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PubMed2006

Morphological and physiological traits of three major Arabidopsis thaliana accessions.

Arabidopsis is currently the most studied organism in plant biology. Its short life cycle and small genome size have rendered it one of the principal model systems. Additionally, numerous large T-DNA insertion mutant collections are available. The advent of molecular biology and the completion of the Arabidopsis genome sequence have contributed to helping researchers discover a large variety of mutants identified for their phenotypes. Yet, it is important to consider that natural phenotypic variations exist and appear in natural ecotypes, differing greatly in several traits. Although there are a vast number of ecotypes available, only a few have been extensively studied, and some have been created in laboratories. In order to identify new phenotypic differences, we chose to study the differences observed between three ecotypes: Columbia (Col-0), Landsberg erecta (Laer-0) and Wassilewskija (Ws-0). Our research focuses on observable morphological traits throughout plant growth and development along the entire plant life cycle. We then attempted to shed some light on phenotypic discrepancies through the study of the class III peroxidase protein family, which is involved in many aspects of plant growth and tissue differentiation. Both morphological and molecular aspects reveal that there are major variations between ecotypes, hence indicating a possibly interesting heterotic effect in the F1 from crosses between different Arabidopsis ecotypes.

Arabidopsis↗

PubMed2000

Drugs for rapid treatment of very high blood pressure during pregnancy.

BACKGROUND: Very high blood pressure during pregnancy poses a serious threat to women and their fetuses. The use of drugs to lower blood pressure may reduce this risk. OBJECTIVES: The objective of this review was to compare different antihypertensive drugs used for rapid treatment of severe hypertension during pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. SELECTION CRITERIA STUDIES: All randomised trials. Quasi random designs were excluded. PARTICIPANTS: Women with severe hypertension during pregnancy. Women postpartum at trial entry were excluded. INTERVENTIONS: Comparisons of one antihypertensive agent with another. OUTCOMES: For the women: blood pressure control, eclampsia, serious maternal morbidity (such as kidney failure and liver failure), Caesarean section, and use of health service resources (such as admission to hospital or intensive care unit). For the baby: death, serious neonatal morbidity, infant and child development, and use of health service resources (such as admission to a special care nursery). DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers to assess eligibility and describe the trial characteristics, and by one reviewer for the meta-analyses. Discrepancies were resolved by discussion. There was no blinding of authorship or results. Whenever possible, unpublished data were sought from investigators. MAIN RESULTS: Thirteen of the 14 trials included in this review were small (range 19-627 women). Of the eight comparisons, five included hydralazine. Diazoxide given as 75mg bolus injections appears to be associated with profound hypotension requiring treatment, and ketanserin is less effective than hydralazine at reducing blood pressure. There is no other evidence that any one of the other antihypertensive agents is better than another for women with severe hypertension during pregnancy. REVIEWER'S CONCLUSIONS: Until better evidence is available, the choice of antihypertensive should depend on the experience and familiarity of an individual clinician with a particular drug, and on what is known about adverse maternal and fetal side-effects. Exceptions are diazoxide and ketanserin, which are probably not good choices.

Antihypertensive Agents↗

PubMed2005

Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy.

BACKGROUND: Bacterial infections are a major cause of morbidity and mortality in neutropenic patients following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in decreasing the incidence of bacterial infections, but not in reducing mortality rates. OBJECTIVES: This review aimed to evaluate whether antibiotic prophylaxis in afebrile neutropenic patients reduced mortality when compared to placebo or no intervention. SEARCH STRATEGY: Electronic searches on The Cochrane Cancer Network Register of Trials (2004), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004) and EMBASE (1980 to 2004) and abstracts of conference proceedings; references of identified studies; the first author of each included trial was contacted. SELECTION CRITERIA: RCTs or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic to prevent bacterial infections in afebrile neutropenic patients. DATA COLLECTION AND ANALYSIS: Two authors independently appraised the quality of each trial and extracted data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated. MAIN RESULTS: One hundred trials (10,274 patients) performed between the years 1973 to 2004 met inclusion criteria. Antibiotic prophylaxis significantly decreased the risk for death when compared with placebo or no intervention (RR, 0.66 [95% CI 0.54 to 0.81]). The authors estimated the number needed to treat (NNT) in order to prevent 1 death from all causes as 60 (95% CI 34 to 268). Prophylaxis resulted in a significant decrease in the risk of infection-related death, RR 0.58 (95% CI 0.45 to 0.74) and in the occurrence of fever, RR 0.78 (95% CI 0.75 to 0.82). A reduction in mortality was also evident when the more recently conducted quinolone trials were analysed separately. Quinolone prophylaxis reduced the risk for all-cause mortality, RR 0.52 (95% CI, 0.37 to 0.84). AUTHORS' CONCLUSIONS: Our review demonstrated that prophylaxis significantly reduced all-cause mortality. The most significant reduction in mortality was observed in trials assessing prophylaxis with quinolones. The benefit demonstrated in our review outweighs harm, such as adverse effects, and development of resistance, since all-cause mortality is reduced. Since most trials in our review were of patients with haematologic cancer, prophylaxis, preferably with a quinolone, should be considered for these patients.

