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PubMed1989

Two forms of omega-hydroxylase toward prostaglandin A and laurate. cDNA cloning and their expression.

We have isolated cDNA clones for two forms of P-450s, P-450ka-1 and P-450ka-2, from a rabbit kidney cDNA library, using the cDNA for rabbit pulmonary cytochrome P-450p-2, a prostaglandin omega-hydroxylase (Matsubara, S., Yamamoto, S., Sogawa, K., Yokotani, N., Fujii-Kuriyama, Y., Haniu, M., Shively, J.E., Gotoh, O., Kusunose, E., and Kusunose, M. (1987) J. Biol. Chem. 262, 13366-13371), as a hybridization probe. The cDNAs for P-450ka-1 and P-450ka-2 encode polypeptides of 510 and 511 amino acids, respectively, with sequence similarity of 85% and 87% to P-450p-2. The two deduced primary structures have 87% identity. RNA blot analysis demonstrated that the mRNAs for P-450ka-1 and P-450ka-2 formed single bands at approximately 3.0- and 2.6-kilobase positions, respectively. The mRNA for P-450ka-1 was expressed only in the liver and kidney and was increased remarkably in these tissues by the administration of clofibrate. In contrast, the mRNA for P-450ka-2 was expressed constitutively in the liver, kidney, and small intestine, but its transcription was enhanced only in the liver by clofibrate treatment. Thus, in spite of their high sequence similarity, these P-450 species have different modes of regulatory expression. Comparison of the nucleotide sequences among P-450ka-1, P-450ka-2, and P-450p-2 shows about 90% overall sequence similarity in any pair of the three sequences. Nucleotide replacements are not evenly distributed, but are rather biased. There is a region of approximately 500 base pairs of exceptionally high homology among the three sequences. These results indicate that the gene conversion event occurred during the evolutionary process of these genes.

Amino Acid Sequence↗

PubMed1992

Composite resident work week.

During a 4-week period, all residents in the Wright State University School of Medicine Department of Surgery residency program were required to keep a log of their daily activities. Times were collected for the following resident activities: patient rounds, work-ups, laboratory data review, consults, meetings with attending physicians or patient families, phone calls, teaching conferences, medical student teaching, library time, clinics, attendance at codes, emergency department visits, on-call time, medical records committee meetings, and time scrubbed. The composite average weekly hours by resident year were 83.4 hours [postgraduate year (PGY)-1], 78.4 hours (PGY-2), 60.2 hours (PGY-3), 79.6 hours (PGY-4), and 80.9 hours (PGY-5). More than 50% of the resident work week cards were for less than 80 hours. Three activities (patient rounds, time scrubbed, and on-call) accounted for the majority of the residents' hours, but the average week, deleting educational and administrative hours, was less than 80 hours for all residents.

General Surgery↗

PubMed2002

Attenuation of thermal nociception and hyperalgesia by VR1 blockers.

Vanilloid receptor subunit 1 (VR1) appears to play a critical role in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues. Thus, VR1 antagonists are useful compounds to unravel the contribution of this receptor to pain perception, as well as to induce analgesia. We have used a combinatorial approach to identify new, nonpeptidic channel blockers of VR1. Screening of a library of trimers of N-alkylglycines resulted in the identification of two molecules referred to as DD161515 [N-[2-(2-(N-methylpyrrolidinyl)ethyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide] and DD191515 [[N-[3-(N,N-diethylamino)propyl]glycyl]-[N-[2,4-dichlorophenethyl]glycyl]-N-(2,4-dichlorophenethyl)glycinamide] that selectively block VR1 channel activity with micromolar efficacy, rivaling that characteristic of vanilloid-related inhibitors. These compounds appear to be noncompetitive VR1 antagonists that recognize a receptor site distinct from that of capsaicin. Intraperitoneal administration of both trialkylglycines into mice significantly attenuated thermal nociception as measured in the hot plate test. It is noteworthy that these compounds eliminated pain and neurogenic inflammation evoked by intradermal injection of capsaicin into the animal hindpaw, as well as the thermal hyperalgesia induced by tissue irritation with nitrogen mustard. In contrast, responses to mechanical stimuli were not modified by either compound. Modulation of sensory nerve fibers excitability appears to underlie the peptoid analgesic activity. Collectively, these results indicate that blockade of VR1 activity attenuates chemical and thermal nociception and hyperalgesia, supporting the tenet that this ionotropic receptor contributes to chemical and thermal sensitivity and pain perception in vivo. These trialkylglycine-based, noncompetitive VR1 antagonists may likely be developed into analgesics to treat inflammatory pain.

