bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventive effects of batroxobin on experimental canine coronary thrombosis
Authors: Tomaru T. , Uchida Y. , Sonoki H. , Sugimoto T.
Published: February 2009

The thrombolytic effects of urokinase (UK) and preventive effects of batroxobin, heparin, and aspirin on the recurrence of thrombosis in the coronary artery were studied in 118 anesthetized dogs with severe endothelial denudation and luminal stenosis of the coronary artery. Occlusive thrombi developed in 68 (58%) preparations (dogs), accompanied by a decrease of coronary blood flow and pressure, an electrocardiographic ST elevation, and epicardial cyanosis. An intravenous infusion of 20,000 IU/kg of UK reopened the occluded coronary artery in all 32 preparations with 1‐h‐old thrombi, in 6 (86%) of 7 preparations with 2‐h‐old thrombi, and in 5 (83%) of 6 preparations with 3‐h‐old thrombi. However, recanalization was not observed in preparations with thrombi more than 4‐h‐old. Occlusion recurred within 6 h after recanalization in 2 (18%) of 18 preparations pretreated with batroxobin (1‐2 BU/kg) (p> .005 vs. control UK group), in 1 (14%) of 7 preparations administered a continuous infusion of 30 U/kg per h of heparin (p > .05 vs. control UK group), in 4 (57%) of 7 preparations pretreated with 2 mg/kg of aspirin, and in 7 (64%) of 11 preparations not pretreated (control UK group). Complete prevention was observed only in the group administered 2 BU/kg of batroxobin. Histologically, these thrombi closely simulated clinical arterial thrombi. Myocardial hemorrhage and contraction band necrosis were observed in the reperfused hearts. In conclusion, experimental canine coronary thrombi more than 4‐h‐old were resistant to thrombolytic therapy, and batroxobin and heparin were effective in the prevention of coronary reocclusion.
Thallium‐201 scintigraphy perfusion defect with dipyridamole in a patient with a myocardial bridge
Authors: Bennett J. M. , Blomerus P.
Published: February 2009

A patient with myocardial bridging and a thallium‐201 scintigraphy perfusion defect after the administration of intravenous dipyridamole is presented. The same patient had a normal perfusion study on exercise stress testing. The effects of coronary vasodilators and dipyridamole on coronary artery flow patterns in patients with myocardial bridging are discussed. We suggest that coronary vasodilators may induce perfusion defects in patients with myocardial bridging and should be avoided in such patients.
Clinical assessment of beta blockade
Authors: Weston M. W. , Glasser S. P. , Stoner D. J. , Lyman G. H.
Published: February 2009

This study was undertaken to assess a clinical measurement (leg squats) in order to determine the adequacy of beta‐adrenergic blockade (AdBB) utilizing the symptom‐limited exercise test heart rate of less than 120 beats/min as the standard. Seventy subjects were tested, 35 receiving beta‐adrenergic‐blocking drugs in clinically determined maximal doses, and 35 subjects not receiving these agents. Sensitivity (Se), specificity (Sp), and positive (Pv +) and negative (Pv ‐) predictive values were calculated for post‐leg squat heart rates of ≤ 100, ≤ 110 and < 120 beats/min. Other variables analyzed for AdBB were resting heart rates and post‐leg squat heart rate increase > 50% over baseline. A cost‐benefit analysis was also performed. It was concluded that: (1) Neither the resting heart rate or percent increase in heart rate compared to baseline reliably predicted AdBB. (2) In patients receiving beta‐blocking drugs, a post‐squat heart rate of ≤ 100 beats/min had a Se = .82, Sp = .67, Pv + .70, and Pv ‐ .80, values not high enough to be reliably used in many clinical situations. (3) If the post‐squat heart rate was > 110 beats/min, however, AdBB is probably absent, since no subjects on beta blockers with maximum exercise test heart rate ≤ 120 beats/min had a post‐leg squat heart rate > 110 beats/min. (4) For a reasonable range of cost and test performance estimates, utilization of the leg squat test as described here is favored on the basis of cost‐benefit analysis.
Myocarditis with multinucleated giant cells detected in biopsy specimens
Authors: Fukuhara T. , Morino M. , Sakoda S. , Bito K. , Kinoshita M. , Kawakita S.
Published: February 2009

A 42‐year‐old woman was transferred to our hospital for evaluation of bradycardia with a complete atrioventricular block. Her pulse was 41 regular beats/min with blood pressure 166/92 mmHg. There were no skin lesions, edema, or lymphadenopathy. The white blood cell count was 6300/mm3. The serum glutamic oxaloacetic transaminase was 21 IU and creatine phosphokinase was 34 IU. C‐reactive protein was negative. The level of serum angiotensin converting enzyme was slightly increased at 25.8 IU/1/37.0°C (normal range: 7–24.0). Chest radiography showed congestive heart failure with a cardiothoracic ratio of 54%. There was no bilateral lymphadenopathy or fibrous changes during her clinical course. The coronary arteries were completely normal angiographically. Left ventriculograms revealed slight hypokinesis and dilatation (end‐diastolic volume index of 112 ml/m2, ejection fraction of 53%). Left ventricular end‐diastolic pressure was slightly abnormal at 16 mmHg. Two right and two left ventricular endomyocardial biopsies were performed. Right ventricular biopsy demonstrated edematous tissue and a slight mononuclear cell infiltration with little fibrosis. Left ventricular specimens showed an extensive area of fibrosis, with large, multinucleated giant cells with an asteroid body and chronic inflammation without epitheloid cells. The less affected areas of another specimen showed mild interstitial fibrosis and degenerative myocytes with vacuolation, and some multinucleated myocytes without an asteroid body were present. This case was diagnosed as cardiac sarcoidosis rather than idiopathic giant cell myocarditis. The patient has been implanted with a permanent pacemaker. This case is of clinical interest from three aspects: (1) the specific lesion in the myocardium was confirmed by examination of several biopsy specimens; (2) the multinucleated giant cells are of two sizes: the larger cells, having an asteroid body in the cytoplasm, appear to be derived from histiocytes, and the smaller cells are considered to be derived from myocyte; (3) the patient is doing well with a permanent pacemaker and requires no immunosuppressive therapy at one and half years later.
“A‐wave” liver
Authors: George D. S. , Marsh C. , Leier C. V.
Published: February 2009