Anti-Bacterial Agents↗

PubMed2006

Developmental care for promoting development and preventing morbidity in preterm infants.

BACKGROUND: Preterm infants experience a range of morbidity related to the immaturity of their organ systems and to concurrent disease states. There is concern that an unfavourable environment in the neonatal intensive care unit (NICU) may compound this morbidity. Modification of the environment could minimize the iatrogenic effects. Developmental care is a broad category of interventions designed to minimize the stress of the NICU environment. These interventions may include elements such as control of external stimuli (vestibular, auditory, visual, tactile), clustering of nursery care activities, and positioning or swaddling of the preterm infant. Individual strategies have also been combined to form programs, such as the 'Newborn Individualized Developmental Care and Assessment Program' (NIDCAP) (Als 1986). OBJECTIVES: In preterm infants, do developmental care interventions reduce neurodevelopmental delay, poor weight gain, length of hospital stay, length of mechanical ventilation, physiological stress and other clinically relevant adverse outcomes? SEARCH STRATEGY: The Neonatal Review Group search strategy was utilized. Searches were made of MEDLINE from 1966 to June, 2005 and of CINAHL, The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), and conference and symposia proceedings in the English language from 1990 to June, 2005. A search of EMBASE was also made from 2003 to June 2005. A list of all relevant articles was sent to two experts in the field to identify any omissions or additional unpublished studies. SELECTION CRITERIA: Randomized trials in which elements of developmental care are compared to routine nursery care for infants < 37 weeks gestation and that measured clinically relevant outcomes. Reports were in English or a language for which a translator was available. Computerized searches were conducted and all potentially relevant titles and abstracts were extracted. Retrieved articles were assessed for relevance independently by two reviewers, based on predetermined criteria. Articles that met all criteria for relevance were assessed for methodological quality based on predetermined criteria. 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. Meta-analyses were conducted for each intervention where the same outcome measures and/or instruments were used within comparable time points. MAIN RESULTS: This review detected 36 eligible randomized controlled trials involving four major groups of developmental care interventions, 19 sub-groups and multiple clinical outcomes. In addition, the long-term outcomes of a previously included trial were added to the review. The results of the review indicate that developmental care interventions demonstrate limited benefit to preterm infants with respect to: decreased moderate-severe chronic lung disease, decreased incidence of necrotizing enterocolitis and improved family outcome. Conversely, an increase in mild lung disease and an increase in the length of stay were demonstrated in infants receiving developmental care compared to controls. There is also very limited evidence of the long-term positive effect of NIDCAP on behavior and movement at 5 years corrected age but no effect on cognition. Other individualized developmental care interventions have also demonstrated some effect in enhancing neurodevelopmental outcome. Although a limited number of other benefits were demonstrated, those results were from single studies with small sample sizes. The lack of blinding of the assessors was a significant methodological flaw in half of the studies. The cost of the interventions and personnel was not considered in any of the studies. AUTHORS' CONCLUSIONS: Because of the inclusion of multiple interventions in most studies, the determination of the effect of any single intervention is difficult. Although there is evidence of limited benefit of developmental care interventions overall, and no major harmful effects reported, there were a large number of outcomes for which no or conflicting effects were demonstrated. The single trials that did show a significant effect of an intervention on a major clinical outcome were based on small sample sizes, and the findings were often not supported in other small trials. Before a clear direction for practice can be supported, evidence demonstrating more consistent effects of developmental care interventions on important short- and long-term clinical outcomes is needed. The economic impact of the implementation and maintenance of developmental care practices should be considered by individual institutions.

Developmental Disabilities↗

PubMed2001

Research output of Australian general practice: a comparison with medicine, surgery and public health.

OBJECTIVES: To compare the productivity of Australian general practice in terms of research publications with the productivity of other medical disciplines. DESIGN: A survey of Australian general practice, medicine, surgery and public health publications carried out by manual searching of specific journals and an electronic search of the US National Library of Medicine's "PubMed" database. MAIN OUTCOME MEASURES: The number of original research publications by Australian general practitioners, physicians, surgeons and public health physicians during 1999; the relative publication rate of Australian general practice, medicine, surgery and public health over the period 1990-1999. RESULTS: Of original research articles published in 1999, GPs authored 65% (17/26) in Australian Family Physician and 3% (3/90) in the Medical Journal of Australia; physicians published 4% and 37%, respectively. The electronic search identified 54 research articles relating to Australian general practice published in 1999 in 21 different journals, only two of which were primary care journals. Over the period 1990-1999, there was a publication rate of one general practice [discipline] article per 1000 GPs in practice per year. Corresponding rates for medicine, surgery and public health were 105/1000, 61/1000 and 148/1000, respectively. CONCLUSIONS: There is considerable disparity between the level of research output of general practice and that of the disciplines of medicine, surgery and public health. If we are to have effective general practice research, we urgently need to develop research skills, a supportive infrastructure and a culture that nurtures research.

