bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized trial of tolcapone versus pergolide as add‐on to levodopa therapy in Parkinson's disease patients with motor fluctuations
Authors: Koller William , Lees Andrew , Doder Miroslava , Hely Mariese ,   the Tolcapone/Pergolide Study Group
Published: August 2002

AbstractIn this 12‐week, randomized, open‐label, blinded‐rater, parallel‐group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included “off” time (reduced by 2–3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)‐39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ‐39 score at week 12 were −8.7 and −14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone‐treated patients and in 78% of pergolide‐treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3‐month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of fife, was better tolerated, and had a more favorable adverse‐event profile than pergolide. © 2001 Movement Disorder Society.
Life‐threatening parkinsonism induced by kava‐kava
Authors: Meseguer Elena , Taboada Rocio , Sánchez Vicenta , Mena María Angeles , Campos Victor , García de Yébenes Justo 
Published: August 2002

AbstractWe present a 45‐year‐old female with severe parkinsonism induced by kava‐kava. The patient, who had a family history of essential tremor, developed severe and persistent parkinsonism after days of treatment with kava extract for anxiety. The symptoms improved with anticholinergics. Kava derivatives could produce severe parkinsonism in individuals with genetic susceptibility. © 2002 Movement Disorder Society.
Randomised, double‐blind, placebo‐controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia
Authors: Fox Susan H. , Kellett Mark , Moore A. Peter , Crossman Alan R. , Brotchie Jonathan M. 
Published: August 2002

AbstractCannabis may have medicinal uses in a variety of diseases. The neural mechanisms underlying dystonia involve abnormalities within the basal ganglia—in particular, overactivity of the lateral globus pallidus (GPl). Cannabinoid receptors are located presynaptically on GABA terminals within the GPi, where their activation reduces GABA reuptake. Cannabinoid receptor stimulation may thus reduce overactivity of the GPl and thereby reduce dystonia. A double‐blind, randomised, placebo‐controlled, crossover study using the synthetic cannabinoid receptor agonist nabilone in patients with generalised and segmental primary dystonia showed no significant reduction in dystonia following treatment with nabilone. © 2001 Movement Disorder Society.
Role of drug metabolism in drug discovery and development
Authors: Kumar Gondi N. , Surapaneni Sekhar 
Published: August 2002

AbstractMetabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. High metabolic lability usually leads to poor bioavailability and high clearance. Formation of active or toxic metabolites will have an impact on the pharmacological and toxicological outcomes. There is also potential for drug–drug interactions with coadministered drugs due to inhibition and/or induction of drug metabolism pathways. Hence, optimization of the metabolic liability and drug–drug interaction potential of the new chemical entities are some of the most important steps during the drug discovery process. The rate and site(s) of metabolism of new chemical entities by drug metabolizing enzymes are amenable to modulation by appropriate structural changes. Similarly, the potential for drug–drug interactions can also be minimized by appropriate structural modifications to the drug candidate. However, the optimization of the metabolic stability and drug–drug interaction potential during drug discovery stage has been largely by empirical methods and by trial and error. Recently, a lot of effort has been applied to develop predictive methods to aid the optimization process during drug discovery and development. This article reviews the role of drug metabolism in drug discovery and development. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 5, 397–411, 2001
In vivo monitoring of microvessels in skin flaps: Introduction of a novel technique
Authors: Langer Stefan , Biberthaler Peter , Harris Anthony Gustave , Steinau Hans‐Ulrich , Messmer Konrad 
Published: August 2002

