SEARCH · Search PubMed

Results for “Library Collection Development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,261 records · Page 70Linked to original sources

PubMed2003

Identification of a novel glial cell line-derived neurotrophic factor-inducible gene required for renal branching morphogenesis.

In the developing kidney, activation of the rearrangement during transfection tyrosine kinase by glial cell line-derived neurotrophic factor (GDNF) is required for normal branching of the ureteric bud epithelium [corrected]. By differential display analysis we identified a novel GDNF-inducible gene (named GZF1) with a BTB/POZ (broad complex, tramtrack, and bric-a-brac)/(poxvirus and zinc finger) domain and 10 tandemly repeated zinc finger motifs. The up-regulation of the GZF1 gene showed two peaks at 1 h and 24-48 h after GDNF stimulation by Northern blotting. The late induction was also found at protein levels by Western blotting with anti-GZF1 antibody. As observed for other proteins with the BTB/POZ domain, the GZF1 protein had strong transcriptional repressive activity. Intriguingly, its expression was detected at high levels in branching ureteric buds and collecting ducts of mouse metanephric kidney in which RET was also expressed. Antisense phosphorothioated oligodeoxynucleotides of the GZF1 gene markedly impaired the ureteric bud branching in the metanephric organ culture, suggesting that the induction of GZF1 expression via the GDNF/RET signaling system is required for renal branching morphogenesis.

Amino Acid Sequence↗

PubMed2004

Development of an expressed sequence tag (EST) resource for wheat (Triticum aestivum L.): EST generation, unigene analysis, probe selection and bioinformatics for a 16,000-locus bin-delineated map.

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid (2n = 6x = 42) wheat genome (Triticum aestivum L.). Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags (ESTs) representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection (113,220 ESTs). Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of ESTs into contigs. These contigs plus singletons (unassembled ESTs) were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5' and 3' sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics.

Blotting, Southern↗

PubMed2003

Treatment of Kaposi's sarcoma in HIV-1 infected individuals with emphasis on resource poor settings.

BACKGROUND: In many countries, Kaposi's sarcoma (KS) is the commonest malignancy among individuals infected with the human immunodeficiency virus-1 (HIV) and is a cause of substantial morbidity and mortality. OBJECTIVES: The aim of this review was to assess the effectiveness of current therapeutic regimens for the treatment of HIV associated KS, with a focus on options that may be available in resource poor settings. SEARCH STRATEGY: We searched Cochrane HIV/AIDS Group trials register, Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2002), MEDLINE, EMBASE, AIDSLINE, CINAHL, CANCER LIT, AIDSDRUGS, AIDSTRIALS, African index medicus, physicians data query protocols, United Kingdom Co-ordinating committee on Cancer Research Register of Cancer trials, proceedings and abstracts from AIDS and cancer conferences. The search was conducted between 1st October 2001 and completed 14th December 2002. We also contacted experts in the field of cancer. SELECTION CRITERIA: Randomised trials of therapy for KS in HIV infected adults. DATA COLLECTION AND ANALYSIS: All reviewers assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: Five trials involving 915 people were included. Two trials involving 499 people compared pegylated liposomal doxorubicin (PLD) to a standard regimen among patients with advanced KS were analysed together. There was no difference in mortality between the two regimens RR1.26 (95% confidence interval (CI) 0.83 to 1.91). The response to PLD was superior to that of the control regimen RR 2.16, (95% CI 1.68 to 2.78). Two other trials involving 402 people demonstrated that topical alitretinoin was effective treatment compared to placebo among patients with cutaneous Kaposi's sarcoma. The results were analysed separately due to heterogeneity; (1) the relative risk (RR) was 5.34 (95%CI 2.16 to 13.21) and (2) RR 1.96, 95% CI 1.27 to 3.01). The final trial compared different radiotherapy regimens for treatment of cutaneous KS. The initial complete response of lesions to 20Gy given in 10 fractions or 40Gy in 20 fractions was similar and slightly superior to that of lesions treated with 8Gy as a single fraction, RR 1.58, (95% CI 1.01 to 2.48) and RR 1.65, (95% CI 1.06 to 2.57) respectively. REVIEWER'S CONCLUSIONS: Alitretinoin gel is effective in treating cutaneous KS, PLD is effective treatment for advanced KS and radiotherapy appears effective in treating cutaneous lesions. Apart from the trial of radiotherapy no trials applicable to developing settings were identified.

