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PubMed2000

The mouse brain transcriptome by SAGE: differences in gene expression between P30 brains of the partial trisomy 16 mouse model of Down syndrome (Ts65Dn) and normals.

Trisomy 21, or Down syndrome (DS), is the most common genetic cause of mental retardation. Changes in the neuropathology, neurochemistry, neurophysiology, and neuropharmacology of DS patients' brains indicate that there is probably abnormal development and maintenance of central nervous system structure and function. The segmental trisomy mouse (Ts65Dn) is a model of DS that shows analogous neurobehavioral defects. We have studied the global gene expression profiles of normal and Ts65Dn male and normal female mice brains (P30) using the serial analysis of gene expression (SAGE) technique. From the combined sample we collected a total of 152,791 RNA tags and observed 45,856 unique tags in the mouse brain transcriptome. There are 14 ribosomal protein genes (nine under expressed) among the 330 statistically significant differences between normal male and Ts65Dn male brains, which possibly implies abnormal ribosomal biogenesis in the development and maintenance of DS phenotypes. This study contributes to the establishment of a mouse brain transcriptome and provides the first overall analysis of the differences in gene expression in aneuploid versus normal mammalian brain cells.

Animals↗
PubMed2005

ParPEST: a pipeline for EST data analysis based on parallel computing.

BACKGROUND: Expressed Sequence Tags (ESTs) are short and error-prone DNA sequences generated from the 5' and 3' ends of randomly selected cDNA clones. They provide an important resource for comparative and functional genomic studies and, moreover, represent a reliable information for the annotation of genomic sequences. Because of the advances in biotechnologies, ESTs are daily determined in the form of large datasets. Therefore, suitable and efficient bioinformatic approaches are necessary to organize data related information content for further investigations. RESULTS: We implemented ParPEST (Parallel Processing of ESTs), a pipeline based on parallel computing for EST analysis. The results are organized in a suitable data warehouse to provide a starting point to mine expressed sequence datasets. The collected information is useful for investigations on data quality and on data information content, enriched also by a preliminary functional annotation. CONCLUSION: The pipeline presented here has been developed to perform an exhaustive and reliable analysis on EST data and to provide a curated set of information based on a relational database. Moreover, it is designed to reduce execution time of the specific steps required for a complete analysis using distributed processes and parallelized software. It is conceived to run on low requiring hardware components, to fulfill increasing demand, typical of the data used, and scalability at affordable costs.

Algorithms↗
PubMed2006

Books for free? How can this be? - A PubMed resource you may be overlooking.

The NCBI (National Center for Biotechnology Information) at the National Institutes of Health collects a wide range of molecular biological data, and develops tools and databases to analyse and disseminate this information. Many life scientists are familiar with the website maintained by the NCBI (http://www.ncbi.nlm.nih.gov), because they use it to search GenBank for homologues of their genes of interest or to search the PubMed database for scientific literature of interest. There is also a database called the Bookshelf that includes searchable popular life science textbooks, medical and research reference books and NCBI reference materials. The Bookshelf can be useful for researchers and educators to find basic biological information. This article includes a representative list of the resources currently available on the Bookshelf, as well as instructions on how to access the information in these resources.

Biological Science Disciplines↗
PubMed2002

FANTOM DB: database of Functional Annotation of RIKEN Mouse cDNA Clones.

FANTOM DB, the database of Functional Annotation of RIKEN Mouse cDNA Clones, is designed to store sequence information of RIKEN full-length enriched mouse cDNA clones, graphical views of sequence analysis results, curated functional annotation information and additional descriptions, including Gene Ontology terms. RIKEN's Mouse Gene Encyclopedia Project aims to collect full-length enriched cDNA clones from various mouse tissues, determine the full-length nucleotide sequences, infer their chromosomal locations by computer and characterize gene expression patterns. FANTOM DB has been developed to facilitate this work and to facilitate functional genomic studies such as positional candidate cloning, cDNA microarrays and protein interaction analyses. FANTOM DB contains 21 076 full-length cDNA sequences with rich functional annotations and is publicly available. FANTOM DB thus provides curated functional annotation to RIKEN full-length enriched mouse clones, and has links to other public resources. FANTOM DB can be accessed at http://fantom.gsc.riken.go.jp/db/.

