bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of tumor necrosis factor α blockade in systemic lupus erythematosus: An open‐label study
Authors: Aringer Martin , Graninger Winfried B. , Steiner Günter , Smolen Josef S. 
Published: October 2004

AbstractObjectiveTo investigate the safety of therapeutic tumor necrosis factor α (TNFα) blockade in patients with systemic lupus erythematosus (SLE), in whom this proinflammatory cytokine is significantly increased and may be involved in the disease pathogenesis.MethodsIn an open‐label study, 6 patients with moderately active SLE (4 with nephritis and 3 with arthritis refractory to other therapies) were given 4 300‐mg doses of infliximab, a chimeric anti‐TNFα antibody, in addition to immunosuppression with azathioprine or methotrexate.ResultsThe only significant adverse events observed were urinary tract infection in 3 patients, 1 of which was accompanied by Escherichia coli bacteremia, and a prolonged febrile episode of putatively viral origin in 1 of them. These patients had similar infectious conditions in the past. In none of the patients was it necessary to terminate the treatment prematurely. Levels of antibodies to double‐stranded DNA and cardiolipin increased in 4 patients each, but this was not associated with a decrease in serum complement levels, with vascular events, or with flares. In contrast, disease activity declined during therapy. All 3 patients with joint involvement experienced remission of arthritis, which relapsed 8–11 weeks after the last infliximab infusion. In the 4 patients with lupus nephritis, proteinuria decreased significantly within 1 week after initiation of therapy and was diminished by ≥60% within 8 weeks, remaining at low levels until the end of the observation period (at least several months).ConclusionInfliximab did not lead to adverse events related to an increase in SLE activity, although autoantibodies to double‐stranded DNA and cardiolipin increased, as expected. This finding, coupled with the clinical improvement in the inflammatory manifestations of the disease, indicates that further study in larger controlled trials is warranted.
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII. Predictors of time to the occurrence of initial damage
Authors: Toloza Sergio M. A. , Roseman Jeffrey M. , Alarcón Graciela S. , McGwin Gerald , Uribe América G. , Fessler Barri J. , Bastian Holly M. , Vilá Luis M. , Reveille John D. 
Published: October 2004

AbstractObjectiveTo examine the factors predisposing to initial damage in patients in the LUMINA (lupus in minorities: nature versus nurture) cohort, a multiethnic cohort of patients with systemic lupus erythematosus (SLE) in the US.MethodsOne hundred fifty‐eight LUMINA patients with no damage at baseline (time 0) according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI) and with disease duration >6 months were followed up for a median of 24 months (range 5–112 months). Damage was assessed from time 0 to the last visit. Predictors of time to initial damage were examined by univariable and multivariable Cox proportional hazard regression models. Results were reported as hazard ratios (HRs); HR values ≥1 indicated a shorter time to initial damage, and values <1 indicated a longer time.ResultsInitial damage occurred in 54 patients (34%), of whom 21 were Hispanics from Texas (39%), 2 were Hispanics from Puerto Rico (4%), 21 were African Americans (39%), and 10 were Caucasians (19%). The most frequently observed initially involved SDI domains (and items) were as follows: renal (primarily proteinuria) in Hispanics from Texas and African Americans, integument (primarily scarring alopecia) in Hispanics from Puerto Rico, and ocular (primarily cataracts) in Caucasians. By multivariable analyses, independent predictors of a shorter time to initial damage were Hispanic ethnicity from Texas (HR 2.11, 95% confidence interval [95% CI] 1.15–3.88), greater disease activity according to the Systemic Lupus Activity Measure (HR 1.09, 95% CI 1.04–1.15), the occurrence of thrombotic events in visceral and/or peripheral veins or arteries (HR 7.66, 95% CI 2.13–27.51), and prednisone at a dosage of <10 mg/day (HR 2.53, 95% CI 1.15–5.55). Prednisone at a dosage of 10–30 mg/day was found to be protective against the occurrence of initial damage (HR 0.46, 95% CI 0.22–0.96).ConclusionGiven that damage is a predictor of further damage, identifying the factors that may herald the occurrence of initial damage has very practical implications for the management of patients with SLE. These results need to be considered when evaluating therapies for SLE.
Amelioration of symptoms by enhancement of proprioception in patients with joint hypermobility syndrome
Authors: Ferrell William R. , Tennant Nicola , Sturrock Roger D. , Ashton Linda , Creed Gisela , Brydson Gillian , Rafferty Daniel 
Published: October 2004