Alitretinoin↗

PubMed2004

[Evidence based surgery of cancer of head of pancreas].

Physicians and surgeons who treat patients with gastrointestinal or hepatic disease must prescribe the most appropriate diagnostic tests, together with an accurate prognosis and effective and safe therapy. This paper examines the best modalities of surgical treatment for cancer of the pancreas, in an evidence-based approach. Evidence was classified as follows: Grade A : evidence from large randomized controlled trials (RCT) or systematic reviews (including meta-analyses) of multiple randomized trials which collectively have at least as much data as one single well-defined trial. Grade B: evidence from at least one high-quality study of non-randomized cohorts or evidence from at least one high-quality case-control study or one high-quality case series. Grade C: opinions from experts without references or access to any of the foregoing The data were obtained from Medline and from controlled randomized trials listed in the Cochrane Library up to the end of 2003. Two series (grade B) showed the superiority of Whipple over total pancreatectomy, with respective median survival times of 12.6 months and 9.6 months. Extensive lymphadenectomy (grade A) in patients with positive lymph nodes gave significantly better survival than standard resection in one trial, but this was not confirmed in the other trial. Results of pylorus-preserving pancreaticoduodenectomy (PPPD) were not different from those of the Whipple procedure on postoperative mortality, morbidity or survival (grade A). Portal vein resection increased the resectability rate. Post-operative mortality was not increased: survival was not different in four studies and was shorter in another four studies (grade C). Low-dose postoperative erythromycin accelerates gastric emptying if the right gastric artery is preserved (grade A). One trial suggests that pancreaticogastrostomy reduces the risk of pancreatic fistula. The two other trials are controversial and showed no difference. One prospective non randomized study showed that stenting in pancreaticojejunostomy reduces the risk of pancreatic fistulae and intraabdominal abscess. To prevent this risk of pancreatic fistula, six controlled trials involving patients receiving octreotride were performed Three European trials showed a smaller volume of abdominal drainage fluid and an abnormal amylase concentration; however, two American trials failed to demonstrate a significant difference. Occlusion of the pancreatic duct with fibrin glue did not reduce the risk of pancreatic fistula, but increased the risk of developing diabetes. Intraabdominal drainage after pancreatic resection significantly increased post-operative complications (grade A). Surgical resection and reconstruction procedures for pancreatic cancer must be based on evidence-based studies. However, the most important prognostic factor is the surgeon's experience, not only with regard to the post-operative course, but also survival. Specific teaching and training is thus essential.

Evidence-Based Medicine↗

PubMed2006

Common plantain. A collection of expressed sequence tags from vascular tissue and a simple and efficient transformation method.

The vascular tissue of higher plants consists of specialized cells that differ from all other cells with respect to their shape and size, their organellar composition, their extracellular matrix, the type of their plasmodesmata, and their physiological functions. Intact and pure vascular tissue can be isolated easily and rapidly from leaf blades of common plantain (Plantago major), a plant that has been used repeatedly for molecular studies of phloem transport. Here, we present a transcriptome analysis based on 5,900 expressed sequence tags (ESTs) and 3,247 independent mRNAs from the Plantago vasculature. The vascular specificity of these ESTs was confirmed by the identification of well-known phloem or xylem marker genes. Moreover, reverse transcription-polymerase chain reaction, macroarray, and northern analyses revealed genes and metabolic pathways that had previously not been described to be vascular specific. Moreover, common plantain transformation was established and used to confirm the vascular specificity of a Plantago promoter-beta-glucuronidase construct in transgenic Plantago plants. Eventually, the applicability and usefulness of the obtained data were also demonstrated for other plant species. Reporter gene constructs generated with promoters from Arabidopsis (Arabidopsis thaliana) homologs of newly identified Plantago vascular ESTs revealed vascular specificity of these genes in Arabidopsis as well. The presented vascular ESTs and the newly developed transformation system represent an important tool for future studies of functional genomics in the common plantain vasculature.

Arabidopsis↗

PubMed1990

Stored mRNA in cotyledons of Vigna unguiculata seeds: nucleotide sequence of cloned cDNA for a stored mRNA and induction of its synthesis by precocious germination.

