bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timolol 0.1% Gel (Nyogel 0.1%<sup>®</sup>) Once Daily versus Conventional Timolol 0.5% Solution Twice Daily: A Comparison of Efficacy and Safety
Authors: Rouland Jean-François , Morel-Mandrino Patricia , Elena Pierre-Paul , Polzer Heinz , Sunder Raj Palaniswamy 
Published: April 2003

In a prospective, randomised, double-masked, parallel-group, multi-centre study, 210 patients with primary open angle glaucoma or ocular hypertension were enrolled of whom 167 (timolol 0.1% gel 82, timolol 0.5% 85) completed the study as per protocol. The change in intraocular pressure between baseline and week 12 in the worse eye (‘at trough’) was 6.3 (SD 3.3) mm Hg on timolol 0.1% gel and 7.0 (2.9) mm Hg on timolol 0.5%; this difference was not statistically significant (p = 0.19). The difference between the two study groups in the change of intraocular pressure from baseline was 0.62 mm Hg; the 90% CI of –0.09 to +1.33 mm Hg was within the pre-specified limits of –1.5 to +1.5 mm Hg demonstrating equivalence between timolol 0.1% gel and timolol 0.5%. The plasma levels of timolol (ng/ml) at 12 weeks in the timolol 0.1% gel group were significantly less than that with timolol 0.5% both before instillation (mean 0.057, SD 0.131 and mean 0.470, SD 0.519 respectively, p = 0.025) and after instillation (mean 0.552, SD 0.992 and mean 2.473, SD 1.780 respectively, p = 0.008). Both treatments were well tolerated with no statistically significant difference between the groups in the occurrence of ocular or systemic adverse events.
Inhibition of Prostaglandin Biosynthesis in Human Endotoxin-Stimulated Peripheral Blood Monocytes: Effects of Caffeine
Authors: Ulcar R. , Schuligoi R. , Heinemann A. , Santner B. , Amann R. 
Published: April 2003

There is an ongoing debate about possible advantages of the coadministration of caffeine with cyclooxygenase (COX) inhibitors in the treatment of pain. There are results suggesting interference by caffeine with COX expression and activity in rat immune cells. In the present study, we have used, therefore, human endotoxin-stimulated monocytes to investigate a possible influence of caffeine on indometacin-induced inhibition of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) formation. Endotoxin caused a concentration- and time-dependent increase in immunoreactive PGE<sub>2</sub> that was dependent on CD14-mediated mechanisms. In order to investigate pharmacological inhibition of the COX activity, a submaximal concentration of 1 ng/ml endotoxin (4 h exposure time) was used. Indometacin caused a concentration-dependent inhibition of PGE<sub>2</sub> with an apparent IC<sub>50</sub> of 8.9 ± 1.4 × 10<sup>–9</sup> mol/l and an I<sub>max</sub> of 1 x 10<sup>–7</sup> mol/l. Caffeine (5 × 10<sup>–6</sup> to 1.5 × 10<sup>–4</sup> mol/l) on its own produced no statistically significant effect on endotoxin-induced PGE<sub>2</sub> formation. In the presence of caffeine (5 × 10<sup>–6</sup> to 1.5 × 10<sup>–4</sup> mol/l), inhibition of PGE<sub>2</sub> biosynthesis by indometacin (1 × 10<sup>–8</sup> mol/l) was not significantly altered. These results show that, in human monocytes, caffeine, up to concentrations severalfold higher than those reached in patients, has no significant effect on endotoxin-induced PGE<sub>2</sub> formation nor on its inhibition by indometacin.
A Case-Control Study of Endometrial Cancer after Antipsychotics Exposure in Premenopausal Women
Authors: Yamazawa Koji , Matsui Hideo , Seki Katsuyoshi , Sekiya Souei 
Published: April 2003

