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PubMed2004

The U.S. National Library of Medicine's Toxicology and Environmental Health Information Program.

For nearly 40 years, the National Library of Medicine's (NLM) Toxicology and Environmental Health Information Program (TEHIP) has been a significant leader in organizing and providing public access to an extensive storehouse of toxicological information through its online databases. With the advent of the Internet, TEHIP has expanded its role to also serve as a pre-eminent portal to toxicological information worldwide. Its primary databases reside within the web-based TOXNET system, and include the scientifically peer-reviewed Hazardous Substances Data Bank (HSDB), the U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) and Toxics Release Inventory, the National Cancer Institute's Chemical Carcinogenesis Research Information System (CCRIS) and the TOXLINE file of over 3 million bibliographic references. TEHIP's ChemIDplus is an extensive chemical dictionary that extends beyond simple nomenclature to offer displays of molecular structures and links from particular chemicals to other databases containing more information. Specialty files in occupational safety and health, and household products have recently been added to TEHIP's suite of resources. Additional databases in risk assessment, drugs, toxicology education, and global resources, are under development. "Special Topics" pages lead users to structured summaries and links in areas such as arsenic, chemical warfare agents, biological warfare, and West Nile Virus. A database on alternatives to the use of live animals, a three-module toxicology tutor, and a glossary of terms in toxicology are among TEHIP's other information aids, as well an increasing commitment to serving consumers, as witnessed by the animated ToxTown program. Outside the sphere of TEHIP, NLM offers additional databases, such as PubMed, of significant value to toxicology researchers.

Animals↗
PubMed2006

Effect of sparse basis selection on ultrasonic signal representation.

Recently, adaptive sparse representations of ultrasonic signals have been utilized to improve the performance of scanning acoustic microscopy (SAM), a common nondestructive tool for failure analysis of microelectronic packages. The adaptive sparse representation of an ultrasonic signal is generated by decomposing it in a learned overcomplete dictionary using a sparse basis selection algorithm. Detection and location of ultrasonic echoes are then performed on the basis of the resulting redundant representation. This paper investigates the effect of sparse basis selection algorithms on ultrasonic signal representation. The overcomplete independent component analysis, focal underdetermined system solver (FOCUSS), and sparse Bayesian learning algorithms are examined. Numerical simulations are performed to quantitatively analyze the efficiency of ultrasonic signal representations. Experiments with ultrasonic A-scans acquired from flip-chip packages are also carried out in the study. The efficiency of ultrasonic signal representations are evaluated in terms of the different criteria that can be used to measure its performance for different SAM applications, such as waveform estimation, echo detection, echo location and C-scan imaging. The results show that the FOCUSS algorithm performs best overall.

Algorithms↗
PubMed2006

The long-term international safety experience of imiglucerase therapy for Gaucher disease.

BACKGROUND: Gaucher disease is a lysosomal storage disorder resulting from a deficiency of the lysosomal enzyme glucocerebrosidase. Since approval by the FDA in 1994 and EMEA in 1997, enzyme replacement therapy with Cerezyme (imiglucerase for injection) has been the standard of care for the treatment of Gaucher disease. OBJECTIVE: To review the long-term international safety experience of imiglucerase from 1994 through 2004. MATERIALS AND METHODS: All spontaneous adverse event reports captured in the pharmacovigilance database for imiglucerase from 1994 through 2004 were analyzed. All adverse events were classified using the current version of the Medical Dictionary for Regulatory Activities (MedDRA). Patients without prior exposure to imiglucerase from 1994 through 2005 were assessed for the development of antibodies to imiglucerase as detected by enzyme-linked immunosorbant and radioimmunoprecipitation assays. RESULTS: Analysis of the long-term safety experience with imiglucerase therapy demonstrates a stable and low rate of adverse events and seroconversion from 1994 through 2005. The majority of frequently reported adverse events related to imiglucerase were infusion-associated reactions which were predominantly self-limiting in nature and did not require discontinuation of treatment. Between 1994 and 2005, IgG antibodies to imiglucerase were detected in approximately 15% of treatment-naïve patients. CONCLUSIONS: The long-term stability of reported events and seroconversion is a reflection of a well-characterized cell expression system and a mature quality-controlled manufacturing process. Imiglucerase is a safe therapy for the treatment of Gaucher disease with a stable and low rate of reported adverse events and seroconversion.