Australia↗

PubMed2004

Quantitative evaluation of recall and precision of CAT Crawler, a search engine specialized on retrieval of Critically Appraised Topics.

BACKGROUND: Critically Appraised Topics (CATs) are a useful tool that helps physicians to make clinical decisions as the healthcare moves towards the practice of Evidence-Based Medicine (EBM). The fast growing World Wide Web has provided a place for physicians to share their appraised topics online, but an increasing amount of time is needed to find a particular topic within such a rich repository. METHODS: A web-based application, namely the CAT Crawler, was developed by Singapore's Bioinformatics Institute to allow physicians to adequately access available appraised topics on the Internet. A meta-search engine, as the core component of the application, finds relevant topics following keyword input. The primary objective of the work presented here is to evaluate the quantity and quality of search results obtained from the meta-search engine of the CAT Crawler by comparing them with those obtained from two individual CAT search engines. From the CAT libraries at these two sites, all possible keywords were extracted using a keyword extractor. Of those common to both libraries, ten were randomly chosen for evaluation. All ten were submitted to the two search engines individually, and through the meta-search engine of the CAT Crawler. Search results were evaluated for relevance both by medical amateurs and professionals, and the respective recall and precision were calculated. RESULTS: While achieving an identical recall, the meta-search engine showed a precision of 77.26% (+/-14.45) compared to the individual search engines' 52.65% (+/-12.0) (p < 0.001). CONCLUSION: The results demonstrate the validity of the CAT Crawler meta-search engine approach. The improved precision due to inherent filters underlines the practical usefulness of this tool for clinicians.

Data Collection↗

PubMed1998

Impaired granulocytic differentiation in vitro in hematopoietic cells lacking retinoic acid receptors alpha1 and gamma.

Transcripts for the retinoic acid receptors (RARs) alpha1, alpha2, gamma1, and gamma2 were found in the granulocytic lineage (Gr-1+ cells) through semiquantitative polymerase chain reaction (PCR) analysis. The screening of single cell cDNA libraries derived from hematopoietic progenitors also showed the presence of RARalpha and, to a lesser extent, RARgamma transcripts in committed granulocyte (colony-forming unit-granulocyte [CFU-G]) or granulocyte-macrophage (CFU-GM) colony-forming cells. The contribution of RARalpha1 and gamma to hematopoietic cell differentiation was therefore investigated in mice bearing targeted disruption of either one or both of these loci. Because RARgamma and RARalpha1gamma compound null mutants die shortly after birth, bone marrow cells were collected from fetuses at 18.5 days postcoitum (dpc) and evaluated for growth and differentiation in culture in the presence of Steel factor (SF), interleukin-3 (IL-3), and erythropoietin (Epo). The frequency of colony-forming cells from bone marrow populations derived from RARalpha1/gamma double null mice was not significantly different from that of RARgamma or RARalpha1 single nulls or from wild-type controls. In addition, the distribution of erythroid, granulocyte, and macrophage colonies was comparable between hematopoietic cells from all groups, suggesting that lineage commitment was not affected by the lack of RARalpha1 and/or RARgamma. Colony cells were then harvested individually and evaluated by morphologic criteria. While terminal granulocyte differentiation was evident in wild-type cells and colonies from either single null mutant, colonies derived from RARalpha1-/-gamma-/- bone marrow populations were blocked at the myelocyte and, to a lesser extent, at the metamyelocyte stages, whereas erythroid and macrophage differentiation was not affected. Together, these results indicate that both RARalpha1 and gamma are required for terminal maturation in the granulocytic lineage in vitro, but appear to be dispensable for the early stages of hematopoietic cell development. Our results raise the possibility that in acute promyelocytic leukemia (APL), the RARalpha fusion proteins cause differentiation arrest at a stage when further maturation requires not only RARalpha, but also RARgamma. Finally, bone marrow cells appear to differentiate normally in vivo, suggesting an effective compensation mechanism in the RARalpha1/gamma double null mice.

Animals↗

PubMed2005

Surgical interventions for pharyngeal pouch.

