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PubMed2006

Identification and characterization of novel and unknown mouse epididymis-specific genes by complementary DNA microarray technology.

To examine epididymal function, we attempted to identify highly expressed genes in mouse epididymis using a cDNA microarray containing PCR products amplified from a mouse epididymal cDNA library. We isolated one novel and four known genes-lymphocyte cytosolic protein 1 (Lcp1), complement subcomponents C1r/C1s, Uegf protein, and bone morphogenetic protein and zona pellucida-like domains 1 (Cuzd1), transmembrane epididymal protein 1 (Teddm1), and whey acidic protein 4-disulfide core domain 16 (Wfdc16)-with unknown functions in the epididymis. The novel gene, designated Serpina1f (serine peptidase inhibitor [SERPIN], clade A, member 1f), harbors an open reading frame of 1 233 bp encoding a putative protein of 411 amino acids, including a SERPIN domain. These five genes were predominantly expressed in the epididymis as compared to other organs. In situ hybridization analysis revealed their epididymal region-specific expression patterns. Real-time RT-PCR analysis revealed a significant increase in mRNA expression of these genes around puberty. Castration decreased their expression, except forLcp1. Testosterone (T) restored these reduced expressions, except forTeddm1; however, this restoration was not observed with 17 beta-estradiol (E2). Administration of T and E2 combination recovered the Serpina1f mRNA concentration; this recovery was also observed with T alone. However, the recovery of Cuzd1and Wfdc16mRNA concentrations was inadequate. Neonatal diethylstilbestrol treatment suppressed the Cuzd1, Wfdc16, and Serpina1f mRNA expression in the epididymis of 8-week-old mice; this was not observed with E2. These results suggest that our microarray system can provide a novel insight into the epididymal function on a molecular basis, and the five genes might play important roles in the epididymis.

Animals↗
PubMed1998

Cloning and characterization of Syrian hamster testosterone 7 alpha-hydroxylase, CYP2A9.

We report here the cloning of a cDNA encoding testosterone 7 alpha-hydroxylase in the Syrian hamster, designated CYP2A9. Overlapping clones encoding Syrian hamster CYP2A9 were isolated by screening a liver cDNA library and by performing rapid amplification of cDNA ends polymerase chain reaction on the cDNA library. The sequence of the CYP2A9 cDNA contains an open reading frame of 1482 nucleotides encoding a polypeptide of 493 amino acids with a calculated molecular mass of 56,295 Da. The sequence is flanked by a 5'-untranslated region of 10 bp and a 3'-untranslated region of 178 bp including the poly(A) tail. The deduced amino acid sequence shares significant homology with members of CYP2A subfamily, notably with CYP2A1 and CYP2A12 which have testosterone 7 alpha-hydroxylase activity. We characterized the catalytic activity of CYP2A9 using microsomes obtained by transient expression of its cDNA in transfected COS-7 cells. CYP2A9 was found to hydroxylate testosterone at position 7 alpha. In Syrian hamster livers, a higher level of testosterone 7 alpha-hydroxylase activity as well as the mRNA of CYP2A9 in male than in female was obtained. The testosterone 7 alpha-hydroxylase activity and the mRNA level in liver were both decreased moderately by administration of 3-methylcholanthrene and slightly by administration of phenobarbital. In contrast, in kidney, both 3-methylcholanthrene and phenobarbital significantly decreased the mRNA level. These facts indicate that the regulation of the hamster testosterone 7 alpha-hydroxylase (CYP2A9) expression is different from that of the rat (CYP2A1) and hamster reported previously by other workers.

Amino Acid Sequence↗
PubMed1996

1995 update of the working group reports on chronic renal failure and renovascular hypertension. National High Blood Pressure Education Program Working Group.