Animals↗

PubMed2002

Recombinant human erythropoietin use in intensive care.

OBJECTIVE: To review the literature concerning the role of recombinant human erythropoietin (rHuEPO) in reducing the need for transfusion in critically ill patients. DATA SOURCES: Articles were obtained through searches of the MEDLINE database (from 1990 to June 2001) using the key words erythropoietin, epoetin alfa, anemia, reticulocytes, hemoglobin, critical care, intensive care, critical illness, and blood transfusion. Additional references were found in the bibliographies of the articles cited. The Cochrane library was also consulted. STUDY SELECTION AND DATA EXTRACTION: Controlled, prospective, and randomized studies on the use of rHuEPO in critically ill adults were selected. DATA SYNTHESIS: Anemia is a common complication in patients requiring intensive care. It is caused, in part, by abnormally low concentrations of endogenous erythropoietin and is mainly seen in patients with sepsis and multiple organ dysfunction syndrome, in whom inflammation mediator concentrations are often elevated. High doses of rHuEPO produce a rapid response in these patients, despite elevated cytokine concentrations. There have been 3 studies on rHuEPO administration in intensive care and 1 trial in acutely burned patients. Only 2 of these studies looked at the impact of rHuEPO administration on the need for transfusion. CONCLUSIONS: Few randomized, controlled trials explore the role of rHuEPO in critical care. Only 1 was a large, randomized clinical trial, but it presents many limitations. Future outcome and safety studies comparing rHuEPO with placebo must include clinical endpoints such as end-organ morbidity, mortality, transfusion criteria, and pharmacoeconomic analysis. rHuEPO appears to provide an erythropoietic response. Optimal dosage and the real impact of rHuEPO on the need for transfusion in intensive care remain to be determined. Currently, based on the evidence available from the literature, rHuEPO cannot be recommended to reduce the need for red blood cell transfusions in anemic, critically ill patients.

Anemia↗

PubMed1988

Implementing meaningful CME as an essential component in a community hospital quality assurance plan.

The pursuit of high-quality patient care within a community hospital highlights the tenuous relationship between the hospital board and administration on one side and the voluntary medical staff on the other. Craddick describes the need to monitor and improve patient management, the commitment of physicians and administrators to high quality care, and the unfortunate failure of most hospital programs to go beyond paper exercises designed to satisfy the Joint Commission of Accreditation of Hospitals (JCAH). The American College of Surgeons summarizes current methods of monitoring the quality of patient care, and gives four examples of successful programs. The JCAH Manual sets standards for hospitals and medical staffs to achieve. However, thus far no one has described how a hospital's medical staff, board, and administration join forces to implement a comprehensive quality assurance program. This paper presents the experience of one community hospital in dealing with this problem over a two-year period.