By differential hybridization screening, we previously selected a class of cDNA clones from a lambda gt10 cDNA library that was constructed from the total poly(A)+ RNA of mature cowpea cotyledons (Plant Cell Physiol 31: 39-44, 1990). pSAS10, a clone of this class, hybridized with a cDNA probe complementary to poly(A)+ RNA from cotyledons collected 1 day after the onset of imbibition (DAI), but not with the cDNA probe from cotyledons at developmental stage II (13 to 15 days after flowering, DAF). pSAS10 mRNA was detectable only in cotyledons at developmental stage III (17 to 19 DAF) or later, and its level began to decline when seeds germinated. We have suggested that pSAS10 mRNA is likely to belong to the class of 'stored' mRNA or the mRNA that is formed at the late stage of seed maturation, is conserved in quiescent seeds and becomes functional at the early stage of germination. We determined the nucleotide sequence of pSAS10 cDNA consisting of 459 bp and an approximately 36 bp poly(A) tract, and deduced the amino acid sequence of its product, a 10-kDa cysteine-rich polypeptide. Synthesis of pSAS10 mRNA was induced just before germination began, not only in mature seeds but also in immature seeds even at stages I (9 to 11 DAF) and II (13 to 15 DAF) if they were placed under conditions suitable for germination.

Amino Acid Sequence↗

PubMed2005

Non-nutritive sucking for promoting physiologic stability and nutrition in preterm infants.

BACKGROUND: Non-nutritive sucking is used during gavage feeding and in the transition from gavage to breast/bottle feeding in preterm infants. The rationale for this intervention is that non-nutritive sucking facilitates the development of sucking behaviour and improves digestion of enteral feedings. Non-nutritive sucking has been considered to be a benign intervention, although it has the potential to have a negative effect on breastfeeding or on the incidence of later oral aversion. OBJECTIVES: To determine whether non-nutritive sucking (NNS) in preterm infants influences: a) weight gain, b) energy intake, c) heart rate, d) oxygen saturation, e) length of hospital stay, f) intestinal transit time, g) age at full oral feeds, or h) any other clinically relevant outcomes. SEARCH STRATEGY: MEDLINE and CINAHL databases back to 1976 and The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005) were searched. The EMBASE database was added to the search strategy for 2005. Reference lists/bibliographies of relevant articles and reviews were also searched. A comprehensive list of relevant articles was sent to two major authors in this area. They were asked if they knew of any other published or unpublished studies relevant to the area that had not been included in the original list. SELECTION CRITERIA: All trials utilizing experimental or quasi-experimental designs in which non-nutritive sucking in preterm infants was compared to no provision of non-nutritive sucking. Measured clinically relevant outcomes. Reports were in English or a language for which a translator was available.Computerized searches were conducted by both reviewers. All potentially relevant titles and abstracts identified by either reviewer were extracted. All retrieved articles were assessed for relevance independently by each reviewer, based on a pre-determined set of criteria. The reference lists/bibliographies of each article were reviewed independently for additional relevant titles and were also retrieved and assessed for relevance. Articles that met all relevance criteria were then assessed for methodologic quality based on a predetermined set of criteria. Those articles judged to have the appropriate quality by both reviewers were included in the analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two authors. No subgroup analyses were performed because of the small number of studies related to the relevant outcomes. MAIN RESULTS: This review consisted of 21 studies, 15 of which were randomized controlled trials. NNS was found to decrease significantly the length of hospital stay in preterm infants. The review did not reveal a consistent benefit of NNS with respect to other major clinical variables (weight gain, energy intake, heart rate, oxygen saturation, intestinal transit time, age at full oral feeds and behavioral state). The review identified other positive clinical outcomes of NNS: transition from tube to bottle feeds and better bottle feeding performance. No negative outcomes were reported in any of the studies. AUTHORS' CONCLUSIONS: This review found a significant decrease in length of stay in preterm infants receiving a NNS intervention. The review did not reveal a consistent benefit of NNS with respect to other major clinical variables (weight gain, energy intake, heart rate, oxygen saturation, intestinal transit time, age at full oral feeds and behavioral state). The review identified other positive clinical outcomes of NNS: transition from tube to bottle feeds and better bottle feeding performance. No negative outcomes were reported in any of the studies. There were also a number of limitations of the presently available evidence related to the design of the studies, outcome variability, and lack of long-term data. Based on the available evidence, NNS in preterm infants would appear to have some clinical benefit. It does not appear to have any short-term negative effects. In view of the fact that there are no long-term data, further investigations are recommended. In order to facilitate meta-analysis of these data, future research in this area should involve outcome measures consistent with those used in previous studies. In addition, published reports should include all relevant data.

