bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining Gemcitabine and Capecitabine in Patients With Advanced Biliary Cancer: A Phase II Trial
Authors: Knox Jennifer J. , Hedley David , Oza Amit , Feld Ron , Siu Lillian L. , Chen Eric , Nematollahi Mahsan , Pond Gregory R. , Zhang Jessica , Moore Malcolm J. 
Published: March 2005

Purpose Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. Patients and Methods Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m2 orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m2 intravenously over 30 minutes on days 1 and 8. Results Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, for a disease control rate of 73%. The median overall survival time was 14 months (95% CI, 7.3 months to not available), and the median progression-free survival time was 7 months (95% CI, 4.6 to 11.8 months). This chemotherapy combination was generally well tolerated. Transient neutropenia, thrombocytopenia, fatigue, and hand-foot syndrome were commonly observed but were easily managed without discontinuing further treatment. Conclusion The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer. This regimen warrants further evaluation in a randomized study with survival and quality of life end points.
Terpinen-4-ol: mechanisms of relaxation on rabbit duodenum
Authors: Nascimento Nilberto R F , Leal-Cardoso José H , Lessa Lucília M A , Roriz-Filho Jarbas S , Cunha Karina M A , Fonteles Manassés C 
Published: March 2005

Abstract
The effect of terpinen-4-ol was studied on rabbit duodenum in-vitro. Terpinen-4-ol induced relaxation of the basal tonus (IC50 170.2 (95% confidence interval, 175–204) μm) with a maximal relaxant response of 180.4 ± 3.9% (n = 6) of the contraction induced by 60 mm [K+]. The maximal relaxation induced in control conditions was not affected (P&gt;0.05) by pretreatment of the tissues with phentolamine (50 μm) or propranolol (10 μm), Ng nitro-l-arginine methyl ester (L-NAME; 1 mm), 1H-(1,2,4)-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 100 μm), hexamethonium (1 mm), tetrodotoxin (1 μm), the mixture charybdotoxin-apamin (1 μm), glibenclamide (10 μm), 4-aminopyridine (10 μm) or tetraethylammonium (100 μm). In addition, terpinen-4-ol completely relaxed tissues precontracted with 60 mm [K+] solutions (IC50 325.9 (245.1–433.1) μm) and also blocked (IC50 154.7 (117.7–191.7) μm) the phasic component of this contraction. At a concentration of 195 and 650 μm it reduced by 41.3 ± 3.4% and 75.4 ± 3.1%, respectively the maximal contractile response to Ca2+ in depolarized duodenum. Terpinen-4-ol completely blocked the component of carbachol-induced contraction, which was resistent to nifedipine (100 μm) pretreatment or to a Ca2+-free solution. These data show that terpinen-4-ol relaxes intestinal smooth muscle and suggest that this effect is myogenic in nature and depends on calcium antagonism.
Effect of enzyme inducers and inhibitors on the pharmacokinetics of oltipraz in rats
Authors: Bae Soo Kyung , Lee Shin Jung , Kim Young Hoon , Kim Taekrho , Lee Myung Gull 
Published: March 2005

Abstract
A series of in-vitro and in-vivo experiments, using various inducers and inhibitors of hepatic microsomal cytochrome P450 (CYP) isozymes, was conducted to study oltipraz pharmacokinetics in rats. In in-vivo studies, oltipraz at a dose of 10 mg kg−1 was administered intravenously to rats. In rats pretreated with SKF 525-A (a nonspecific CYP isozyme inhibitor in rats; n = 9), the time-averaged total body clearance (CL) of oltipraz was significantly slower (56.6% decrease) than that in untreated rats (n = 9). This indicated that oltipraz is metabolized via CYP isozymes in rats. Hence, various enzyme inducers or inhibitors were used in in-vitro and in-vivo studies in rats. In rats pretreated with 3-methylcholanthrene (n = 9 and 8 for untreated and treated groups, respectively), phenobarbital (n = 7 and 10 for untreated and treated groups, respectively) or dexamethasone (n = 7 and 12 for untreated and treated groups, respectively) (main inducers of CYP1A1/2, 2B1/2 and 3A1/2 in rats, respectively), the CL values were significantly faster (38.4, 94.4 and 33.6% increase, respectively). In rats pretreated with sulfaphenazole (n = 8 and 9 for untreated and treated groups, respectively), quinine (n = 7 and 9 for untreated and treated groups, respectively) or troleandomycin (n = 8 and 9 for untreated and treated groups, respectively) (main inhibitors of CYP2C11, 2D1 and 3A1/2 in rats, respectively), the CL values were significantly slower (31.0, 27.6 and 36.3% decrease, respectively). The in-vivo results with various enzyme inhibitors correlated well with the in-vitro intrinsic clearance for disappearance of oltipraz (CLint) (n = 5, each). The above data suggested that oltipraz could be metabolized in male rats mainly via CYP1A1/2, 2B1/2, 2C11, 3A1/2 and 2D1.
Dermal delivery of desmopressin acetate using colloidal carrier systems
Authors: Getie Melkamu , Wohlrab Johannes , Neubert Reinhard H H 
Published: March 2005

