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At least 73 records · Page 4Linked to original sources

PubMed2005

Impact of nonsteroidal antiinflammatory drugs on the cardioprotective effects of aspirin.

OBJECTIVE: To examine the evidence of a pharmacodynamic interaction between aspirin and nonsteroidal antiinflammatory drugs (NSAIDs); specifically, to determine whether a deleterious relationship exists with respect to the cardioprotective effects of aspirin. DATA SOURCES: Primary articles were identified by a MEDLINE search (1966-May 2004). Search terms included aspirin, nonsteroidal antiinflammatory drug, drug interaction, mortality, myocardial infarction, and stroke. STUDY SELECTION AND DATA EXTRACTION: All prospective and retrospective studies conducted in human subjects and investigating the potential interaction between aspirin and NSAIDs were included. DATA SYNTHESIS: Several controlled pharmacodynamic studies indicate that the sustained inhibition of cyclooxygenase activity by aspirin is blunted in the presence of some NSAIDs. While these data are fairly consistent, they are limited in that they rely on surrogate markers and not clinical outcomes. Observational studies have shown conflicting results regarding the effect of combination NSAID and aspirin therapy on mortality risk and incidence of myocardial infarction. CONCLUSIONS: Pharmacodynamic data indicating an interaction between aspirin and NSAIDs have not translated to a consistent clinical effect in observational studies. In the absence of a randomized, controlled, clinical outcomes study, there is insufficient evidence to dictate a change in therapy.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

Time sequence of coagulation data in patients with decompensated liver cirrhosis and suspected disseminated intravascular coagulation.

In patients with liver cirrhosis, especially in the advanced stage, the coexistence of low clotting factor levels, hypofibrinogenemia, thrombocytopenia and elevated fibrin(ogen) degradation product (FDP) and D-dimer levels may suggest the presence of disseminated intravascular coagulation (DIC). In this study we evaluated, in 21 patients with decompensated liver cirrhosis and elevated FDP and D-dimer levels, the time sequence of their coagulation data during a follow-up period of 15 days after the first observation; our aim was to clarify if these patients tend to develop during this time interval a severe consumption coagulopathy as an expression of overt DIC. We evaluated serum fibrinogen, platelet count, prothrombin activity, serum FDP and plasma D-dimer levels at days 1, 3, 6, 10 and 15. The coagulation data were fairly stable during the study period in all patients, even in the two patients who had upper digestive tract bleeding during the study time. Only two patients affected by infectious diseases showed a decrease of D-dimer and FDP levels after healing. Our data suggest that in decompensated liver cirrhosis the detection of elevated FDP and D-dimer levels is seldom related to the occurrence of an overt DIC, at least during a short time interval; in this condition heparin therapy seems therefore not advisable and even potentially dangerous.

Aged↗

PubMed2003

Learning to predict protein-protein interactions from protein sequences.

In order to understand the molecular machinery of the cell, we need to know about the multitude of protein-protein interactions that allow the cell to function. High-throughput technologies provide some data about these interactions, but so far that data is fairly noisy. Therefore, computational techniques for predicting protein-protein interactions could be of significant value. One approach to predicting interactions in silico is to produce from first principles a detailed model of a candidate interaction. We take an alternative approach, employing a relatively simple model that learns dynamically from a large collection of data. In this work, we describe an attraction-repulsion model, in which the interaction between a pair of proteins is represented as the sum of attractive and repulsive forces associated with small, domain- or motif-sized features along the length of each protein. The model is discriminative, learning simultaneously from known interactions and from pairs of proteins that are known (or suspected) not to interact. The model is efficient to compute and scales well to very large collections of data. In a cross-validated comparison using known yeast interactions, the attraction-repulsion method performs better than several competing techniques.

Algorithms↗

PubMed1993

Tetanus in Switzerland 1980-1989.

