bluuebunny/crossref_metadata_2025 huggingface dataset:
The preparation and aqueous basic oxidation of diethyl 1‐methyl‐3‐hydroxy‐5‐phenylpyrrole‐2,4‐dicarboxylate
Authors: Campaigne E. , Shutske G. M.
Published: April 2009

Diethyl 1‐methyl‐3‐hydroxy‐5‐phenylpyrrole‐2,4‐dicarboxylate has been synthesized in good yield from readily available materials, diethyl benzylidenemalonate and ethyl sarcosinate. It was found to react with oxygen in aqueous base to give two oxidation products, ethyl 1‐methyl‐2‐oxo‐3‐hydroxy‐5‐phenyl‐3‐pyrroline‐4‐carboxylate (9) and ethyl 1‐methyl‐2,3‐dioxo‐5‐phenyl‐4‐pyrroline‐4‐carboxylate (10). These two oxidation products are postulated to arise from the decomposition of a common intermediate, diethyl 1‐methyl‐2‐hydroperoxy‐3‐oxo‐5‐phenyl‐4‐pyrroline‐2,4‐dicarboxylate. Reaction of the title compound with oxygen in pyridine containing Triton B again produced two products, the dioxo compound (10) and diethyl 1‐methyl‐2‐hydroxy‐3‐oxo‐5‐phenyl‐4‐pyrroline‐2,4‐dicarboxylate (12). Compound 12 was shown to react in aqueous base to give exclusively 9. The hydration of 10 in acidic and basic media is also discussed.
Bridged 1,4‐benzoxazocines from 5‐hydroxy‐3‐phenyl‐2‐benzofuranone
Authors: Zaugg H. E. , Holland J. B. , Dunnigan D. A. , Denet R. W.
Published: April 2009

A previously described neighboring group reaction has been extended to the synthesis of hydroxy‐substituted bridged 1,4‐benzoxazocines (i.e., 7, 8) bearing a structural analogy to potent analgetics of the hydroxy‐6,7‐benzomorphan series. In contrast to the latter, the presence of a hydroxyl group in the aromatic ring of the present series destroys all analgesic activity possessed by the unsubstituted system.
Preparation of certain 2‐N‐alkylamino‐and 2‐N,N‐dialkylamino‐10‐methylphenothiazines via phenothiazyne
Authors: Biehl E. R. , Patrizi V. , Lapis S. , Reeves P. C.
Published: April 2009

The treatment of 2‐chloro‐10‐methylphenothiazine, 1, with lithium alkylamide/alkylamine or lithium dialkylamide/dialkylamine yields the corresponding 2‐N‐alkylamino‐or 2‐N,N‐dialkylaminophenothiazines in good yields via phenothiazyne. No significant reduction of 1 to 10‐methylphenothiazine is observed. Yields of amines obtained by this method are considerably higher than those obtained by reacting 1 with sodamide in refluxing amine solvent. Attempts to introduce the ‐CH2CN moiety onto the phenothiazine nucleus by treating 1 with sodamide and acetonitrile in liquid ammonia produced only 2‐amino‐10‐methylphenothiazine.
Acetylation and methylation of flavins and the effects on isoalloxazinc ring protonation
Authors: McCormick Donald B.
Published: April 2009

The acetylation of N10‐(poly)hydroxy side chains of 7,8‐dimethylisoalloxazines has been accomplished in conventional ways using perchloric acid as catalyst with excess acetic anhydride in acetic acid for flavins or in pyridine for the coenzyme, D‐riboflavin‐5′‐phosphate (FMN). Although complete acetylation of the primary and secondary alcoholic functions of flavins with various hydroxyalkyl chains occurs, the primary product purified by DEAE‐cellulose chromatotraphy of the reaction with FMN, followed by neutralization, is the 2′,3′‐diacetyl derivative. Diacetyl FMN and other acetylated flavins exhibit the usual absorption spectra of prolonated isoalloxazinium compounds, with λ max values of 390, 264, and 222 nm, only upon greater acidification than necessary for their hydroxy or especially deoxy counterparts. A similar though less marked effect is found with flavins methylated by treatment with methyl iodide and silver oxide in dimethylformamide. Protonation of the isoalloxazine ring, which occurs on the most basic nitrogen 1, is most effectively impaired by acetylation or methylation of the proximal 2′‐hydroxyl group.
Synthesis of pyrido[3′,2′:4,5] thieno[3,2‐d]pyrimidine derivatives
Authors: Schneller S. W. , Clough F. W.
Published: April 2009

Pyrido [3′,2′:4,5]thieno[3,2‐d] pyrimidine and several of its derivatives have been synthesized.
N‐methyl chemical shifts in quaternized azoles, isazoles, diazoles, and their benzologs
Authors: Davis M. , Deady L. W. , Homfeld E.
Published: April 2009

The N‐methyl chemical shifts in the title compounds arc reported. In the 1,3‐orientation, the shift appears to be determined by resonance from the heteroatom, with the order of donating ability being NMe > O > S ˜ Se. In the 1,2‐orientation, electronegativity effects are also important as evidenced by a general downfield shift, and the order of donation is NMe > S ˜ Se > O.
Studies on the syntheses of heterocyclic compounds. Part DLXXXII . Synthesis of benzo[a] quinolizine derivatives and pyrrolo[2,1‐a] isoquinoline derivatives by phenolic cyclization
Authors: Kametani Tetsuji , Kigasawa Kazuo , Hüragi Mineharu , Ishimaru Hazuhide , Haga Seiji
Published: April 2009

Phenolic cyclization of 3‐hydroxy phenethylamine with acylbutyric acid and acylpropionic acid afforded the lactam of the corresponding benzol[a] quinolizine and pyrrolo[2, 1‐a]isoquinoline derivatives, which were reduced with lithium aluminum hydride to give the benzol[a]quinolizine and pyrrolo[2,1 ‐a] isoquinoline derivatives, respectively. The configurations of acetyl derivatives of these products were determined.
Novel sultones. II. 1,4‐dialkyl‐9‐oxo‐9H‐indeno [1,2‐d] [1,2] oxathiin 3,3‐dioxides
Authors: Paull Kenneth D. , Cheng C. C.
Published: April 2009

