-associated p85α in abdominal fat were reduced ( P < 0.05) in LPs. Hyperinsulinemia in response to glucose challenge coupled with attenuation of certain insulin-signaling molecules imply the development of insulin resistance in LP muscle and fat. These observations suggest that intrauterine protein restriction leads to insulin resistance in females in old age and, hence, an increased risk of type 2 diabetes.
Probucol Inhibits ABCA1-Mediated Cellular Lipid Efflux
Authors: Favari Elda , Zanotti Ilaria , Zimetti Francesca , Ronda Nicoletta , Bernini Franco , Rothblat George H.
Published: October 2004

Objective—

ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of lipids from cells to lipid-poor apolipoproteins. In this article, we characterize the effect of probucol on cellular ABCA1-mediated lipid efflux.

Methods and Results—

Probucol inhibited cholesterol efflux up to 80% in J774 macrophages expressing ABCA1. In Fu5AH hepatoma cells that contain scavenger receptor class B, type I, but not functional ABCA1, we observed no effect of probucol on cholesterol efflux. Probucol inhibited cholesterol efflux from normal human skin fibroblasts but not from fibroblasts from a Tangier patient. Fluorescent confocal microscopy and biotinylation assay demonstrated that in J774 cells probucol impaired the translocation of ABCA1 from intracellular compartments to the plasma membrane. Probucol also inhibited the formation of an ABCA1-linked cholesterol oxidase sensitive plasma membrane domain. Consistent with the inhibitory effect on ABCA1 translocation to the plasma membrane, probucol reduced cell surface–specific [
125
I]-labeled apolipoprotein-AI binding.

Conclusions—

We conclude that probucol is an effective inhibitor of ABCA1-mediated cholesterol efflux without influencing scavenger receptor class B type I–mediated efflux. The inhibition of ABCA1 translocation to the plasma membrane may in part explain the reported in vivo high-density lipoprotein–lowering action of probucol.
Dimorphism in the P2Y1 ADP Receptor Gene Is Associated With Increased Platelet Activation Response to ADP
Authors: Hetherington Simon L. , Singh Ravi K. , Lodwick David , Thompson John R. , Goodall Alison H. , Samani Nilesh J.
Published: October 2004

Objective—

The platelet ADP receptors P2Y1 and P2Y12 play a pivotal role in platelet aggregation. There is marked interindividual variation in platelet response to ADP. We studied whether genetic variants in the P2Y1 or P2Y12 genes affect platelet response to ADP.

Methods and Results—

The P2Y1 and P2Y12 genes were screened for polymorphisms. Associations between selected polymorphisms and the platelet response to ADP (0.1, 1.0, and 10 μmol/L), assessed by whole blood flow cytometric measurement of fibrinogen binding to activated glycoprotein IIb-IIIa, were then determined in 200 subjects. Five polymorphisms were found in the P2Y1 gene and 11 in the P2Y12 gene. All polymorphisms were silent. A P2Y1 gene dimorphism, 1622A〉G, was associated with a significant (
P
=0.007) effect on platelet ADP response, with a greater response in carriers of the G allele (frequency 0.15). The effect was seen at all concentrations of ADP but greatest at 0.1 μmol/L ADP, where the response in GG homozygotes was on average 130% higher than that seen in AA homozygotes (
P
=0.006).

Conclusions—

A common genetic variant at the P2Y1 locus is associated with platelet reactivity to ADP. This genotype effect partly explains the interindividual variation in platelet response to ADP and may have clinical implications with regard to thrombotic risk.
Immunomodulation of Atherosclerosis
Authors: Nilsson Jan , Hansson Göran K. , Shah Prediman K.
Published: October 2004

A number of studies have shown activation of the immune system throughout various stages of atherosclerosis. Recent observations have suggested that activation of immune responses may promote atherosclerosis on one hand by inducing and perpetuating arterial inflammation, whereas on the other hand, selective activation of certain immune functions may inhibit atherosclerosis and arterial inflammation. These observations suggest the possibility that selective suppression of proatherogenic immune responses or selective activation of antiatherogenic immune responses may provide new approaches for atherosclerosis prevention and treatment. Several antigens activating immune responses affecting development of atherosclerosis have been identified. These immune responses may be modulated by presenting the antigens together with different types of adjuvants as well as through the route of administration. In this review, we summarize recent experimental studies using immunomodulatory approaches for treatment of atherosclerosis.
Redox Mechanisms in Blood Vessels
Authors: Mueller Cornelius F.H. , Laude Karine , McNally J. Scott , Harrison David G.
Published: October 2004

