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At least 325 records · Page 18Linked to original sources
PubMed2002

[Use of ropivacaine for peridural postoperative analgesia].

OBJECTIVES: To describe pharmacology and toxicology of ropivacaine. To assess the clinical efficacy of ropivacaine when used for postoperative epidural analgesia and to provide recommendations for clinical practice. DATA SOURCES: Search in the Medline data base of original articles in French and English published since 1995, using the following key words: ropivacaine, postoperative analgesia, epidural, caudal block. STUDY SELECTION: Prospective randomised studies in adults and children were selected. Letters to editors and editorials were excluded. DATA EXTRACTION: Articles have been analyzed: to determine the dose of ropivacaine required for postoperative epidural analgesia, to assess the benefits of combination of epidural ropivacaine and additives (opioids or other), to compare epidural ropivacaine and bupivacaine and to assess the use of ropivacaine via caudal route for paediatric postoperative analgesia. DATA SYNTHESIS: 20 mg h-1 of ropivacaine is required to provide effective analgesia. This dose produces a motor block in a significant number of patients. Combination with an opioid allows for a reduction in ropivacaine requirement and subsequently in the incidence of motor blockade. In adults, equipotency ratio of ropivacaine and bupivacaine varies between 1.5/1 and 1/1 depending upon the concentration used. At equipotent doses, early postoperative mobilisation is facilitated with ropivacaine. In case of paediatric caudal analgesia, this ratio is close to 1. CONCLUSIONS: Epidural ropivacaine combined with opioid provide good postoperative pain relief. Reduction in the incidence of motor blockade and safe toxicological profile make this local anaesthetic a suitable alternative of bupivacaine for postoperative epidural analgesia.

Amides↗
PubMed2025

Integrated epigenetic and genetic programming of primary human T cells.

Targeted epigenetic engineering of gene expression in cell therapies would allow programming of desirable phenotypes without many of the challenges and safety risks associated with double-strand break-based genetic editing approaches. Here, we develop an all-RNA platform for efficient, durable and multiplexed epigenetic programming in primary human T cells, stably turning endogenous genes off or on using CRISPRoff and CRISPRon epigenetic editors. We achieve epigenetic programming of diverse targeted genomic elements without the need for sustained expression of CRISPR systems. CRISPRoff-mediated gene silencing is maintained through numerous cell divisions, T cell stimulations and in vivo adoptive transfer, avoiding cytotoxicity or chromosomal abnormalities inherent to multiplexed Cas9-mediated genome editing. Lastly, we successfully combined genetic and epigenetic engineering using orthogonal CRISPR Cas12a-dCas9 systems for targeted chimeric antigen receptor (CAR) knock-in and CRISPRoff silencing of therapeutically relevant genes to improve preclinical CAR-T cell-mediated in vivo tumor control and survival.

Humans↗
PubMed1988

'DNA Strider': a 'C' program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers.

DNA Strider is a new integrated DNA and Protein sequence analysis program written with the C language for the Macintosh Plus, SE and II computers. It has been designed as an easy to learn and use program as well as a fast and efficient tool for the day-to-day sequence analysis work. The program consists of a multi-window sequence editor and of various DNA and Protein analysis functions. The editor may use 4 different types of sequences (DNA, degenerate DNA, RNA and one-letter coded protein) and can handle simultaneously 6 sequences of any type up to 32.5 kB each. Negative numbering of the bases is allowed for DNA sequences. All classical restriction and translation analysis functions are present and can be performed in any order on any open sequence or part of a sequence. The main feature of the program is that the same analysis function can be repeated several times on different sequences, thus generating multiple windows on the screen. Many graphic capabilities have been incorporated such as graphic restriction map, hydrophobicity profile and the CAI plot- codon adaptation index according to Sharp and Li. The restriction sites search uses a newly designed fast hexamer look-ahead algorithm. Typical runtime for the search of all sites with a library of 130 restriction endonucleases is 1 second per 10,000 bases. The circular graphic restriction map of the pBR322 plasmid can be therefore computed from its sequence and displayed on the Macintosh Plus screen within 2 seconds and its multiline restriction map obtained in a scrolling window within 5 seconds.

Amino Acid Sequence↗
PubMed2004

Suicidality as a Possible Side Effect of Antidepressant Treatment.