AbstractOrthogonal polarization spectral (OPS) imaging was validated against intravital fluorescence microscopy (IFM) for microvascular measurements in skin flaps of hairless mice. Examinations were performed 1, 6, and 24 hours after elevation (n = 8) with both OPS imaging and IFM. A fluorescent dye was a prerequisite for IFM measurements but not for OPS imaging. Our findings show that OPS imaging can visualize the skin flap microcirculation independent from the application of fluorescent tracers. From these images, quantitative analysis of functional capillary density (FCD) was feasible. As expected, FCD was significantly lower in the distal part of the flap compared with its base (171.8 ± 34.7 versus 62.0 ± 25.6, mean ± SD; 1 hour data). Comparison of OPS imaging and IFM revealed a significant correlation of FCD values (P < 0.001) at all time points. Given the success of this validation study on mouse skin flaps, clinical investigations will have to prove that OPS imaging can also successfully be used to monitor flaps in humans. © 2001 Wiley‐Liss, Inc. MICROSURGERY 21:317–324 2001
Use of osteocutaneous “double‐barrel fibular flaps” in limb reconstruction: Four clinical cases
Authors: Dautel G. , Duteille F. , Merle M. 
Published: August 2002

AbstractThe use of a vascularized fibular transfer is a technique used for the reconstruction of large defects in long bones. A technical variation that consists of osteotomizing the transplant, giving two distinct segments, is adapted in the reconstruction of long bones with a large diameter, in particular, the femur or the proximal tibia. The results obtained using this technique in four clinical cases are presented here. The length of the bone defects was between 7.5 and 11 cm. There were two cases involving the tibia, one case the distal humerus, and one case the pelvis. © 2001 Wiley‐Liss, Inc. MICROSURGERY 21:340–344 2001
Bow‐tie wide‐band monopole antenna with the novel impedance‐matching technique
Authors: Lee Jong‐Pil , Park Seong‐Ook , Lee Sang‐Keun 
Published: August 2002

AbstractA staircase bow‐tie monopole‐type antenna that features a novel broadband technique is investigated experimentally and numerically. A bandwidth of 77.1% (VSWR ≤ 2) can be achieved, and an omnidirectional radiation pattern is obtained. The electrical characteristics of the proposed antenna make it attractive for use in multiband mobile systems. © 2002 Wiley Periodicals, Inc. Microwave Opt Technol Lett 33: 448–452, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10347
A compact microstrip antenna with meandering slots in the ground plane
Authors: Kuo Jieh‐Sen , Wong Kin‐Lu 
Published: August 2002

AbstractA novel compact microstrip antenna design is demonstrated. By embedding meandering slots in the antenna's ground plane, it is observed that the resonant frequency of the microstrip antenna is significantly lowered, which can lead to a large antenna size reduction for a fixed frequency operation. In addition, enhanced impedance bandwidth and antenna gain are also observed for the proposed antenna. Details of the proposed design and experimental results of the constructed prototypes are presented and discussed. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 29: 95–97, 2001.
Wind direction azimuthal signature in the Stokes emission vector from the ocean surface at microwave frequencies
Authors: Camps A. J. , Reising S. C. 
Published: August 2002

AbstractAn ocean polarimetric emission model is presented. It is found that skewness and upwind/cross‐wind rms slopes are responsible for the first and second azimuthal harmonic, respectively. Atmospheric effects contribute significantly at low wind speeds, and at horizontal polarization at certain observation angles. Simulation results compare favorably with reported JPL–WINDRAD measurements. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 29: 426–432, 2001.
Radiation‐induced skin cancer in humans*
Authors: Shore Roy E. 
Published: August 2002

AbstractThe principal epidemiologic studies of ionizing radiation and skin cancer have all shown that radiation causes basal cell carcinoma but have not found dose‐related excesses of squamous cell carcinoma or malignant melanoma. The Japanese atomic bomb study indicates that doses of radiation under about 1 Gy confer less risk per unit dose than higher doses do. All available studies show that skin cancer risk is greater from radiation exposure at young ages than at older ages. Finding few excess skin cancers among irradiated African‐Americans as compared to Caucasians with a comparable dose indicates that skin susceptibility to ultraviolet exposure modifies the excess risk from ionizing radiation. Available evidence indicates that the excess risk of skin cancer lasts for 45 years or more following irradiation. Several studies indicate a risk of nonmelanoma skin cancer (NMSC) following cancer therapy; however, most of the studies reporting on NMSC have not distinguished between patients who received radiotherapy versus chemotherapy. Some, but not all, follow‐up studies of cancer patients have reported excesses of malignant melanoma as second malignant neoplasms. It is not clear from the studies how much, if any, of the excess melanoma risk is attributable to radiotherapy. Med. Pediatr. Oncol. 36:549–554, 2001. © 2001 Wiley‐Liss, Inc.
Natural J coupling (NJC) analysis of the electron lone pair effect on NMR couplings: Part 1. The lone pair orientation effect of an α‐nitrogen atom on 1J(C,C) couplings
Authors: Barone Verónica , Peralta Juan E. , Contreras Rubén H. , Sosnin Anton V. , Krivdin Leonid B. 
Published: August 2002