Humans↗

PubMed2004

Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis.

BACKGROUND: Antibiotic therapy for suspected acute bacterial meningitis (ABM) needs to be started immediately, even before the results of cerebrospinal fluid culture and antibiotic sensitivity are available. It is not clear whether the available evidence supports the choice of third generation cephalosporins over the conventional antibiotic combination of ampicillin and chloramphenicol. Immediate institution of effective treatment through intravenous route may reduce death and disability in survivors. OBJECTIVES: The objective of this review is to determine the effectiveness and safety of the third generation cephalosporins and conventional treatment with penicillin/ampicillin-chloramphenicol in patients with community-acquired acute bacterial meningitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003) which contains the Cochrane Acute Respiratory Infections Group trials register, MEDLINE (January 1966 to November 2003), and EMBASE (January 1990 to November 2003). We also searched the reference list of review articles and textbook chapters and contacted experts for any unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing ceftriaxone or cefotaxime with conventional antibiotics as empirical therapy of acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: Two independent reviewers applied the study selection criteria, assessed methodological quality and extracted data. MAIN RESULTS: Eighteen trials included 993 patients in the analysis. The kappa (chance-corrected agreement) between the observers in study selection and data extraction was substantial. There was no heterogeneity of results among the studies in any outcome except diarrhoea. There was no statistically significant difference between the groups in the risk of death (risk difference -1%; 95% confidence interval (CI) -4% to +3%), risk of deafness (risk difference -4%; 95% CI -9% to +1%), risk of treatment failure (risk difference -2%; 95% CI -5% to +2%). However, there were significantly decreased risk of culture positivity of CSF after 10-48 hours (risk difference -6%; 95% CI -11% to 0%) and statistically significant increased in the risk of diarrhoea between the groups (risk difference +8%; 95% CI +3% to +13%) with the third generation cephalosporins. The risk of neutropenia and skin rash were not significantly different between the two groups. However, all the studies have been conducted in the eighties except two, which have been conducted in 1993 and 1996. REVIEWERS' CONCLUSIONS: Although the review shows no clinically important difference between ceftriaxone or cefotaxime and conventional antibiotics, the studies are done decades ago and may not apply to current routine practice. However, in situations where ceftriaxone or cefotaxime are not available or affordable, ampicillin-chloramphenicol combination may be used as an alternative. The antimicrobial resistance pattern against various antibiotics needs to be closely monitored in developing as well as developed countries. The factors determining overuse of antibiotics in developing countries and educational interventions to limit such practice are priority area for research in developing countries.

Acute Disease↗

PubMed2026

Expression profiles of miRNAs in ruminant intermediate hosts with cystic echinococcosis.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a parasitic zoonotic disease recognized by the World Health Organization as a neglected tropical disease of significant public health concern. Despite ongoing control programs, CE remains endemic, underlining the need for integrated control strategies that involve new diagnostic and therapeutic tools. Recent investigations have spotlighted microRNAs (miRNAs) as key regulators in parasite development, immunomodulation, and as potential diagnostic and therapeutic targets. In the present research, a molecular study was conducted to investigate hydatid cyst samples (protoscoleces and germinal membranes) collected in southern Italy from different ruminant species (sheep, cattle, and water buffaloes), naturally infected with CE, with the ultimate goal of establishing a more comprehensive picture of miRNA expression patterns in these intermediate hosts. The bioinformatic analysis of hydatid cyst samples revealed 168 mature miRNAs. Among these, egr-miR-10-5p, egr-let-7-5p, and egr-miR-71-5p were the most abundant, with egr-miR-10-5p showing particularly high expression levels. No significant differences in miRNA abundance between host species were found. In contrast, when focusing on the comparison between protoscoleces and sterile germinal membranes, 24 miRNAs were found to be differentially expressed. Targeted qPCR of four selected miRNAs (egr-miR-71-5p, egr-let-7-5p, egr-miR-125-5p, and egr-miR-10-5p) showed clear overexpression in protoscoleces and in fertile germinal membranes compared with sterile ones. The differential miRNA expression patterns provide insight into the molecular mechanisms controlling the parasite's lifecycle and may guide the development of novel intervention methods to enhance CE control in endemic areas.

