SEARCH · Search PubMed

Results for “Library Administration”

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

SourceResearch connectionFrom yearThrough year

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

At least 1,081 records · Page 60Linked to original sources

PubMed1993

Pharmacokinetics and metabolism of vinca alkaloids.

The anti-mitotic vinca alkaloids, vinblastine, vincristine, vindesine and navelbine, are widely used both as single agents and in combination with other antitumour drugs in cancer chemotherapy. Data on clinical pharmacokinetics following intravenous bolus injection, continuous infusion and oral administration show that vinca alkaloids are characterized by a large apparent total distribution volume, rapid total plasma clearance and a long terminal half-life. Faecal excretion is the main elimination route of vinca alkaloids in humans. Urinary excretion of these agents is generally low. Moreover, vinca alkaloid pharmacokinetics are time- and dose-dependent and show large inter- and intraindividual variability. When studied in various in vitro hepatic models (freshly isolated human and animal hepatocytes in suspension and in primary culture, isolated liver perfusion and human hepatic microsomal fractions), the vinca alkaloids were extensively biotransformed into a number of metabolites which have not yet been identified structurally. Incubation of vindesine and vinblastine with a library of human liver microsomal fractions demonstrated the involvement of the human hepatic cytochromes P4503A in the biotransformation of these and probably other vinca alkaloids. This finding is of great importance with regard to possible drug interactions between vinca alkaloids and other drugs administered concurrently in combination cancer chemotherapy.

Biotransformation↗

PubMed2001

Solution-Phase parallel synthesis of 5-carboxamido 1-benzyl-3-(3-dimethylaminopropyloxy)-1H-pyrazoles as activators of soluble guanylate cyclase with improved oral bioavailability.

A lipophilicity constrained library of 5-carboxamido 1-benzyl-3-(3-dimethylaminopropyloxy)-1H-pyrazoles was prepared by solution-phase parallel synthesis with removal of acidic by-products using the strongly basic MP-carbonate resin. Compounds show both activation of soluble guanylate cyclase and inhibition of platelet aggregation. Compound 12 also shows 22% oral bioavailability in rats.

Administration, Oral↗

PubMed2001

Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.

BACKGROUND: Chronic lung disease (CLD) occurs frequently in preterm infants (< 37 weeks gestational age) and has a multifactorial etiology. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increase in compliance and tidal volume and decrease in pulmonary resistance have been documented with use of bronchodilators in short term studies of pulmonary mechanics in infants with CLD. Therefore it is possible that bronchodilators might have a role in the prevention and treatment of CLD. OBJECTIVES: To evaluate the effect of bronchodilators, given prophylactically or as treatment for chronic lung disease, on mortality and other complications of preterm births. SEARCH STRATEGY: The search strategy used to identify studies was according to the guidelines of the Cochrane Neonatal Review Group. Searches were made of MEDLINE 1966 to December 2000, EMBASE 1980 to January 2001, CINAHL 1982 to December 2000, the Cochrane Library Issue 1, 2001, personal files and reference lists of identified trials. The following terms were used: bronchopulmonary dysplasia, chronic lung disease, bronchodilator agents, adrenergic agents, anticholinergic agents, albuterol, aminophylline, atropine, caffeine, clenbuterol, cromakalim, ephedrine, epinephrine, fenoterol, hexoprenaline, ipratropium, isoetharine, isoproterenol, orciprenaline, procaterol, terbutaline, theophylline, tretoquinol. LIMITS: newborn, infant; human, clinical trial or controlled clinical trial, meta analysis, multicenter study or randomised controlled trial. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled clinical trials involving preterm infants. Initiation of bronchodilator therapy had to occur within two weeks of birth for prevention of CLD. For treatment of CLD treatment should have been initiated before discharge from the neonatal unit. The intervention had to include the randomised administration of a bronchodilator either by nebulisation, metered dose inhaler with or without a spacer device, intravenously or orally, versus placebo or no intervention. Eligible studies had to include at least one of the following outcomes: mortality, CLD at 28 days or at 36 weeks corrected GA, number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, any grade of intraventricular haemorrhage, necrotizing enterocolitis (NEC), sepsis and adverse effects of bronchodilators. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration as described in the Cochrane Collaboration handbook. Two investigators (GN, AO) extracted and assessed all data for each study. Any disagreement was resolved by discussion. Relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) are reported for dichotomous outcomes and mean difference (WMD) for continuous data. MAIN RESULTS: One eligible study was found dealing with prevention of CLD; this study used salbutamol and enrolled 173 infants. No eligible studies were found dealing with treatment of CLD. Prophylaxis with salbutamol did not show a statistically significant difference in mortality [RR 1.08 (95% CI 0.50, 2.31); RD 0.01 (95% CI -0.09, 0.11)], CLD (mild, moderate or severe) [RR 1.03 (95% CI 0.78, 1.37); RD 0.02 (95% CI -0.13, 0.17)], need for iv dexamethasone [RR 0.77 (95% CI 0.49, 1.19); RD -0.08 (95% CI -0.22, 0.05)], respiratory infections [RR 0.61 (95% CI 0.27, 1.39); RD -0.06 (95% CI -0.16, 0.04)] or positive blood culture [RR 1.06 (95% CI 0.54, 2.06); RD 0.01 (95% CI -0.10, 0.12)]. There was no statistically significant difference in duration of ventilatory support [MD -1.63 days (95% CI -5.63, 2.37)], duration of oxygen supply [MD -2.82 days (95% CI -11.91, 6.27)] or age of weaning from respiratory support (defined as assisted ventilation or oxygen supplementation) [MD -2.87 days (95% CI -11.28, 5.54)]. No side effects due to salbutamol were commented on in this study. REVIEWER'S CONCLUSIONS: There are insufficient data to reliably assess the use of salbutamol for the prevention of CLD. Further clinical trials are necessary to assess the role of salbutamol or other bronchodilator agents in prophylaxis or treatment of CLD.

