bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose-Related Inhibition of Proinflammatory Cytokine Release from Neutrophils of the Newborn by Dexamethasone, Betamethasone, and Hydrocortisone
Authors: Irakam Anitha , Miskolci Veronika , Vancurova Ivana , Davidson Dennis 
Published: April 2003

The objective of this study was to determine the doses of dexamethasone (DEX), betamethasone (BET), and hydrocortisone (HC) that effectively inhibit the release of two potent proinflammatory chemokines, interleukin 8 (IL-8) and macrophage inflammatory protein alpha (MIP), from polymorphonuclear neutrophils (PMNs) of the newborn. Human PMNs were isolated from cord blood (n = 18). Chemokines were measured from PMN cell culture supernatants after 18 h of stimulation using tumor necrosis factor (1 ng/ml), with and without pretreatment by DEX (10<sup>–10</sup> to 10<sup>–6</sup> <i>M</i>) versus HC or BET (10<sup>–10</sup> to 10<sup>–5</sup> <i>M</i>). Maximal inhibitions of IL-8 release by BET, DEX, and HC were 97, 91, and 91%, respectively. For MIP, the maximal inhibitions by BET, DEX, and HC were 88, 69, and 70%, respectively. The 50% inhibitory concentrations by DEX, BET, and HC for IL-8 release were 3.4 ± (SE) 1.6 × 10<sup>–9</sup>, 1.8 ± 7.4 × 10<sup>–8</sup>, and 1.8 ± 0.5 × 10<sup>–7</sup> <i>M,</i> respectively. The 50% inhibitory concentrations by DEX, BET, and HC for MIP release were 1.0 ± (SE) 0.5 × 10<sup>–8</sup>, 3.8 ± 3.1 × 10<sup>–8</sup>, and 4.8 ± 1.6 × 10<sup>–7</sup> <i>M,</i> respectively. In vitro, these corticosteroids effectively inhibited the release of two structurally different chemokines that are found in the airway lavage fluids of infants developing bronchopulmonary dysplasia. When compared to plasma DEX levels previously reported during the treatment of bronchopulmonary dysplasia, our results suggest that the doses of DEX, and potentially BET, needed to treat chronic lung disease may be more than five to ten times lower than those of current DEX regimens.
Predictors of Clinical Recurrence after Successful Electrical Cardioversion of Chronic Persistent Atrial Fibrillation: Clinical and Electrophysiological Observations
Authors: Lin Jih-Min , Lin Jiunn-Lee , Lai Ling-Ping , Tseng Yung-Zu , Stephen Huang Shoei K. 
Published: April 2003

Recurrence of atrial fibrillation (AF) after electrical cardioversion of chronic AF is not uncommon. However, it remains unclear which parameter(s) predict clinical recurrence. To assess the potential predictors of clinical recurrence after successful electrical cardioversion, we analyzed clinical, echocardiographic and electrophysiologic parameters in 36 patients (age 63 ± 11 years; 26 males, 10 females) with chronic persistent AF lasting more than 3 months. The dimensions of the left atrium and left ventricular end diastole and end systole were measured by echocardiography. The P wave characteristics from the surface 12-lead electrocardiogram (ECG) were studied in sinus rhythm. Atrial local activations were studied by biatrial basket electrode mapping in AF. With a mean of 7 ± 2 months of follow-up, 17 (47%) patients had AF recurrence despite multiple antiarrhythmic drug therapy. None of the clinical or echocardiographic parameters were relevant to the recurrence. However, among the surface ECG and intraatrial electrophysiological parameters, the mean P wave duration was the only independent predictor of the risk of clinical recurrence after successful electrical cardioversion. The sensitivity and predictive accuracy of recurrence were 82 and 70%, respectively, when the mean P wave duration was more than 125 ms.
Serum Insulin-Like Growth Factor 1 Level and Nutritional Assessment in Nondialytic Patients with Chronic Renal Failure
Authors: Lu Fangping , Li Ping , Zheng Falei , Zhang Zhaoquan , Tomino Yasuhiko 
Published: April 2003