BACKGROUND: A pharyngeal pouch is an out-pouching or pocket that develops from the posterior wall of the pharynx just above the entrance to the oesophagus (gullet). Pouches may give rise to difficulty in swallowing, sensation of a lump in the throat or of food sticking in the throat and may lead to troublesome regurgitation of food. Food may enter the pouch rather than passing down the oesophagus and this and regurgitation may result in weight loss, hoarseness of voice and/or recurrent chest infections. The management of patients with a pharyngeal pouch may be either conservative or surgical. The surgical management can be further divided into two broad categories: endoscopic and open procedures. In the first half of the twentieth century an open surgical approach to the pouch was most frequently used, and remains common in some parts of the world. In recent decades endoscopic procedures (where the approach is made through the mouth) have become popular. The superiority of one approach over another has yet to be clearly demonstrated. OBJECTIVES: To assess the effectiveness and safety of open and endoscopic surgical procedures for the management of a pharyngeal pouch. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2004, MEDLINE (1966 to 2004) and EMBASE (1974 to 2004). Reference lists of all identified trials and previous reviews were searched for additional trials. Further electronic searches for key authors identified were made. There were no language restrictions. The date of the last search was September 2004. SELECTION CRITERIA: We sought to identify all randomised controlled trials (RCTs) comparing two or more interventions. DATA COLLECTION AND ANALYSIS: Three reviewers assessed the eligibility of trials for inclusion in the review, based on pre-determined criteria. MAIN RESULTS: No trials were identified which fulfilled the criteria. AUTHORS' CONCLUSIONS: There is no evidence from high quality randomised controlled trials to demonstrate the effectiveness of endoscopic compared with open procedures for pharyngeal pouch. There is no good evidence to establish whether one endoscopic procedure is superior to another.

Diverticulum↗

PubMed2004

Minilaparotomy and endoscopic techniques for tubal sterilisation.

BACKGROUND: Worldwide, the most commonly used method of fertility regulation is tubal sterilisation. In developed countries sterilisation is generally performed by laparoscopy rather than by minilaparotomy, based on the belief that this approach is both safe and effective. In developing countries, where the resources are limited for the purchase and maintenance of the more sophisticated laparoscopic equipment, minilaparotomy may still be the most common approach. In both resource poor and industrialised countries using the technique with the greatest effectiveness and safety, together with the least costs, is extremely important. Though both methods are widely used, the advantages and disadvantages of laparoscopic sterilisation compared to mini-laparotomy have not been systematically evaluated. The ideal method would be one which is highly effective, economical, able to be performed on an outpatient basis, allowing rapid resumption of normal activity, producing a minimal or invisible scar and having a potential for reversibility. This review considers the methods to enter the abdominal cavity through the abdominal wall, either by minilaparotomy, laparoscopy or culdoscopy regardless of the technique used for tubal sterilisation. OBJECTIVES: To evaluate laparoscopic tubal sterilisation, as compared to minilaparotomy in terms of operative morbidity and mortality. Trials comparing laparoscopy or minilaparotomy with culdoscopy were also included in the review. Different methods used to interrupt tubal patency (excision, occlusion and coagulation) and comparison of different forms of anaesthesia will be considered in different reviews. SEARCH STRATEGY: Randomised controlled trials (RCTs) have been identified by using the search strategy of the Cochrane Collaboration. The Cochrane Controlled Trials Register was last searched in 1999 (Cochrane Library Issue 4, 1999). Reference lists of identified trials have been searched. SELECTION CRITERIA: All randomised controlled trials comparing laparoscopy, minilaparotomy and/or culdoscopy for tubal sterilisation. Except in one trial [Taner 1994] where 4 women underwent curettage at the same time, all women requested tubal sterilisation as an interval procedure. DATA COLLECTION AND ANALYSIS: Trials under consideration were evaluated for methodological quality and appropriateness for inclusion. Data were extracted independently by the reviewers. Results are reported as odds ratio for dichotomous outcomes and weighted mean differences for continuous outcomes. MAIN RESULTS: Minilaparotomy vs laparoscopy: There was no difference in major morbidity between the 2 groups. Minor morbidity was significantly less in the laparoscopy group (Peto OR 1.89; 95% CI 1.38, 2.59). Duration of operation was about 5 minutes shorter in the laparoscopy group (WMD 5.34; 95% CI 4.52, 6.16). Minilaparotomy vs culdoscopy: Women undergoing culdoscopy had more major morbidity than women for whom minilaparotomy was performed (Peto OR 0.14; 95% CI 0.02, 0.98). Duration of operation was about 5 minutes shorter in women undergoing culdoscopy (WMD 4.91; 95% CI 3.82, 6.01). Laparoscopy vs culdoscopy: In the one trial comparing the two interventions there were no significant differences between the groups with regard to major morbidity. Significantly more women suffered from minor morbidities in the culdoscopy group compared to the laparoscopy group (Peto OR 0.20; 95% CI 0.05, 0.77). REVIEWERS' CONCLUSIONS: Major morbidity seems to be a rare outcome for both, laparoscopy and minilaparotomy. The included studies had limited power to demonstrate significant differences especially for the relatively rare but potentially serious outcomes. Personal preference of the woman and/or of the surgeon can guide the choice of technique. Practical aspects (e.g. cost, maintenance, and sterilisation of the instruments) must be taken into account before implementing the more sophisticated endoscopic techniques in settings with limited resources. Culdoscopy is not recommended as it carries a higher complication rate.

Culdoscopy↗

PubMed2006

TIPS versus paracentesis for cirrhotic patients with refractory ascites.