A new type of sultone, 1,4‐dialkyl‐9‐oxo‐9H‐indeno[1,2‐d] [1,2]oxathiin 3,3‐dioxides, can be readily synthesized by treating 3 hydroxy‐3‐phenylalkanoic acid with a mixture of acid anhydride and sulfuric acid. A mechanism for the formation of these sultones is proposed. A postulated intermediate in the preparation of the 1,4‐dimethyl analog, 3‐ethylideneindan‐1‐one, was prepared and subsequently converted to the same 1,4‐dimethyl compound by the same reagents. Bromination of these sultones gave the I‐bromalkyl derivatives while treatment with hydrazine yielded pyrazolium sulfonates. Under different reaction conditions, 3‐ethylidene‐indan‐1‐one formed a pyrylium salt, which, in turn, was converted to a fused tricyclic pyridine derivative with ammonia.
Pyrazolopyrimidine nucleosides. Part VII. The synthesis of certain pyrazolo [3,4‐d] pyrimidine nucleosides related to the nucleoside antibiotics toyocamycin and sangivamycin
Authors: Earl Robert A. , Townsend Leroy B.
Published: April 2009

The condensation of 4‐acetamido‐3‐cyanopyrazolo[3,4‐d]pyrimidine (5) with crystalline 2,3,5‐tri‐O‐acetyl‐β‐D‐ribofuranosyl chloride (6) has furnished a good yield of nucleoside material (7) which on treatment with sodium methoxide in methanol provided a high yield of nucleoside which was subsequently established as methyl 4‐amino‐1‐(β‐D‐ribofuranosyl)pyrazolo[3,4‐d]‐pyrimidine‐3‐formimidate monohydrate (11). The formimidate function of 11 was found to be highly reactive and 11 was readily converted into the corresponding carhoxamidine (8), carboxamidoxime (14) and carboxamidrazone (15) when treated with the appropriate nucleophiles. Treatment of the imidate (11) with sodium hydrogen sulfide gave a high yield of the thiocarboxamide (12) which was then readily converted into 4‐amino‐3‐cyano‐1‐(β‐D‐ribofuranosyl)pyrazolo[3,4‐d]pyrimidine (16). Aqueous base transformed 11 into 4‐amino‐1‐(β‐D‐ribofuranosyl)‐pyrazolo[3,4‐d]pyrimidine‐3‐carboxamide (10) while more vigorous basic hydrolysis provided the corresponding carboxylic acid (9) in nearly quantitative yield. Decarboxylation of 9 proceeded smoothly in hot sulfolane to provide the known 4‐amino‐1‐(β‐D‐ribofuranosyl)pyrazolo[3,4‐d]pyrimidine (13) in 68% yield which unequivocally established the site of ribosylation and anomeric configuration for all nucleosides reported in this investigation.
Spirans XXII. Synthesis of 4,4‐dialkyl‐4‐germacyclohexanone and 8,8‐dialkyl‐8‐germaazaspiro [4.5] decanes
Authors: Rice Leonard M. , Wheeler James W. , Geschickter Charles F.
Published: April 2009

4,4‐Dialkyl‐4‐germacyclohexanones have been synthesized and their reactions studied. The diethyl ketone has been converted into N‐(‐dimethylaminopropyl)‐2 aza‐8,8‐diethyl‐8‐germaspiro[4.5]decane (16). The biological properties of 16 have been examined in some detail. The reactions of this new ketone with some other reagents are reported.
On the behavior of α‐brominated dimethyl o‐benzenediacetate toward nitrogen nucleophiles . Part I. Reaction of dimethyl α,α'‐dibromo o‐benzenediacetate with hydrazines
Authors: Cignarella G. , Savelli F. , Cerri R. , Sanna P.
Published: April 2009

Meso‐ (1a) and racemic dimethyl α,α'‐dibromo o‐benzenediacetate (1b) when condensed with hydrazine and methylhydrazine furnished respectively 1,3‐dicarbomethoxyisoindole (5a) and its N‐methyl derivative (5b). Reaction of phenylhydrazine with 1a led to the N‐phenylisoindole (5c) and to the N‐anilino isoindoline (6) as the cis isomer; conversely, 1b was transformed into a mixture of the 2‐phenyl‐1,2,3,4‐tetrahydrophthalazine (7), the trans isomer of (6), the N‐anilinoisoindole (5d) and dimethyl α‐(N'‐phenylhydrazino)‐o‐benzenediacetate (8). Compounds 1a and 1b were also condensed with acetylhydrazine to give a mixture of the N‐acetylaminoisoindoline (12) and of the 2‐acetyl‐1,2,3,4‐tetrahydrophthalazine (13).
N1‐Substitution in 2‐methyl‐4(5)nitroimidazole. III. New syntheses of 1‐(2′‐(ethylsulfonyl)ethyl)‐2‐methyl‐5‐nitroimidazole
Authors: Čaplar V. , Šunjić V. , Kafjež F.
Published: April 2009

Some new syntheses of 1‐[2′‐(ethylsulfonyl)ethyl]‐2‐methyl‐5‐nitroimidazole (IV), a new antitrichomonal agent are described. The most successful method proved to be alkylation of sodium ethanesulfinate (XXI) with 1‐(2′‐haloethyl)‐2‐methyl‐5‐nitroimidazoles (1a,b) in dimethylformamide.
Anilinopyrylium salts. Their synthesis and conversion to other heterocyclic systems
Authors: Van Allan J. A. , Chang S. Chie
Published: April 2009

