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PubMedDate not supplied

Acute coalescent mastoiditis.

A retrospective review of 11 cases of acute coalescent mastoiditis from 1974 to 1979 is presented. The common historical data include the recent onset of purulent otitis media, which was often incompletely treated with antibiotics, and fever, lethargy, and irritability. The eardrums were red, bulging, and usually intact. A postauricular abscess was present, and the affected ear protruded downward and outward. The mastoid radiographs invariably showed cloudiness and dissolution of the air cell septations. Initial therapy included paracentesis for culture and sensitivity, and initiation of parenteral antibiotics. Surgical therapy consisted of wide myringotomy, drainage of the postauricular abscess, and complete mastoidectomy. Hearing was normal postoperatively in all cases.

Acute Disease↗

PubMed1999

Maximum likelihood analysis of generalized linear models with missing covariates.

Missing data is a common occurrence in most medical research data collection enterprises. There is an extensive literature concerning missing data, much of which has focused on missing outcomes. Covariates in regression models are often missing, particularly if information is being collected from multiple sources. The method of weights is an implementation of the EM algorithm for general maximum-likelihood analysis of regression models, including generalized linear models (GLMs) with incomplete covariates. In this paper, we will describe the method of weights in detail, illustrate its application with several examples, discuss its advantages and limitations, and review extensions and applications of the method.

Algorithms↗

PubMed1990

Potentiation of pain relief with hydroxyzine: a therapeutic myth?

Opioid analgesics are among the oldest known medications. In spite of long usage, clinical success in controlling pain in many settings appears to be limited by a lack of understanding of the clinical pharmacology of these agents. Efforts to achieve better outcomes often focus on the use of adjunctive agents, such as hydroxyzine, in an attempt to control postoperative pain with a minimum of toxicity. Although such combined therapies are exceedingly common, clinical data supporting a hypothesis of an "opioid-sparing" effect of hydroxyzine are marked by serious methodologic flaws, including lack of placebo control, lack of statistical analyses, and use of subjective assessments, all of which compromise the validity of such conclusions. In doses that may contribute to pain relief, hydroxyzine demonstrates a significant potential for causing respiratory depression which is additive to that of opioids, but not reversible with naloxone. In total, the data do not confirm the purported clinical benefits of hydroxyzine-opioid combinations in comparison with appropriate regimens of opioids alone.

Drug Synergism↗

PubMed1992

Over-the-counter medications in cardiac transplant recipients: guidelines for use.

OBJECTIVE: The purpose of this article is to review the pathophysiology of the denervated heart and the factors that need to be considered before recommending the use of over-the-counter (OTC) medications in the cardiac transplant recipient. DATA SOURCES: Pharmacology and therapeutic textbooks, English-language journal articles, and physiology textbooks published between 1969 and 1991. DATA EXTRACTION: Case reports, controlled case studies, and textbook chapters evaluating drug interactions with immunosuppressive agents were reviewed. The effects of various OTC medications on the denervated heart were examined and relevant material was extrapolated. DATA ANALYSIS: The number of cases or studies in which a particular effect or interaction occurred was reported. Those findings that were less well documented were either identified as such or were not included in the review. DATA SYNTHESIS: Common pharmacokinetic and pharmacodynamic interactions with the primary immunosuppressive agents (e.g., cyclosporine, azathioprine, prednisone) are reviewed. The physiology and altered responses of the denervated heart to various medications are also explained. Using this information recommendations are given for the use and monitoring of OTC analgesics, antacids, laxatives, sleep aids, stimulants, and other medications that may be used in the cardiac transplant recipient. CONCLUSIONS: Many OTC medications can be used safely in the cardiac transplant recipient. In each situation, risk/benefit assessments must always be made and therapy should be monitored closely. Most important, patients should always notify the transplant team before adding an OTC product to their immunosuppressive regimen.

Analgesics↗

PubMed1995

Aortic aneurysm morphology for planning endovascular aortic grafts: limitations of conventional imaging methods.

