Suboptimal reporting of notifiable diseases in Canadian emergency departments: a survey of emergency physician knowledge, practices, and perceived barriers.
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Canada↗
Biomedical subjects
S M Friedman
Publications and source records attributed to S M Friedman.
Role of crevice in the occurrence of hemoglobin in saliva.
The aim of the present study was to analyze the role of the gingival-periodontal component in the presence of blood in saliva. We studied a population of 184 adult patients composed of 101 totally edentulous patients with no oral mucosa lesions and 83 dentulous patients with clinically healthy gums. Saliva samples obtained by spontaneous salivation were collected in sterile containers. Qualitative and quantitative evaluation of each of the samples was performed. 67% of the dentulous patients tested positive for hemoglobin in saliva. None of the patients in the totally edentulous group exhibited hemoglobin in saliva. These data suggest that the periodontal condition is an essential factor for the presence of hemoglobin in saliva.
Adolescent↗
Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha.
The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 microM. Detailed evaluation of this and related molecules revealed that compounds in this class are "photochemically enhanced" inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.
Antigens, CD↗
Differential regulation of IL-1beta and TNF-alpha RNA expression by MEK1 inhibitor after focal cerebral ischemia in mice.
Activation of the extracellular-signal-responsive kinase (ERK 1/2) by MAP kinase/ERK kinase (MEK1/2) following ischemia/reperfusion in the brain has been associated with cell death since inhibition of MEK1/2 provides neuroprotection in cerebral ischemia injury. Since inflammation has been implicated in ischemic brain injury, the present study investigated whether MEK1/2 modifies expression of two key inflammatory cytokines, IL-1beta and TNFalpha, that have been shown to exacerbate ischemic brain injury. A mouse model of transient cerebral ischemia was deployed to test the effect of selective MEK1/2 inhibitor (SL327) on infarct size and cytokine expression. SL327 (100 mg/kg, i.p.) administered 15 min prior to ischemia resulted in 64% reduction in infarct size over controls (n = 8, P < 0.01). Under the same condition, SL327 significantly reduced peak expression of IL-1beta mRNA (59% reduction compared to vehicle, P < 0.01, n = 4) but not TNF-alpha mRNA. A parallel reduction in IL-1beta protein (67%, P < 0.05, n = 6) was also observed using ELISA analysis. These data suggest that the neuroprotective effect of MEK1/2 inhibition may be mediated by suppression of IL-1beta. The study also demonstrates for the first time that these two cytokines are differentially regulated by kinase mediated signaling pathways.
Aminoacetonitrile↗
Growth deceleration and bone metabolism in nutritional dwarfing rats.
Nutritional status as well as energy and protein intake are critical regulators of IGF-1 and IGFBP-3 and contribute to the modulation of bone remodeling and formation. The purpose of this study was to investigate on an experimental model with nutritional dwarfing (ND), whether the alterations on body growth velocity, energy metabolism and body composition could affect serum concentrations of IGF-1 and IGFBP-3 and bone (tibiae and mandible) histology and histomorphometry. Twenty-one male weanling Wistar rats (body weight = 38.20 +/- 0.94 g) were randomized to three groups: seven of them were killed at day = 0 (CO, n = 7); control (C, n = 7); and experimental 80 (E80, n = 7). During 4 weeks, C was fed ad libitum with a 1:1 carbohydrate to fat diet. E80 was being underfed with the same diet by 80% and the following parameters were measured: weight (Wt) for length (L) ratio z-score; oxygen consumption (VO2); body composition (BC) by EM-SCAN SA 3000. At t = 28, E80 and C were killed. Serum IGF-1 and IGFBP-3 and bone histology and histomorphometry were performed on C0, E80 and C. E80 showed Wt for L z-score between lean and adequate, a decrease in VO2 according to body proportions, a BC of a delayed puberty individual, IGF-1 and IGFBP-3 decreased by 56 and 53%, respectively. Tibiae's hematopoyetic and adipose bone marrow areas were combined, with sealing trabeculae on metaphyseal areas. This study suggests that there is a relationship among growth deceleration in ND rats and structural alterations on tibiae.
Animals↗
Mutation in the DNA gyrase A Gene of Escherichia coli that expands the quinolone resistance-determining region.
In three Escherichia coli mutants, a change (Ala-51 to Val) in the gyrase A protein outside the standard quinolone resistance-determining region (QRDR) lowered the level of quinolone susceptibility more than changes at amino acids 67, 82, 84, and 106 did. Revision of the QRDR to include amino acid 51 is indicated.
