Monitoring trends in acute rheumatic fever in the United States.
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Bias↗
Biomedical subjects
B Schwartz
Publications and source records attributed to B Schwartz.
Ethics, occupational medicine, and ACOEM.
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Conflict of Interest↗
Decrease of optic disc cupping and pallor of ocular hypertensives with timolol therapy.
PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on optic disc cupping and pallor in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to placebo or 0.5% timolol drops to both eyes in a double masked clinical trial. Measurements of ocular pressure and photographs of the optic disc for cupping by photogrammetry and pallor by computerized image analysis were made at about 3 month intervals, for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with timolol developed a significant decrease in ocular pressure and a significant decrease in optic disc cupping with a smaller decrease in pallor compared to subject treated with placebo. Multivariate analyses indicated that the decrease of optic disc cupping and pallor was not associated with the ocular pressure on treatment or the decrease in ocular pressure during the trial. CONCLUSION: Timolol treatment was associated with a decrease in optic disc cupping and pallor. The effect of timolol appears to be related to mechanisms other than the decrease in ocular pressure.
Double-Blind Method↗
Increase of retinal nerve fiber layer thickness in ocular hypertensives with timolol therapy.
PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on retinal nerve fiber layer thickness in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to receive placebo or 0.5% timolol drops to both eyes for 18 to 24 months in a double masked clinical trial. Measurements of ocular pressure and photographs of retinal nerve fiber layer using stereophotogrammetric techniques were made at about 3 month intervals for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with timolol had a significant decrease in ocular pressure and developed a significant increase in retinal nerve fiber layer thickness compared to subjects treated with placebo. Multivariate analyses indicated that the increase of retinal nerve layer thickness was not associated either with the ocular pressure on treatment or the decrease in ocular pressure on treatment. CONCLUSION: Timolol treatment was associated with an increase of retinal nerve fiber thickness. The effect of timolol appears to be related to mechanisms other than the decrease in ocular pressure.
Double-Blind Method↗
Retinal blood vessel width measured on color fundus photographs by image analysis.
The purpose of this paper was to develop a technique using computerized image analysis to measure the width of retinal arteries and veins on color fundus photographs. The width of the retinal vessel was determined from digitized fundus photographs by programs based on edge detection and boundary tracing. The average vessel width was determined at different distances or eccentricities from the center of the optic disc and using various lengths of vessel segment. Measurements of superior and inferior temporal vessel width for 20 eyes by 2 operators showed that about 75% of the measurements could be obtained without the use of plan points. The average percent coefficient of variation of the measurements was 2.17% for 3 measurements of each vessel. This technique provides a reproducible and objective method for obtaining the following parameters: the edges of the vessel, the length of the vessel segment to be measured, location of the measurement along the vessel and subsequent retinal vessel width. This technique is readily suitable for application to clinical studies particularly clinical trials.
Adult↗
Increase of retinal vessel width in ocular hypertensives with timolol therapy.
PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on retinal vessel width in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to receive placebo or 0.5% timolol drops to both eyes for 18 to 24 months in a double masked clinical trial. Measurements of ocular pressure and retinal vessel width by computerized image analysis from fundus photographs were made at about 3 month intervals for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with the placebo showed no change in ocular pressure and a significant decrease in retinal vessel width over time especially in the right eye. Subjects treated with timolol had an increase in retinal vessel width compared to the placebo group significant especially for the superior temporal vein. Multivariate analyses indicated that the increase of retinal vessel width was not associated mainly with the ocular pressure on treatment or decrease in ocular pressure on treatment. CONCLUSION: Timolol treatment was associated with an increase of retinal vessel width. The effect of timolol appears to be related primarily to mechanisms other than the decrease in ocular pressure.
Double-Blind Method↗
Optic nerve head circulation in untreated ocular hypertension.