AbstractObjectiveJoint hypermobility syndrome (JHS) is characterized by an association between joint hypermobility and musculoskeletal pains, the latter occurring in the absence of any objective indicator of rheumatic disease. The lack of a recognizable disease marker makes this condition difficult to identify and manage. We previously observed that patients with JHS have impaired proprioception compared with that of a matched control group. The purpose of this study was to investigate whether a home‐based exercise program could produce objective enhancement of proprioception as well as alleviate symptoms in JHS.MethodsA threshold detection paradigm was used to assess knee joint proprioception, balance was assessed using a balance board, and quadriceps and hamstring strength were measured by an isokinetic dynamometer. A visual analog scale was used to assess musculoskeletal pain, and quality of life was evaluated by a Short Form 36 questionnaire. Assessments were performed before and after an 8‐week program of progressive closed kinetic chain exercises.ResultsFollowing the exercise program, proprioceptive acuity increased in 16 of 18 subjects and was very significantly improved overall (P < 0.001). There was a comparable improvement in performance on the balance board (P < 0.001), and quadriceps and hamstring strength also increased significantly. Symptomatic improvement also occurred, in terms of both pain (P = 0.003) and quality‐of‐life (P = 0.029 for physical functioning; P = 0.008 for mental health) scores.ConclusionAppropriate exercises lead not only to symptomatic improvement, but also to demonstrable enhancement of objective parameters such as proprioception.
High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury
Authors: Lohmander L. S. , Östenberg A. , Englund M. , Roos H. 
Published: October 2004

AbstractObjectiveTo determine the prevalence of radiographic knee osteoarthritis (OA) as well as knee‐related symptoms and functional limitations in female soccer players 12 years after an anterior cruciate ligament (ACL) injury.MethodsFemale soccer players who sustained an ACL injury 12 years earlier were examined with standardized weight‐bearing knee radiography and 2 self‐administered patient questionnaires, the Knee Injury and Osteoarthritis Outcome Score questionnaire and the Short Form 36‐item health survey. Joint space narrowing and osteophytes were graded according to the radiographic atlas of the Osteoarthritis Research Society International. The cutoff value to define radiographic knee OA approximated a Kellgren/Lawrence grade of 2.ResultsOf the available cohort of 103 female soccer players, 84 (82%) answered the questionnaires and 67 (65%) consented to undergo knee radiography. The mean age at assessment was 31 years (range 26–40 years) and mean body mass index was 23 kg/m2 (range 18–40 kg/m2). Fifty‐five women (82%) had radiographic changes in their index knee, and 34 (51%) fulfilled the criterion for radiographic knee OA. Of the subjects answering the questionnaires, 63 (75%) reported having symptoms affecting their knee‐related quality of life, and 28 (42%) were considered to have symptomatic radiographic knee OA. Slightly more than 60% of the players had undergone reconstructive surgery of the ACL. Using multivariate analyses, surgical reconstruction was found to have no significant influence on knee symptoms.ConclusionA very high prevalence of radiographic knee OA, pain, and functional limitations was observed in young women who sustained an ACL tear during soccer play 12 years earlier. These findings constitute a strong rationale to direct increased efforts toward prevention and better treatment of knee injury.
Crystal and Magnetic Structure of the System Li0.5+0.5xFe2.5−1.5xTixO4 (x=0.16, 0.44, and 0.72)
Authors: Arillo María Angeles , Cuello Gabriel , López María Luisa , Pico Carlos , Veiga María Luisa 
Published: October 2004

AbstractThe influence of thermal treatment on the structure of lithium titanium ferrite spinels of general formula Li0.5+0.5xFe2.5−1.5xTixO4 (x=0.16, 0.44, and 0.72) has been studied by X‐ray and neutron diffraction and analysed by the Rietveld method. The results allow us to conclude the presence of an ordered phase (space group P4332) at room temperature for the sample with x=0.16; this phase does not appear for the remaining compositions. The magnetic properties evidence a ferrimagnetic ordering in the structures when a random cation distribution (space group Fd3 m) is obtained. An exhaustive study carried out by neutron diffraction measurements on these samples shows a different behaviour when the titanium content is increased, concluding that the lower substituted phase (x=0.16) exhibits a Néel's collinear ferrimagnetic structure, with the higher substituted structures being noncollinear (x=0.44 and 0.72).
New Chiral 1,2‐Diamines and Their Use in Zinc‐Catalyzed Asymmetric Hydrosilylation of Acetophenone.
Authors: Bette Virginie , Mortreux Andre , Ferioli Federico , Martelli Gianluca , Savoia Diego , Carpentier Jean‐Francois 
Published: October 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Concomitant Ring Contraction Cyclization Strategy for the Synthesis of Novel 4‐Oxo‐4,5‐dihydro‐pyrroloquinolines.
Authors: Manh Gabriel Thia , Bakkali Hicham , Maingot Lucie , Pipelier Muriel , Joshi Uday , Pradere Jean Paul , Sabelle Stephane , Tuloup Remy , Dubreuil Didier 
Published: October 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Antileukemic Activity of New 3‐(5‐Methylisoxazol‐3‐yl) and 3‐(Pyrimidin‐2‐yl)‐2‐styrylquinazolin‐4(3H)‐ones.
Authors: Raffa Demetrio , Daidone Giuseppe , Maggio Benedetta , Cascioferro Stella , Plescia Fabiana , Schillaci Domenico 
Published: October 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Synthesis and Antibacterial Evaluation of 1β‐Methyl‐2‐(5‐substituted heterocyclic carbamoyl‐pyrrolidin‐3‐ylthio)carbapenem Derivatives.
Authors: Lee Joo‐Shin , Cho Jung‐Hyuck Cho Jung‐Hyuck , Cho Heeyeong , Oh Chang‐Hyun 
Published: October 2004

