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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↗
PubMed1999

Cloning and expression of a novel chicken sulfotransferase cDNA regulated by GH.

We have used mRNA differential display to compare gene expression in normal and GH receptor-deficient dwarf chickens, and report here the characterization of one differentially expressed gene, which shows significant sequence identity to the sulfotransferase gene family. Partial cDNA clones were isolated from a chicken liver cDNA library and an additional sequence was obtained using 5' rapid amplification of cDNA ends. A complete cDNA probe hybridizes to three transcripts (2.4, 2.0 and 1.45 kb) on Northern blots of chicken liver RNA, which differ in the length of the 3' untranslated region. All three transcripts are expressed at higher levels in normal vs dwarf chickens, as expected for a GH-regulated gene. The expression of this sulfotransferase mRNA was also detected in skeletal muscle, but not other tissues. The administration of GH to chickens increased the hepatic expression within 1 h, suggesting this sulfotransferase could be directly regulated by GH. Sulfotransferase activity, using estradiol or corticosterone as substrate, is detected in cells transfected with an expression vector containing the full-length cDNA. The sequence of this sulfotransferase does not show significant similarity with any subfamily of the sulfotransferases and its endogenous substrate is presently unknown. However, we speculate that GH activation of sulfotransferase activity could play a role in reducing concentrations of growth-antagonistic steroid hormones in GH target tissues. These results demonstrate the usefulness of differential display in this model system to identify genes that play a role in mediating GH action.

Amino Acid Sequence↗
PubMed1997

Blunt trauma and operative care in microgravity: a review of microgravity physiology and surgical investigations with implications for critical care and operative treatment in space.

BACKGROUND: The assembly of the International Space Station in a low earth orbit will soon become a reality. The National Aeronautics and Space Administration envisions inhabited lunar bases and staffed missions to Mars in the future. Increasing numbers of astronauts, construction of high-mass structures, increased extra-vehicular activity, and prolonged if not prohibitive medical evacuation times to earth underscore the need to address requirements for trauma care in nonterrestrial environments. STUDY DESIGN: A search was carried out to review the relevant literature in the MEDLINE and SPACELINE databases. All related Technical, Corporate, and Flight Test Reports in the KRUG Life Sciences corporate library were also reviewed. Bibliographies of all articles were then reviewed from these papers to identify additional pertinent literature. Senior Russian investigators reviewed the Russian literature and translated Russian publications when appropriate. Personal communication and discussion with active microgravity investigators and ongoing microgravity research supplemented published reports. RESULTS: A large volume of data exist to document the multiple detrimental physiologic effects of microgravity exposure on human physiology. Organs systems such as cardiovascular, neurohumoral, immune, hematopoetic, and musculoskeletal systems may be particularly affected. These physiologic changes suggest an impaired ability to withstand major systemic trauma. Observational data also suggest adverse changes in numerous aspects of response to wounding and injury, and in areas such as the behavior of hemorrhage, microbiologic flora, and wound healing. In addition to an increased volume of ongoing and anticipated basic science research in microgravity physiology, preliminary studies of clinical diagnosis and therapy have been carried out in microgravity and microgravity laboratories. The feasibility of a wide range of ancillary critical care techniques has been verified in the parabolic flight model of microgravity. Although Russian investigators first performed laparotomies on rabbits in parabolic flight in 1967, only recently have American investigators demonstrated the reproducible feasibility of open and endoscopic surgical procedures under general anesthetic in animal models in a microgravity environment. CONCLUSIONS: With appropriate instrumentation and personnel, the majority of resuscitative and surgical interventions required to stabilize a severely injured astronaut are feasible in a microgravity environment. Onboard limitations in mass, volume, and power that are ever present in any spacecraft design will limit the realistic capabilities of the medical system. Standard proved and tested trauma and operative management protocols will constitute the basis for extra-terrestrial care. Surgeons should familiarize themselves with the microgravity environment and remain active in planning trauma care for the continued exploration of space.