The finding and timing of hepatic pulsations can provide important information regarding the status of right heart structures and function. We report a 54‐year‐old woman with idiopathic dilated cardiomyopathy, who had prominent hepatic presystolic pulsations (“A‐wave” liver). The clinical findings and the venous and hepatic pulse recordings are presented and discussed in terms of clinical pathophysiology and significance.
One‐year death rate in 270 patients with suspected acute myocardial infarction, initially treated with intravenous magnesium or placebo
Authors: Rasmussen H. S. , Grønbaek M. , Cintin C. , Balsløv S. , Nørregård P. , Mcnair P.
Published: February 2009

In a double‐blind, placebo‐controlled study, 273 patients with suspected acute myocardial infarction (AMI) were randomized to receive either 48‐h magnesium (Mg) or placebo therapy intravenously, initiated immediately on admission to hospital. We describe the results from a 1‐year survey in 270 of the patients, who were available for follow‐up. Patients were equally divided: 135 received Mg and 135 received placebo. Mg treatment was associated with a marked reduction in 1‐year death rate from 32% in the placebo group to 20% in the Mg group (p = 0.018). If only death from ischemic heart disease is considered, the figures were 28% in the placebo group as opposed to 15% in the Mg group (p = 0.006). This reduction was mainly due to a reduction in mortality during the initial 30 days after inclusion in the study (17% vs. 7%), after which the difference in mortality between the two groups did not reach statistical significance (18% vs. 15%, p = 0.56). The beneficial effect of Mg on mortality was partly linked to a reduced incidence of arrhythmias (27% vs. 16%), and partly to a reduced incidence of infarction (63% vs. 48%) during the initial hospitalization. However, factors unknown to us were also involved, as revealed by a remaining statistically significant partial regression coefficient, when sex, age, cardiovascular history, development of AMI, and development of arrhythmias were considered. It is concluded that intravenous Mg treatment is beneficial to patients with acute ischemic heart disease and should be adopted as part of the routine treatment of these patients.
Reliability of qt intervals as indicators of clinical hypercalcemia
Authors: Ahmed R. , Hashiba K.
Published: February 2009

Reliability of corrected QT intervals (QoTc, QaTc, and QeTc) as indicators of clinical hypercalcemia was assessed in 14 hypercalcemic patients. Hypercalcemia was severe to extreme (serum calcium 14.9 to 22.8 mg/dl) in 11, moderate (13.4 mg/dl) in 1, and mild (12.2 and 11.8 mg/dl) in 2 patients. QT intervals during hypercalcemia were compared with those during normocalcemia either before or after development of hypercalcemia. QeTc interval showed neither significant correlation with serum calcium nor any consistent pattern of change with development of hypercalcemia or normalization of serum calcium. In contrast, QoTc and QaTc intervals shortened with development of hypercalcemia and returned toward normal with normalization of serum calcium in all the patients, and showed significant correlation with serum calcium (QoTc: r = ‐0.77, p < 0.001, n = 35; QaTc: r = 0.82, p < 0.001, n = 35). QaTc was short (> 0.30 s) in all the ECGs in severe and moderate hypercalcemia and in 2 of the 5 ECGs in mild hypercalcemia. Combination of short QoTc ( < 0.18 s) and short QaTc was found to be highly specific for, and was present in 65% of ECGs, in moderate and severe hypercalcemia. Combination of normal QoTc (> 0.18 s) and normal QaTc (> 0.30 s) was not observed in moderate or severe hypercalcemia. We conclude that QoTc and QaTc intervals are reliable indicators of clinical hypercalcemia.
Coronary artery spasm and its relationship to exercise in patients without severe coronary obstructive disease
Authors: Hill J. A. , Conti C. R. , Feldman R. L. , Pepine C. J.
Published: February 2009

Coronary artery spasm is reported to occur with exercise. In patients without severe coronary atherosclerosis, the evidence for exercise‐induced coronary artery spasm is limited. Three patients with positive exercise tests but no severe coronary atherosclerosis are presented. Coronary artery spasm was provoked and verified by angiography in all three, but coronary angiography during exercise failed to demonstrate spasm. The literature is reviewed and the value of a routine protocol for evaluation is discussed.
Severe constrictive pericarditis as an unsuspected cause of death in a patient with idiopathic hypereosinophilic syndrome and restrictive cardiomyopathy
Authors: Lui C. Y. , Makoui C.
Published: February 2009

A 43‐year‐old man with idiopathic hypereosinophilic syndrome survived a relatively long term (6 1/2 years) before he succumbed to intractable heart failure. Six months before death, his chronic heart failure from restrictive cardiomyopathy was well compensated. Autopsy demonstrated severe constrictive pericarditis which was not suspected antemortem. Constrictive pericarditis as a late complication of idiopathic hypereosinophilic syndrome is discussed.
Nifedipine overdose
Authors: Whitebloom D. , Fitzharris J.
Published: February 2009