To update 2 National High Blood Pressure Education Program working group reports on hypertension and chronic renal failure and renovascular hypertension, a working group was appointed by the director of the National Heart, Lung, and Blood Institute. Literature was searched through MEDLINE and the National Heart, Lung, and Blood Institute information center library. Scientific evidence was given precedence over clinical anecdotal experience. The working group members produced initial draft documents that were circulated to additional experts on hypertension and renal disease. This reiterative process occurred for 18 draft documents. The final report was sent to the representatives of the 44 organizations on the Coordinating Committee for vote and unanimously approved September 1, 1995. The report recommended treatment of hypertension to the goal of 130/85 mm Hg with whatever therapy is necessary to prevent the development of hypertensive nephrosclerosis or the progression of established renal disease of diverse causes. It seems reasonable to recommend angiotensin-converting enzyme inhibitors as initial therapy for patients with diabetes and microalbuminuria or overt diabetic nephropathy with and without hypertension. Renovascular disease has emerged as a major cause of end-stage renal disease, especially in the elderly. Newer screening procedures for the noninvasive screening of renovascular disease include the captopril test, renal scintigraphy following captopril administration, duplex scanning, and magnetic resonance angiography.

Antihypertensive Agents↗
PubMed2002

Classification of medical errors and preventable adverse events in primary care: a synthesis of the literature.

OBJECTIVE: To describe and classify process errors and preventable adverse events that occur from medical care in outpatient primary care settings. STUDY DESIGN: Systematic review and synthesis of the medical literature. DATA SOURCES: We searched MEDLINE and the Cochrane Library from 1965 through March 2001 with the MESH term medical errors, modified by adding family practice, primary health care, physicians/family, or ambulatory care and limited the search to English-language publications. Published bibliographies and Web sites from patient safety and primary care organizations were also reviewed for unpublished reports, presentations, and leads to other sites, journals, or investigators with relevant work. Additional papers were identified from the references of the papers reviewed and from seminal papers in the field. OUTCOMES MEASURED: Process errors and preventable adverse events. RESULTS: Four original research studies directly studied and described medical errors and adverse events in primary care, and 3 other studies peripherally addressed primary care medical errors. A variety of quantitative and qualitative methods were used in the studies. Extraction of results from the studies led to a classification of 3 main categories of preventable adverse events: diagnosis, treatment, and preventive services. Process errors were classified into 4 categories: clinician, communication, administration, and blunt end. CONCLUSIONS: Original research on medical errors in the primary care setting consists of a limited number of small studies that offer a rich description of medical errors and preventable adverse events primarily from the physician's viewpoint. We describe a classification derived from these studies that is based on the actual practice of primary care and provides a starting point for future epidemiologic and interventional research. Missing are studies that have patient, consumer, or other health care provider input.

Adverse Drug Reaction Reporting Systems↗
PubMed1996

The changing face of health information and health information work: a conceptual framework.

The purpose of this paper is to examine the changes in health information and health information work using a conceptual framework and to consider the implication of these changes for health sciences librarians. The notion of what constitutes information depends heavily on the perspective of those defining the term. In the health care domain, numerous established concepts of information exist, many clustering around disciplines and professions. Various information professions-for example, health sciences librarians, information-systems managers, and medical-records administrators--have differing core concepts of information. Although these established concepts of information may seem immutable, they are cultural facts and can and do change. Global networking and changes in health care delivery are just two of many environmental forces that are changing the way the health domain views health information and the way it values the patterns and practices traditionally associated with established types of information and information professions. As new concepts of information arise, the possibility for new expert work surrounding information also arises. Andrew Abbott's systems theory of professions, adapted to the health domain, suggests that some forms of established expert information work may diminish while new types may arise and that both established and new information professions will struggle with each other for official sanction, or jurisdiction, to perform new expert work. This competitive struggle is likely to produce a new balance of information work and roles among the information professions. The specialty areas of library and information science, the heartland of our knowledge base, are as relevant in the electronic environment as in the print environment. Our profession's challenge now is to redefine and communicate our jurisdictional place in the emerging health information environment.

Computer Communication Networks↗
PubMedDate not supplied

Early postoperative feeding and abdominal gynaecological surgery.

Since the 1990s, the traditional postoperative feeding protocol has been challenged for patients who have undergone major abdominal gynaecological surgery, and value of extended delays in commencing oral intake has been questioned. This review aims to determine whether early rather than delayed postoperative feeding following major abdominal gynaecological surgery has an impact upon recovery as measured by length of hospital stay. The Cochrane Library, Embase, CINAHL and Medline were searched for randomized controlled trials (RCTs) which compared early postoperative oral intake with delayed (traditional) postoperative oral intake for patients who had undergone major abdominal gynaecological surgery. Three RCTs were identified and available for consideration. Although study quality was variable, they suggest that early postoperative feeding appears to be safe and well tolerated after most abdominal gynaecological surgery and leads to a considerable reduction in hospital stay of approximately one day. However, patients' preference and costs remain unclear. Therefore, further well-designed studies are needed to identify the comprehensive effectiveness of early postoperative feeding protocol.