Concurrent Review↗

PubMed2002

Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is used to support preterm infants recently extubated, those experiencing significant apnoea of prematurity and those with respiratory distress soon after birth as an alternative to intubation and ventilation. This review will focus exclusively on identifying the most effective pressure source and interface for NCPAP delivery in preterm infants. OBJECTIVES: In preterm infants extubated to NCPAP following intermittent positive pressure ventilation (IPPV) for respiratory distress syndrome (RDS) or in those treated with NCPAP soon after birth, which technique of pressure generation and which type of nasal interface for NCPAP delivery most effectively reduces the need for additional respiratory support? SEARCH STRATEGY: The strategy included searches of MEDLINE (1966-2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), CINAHL, abstracts from conference proceedings, cross-referencing of previous reviews and the use of expert informants. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing different techniques of NCPAP pressure generation and/or nasal interfaces in preterm infants extubated to NCPAP following IPPV for RDS or treated with NCPAP soon after birth. DATA COLLECTION AND ANALYSIS: Data was extracted and analysed by the first three authors. Dichotomous results were analysed using the relative risk (RR), risk difference (RD) and number needed to treat (NNT). MAIN RESULTS: 1. Preterm infants being extubated to NCPAP following a period of IPPV for RDS: Meta-analysis of the results from Davis 2001 and Roukema 1999a demonstrated that short binasal prongs are more effective at preventing re-intubation than single nasal or nasopharyngeal prongs [typical RR 0.59 (CI: 0.41, 0.85), typical RD -0.21 (CI: -0.35, -0.07), NNT 5 (CI: 3, 14)]. In the single study comparing short binasal prong devices (Sun 1999) the re-intubation rate was significantly lower with the Infant Flow Driver than with the Medicorp prong [RR 0.33 (CI: 0.17, 0.67), RD -0.32 (CI: -0.49, -0.15), NNT 3 (CI: 2, 7)]. 2. Preterm infants primarily treated with NCPAP soon after birth: The one trial identified, Mazzella 2001, found a significantly lower oxygen requirement and respiratory rate in those randomised to short binasal prongs when compared with CPAP delivered via nasopharyngeal prong. The requirement for intubation beyond 48 hours from randomisation was not assessed. No studies comparing different techniques of pressure generation were identified. REVIEWER'S CONCLUSIONS: Short binasal prong devices are more effective than single prongs in reducing the rate of re-intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer-term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP.

Humans↗

PubMed2005

A combinatorial approach to the selective capture of circulating malignant epithelial cells by peptide ligands.

Early detection is critical in the administration of definitive and curative therapy of cancer. However, current detection methods are ineffective at identifying the presence of circulating metastatic cancer cells in the blood because they typically sample only a relatively small volume of blood. One strategy for sampling larger blood volumes would be to capture circulating cells in vivo over an extended period of time. The development of such a method would be substantially facilitated by the identification of peptide ligands that bind selectively to metastatic cancer cells in the blood with high affinity. To identify such ligands a combinatorial peptide library was synthesized on polyethylene acrylamide (PEGA) resin and screened for binding to malignant epithelial cells. Using Biacore, cell binding assays were performed to demonstrate that peptides selected from PEGA bead screen can bind selectively to malignant epithelial cancer cells and not to circulating leukocytes under physiologic shear stress conditions. One peptide, with the sequence QMARIPKRLARH, was used to demonstrate selective labeling of malignant epithelial cells spiked in whole blood. When immobilized on appropriate surfaces, these peptides could be used in both in vivo and ex vivo cell separation devices to efficiently and selectively capture metastatic epithelial cancer cells from flowing blood.

Acrylamides↗

PubMed1994

Evaluating the accuracy of citations in drug promotional brochures.

OBJECTIVE: To evaluate the accuracy of statements cited in 3 x 5 inch promotional cards for the 50 most frequently prescribed drugs. MEASUREMENTS: The 50 most frequently prescribed drugs were identified in the April 1992 issue of Pharmacy Times. File cards were requested from the pharmaceutical companies. References in the file card were retrieved and cited statements identified. Criteria used to evaluate reference accuracy were: type of study design, use of peer review journals, retrievability of references in area libraries, and reference documentation as no error, major error, or minor error. Referenced statements were classified as correct, incorrect, misleading, or taken from the abstract, discussion, or conclusion section of a study. RESULTS: Of the 50 most frequently prescribed products, 21 file cards were obtained. One hundred forty-two cited references were retrieved (average +/- SD per file card 6.9 +/- 8.4). Three hundred thirty-four cited statements were verified (average per file card 15.9 +/- 24.7). Forty-two percent of references were human controlled trials, 17 percent not available, 11 percent review articles, 10 percent manufacturer information, 8 percent human uncontrolled, 4 percent nonhuman controlled, 3 percent retrospective, 2 percent tertiary literature, 1 percent epidemiologic studies, 1 percent prospective, and 1 percent editorial. Thirty-three percent of references were found in peer-review journals. Of all cited references, 73 percent were retrievable. Thirty-nine references were not retrievable: 24 were not held by local libraries and 15 were manufacturers' information. Eighty-five percent of references contained no errors in reference documentation. For accuracy of statements, 46.1 percent were correct, 29 percent not available, 15.3 percent misleading, 4.2 percent incorrect, and 5.4 percent were cited from the abstract, discussion, or conclusion section of the study. CONCLUSIONS: Most references cited in pharmaceutical promotional brochures referenced controlled studies that are retrievable. However, incorporation of more adequately controlled studies, more references from peer review journals, and careful evaluation of referenced statements by the pharmaceutical company, journals' editorial board. Food and Drug Administration, and healthcare professionals may be beneficial.