Overdose with 300 mg of nifedipine in a 54‐year‐old woman led to profound hypotension and reflex tachycardia. The patient was treated with intravenous fluids, calcium gluconate, and dopamine. Cardiac rhythm disturbances, hypoglycemia, and myocardial depression were not found. Recovery was rapid and uneventful. The clinical aspects of nifedipine overdose are discussed and possible treatment modalities are given.
Effects of acute smoking on the hemostatic system in humans
Authors: Vicari A. M. , Margonato A. , Macagni A. , Luoni R. , Vicedomini G. , Pozza G. , Seveso M. P.
Published: February 2009

Habitual smoking is one of the best established risk factors for cardiovascular disease. The pathogenesis of smoke‐induced damage is not so well clarified, but it probably includes—among some other aspects—an activation of the hemostatic system. Recently it has been shown that smoking a single cigarette can significantly decrease the coronary blood flow in coronary patients as well as in normal subjects. We tested the hypothesis that the acute effects of smoke are mediated by the hemostatic system. Seven healthy male volunteers, aged 20–40 years (mean 32±6 years), entered the study. All were habitual smokers, but had abstained from smoking in the 12 hours preceding the test. After lying in absolute rest for about 30 minutes, each subject smoked a cigarette containing 1.2 mg of nicotine. Immediately before and after smoking, blood was drawn by clear venipuncture for the evaluation of the following hemostatic variables: collagen‐induced platelet aggregation by the method of Born; thromboxane B2 (TxB2) production by platelets stimulated with collagen, radioimmunoassay (RIA); plasma beta thromboglobulin (TG) (RIA); plasma fibrinopeptide A (FPA) (RIA); plasma fibrinolytic activity in the euglobulin fraction (NEF) (fibrin plate method). The following results, respectively before and after smoking, were observed: collagen‐induced platelet aggregation 55±3 vs. 57±6%; TxB2 100.5±5.9 vs. 90.3±9.0 ng/108 platelets; plasma beta‐TG 20.8±2.2 vs. 19.2±2.3 ng/ml; plasma FPA 2.3±0.3 vs. 2.2±0.1 ng/ml; NEF, lysis diameter 16.8±1.6 vs. 16.7±1.7 mm; NEF + C1 inhibitor lysis diameter 8.8±0.7 vs. 9.1±0.7 mm. None of these variables was significantly changed after smoking. We conclude that acute smoking does not induce a prothrombotic state.
A phase 2 study of cetuximab in combination with docetaxel in chemotherapy‐refractory/resistant patients with advanced nonsmall cell lung cancer
Authors: Kim Edward S. , Mauer Ann M. , William William N. , Tran Hai T. , Liu Diane , Lee Jack J. , Windt Paul , Hong Waun K. , Vokes Everett E. , Herbst Roy S.
Published: February 2009

BACKGROUND:

Cetuximab in combination with docetaxel was examined in chemotherapy‐refractory/resistant patients with advanced nonsmall‐cell lung cancer (NSCLC) to determine response rate, survival, safety, and pharmacokinetics (PK).

METHODS:

Patients had evidence of epidermal growth factor receptor (EGFR) expression (≥1 +) and tumor progression during or disease recurrence within 3 months after chemotherapy. Cetuximab was administered weekly (400 mg/m2 initial; 250 mg/m2 thereafter). Docetaxel was administered every 3 weeks (75 mg/m2). A response in 3 of the first 21 patients was required to continue accrual to the target sample size of 50 patients.

RESULTS:

Confirmed responses included 1 complete response (1.8%), 10 partial responses (18.2%), and 20 with stable disease (36.4%). The response rate was 20% (95% confidence interval [CI], 10.4% to 33.0%) and median time to disease progression was 104 days. There were no differences in PK parameters of docetaxel alone or with cetuximab. The most common grade 3 of 4 adverse events were leukopenia (27.3%) and acne (21.8%). Four patients (7.3%) discontinued due to allergic reaction. The median overall survival (OS) was 7.5 months with a 1‐year survival of 35%.

CONCLUSIONS:

Cetuximab in combination with docetaxel was well tolerated. The response rate supports more definitive evaluation of this combination in the second‐line setting. Cancer 2009. © 2009 American Cancer Society.
Carbonic anhydrase IX in bladder cancer
Authors: Klatte Tobias , Seligson David B. , Rao Jian Yu , Yu Hong , de Martino Michela , Kawaoka Kelly , Wong Steven G. , Belldegrun Arie S. , Pantuck Allan J.
Published: February 2009

BACKGROUND:

The objective of this study was to evaluate the role of carbonic anhydrase IX (CAIX) in urothelial carcinoma of the bladder.

METHODS:

A tissue microarray was constructed that contained 724 tissue samples from 340 patients. Immunohistochemical staining was performed using the antibody MN‐75, the percentage of positive cells was evaluated, and their association with tumor (T) classification, grade, and survival was assessed.

RESULTS:

All normal urothelial tissue samples were negative for CAIX expression, whereas 71% of bladder cancers expressed CAIX. CAIX expression was higher in noninvasive (Ta) versus invasive (T1‐T4) tumors (P < .001), in low‐grade versus high‐grade bladder cancer (P < .001), and in metastases versus the corresponding primary tumor (P = .032). For patients with nonmuscle invasive carcinoma who underwent transurethral resection (TUR), higher CAIX expression was associated with poorer recurrence‐free survival (P = .001). In addition, for patients with T1 tumors who underwent TUR, higher CAIX expression conveyed a 6.5‐fold higher risk of progression into muscle‐invasive disease (P = .006). In patients who underwent cystectomy, higher CAIX expression was associated with worse overall survival (P = .003). Multivariate Cox models revealed that CAIX expression was the strongest, independent prognostic factor of recurrence‐free survival (hazard ratio, 2.29; P = .001) and overall survival (hazard ratio, 1.9; P < .001).