BACKGROUND: Refractory ascites (ie, ascites that cannot be mobilized despite sodium restriction and diuretic treatment) occurs in 10 per cent of patients with cirrhosis. It is associated with substantial morbidity and mortality with a one-year survival rate of less than 50 per cent. Few therapeutic options currently exist for the management of refractory ascites. OBJECTIVES: To compare transjugular intrahepatic portosystemic stent-shunts (TIPS) versus paracentesis for the treatment of refractory ascites in patients with cirrhosis. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2006), the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 4, 2005), MEDLINE (1950 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to August 2004), and Science Citation Index Expanded (1945 to January 2006). SELECTION CRITERIA: We included randomised clinical trials comparing TIPS and paracentesis with or without volume expanders for cirrhotic patients with refractory ascites. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two authors independently extracted data from each trial. We contacted trial authors for additional information. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Five randomised clinical trials, including 330 patients, met the inclusion criteria. The majority of trials had adequate allocation concealment, but only one employed blinded outcome assessment. Mortality at 30-days (OR 1.00, 95% CI 0.10 to 10.06, P = 1.0) and 24-months (OR 1.29, 95% CI 0.65 to 2.56, P = 0.5) did not differ significantly between TIPS and paracentesis. Transjugular intrahepatic portosystemic stent-shunts significantly reduced the re-accumulation of ascites at 3-months (OR 0.07, 95% CI 0.03 to 0.18, P < 0.01) and 12-months (OR 0.14, 95% CI 0.06 to 0.28, P < 0.01). Hepatic encephalopathy occurred significantly more often in the TIPS group (OR 2.24, 95% CI 1.39 to 3.6, P < 0.01), but gastrointestinal bleeding, infection, and acute renal failure did not differ significantly between the two groups. AUTHORS' CONCLUSIONS: The meta-analysis supports that TIPS was more effective at removing ascites as compared with paracentesis without a significant difference in mortality, gastrointestinal bleeding, infection, and acute renal failure. However, TIPS patients develop hepatic encephalopathy significantly more often.

Ascites↗

PubMed2005

Biological activities encoded by the murine mesenchymal stem cell transcriptome provide a basis for their developmental potential and broad therapeutic efficacy.

We used serial analysis of gene expression to catalog the transcriptome of murine mesenchymal stem cells (MSCs) enriched from bone marrow by immunodepletion. Interrogation of this database, results of which are delineated in the appended databases, revealed that immunodepleted murine MSCs (IDmMSCs) highly express transcripts encoding connective tissue proteins and factors modulating T-cell proliferation, inflammation, and bone turnover. Categorizing the transcriptome based on gene ontologies revealed the cells also expressed mRNAs encoding proteins that regulate mesoderm development or that are characteristic of determined mesenchymal cell lineages, thereby reflecting both their stem cell nature and differentiation potential. Additionally, IDmMSCs also expressed transcripts encoding proteins regulating angiogenesis, cell motility and communication, hematopoiesis, immunity and defense as well as neural activities. Immunostaining and fluorescence-activated cell sorting analysis revealed that expression of various regulatory proteins was restricted to distinct subpopulations of IDmMSCs. Moreover, in some cases, these proteins were absent or expressed at reduced levels in other murine MSC preparations or cell lines. Lastly, by comparing their transcriptome to that of 17 other murine cell types, we also identified 43 IDmMSC-specific transcripts, the nature of which reflects their varied functions in bone and marrow. Collectively, these results demonstrate that IDmMSC express a diverse repertoire of regulatory proteins, which likely accounts for their demonstrated efficacy in treating a wide variety of diseases. The restricted expression pattern of these proteins within populations suggests that the cellular composition of marrow stroma and its associated functions are more complex than previously envisioned.

Animals↗

PubMed2005

Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants.