Tetanus cases that occurred in Switzerland between 1980 and 1989 have been reviewed with the help of three data surveillance systems: a) morbidity data from the Federal Office of Public Health (FOPH), b) mortality data from the Swiss Federal Statistical Office (SFSO), and c) data from the Association of Swiss Hospitals and Clinics (VESKA), completed by a written enquiry to clinics which did not (or only partly) participate in the VESKA system during the study period. For every case, a questionnaire was sent to the clinic to verify the diagnosis and to obtain additional information on the circumstances of occurrence. Ninety-one cases were identified. This corresponds to a yearly incidence of 1.93 per million population between 1980-84 and 0.88 for the 1985-89 period (p < 0.01). Eighty-one percent of the cases were older than 50 years of age and women were significantly more frequently affected than men. None of the cases identified had a documented primary immunization series. Data available at the FOPH and SFSO level have been compared to data obtained through the VESKA system using the Chandra Sekhar and Deming method. It is estimated that 134 tetanus cases (95% CI: 91-197) have occurred in Switzerland between 1980 and 1989, together with 28 deaths (95% CI: 27-31). Based on these estimates, FOPH appears to detect only 6-13% of tetanus cases occurring in Switzerland. By contrast, SFSO had fairly consistent data for 81-100% of tetanus associated deaths. The low rate of tetanus reported by physicians necessitates a sustained effort to increase the understanding of epidemiological surveillance by Swiss practitioners.

Adolescent↗

PubMed2004

Comparison of different melting temperature calculation methods for short DNA sequences.

MOTIVATION: The overall performance of several molecular biology techniques involving DNA/DNA hybridization depends on the accurate prediction of the experimental value of a critical parameter: the melting temperature Tm. Till date, many computer software programs based on different methods and/or parameterizations are available for the theoretical estimation of the experimental Tm value of any given short oligonucleotide sequence. However, in most cases, large and significant differences in the estimations of Tm were obtained while using different methods. Thus, it is difficult to decide which Tm value is the accurate one. In addition, it seems that most people who use these methods are unaware about the limitations, which are well described in the literature but not stated properly or restricted the inputs of most of the web servers and standalone software programs that implement them. RESULTS: A quantitative comparison on the similarities and differences among some of the published DNA/DNA Tm calculation methods is reported. The comparison was carried out for a large set of short oligonucleotide sequences ranging from 16 to 30 nt long, which span the whole range of CG-content. The results showed that significant differences were observed in all the methods, which in some cases depend on the oligonucleotide length and CG-content in a non-trivial manner. Based on these results, the regions of consensus and disagreement for the methods in the oligonucleotide feature space were reported. Owing to the lack of sufficient experimental data, a fair and complete assessment of accuracy for the different methods is not yet possible. Inspite of this limitation, a consensus Tm with minimal error probability was calculated by averaging the values obtained from two or more methods that exhibit similar behavior to each particular combination of oligonucleotide length and CG-content class. Using a total of 348 DNA sequences in the size range between 16mer and 30mer, for which the experimental Tm data are available, we demonstrated that the consensus Tm is a robust and accurate measure. It is expected that the results of this work would be constituted as a useful set of guidelines to be followed for the successful experimental implementation of various molecular biology techniques, such as quantitative PCR, multiplex PCR and the design of optimal DNA microarrays.

Algorithms↗

PubMed1994

Changes to National Practitioner Data Bank reporting--effective or not?

Unless a physician has been living in another galaxy far, far away with Luke Skywalker, he or she is aware of the National Practitioner Data Bank. On March 31, 1994, the Department of Health and Human Services (HHS) announced that each practitioner can now place in the Data Bank a six-hundred character "rebuttal" of a report, without formally disputing the factual accuracy of the report. Does this change make the Data Bank fair? Not really. It is a step in the right direction, but further reform is needed. "Health Law" is a regular feature of Physician Executive contributed by Epstein Becker & Green. Mark Lutes of the law firm's Washington, D.C., offices serves as editor of the column.

Conflict, Psychological↗

PubMed2005

Heterogeneity: GAW Group 15.

This paper summarizes the contributions to Group 15 of Genetic Analysis Workshop (GAW) 14, which focused on methods for dealing with heterogeneity in linkage and association analysis. A variety of methods were employed, ranging from manipulation of the phenotype and/or identification of endophenotypes prior to analysis, to statistical methods allowing for heterogeneity in the analysis of simple dichotomous phenotypes as provided with the data. Overall, it was difficult to draw broad conclusions from these applications. Groups that focused on the simulated data had fairly consistent success in mapping the major genes (but not the two minor genes). However, this appeared to be the case regardless of whether heterogeneity was explicitly modeled, either at the phenotypic or statistical level, with relatively crude statistical methods applied to the simulated simple dichotomous trait Kofendrerd personality disorder also enjoying considerable success.

Alcoholism↗

PubMed2004

Development of a 3D model for the human cannabinoid CB1 receptor.

