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PubMed2003

Murine leukemia RL male 1 and sarcoma Meth A antigens recognized by cytotoxic T lymphocytes (CTL).

Peptide elution and expression cloning methods have been used to identify T cell-recognized antigens for which no molecular information is available. We identified a unique tumor antigen peptide pRL1a, IPGLPLSL that is recognized by CTL on BALB/c RL male 1 leukemia by peptide elution. The sequence of the peptide corresponded to the normally untranslated 5' region of akt. Cytotoxicity was generated in BALB/c spleen cells by in vivo and in vitro sensitization with pRL1a peptide in the form of multiple antigen peptide (MAP), but not the original form. pRL1a MAP immunization had a significant growth-inhibitory effect. pRL1a MAP was mostly internalized into the endosomal compartment of antigen-presenting cells, leaked to the cytosol, and degraded, and the pRL1a peptide produced was presented through the MHC class I pathway. In vivo depletion of CD4 T cells from tumor-inoculated BALB/c mice caused RL male 1 regression. Overexpression of the RLakt molecule seemed to induce CD4 immunoregulatory cells, which resulted in progressive RL male 1 growth in BALB/c mice. In vivo administration of anti-CD25 mAb (PC61) caused regression of RL male 1, suggesting that CD4(+) CD25(+) immunoregulatory cells were involved in the tumor growth. Recently, we improved the sensitivity and the efficacy of T cell antigen cloning from cDNA expression libraries by using large- and small-scale ELISPOT assays. Using the IFN-gamma ELISPOT method, we obtained a cDNA clone S35 of 937 bp recognized by AT-1 CTL on BALB/c Meth A sarcoma. S35 was a part of the retinoic acid-regulated nuclear matrix-associated protein (ramp). AT-1 CTL recognized the peptide LGAEAIFRL, which was derived from a newly created open reading frame due to the exon 14 extension.

Animals↗
PubMedDate not supplied

Organizing the present, looking to the future: an online knowledge repository to facilitate collaboration.

BACKGROUND: Comprehensive data available in the Canadian province of Manitoba since 1970 have aided study of the interaction between population health, health care utilization, and structural features of the health care system. Given a complex linked database and many ongoing projects, better organization of available epidemiological, institutional, and technical information was needed. OBJECTIVE: The Manitoba Centre for Health Policy and Evaluation wished to develop a knowledge repository to handle data, document research Methods, and facilitate both internal communication and collaboration with other sites. METHODS: This evolving knowledge repository consists of both public and internal (restricted access) pages on the World Wide Web (WWW). Information can be accessed using an indexed logical format or queried to allow entry at user-defined points. The main topics are: Concept Dictionary, Research Definitions, Meta-Index, and Glossary. The Concept Dictionary operationalizes concepts used in health research using administrative data, outlining the creation of complex variables. Research Definitions specify the codes for common surgical procedures, tests, and diagnoses. The Meta-Index organizes concepts and definitions according to the Medical Sub-Heading (MeSH) system developed by the National Library of Medicine. The Glossary facilitates navigation through the research terms and abbreviations in the knowledge repository. An Education Resources heading presents a web-based graduate course using substantial amounts of material in the Concept Dictionary, a lecture in the Epidemiology Supercourse, and material for Manitoba's Regional Health Authorities. Confidential information (including Data Dictionaries) is available on the Centre's internal website. RESULTS: Use of the public pages has increased dramatically since January 1998, with almost 6,000 page hits from 250 different hosts in May 1999. More recently, the number of page hits has averaged around 4,000 per month, while the number of unique hosts has climbed to around 400. CONCLUSIONS: This knowledge repository promotes standardization and increases efficiency by placing concepts and associated programming in the Centre's collective memory. Collaboration and project management are facilitated.

Databases as Topic↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. RESULTS: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2000

Nursing record systems: effects on nursing practice and health care outcomes.