PURPOSE: To test whether conventional computed tomography scanning (CT) and contrast aortography (CA) provide adequate data for planning endovascular aortic grafting by measuring 33 parameters in patients having both imaging examinations for evaluation of abdominal aortic aneurysms (AAA). METHODS: Fifty consecutive patients with AAA (41 men, 9 women; average age 65 years) had CT and CA (mean 26 days between exams). The data collected and analyzed included: 8 sites of diameter, 4 lengths, 6 angles, and 15 other dimensional measurements. RESULTS: Conflicts between CA and CT data were common. Eighteen patients appeared to have a distal cuff by CA but not by CT. Proximal neck length could not be assessed by CT in 5 and had a difference between CA and CT > 1 cm in 25 patients. CA overestimated neck length in 11 patients. Common iliac artery angulation > 60 degrees unilaterally in 27 patients and bilaterally in 5. Seven patients had both iliac aneurysm and > 60 degree iliac angulation. Thirteen patients had one or more iliac aneurysms (> 2 cm) shown by CT but not by CA. CONCLUSIONS: For endovascular graft planning: (1) more detailed measurement is required than for traditional surgery; and (2) conventional CT and CA are complementary imaging studies, but each has important limitations.

Aged↗

PubMed2005

ProMiner: rule-based protein and gene entity recognition.

BACKGROUND: Identification of gene and protein names in biomedical text is a challenging task as the corresponding nomenclature has evolved over time. This has led to multiple synonyms for individual genes and proteins, as well as names that may be ambiguous with other gene names or with general English words. The Gene List Task of the BioCreAtIvE challenge evaluation enables comparison of systems addressing the problem of protein and gene name identification on common benchmark data. METHODS: The ProMiner system uses a pre-processed synonym dictionary to identify potential name occurrences in the biomedical text and associate protein and gene database identifiers with the detected matches. It follows a rule-based approach and its search algorithm is geared towards recognition of multi-word names. To account for the large number of ambiguous synonyms in the considered organisms, the system has been extended to use specific variants of the detection procedure for highly ambiguous and case-sensitive synonyms. Based on all detected synonyms for one abstract, the most plausible database identifiers are associated with the text. Organism specificity is addressed by a simple procedure based on additionally detected organism names in an abstract. RESULTS: The extended ProMiner system has been applied to the test cases of the BioCreAtIvE competition with highly encouraging results. In blind predictions, the system achieved an F-measure of approximately 0.8 for the organisms mouse and fly and about 0.9 for the organism yeast.

Computational Biology↗

PubMed2007

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial.

BACKGROUND: Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. METHODS: Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. RESULTS: Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35-0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33-3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96-2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84-2.49). CONCLUSION: Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.

Adult↗

PubMed2001

21st European Workshop for Rheumatology Research, Vienna, Austria, 1-4 March 2001.

Major advances in technology now drive how we approach questions in immunology, particularly in analyzing complex data sets commonly encountered in genomics and proteomics studies. Active areas of investigation include development of novel technologies, identification of elusive target antigens for RA and other diseases, dissection of signaling pathways connecting the lymphocyte cell surface with the nucleus, and exploration of new avenues for therapeutic interventions. The European Workshop for Rheumatology Research (EWRR) is a forum for many European and non-European scientists to present research findings of high quality. Arthritis researchers from around the globe should be strongly encouraged to attend future meetings, the next of which is the 22nd EWRR meeting in Leiden, the Netherlands, in 2002.

Animals↗

PubMed2004

Computational identification of developmental enhancers: conservation and function of transcription factor binding-site clusters in Drosophila melanogaster and Drosophila pseudoobscura.

BACKGROUND: The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. RESULTS: We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. CONCLUSIONS: Measuring conservation of sequence features closely linked to function--such as binding-site clusterin--makes better use of comparative sequence data than commonly used methods that examine only sequence identity.

Animals↗

PubMed2005

Handheld computer-based decision support reduces patient length of stay and antibiotic prescribing in critical care.

