bluuebunny/crossref_metadata_2025_split huggingface dataset:
The transcription factor Gli3 regulates differentiation of fetal CD4–CD8– double-negative thymocytes
Authors: Hager-Theodorides Ariadne L. , Dessens Johannes T. , Outram Susan V. , Crompton Tessa 
Published: April 2005

AbstractGlioblastoma 3 (Gli3) is a transcription factor involved in patterning and oncogenesis. Here, we demonstrate a role for Gli3 in thymocyte development. Gli3 is differentially expressed in fetal CD4–CD8– double-negative (DN) thymocytes and is most highly expressed at the CD44+ CD25– DN (DN1) and CD44–CD25– (DN4) stages of development but was not detected in adult thymocytes. Analysis of null mutants showed that Gli3 is involved at the transitions from DN1 to CD44+ CD25+ DN (DN2) cell and from DN to CD4+CD8+ double-positive (DP) cell. Gli3 is required for differentiation from DN to DP thymocyte, after pre–T-cell receptor (TCR) signaling but is not necessary for pre-TCR–induced proliferation or survival. The effect of Gli3 was dose dependent, suggesting its direct involvement in the transcriptional regulation of genes controlling T-cell differentiation during fetal development.
Tuberculous dilated cardiomyopathy: an under-recognized entity?
Authors: Agarwal Ritesh , Malhotra Puneet , Awasthi Anshu , Kakkar Nandita , Gupta Dheeraj 
Published: April 2005

AbstractBackgroundTuberculosis (TB) is a common public health problem in many parts of the world. TB is generally believed to spare these four organs-heart, skeletal muscle, thyroid and pancreas. We describe a rare case of myocardial TB diagnosed on a post-mortem cardiac biopsy.Case presentationPatient presented with history suggestive of congestive heart failure. We describe the clinical presentation, investigations and outcome of this case, and review the literature on the involvement of myocardium by TB.ConclusionInvolvement of myocardium by TB is rare. However it should be suspected as a cause of congestive heart failure in any patient with features suggestive of TB. Increasing recognition of the entity and the use of endomyocardial biopsy may help us detect more cases of this "curable" form of cardiomyopathy.
Practical PCR genotyping protocols for Plasmodium vivax using Pvcs and Pvmsp1
Authors: Imwong Mallika , Pukrittayakamee Sasithon , Grüner Anne Charlotte , Rénia Laurent , Letourneur Frank , Looareesuwan Sornchai , White Nicholas J , Snounou Georges 
Published: April 2005

Abstract

Background

Plasmodium vivax is the second most prevalent malaria parasite affecting more than 75 million people each year, mostly in South America and Asia. In addition to major morbidity this parasite is associated with relapses and a reduction in birthweight. The emergence and spread of drug resistance in Plasmodium falciparum is a major factor in the resurgence of this parasite. P. vivax resistance to drugs has more recently emerged and monitoring the situation would be helped, as for P. falciparum, by molecular methods that can be used to characterize parasites in field studies and drug efficacy trials.

Methods
Practical PCR genotyping protocols based on polymorphic loci present in two P. vivax genetic markers, Pvcs and Pvmsp1, were developed. The methodology was evaluated using 100 P. vivax isolates collected in Thailand.

Results and Discussion
Analysis revealed that P. vivax populations in Thailand are highly diverse genetically, with mixed genotype infections found in 26 % of the samples (average multiplicity of infection = 1.29). A large number of distinguishable alleles were found for the two markers, 23 for Pvcs and 36 for Pvmsp1. These were generally randomly distributed amongst the isolates. A total of 68 distinct genotypes could be enumerated in the 74 isolates with a multiplicity of infection of 1.

Conclusion
These results indicate that the genotyping protocols presented can be useful in the assessment of in vivo drug efficacy clinical trials conducted in endemic areas and for epidemiological studies of P. vivax infections.
Effects of dexamethasone on TNF-alpha-induced release of cytokines from purified human blood eosinophils
Authors: Uings Iain , Puxeddu Ilaria , Temkin Vladislav , Smith Susan J , Fattah Dilniya , Ray Keith P , Levi-Schaffer Francesca 
Published: April 2005