Abdomen↗
PubMedDate not supplied

Building and growing a hospital intranet: a case study.

BACKGROUND: The Intranet is a rapidly evolving technology in large hospitals. In this paper, we describe the first phase of an Intranet project in a multi-hospital system in New York City. OBJECTIVES: (1) To encourage the use of the Intranet among physicians, nurses, managers, and other associates in a multi-hospital system; and (2) to build the Intranet in a cost-effective manner using existing resources. METHODS: A WebTrends Log Analyzer assessed the Intranet use in terms of the number of accesses from each department. RESULTS: A broad range of features, including medical knowledge resources, clinical practice guidelines, directions, patient education, online forms, phone directory, and discussion forums were developed. Analysis of more than 890,000 hits revealed the departments with hits greater than 1,000 were the Library (6,130), Physicians Gateway (2,539), Marketing (1,321), Information Systems (1,241), and Nutrition (1,221). Of 819 unique visitors, 74 per cent visited more than once. CONCLUSIONS: It is possible to create and diffuse an Intranet in a multi-hospital system in a cost-effective manner. However, the key challenges were selling the potential of this new technology to opinion leaders and other stakeholders, and converting pre-existing printed content by obtaining word processed and image files from other departments or contracted print publishers.

Computer Communication Networks↗
PubMed2004

Molecular cloning and expression analysis of alpha 2-macroglobulin in the kuruma shrimp, Marsupenaeus japonicus.

The cDNA encoding the kuruma shrimp, Marsupenaeus japonicus alpha(2)-macroglobulin (alpha(2)M) was obtained by screening a haemocyte cDNA library and 5' RACE PCR amplification. The full length cDNA of 4748 bp contains an open reading frame of 4518 nucleotides that translates into a 1505-amino acid putative peptide, with a 5'untranslated region (UTR) of 59 bp and a 3'UTR of 171 bp. The open reading frame encodes an N-terminal signal sequence of 17 residues and a mature protein of 1488 residues. The entire amino acid sequence is similar to the alpha(2)M sequences of arthropods (30-31% identity), mammals (26-27% identity) and fish (25-28% identity). The M. japonicus alpha(2)M sequence contains putative functional domains including a bait region, an internal thiol ester site, and a receptor-binding domain, which are present in mammalian alpha(2)Ms. In a healthy shrimp, the mRNA of alpha(2)M was mainly expressed in haemocytes. In addition, the expression level of alpha(2)M mRNA was dramatically increased by through time upon oral administration of peptidoglycan (PG), which is an immune stimulant. The highest expression of alpha(2)M mRNA was observed 7 days after feeding with PG. These results suggest that the shrimp alpha(2)M is an important molecule in immune system.

Amino Acid Sequence↗
PubMed2003

Identification of upregulated SCG10 mRNA expression associated with late-phase long-term potentiation in the rat hippocampal Schaffer-CA1 pathway in vivo.

The maintenance of long-term potentiation (LTP) depends on alteration of gene transcription. By screening a subtracted cDNA library that is enriched in upregulated transcripts in rat hippocampus 3 hr after Schaffer-CA1 LTP induction in vivo, we identified a neural growth-associated protein SCG10 (superior cervical ganglia clone 10) gene. The semiquantitative reverse transcription-PCR and Northern blot experiments confirmed that SCG10 mRNA levels were elevated in tetanized rat hippocampi compared with those of sham controls that received only low-frequency stimulation. Both 1 and 2 kb forms of SCG10 mRNAs contributed to the increased expression. Using a riboprobe with a sequence specific to the 3'-untranslated region of rat SCG10 mRNA, in situ hybridization further revealed a significant increase of the SCG10 mRNA 2 kb form in the ipsilateral CA3 and CA1 regions of LTP animals. In addition, we systemically injected the competitive NMDA receptor antagonist d,l-3[(+/-)-2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid (CPP) to determine whether the alteration of SCG10 expression depends on NMDA receptor activation or tetanus alone. Administration of CPP 1 hr before tetanus completely blocked LTP induction and the increase of SCG10 mRNA levels. Thus, these results suggest that the transcription of SCG10 in vivo is regulated by long-lasting synaptic activity and may contribute to the maintenance of long-term synaptic plasticity via a presynaptic remodeling mechanism.

