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Compounds blocking mutant huntingtin toxicity identified using a Huntington's disease neuronal cell model.

Neuronal cell death in HD is believed to be largely a dominant cell-autonomous effect of the mutant huntingtin protein. We previously developed an inducible PC12 cell model which expresses an N-terminal huntingtin fragment with an expanded poly Q repeat (N63-148Q) under the control of the tet-off system. In order to evaluate the ability of compounds to protect against mutant huntingtin toxicity in our model, we measured LDH released by dead cells into the medium. We have now screened the library of 1040 compounds from the NINDS Custom Collection as part of a National Institute of Neurological Disorders and Stroke (NINDS) collaborative project. Each positive compound was tested at 3-8 concentrations. Five compounds significantly attenuated mutant huntingtin (htt)-induced LDH release without affecting the expression level of huntingtin and independent of effect on aggregates. We also tested a broad spectrum caspase inhibitor Z-VAD-fmk and previously proposed candidate compounds. This cell model can provide a method to screen potential therapeutic compounds for treating Huntington's disease.

Amino Acid Chloromethyl Ketones↗

Computerization of intraocular lens data.

We have developed a method of computerization to collect intraocular lens research data in a private office practice. More than 30 separate variables are now being collected on all patients, and over 1300 cases have been studied. Information is transcribed from patient records to data sheets and typed directly into an office Teletype 43 terminal, which is connected by an acoustic coupler to an IBM 370-148 computer. The data are stored in a systems library which is equipped with an editing mode for rapid updating and addition of data. It also allows jobs to be submitted and returned through the remote terminal. The system is compatible with a statistical package which allows a wide range of statistical analyses.

Aged↗

A systematic review of training in acute obstetric emergencies.

OBJECTIVE: To describe models used for the training of labour ward personnel in acute obstetric emergencies and to describe how these models have been evaluated and compared. DESIGN: A systematic review of the following databases: Medline, the Cumulative Index of Nursing and Allied Health Literature, Embase, PsycLit, Allied and Alternative Medicine, Education Resources Information Center and the Cochrane Library using a structured search strategy. SETTING: Labour ward. POPULATION OR SAMPLE: Labour ward personnel. INCLUSION CRITERIA: All papers that described or evaluated any form of drill or training in acute obstetric emergencies involving any personnel in a labour ward environment were included. Descriptions of training in developing countries were excluded. METHODS: Papers were classified as editorials or commentaries, papers describing a training programme or papers evaluating a training method. A data collection form was used to extract relevant information by two investigators independently. MAIN OUTCOME MEASURE: Description of training models. RESULTS: Of 44 relevant papers, 22 were classed as editorials or commentaries. Six descriptions of training programmes were found and four papers involved an evaluation of such programmes. All evaluations involved the use of questionnaires to course participants. No studies comparing one form of training with another were found. CONCLUSIONS: With regard to training in acute obstetric emergencies, few training programmes have been described, and even fewer have been evaluated. Training methods need to be developed, described and evaluated; further well-conducted research for this important intervention is urgently required.

Acute Disease↗

Approaches and informatics tools to assist in the integration of similar clinical research questionnaires.

OBJECTIVE: The integration of similar clinical research questionnaires is a complex process that can benefit from informatics approaches and tools that provide a systematic structure for performing mapping and integration. This systematic approach is necessary to address complex issues in integration such as data heterogeneity, differing levels of granularity of questions and responses, and other issues involving semantic differences. Informatics tools and approaches have been successfully applied to various standard clinical vocabulary integration processes but not for questionnaire integration or mapping. METHODS: A systematic approach to questionnaire integration was developed in the context of a collaboration of researchers using Trial/DB, a database designed to support clinical research. This approach was applied to the integration of questionnaires involving breast cancer risk factors from each of three research sites. RESULTS: From 375 questions on the three original questionnaires, we identified 65 concepts that were measured by two or three of the sites. An algorithm was developed and used to formalize the process of mapping questions and answers across the questionnaires. The approach was applied to previously collected data and prospective data in disparate data-base systems to import and merge the data from these three sites into Trial/DB. CONCLUSION: Informatics tools that support a systematic approach to mapping questionnaires can be used throughout the research process from questionnaire integration and creation, legacy data integration to data library maintenance and curation.