Animals↗
PubMed2005

Features of the expressed sequences revealed by a large-scale analysis of ESTs from a normalized cDNA library of the elite indica rice cultivar Minghui 63.

The indica subspecies of cultivated rice occupies the largest area of rice production in the world. However, a systematic analysis of cDNA sequences from the indica subspecies has not been performed. The aim of the present study was to collect and analyze the expressed sequence tags (ESTs) of indica rice on a large scale. A total of 39 208 raw sequences were generated from a normalized cDNA library prepared by use of 15 different tissues of the indica cultivar Minghui 63. After trimming, processing and analysis, 17 835 unique sequences were obtained, each of which presumably represents a unique gene. Of these sequences, 2663 were novel, and at least 70 were indica specific. Comparison of the Minghui 63 sequences with the ESTs/full-length cDNAs in GenBank revealed a large number of deletion/insertion/substitution (DIS) at both the inter- and intra-subspecific levels. The overall number of polymorphisms in the expressed sequences was higher in the inter-subspecific comparisons than in the intra-subspecific comparisons. However, the extent of DIS-based polymorphism was highly variable among different rice varieties. In total, 15 726 unique sequences, including 697 novel sequences, were assigned to regions where large numbers of quantitative trait loci (QTLs) for agronomic traits had been detected previously. These results may be useful for developing new molecular markers for genetic mapping, detecting allelic polymorphisms associated with phenotypic variations between rice varieties, and facilitating QTL cloning by providing the starting points for candidate-gene identification.

Expressed Sequence Tags↗
PubMed2001

Haloperidol versus placebo for schizophrenia.

BACKGROUND: Haloperidol was developed in the late 1950s for use in the field of analgesia. Research subsequently demonstrated effects on hallucinations, delusions, aggressiveness, impulsiveness and states of excitement and led to the introduction of haloperidol as an antipsychotic. OBJECTIVES: To evaluate the clinical effects of haloperidol for the management of schizophrenia and other similar serious mental illnesses compared to placebo. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (1998, Issue 4), The Cochrane Schizophrenia Group's Register (December 2000), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH (January 1974-December 1998) were undertaken. References of all identified studies were searched for further trial citations. Authors of trials and pharmaceutical companies were contacted for further information and archive material. SELECTION CRITERIA: All relevant randomised controlled trials comparing use of haloperidol (any dose) with placebo for those with schizophrenia or other similar serious, non-affective psychotic illnesses (however diagnosed). The main outcomes of interest were death, loss to follow up, clinical and social response, relapse and severity of adverse effects. DATA COLLECTION AND ANALYSIS: Reviewers evaluated data independently and analysed on an intention-to-treat basis, assuming that people who left the study early, or were lost to follow up, had no improvement. Where possible and appropriate, dichotomous data were analysed using relative risk (RR) and their 95% confidence intervals (CI) calculated. If appropriate, the number needed to treat (NNT) or number needed to harm (NNH) was estimated. For continuous data, weighted mean differences were calculated. Continuous data were excluded if loss to follow up was greater than 50%. All data were inspected for heterogeneity. MAIN RESULTS: Seventy-four trials were identified but only 20 included. More people allocated to haloperidol improved in the first six weeks of treatment than those given placebo (three trials, n=159, RR failing to produce a marked improvement 0.44 CI 0.3 to 0.6, NNT 3 CI 2 to 5). A further eight trials (n=313) also found a difference favouring haloperidol across the 6-24 week period (RR no marked global improvement 0.68 CI 0.6 to 0.8 NNT 3 CI 2.5 to 5) but this may be an overestimate of effect as small negative studies were not identified. About half of those entering studies failed to complete the short trials, although, at 0-6 weeks, 10 studies found a difference that favoured haloperidol (n=686, RR 0.82 CI 0.7 to 0.95, NNT 8 CI 5 to 17). Limited adverse effect data do, nevertheless, support the clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Haloperidol promotes acute dystonia (three trials, n=135, RR 4.7 CI 1.7 to 44, NNH 5 CI 3 to 9 - not assuming those who left early from placebo suffered dystonis), akathisia (three trials, n=129, RR 6.5 CI 1.5 to 28, NNH 6 CI 4 to 14) and parkinsonism (four trials, n=165, RR 8.9 CI 2.6 to 31, NNH 3 CI 2 to 5). REVIEWER'S CONCLUSIONS: Haloperidol is a potent antipsychotic drug but with a high propensity to cause adverse effects. Given no choice of drug, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. If a choice of drug is available, however, people with schizophrenia and clinicians may wish to start another antipsychotic with less likelihood of causing parkinsonism, akathisia and acute dystonias. For countries where haloperidol is not widely used, it should not be a control drug of choice for randomised trials of new antipsychotics.