Bronchodilator Agents↗

PubMed1986

Effect of androgens on mRNA for a secretory protein of rat dorsolateral prostate and seminal vesicles.

The androgen dependence of a highly abundant mRNA found in the rat dorsolateral prostate and seminal vesicles has been investigated using a complementary DNA clone from a rat dorsal prostate library. The 1.5 kilobase (kb) mRNA codes for a 52 000 Da translation product which is processed to 49 000 Da in the presence of microsomal membranes. This product appears to correspond to the previously described SVS II protein secreted by rat seminal vesicles and can be immunoprecipitated with anti-SVS II antiserum. Dot hybridization assays indicated that the mRNA is abundant in the dorsal and lateral prostate glands and in seminal vesicles but not in the ventral prostate, coagulating gland or other non-accessory sex tissues. Castration of mature male rats reduces the 1.5 kb mRNA 10-fold in the seminal vesicles and 7-fold in the dorsolateral prostate in 9 days. Androgen administration to one-week castrates returned the mRNA level to normal in both tissues within 48 h. The levels of the 1.5 kb mRNA are very similar in the dorsolateral prostate and seminal vesicles at maturity but distinct patterns of developmental regulation of this gene exist in the two tissues. Between 3 and 6 weeks of age, the level of the 1.5 kb mRNA increases approximately 3-fold in the dorsolateral prostate while the increase in the seminal vesicles is more than 600-fold.

Age Factors↗

PubMed1987

Regulation of chicken apolipoprotein B: cloning, tissue distribution, and estrogen induction of mRNA.

