TAG (total commitment, access, growth), you're it!
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Efficiency, Organizational↗
Biomedical subjects
C Johnson
Publications and source records attributed to C Johnson.
Frequency doubling perimetry and the detection of eye disease in the community.
PURPOSE: Frequency Doubling Technology (FDT) perimetry is a novel perimetric test that provides rapid screening (45 to 60 seconds) and full-threshold (4 to 5 minutes) testing for detection of vision loss. The purpose of this study was to determine the specificity and sensitivity of FDT perimetry for the detection of ocular disease. METHODS: A total of 130 participants (257 eyes of 42 men and 88 women) recruited from the community completed FDT perimetry, standard achromatic automated perimetry (SAP), anterior segment biomicroscopy, tonometry, and dilated ophthalmoscopy. FDT results were considered abnormal if 1 point was abnormal (depressed below the 5% level on the screening protocol C-20-5). SAP was considered abnormal if the glaucoma hemifield test or pattern standard deviation was outside normal limits (P < .05) or a hemifield cluster of 3 depressed points on the pattern deviation probability plot (P < .05) was present. An abnormal eye examination was defined as the presence of an abnormality in the anterior segment, lens, or posterior segment that was likely to cause a visual field defect or the presence of glaucomatous or other optic neuropathy. RESULTS: The mean age (+/- SD) of participants was 55.5 years (+/- 10.3). Ethnic groups, as reported by participants, included 77 (59%) African Americans, 40 (31%) Caucasians, and 13 (10%) in other groups. On clinical examination, 116 eyes (45%) were normal, 9 eyes (3.5%) had a cataract with best corrected visual acuity worse than 20/30, 16 eyes (6%) had open-angle glaucoma, and 17 eyes (7%) had retinal findings or lesions that were likely to cause a visual field defect. For FDT perimetry, 22 (8.6%) of 257 tests were unreliable, and for SAP, 65 (25.3%) of 257 tests were unreliable. The sensitivity and specificity of FDT perimetry for detecting an abnormal clinical examination were 55% and 90% and for detecting an abnormal examination that included an abnormal SAP, 64% and 86%. CONCLUSIONS: FDP demonstrated reasonable discriminatory power for detecting eye disease.
Adult↗
We made a mistake.
When Annals of Internal Medicine published a paper about the risk-management program at Veterans Affairs Medical Center, Lexington, Ky., readers were surprised at the facility's open policy regarding medication errors. Here's how health care leaders there put their liability on the line for better patient care.
Attitude of Health Personnel↗
An N-terminal nuclear export signal is required for the nucleocytoplasmic shuttling of IkappaBalpha.
The potent transcriptional activities of Rel/NF-kappaB proteins are regulated in the cytoplasm and nucleus by the inhibitor, IkappaBalpha. The mechanism, by which IkappaBalpha can either sequester NF-kappaB in the cytoplasm or act as a nuclear post-induction repressor of NF-kappaB, is uncertain. We find that IkappaBalpha shuttles continuously between the nucleus and cytoplasm. This shuttling requires a previously unidentified CRM1-dependent nuclear export signal (NES) located within the N-terminal domain of IkappaBalpha at amino acids 45-55. Deletion or mutation of the N-terminal NES results in nuclear localization of IkappaBalpha. NF-kappaB (p65) association with IkappaBalpha affects steady-state localization but does not inhibit its shuttling. Endogenous complexes of IkappaBalpha-NF-kappaB shuttle and will accumulate in the nucleus when CRM1 export is blocked. We find TNFalpha can activate the nuclear IkappaBalpha-NF-kappaB complexes by the classical mechanism of proteasome-mediated degradation of IkappaBalpha. These studies reveal a more dynamic nucleocytoplasmic distribution for IkappaBalpha and NF-kappaB suggesting previously unknown strategies for regulating this ubiquitous family of transcription activators.
3T3 Cells↗
Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza.
