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Biomedical subjects

C A Johnson

Publications and source records attributed to C A Johnson.

At least 73 records · Page 4Linked to original sources

Variability components of standard automated perimetry and frequency-doubling technology perimetry.

PURPOSE: To evaluate and compare intra- and intertest variability components for both standard automated perimetry (SAP) and frequency-doubling technology (FDT) perimetry in a small group of normal individuals and patients with glaucoma. METHODS: The method of constant stimuli (MOCS) was used to examine matched test locations with both SAP and FDT perimetry stimuli in a group of eight normal individuals and seven patients with glaucoma. Subjects were tested weekly at three predetermined visual field loci for 5 consecutive weeks. Frequency-of-seeing (FOS) curves were generated and used to quantify threshold sensitivity (50% seen on FOS, in decibels), intratest variability (FOS interquartile range, in decibels), and intertest variability (interquartile range of weekly repeated threshold determinations, in decibels). RESULTS: In patients with glaucoma, SAP intra- and intertest variabilities were found to increase with sensitivity reductions, as previously reported. FDT perimetry revealed that both intra- and intertest variability components did not appreciably change with reductions in sensitivity. With the measurement scales used in this investigation, both intra- and intertest variability components were significantly greater for SAP than for FDT perimetry (P < 0.001 and P = 0.003, respectively). Intratest variability exceeded intertest variability for both SAP (P = 0.001) and FDT perimetry (P < 0.001). CONCLUSIONS: For both SAP and FDT perimetry, variability occurring within a single test session contributed more to total variability than between-session variability. When the measurement scales available on commercial instrumentation were used, FDT perimetry exhibited significantly less variability than SAP, especially within regions of visual field sensitivity loss. FDT perimetry therefore shows promise as an effective test for detecting progressive glaucomatous visual field loss, although prospective longitudinal validation is still required to determine sensitivity to change.

Adult↗

Subcellular localization and PKC-dependent regulation of the human lysophospholipase A/acyl-protein thioesterase in WISH cells.

Lysophospholipases play essential roles in keeping their multi-functional substrates, the lysophospholipids, at safe levels. Recently, a 25 kDa human lysophospholipase A (hLysoPLA I) that is highly conserved among rat, mouse, human and rabbit has been cloned, expressed and characterized and appears to hydrolyze only lysophospholipids among the various lipid substrates. Interestingly, this enzyme also displays acyl-protein thioesterase activity towards a G protein alpha subunit. To target the subcellular location of this hLysoPLA I, we have carried out immunocytochemical studies and report here that hLysoPLA I appears to be associated with the endoplasmic reticulum (ER) and nuclear envelope in human amnionic WISH cells and not the plasma membrane. In addition, we found that the hLysoPLA I can be up-regulated by phorbol 12-myristate 13-acetate (PMA) stimulation, a process in which phospholipase A(2) is activated and lysophospholipids are generated in WISH cells. Furthermore, the PMA-induced hLysoPLA I expression can be blocked by the protein kinase C (PKC) inhibitor Gö6976. The regulated expression of the LysoPLA/acyl-protein thioesterase by PKC may have important implications for signal transduction processes.

Cell Line↗

Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study. Ocular Hypertension Treatment Study Group.

OBJECTIVE: To determine the frequency with which visual field abnormalities observed on follow-up visual fields for patients in the Ocular Hypertension Treatment Study were confirmed on retest. METHODS: Between April 1, 1994, and March 1, 1999, 21,603 visual fields were obtained from 1637 patients in the Ocular Hypertension Treatment Study. When follow-up visual fields are outside the normal limits on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation (P<.05), or both, subsequent follow-up visual fields are monitored to confirm the abnormality. Abnormalities are confirmed if they are again abnormal on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation, or both; if the defect is not artifactual; and if the same index and location are involved. Reliability criteria used by the study consisted of a limit of 33% for false positives, false negatives, and fixation losses. RESULTS: Of the 21,603 regular follow-up visual fields, 1006 were follow-up retests performed because of an abnormality (n = 748) or unreliability (n = 258). We found that 703 (94%) of the 748 visual fields were abnormal and reliable, and 45 (6%) were abnormal and unreliable. On retesting, abnormalities were not confirmed for 604 (85.9%) of the 703 originally abnormal and reliable visual fields. CONCLUSIONS: Most visual field abnormalities in patients in the Ocular Hypertension Treatment Study were not verified on retest. Confirmation of visual field abnormalities is essential for distinguishing reproducible visual field loss from long-term variability. Arch Ophthalmol. 2000;118:1187-1194