AbstractThe known lone pair orientation effect of an α‐nitrogen atom on 1J(C,C) couplings was studied using the natural J coupling (NJC) dissection method for the Fermi contact (FC) term. This dissection was performed at the DFT‐B3LYP level using three different basis sets. It was verified that non‐contact contributions, which are much smaller than the FC term, do not depend on the orientation of the N lone pair. Acetone oxime (1), protonated acetone oxime (2) and ethylamine (3), were taken as model compounds to perform this study. In 1 the difference between 1J(Z) and 1J(E) is mainly determined by three NJC terms, i.e the nitrogen lone pair, the carbon–carbon bond containing the coupled carbon atoms and the carbon inner core orbitals contributions. In 3 the angular dependence of 1J(C,C) vs the amine group conformation is dominated by the same three contributions that define the 1J(Z) and 1J(E) difference in 1. Copyright © 2001 John Wiley & Sons, Ltd.
Identification and characterisation of known and novel transcripts expressed during the final stages of human oocyte maturation
Authors: Goto Tetsuya , Jones Gayle M. , Lolatgis Nick , Pera Martin F. , Trounson Alan O. , Monk Marilyn 
Published: August 2002

AbstractThe final stages of oocyte maturation, from the germinal vesicle (GV) stage to metaphase II (MII) oocytes, are characterised by a series of dynamic events. These include germinal vesicle break down (GVBD), resumption of meiosis, and nuclear and cytoplasmic maturation to produce MII oocytes ready for fertilisation. To investigate the specific genes transcribed during these stages of oogenesis, we have prepared and analysed amplified cDNA representing the transcribed genes in a series of GV and MII oocytes. Differential display analysis disclosed that the overall gene expression profiles between different samples of GV oocytes are very similar, regardless of their source, while those between the MII oocytes are markedly variable. A comparison of expression profiles in oocytes and somatic (cumulus) cells identified several known genes preferentially‐expressed in oocytes (e.g., a zona pellucida gene), as well as five novel sequences. Two of the five novel sequences are homologous to retrotransposon sequences, long terminal repeat (LTR) and long interspersed nuclear element (LINE) 1, and two other sequences show partial homology to known ESTs and genomic sequences. The remaining sequence, which is identical to shorter ESTs isolated from germ cell tumor cDNA libraries, was extended towards its 5′ end by PCR, using the original cDNA preparation from which it was isolated as a template. Expression of the resultant 1.1‐kb transcript is restricted to the testis and ovary, and its expression correlates with cell pluripotency in that it is expressed in embryonal carcinoma cells, but not in their differentiated derivative cells. Mol. Reprod. Dev. 62: 13‐28, 2002. © 2002 Wiley‐Liss, Inc.
Apoptosis in sea urchin oocytes, eggs, and early embryos
Authors: Voronina Ekaterina , Wessel Gary M. 
Published: August 2002