BACKGROUND: Safe and effective antiviral agents are needed to prevent infection with influenza A and B virus. Oseltamivir (GS4104), which can be administered orally, is the prodrug of GS4071, a potent and selective inhibitor of influenzavirus neuraminidases. We studied the use of oseltamivir for long-term prophylaxis against influenza in two placebo-controlled, double-blind trials at different U.S. sites during the winter of 1997-1998. METHODS: We randomly assigned 1559 healthy, nonimmunized adults 18 to 65 years old to receive either oral oseltamivir (75 mg given once or twice daily, for a total daily dose of 75 or 150 mg) or placebo for six weeks during a peak period of local influenzavirus activity. The primary end point with respect to efficacy was laboratory-confirmed influenza-like illness (defined as a temperature of at least 37.2 degrees C accompanied by at least one respiratory and at least one systemic symptom). RESULTS: In the two studies combined, the risk of influenza among subjects assigned to either once-daily or twice-daily oseltamivir (1.2 percent and 1.3 percent, respectively) was lower than that among subjects assigned to placebo (4.8 percent; P<0.001 and P=0.001 for the comparison with once-daily and twice-daily oseltamivir, respectively). The protective efficacy of oseltamivir in the two active-treatment groups combined was 74 percent (95 percent confidence interval, 53 to 88 percent) at all the sites combined and 82 percent (95 percent confidence interval, 60 to 93 percent) at sites in Virginia, where the rate of influenza infection was higher than the overall rate. For culture-proved influenza, the rate of protective efficacy in the two oseltamivir groups combined was 87 percent (95 percent confidence interval, 65 to 96 percent). The rate of laboratory-confirmed influenza infection was lower with oseltamivir than with placebo (5.3 percent vs. 10.6 percent, P<0.001). Oseltamivir was well tolerated but was associated with a greater frequency of nausea (12.1 percent and 14.6 percent in the once-daily and twice-daily groups, respectively) and vomiting (2.5 percent and 2.7 percent, respectively) than was placebo (nausea, 7.1 percent; vomiting, 0.8 percent). However, the frequency of premature discontinuation of drug or placebo was similar among the three groups (3.1 to 4.0 percent). CONCLUSIONS: Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza.
Administration, Oral↗
Clinical and economic assessment of the omeprazole test in patients with symptoms suggestive of gastroesophageal reflux disease.
OBJECTIVE: To evaluate the diagnostic accuracy of a trial of a high-dose proton pump inhibitor (the omeprazole test) in detecting gastroesophageal reflux disease (GERD) in patients with heartburn symptoms. DESIGN: A randomized, double-blind, placebo-controlled, crossover trial. PATIENTS AND SETTING: Forty-three consecutive patients with symptoms suggestive of GERD were enrolled at a Veterans Affairs medical center. MAIN OUTCOME MEASURES: Symptom response to the omeprazole test vs placebo in GERD-positive and GERD-negative patients; sensitivity, specificity, and positive and negative predictive values of the omeprazole test; and cost per correct diagnosis achieved with the omeprazole test compared with traditional diagnostic strategies. RESULTS: Of 42 patients (98%) who completed the study, 35 (83%) were classified as GERD positive and 7 (17%) as GERD negative. Twenty-eight GERD-positive and 3 GERD-negative patients responded to the omeprazole test, providing a sensitivity of 80.0% (95% confidence interval, 66.7%-93.3%) and a specificity of 57.1% (95% confidence interval, 20.5%-93.8%). Economic analysis revealed that the omeprazole test saves $348 per average patient evaluated, and results in a 64% reduction in the number of upper endoscopies performed and a 53% reduction in the use of pH testing. CONCLUSIONS: The omeprazole test is sensitive and fairly specific for diagnosing GERD in patients with typical GERD symptoms. This strategy could result in significant cost savings and decreased use of invasive diagnostic tests.
Adult↗
A new class of selective and potent inhibitors of neuronal nitric oxide synthase.
The synthesis and SAR of a series of 6-(4-(substituted)phenyl)-2-aminopyridines as inhibitors of nitric oxide synthase are described. Compound 3a from this series shows potent and selective inhibition of the human nNOS isoform, with pharmacokinetics sufficient to provide in vivo inhibition of nNOS activity.