CONCLUSIONS:

CAIX was expressed differentially in noninvasive versus invasive tumors, in low‐grade versus high‐grade bladder cancer, and in primary tumors versus metastases. The current results indicated that CAIX is a strong predictor of recurrence, progression, and overall survival of patients with bladder cancer; and the integration of CAIX expression into conventional prognostic models significantly improved their predictive accuracy. The data suggest a tripartite role of CAIX as a diagnostic, prognostic, and therapeutic molecular marker in bladder cancer. Cancer 2009. © 2009 American Cancer Society.
Race impacts outcome in stage III/IV squamous cell carcinomas of the head and neck after concurrent chemoradiation therapy
Authors: Settle Kathleen , Taylor Rodney , Wolf Jeffery , Kwok Young , Cullen Kevin , Carter Kevin , Ord Robert , Zimrin Ann , Strome Scott , Suntharalingam Mohan
Published: February 2009

BACKGROUND:

The purpose of this study was to determine the impact of race on outcome in patients with stage III/IV squamous cell carcinoma of the head and neck (SCCHN) who have completed concurrent chemoradiotherapy.

METHODS:

The authors performed a retrospective analysis of 202 patients with stage III/IV SCCHN who were treated at the University of Maryland. Patients received daily radiation to a total dose of 70.2 Gray (Gy) (1.8 Gy/day), concurrently with weekly carboplatin (area under the curve [AUC] = 2) and paclitaxel (45 mg/m2) chemotherapy.

RESULTS:

There were 108 Caucasian (CA) and 94 African American (AA) patients. The median age was 56 years, and 81% were stage IV. The median follow‐up was 33 months. The median overall survival (OS) and disease‐free survival (DFS) were 33 months and 19 months, respectively. When analyzed by race, the median DFS was 33 months (CA) versus 12 months (AA) (P = .028). The median OS was 44 months (CA) versus 24 months (AA) (P = .071). The 3‐year DFS for stage IV AA versus stage IV CA was 29% versus 50% (P = .031). The 3‐year DFS for N2 disease in AA versus CA was 32% versus 51% (P = .046). The 3‐year DFS for AA versus CA with oropharyngeal tumors was 30% versus 60% (P = .006).

CONCLUSIONS:

This analysis documents the inferior outcome for AA patients. They had inferior DFS and a trend toward worse OS. When stratified by several prognostic variables, the mediocre DFS in the AA patients remains. These data suggest that further investigation into the genetic characteristics of SCCHN in AA patients is warranted. Cancer 2009. © 2009 American Cancer Society.
Grid performance prediction using state‐space model
Authors: Kalantari Mohammad , Akbari Mohammad Kazem
Published: February 2009

One of the main challenges of scheduling algorithms in Grid environment is the autonomy of sites, which makes it difficult for the grid scheduler to estimate the exact cost of a task execution on different sites. In this paper, we present a solution for this problem based on data history (workload traces) and time series techniques. The main focus of this work is devoted to forecasting the task waiting time in a resource queue, which is under the control of a local scheduler with distinctive scheduling policy. The main contribution of this work is the consideration of a special property of the grid resources, the dynamic membership, i.e. a resource may exit and then come back to the grid environment repeatedly. When the resource belongs to the grid environment, its workload trace (log file) is considered as a correct log. On the other hand, when the resource leaves the grid, the log file during this period is considered as a defective part of the trace. As the defective parts contain some useful information, after repairing these defective parts, they can be used for forecasting purposes. Of this, we employ state‐space model along with the associated Kalman recursions in conjunction with the Expectation‐Maximization algorithm to repair the defective waiting time series such as a correct log file by which the resource seems never to have left the grid. The experimental results on a number of workload logs demonstrated that this approach can achieve an average prediction error, between 22 and 64% less than those incurred by other rival methods. Copyright © 2009 John Wiley & Sons, Ltd.
WSPE: a peer‐to‐peer grid programming environment
Authors: Rosinha Romulo B. , Geyer Cláudio F. R. , Vargas Patrícia Kayser
Published: February 2009

Grid programming environments are tools designed to isolate users from issues such as heterogeneity, scalability and adaptability, thus simplifying the use of a Grid infrastructure. This paper presents work stealing programming environment (WSPE), a Grid programming environment for Grid‐unaware applications. WSPE can be defined as a programming environment, since it is a software tool that presents both a programming model and an execution system. The WSPE consists of a simple programming interface and a fully decentralized runtime system following a peer‐to‐peer organization, both presented in this paper. It's runtime system employs a new scheduling mechanism, known as round stealing, inspired by the idea of work stealing. The main focus of our work is to research on methods to achieve efficient execution of parallel applications in a Grid computing infrastructure. By simulation, we show that our scheduling mechanism outperforms a more traditional mechanism in a Grid environment. We also demonstrate how an appropriate choice for a network overlay mechanism can further improve the execution efficiency. Copyright © 2009 John Wiley & Sons, Ltd.
Highly Emissive Nanostructured Thin Films of Organic Host–Guests for Energy Conversion
Authors: Moreau Juliette , Giovanella Umberto , Bombenger Jean‐Philippe , Porzio William , Vohra Varun , Spadacini Laura , Di Silvestro Giuseppe , Barba Luisa , Arrighetti Gianmichele , Destri Silvia , Pasini Mariacecilia , Saba Michele , Quochi Fancesco , Mura Andrea , Bongiovanni Giovanni , Fiorini Mauro , Uslenghi Michela , Botta Chiara
Published: February 2009