Biomedical Research↗

Hybridization selections, using immobilized driver DNA, to enrich for clones unique to a library.

We have developed a technique which allowed us to isolate sex-specific repeats of chickens (Gallus g. domesticus) from a genomic library originally containing one sex-specific repeat clone per 300 clones. Using this plus/minus selection method, we were able to enrich a sub-library in which the sex-specific repetitive clones made up over half of the population (170-fold increase in representation). This enrichment technique used hybridization kinetics to collect clones which are bound (plus selection) or not bound (minus selection) to their respective driver DNAs immobilized on nitrocellulose paper. Plus selections enriched for repetitive sequences and removed from the library most unique sequences as well as vectors containing no inserted sequences. These plus-selected sub-libraries were enriched for repetitive clones, yet still contained sequences representing as little as 10(-4) of the genome. Minus selection removed repetitive sequences shared between the driver and the library. When a plus-selected sub-library was minus selected, the doubly selected sub-library was enriched in repetitive sequences present in the library but not the minus driver.

Animals↗

The influence of follicle size, FSH-enriched maturation medium, and early cleavage on bovine oocyte maternal mRNA levels.

Transcription is arrested in the bovine oocyte within the first few hours of in vitro maturation, thus the stored maternal mRNAs accumulated in the oocyte are essential to sustain development until the Maternal-Zygotic Transition. In vivo matured oocytes have superior blastocyst formation rates than in vitro matured oocytes, suggesting that the mRNA content of these oocytes is of higher quality. To determine which transcripts may be associated with developmental competence, a Suppressive Subtractive Hybridization was performed between oocytes collected by ovariectomy at 6 hr post-LH surge and oocytes from slaughterhouse collected after 6 hr of maturation, resulting in a library enriched in these functionally important mRNAs. The clones were spotted onto a cDNA microarray and transcripts potentially associated with developmental competence were hybridized onto these slides. Hybridizations were performed with transcripts up-regulated in oocytes cultured for 6 hr in the presence or absence of rFSH in vitro, and secondly with transcripts up regulated in early-cleaving embryos versus those at the one-cell stage at 36 hr postfertilization. From these hybridizations, 13 candidates were selected. Their functional association with embryonic competence was validated by measuring their relative transcript levels by quantitative real-time PCR in eight different conditions: oocytes cultured with or without rFSH, early--versus late-cleaving embryos, and oocytes from different follicle sizes (1-3, 3-5, 5-8, and >8 mm of diameter). The gene candidates CCNB2, PTTG1, H2A, CKS1, PSMB2, SKIIP, CDC5L, RGS16, and PRDX1 showed a significant quantitative association with competence compared to BMP15, GDF9, CCNB1, and STK6.

Animals↗

In silico screening of a saturated mutation library of tomato.

A comprehensive mutant population is a basic resource for exploring gene function. We developed an isogenic tomato 'mutation library' in the genetic background of the inbred variety M82. A total of 13 000 M(2) families, derived from EMS (ethyl methane sulfonate) and fast-neutron mutagenesis, were visually phenotyped in the field and categorized into a morphological catalog that includes 15 primary and 48 secondary categories. Currently, 3417 mutations have been cataloged; among them are most of the previously described phenotypes from the monogenic mutant collection of The Tomato Genetics Resource Center, and over a thousand new mutants, with multiple alleles per locus. The phenotypic database indicates that most mutations fall into more than a single category (pleiotropic), with some organs such as leaves more prone to alterations than others. All data and images can be searched and accessed in the Solanaceae Genome Network (SGN) on a site called 'The Genes That Make Tomatoes' (http://zamir.sgn.cornell.edu/mutants/).

Crosses, Genetic↗

Peptide vaccines and peptide libraries.