AIMS: The laser Doppler technique was used to compare the capillary blood speed measured at localised sites of the optic nerve head in stable, untreated ocular hypertensive patients with that measured in healthy normal subjects. The stereophotogrammetric technique was also used to measure the retinal nerve fibre layer thickness at the disc margin in the eyes of the patients. METHODS: Doppler broadening measurements were made at superior and inferior temporal disc sites in 18 eyes of 10 ocular hypertensive patients and in 12 eyes of seven age and sex-matched normal subjects. RESULTS: On average, Doppler broadening and, hence, capillary blood speed were significantly higher (p = 0.018) in the patients than in the normal subjects. The largest values of Doppler broadening in the patients were measured at sites adjacent to the thinnest retinal nerve fibre layer. Linear regression analysis showed a significant inverse relation (p = 0.0004) between Doppler broadening and nerve fibre layer thickness in left eyes, and a nearly significant relation (p = 0.06) in right eyes. At temporal sites of the optic nerve head there is a compensatory relation between a thinning nerve fibre layer and a locally increasing blood supply to the optic nerve head. CONCLUSION: Together with previous observations of fluorescein filling defects in similar patients, these results indicate that there is spatial heterogeneity of blood flow in the optic nerve head in stable, untreated ocular hypertensive patients.
Adult↗
Association of exposure to polycyclic aromatic hydrocarbons (estimated from job category) with concentration of 1-hydroxypyrene glucuronide in urine from workers at a steel plant.
OBJECTIVES: Increased risk of lung cancer has been associated with employment in the steel industry. This association is thought to be due in part to increased concentrations of polycyclic aromatic hydrocarbons (PAHs) in air found in this work environment. Measurement of PAH metabolites in human urine provides a means of assessing individual internal dose of PAHs. This study examined the relative contribution of occupation and smoking to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG) among a group of workers at a steel plant. METHODS: Concentrations of 1-OHPG in urine from 44 workers with jobs associated with increased air concentrations of PAHs and 40 workers with jobs with low or no exposure to PAHs were measured. 20 workers in each group were not current smokers. Urinary 1-OHPG was measured by synchronous fluorescence spectroscopy after immunoaffinity chromatography specific for PAH metabolites. RESULTS: Mean (SEM) urinary 1-OHPG concentration was 2.16 (0.42) pmol/ml urine among the 44 occupationally exposed workers compared with 0.38 (0.05) among the 40 workers with no or low exposure (P < 0.0001). Mean urinary 1-OHPG concentration was 1.82 (0.41) pmol/ml urine among the 44 current smokers compared with 0.75 (0.20) among the 40 non-smokers (P < 0.005). Mean 1-OHPG concentrations in non-smokers were 0.26 (n = 20), 0.70 (n = 15), and 2.84 pmol/ml urine (n = 5) for strata of exposure to PAHs (no or low, mid, and high) based on job category; the corresponding values in smokers were 0.55 (n = 20), 0.94 (n = 12), and 4.91 pmol/ml (n = 12), respectively. Multiple linear regression showed significant differences between subjects in different PAH exposure with increased concentrations of 1-OHPG in urine. Amounts of foods containing PAHs ingested by this group of workers were relatively low and did not contribute significantly to urinary 1-OHPG concentrations. CONCLUSIONS: These results indicate that 1-OHPG is a common urinary metabolite in people with recent occupational exposure to PAHs and is associated with both job category and estimated stratum of PAH exposure.
Adult↗
Catatonia as an unusual presentation of posttraumatic stress disorder.
A patient with posttraumatic stress disorder (PTSD) had several episodes of catatonia in the past 44 years. These episodes were characterized by a sudden onset of intense excitement, mild pyrexia, often moderate elevation of serum creatinine phosphokinase and the development of a full catatonic state. We could not relate the symptomatology exhibited to any one of the accepted etiologies of catatonia. We assume, following careful evaluation of the clinical picture, and thorough biochemical and imaging work-up, that in this case the catatonic states represented an overwhelming psychic response to associated traumatic recollections, bringing to extreme the avoidance, numbness and motor responses usually encountered in PTSD.