4-Quinolones↗
Biology of TACE inhibition.
Studies conducted over the past decade have demonstrated a central role for tumour necrosis factor alpha (TNFalpha) in inflammatory diseases. As a result of this work, a number of biological agents that neutralise the activity of this cytokine have entered the clinic. The recent clinical data obtained with etanercept and infliximab highlight the relevance of this strategy. TNFalpha converting enzyme (TACE) is the metalloproteinase that processes the 26 kDa membrane bound precursor of TNFalpha (proTNFalpha) to the 17 kDa soluble component. Although a number of proteases have been shown to process proTNFalpha, none do so with the efficiency of TACE. A series of orally bioavailable, selective, and potent TACE inhibitors are currently in clinical development. These inhibitors effectively block TACE mediated processing of proTNFalpha and can reduce TNF production by lipopolysaccharide stimulated whole blood by >95%. Through a series of studies it is shown here that >80% of the unprocessed proTNFalpha is degraded intracellularly. The remainder appears to be transiently expressed on the cell surface. Although, in vitro, TACE inhibition has also been implicated in shedding of p55 and p75 surface TNFalpha receptors, the in vivo data cast doubt on the consequences of this finding. In a mouse model of collagen-induced arthritis, the inhibitors are efficacious both prophylactically and therapeutically. The efficacy seen is equivalent to strategies that neutralise TNFalpha. In many studies greater efficacy is observed with the TACE inhibitors, presumably owing to greater penetration to the site of TNFalpha production.
ADAM Proteins↗
Mixed lens opacities and subsequent mortality.
BACKGROUND: Previous studies have found an association between cataract or lens opacity and increased risk of mortality. Further work on determining explanatory factors for this association is needed. OBJECTIVES: To determine, in a population-based cohort of older persons, the 2-year risk of death associated with different types of lens opacities; whether an association of mortality and lens opacity is explained by confounding risk factors such as smoking, diabetes, age, race, and sex, which are known to be related to opacity and mortality; whether lens opacity is a marker for health status; and whether there are differences in cause-specific mortality for persons with and without lens opacity. MAIN OUTCOME MEASURE: Two-year mortality rate. METHODS: The Salisbury Eye Evaluation Project consists of a random sample of 2520 residents of Salisbury, Md, aged 65 to 84 years. At baseline, lens photographs were taken to document nuclear, cortical, posterior subcapsular cataract, and mixed opacities. Data on education, smoking, alcohol use, hypertension, diabetes and other comorbid conditions, handgrip strength, and body mass index were also collected. Two-year follow-up was conducted for mortality and cause of death. RESULTS: Nuclear opacity, particularly severe nuclear opacity, and mixed opacities with nuclear were significant predictors of mortality independent of body mass index, comorbid conditions, smoking, age, race, and sex (mixed nuclear: odds ratio, 2.23; 95% confidence interval, 1.26-3.95). CONCLUSION: Lens opacity status is an independent predictor of 2-year mortality, an association that could not be explained by potential confounders.
Aged↗
The development of the inventory of countertransference behavior.
A measure was developed to assess supervisor-perceived countertransference (CT) behavior during counseling sessions. Eleven experts provided face validity for the items, indicating that each item was at least somewhat an expression of countertransference. Exploratory factor analysis of ratings of 126 supervisors of supervisee counseling sessions revealed, as expected, the existence of two factors. However, rather than reflecting the dimensions of overinvolvement and underinvolvement as hypothesized, the factors were better captured by the terms Negative Countertransference and Positive Countertransference. The total scale and each subscale demonstrated high internal consistency. In addition, both positive and negative CT were found to relate positively with an existing one-item index of countertransference behavior and negatively with an existing measure of countertransference management ability. Research and clinical implications are discussed.
Adult↗
Overexpression of the cat-86 gene is associated with thermosensitivity in Bacillus subtilis.