Animals↗

PubMed1998

Using epidemiological data to guide clinical practice: review of studies on cardiovascular disease and use of combined oral contraceptives.

OBJECTIVE: To explore the usefulness of epidemiological data to guide clinical practice by seeking an answer to the question "What is the risk of cardiovascular disease among users of currently available, low dose, combined oral contraceptives who are aged less than 35 years, do not smoke, and do not have a medical condition known to increase the risk of vascular disease?" DESIGN: Review of all relevant published studies identified from the library of references held by Royal College of General Practitioners' Manchester Research Unit, checking of reference lists of identified studies, and Medline search. MAIN OUTCOME MEASURES: Identification of methodologically sound studies able to address the specific clinical question. RESULTS: Our literature search identified 74 papers about the relation between current use of combined oral contraceptives and cardiovascular disease: 23 papers reporting risk of venous thromboembolism, 22 on ischaemic stroke, 13 on haemorrhagic stroke or subarachnoid haemorrhage, 13 on all stroke, and 33 on myocardial infarction. Only five papers provided information that directly addressed our clinical question; all related to the risk of venous thromboembolism. Fourteen of the discarded papers probably had the potential to answer our clinical question. CONCLUSIONS: Much of the epidemiological data about the risk of cardiovascular disease in users of combined oral contraceptives is not useful to clinicians. Some of the discarded data could be made more useful to clinicians by reanalysis. This situation is unlikely to be unique to use of contraceptives.

Adolescent↗

PubMed2006

Interventions to promote the wearing of hearing protection.

BACKGROUND: Noise induced hearing loss can only be prevented by eliminating or lowering noise exposure levels. Where the source of the noise can not be eliminated workers have to rely on hearing protective equipment. Several trials have been conducted to study the effectiveness of interventions to influence the wearing of hearing protection and to decrease noise exposure. We aimed to establish whether interventions to increase the wearing of hearing protection are effective. OBJECTIVES: To summarise the evidence for the effectiveness of interventions to enhance the wearing of hearing protection among workers exposed to noise in the workplace. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2 2005), MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), NIOSHTIC, CISDOC, CINAHL, LILACS (1982 to June 2005) and Scientific Electronic Library Online. The date of the last search was June 2005. SELECTION CRITERIA: Studies were included if they had a randomised design, if they were among noise exposed (> 80 dB(A)) workers or pupils, if there was some kind of intervention to promote the wearing of hearing protection (compared to another intervention or no intervention), and if the outcome measured was the amount of use of hearing protection or a proxy measure thereof. DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed methodological quality and extracted data. There were no cases where the pooling of data was appropriate. MAIN RESULTS: Two studies were found. One study was a two-phased randomised controlled trial. A computer-based intervention tailored to the risk of an individual worker lasting 30 minutes was not found to be more effective than a video providing general information among workers, around 80% of whom already used hearing protection. The second phase of the trial involved sending a reminder to the home address of participants at 30 days, 90 days or at both 30 and 90 days after the intervention, or no reminder. No significant differences in the mean use of hearing protection were found. A second randomised controlled trial evaluated the effect of a four year school based hearing loss prevention programme among pupils working at their parents farms (N=753) in a cluster randomised controlled trial. The intervention group was twice as likely to wear some kind of hearing protection as the control group that received only minimal intervention. All results are based on self reported use of hearing protection. AUTHORS' CONCLUSIONS: Limited evidence does not show whether tailored interventions are more or less effective than general interventions in workers, 80% of whom already use hearing protection. Long lasting school based interventions may increase the use of hearing protection substantially. These results are based on single studies only. Better interventions to enhance the use of hearing protection need to be developed and evaluated in order to increase the prevention of noise induced hearing loss among workers.

Ear Protective Devices↗

PubMed1993

Systematic literature review for clinical practice guideline development.