<i>Objective:</i> Most endometrial cancers are related to hormonal imbalance, and antipsychotics are a common cause of hyperprolactinemia. We investigated the possible relation between the use of antipsychotics and the risk of endometrial cancer. <i>Methods:</i> A case-control study was conducted on premenopausal women at the Chiba University Hospital between 1989 and 2000. The cases were 41 patients with histologically confirmed endometrial cancer. For each case, there were 3 controls matched by age and date of visit. Subsequently 123 women without endometrial cancer were enrolled as controls. Detailed information including obesity, parity, hypertension, diabetes mellitus, use of exogenous estrogen and use of antipsychotics was analyzed. Odds ratios, two-sided p values and 95% confidence intervals were estimated by a conditional logistic regression analysis. Radioimmunoassays of serum luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol and progesterone were performed in 4 of 5 patients with endometrial cancer who were using antipsychotics. <i>Results: </i>Use of antipsychotics, diabetes mellitus and obesity were identified as independent variables with risk estimates of 5.4, 9.3 and 4.9, respectively. Serum progesterone, estradiol and prolactin levels ranged from 0.4 to 0.7 ng/ml, 32 to 110 pg/ml and 34 to 258 ng/ml, respectively. <i>Conclusions: </i>Use of antipsychotics is a risk factor for endometrial cancer, and hyperprolactinemia associated with antipsychotics may impart the risk of endometrial cancer in premenopausal women.
Phase II Study of Concurrent Administration of Doxorubicin and Docetaxel as First-Line Chemotherapy for Metastatic Breast Cancer
Authors: Aihara Tomohiko , Takatsuka Yuichi , Itoh Kuniaki , Sasaki Yasutsuna , Katsumata Noriyuki , Watanabe Toru , Noguchi Shinzaburo , Horikoshi Noboru , Tabei Toshio , Sonoo Hiroshi , Hiraki Shunkichi , Inaji Hideo 
Published: April 2003

<i>Objective:</i> To evaluate the efficacy and toxicity of concurrent administration of doxorubicin and docetaxel, without prophylactic use of granulocyte colony-stimulating factor, as first-line chemotherapy in patients with metastatic breast cancer (MBC). <i>Methods:</i> This multi-institutional study enrolled 40 women; 37 were assessable for efficacy and all 40 patients were evaluated for toxicity. Treatment consisted of 50 mg/m<sup>2</sup> doxorubicin and 60 mg/m<sup>2</sup> docetaxel on day 1 every 3–4 weeks. <i>Results:</i> Patients received a total of 251 cycles of chemotherapy (median, 5 cycles; range, 1–13 cycles). Of the 37 patients assessable for efficacy, 2 had a complete response and 24 had partial responses, which accounted for a 70% objective response rate (95% confidence interval, 53–84%). The median time to treatment failure was 30.1 weeks (range, 3.3–80.7 weeks). Grade 4 neutropenia was observed in 88% of patients and was the most frequent haematological toxicity. Febrile neutropenia was seen in 40% of patients, but no severe infections were observed. Non-haematological toxicity was generally tolerable. There were 2 grade 4 adverse events, which included 1 bleeding duodenal ulcer and 1 hypersensitivity reaction, but grade 3 episodes were infrequent. None of the patients developed congestive heart failure or asymptomatic decrease of left ventricular ejection fraction to less than 50%. Fluid retention syndrome ≤ grade 2 was observed in 25% of patients at a median cumulative dose of docetaxel of 270 mg/m<sup>2</sup>. <i>Conclusion:</i> Concurrent administration of 50 mg/m<sup>2</sup> doxorubicin and 60 mg/m<sup>2</sup> docetaxel is active with a manageable toxicity profile as first-line chemotherapy for MBC.
Self-Administration of both Ethanol and Nicotine in Rats
Authors: Marshall Cheryl E. , Dadmarz Mitra , Hofford James M. , Gottheil Edward , Vogel Wolfgang H. 
Published: April 2003

Self-administration of either nicotine (NIC) or ethanol (ETH) has been extensively studied. This study addressed for the first time the self-administration of both substances when offered together. Male and female rats of different ages were offered NIC and ETH using the two- or three-bottle free-choice method. When NIC and ETH were offered together at different concentrations to young male rats (about 45 days old), intake of NIC increased with increasing NIC concentrations, and intake of ETH increased with decreasing ETH concentrations, but these effects were independent of the presence of the second drug. These rats also consumed the same amounts of NIC or ETH regardless of whether offered individually or together. A prior choice of only NIC or ETH did not affect a subsequent intake of both drugs offered together. A choice of both drugs for 24 h for several days followed by a choice for only 2 h for several days showed the same intake of NIC but a decreased intake of ETH for the shorter period. Young female rats (about 45 days old) and older male rats (about 75 days old) consumed the same amounts of NIC but less ETH than did the young male rats. These results show that young male rats voluntarily consume NIC and ETH independently of each other and that preexposure to one drug does not affect the subsequent intake of both drugs in combination. The data also suggest that these drugs act on different reward centers which have to be ‘satisfied’ independently of each other.
Assessment of the Single-Occlusion Technique for Measurements of Respiratory Mechanics and Respiratory Drive in Healthy Term Neonates Using a Commercially Available Computerized Pulmonary Function Testing System
Authors: Reiterer F. , Müller W. 
Published: April 2003

