bluuebunny/crossref_metadata_2025_split huggingface dataset:
<i>Helicobacter pylori</i>-Associated Gastric Ulcer Exhibits Enhanced Mucosal Chemokine Activity at the Ulcer Site
Authors: Shimizu Tatsuji , Kusugami Kazuo , Ina Kenji , Imada Akira , Nishio Yuji , Hosokawa Takehiko , Ohsuga Masahiro , Shimada Masaaki , Noshiro Mitsuhiro , Kaneko Hiroshi , Ando Takafumi 
Published: April 2003

<i>Background and Aim:</i> Although mucosal α- and β-chemokines are considered to be involved in the pathogenesis of <i>Helicobacter pylori</i>-associated gastritis, little is known how these chemokines are related to the ulcerogenesis in peptic ulcer patients. We examined the levels of interleukin (IL)-8 and macrophage inflammatory protein-1α (MIP-1α) in organ cultures and the numbers of inflammatory cells infiltrating the lamina propria by using the mucosal tissues obtained from gastric ulcer (GU) patients with and without <i>H. pylori</i> infection. <i>Methods:</i> Levels of IL-8 and MIP-1α secreted in organ cultures were measured by an enzyme-linked immunosorbent assay. Numbers of myeloperoxidase-positive neutrophils, CD68-positive macrophages, and mononuclear cells were determined in tissue sections. <i>Results:</i> The mucosal tissues of both the gastric antrum and the ulcer site obtained from patients with <i>H. pylori</i>-positive GU showed significantly higher levels of IL-8 and MIP-1α and increased numbers of inflammatory cells compared with the corresponding mucosal tissues from those with <i>H. pylori</i>-negative GU or the antral mucosal tissues from <i>H. pylori</i>-negative controls. When the values were compared between the mucosal tissues from the gastric antrum and those from the ulcer site, the latter group of tissues showed significantly higher levels of IL-8 and MIP-1α and increased numbers of neutrophils and macrophages than the former group regardless of its healing process in patients with <i>H. pylori</i>-positive GU. <i>Conclusion:</i> Mucosal α- and β-chemokines may be important to the ulcerogenesis in <i>H. pylori</i>-associated GU disease.
Pharmacokinetic Studies with a Dual-Release Formulation of Levodopa, a Novel Principle in the Treatment of Parkinson’s Disease
Authors: Dingemanse J. , Kleinbloesem C.H. , Crevoisier Ch. , Lankhaar G. , Gasser U.E. 
Published: April 2003

The objectives of the two studies reported here were the investigation of the influence of tablet breaking and food on the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after administration of a new levodopa/benserazide formulation with a biphasic drug delivery profile (Madopar<sup>®</sup> DR). Both studies had an open-label, randomised, two-way crossover design and were conducted in 12 healthy young subjects. The pharmacokinetics of levodopa and 3-OMD after one intact or two halved tablets were very similar with average C<sub>max</sub> and t<sub>max</sub> 1.9 mg·l<sup>–1</sup> and 1.2 h, respectively. Administration of the formulation after a standard breakfast did not influence the extent of levodopa absorption but increased the absorption rate. C<sub>max</sub> and t<sub>max</sub> were on average 2.1 mg·l<sup>–1</sup> and 1.3 h, respectively, in the fed condition and 1.5 mg·l<sup>–1</sup> and 2.5 h in the fasted condition. The presence of food did not markedly affect the plateau in levodopa levels between about 1 and 3 h after intake. In conclusion, the release characteristics in healthy subjects of the new levodopa/benserazide formulation are influenced only to a minor extent by concomitant intake of food or by tablet breaking.
Safety, Pharmacokinetics and Biological Activity of Enlimomab (Anti-ICAM-1 Antibody): An Open-Label, Dose Escalation Study in Patients Hospitalized for Acute Stroke
Authors: Schneider D. , Berrouschot J. , Brandt T. , Hacke W. , Ferbert A. , Norris S.H. , Polmar S.H. , Schäfer E. 
Published: April 2003