Aminopyridines↗
Extraction and high-performance liquid chromatographic separation of selected pyrene and benzo[a]pyrene sulfates and glucuronides: preliminary application to the analysis of smokers' urine.
In the study of the complex mixture of urinary metabolites derived from polycyclic aromatic hydrocarbon compounds, it is desirable to simplify the analysis through separation of classes of compounds. We have developed a liquid chromatography (LC) method for the separation of selected sulfate and glucuronide conjugate isomers derived from hydroxybenzo[a]pyrenes (OH-BaP) and hydroxypyrenes. This LC method was utilized in the preliminary analysis of the urine of smokers by combining it with an extraction technique employing tetra-n-butyl-ammonium ion as a coupling agent to generate a 1:1 complex, extractable in chloroform at low pH prior to LC analysis.
Benzo(a)pyrene↗
Trend spotting: fashions in medical education.
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Computer-Assisted Instruction↗
Three-year maintenance of improved diet and physical activity: the CATCH cohort. Child and Adolescent Trial for Cardiovascular Health.
OBJECTIVE: To assess differences through grade 8 in diet, physical activity, and related health indicators of students who participated in the Child and Adolescent Trial for Cardiovascular Health (CATCH) school and family intervention from grades 3 through 5. DESIGN: Follow-up of the 4-center, randomized, controlled field trial with 56 intervention and 40 control elementary schools. PARTICIPANTS: We studied 3714 (73%) of the initial CATCH cohort of 5106 students from ethnically diverse backgrounds in California, Louisiana, Minnesota, and Texas at grades 6, 7, and 8. RESULTS: Self-reported daily energy intake from fat at baseline was virtually identical in the control (32.7%) and intervention (32.6%) groups. At grade 5, the intake for controls remained at 32.2%, while the intake for the intervention group declined to 30.3% (P<.001). At grade 8, the between-group differential was maintained (31.6% vs 30.6%, P = .01). Intervention students maintained significantly higher self-reported daily vigorous activity than control students (P = .001), although the difference declined from 13.6 minutes in grade 5 to 11.2, 10.8, and 8.8 minutes in grades 6, 7, and 8, respectively. Significant differences in favor of the intervention students also persisted at grade 8 for dietary knowledge and dietary intentions, but not for social support for physical activity. No impact on smoking behavior or stages of contemplating smoking was detected at grade 8. No significant differences were noted among physiologic indicators of body mass index, blood pressure, or serum lipid and cholesterol levels. CONCLUSION: The original CATCH results demonstrated that school-level interventions could modify school lunch and school physical education programs as well as influence student behaviors. This 3-year follow-up without further intervention suggests that the behavioral changes initiated during the elementary school years persisted to early adolescence for self-reported dietary and physical activity behaviors.
Adolescent↗
Cobalt chloride-induced signaling in endothelium leading to the augmented adherence of sickle red blood cells and transendothelial migration of monocyte-like HL-60 cells is blocked by PAF-receptor antagonist.
In response to hypoxia, sickle red blood cells (SS RBC) and leukocytes exhibit increased adherence to the vascular endothelium, while diapedesis of leukocytes through the blood vessel increases. However, the cellular signaling pathway(s) caused by hypoxia is poorly understood. We utilized CoCl2 as a mimetic molecule for hypoxia to study cellular signaling pathways. We found that in human umbilical vein endothelial cells (HUVEC), CoCl2 at 2 mM concentration induced the surface expression of a subset of CAMs (VCAM-1) and activation of transcription factor NF-kappaB in the nuclear extracts of HUVEC. Furthermore, CoCl2 also caused time-dependent tyrosine phosphorylation of mitogen-activated protein (MAP) kinase isoform ERK2 without significantly affecting ERK1, indicating ERK2 is the preferred substrate for upstream kinase of the MAPK pathway. Inhibitors of MAP kinase (PD98059) or platelet-activating factor (PAF)- receptor antagonist (CV3988) inhibited the CoCl2-induced NF-kappaB activation and VCAM-1 expression. Augmented expression of VCAM-1 led to increased SS RBC adhesion, inhibitable by a VCAM-1 antibody. Additionally, CoCl2 caused a two- to threefold increase in the rate of transendothelial migration of monocyte-like HL-60 cells and a twentyfold increase in phosphorylation of platelet endothelial cell adhesion molecules (PECAM-1). The transendothelial migration of monocytes was inhibited by an antibody to PECAM-1. Both phosphorylation of PECAM-1 and transendothelial migration of monocytes in response to CoCl2 were inhibited by protein kinase inhibitor (GF109203X) and augmented by protein phosphatase inhibitor (Calyculin A). Our data suggests that CoCl2-induced cellular signals directing increased expression of VCAM-1 in HUVEC involve downstream activation of MAP kinase and NF-kappaB, while the phosphorylation of PECAM-1 occurs as a result of activation of PKC. We conclude that PAF-receptor antagonist inhibits the CoCl2- or hypoxia-induced increase in the adhesion of SS RBC, PECAM-1 phosphorylation, and the concomitant transendothelial migration of monocytes.