Reactive oxygen species have been implicated in the pathogenesis of virtually every stage of vascular lesion formation, hypertension, and other vascular diseases. We are currently gaining insight into important sources of reactive oxygen species in the vessel wall, including the NADPH oxidases, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondrial sources. Although various reactive oxygen species have pathological roles, some serve as important signaling molecules that modulate vascular tone, growth, and remodeling. In the next several months, a series of articles in
Arteriosclerosis, Thrombosis, and Vascular Biology
attempt to further elucidate how reactive oxygen species are produced by vascular cells and the roles of these in vascular homeostasis. This series promises to provide a valuable update on a wide variety of issues related to the biochemistry, molecular biology, and physiology of these important and fascinating molecules.
Quantitative Trait Locus Mapping of Genetic Modifiers of Metabolic Syndrome and Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Authors: Seidelmann Sara Bretschger , De Luca Carl , Leibel Rudolph L. , Breslow Jan L. , Tall Alan R. , Welch Carrie L.
Published: October 2004

Objective—

The purpose of this study was to examine genetic factors responsible for metabolic syndrome and atherosclerosis in a setting of low-density lipoprotein (LDL) receptor deficiency in a cross between C57BL/6J (B6) and PERA/Ei (PERA) inbred mouse strains.

Methods and Results—

Comparison of metabolic phenotypes in B6 and PERA strains revealed the PERA genetic background to be dramatically more susceptible to hyperleptinemia, hyperglycemia, hypertriglyceridemia, elevated insulin levels, and body fat increase than the B6 background. To facilitate genetic analysis, metabolic syndrome-related traits and atherosclerotic lesion area were measured in 167 [(PERA×B6.129S7-
Ldlr

tm1Her

)×B6.129S7-
Ldlr

tm1Her

]N2 male and female backcross mice that were homozygous for the
Ldlr
null allele. Quantitative trait locus analysis was performed using 153 polymorphic microsatellite markers spanning the genome. On chromosome 4, we identified a locus influencing plasma triglyceride, insulin, and leptin concentrations, body weight, and atherosclerosis. Several other genetic loci were identified with separate effects on plasma insulin, body weight, high-density lipoprotein cholesterol, and atherosclerosis.

Conclusions—

The PERA strain is highly susceptible to the development of metabolic syndrome after feeding a Western-type diet. This susceptibility is due, in part, to a locus on murine chromosome 4 in which PERA alleles predispose to adiposity, increased insulin, and accelerated atherogenesis in the absence of marked hyperlipidemia.
Protein Kinase D Is a Novel Mediator of Cardiac Troponin I Phosphorylation and Regulates Myofilament Function
Authors: Haworth Robert S. , Cuello Friederike , Herron Todd J. , Franzen Gereon , Kentish Jonathan C. , Gautel Mathias , Avkiran Metin
Published: October 2004