BACKGROUND: A nursing record system is the record of care planned and/or given to individual patients/clients by qualified nurses or other caregivers under the direction of a qualified nurse. Nursing record systems may be an effective way of influencing nurse practice. OBJECTIVES: To assess the effects of nursing record systems on nursing practice and patient outcomes. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, Cinahl, Sigle, and databases of the Royal College of Nursing, King's Fund, the NHS Centre for Reviews and Dissemination, and the Institute of Electrical Engineers up to August 1999; and OCLC First Search, Department of Health database, NHS Register of Computer Applications and the Health Visitors' Association database up to the end of 1995. We hand searched the Journal of Nursing Administration (1971-1999), Computers in Nursing (1984-1999), Information Technology in Nursing (1989-1999) and reference lists of articles. We also hand searched the major health informatics conference proceedings. We contacted experts in the field of nursing informatics, suppliers of nursing computer systems, and relevant Internet groups. SELECTION CRITERIA: Randomised trials, controlled before and after studies and interrupted time series comparing one kind of nursing record system with another, in hospital, community or primary care settings. The participants were qualified nurses, students or health care assistants working under the direction of a qualified nurse and patients receiving care recorded and/or planned using nursing record systems. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Six trials involving 1407 people were included. In three studies of client held records, there were no overall positive or negative effects, although some administrative benefits through fewer missing notes were suggested. A paediatric pain management sheet study showed a positive effect on the children's pain intensity. A computerised nursing care planning study showed a negative effect on documented nursing care planning. A controlled before-and-after study of two paper nursing record systems showed improvement in meeting documentation standards. REVIEWER'S CONCLUSIONS: No evidence was found of effects on practice attributable to changes in record systems. Although there is a paucity of studies of sufficient methodological rigour to yield reliable results in this area, it is clear from the literature that it is possible to set up randomised trials or other quasi-experimental designs needed to produce evidence for practice. The research undertaken so far may have suffered both from methodological problems and faulty hypotheses.

Humans↗
PubMed2006

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn infants (< 35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular haemorrhage, or neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2005. In addition, we searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Randomised and quasi randomised studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide compared to control with or without placebo. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular haemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Seven randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia (Subhedar 1997). One study studied routine use of inhaled NO in all ventilated preterm infants (Schreiber 2003). The remaining studies consisted of infants with high predicted mortality based on poor oxygenation (Kinsella 1999; Hascoet 2005; INNOVO 2005; Van Meurs 2005; Mercier 1999). No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. There was no evidence of effect on the risk of intraventricular haemorrhage. There may be short term improvements in oxygenation. Two studies (Schreiber 2003; INNOVO 2005) have so far presented data on long term neurodevelopmental outcome, one of which demonstrated improved outcome at two years corrected age. AUTHORS' CONCLUSIONS: The currently published evidence from randomised trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. Further studies may need to be performed to evaluate the potential benefit of routine use of this therapy in infants with milder forms of respiratory failure, and these trials will need to be designed to evaluate not only neonatal survival, and the occurrence of neonatal morbidities, but should be powered to evaluate neurodevelopmental outcome at a minimum of two years of age.

Administration, Inhalation↗
PubMed2000

Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain.

BACKGROUND: Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Paracetamol (acetaminophen) is an important non-opiate analgesic, commonly prescribed, as well as being available for retail sale. This review seeks to examine the efficacy of paracetamol alone and in combination with codeine, and also considers adverse effects. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single dose of oral paracetamol (acetaminophen) alone and in combination with codeine for moderate to severe postoperative pain. SEARCH STRATEGY: Published trials were identified from: Medline (1966 to May 1996), Embase (1980 to 1996), Cochrane Library (Issue 2 1996) and the Oxford Pain Relief Database (1950 to 1994). Additional trials were identified from reference lists of retrieved studies. Date of most recent searches: July 1998. SELECTION CRITERIA: Inclusion criteria were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which compared paracetamol with placebo or a combination of paracetamol and codeine with either placebo or the same dose of paracetamol alone. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief over 4 to 6 hours compared with placebo. Adverse effects were used to calculate relative risk and number-needed-to-harm (NNH). MAIN RESULTS: We found 40 trials of paracetamol against placebo (4171 patients), 22 trials of paracetamol plus codeine against placebo (1407 patients) and 12 trials of paracetamol plus codeine against the same dose of paracetamol (794 patients). In postoperative pain paracetamol 1000 mg had an NNT of 4.6 (3.8-5.4) for at least 50% pain relief when compared with placebo, and paracetamol 600/650 mg had an NNT of 5.3 (4.1-7.2). Paracetamol 600/650 mg plus codeine 60 mg had an NNT of 3. 6 (2.9-4.5). Comparing paracetamol plus codeine 60 mg with the same dose of paracetamol alone gave an NNT of 7.7 (5.1-17) for at least 50% pain relief. Adverse effects: Relative risk estimates for paracetamol 600/650 mg plus codeine 60 mg versus placebo showed a significant difference for 'drowsiness'/somnolence (NNH 11 (7.5- 0)) and dizziness (NNH 27 (15-164)) but no significant difference for nausea/vomiting. REVIEWER'S CONCLUSIONS: Paracetamol is an effective analgesic with a low incidence of adverse effects. The addition of codeine 60 mg to paracetamol produces additional pain relief even in single oral doses, but may be accompanied by an increase in drowsiness and dizziness.