SummaryBackgroundTNF-alpha is an important mediator in allergy also for its effects on eosinophils.MethodsThe effect of dexamethasone on TNF-alpha induced eosinophils survival, degranulation (ECP), cytokines release (IL-8, GM-CSF) and adhesion to VCAM-1, ICAM-1 and IgG coated wells (EPO release) were evaluated.ResultsThe drug inhibited IL-8 and GM-CSF production, but not viability, degranulation or adhesion in human peripheral blood eosinophils.ConclusionThese results indicate that part of the activity of glucocorticosteroids on eosinophils may be mediated by their ability to inhibit cytokine secretion that in turn is important for the perpetuation of the allergic inflammation.
The relations between symptoms, somatic and psychiatric conditions, life satisfaction and perceived health. A primary care based study
Authors: Al-Windi Ahmad 
Published: April 2005

Abstract

Background
In spite of the fact that self-rated health is such an important factor, little is known about the aetiological background to poor perceived health and also less is known about the impact of life satisfaction on health in a primary care practice population. The aim of this study was to evaluate the effect of socio-demographic characteristics, lifestyle factors, symptoms, somatic and psychiatric conditions as well as health status measures and life satisfaction on perceived health in a multi-ethnic Swedish health practice population.

Methods
Four-hundred and seventy adult patients, who visited the Jordbro Health Care Centre District (JHC), Haninge Municipality, participated in this study. A general questionnaire with questions about socio-demographic characteristics, lifestyle, health status and chronic disease were used. In addition to that, the Primary Care Evaluation of Mental Disorders (PRIME-MD) was used. Furthermore, physical examinations were conducted. Unconditional logistic regression in successive models was used, adjusted for socio-demographic variables and other confounders.

Results
Life satisfaction is the strongest predictor of poor perceived health in addition to country of birth, number of symptoms and depression. Being born in Sweden or other Nordic countries were related to lower OR as compared to those born outside Europe. The OR for non-depressed vs. depressed was 0.29 (0.17–0.48) and for non-symptomatic vs. symptomatic (1–3 symptoms) 0.25 (0.46–0.48). The OR and 95% CI for low satisfaction with life was 15.40 (5.28–44.97) in comparison to those who are satisfied with life.

Conclusion
Country of birth, depression, number of symptoms and life satisfaction are factors related significantly and independently to perceived health. Life satisfaction is the strongest predictor of perceived poor health.
Reported use of data monitoring committees in the main published reports of randomized controlled trials: a cross-sectional study
Authors: Sydes Matthew R , Altman Douglas G , Babikera Abdel B , Parmar Mahesh KB , Spiegelhalter David J ,   DAMOCLES group
Published: April 2005

Background We describe a review of published main reports of randomized controlled trials (RCTs), in order to measure the frequency of reported use of data monitoring committees (DMCs) and factors associated with reported DMC use. Methods Twenty-four higher impact general and specialist medical journals were handsearched for main reports of RCTs in order to provide a cross-sectional sample of trials published in the year 2000. Additionally, the same general medical journals were handsearched for 1990 to allow a comparison across time. Results Of 662 RCTs published in 2000, 120 (18%) explicitly reported using a DMC, while 107 (16%) reported planned interim analyses. Overall, about a quarter (24%) reported at least one of these. A higher proportion of trials reported using a DMC in 2000 than 1990 (70/282, 25% versus 21/204, 10%) in the general medical journals. Logistic regression models suggested the more important variables associated with increased reported DMC use were: later year of publication, publication in general medical journal, survival-based endpoint, multicentre trial, increasing number of patients recruited, at least one arm involving a placebo, at least one arm involving a drug, factorial design and USA involvement in the trial. Conclusions In 2000, about a quarter of main RCT reports mention use of a DMC. Actual use of DMCs is likely to be somewhat greater. Reporting use of a DMC was more likely for larger and longer trials among other factors. We believe the factors affecting reported use affect actual use. It is recommended that when a DMC oversees a trial, brief details should be explicitly included in the main trial paper. Standard nomenclature for DMCs is recommended.
Systematic qualitative review of the literature on data monitoring committees for randomized controlled trials
Authors: Sydes Matthew R , Spiegelhalter David J , Altman Douglas G , Babiker Abdel B , Parmar Mahesh KB ,   DAMOCLES Group
Published: April 2005