Abstract
Recently, the transdermal route has received attention as a promising means to enhance the delivery of drug molecules, particularly peptides, across the skin. In this work, the skin penetration profiles of desmopressin acetate from a colloidal system (water-in-oil microemulsion) and an amphiphilic cream, a standard formulation, were determined using Franz diffusion cells and compared. In the case of the microemulsion, the total percentages of dose obtained from different skin layers (stratum corneum to subcutaneous tissue) were 3.30 ± 0.67, 7.37 ± 2.43 and 15.54 ± 2.72 at 30, 100 and 300 min, respectively. Similarly, 5.19 ± 0.96, 8.04 ± 0.97 and 14.4 ± 5.15% of the dose applied was extracted from the skin treated with the cream. About 6% of the applied dose reached the acceptor compartment from the microemulsion instead of 2% from the cream within 300 min. The concentration of drug that penetrated into the upper layers of the skin was higher from the cream than from the microemulsion at all time intervals. On the other hand, a higher amount of drug was found in the deeper skin layers and in the acceptor compartment from the microemulsion.
Hydroquinone modulates reactivity of peroxynitrite and nitric oxide production
Authors: Kim Ae Ra , Cho Jae Youl , Lee Ji Yeon , Choi Jae Sue , Chung Hae Young 
Published: March 2005

Abstract
Peroxynitrite (ONOO−), a potent cytotoxic oxidant formed by the reaction of nitric oxide (*NO) and superoxide radical (*O2−), may be rapidly lethal in a cellular milieu due to oxidization and nitration processes. In the present study, hydroquinone displayed strong ONOO− scavenging activity and inhibitory effect on NO production in murine macrophage RAW264.7 cells. Hydroquinone strongly scavenged ONOO− induced dihydrorhodamine 123 oxidation in a dose-dependent manner compared with other reactive species such as *O2− and *NO. Hydroquinone also decreased levels of ONOO− induced nitrotyrosine of glutathione reductase and consequently prevented the enzyme from ONOO− induced damage. Furthermore, hydroquinone suppressed NO production, a cellular pathway for ONOO− formation, in lipopolysaccharide-activated RAW264.7 cells via inhibition of inducible NO synthase expression. The inhibitory effect by hydroquinone seems to be mediated by interruption of lipopolysaccharide-induced signalling such as activation of nuclear factor-kB and extracellular signal-related kinases 1 and 2. The results suggest that hydroquinone may potently modulate reactivity of ONOO− and may therefore be a useful agent against ONOO− mediated diseases.
Nicardipine, a calcium antagonist, does not aggravate intracerebral haemorrhage in an intracerebral haemorrhage model in rats
Authors: Suzuki Masanori , Hayashi Aska , Sasamata Masao 
Published: March 2005

Abstract
Despite controversy over their safety in patients with intracerebral haemorrhage, calcium antagonists are widely used in the treatment of hypertensive emergencies. Here, we investigated the effects of nicardipine on haematoma size and neurological deficit in a rat model of collagenase-induced intracerebral haemorrhage. Injection of collagenase (0.014 U) into the striatum induced haematoma (19.9 ± 3.4 mm3) in the striatum and brain oedema. Drugs were infused from 30 min after collagenase injection for 3 h under conscious conditions. Nicardipine intravenously at 0.1, 1 and 10 μg kg−1 min−1 affected neither haematoma size nor the degree of brain oedema. Nicardipine at these doses provided a stable and dose-dependent decrease in mean blood pressure of 6%, 13% and 33%, respectively, with an increase in heart rate that was apparently caused reflexively. Further, nicardipine did not aggravate the neurological deficits in these intracerebral haemorrhage rats, primarily forearm flexion behaviour on suspension by the tail and circling behaviour. These results indicate that nicardipine infusion stably decreased blood pressure without affecting intracerebral haemorrhage in an intracerebral haemorrhage model in rats.
High-speed digital imaging method for ciliary beat frequency measurement
Authors: Dimova Svetlana , Maes Frederik , Brewster Marcus E , Jorissen Mark , Noppe Mark , Augustijns Patrick 
Published: March 2005