A novel comparison model of the human cannabinoid CB1 receptor has been constructed using the bovine rhodopsin X-ray structure as a template. The model was subjected to a 500-ps molecular dynamics simulation, and thereafter new conformers of the receptor model were produced in a simulated annealing procedure. Using an automated docking procedure, well-known cannabimimetic ligands were docked into six different model conformers, of which one was chosen for a detailed study of receptor-ligand interactions. The docking results confirm, for example, the importance of lysine K3.28(192) in the binding of these ligands. Also, other experimental data are fairly consistent with the present model, though there are some differences when compared to other recent CB1 comparison models. The present model will serve as a tool to investigate the receptor-ligand interactions and facilitate the design of novel cannabimimetic drugs.

Amino Acid Sequence↗

PubMed2007

Transformation of arbitrary distributions to the normal distribution with application to EEG test-retest reliability.

Many variables in the social, physical, and biosciences, including neuroscience, are non-normally distributed. To improve the statistical properties of such data, or to allow parametric testing, logarithmic or logit transformations are often used. Box-Cox transformations or ad hoc methods are sometimes used for parameters for which no transformation is known to approximate normality. However, these methods do not always give good agreement with the Gaussian. A transformation is discussed that maps probability distributions as closely as possible to the normal distribution, with exact agreement for continuous distributions. To illustrate, the transformation is applied to a theoretical distribution, and to quantitative electroencephalographic (qEEG) measures from repeat recordings of 32 subjects which are highly non-normal. Agreement with the Gaussian was better than using logarithmic, logit, or Box-Cox transformations. Since normal data have previously been shown to have better test-retest reliability than non-normal data under fairly general circumstances, the implications of our transformation for the test-retest reliability of parameters were investigated. Reliability was shown to improve with the transformation, where the improvement was comparable to that using Box-Cox. An advantage of the general transformation is that it does not require laborious optimization over a range of parameters or a case-specific choice of form.

Algorithms↗

PubMed2026

Dataset Readiness Assessment With Large Language Model (DRAFT-LLM): A Multi-Axis Audit Guided by LLM.

This article details the Dataset Readiness Assessment for Training (DRAFT), a systematic method for determining whether a high-dimensional biological dataset is suitable for developing reliable, equitable (i.e., the extent to which model performance, error patterns, and potential benefits or harms are evaluated and found to be acceptably distributed across relevant demographic, biological, clinical, and contextual subgroups), and scientifically meaningful machine-learning models, and DRAFT Large Language Model (DRAFT-LLM), its optional human-in-the-loop extension for calibrating study-specific audits through structured, critically reviewed LLM guidance. Standard model validation often fails to detect when apparent performance is driven by spurious correlations, technical artifacts, or hidden stratification, leading to irreproducible and inequitable findings. DRAFT-LLM addresses this gap by shifting the focus from model tuning to structured dataset auditing, organized around Support Protocols 1 to 4 that capture the scientific intent, data structure, and governance constraints of a given study. These Support Protocols: (1) elicit and formalize investigator input into a study intake and dataset card; (2) compute standardized dataset statistics and structural summaries suitable for downstream analysis and LLM context; (3) configure the language model using form-based responses, safety guardrails, and governance rules; and (4) generate personalized instructions, prompts, and code templates for running DRAFT audits. Basic Protocols 1 to 3 are instantiated from this support layer for generalization, equity, and stability: they are reusable execution patterns whose concrete behavior is determined by the cards, statistics, and configurations defined in the Support Protocols. DRAFT-LLM and DRAFT are demonstrated in this article through an end-to-end case study on The Cancer Genome Atlas (TCGA). © 2026 Wiley Periodicals LLC. Support Protocol 1: Study intake and dataset card construction Support Protocol 2: Dataset structure and advanced summary statistics for LLM context Support Protocol 3: LLM configuration using structured form responses Support Protocol 4: Generation of personalized instructions for DRAFT audits Basic Protocol 1: Generalization audit Basic Protocol 2: Equity audit Basic Protocol 3: Stability audit.

Large Language Models↗

PubMed2005

Long-term results of bone-anchored hearing aid recipients who had previously used air-conduction hearing aids.