Protein kinase D (PKD) is a serine kinase whose myocardial substrates are unknown. Yeast 2-hybrid screening of a human cardiac library, using the PKD catalytic domain as bait, identified cardiac troponin I (cTnI), myosin-binding protein C (cMyBP-C), and telethonin as PKD-interacting proteins. In vitro phosphorylation assays revealed PKD-mediated phosphorylation of cTnI, cMyBP-C, and telethonin, as well as myomesin. Peptide mass fingerprint analysis of cTnI by liquid chromatography–coupled mass spectrometry indicated PKD-mediated phosphorylation of a peptide containing Ser22 and Ser23, the protein kinase A (PKA) targets. Ser22 and Ser23 were replaced by Ala, either singly (Ser22Ala or Ser23Ala) or jointly (Ser22/23Ala), and the troponin complex reconstituted in vitro, using wild-type or mutated cTnI together with wild-type cardiac troponin C and troponin T. PKD-mediated cTnI phosphorylation was reduced in complexes containing Ser22Ala or Ser23Ala cTnI and completely abolished in the complex containing Ser22/23Ala cTnI, indicating that Ser22 and Ser23 are both targeted by PKD. Furthermore, troponin complex containing wild-type cTnI was phosphorylated with similar kinetics and stoichiometry (≈2 mol phosphate/mol cTnI) by both PKD and PKA. To determine the functional impact of PKD-mediated phosphorylation, Ca
2+
sensitivity of tension development was studied in a rat skinned ventricular myocyte preparation. PKD-mediated phosphorylation did not affect maximal tension but produced a significant rightward shift of the tension–
p
Ca relationship, indicating reduced myofilament Ca
2+
sensitivity. At submaximal Ca
2+
activation, PKD-mediated phosphorylation also accelerated isometric crossbridge cycling kinetics. Our data suggest that PKD is a novel mediator of cTnI phosphorylation at the PKA sites and may contribute to the regulation of myofilament function.
Microembolic Signal Predicts Recurrent Cerebral Ischemic Events in Acute Stroke Patients With Middle Cerebral Artery Stenosis
Authors: Gao Shan , Wong Ka Sing , Hansberg Tjark , Lam Wynnie W. M. , Droste Dirk W. , Ringelstein E. Bernd
Published: October 2004

Background and Purpose—

Cerebral embolism is a common cause of stroke. Microembolic signals (MES) detected by transcranial Doppler represent ongoing embolisms, but the lack of reliable data about its clinical relevance hinders its widespread use in clinical practice.

Methods—

We prospectively monitored 114 consecutive acute ischemic stroke patients with middle cerebral artery (MCA) stenosis for MES. The signals on digital audio tape were analyzed by an independent observer who was blinded to all other data. All patients were followed-up for the occurrence of recurrent stroke or transient ischemic attack (TIA) in the indexed MCA territory.

Results—

MES was detected in 25 (22%) patients. The mean number of MES was 18 (range, 1 to 102). MES were more common in patients with severe stenosis (10/21, 48%) than in those with mild–moderate stenosis (4/26, 15%) (Pearson χ
2
P
=0.02). During follow-up for a mean of 13.6 months (range, 1 to 32), 12 (12%) patients had further ischemic events (10 strokes and 2 TIAs) in the affected MCA region during follow-up. Among these, 7 (58%) had recurred within 1 month (1 recurred within 1 week, the other 6 patients had recurrences in week 3 or 4 after discharge), 3 within 6 months, 1 within 6 to 12 months, and the remaining 1 recurred after 1 year. The presence of MES was the only predictor of a further ischemic stroke/TIA by Cox regression (adjusted odds ratio, 8.45; 95% CI, 1.69 to 42.22;
P
=0.01) even after controlling for age, sex, diabetes, hypertension, previous stroke, smoking, and acute treatment.

Conclusions—

In acute stroke patients with MCA stenosis, MES predicts further cerebral ischemia. This procedure should be considered as part of routine investigation and might identify a group of patients who are most likely to benefit from antithrombotic treatment.
Anteromedian, Central, and Posterolateral Infarcts of the Thalamus
Authors: Carrera Emmanuel , Michel Patrik , Bogousslavsky Julien
Published: October 2004

Background and Purpose—

Thalamic infarcts have traditionally been classified into 4 territories: anterior, paramedian, inferolateral, and posterior. The purpose of this study was to review this classical versus variant distribution in patients with thalamic stroke.

Methods—

We reviewed all patients with a first clinical stroke included in the Lausanne Stroke Registry between 1990 and 2002. Among 71 patients with an acute stroke isolated to the thalamus confirmed by MRI, we selected all patients with lesions outside the classical territories and studied their clinical, etiological, and radiological features.