Antipsychotic Agents↗
PubMed2004

Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is a central nervous system deficit resulting from a non-progressive lesion in the developing brain. Although the brain lesions are static, the movement disorders that arise are not unchanging and are characterised by atypical muscle tone, posture and movement (Rang 1990). The spastic motor type is the most common form of CP and its conventional therapeutic management may include splinting/casting, passive stretching, facilitation of posture and movement, spasticity-reducing medication and surgery. More recently, health care professionals have begun to use botulinum toxin A (BtA) as an adjunct to interventions in an attempt to reduce muscle tone and spasticity to improve function OBJECTIVES: To assess the effectiveness of intramuscular BtA injections as an adjunct to managing the upper limb in children with spastic CP. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1966 to March Week 3 2004), EMBASE (1980 to 2003 Week 16) and CINAHL (1982 to Week 3 March 2004). SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing intramuscular BtA injections into any muscle group of the upper limb with placebo, no treatment or other interventions. DATA COLLECTION AND ANALYSIS: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity with differences resolved by discussion. Data was extracted and entered into RevMan 4.2.3. MAIN RESULTS: Two trials met the inclusion criteria, each having short-term follow up, a small number of subjects and using a single set of injections. The study by Corry 1997 compared BtA with an injection of normal saline and found promising results in elbow extension, elbow and wrist muscle tone. At three months, encouraging results for wrist muscle tone and grasp and release were noted. The trial reported median change, range of changes and the difference in these measures between groups. The study by Fehlings 2000 compared BtA with no intervention. When data were analysed no treatment effect was found for quality of upper limb function, passive range of motion, muscle tone, grip strength or self-care ability. REVIEWERS' CONCLUSIONS: This systematic review has not found sufficient evidence to support or refute the use of intramuscular injections of BtA as an adjunct to managing the upper limb in children with spastic cerebral palsy. Only one of the two identified RCTs reported some promising results in support of reduced muscle tone following BtA injections. Further research incorporating larger sample sizes, rigorous methodology, measurement of upper limb function and functional outcomes is essential.