The purpose of this paper was to evaluate the quality and scope of the published literature on functional impairment due to cataract in adults as reviewed for the Agency for Health Care Policy and Research Clinical Practice Guideline. We examined the method of literature retrieved and analysis performed in the course of development of literature-based recommendations for the guideline panel. To collect data, we reviewed the process of literature acquisition and identification and the quality assessments made by reviewers of 14 individual topics composed of 77 issues related to the guideline. We collated this information to provide an assessment of the quality and scope of the relevant literature. Less than 4% (310) of the approximately 8,000 articles initially identified as potentially relevant to the guideline were ultimately used. The majority covered three topics (surgery and complication, 100; Nd:YAG capsulotomy, 77; and potential vision testing, 40). Three other topics--indications for surgery, preoperative medical evaluation, and rehabilitation--were devoid of articles meeting inclusion criteria. For 43 issues, there was no identifiable relevant literature. With few exceptions, the quality of the literature was rated fair to poor owing to major flaws in experimental design. Case series (256 reports) of one type or another accounted for the majority of the included literature. There were 17 random controlled trials. This review revealed a sparse and generally low-quality literature relevant to the management of functional impairment due to cataract, despite a relatively large data base in reputable peer-reviewed journals.

Adult↗

PubMed1995

Merging terminologies.

A terminology is a systematic, authoritative collection of concept names, or terms, in some domain. No single terminology names all the important concepts in biomedicine. One approach to creating a more comprehensive biomedical terminology is to merge existing biomedical terminologies, as the UMLS( Metathesaurus( has done for the last six years. Because existing terminologies may overlap--for example, one terminology may name a concept also named by another terminologyQthe terminologies in the Metathesaurus must be merged. Some terminologies suggest merges through their structure or content e.g., they suggest synonyms or connections to other terminologies; other merges can be suggested by algorithm. Regardless, all merges in the Metathesaurus must be approved by a human editor with appropriate domain knowledge. By the time Meta-U96 is released early in 1996, one prototype and seven released versions of the Metathesaurus will have been produced by a sequence of four qualitatively different methods, named for the way in which they merge terms: #1 "Term Rewrite Rules, #2 "Transitive Closure on Facts," #3 "Fact-at-a-Time Concept Merging," and #4 "Action-at-a-Time Object Processing." The development of each method has been constrained by the annual Metathesaurus release schedule. The first two methods made the best use of limited computational resources, and the last two make better use of human editing resources.

National Library of Medicine (U.S.)↗

PubMed2006

Cyclosporin versus tacrolimus for liver transplanted patients.

BACKGROUND: Most liver transplant recipients receive either cyclosporin or tacrolimus to prevent rejection. Both drugs inhibit calcineurin phosphatase which is thought to be the mechanism of their anti-rejection effect and principle toxicities. The drugs have different pharmacokinetic profiles and potencies. Several randomised clinical trials have compared cyclosporin and tacrolimus in liver transplant recipients, but it remains unclear which is superior. OBJECTIVES: To evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded, and conference proceedings were searched (August 2005) to identify relevant randomised clinical trials. Our search included scanning of reference lists in relevant articles and correspondence with investigators and pharmaceutical companies. SELECTION CRITERIA: All randomised clinical trials where tacrolimus was compared with cyclosporin for the initial treatment of first-time liver transplant recipients. We included randomised trials irrespective of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS: The primary outcome measure was all-cause mortality. Data were synthesised (fixed-effect model) and results expressed as relative risk (RR), values less than 1.0 favouring tacrolimus, with 95% confidence intervals (CI). Two authors assessed trials for eligibility, quality, and extracted data independently. MAIN RESULTS: We included 16 randomised trials. The number of deaths was 254 in the tacrolimus group (1899 patients) and 302 in the cyclosporin group (1914 patients). At one year, mortality (RR 0.85, 95% CI 0.73 to 0.99) and graft loss (RR 0.73, 95% CI 0.61 to 0.86) were significantly reduced in tacrolimus-treated recipients. Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75 to 0.88), and steroid-resistant rejection (RR 0.54, 95% CI 0.47 to 0.74) in the first year. Differences were not seen with respect to lymphoproliferative disorder or de-novo dialysis rates, but more de-novo insulin-requiring diabetes mellitus (RR 1.38, 95% CI 1.01 to 1.86) occurred in the tacrolimus group. More patients were withdrawn from cyclosporin therapy than from tacrolimus (RR 0.57, 95% CI 0.49 to 0.66). AUTHORS' CONCLUSIONS: Tacrolimus is superior to cyclosporin in improving survival (patient and graft) and preventing acute rejection after liver transplantation, but it increases the risk of post-transplant diabetes. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid acute rejection and steroid-resistant rejection in nine and seven patients, respectively, and graft loss and death in five and two patients, respectively, but four additional patients would develop diabetes after liver transplantation.