Aims To systematically review the published literature on data monitoring committees (DMCs) for randomized controlled trials (RCT) and summarize information and opinions on best practice. This was part of the DAMOCLES project. Methods A systematic and comprehensive search of five online bibliographic databases was performed, identifying 4007 potentially relevant articles. These were assessed in two stages by the authors. The 84 most relevant articles were agreed and were supplemented with extracts from 16 books: ultimately, 100 sources were reviewed. A series of 23 questions plus subquestions were developed to structure the data extraction and interpretation process. Results Much has been written about DMCs but by a rather small community of authors. The papers included some results of surveys, but were mainly opinion pieces based on the authors' beliefs, practices and experiences. There is a lack of empirical evidence for many aspects of DMCs. There was a great range of detail in the literature relating to the prespecified questions. It was generally agreed that interim monitoring of accumulating data was necessary in some form for most trials. Questions such as membership of the DMC featured widely in the literature with opinions and practice ranging from 3–20 members, of whom between none and all should be independent. There was a consensus that formal statistical methods should be used as tools to guide decision making rather than as hard rules. Conversely, topics such as the training and experience required for DMC membership were discussed in very few papers. Conclusions There is a consensus in the published literature in a number of areas, although there are many different models for structure and functions of a DMC. While uncertainty remains about some issues, it is strongly recommended that an explicit set of guidelines (Charter) is prepared for each DMC prior to the start of the trial specifying clearly how it will operate.
The isolated working heart model in infarcted rat hearts
Authors: Itter G , Jung W , Schoelkens B A , Linz W 
Published: April 2005

Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties. CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall. We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8–12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III–IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd). The aim for the future is to find a causal therapy of heart failure treatment. At present, only palliative therapy is possible for patients with heart failure. For this reason the working heart model in CHF rat hearts should provide a valuable method for early testing of new therapeutic approaches for patients with CHF.
A novel method for activity monitoring in small non-human primates
Authors: Mann T M , Williams K E , Pearce P C , Scott E A M 
Published: April 2005

Patterns of spontaneous activity are valuable reflections of well-being in animals and humans and, because of this, investigations have frequently incorporated some form of activity monitoring into their studies. It is widely believed that activity monitoring, alongside assessments of general behaviour, should be included in initial CNS safety pharmacology screening. As the number of marmoset studies having actimetry as their focus, or as an adjunct, is increasing, we wished to evaluate an alternative approach to those commonly used. The method is based on miniaturized accelerometer technologies, currently used for human activity monitoring. Actiwatch®-Minis were used to monitor the activity of two groups of differently housed marmosets for 14 consecutive days. Group A consisted of four mixed-sex pairs of animals and group B comprised eight group-housed males. Activity profiles were generated for weekday and weekend periods. The devices captured quantifiable data which showed differences in total activity between the two differently housed groups and revealed intragroup variations in the temporal spread of activity between weekdays and weekends. The Actiwatch®-Mini has been shown to generate retrospective, data-logged activity counts recorded from multiple animals in a single arena by means of non-invasive monitoring.
Quantitative assessment of mouse skin transplant rejection using digital photography
Authors: Schwoebel F , Barsig J , Wendel A , Hamacher J 
Published: April 2005

Mouse skin transplantation is an established in vivo model used to investigate the T-cell-mediated immune response of acute allograft rejection. The critical endpoint of this model is complete rejection of the allograft. However, visual judgement of this end stage of rejection is an arbitrary process and difficult to standardize. To overcome this problem, we established a monitoring method based on digital photography. Serial pictures from skin allografts of individual animals (C57BL/6 on BALB/c) were taken with a digital camera mounted on a microsurgical microscope. Thereby, the description and the correct assessment of early stages of rejection were possible due to the magnification of grafts by the microscope. Rejection scores were introduced to describe different stages from retained to completely rejected grafts. With cyclosporine A as a standard immunosuppressive treatment, we showed that early stages of skin rejection were unambiguously identified. This procedure allows the earlier termination of the experiment and reduction of animal distress, and it can be re-evaluated anywhere and any time after completion. This study demonstrates the suitability of monitoring experimental skin allograft rejection by digital photography, entailing several refinements in animal experimentation, both for the researcher and for the animal.
Anticoagulation Monitoring Part 1: Warfarin and Parenteral Direct Thrombin Inhibitors
Authors: Spinler Sarah A , Nutescu Edith A , Smythe Maureen A , Wittkowsky Ann K 
Published: April 2005

OBJECTIVE: To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in the management of warfarin and parenteral direct thrombin inhibitors. DATA SOURCES: Scientific articles were identified through a MEDLINE search (1966–August 2004), manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS: The prothrombin time expressed as the international normalized ratio (PT—INR) is a well-established test for monitoring warfarin anticoagulation. Multiple devices are available for POC testing. Because there is no universally accepted standard, the performance of each device is typically tested against a standard test performed in a reference laboratory. Performance of currently available devices, as measured by correlations to a standard reference laboratory PT—INR, may be considered very good and acceptable for use in patient care. Utilization of patient self-testing and patient self-monitoring of warfarin anticoagulation using POC devices is increasing. Parenteral direct thrombin inhibitors are typically monitored using a standard laboratory activated partial thromboplastin time. Some research has shown that POC monitoring of direct thrombin inhibitors using the ecarin clotting time is helpful for patients undergoing cardiopulmonary bypass surgery, although that test is not readily available. CONCLUSIONS: POC testing for anticoagulation therapy has been available for >20 years. Multiple POC devices are available to monitor warfarin. There is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC monitoring of warfarin via the PT—INR is an integral part of clinical practice. Additional research evaluating POC monitoring of direct thrombin inhibitors is necessary.
Potential Elevation of Tacrolimus Trough Concentrations with Concomitant Metronidazole Therapy
Authors: Lee Page Robert , Klem Patrick M , Rogers Christin 
Published: April 2005