Botulinum Toxins, Type A↗
PubMed2004

Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is a central nervous system deficit resulting from a non-progressive lesion in the developing brain. Although the brain lesions are static, the movement disorders that arise are not unchanging and are characterised by atypical muscle tone, posture and movement (Rang 1990). The spastic motor type is the most common form of CP and its conventional therapeutic management may include splinting/casting, passive stretching, facilitation of posture and movement, spasticity-reducing medication and surgery. More recently, health care professionals have begun to use botulinum toxin A (BtA) as an adjunct to interventions in an attempt to reduce muscle tone and spasticity to improve function OBJECTIVES: To assess the effectiveness of intramuscular BtA injections as an adjunct to managing the upper limb in children with spastic CP. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1966 to March Week 3 2004), EMBASE (1980 to 2003 Week 16) and CINAHL (1982 to Week 3 March 2004). SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing intramuscular BtA injections into any muscle group of the upper limb with placebo, no treatment or other interventions. DATA COLLECTION AND ANALYSIS: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity with differences resolved by discussion. Data was extracted and entered into RevMan 4.2.3. MAIN RESULTS: Two trials met the inclusion criteria, each having short-term follow up, a small number of subjects and using a single set of injections. The study by Corry 1997 compared BtA with an injection of normal saline and found promising results in elbow extension, elbow and wrist muscle tone. At three months, encouraging results for wrist muscle tone and grasp and release were noted. The trial reported median change, range of changes and the difference in these measures between groups. The study by Fehlings 2000 compared BtA with no intervention. When data were analysed no treatment effect was found for quality of upper limb function, passive range of motion, muscle tone, grip strength or self-care ability. REVIEWERS' CONCLUSIONS: This systematic review has not found sufficient evidence to support or refute the use of intramuscular injections of BtA as an adjunct to managing the upper limb in children with spastic cerebral palsy. Only one of the two identified RCTs reported some promising results in support of reduced muscle tone following BtA injections. Further research incorporating larger sample sizes, rigorous methodology, measurement of upper limb function and functional outcomes is essential.

Adolescent↗
PubMed1977

Foundations of medical librarianship.

The development of medical librarianship during the last forty years is examined as reflected in the changes of its resources, technology, education, and knowledge base. A shift from historical to scientific inquiry constitutes the direction of medical librarianship. Its nexus is the gathering of information and the transfer of knowledge. The social and human resources for this ongoing change and the basis for a quest for excellence is seen in the pool of talent represented by hospital librarians and the aspirations of the women's movement for equality.

Bibliographies as Topic↗
PubMed2004

Specialist outreach clinics in primary care and rural hospital settings.

BACKGROUND: Specialist medical practitioners have conducted clinics in primary care and rural hospital settings for a variety of reasons in many different countries. Such clinics have been regarded as an important policy option for increasing the accessibility and effectiveness of specialist services and their integration with primary care services. OBJECTIVES: To undertake a descriptive overview of studies of specialist outreach clinics and to assess the effectiveness of specialist outreach clinics on access, quality, health outcomes, patient satisfaction, use of services, and costs. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) specialised register (March 2002), the Cochrane Controlled Trials Register (CCTR) (Cochrane Library Issue 1, 2002), MEDLINE (including HealthStar) (1966 to May 2002), EMBASE (1988 to March 2002), CINAHL (1982 to March 2002), the Primary-Secondary Care Database previously maintained by the Centre for Primary Care Research in the Department of General Practice at the University of Manchester, a collection of studies from the UK collated in "Specialist Outreach Clinics in General Practice" (Roland 1998), and the reference lists of all retrieved articles. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series analyses of visiting specialist outreach clinics in primary care or rural hospital settings, either providing simple consultations or as part of complex multifaceted interventions. The participants were patients, specialists, and primary care providers. The outcomes included objective measures of access, quality, health outcomes, satisfaction, service use, and cost. DATA COLLECTION AND ANALYSIS: Four reviewers working in pairs independently extracted data and assessed study quality. MAIN RESULTS: 73 outreach interventions were identified covering many specialties, countries and settings. Nine studies met the inclusion criteria. Most comparative studies came from urban non-disadvantaged populations in developed countries. Simple 'shifted outpatients' styles of specialist outreach were shown to improve access, but there was no evidence of impact on health outcomes. Specialist outreach as part of more complex multifaceted interventions involving collaboration with primary care, education or other services was associated with improved health outcomes, more efficient and guideline-consistent care, and less use of inpatient services. The additional costs of outreach may be balanced by improved health outcomes. REVIEWER'S CONCLUSIONS: This review supports the hypothesis that specialist outreach can improve access, outcomes and service use, especially when delivered as part of a multifaceted intervention. The benefits of simple outreach models in urban non-disadvantaged settings seem small. There is a need for good comparative studies of outreach in rural and disadvantaged settings where outreach may confer most benefit to access and health outcomes.