Adult↗
Athletes and eating disorders: the National Collegiate Athletic Association study.
OBJECTIVE: To present findings from a collaborative study with the National College Athletic Association regarding the prevalence of disordered eating among student athletes. METHOD: 1,445 student athletes from 11 Division 1 schools were surveyed using a 133-item questionnaire. RESULTS: Results indicated that 1.1% of the females met DSM-IV criteria for bulimia nervosa versus 0% for males. None of the student athletes met DSM-IV criteria for anorexia nervosa. 9.2% of the females were identified as having clinically significant problems with bulimia versus .01% of the males. 2.85% of the females were identified as having a clinically significant problem with anorexia nervosa versus 0% for males. 10.85% of the females reported binge eating on a weekly or greater basis versus 13.02% of the males 5.52% of the females reported purging behavior (vomiting, laxatives, diuretics) on a weekly or greater basis versus 2.04% for the males. DISCUSSION: Results from the current investigation are more conservative than previous studies of student athletes, but comparable to another large study of elite Norwegian athletes. Reasons for these differences are discussed. Clearly female athletes report more difficulty with disordered eating than male athletes. Some specific risk factors for female athletes are discussed.
Adipose Tissue↗
Effect of doses of glucagon used to treat food impaction on esophageal motor function of normal subjects.
We studied 10 normal subjects to determine the effect of doses of intravenous glucagon used to treat food impaction on esophageal motor function. With a multilumen assembly perfused by a low compliance pneumohydraulic infusion pump, esophageal manometry was performed during baseline and after randomized administration of 0. 25, 0.5, and 1 mg intravenous glucagon. Mean proximal and distal amplitudes of contraction, proximal and distal amplitude of contraction duration, lower esophageal sphincter (LES) resting pressure, percentage of LES relaxation, and glucagon-related side effects were evaluated. No effect on proximal amplitude of contraction and proximal or distal esophageal contraction duration was noted. Mean amplitude of contraction in the distal esophagus was further reduced with increased dosage of glucagon but did not achieve statistical significance. Mean LES resting pressure was significantly reduced after 0.25 mg (18.7 +/- 1.8 vs. 10.2 +/- 1.5 mmHg, p = 0.0001) and further reduced after 0.5 mg (5.9 +/- 1.2 mmHg, p = 0.0009). Mean LES relaxation was significantly reduced after 0. 25 mg (93.1 +/- 2.4% vs. 63.6 +/- 8.8%, p = 0.0031). The 1-mg dose versus the 0.5-mg did not provide further reduction in any LES function parameters. One subject experienced transient nausea after 0.5 mg, and 4 subjects experienced nausea after 1 mg glucagon. In conclusion, increased doses of glucagon further reduce mean distal esophageal amplitude of contraction. Although maximum reduction in mean LES resting pressure was achieved with 0.5 mg, it did not provide any potential therapeutic advantage over 0.25 mg glucagon. Nausea is a common, transient side effect predominantly affecting subjects treated with the 1-mg dose.
Adult↗
Knowledge, attitudes, and practices related to fruit and vegetable consumption of high school students.