Aerospace Medicine↗
PubMed1999

Selection of a C5a receptor antagonist from phage libraries attenuating the inflammatory response in immune complex disease and ischemia/reperfusion injury.

A C5a-receptor antagonist was selected from human C5a phage display libraries in which the C terminus of des-Arg74-hC5a was mutated. The selected molecule is a competitive C5a receptor antagonist in vitro and in vivo. Signal transduction is interrupted at the level of G-protein activation. In addition, the antagonist does not cause any C5a receptor phosphorylation. Proinflammatory properties such as chemotaxis or lysosomal enzyme release of differentiated U937 cells, as well as C5a-induced changes in intracellular Ca2+ concentration of murine peritoneal macrophages, are inhibited. The in vivo efficacy was evaluated in three different animal models of immune complex diseases in mice, i.e., the reverse passive Arthus reaction in the peritoneum, skin, and lung. The i.v. application of the C5a receptor antagonist abrogated polymorphonuclear neutrophil accumulation in peritoneum and markedly attenuated polymorphonuclear neutrophil migration into the skin and the lung. In a model of intestinal ischemia/reperfusion injury, i.v. administration of the C5a receptor antagonist decreased local and remote tissue injury: bowel wall edema and hemorrhage as well as pulmonary microvascular dysfunction. These data give evidence that C5a is an important mediator triggering the inflammatory sequelae seen in immune complex diseases and ischemia/reperfusion injury. The selected C5a receptor antagonist may prove useful to attenuate the inflammatory response in these disorders.

Amino Acid Substitution↗
PubMed2003

Growth promoting effect of thioredoxin on intestinal epithelial cells.

Paneth cells are located at the bases of intestinal crypts, and their cytoplasmic granules contain large amounts of zinc. We previously showed that administration of diphenylthiocarbazone (dithizone), a zinc chelater, to rats induced the selective death of Paneth cells. This was followed by a transient wave of epithelial cell proliferation in the entire crypts. In the study described here, we again applied this experimental model in an attempt to identify novel growth-promoting factors in the small intestine. Male Wistar rats were injected with dithizone and killed 6 hr later. Messenger RNAs (mRNAs) were extracted from the terminal ileum for the construction of a cDNA library. This library was then transfected into the human intestinal cell line Caco-2, and the cells that continued to grow in the medium containing only 1% FBS were cloned. One of the cDNA sequences identified from those transfection experiments was the full-length rat thioredoxin (TRX) gene. To confirm the growth-promoting effect of this cDNA, we transfected it into Caco-2 cells again. These clones proliferated in the medium containing only 1% FBS, while the control clones failed to show any growth. Transient oxidative stress exerted by the addition of oxidative reagents diamide and hydrogen peroxide partially suppressed the growth of TRX-transfected cells. Northern hybridization analysis revealed that TRX expression in rat ileum after dithizone treatment was altered in accordance with intestinal epithelial regeneration in the crypts. Single-cell RT-PCR also showed TRX mRNA expression in Paneth cells. These studies identify rat thioredoxin as a growth-promoting factor for intestinal epithelial cells.

Animals↗
PubMed2004

Sucrose for analgesia in newborn infants undergoing painful procedures.