Two methods for the preparation of anilinopyrylium salts are described. The conversion of these salts to pyrans, pyridines, and nitrobenzenes is discussed. Azepines, benzimidazoles, and benxotriazoles are readily obtained from the o‐aminoanilinopyrylium salts.
Alkaline condensation of 9,10‐phenanthrenedione with N,N‐dialkylguanidines. A novel synthesis of 2′‐(dialkylamino)spiro[9H‐fluorene‐9,4′‐[4H]imidazol]‐5′(3′H)ones
Authors: Itano Harvey A.
Published: April 2009

9,10‐Phenanthrenedione was reacted with equimolar amounts of N,N‐dimethylguanidine or creatine in 0.2 N potassium hydroxide in ethanol‐water, 7:3 to obtain 2′‐(dimethylamino)spiro‐[9H‐fluorene‐9,4′‐[4H]imidazol]‐5′(3′H)one or N‐(3′,5′‐dihydro‐5′‐oxospiro[9H‐fluorene‐9,4′‐[4H]imidazol]‐2′‐yl)‐N‐methylglycine, respectively. These products are the first derivatives of this ring system with 2′‐amino substituents. Formation of these products accounts for the previously reported absence of fluorescence when 9,10‐phenanthrenedione reacts with N,N‐di‐substituted guanidines.
Analysis of full and partial agonists binding toβ2‐adrenergic receptor suggests a role of transmembrane helix V in agonist‐specific conformational changes
Authors: Katritch Vsevolod , Reynolds Kimberly A. , Cherezov Vadim , Hanson Michael A. , Roth Christopher B. , Yeager Mark , Abagyan Ruben
Published: April 2009

The 2.4 Å crystal structure of theβ2‐adrenergic receptor (β2AR) in complex with the high‐affinity inverse agonist (−)‐carazolol provides a detailed structural framework for the analysis of ligand recognition by adrenergic receptors. Insights into agonist binding and the corresponding conformational changes triggering G‐protein coupled receptor (GPCR) activation mechanism are of special interest. Here we show that while the carazolol pocket captured in theβ2AR crystal structure accommodates (−)‐isoproterenol and other agonists without steric clashes, a finite movement of the flexible extracellular part of TM‐V helix (TM‐Ve) obtained by receptor optimization in the presence of docked ligand can further improve the calculated binding affinities for agonist compounds. Tilting of TM‐Ve towards the receptor axis provides a more complete description of polar receptor–ligand interactions for full and partial agonists, by enabling optimal engagement of agonists with two experimentally identified anchor sites, formed by Asp113/Asn312 and Ser203/Ser204/Ser207 side chains. Further, receptor models incorporating a flexible TM‐V backbone allow reliable prediction of binding affinities for a set of diverse ligands, suggesting potential utility of this approach to design of effective and subtype‐specific agonists for adrenergic receptors. Systematic differences in capacity of partial, full and inverse agonists to induce TM‐V helix tilt in theβ2AR model suggest potential role of TM‐V as a conformational “rheostat” involved in the whole spectrum ofβ2AR responses to small molecule signals. Copyright © 2009 John Wiley & Sons, Ltd.
Hepatic regeneration is decreased in a rat model of sinusoidal obstruction syndrome
Authors: Schiffer Eduardo , Frossard Jean‐Louis , Rubbia‐Brandt Laura , Mentha Gilles , Pastor Catherine M.
Published: April 2009

Background and Objectives

Oxaliplatin is a chemotherapeutic drug for colorectal adenocarcinoma able to extend the indications for resection of colorectal liver metastases. However, the drug may severely injure hepatic sinusoids, inducing a sinusoidal obstruction syndrome in non‐tumoral parenchyma with a risk of decreased regeneration in the remnant liver following partial hepatectomy.

Methods

We then investigated the evolution of hepatic functions and liver regeneration following partial hepatectomy in rats with sinusoidal obstruction syndrome. The sinusoidal obstruction syndrome was induced with a single intragastric administration of monocrotaline (MCT).

Results

MCT administration induced obstruction of the hepatic microcirculation and increased portal pressure, hepatic VEGF expression, and Ki67 positive hepatocytes. A mild cholestasis was present without modification of hepatic tests. Following a 70% hepatectomy, liver regeneration was significantly impaired by MCT administration and this impaired regeneration was associated with hepatocellular injury evidenced 1 week after hepatectomy.

Conclusions

The presence of sinusoidal obstruction syndrome impairs hepatic regeneration in this rat model of sinusoidal obstruction syndrome. J. Surg. Oncol. 2009;99:439–446. © 2009 Wiley‐Liss, Inc.
Hypertonia in childhood secondary dystonia due to cerebral palsy is associated with reflex muscle activation
Authors: van Doornik Johan , Kukke Sahana , Sanger Terence D.
Published: April 2009

It is often assumed that co‐contraction of antagonist muscles is responsible for increased resistance to passive movement in hypertonic dystonia. Although co‐contraction may certainly contribute to hypertonia in some patients, the role of reflex activation has never been investigated. We measured joint torque and surface electromyographic activity during passive flexion and extension movements of the elbow in 8 children with hypertonic arm dystonia due to dyskinetic cerebral palsy. In all cases, we found significant phasic electromyographic activity in the lengthening muscle, consistent with reflex activity. By correlating activation with position or velocity of the limb, we determined that some children exhibit position‐dependent activation, some exhibit velocity‐dependent activation, and some exhibit a mixed pattern of activation. We conclude that involuntary or reflex muscle activation in response to stretch may be a significant contributor to increased tone in hypertonic dystonia, and we conjecture that this activation may be more important than co‐contraction for determining the resistance to passive movement. © 2009 Movement Disorder Society
Telemedicine for the care of nursing home residents with Parkinson's disease
Authors: Biglan Kevin M. , Voss Tiffini S. , Deuel Lisa M. , Miller David , Eason Sheelah , Fagnano Maria , George Benjamin P. , Appler Anna , Polanowicz Joyce , Viti Lucy , Smith Sandy , Joseph Anthony , Dorsey E. Ray
Published: April 2009