Acetaminophen↗
PubMed2000

Single dose oral ibuprofen and diclofenac for postoperative pain.

BACKGROUND: Ibuprofen and diclofenac are two widely used non-steroidal anti-inflammatory (NSAID) analgesics. It is therefore important to know which drug should be recommended for postoperative pain relief. This review seeks to compare the relative efficacy of the two drugs, and also considers the issues of safety and cost. OBJECTIVES: To assess the analgesic efficacy of ibuprofen and diclofenac in single oral doses for moderate to severe postoperative pain. SEARCH STRATEGY: Randomised trials were identified by searching Medline (1966 to December 1996), Embase (1980 to January 1997), the Cochrane Library (Issue 3 1996), Biological Abstracts (January 1985 to December 1996) and the Oxford Pain Relief Database (1950 to 1994). Date of the most recent searches: July 1998. SELECTION CRITERIA: The inclusion criteria used were: full journal publication, postoperative pain, postoperative oral administration, adult patients, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which compared either ibuprofen or diclofenac with placebo. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers, and trials were quality scored. Summed pain relief or pain intensity difference over four to six hours was extracted, and converted into dichotomous information yielding the number of patients with at least 50% pain relief. This was then used to calculate the relative benefit and the number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: Thirty-four trials compared ibuprofen and placebo (3,591 patients), six compared diclofenac with placebo (840 patients) and there were two direct comparisons of diclofenac 50 mg and ibuprofen 400 mg (130 patients). In postoperative pain the NNTs for ibuprofen 200 mg were 3.3 (95% confidence interval 2.8 to 4.0) compared with placebo, for ibuprofen 400 mg 2.7 (2.5 to 3.0), for ibuprofen 600 mg 2.4 (1.9 to 3.3), for diclofenac 50 mg 2.3 (2.0 to 2.7) and for diclofenac 100 mg 1.8 (1.5 to 2.1). Direct comparisons of diclofenac 50 mg with ibuprofen 400 mg showed no significant difference between the two. REVIEWER'S CONCLUSIONS: Both drugs work well. Choosing between them is an issue of dose, safety and cost.

Analgesics, Non-Narcotic↗
PubMed2003

Serial analysis of gene expression in mouse kidney following angiotensin II administration.

As a new line of inquiry into the molecular mechanisms underlying pathophysiological processes associated with angiotensin (ANG II)-dependent hypertension, we applied the method of serial analysis of gene expression (SAGE) to examine genome-wide transcription changes in the kidneys of mice that developed hypertension in response to chronic ANG II administration. Mice were infused subcutaneously via osmotic minipumps with ANG II for 7 days, and systolic blood pressure was measured by tail-cuff plethysmography. Subsequently, mice were euthanized, and the total RNA isolated from the kidneys was used to construct SAGE libraries. Comparison of 11,447 SAGE tags from the hypertensive kidneys, representing 5,740 unique transcripts, and 11,273 tags from the control kidneys, corresponding to 5,619 different transcripts, identified genes that are significantly (P < 0.05) down- or upregulated in the hypertensive kidney. Our assessment of the genome-wide influence of ANG II resulted in the detection of several novel genes and in a recognition of potential new roles for the previously characterized genes, thus providing new probes with which to further explore the ANG II effects in normal and disease states.