Drug Approval↗
PubMed2002

Safety of intravitreous fomivirsen for treatment of cytomegalovirus retinitis in patients with AIDS.

PURPOSE: To report data regarding the safety of intravitreous fomivirsen for treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: Critical review of safety data from three randomized controlled clinical trials with supplemental information from an expanded drug access program. METHODS: Adverse ocular events reported by clinician investigators were listed using terms modified from the COSTART dictionary. Data for two doses (165-microg/injection [35 eyes, 30 patients] and 330-microg/injection [153 eyes, 120 patients]) and two 330-microg/injection dose schedules of different intensity were pooled to calculate incidence rates for each event. Rates were calculated as "events/patient-year" (based on total cumulative reported events and duration of treatment) for events that could recur during treatment. Rates were calculated as "patients with events/person-year" for the following events: retinal detachment, cataract, visual field disturbance, and retinal pigment epitheliopathy. To assess the ability to manage events, we reviewed treatments given for two events (anterior chamber inflammation, increased intraocular pressure) in one trial. We also report an analysis comparing the proportion of eyes that developed one or more key events to the cumulative number of injections. RESULTS: Incidence rates were dose and schedule dependent (165 microg/injection, 4.06 events/patient-year; 330 microg/injection, 6.58 events/patient-year [less intense regimen] and 8.35 events/patient-year [more intense regimen]). The most frequently reported events were anterior chamber inflammation and increased intraocular pressure. We found no evidence that the proportion of patients with events increased as the number of injections increased. CONCLUSIONS: Intravitreous fomivirsen is well tolerated with an acceptable safety profile. Adverse ocular events associated with doses and schedules used clinically can be managed successfully with medical therapy.

AIDS-Related Opportunistic Infections↗
PubMed2005

[Placebo and placebo effect].

The word placebo appeared for the first time in an English medical dictionary in 1785. In French, it appeared much latter in 1958. This word defines an experimental tool used for rigourous evaluation of a specific effect of pharmacological treatment and the non specific effect of any therapy. The placebo effect is the strictly psychological or psychophysiological effect of a placebo. The two principal components of placebo effect as a pain killer, which has been extensively studied in this field, are positive expectancies of both the patient and the physician. Although the mechanisms of action of placebo effect are not well understood, results of several recent works are particularly interesting.

Humans↗
PubMed1999

Evolution and devolution of folkbiological knowledge.

In this paper we present evidence in support of the hypothesis that the average person's knowledge about trees, and about the natural world in general, has declined during the 20th century. Our investigations are based on examination of a large sample of written material from the 16th through 20th centuries contained in the Oxford English Dictionary. In Analysis 1, we show a precipitous decline in the use of tree terms after, but not before, the 19th century. In Analysis 2, we analyze tree terms at different levels of organization and show that the decline observed in Analysis 1 occurs for all levels of organization. This second analysis also reveals that during the 16th to 19th centuries tree terms became progressively more specific, suggesting that during these periods knowledge about trees increased. In Analysis 3, we show similar rates of decline in other folkbiological categories, indicating that the change in tree terms reflects a general decline in knowledge about living kinds. Also in Analysis 3, we show that several non-biological categories have experienced evolution during the 20th century, indicating that the declines in the 20th century for folkbiological categories are not an inevitable outcome of the corpus. Finally, Analysis 4 also shows declines in the frequency of quotations for which the tree term was not the topic of the sentence, and thus incidental to the purposes of the writer. The results from Analysis 4 reassure us that the results from Analyses 1-3 were not solely due to change in the aims and purposes of writers over the centuries. In sum, the analyses indicate that in the domain of trees, there has been a long and sustained period of conceptual evolution followed by a recent pronounced period of devolution.

Awareness↗
PubMed2003

An ER-fMRI investigation of morphological inflection in German reveals that the brain makes a distinction between regular and irregular forms.