Individuals with Parkinson's disease (PD) often require nursing home care, where access to neurologists is limited. Telemedicine uses information and communication technologies to provide health care to individuals who are geographically separate from providers. We present a video report of a nursing home resident with PD who received telemedicine visits over 8 months from a movement disorders specialist. The visits resulted in improvements in motor and cognitive symptoms and suggest that telemedicine may be useful for delivering care to this population. © 2009 Movement Disorder Society
Immunopathogenic mechanisms in tourette syndrome: A critical review
Authors: Martino Davide , Dale Russell C. , Gilbert Donald L. , Giovannoni Gavin , Leckman James F.
Published: April 2009

Tourette syndrome (TS) has a multifactorial etiology, in which genetic, environmental, immunological and hormonal factors interact to establish vulnerability. This review: (i) summarizes research exploring the exposure of TS patients to immune‐activating environmental factors, and (ii) focuses on recent findings supporting a role of the innate and adaptive immune systems in the pathogenesis of TS and related disorders. A higher exposure prior to disease onset to group A β‐haemolytic streptococcal (GABHS) infections in children with tics and obsessive‐compulsive (OC) symptoms has been documented, although their influence upon the course of disease remains uncertain. Increased activation of immune responses in TS is suggested by changes in gene expression profiles of peripheral immune cells, relative frequency of lymphocyte subpopulations, and synthesis of immune effector molecules. Increased activity of cell‐mediated mechanisms is suggested by the increased expression of genes controlling natural killer and cytotoxic T cells, increased plasma levels of some pro‐inflammatory cytokines which correlate with disease severity, and increased synthesis of antineuronal antibodies. Important methodological differences might account for some inconsistency among results of studies addressing autoantibodies in TS. Finally, a general predisposition to autoimmune responses in TS patients is indicated by the reduced frequency of regulatory T cells, which induce tolerance towards self‐antigens. Although the pathogenic role of immune activation in TS has not been definitively proven, a pathophysiological model is proposed to explain the possible effect of immunity upon dopamine transmission regulation and the generation of tics. © 2009 Movement Disorder Society
Motor complications in patients form the German Competence Network on Parkinson's disease and the DRD3 Ser9Gly polymorphism
Authors: Paus Sebastian , Gadow Franziska , Knapp Michael , Klein Christine , Klockgether Thomas , Wüllner Ullrich
Published: April 2009

In addition to levodopa treatment and disease duration, genetic predisposition might contribute to the development of medication‐related complications in Parkinson's disease (PD). As recent observations indicate the dopamine D3 receptor (DRD3) to modulate both therapeutic action of levodopa and dyskinesia, we reappraised the impact of the DRD3 Ser9Gly polymorphism on development of motor complications in a large scale association study based on the gene bank of the German Competence Network on Parkinson's disease. Stepwise regression analysis revealed no effect of DRD3 Ser9Gly on chorea, dystonia, or motor fluctuations in PD, despite incorporating established clinical risk factors to avoid overlooking an effect of genotype. Duration of PD was confirmed as the most important clinical risk factor, followed by age of disease onset and female sex. Additional studies incorporating grading of motor complications, and combinations of risk genotypes, are warranted. © 2009 Movement Disorder Society
Hyperhomocysteinemia in levodopa‐treated patients with Parkinson's disease dementia
Authors: Zoccolella Stefano , dell'Aquila Claudia , Abruzzese Giovanni , Antonini Angelo , Bonuccelli Ubaldo , Canesi Margherita , Cristina Silvano , Marchese Roberta , Pacchetti Claudio , Zagaglia Roberto , Logroscino Giancarlo , Defazio Giovanni , Lamberti Paolo , Livrea Paolo
Published: April 2009

Dementia is a frequent non‐motor feature of Parkinson's disease (PD). Elevated plasma homocysteine (Hcy) levels have been associated with both cognitive impairment and dementia. Increased Hcy levels have been observed in levodopa‐treated patients with PD. The objective of our study was to evaluate the association between plasma Hcy levels and dementia in PD. We performed a multicenter cross‐sectional study on patients with PD with (PDD) and without (PDnD) dementia and age‐ and sex‐matched healthy controls. We compared Hcy levels in patients with PDD and PDnD and healthy controls, and we performed logistic regression analysis to search for an association between the presence of dementia and increased Hcy levels in PD. Patients with PD (121), PDD (42), and PDnD (79), and age‐ and sex‐matched controls (154) were enrolled. Hcy levels were higher in patients with PD compared to controls (17.5 μmol/L ± 10.2 vs. 11 ± 4.1;P< 0.00001). Among patients with PD, Hcy levels were higher in the PDD group compared to the PDnD group (20.7 μmol/L ± 12.1 vs. 15.8 ± 8.5;P= 0.002). In a multivariate logistic regression model, higher Hcy levels [Odds ratios comparing the top (>18.9 μmol/L) with the bottom tertile (<12.4 μmol/L): 3.68; 95% CI: 1.14–11.83] were significantly associated with dementia. These data support the association between elevated Hcylevels and the presence of dementia in PD. © 2009 Movement Disorder Society
Motor patterns in Parkinson's disease: A data‐driven approach
Authors: van Rooden Stephanie M. , Visser Martine , Verbaan Dagmar , Marinus Johan , van Hilten Jacobus J.
Published: April 2009

