bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II open-label study of the biologic effects of the interleukin-2 immunocytokine EMD 273063 (hu14.18-IL2) in patients with metastatic malignant melanoma
Authors: Ribas Antoni , Kirkwood John M , Atkins Michael B , Whiteside Theresa L , Gooding William , Kovar Andreas , Gillies Stephen D , Kashala Oscar , Morse Michael A 
Published: July 2009

AbstractBackgroundTo explore the biological activity of EMD 273063 (hu14.18-IL2), a humanized anti-GD2 monoclonal antibody fused to interleukin-2 (IL2), in patients with unresectable, stage IV cutaneous melanoma as measured by induction of immune activation at the tumor site and in peripheral blood.MethodsNine patients were treated with 4 mg/m2per day of EMD 273063 given as a 4-h intravenous infusion on days 1, 2, and 3 every four weeks (one cycle). Peripheral blood was analyzed for T cell and natural killer cell phenotype and frequency, as well as levels of soluble IL2 receptor (sIL2R), IL10, IL6, tumor necrosis factor alpha and neopterin. Biopsies of tumor metastasis were performed prior to therapy and at day 10 of the first 2 cycles to study lymphocyte accumulation by immunohistochemistry.ResultsTreatment was generally well tolerated and there were no study drug-related grade 4 adverse events. Grade 3 events were mainly those associated with IL2, most commonly rigors (3 patients) and pyrexia (2 patients). Best response on therapy was stable disease in 2 patients. There were no objective tumor regressions by standard response criteria. Systemic immune activation was demonstrated by increases in serum levels of sIL2R, IL10, and neopterin. There was evidence of increased tumor infiltration by T cells, but not NK cells, in most post-dosing biopsies, suggesting recruitment of immune cells to the tumor site.ConclusionEMD 273063 demonstrated biologic activity with increased immune-related cytokines and intratumoral changes in some patients consistent with the suspected mechanism of action of this immunocytokine.
Clinical e valuation of magnetic resonance imaging in coronary heart disease: The CE-MARC study
Authors: Greenwood John P , Maredia Neil , Radjenovic Aleksandra , Brown Julia M , Nixon Jane , Farrin Amanda J , Dickinson Catherine , Younger John F , Ridgway John P , Sculpher Mark , Ball Stephen G , Plein Sven 
Published: July 2009

AbstractBackgroundSeveral investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness.Methods/designThis is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness.DiscussionThe CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT.Trial RegistrationCurrent Controlled Trials ISRCTN77246133
Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model
Authors: Liu Yue-Fang , Zha Bin-Shan , Zhang Hui-Lin , Zhu Xiao-Jing , Li Yu-Hua , Zhu Jin , Guan Xiao-Hong , Feng Zhen-Qing , Zhang Jian-Ping 
Published: July 2009

Abstract

Background
Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma.

Methods
A rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues.

Results
The pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated.

Conclusion
In this study, we provide the global gene expression profiles during the development and progression of liver cancer in rats. The data obtained from the gene expression profiles will allow us to acquire insights into the molecular mechanisms of hepatocarcinogenesis and identify specific genes (or gene products) that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies.
Complexity, cofactors, and the failure of AIDS policy in Africa
Authors: Stillwaggon Eileen 
Published: July 2009

Global AIDS policy still treats HIV as an exceptional case, abstracting from the context in which infection occurs. Policy is based on a simplistic theory of HIV causation, and evaluated using outdated tools of health economics. Recent calls for a health systems strategy – preventing and treating HIV within a programme of comprehensive health care – have not yet influenced the silo approach of AIDS policy.Evidence continues to accumulate, showing that multiple factors, such as malnutrition, malaria and helminthes, increase the risk of sexual and vertical transmission of HIV. Moreover, complementary interventions that reduce viral load, improve immune response, and interrupt pathways of transmission could increase the effectiveness of antiretroviral drugs and other tools of AIDS policy.In health economics, the omission of estimates of increasing returns generated by disease or treatment synergies biases cost‐effectiveness analysis against multiple, yet inexpensive, interventions. Current tools of cost‐effectiveness analysis only identify local maxima in a complex landscape, and can play, at best, a marginal role in the epidemic, especially where it is already generalized.Cost‐effectiveness analyses for HIV that are based on the wrong epidemiological model can generate Type III errors: we get precise answers to the wrong questions about how to intervene. To control the epidemic, AIDS policy needs to utilize an epidemiological model that reflects the interactions of biological as well as behavioural variables that determine the course of HIV epidemics around the world. Cost‐effectiveness analysis can benefit from using economic concepts of externalities and increasing returns to incorporate disease interactions and beneficial treatment spillovers for coinfections in HIV‐prevention policy.
Legionella pneumophilamultiplication is enhanced by chronic AMPK signalling in mitochondrially diseased Dictyostelium cells
Authors: Francione Lisa , Smith Paige K. , Accari Sandra L. , Taylor Philip E. , Bokko Paul B. , Bozzaro Salvatore , Beech Peter L. , Fisher Paul R. 
Published: July 2009