Synthetic immunogens, containing built-in adjuvanticity, B cell, T helper cell and CTL epitopes or mimotopes, are ideal and invaluable tools to study the immune response with respect to antigen processing and presentation. This serves as a basis for the development of complete and minimal vaccines which do not need large carrier proteins, further adjuvants, liposome formulations or other delivery systems. Combinatorial peptide libraries, either completely random or characterized by one or several defined positions, are useful tools for the identification of the critical features of B cell epitopes and of MHC class I and class II binding natural and synthetic epitopes. The complete activity pattern of an O/Xn library with hundreds of peptide collections, each made up from billions of different peptides, represents the ranking of amino acid residues mediating contact to the target proteins of the immune system. Combinatorial libraries support the design of peptides applicable in vaccination against infectious agents as well as therapeutic tumour vaccines. Using the principle of lipopeptide vaccines, strong humoral and cellular immune responses could be elicited. The lipopeptide vaccines are heat-stable, non-toxic, fully biodegradable and can be prepared on the basis of minimized epitopes by modern methods of multiple peptide synthesis. The lipopeptides activate the antigen-presenting macrophages and B cells and have been recently shown to stimulate innate immunity by specific interaction with receptors of the Toll family.

Animals↗

The NZB X SWR model of lupus nephritis. I. Cross-reactive idiotypes of monoclonal anti-DNA antibodies in relation to antigenic specificity, charge, and allotype. Identification of interconnected idiotype families inherited from the normal SWR and the autoimmune NZB parents.

The incidence of lupus nephritis is low in autoimmune NZB mice, but when they are crossed with normal SWR mice, almost 100% of the female F1 hybrids (SNF1) develop lethal glomerulonephritis. In a previous study we showed that anti-DNA auto-antibodies produced by the SNF1 mice were qualitatively different from those made by the NZB parents with respect to their isotype, charge, and antigenic specificity patterns. Here we studied idiotypic cross-reactions among the 65 monoclonal anti-DNA antibodies that were derived from four NZB and seven SNF1 mice. A library of 15 anti-idiotypic antibodies were prepared by immunizing rabbits with 15 monoclonal anti-DNA antibodies selected from the panel of 65. We identified 10 cross-reactive idiotype (CRI) families among this large collection of autoantibodies. Five of these CRI families were restricted to cationic anti-DNA antibodies that were exclusively of SNF1 origin, and the strongly cross-reacting members were predominantly IgG2b auto-antibodies with the allotype of the normal SWR parent. The cationic anti-DNA CRI families could be grouped into an interrelated cluster called the Id564 cluster. The other five anti-DNA CRI families were not restricted to any particular parental allotype or charge, although two of these CRI were shared exclusively by SNF1-derived autoantibodies and four of these CRI families could also be grouped into an idiotypically interrelated cluster called the Id512 cluster. In the case of seven out of the 10 CRI families, the idiotypic determinants detected were close to the antigen-binding site of the anti-DNA antibodies. The results indicate that the idiotypic repertoire of anti-DNA autoantibodies produced by the SNF1 mice is different from the NZB parents, and potentially pathogenic (cationic) antibodies produced by the SNF1 mice that are encoded by genes from the normal SWR parent can be identified as distinct CRI families. In the accompanying paper we demonstrate the role of these anti-DNA CRI families in the development of lupus nephritis.

Animals↗

Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than one atmosphere absolute (ATA) in a pressure vessel. This technology has been used to treat a variety of diseases and has been described as helping patients who have delayed healing or established non-union of bony fractures. OBJECTIVES: The aim of this review was to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of delayed bony healing and established non-union of bony fractures. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register (to January week 3, 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2003), MEDLINE (OVID 1966 to January week 3, 2004), CINAHL (OVID 1982 to January week 3, 2004), EMBASE (OVID 1980 to February 2004), the locally developed Database of Randomised Controlled Trials in Hyperbaric Medicine (available at www.hboevidence.com) from inception to March 2004, and reference lists of articles. SELECTION CRITERIA: We aimed to include all randomised controlled trials that compared the effect of HBOT with no HBOT (no treatment or sham). DATA COLLECTION AND ANALYSIS: Two authors using standardised forms attempted to extract data independently. MAIN RESULTS: No trials met the inclusion criteria. We excluded one trial that compared HBOT with no treatment because no clinical outcomes were reported. AUTHORS' CONCLUSIONS: This systematic review failed to locate any relevant clinical evidence to support or refute the effectiveness of HBOT for the management of delayed union or established non-union of bony fractures. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of these injuries.

Fracture Healing↗

Getting evidence into practice: the work of the Cochrane Effective Practice and Organization of care Group (EPOC).