Results—

A total of 21 patients (30% of all thalamic stroke patients) showed infarction outside the classical territories, allowing us to delineate 3 variant distributions: (1) Anteromedian territory (9 patients [13%]) involving anterior and paramedian territories, with predominantly cognitive impairment, including executive dysfunction, anterograde amnesia, and aphasia in left-sided or bilateral lesions. The most frequent stroke mechanism was cardiac embolism. (2) Central territory (4 patients [6%]), with lesions on the central part of the thalamus, resulting in a variety of neurological and neuropsychological signs, reflecting the involvement of several adjacent structures. Microangiopathy was the most frequent etiology. (3) Posterolateral territory (8 patients [11%]), involving inferolateral and posterior territories, with hemihypesthesia as the most frequent manifestation, followed by hemiataxia, executive dysfunction, and aphasia in left-sided lesions. Artery-to-artery embolism and microangiopathy were the main stroke mechanisms.

Conclusions—

We describe 3 variant topographic patterns of thalamic infarction with distinct manifestations and etiologies. We postulate that these infarcts are the result of a variation in thalamic arterial supply or reflect borderzone ischemia.
Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis
Authors: Zanchetti Alberto , Crepaldi Gaetano , Bond M. Gene , Gallus Giuseppe , Veglia Fabrizio , Mancia Giuseppe , Ventura Alessandro , Baggio Giovannella , Sampieri Lorena , Rubba Paolo , Sperti Giovanni , Magni Alberto
Published: October 2004

Background and Purpose—

The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies.

Methods—

A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBM
max
).

Results—

CBM
max
significantly progressed (0.010±0.004 mm per year;
P
=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBM
max
changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. “Clinic” and “ambulatory” blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by ≈1 mmol/L in groups C and D.

Conclusions—

Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.
Which Time-to-Peak Threshold Best Identifies Penumbral Flow?
Authors: Sobesky J. , Weber O. Zaro , Lehnhardt F.-G. , Hesselmann V. , Thiel A. , Dohmen C. , Jacobs A. , Neveling M. , Heiss W.-D.
Published: October 2004

Background and Purpose—

In acute ischemic stroke, the hypoperfused but viable tissue is the main therapeutic target. In clinical routine, time-to-peak (TTP) maps are frequently used to estimate the hemodynamic compromise and to calculate the mismatch volume. We evaluated the accuracy of TTP maps to identify penumbral flow by comparison with positron emission tomography (PET).

Methods—

Magnetic resonance imaging (MRI) and PET were performed in 11 patients with acute ischemic stroke (median 8 hours after stroke onset, 60 minutes between MRI and PET imaging). The volumes defined by increasing TTP thresholds (relative TTP delay of >2, >4, >6, >8, and >10 seconds) were compared with the volume of hypoperfusion (<20 mL/100 g per min) assessed by
15
O-water PET. In a volumetric analysis, each threshold’s sensitivity, specificity, and predictive values were calculated.

Results—

The median hypoperfusion volume was 34.5 cm
3
. Low TTP thresholds included large parts of the hypoperfused but also large parts of normoperfused tissue (median sensitivity/specificity: 93%/60% for TTP >2) and vice versa (50%/91% for TTP >10). TTP >4 seconds best identifies hypoperfusion (84%/77%). The positive predictive values increased with the size of hypoperfusion.

Conclusion—

This first comparison of quantitative PET-CBF with TTP maps in acute ischemic human stroke indicates that the TTP threshold is crucial to reliably identify the tissue at risk; TTP >4 seconds best identifies penumbral flow; and TTP maps overestimate the extent of true hemodynamic compromise depending on the size of ischemia. Only if methodological restrictions are kept in mind, relative TTP maps are suitable to estimate the mismatch volume.
Multicenter Randomized Controlled Trial of an Outreach Nursing Support Program for Recently Discharged Stroke Patients
Authors: Boter Han
Published: October 2004

Background and Purpose—

Many stroke patients and informal carers experience a decreased quality of life after discharge home and are dissatisfied with the care received. We assessed the effectiveness of an outreach nursing care program.

Methods—

In a multicenter trial, 536 stroke patients were randomized at discharge to standard care (n=273) or standard care plus outreach care (n=263). The outreach care consisted of 3 telephone calls and 1 home visit within 5 months after discharge by 1 of 13 stroke nurses. Patients were masked for the trial objectives. Six months after discharge, they assessed the 2 primary outcomes: quality of life (Short Form 36 [SF-36]) and dissatisfaction with care. Secondary measures of outcome were disability, handicap, depression, anxiety, and use of health care services and secondary prevention drugs. Informal carers assessed strain, and social support. Analysis was by intention to treat.