Aged↗
Comparison of M and T type antigen testing to field inversion gel electrophoresis in the differentiation of strains of group A streptococcus.
Recent clusters of patients with acute rheumatic fever and invasive group A Streptococcus (GAS) have stimulated renewed interest in the epidemiology of streptococcal infections. We compared conventional serotyping for M and T antigens and serum opacity factor with field inversion gel electrophoresis (FIGE) for distinguishing among GAS. Fifteen pairs of throat isolates obtained from children positive for GAS before and after therapy were evaluated by conventional serotyping and by FIGE after SmaI digestion. Ten of the 15 pairs were identical by serotyping. FIGE correctly identified the 10 concordant and 5 discordant pairs. Individual clones were identified within each M type tested, including analysis performed on additional isolates of M1 and M3 obtained from the Centers for Disease Control and Prevention. This preliminary experience suggests that FIGE can successfully determine whether serial isolates from a given patient represent persistence of one strain or acquisition of a new strain of GAS and that this method might provide an alternative typing system for GAS.
Antigens, Bacterial↗
Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children--implications for vaccine strategies.
Streptococcus pneumoniae is a leading cause of fatal bacterial pneumonia in young children. Pneumococcal polysaccharide vaccines have not been promoted for use in young children because many constituent serotypes are not immunogenic in children < 2 years old. Conjugating pneumococcal polysaccharide epitopes to a protein carrier would likely increase vaccine immunogenicity in children. We reviewed published and unpublished pneumococcal serotype and serogroup data from 16 countries on 6 continents to determine geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates among children and to estimate coverage of proposed and potential pneumococcal conjugate vaccine formulas. The most common pneumococcal serotypes or groups from developed countries were, in descending order, 14, 6, 19, 18, 9, 23, 7, 4, 1 and 15. In developing countries the order was 6, 14, 8, 5, 1, 19, 9, 23, 18, 15 and 7. Development of customized heptavalent vaccine formulas, one for use in all developed countries and one for use in all developing countries, would not provide substantially better coverage against invasive pneumococcal disease than two currently proposed heptavalent formulas. An optimal nanovalent vaccine for global use would include serotypes 1, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Geographic and temporal variation in pneumococcal serotypes demonstrates the need for a species-wide pneumococcal vaccine.
Age Distribution↗
Induction of the differentiated phenotype in human colon cancer cell is associated with the attenuation of subcellular tyrosine phosphorylation.
In the present study we have determined membrane, cytosolic, and cytoskeleton-associated tyrosine protein kinase (TPK) activity in human colon cancer cell lines exposed to (i) the differentiation-promoting agents sodium butyrate and 8-chloro-cyclic-adenosine 3',5'-monophosphate (8-Cl-cAMP), (ii) tyrphostins, specific TPK inhibitors, or (iii) differentiation-inducing culture manipulations. Treatment of human colon cancer cell lines, LS 174T, COLO 205, and SW620, with sodium butyrate and 8-Cl-cAMP or tyrphostins AG-30 and AG-34, significantly attenuated TPK activity concomitantly with an increase in the activity of alkaline phosphatase, an enzymatic marker of intestinal cell differentiation. The differentiated phenotype induced in Caco-2 and HT-29 colon cancer cells by culture manipulation was associated with a significant decrease in cytoskeleton-associated TPK activity and marked activity of alkaline phosphatase (AP). Electron microscopy and freeze-fracturing analysis of HT-29 cells showed that the gradual transition from the undifferentiated to the differentiated phenotype resulted in the acquisition of a distinct polarized morphology. Immunocytochemical phosphotyrosine analysis of cultured SW620 cells showed positive staining mostly localized in zones of focal contacts. A marked reduction in phosphotyrosine staining with notable changes in cell morphology was observed in SW620 cells exposed to tyrphostins. Cumulatively, the present results indicate that the induction of the differentiated phenotype in colon cancer cells is associated with a marked decrease in TPK activity and tyrosine phosphorylation.