Community-Institutional Relations↗
PubMed2002

Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages.

Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi.

Animals↗
PubMed2004

Vitamin C for preventing and treating the common cold.

BACKGROUND: The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment. OBJECTIVES: To discover whether oral vitamin C in doses of 200 mg or more daily, reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms. SEARCH STRATEGY: This updated review added to earlier searches, a full search of the following electronic databases: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June 2004); and EMBASE (1990 to June 2004). SELECTION CRITERIA: Papers were excluded if a dose less than 200 mg daily of vitamin C was used; if there was no placebo comparison; if methods of outcome assessment were inadequately described; and if the report did not record any of the three study outcomes (incidence, duration or severity) in sufficient detail to enter into the meta-analysis. Three criteria of study quality were assessed: Jadad scores, placebo distinguish-ability, and allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes and 'severity' of these episodes was assessed by days confined indoors, off work or school. or by symptom severity scores. MAIN RESULTS: Twenty-nine trial comparisons involving 11,077 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold while taking prophylaxis. The pooled RR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). Thirty comparisons that involved 9,676 respiratory episodes contributed to the meta-analysis on common cold duration during prophylaxis . A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adult participants and 13.5% (95% CI 5% to 21%) for child participants. Fifteen trial comparisons that involved 7,045 respiratory episodes contributed to the meta-analysis of severity of episodes experienced while on prophylaxis. The pooled results revealed a difference favouring those on vitamin C when days confined to home and off work or school were taken as a measure of severity (p = 0.02), and when restricting to studies which used symptom severity scores (p = 0.16), and for the both measures of severity combined (p = 0.004). Seven trial comparisons that involved 3,294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C that was initiated after the onset of cold symptoms, and no significant difference from placebo was seen. Four trial comparisons that involved 2,753 respiratory episodes, contributed to the meta-analysis of cold severity during therapy and no significant difference from placebo was seen.In laboratory studies, differing methods of artificial transmission of virus to vitamin C or placebo treated volunteers in residential experiments gave different results. Volunteers infected by nasal installation showed small or no benefit from vitamin C, whereas a group who were infected more naturally, reported less severe symptom severity scores (p = 0.04). REVIEWERS' CONCLUSIONS: The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and/or cold environments. Also, the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms. The trials in which vitamin C was introduced at the onset of colds as therapy did not show any benefit in doses up to 4 grams daily, but one large trial reported equivocal benefit from an 8 gram therapeutic dose at onset of symptoms.

Administration, Oral↗
PubMed2002

Characterization of RFLP probe sequences for gene discovery and SSR development in Sorghum bicolor (L.) Moench.

In this study, we collected and analyzed DNA sequence data for 789 previously mapped RFLP probes from Sorghum bicolor (L.) Moench. DNA sequences, comprising 894 non-redundant contigs and end sequences, were searched against three GenBank databases, nucleotide (nt), protein (nr) and EST (dbEST), using BLAST algorithms. Matching ESTs were also searched against nt and nr. Translated DNA sequences were then searched against the conserved domain database (CDD) to determine if functional domains/motifs were congruent with the proteins identified in previous searches. More than half (500/894 or 56%) of the query sequences had significant matches in at least one of the GenBank searches. Overall, proteins identified for 148 sequences (17%) were consistent among all searches, of which 66 sequences (7%) contained congruent coding domains. The RFLP probe sequences were also evaluated for the presence of simple sequence repeats (SSRs) and 60 SSRs were developed and assayed in an array of sorghum germplasm comprising inbreds, landraces and wild relatives. Overall, these SSR loci had lower levels of polymorphism ( D = 0.46, averaged over 51 polymorphic loci) compared with sorghum SSRs that were isolated by library hybridization screens ( D = 0.69, averaged over 38 polymorphic loci). This result was probably due to the relatively small proportion of di-nucleotide repeat-containing markers (42% of the total SSR loci) obtained from the DNA sequence data. These di-nucleotide markers also contained shorter repeat motifs than those isolated from genomic libraries. Based on BLAST results, 24 SSRs (40%) were located within, or near, previously annotated or hypothetical genes. We determined the location of 19 of these SSRs relative to putative coding regions. In general, SSRs located in coding regions were less polymorphic ( D = 0.07, averaged over three loci) than those from gene flanking regions, UTRs and introns ( D = 0.49, averaged over 16 loci). The sequence information and SSR loci generated through this study will be valuable for application to sorghum genetics and improvement, including gene discovery, marker-assisted selection, diversity and pedigree analyses, comparative mapping and evolutionary genetic studies.