Results—

Twelve patients died before follow-up, 38 declined outcome assessment, and 486 completed the primary outcome assessments. Outreach care patients had better scores on the SF-36 domain “Role Emotional” than controls (mean difference 7.9 [95% confidence limit, 0.1 to 15.7]). No statistically significant differences were found on the other primary outcome measures. For secondary outcomes, no statistically significant differences were found, except that intervention patients used fewer rehabilitation services (relative risk, 0.66 [0.44 to 1.00]) and had lower anxiety scores (median difference 1 [0.19 to 2.79]).

Conclusions—

This outreach nursing stroke care was not effective in improving quality of life and dissatisfaction with care of recently discharged patients.
Distribution and Cross-Sectional Age-Related Increases of Carotid Artery Intima-Media Thickness in Young Adults
Authors: Stein James H. , Douglas Pamela S. , Srinivasan Sathanur R. , Bond M. Gene , Tang Rong , Li Shengxu , Chen Wei , Berenson Gerald S.
Published: October 2004

Background and Purpose—

Reference values and age-related changes of carotid intima-media thickness (CIMT) have not been described in a community-based sample of young asymptomatic adults. CIMT measurements from the Bogalusa Heart Study, a study of the natural history of atherosclerosis in young adults and children, were used to characterize age-, race-, and sex-specific CIMT distributions and yearly rates of change.

Methods—

Age-, sex-, and race-specific CIMT percentile values and cross-sectional changes with age were estimated using B-mode carotid ultrasound images from 519 young adults (mean age 32 years, 61% female, 29% black). Nomograms of CIMT percentiles between the ages of 25 and 40 years are provided in 5-year increments.

Results—

CIMT was thickest in the carotid bulb and increased linearly with age, most rapidly in the bulb. With age, composite CIMT increased most slowly in white females and most rapidly in white males. Sample size estimates projected that 268 to 462 subjects are needed to detect CIMT changes ≥0.010 mm/year.

Conclusions—

These estimated CIMT distributions and percentiles can serve as reference values for assessment of subclinical atherosclerosis in young adults. The observed age-related differences in CIMT can be used to plan epidemiological and clinical trials investigating atherosclerosis and anti-atherosclerotic interventions.
Statins in Stroke Prevention and Carotid Atherosclerosis
Authors: Amarenco Pierre , Labreuche Julien , Lavallée Philippa , Touboul Pierre-Jean
Published: October 2004

Background and Purpose—

Previously published meta-analyses exploring the effect of statins on stroke incidence included 20 000 patients and found a 2% to 30% risk reduction. It is not clear whether this is attributable to low-density lipoprotein–cholesterol (LDL-C) reduction. Statin trials have now included >90 000 patients. We have determined the effect of statins and LDL-C reduction on stroke prevention

Summary of Review—

We performed a systematic review and meta-analysis of all randomized trials testing statin drugs published before August 2003. The trials were identified using a computerized PubMed search. We analyzed separately statin effect on incident strokes and on carotid intima-media thickness (IMT) according to LDL-C reduction. The relative risk reduction for stroke was 21% (odds ratio [OR], 0.79 [0.73 to 0.85]), with no heterogeneity between trials. Fatal strokes were reduced but not significantly: by 9% (OR, 0.91 [0.76 to 1.10]). There was no increase in hemorrhagic strokes (OR, 0.90 [0.65 to 1.22]). Statin size effect was closely associated with LDL-C reduction. Each 10% reduction in LDL-C was estimated to reduce the risk of all strokes by 15.6% (95% CI, 6.7 to 23.6) and carotid IMT by 0.73% per year (95% CI, 0.27 to 1.19).