AbstractCertain experimental manipulations with sea urchin oocytes, eggs, and early embryos result in induction of cell death. We were interested in whether or not these cells posessed functional apoptotic machinery, and whether cellular demise under certain experimental conditions is due to activation of a programmed cell death pathway. Therefore, we evaluated a number of apoptosis assays in sea urchin oocytes, eggs, and early embryos experimentally induced to apoptose with staurosporine. Our results indicate that these cells each possess and activate necessary apoptotic machinery that leads to characteristic apoptotic phenotypes. The eggs of this animal have completed meiosis, and are quiescent transcriptionally, translationally, and metabolically. Suprisingly, they still undergo apoptosis. The progression through apoptosis of treated specimens could be followed by morphological changes of the cells, by chromatin condensation and degradation, and by activation of caspases. The similarities and differences in the execution of apoptosis between the cell types studied are discussed. Results of this study will be useful for interpreting experiments in these model systems in which different molecules are targeted for interference and which brings about cell death. Mol. Reprod. Dev. 60: 553–561, 2001. © 2001 Wiley‐Liss, Inc.
Seminal plasma proteins reduce protein tyrosine phosphorylation in the plasma membrane of cold‐shocked ram spermatozoa
Authors: Pérez‐Pé Rosaura , Grasa Patricia , Fernández‐Juan Marta , Peleato Maria Luisa , Cebrián‐Pérez José Álvaro , Muiño‐Blanco Teresa 
Published: August 2002

AbstractCapacitation of spermatozoa, a complex process occurring after sperm ejaculation, is required to produce fertilization of the oocyte in vivo and in vitro. Although this process results from a poorly understood series of morphological and molecular events, protein tyrosine phosphorylation has been associated with sperm capacitation in several mammalian species, but it still remains to be demonstrated in ram spermatozoa. Studies of capacitation in ram spermatozoa are of great interest, since several reports have suggested that the reduced fertility of cryopreserved spermatozoa is due to their premature capacitation. In this work, we report for the first time, to our knowledge, that tyrosine phosphorylation of ram sperm membrane proteins is related to the capacitation state of these cells.Capacitation induced tyrosine phosphorylation of some plasma membrane proteins of ram spermatozoa freed from seminal plasma by a dextran/swim‐up procedure. It has also been proved that cold‐shock induces protein tyrosine phosphorylation as well as a decrease in plasma membrane integrity. Addition of seminal plasma proteins prior to cold‐shock not only improved sperm survival but also promoted a decrease in protein tyrosine phosphorylation. Mol. Reprod. Dev. 61: 226–233, 2002. © 2002 Wiley‐Liss, Inc.
EPR/NMR co‐imaging for anatomic registration of free‐radical images
Authors: He Guanglong , Deng Yuanmu , Li Haihong , Kuppusamy Periannan , Zweier Jay L. 
Published: August 2002

AbstractWhile electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals in the whole body of small animals, it solely visualizes the free‐radical distribution and does not typically provide anatomic visualization of the body. However, anatomic registration is often required for meaningful interpretation of the EPRI‐derived free‐radical images. An approach is reported for whole‐body, EPRI‐based, free‐radical imaging along with proton MRI in mice. EPRI instrumentation with a 750‐MHz narrow band microwave bridge and transverse oriented electric field reentrant resonator, with automatic coupling control and automatic tuning control capability, was used to map the spatial distribution of nitroxide free radicals in phantoms and in living mice, while low‐field proton MRI at 16 MHz was used to define the anatomic structure to register the EPR images. Small capillary tubes containing an aqueous radical label were used as markers to enable image superimposition. With this coregistration technique, the EPRI free‐radical images were precisely registered, enabling assignment of the location of the observed free‐radical distribution within the organs of the mice. This technique enabled differentiation of the distribution and metabolism of nitroxide radicals within the major organs and body sites of living mice. Magn Reson Med 47:571–578, 2002. © 2002 Wiley‐Liss, Inc.
Biexponential diffusion attenuation in the rat spinal cord: Computer simulations based on anatomic images of axonal architecture
Authors: Chin Chih‐Liang , Wehrli Felix W. , Hwang Scott N. , Takahashi Masaya , Hackney David B. 
Published: August 2002