AbstractFor Abstract see ChemInform Abstract in Full Text.
Dynamics of endocytic traffic of Entamoeba histolytica revealed by confocal microscopy and flow cytometry
Authors: Meza Isaura , Clarke Margaret 
Published: October 2004

AbstractEntamoeba histolytica, the protozoan parasite of humans, manifests constitutive endocytosis to obtain nutrients and, when induced to express invasive behavior, as a means of ingesting and processing host cells and tissue debris. E. histolytica trophozoites were grown in liquid axenic medium that contained fluorescently labeled fluid‐phase markers, so that the kinetics of uptake, the transit of loaded endosomes through the cytoplasm, and the time of release of the markers could be monitored by flow cytometry. Confocal microscopy of live trophozoites revealed uptake of fluid by avid macropinocytosis and the occurrence of fusion between young and older endosomes, as well as between pinosomes and phagosomes containing bacteria. Endosomes were rapidly acidified, then gradually neutralized; finally, indigestible material was released. Transit of endosomes containing fluid‐phase markers required about 2 h. Uptake and release of fluid‐phase markers were impaired by drugs that inhibited actin dynamics and actin‐myosin interaction; uptake was also impaired by inhibition of PI 3‐kinase. A striking feature of the trophozoites was the great heterogeneity of their endocytic behavior. Cell Motil. Cytoskeleton 59:215–226, 2004. © 2004 Wiley‐Liss, Inc.
Nuclear factor‐κB and IκB kinase are constitutively active in human pancreatic cells, and their down‐regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis
Authors: Li Lan , Aggarwal Bharat B. , Shishodia Shishir , Abbruzzese James , Kurzrock Razelle 
Published: October 2004

AbstractBACKGROUNDPancreatic carcinoma is a lethal malignancy, with the best available therapeutic option—gemcitabine—yielding response rates of < 10%. Because nuclear factor‐κB (NF‐κB) has been determined to play a role in cell survival/proliferation in human pancreatic carcinoma, this transcription factor is a potential therapeutic target.METHODSThe authors investigated the ability of curcumin (diferuloylmethane), an agent that is pharmacologically safe in humans, to modulate NF‐κB activity.RESULTSNF‐κB and IκB kinase (IKK) were constitutively active in all human pancreatic carcinoma cell lines examined, and curcumin consistently suppressed NF‐κB binding (as assessed using an electrophoretic mobility gel‐shift assay) and IKK activity. Curcumin decreased the expression of NF‐κB–regulated gene products, including cyclooxygenase‐2 (as assessed using immunoblot analysis), prostaglandin E2, and interleukin‐8 (as assessed using an enzyme‐linked immunoassay), all of which have been implicated in the growth and invasiveness of pancreatic carcinoma. These changes were associated with concentration‐ and time‐dependent antiproliferative activity (as assessed using a 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide [MTT] assay) and proapoptotic effects (as assessed via annexin V/propidium iodide staining [fluorescence‐activated cell sorting, as well as with the induction of polyadenosine‐5′‐diphosphate‐ribose polymerase cleavage).CONCLUSIONSCurcumin down‐regulated NF‐κB and growth control molecules induced by NF‐κB in human pancreatic cells. These effects were accompanied by marked growth inhibition and apoptosis. Through these findings, the authors provided a biologic rationale for the treatment of patients with pancreatic carcinoma using this nontoxic phytochemical. Cancer 2004. © 2004 American Cancer Society.
Pancreatic carcinoma cells express neuropilins and vascular endothelial growth factor, but not vascular endothelial growth factor receptors
Authors: Li Min , Yang Hui , Chai Hong , Fisher William E. , Wang Xiaoping , Brunicardi F. Charles , Yao Qizhi , Chen Changyi 
Published: October 2004