In this study, a critical assessment of the single-occlusion technique as a means of measuring passive respiratory mechanics and respiratory drive (P0.1) was performed in nonintubated spontaneously breathing healthy term neonates using commercially available computerized equipment (PEDS system). In general, we found that quality parameters only partially conformed to the international established standards for measuring passive respiratory mechanics. There was a failure rate of technically acceptable occlusions of about 50% for respiratory mechanics measurements and 20% for P0.1 measurements. Intersubject variability of the data was between 10 and 40%. After studying different lengths of occlusion times (Tocc; 0.2, 0.3, 0.4 and 0.5 s), it was found that acceptable occlusions for passive respiratory mechanics were obtained only if the expiratory Tocc exceeded 0.2 s. Increasing the Tocc had no effect on the absolute values of respiratory mechanics but showed a significant trend towards more technically acceptable occlusions. We speculate that a Tocc of at least 0.4 s may be a prerequisite for obtaining reliable results for respiratory mechanics in healthy term neonates.
No Priming of the Immune Response in Newborn Brown Norway Rats Dosed with Ovalbumin in the Mouth
Authors: Madsen C. , Pilegaard K. 
Published: April 2003

<i>Background:</i> Other researchers have reported that the specific immune response to subsequent antigen challenge is primed in newborn mice or rats dosed orally by gavage. We wanted to investigate if priming of a subsequent specific IgE response could be achieved by dosing newborn rats orally with ovalbumin and if this method could be used in an animal model for food allergy. <i>Methods:</i> Newborn Brown Norway rats were dosed with ovalbumin in the mouth (100 µg or 6 mg). As young adults, the animals were dosed by gavage for 35 days with 1 mg ovalbumin/day or once intraperitoneally with 100 µg. Control groups were dosed by gavage or intraperitoneally but not as neonates. Additionally, young adult rats were dosed with 1 mg ovalbumin/day in the mouth for 35 days. Sera from individual animals were analysed for specific IgE and specific IgG. <i>Results:</i> In all experiments with neonatal rats the specific IgE and IgG responses were decreased compared to the control groups, however, not always reaching statistical significance. A statistical significant decrease in the specific immune response was found in young adult rats dosed in the mouth as compared to by gavage. <i>Conclusions:</i> Dosing Brown Norway rats with ovalbumin in the mouth as neonates do not prime the specific immune response. The decrease in immune response found in our experiments when dosing newborn animals in the mouth in opposition to the priming seen by others when dosing by intragastric intubation may be explained by a dissimilar antigen presentation when dosing includes both oral mucosa and gut.
Induction of Basophil Desensitization in Physiological Medium: Enhancement after IgE-Dependent Upregulation of Surface IgE Binding on Basophils
Authors: Komiya Akiko , Hirai Koichi , Iikura Motoyasu , Nagase Hiroyuki , Yamada Hirokazu , Miyamasu Misato , Ohta Ken , Morita Yutaka , Ra Chisei , Yamamoto Kazuhiko , Yamaguchi Masao 
Published: April 2003

<i>Background:</i> Although the ability of basophils to release mediators, called releasability, may be an important aspect which influences the proinflammatory role of these cells, clinical approaches aiming at the depletion of the releasability have not been established. We examined whether the desensitization procedure in Ca<sup>2+</sup>-containing physiological conditions can make basophils completely unresponsive to IgE-mediated stimulation, and whether basophil desensitization is affected by the surface IgE levels. <i>Methods:</i> Human peripheral blood basophils were cultured with low concentrations of anti-IgE antibody or recombinant mite allergen. Following culture, cells were stimulated and their histamine release was measured. <i>Results:</i> Culturing with mite allergen or anti-IgE antibody below threshold concentrations induced potent desensitization in basophils. The desensitizing effect of anti-IgE was dose- and time-dependent; IgE-dependent releasability was completely suppressed when basophils were incubated with a near-threshold concentration of anti-IgE for ≧4 h. In the continuous presence of subthreshold doses of anti-IgE, basophils remained desensitized even after 3 days. Basophils which had undergone an increase in surface IgE levels after 24-hour culture with IgE demonstrated enhanced desensitization. <i>Conclusions:</i> Near-threshold stimulation in physiological medium can affect basophils, thereby inducing complete and sustained deprivation of releasability without triggering degranulation. Basophil desensitization is regulated by their surface IgE levels. Induction of full desensitization may represent a potentially important therapeutic strategy for IgE-mediated allergic diseases in which basophils play pathogenic roles.
A New Isoquinolinone Derivative with Noble Vasorelaxation Activity
Authors: Hsien Lin Chia , Shan Lin Mei , Hsiu Lin Ying , Ming Chen I. , Rong Lin Pen , Cheng Chen-Yu , Cheng Tsai Ming 
Published: April 2003