Bibliographies as Topic↗

PubMed2000

Phenobarbital prior to preterm birth for preventing neonatal periventricular haemorrhage.

BACKGROUND: Preterm infants are at risk of periventricular haemorrhage. This can damage the brain and lead to neurodevelopmental abnormalities, including cerebral palsy. Phenobarbital might prevent ischaemic injury or reduce fluctuations in blood pressure and blood flow in the brain. OBJECTIVES: The objective of this review was to assess the benefits and harms of giving phenobarbital to women at risk of imminent very preterm birth with the primary aim of preventing periventricular haemorrhage in the infant. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register and bibliographies. Date of last search: December 1998. SELECTION CRITERIA: Randomised trials with reported data which compare outcomes, such as neonatal mortality, neonatal neurological and other morbidity, longterm neurodevelopment and maternal morbidity, following prenatal exposure to phenobarbital, with outcomes in controls with or without placebo. DATA COLLECTION AND ANALYSIS: Assessments of trial eligibility, quality and data extractions were done by the two authors independently. Eligible trials were included in the initial analysis and prespecified sensitivity analyses done to evaluate the effect of trial quality. MAIN RESULTS: Over 1600 women were entered into the eight trials included. Analyses showed a significant reduction in the rates of all grades of periventricular haemorrhage (PVH) (relative risk 0.75, 95% confidence interval 0.65 to 0.88) and severe grades PVH (3 and 4) (relative risk 0.49, 95% confidence interval 0.32 to 0.74) in infants whose mothers had been given prenatal phenobarbital. These results were influenced by the earlier trials which were of poorer quality and contributed excessive weight in the analysis due to their higher rates of severe PVH. Over time, and with improved trial quality, these beneficial effects disappeared. No difference was found in the incidence of neurodevelopmental abnormalities at paediatric follow-up assessed between 18-36 months of age. Maternal sedation was more likely in women receiving phenobarbital. REVIEWER'S CONCLUSIONS: Phenobarbital administration to women prior to preterm birth cannot be recommended for routine clinical practice. Any future trials should examine the effects of phenobarbital prior to preterm birth at gestational ages with a high risk of PVH, stratify for gestational age and ensure minimal exclusions after randomisation. Neurodevelopmental status at follow-up should be measured as the most important outcome.

Central Nervous System Agents↗

PubMed1973

Professionals: their problems, their fears, and their social responsibilities.

Professional societies have been reluctant to enter actively into the public processes by which decisions are made on economic, social, and political issues. This reluctance comes from (1) fears about the status of the profession and the professional society, (2) fears about economic reprisal, (3) potential conflicts between the goals of a philosophy of trade unionism and the goals of a philosophy of professional social responsibility, and (4) domination of some professional societies by nonprofessional business, industrial, or administrative groups. This reluctance has been justified by the development of a myth that the professional can exercise individual social responsibility while maintaining the neutrality of his institutions and societies. This myth must be ignored because our public decision-making processes can only function properly if groups, such as professional societies, actively enter that decision-making process.

Economics↗

PubMed1992

Structure and tissue-specific expression of 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase genes in human and rat classical and peripheral steroidogenic tissues.