<i>Aim:</i> In order to understand the nutritional status of nondialytic patients with chronic renal failure (CRF), nutritional assessment was made in 20 nondialytic patients (15 males and 5 females; mean age 43.7 ± 15.1 years). <i>Methods:</i> Twenty CRF inpatients were selected for nutritional assessment, and 20 normal subjects served as controls. The serum insulin-like growth factor 1 (IGF-1) concentration was measured by ELISA. Serum albumin, prealbumin, and transferrin levels were also determined. <i>Results:</i> The mean IGF-I and transferrin levels in the CRF patients were significantly lower than those in normal subjects (IGF-1: 176.2 ± 92.5 µg/l vs. 266.7 ± 101.7 µg/l, p < 0.01; transferrin: 2.57 ± 0.58 g/l vs. 3.18 ± 0.27 g/l, p < 0.05). The IGF-1 levels in 7 patients with a serum albumin concentration <40.0 g/l were significantly lower than those in 13 patients with a serum albumin concentration >40.0 g/l (95.6 ± 42.4 µg/l vs. 219.6 ± 82.7 µg/l, p < 0.01). The IGF-1 levels in cases treated with α-ketoacid were higher than in those without α-ketoacid treatment. The IGF-1 levels were positively correlated with creatinine clearance (r = 0.7066, p < 0.01) and serum transferrin concentration (r = 0.5347, p < 0.05). <i>Conclusions:</i> The fact that serum IGF-1 was correlated with serum transferrin and creatinine clearance suggests that IGF-1 may be a good indicator for assessing the nutritional status of CRF patients. The serum IGF-1 level in CRF patients is probably lower than that in normal subjects and could be improved by nutritional therapy.
Alzheimer Disease – Effect of Continuous Intracerebroventricular Treatment with GM1 Ganglioside and a Systematic Activation Programme
Authors: Svennerholm Lars , Bråne Görel , Karlsson Ingvar , Lekman Annika , Ramström Ingalill , Wikkelsö Carsten 
Published: April 2003

Five patients with the early-onset form of Alzheimer disease (AD) received GM1 ganglioside by continuous injection into the frontal horns of the lateral ventricles for a period of 12 months. The optimal GM1 dose varied between 20 and 30 mg/24 h. The patients were trained twice a week for 4–5 h with an individually designed cognitive programme, which included the use of a word processor. Neurological, neuropsychological, psychiatric and neurochemical examinations were performed a week before surgery and on days 30, 90, 180, 270 and 365 after surgery. The cerebrospinal fluid levels of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased. The regional cerebral blood flow showed a tendency to increase. The progression of deterioration was stopped, and motor performance and neuropsychological assessments improved. The patients became more active and felt safer in relation to other people and performing various activities. They had improved reading comprehension and a better feeling for language. They were able to write reports and short letters on a word processor. When interviewed at the end of the study, all 5 patients stated that they felt better, and their relatives reported that they had regained integrity and their joie de vivre.
In vivo Platelet Activation Is Increased during Sleep in Patients with Obstructive Sleep Apnea Syndrome
Authors: Geiser Thomas , Buck Florian , Meyer Beat J. , Bassetti Claudio , Haeberli André , Gugger Matthias 
Published: April 2003

<i>Background:</i> Patients with obstructive sleep apnea syndrome (OSAS) have an increased risk of cardiovascular events including myocardial infarction and stroke. <i>Objective:</i> To determine whether in vivo platelet activation and the generation of procoagulant platelet-derived microparticles (PMP) are increased during sleep in patients with OSAS. <i>Methods:</i> In vivo platelet activation and PMP formation was determined using flow cytometry in 12 patients with untreated OSAS during and after sleep (4 and 7 a.m.). To study the effect of treatment with continuous positive airway pressure (CPAP), the measurements were repeated at the same time points after initiation of CPAP therapy. Healthy volunteers served as controls (n = 6). <i>Results:</i> Patients with OSAS had an increased percentage of platelets positive for the activation-dependent epitopes CD63 and CD62P during sleep (4 a.m.) compared to controls (4.8 ± 0.8 vs. 1.9 ± 0.4% for CD63, p < 0.01, and 2.0 ± 0.5 vs. 1.1 ± 0.3% for CD62P, p < 0.05). In OSAS patients, the amount of CD63- and CD62P-positive platelets was significantly elevated at 4 compared to 7 a.m. (4.8 ± 0.8 vs. 2.6 ± 0.4% for CD63 and 2.0 ± 0.5 vs. 1.1 ± 0.2% for CD62P, p < 0.05), but not in the control group. The levels of PMP were similar in patients with OSAS and controls at 4 and 7 a.m. After 1 night of CPAP therapy, there was a trend to reduced levels of CD63- and CD62P-positive platelets at 4 a.m. <i>Conclusions:</i> Patients with OSAS have increased in vivo platelet activation during sleep, which may contribute to the increased incidence of cardiovascular events in patients with OSAS.
The PICM-19 Cell Line as an in vitro Model of Liver Bile Ductules: Effects of cAMP Inducers, Biopeptides and pH
Authors: Talbot Neil C. , Caperna Thomas J. , Wells Kevin D. 
Published: April 2003