Bacillus subtilis harboring the cat-86 constitutive plasmid pPL708C2 with an ochre mutation at the 9th codon (terc 9) was sensitive to chloramphenicol (Cm(s)) and exhibited relative thermostability when heated at 47 degrees C. Reversion to chloramphenicol resistance (Cm(r)) occurred at a frequency of 5.4 x 10(-8). All of the plasmid Cm(r) revertants tested were thermosensitive. Similarly, wild-type pPL708C2 present in B. subtilis also rendered the bacterium thermosensitive. When a nonsense mutation is introduced at codon 141, however, this terc 141 variant of pPL708C2 failed to thermosensitize B. subtilis. Another variant of pPL708C2 that produces intact yet catalytically inactive CAT-86 has both His-16 and His-17 at the active site replaced by Pro. Nevertheless, cells of B. subtilis carrying this variant were thermosensitive. Plasmid-free and pPL708C2-bearing strains did not exhibit differences in major heat shock proteins. Electron micrographs revealed a threefold increase of inclusion bodies present in a strain harboring pPL708C2 when compared with those in an isogenic plasmid-free strain.
Bacillus subtilis↗
Choroidal neovascular membranes: reproducibility of angiographic interpretation.
PURPOSE: To determine interobserver agreement for classifying choroidal neovascular membranes in age-related macular degeneration. METHODS: Six fluorescein angiograms of choroidal neovascular membranes were interpreted by 21 retina specialists. Reliability was measured by percent agreement and kappa coefficient. RESULTS: Interobserver agreement of membrane types ranged from perfect concordance for a small, classic membrane to near-random classification for a complex pattern. Mean kappa coefficient was.64. Interobserver agreement of membrane size was most variable for intermediate size lesions (mean kappa coefficient =.40). CONCLUSION: Fluorescein angiographic interpretation of choroidal neovascular membrane type and size can vary considerably. Interobserver agreement is better for membrane type than for membrane size.
Choroidal Neovascularization↗
Proliferative response of mantle cell lymphoma cells stimulated by CD40 ligation and IL-4.
Mantle cell lymphoma (MCL) is a tumor of intermediate-size, IgM+, IgD+ B cells derived from the mantle zone of the germinal center. Little is known about its specific immunologic features or responsiveness to T cell-derived signals. In this work, we evaluated the proliferation and cell cycle properties of freshly isolated MCL cells after CD40 ligation, in the absence and presence of interleukin 4 (IL-4). In each MCL case examined, there was a marked growth-enhancing effect of these two stimuli characterized by improved viability, augmented expression of Ki-67, and induction of the proliferating cell nuclear antigen (PCNA). Cyclin D1 was expressed throughout the cell cycle in MCL cells induced to enter S phase. From these investigations, we conclude that the biology of MCL B lymphocytes is affected by CD154 (CD40 ligand) and IL-4, two signals usually provided by CD4+ T cells. The capacity to manipulate the activation and cell cycle state of MCL cells by these specific immunological stimuli may be exploited to confer susceptibility to chemotherapy agents and develop novel therapies in this disease.
B-Lymphocytes↗
Ocular findings in aplastic anemia.
OBJECTIVE: To analyze the ocular findings in aplastic anemia. DESIGN: Eighteen patients with aplastic anemia were examined. RESULTS: Ocular findings included cotton wool spots (38%), nerve fiber layer or preretinal hemorrhages (67%), vitreous hemorrhages (13%), a picture resembling central retinal vein occlusion (13%) and optic disk edema (6%). Preretinal hemorrhages were the presenting sign of aplastic anemia in 2 patients (13%). CONCLUSIONS: A blood profile is needed in patients with unexplained retinal hemorrhages. Patients with aplastic anemia need to avoid ocular massage and Valsalva maneuvers to decrease ocular morbidity.
Adolescent↗
Bone growth in nonorganic nutritional dwarfing rats.
Since no data are available to characterize mandibular growth in nonorganic nutritional dwarfing (ND), the purpose of the present study was to describe the effects of a diet on mandible and femur growth in a nutritional dwarfish animal model. Male Wistar rats were divided into two groups of 10 animals each: Control (C) and Experimental (E80: diet-restricted group). C rats were fed a standard diet ad libitum. E80 rats received 80% of the amount of standard diet eaten by group C. Food intake and body weight (Wt) and length (Lt) were recorded periodically. Growth data (Wt and Lt) were expressed as a Z-score of weight-for-length (WLZ) ratio, an index of body size. Five animals of each group were selected at random at 4 and 8 weeks and sacrificed. Additionally at t = 0, 5 animals were sacrificed for baseline measurements. Mandibular growth was estimated directly on the right mandible by measuring ten dimensions. Femur growth was estimated from Wt and Lt measurements of the bone. Mandibular weight, area, length and height were negatively affected by dietary restriction during the first 4 weeks of the experimental period. Mandibular growth ceased after this point. Dimensions corresponding to the alveolar unit did not change with time. However, all other dimensions were negatively influenced but not to the same extent. Femur rather than mandibular weight was severely affected. Therefore, the negative effects of the nutritional stress that occurs after weaning would be stronger for the femur, than for the mandible. Femur length was also negatively affected by suboptimal nutrition. In summary, the results of the present study showed that mandible and femur growth respond differently to mild chronic food restriction. These observations could be explained in terms of the different critical bone growth periods and of the time at which nutritional stress was imposed.