Apolipoprotein (apo) B is a major protein component of plasma very low-density and low-density lipoproteins (VLDL and LDL, respectively) and serves as a recognition signal for the cellular binding and internalization of LDL by the apoB/E receptor. In contrast to the situation in mammals, avian apoB is also a component of specialized VLDL particles that are produced by the liver in response to estrogen. These particles transport cholesterol and triglyceride from the liver to the ovary for deposition in egg yolk. We report here the identification and characterization of cDNA clones for chicken apoB and their use in examining the tissue distribution and hormonal regulation of chicken apoB mRNA. The cDNA clones were identified by immunological screening of a phage lambda gt11 library constructed with hen liver mRNA and their identity was supported by sequence comparisons with mammalian apoB. The chicken apoB mRNA is approximately the same size as mammalian apoB mRNA (14 kb), and, as occurs in mammals, is present at high levels in liver and small intestine. Unlike mammals, the chicken apoB mRNA is also found at high levels in the kidney, consistent with previous protein biosynthetic studies. A DNA-excess solution-hybridization assay was used to quantitate apoB mRNA in these tissues and to examine its hormonal regulation. In control roosters the liver and kidney contained 65% and 10%, respectively, as much apoB mRNA as the small intestine. Within 24 h after estradiol administration, apoB mRNA was increased five- to seven-fold in liver but was unchanged in intestine and kidney. The increase in apoB mRNA content and the kinetics of induction parallel hepatic apoB synthesis, indicating that estrogen regulates apoB production through changes in the cellular abundance of apoB mRNA. The apoB mRNA increased rapidly following hormone treatment while the mRNA for another VLDL protein (apoII) showed a lag or slow phase of several hours before significant mRNA accumulation occurred. These data indicate that the liver can respond immediately to estrogen to increase apoB mRNA accumulation, while apoII mRNA accumulation appears to involve additional events or signals which occur slowly and are specific to this gene.

Amino Acid Sequence↗

PubMed1994

Recombinant human Fab to glycoprotein D neutralizes infectivity and prevents cell-to-cell transmission of herpes simplex viruses 1 and 2 in vitro.

Herpes simplex viruses 1 and 2 (HSV-1 and -2) are associated with a number of conditions of varying severity, which are only partially responsive to current therapies. Human antibodies to the viruses offer a potential alternative. We describe here the generation of panels of human monoclonal Fab fragments to HSV-1 and -2 by panning a phage display combinatorial antibody library against whole lysates from the two viruses. Each lysate selected a largely distinct set of Fabs, although all of the Fabs were cross-reactive with both viruses. In a plaque-reduction assay, one Fab neutralized HSV-1 at 0.25 microgram/ml (50% reduction) and HSV-2 at 0.05 microgram/ml. This Fab also inhibited plaque formation when applied to virus-infected monolayers, completely abolishing HSV-2 plaque development at 25 micrograms/ml 72 hr postinfection, indicating the ability of the Fab to prevent cell-to-cell spread of virus. The Fab was shown to recognize viral glycoprotein D and to neutralize virus primarily by a postattachment mechanism. Recombinant Fabs may be useful for topical administration, although whole antibody will probably be required for systemic use.

Amino Acid Sequence↗

PubMed2005

[Controversies about the resuscitation of extremely preterm infants in the delivery room].

OBJECTIVE: To describe the main controversies about resuscitation procedures performed in extremely low birth weight infants in the delivery room. SOURCES OF DATA: Systematic review including articles from MEDLINE, SciELO and Cochrane Library, and abstracts published in national and international proceedings, using the keywords resuscitation, asphyxia, and newborn infant. SUMMARY OF THE FINDINGS: The main controversies concern the oxygenation and ventilation of extremely low birth weight infants. The effects of oxygen concentrations between 21 and 100% need to be addressed. Appropriate inspiratory pressure, lung volume, and positive end-expiratory pressure parameters also need to be established in order to decrease barotrauma and volutrauma. The benefits of nasal continuous positive airway pressure may be determined through randomized clinical trials. On top of that, manual resuscitation devices have to be developed in order to optimize these ventilatory parameters and to reduce lung injury. So far, clinical trials on the administration of epinephrine, volume expanders, and sodium bicarbonate to extremely low birth weight infants have not been published. In addition, the main ethical dilemma concerns the decision of health professionals and parents not to initiate resuscitation procedures at very low gestational ages. CONCLUSIONS: In the future, guidelines may be modified based on the results of randomized and controlled clinical trials, as well as neurodevelopmental follow-up studies, involving extremely low birth weight infants submitted to resuscitation procedures in the delivery room.

Delivery Rooms↗

PubMed1990

Resources for pediatric drug information.