All‐organic nanostructured host–guest materials (see picture) show enhanced, tunable fluorescence due to a high concentration of dyes with controlled spatial and geometrical organization that allows controlled resonant energy transfer. Homogeneous films of deoxycholic acid host–guests, provide coatings that convert near‐UV light into blue light with an efficiency higher than that of the standard polymeric blends.

magnified image

All‐organic nanostructured host–guest systems, based on dyes inserted in the nanochannels of perhydrotriphenylene (PHTP) and deoxycholic acid (DCA), show enhanced fluorescence properties with quantum yields even higher than those of the dyes in solution, thanks to the high concentration of emissive molecules with controlled spatial and geometrical organization that prevents aggregation quenching. Both host molecules crystallize, growing with the long axis oriented along the direction of the nanochannels where the linear‐chain dyes are inserted, to yield crystals emitting well‐polarized light. For the DCA‐based host–guests, homogeneous thin films suitable for several applications are obtained. Colour emission in such films can be tuned by co‐inclusion of two or three dyes due to resonant energy‐transfer processes. We show that films obtained by low‐cost techniques, such as solution casting and spin‐coating, convert UV light into visible light with an efficiency much higher than that of the standard polymeric blends.
Targeted gene modification in mouse ES cells using integrase‐defective lentiviral vectors
Authors: Okada Yuka , Ueshin Yuko , Hasuwa Hidetoshi , Takumi Kazuhiro , Okabe Masaru , Ikawa Masahito
Published: February 2009

Lentiviral vectors efficiently integrate into the host genome of both dividing and nondividing cells, and so they have been used for stable transgene expression in biological and biomedical studies. However, recent studies have highlighted the risk of insertional mutagenesis and subsequent oncogenesis. Here, we used an integrase‐defective lentiviral (IDLV) vector to decrease the chance of random integration and examined the feasibility of lentiviral vector‐mediated gene targeting into murine embryonic stem (ES) cells. After transduction with wild‐type lentiviral vectors, none of the 512 G418 resistant clones were found to be homologous recombinant clones. Although the transduction efficiency was lower with the IDLV vectors (5.9% of wild‐type), successful homologous recombination was observed in nine out of the 941 G418 resistant clones (0.83 ± 1.32%). Pluripotency of the homologous recombinant ES cells was confirmed by the production of chimeric mice and subsequent germ line transmission. Because lentiviral vectors can efficiently transduce a variety of stem cell types, our strategy has potential relevance for secure gene‐manipulation in therapeutic applications. genesis 47:217–223, 2009. © 2009 Wiley‐Liss, Inc.
Formation of Homoleptic Tetracarbene versus cis‐Chelating Dicarbene Complexes of Nickel(II) and Applications in Kumada–Corriu Couplings
Authors: Vinh Huynh Han , Jothibasu Ramasamy
Published: February 2009

The formation of mono‐ versus bis(chelate) NiII complexes bearing N‐heterocyclic dicarbene ligands can be controlled by the flexibility of the ligand bridge. A short methylene spacer exclusively gives rise to a dicationic bis(chelate) complex [Ni(MeCCmeth)2]Br2 (1), whereas a more flexible propylene spacer affords a neutral monochelate complex [NiBr2(MeCCprop)] (2). Complex 2 was found to autoionize very slowly to the corresponding dicationic bis(chelate) over ca. 45 d in [D6]dmso. The formation of the bis‐ versus monochelate complex can be attributed to the different stabilities of the resulting metallacycles. The catalytic activity of monochelate 2 was tested in the Kumada–Corriu coupling of aryl halides with arylmagnesium reagents at ambient temperature. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
NMR Quantification of Tautomeric Populations in Biogenic Purine Bases
Authors: Bartl Tomáš , Zacharová Zuzana , Sečkářová Pavlína , Kolehmainen Erkki , Marek Radek
Published: February 2009

Purine bases such as purine, adenine, hypoxanthine, and mercaptopurine are known to exist in several tautomeric forms. Characterization of their tautomeric equilibria is important not only for predicting the regioselectivity of their N‐alkylation reactions, but also for gaining knowledge of the patterns with which these compounds of significant biological activity form hydrogen bonds with their biological targets. The tautomeric equilibria of purine and some purine derivatives in methanol and N,N‐dimethylformamide solutions were investigated by low‐temperature 1H and 13C NMR spectroscopy. The N(7)H and N(9)H tautomeric forms were quantified by integrating the individual 1H NMR signals at low temperatures. The Gibbs free energy differences were calculated and the effects of substitution on the N(7)H/N(9)H ratio discussed. A previously published theoretically predicted mechanism of the tautomeric exchange is compared with our measurements in deuteriated solvents. The influence of concentration on the temperature of coalescence indicates that supramolecular clusters play a significant role in this proton transfer process. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Phase uncertainty in case‐control association studies
Authors: Won Sungho , Kim Sulgi , Elston Robert C.
Published: February 2009