Angiotensin II↗
PubMed2002

Frequency of administration of recombinant human erythropoietin for anaemia of end-stage renal disease in dialysis patients.

BACKGROUND: Although the benefits of recombinant human erythropoietin (rHu EPO) administration in dialysis patients have been demonstrated the optimal frequency regimen has not as yet been established. Treatment with rHu EPO is expensive, there is therefore a need for optimising the efficiency of its administration. OBJECTIVES: The objectives of this review were to assess the effects of different frequency regimens of rHu EPO administration in dialysis patients in terms of i) effectiveness (correction of anaemia, quality of life and freedom from adverse events) ii) efficiency (optimal resource use) of different rHu EPO dose regimen policies. SEARCH STRATEGY: We searched MEDLINE (1980 to May Week 3 2001), EMBASE (1984 to Week 24 2001), BIOSIS (1985 to January 1997), CINAHL (1982 to October 1997), The Cochrane Library (Issue 1, 1997), CHEMABS (1984 to November 1996), SIGLE (1980 to June 1996), CRIB (10th edition, 1995), UK NRR (14th consolidation, September 1996), RSC ( 1980 to February 1997), HealthSTAR (1995 to October 1997), IBSS (1984 to July 1997), NEED (July 1997) and reference lists of relevant articles. We contacted biomedical companies and investigators in the field and we hand searched Kidney International (including all supplements but excluding all conference proceedings except for 1994) July 1983 to May 1997 inclusive. The Internet was also searched on: August 1997. We had also identified some studies from a previous broad search for all randomised controlled trials (RCTs) relevant to the management of end-stage renal disease. Date of the most recent search: June 2001. SELECTION CRITERIA: All randomised or quasi randomised controlled trials comparing different frequencies of rHu EPO administration in dialysis patients. Subgroup analyses were performed comparing haemodialysis and CAPD patients and also subcutaneous and intravenous administration. DATA COLLECTION AND ANALYSIS: Only published data were used. Data were abstracted by a single investigator on to a standard form. The data abstracted were relevant to the predetermined outcome measures: measures of correction of anaemia, rHu EPO dose, quality of life measures, adverse events, number of withdrawals from study, mortality. Where appropriate, a summary relative risk (RR) was calculated for dichotomous data and a weighted mean difference (WMD) or standardised mean difference (SMD) for continuous data. MAIN RESULTS: Eight studies met our inclusion criteria. When once a week administration was compared with twice weekly there was no significant difference in the ability to maintain the target haemoglobin (RR 1.00, 95% CI 0.42 to 2.40). Mean haemoglobin after twelve weeks of therapy was not different between the two groups (WMD -0.21g/dl, 95% CI -0.98 to 0.56). No difference was found in mean haemoglobin or haematocrit at the end of any studies which compared once with thrice weekly administration of rHu EPO (SMD -0.31, 95% CI -0.67 to 0.06). A single study which compared once with more that thrice weekly administration showed no significant difference in mean haemoglobin at the end of the maintenance phase (mean difference -0.2g/dl, 95% CI -0.65 to 0.25). The dosage of erythropoietin required by those on haemodialysis receiving rHu EPO once weekly was just significantly more (WMD 12.0 U/kg, 95% CI 0.24 to 23.76) than those receiving it twice weekly but the confidence interval is wide. No such difference was found for CAPD patients nor when the results were combined (WMD 5.15 U/kg, 95% CI -3.74 to 14.05). The result was not significant when comparing once weekly with thrice weekly administration (WMD 10.00 U/kg, 95% CI -80.87 to 100.87). There was no difference in the frequency of adverse events between any of the groups studies. REVIEWER'S CONCLUSIONS: There is no significant difference between once weekly versus thrice weekly subcutaneous administration of rHu EPO. Once weekly administration of rHu EPO would require an additional 12U/kg/week for patients on haemodialysis, however this is based on one very small study. The cost of this additional hRu EPO nee, however this is based on one very small study. The cost of this additional hRu EPO needs to assessed, in particular with regard to patient preference and compliance.