OBJECTIVE: This study assessed the effect of a handheld computer-based decision support system (DSS) on antibiotic use and patient outcomes in a critical care unit. DESIGN: A DSS containing four types of evidence (patient microbiology reports, local antibiotic guidelines, unit-specific antibiotic susceptibility data for common bacterial pathogens, and a clinical pulmonary infection score calculator) was developed and implemented on a handheld computer for use in the intensive care unit at a tertiary referral hospital. System impact was assessed in a prospective "before/after" cohort trial lasting 12 months. Outcome measures were defined daily doses (DDDs) of antibiotics per 1,000 patient-days, patient length of stay, and mortality. RESULTS: The number of admissions, APACHE (Acute Physiology, Age, and Chronic Health Evaluation) II and SAPS (Simplified Acute Physiology Score) II for patients in preintervention, and intervention (DSS use) periods were statistically comparable. The mean patient length of stay and the use of antibiotics in the unit during six months of the DSS use decreased from 7.15 to 6.22 bed-days (p = 0.02) and from 1,767 DDD to 1,458 DDD per 1,000 patient-days (p = 0.04), respectively, with no change in mortality. The DSS was accessed 674 times during 168 days of the trial. Microbiology reports and antibiotic guidelines were the two most commonly used (53% and 22.5%, respectively) types of evidence. The greatest reduction was observed in the use of beta-lactamase-resistant penicillins and vancomycin. CONCLUSION: Handheld computer-based decision support contributed to a significant reduction in patient length of stay and antibiotic prescribing in a critical care unit.

APACHE↗

PubMed2003

Tbx5 is essential for forelimb bud initiation following patterning of the limb field in the mouse embryo.

Transcriptional cascades responsible for initiating the formation of vertebrate embryonic structures such as limbs are not well established. Limb formation occurs as a result of interplay between fibroblast growth factor (FGF) and Wnt signaling. What initiates these signaling cascades and thus limb bud outgrowth at defined locations along the anteroposterior axis of the embryo is not known. The T-box transcription factor TBX5 is important for normal heart and limb formation, but its role in early limb development is not well defined. We report that mouse embryos lacking Tbx5 do not form forelimb buds, although the patterning of the lateral plate mesoderm into the limb field is intact. Tbx5 is not essential for an early establishment of forelimb versus hindlimb identity. In the absence of Tbx5, the FGF and Wnt regulatory loops required for limb bud outgrowth are not established, including initiation of Fgf10 expression. Tbx5 directly activates the Fgf10 gene via a conserved binding site, providing a simple and direct mechanism for limb bud initiation. Lef1/Tcf1-dependent Wnt signaling is not essential for initiation of Tbx5 or Fgf10 transcription, but is required in concert with Tbx5 for maintenance of normal levels of Fgf10 expression. We conclude that Tbx5 is not essential for the early establishment of the limb field in the lateral plate mesoderm but is a primary and direct initiator of forelimb bud formation. These data suggest common pathways for the differentiation and growth of embryonic structures downstream of T-box genes.

Animals↗

PubMed1983

The changing role of animal toxicology in support of regulatory decisions.

The Clean Air Act is the basic U.S. Federal law for controlling air pollution. Under Sections 108 and 109, primary (health) national ambient air quality standards (NAAQS) can be set for pollutants which are ubiquitous in the ambient air. The standard-setting process includes a comprehensive summary of scientific information on effects and controls in criteria and control techniques, and the selection of an appropriate standard which, in the judgment of the Administrator, protects the health of normal and susceptible subpopulations with an adequate margin of safety. Determining the adequacy of existing NAAQS or establishing new standards requires that the scientific information base be evaluated to assess pollutant effects on public health. Improvements in this process can be accomplished not only through new health effects research, but also through improved use of currently available data. The commonality joining these two efforts is in the area of extrapolation modeling, which is the topic of this paper. Extrapolation modeling involves determining the effective dose delivered to the target organ of several species and the sensitivity of the target organ to that dose so that effective pollutant concentrations can be estimated across species. This in turn allows greater utilization of the results from animals in making judgments about the effects in man from exposure to a given pollutant.