To identify patterns of motor disturbances in Parkinson's disease (PD) and evaluate their relation with other PD domains. A cohort of 399 PD patients was randomly divided into two samples. Factors within the motor section of the SPES/SCOPA were identified by exploratory factor analysis on data from the first sample and next tested by confirmatory factor analysis in the second sample. Relations with other PD domains were evaluated by regression analyses. A four factor model was found to be valid. This included a tremor, a bradykinetic‐rigid, and two axial factors. One axial factor (“rise”, “gait”, “postural instability”) was associated with age and cognition, while the other axial factor (“freezing”, “speech”, “swallowing”) was related to dopaminergic medication and complications of therapy. Both other factors showed no relevant associations with demographic and clinical characteristics. The identification of motor factors and their relation with other domains of the disease may help to elucidate the mechanisms responsible for these associations and provide an objective base for further research on subtypes in PD. © 2009 Movement Disorder Society
Dystonic storm due to Batten's disease treated with pallidotomy and deep brain stimulation
Authors: Elkay Muruvet , Silver Kenneth , Penn Richard D. , Dalvi Arif
Published: April 2009

To report a novel treatment approach, pallidotomy and deep brain stimulation (DBS), in two sisters with dystonic storm due to Batten's disease. This study is based on long‐term follow‐up of two sisters, presenting with dystonic storm and their response to pallidotomy and DBS. These sisters, who had visual loss, seizures, and progressive psychomotor decline, experienced progressive disabling abnormal movements culminating in dystonic storm at the age of 15 and 17 years, respectively. In addition to intubation and sedation, multiple medications, including botulinum toxin injections and intrathecal baclofen infusion were tried in both patients without any benefit. The old sister underwent bilateral pallidotomy. Within 10 days postoperatively, there was marked improvement in dystonic storm. She was free of abnormal movements for 9 months. Then she started having opisthotonus lasting 20 seconds to an hour several times/day, but over 6 years abnormal movements are markedly improved, and not returned to pre‐pallidotomy level. The young sister underwent both bilateral pallidotomy and DBS, 3 weeks apart. She was free of abnormal movements for 7 months and able to maintain reduction in the abnormal movements by adjusting DBS settings. Pallidotomy and DBS should be considered in dystonic storm due to Batten's disease. © 2009 Movement Disorder Society
Pathological gambling amongst Parkinson's disease and ALS patients in an online community (PatientsLikeMe.com)
Authors: Wicks Paul , MacPhee Graeme J.A.
Published: April 2009

Pathological gambling (PG) has been identified in Parkinson's disease (PD), but such gambling behaviors may also occur in amyotrophic lateral sclerosis (ALS). We sought to estimate the prevalence of PG amongst members of a web‐based community, PatientsLikeMe.com. A survey was constructed, consisting of demographic information, the South Oaks Gambling Screen (SOGS), the K‐6 measure of distress, and items related to motivation for gambling. Data were obtained from 236 ALS patients and 208 PD patients. Of the PD patients, 13% were classified as problem gamblers compared with 3% of ALS patients (χ2 = 14.005, P ≤ 0.001). PD patients reported thoughts about gambling to be more distressing, harder to resist and more outside their control than ALS patients. Thus, the higher prevalence of compulsive behavior in PD may relate to damaged reward pathways or medication rather than to the effects of living with a chronic progressive neurological disorder per se. © 2009 Movement Disorder Society
Subthalamic nucleus deep brain stimulation for camptocormia associated with Parkinson's disease
Authors: Sako Wataru , Nishio Masami , Maruo Tomoyuki , Shimazu Hideki , Matsuzaki Kazuhito , Tamura Tetsuya , Mure Hideo , Ushio Yukitaka , Nagahiro Shinji , Kaji Ryuji , Goto Satoshi
Published: April 2009

Camptocormia becomes increasingly recognized as a disabling symptom associated with Parkinson's disease (PD). We here report six patients with advanced PD in whom continuous bilateral stimulation of the subthalamic nucleus produced substantial (mean 78% ± 9.1% of the thoracolumbar angle) improvement of camptocormia along with other motor symptoms. © 2009 Movement Disorder Society
Nigrostriatal upregulation of 5‐HT2A receptors correlates with motor dysfunction in progressive supranuclear palsy
Authors: Stamelou Maria , Matusch Andreas , Elmenhorst David , Hurlemann René , Eggert Karla M. , Zilles Karl , Oertel Wolfgang H. , Höglinger Günter U. , Bauer Andreas
Published: April 2009

A dysfunction of multiple neurotransmitter systems is assumed as a neurochemical basis of the akinetic‐rigid syndrome of progressive supranuclear palsy (PSP). In vitro studies have produced conflicting results on the serotoninergic system in PSP. We, therefore, studied the binding potential of the serotonin 2A (5‐HT2A) receptor ligand [18F]altanserin in 8 patients with clinically probable PSP and 13 healthy controls using positron emission tomography. We found an up‐regulation of 5‐HT2A receptors in the substantia nigra and, to a lower degree, in the striatum, while neocortical 5‐ HT2A receptor densities showed no changes upon partial‐volume correction. Nigral and striatal receptor changes were significantly correlated with patients' scores of motor dysfunction (UPDRS III, PSP‐rating scale) pointing to a functional relevance of the described findings. © 2009 Movement Disorder Society
Motion corrected intracranial MRA using PROPELLER with RF quadratic encoding
Authors: Zwart Nicholas R. , Pipe James G.
Published: April 2009

A new motion corrected Time‐of‐Flight MRA technique named Variable Pitch PROPELLER is presented. This technique employs the PROPELLER acquisition and reconstruction scheme for in‐plane bulk motion correction. A non‐ Fourier through‐plane encoding mechanism called quadratic encoding boosts SNR, relative to conventional 2D MRA, in lieu of traditional 3D encoding. Partial Fourier encoding is applied in the slice direction for a further reduction in scan time. This work details the construction and optimization of this technique. VPPROP MRAs are compared with a clinical MOTSA protocol. Initial results show promising robustness to bulk motion effects. The comparisons with MOTSA provide insight as to the additions required to create a comparable scan. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Accelerated three‐dimensional upper airway MRI using compressed sensing
Authors: Kim Yoon‐Chul , Narayanan Shrikanth S. , Nayak Krishna S.
Published: April 2009