BACKGROUND: Management of pain for neonates is less than optimal. The administration of sucrose with and without non-nutritive sucking (pacifiers) has been the most frequently studied non-pharmacological intervention for relief of procedural pain in neonates. OBJECTIVES: To determine the efficacy, effect of dose, and safety of sucrose for relieving procedural pain as assessed by validated individual pain indicators and composite pain scores. SEARCH STRATEGY: Standard methods as per the Neonatal Collaborative Review Group. A MEDLINE search was carried out for relevant randomized controlled trials (RCTs) published from January 1966 - March 2004, EMBASE from 1980-2004 and search of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004). Key words and (MeSH) terms included infant/newborn, pain, analgesia and sucrose. Language restrictions were not imposed. Bibliographies, personal files, the most recent relevant neonatal and pain journals and recent major pediatric pain conference proceedings were searched manually. Unpublished studies, or studies reported only as abstracts, were not included. Additional information from published studies was obtained. SELECTION CRITERIA: RCTs in which term and/or preterm neonates (postnatal age maximum of 28 days after reaching 40 weeks corrected gestational age) received sucrose via oral syringe, NG-tube, dropper or pacifier for procedural pain from heel lance or venepuncture. In the control group, water, pacifier or positioning/containing were used. Studies in which the painful stimulus was circumcision were excluded. DATA COLLECTION AND ANALYSIS: Trial quality was assessed according to the methods of the Neonatal Collaborative Review Group. Quality measures included blinding of randomization, blinding of intervention, completeness of follow up and blinding of outcome measurement. Data were abstracted and independently checked for accuracy by the three investigators. STATISTICAL ANALYSIS: The statistical package (RevMan 4.2) of the Cochrane Collaboration was used. For meta-analysis, a weighted mean difference (WMD) with 95% confidence intervals (CI) using the fixed effects model was reported for continuous outcome measures. MAIN RESULTS: Forty-four studies were identified for possible inclusion in this review. Seven studies reported only as abstracts, and sixteen additional studies were excluded, leaving 21 studies (1,616 infants) included in this review. Sucrose in a wide variety of dosages was generally found to decrease physiologic (heart rate) and behavioural (the mean percent time crying, total cry duration, duration of first cry, and facial action) pain indicators and composite pain scores in neonates undergoing heel stick or venepuncture. When pain scores (Premature Infant Pain Profiles) were pooled across 3 studies (Gibbins 2001; Johnston 1999a; Stevens 1999), they were significantly reduced in infants who were given sucrose (dose range 0.012 g to 0.12 g) compared to the control group, [WMD -1.64 (95% CI -2.47,- 0.81); p = 0.0001] at 30 seconds and [WMD -2.05, (95% CI -3.08, -1.02); p = 0.00010] at 60 seconds after heel lance. When results for change in heart rate were pooled for two studies (Haouari 1995, Isik 2000), there were no significant differences between changes in heart rate for infants given sucrose (dose range 0.5 g to 0.6 g) compared to the control group, [WMD 0.90 (95% CI -5.81, 7.61); p = 0.8] at one minute and [WMD -6.20 (95% CI -15.27, 2.88); p = 0.18] at three minutes after heel lance. REVIEWERS' CONCLUSIONS: Sucrose is safe and effective for reducing procedural pain from single painful events (heel lance, venepuncture). There was inconsistency in the dose of sucrose that was effective (dose range of 0.012 g to 0.12 g), and therefore an optimal dose to be used in preterm and/or term infants could not be identified. The use of repeated administrations of sucrose in neonates needs to be investigated as does the use of sucrose in combination with other behavioural (e.g., facilitated tucking, kangaroo care) and pharmacologic (e.g., morphine, fentanyl) interventions. Use of sucrose in neonates who are of very low birth weight, unstable and/or ventilated also needs to be addressed.

Analgesics↗
PubMed2000

Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants.