The hypothesis that morphological processing is supported by a mental dictionary of stored entries plus a set of mental computations based on rules is examined using event-related fMRI. If a rules-plus-memory model () reflects the actual organization of the language faculty, two distinct patterns of brain activation should be observed for production of German irregular and regular noun and verb inflections. If a connectionist alternative to the rules-and-memory model (, and many others since), which seeks to explain the production of both irregular and regular forms within a single associative memory mechanism, is correct, there should be no neural differentiation between German regular and irregular inflection. The results we report support the existence of substantially differing patterns of activation for regulars vs. irregulars, an outcome that is consistent with the two-component rules-plus-memory account.

Adult↗
PubMed2001

Thomas Bowdler: censor, philanthropist, and doctor.

A recent biography of the physician William Osler credits him with having generated a verb, to "oslerize", as a synonym for euthanasia. Actually, Osler had been mocking his own impending senescent uselessness at the time of his move from Baltimore to Oxford. That neologism did not last. Two earlier doctors who did make it to the dictionaries in a verbally eponymous way were F A Mesmer and Thomas Bowdler, and Bowdler, at least, would not have liked the recognition. The first use of the verb to "bowdlerise" seems to have been in 1836, with a reference to "names in the writings of the apostles which modern ultrachristians would probably have Bowdlerized". However, Bowdler is better remembered for his cleaning up of the plays of Shakespeare.

Drama↗
PubMed2004

Association of asthma therapy and Churg-Strauss syndrome: an analysis of postmarketing surveillance data.

BACKGROUND: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear. OBJECTIVE: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary for the Adverse Event Reporting System [AERS]) by applying an iterative method of disproportionally analysis to th AERS database maintained by the US Food and Drug Administration. METHODS: The public-release version of the AERS database was used to identify reports of AGA in patients receiving asthma therapy. Reporting of AGA was examined using iterative disproportionality methods in patients receiving > or =1 of the following drug classes: inhaled corticosteroid (ICS), leukotriene receptor antagonist (LTRA), short-acting beta(2)-agonist (SABA), or long-acting beta(2)-agonist (LABA). The Bayesian data-mining algorithm known as the multi-item gamma poisson shrinker was used to determine the relative reporting rates by calculation of the empirical Bayes geometric mean (EBGM) and its 90% CI (EB05 = lower limit and EB95 = upper limit) for each drug. Subset analyses were performed for each drug with different medication combinations to differentiate the relative reporting of AGA for each. RESULTS: A strong association was found between LTRA use and AGA (EBGM = 104.0, EB05 = 95.0, EB95 = 113.8) that persisted with all combinations of therapy studied. AGA was also associated with the ICS, SABA and LABA classes (EBGM values of 27.8, 14.6 and 40.4, respectively). However, the latter associations were mostly dependent on the presence of concurrent LTRA and, to a lesser extemt, oral corticosteroid therapy and became negligible (ie, EB05 < 2) for patients who were not receiving these concurrent treatments. CONCLUSIONS: Differences based on relative reporting were observed in the patterns of association of AGA with LTRA, ICS, and beta(2)-agonist therapies. A strong association between LTRA use and AGA was present regardless of the use of other asthma drugs.

Administration, Inhalation↗
PubMed1998

Time-frequency analysis of vibrotactile driving responses by matching pursuit.

A new method of time-frequency analysis, based on the Matching Pursuit (MP) algorithm, was used to extract and quantify EEG 'driving' or frequency-following responses produced in human primary somatosensory cortex (SI) by 33 Hz vibrotactile stimulation of the right index fingertip in a single subject. EEG signals were recorded from a 5 x 5 array of electrodes centered over the left hand area, time-locked to repeated presentations of four vibratory stimulus amplitudes. The MP algorithm was used to decompose the edited and and filtered EEG signals into waveforms selected from a large and redundant dictionary. Statistical discrimination of the vibratory stimulus amplitudes was then readily achieved in terms of trial-by-trial measures of response amplitude constructed in automated fashion from the calculated MP parameters. The results were orderly and physiologically coherent, and potentially open the way to correlation of psychophysical magnitude estimates with measures of neurophysiological response on a trial-by-trial basis. The approach developed here appears well suited to detection and characterisation of time dependent or transient target signals embedded in a noisy background.