Anemia↗
PubMed2004

Meta-analysis of the results of intravenous gamma globulin treatment of coronary artery lesions in Kawasaki disease.

The objective of this study was to evaluate the efficacy of intravenous gamma globulin (IVGG) therapy on the prevention of coronary artery lesions (CALs) in patients with Kawasaki disease (KD), with reference to the literature on meta-analyses in randomized controlled studies. Studies from 1984 to the end of 2000 obtained from the National Library of Medicine or from the bibliographies of these articles were used in the analysis. The total number of patients with KD covered in 17 articles was 4020. All the articles were examined for the number of doses per day, the duration of administration, and the total number of IVGG doses. The number of patients in each group was counted, and the incidence of CALs was evaluated at 30 or 60 days after onset. The results of these searches were further analyzed by meta-analytical methods. The administration of IVGG significantly decreased the incidence of CALs in a dose-dependent manner: at 30 days after onset the incidence of CALs was 29.4% without IVGG but 21.6% with a total dosage of IVGG < 1000 mg/kg, 10.8% with a total dosage of 1000-2000 mg/kg, and 10.2% with a total dosage of > or =2000 mg/kg. Compared with the incidence of CALs without IVGG, the odds ratio (OR) was 0.662 [95% confidence interval (CI) 0.519-0.815)] at <1000 mg/kg, 0.292 (95% CI 0.222-0.371) with 1000-2000 mg/kg, and 0.274 (95% CI 0.207-0.349) with > or =2000 mg/kg. At 60 days, the values had decreased to 17.3%, 13.8% [OR 0.767 (95% CI 0.585-1.005)], 5.8% [OR 0.296 (95% CI 0.200-0.436)], and 4.9% [OR 0.244 (95% CI 0.170-0.349)], respectively. The meta-analyses also indicated that high doses of IVGG (> or =2000 mg/kg per day) given in a single dose prevented CALs more effectively than the same dosages divided into five daily doses in the patients with KD: The incidence of CALs at 30 days after disease onset was 2.4% with a single dose versus 12.9% with divided doses. Compared with divided doses, the OR with a single dose was 0.164 (95% CI 0.064-0.393) and 2.8% versus 6.1% at 60 days [OR 0.450 (95% CI 0.206-0.956)]. We clearly confirmed that higher doses of IVGG (> or =2000 mg/kg per day) administered in a single infusion were more effective for preventing CALs, as evaluated during both the subacute and convalescent phases of KD.

Journal Article↗
PubMed1997

Glutamate dehydrogenase mRNA is immediately induced after phencyclidine treatment in the rat brain.

To clarify the molecular mechanism of phencyclidine (PCP)-induced schizophreniform psychosis in humans and of behavioral abnormalities in experimental animals, we used differential screening of a cDNA library from the cerebral cortex of rats treated with PCP. We identified a PCP-induced cDNA clone as the gene encoding glutamate dehydrogenase (GDH), an enzyme central to glutamate metabolism. GDH mRNA levels significantly increased as early as 15 min following PCP administration in both the cerebral cortex and the cerebellum. This effect was observed even in the presence of a protein synthesis inhibitor, cycloheximide. In contrast to a transient increase in c-fos expression, the elevation of GDH mRNA levels lasted up to 8 days after a single PCP injection. These results suggest that GDH mRNA induction may be involved in the pathology of PCP-induced psychosis, and that GDH may be one of the candidate genes that are vulnerable in subjects with schizophrenia.

Animals↗
PubMed2004

Evaluation of evidence-based medicine search skills in the clinical years.

The librarians of the Health Sciences Library worked with the director of the Primary Care Clerkship to reinforce the principles of Evidence-Based Medicine (EBM) searching, taught during the first two years of medical school, through an intensive workshop. The purpose of the program was to ensure that students apply EBM principles in a timely and effective manner in clinical situations. Working in teams led by a resident and librarian, students researched real cases and then evaluated the effectiveness of their approach to the problems. This paper outlines the rationale for the team approach, reviews the administration of a computer-based workshop, and discusses the evaluation process. Evaluation focused on both the current workshop and its implications for the informatics program presented to students during years one and two.