The possible evidence for association comprises three types of information: differences between cases and controls in allele frequencies, in parameters for Hardy‐Weinberg disequilibrium (HWD), and in parameters for linkage disequilibrium (LD). LD between marker and disease alleles results in a difference in at least one of the three types of parameters [Won and Elston, 2008]. However, the parameters for LD require knowledge about phase, which is usually unknown, making the LD contrast test without modification infeasible in practice. Methods for handling phase uncertainty are: (1) the most probable haplotype pair for each individual can be considered as the true phase; (2) a weighted average of haplotypes can be used; (3) we can consider the composite LD, which does not require any information about phase. We compare these methods to handle phase uncertainty in terms of validity and efficiency, and the effect on them of HWD in the population, at the same time confirming results for the three types of information. When the LD between markers is high, the LD contrast test that uses a weighted average of haplotypes or the most probable haplotypes to calculate the LD is recommended, but otherwise the LD contrast test that uses the composite LD is recommended. We conclude that, even though the difference in allele frequencies is usually the most informative test except in the case of a recessive disease, the LD contrast test can be more powerful if the markers are dense enough. Genet. Epidemiol. 33:463–478, 2009. © 2009 Wiley‐Liss, Inc.
Testing Hardy‐Weinberg equilibrium using mother‐child case‐control samples
Authors: Chen Jinbo , Zheng Haitao , Wilson Melissa L. , Kraft Peter
Published: February 2009

Genetic association studies of obstetric complications may genotype case and control mothers, or their respective newborns, or both case‐control mothers and their children. The relatively high prevalence of many obstetric complications and the availability of both maternal and offspring's genotype data have provided motivation to study new methods for testing for deviations from Hardy‐Weinberg equilibrium (HWE). We propose four novel test statistics, each of which uses a different type of data as follows: (1) a test using maternal case‐control genotype data, (2) a test using offspring genotype data, (3) a combination of the first and second tests, and (4) a test based on the joint classification of case‐control maternal‐child genotype data. The selection of case and control mothers (and thus their children) is accounted for by weighting both maternal and child contributions to the test statistics with sampling probabilities. Our tests thus do not require that the phenotype be rare as is the case for HWE tests using only controls, and are particularly suitable for genetic association studies of relatively common complications such as premature birth. The third and fourth tests described above utilize both maternal and child genotype data and appropriately account for the correlation between maternal and child genotypes. On the basis of extensive simulation studies to compare the type‐I error and power for proposed tests, we recommend the third combined test statistic for routine use in the analysis of case‐control studies of mother‐child pairs. Genet. Epidemiol. 33:539–548, 2009. © 2009 Wiley‐Liss, Inc.
Cholesterol 24‐hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two‐year follow up study
Authors: Fu Brenda Yan , Ma Suk Ling , Tang Nelson Leung Sang , Tam Cindy Woon Chi , Lui Victor Wing Cheong , Chiu Helen Fung Kum , Lam Linda Chiu Wa
Published: February 2009

Objectives

We previously found that the polymorphisms of cholesterol 24‐hydroxylase (CYP46A1) gene were associated with the risk of Alzheimer's disease (AD) in Chinese. However, its effect in predicting progression of cognitive decline remains unknown.

Methods

Two hundred and eighty‐one Chinese subjects (121 cognitively intact, 101 with mild cognitive impairment and 59 with mildly dementia) were followed‐up with a mean (SD) duration of 25.22(5.74) months. Association between the CYP46A1 gene polymorphisms and 2‐year cognitive deterioration were evaluated.

Results

At follow‐up, 225(80.0%) subjects were reassessed. Sixty‐three subjects were diagnosed as AD, 68 were MCI and 94 were cognitively intact. Among them, 158 had improved or remained stable while 67 deteriorated. The ‘deteriorated’ group was older than ‘improved or stable’ group (t‐test, t = −2.87, p < 0.001). IVS2‐150 polymorphism was associated with a higher risk of cognitive deterioration. Subjects with T allele were more likely to deteriorate compared with those without T allele (Pearson χ2 = 8.98, df 2, p = 0.011). IVS3‐128 CC genotype was higher in ‘improved or stable’ group (Likelihood Ratio = 6.55, df 2, p = 0.038), suggesting a protective role for this allele. The two other polymorphisms, IVS1‐192 and IVS4‐122, did not show any significant association with cognitive function.

Conclusion

CYP46A1 gene may act to modulate the course of cognitive deterioration in late life. Copyright © 2009 John Wiley & Sons, Ltd.
Physical exercise leads to rapid adaptations in hippocampal vasculature: Temporal dynamics and relationship to cell proliferation and neurogenesis
Authors: Van der Borght Karin , Kóbor‐Nyakas Dóra É. , Klauke Karin , Eggen Bart J.L. , Nyakas Csaba , Van der Zee Eddy A. , Meerlo Peter
Published: February 2009

Increased levels of angiogenesis and neurogenesis possibly mediate the beneficial effects of physical activity on hippocampal plasticity. This study was designed to investigate the temporal dynamics of exercise‐induced changes in hippocampal angiogenesis and cell proliferation. Mice were housed with a running wheel for 1, 3, or 10 days. Analysis of glucose transporter Glut1‐positive vessel density showed a significant increase after 3 days of wheel running. Cell proliferation in the dentate gyrus showed a trend towards an increase after 3 days of running and was significantly elevated after 10 days of physical exercise. Ten days of wheel running resulted in a near‐significant increase in the number of immature neurons, as determined by a doublecortin (DCX) staining. In the second part of the study, the persistence of the exercise‐induced changes in angiogenesis and cell proliferation was determined. The running wheel was removed from the cage after 10 days of physical activity. Glut‐1 positive vessel density and hippocampal cell proliferation were determined 1 and 6 days after removal of the wheel. Both parameters had returned to baseline 24 h after cessation of physical activity. The near‐significant increase in the number of DCX‐positive immature neurons persisted for at least 6 days, indicating that new neurons formed during the period of increased physical activity had survived. Together these experiments show that the hippocampus displays a remarkable angiogenic and neurogenic plasticity and rapidly responds to changes in physical activity. © 2009 Wiley‐Liss, Inc.
Performance measurement in mental health care: present situation and future possibilities
Authors: Baars Irma J. , Evers Silvia M. A. A. , Arntz Arnoud , van Merode Godefridus G.
Published: February 2009