Finding information on the use of drugs fro infants and children is becoming easier with the publication of excellent resources for pediatric and neonatal drug information. Useful pediatric texts and journals are listed. Texts are graded A and B. Category A books would be useful to include in a basic pharmacy library; Category B books are more comprehensive but expensive, or texts that are not as highly recommended as those in Category A. Some of the resources listed include: (1) Pediatrics--Nelson Textbook of Pediatrics, Rudolph's Pediatrics, Current Pediatric Diagnosis and Treatment, Manual of Pediatric Therapeutics; (2) Dosage Guides--The Pediatric Drug Handbook, Harriet Lane Handbook, Problems in Pediatric Drug THerapy; (3) Intensive Care--Textbook of Pediatric Intensive Care; (4) Infectious Disease--Report of the Committee on Infectious Diseases, Pocketbook of Pediatric Antimicrobial Therapy; (5) Poisoning--Handbook of Poisoning, Medical Toxicology; (6) Parenteral Nutrition--Manual of Pediatric Parenteral Nutrition; (7) Pregnancy and Lactation--Drugs in Pregnancy and Lactation; (8) Compounding--Handbook on Extemporaneous Formulation; (9) IV Administration--Guidelines for Administration of Intravenous Medications to Pediatric Patients; (1) Neonatology--Schaffers Diseases of the Newborn, Neonatology, Basic Management, On-Call Problems, Diseases, Drugs, Drug Therapy in Infants; (11) Pediatric Journals--Pediatrics, Journal of Pediatrics, American Journal of Diseases of Children, Pediatric Infectious Disease Journal, Pediatric Alert, Clinics in Perinatology, Pediatric Clinics of North America, Pediatric Clinical Oncology Journal, and Pediatric Surgery.

Child↗

PubMed2002

Embryo freezing for preventing ovarian hyperstimulation syndrome: a Cochrane review.

UNLABELLED: This paper is based on a Cochrane review published in The Cochrane Library, issue 3, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration and Update Software. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition resulting from an excessive ovarian response to superovulation medication. The objective of this review was to evaluate the effectiveness of cryopreservation (embryo freezing) when compared with human i.v. albumin infusion and with fresh embryo transfer for the prevention of OHSS. METHODS: This was based on a Cochrane Review. Randomized controlled trials in which either human i.v. albumin or cryopreservation of all embryos was used as a therapeutic approach to OHSS were included. The participants were women down-regulated by GnRH agonist, undergoing superovulation in IVF/ICSI cycles. The interventions compared were cryopreservation versus i.v. human albumin administration and elective cryopreservation of all embryos versus fresh embryo transfer. The primary outcomes were: incidence of moderate and severe OHSS versus nil/mild OHSS, and clinical pregnancies/woman. Statistical analysis was performed in accordance with the Cochrane Menstrual Disorders and Subfertility Group guidelines. RESULTS: Seventeen studies were identified, two of which met our inclusion criteria. One study was included where cryopreservation was compared with i.v. human albumin administration and another where elective cryopreservation of all embryos was compared with fresh embryo transfer. In both interventions no difference was found in all the outcomes examined between the two groups. CONCLUSIONS: This review has shown that there is insufficient evidence to support routine cryopreservation and insufficient evidence for the relative merits of i.v. albumin versus cryopreservation.

Cryopreservation↗

PubMed1989

Sheep antiluteolytic interferon: cDNA sequence and analysis of mRNA levels.

A cloned cDNA has been isolated by probing a sheep blastocyst cDNA library using a synthetic oligonucleotide representing the N-terminal amino acid sequence of the antiluteolytic protein, ovine trophoblast protein-1. Sequence analysis of the cDNA confirms the 70% homology between the antiluteolysin and the interferon-alpha family of proteins; however, the sequence reported here differs at several points from previously reported amino acid and cDNA sequences for the antiluteolysin. In-vitro translation of day-16 poly(A)+ RNA indicated that antiluteolysin mRNA is a major constituent of total mRNA at this stage of blastocyst development, and Northern blotting confirmed that antiluteolysin mRNA production occurred between days 13 and 22 after oestrus. This is consistent with the stage at which embryonic extracts are antiluteolytic on administration in vivo. These and other data confirm that the ovine trophoblast antiluteolysin is an interferon, and suggest that at least five isoforms of this protein may exist.