Algorithms↗
PubMed1999

Psychomotor agitation: poorly defined and badly measured.

BACKGROUND: Psychomotor agitation is commonly associated with various psychiatric disorders. This article reviews the definition and measurement of agitation over the past 100 years. METHODS: Definitions and descriptions of agitation were taken from dictionaries of etymology, medicine and psychiatry, and from psychiatric textbooks. A systematic MEDLINE (1966-1996) search of 'psychomotor', 'agitation', and 'restlessness' was conducted. This was augmented by a search for other relevant references cited in the articles identified by MEDLINE. RESULTS: The definition of psychomotor agitation has varied in ambiguous and contradictory ways, both over time and in contemporary writings. Tools developed to measure agitation are either too unreliable, or else reflect this conflict of definition and are not comparable. CONCLUSIONS: A preferred definition of agitation is proposed which takes into account both theoretical and empirical data. This has implications for further research into psychomotor agitation in classification of and treatment response in affective disorders, old age psychiatry and the evaluation of putative anti-agitation drugs.

Aged↗
PubMed2001

Pathophysiologic characteristics of hypovolemic shock.

In the late 1800s, while caring for a trauma victim, Warren characterized shock as "a momentary pause in the act of death." A great deal about shock has been discovered since this first description. Dorland's Medical Dictionary defines shock as a condition of profound hemodynamic and metabolic disturbance characterized by failure of the circulatory system to maintain adequate perfusion of vital organs. Shock is now being defined at the cellular level as the inadequate delivery of nutrients to the cells of the body. Because oxygen is the only nutrient that cells cannot store in any appreciable quantity, shock is also equivalent to inadequate oxygen delivery (DO2). Although there are many types of shock, this article concentrates on the pathophysiologic characteristics of hypovolemic shock.

Animals↗
PubMedDate not supplied

[Incidence and severity of drug interactions in the elderly: a prospective study of 639 patients].

The medicinal treatments of 639 patients aged over 65 were recorded on admission to hospital. The mean number of drugs consumed was 4.4 +/- 2.8 per patient. Drug interaction was found in 37 p. 100 of the patients on the basis of data published in the Vidal dictionary. The prevalence of interactions increased with the number of drugs prescribed. The medicinal families most frequently involved were digitalis derivatives, antiarrythmic agents, diuretics, anticoagulants and psychotropic drugs. Thirty patients (4.7 p. 100) presented with a side-effect that was directly ascribable to an interaction. Among the iatrogenic adverse reactions 11 were life-threatening, including 8 cases of severe dysrhythmia and 3 cases of gastrointestinal haemorrhages. Altogether, one-third of all iatrogenic disorders were consecutive to a drug interaction. Simple precautions would have considerably reduced the frequency of such side-effects.

Aged↗
PubMed1999

Disease and immunity in the pre-Spanish Philippines.

It is generally asserted that Filipino populations did not suffer the same demographic collapse that followed Spanish conquest in the Americas because they had previously acquired immunity to Old World diseases through trading contacts with Asia. This assertion is examined by trying to establish which diseases were present in the islands in pre-Spanish times and whether populations there could have acquired immunity to them. This is done through an analysis of the evidence for the presence of infections in China and Japan in particular and the existence of trading contacts with and between the Philippine islands. The likelihood of immunity being acquired is addressed first through a discussion of the physical and human geography of the islands and what is known of the epidemiology of individual diseases from modern scientific research. Second, it reviews evidence from early colonial documents and Filipino dictionaries for the presence and impact of Old World diseases in the early colonial period. The study suggests that Filipino populations had not acquired significant immunities to acute infections in pre-Spanish times, and that their limited demographic impact in the colonial period derived more from the particular geography of the islands. It suggests that in terms of its disease history, the Philippines had more in common with the Pacific islands than mainland Asia, and that the microbiological boundary between the Old World and the New is better conceived of as a broad zone.

China↗
PubMed2002

Reconstructed materia medica of the Medieval and Ottoman al-Sham.