This paper describes performance measurement and its indicators for mental health care services. Performance measurement can serve several goals such as accountability, quality improvement and performance management. For all three purposes structure, process and outcome indicators should be measured. Literature was retrieved from Medline and PsychInfo in order to see which performance indicators were used for the three purposes of performance measurement in mental health care. The indicators were classified in structure, process and outcome indicators. The results show no big differences in the indicators used among studies. Performance management is the performance measurement purpose most referred to, followed by accountability, and quality improvement. Outcome and process indicators are used most, structure indicators are in the minority. Several levels of measurement, that is national or service level, came forward in the literature review. To overcome misinterpretation of data and to be able to improve quality and manage performances, performance indicator sets should refer to structure, process and outcome. Indicators should be chosen carefully with the aim of the measurement taken into mind. Based on this review, a conceptual framework is presented to support managers in their decisions about which indictors can best be used for performance measurement. Additionally, a model that provides an understanding of the use of information gained by performance measurement is given. Copyright © 2009 John Wiley & Sons, Ltd.
Verapamil in treatment resistant depression: a role for the P‐glycoprotein transporter?
Authors: Clarke Gerard , O'Mahony Siobhain M , Cryan John F , Dinan Timothy G
Published: February 2009

Introduction

Verapamil is a calcium channel blocker that also inhibits the P‐glycoprotein (Pgp) membrane transporter. We have found that administration of verapamil with a recognised antidepressant improves clinical outcome in previously treatment resistant cases despite the fact that verapamil does not possess inherent antidepressant activity. In this study we examined the hypothesis that the antidepressant‐like effects of verapamil are mediated through its blockade of the Pgp transporter in the blood brain barrier (BBB).

Methods

Following pre‐treatment with verapamil (20 mg/kg) or a saline solution male Sprague Dawley rats were injected with imipramine (15 mg/kg). Two hours later, the animals were sacrificed, trunk blood collected and brain regions dissected out. High performance liquid chromatography (HPLC) was used to quantitate antidepressant drug concentrations in all samples.

Results

Verapamil pre‐treatment significantly elevated imipramine concentrations in all brain regions studied. The effect was most pronounced in the brainstem and frontal cortex where we observed in excess of a doubling in the brain region: serum ratios.

Conclusion

Our results verify inhibition of Pgp as a potential mechanism of action for verapamil during treatment resistant depression. The implications of these findings are discussed in the context of novel treatment strategies in depression. Copyright © 2009 John Wiley & Sons, Ltd.
Parental depression, parenting behaviours, and behaviour problems in young children
Authors: Middleton Melissa , Scott Samantha L. , Renk Kimberly
Published: February 2009

In the past, research has demonstrated that parental depression and parenting practices are related. More recently, there has been an increase in research examining child outcomes as they are related to maternal and paternal psychopathology. To continue with this line of research, this study examined the relationships among mothers' and fathers' symptoms of depression, characteristics of their parenting practices, and their ratings of their young children's internalizing and externalizing behaviour problems. The results of this study demonstrated that these variables are related significantly. Further, the results of this study suggested that mothers' parenting, particularly their limit setting with their young children, is an important predictor of their ratings of their young children's externalizing behaviour problems in the context of their own symptoms of depression. A different pattern of relationships may be present for fathers, as both their symptoms of depression and their parenting characteristics predicted their ratings of their young children's externalizing behaviour problems. Such findings were not supported for young children's internalizing behaviour problems. These findings suggested that interventions should have different targets for mothers and fathers. Copyright © 2009 John Wiley & Sons, Ltd.
Biofunctionalization of dispense‐plotted hydroxyapatite scaffolds with peptides: Quantification and cellular response
Authors: Detsch Rainer , Dieser Irina , Deisinger Ulrike , Uhl Franziska , Hamisch Sabine , Ziegler Günter , Lipps Georg
Published: February 2009

Hydroxyapatite (HA) ceramic is a widely used synthetic bone substitute material for the regeneration of bone defects. We manufactured HA scaffolds with adjustable pore sizes and pore geometry by dispense‐plotting. In addition, we attached peptides covalently onto the HA surface and are able to simultaneously quantify the amount of covalently attached and adsorbed peptide down to the picomolar range with a novel fluorescence‐based detection method. In cell culture assays with stromal bone marrow cells, we observed a positive effect of biofunctionalization on cell differentiation after 21 days of culture when comparing the scaffold functionalized with the RGD motif containing adhesion peptide to an unmodified scaffold. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Assessment of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) as a carrier for the oral delivery of therapeutic proteins using Caco‐2 and HT29‐MTX cell lines
Authors: Carr Daniel A. , Peppas Nicholas A.
Published: February 2009

Hydrogels of poly(methacrylic acid‐co‐N‐vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%. Although no insulin was released in gastric conditions, as desired, near instantaneous release occurred when the pH was raised to values typical of the intestinal area. Cytocompatibility studies with Caco‐2 and Caco‐2/HT29‐MTX cultures demonstrated that microparticles did not elicit toxic effects at concentrations up to 5.0 mg/mL. Insulin transport studies revealed that the carriers did not disrupt the cell layer and thus did not change the insulin permeability in the apical‐to‐basolateral direction. Therefore, microparticles of this system were best suited for oral delivery of therapeutic agents that do not require transport facilitation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Effect of the sterilization method on the performance of collagen type I on chronic wound parameters in vitro
Authors: Wiegand Cornelia , Abel Martin , Ruth Peter , Wilhelms Tim , Schulze Daniel , Norgauer Johannes , Hipler Uta‐Christina
Published: February 2009