Amino Acid Sequence↗

PubMed1983

Use of a cloned cDNA sequence to measure changes in 6-phosphogluconate dehydrogenase mRNA levels caused by thyroid hormone and dietary carbohydrate.

A cDNA clone containing sequences complementary to the mRNA coding for rat hepatic 6-phosphogluconate dehydrogenase has been isolated and used to measure changes in specific mRNA levels during dietary and hormonal regulation of this enzyme. Hepatic mRNA was fractionated by sucrose gradient centrifugation to enrich for 6-phosphogluconate dehydrogenase mRNA sequences. A cDNA library was prepared from the fraction with maximal activity and then screened by differential colony hybridization using probes synthesized either from 6-phosphogluconate dehydrogenase mRNA enriched by polysome immunoadsorption or from unenriched hepatic mRNA. A single colony giving an appropriate differential signal was confirmed to contain sequences encoding 6-phosphogluconate dehydrogenase by specific immunoprecipitation of hybrid-selected translational products. 6-Phosphogluconate dehydrogenase mRNA contains about 2400 bases. The cloned cDNA comprises about 880 bases, or 35% of the mRNA. Southern analysis of restriction endonuclease digests of genomic DNA suggests that the major 6-phosphogluconate dehydrogenase gene is probably present in a single copy in the rat genome. Feeding a fat-free, high carbohydrate diet and administration of thyroid hormone increased the concentration of hybridizable 6-phosphogluconate dehydrogenase mRNA in liver. Thus, both dietary and hormonal regulation of 6-phosphogluconate dehydrogenase synthesis occurs at a pretranslational level.

Animals↗

PubMed1993

Documenting nursing and health care history in the mid-Atlantic region.

The records of health care institutions can be of great value to library patrons. Yet, librarians rarely provide these unique resources because records must be collected, arranged, and described before they can be useful to patrons. The University of Pennsylvania's Center for the Study of the History of Nursing conducted a survey of health care agencies in the mid-Atlantic region to locate records created by area health care institutions. The goals of this project were to develop a database of primary source materials, to place organizational records with enduring value at suitable repositories, and to assist in the development of in-house archival programs at agencies keeping records. In-house programs provide health care institutions with a systematic way to preserve their records for administrative, legal, fiscal, and research use. Such programs also facilitate access to information, reduce cost through records management, and promote an institution through preservation and use of its historical records. The survey demonstrated that record keeping is not coordinated in most institutions, and that institutional awareness of the organization or content of records is minimal.

Archives↗

PubMed2026

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

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

Adolescent↗

PubMed2006

Hypoallergens for allergen-specific immunotherapy by directed molecular evolution of mite group 2 allergens.

Allergen-specific immunotherapy is the only treatment that provides long lasting relief of allergic symptoms. Currently, it is based on repeated administration of allergen extracts. To improve the safety and efficacy of allergen extract-based immunotherapy, application of hypoallergens, i.e. modified allergens with reduced IgE binding capacity but retained T-cell reactivity, has been proposed. It may, however, be difficult to predict how to modify an allergen to create a hypoallergen. Directed molecular evolution by DNA shuffling and screening provides a means by which to evolve proteins having novel or improved functional properties without knowledge of structure-function relationships of the target molecules. With the aim to generate hypoallergens we applied multigene DNA shuffling on three group 2 dust mite allergen genes, two isoforms of Lep d 2 and Gly d 2. DNA shuffling yielded a library of genes from which encoded shuffled allergens were expressed and screened. A positive selection was made for full-length, high-expressing clones, and screening for low binding to IgE from mite allergic patients was performed using an IgE bead-based binding assay. Nine selected shuffled allergens revealed 80-fold reduced to completely abolished IgE binding compared with the parental allergens in IgE binding competition experiments. Two hypoallergen candidates stimulated allergen-specific T-cell proliferation and cytokine production at comparable levels as the wild-type allergens in patient peripheral blood mononuclear cell cultures. The two candidates also induced blocking Lep d 2-specific IgG antibodies in immunized mice. We conclude that directed molecular evolution is a powerful approach to generate hypoallergens for potential use in allergen-specific immunotherapy.