Evidence-Based Medicine↗
PubMedDate not supplied

iMPACT3: Internet-based development and administration of utility elicitation protocols.

iMPACT3 (Internet Multimedia Preference Assessment Instrument Construction Tool, version 3) is a software development environment that helps researchers build Internet-capable multimedia utility elicitation software programs. The program is a free, openly accessible Web site (http.// preferences.ucsd.edu/impact3/asp). To develop a utility elicitation software program using iMPACT3, a researcher selects modular protocol components from a library and custom tailors the components to the details of his or her research protocol. iMPACT3 builds a Web site implementing the protocol and downloads it to the researcher's computer. In a study of 75 HIV-infected patients, an iMPACT3-generated protocol showed substantial evidence of construct validity and good internal consistency (logic error rates of 4% to 10% and procedural invariance error rates of 10% to 28%, depending on the elicitation method) but only fair 3- to 6-week test-retest reliability (intraclass correlation coefficient= 0.42 to 0.55). Further work may be needed on specific utility assessment procedures, but this study's results confirm iMPACT3's feasibility in facilitating the collection of health state utility data.

Adult↗
PubMed2003

Identification of hemopexin as a GH-regulated gene.

A cDNA library from the liver of a growth hormone (GH)-treated hypophysectomized rat was constructed and screened for GH-inducible genes (GIGs). Three cDNAs specific for putative GIG mRNAs (GIG-3, -7 and -12) were isolated and, when sequenced, were found to be homologous to portions of rat hemopexin, a Class 2 acute-phase gene. Hemopexin is an essential heme scavenger produced primarily in the liver, which upon binding to free heme, transports it to the liver where the heme iron is re-utilized. Hemopexin has not been previously described as being GH-responsive. GIG-3 and GIG-12 encode overlapping portions of the entire coding sequence starting within a few hundred base pairs from the 5' end of the hemopexin mRNA, and GIG-7 encodes the 3'-most end of the hemopexin mRNA. Northern analysis and ribonuclease protection assays of RNA from livers of control rats using the cDNA probes demonstrated a major transcript of approximately 2.0 kb. The hemopexin mRNA was low or undetectable in livers of hypophysectomized rats. Daily treatment with bovine growth hormone (bGH) for 10 days restored hemopexin mRNA to levels comparable or greater than that of intact rats. GH-dependence in cultured rat H4IIE hepatoma cells was then examined. Using hemopexin cDNA probes (GIG-3, -7, and -12) we identified a mRNA on Northern blots, which increased in concentration following bGH, compared with untreated cells. When measured by ribonuclease protection assay, a maximal increase in hemopexin mRNA concentration was obtained following 4-6 h of bGH administration. We conclude that hemopexin is a GH-inducible gene in rat liver in vivo and in cultured rat hepatoma cells.

Animals↗
PubMed1998

UDP-glucuronosyltransferase UGT1A7 induced in rat small intestinal mucosa by oral administration of 2-naphthoflavone.

In the rat intestine, UDP-glucuronosyltransferase (UGT) isoforms were highly induced by oral administration of 2-naphthoflavone, as shown by intestinal UGT activity toward 1-naphthol (1-NA). The greatest increase in UGT activity occurred in the duodenum. Using UGT1A6 cDNA as a probe, we obtained three types of clones corresponding to UGT1A2, UGT1A6 and UGT1A7, in a ratio of 1:1:8, from a cDNA library constructed from the 2-naphthoflavone-treated rat intestine. The induction of each isoform was evaluated by means of Northern blotting with isoform-specific probes. The mRNAs of UGT1A6 (glucuronizing various phenolic xenobiotics) and the mRNAs of UGT1A7 (glucuronizing the ultimate carcinogenic metabolite of benzo(a)pyrene) were expressed constitutively and were highly induced in the duodenum and proximal jejunum. S1 mapping showed that induction of the isoforms of the UGT1 family was more pronounced in the liver than in the small intestine and that UGT1A7 was the major UGT1 isoform in the small intestine of vehicle-treated rats and in that of 2-naphthoflavone-treated rats. These results indicate that, in rats, UGT1A7 is expressed constitutively and is particularly inducible in the small intestine. In the light of these results, we believe that the UGT1A7 isoform would play an important role in glucuronidation in the small intestinal mucosa of rats.