Policy makers and continuing educators often face difficult decisions about which educational and quality assurance interventions to provide. Where possible, such decisions are best informed by rigorous evidence, such as that provided by systematic reviews. The Cochrane Collaboration is an international organization that aims to help people make well-informed decisions about health care by preparing, maintaining, and ensuring the accessibility of systematic reviews of the benefits and risks of health care interventions. International collaborative review groups prepare Cochrane reviews for publication in The Cochrane Library, a collection of databases available on CD-ROM and the World Wide Web and updated quarterly. The Cochrane Effective Practice and Organization of Care Group (EPOC) aims to prepare and maintain systematic reviews of professional, financial, organizational, and regulatory interventions that are designed to improve professional practice and the delivery of effective health services. EPOC has 17 reviews and 20 protocols published in Issue 3, 2000, of the Cochrane Library, with further protocols in development. We also have undertaken an overview of previously published systematic reviews of professional behavior change strategies. Our specialized register contains details of over 1,800 studies that fall within the group's scope. Systematic reviews provide a valuable source of information for policy makers and educators involved in planning continuing education and quality assurance initiatives and organizational change. EPOC will attempt to keep the Journal of Continuing Education in the Health Professions informed on an ongoing basis about new systematic reviews that it produces in the area of continuing medical education and quality assurance.

CD-ROM↗

The SBASE protein domain library, release 8.0: a collection of annotated protein sequence segments.

SBASE 8.0 is the eighth release of the SBASE library of protein domain sequences that contains 294 898 annotated structural, functional, ligand-binding and topogenic segments of proteins, cross-referenced to most major sequence databases and sequence pattern collections. The entries are clustered into over 2005 statistically validated domain groups (SBASE-A) and 595 non-validated groups (SBASE-B), provided with several WWW-based search and browsing facilities for online use. A domain-search facility was developed, based on non-parametric pattern recognition methods, including artificial neural networks. SBASE 8.0 is freely available by anonymous 'ftp' file transfer from ftp.icgeb.trieste.it. Automated searching of SBASE can be carried out with the WWW servers http://www.icgeb.trieste.it/sbase/ and http://sbase.abc. hu/sbase/.

Binding Sites↗

In vitro selection of tRNAs for efficient four-base decoding to incorporate non-natural amino acids into proteins in an Escherichia coli cell-free translation system.

Position-specific incorporation of non-natural amino acids into proteins is a useful technique in protein engineering. In this study, we established a novel selection system to obtain tRNAs that show high decoding activity, from a tRNA library in a cell-free translation system to improve the efficiency of incorporation of non-natural amino acids into proteins. In this system, a puromycin-tRNA conjugate, in which the 3'-terminal A unit was replaced by puromycin, was used. The puromycin-tRNA conjugate was fused to a C-terminus of streptavidin through the puromycin moiety in the ribosome. The streptavidin-puromycin-tRNA fusion molecule was collected and brought to the next round after amplification of the tRNA sequence. We applied this system to select efficient frameshift suppressor tRNAs from a tRNA library with a randomly mutated anticodon loop derived from yeast tRNA CCCG Phe. After three rounds of the selection, we obtained novel frameshift suppressor tRNAs which had high decoding activity and good orthogonality against endogenous aminoacyl-tRNA synthetases. These results demonstrate that the in vitro selection system developed here is useful to obtain highly active tRNAs for the incorporation of non-natural amino acid from a tRNA library.

Amino Acids↗

Mouse beta(6) integrin sequence, pattern of expression, and role in kidney development.