<b>Background and Purpose:</b> To obtain information on the safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody) in stroke patients. <b>Methods:</b> An open, uncontrolled, dose titration study was conducted in 32 patients hospitalized for stroke. Patients received one of four fixed dose regimens of enlimomab. A loading dose of enlimomab administered within 24 h of the onset of stroke symptoms was followed by four daily maintenance doses; total doses ranged from 140 to 480 mg. <b>Results:</b> The pharmacokinetic target levels (enlimomab serum levels of ≥10 µg/ml) were consistently achieved in all patients receiving dose regimens III and IV. Non-serious adverse events thought to be causally related to enlimomab administration included headache, vomiting and extrasystoles. Serious events occurred in 14 patients, including pneumonia, sepsis, cardiac failure and cardiac arrest. The only serious adverse event considered to be related to enlimomab administration was an anaphylactoid reaction, in a patient who received an unfiltered loading dose of antibody; the patient recovered. The overall mortality in the study was 15.6% and the 30-day mortality was 12.5%. There was no increase in the frequency of adverse events with increasing doses of enlimomab. <b>Conclusions:</b> Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 ± 10 days. A loading dose of 160 mg followed by four daily maintenance doses of 40 mg appears to be suitable for further study.
Transcranial Doppler Monitoring of Intracranial Pressure Therapy with Mannitol, Sorbitol and Glycerol in Patients with Acute Stroke
Authors: Treib Johannes , Becker Susanne Christiane , Grauer Markus T. , Haass Anton 
Published: April 2003

<b>Introduction:</b> The noninvasive management of the conservative therapy for intracranial pressure (ICP) with hyperosmolar substances is a central problem in the treatment of brain edema. Using transcranial Doppler (TCD), a continuous monitoring of ICP is now possible, because the TCD pulsatility index (PI) intraindividually closely correlates with the level of ICP. <b>Patients and Methods:</b> We administered an ICP-lowering treatment 113 times in 10 patients with intracranial bleeding or ischemic stroke who also had signs of elevated ICP in the computer tomogram. The treatment was carried out over a period of 9 days, using 50 g each of intravenous sorbitol (n = 38) and mannitol (n = 32) or oral glycerol (n = 43). <b>Results:</b> PI was significantly lowered between 20.0 and 23.9% (p < 0.01) by all substances in the affected and unaffected sides. The differences between the three substances and the differences between the affected and unaffected sides were not significant. The duration of the therapeutic effect of glycerol (190 ± 41 min) was significantly longer (p < 0.01) than that of sorbitol (150 ± 28 min) or mannitol (130 ± 20 min). The duration of the therapeutic effect was also significantly shorter (p < 0.01) in patients with a high PI (> 1.5). All three substances led to a significant increase (p < 0.01) in minimal (= diastolic) flow velocity (V<sub>min</sub>). The increase was highest for glycerol (56.3 ±72.6%). <b>Summary:</b> The decrease in PI under therapy was caused by an increase in V<sub>min</sub>. This indicates that ICP therapy with hyperosmolar substances improves brain edema and does not suggest a therapy-induced vasoconstriction.
Dolicho-Vertebrobasilar Abnormality and Migraine-Like Attacks
Authors: Zambrino Carlo Alberto , Berardinelli Angela , Martelli Adelaide , Vercelli Paola , Termine Cristiano , Lanzi Giovanni 
Published: April 2003

This is a study of two children with neuroradiologically diagnosed dolichobasilar anomaly: in both cases, the diagnosis was based on magnetic resonance imaging and magnetic resonance angiography findings. We examined the first child (R., aged 6 years and 8 months) following four episodes of intense pain in the left orbit, lasting between 10 and 30 min and accompanied by photophobia and vomiting. The second child (S., aged 9 years and 2 months), suffering from Marfan’s syndrome, was examined following recurrent episodes of intense pain that started above the left orbit, moving to the homolateral orbit after a few minutes. These episodes, which lasted between 20 and 30 min, took place mainly at night and were accompanied by phono-photophobia and vomiting. In both cases, the pain attacks can be interpreted as a result of compression of the root of the trigeminal nerve caused by an arterial malformation.
Comparison of Rizatriptan 10 mg vs. Naratriptan 2.5 mg in Migraine
Authors: Bomhof Martin , Paz Jose , Legg Nigel , Allen Christopher , Vandormael Kristel , Patel Krupa 
Published: April 2003