OBJECTIVE: To study the long-term results (use, care, satisfaction, ear infections, and audiometry) of the application of a bone-anchored hearing aid (BAHA) to patients with conventional indications who had previously used air-conduction hearing aids. DESIGN: Follow-up study (mean duration, 9 years). SETTING: Tertiary referral center. PATIENTS: The study population comprised 27 patients with conductive or mixed hearing loss and who had participated in a previous study (N = 34). Seven could not be included anymore as a result of death, Alzheimer disease, or problems related to the implant. Everyone filled out the questionnaire, and 23 patients underwent audiometric evaluation. MAIN OUTCOME MEASURES: The patients filled out the adapted Nijmegen questionnaire. Aided free-field thresholds were measured as well as scores for speech in noise and in quiet. Results were compared with those obtained in the initial study. RESULTS: All 27 patients were still using their BAHA and appreciated it with regard to speech recognition in quiet, sound comfort, and improvements in ear infections. The audiometric results showed that most patients tested had stable bone-conduction thresholds over the years (after correction for age). Despite the treatment with BAHA, a significant deterioration in the cochlear hearing was observed in the other patients in the ear under study (their best hearing ear). CONCLUSIONS: Positive patient outcome measures emphasized the importance of BAHA application to patients with conventional indications. The audiometric data showed fairly stable cochlear function but not for all patients. This underlines that conservative treatment should be chosen (fitting of bone-conduction devices).

Audiometry↗

PubMed1984

Particle size and surface area distributions of pharmaceutical powders by microcomputerized mercury porosimetry.

The Mayer-Stowe theory was applied to derive the particle size distribution of powders of pharmaceutical interest using mercury porosimetry. Particle size data obtained by this approach are fairly comparable with data derived by other, more popular, techniques such as the electrical sensing zone or the air jet sieving methods provided that the experimental value of the mercury-powder contact angle and the state of aggregation of the powder are carefully studied. Furthermore, by applying the Rootare-Prenzlow method a surface area distribution can also be derived from the same porosimetry data used to obtain the particle size distribution. All experiments were carried out with a microcomputerized mercury porosimeter, which allows storage of data during the analysis and a subsequent fast elaboration at the end of the run, with fully printed data on pore size, pore volume, surface area, and particle size of the powder sample.

Chemistry, Pharmaceutical↗

PubMed1999

Probing the physical basis for trp repressor-operator recognition.

The bacterial repressor protein, trp repressor, is one of the best studied transcriptional regulatory proteins in terms of function, structure, dynamics and stability. Despite these significant advances, the structural and energetic basis for the specific recognition of its operator sites by trp repressor remains poorly understood. In fact, recognition in this system is controled by the binding of the co-repressor ligand, l-tryptophan, as well as by conformational and dynamic properties of the operator targets, DNA sequence-dependent control of the oligomerization properties of the repressor, water-mediated interactions, and specific interactions involving the peptide backbone and phosphate moieties. Moreover, only one direct contact between the protein and the DNA is evident from the crystallographically determined structure of the complex. In an attempt to better define how the various sequence elements in the operator target contribute to this complex control of affinity and cooperativity of trp repressor binding, we have studied the binding of trp repressor to a series of mutated operator targets using fluorescence anisotropy, which provides very high quality data allowing fairly precise estimations of the affinities involved. We conclude from these studies that even on very small (25 bp) targets, the repressor binds slightly cooperatively, populating a 2:1 dimer/DNA complex, and then at higher concentrations a third dimer is bound with significantly lower affinity, revealing an inherent asymmetry in the trpEDCBA-derived target. Investigation of the basis for the asymmetry implicates the identity of the second base in the so-called structural half-site GNACT, which apparently influences the switch between tandem and simple binding. Mutation of the C or the T bases in the structural half-site abolishes all specificity in binding, and alteration of the single direct contact, the G of the structural half-site, or the central TTAA significantly lowers the affinity of the dimer for its site, without modifying the apparent cooperativity. Finally, we note that the order of affinity is conserved in the absence of the co-repressor, and moreover, it is in all cases significantly higher than that observed for holo-repressor binding to non-specific DNA, indicating that one cannot simply equate apo-repressor and non-specific binding.

Bacterial Proteins↗

PubMed1990

On the origins of tandemly repeated genes: does histone gene copy number in Drosophila reflect chromosomal location?

Widely regarded beliefs about Drosophila histone gene copy numbers and developmental requirements have been generalized from fairly limited data since studies on histone gene arrangements and copy numbers have been largely confined to a single species, D. melanogaster. Histone gene copy numbers and chromosomal locations were examined in three species: D. melangaster, D. hydei and D. hawaiiensis. Quantitative whole genome blot analysis of DNA from diploid tissues revealed a tenfold variability in histone gene copy numbers for these three species. In situ hybridization to polytene chromosomes showed that the histone DNA (hDNA) chromosomal location is different in all three species. These observations lead us to propose a relationship between histone gene reiteration and chromosomal position.