AbstractWater diffusion in neurological tissues is known to possess multicomponent diffusion behavior. The fractions of fast and slow apparent diffusion components have often been attributed to the volume fractions of extracellular space (ECS) and intracellular space (ICS) although diffusion fractions are at variance with the tissue compartment volume ratios. In this article this puzzle was examined with a finite difference diffusion simulation model on the basis of optical images from sectioned rat spinal cord. Here the results show that assignment of fractions obtained from biexponential fits of fast and slow diffusion attenuation to ECS and ICS volume ratios is not correct. Rather, the observed multicomponent diffusion behavior is caused by motional restriction and limited intercompartmental water exchange in that at long diffusion times diffusion attenuation is shown to become monoexponential. Although the measured apparent diffusion fractions also depend on T2 relaxation time of water protons in the various compartments, the sensitivity to T2 is small and thus T2 differences are unlikely to explain the mismatch between apparent diffusion fractions and cellular volume fractions. Magn Reson Med 47:455–460, 2002. © 2002 Wiley‐Liss, Inc.
Dynamic 19F‐MRI of pulmonary ventilation using sulfur hexafluoride (SF6) gas
Authors: Schreiber Wolfgang Günther , Eberle Balthasar , Laukemper‐Ostendorf Simone , Markstaller Klaus , Weiler Norbert , Scholz Alexander , Bürger Katja , Heussel Claus Peter , Thelen Manfred , Kauczor Hans‐Ulrich 
Published: August 2002

AbstractA new method for dynamic imaging of pulmonary wash‐in and wash‐out kinetics of inhaled sulfur hexafluoride (SF6) gas was developed. Measurements at the fluorine‐19 Larmor frequency were performed in pigs using a gradient echo pulse sequence with 0.5 ms echo time and a measurement time of 9.1 s per image. Dynamic MRI was performed during wash‐in and wash‐out of SF6 gas in mechanically ventilated porcine lungs. A postprocessing strategy was developed for quantitative determination of wash‐out time constants in the presence of noise. Mean wash‐out constants were 4.78 ± 0.48 breaths vs. 4.33 ± 0.76 breaths for left and right lung when ventilation was performed with low tidal volume, and 1.73 ± 0.16 breaths vs. 1.85 ± 0.11 breaths with high tidal volume ventilation. In conclusion, breath‐hold MRI of SF6 gas is feasible in large animals. Moreover, regional wash‐in and wash‐out kinetics of SF6 can be determined noninvasively with this new method. Potential human applications are discussed. Magn Reson Med 45:605–613, 2001. © 2001 Wiley‐Liss, Inc.
Abnormal lipid profile of dystrophic cardiac tissue as demonstrated by one‐ and two‐dimensional magic‐angle spinning 1H NMR spectroscopy
Authors: Griffin J.L. , Williams H.J. , Sang E. , Nicholson J.K. 
Published: August 2002

AbstractDystrophin, a protein associated with sarcolemma and cell membranes, is not expressed in sufferers of Duchenne muscular dystrophy (DMD), or in the mdx mouse. DMD is a fatal disorder, with a significant proportion of fatalities associated with cardiac failure (∼40% having dilated cardiomyopathy and >90% clinically significant cardiac defects at death). In this study, the metabolic composition of intact dystrophic cardiac tissue was investigated using high‐resolution magic‐angle spinning (HRMAS) 1H NMR spectroscopy with both 1‐ and 2D pulse sequences coupled with pattern recognition (PR). While conventional solvent presaturation spectra indicated increases in CH2 chain length in lipids, PR analysis of correlation spectroscopy (COSY) spectra demonstrated that this was also accompanied by an increase in concentration of lactate or threonine along with a relative decrease in CH = CHCH2CO groups in these lipids. To investigate the physical environment of these lipids, T2‐ and diffusion‐weighted 1H MAS NMR spectra were acquired on whole‐tissue samples. The relatively increased lipid signal intensity in dystrophic tissue was due to an increase in molecules with long T2 and short diffusion rates. The use of a range of pulse programs allowed the direct probing of the biochemical environment in which the lipid infiltration occurred, and by coupling the experiments to PR the significance of lipid infiltration and accumulation was also assessed. Magn Reson Med 46:249–255, 2001. © 2001 Wiley‐Liss, Inc.