Conclusions—

Statins may reduce the incidence of all strokes without any increase in hemorrhagic strokes, and this effect is mainly driven by the extent of between-group LDL-C reduction. Carotid IMT progression also strongly correlated with LDL-C reduction.
In-Hospital Initiation of Secondary Stroke Prevention Therapies Yields High Rates of Adherence at Follow-up
Authors: Ovbiagele Bruce , Saver Jeffrey L. , Fredieu Andre , Suzuki Shuichi , Selco Scott , Rajajee Venkatakrishna , McNair Norma , Razinia Tannaz , Kidwell Chelsea S.
Published: October 2004

Background and Purpose—

The Stroke PROTECT (Preventing Recurrence Of Thromboembolic Events through Coordinated Treatment) program systematically implements, at the time of acute transient ischemic attack (TIA) or ischemic stroke admission, 8 medication/behavioral secondary prevention measures known to improve outcome in patients with cerebrovascular disease. The objective of this study was to determine if the high utilization rates previously demonstrated at hospital discharge were maintained at 90 days after discharge.

Methods—

Data were prospectively collected on consecutively encountered ischemic stroke and TIA patients admitted to a university hospital stroke service beginning September 1, 2002. PROTECT interventions were initiated before hospital discharge in all PROTECT–target (underlying stroke mechanism large vessel atherosclerosis or small vessel disease) and PROTECT–ACS (At-risk for Coronary Sequelae) patients. Adherence to program goals was assessed 3 months after discharge.

Results—

During the period from September 2002 to August 2003, 144 individuals met criteria for PROTECT intervention. Of the 130 patients (90%) with available day 90 follow-up data, mean age was 72 (range, 37 to 95), and 63% were male. Adherence rates in patients without specific contraindications were 100% for antithrombotics, 99% for statins, 92% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 80% for thiazides. Awareness of the importance of calling 911 in response to stroke was 87%. Adherence to diet and exercise guidelines were 78% and 70%, respectively. Of the 24 smokers, tobacco cessation was maintained in 20 (83%).

Conclusions—

High rates of adherence to PROTECT therapies were maintained at 90 days after hospital discharge.
Generation of CMV-specific T lymphocytes using protein-spanning pools of pp65-derived overlapping pentadecapeptides for adoptive immunotherapy
Authors: Trivedi Deepa , Williams Roxanne Y. , O'Reilly Richard J. , Koehne Guenther
Published: October 2004

Cell-mediated immunity is essential for control of human cytomegalovirus (HCMV) infection. We used a pool of 138 synthetic overlapping pentadecapeptides overspanning the entire pp65 protein to generate polyclonal CMV-specific T-cell lines from 12 CMV-seropositive donors inheriting different HLA genotypes. Autologous monocyte-derived dendritic cells (DCs) pulsed with this complete pool consistently induced highly specific T cells that selectively recognized 1-3 pentadecapeptides identified by secondary responses to a mapping grid of pentadecapeptide subpools with single overlaps. Responses against peptide-loaded targets sharing single HLA class I or II alleles identified the restricting HLAalleles. HLA-A*0201+ donors consistently responded to pentadecapeptides containing HLA-A*0201-binding epitopeaa495-503NLVPMVATV. T-cell lines from other donors contained high frequencies of CD4 and/or CD8 T cells selectively reactive against peptides presented by other HLA alleles, including both known epitopes such as aa341-350QYDPVAALF (HLA-A*2402) as well as unreported epitopes such as aa267-275HERNGFTVL (HLA-B*4001 and B*4002) and aa513-523FFWDANDIYRI (HLA-DRB1*1301). These T cells consistently lysed CMV-infected target cells. Thus, this approach fosters expansion and selection of HLA-restricted CMV-pp65–reactive T-cell lines of high specificity that also lyse CMV-infected targets, and from a functional and regulatory perspective, may have advantages for generating virus-specific T cells for adoptive immunotherapy.
ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia
Authors: Chen Liguang , Apgar John , Huynh Lang , Dicker Frank , Giago-McGahan Teresa , Rassenti Laura , Weiss Arthur , Kipps Thomas J.
Published: October 2004