PURPOSE: To assess the level of nutrition knowledge, attitudes and practices related to fruit and vegetable consumption of high school students attending participating parochial schools in the New Orleans area. METHODS: The baseline data reported in this study, "Gimme 5: A Fresh Nutrition Concept for Students," represents one of the nine National Cancer Institute-funded projects from the national "5-A-Day for Better Health Program" initiated in 1991. A survey containing 22 nutrition-related items about fruit and vegetables was used to assess knowledge in 2213 students. RESULTS: On average, adolescents reported 39% correct knowledge scores. A significant ethnic effect (p < .001) was noted, with White adolescents scoring higher than African American adolescents. Significant ethnic differences in the frequency of fruit and vegetable consumption were also observed, with African-American adolescents reporting a lower mean consumption (2.17 servings) than white adolescents (2.69 servings). Consumption by Hispanic youth (2.48 servings) was similar to those in the "other" ethnic category (2.55 servings). Girls reported being more confident in their ability to eat five servings of fruits and vegetables per day than did boys (p < .05). CONCLUSIONS: Although the knowledge and consumption levels of adolescents with regard to fruits and vegetables were low, their attitudes toward learning about healthier eating practices were favorable.
Adolescent↗
Coping responses and posttraumatic stress symptomatology in urban fire service personnel.
Emergency workers, including urban fire fighters and paramedics, must cope with a variety of duty-related stressors including traumatic incident exposures. Little is known about coping responses of emergency workers or whether their coping responses predict future mental health outcomes. The previously formulated Coping Responses of Rescue Workers Inventory (CRRWI) underwent a principal components analysis employing a sample (N = 220) of urban fire fighters and paramedics. Six empirically and theoretically distinct CRRWI components were identified which were relatively stable over a 6-month period. Scores on one of the CRRWI scales, but neither years of service nor their past half year's traumatic incident exposures, predicted future changes in self-reports of posttraumatic stress symptomatology.
Adaptation, Psychological↗
Effect of ambulatory 24-hour esophageal pH monitoring on reflux-provoking activities.
Ambulatory 24-hr esophageal pH monitoring is considered the gold standard for diagnosing gastroesophageal reflux disease (GERD). The current approach is to encourage patients to pursue their everyday activity in order to obtain near-physiological recordings. However, the effect of the test itself on reflux-provoking activities has never been evaluated. Thus, the aim of our study was to assess daily food consumption, habits, symptoms, sleep, and perceived experience of patients undergoing pH testing as compared to an off test (normal) day. Patients reported type and time spent in each activity pursued, food ingested and length of each meal, habits, frequency and severity of GERD and other related symptoms, sleep disturbances, side effects, and overall perceived experience during pH testing and four weeks later, during a normal day. Fifty-four patients enrolled. pH testing significantly reduced time spent being active, number of meals and cups of coffee consumed, and frequency of GERD symptoms. Almost half of the patients reported having dysphagia during the test. Most patients experienced side effects and stated that the test bothered them most of the time. In conclusion, pH testing has a significant effect on decreasing reflux-provoking activities-patients tend to assume a more sedentary lifestyle. This may influence the reliability of the test as a physiologic measure of acid reflux.
Activities of Daily Living↗
Exposure to traumatic incidents and prevalence of posttraumatic stress symptomatology in urban firefighters in two countries.
Urban firefighters are at risk for posttraumatic stress disorder (PTSD) due in part to their exposure to duty-related trauma. This study compared duty-related trauma exposures and the prevalences of posttraumatic stress in U.S. and Canadian firefighters. Both samples reported relatively numerous and frequent posttrauma symptoms, and the rates of self-reported PTSD prevalence did not differ significantly. However, analysis of departmental records for respondents' previous year on duty revealed significant differences in both frequencies and categories of traumatic incident exposures. Some of the vulnerability and moderating risk factors associated with PTSD caseness differed between the U.S. and Canadian samples. Potential explanations for the observed differences in risk factors for PTSD in these 2 firefighter samples are considered.
Adult↗
Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.
Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.
Amino Acid Sequence↗