Abstract
The aim of this study was to develop a high-speed digital imaging system and related software for ciliary beat frequency (CFB) analysis in order to establish an automated and reliable method that is observer independent and faster compared to the conventional computerized microscope photometry method. Using primary human nasal epithelial cell cultures, the CBF was recorded with a computerized microscope photometry system and a high-speed digital imaging system. To obtain a wide range of frequencies, glycocholate (0.5%) and chlorocresol (0.005%) were used as ciliostimulatory and cilio-inhibitory reference compounds, respectively. The mean values in hertz (± s.d.) obtained with the photometry and high-speed digital imaging systems were: controls 8.2 ± 0.9 and 7.9 ± 1.1; chlorocresol 5.0 ± 0.9 and 5.1 ± 1.1; glycocholate 9.8 ± 1.0 and 9.7 ± 0.8. A similar increase (by 20 and 24%) and decrease (by 38 and 35%) in CBF was determined by the two methods after glycocholate and chlorocresol treatment, respectively. The mean difference between the photometry and high-speed digital imaging methods was 0.2 ± 0.6 Hz, and the Bland-Altman limits of agreement were from −1.0 to + 1.4 Hz, suggesting that the results obtained by these two methods could be used interchangeably. These results show the reliability of the high-speed digital imaging system and the software developed for in-vitro CBF measurements. The advantages of the system include: (i) fast data acquisition and calculation, (ii) whole field automated CBF analysis and (iii) reduction in selection bias.
Investigation of oral bioavailability and brain distribution of the Ind(8)-Val conjugate of indinavir in rodents
Authors: de Oliveira Manuela Pereira , Olivier Jean-Christophe , Pariat Claudine , Roche Dominique , Greiner Jacques , Vierling Pierre , Couet William 
Published: March 2005

Abstract
Protease inhibitors are successfully used for the treatment of acquired immune deficiency syndrome (AIDS) although their biopharmaceutical characteristics are not optimal. Prodrugs have therefore been synthesized to increase protease inhibitor bioavailability and brain distribution. Among several compounds tested, a valine derivative of indinavir (Ind(8)-Val) showed promising characteristics using an in-vitro Caco-2 cell model. The objective of this study was to further investigate this compound using in-situ and in-vivo approaches. The pharmacokinetics of indinavir (Ind) and Ind(8)-Val were investigated in rats after intravenous and oral administration. Free indinavir resulting from in-vivo hydrolysis of Ind(8)-Val could not be detected in the plasma of rats receiving Ind(8)-Val. Furthermore Ind(8)-Val bioavailability was only 32% on average compared with 76% for indinavir, and effective permeability coefficients determined with a single-pass intestinal perfusion method were close to 25 times 106 cms−1 for the two compounds. Brain-to-plasma concentration ratios in the post equilibrium phase after intravenous administration to mice were 9.7 ± 8.1% for indinavir and 2.5 ± 2.7% for Ind(8)-Val. In conclusion, the promising biopharmaceutical characteristics of Ind(8)-Val suggested from previous in-vitro experiments with the Caco-2 cell model were not confirmed by in-situ and in-vivo experiments.
Influence of magnesium aluminium silicate on rheological, release and permeation characteristics of diclofenac sodium aqueous gels in-vitro
Authors: Pongjanyakul Thaned , Priprem Aroonsri , Puttipipatkhachorn Satit 
Published: March 2005

Abstract
The effect of magnesium aluminium silicate (MAS) on rheological, release and permeation characteristics of diclofenac sodium (DS) aqueous gels was investigated. DS aqueous gels were prepared using various gelling agents, such as 15% w/w poloxamer 407 (PM407), 1% w/w hydroxypropylmethylcellulose (HPMC), and 1% w/w high and low viscosity grades of sodium alginate (HV-SA and LV-SA, respectively). Different amounts of MAS (0.5, 1.0 and 1.5% w/w) were incorporated into the DS gels. Incorporation of MAS into the DS gels prepared using SA or PM407 caused a statistical increase in viscosity (P&lt;0.05) and a shift from Newtonian flow to pseudoplastic flow with thixotropic property. The DS release rates of these composite gels were significantly decreased (P&lt;0.05) when compared with the control gels. This was due to an interaction between MAS and PM407 or SA, and adsorption of DS onto MAS particles. Moreover, a longer lag time and no change in DS permeation flux were found when MAS was added to the gels. The findings suggest that the rheological characteristics of gels prepared using PM407 or SA could be improved by incorporating MAS. However, the use of MAS could retard the DS release and extend the lag time of DS permeation.
Development of simple thiol-reactive liposome formulations, one-step analysis and physicochemical characterization
Authors: Kaourma E , Hatziantoniou S , Georgopoulos A , Kolocouris A , Demetzos C 
Published: March 2005