AbstractBACKGROUNDNeuropilins (NRPs) are characterized as coreceptors of vascular endothelial growth factor (VEGF). In the current study, the authors assessed the expression of NRPs, VEGF, and vascular endothelial growth factor receptors (VEGFRs), as well as VEGF‐induced cell proliferation, in pancreatic carcinoma cell lines and tissue specimens.METHODSHuman pancreatic carcinoma cell lines (Panc‐1 and MIA PaCa‐2), normal human pancreatic ductal epithelial cells (HPDE), and human umbilical vein endothelial cells (HUVECs) were cultured. Human pancreatic adenocarcinoma tissue specimens were also studied. Expression levels of NRPs, VEGFRs, and VEGF were determined by real‐time polymerase chain reaction analysis and immunostaining. Cell proliferation was examined using a [3H]thymidine incorporation assay.RESULTSBoth NRP‐1 and NRP‐2 were expressed in Panc‐1 cells, HPDE cells, and HUVECs but were expressed minimally in MIA PaCa‐2 cells. Panc‐1 expressed 30 times more NRP‐1 mRNA than NRP‐2 mRNA. NRP‐1 levels in Panc‐1 cells were 5.3 times higher than in HPDE cells but were similar to NRP‐1 levels in HUVECs. NRP‐2 levels in Panc‐1 cells were similar to NRP‐2 levels in HPDE cells but lower than NRP‐2 levels in HUVECs. Expression of all three VEGFRs was observed only in HUVECs. However, VEGF mRNA was detected in all cell types except for HUVECs. NRP‐1 immunoreactivity levels were much higher than NRP‐2 immunoreactivity levels in Panc‐1 and human pancreatic adenocarcinoma tissue specimens, whereas VEGFRs were not detected in either of these two settings. In response to VEGF165, [3H]thymidine incorporation in Panc‐1 cells increased significantly (by 61%; P < 0.01). A monoclonal antibody against human NRP‐1 significantly blocked VEGF‐induced cell proliferation in Panc‐1 cells.CONCLUSIONSThe pancreatic carcinoma cell line Panc‐1 and adenocarcinoma tissue specimens expressed high levels of NRP‐1 and VEGF, but not VEGFRs, and exogenous VEGF significantly increased NRP‐1‐mediated, but not VEGFR‐mediated, Panc‐1 cell proliferation. These data suggested that NRP‐1 may be involved in the pathogenesis of pancreatic carcinoma. Cancer 2004. © 2004 American Cancer Society.
Preclinical evaluation of antisense bcl‐2 as a chemosensitizer for patients with gastric carcinoma
Authors: Kim Ryungsa , Emi Manabu , Tanabe Kazuaki , Toge Tetsuya 
Published: October 2004

AbstractBACKGROUNDBecause bcl‐2 is a critical factor for anticancer drug‐induced apoptosis, the authors conducted a preclinical evaluation of antisense (AS) bcl‐2 as an enhancer of the chemotherapeutic effect in the treatment of patietns with gastric carcinoma.METHODSAS bcl‐2 was used with 18‐mer phosphorothiated oligonucleotides in the MKN‐45 gastric carcinoma cell line. Drug sensitivity in vitro was evaluated using the methyl‐thiazoldiphenyl tetrazolium assay, and antitumor effects in vivo were evaluated using the nude mouse xenograft. Apoptosis was determined with the terminal deoxyuridine triphosphate nick‐end labeling assay. AS bcl‐2 in vitro was treated with lipofectin, whereas it was administered intraperitoneally for 6 consecutive days twice every 2 weeks in vivo. Anticancer drugs were administered intraperitoneally four times per week.RESULTSbcl‐2 was down‐regulated to 60% of its initial value after treatment with 1.0 μM AS bcl‐2 compared with the controls of random and mismatched oligonucleotides. Drug sensitivity to doxorubicin, cisplatin, and paclitaxel (TXL) was increased 3–4‐fold when used in combination with AS bcl‐2, which was determined with 50% inhibitory concentration values, compared with the control group. Increased drug sensitivity was associated with apoptosis, which increased in Bax and poly‐adenosine diphosphate (ADP‐ribose) polymerase and decreased in phosphorylated Akt (pAkt). The antitumor effect of cisplatin and TXL in vivo was enhanced significantly in combination with AS bcl‐2. Down‐regulation of bcl‐2 was observed on Day 4 after the treatment with AS bcl‐2.CONCLUSIONSCombination treatment with AS bcl‐2 and anticancer drugs, including cisplatin and TXL, may be a new strategy for enhancing chemotherapeutic effects in the treatment of gastric carcinoma. Cancer 2004. © 2004 American Cancer Society.
Preoperative somatic symptoms are associated with disease progression in patients with bladder carcinoma after cystectomy
Authors: Palapattu Ganesh S. , Bastian Patrick J. , Slavney Phillip R. , Haisfield‐Wolfe Mary Ellen , Walker Joanne M. , BrintzenhofeSzoc Karlynn , Trock Bruce , Zabora James , Schoenberg Mark P. 
Published: October 2004