Animals↗
PubMed2000

Characterization of a class of cationic peptides able to facilitate efficient protein transduction in vitro and in vivo.

Protein transduction domains (PTDs), such as the third helix of the Drosophila Antennapedia homeobox gene (Antp) and the HIV TAT PTD, possess a characteristic positive charge on the basis of their enrichment for arginine and lysine residues. To determine whether cationic peptides are able to function as protein transduction domains, 12-mer peptide sequences from an M13 phage library were selected for synthesis on the basis of their varying cationic charge content. In addition, polylysine and polyarginine peptides were synthesized in order to assess the effect of charge contribution in protein transduction. Coupling of the biotinylated peptides to avidin-beta-galactosidase facilitated transduction in a wide variety of cell lines and primary cells, including islet beta-cells, synovial cells, polarized airway epithelial cells, dendritic cells, myoblasts, and tumor cells. Two of the peptides, PTD-4 and PTD-5, mediated transduction nearly 600-fold more efficiently than a random control peptide, but with an efficiency similar to the TAT PTD and the 12 mers of polylysine and polyarginine. Furthermore, confocal analysis of biotinylated peptide-streptavidin-Cy3 conjugates demonstrated that the internalized PTDs are found in both the nuclei and the cytoplasm of treated cells. When tested in vivo, the PTDs were able to facilitate efficient and rapid protein delivery into rabbit synovium and mouse solid tumors following intraarticular and intratumoral administration, respectively. These novel PTDs can be used to transfer therapeutic proteins and DNA for the treatment of a wide variety of diseases, including arthritis and cancer.

Amino Acid Sequence↗
PubMed1993

Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression.

Two isoforms of cyclooxygenase (COX) have been identified in eukaryotic cells: COX-1 encoded by a 2.8-kb mRNA, and a mitogen-inducible COX-2 encoded by a 4-kb mRNA. We have cloned the COX-1 and COX-2 cDNAs from the cDNA library constructed from lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages. The deduced amino acid sequence showed that COX-1 contained 602 amino acids, whereas COX-2 contained 604 amino acids. There is 95% conservation of the nucleotide sequence in the open reading frame of COX-1 between the rat and the mouse, while the homology of the 3' untranslated region is 68% except for a 150 bp segment adjacent to the stop codon which is nonhomologous with the mouse. Transfection of both COX cDNAs into Cos-7 cells resulted in increased COX activity. In rat vascular smooth muscle cells, interleukin-1 beta selectively increased the expression of COX-2, but not that of COX-1, as assessed by enzyme activity, immunoprecipitation of COX proteins, and mRNA analysis. Only the brain among tissues tested exhibits basal expression of COX-2 as the major form of the enzyme. However, COX-2 mRNA was expressed in vivo in the lung and kidney, but not in the heart, after systemic administration of LPS, suggesting that COX-2 but not COX-1 plays a major role in producing COX-derived products of arachidonic acid during endotoxic shock. Thus, the two COX isoforms were differentially expressed, and COX-2 was selectively induced in response to inflammatory stimuli in rats.

Amino Acid Sequence↗
PubMedDate not supplied

A screening procedure for the determination of 13 oral anticoagulants and rodenticides.

A technique for the simultaneous identification and quantitation of 13 hydroxycoumarin and indandione anticoagulant drugs and rodenticides from human serum by reversed-phase liquid chromatography with diode-array detection has been developed. High-performance liquid chromatography was performed using gradient elution with an acetonitrile and phosphate buffer on a Nucleosil ODS column. Ultraviolet spectra from 200 to 400 nm were recorded on-line during the analysis and compared with spectra stored in a library. For the spiked 2 mL of serum, acidic and alkaline liquid-liquid double extraction with diethylether-ether acetate (50:50, v/v) was conducted, and recoveries greater than 60% for most compounds were found. The detection limit was approximately 25 or 50 ng/mL for all components except for difethialone and fluindione, for which it was approximately 100 ng/mL. The standard calibration curves were linear from the detection limit to 5000 ng/mL. The within-run precision coefficient of variation (CV) was less than 10%, and the between-run precision CV was less than 20%.