False Positive Reactions↗

Acute keratinocyte damage stimulates platelet-activating factor production.

Recent evidence suggests that the phosphocholine-derived lipid mediator platelet-activating factor (PAF) is involved in keratinocyte function and cutaneous inflammation. PAF is found in various inflammatory skin diseases, and intradermal injection of PAF directly results in cutaneous inflammation. Keratinocytes also synthesize PAF and related 1-acyl species in response to ionophores, cytokines and growth factors, and in response to activation of the epidermal PAF receptor. Since keratinocytes are routinely exposed to potential damage by thermal or oxidative stressors with resultant induction of cutaneous inflammation, the objective of these studies was to assess whether exogenous thermal or oxidative damage can induce the production of PAF and related 1-acyl species. Cells of the immortalized human keratinocyte cell line HaCaT were subjected to acute heat or cold, or treatment with the pro-oxidant lipid tertiary butyl hydroperoxide, and PAF and 1-palmitoyl-2-acetyl-GPC were measured by gas chromatography/mass spectrometry. We report that these diverse toxic stimuli resulted in the accumulation of these biologically active lipids. These studies suggest that the PAF system is involved in the inflammatory response seen following acute epidermal damage.

Cell Line↗

Frequency doubling technology perimetry for detection of glaucomatous visual field loss.

PURPOSE: To evaluate the ability of frequency doubling technology perimetry to detect early, moderate, and advanced glaucomatous visual field loss. METHODS: In a prospective study, frequency doubling technology perimetry (C-20 full threshold) was performed in the right eye of 254 normal control subjects and 230 patients with early (n = 85), moderate (n = 114), or advanced (n = 31) glaucomatous visual field loss. Previous Humphrey Field Analyzer test results were used to classify glaucomatous visual field loss as early (mean deviation no worse than -6 dB), moderate (mean deviation between -6 and -12 dB) or advanced (mean deviation between -12 and -22 dB). RESULTS: Receiver operating characteristic curves showed 100% sensitivity and specificity (area under the curve, 1.0) for detecting advanced glaucomatous visual field loss, approximately 96% sensitivity and 96% specificity (area under the curve, 0.9751) for detecting moderate glaucomatous visual field loss, and approximately 85% sensitivity and 90% specificity (area under the curve, 0.9261) for early glaucomatous visual field loss. CONCLUSIONS: Frequency doubling technology perimetry demonstrates high sensitivity and specificity for detection of early, moderate, and advanced glaucomatous visual field loss.

Adolescent↗

Parenteral iron use in the management of anemia in end-stage renal disease patients.

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Anemia, Iron-Deficiency↗

English language use as a risk factor for smoking initiation among Hispanic and Asian American adolescents: evidence for mediation by tobacco-related beliefs and social norms.

Acculturation increases the risk of smoking among Hispanic and Asian American adolescents, but the underlying mechanisms are not understood. This study examined associations between English language use and smoking among 4,167 Hispanic and 2,836 Asian American adolescents in California. Potential mediators were assessed, including access to cigarettes, perceived consequences, friends' smoking, cigarette offers, refusal self-efficacy, and prevalence estimates of peer smoking. English language use was associated with increased risk of lifetime smoking in both groups. This association became nonsignificant after access, perceived consequences, friends' smoking, and offers were controlled for. The acculturation process (as indicated by English language use) may be associated with smoking-related psychosocial variables, which may lead to an increased risk of experimentation with smoking.