PHYSICIANS RESPOND TO THE FDA PUBLIC HEALTH ADVISORY ON WORSENING DEPRESSION AND SUICIDALITY IN PATIENTS BEING TREATED WITH ANTIDEPRESSANTS: On March 22, 2004, the U.S. Food and Drug Administration (FDA) issued a health advisory informing the public that manufacturers of several popular antidepressants have been asked to include a warning statement on product labeling. This warning statement recommends that antidepressant-treated patients-both children and adults-should be closely monitored for worsening of depression or emergence of suicidal behavior. The full text of the advisory, along with supporting information and presentations from the February 2004 meeting on which this advisory was based, can be found on the FDA's Web site at http://www.fda.gov/cder/drug/antidepressants/default.htm. Recently, the CME Institute, as a service to its members-you, the readers of this journal-and Larry Culpepper, M.D., Editor in Chief of the Primary Care Companion, assembled a group of psychiatrists and primary care physicians to discuss the FDA advisory and advise clinicians how it will affect their treatment of depressed patients. Their discussion and recommendations appear here. Faculty affiliations and disclosures appear at the end of this Commentary.

Journal Article↗
PubMed1999

[The identification and description of clinical trials published in Spanish journals of general and internal medicine during the period of 1971-1995].

BACKGROUND: When faced with a therapeutic issue, the practice of evidence-based medicine requires efficient access to information derived from controlled clinical trials. The objectives of the study were to locate, with the greatest possible exhaustivity, all controlled clinical trials published in Spanish journals of general medicine, between 1971 and 1995 (25 years), to characterize them, and to incorporate them into the worldwide database of clinical trials maintained by the Cochrane Collaboration. METHODS: The controlled clinical trials have been identified by a systematic, manual review of all the Spanish journals of general and internal medicine. The results obtained have been compared with an exclusive electronic search in MEDLINE. A descriptive analysis of the characteristics of the localized controlled clinical trials was done. RESULTS: 68 journals of general and internal medicine have been identified, only 6 being indexed in MEDLINE. A search carried out exclusively using MEDLINE would imply the loss of one third of all controlled clinical trials. About 16 controlled clinical trials per year have been published in Spain in the area of general and internal medicine, most of them with important missing information. CONCLUSIONS: The limitations of searching only in MEDLINE have been shown once again. There are few controlled clinical trials published in Spain in the area of general and internal medicine, and in order to improve their quality and their diffusion is recommended that authors and editors adhered to the international consensus initiatives that are under way.

Bibliometrics↗
PubMed2004

Redundant publications in scientific ophthalmologic journals: the tip of the iceberg?

OBJECTIVE: The number of scientific publications is often used to measure scientific achievement. This practice can motivate unethical conduct, such as redundant or duplicate publications, defined as publication of the same scientific contents in more than 1 journal. The aim of this study was to estimate the amount of redundant publications in ophthalmologic journals. DESIGN: Retrospective analysis of published literature. METHODS: We developed an electronic search engine for redundancies to estimate the amount of duplicate publications in scientific journals. When redundancies reached a given degree (matching score), the articles were screened manually based on authors, titles, and abstracts. We applied this method to the 22 433 articles that were published between 1997 and 2000 in 70 ophthalmologic journals indexed by MEDLINE. MAIN OUTCOME MEASURES: The number of duplicate publications with a matching score of 0.6 or more, the number of involved journals, and the number of authors. RESULTS: Redundancies reached a matching score of 0.6 or more in 13 967 pairs of articles. Out of them, a sample of 2210 was reviewed manually. We found 60 redundant articles and estimated that 1.39% of the publications were redundant. Thirty-two journals and an estimate of 1092 authors were involved. In 5% of cases, the scientific conclusions were modified. CONCLUSIONS: Because of the restrictive selection process, the impracticability of detecting all redundant publications, and the estimated amount of duplicates increases with lower matching scores, we regard our estimate to be the tip of the iceberg. Duplicate publications have several negative impacts, but neither peer reviewers nor editors can protect their journal from them completely. Several deterrents for duplicate publications are possible, but as long as publications remain the central requirement for academic advancement, a solution seems unlikely. Nevertheless, it is the responsibility of all those who care about objective research and evidence-based medicine to address this problem-not only in ophthalmology.

Algorithms↗
PubMed2003

A critical guide to case series reports.

OBJECTIVE: Provide guidance to investigators and authors regarding appropriate conduct and reporting of case-series studies. SUMMARY OF BACKGROUND DATA: Evidence-based practice has provided a substantial contribution to advancing clinical science. Many study designs have been critically examined, and the quality of the research literature has improved. A common study design in musculoskeletal medicine is the case series: a description of the course of patients over time. Case series can provide valuable information as to: case definition, trend analyses regarding outcomes, and clues as to causation. Case series cannot be used to draw inferences regarding treatment effect. METHODS: Examination of previous work on identification of characteristics of high quality study designs such as cohort studies; extending this work to case series. RESULTS: We identified draft characteristics that good case series studies should address: clearly defined study question; well- described study population; well-described intervention; use of validated outcome measures; appropriate statistical analyses; well-described results; discussion/conclusions supported by the data presented; funding sources acknowledged. CONCLUSIONS: We propose these measures to authors and journal editors as one mechanism to improve the quality of the case series study.