Chronic lymphocytic leukemia (CLL) B cells that express unmutated immunoglobulin heavy-chain variable region genes (IgVH) generally express ZAP-70, in contrast to normal B cells or most CLL cases with mutated IgVH. Following IgM ligation, ZAP-70+ CLL cells had significantly higher levels of phosphorylated p72Syk, BLNK, and phospholipase-Cγ (PLCγ) and had greater[Ca2+]i flux than did ZAP-70–negative CLL cases, including unusual ZAP-70–negative cases with unmutated IgVH. IgM ligation of ZAP-70–negative CLL B cells infected with an adenovirus vector encoding ZAP-70 induced significantly greater levels of phosphorylated p72Syk, BLNK, and PLCγ and had greater[Ca2+]i flux than did similarly stimulated, noninfected CLL cells or CLL cells infected with a control adenovirus vector. We conclude that expression of ZAP-70 in CLL allows for more effective IgM signaling in CLL B cells, a feature that could contribute to the relatively aggressive clinical behavior generally associated with CLL cells that express unmutated IgVH.
A touchdown nucleic acid amplification protocol as an alternative to culture backup for immunofluorescence in the routine diagnosis of acute viral respiratory tract infections
Authors: Coyle Peter V , Ong Grace M , O'Neill Hugh J , McCaughey Conall , De Ornellas Dennis , Mitchell Frederick , Mitchell Suzanne J , Feeney Susan A , Wyatt Dorothy E , Forde Marian , Stockton Joanne
Published: October 2004

Background

Immunofluorescence and virus culture are the main methods used to diagnose acute respiratory virus infections. Diagnosing these infections using nucleic acid amplification presents technical challenges, one of which is facilitating the different optimal annealing temperatures needed for each virus. To overcome this problem we developed a diagnostic molecular strip which combined a generic nested touchdown protocol with in-house primer master-mixes that could recognise 12 common respiratory viruses.

Results

Over an 18 month period a total of 222 specimens were tested by both immunofluorescence and the molecular strip. The specimens came from 103 males (median age 3.5 y), 80 females (median age 9 y) and 5 quality assurance scheme specimens. Viruses were recovered from a number of specimen types including broncho-alveolar lavage, nasopharyngeal secretions, sputa, post-mortem lung tissue and combined throat and nasal swabs. Viral detection by IF was poor in sputa and respiratory swabs. A total of 99 viruses were detected in the study from 79 patients and 4 quality control specimens: 31 by immunofluorescence and 99 using the molecular strip. The strip consistently out-performed immunofluorescence with no loss of diagnostic specificity.

Conclusions

The touchdown protocol with pre-dispensed primer master-mixes was suitable for replacing virus culture for the diagnosis of respiratory viruses which were negative by immunofluorescence. Results by immunofluorescence were available after an average of 4–12 hours while molecular strip results were available within 24 hours, considerably faster than viral culture. The combined strip and touchdown protocol proved to be a convenient and reliable method of testing for multiple viruses in a routine setting.
Screening for known mutations in EIF2Bgenes in a large panel of patients with premature ovarian failure
Authors: Fogli Anne , Gauthier-Barichard Fernande , Schiffmann Raphael , Vanderhoof Vien H , Bakalov Vladimir K , Nelson Lawrence M , Boespflug-Tanguy Odile
Published: October 2004

Background

Premature Ovarian Failure (POF), defined as the development of hypergonadotropic amenorrhea before the age of 40 years, occurs in about 1% of all women. Other than karyotype abnormalities, very few genes are known to be associated with this ovarian dysfunction. Recently, in seven patients who presented with POF and white matter abnormalities on MRI (ovarioleukodystrophy) eight mutationswere found in EIF2B2, 4 and 5.

Methods

To further test the involvement of known mutations of EIF2B genes in POF, we screened 93 patients with POF who did not have identified leukodystrophy or neurological symptoms. We evaluated these eight mutations and two additional mutations that had been found in patients with milder forms of eIF2B-related disorders. We used restriction enzymes and direct sequencing.

Results

None of the known mutations in EIF2B genes, either homozygous or heterozygous, were identified in our 93 patients with pure 46,XX POF. The upper 95 % confidence limit of the proportion 0/93 is 3.2%.