BACKGROUND: A patent ductus arteriosus (PDA) complicates the clinical course of preterm infants, increasing their risks of developing chronic lung disease (CLD), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH). Indomethacin is used as standard therapy to close a PDA, but is associated with reduced blood flow to the brain, kidneys and gut. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective with fewer side effects. OBJECTIVES: To determine the effectiveness and safety of ibuprofen compared to placebo or no intervention for closing a PDA in preterm and/or low birth weight infants. To determine the effectiveness and safety of ibuprofen compared to other cyclo-oxygenase inhibitors (including indomethacin, mefenamic acid) for closing a PDA in preterm and/or low birth weight infants. SEARCH STRATEGY: Randomized or quasi-randomized controlled trials (RCTs) comparing ibuprofen to placebo or indomethacin or mefenamic acid for therapy of PDA were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2005), MEDLINE (1996 - July 2005), CINAHL (1982 - July 2005), EMBASE (1980 - July 2005), reference lists of published RCTs and abstracts from the Pediatric Academic Societies and the European Society for Pediatric Research meetings published in Pediatric Research (1991 - April 2005). No language restrictions were applied. SELECTION CRITERIA: 1) DESIGN: Randomized or quasi-randomized controlled trials 2) POPULATION: Preterm (< 37 weeks gestational age) or low birth weight infants (< 2500 grams) with a clinically or echocardiographically diagnosed PDA 3) INTERVENTION: Administration of ibuprofen for the closure of PDA 4) OUTCOMES: At least one of the following outcomes were reported: failure to close a PDA, mortality, surgical ligation, intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), NEC, decreased urine output, retinopathy of prematurity (ROP), chronic lung disease (CLD), sepsis, days on supplementary oxygen. DATA COLLECTION AND ANALYSIS: At least two authors worked independently at each step of the original review, then compared results and resolved differences. The current update was conducted by one author (AO). Methodological quality of eligible studies was assessed according to blinding of randomization, of intervention and of outcome assessment, and completeness of follow up. Weighted treatment effects, calculated using RevMan 4.2, included typical relative risk (RR), typical risk difference (RD), number needed to treat (NNT) or harm (NNH), and weighted mean difference (WMD), all with 95% confidence intervals (CI). A fixed effect model was used for meta-analyses. Heterogeneity tests including I(2 )were performed to assess the appropriateness of pooling the data. MAIN RESULTS: No study using mefenamic acid was identified. One study compared ibuprofen to placebo but results were not reported unblinded to group. Eleven studies including 620 patients compared the effectiveness of ibuprofen to indomethacin for the closure of a PDA. There was no statistically significant heterogeneity of treatment effect for any of the outcomes. For the primary outcome (failure of ductal closure), there was no statistically significant difference between ibuprofen and indomethacin groups [typical RR 0.96 (95% CI 0.74, 1.25)]. There were no statistically significant differences in mortality, surgical duct ligation, duration of ventilator support, IVH, PVL, NEC, time to full enteral feeds, ROP, sepsis, duration of hospital stay or gastrointestinal bleed. For many of these outcomes the sample size was small and the estimates imprecise. The incidence of decreased urine output (< 1cc/kg/hr) was lower in the ibuprofen group as compared to the indomethacin group [NNT 9 (95% CI 5-14)]. This was the only statistically significant clinical finding favouring ibuprofen. CLD defined as oxygen requirement at 28 days post-natally was statistically significantly more likely to occur in the ibuprofen group [typical RR 1.37 (95% CI 1.01, 1.86); NNH 7 (95% CI 3 - 100)]. There was a similar trend for CLD at 36 weeks corrected gestational age. AUTHORS' CONCLUSIONS: We found no statistically significant difference in the effectiveness of ibuprofen compared to indomethacin in closing the PDA. Ibuprofen reduces the risk of oliguria. However, ibuprofen may increase the risk for CLD, and pulmonary hypertension has been observed in three infants after prophylactic use of ibuprofen. Based on currently available information ibuprofen does not appear to confer a net benefit over indomethacin for the treatment of a PDA. We conclude that indomethacin should remain the drug of choice for the treatment of a PDA. The most urgent research question to be answered is weather ibuprofen compared to indomethacin confers an improved rate of intact survival (survival without impairment) at 18 months corrected age.

Cyclooxygenase Inhibitors↗

PubMed1992

Bacteriophage lambda as a cloning vector.

Extensive research has been directed toward the development of multipurpose lambda vectors for cloning ever since the potential of using coliphage lambda as a cloning vector was recognized in the late 1970s. An understanding of the intrinsic molecular organization and of the genetic events which determine lysis or lysogeny in lambda has allowed investigators to modify it to suit the specific requirements of gene manipulations. Unwanted restriction sites have been altered and arranged together into suitable polylinkers. The development of a highly efficient in vitro packaging system has permitted the introduction of chimeric molecules into hosts. Biological containment of recombinants has been achieved by introducing amber mutations into the lambda genome and by using specific amber suppressor hosts. Taking advantage of the limited range of genome size (78 to 105% of the wild-type size) for its efficient packaging, an array of vectors has been devised to accommodate inserts of a wide size range, the limit being 24 kbp in Charon 40. The central dispensable fragment of the lambda genome can be replaced by a fragment of heterologous DNA, leading to the construction of replacement vectors such as Charon and EMBL. Alternatively, small DNA fragments can be inserted without removing the dispensable region of the lambda genome, as in lambda gt10 and lambda gt11 vectors. In addition, the introduction of many other desirable properties, such as NotI and SfiI sites in polylinkers (e.g., lambda gt22), T7 and T3 promoters for the in vitro transcription (e.g., lambda DASH), and the mechanism for in vivo excision of the intact insert (e.g., lambda ZAP), has facilitated both cloning and subsequent analysis. In most cases, the recombinants can be differentiated from the parental phages by their altered phenotype. Libraries constructed in lambda vectors are screened easily with antibody or nucleic acid probes since several thousand clones can be plated on a single petri dish. Besides the availability of a wide range of lambda vectors, many related techniques such as rapid isolation of lambda DNA, a high efficiency of commercially available in vitro packaging extracts, and in vitro amplification of DNA via the polymerase chain reaction have collectively contributed to lambda's becoming one of the most powerful and popular tools for molecular cloning.

Bacteriophage lambda↗

PubMed2026

Effect of repeated mass drug administration on the transmission of yaws: a retrospective genomic epidemiology study.