Abstract
The aim of this study was to synthesize simple thiol-reactive conjugates from maleimide and lipoamines (stearylamine or oleylamine) and to develop a simple, fast and low-cost method for the preparation of lyophilized general-purpose thiol-reactive liposomes. A formulation of egg phosphatidylcholine-dipalmitoylphoshatidylglycerol (9:0.1 molar ratio) was developed and characterized. Freeze-drying methodology was established to produce a stock of liposomes and the physicochemical characteristics of the reconstituted liposomes were compared with those of the initial preparation. The physicochemical properties (size and ζ-potential) of the new liposomal formulations were studied. High-performance thin-layer chromatography coupled to a flame ionization detector was applied for one-step analysis of the liposomal components and for determining the maleimide-lipoamine conjugates phospholipid molar ratio. The differences concerning the incorporation efficiency of the synthetic conjugates into liposomes were discussed on the basis of their conformational properties. The small difference in structure between the two thiol-reactive conjugates (i.e., the C18 alkyl chain double bond) causes a considerable difference in phospholipids packing of the resulting lipidic bilayers of the liposomes; the conformational bending of conjugate maleimide-oleylamine may contribute to the final architecture of liposomes.
Clinical Features of Aneurysms of the Posterior Cerebral Artery: A 15-year Experience with 21 Cases
Authors: Hamada Jun-ichiro , Morioka Motohiro , Yano Shigetoshi , Todaka Tatemi , Kai Yutaka , Kuratsu Jun-ichi 
Published: March 2005

AbstractOBJECTIVE:To investigate the characteristic clinical behavior and develop guidelines for the clinical management of posterior cerebral artery aneurysms, we reviewed 21 cases treated during a 15-year period.METHODS:Between 1988 and 2002, we treated 21 patients (10 male, 11 female; mean age, 49.8 yr) with posterior cerebral artery aneurysms at Kumamoto University Hospital and its affiliated hospitals. Data relating to the clinical, radiological, and surgical approaches were analyzed.RESULTS:There were 20 saccular aneurysms, 6 of which were giant or large aneurysms, and 1 dissecting aneurysm. Of the 21 patients, 15 presented with subarachnoid hemorrhage; in 3 patients, an unruptured saccular aneurysm was found incidentally during an evaluation for other cerebral pathological conditions. Two patients presented with progressive homonymous hemianopsia because of the mass effect of the aneurysm, and 1 patient experienced the sudden onset of homonymous hemianopsia because of thrombosis of the aneurysm and afferent artery. Open or endovascular surgery was performed in 19 patients: 14 made a good recovery, 2 had a moderate disability because of angiospasm or infarction after aneurysm trapping, 1 had a severe disability because of angiospasm and cerebral contusion, and 2 died because of severe angiospasm. Of 2 conservatively treated patients, 1 made a good recovery but the other died as a result of rebleeding.CONCLUSION:Posterior cerebral artery aneurysms have specific clinical characteristics compared with aneurysms located elsewhere. The aneurysmal site and size and the surgical technique did not significantly influence treatment outcomes.
Factors Associated with Neurological Outcome and Lesion Progression in Traumatic Subarachnoid Hemorrhage Patients
Authors: Chieregato Arturo , Fainardi Enrico , Morselli-Labate Antonio Maria , Antonelli Vincenzo , Compagnone Christian , Targa Luigi , Kraus Jess , Servadei Franco 
Published: March 2005

Abstract

OBJECTIVE:
Traumatic subarachnoid hemorrhage (tSAH) is a frequent finding after closed-head injuries, and its presence is a powerful factor associated with poor outcome. The exact mechanism linking tSAH and an adverse outcome is poorly understood. The aim of this study was to identify the factors that may predict outcomes and changes in the computed tomographic (CT) scans of lesions in a selected population of tSAH patients.