AbstractBACKGROUNDA link between patient psychologic factors and bladder carcinoma outcome has not been demonstrated. The purpose of the current study was to assess the association of psychologic factors measured preoperatively with bladder carcinoma progression after cystectomy.METHODSThe Brief Symptom Inventory (BSI)‐18 was administered prospectively to 65 patients with clinically localized bladder carcinoma before surgery. The BSI‐18 measures distress in three specific domains—depression, anxiety, and somatization (i.e., distress due to somatic symptoms)—as well as general distress. Preoperative BSI‐18 scores, tumor pathologic stage, and certain clinical variables were compared with disease status. Disease progression was defined as the development of either local disease recurrence or distant metastasis. Univariate and multivariate Cox proportional hazards models were constructed for statistical analysis.RESULTSOf the 65 patients, 49 (79.4%) had no evidence of disease, 4 (6.2%) had local disease recurrence, and 12 (18.5%) had metastatic disease at last follow‐up. The mean follow‐up time was 1.3 years and did not differ significantly between survival outcomes (P = 0.577). Both tumor pathologic stage and preoperative somatic distress scores were associated with time to disease progression by univariate analysis (P = 0.038 and P = 0.055, respectively). After adjusting for tumor pathologic stage, a somatic distress score of ≥ 2.00 was a significant predictor of disease progression (P = 0.044, hazard ratio = 3.31, 95% confidence interval = 1.03–10.60). Patient age, gender, reconstruction type, and BSI‐18 scores for depression, anxiety, and general distress were not significantly associated with disease outcome.CONCLUSIONSThe authors found no correlation between psychologic symptoms measured preoperatively (i.e., depression, anxiety, and general distress) and bladder carcinoma progression. However, they reported an association between somatic symptoms and cancer outcome. If confirmed by other studies, these results may have important implications for the diagnosis, staging, and potential treatment of patients with bladder carcinoma. Cancer 2004. © 2004 American Cancer Society.
Anagrelide for thrombocytosis in myeloproliferative disorders
Authors: Steurer Michael , Gastl Guenther , Jedrzejczak Wieslaw‐Wiktor , Pytlik Robert , Lin Werner , Schlögl Ernst , Gisslinger Heinz 
Published: October 2004

AbstractBACKGROUNDAlthough the platelet count does not correlate with the rate of thrombosis, there is evidence that a strict control of the platelet count decreases the incidence of thromboembolic complications in essential thrombocythemia. In the current study, the authors evaluated the efficacy and tolerability of anagrelide in thrombocytosis associated with myeloproliferative disorders.METHODSThe study cohort comprised 97 patients (n = 69 females, n = 28 males) with a median age of 59 years (range, 21–80 years). Patients with essential thrombocythemia (n = 79) or with thrombocytosis due to polycythemia vera (n = 16) or to chronic idiopathic myelofibrosis (n = 2) were enrolled in the multicenter, prospective study. Patients received anagrelide at a starting dose of 0.5 mg twice per day, which was then adjusted for each patient.RESULTSTreatment with anagrelide resulted in a rapid decrease in the platelet count, from a median baseline platelet count of 743 × 109/L to a median platelet count of 441 × 109/L after 6 months (P < 0.0001). The proportion of patients with a platelet count < 600 × 109/L increased from 30% at baseline to 77% after the 6‐month study period. The rate of major thrombotic complications significantly decreased from 5% to 2% (P = 0.2568). For patients with essential thrombocythemia, the reduction of major thromboembolic complications was significant (P = 0.0455). The rate of minor thromboembolic complications decreased from 25% before anagrelide treatment to 14% during anagrelide treatment (P = 0.0278). No severe side effects were observed during the study period. There was, however, evidence that concomitant administration of acetylsalicylic acid may increase bleeding tendency.CONCLUSIONSAnagrelide was an effective and well tolerated treatment modality for reducing platelet counts in both newly diagnosed and pretreated patients with thrombocytosis due to myeloproliferative disorders. Cancer 2004. © 2004 American Cancer Society.