BACKGROUND: Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue (T p pertenue), has evaded eradication, in part due to a high proportion of asymptomatic cases. Repeated mass drug administration (MDA), whereby an entire population is repeatedly treated irrespective of disease, could provide a solution. Here, we aimed to investigate the effect of MDA on the genomic epidemiology of T p pertenue. METHODS: We conducted a retrospective genomic epidemiology study on samples collected during a cluster-randomised trial of mass administration of azithromycin for yaws eradication in the Namatanai District of Papua New Guinea. Participants were in 38 wards (administrative units encompassing several villages) in three local-level government areas (LLGs). The experimental group received an initial round of MDA followed by two further rounds 6 months and 12 months after the first round. The control group received one round of MDA followed by two rounds of treatment targeting clinical cases and contacts only, on the same schedule as the MDA in the experimental group. A follow-up survey on both groups was done 18 months after the first MDA round. Swab samples were collected at each round from ulcerative and nodular skin lesions, and blood was collected by finger-prick for serological testing at 18 months. Metadata on ulcer size (cm) and duration (days) were recorded at each round, and treponemal and non-treponemal antibodies were recorded at 18 months. Samples from swabs positive for T p pertenue underwent library preparation and whole-genome sequencing. We examined the phylogenetic relationships between genomes, linking them with geospatial and patient metadata to understand the impact of MDA on T p pertenue diversity and transmission. FINDINGS: Swabs collected from 297 individuals with active yaws from April 30, 2018, to Nov 2, 2019, yielded 222 good-quality Tp pertenue genomes. We identified 20 sublineages of T p pertenue in the control group and 21 in the experimental group at the beginning of the study. At the end of the study, there were 13 sublineages in the control group and three in the experimental group, of which two persisted in both groups. Three sublineages not detected at baseline were observed in the control group after commencing MDA. The two sublineages that persisted in both groups had non-synonymous mutations in penicillin-binding proteins. One of these sublineages evolved macrolide resistance in three individuals and was associated with lowered treponemal antibody (p=0·0036) and longer ulcer duration (p=0·015). Despite the study taking place within a small island, sublineages were geographically clustered, with pairs of samples from the same ward (odds ratio 7·1, 95% CI 5·7-8·8; p<0·0001) or neighbouring wards (4·3, 3·3-5·4; p<0·0001) more likely to share the same sublineages compared with pairs from different LLGs. Additionally, older individuals were more likely to share sublineages than were younger individuals (1·5, 1·2-1·9; p<0·0001). INTERPRETATION: Repeated MDA was successful in reducing and maintaining the genetic diversity of T p pertenue at a low level but was associated with the development of macrolide resistance. Yaws re-emergence after MDA was attributed to multiple sublineages, of which the majority were detected in the population before MDA. Participants within the same ward were more likely to share sublineages than those that were more widely geographically separated, suggesting that re-emergence was driven by local transmission. These findings could inform future yaws elimination strategies. FUNDING: European Research Council, EU, Provincial Deputation of Barcelona, Barberà Solidària Foundation, Wellcome, and Fundació "la Caixa".

Adolescent↗

PubMed1998

Obituary

Sheila Willmott, (1921-1998)CAB International and the Editor, Assistant Editor and Editorial Board of the Journal of Helminthology wish to express their deepest sympathy to the family and friends of Sheila Willmott who died on 8 May 1998 after a very short illness. Sheila served as Editor of the Journal of Helminthology from 1980 to 1986.Dr Lotfi Khalil, formerly Deputy Director of the International Institute of Parasitology at St Albans, worked closely with Sheila and has written the following tribute.John W. Lewis, EditorSheila Willmott was a leading contributor to the dissemination of parasitic information before the development of computerization and information technology. She was born on 8 June, 1921, in London, and was educated at Tollington High School for Girls, Chelsea Polytechnic and University College, London. She did her PhD at the London School of Hygiene and Tropical Medicine under the supervision of Professor John Buckley, the subject of her thesis being the study of amphistome digeneans. Her studies were interrupted as a result of the Second World War when she was 'drafted' as a Rodent Instructor at the Ministry of Agriculture, Fisheries and Food. After completing her PhD, she was appointed Assistant Lecturer in Zoology at the University College of South Wales and Monmouthshire, Cardiff. In 1951, Professor R.T. Leiper, the Director of the Bureau of Agricultural Parasitology (Helminthology) recruited her as a Scientific Information Officer. She was appointed Assistant Director of the Bureau in 1954, and Director in 1961, where she stayed until her retirement in 1980.During her period as Director of the Bureau, which was sited in the White House in the centre of St Albans, she maintained and improved the high quality of Helminthological Abstracts and, in 1976, accepted the extra burden of starting and producing Protozoological Abstracts. In 1979, she initiated and edited a primary journal, Systematic Parasitology, devoted to papers on the taxonomy and systematics of parasites, published by Junk. The activities of the Bureau were greatly expanded and she initiated the taxonomic laboratories to provide a worldwide service for the identification of animal helminths and plant-parasitic nematodes and to undertake taxonomic research. A vast helminth reference collection was started, and the Bureau became a recognized centre for the deposition of type specimens. The library of the Bureau accumulated an enormous number of reference books, journals and reprints, and provided a photocopying service supplying, at short notice, copies of papers and publications. A number of books and other publications, including the CIH Keys to the Nematode Parasites of Vertebrates, were produced and edited by her and others. She also persuaded the Natural Environment Research Council to finance the Fisheries Helminthology Unit which she established at the Bureau in 1960, where it remained until it was transferred to Plymouth as part of the Institute for Marine Environmental Research. The Bureau's name and status were changed to the Commonwealth Institute of Helminthology, Commonwealth Institute of Parasitology and, finally, the International Institute of Parasitology.As Director, she travelled extensively and visited Commonwealth and other countries, where she gave a number of seminars on information services and the work of the Institute and the Commonwealth Agricultural Bureaux (CAB) as a whole. She encouraged contact with Eastern Europe and visited Poland, Czechoslovakia, Hungary, Bulgaria and the USSR. She initiated the system of exchange publications with these countries, and this resulted in the exposure of the literature from these countries to other research workers when abstracts of these papers appeared in Helminthological Abstracts in English. Her links with Eastern Europe resulted in her editing three volumes of taxonomic monographs produced in English by Czech and Russian scientists. (ABSTRACT TRUNCATED)