Administration, Oral↗
PubMed2003

Outcome measures and needs assessment tools for schizophrenia and related disorders.

BACKGROUND: There has been a recent trend to encourage routine outcome measurement and needs assessment as an aid to decision making in clinical practice and patient care. Standardised instruments have been developed which measure clinical symptoms of disorders such as schizophrenia, wider health related quality of life and patients' needs. Such measures might usefully be applied to aid the recognition of psychosocial problems and to monitor the course of patients' progress over time in terms of disease severity and associated deficits in health related quality of life. They might also be used to help clinicians to make decisions about treatment and to assess subsequent therapeutic impact. Such an approach is not, however, without cost and the actual benefit of the adoption of routine outcome and needs assessment in the day-to-day care of those with schizophrenia remains unclear. OBJECTIVES: To establish the value of the routine administration of outcome measures and needs assessment tools and the feedback they provide in improving the management and outcome of patients with schizophrenia and related disorders. SEARCH STRATEGY: The reviewers undertook electronic searches of the British Nursing Index (1994 to Sept 1999), the Cochrane Library (Issue 2, 2002), the Cochrane Schizophrenia Group Trials Register (2002), EMBASE (1980-2002), MEDLINE (1966-2002), and PsycLIT (1887-2002), together with hand searches of key journals. References of all identified studies were searched for further trials, and the reviewers contacted authors of trials. SELECTION CRITERIA: Randomised controlled trials comparing the feedback of routine standardised outcome measurement and needs assessment, to routine care for those with schizophrenia. DATA COLLECTION AND ANALYSIS: Reviewers evaluated data independently. Studies which randomised clinicians or clinical teams (rather than individual patients) were considered to be the most robust. However only those which took account of potential clustering effects were considered further. Where possible and appropriate, risk ratios (RR) and their 95% confidence intervals (CI) were calculated. For continuous data Weighted Mean Differences (WMD) were calculated. Data were inspected for heterogeneity. MAIN RESULTS: No randomised data were found which addressed the specified objectives. One unpublished and one ongoing trial was identified. REVIEWER'S CONCLUSIONS: The routine use of outcomes measures and needs assessment tools is, as yet, unsupported by high quality evidence of clinical and cost effectiveness. Clinicians, patients and policy makers alike may wish to see randomised evidence before this strategy is routinely adopted.

Humans↗
PubMedDate not supplied

Biochemical characterization of atroxase and nucleotide sequence encoding the fibrinolytic enzyme.

Atroxase, isolated from the venom of Crotalus atrox (western diamondback rattlesnake), is a non-hemorrhagic protease which has fibrinolytic activity in vitro and in vivo. Fibrin solubilization occurs primarily from the hydrolysis of alpha-polymer and unpolymerized alpha- and beta-chains. The enzyme also cleaves the A alpha-chain of fibrinogen first, followed by the B beta-chain, and shows no effect on the gamma-chain. Although crude venom induces platelet aggregation, atroxase demonstrated no ability to induce or inhibit aggregation. Intravenous administration of atroxase at a dosage of 6.0 mg/kg resulted in thrombolysis within 1 hr followed by recanalization. The primary structure of atroxase was deduced from the cDNA encoding the atroxase protein. The venom glands of C. atrox were used to prepare a cDNA library. Degenerate oligonucleotides were synthesized based on the partial amino acid sequence of atroxase and were used as primers in the polymerase chain reaction to amplify overlapping cDNA fragments from the C. atrox cDNA library. The resulting cDNA fragments were subcloned, sequenced, and translated. The final nucleotide sequence shows high homology to previously described primary structures of non-hemorrhagic fibrinolytic proteases isolated from snake venom. The base sequence of cDNA obtained from colony hybridization also showed comparable results to the cDNA fragment amplified by PCR.

Amino Acid Sequence↗