Case-Control Studies↗
PubMedDate not supplied

Database management in autoradiography.

Experiments in autoradiography involve the use of radiotracers to achieve a "functional mapping" between structures of the central nervous system and observed behavior in animals. A typical experiment produces 100-300 sections per animal. Computer systems such as DUMAS (Drexel's Unix based iMage Analysis System) are used to analyze these sections. Each section has two images associated with it--an autoradiographic image and a histological image. The latter is used to establish a correlation between anatomical structures and areas on the autoradiogram. User drawn outlines on the histological image are transferred to the autoradiographic image to obtain quantitative measures (such as average gray level). Existing systems do not take advantage of the fact that consecutive sections obtained from a brain are often similar. As a result, much of the effort involved with region outlining is repetitive. Also, the criteria for region selection varies not only across experiments, but also between users. This paper presents an approach to design an integrated database management system to manage both pictorial and quantitative data in autoradiography. Briefly, such a system is used to (a) store sets of reference outlines and images for use during the analysis of sections, (b) provide a bank of information to the user from across experiments, (c) provide an on-line help facility to the novice, and a reference guide to the expert. Based on specific requirements, we chose the relational model for data management. We developed a preliminary version of the database using INFORMIX-ESQL/C, which is a commercially available relational system. We also developed a graphics editor that is actively linked to the database. The results of our efforts have established the feasibility of using a commercially available relational system for autoradiographic data management.

Animals↗
PubMed2000

Generating interactive molecular documentaries using a library of graphical actions.

Paper-based publishing of scientific articles limits the types of presentations that can be used. The emergence of electronic publishing has created opportunities to increase the range of formats available for conveying scientific content. We introduce the Graphical Explanation Markup Language, GEML, implemented as an XML format for defining molecular documentaries which exploit the interactive capabilities of electronic publishing. GEML builds upon existing molecular structure definitions such as the Protein Data Bank (PDB) standard file format. GEML provides a library of gestures (or actions) commonly used for structural explanations, and is extensible. XML allows us to separate explicit statements about how to highlight a molecular structure from the implementation of these instructions. We also present GEIS (Generator of Explanatory Interactive Systems), a program that takes as input a GEML documentary definition file and produces all the files necessary for an interactive, web-based molecular documentary. To demonstrate GEML and GEIS, we constructed a documentary capturing the difficult 3D notions expressed in two selected published reports about human topoisomerase I. We have created a prototype Java application, GEMLBuilder, as an editor of GEML files.

Computer Graphics↗
PubMed2005

Use of methadone for the treatment of diabetic neuropathy.

Editor's comment: This is the second Commentary of those that will appear from time to time describing treatments that may not have been validated by appropriate clinical trials but seem to be effective in diabetic patients based on small studies and/or extensive clinical experience. This one describes effective opioid treatment for those diabetic patients failing nonopioid therapies for painful neuropathy.

Aged↗
PubMed1982

Autopsy pathology storage and coding by microcomputer.

Storage and coding of anatomic pathology data usually is accomplished by expensive main frame systems. The authors of this article have developed a microcomputer based program package for autopsy pathology which stores patient demographic data, provisional or final anatomic diagnoses, and coded diagnoses obtained from an on-line Systematized Nomenclature of Pathology (SNOP) code lexicon. The system includes limited text editor functions as well as rapid data retrieval with the generation of final reports. Data files containing SNOP codes and diagnoses are searched easily by a variety of parameters, making data retrieval of autopsy material simple and efficient.

Abstracting and Indexing↗
PubMed2000

[The systematic review is the foundation of evidence based medicine. One of the most important contributions to clinical medicine of the past decade].

The traditional narrative review has been shown repeatedly to be biased, mostly towards exaggerated treatment size effects. In contrast, the systematic review follows a strict protocol regarding focused questions, explicit criteria for literature searches, inclusion and exclusion criteria, critical appraisal and a synthesis which is quantitative when appropriate. There is empirical evidence that bias is reduced and that the conclusions reached have greater validity for the construction of treatment guidelines. In this paper three sources of systematic reviews are identified: the Cochrane Library, reviews published in peer-reviewed journals, and assessments of health technology (HTA-reports). Editors are encouraged to publish systematic reviews after proper critical appraisal, and readers are advised to search for such reviews when in need of guidance on important clinical questions.

Bias↗
PubMed2025

CRISPRoff epigenome editing for programmable gene silencing in human cell lines and primary T cells.