The PICM-19 fetal liver cell line was isolated from the primary culture and spontaneous differentiation of pig epiblast cells, i.e. embryonic stem cells. PICM-19 cells were induced to differentiate into mostly ductular formations by culturing at pH 7.6–7.8. The ductules were functionally assayed by treatment with cAMP inducing agents and bioactive peptides reported to influence the secretory activity of liver bile ductules. The secretory response of the cells was assessed by qualitative or quantitative measurement of the cross-sectional area of the ductal lumens and the appearance of biliary canaliculi in between PICM-19 cells that had formed monolayers instead of ducts. Forskolin (10 µ<i>M</i>) and 8-bromoadenosine 3′:5′-cyclic monophosphate (bcAMP; 2 m<i>M</i>) stimulated fluid transport and expansion of ductal structures in 15–20 min and stimulated the appearance and expansion of biliary canaliculi in 30–60 min. Cholera toxin (50 ng/ml) stimulates fluid transport in both ductules and canaliculi in 1–2 h, while 8-bromoguanosine 3′:5′-cyclic monophosphate (bcGMP; 2 m<i>M</i>) stimulated only biliary canaliculi in 2 h. Glucagon (1.4 n<i>M</i>) produced a similar response in 5–10 min in ductal structures only, but the response was transitory and was almost completely reversed within 30 min. Secretin (100 p<i>M</i>) and vasoactive intestinal peptide (75 p<i>M</i>) produced a sustained response with maximal ductal lumen expansion occurring in 5–10 min and neither had an immediate effect on canaliculi. Somatostatin (0.5 µ<i>M</i>) and gastrin (1 µ<i>M</i>) caused marked reduction or disappearance of ductal lumens in 30–60 min, but was ineffective in reversing secretin (100 n<i>M</i>)-induced duct distension. Application of the adrenergic agonists, epinephrine, isoproterenol, and phenylephrine (100 µ<i>M</i>), resulted in the complete shrinkage of ductal lumens in 20–30 min. A shift to pH 7.0–7.2 resulted in almost complete reduction of ductal lumens, while a shift to pH 7.8–8.0 resulted in expansion, although not full expansion, of the ductal lumens. PICM-19 bile duct cultures were positive for cytokeratin-7, aquaporin-1 and aquaporin-9 by Western blot analysis. The amounts of these proteins increased in the cultures as differentiation proceeded over time. Transmission electron microscopy revealed that the ductal structures were usually sandwiched between SIM mouse, thioguanine- and ouabain-resistant (STO) feeder cells that had produced a collagen matrix. Also, the ductular PICM-19 cells possessed cilia, probably occurring as a single cilium in each cell, that projected into the lumens of the ducts. The results indicated that the in vitro-produced ductal structures of the PICM-19 cell line are a functional model for biliary epithelium.
Morphological and Biochemical Changes of Pituitary Gonadotropes in Male Golden Hamsters Submitted to Short and Long Photoperiods
Authors: Cónsole Gloria M. , Jurado Susana B. , Camihort Gisela , Calandra Ricardo S. , Zitta Karina , Gómez Dumm César L.A. 
Published: April 2003

Golden hamsters are seasonal breeders, and a pattern of regression-recrudescence in their hypothalamic-pituitary axis is observed when adult animals are exposed to less than 12.5 h daylight for a prolonged period of time. The purpose of the present work was to investigate the possible morphological and biochemical changes of gonadotrope cell population in male golden hamsters submitted to both short (SP) and long photoperiods (LP). Thus, adult male golden hamsters were exposed to SP (6 h light, 18 h darkness) for 8, 16, 22 and 28 weeks or maintained under LP (14 h light, 10 h darkness). Pituitaries were processed using both light and electron microscopy, and serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were assessed by heterologous radioimmunoassay. Volume density [VD = Σ cell area/reference area (RA)] and cell density (CD = number of cells/RA) of gonadotropes were measured with an image analysis system (Imaging Technology, Software Optimas 5.2). When analyzing the gonadotrope population from animals submitted either to SP or LP, no significant differences were found. At the ultrastructural level, we found a decrease (p < 0.05) in the exocytotic profiles and the individual mean area of secretory granules of both gonadotropes in hamsters maintained under SP for 16 and 22 weeks. Exposure to short days resulted in a decline in serum levels showing a nadir after 16 weeks (p < 0.05). Gonadotropin levels of the hamsters under prolonged exposure to short cycles spontaneously returned to normal values after 22 weeks. In summary, we found a decrease in the ultrastructural and biochemical parameters suggesting an altered release of FSH and LH in male golden hamsters submitted to SP, with a spontaneous recrudescence phase appearing at the end of the study.
Enhanced Expression of Thymidylate Synthase Mediates Resistance of Uterine Cervical Cancer Cells to Radiation
Authors: Saga Yasushi , Suzuki Mitsuaki , Mizukami Hiroaki , Urabe Masashi , Fukushima Masakazu , Ozawa Keiya , Sato Ikuo 
Published: April 2003