Administration, Oral↗
PubMed1989

Copia RNA levels are elevated in dunce mutants and modulated by cAMP.

Clones carrying sequences expressed at altered abundance levels in dunce mutants were isolated by differentially screening a genomic library with cDNA probes representing the RNA population from dunce+ flies and the RNA population from dunce mutant flies. These mutants have an elevated cAMP content, so some isolates potentially contain cAMP responsive genes. Two classes of clones were isolated. One class contains genes expressed at a higher steady state abundance level in dunce mutants compared to dunce+ flies and the other contains genes expressed at a lower steady state level in the mutants. The recovery of clones from the differential screen demonstrates that in addition to altering normal behavior, fertility, and cAMP metabolism, dunce mutation confers an alteration in the level of expression of certain genes. The class of clones carrying sequences which are overexpressed in the mutants have been characterized. These clones carry a common repetitive sequence which codes for a 5.5 kb poly(A)+ RNA - the RNA species found to be overexpressed in the mutants. Restriction analysis and hybridization experiments show these repetitive sequences to be members of the copia family of transposable elements. Administration of pharmacological agents to normal flies to increase cAMP levels leads to an increased steady state level of copia RNA. Thus, copia RNA metabolism appears to be influenced by cAMP levels.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Human endometrial proteins.

Human endometrium synthesizes a number of proteins. Two of the major proteins are the low molecular weight insulin-like growth factor-binding protein (IGF-bp25) and endometrial protein PP14 (placental protein 14). Both proteins have been cloned from human decidual cDNA library and their complete amino acid sequences have been deduced. IGF-bp25 is found in various tissues and body fluids including secretory and decidualized endometrium, amniotic fluid, liver, follicular fluid and luteinized granulosa cells of preovulatory ovarian follicles. Clinical studies have shown that there is no systematic variation in the circulating levels during normal menstrual cycle, whereas in hyperstimulated cycles the levels are higher when there are many preovulatory follicles and immediately after follicle aspiration for in vitro fertilization (IVF). Some women with polycystic ovarian disease have a subnormal level of IGF-bp25 in serum. The other protein, PP14, is synthesized by secretory and decidualized endometrium, and it is also abundant in amniotic fluid. PP14 is mainly released by secretory endometrial glands during the last week of ovulatory cycles. There is a consistent variation in serum PP14 levels during normal menstrual cycle. The levels are lowest at the time of ovulation and rise steeply during the last week of luteal phase and peak at the onset of menstruation. Administration of micronized oral progesterone to normally ovulating infertile women brings about elevation in their serum PP14 levels during late luteal phase. In postmenopausal women cyclical estrogen-progestogen replacement causes elevation of serum PP14 level, but this does not take place in hysterectomized postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrium↗
PubMed1997

Molecular genetics of the renin-angiotensin-aldosterone system in human hypertension.

Blood pressure is a quantitative trait that varies along a continuum in the general population and is regulated via multiple mechanisms involving many genetic loci and environmental factors. Family studies and twin studies suggest that about 30% of blood pressure variance is attributable to genetic factors and 50% to environmental factors. Two forms of hypertension transmitted on an autosomal recessive basis have been identified: one is glucocorticoid-suppressible hyperaldosteronism (GSH) and the other is Liddle's syndrome (amiloride-suppressible hyperactivity of the epithelial sodium channel). The molecular basis for these two forms of severe hypertension has recently been elucidated. GSH is due to expression of a chimeric gene produced by fusion of the 11 beta-hydroxylase promoter with the region encoding the enzyme aldosterone-synthase. Expression of this chimeric gene occurs in the zona fasciculata of the adrenal cortex, under the control of ACTH, and can be suppressed by administration of glucocorticoids. Liddle's syndrome is due to mutations in the beta or gamma chain of the epithelial sodium channel in distal renal tubule cells. The hyperactivity of this channel caused by the mutations results in increased sodium reabsorption, which can be suppressed by administration of amiloride or triamterene. Apart from these rare genetic defects, a number of susceptibility genes can increase the risk of hypertension in a given environment. Their presence is neither necessary nor sufficient to cause hypertension. The best documented example is the angiotensinogen gene. Angiotensiongen is the substrate of renin, and the renin-angiotensinogen reaction is the first and limiting step in the pathway that leads to production of angiotensin II, a peptide with important effects on blood pressure control and the metabolism of water and sodium. Several studies have demonstrated a link between the angiotensinogen gene and familial hypertension or hypertension of pregnancy. The M235T variant of angiotensinogen is more prevalent among hypertensive than among normotensive subjects in several Caucasian and Japanese populations. The M235T variant is also associated with plasma angiotensinogen elevation, which is potentially responsible for increased production of angiotensin II. In other terms, relationships exist between the angiotensinogen genotype, the intermediate phenotype (i.e., plasma angiotensinogen elevation), and the distal phenomenon (i.e., blood pressure elevation). DNA libraries for the study of hypertension have been set up, and many informative genetic markers distributed along the genome have been identified. Using position cloning techniques, these markers could be used in the search for genetic links between arterial hypertension and a chromosomal locus.