SUMMARYHuman patients with mitochondrial diseases are more susceptible to bacterial infections, particularly of the respiratory tract. To investigate the susceptibility of mitochondrially diseased cells to an intracellular bacterial respiratory pathogen, we exploited the advantages of Dictyostelium discoideum as an established model for mitochondrial disease and for Legionella pneumophila pathogenesis. Legionella infection of macrophages involves recruitment of mitochondria to the Legionella-containing phagosome. We confirm here that this also occurs in Dictyostelium and investigate the effect of mitochondrial dysfunction on host cell susceptibility to Legionella. In mitochondrially diseased Dictyostelium strains, the pathogen was taken up at normal rates, but it grew faster and reached counts that were twofold higher than in the wild-type host. We reported previously that other mitochondrial disease phenotypes for Dictyostelium are the result of the activity of an energy-sensing cellular alarm protein, AMP-activated protein kinase (AMPK). Here, we show that the increased ability of mitochondrially diseased cells to support Legionella proliferation is suppressed by antisense-inhibiting expression of the catalytic AMPKα subunit. Conversely, mitochondrial dysfunction is phenocopied, and intracellular Legionella growth is enhanced, by overexpressing an active form of AMPKα in otherwise normal cells. These results indicate that AMPK signalling in response to mitochondrial dysfunction enhances Legionella proliferation in host cells.
Acute Hepatic Injury Associated with Varenicline in a Patient with Underlying Liver Disease
Authors: Franck Andrew J , Sliter Lisa R 
Published: July 2009

Objective: To report a case of acute hepatic injury associated with varenicline. Case Summary: A 53-year-old white male with underlying alcoholic liver disease and history of hepatitis C virus infection experienced elevated aminotransferase and alkaline phosphatase levels consistent with acute hepatic injury after initiation of varenicline for smoking cessation. The hepatic injury manifested 4 weeks after initiation of varenicline therapy at 0.5 mg once daily for 3 days, 0.5 mg twice daily for 4 days, and then 1 mg twice daily. Following discontinuation of varenicline, the patient's aminotransferase levels continued to rise for 2 days before steadily decreasing and returning to baseline levels in approximately 4 months. Alkaline phosphatase continued to rise for 8 days after discontinuation of varenicline before returning to baseline within 1 month. Rechallenge was not attempted. Discussion: Varenicline is a novel, first-line agent for smoking cessation. The presentation of this patient is most consistent with an acute hepatic injury related to drug toxicity. The pattern of the patient's elevated hepatic enzyme levels is not consistent with his underlying alcoholic liver disease or hepatitis C. Using the Naranjo probability scale, as well as the Counsel for International Organizations of Medical Science/Roussel Uclaf Causality Assessment Method algorithm for drug-induced liver toxicity, we determined that varenicline was the probable cause of the acute hepatic injury. Varenicline was a possible cause of the acute hepatic injury using the algorithm for drug-induced liver toxicity developed by Maria and Victorino. To our knowledge, this is the first report of acute hepatic injury associated with varenicline. Conclusions: While the benefits of smoking cessation are likely greater than the risk of hepatic injury, clinicians should be cognizant of this reaction associated with varenicline.
Cortical Oscillatory Activity Is Critical for Working Memory as Revealed by Deficits in Early-Onset Schizophrenia
Authors: Haenschel Corinna , Bittner Robert A. , Waltz James , Haertling Fabian , Wibral Michael , Singer Wolf , Linden David E. J. , Rodriguez Eugenio 
Published: July 2009

Impairments in working memory (WM) are a core cognitive deficit in schizophrenia. Neurophysiological models suggest that deficits during WM maintenance in schizophrenia may be explained by abnormalities in the GABAergic system, which will lead to deficits in high-frequency oscillations. However, it is not yet clear which of the three WM phases (encoding, maintenance, retrieval) are affected by dysfunctional oscillatory activity. We investigated the relationship between impairments in oscillatory activity in a broad frequency range (3–100 Hz) and WM load in the different phases of WM in 14 patients with early-onset schizophrenia and 14 matched control participants using a delayed matching to sample paradigm.During encoding, successful memorization was predicted by evoked theta, alpha, and beta oscillatory activity in controls. Patients showed severe reductions in the evoked activity in these frequency bands. During early WM maintenance, patients showed a comparable WM load-dependent increase in induced alpha and gamma activity to controls. In contrast, during the later maintenance phase, patients showed a shift in the peak of induced gamma activity to the lower WM load conditions. Finally, induced theta and gamma activity were reduced in patients during retrieval.Our findings suggest that the WM deficit in schizophrenia is associated with impaired oscillatory activity during all phases of the task and that the cortical storage system reaches its capacity limit at lower loads. Inability to maintain oscillatory activity in specific frequency bands could thus result in the information overload that may underlie both cognitive deficits and psychopathological symptoms of schizophrenia.
Modellreduktion für parametrisierte Systeme durch balanciertes Abschneiden und InterpolationModel Reduction for Parametric Systems Using Balanced Truncation and Interpolation
Authors: Baur Ulrike , Benner Peter 
Published: July 2009