It has been shown that there is an inverse relationship between the level of thymidylate synthase (TS) and therapeutic outcomes in patients with malignancies including cervical cancer. To clarify the mechanism of the poor prognosis of cervical cancer with high TS expression, we introduced TS cDNA to the human uterine cervical cancer cell line SKG-II and evaluated the effect of TS expression on its radiosensitivity. After selection, stable transformants of SKG-II cells expressing high level of TS (SKG-II/TS) and control cells (SKG-II/luciferase) were obtained. The level of TS measured by the FdUMP-TS binding assay was significantly higher (p < 0.05) in SKG-II/TS than in control (2.0 ± 0.1 and 1.3 ± 0.1 pmol/mg, respectively). No difference was observed in in vitro cell growth or in vivo tumor growth. On evaluation of in vitro radiosensitivity, the 50% growth inhibitory dose (ID<sub>50</sub>) was 3.1 ± 0.1 Gy in SKG-II/TS and was significantly higher (p < 0.01) than that in control (2.2 ± 0.1 Gy). From these results, it is suggested that one of the reasons of poor outcome of cervical cancer to radiation is high TS expression.
Evaluating Geometric Accuracy of Multi-Platform Stereotactic Neuroimaging in Radiosurgery
Authors: Wu T.H. , Lee J.S. , Wu H.M. , Chu W.F. , Guo W.Y. 
Published: April 2003

We used a spherical phantom to evaluate geometric accuracy in multi-platform stereotactic neuroimaging for radiosurgery. The phantom consisted of two plastic 16-cm-diameter hemispheres in which an exchangeable 8-cm plastic functional cube was incorporated. The functional cube contained cylinder and point targets. The targets were filled with a mixed aqueous solution of 2-m<i>M</i> copper sulfate and 300-mg/ml iodinated contrast medium and were visible on both MR and X-ray images. Two MR scanners and a biplane X-ray angio-suite were used to scan the phantom stereotactically in two sessions of the experiment. The angio-suite was equipped with digital subtraction and distortion-correction software. The resulting stereotactic images were transferred to a dose-planning computer for length measurement and coordinate determination of the targets. The mean errors of the measured cylinder length on distortion non-corrected X-ray stereotactic images were 0.24 ± 0.14 and 0.73 ± 0.10 mm, respectively, in the experiments; on distortion-corrected images 0.22 ± 0.10 and 0.35 ± 0.39 mm. They were 0.50 ± 0.24, 0.25 ± 0.19 and 0.49 ± 0.34, 0.23 ± 0.25 mm, respectively, of the two MR scanners. The mean errors of coordinate determination of point targets between the stereotactic MR and the distortion-corrected X-ray images were 0.70 ± 0.18, 0.52 ± 0.22 and 0.76 ± 0.25, 0.40 ± 0.10 mm, respectively, in the experiments. We found that the overall geometric errors of target delineation between stereotactic MR and X-ray images were in the submillimeter range. The current study validates the multi-platform and multi-facility stereotactic neuroimaging practice and ensures imaging accuracy in radiosurgery.
Phase I Study of Weekly Irinotecan Combined with Weekly Cisplatin in Patients with Advanced Solid Tumors
Authors: Nakanishi Yoichi , Takayama Koichi , Wataya Hiroshi , Izumi Miiru , Minami Takahiro , Takano Koichi , Inoue Koji , Osaki Shin’ichi , Kimotsuki Kanehito , Harada Taishi , Hara Nobuyuki 
Published: April 2003

<i>Background:</i> Previous studies have reported a synergistic effect between irinotecan and cisplatin. We have conducted a phase I trial combining these agents to find the optimal dose of irinotecan in combination with a fixed dose of cisplatin. <i>Methods:</i> Patients with advanced solid tumors, aged ≤75 years, performance status ≤2, and adequate organ function were enrolled in this study. They were treated at 4-week intervals with irinotecan plus 20 mg/m<sup>2</sup> cisplatin on days 1, 8, and 15. The starting dose of irinotecan of 40 mg/m<sup>2</sup> was escalated in 10 mg/m<sup>2</sup> increments until a maximum dose of 90 mg/m<sup>2</sup> was reached. <i>Results:</i> The recommended dose for phase II studies is 90 mg/m<sup>2</sup> of irinotecan and 20 mg/m<sup>2</sup> of cisplatin on days 1, 8, and 15. Overall response to the chemotherapy was 35% (95% confidential interval, 19.2–54.6%). <i>Conclusion:</i> This combination seems to be active against lung cancer with acceptable toxicity. A phase II study is now ongoing.
Significant Elevations in Serum Mannose-Binding Lectin Levels in Patients with Chronic Renal Failure
Authors: Satomura Atsushi , Endo Morito , Ohi Hiroyuki , Sudo Sukemasa , Ohsawa Isao , Fujita Takayuki , Matsushita Misao , Fujita Teizo 
Published: April 2003