BACKGROUND: Preterm infants being extubated following a period of intermittent positive pressure ventilation via an endotracheal tube are at risk of developing respiratory failure as a result of apnea, respiratory acidosis and hypoxia. Nasal continuous positive airway pressure appears to stabilise the upper airway, improve lung function and reduce apnea and may therefore have a role in facilitating extubation in this population. OBJECTIVES: In preterm infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation (IPPV), does management with nasal continuous positive airways pressure (NCPAP) lead to an increased proportion remaining free of additional ventilatory support, compared to extubation directly to headbox oxygen? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline, previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language and expert informant searches in the Japanese language by Prof. Ogawa. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which NCPAP (delivered by any method) was compared with headbox oxygen for post-extubation care were included. Methodological quality was assessed independently by the two authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two authors. Prespecified subgroup analysis to determine the impact of different levels of NCPAP, differences in duration of IPPV and use of aminophylline were also performed using the same package. MAIN RESULTS: Nasal CPAP, when applied to preterm infants being extubated following IPPV, reduces the incidence of adverse clinical events (apnea, respiratory acidosis and increased oxygen requirements) indicating the need for additional ventilatory support. A reduction in the incidence of chronic lung disease at 28 days of age is also seen in the group extubated to NCPAP. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: nasal CPAP is effective in preventing failure of extubation and reducing oxygen use at 28 days of life in preterm infants following a period of endotracheal intubation and IPPV. Implication for research: further definition of the patient gestational age and weight groups in whom these results apply is required. Optimal levels of NCPAP as well as methods of administration remain to be determined.

Humans↗
PubMed1988

Integrated Academic Information Management Systems (IAIMS). Part III. Implementation of Integrated Information Services. Integration across institutions: IAIMS extended.

The technologies contributing to today's information world are profound. Electronic technologies are transforming the way we handle information and the medium used to pursue knowledge. What once seemed beyond reach--that computers, communications, information, and knowledge systems could be merged harmoniously to transmit information via networks--is reality today. The Integrated Academic Information Management System (IAIMS) approach for transfer of biomedical information within a medical center also offers opportunities for networks across institutional lines. The tradition of cooperation and resource sharing among libraries makes them logical facilitators of the emerging, universal information environment. The authors present a course of action based on visions of a new era, realities of the present, and strategies for the future.

Academic Medical Centers↗
PubMed2005

Vitamin K for upper gastrointestinal bleeding in patients with liver diseases.

BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in patients with liver diseases. However, supplementary interventions are often used as well. One of them is vitamin K administration, but it is unknown whether it benefits or harms patients with liver disease and upper gastrointestinal bleeding. OBJECTIVES: To assess the beneficial and harmful effects of vitamin K for patients with liver disease and upper gastrointestinal bleeding. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (February 2004), which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1988 to March 2004), and LILACS (1982 to March 2004). Additional randomised trials were sought from the reference lists of the trials found and reviews identified by the electronic searches. SELECTION CRITERIA: We intended to include randomised clinical trials. DATA COLLECTION AND ANALYSIS: We intended to summarise data by standard Cochrane Collaboration methodologies. MAIN RESULTS: We could not find any randomised trials on vitamin K for upper gastrointestinal bleeding in patients with liver diseases. AUTHORS' CONCLUSIONS: We were unable to identify randomised trials on the safety and efficacy of vitamin K for upper gastrointestinal bleeding in patients with liver diseases. The effects of vitamin K need to be tested in randomised clinical trials.

Antifibrinolytic Agents↗
PubMed2002

Novel potent antagonists of human neuropeptide Y-Y5 receptor. Part 4: tetrahydrodiazabenzazulene derivatives.

Novel tetrahydrodiazabenzazulene derivatives, designed from the lead compound 1 discovered by screening of our in-house chemical library, were prepared and found to be potent neuropeptide Y-Y5 (NPY-Y5) receptor antagonists. The structure-activity relationships are described. Compounds 7 (FR240662) and 16 (FR252384) were especially attractive owing to their high affinities for the NPY-Y5 receptors, oral absorption and permeability to brain.