Allergens↗

PubMed2006

Renal vascular resistance in sepsis.

AIMS: To assess changes in renal vascular resistance (RVR) in human and experimental sepsis and to identify determinants of RVR. METHODS: We performed a systematic interrogation of two electronic reference libraries using specific search terms. Subjects were animals and patients involved in experimental and human studies of sepsis and septic acute renal failure, in which the RVR was assessed. We obtained all human and experimental articles reporting RVR during sepsis. We assessed the role of various factors that might influence the RVR during sepsis using statistical methods. RESULTS: We found no human studies, in which the renal blood flow (and, therefore, the RVR) was measured with suitably accurate direct methods. Of the 137 animal studies identified, 52 reported a decreased RVR, 16 studies reported no change in RVR, and 69 studies reported an increased RVR. Consciousness of animals, duration of measurement, method of induction of sepsis, and fluid administration had no effect on the RVR. On the other hand, on univariate analysis, size of the animals (p < 0.001), technique of measurement (p = 0.017), recovery after surgery (p = 0.004), and cardiac output (p < 0.001) influenced the RVR. Multivariate analysis, however, showed that only cardiac output (p = 0.028) and size of the animals (p = 0.031) remained independent determinants of the RVR. CONCLUSIONS: Changes in RVR during sepsis in humans are unknown. In experimental sepsis, several factors not directly related to sepsis per se appear to influence the RVR. A high cardiac output and the use of large animals predict a decreased RVR, while a decreased cardiac output and the use of small animals predict an increased RVR.

Acute Kidney Injury↗

PubMed2006

A2-agonists in sheep: a review.

OBJECTIVE: To review the use and adverse effects of alpha(2)-agonists in sheep. STUDY DESIGN: Literature review. MATERIAL AND METHODS: 'Pubmed' of the United States National Library of Medicine and 'Veterinary Science' of CAB International were searched for references relating sheep to alpha(2)-agonists. The bibliographies of retrieved articles were further scrutinized for pertinent references, and relevant articles were selected manually. RESULTS: Reports on the use of clonidine, xylazine, detomidine, romifidine, medetomidine and dexmedetomidine, MPV-2426 and ST-91 in sheep were found in the literature. Most of the studies described xylazine followed by medetomidine and clonidine. The literature on detomidine and romifidine in sheep was sparse. Reports included pharmacokinetic studies, evaluation of sedative, analgesic, and anaesthetic techniques with or without cardiovascular effects, and experimental investigations of adverse effects (mainly hypoxaemia) including the mechanisms of pulmonary oedema and impaired oxygenation after alpha(2)-agonist administration. CONCLUSIONS: A(2)-agonists are potent and effective analgesics in sheep. In combination with ketamine, they are frequently used for the induction and maintenance of anaesthesia, in this case analgesia is satisfactory. The degree of hypoxaemia which occurs with all commercially available alpha(2)-agonists is highly variable and depends on individual or breed-related factors; the most severe reactions occur after intravenous (IV) injection and during general anaesthesia. Clinical relevance Subclinical respiratory disease is common in sheep. Rapid IV injection of alpha(2)-agonists without supplementary oxygen should be avoided whenever hypoxaemia may be critical.

Adrenergic alpha-Antagonists↗

PubMed1991

Tolerance to organic nitrates: evidence, mechanisms, clinical relevance, and strategies for prevention.