The enzyme 3 beta-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3 beta-HSD) catalyzes the oxidation and isomerization of 5-ene-3 beta-hydroxypregnene and 5-ene-hydroxyandrostene steroid precursors into the corresponding 4-ene-ketosteroids necessary for the formation of all classes of steroid hormones. We have recently characterized two types of human 3 beta-HSD cDNA clones and the corresponding genes which encode deduced proteins of 371 and 372 amino acids, respectively, and share 93.5% homology. The human 3 beta-HSD genes containing 4 exons were assigned by in situ hybridization to the p11-p13 region of the short arm of chromosome 1. We have also recently elucidated the structure of three types of rat 3 beta-HSD cDNAs as well as that of one type of 3 beta-HSD from bovine and macaque ovary lambda gt11 cDNA libraries which all encode 372 amino acid proteins. The human type I 3 beta-HSD is the almost exclusive mRNA species detected in the placenta and skin, while the human type II is the predominant mRNA species in the adrenals, ovaries and testes. The predicted rat type I and type II 3 beta-HSD proteins expressed in adrenals, gonads and adipose tissue share 94% homology while they share 80% similarity with the liver-specific type III 3 beta-HSD. Transient expression of human type I and type II as well as rat type I and type II 3 beta-HSD cDNAs in HeLa human cervical carcinoma cells reveals that 3 beta-ol dehydrogenase and 5-ene-4-ene isomerase activities reside within a single protein and these cDNAs encode functional 3 beta-HSD proteins that are capable of converting 3 beta-hydroxy-5-ene-steroids into 3-keto-4-ene derivatives as well as the interconversion of 3 beta-hydroxy and 3-keto-5 alpha-androstane steroids. We have found that the rat type III mRNA species was below the detection limit in intact female liver while, following hypophysectomy, its accumulation increased to 55% of the levels measured in intact or HYPOX male rats, an increase which can be blocked by administration of ovine prolactin (oPRL). In addition, in female rats, treatment with oPRL for 10 days starting 15 days after HYPOX, markedly decreased ovarian 3 beta-HSD mRNA accumulation accompanied by a similar decrease in 3 beta-HSD activity and protein levels. Treatment with the gonadotropin hCG reversed the potent inhibitory effect of oPRL on these parameters and stimulated 3 beta-HSD mRNA levels in ovarian interstitial cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1991

A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA).

Carcinoembryonic antigen (CEA) is a 180-kDa glycoprotein expressed on most gastrointestinal carcinomas. A 2.4-kb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and inserted into a vaccinia virus genome. This newly developed construct was characterized by Southern blotting, DNA hybridization studies, and polymerase chain reaction analysis. The CEA gene was stably integrated into the vaccinia virus thymidine kinase gene. The recombinant was efficiently replicated upon serial passages in cell cultures and in animals. The recombinant virus expresses on the surface of infected cells a protein product recognized by a monoclonal antibody (COL-I) directed against CEA. Immunization of mice with the vaccinia construct elicited a humoral immune response against CEA. Pilot studies also showed that administration of the recombinant CEA vaccinia construct was able to greatly reduce the growth in mice of a syngeneic murine colon adenocarcinoma which had been transduced with the human CEA gene. The use of this new recombinant CEA vaccinia construct may thus provide an approach in the specific active immunotherapy of human GI cancer and other CEA expressing carcinoma types.

Adenocarcinoma↗

PubMed2002

L-arginyl-3,4-spermidine is neuroprotective in several in vitro models of neurodegeneration and in vivo ischaemia without suppressing synaptic transmission.