METHODS:
We evaluated 141 patients admitted consecutively from January 1, 1997, to January 31, 1999, with a CT diagnosis of tSAH. The admission and “worst” CT scans were recorded. CT scan changes were reported as “significant CT progression” (changes in the Marshall classification) or “any CT progression.” The amount of subarachnoid blood was recorded using a modified Fisher classification. Outcome was assessed at 6 months after injury with the Glasgow Outcome Scale.

RESULTS:
Twenty-eight patients (19.9%) had an unfavorable Glasgow Outcome Scale outcome. In the univariate analysis, prognosis was significantly related to age, admission Glasgow Coma Scale score, Marshall CT classification score at admission and on the worst CT scan, amount of tSAH, and volume of the associated brain contusions. From multivariate analysis, the only factors independently related to outcome were the Glasgow Coma Scale score (P &lt; 0.01) and size of the tSAH at admission (P &lt; 0.001). Thirty-four patients (24.1%) had significant CT lesion progression, and 66 patients (46.8%) had some lesion progression. Patients having significant progression of the lesion had a higher risk of an unfavorable outcome (32 versus 10%; P = 0.004). Unadjusted factors predicting CT progression were the Glasgow Coma Scale score at admission, the Marshall classification at admission, the amount of subarachnoid blood, and the presence or volume of associated brain contusions at admission. Independent factors associated with significant CT progression were the amount of tSAH (P &lt; 0.001) and the presence or volume of brain contusions at admission (P &lt; 0.001).

CONCLUSION:
The outcome of patients with tSAH at admission is related in a logistic regression analysis to the admission Glasgow Coma Scale score and to the amount of subarachnoid blood. These patients also have a significant risk of CT progression. The amount of subarachnoid blood and the presence of associated parenchymal damage are powerful independent factors associated with CT progression, thus linking poor outcomes and CT changes.
Risk Factors for Hemorrhage during Microelectrode-guided Deep Brain Stimulator Implantation for Movement Disorders
Authors: Binder Devin K. , Rau Geoff M. , Starr Philip A. 
Published: March 2005

Abstract

OBJECTIVE:
Although hemorrhage is a well-known complication of microelectrode-guided deep brain stimulation (DBS) surgery, risk factors for the development of hemorrhage have not been well defined. We analyzed the risk factors for symptomatic and asymptomatic hemorrhage in a large series of DBS implantations into the subthalamic nucleus, ventrolateral thalamus, and internal globus pallidus.

METHODS:
All DBS procedures performed by a single surgeon at our institution between June 1998 and May 2004 were included in this study. All patients had postoperative imaging (magnetic resonance imaging or computed tomography) 4 to 24 hours after surgery. Hematomas were noted and scored as symptomatic or asymptomatic. Statistical correlation of factors affecting risk of hematoma formation was performed by use of logistic regression analysis.

RESULTS:
The total number of lead implantations was 481. There were 6 symptomatic hematomas and 10 asymptomatic hematomas. Three of the symptomatic hematomas resulted in permanent new neurological deficit. The risk of hematoma (of any type) per lead implantation was 3.3%, whereas the risk of permanent deficit from hematoma was 0.6%. Patients who developed hematomas had a slightly greater number of microelectrode recording penetrations than patients who did not have hematomas, but this difference did not reach statistical significance. There was not a statistically significant relationship between risk of hematoma and patient age or diagnosis. There was a significant effect of brain target (P = 0.001), with only 1 hemorrhage detected after thalamic DBS.

CONCLUSION:
DBS is generally safe, with only 0.6% of implantations associated with permanent neurological deficit. The incremental risk of successive serial microelectrode penetrations is small.
Hemothorax as a Complication after Anterior Cervical Discectomy: Case Report
Authors: Harhangi B Sanjay , Menovsky Tomas , Wurzer Hans A.L. 
Published: March 2005

Abstract

OBJECTIVE AND IMPORTANCE:
Anterior cervical discectomy is one of the most frequently performed surgical procedures of the cervical spine.

CLINICAL PRESENTATION:
We describe a patient with a postoperative hemothorax as a complication after an anterior cervical discectomy.

INTERVENTION:
The patient was intubated, and reoperation and bronchoscopy were performed.

CONCLUSION:
To the best of our knowledge, such a complication has not been described before in the English-language literature. We conclude that hemothorax is a rare, although serious, complication after anterior cervical discectomy and should be included in the differential diagnosis for patients with respiratory failure after an anterior cervical discectomy.