Integrins mediate cell-cell and cell-extracellular matrix interactions and play key roles in development. beta(6) integrin expression has been demonstrated in human fetal kidney at a higher level than in the adult, making beta(6) integrin a marker of interest for the study of development of the nephron. The aims of this study were to determine the cDNA sequence for the mouse beta(6) integrin and to characterize beta(6) integrin expression in the developing mouse kidney. Two embryonic mouse kidney cDNA libraries were screened, and the coding region was sequenced. The mouse beta(6) nucleotide coding region sequence shows 82% nucleotide identity to the human sequence. The putative amino acid sequence has 89.5% identity to human beta(6) integrin and contains many conserved domains. By reverse transcription-PCR, beta(6) integrin mRNA expression is very low at 11 d of gestation in the mouse, increases dramatically by E14 and E17 (20-fold, normalized for increases in ss actin), and plateaus by 2 wk of age. beta(6) integrin expression is induced 15- to 20-fold after 5 d in metanephric explant culture. Reverse transcription-PCR of adult rat microdissected nephron segments demonstrates ss(6) integrin mRNA expression in proximal tubule, cortical thick ascending limb, distal nephron segments (inner and outer medullary collecting ducts), and macula densa-containing segments. Lectin-peroxidase and in situ colocalization studies demonstrated expression of ss(6) integrin mRNA in developing proximal tubules and thick ascending limb. Culture of mouse metanephric kidneys with antisense oligonucleotides to beta(6) integrin resulted in inhibition of ureteric bud branching and complete lack of mesenchyme condensation. These studies demonstrate a high homology between the human and mouse beta(6) integrin sequence, a different pattern of expression in the developing mouse kidney compared with the primate kidney, and abnormal metanephric development in culture in the absence of beta(6) integrin. These findings suggest an important role for beta(6) integrin in normal development of the mouse kidney.

Aging↗

A subtracted cDNA library from the zebrafish (Danio rerio) embryonic inner ear.

A database was built that consists of 4694 sequence contigs of approximately 18,000 reads of cDNAs isolated from the microdissected otocysts of zebrafish embryos at 20-30 hour postfertilization, following subtraction with a pool of liver cDNAs from adult fish. These sequences were compared with those of public databanks. Significant similarity were recorded and organized in a relational database at http://www.genoscope.cns.fr/zie. A first group of 2067 sequences correspond to 1428 known zebrafish genes or ESTs present in the Danio rerio section of UniGene. A second group of 302 sequences encode putative proteins that showed significant similarity (50%-100%) with 302 nonzebrafish proteins in the nr databank, a public databank containing an exhaustive nonredundant collection of protein sequences from different species (ftp://ftp.ncbi.nlm.nih.gov/blast/db/nr). The remaining 2325 (49.5%) sequence contigs or singletons showed no significant similarity with sequences available in public databanks. Several genes known to be expressed in the developing inner ear were represented in the present database, in particular genes involved in hair cell differentiation or innervation The occurrence of these genes validates the outcome of this study as the first collection of ESTs preferentially expressed in the zebrafish inner ear during the period of hair cell differentiation and neuroblast delamination from the otic vesicle epithelium. Novel zebrafish genes also involved in these processes are thus likely to be represented among the sequences obtained herein, for which no homology was found in the D. rerio section of UniGene. [The sequence data from this study have been submitted to EMBL under accession nos. AL714032-AL731531].

Animals↗

Chest physiotherapy for preventing morbidity in babies being extubated from mechanical ventilation.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To assess the effects of active chest physiotherapy on babies being extubated from mechanical ventilation for neonatal respiratory failure. SEARCH STRATEGY: The standard search strategy for the Neonatal Review Group was used as outlined in the Cochrane Handbook in the Cochrane Library. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which active chest physiotherapy was compared with non-active techniques (eg positioning and suction alone) or no intervention in the periextubation period. The methodological quality of each trial was assessed by two independent authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors. The data were analysed from 3 trials. Subgroup analysis was performed on different treatment frequencies. MAIN RESULTS: In this review of 3 small trials, 2 of which were carried out 10 & 20 years ago, no clear benefit of periextubation active chest physiotherapy can be seen. Active chest physiotherapy did not significantly reduce the rate of postextubation lobar collapse (RR 0.69;0.33,1.45), though a reduction in the use of reintubation was shown in the overall analysis (RR 0.24;0.08,0.75). Subgroup analysis of different treatment frequencies showed the same effect with more frequent treatment (1 & 2 hourly) but showed a trend to increased lobar collapse, and no reduction in the use of reintubation, with less frequent treatment (4 hourly). There is insufficient information to assess other important short and long term outcomes, including adverse effects. REVIEWER'S CONCLUSIONS: The results of this review do not allow development of clear guidelines for clinical practice. Caution is required when interpreting the possible positive effects of chest physiotherapy of a reduction in the use of reintubation and the trend for decreased post-extubation atelectasis as the numbers of babies studied are small, the results are not consistent across trials, data on safety are insufficient, and applicability to current practice may be limited.