Administration, Oral↗
PubMed2003

Enhanced expression of beta-thymosin mRNA in the ovary of GnRH analog or estradiol-17beta-treated paradise fish, Macropodus opercularis.

cDNA clones were isolated as expressed sequence tags (ESTs) from the ovarian cDNA library of Macropodus opercularis. The EST sequences showed similarity with many housekeeping genes and ribosomal proteins. One of the ESTs showed similarity to beta-thymosin, a 5-kDa polypeptide expressed under different physiological conditions. The cDNA corresponding to beta-thymosin of M. opercularis is 368 bp in length and codes for a putative polypeptide of 42 amino acids. Multiple alignment of the deduced amino acid sequence showed 61% similarity with piscine beta-thymosins and 56% similarity with mammalian beta-thymosins. Administration of a gonadotropin releasing hormone analog or estradiol-17beta induced an increase in the gonadosomatic index, oocyte diameter and also enhanced expression of beta-thymosin m-RNA in the recrudizing ovary. This report indicates that both GnRH analog and E(2) might induce similar pathways for the differentiation of ovarian cells for the maturation of oocytes.

Amino Acid Sequence↗
PubMed1993

A novel aldehyde reductase with activity towards a metabolite of aflatoxin B1 is expressed in rat liver during carcinogenesis and following the administration of an anti-oxidant.

In contrast with fractions from control animals, an aldehyde reductase, which catalyses the reduction of aflatoxin B1-dihydrodiol, in the dialdehyde form at physiological pH values, to aflatoxin B1-dialcohol, is expressed in cytosolic fractions prepared from rat livers bearing pre-neoplastic lesions, or following treatment with the anti-oxidant ethoxyquin. This expression parallels the development of resistance to the toxin. Unlike the aflatoxin B1-dihydrodiol, the dialcohol does not undergo binding to protein. This enzyme activity could play a mechanistic role in hepatocarcinogenesis and chemoprotection in the rat. Correlated n.m.r. and m.s. spectra are provided in Supplementary Publication SUP 50171 (3 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1993) 289, 9.

Aflatoxin B1↗
PubMed1993

Regulation of two members of the steroid-inducible cytochrome P450 subfamily (3A) in rats.

Monoclonal antibodies have been successfully isolated which are isozyme-specific for cytochrome P450p (3A1) or P4501 (3A2), two members of the steroid-inducible cytochrome P450 subfamily exhibiting 89% amino acid sequence homology, and these antibodies show less than 5% cross-reaction with 11 other cytochromes P450 (P450a-P450k). A library of 28 purified monoclonal antibodies was established and characterized as to epitope specificity. Appropriate antibodies were selected and utilized to investigate the regulation of expressed cytochrome P450p and P4501 proteins as a function of age, sex, and treatment of rats with various inducing agents. Cytochrome P450p is not detectable in hepatic microsomes from untreated immature or adult male and female rats. Following dexamethasone treatment, expression of cytochrome P450p is observed in all groups with the levels reaching 30-37% of total microsomal cytochrome P450. Administration of other inducers such as pregnenolone 16 alpha-carbonitrile also yield enhanced levels of cytochrome P450p. Measurable amounts of constitutive cytochrome P4501 were detected in hepatic microsomes from immature and adult males as well as immature females but not in adult females. Cytochrome P4501 expression is inducible by dexamethasone in immature rats of both sexes and adult males, although dexamethasone is more effective as an inducer of cytochrome P450p than cytochrome P4501. Hence, not only is cytochrome P4501 protein expressed in immature animals of both sexes, it is also inducible in both sexes. These studies show that constitutive expression and induction of steroid-inducible cytochrome P450s may vary as a function of age.

Age Factors↗
PubMed2006

[What are the epidemiologic data in regard to episiotomy?].

OBJECTIVES: Description of episiotomy rates and current trends in France. Description of episiotomy variation according to medical situations and inter or intra country in obstetrical variation practices. MATERIALS AND METHODS: We analyzed the AUDIPOG Perinatal network. The medical literature review used Pubmed and the Cochrane Library databases. RESULTS: The episiotomy rate has decreased, in France, from 1996-97 to 2002-03. The percentage of episiotomies among nulliparae is 68% and 31% among multiparae. The episiotomy rate increases with maternal age. The risk of perineal traumatism is variable according to women's ethnic background. The risk of episiotomy is linked to obstetrical situations. It remains an international variation of the global episiotomy rate. However, national rates include regional and hospital variations. French data do not find important variations according to hospital administrative status. We found inter professional variations in the literature. CONCLUSION: Episiotomy is a frequent obstetrical intervention in the world and in France. This intervention is linked with variations in obstetrical practice and with other medical factors at the time of delivery. We note a reduction of episiotomy rate in western countries but this reduction is not the same in these countries.