Adolescent↗

Anemia management of adult hemodialysis patients in the US results: from the 1997 ESRD Core Indicators Project.

BACKGROUND: The Health Care Financing Administration's End-Stage Renal Disease (ESRD) Core Indicators Project collects clinical information on prevalent adult patients receiving in-center hemodialysis (HD) care in the United States to assess the quality of care delivered. Although hematocrit values, transferrin saturations, and iron prescription practices have improved over the last five years, we sought to determine whether continued opportunities for improvement of this domain of care exist. METHODS: A random sample of 7292 adult in-center HD patients was selected. Dialysis facility staff provided clinical information for the period of October through December 1996 for 6858 (94%) patients; complete laboratory information was available from 4991 (73%) returned forms. Hematocrit values, transferrin saturations, serum ferritin concentrations, epoetin alfa dosing, and iron prescriptions were abstracted from patient medical records to assess anemia management practices. RESULTS: The mean hematocrit for this cohort was 32.6 +/- 3.5%. Seventy-two percent of patients had hematocrit values> 30%. Forty-two percent had hematocrit values of 33 to 36%, and 10% were severely anemic (hematocrit <28%). Ninety-four percent of the patients received epoetin alfa intravenously (i.v.) and 6% subcutaneously. The mean weekly dose was 202.4 +/- 137.2 units/kg. The mean transferrin saturation was 27.4 +/- 12.6%; 73% of patients had a mean transferrin saturation > or = 20%. The mean serum ferritin concentration was 386 +/- 422 ng/mL; 79 and 12% of patients had a serum ferritin concentration of> 100 and> 800 ng/mL, respectively. Nine percent of the sample (N = 434) had a transferrin saturation <20% and serum ferritin concentration <100 ng/mL. Regardless of the patient's transferrin saturation, approximately three fourths of the patients received either oral or i.v. iron, and only approximately one half of the patients received i.v. iron. Of the subset of patients with transferrin saturation <20% and serum ferritin concentration <800 ng/mL, only 53% were prescribed intravenous iron. Multivariate linear regression analysis revealed that serum albumin, urea reduction ratio, age, and transferrin saturation were significantly positively associated with hematocrit. Epoetin alfa dose and serum ferritin concentration were significantly and negatively associated with the hematocrit (P < 0.001). CONCLUSION: Although substantial improvements have been made in anemia management for adult in-center HD patients over the past five years, significant opportunities persist to improve iron prescription practices.

Adult↗

Isolation of short-wavelength sensitive mechanisms in normal and glaucomatous visual field regions.

PURPOSE: To determine whether "isolation" of short wavelength sensitive mechanisms (i.e., exclusive detection of a threshold stimulus by a short wavelength sensitive mechanism) is maintained in areas of glaucomatous visual field damage as measured with short-wavelength automated perimetry (SWAP). METHODS: Data from conventional automated perimetry and SWAP were analyzed for both eyes of 60 normal control subjects, 38 patients with ocular hypertension, and 22 patients with early to moderate glaucomatous field damage (mean defect better than -12 dB). Comparisons of results of SWAP and conventional perimetry were performed by determining the deviation from the mean normal sensitivity for the two procedures. Locations with sensitivity <3 dB for either procedure were rejected, as 3 dB is near the maximum stimulus luminance and may have introduced a bias by underestimating defects. The interval between deviation from normal (the isolation interval) on conventional perimetry and SWAP was examined to determine the likelihood of short wavelength mechanism isolation loss for different levels of glaucomatous visual field damage. RESULTS: Using normal isolation estimates of 13 dB and 10 dB as bases for determining the likelihood that isolation of short wavelength sensitive mechanisms may have been lost, it was found that this was an infrequent possibility, as low as 0.39 to 1.63% for normal control subjects and 2.53 to 10.44% for patients with glaucoma. CONCLUSION: Analyses indicate that isolation of short wavelength sensitive mechanisms is mostly maintained for SWAP, even in areas of moderate glaucomatous field damage. One limitation of SWAP for evaluating extensive glaucomatous damage is its dynamic range. This could be overcome by using a more intense stimulus light source.