Humans↗

Treatments for secondary postpartum haemorrhage.

BACKGROUND: Secondary postpartum haemorrhage is any abnormal or excessive bleeding from the birth canal occurring between 24 hours and 12 weeks postnatally. In developed countries, two per cent of postnatal women are admitted to hospital with this condition, half of them undergoing uterine surgical evacuation; in developing countries it is a major contributor to maternal death. OBJECTIVES: To evaluate the relative effectiveness and safety of the treatments used for secondary postpartum haemorrhage. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2001), the Cochrane Controlled Trials Register (The Cochrane Library, issue 2, 2001), MEDLINE (back to 1966) and EMBASE (back to 1988). The National Research Register was also searched. The reference lists of trial reports and reviews were searched by hand. Where possible, further sources were sought from the first named authors of the papers identified. SELECTION CRITERIA: All randomised or quasi randomised comparisons between drug therapies, surgical therapies and placebo or no treatment for the management of secondary postpartum haemorrhage occurring between 24 hours and three months following a pregnancy of at least 24 weeks gestation. DATA COLLECTION AND ANALYSIS: Reports of possibly eligible studies were scrutinised by two investigators. The third investigator acted as an advisor/arbitrator. MAIN RESULTS: Of the 45 papers identified, none met the inclusion criteria. REVIEWER'S CONCLUSIONS: No information is available from randomised controlled trials to inform the management of women with secondary postpartum haemorrhage. This topic may have received little attention because it is perceived as being associated with maternal morbidity rather than mortality in developed countries; it is only recently that the extent and importance of postnatal maternal morbidity has been recognised. A well designed randomised controlled trial comparing the various drug therapies for women with secondary postpartum haemorrhage against each other and against placebo or no treatment groups is needed.

Female↗

Transpyloric versus gastric tube feeding for preterm infants.

BACKGROUND: Enteral feeding tubes for preterm infants may be placed in the stomach (gastric tube feeding) or in the upper small bowel (transpyloric tube feeding). There are potential advantages and disadvantages to both routes. OBJECTIVES: In preterm infants who require enteral tube feeding, does feeding via the transpyloric route versus the gastric route improve feeding tolerance, and growth and development, without increasing adverse consequences? SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included electronic searches of MEDLINE and EMBASE (up to December 2001) and of The Cochrane Controlled Trials Register in The Cochrane Library (Issue 3, 2001), and searches of the references in previous reviews including cross references. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing transpyloric with gastric tube feeding in preterm infants. DATA COLLECTION AND ANALYSIS: Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk and weighted mean difference. MAIN RESULTS: Data from eight trials were available. We did not find any evidence of an effect on growth rates: short term weight gain, weighted mean difference -0.7 g/week (95% confidence interval -25.2, 23.8); short term increase in crown heel length, weighted mean difference -0.7 mm/week (95% confidence interval -2.4, 1.0); short term increase in head circumference, weighted mean difference 0.6 mm/wk (95% confidence interval -0.9, 2.1). Longer term growth was reported in one study. There were not any statistically significant differences between the groups in the mean body weight or occipitofrontal head circumference at three months or at six months corrected age. None of the included studies provided data on neurodevelopmental outcomes during infancy or beyond. Transpyloric feeding was associated with a greater incidence of gastro-intestinal disturbance, RR 1.45, 95% CI 1.05, 2.09. There was some evidence that feeding via the transpyloric route increased mortality, RR 2.46, 95% CI 1.36, 4.46; however, the outcomes of the study that contributed most to this finding were likely to have been affected by selective allocation of the less mature and sicker infants to transpyloric feeding. We did not detect any statistically significant differences in the incidence of other adverse events, including necrotising enterocolitis, intestinal perforation, and aspiration pneumonia. REVIEWER'S CONCLUSIONS: We did not find any evidence of benefit, but did find evidence of adverse effects, of transpyloric feeding in preterm infants. Feeding via the transpyloric route cannot be recommended for preterm infants.

Enteral Nutrition↗