In speech‐production research, three‐dimensional (3D) MRI of the upper airway has provided insights into vocal tract shaping and data for its modeling. Small movements of articulators can lead to large changes in the produced sound, therefore improving the resolution of these data sets, within the constraints of a sustained speech sound (6–12 s), is an important area for investigation. The purpose of the study is to provide a first application of compressed sensing (CS) to high‐resolution 3D upper airway MRI using spatial finite difference as the sparsifying transform, and to experimentally determine the benefit of applying constraints on image phase. Estimates of image phase are incorporated into the CS reconstruction to improve the sparsity of the finite difference of the solution. In a retrospective subsampling experiment with no sound production, 5× and 4× were the highest acceleration factors that produced acceptable image quality when using a phase constraint and when not using a phase constraint, respectively. The prospective use of a 5× undersampled acquisition and phase‐constrained CS reconstruction enabled 3D vocal tract MRI during sustained sound production of English consonants /s/, /∫/, /l/, and /r/ with 1.5 × 1.5 × 2.0 mm3 spatial resolution and 7 s of scan time. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Online correction of respiratory‐induced field disturbances for continuous MR‐thermometry in the breast
Authors: Hey S. , Maclair G. , de Senneville B. D. , Lepetit‐Coiffe M. , Berber Y. , Köhler M. O. , Quesson B. , Moonen C. T. W. , Ries M.
Published: April 2009

MR‐thermometry allows monitoring of the local temperature evolution during minimally invasive interventional therapies. However, for the particular case of MR‐thermometry in the human breast, magnetic field variations induced by the respiratory cycle lead to phase fluctuations requiring a suitable correction strategy to prevent thermometry errors. For this purpose a look‐up‐table‐based multibaseline approach as well as a model‐based correction algorithm were applied to MR‐thermometry to correct for the periodic magnetic field changes. The proposed correction method is compatible with a variety of sensors monitoring the current respiratory state. The ability to remove phase artefacts during MR‐thermometry of the human breast was demonstrated experimentally in five healthy volunteers during 3 min of free‐breathing using pencil‐beam navigators for respiratory control. An increase of 170–530% in temperature precision was observed for the look‐up‐table‐based approach, whereas a further improvement by 16–36% could be achieved by applying the extended model‐based correction. Magn Reson Med, 61:1494–1499, 2009. © 2009 Wiley‐Liss, Inc.
In vivo measurement of local aortic pulse‐wave velocity in mice with MR microscopy at 17.6 tesla
Authors: Herold Volker , Parczyk Marco , Mörchel Philipp , Ziener Christian H. , Klug Gert , Bauer Wolfgang R. , Rommel Eberhard , Jakob Peter M.
Published: April 2009

Transgenic mouse models of human diseases have gained increasing importance in the pathophysiology of cardiovascular diseases (CVD). As an indirect measure of vascular stiffness, aortic pulse‐wave velocity (PWV) is an important predictor of cardiovascular risk. This study presents an MRI approach that uses a flow area method to estimate local aortic pulse‐wave velocity at different sites in the murine aorta. By simultaneously measuring the cross‐sectional area and the through‐plane velocity with a phase‐contrast CINE method, it was possible to measure average values for the PWV in the ascending and descending aorta within the range of 2.4–4.3 m/s for C57BL/6J mice (ages 2 and 8 months) and apoE‐knockout mice (age 8 months). Statistically significant differences of the mean values of the PWV of both groups could be determined. By repeating CINE measurements with a time delay of 1 ms between two subsequent data sets, an effective temporal resolution of 1000 frames/s (fps) could be achieved. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Temporal changes in the T1 and T2 relaxation rates (ΔR1 and ΔR2) in the rat brain are consistent with the tissue‐clearance rates of elemental manganese
Authors: Chuang Kai‐Hsiang , Koretsky Alan P. , Sotak Christopher H.
Published: April 2009

Temporal changes in the T1 and T2 relaxation rates (ΔR1 and ΔR2) in rat olfactory bulb (OB) and cortex were compared with the absolute manganese (Mn) concentrations from the corresponding excised tissue samples. In vivo T1 and T2 relaxation times were measured before, and at 1, 7, 28, and 35 d after intravenous infusion of 176 mg/kg MnCl2. The values of ΔR1, ΔR2, and absolute Mn concentration peaked at day 1 and then declined to near control levels after 28 to 35 d. The Mn bioelimination rate from the rat brain was significantly faster than that reported using radioisotope techniques. The R1 and R2 relaxation rates were linearly proportional to the underlying tissue Mn concentration and reflect the total absolute amount of Mn present in the tissue. The in vivo Mn r1 and r2 tissue relaxivities were comparable to the in vitro values for aqueous Mn2+. These results demonstrate that loss of manganese‐enhanced MRI (MEMRI) contrast after systemic Mn2+ administration is due to elimination of Mn2+ from the brain. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Myelin water imaging: Implementation and development at 3.0T and comparison to 1.5T measurements
Authors: Kolind Shannon H. , Mädler Burkhard , Fischer Stefan , Li David K.B. , MacKay Alex L.
Published: April 2009

Multicomponent T2 relaxation imaging can be used to measure signal from water trapped between myelin bilayers; the ratio of myelin water signal to total water is termed the myelin water fraction (MWF). The goal of this study was to implement and develop the single‐slice T2‐imaging technique proposed by Poon and Henkelman. For refinement, scan parameters (gradient crusher height and slew rate, bandwidth, echo spacing, matrix size, repetition time, and phase rewinding) were varied in water‐based phantoms and in fixed and in vivo brain. Changes in the standard deviation of the residuals of the multiexponential fit, MWF, T2, and peak width of the intra/extracellular water were monitored to determine which scan parameters minimized artifacts. Subsequently, we compared multicomponent T2 measurements at 1.5T and 3.0T for 10 healthy volunteers, and investigated the differences in SNR, fit residuals, MWF, and T2 and peak width of the intra/extracellular water, at higher magnetic field. MWF maps were found to be qualitatively similar between field strengths. MWFs were found to be significantly higher at 3.0T than at 1.5T, but with a strongly significant correlation between measurements (R2 > 0.92, P < 0.0005). The signal‐to‐noise ratio (SNR) was nearly double at 3.0T, but the standard deviation of residuals was increased in most cases. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Rapid single‐scan T‐mapping using exponential excitation pulses and image‐based correction for linear background gradients
Authors: Baudrexel Simon , Volz Steffen , Preibisch Christine , Klein Johannes C. , Steinmetz Helmuth , Hilker Rüdiger , Deichmann Ralf
Published: April 2009