Cyclosporine↗

PubMed2005

Gene expression profiles in prostate cancer: association with patient subgroups and tumour differentiation.

Prostate carcinoma is the most common cancer of western men and is a markedly heterogeneous disease. The aim of this study was to identify signatures of differentially expressed genes in prostate cancer using DNA microarray technology, evaluating expression profiles in matched pairs of benign and malignant tissue. Samples were collected from 33 radical prostatectomies, and 52 specimens were included, representing 29 histologically verified primary tumours, 19 paired samples of malignant and benign tissue, and 4 non-paired benign tissue samples. Microarray analysis was performed using an expanded sequence verified set of 40,000 human cDNA clones, revealing several genes with significant differences between malignant and benign tissue, including recently reported genes like alpha-methylacyl-CoA racemase (AMACR) and hepsin, as well as genes relevant for tumour development and progression. Leave out cross validation (LOCV) test correctly predicted tumour or benign tissue in 47 (90.3%) out of 52 cases, significantly better than cross validation tests using randomly permuted tissue labels. Unsupervised clustering analysis revealed 3 distinct patient clusters significantly associated with Gleason score, and high grade tumours (Gleason score >/=7) accumulated in cluster 1 (C1). Gene expression profiles correctly predicted 100% of tumour samples segregating to C1, as also validated by LOCV. Gene expression profiles were analysed in filtered and floored datasets with similar results, and a pair-wise design was also tested. Gene expression profiles provided tumour clusters linked to differentiation, and revealed novel markers relevant for molecular classification, grading and therapy of prostate cancer.

Cluster Analysis↗

PubMed2004

Anticonvulsants for neonates with seizures.

BACKGROUND: Neonatal seizures are a common problem and most neonates with seizures are treated with anticonvulsants. There is wide variation in clinical practice in both diagnosis and treatment of such seizures and this reflects the lack of clear evidence of the relative benefit and harm of the anticonvulsants used. The routine use of anticonvulsants to treat seizures in neonates needs to be evaluated. OBJECTIVES: To assess and compare (with respect to benefits and harm) different anticonvulsants administered to neonates for the treatment of established seizures. SEARCH STRATEGY: Relevant randomised controlled trials were identified using a combination of electronic database searches (MEDLINE 1966 - March 2004, EMBASE 1980 - March 2004), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and hand searches. Identification of ongoing or unpublished trials was attempted by contacting prominent authors in the field and searching electronic registers of ongoing trials. SELECTION CRITERIA: All randomised or quasi-randomised controlled clinical trials with reported data comparing the following outcomes: mortality, neurodevelopmental disability, need for additional anticonvulsants, need for maintenance anticonvulsants at discharge and adverse events (hypotension requiring volume or inotropic support, arrhythmia, respiratory depression, hepatotoxicity) in neonates treated for seizures with systemic anticonvulsants compared to placebo, no drug or alternative anticonvulsants. DATA COLLECTION AND ANALYSIS: Methodological quality and validity were assessed without consideration of the results. The first reviewer screened the title and abstracts of studies identified by the above search strategy. Full text versions of studies of potential relevance were re-screened by both reviewers. Studies meeting the pre-specified inclusion criteria were included. Relevant data were extracted and analysed separately and any disagreements were resolved by discussion. MAIN RESULTS: Only two randomised controlled trials published in full could be identified. Painter 1999 showed that both of the two most commonly used anticonvulsants (phenobarbital and phenytoin) were similarly effective (RR 1.03 95% CI 0.96 to 1.62), controlling seizures in less than fifty percent of infants. Painter 1999 did not report mortality or neurodevelopmental outcome. Boylan 2004 randomised infants who failed to respond to phenobarbital to receive either lidocaine or midazolam as second-line agents. There was a trend for lidocaine to be more effective in reducing seizure burden (RR 0.40 95% CI 0.14 to 1.17) but both groups had similarly poor long term outcomes assessed at one year. REVIEWERS' CONCLUSIONS: At present there is little evidence from randomised controlled trials to support the use of any of the anticonvulsants currently used in the neonatal period. In the literature, there remains a body of opinion that seizures should be treated because of the concern that seizures in themselves may be harmful, although this is only supported by relatively low grade evidence (Levene 2002; Massingale 1993). Development of safe and effective treatment strategies relies on future studies of high quality (randomised controlled trials with methodology that assures validity) and of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability in addition to any short term reduction in seizure burden.