Rizatriptan (MAXALT<sup>TM</sup>, Merck & Co., Inc.) is a selective 5-HT<sub>1B/1D</sub> receptor agonist with rapid oral absorption and early onset of action for the acute treatment of migraine. This randomized, double-masked, double-dummy, placebo-controlled study compared rizatriptan 10 mg to naratriptan (NARAMIG<sup>TM</sup>, AMERGE<sup>TM</sup>, both Glaxo Wellcome plc) 2.5 mg in 522 patients treating a single migraine attack. Rizatriptan was more effective than naratriptan. Rizatriptan provided earlier headache relief than naratriptan (hazard ratio 1.62, p < 0.001), acting as early as 30 min. More patients were pain free at 2 h on rizatriptan than on naratriptan (44.8 vs. 20.7%, p < 0.001). Rizatriptan also provided earlier relief of associated migraine symptoms within 2 h than naratriptan and more patients had normal function at 2 h (39.3 vs. 22.6%, p < 0.001). Both active treatments were effective compared to placebo. Both active treatments were well tolerated. The most common side effects with rizatriptan were dizziness, asthenia/fatigue, nausea and somnolence, while the most common side effects with naratriptan were dizziness and asthenia/fatigue.
Influence of Intermittent Ischemia on Thioacetamide-Induced Rat Liver Cirrhosis
Authors: Matsutomo H. , Hirose H. , Senga S. , Fukuchi T. , Imai N. , Hayashi M. , Katagiri Y. , Onitsuka A. 
Published: April 2003

We studied the influence of intermittent ischemic injury on thioacetamide-induced liver cirrhosis in rats. Wistar rats were divided into group A, intermittent ischemic injury to liver cirrhosis, and group B, continuous ischemic injury to liver cirrhosis. Total ischemic time was 60 min in both groups. In group A, ischemic injury consisted of a repetition 4 times of 15 min ischemia and 5 min reperfusion. The ATP level of the liver was measured before ischemia, before reperfusion, and 60 min after reperfusion. Bile was collected to determine bile flow rate. The ATP level in the liver tissue 60 min after reperfusion was significantly (p < 0.05) higher in group A than in group B. The ATP level immediately before reperfusion was also significantly (p < 0.05) higher in group A than in group B. The survival rate 1 week after ischemic injury and bile flow rate 60 min after reperfusion were significantly (p < 0.01) higher in group A compared with those in group B. The energy level was much higher in intermittent ischemic injury than in continuous ischemic injury immediately before reperfusion and after reperfusion. Survival rate and bile flow rate were higher in intermittent ischemic injury than in continuous ischemic injury. Therefore it suggests that the viability of the liver was maintained better in intermittent ischemic injury than in continuous ischemic injury.
Isolated Lung Perfusion with Melphalan Prolongs Survival in a Rat Model of Metastatic Pulmonary Adenocarcinoma
Authors: Hendriks J.M.H. , van Schil P.E.Y. , van Oosterom A.A.T. , Kuppen P.J.K. , van Marck E. , Eyskens E. 
Published: April 2003

<i>Introduction:</i> Survival after isolated lung perfusion (ILuP) with melphalan was tested in a model of unilateral pulmonary adenocarcinoma. <i>Methods:</i> On day 0, rats were randomized into four groups: Group 1 (n = 9) reveived tumor cells intravenously for induction of bilateral lung metastases, whereas groups 2–4 (n = 21) underwent a 10-min occlusion of the right pulmonary artery during tumor cell injection for induction of unilateral left lung metastases. On day 7, groups 1 and 2 received no treatment. Group 3 underwent left ILuP with melphalan (2.0 mg/kg) while group 4 received melphalan intravenously (0.5 mg/kg). The end point of the study was death from metastatic disease. <i>Results:</i> Median survival of ILuP-treated animals (81 ± 12 days) was significantly longer compared to group 1 (18 ± 1 days; p = 0.0001), group 2 (28 ± 3 days; p = 0.0002) and group 4 (37 ± 6; p = 0.0004). <i>Conclusions:</i> ILuP with melphalan prolongs survival in the treatment of experimental metastatic pulmonary carcinoma.
Isolated Hyperthermic Liver Perfusion with High Dose Tumor Necrosis Factor Alpha in Pigs: An Experimental Study in Preparation of Clinical Use
Authors: Lang H. , Thyen A. , Nadalin S. , Frerker M. , Moreno L. , Flemming P. , Martin M. , Oldhafer K.J. , Raab R. 
Published: April 2003

Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2°C. In two study groups B and C (n = 9 pigs each) 50 μg recombinant human tumor necrosis factor-α (rhTNFα) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFα. Before reperfusion the livers were washed out with Ringer’s solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFα concentrations were significantly higher in group B with 68 and 61 ng/ml compared to 14.5 and 14.9 ng/ml in group C (p < 0.05). Mean systemic porcine TNFα concentration was significantly higher in group B (217 pg/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). Survival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dying due to severe cardiopulmonary failure within 12 h after operation. In surviving pigs of group A and C only mild and transient hepatotoxicity was registered. The presented study underlines the feasibility of high dose rhTNFα application in an isolated hyperthermic liver perfusion system. Washout of the liver with a protein solution before reperfusion reduces systemic TNFα levels as well as associated lethal cardiocirculatory and hepatotoxic side effects.
Computer-Assisted ex vivo, Normothermic Small Bowel Perfusion
Authors: Stangl M.J. , Krapp J. , Theodorou D. , Eder M. , Hammer C. , Land W. , Schildberg F.W. 
Published: April 2003

<i>Background:</i> In the present study, a technique for computer-assisted, normothermic, oxygenated, ex vivo, recirculating small bowel perfusion was established as a tool to investigate organ pretreatment protocols and ischemia/reperfusion phenomena. A prerequisite for the desired setup was an organ chamber for ex vivo perfusion and the use of syngeneic whole blood as perfusate. <i>Methods:</i> The entire small bowel was harvested from Lewis rats and perfused in an organ chamber ex vivo for at least 2 h. The temperature was kept at 37°C in a water bath. Three experimental groups were explored, characterized by different perfusion solutions. The basic perfusate consisted of syngeneic whole blood diluted with either NaCl, Krebs’ solution or Krebs’ solution and norepinephrine to a hematocrit of 30%. In addition, in each group <i>l</i>-glutamine was administered intraluminally. The desired perfusion pressure was 100 mm Hg which was kept constant with a computer-assisted data acquisition software, which measured on-line pressure, oxygenation, flow, temperature and pH and adjusted the pressure by changing the flow via a peristaltic pump. The viability of the preparation was tested by measuring oxygen consumption and maltose absorption, which requires intact enzymes of the mucosal brush border to break down maltose into glucose. <i>Results:</i> Organ perfusion in group 1 (dilution with NaCl) revealed problems such as hypersecretion into the bowel lumen, low vascular resistance and no maltose uptake. In contrast a viable organ could be demonstrated using Krebs’ solution as dilution solution. The addition of norepinephrine led to an improved perfusion over the entire perfusion period. Maltose absorption was comparable to tests conducted with native small bowel. Oxygen consumption was stable during the 2-hour perfusion period. <i>Conclusions:</i> The ex vivo perfusion system established enables small bowel perfusion for at least 2 h. The viability of the graft could be demonstrated. The perfusion time achieved is sufficient to study leukocyte/lymphocyte interaction with the endothelium of the graft vessels. In addition, a viable small bowel, after 2 h of ex vivo perfusion, facilitates testing of pretreatment protocols for the reduction of the immunogenicity of small bowel allografts.
Beneficial Effects of Prostaglandin E<sub>1</sub> Incorporated in Lipid Microspheres on Liver Injury and Regeneration after 90% Partial Hepatectomy in Rats
Authors: Ando K. , Miyazaki M. , Shimizu H. , Okuno A. , Nakajima N. 
Published: April 2003

The aim of this study was to assess how the administration of prostaglandin E<sub>1</sub> incorporated in lipid microspheres (Lipo PGE<sub>1</sub>) affects liver injury and regeneration after massive hepatectomy in rats. Two hundred and eight male Wistar rats underwent 90% partial hepatectomy. Lipo PGE<sub>1</sub> of 1, 10 or 30 μg/kg were administered intraperitoneally at 6 h prior to and 0 and 6 h after hepatectomy. Postoperative increases in serum GOT, total bilirubin, IL-6 and plasma endotoxin levels were significantly suppressed by Lipo PGE<sub>1</sub>. The depressed phagocytic index and arterial ketone body ratio and hepatic DNA synthesis after 90% partial hepatectomy were significantly enhanced by Lipo PGE<sub>1</sub>, which resulted in the improvement of survival. Lipo PGE<sub>1</sub> might bring about a protective effect on liver injury and an enhancement of liver regeneration after massive hepatectomy.
Stimulated Polymorphonuclear Leukocytes in Vaginal Secretions from Patients with Preterm Labor
Authors: Matsubara Shigeki , Yamada Tetsuo , Minakami Hisanori , Sato Ikuo 
Published: April 2003