8-Bromo Cyclic Adenosine Monophosphate↗
Expression of a functional human type I interferon receptor in hamster cells: application of functional yeast artificial chromosome (YAC) screening.
The previously cloned human interferon alpha/beta (Hu-IFN-alpha/beta; Type I interferon) receptor cDNA appears to be only one component of a receptor complex since expression of the cDNA in mouse cells confers sensitivity only to Hu-IFN-alpha B2, but a monoclonal antibody against this cloned receptor subunit inhibits biological activities of Hu-IFN-alpha A, Hu-IFN-alpha B2, Hu-IFN-omega, and Hu-IFN-beta. Here we report that a yeast artificial chromosome (YAC) containing a segment of human chromosome 21 introduced into Chinese hamster ovary (CHO) cells confers upon these cells a greatly enhanced response to Hu-IFN-alpha A and Hu-IFN-alpha B2 as well as an increased response to Hu-IFN-omega, Hu-IFN-alpha A/D(Bgl), andd Hu-IFN-beta. These responses were measured by induction of class I MHC antigens and by protection against encephalomyocarditis virus and vesicular stomatitis virus. Furthermore, these cells exhibit specific high affinity binding of Hu-IFN-alpha A and Hu-IFN-alpha B2, Hu-IFN-beta, and Hu-IFN-omega. The results indicate that all the genes necessary to reconstitute a biologically active Type I human IFN receptor complex are located within the human DNA insert of this YAC clone.
Animals↗
Sensory maps in the human brain.
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Adaptation, Physiological↗
Identification and sequence of an accessory factor required for activation of the human interferon gamma receptor.
Human chromosomes 6 and 21 are both necessary to confer sensitivity to human interferon gamma (Hu-IFN-gamma), as measured by induction of class I human leukocyte antigen (HLA) and protection against encephalomyocarditis virus (EMCV) infection. Whereas human chromosome 6 encodes the Hu-IFN-gamma receptor, human chromosome 21 encodes accessory factors for generating biological activity through the Hu-IFN-gamma receptor. Probes from a genomic clone were used to identity cDNA clones expressing a species-specific accessory factor. These cDNA clones are able to substitute for human chromosome 21 to reconstitute the Hu-IFN-gamma receptor-mediated induction of class I HLA antigens. However, the factor encoded by the cDNA does not confer full antiviral protection against EMCV, confirming that an additional factor encoded on human chromosome 21 is required for reconstitution of antiviral activity against EMCV. We conclude that this accessory factor belongs to a family of such accessory factors responsible for different actions of IFN-gamma.
Amino Acid Sequence↗
Sublocalization of the human interferon-gamma receptor accessory factor gene and characterization of accessory factor activity by yeast artificial chromosomal fragmentation.
A chromosomal fragmentation procedure was employed to produce a deletion set of yeast artificial chromosomes (YACs) from a parental YAC, GART D142H8, known to map to human chromosome 21q and to encode the human interferon-gamma receptor (Hu-IFN-gamma R) accessory factor gene as well as the phosphoribosylglycinamide formyltransferase (GART) gene. When expressed in Chinese hamster ovary cells, these deleted YACs retain accessory factor activity, as judged by major histocompatibility complex class I antigen inducibility, until the deletions from the acentric end exceed 390 kilobases (kb). Therefore, the accessory factor (AF-1) gene can be localized to a 150-kb region at the left (centric) end of the parental 540-kb GART YAC. Cells containing functional YACs are also able to induce the ISGF3 gamma and gamma-activated factor (GAF) transcription factors, but were not protected against encephalomyocarditis virus (EMCV) upon treatment with Hu-IFN-gamma. Therefore, the Hu-IFN-gamma R and the AF-1 are sufficient for some, but not all, of the actions of Hu-IFN-gamma. We postulate that an additional accessory factor (AF-2) required for antiviral activity against EMCV is encoded on chromosome 21q.