Anticonvulsants↗

PubMed2005

Cognitive-behavioural training interventions for assisting foster carers in the management of difficult behaviour.

BACKGROUND: The provision of training for foster carers is now seen as an important factor contributing to the successful outcome of foster care placements. It is believed to be associated with enhancing caring attitudes and skills, reducing behaviour problems in foster children, improving relationships between foster carers and child welfare agencies, and decreasing foster carer attrition. Since the late 1960s, foster carer training programs have proliferated, and few of the many published and unpublished training curricula have been systematically assessed and evaluated. The advent of cognitive-behavioural therapy (CBT) and the research evidence demonstrating its effectiveness as a psychotherapeutic treatment of choice, has prompted many working in the social care field to devise CBT-based training programmes. CBT approaches to foster care training derive from a 'skill-based' training format that also seeks to identify and correct problematic thinking patterns that are associated with dysfunctional behaviour by changing and/or challenging maladaptive thoughts and beliefs. OBJECTIVES: To assess the effectiveness of cognitive-behavioural training interventions in improving a) looked-after children's behavioural/relationship problems, b) foster carers' psychological well-being and functioning, c) foster family functioning, d) foster agency outcomes. SEARCH STRATEGY: We searched databases including: CENTRAL (Cochrane Library Issue 2, 2004), MEDLINE (January 1966 to April 2004), EMBASE (January 1980 to April 2004), CINAHL (January 1982 to April 2004), PsycINFO (January 1872 to April 2004), ASSIA (January 1987 to April 2004), LILACS (up to April 2004), ERIC (January 1965 to April 2004), Sociological Abstracts (January 1963 to April 2004), and the National Research Register 2004 (Issue 1). We contacted experts in the field concerning current research. SELECTION CRITERIA: All studies in which participants were foster parents/carers, and who were allocated by random or quasi-random methods to a CBT-based training intervention (in a group and/or one-to-one settings) versus a no-treatment or wait-list control, were selected. DATA COLLECTION AND ANALYSIS: Results from the five eligible trials (total n = 443 ) are reported narratively. Due to the diversity of measures employed, no meta-analysis was performed. MAIN RESULTS: Training interventions evaluated to date appear to have very little effect on outcomes relating to looked-after children, assessed in relation to psychological functioning, extent of behavioural problems and interpersonal functioning. Results relating to foster carer(s) outcomes indicate some improvements in measures of behavioural management skills, attitudes and psychological functioning. Analysis pertaining to fostering agency outcomes did not show any significant results. AUTHORS' CONCLUSIONS: Inconclusive evidence exists about the efficacy of CBT-based training intervention for foster carers. The need for further research in this area is highlighted.

Aggression↗

PubMedDate not supplied

The vacuolar-atpase of Paramecium multimicronucleatum: gene structure of the B subunit and the dynamics of the V-ATPase-rich osmoregulatory membranes.

Previous studies have shown that the vacuolar-ATPase (V-ATPase) of the contractile vacuole complexes (CVCs) in Paramecium multimicronucleatum is necessary for fluid segregation and osmoregulation. In the current study, immunofluorescence showed that the development of a new CVC begins with the formation of a new pore around which the collecting canals form. The decorated membranes are then deposited around the newly formed collecting canals. Quick-freeze deep-etch techniques reveal that six 10-nm-wide V-ATPase V, sectors, tightly packed into a 20 x 30-nm rectangle, form two rows of these compacted sectors that helically wrap around the cytosolic side of decorated membrane tubules. During new CVC formation, packing of decorated tubules around mature CVCs was temporarily disrupted so that some of these decorated tubules became transformed into decorated vesicles. Freeze-fracturing of these decorated vesicles revealed a highly pitted E-face and a particulate P-face. The V-ATPase was purified for the first time in any ciliated protozoan and shown to contain, as in other cells, the V1 subunits A to E, and four 14-20 kDa polypeptides. The B subunit was cloned and found to be encoded by one gene containing four short introns. This subunit has 510 amino acid residues with a predicted molecular weight of 56.8 kDa, a value similar to B subunits of other organisms. Except for the N- and C-termini, it has a 75% sequence identity with other B subunits, suggesting that the B subunits in Paramecium, like other species, have been conserved and that the entire surface of this subunit may be important in interacting with other subunits.

Amino Acid Sequence↗