Air Pollutants↗

PubMed1985

PCB levels in breast milk: data from the UNEP/WHO pilot project on biological monitoring and some other recent studies.

The levels of polychlorinated biphenyls (PCBs) in human milk provide an index of exposure of the mother to these compounds and enable the intake by the breast-fed child to be estimated. For valid comparisons between different studies, concentrations should be expressed on a milk fat basis. In a recently completed UNEP/WHO pilot project on monitoring of organochlorine compounds in human milk in ten countries, great emphasis was placed on analytical quality assurance. To obtain comparable data, a common procedure, that of Sawyer, was adopted for quantitation of PCBs, using Aroclor 1260 as standard. In addition, certain criteria (e.g., age and parity) were established for selection of the mothers to be sampled. In contrast to the situation with p,p'-DDT and p,p'-DDE, the levels of PCBs in human milk fat were higher in the European countries and Japan than in China, India and Mexico. In fact, PCBs were not detected in human milk in the latter three countries. Although PCBs were detected in some samples in the USA, the median level was below the limit of detection of the method used there (1 mg/kg fat). The median PCB levels reported from Belgium, Israel, Japan and Yugoslavia were 0.81, 0.45, 0.35 and 0.63 mg/kg fat, respectively. Higher median levels were reported from Sweden and the Federal Republic of Germany (0.97 and 2.1 mg/kg fat, respectively). The German samples were not analyzed by the Sawyer method.

Adolescent↗

PubMed1996

Behavioral effects of lead: commonalities between experimental and epidemiologic data.

Enormous effort has been focused over the last decade and a half on characterizing the behavioral effects of lead in the developing organism. While age-appropriate standardized measures of intelligence (IQ) have been the dependent variable most often used to assess lead-induced cognitive impairment in epidemiologic studies, researchers have also used a variety of other methods designed to assess specific behavioral processes sensitive to lead. Increased reaction time and poorer performance on vigilance tasks associated with increased lead body burden suggest increased distractibility and short attention span. Assessment of behavior on teachers' rating scales identified increased distractibility, impulsivity, nonpersistence, inability to follow sequences of directions, and inappropriate approach to problems as hallmarks of lead exposure. Robust deficits in learned skills such as reading, spelling, math, and word recognition have also been found. Spatial organizational perception and abilities seem particularly sensitive to lead-induced impairment. Assessment of complex tasks of learning and memory in both rats and monkeys has revealed overall deficits in function over a variety of behavioral tasks. Exploration of behavioral mechanisms responsible for these deficits identified increased distractibility perseveration, inability to inhibit inappropriate responding, and inability to change response strategy as underlying deficits. Thus, there is remarkable congruence between the epidemiologic and experimental literatures with regard to the behavioral processes identified as underlying the deficits inflicted by developmental lead exposure. However, careful behavioral analysis was required from researchers in both fields for such understanding to emerge.

Animals↗

PubMed2000

Transdermal nitroglycerin for the prevention of intravenous infusion failure due to phlebitis and extravasation.

OBJECTIVE: To evaluate the clinical use of transdermal nitroglycerin for the prevention of intravenous infusion failures due to phlebitis or extravasation. DATA SOURCES: Clinical literature was accessed through a MEDLINE search (1966-May 2000). Key search terms included nitroglycerin, transdermal, phlebitis, extravasation, intravenous, and infusion. DATA SYNTHESIS: Common and serious consequences of intravenous therapy include the occurrence of postinfusion phlebitis and failure to maintain intravenous therapy due to intravenous fluid extravasation. Transdermal application of nitroglycerin has been evaluated as a treatment and preventive method for intravenous infusion failures related to phlebitis or extravasation. An evaluation of studies focusing on transdermal nitroglycerin in the prevention of infusion failures due to phlebitis or extravasation was conducted. CONCLUSIONS: Use of transdermal nitroglycerin as a prophylactic measure for intravenous infusion failures is a therapeutic option for patients requiring long-term intravenous therapy (i.e., > 50 h).