Animals↗
Impact of community volunteers on immunization rates of children younger than 2 years.
OBJECTIVE: To assess the effectiveness of a volunteer-driven outreach program on immunization rates in children younger than 2 years. DESIGN: Randomized controlled trial. SETTING: Pediatric ambulatory clinics in New York, NY. PATIENTS: A total of 163 children were randomly assigned to receive services from the volunteer-driven outreach program or to serve as control subjects. All children were (1) younger than 2 years, (2) no-shows for a scheduled appointment in the pediatric clinic, and (3) due or overdue for a vaccine. INTERVENTION: Immunization outreach, tracking, and follow-up were provided by community volunteers throughout follow-up (mean, 6.5 months). Control children were notified of immunization status at enrollment but received no further contact until the conclusion of follow-up (mean, 6.4 months). MAIN OUTCOME MEASURE: Immunization status 6 months after enrollment. RESULTS: Significantly more intervention children were up-to-date with their vaccination series than controls (75% vs. 54%; P = .03). Children in the control group were 2.8 times more likely to be late for a vaccine than intervention children (odds ratio = 2.8; P = .02). In addition, an immunization delay of longer than 30 days at enrollment was a significant predictor of final immunization delay (odds ratio = 2.6; P = .02). CONCLUSIONS: This volunteer-driven program significantly improved immunization rates among intervention children compared with controls. Results confirm previous findings that indicate an increased risk of an incomplete immunization series by 2 years of age among children who fall behind early in their primary vaccination series. However, control children were almost 3 times more likely to be late (for > or =1 vaccines) than intervention children, regardless of whether an earlier immunization delay was present.
Ambulatory Care↗
A comparison of job satisfaction among nursing assistants in nursing homes and the Program of All-inclusive Care for the Elderly (PACE).
Three hundred forty-nine full-time nursing assistants (NAs) in 5 PACE programs and their neighboring nursing homes were surveyed to assess job satisfaction. There were no significant differences between NAs in the two models of care with respect to demographics, job description, or importance placed on job elements. Job satisfaction, however, was higher among the PACE NAs. PACE NAs reported a significantly higher prevalence of the chance to form close relationships with patients, variety, respect for suggestions by people who make decisions about patient care, the chance to use one's own judgment, the chance to discuss patients with other team members, and respect for choices in assignment type.
Adult↗
Choroidal metastasis from adenocarcinoma of the parotid gland.
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Adenocarcinoma↗
Characteristics of discrepancies between self-reported visual function and measured reading speed. Salisbury Eye Evaluation Project Team.
PURPOSE: Visual impairment is a risk factor for morbidity in the elderly and is often screened for by self-report. This study evaluates whether there are subsets for whom there is a discrepancy between self-reported and measured function. METHODS: The prevalence of a discrepancy between self-reported difficulty reading a newspaper and measured reading speed was determined in 2520 community-based men and women, aged 65 to 84 years, and the discrepant group characterized by polychotomous regression. RESULTS: Of subjects who reported minimal difficulty reading a newspaper, 10.8% (227/2107) read newsprint-sized text (0.21 degrees) more slowly than 80 words/min, a level previously shown to be necessary for sustained reading. Poor visual acuity, presence of psychiatric symptoms, and less satisfaction with vision were associated with being in the group that read slowly and reported difficulty with reading. Better cognition, better visual acuity, more years of education, white race, and fewer psychiatric symptoms were associated with being in the group that read more quickly and reported minimal difficulty. When reading the text size at which subjects read their fastest, only 2.6% of those with minimal difficulty remained discrepant. These individuals were more likely to have less education, be male, be African American, and have poorer cognitive status than those who did not remain discrepant. CONCLUSIONS: A subset of the elderly population have a substantial discrepancy between self-reported reading difficulty and measured reading speed. In some, this discrepancy may be based on underlying expectations and experiences, and in others it may represent a transition from no visual impairment to visual impairment.
Aged↗