The pharmacological effects of BDPBI (7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride) were tested on isolated endothelium-containing or denuded aorta of the guinea pig. BDPBI with the formula C<sub>27</sub>H<sub>24</sub>BrCl<sub>2</sub>N<sub>3</sub>O was synthesized starting with 3-isochromanone. In the endothelium-containing preparations of the aortic rings, phenylephrine (PHE; 10 µmol/l) elicited contracture and acetylcholine (ACh; 10 µmol/l) or BDPBI (0.01–10 µmol/l) elicited relaxation effects on the PHE-precontracted preparations. The BDPBI-elicited effect on the PHE-precontracted aortic rings was not altered in the presence of adrenergic blockers (propranolol or yohimbine; 1 µmol/l) or pretreated preparations with aspirin, indomethacin (10 µmol/l) or L-NAME (1 mmol/l). However, the relaxation effects of BDPBI were blocked if the preparations were pretreated with diphenhydramine (10 µmol/l) or chloropheniramine maleate (10 µmol/l). In contrast to lower concentrations of atropine (1 µmol/l), higher concentrations of atropine (30 µmol/l) did block the effects of BDPBI on the PHE-precontracted aortic rings. HTMT dimaleate (0.01–10 µmol/l), a histamine H<sub>1</sub> receptor agonist, also elicited relaxation effects on the PHE-precontracted preparation, and the effects were blocked if the preparations were pretreated with diphenhydramine or chloropheniramine maleate. On isolated denuded aorta of the guinea pig, BDPBI did not elicit relaxation effects on the PHE-precontracted aortic rings. These results demonstrated that the vasorelaxation effect of BDPBI on PHE-precontracted aortic rings is partly dependent on the activation of a histaminergic receptor from the vascular endothelium. We suggested that BDPBI would be an effective vasorelaxant for cardiovascular systems.
Early Use of Beta-Blockers Is Associated with Attenuation of Serum C-Reactive Protein Elevation and Favorable Short-Term Prognosis after Acute Myocardial Infarction
Authors: Anzai Toshihisa , Yoshikawa Tsutomu , Takahashi Toshiyuki , Maekawa Yuichiro , Okabe Teruo , Asakura Yasushi , Satoh Toru , Mitamura Hideo , Ogawa Satoshi 
Published: April 2003

<i>Background:</i> We have reported that a marked elevation in serum C-reactive protein (CRP) level is a predictor for infarct expansion and cardiac rupture after AMI. Although β-blockers prevent cardiac rupture after AMI, their effect on serum CRP elevation has not been determined. <i>Methods:</i> We studied a total of 154 patients with first Q-wave AMI. Patients complicated by pump failure were excluded from this study. Eighty-two patients received β-blocker treatment within 24 h of the onset of AMI, while 72 patients received no β-blocker treatment. Peak serum creatine kinase (CK) and CRP levels were determined by serial measurements. <i>Results:</i> There was no difference between the groups according to age, sex, coronary risk factors, pre-infarction angina, infarct site, prior use of cardiovascular drugs, use of revascularization therapy, and prevalence of multivessel disease. β-Blocker treatment was associated with a lower peak CRP level (6.9 ± 6.1 vs.10.8 ± 9.3 mg/dl, p = 0.002), a shorter duration from the onset to the peak CRP level (2 ± 1 vs. 3 ± 2 days, p < 0.0001), a lower incidence of cardiac rupture (p = 0.03) and lower in-hospital cardiac mortality (p = 0.02), despite similar peak CK levels.<i> Conclusion:</i> The early use of β-blockers is associated with decreased serum CRP level and a favorable clinical outcome after first Q-wave AMI, suggesting some beneficial effects of β-blockers on infarct healing after AMI.
Steroidogenic Isoenzymes in Human Hair and Their Potential Role in Androgenetic Alopecia
Authors: Hoffmann Rolf 
Published: April 2003