Conclusions

We conclude that eIF2B mutations, already described in cases of POF associated with white matter abnormalities, are an uncommon cause of pure spontaneous premature ovarian failure.
Genomic imprinting and assisted reproduction
Authors: Paoloni-Giacobino Ariane , Chaillet J Richard
Published: October 2004

Imprinted genes exhibit a parent-of-origin specific pattern of expression. Such genes have been shown to be targets of molecular defects in particular genetic syndromes such as Beckwith-Wiedemann and Angelman syndromes. Recent reports have raised concern about the possibility that assisted reproduction techniques, such as in vitro fertilization or intracytoplasmic sperm injection, might cause genomic imprinting disorders. The number of reported cases of those disorders is still too small to draw firm conclusions and the safety of these widely used assisted reproduction techniques needs to be further evaluated.
Thumb force deficit after lower median nerve block
Authors: Li Zong-Ming , Harkness Daniel A , Goitz Robert J
Published: October 2004

Purpose

The purpose of this study was to characterize thumb motor dysfunction resulting from simulated lower median nerve lesions at the wrist.

Methods

Bupivacaine hydrochloride was injected into the carpal tunnel of six healthy subjects to locally anesthetize the median nerve. Motor function was subsequently evaluated by measuring maximal force production in all directions within the transverse plane perpendicular to the longitudinal axis of the thumb. Force envelopes were constructed using these measured multidirectional forces.

Results

Blockage of the median nerve resulted in decreased force magnitudes and thus smaller force envelopes. The average force decrease around the force envelope was 27.9%. A maximum decrease of 42.4% occurred in a direction combining abduction and slight flexion, while a minimum decrease of 10.5% occurred in a direction combining adduction and slight flexion. Relative decreases in adduction, extension, abduction, and flexion were 17.3%, 21.2%, 41.2% and 33.5%, respectively. Areas enclosed by pre- and post-block force envelopes were 20628 ± 7747 N.N, and 10700 ± 4474 N.N, respectively, representing an average decrease of 48.1%. Relative decreases in the adduction, extension, abduction, and flexion quadrant areas were 31.5%, 42.3%, 60.9%, and 52.3%, respectively.

Conclusion

Lower median nerve lesion, simulated by a nerve block at the wrist, compromise normal motor function of the thumb. A median nerve block results in force deficits in all directions, with the most severe impairment in abduction and flexion. From our results, such a means of motor function assessment can potentially be applied to functionally evaluate peripheral neuropathies.
Rehabilitation robotics: pilot trial of a spatial extension for MIT-Manus
Authors: Krebs Hermano I , Ferraro Mark , Buerger Stephen P , Newbery Miranda J , Makiyama Antonio , Sandmann Michael , Lynch Daniel , Volpe Bruce T , Hogan Neville
Published: October 2004

Background

Previous results with the planar robot MIT-MANUS demonstrated positive benefits in trials with over 250 stroke patients. Consistent with motor learning, the positive effects did not generalize to other muscle groups or limb segments. Therefore we are designing a new class of robots to exercise other muscle groups or limb segments. This paper presents basic engineering aspects of a novel robotic module that extends our approach to anti-gravity movements out of the horizontal plane and a pilot study with 10 outpatients. Patients were trained during the initial six-weeks with the planar module (i.e., performance-based training limited to horizontal movements with gravity compensation). This training was followed by six-weeks of robotic therapy that focused on performing vertical arm movements against gravity. The 12-week protocol includes three one-hour robot therapy sessions per week (total 36 robot treatment sessions).

Results

Pilot study demonstrated that the protocol was safe and well tolerated with no patient presenting any adverse effect. Consistent with our past experience with persons with chronic strokes, there was a statistically significant reduction in tone measurement from admission to discharge of performance-based planar robot therapy and we have not observed increases in muscle tone or spasticity during the anti-gravity training protocol. Pilot results showed also a reduction in shoulder-elbow impairment following planar horizontal training. Furthermore, it suggested an additional reduction in shoulder-elbow impairment following the anti-gravity training.

Conclusion

Our clinical experiments have focused on a fundamental question of whether task specific robotic training influences brain recovery. To date several studies demonstrate that in mature and damaged nervous systems, nurture indeed has an effect on nature. The improved recovery is most pronounced in the trained limb segments. We have now embarked on experiments that test whether we can continue to influence recovery, long after the acute insult, with a novel class of spatial robotic devices. This pilot results support the pursuit of further clinical trials to test efficacy and the pursuit of optimal therapy following brain injury.