Zusammenfassung
Der Beitrag stellt einen neuen Ansatz zur Parameter-erhaltenden Modellreduktion parametrisierter, linearer Systeme vor. Das Verfahren ist eine Kopplung des balancierten Abschneidens mit Interpolation, sodass Fehlerabschätzungen für die Qualität des reduzierten Systems ableitbar sind. Durch die Verwendung dünner Gitter zur Diskretisierung des Parameterraumes kann das Verfahren auch auf Systeme mit mehreren Parametern angewendet werden.
Disparities in Access to Over-the-Counter Nicotine Replacement Products in New York City Pharmacies
Authors: Bernstein Steven L. , Cabral Lisa , Maantay Juliana , Peprah Dorothy , Lounsbury David , Maroko Andrew , Murphy Mary , Shelley Donna 
Published: July 2009

Objectives. We surveyed the availability of tobacco products and nonprescription nicotine replacement therapy (NRT) in pharmacies in New York City, stratified by the race, ethnicity, and socioeconomic status (SES) of the surrounding neighborhoods to determine whether disparities in availability existed.Methods. Surveyors visited a random sample of retail pharmacies to record the availability of tobacco products and nonprescription NRT. We used census data and geographic information systems analysis to determine the SES of each neighborhood. We used logistic modeling to explore relations between SES and the availability of NRT and tobacco products.Results. Of 646 pharmacies sampled, 90.8% sold NRT and 46.9% sold cigarettes. NRT and cigarettes were slightly more available in pharmacies in neighborhoods with a higher SES. NRT was more expensive in poorer neighborhoods.Conclusions. Small disparities existed in access to nonprescription NRT and cigarettes. The model did not adequately account for cigarette access, because of availability from other retail outlets. These results may explain some of the excess prevalence of cigarette use in low-SES areas.
Der Spielraum bei der Vermarktung von Waldleistungen ist eingeschränkt (Essay) | The scope for the commercialization of forest services is limited (essay)
Authors: Walther Hansruedi 
Published: July 2009

A forest owner can only commercialize non-wood products and services within a tightly restricted market niche. On account of free access being permitted to the forest it is impossible to deny to third parties the consumption of many non-wood products and services: everybody has the right to be in the forest for recreation. As a result many non-wood services cannot be commercialized by the forest owner, or not exclusively.
What would seem unthinkable elsewhere on private property seems to be taken for granted in the forest: third parties may take products from the forest and even sell them without being the forest owners. For certain nonwood services or products, such as the installation of rope parks or for burial in the forest, the organizer must conclude an agreement with the forest owner or draw up a contract for servitude or benefit. In addition, for these activities a permit from the Forestry Department is necessary. On the other hand, for an itinerant school class or for the production of forest honey neither a binding regulation with the forest owner nor a permit from the Forestry service is necessary, provided that no constructions are erected in the forest. The only exclusive right which remains to the forest owner, besides the sale of his property, is the exploitation of his trees within the legal framework.
Rapid Diagnosis of Malaria by Antigen Detection
Authors: Ahmed Mesbah Uddin , Hossain Md Akram , Shamsuzzaman AKM , Alam Md Murshed , Khan Abdul Hossain , Sumona Asma Azad , Alam Ahmed Nawsher , Ahmed Salma , Siddiqua Mahmuda 
Published: July 2009

The study was conducted to evaluate the sensitivity and specificity of Immunochromatographic test (ICT) for antigen, using microscopy as the "gold standard" method for diagnosis of malaria. A total of 98 clinically suspected malaria patients and another 30 age and sex-matched healthy controls were included in this study. Thick and thin films were also prepared and examined under microscope as well as Immunochromatographic test (ICT) was performed for malaria antigen. Sensitivity and specificity of ICT for antigen were 93.22% and 94.87% respectively. Keywords: Detection of malaria antigen, Immunochromatographic test doi: 10.3329/bjmm.v3i1.2965 Bangladesh J Med Microbiol 2009; 03 (01): 14-16
Studies on Antibacterial Activity and Brine Shrimp Toxicity of Leaf Extract of <i>Cassia grandis</i>
Authors: Awal MA , Ashrafuzzaman Syed , Haque E Ekramul 
Published: July 2009