Journal Article↗
PubMed2002

High-throughput mass-directed parallel purification incorporating a multiplexed single quadrupole mass spectrometer.

We report on the development of a parallel HPLC/MS purification system incorporating an indexed (i.e., multiplexed) ion source. In the method described, each of the flow streams from a parallel array of HPLC columns is directed toward the multiplexed (MUX) ion source and sampled in a time-dependent, parallel manner. A visual basic application has been developed and monitors in real-time the extracted ion current from each sprayer channel. Mass-directed fraction collection is initiated into a parallel array of fraction collectors specific for each of the spray channels. In the first embodiment of this technique, we report on a four-column semipreparative parallel LC/MS system incorporating MUX detection. In this parallel LC/MS application (in which sample loads between 1 and 10 mg on-column are typically made), no cross talk was observed. Ion signals from each of the channels were found reproducible over 192 injections, with interchannel signal variations between 11 and 17%. The visual basic fraction collection application permits preset individual start collection and end collection thresholds for each channel, thereby compensating for the slight variation in signal between sprayers. By incorporating postfraction collector UV detection, we have been able to optimize the valve-triggering delay time with precut transfer tubing between the mass spectrometer and fraction collectors and achieve recoveries greater than 80%. Examples of the MUX-guided, mass-directed fraction purification of both standards and real library reaction mixtures are presented within.

Chromatography, High Pressure Liquid↗
PubMed2000

Minilaparotomy and endoscopic techniques 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 has been searched. 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). REVIEWER'S 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.

Female↗
PubMed2004

Iodine supplementation for preventing iodine deficiency disorders in children.

BACKGROUND: Iodine deficiency is the main cause of potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. OBJECTIVES: To assess the effects of iodine supplementation overall, and of different forms and dosages of iodine supplementation separately, in the prevention of iodine deficiency disorders in children. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE and reference lists, databases of ongoing trials and the Internet were searched. Date of latest search: October 2003. SELECTION CRITERIA: We included randomised controlled trials and prospective controlled trials not using randomisation of iodine supplementation in children living in areas of iodine deficiency. DATA COLLECTION AND ANALYSIS: Two reviewers did the initial data selection and quality assessment of trials independently. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. MAIN RESULTS: Twenty-six prospective controlled trials were related to our question, assessing a total of 29613 children. Twenty of them were classified as being of low quality, six of moderate quality. Most studies used iodised oil as a supplement, but other supplements were also used. The intervention groups were compared to a non-supplemented control group, different doses or different forms of iodine supplementation. There was a clear tendency towards goitre reduction with iodine supplementation; this was significant in several studies. Significant differences in physical development were not seen, except in one study. Results for differences in cognitive and psychomotor measures were mixed, with only few studies showing a positive intervention effect. One study suggested that infant mortality was lowered after iodine supplementation. Most studies showed a significant increase in urinary iodine excretion and levels recommended by the WHO were reached in most cases after supplementation. Thyroid-stimulating hormone (TSH) levels were significantly reduced in one study. In 1.8% of the children investigated, adverse effects were found, most of them were minor and transient. REVIEWERS' CONCLUSIONS: Despite most of the included studies being of low quality, the results suggest that iodine supplementation, especially iodised oil, is an effective means of decreasing goitre rates and improving iodine status in children. Indications of positive effects on physical and mental development and mortality were seen, although results were not always significant. Adverse effects were generally minor and transient. Insufficient evidence was available on non-oil supplements. High quality controlled studies investigating relevant long term outcome measures are needed to address the question of the best form of iodine supplementation in different population groups and settings.