OBJECTIVE: To report the occurrence of a potential tacrolimus elevation in a renal transplant recipient after adding metronidazole to the medication regimen. CASE SUMMARY: A 24-year-old white man status post living-related renal transplant who had been stabilized on tacrolimus 4 mg twice daily (trough concentrations 7–10 ng/mL) for 2 months and prednisone 20 mg daily presented to the clinic with severe diarrhea. Stool cultures were positive for Clostridium difficile, and therapy with metronidazole 500 mg 4 times daily was initiated. Between days 4 and 14 of metronidazole therapy, the patient's tacrolimus trough concentration and serum creatinine level increased to maximum levels of 26.3 ng/mL and 3.3 mg/dL (baseline 1.6–1.8 mg/dL), respectively. Tacrolimus was withheld for one dose and then decreased to 1 mg twice daily. Two days after metronidazole discontinuation, tacrolimus trough concentrations dropped to 9.4 ng/mL and serum creatinine to 2.3 mg/dL, warranting a tacrolimus dose increase to 3 mg daily. DISCUSSION: As of April 15, 2005, one other case has been reported documenting an elevation in tacrolimus concentrations with the addition of metronidazole. The possible mechanism may be related to metronidazole's weak inhibition of CYP3A4 and, possibly, P-glycoprotein. According to the Naranjo probability scale, metronidazole was the probable cause of this adverse reaction. CONCLUSIONS: Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function.
Efficacy of Sucrose to Reduce Pain in Premature Infants during Eye Examinations for Retinopathy of Prematurity
Authors: Gal Peter , Kissling Grace E , Young William O , Dunaway Kimberly K , Marsh Virginia A , Jones Susan M , Shockley Dawn H , Weaver Nicole L , Carlos Rita Q , Ransom J Laurence 
Published: April 2005

BACKGROUND: Eye examinations for retinopathy of prematurity (ROP) are painful to the neonate. The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit (NICU), but does not completely suppress painful responses. Sweet solutions have been shown to reduce procedural pain in newborns. OBJECTIVE: To examine whether the addition of sucrose 24% to topical anesthetic improves procedural pain control during the ROP eye examination. METHODS: Neonates born at ⩽30 weeks' gestation were included in this placebo-controlled, double-blind, crossover study. Patients were randomly assigned to receive treatment with either proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sucrose 24% or proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sterile water (placebo) prior to an eye examination. In a subsequent eye examination, each patient received the alternate treatment. Oral sucrose and sterile water were prepared in the pharmacy in identical syringes, and physicians, nurses, and pharmacists in the NICU were blinded to the treatment given. Pain was measured using the Premature Infant Pain Profile (PIPP) scoring system, which measures both physical and physiologic measures of pain, and the scores were simultaneously assessed by 2 study nurses. PIPP scores were recorded 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all eye examinations. Several different definitions of a pain response were investigated. RESULTS: Twenty-three infants were studied, with 12 receiving sucrose and 11 receiving placebo as the first treatment. For 3 of the 5 definitions of pain response, patients experienced significantly less pain at speculum insertion with sucrose than with placebo. After the ROP examination, pain responses were similar with either sucrose or placebo. CONCLUSIONS: Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP.
Liquefaction of CCA-treated wood and elimination of metals from the solvent by precipitation
Authors: Lin Lianzhen , Hse Chung-Yun 
Published: April 2005

Abstract
Spent chromated copper arsenate (CCA)-treated wood was liquefied in polyethylene glycol 400/glycerin (2:1w/w). Sulfuric acid (95–98%) and ferrous salts (FeSO4·7H2O or FeCl2·4H2O) were used as catalysts and additives, respectively. The resulting liquefied CCA-treated wood was diluted with aqueous solvents and was then mixed with complexion/precipitation agents, followed by precipitation or filtration to remove the toxic metal-bearing sediment. As a result, more than 90% of Cu, Cr or As was removed.