Administration, Cutaneous↗

PubMed2003

Implications of SARS: medical geography and surveillance in disease detection.

OBJECTIVE: To expose pharmacy educators and practitioners to concepts of medical geography and medical surveillance. Severe acute respiratory syndrome (SARS) is used as a case example because it is an emerging infection and a prime example of the type of disease that pharmacists may encounter in daily practice (e.g., easily transmitted, resembles the common cold). DATA SOURCES: We retrieved data from publications related to medical geography, medical surveillance, and SARS. Data on current SARS cases in Hong Kong were obtained from the Hong Kong Department of Health Web site. STUDY SELECTION AND DATA EXTRACTION: Variables regarding new cases and deaths due to SARS were evaluated. DATA SYNTHESIS: Background information on medical geography and medical surveillance was reviewed. Descriptive statistics were calculated for incidence, prevalence, and the number of deaths due to SARS in Hong Kong from March 14 to May 31, 2003. CONCLUSIONS: Emerging infections are a serious concern for both the public and healthcare practitioners. The recent global diffusion of SARS highlights the ease in which diseases can diffuse from place to place. Understanding concepts related to medical geography and medical surveillance can help pharmacists be better prepared to anticipate disease diffusion and to evaluate signs of emerging infections. In turn, this can help pharmacists be better prepared to provide information and care to their patients. The long-term benefit of understanding how diseases spread and the specific activities related to disease detection is an opportunity for expanding the scope of pharmacy practice.

Canada↗

PubMed2004

Implications of absence of measurement invariance for detecting sex limitation and genotype by environment interaction.

Using univariate sum scores in genetic studies of twin data is common practice. This practice precludes an investigation of the measurement model relating the individual items to an underlying factor. Absence of measurement invariance across a grouping variable such as gender or environmental exposure refers to group differences with respect to the measurement model. It is shown that a decomposition of a sum score into genetic and environmental variance components leads to path coefficients of the additive genetic factor that are biased differentially across groups if individual items are non-invariant. The arising group differences in path coefficients are identical to what is known as "scalar sex limitation" when gender is the grouping variable, or as "gene by environment interaction" when environmental exposure is the grouping variable. In both cases the interpretation would be in terms of a group-specific effect size of the genetic factor. This interpretation may be incorrect if individual items are non-invariant.

Algorithms↗

PubMed2005

Molecular control of physiological and pathological T-cell recruitment after mouse spinal cord injury.

The intraspinal cues that orchestrate T-cell migration and activation after spinal contusion injury were characterized using B10.PL (wild-type) and transgenic (Tg) mice with a T-cell repertoire biased toward recognition of myelin basic protein (MBP). Previously, we showed that these strains exhibit distinct anatomical and behavioral phenotypes. In Tg mice, MBP-reactive T-cells are activated by spinal cord injury (SCI), causing more severe axonal injury, demyelination, and functional impairment than is found in non-Tg wild-type mice (B10.PL). Conversely, despite a robust SCI-induced T-cell response in B10.PL mice, no overt T-cell-mediated pathology was evident. Here, we show that chronic intraspinal T-cell accumulation in B10.PL and Tg mice is associated with a dramatic and sustained increase in CXCL10/IP-10 and CCL5/RANTES mRNA expression. However, in Tg mice, chemokine mRNA were enhanced 2- to 17-fold higher than in B10.PL mice and were associated with accelerated intraspinal T-cell influx and enhanced CNS macrophage activation throughout the spinal cord. These data suggest common molecular pathways for initiating T-cell responses after SCI in mice; however, if T-cell reactions are biased against MBP, molecular and cellular determinants of neuroinflammation are magnified in parallel with exacerbation of neuropathology and functional impairment.

Animals↗