Child↗
PubMed1995

Derivation of vaccines from mimotopes. Immunologic properties of human hepatitis B virus surface antigen mimotopes displayed on filamentous phage.

We have previously reported the identification, using human immune sera, of mimotopes of human hepatitis B virus surface Ag (HBsAg) displayed on filamentous phage. To test if these mimotopes could be useful in developing a vaccine against the human hepatitis B virus (HBV), we have compared the humoral immune response of animals immunized either with a recombinant HBsAg vaccine, or with mimotopes. Immunogens were prepared by fusing the mimotopes on different carrier molecules (phage coat protein pIII and pVIII, recombinant human H ferritin, HBV core peptide) and by synthesizing multiple antigenic peptides carrying the mimotopes' amino acid sequences. These immunogens were injected into mice and rabbits and sera were collected and tested for the presence of HBsAg-specific Abs. Our data confirm that mimotopes can induce a humoral immune response resembling that induced by the original Ag, and HBsAg mimotopes displayed on phage prove to be the best immunogens, inducing the most reproducible and potent immunization. Mimotopes that react as HBV subtype-specific Ags do not show this specificity as immunogen and induce a nonsubtype-restricted response. Furthermore, mimotopes displayed on phage elicit a strong response to HBsAg in a strain of mouse reported to show a low response to it. These results indicate that mimotopes identified from random peptide libraries through utilizing human immune sera could be important leads for the derivation of new vaccines.

Amino Acid Sequence↗
PubMed2006

Oral antibiotics versus parenteral antibiotics for severe pneumonia in children.

BACKGROUND: Acute respiratory infection (ARI) is one of the leading causes of morbidity and mortality in children under five years of age in developing countries. When hospitalisation is required, the usual practice includes administering parenteral antibiotics if a bacterial infection is suspected. This has disadvantages as it causes pain and discomfort to the children, which may lead to treatment refusal or reduced compliance. It is also associated with needle-related complications. In some settings this equipment is in short supply or unavailable necessitating transfer of the child, which increases risks and healthcare costs. OBJECTIVES: To determine the equivalence in effectiveness and safety of oral antibiotic compared to parenteral antibiotic therapies in the treatment of severe pneumonia in children between three months and five years of age. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005); MEDLINE (January 1966 to July 2005); EMBASE (January 1990 to July 2005) and LILACS (February 2005). SELECTION CRITERIA: The review included published or unpublished randomised controlled trials (RCTs) and quasi-RCTs comparing any oral antibiotic therapy with any parenteral antibiotic therapy for the treatment of severe pneumonia in children from three months to five years of age. DATA COLLECTION AND ANALYSIS: The search yielded more than 1300 titles. Only three studies met all criteria for eligibility. One of the identified trials is yet to publish its results. We did not perform a meta-analysis because of clinical heterogeneity of therapies compared in the included trials. MAIN RESULTS: Campbell 1988 compared oral co-trimoxazole versus intramuscular procaine penicillin followed by oral ampicillin in 134 children. At the seventh day of follow up, treatment failure occurred in 6/66 (9.1%) in the oral co-trimoxazole group and 7/68 (10.2%) in the combined-treatment group. The risk difference was -0.01% (95% confidence interval (CI) -0.11 to 0.09). The APPIS Group 2004 evaluated 1702 patients comparing oral amoxicillin versus intravenous penicillin for two days followed by oral amoxicillin. After 48 hours, treatment failure occurred in 161/845 (19%) in the amoxicillin group and 167/857 (19%) in the parenteral penicillin group. The risk difference was -0.4% (95% CI -4.2 to 3.3). The authors reported similar recovery in both groups at 5 and 14 days. AUTHORS' CONCLUSIONS: Oral therapy appears to be an effective and safe alternative to parenteral antibiotics in hospitalised children with severe pneumonia who do not have any serious signs or symptoms.

Administration, Oral↗