Antibacterial activity and toxicity of ethanol extract of Cassia grandis leaves to Brine Shrimp was evaluated. Five Gram-positive and 4 Gram-negative bacteria, namely Sarcina lutea, Bacillus megaterium, Bacillus subtilis, Streptococcus ß-haemolyticus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi and Klebsiella pneumoniae were tested using disc diffusion method. The extract was inactive at the concentration of 30 μg/disc but exhibited moderate to good activity at concentration of 200 μg/disc against the tested bacteria. In Brine Bhrimp lethality bioassay test, it was observed that LC50 value of the extract was 10.68 μg/ml. From these findings, it is indicative that C. grandis may be useful against microbial diseases. Key words: Antibacterial activity, Brine shrimp, Cassia grandis doi: 10.3329/bjmm.v3i1.2966 Bangladesh J Med Microbiol 2009; 03 (01): 17-19
Prevalence of Sexually Transmitted Diseases and Transmission of HIV in Dhaka, Bangladesh
Authors: Shirin Tahmina , Rahman Saidur , Rabbi Fareha Jesmin , Kabir Md Humayun , Mamun KZ 
Published: July 2009

The prevalence of sexually transmitted diseases (STDs) among patients attending out patients department of Skin and Venereal diseases of Dhaka Medical College Hospital, Dhaka and Shahid Sohrawardy Hospital, Dhaka was studied. A total of 230 patients were enrolled in the study during the period of July, 2006 to May, 2007. Urethral and endocervical swabs were collected from the participants for detection of Neisseria gonorrheae (by culture), Chlamydia trachomatis (by immunochromatoghraphy) and blood samples for the detection of Treponema pallidum antibody (by rapid plasma regain and Treponema pallidum haemagglutination assay), Herpes simplex virus type 2 antibody (both IgM and IgG by enzyme linked immunosorbent assay) and Human Immunodeficiency virus antibody (by enzyme linked immunosorbent assay). Socio-demographic data and data regarding high-risk sexual behavior were also collected. Out of 230 participants, 199 (86.5%) were positive for STDs pathogens studied, among them, 98 (42.6%) were infected with single pathogen and 101 (43.9%) were suffering from multiple infections. The prevalences of N. gonorrheae, C. trachomatis, T. pallidum, and HSV type 2 were 90 (39.1%), 110 (47.8%), 28 (12.2%) and 88 (38.2%) respectively. However, none of them were positive for HIV infection. Use of condom was significantly associated with protection of the participants against STDs. Keywords: Sexually Transmitted Diseases, Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum, Herpes simplex virus type-2, Human Immunodeficiency virus doi: 10.3329/bjmm.v3i1.2968 Bangladesh J Med Microbiol 2009; 03 (01): 27-33
The utility of FDG-PET for detecting multiple primary cancers in hypopharyngeal cancer patients
Authors: Ishibashi M. , Kurata S. , Uchiyama Y. , Tanaka N. , Abe T. , Kobayashi M. , Kaibara H. , Uchida M. , Nakashima T. , Fujita H. , Hayabuchi N. , Kaida H. 
Published: July 2009

Summary
Aim: To examine the utility of 2'-[18F]-fluoro-2'-deoxy-D-glucose positron emission tomography (FDG-PET) for detecting multiple primary cancers (MPC) in patients with hypopharyngeal cancer (HPC). Patients, methods: Seventy patients with HPC underwent FDGPET to determine the staging. Routine clinical examinations were carried out, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and oesophagealgastroduodenoscopy (EGDS). The detection rate of synchronous and metachronous cancer was calculated based on FDG-PET alone or FDG-PET combined with clinical routine examination. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and accuracy were used to diagnose oesophageal cancer using FDG-PET. Results: Of the 70 patients, 12 (17.1%) had 15 synchronous tumours, and 2 of the 58 remaining patients (3.4%) had metachronous tumours. Oesophageal cancer was discovered most frequently: superficial type (n = 6), advanced type (n = 4). On a per-patient basis, 11 of 12 patients (91.6%) were diagnosed with synchronous tumours, and on a per-lesion basis, 12 of 15 lesions (80.0%) were detected by FDG-PET. The sensitivity, specificity, accuracy, PPV, and NPV of FDG-PET regarding oesophageal cancer were 70%, 100%, 95.7%, 100%, and 95.2% respectively. Three of the six superficial types were positive on FDG-PET. Both of the metachronous tumour lesions were detected by FDG-PET. Conclusion: FDG-PET is useful for estimating the MPC in HPC patients. Since 3 of 10 synchronous oesophageal cancer were missed with PET alone, a combination with EGDS should be considered to exclude synchronous oesophageal cancer.