The purpose of this study was to examine evidence for the presence of activated vaginal leukocytes in women with preterm labor. Vaginal polymorphonuclear leukocytes from 7 patients in preterm labor (24–32 weeks of gestation) as well as from 7 control women with uncomplicated pregnancy were analyzed morphologically using transmission electron microscopy. Peroxidase and NADPH oxidase cytochemistry was also performed. Viable leukocytes were abundant in patients in preterm labor. Phagosomes, phagocytosis of bacteria, attachment of primary granules to the phagosomal membrane, and cell surface projections were observed in the vaginal leukocytes but not in the peripheral blood leukocytes. Peroxidase activity was visible on the cell surface, the phagosomal membrane, and the primary granules. NADPH oxidase activity was demonstrated on the cell surface of leukocytes. Morphological and cytochemical features indicated that vaginal polymorphonuclear leukocytes were stimulated in situ. Such stimulated leukocytes may play a role in the pathogenesis or pathophysiology of preterm labor.
Postpartum Uterine-Artery Velocity Waveforms in Women with Sickle Cell Disease
Authors: Anyaegbunam A. , Garcia J. , Mikhail M.S. 
Published: April 2003

<b>Objective:</b> To investigate the changes in uterine Doppler velocimetry during the postpartum period in women with homozygous sickle cell (SS) disease and to correlate these findings with values in the third trimester and with neonatal outcomes. <b>Methods:</b> We studied the postpartum changes in uterine Doppler velocimetry in 16 women with SS disease in relation to third-trimester systolic/diastolic (S/D) ratios and neonatal outcome. All patients had repeated measures of uterine S/D ratios biweekly in the third trimester from 28 weeks of pregnancy until delivery, and at 24 h, and 3 and 6 weeks postpartum. <b>Results:</b> Overall the mean S/D ratio in the first 24 h for these 16 women was 2.72 ± 0.72 and increased progressively to a mean S/D ratio of 6.88 ± 0.96 at 6 weeks postpartum, with the reappearance of a diastolic notch by the 3rd postpartum week. Twelve women who had normal (≤2.6) uterine S/D ratios during pregnancy delivered appropriate-for-gestational-age (AGA) infants. The remaining 4 women had abnormal uterine S/D ratios, and in 3 of these pregnancies, small-for-gestational-age (SGA) infants were delivered. The mean S/D ratios for the subgroups with abnormal value at each of the three postpartum periods were significantly higher than for the 12 SS patients with normal third-trimester values. Postpartum S/D ratios for the 3 women with SGA births were also significantly higher at 24 h and 6 weeks postpartum when compared to SS patients with AGA infants. <b>Conclusion:</b> We concluded that postpartum S/D ratios are higher in women with SS disease that have abnormal values in the third trimester and that they are associated with SGA births. In SS patients the nonpregnant pattern of uterine artery velocity waveforms which reappears postpartum may reflect an increase in the uteroplacental circulatory impedence due to reversal of the alterations in the spiral arteries induced by trophoblastic invasion during pregnancy or subinvolution of the placental bed. Additional studies are needed to further elucidate these important hemodynamic changes in women with hemoglobinopathies and to identify patterns predictive of neonatal outcomes in these high-risk patients.
Characterization of α<sub>2</sub>-Adrenoceptor Subtypes in Pregnant Human Myometrium
Authors: Adolfsson Per I. , Dahle Lars Olav , Berg Göran , Svensson Samuel P.S. 
Published: April 2003

The aim of the present investigation was to determine which subtypes of the α<sub>2</sub>-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [<sup>3</sup>H]rauwolscine to human myometrial membranes was specific and of high affinity with K<sub>d</sub> of 2.8 ± 0.6 n<i>M</i> and B<sub>max</sub> of 95 ± 5 fmol/mg protein. Results from competition for the binding of [<sup>3</sup>H]rauwolscine using subtype-selective ligands, oxymetazoline (α<sub>2</sub>A-subptype), chlorpromazine (α<sub>2</sub>B-subtype) and prazosin (α<sub>2</sub>B-α<sub>2</sub>C-subtype), suggested that the α<sub>2</sub>A- and α<sub>2</sub>B-subtypes are being co-expressed. In order to examine if also the α<sub>2</sub>C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α<sub>2</sub>A- and α<sub>2</sub>B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α<sub>2</sub>C-subtype also is being expressed. The expression of α<sub>2</sub>C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.In conclusion, our results suggest that all three subtypes of α<sub>2</sub>-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α<sub>2</sub>-expression is dominated by the α<sub>2</sub>A-subtype.