Adult↗
PubMed2005

Base administration or fluid bolus for preventing morbidity and mortality in preterm infants with metabolic acidosis.

BACKGROUND: Metabolic acidosis in the early newborn period is associated with adverse outcomes in preterm infants. The most commonly used strategies to correct metabolic acidosis are intravascular infusion of base, for example sodium bicarbonate, and intravascular infusion of a fluid bolus, usually a crystalloid or colloid solution. OBJECTIVES: To evaluate the available evidence from randomised controlled trials that either infusion of base, or of a fluid bolus, reduces mortality and adverse neurodevelopmental outcomes in preterm infants with metabolic acidosis. SEARCH STRATEGY: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), MEDLINE (1966 - January 2005), EMBASE (1980 - January 2005), CINAHL (1982 - January 2005). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that evaluated the following treatments for preterm infants with metabolic acidosis:1. Infusion of base versus no treatment.2. Infusion of fluid bolus versus no treatment.3. Infusion of base versus fluid bolus. DATA COLLECTION AND ANALYSIS: We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two authors, and synthesis of data using relative risk and risk difference. MAIN RESULTS: We found two small randomised controlled trails that fulfilled the eligibility criteria (Corbet 1977; Dixon 1999). Corbet 1977 compared treating infants with sodium bicarbonate infusion (N = 30) versus no treatment (N = 32) and did not find evidence of an effect on mortality [Relative risk 1.39 (95% confidence interval 0.72 to 2.67), risk difference 0.12 (95% confidence interval -0.12 to 0.36)], or in the incidence of intra/peri-ventricular haemorrhage [Relative risk 1.24 (95% confidence interval 0.47 to 3.28), risk difference 0.05 (95% confidence interval -0.16 to 0.25)]. Dixon 1999 compared treatment with sodium bicarbonate (N = 16) versus fluid bolus (N = 20). The primary outcome assessed was arterial blood pH/base excess two hours after the intervention. Other clinical outcomes were not reported. Neither trial assessed longer term neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised controlled trials to determine whether infusion of base or fluid bolus reduces morbidity and mortality in preterm infants with metabolic acidosis. Further large randomised trials are needed.

Acidosis↗
PubMed2010

AAV's anatomy: roadmap for optimizing vectors for translational success.

Adeno-Associated Virus based vectors (rAAV) are advantageous for human gene therapy due to low inflammatory responses, lack of toxicity, natural persistence, and ability to transencapsidate the genome allowing large variations in vector biology and tropism. Over sixty clinical trials have been conducted using rAAV serotype 2 for gene delivery with a number demonstrating success in immunoprivileged sites, including the retina and the CNS. Furthermore, an increasing number of trials have been initiated utilizing other serotypes of AAV to exploit vector tropism, trafficking, and expression efficiency. While these trials have demonstrated success in safety with emerging success in clinical outcomes, one benefit has been identification of issues associated with vector administration in humans (e.g. the role of pre-existing antibody responses, loss of transgene expression in non-immunoprivileged sites, and low transgene expression levels). For these reasons, several strategies are being used to optimize rAAV vectors, ranging from addition of exogenous agents for immune evasion to optimization of the transgene cassette for enhanced therapeutic output. By far, the vast majority of approaches have focused on genetic manipulation of the viral capsid. These methods include rational mutagenesis, engineering of targeting peptides, generation of chimeric particles, library and directed evolution approaches, as well as immune evasion modifications. Overall, these modifications have created a new repertoire of AAV vectors with improved targeting, transgene expression, and immune evasion. Continued work in these areas should synergize strategies to improve capsids and transgene cassettes that will eventually lead to optimized vectors ideally suited for translational success.