Animals↗

PubMed2002

Sedation, cognition, and antihistamines.

First-generation antihistamines are well-known to cause subjective drowsiness. A myriad of studies has also been published that suggest a clear relationship between the use of these drugs and objective performance impairment. Although not all of the tests used in these studies have been validated, the data are fairly consistent, and suggest a difference between earlier (first-generation) sedating antihistamines and the newer (second-generation) nonsedating antihistamines.

Cognition↗

PubMed1985

Note on wave propagation in a thin elastic tube containing a viscous fluid.

This paper deals with the theoretical and experimental investigation of the propagation of pressure waves through a straight thin-walled elastic tube, filled with a streaming Newtonian fluid. The tube used was of silicon rubber and measured 200 mm in length, 8 mm in internal diameter and 1 mm in wall thickness. The velocity profiles across the diameter of the tube were measured at the beginning, at the middle and the end of the elastic pipe and compared with the results of a mathematical-computational model. The test data agree fairly well with the calculated values.

Diffusion↗

PubMedDate not supplied

Coffee and coronary heart disease: a review.

Since the early 1900s, coffee has been implicated as having adverse effects on human health. Recent attention has focused on coffee's relation to CHD, but because of conflicting results of epidemiologic studies on coffee and CHD mortality, attention has turned to the effects of coffee and caffeine on individual CHD risk factors. Coffee's effect on serum lipids does not appear to be due to caffeine. If in fact an adverse effect on lipids exists, it may be related to other factors including biochemical constituents other than caffeine, hardness of the water used in preparation, and the method of preparation, filtered coffee having no effect. The data are fairly convincing that chronic coffee ingestion does not induce hypertension, although acute consumption produces a small, short-lived increase in BP. The least well understood effect of coffee is its potential to induce cardiac arrhythmias, including potentially lethal ventricular ectopy in certain individuals. More work is needed in this area of arrhythmias before any concrete recommendations can be made. Until more convincing evidence against coffee is compiled, it appears that, at least in moderate amounts in otherwise healthy persons, coffee is a safe beverage.

Animals↗

PubMed1989

Enhancement of 5-fluorouracil's anticancer activity by dipyridamole.

Although the interaction between FUra and DP in HCT 116 cells is fairly complex, data from other investigators indicate that in cell lines in which inhibition of TS is growth limiting at relatively low concentrations of fluoropyrimidines, DP appears to augment the cytotoxicity of FUra and FdUrd by blocking the salvage of dThd (Miller et al., 1987; Schwartz et al., 1987). The previous in vitro data regarding the ability of DP to modulate the toxicity of fluoropyrimidines was obtained in exponentially growing cells. An additional observation that warrants consideration is a report that the inhibition of nucleoside incorporation by DP changed as a function of time in culture (Zhen et al., 1986). Hepatoma 3924A cells in lag and log phase were highly sensitive to DP with IC50 values for dThd incorporation of 0.2 and 0.32 microM, respectively. In contrast, stationary phase cells were insensitive to DP (IC50 = 38.9 microM). Amphotericin B, an antifungal agent which perturbs cell membranes, restored the sensitivity to DP in stationary cells. Several investigators have presented information on the effect of DP on fluoropyrimidines in normal tissues. Lee and Park (1987) examined the effect of DP on FUra and MTX toxicity in a soft-agar cloning assay against two human cancer cell lines and on pooled normal human bone marrow (CFU-C). DP (1 microM) potentiated the action of both MTX (0.1 microM) and FUra (5 microM) on Hep-2 (epidermoid carcinoma), MCF-7 (breast carcinoma) and CFU-C in medium supplemented with either non-dialyzed or dialyzed serum. Woodcock et al. (1987) incubated gallbladder mucosa, obtained from patients undergoing elective surgery for cholelithiasis, with control medium or varying concentrations of DP for 1 hr, and then exposed the mucosal cells to 2.5 microCi [3H]-FdUrd (2.5 microM). After 1 hr, the uptake of FdUrd into the tissue was inhibited to 49% and 42% of control by 0.1 microM and 1 microM, respectively.

Animals↗