Acyltransferases↗
Endothelial cells are activated by cytokine treatment to kill an intravascular parasite, Schistosoma mansoni, through the production of nitric oxide.
Like many pathogens that undergo an intravascular stage of development, larvae of the helminth parasite Schistosoma mansoni migrate through the blood vessels, where they are in close contact with endothelial cells. In vitro exposure of murine endothelial cells to various cytokines (interferon gamma, tumor necrosis factor alpha, and interleukin 1 alpha or 1 beta) resulted in their activation to kill schistosomula through an arginine-dependent mechanism involving production of nitric oxide (NO). Cytokine-treated endothelial cells showed increased expression of mRNA for the inducible form of the NO synthase, and both NO production and larval killing were suppressed by treatment with competitive inhibitors. The effector function of cytokine-treated endothelial cells was similar to that of activated inflammatory tissue macrophages, although activation appeared to be differentially regulated in these two cell types. Activated endothelial cells killed older (18-day) forms of the parasite, such as those currently thought to be a primary target of immune elimination in the lungs of mice previously vaccinated with radiation-attenuated cercariae, as well as newly transformed larvae. In C57BL/6 mice, which become resistant to S. mansoni infection as a result of vaccination with irradiated cercariae, endothelial cell morphology characteristic of activation was observed in the lung by 1-2 weeks after challenge infection. Similar endothelial cell changes were absent in P-strain mice, which do not become resistant as a result of vaccination. Together, these observations indicate that endothelial cells, not traditionally considered to be part of the immune system, may play an important role in immunity to S. mansoni and, by means of NO-dependent killing, could serve as effectors of resistance to other intravascular pathogens.
Amino Acid Oxidoreductases↗
Pediatricians' diagnostic approach to pharyngitis and impact of CLIA 1988 on office diagnostic tests.
OBJECTIVE: To determine the factors associated with an optimal diagnostic approach to a child with pharyngitis, characterize office laboratory methods for throat swab culture and group A streptococcal rapid antigen testing, and assess the potential impact of the Clinical Laboratory Improvement Amendments (CLIA) of 1988 on the performance of these tests. DESIGN AND SETTING: Mailed survey to all board-certified primary care pediatricians from seven western states with telephone follow-up for nonrespondents. OUTCOME MEASURES: Differences in practice characteristics and use of office laboratory tests for physicians who usually (> 80%) diagnose pharyngitis using a recommended approach vs those who follow this approach less often (< 50%); characteristics of physicians who indicate that they intend to discontinue office throat culture because of CLIA and those who will continue to perform this test also are compared. RESULTS: Responses from 531 pediatricians were analyzed. Forty-four percent diagnosed pharyngitis appropriately for more than 80% of patients, and 17% did so for fewer than 50%. Optimal diagnosis was significantly more common among physicians who cultured throat swabs in their office (relative risk, 1.40; 95% confidence interval, 1.19 to 1.66) and less common among solo practitioners (relative risk, 0.71; 95% confidence interval, 0.56 to 0.88). Factors that may decrease the sensitivity of office throat culture include short duration of incubation (59%), lack of quality control (51%), and limited education of the persons reading results (6%). With implementation of CLIA, 24% of pediatricians reported that they already have discontinued or will discontinue office throat culture, and 23% have discontinued or will discontinue antigen detection testing for group A streptococci. Those most likely to stop office culture include solo practitioners and practitioners who do not currently perform quality control of culture methods. CONCLUSIONS: Office culture for group A streptococci is strongly associated with an optimal diagnostic approach. Implementation of CLIA regulations may substantially decrease the number of physicians who perform this test. The balance between potential improvements in the quality of office culture with CLIA implementation and the decreased availability of this test needs to be assessed.
Antigens, Bacterial↗