Cystic Fibrosis↗
PubMed1987

Effect of estrogen on the expression of mRNAs of different actin isoforms in immature rat uterus. Cloning of alpha-smooth muscle actin message.

Cytoplasmic beta- and gamma-actin mRNAs as well as smooth muscle actin mRNAs have been shown to be transiently increased in rat uterus after treatment with the steroid hormone estradiol. A clone isolated as an estradiol-induced message from a lambda-gt10 cDNA library prepared from the mRNA of estrogen-stimulated immature rat uterus was identified as alpha-smooth muscle actin. A single-stranded RNA probe composed mainly of the 3'-untranslated region of this clone, as well as DNA probes derived from the 3'-untranslated regions of other actin genes, were used to study the induction kinetics of different actin isoforms in rat uterus after being stimulated by estradiol. The beta- and gamma-cytoskeletal actins showed an induction peak at 4 h after estradiol administration with 1.4- and 1.8-fold increases, respectively. The smooth muscle actin was maximally increased 2.1-fold at 8-12 h. Messages of alpha-skeletal and alpha-cardiac actins were neither expressed nor induced by estradiol in this tissue. The different induction kinetics of the cytoplasmic and smooth muscle actins suggest that they are regulated by different mechanisms and possibly in different cell types of the uterus.

Actins↗
PubMed2003

Selenium supplementation to prevent short-term morbidity in preterm neonates.

BACKGROUND: Selenium is an essential trace element and component of a number of selenoproteins including glutathione peroxidase, which has a role in protecting against oxidative damage. Selenium is also known to play a role in immunocompetence. Blood selenium concentrations in newborns are lower than those of their mothers and lower still in preterm infants. In experimental animals low selenium concentrations appear to increase susceptibility to oxidative lung disease. In very preterm infants low selenium concentrations have been associated with an increased risk of chronic neonatal lung disease and retinopathy of prematurity. OBJECTIVES: To assess the benefits and harms of selenium supplementation in preterm or very low birthweight infants. SEARCH STRATEGY: Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), MEDLINE (1966-May 2003), and Embase (1980-May 2003). The reference lists of recent trials were also searched and abstracts from the Society for Pediatric Research from 1990 were hand-searched. SELECTION CRITERIA: Randomised controlled trials which compared selenium supplementation either parenterally or enterally with placebo or nothing from soon after birth in preterm or very low birthweight infants and which reported clinical outcomes were considered for the review. DATA COLLECTION AND ANALYSIS: Data on selenium supplementation dose, formulation and route of administration; mortality, oxygen requirement at 28 days and 36 weeks post-menstrual age, retinopathy of prematurity, and one or more episodes of sepsis; blood selenium and glutathione peroxidase concentrations at or close to 28 days, were excerpted by both reviewers independently. Data analysis was conducted according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Three eligible trials were identified. Two trials, including one trial with a much larger sample size than the others combined, were from geographical areas with low population selenium concentrations. Meta-analysis of the pooled data showed a significant reduction in the proportion of infants having one or more episodes of sepsis associated with selenium supplementation [summary RR 0.73 (0.57, 0.93); RD -0.10 (-0.17, -0.02); NNT 10 (5.9, 50)]. Supplementation with selenium was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. REVIEWER'S CONCLUSIONS: Supplementing very preterm infants with selenium is associated with benefit in terms of a reduction in one or more episodes of sepsis. Supplementation was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. Supplemental doses of selenium for infants on parenteral nutrition higher than those currently recommended may be beneficial. The data are dominated by one large trial from a country with low selenium concentrations and may not be readily translated to other populations.

Chronic Disease↗