Journal Article↗

PubMed2003

RIKEN mouse genome encyclopedia.

We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

Animals↗

PubMed1993

Differential expression of distinct mRNAs for ovine trophoblast protein-1 and related sheep type I interferons.

An antiluteolytic substance secreted by the ovine conceptus and primarily responsible for maternal recognition of pregnancy is ovine trophoblast protein-1 (oTP-1), a new type I interferon (IFN). The objectives of this research were 1) to investigate whether multiple, distinct genes encode oTP-1 and other type I IFNs in the ovine genome and 2) to examine expression of oTP-1 and other IFN mRNAs during conceptus development. Genes for type I IFNs were isolated from a subgenomic library constructed from Day 25 (Day 0 = estrus) ovine conceptus high-molecular-weight DNA. Six clones were isolated and nucleotide-sequenced from -1000 to +900 (bases relative to cap site). Comparisons of inferred amino acid sequences demonstrated that four clones were distinct oTP-1 genes and that two clones, defined as o9 and o12, were related type 1 IFNs (deduced aa homology of o9 and o12 to oTP-1 was 71% and 54%, respectively). The presence of mRNAs encoded by oTP-1 and type I IFN genes was examined quantitatively via reverse transcription-polymerase chain reaction (RT-PCR) analysis of total cellular RNA (tcRNA) extracted from Day 13-45 concepti. Total cellular RNA obtained from Day 75 placenta and adult lymphocytes was also analyzed by RT-PCR, coupled with Southern blot hybridization of the PCR reaction products with specific DNA probes. PCR products were sequenced in order to confirm primer specificity, and mRNAs corresponding to two of the four oTP-1 genes and to both related IFN clones (o9 and o12) were identified. Furthermore, quantitation of the PCR products revealed that of the two oTP-1 genes examined, one was highly expressed on Days 13-20 and transcripts were weakly detectable on Days 30 and 45. In contrast, the other oTP-1 gene examined was weakly expressed on Days 13-20 only. Densitometric analysis of hybridization signals revealed that IFN o9 mRNA was detected in Day 75 placenta but only weakly detected in conceptus (Days 13-45) and adult lymphocytes. IFN o12 mRNA was abundant in lymphocytes relative to the other tissues examined. Collectively, these results demonstrate the existence of distinct oTP-1 and related type I IFN genes. The data suggest that these genes display differential, tissue-specific expression and developmental regulation during pregnancy.

Amino Acid Sequence↗

PubMed1998

The use and selection of sources in information seeking: the Cancer Information Service experience. Part 8.

The Cancer Information Service (CIS), the voice of the National Cancer Institute (NCI) for more than 20 years, disseminates information through two channels: a toll-free telephone service (1-800-4-CANCER) and an outreach program which develops partnerships with organizations that reach underserved populations. In 1996, the telephone service handled approximately 500,000 calls on a range of topics, including cancer treatment, clinical trials, coping issues, referrals to services, prevention, causes, and symptoms of cancer. As part of a national telephone service user survey, conducted in 1996, that examined the impact of the CIS program, callers were asked what additional sources they went to for the same information that they requested from the CIS. The survey revealed that the CIS plays a critical role for information seekers. Almost 59% of surveyed callers contacted no other sources to address the topic they discussed with the CIS. Almost half of the callers who contacted other sources made all of those contacts before calling the CIS. Younger callers (under 40), those with a higher level of education, and those seeking information about treatment and causes of cancer were more likely to contact other sources for the same information. Health professionals, libraries, and bookstores were the most commonly used non-CIS sources. This variety in information seeking highlights the need for services, like the CIS, that can meet the diverse information needs of callers.

Adolescent↗