Androgenetic alopecia (AGA) is the most common type of hair loss. The relatively strong concordance of the degree of baldness in fathers and sons is not consistent with a simple Mendelian trait, and a polygenic basis is considered to be most likely. So far, the predisposing genes for AGA are unknown and we do not understand the molecular steps involved in androgen-dependent beard growth versus androgen-dependent hair loss, but AGA can be defined as a dihydrotestosterone (DHT)-dependent process with continuous miniaturization of sensitive hair follicles. The type 2 5α-reductase plays a central role by the intrafollicular conversion of testosterone to DHT. However, due to the increasing knowledge in this field, we now know that there are many more steroidogenic enzymes involved in the onset and development of AGA, and this article shall provide a critical overview of recent discoveries.
Familial High Myopia Linkage to Chromosome 18p
Authors: Lam Dennis S.C. , Tam Pancy O.S. , Fan Dorothy S.P. , Baum Larry , Leung Yuk-fai , Pang Chi Pui 
Published: April 2003

A locus for autosomal dominant high myopia was reported on chromosome 18p. We sought to confirm this finding and narrow the reported interval by analyzing high myopia among families of Hong Kong Chinese, in whom myopia is common. In 15 families with a possibly autosomal dominant inheritance of high myopia (≧–6 dpt) in at least 2 generations, 10 chromosome 18p markers were analyzed for linkage with high myopia. Two-point linkage analysis showed trends toward linkage of markers D18S476 and D18S62 with high myopia, with maximum logarithm of odds (LOD) scores of at least 1.1 and 1.7, respectively. Multipoint analysis of those 2 markers gave a maximum LOD score of at least 2.1. To attempt to account for likely genetic heterogeneity, 5 families showing evidence of linkage of the 2 markers with high myopia were selected for further multipoint linkage analysis, resulting in a maximum LOD score of 2.4 at D18S476. While multiple genetic and environmental factors likely contribute to myopia, these data are consistent with the possibility of a locus on chromosome 18p.
Activation of Na<sup>+</sup>/K<sup>+</sup>-ATPase by the Serum and Glucocorticoid-Dependent Kinase Isoforms
Authors: Henke Guido , Setiawan Iwan , Böhmer Christoph , Lang Florian 
Published: April 2003

<i>Background/Aim:</i> Expression of the constitutively active form of serum and glucocorticoid-dependent kinase (<sup>S422D</sup>SGK1) in <i>Xenopus</i> oocytes has recently been shown to upregulate endogenous Na<sup>+</sup>/K<sup>+</sup>-ATPase activity, an effect presumably participating in the regulation of cellular K<sup>+</sup> uptake and transepithelial Na<sup>+</sup> transport. SGK1 and the two isoforms SGK2 and SGK3 are stimulated by insulin and insulin-like growth factor-1 (IGF-1), which have been shown to enhance Na<sup>+</sup>/K<sup>+</sup>-ATPase activity in a variety of cells. The present experiments have been performed to elucidate whether or not wild-type SGK1, SGK2 and SGK3 are similar to <sup>S422D</sup>SGK1 in being effective regulators of Na<sup>+</sup>/K<sup>+</sup>-ATPase. <i>Methods:</i> To this end, dual-electrode voltage clamp experiments were performed in <i>Xenopus</i> oocytes injected either with water or with mRNA of constitutively active <sup>S422D</sup>SGK1 and wild-type SGK1, SGK2 or SGK3. Na<sup>+</sup>/K<sup>+</sup>-ATPase activity was estimated from the outward-directed current created by readdition of extracellular K<sup>+</sup> in the presence of K<sup>+</sup> channel blocker Ba<sup>2+</sup> following a 10-min exposure to K<sup>+</sup>-free extracellular fluid. <i>Results:</i> The outward-directed current was fully abolished by incubation with 1 m<i>M</i> ouabain and was significantly larger in oocytes expressing <sup>S422D</sup>SGK1, SGK1, SGK2 or SGK3, as compared to those injected with water. <i>Conclusion:</i> The stimulating effect of SGK1 on the <i>Xenopus</i> oocyte Na<sup>+</sup>/K<sup>+</sup>-ATPase is mimicked by the isoforms SGK2 and SGK3. Thus, all three kinases may participate in the regulation of Na<sup>+</sup>/K<sup>+</sup>-ATPase activity by hormones such as insulin and IGF-1.