A method for fast quantitative T mapping based on multiple gradient‐echo (multi‐GE) imaging with correction for static magnetic field inhomogeneities is described, using an exponential excitation pulse. Field gradient maps are obtained from the phase information and modulus data are subsequently corrected, allowing for simple monoexponential T fitting. Echoes with long echo times suffering from major signal losses due to field inhomogeneities are excluded from the analysis. The acquisition time for a matrix size of 256 × 256, 1 mm in‐plane resolution, and 2 mm slice thickness amounts to 15 s per slice. An additional correction for in‐plane field gradients further improves accuracy. Phantom experiments show that the method provides accurate T values for field gradients up to 200 μT/m; for gradients up to 300 μT/m errors do not exceed 15%. In vivo T values acquired on healthy volunteers at 3T are in excellent agreement with results from the literature. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Aldehyde fixative solutions alter the water relaxation and diffusion properties of nervous tissue
Authors: Shepherd Timothy M. , Thelwall Peter E. , Stanisz Greg J. , Blackband Stephen J.
Published: April 2009

Chemically‐fixed nervous tissues are well‐suited for high‐resolution, time‐intensive MRI acquisitions without motion artifacts, such as those required for brain atlas projects, but the aldehyde fixatives used may significantly alter tissue MRI properties. To test this hypothesis, this study characterized the impact of common aldehyde fixatives on the MRI properties of a rat brain slice model. Rat cortical slices immersion‐fixed in 4% formaldehyde demonstrated 21% and 81% reductions in tissue T1 and T2, respectively (P < 0.001). The T2 reduction was reversed by washing slices with phosphate‐buffered saline (PBS) for 12 h to remove free formaldehyde solution. Diffusion MRI of cortical slices analyzed with a two‐compartment analytical model of water diffusion demonstrated 88% and 30% increases in extracellular apparent diffusion coefficient (ADCEX) and apparent restriction size, respectively, when slices were chemically‐fixed with 4% formaldehyde (P ≤ 0.021). Further, fixation with 4% formaldehyde increased the transmembrane water exchange rate 239% (P < 0.001), indicating increased membrane permeability. Karnovsky's and 4% glutaraldehyde fixative solutions also changed the MRI properties of cortical slices, but significant differences were noted between the different fixative treatments (P < 0.05). The observed water relaxation and diffusion changes help better define the validity and limitations of using chemically‐fixed nervous tissue for MRI investigations. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Quantitative analysis of peristaltic and segmental motion in vivo in the rat small intestine using dynamic MRI
Authors: Ailiani Amit C. , Neuberger Thomas , Brasseur James G. , Banco Gino , Wang Yanxing , Smith Nadine B. , Webb Andrew G.
Published: April 2009

Conventional methods of quantifying segmental and peristaltic motion in animal models are highly invasive; involving, for example, the external isolation of segments of the gastrointestinal (GI) tract either from dead or anesthetized animals. The present study was undertaken to determine the utility of MRI to quantitatively analyze these motions in the jejunum region of anesthetized rats (N= 6) noninvasively. Dynamic images of the GI tract after oral gavage with a Gd contrast agent were acquired at a rate of six frames per second, followed by image segmentation based on a combination of three‐dimensional live wire (3D LW) and directional dynamic gradient vector flow snakes (DDGVFS). Quantitative analysis of the variation in diameter at a fixed constricting location showed clear indications of both segmental and peristaltic motions. Quantitative analysis of the frequency response gave results in good agreement with those acquired in previous studies using invasive measurement techniques. Principal component analysis (PCA) of the segmented data using active shape models resulted in three major modes. The individual modes revealed unique spatial patterns for peristaltic and segmental motility. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Ultrashort TE spectroscopic imaging (UTESI) using complex highly‐constrained backprojection with local reconstruction (HYPR LR)
Authors: Wang Kang , Du Jiang , O'Halloran Rafael , Fain Sean , Kecskemeti Steven , Wieben Oliver , Johnson Kevin M. , Mistretta Charles
Published: April 2009

Recently, the highly‐constrained backprojection (HYPR) and HYPR with local reconstruction (HYPR LR) methods have been introduced to reconstruct magnitude images from a series of highly undersampled data while preserving high spatial and temporal resolution and high signal‐to‐noise ratio (SNR) in applications with spatiotemporal correlations. However, these conventional HYPR algorithms are limited to the generation of magnitude images and, therefore, have limitations in their potential applications. In this work, the HYPR LR algorithm has been modified to extend the use of algorithms in the HYPR family to applications that require processing of complex data, such as MR chemical shift imaging (CSI) or spectroscopic imaging. The proposed method processes the magnitude information the same way as in original HYPR LR processing. In addition, it improves the phase images by subtracting the phase map of a synthesized composite image. The feasibility and efficiency of this algorithm has been demonstrated on CSI of cortical bone, Achilles tendon, and a healthy volunteer on a clinical 3T scanner. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Radiofrequency current source (RFCS) drive and decoupling technique for parallel transmit arrays using a high‐power metal oxide semiconductor field‐effect transistor (MOSFET)
Authors: Lee WonJe , Boskamp Eddy , Grist Thomas , Kurpad Krishna
Published: April 2009