Angiotensinogen↗
PubMed2006

Anthrax vaccine powder formulations for nasal mucosal delivery.

Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6-8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7-8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization.

Administration, Intranasal↗
PubMed1999

Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides.

Antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, repeated thromboembolic phenomena, and thrombocytopenia. The syndrome is believed to be caused by antiphospholipid beta-2-glycoprotein-I (beta2GPI)-dependent Abs or anti-beta2GPI Abs by themselves. Using a hexapeptide phage display library, we identified three hexapeptides that react specifically with the anti-beta2GPI mAbs ILA-1, ILA-3, and H-3, which cause endothelial cell activation and induce experimental APS. To enhance the binding of the peptides to the corresponding mAbs, the peptides were lengthened to correspond with the site of the beta2GPI epitope being recognized by these mAbs. As a result, the following three peptides were prepared: A, NTLKTPRVGGC, which binds to ILA-1 mAb; B, KDKATFGCHDGC, which binds to ILA-3 mAb; and C, CATLRVYKGG, which binds to H-3 mAb. Peptides A, B, and C specifically inhibit both in vitro and in vivo the biological functions of the corresponding anti-beta2GPI mAbs. Exposure of endothelial cells to anti-beta2GPI mAbs and their corresponding peptides led to the inhibition of endothelial cell activation, as shown by decreased expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1) and monocyte adhesion. In vivo infusion of each of the anti-beta2GPI mAbs into BALB/c mice, followed by administration of the corresponding specific peptides, prevented the peptide-treated mice from developing experimental APS. The use of synthetic peptides that focus on neutralization of pathogenic anti-beta2GPI Abs represents a possible new therapeutic approach to APS.

Animals↗
PubMed2005

Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review).

BACKGROUND: Post-operative pain management is usually limited by adverse effects such as nausea and vomiting. Adjuvant treatment with an inexpensive opioid-sparing drug such as ketamine may be of value in giving better analgesia with fewer adverse effects. The objective of this systematic review was to evaluate the effectiveness and tolerability of ketamine administered peri-operatively in the treatment of acute post-operative pain in adults. METHODS: Studies were identified from MEDLINE (1966-2004), EMBASE (1980-2004), the Cochrane Library (2004) and by hand searching reference lists from review articles and trials. The manufacturer of ketamine (Pfizer AS, Lysaker, Norway) provided search results from their in-house database, PARDLARS. Randomized and controlled trials (RCTs) of adult patients undergoing surgery, being treated with peri-operative ketamine, placebo or an active control were considered for inclusion. RESULTS: Eighteen trials were excluded. Thirty-seven trials were included. Twenty-seven out of 37 trials found that peri-operative ketamine reduced rescue analgesic requirements or pain intensity, or both. Quantitative analysis showed that treatment with ketamine reduced 24-h patient-controlled analgesia (PCA) morphine consumption and post-operative nausea and vomiting (PONV). Adverse effects were mild or absent. CONCLUSION: In the first 24 h after surgery, ketamine reduces morphine requirements. Ketamine also reduces PONV. Adverse effects are mild or absent. These data should be interpreted with caution as the retrieved studies were heterogenous and the result of the meta-analysis can not be translated into any specific administration regimen with ketamine.

Adult↗