1. Stroke is the third most common cause of death in the world, and there is a clear need to develop new therapeutics for the stroke victim. To address this need, we generated a combinatorial library of polyamine compounds based on sFTX-3.3 toxin from which L-Arginyl-3,4-Spermidine (L-Arg-3,4) emerged as a lead neuroprotective compound. In the present study, we have extended earlier results to examine the compound's neuroprotective actions in greater detail. 2. In an in vitro ischaemia model, L-Arg-3,4 significantly reduced CA1 cell death when administered prior to induction of 60 min of ischaemia as well as when administered immediately after ischaemia. Surprisingly, L-Arg-3,4 continued to prevent cell death significantly when administration was delayed for as long as 60 min after ischaemia. 3. L-Arg-3,4 significantly reduced cell death in excitotoxicity models mediated by glutamate, NMDA, AMPA, or kainate. Unlike glutamate receptor antagonists, 300 microM L-Arg-3,4 did not suppress synaptic transmission as measured by evoked responses in acute hippocampal slices. 4. L-Arg-3,4 provided significant protection, in vitro, in a superoxide mediated injury model and prevented an increase of superoxide production after AMPA or NMDA stimulation. It also decreased nitric oxide production after in vitro ischaemia and NMDA stimulation, but did so without inhibiting nitric oxide synthase directly. 5. Furthermore, L-Arg-3,4 was significantly neuroprotective in an in vivo model of global forebrain ischaemia, without any apparent neurological side-effects. 6. Taken together, these results demonstrate that L-Arg-3,4 is protective in several models of neurodegeneration and may have potential as a new therapeutic compound for the treatment of stroke, trauma, and other neurodegenerative diseases.

Animals↗

PubMed2000

Literature searching and document delivery: organisational issues.

An overview of financial, staffing and administrative issues regarding online literature searching and document supply is given in this article. Online literature searching and the requesting of documents have been problematic in the past due to costs and lack of information technology. Electronic document delivery requires better Internet access but MIME compatible e-mail can be used. Institutional issues regarding requests include the question 'who should order?'--the end user or intermediary ordering by the institution, and the need for trained information professionals within medical institutions. Payment mechanisms can be by credit card, institutional subscription, institutional account with the supplying library or by voucher system. Organisational Document Supply Networks (LoansomeDoc) now exist that have set charges for certain services between members or different costs for different member types and with agreed payment mechanisms. An area of increasing importance for document delivery (due to international treaties) is copyright. If such legislation is not to adversely affect information access, professionals must be involved in the creation and amendment of such legislation. Finally, a list of references are given many of which include internet addresses.

Humans↗

PubMed2005

Emergency interventions for hyperkalaemia.

BACKGROUND: Hyperkalaemia occurs in outpatients and in between 1% and 10% of hospitalised patients. When severe, consequences include arrhythmia and death. OBJECTIVES: To review randomised evidence informing the emergency (i.e. acute, rather than chronic) management of hyperkalaemia SEARCH STRATEGY: We searched MEDLINE (1966-2003), EMBASE (1980-2003), The Cochrane Library (issue 4, 2003), and SciSearch using the text words hyperkal* or hyperpotass* (* indicates truncation). We also searched selected journals and abstracts of meetings. The reference lists of recent review articles, textbooks, and relevant papers were reviewed for additional potentially relevant titles. SELECTION CRITERIA: All selection was performed in duplicate. Articles were considered relevant if they were randomised, quasi-randomised or cross-over randomised studies of pharmacological or other interventions to treat non-neonatal humans with hyperkalaemia, reporting on clinically-important outcomes, or serum potassium levels within the first six hours of administration. DATA COLLECTION AND ANALYSIS: All data extraction was performed in duplicate. We extracted quality information, and details of the patient population, intervention, baseline and follow-up potassium values. We extracted information about arrhythmias, mortality and adverse effects. Where possible, meta-analysis was performed using random effects models. MAIN RESULTS: None of the studies of clinically-relevant hyperkalaemia reported mortality or cardiac arrhythmias. Reports focussed on serum potassium levels. Many studies were small, and not all intervention groups had sufficient data for meta-analysis to be performed. On the basis of small studies, inhaled beta-agonists, nebulised beta-agonists, and intravenous (IV) insulin-and-glucose were all effective, and the combination of nebulised beta agonists with IV insulin-and-glucose was more effective than either alone. Dialysis is effective. Results were equivocal for IV bicarbonate. K-absorbing resin was not effective by four hours, and longer follow up data on this intervention were not available from RCTs. AUTHORS' CONCLUSIONS: Nebulised or inhaled salbutamol, or IV insulin-and-glucose are the first-line therapies for the management of emergency hyperkalaemia that are best supported by the evidence. Their combination may be more effective than either alone, and should be considered when hyperkalaemia is severe. When arrhythmias are present, a wealth of anecdotal and animal data suggests that IV calcium is effective in treating arrhythmia. Further studies of the optimal use of combination treatments and of the adverse effects of treatments are needed.