A radiofrequency current source (RFCS) design using a high‐power metal oxide semiconductor field effect transistor (MOSFET) that enables independent current control for parallel transmit applications is presented. The design of an RFCS integrated with a series tuned transmitting loop and its associated control circuitry is described. The current source is operated in a gated class AB push‐pull configuration for linear operation at high efficiency. The pulsed RF current amplitude driven into the low impedance transmitting loop was found to be relatively insensitive to the various loaded loop impedances ranging from 0.4 to 10.3 ohms, confirming current mode operation. The suppression of current induced by a neighboring loop was quantified as a function of center‐to‐center loop distance, and was measured to be 17 dB for nonoverlapping, adjacent loops. Deterministic manipulation of the B1 field pattern was demonstrated by the independent control of RF phase and amplitude in a head‐sized two‐channel volume transmit array. It was found that a high‐voltage rated RF power MOSFET with a minimum load resistance, exhibits current source behavior, which aids in transmit array design. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Modified PROPELLER approach for T2‐mapping of the abdomen
Authors: Deng Jie , Larson Andrew C.
Published: April 2009

Quantitative abdominal T2 measurements may be useful for lesion differentiation and functional tissue characterization. However, T2 mapping of the abdomen with conventional spin‐echo (SE) and turbo‐spin‐echo (TSE) approaches can be challenging due to physiologic motion artifacts. Multishot TSE‐based PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction) can provide superior image quality due to reduced sensitivity to motion artifacts. With echo‐reordering to accurately estimate effective echo times and an extended slice thickness ratio to reduce stimulated echo effects, a modified PROPELLER approach may permit accurate, robust abdominal T2 measurements. We validated the accuracy of our modified PROPELLER T2‐mapping approach by comparison to conventional SE measurements in a phantom model and demonstrated the feasibility of acquiring accurate, high‐quality abdominal T2 maps in normal volunteers. Magn Reson Med 61:1269–1278, 2009. © 2009 Wiley‐Liss, Inc.
Relaxation effects of ferucarbotran‐labeled mesenchymal stem cells at 1.5T and 3T: Discrimination of viable from lysed cells
Authors: Henning Tobias D. , Wendland Michael F. , Golovko Daniel , Sutton Elizabeth J. , Sennino Barbara , Malek Farbod , Bauer Jan S. , McDonald Donald M. , Daldrup‐Link Heike
Published: April 2009

Human mesenchymal stem cells (hMSCs) were labeled with Ferucarbotran by simple incubation and cultured for up to 14 d. Iron content was determined by spectrometry and the intracellular localization of the contrast agent uptake was studied by electron and confocal microscopy. At various time points after labeling, ranging from 1 to 14 d, samples with viable or lysed labeled hMSCs, as well as nonlabeled controls, underwent MRI. Spin‐echo (SE) and gradient‐echo (GE) sequences with multiple TRs and TEs were used at 1.5T and 3T on a clinical scanner. Spectrometry showed an initial iron oxide uptake of 7.08 pg per cell. Microscopy studies revealed lysosomal compartmentalization. Contrast agent effects of hMSCs were persistent for up to 14 d after labeling. A marked difference in the T2 effect of compartmentalized iron oxides compared to free iron oxides was found on T2‐weighted sequences, but not on T‐weighted sequences. The observed differences may be explained by the loss of compartmentalization of iron oxide particles, the uniformity of distribution, and the subsequent increase in dephasing of protons on SE images. These results show that viable cells with compartmentalized iron oxides may—in principle—be distinguished from lysed cells or released iron oxides. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Robust estimation of the apparent diffusion coefficient (ADC) in heterogeneous solid tumors
Authors: Walker‐Samuel Simon , Orton Matthew , McPhail Lesley D. , Robinson Simon P.
Published: April 2009

The least‐squares algorithm is known to bias apparent diffusion coefficient (ADC) values estimated from magnitude MR data, although this effect is commonly assumed to be negligible. In this study the effect of this bias on tumor ADC estimates was evaluated in vivo and was shown to introduce a consistent and significant underestimation of ADC, relative to those given by a robust maximum likelihood approach (on average, a 23.4 ± 12% underestimation). Monte Carlo simulations revealed that the magnitude of the bias increased with ADC and decreasing signal‐to‐noise ratio (SNR). In vivo, this resulted in a much‐reduced ability to resolve necrotic regions from surrounding viable tumor tissue compared with a maximum likelihood approach. This has significant implications for the evaluation of diffusion MR data in vivo, in particular in heterogeneous tumor tissue, when evaluating bi‐ and multiexponential tumor diffusion models for the modeling of data acquired with larger b‐values (b > 1000 s/mm2) and for data with modest SNR. Use of a robust approach to modeling magnitude MR data from tumors is therefore recommended over the least‐squares approach when evaluating data from heterogeneous tumors. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.
Treatment of intestinal and hepatic mucormycosis in an immunocompromized child
Authors: Lüer Sonja , Berger Steffen , Diepold Miriam , Duppenthaler Andrea , von Gunten Michael , Mühlethaler Konrad , Wolf Rainer , Aebi Christoph
Published: April 2009

During ALL chemotherapy, a 4‐year‐old patient presented with febrile neutropenia and abdominal pain. Ultrasound examinations were repeatedly normal. Computerized tomography on day 7 demonstrated appendicitis and multiple hepatic foci identified as mucormycosis (Absidia corymbifera). Successful outcome was achieved by aggressive re‐surgery, long‐term antifungal therapy with serum level‐monitored posaconazole, and recovery of neutrophil counts. Considering the interference of posaconazole with CYP3A4, vincristine was administered during 72 hr posaconazole windows. Pediatric intestinal mucormycosis, still associated with a >70% case‐fatality rate, calls for early imaging and surgery to establish the diagnosis, reduce the fungal mass, and provide a rationale for using posaconazole. Pediatr Blood Cancer 2009;52:872–874. © 2009 Wiley‐Liss, Inc.