<i>Background/Aims:</i> Mannose-binding lectin (MBL), a liver-derived C-type serum lectin, activates the complement cascade through the lectin pathway. Since the complement system contributes to the host defense against infections and mediates inflammatory processes including atherosclerosis, and since chronic renal failure (CRF) patients are prone to the development of infectious complications and cardiovascular disease, we focused on serum MBL levels in CRF patients who were either uremic, or who were receiving hemodialysis treatment. <i>Methods:</i> MBL levels were measured in the sera of subjects with CRF before they began dialysis treatment (pre-HD patients; n = 23) and in the sera of subjects who were receiving maintenance hemodialysis (HD patients; n = 178), by ELISA using polyclonal anti-rabbit IgG and a monoclonal antibody directed against MBL (3E7). <i>Results:</i> Mean levels (± SD) of serum MBL were significantly higher in pre-HD subjects (4.343 ± 2.533 µg/ml, p < 0.05) and in HD subjects (8.897 ± 4.920 µg/ml, p < 0.05), than in healthy controls (1.452 ± 0.692 µg/ml). Levels were also significantly higher in HD subjects than in pre-HD subjects (p < 0.05). <i>Conclusions:</i> Elevated serum MBL levels in patients with CRF might have significantly influence pathologic conditions such as alterations of the immune system and acceleration of atherogenesis.
Plasma Exchange and Interferon-Alpha Pharmacokinetics in Patients with Hepatitis C Virus-Associated Systemic Vasculitis
Authors: Hausfater P. , Cacoub P. , Assogba U. , Lebon P. , Piette J.C. 
Published: April 2003

Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE. <i>Patients and Methods:</i> We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE. <i>Results:</i> Without PE, IFN C<sub>max </sub>(range: 100–750 IU/ml) was obtained 3–6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-α area under the curve decreased from 3,005 IU·h/ml (1,563–4,614) on days without PE to 2,142 IU·h/ml (973–4,123) on day with PE. <i>Conclusions:</i> In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-α and PE therapy schedule have to be further studied to optimize its biological activity.
Genetics in Primary Care: A USA Faculty Development Initiative
Authors: Burke Wylie , Acheson Louise , Botkin Jeffery , Bridges Kenneth , Davis Ardis , Evans James , Frias Jaime , Hanson James , Kahn Norman , Kahn Ruth , Lanier David , Pinsky Linda E. , Press Nancy , Lloyd-Puryear Michele A. , Rich Eugene , Stevens Nancy , Thomson Elizabeth , Wartman Steven , Wilson Modena 
Published: April 2003

The Genetics in Primary Care (GPC) project is a USA national faculty development initiative with the goal of enhancing the training of medical students and primary care residents by developing primary care faculty expertise in genetics. Educational strategies were developed for the project by an executive committee with input from an advisory committee, comprising individuals with primary care, medical education and genetics expertise. These committees identified the key issues in genetics education for primary care as (1) considering inherited disease in the differential diagnosis of common disorders; (2) using appropriate counseling strategies for genetic testing and diagnosis, and (3) understanding the implications of a genetic diagnosis for family members. The group emphasized the importance of a primary care perspective, which suggests that the clinical utility of genetic information is greatest when it has the potential to improve health outcomes. The group also noted that clinical practice already incorporates the use of family history information, providing a basis for discussing the application of genetic concepts in primary care. Genetics and primary care experts agreed that educational efforts will be most successful if they are integrated into existing primary care teaching programs, and use a case-based teaching format that incorporates both clinical and social dimensions of genetic disorders. Three core clinical skills were identified: (1) interpreting family history; (2) recognizing the variable clinical utility of genetic information, and (3) acquiring cultural competency. Three areas of potential controversy were identified as well: (1) the role of nondirective counseling versus shared decision-making in discussions of genetic testing; (2) the intrinsic value of genetic information when it does not influence health outcomes, and (3) indications for a genetics referral. The project provides an opportunity for ongoing discussion about these important issues.