Adrenergic beta-Agonists↗

PubMed2006

What is the best dementia screening instrument for general practitioners to use?

OBJECTIVE: The objective of this study was to review existing dementia screening tools with a view to informing and recommending suitable instruments to general practitioners (GPs) based on their performance and practicability for general practice. METHOD: A systematic search of pre-MEDLINE, MEDLINE, PsycINFO, and the Cochrane Library Database was undertaken. Only available full-text articles about dementia screening instruments written in English or with an English version were included. Articles using a translation of an English language instrument were excluded unless validated in a general practice, community, or population sample. RESULTS: The General Practitioner Assessment of Cognition (GPCOG), Mini-Cog, and Memory Impairment Screen (MIS) were chosen as most suitable for routine dementia screening in general practice. The GPCOG, Mini-Cog, and MIS were all validated in community, population, or general practice samples, are easy to administer, and have administration times of 5 minutes or less. They also have negative predictive validity and misclassification rates, which do not differ significantly from those of the Mini-Mental Status Examination. CONCLUSIONS: It is recommended that GPs consider using the GPCOG, Mini-Cog, or MIS when screening for cognitive impairment or for case detection.

Aged↗

PubMed2005

MicroGen: a MIAME compliant web system for microarray experiment information and workflow management.

BACKGROUND: Improvements of bio-nano-technologies and biomolecular techniques have led to increasing production of high-throughput experimental data. Spotted cDNA microarray is one of the most diffuse technologies, used in single research laboratories and in biotechnology service facilities. Although they are routinely performed, spotted microarray experiments are complex procedures entailing several experimental steps and actors with different technical skills and roles. During an experiment, involved actors, who can also be located in a distance, need to access and share specific experiment information according to their roles. Furthermore, complete information describing all experimental steps must be orderly collected to allow subsequent correct interpretation of experimental results. RESULTS: We developed MicroGen, a web system for managing information and workflow in the production pipeline of spotted microarray experiments. It is constituted of a core multi-database system able to store all data completely characterizing different spotted microarray experiments according to the Minimum Information About Microarray Experiments (MIAME) standard, and of an intuitive and user-friendly web interface able to support the collaborative work required among multidisciplinary actors and roles involved in spotted microarray experiment production. MicroGen supports six types of user roles: the researcher who designs and requests the experiment, the spotting operator, the hybridisation operator, the image processing operator, the system administrator, and the generic public user who can access the unrestricted part of the system to get information about MicroGen services. CONCLUSION: MicroGen represents a MIAME compliant information system that enables managing workflow and supporting collaborative work in spotted microarray experiment production.

Computational Biology↗

PubMed2001

Isolation and characterization of a novel member of the relaxin/insulin family from the testis of the frog Rana esculenta.

A complementary DNA (cDNA) encoding a frog relaxin/insulin member family (fRLX) from testis cDNA library was isolated and characterized. The fRLX cDNA predicted a 155-amino acid protein with a low homology to mammalian RLF and relaxin. Northern blot analysis revealed a single transcript expressed in the interstitial compartment, RT-PCR, evidenced that fRLX is expressed at low levels in the oviduct and ovary too. The predicted mature fRLX protein, composed of the signal peptide, B, C, and A domains, has conserved amino acid sequences in the characteristic functional domains. A different expression of the transcript was found during the frog reproductive cycle, with a peak in Spring. After administration of ethane dimethane sulfonate, by in situ hybridization, fRLX messenger RNA disappeared from the interstitial compartment and reappeared again at the time of generating of a new population of Leydig cells (LC), strongly indicating that LC are the interstitial cell type expressing fRLX. Preliminary results obtained by in situ hybridization, performed on testis of hypophysectomized frogs evidenced a pituitary control of fRLX expression. This study is the first cloning of a relaxin/insulin family member in a nonmammalian vertebrate. In addition, because fRLX expression changes during the annual cycle suggesting its involvement in spermatogenesis, fRLX may be considered a new marker for the study of spermatogenesis in the Rana esculenta.

Amino Acid Sequence↗