This article presents the results of a study of the medicinal uses of natural substances in medieval and Ottoman al-Sham (the Levant). It involved a meticulous survey of a wide range of historical sources spanning approximately 1100 years and including medical and pharmacological literature, travelogues, geographical and agricultural literature, dictionaries, archives, the Genizah and other medieval sources. Our main goal was to arrive at a reconstruction of the unwritten materia medica of the medieval and Ottoman Levant. Of the many and varied medicinal substances on which we were able to extract information, we were able to identify 286. These are presented according to the following classification: 234 species of plants (81.8%); 27 species of animals (9.5%); 15 kinds of minerals (5.2%) and 10 substances of other or mixed origin (3.5%). Analysis of the data showed that the region under study served as the geographic origin of the majority of the substances, only a minority of the materials was imported. The main reason for this is the geographic location of the Levant as a junction between three continents, as a cultural meeting point and as trade center. Finally, our data revealed that the al-Sham region was an independent source of production and marketing of medicinal substances during the medieval and Ottoman periods.

Animals↗
PubMed2001

Adaptive data acquisition in MRI.

We propose an adaptive data acquisition technique that depends on the object to be imaged in magnetic resonance (MR) imaging. In this paper, we employed a matching pursuit (MP) algorithm to achieve the adaptive data acquisition. Since the matching pursuit is a greedy algorithm to find RF and gradient waveforms which are the best match for an object-signal, the signal can be decomposed with a few iterations and thereby lead reduction of imaging time in MR. To adopt the matching pursuit algorithm to the adaptive data acquisition in MRI, we have designed a dictionary which contains a windowed Fourier basis set. Because the basis set is localized spatially, the image signal could be divided into segmented signals so that matching pursuit with the segmented signals could lead to effective and object-dependent data acquisition. To verify the proposed technique, computer simulations and experiments are performed with a 1.0 T whole body MRI system.

Algorithms↗
PubMed2002

[Statutory pediatric informations available for anticancer drugs: inventory and proposals].

UNLABELLED: Paediatric medicines are often prescribed off label because appropriate clinical and pharmacological studies have not been conducted in children. A European directive is being written to promote the development of paediatric medicines through incentives to pharmaceutical companies, as is already the case in the US. METHOD: In order to evaluate the status of anticancer drugs, we analyzed the paediatric information available in the Vidal 2000 dictionary for cytotoxic chemotherapy. RESULTS: Among the 76 products, 48 were currently used to treat children with cancer. An indication for paediatric use was described in only 29% of them. Paediatric use was mentioned in the posology chapter in 56% of cases, and in the warning or contra-indication chapter in 17% of cases. Ten products (21%) were devoid of paediatric information. DISCUSSION: The paucity of this official paediatric information contrasts with the number of clinical and pharmacological studies that have been conducted and published by paediatric oncology societies and groups. Indeed, almost 80% of children with cancer are treated using prospective therapeutic research protocols. In conclusion, anticancer medicines have been evaluated in children, but official paediatric information is poor. This situation can be significantly improved with the literature currently available. On the other hand, prospective clinical studies are needed to better define the optimal dose in children under one year of age, to evaluate long-term sequelae in cured patients and to provide appropriate galenic forms for oral chemotherapy. CONCLUSION: Incentives are urgently needed to facilitate access to therapeutic innovations in oncology and their development in children with cancer.

Adult↗
PubMed1997

Ethical decision-making in intensive care: are nurses suitable patient advocates?

According to the United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) code of conduct (1992), nurses in Britain are expected to act as patient advocates. An advocate is someone who 'pleads for another' (Concise Oxford Dictionary 1982). However, it has been shown that advocacy is a complex issue and it is debatable as to whether or not it is a legitimate attribute of the role of the nurse (Gates 1995). Mallik (1997) also finds that advocacy can be a risky career option. Professional codes of conduct spell out duties, but do not give moral guidance. Phrases such as 'promote and safeguard the well-being of the patient' (UKCC 1992) are used, but although undoubtedly well-intentioned, this is platitudinous and these codes commonly shed little light on how to define an action that is to the patient's benefit or detriment. It is tempting to suggest that they are used as a drunken man uses a street lamp; more for support than illumination. Castledine (1981) identified a number of factors that would make a nurse an inappropriate advocate and these will be discussed within the context of intensive care units (ICUs).

Critical Care↗