The advent of CRISPR-based technologies has enabled the rapid advancement of programmable gene manipulation in cells, tissues, and whole organisms. An emerging platform for targeted gene perturbation is epigenetic editing, the direct editing of chemical modifications on DNA and histones that ultimately results in repression or activation of the targeted gene. In contrast to CRISPR nucleases, epigenetic editors modulate gene expression without inducing DNA breaks or altering the genomic sequence of host cells. Recently, we developed the CRISPRoff epigenetic editing technology that simultaneously establishes DNA methylation and repressive histone modifications at targeted gene promoters. Transient expression of CRISPRoff and the accompanying single guide RNAs in mammalian cells results in transcriptional repression of targeted genes that is memorized heritably by cells through cell division and differentiation. Here, we describe our protocol for the delivery of CRISPRoff through plasmid DNA transfection, as well as the delivery of CRISPRoff mRNA, into transformed human cell lines and primary immune cells. We also provide guidance on evaluating target gene silencing and highlight key considerations when utilizing CRISPRoff for gene perturbations. Our protocols are broadly applicable to other CRISPR-based epigenetic editing technologies, as programmable genome manipulation tools continue to evolve rapidly.

Humans↗
PubMed2003

Minimal prevalence of authorship misrepresentation among internal medicine residency applicants: do previous estimates of "misrepresentation" represent insufficient case finding?.

BACKGROUND: High rates of authorship misrepresentation have been documented among medical trainees. OBJECTIVE: To assess misrepresentation among internal medicine residency applicants while comparing searches used by previous authors (searches 1 and 2) to a more comprehensive strategy (search 3). DESIGN: Review of 497 residency applications. SETTING: Two university-based internal medicine residency programs. MEASUREMENTS: Search 1 was limited to MEDLINE. Search 2 added Current Contents, Science Citation Index, and BIOSIS and included searching journals by hand. Search 3 added seven other databases and contacts to librarians, editors, and coauthors. RESULTS: 224 applicants reported 634 articles; 630 (99%) were verified. The number of applicants with misrepresented citations varied depending on the search used (56 applicants [25%] in search 1 vs. 34 applicants [15%] in search 2 vs. 4 applicants [1.8%] in search 3). CONCLUSIONS: Using a comprehensive search, we found substantially less misrepresentation than had been reported. Previous studies probably overestimated the magnitude of the problem.

Adult↗
PubMedDate not supplied

[Costing nuclear medicine diagnostic procedures].

To the Editor: Referring to a recent special report about the cost analysis of twenty-nine nuclear medicine procedures, I would like to clarify some basic aspects for determining costs of nuclear medicine procedure with various costing methodologies. Activity Based Costing (ABC) method, is a new approach in imaging services costing that can provide the most accurate cost data, but is difficult to perform in nuclear medicine diagnostic procedures. That is because ABC requires determining and analyzing all direct and indirect costs of each procedure, according all its activities. Traditional costing methods, like those for estimating incomes and expenses per procedure or fixed and variable costs per procedure, which are widely used in break-even point analysis and the method of ratio-of-costs-to-charges per procedure may be easily performed in nuclear medicine departments, to evaluate the variability and differences between costs and reimbursement - charges.

Costs and Cost Analysis↗
PubMed1994

[Rehabilitation relevant diagnostic procedures].

Presented are four instruments current in rehabilitation diagnostics. They are investigated concerning their usefulness and merit as well as their possibly specific approach, starting out from the World Health Organization's International Classification of Impairments, Disabilities, and Handicaps (ICIDH), which so far has hardly been commented on in the German-language area, with its effort of enabling severity-specific assessment of need and its extensive exposition on the part of the editor of "problem awareness" in relation to the subsequent planes of consideration. The EAM system is focussed on occupationally integrative, job-specific appraisal, attempting to implement standardized performance/adaptation analysis. This is contrasted with the subjective criteria-based, very consistent IRES questionnaire, which however lacks objective severity appraisal. Additionally dealt with is the "RPK" procedure used in evaluating the rehabilitation of persons with chronic mental illness. Overall, it is found that each of the different instruments has its value and merits, although major aspects of rehabilitation and, above all, integration prognosis require differentiated, systemic appraisal and on-going rehabilitation-specific consideration. What is needed is "understanding" the nature of disease consequences at the different planes of experience.

Activities of Daily Living↗
PubMedDate not supplied

Evaluation of a journal club as a forum to practise critical appraisal skills.

Critical appraisal skills are important if clinicians are to practise evidence-based medicine. This is an evaluation of the first six months of a journal club in a department of public health medicine. We analysed attendance, types of paper reviewed, impact on commissioning policy and publication of letters to editors and conclude that journal clubs can be an effective learning environment and further the Clinical Effectiveness Initiative.

Correspondence as Topic↗