In the treatment of chronic wounds, it is necessary to establish a physiological wound milieu to improve healing. Application of collagen as wound dressing has been described as beneficial as it possesses the ability to reduce elevated levels of proteases, cytokines, and free radicals. Consequently, a wide range of wound dressings based on collagen have been developed. Native collagen is susceptible to alterations because of influences during the production process; to minimize effects on the molecule itself collagen wound dressings are usually aseptically produced. Common sterilization methods (autoclaving, irradiation, and ethylene oxide (EtO) treatment) can induce changes in the protein chemistry and physical properties, potentially affecting the absorption rate, mechanical strength, or performance. In this study, we have evaluated the influence of γ‐ and β‐irradiation as well as EtO sterilization on the binding capacity of collagen type I for selected proteases and cytokines associated with nonhealing wounds. Although a pronounced effect on the physical properties of the collagen was found, there was no significant loss in the binding affinity for polymorphonuclear elastase, matrix metalloproteinase‐2, and interleukin‐1β, or in the antioxidant capacity. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
2H‐Pyran‐2‐one‐3‐carbothioamide derivatives: Synthesis and reaction with hydrazine hydrate
Authors: Makhloufi‐Chebli Malika , Hamdi Maamar , Silva Artur M. S. , Duval Olivier , Helesbeux Jean‐Jacques
Published: February 2009

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N‐Aryl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one‐3‐carbothiamides and N‐aryl‐4‐hydroxycoumarin‐3‐carbothiamides were synthesized by the reaction of arylisothiocyanates with 4‐hydroxy‐6‐methylpyran‐2‐one and 4‐hydroxycoumarin, respectively. Novel products 3‐[bis(arylamino)methylene]‐6‐methyl‐2H,4H‐pyran‐2,4‐diones and N,N′‐diaryl‐4‐hydroxycoumarin‐3‐carboximidamides have also been obtained in the same reactions. Novel 4‐acetoacetyl‐3‐phenylamino‐4,5‐dihydro‐5H‐pyrazol‐5‐ones were synthesized from the reaction of N‐aryl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one‐3‐carbothiamides with an excess of hydrazine. The structure of all compounds was established by NMR and mass spectra. J. Heterocyclic Chem., (2009).
Synthesis of new 1‐(2‐, 3‐, or 4‐methanesulfonylphenyl)‐2‐[5‐(N‐hydroxypyridin‐2(1H)‐one)]acetylene regioisomers: A search for novel cyclooxygenase and lipoxygenase inhibitors
Authors: Chowdhury Morshed A. , Chen Hua , Abdellatif Khaled R. A. , Dong Ying , Petruk Kenneth C. , Knaus Edward E.
Published: February 2009

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A group of acetylene regioisomers were designed such that a cyclooxygenase‐2 (COX‐2) SO2Me pharmacophore was located at the ortho‐, meta‐, or para‐position of the acetylene C‐1 phenyl ring, and an iron‐chelating 5‐lipoxygenase (5‐LOX) N‐hydroxypyridin‐2(1H)‐one moiety was attached via its C‐5 position to the C‐2 position on an acetylene template (scaffold). These target linear acetylene regioisomers were synthesized via a palladium‐catalyzed Sonogashira cross‐coupling reaction. Structure‐activity data acquired using in vitro cell‐based inhibition assays indicated that this novel class of 1‐(2‐, 3‐, or 4‐methanesulfonylphenyl)‐2‐[5‐(N‐hydroxypyridin‐2(1H)‐one)]acetylene regioisomers did not inhibit the COX‐2 or (5‐LOX) enzymes, and that they are devoid of in vivo anti‐inflammatory activities. J. Heterocyclic Chem., 46, 58 (2009).
A new route to allyl thiols and allyl thiocarbamates from Baylis‐Hillman adducts
Authors: Kim Young‐Gi , Lim Hee Nam , Lee Kee‐Jung
Published: February 2009

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A facile synthesis of trisubstituted allyl thiols and allyl thiocarbamates has been accomplished from Baylis‐Hillman adducts through bromination, thiocyanation, and acid‐assisted hydrolysis reaction. J. Heterocyclic Chem., (2009)
Regioselective unusual formation of spirocyclic 4‐{3′‐benzo(2′,3′‐dihydro)furo}‐9‐methyl‐2,3,9‐trihydrothiopyrano [2,3‐b]indole by acid‐catalyzed reaction of enol ethers
Authors: Majumdar K. C. , Alam S. , Chattopadhyay B.
Published: February 2009

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Spirocyclic 4‐{3′‐benzo(2′,3′‐dihydro)furo}‐9‐methyl‐2,3,9‐trihydrothiopyrano[2,3‐b]indoles are regioselectively synthesized by treating suitable enol ethers, 4‐aryloxymethylene‐9‐methyl‐2,3,9‐trihydrothio‐pyrano[2,3‐b]indoles with H2SO4 in dichloromethane‐methanol‐water. The substrates for the aforesaid reaction are in turn synthesized by the thio‐Claisen rearrangement of 2‐(4′‐aryloxybut‐2′‐ynylthio)‐1‐methylindoles. J. Heterocyclic Chem., 46, 62 (2009).