OBJECTIVE: To review the available information about nitrate tolerance, its potential mechanisms, clinical implications, and strategies for prevention. DATA IDENTIFICATION: A survey of the National Library of Medicine MEDLINE database and bibliographies of the reviewed articles. STUDY SELECTION AND DATA EXTRACTION: Studies were selected from the English language literature with an emphasis on recent studies and, when available, randomized placebo-controlled studies. Old studies were selected on the basis of their historical value and originality. A total of 134 retrieved articles were considered relevant and were reviewed in depth. RESULTS: The available information about the experimental as well as the clinical evidence for tolerance to organic nitrates has been summarized. In addition, information related to potential mechanisms, clinical implications, and possible methods for prevention have been reviewed. CONCLUSIONS: Evidence indicates that prolonged in-vitro exposure to organic nitrates, continuous intravenous or topical administration of nitrates, and frequent in-vivo oral dosing result in the rapid development of tolerance to the peripheral as well as to the coronary vasodilatory effects of the drugs. This phenomenon leads to the rapid attenuation of the hemodynamic and anti-ischemic effects of nitrates in patients with ischemic heart disease or congestive heart failure, or both. Tolerance development seems to be dose- and time-dependent, and its main mechanism seems to be a depletion of sulfhydryl groups at the vascular cell. Although the repletion of sulfhydryl groups with the use of sulfhydryl-containing drugs may help to prevent tolerance, the efficacy and safety of this approach requires further evaluation. Intermittent therapy allowing a sufficiently long, daily nitrate-washout interval seems to be the most effective and the most safe strategy currently available for the prevention of nitrate tolerance.

Cardiovascular Agents↗

PubMedDate not supplied

[Evaluation of the pediatric aspects of the WHO document and meta-analysis of immunotherapy].

In spite of the existence of numerous scientific studies on the beneficial effect of immunotherapy with specific allergens in the treatment of allergic diseases, their results have not been easily accepted as the methodology and the valuation of the studies have been very heterogeneous. Over the last few years the meta-analysis technology has been developed as a useful tool to globally value the results on the different research studies related to a specific problem. When meta-analyse are carried out correctly, they are accepted as an optimum way to express the results obtained from the different studies from a common view point. In 1995 Abramson MJ, Puy RM and Weiner INI published the first meta-analysis on the efficiency of immunotherapy with specific allergens in the treatment of asthma. The same authors continued to carry out systematic reviews of this theme, and their results were published in the Cochrane Library Document. In october 1999 the latest meta-analysis on immunotherapy in asthma, also carried out by Abramson et al was published in Allergy. In this study 62 investigations published from 1954 to 1998 were included. None of the meta-analyses published to date have separately analysed the studies carried out on children, nor have special considerations been made with respect to the 105 patients who were of paediatric age. The first meta-analysis studies, as well as the ones carried out in 1999, only value random clinical tests, in which there is a valuation of the evolution of asthma and in which mite, pollen, animal, fungi or epithelial allergenic vaccinations are used. Only the subcutaneous administration of the vaccine was allowed. Although this meta-analysis has not been designed to obtain specific conclusions of the effectiveness of immunotherapy in children, probably of conclusions of some of the sections can be applied to the children and/or adolescent population. The authors point out, by valuing the results of the effect of immunotherapy on the clinical evolution, that the studies carried out on children were more homogenous than on adults, which means that their significance on this population is more important. Approximately 50% of the studies that evaluate the clinical evolution, the medicines taken and the specific BHR study with allergens, included children and/or adolescents. It is very probable that these conclusions can be applied to the population between 5 and 18 years old that suffer from allergic asthma, but it is clear that a meta-analysis of the efficiency of immunotherapy in paediatrics is needed. Recently regulations on immunotherapy have been published that appeared after the immunotherapy experts from the World Health Organisation met in Geneva in 1997 (1). The recommendations for immunotherapy in children are clear and similar to those applied to adults: 1. Rhonoconjunctivitis and allergic asthma mediated by IgE. 2. Serious anaphylactic reactions caused by hymenoptera bites. 3. The same diagnosis and treatment considerations recommended are applied to children as well as adults. It is not indicated for allergies to food substances and atopic dermatitis. The patients age is another factor to be considered and, except in the case of allergy to hymenoptera poison, when the patient is under 5 it is a relative counter indication to administer immunotherapy. In general it is admitted that immunotherapy is more efficient on children than on adults, but more studies need to be carried out on the efficiency and safety on children under 5. The early treatment with immunotherapy in children who suffer from allergic respiratory illnesses can have an important significance, as this type of treatment could have a preventive nature as it prevents the rhinitis developing into asthma, as well as the beneficial effect that has been shown on children with allergic asthma.

Adolescent↗