Adult↗

Interior-point methodology for 3-D PET reconstruction.

Interior-point methods have been successfully applied to a wide variety of linear and nonlinear programming applications. This paper presents a class of algorithms, based on path-following interior-point methodology, for performing regularized maximum-likelihood (ML) reconstructions on three-dimensional (3-D) emission tomography data. The algorithms solve a sequence of subproblems that converge to the regularized maximum likelihood solution from the interior of the feasible region (the nonnegative orthant). We propose two methods, a primal method which updates only the primal image variables and a primal-dual method which simultaneously updates the primal variables and the Lagrange multipliers. A parallel implementation permits the interior-point methods to scale to very large reconstruction problems. Termination is based on well-defined convergence measures, namely, the Karush-Kuhn-Tucker first-order necessary conditions for optimality. We demonstrate the rapid convergence of the path-following interior-point methods using both data from a small animal scanner and Monte Carlo simulated data. The proposed methods can readily be applied to solve the regularized, weighted least squares reconstruction problem.

Algorithms↗

Performance characteristics of the 3-D OSEM algorithm in the reconstruction of small animal PET images. Ordered-subsets expectation-maximixation.

Rat brain images acquired with a small animal positron emission tomography (PET) camera and reconstructed with the three-dimensional (3-D) ordered-subsets expectation-maximization (OSEM) algorithm with resolution recovery have better quality when the brain is imaged by itself than when inside the head with surrounding background activity. The purpose of this study was to characterize the dependence of this effect on the level of background activity, attenuation, and scatter. Monte Carlo simulations of the imaging system were performed. The coefficient of variation from replicate images, full-width at half-maximum (FWHM) from point sources and image profile fitting, and image contrast and uniformity were used to evaluate algorithm performance. A rat head with the typical levels of five and ten times the brain activity in the surrounding background requires additional iterations to achieve the same resolution as the brain-only case at a cost of 24% and 64% additional noise, respectively. For the same phantoms, object scatter reduced contrast by 3%-5%. However, attenuation degraded resolution by 0.2 mm and was responsible for up to 12% nonuniformity in the brain images suggesting that attenuation correction is useful. Given the effects of emission and attenuation distribution on both resolution and noise, simulations or phantom studies should be used for each imaging situation to select the appropriate number of OSEM iterations to achieve the desired resolution-noise levels.

Algorithms↗

Ethnic differences in adolescent smoking prevalence in California: are multi-ethnic youth at higher risk?

OBJECTIVE: Although ethnic differences in adolescent smoking have been well documented, smoking among multi-ethnic adolescents has received little research attention. This study examined smoking prevalence and tobacco related psychosocial risk factors among multi-ethnic adolescents in California, as compared with white, African American, Asian American, and Hispanic adolescents. DESIGN: This study used a cross sectional design. Data were obtained from the independent evaluation of the California Tobacco Control, Prevention, and Education Program. SETTING: Students completed a paper-and-pencil survey in their classrooms. SUBJECTS: Data were collected from a stratified random sample of 5072 eighth grade students (age 13-14 years) in California during the 1996-97 school year. The data were weighted by school enrollment in analyses to make the estimates representative of the population of California students attending public schools. MAIN OUTCOME MEASURES: Outcome variables included self reported smoking prevalence, susceptibility to smoking, access to tobacco, and related attitudes, beliefs, and behaviours. Ethnicity was assessed with a self reported, "check all that apply" question. RESULTS: Results indicated that multi-ethnic adolescents were at higher risk than single-ethnic adolescents on several variables, including 30 day cigarette smoking prevalence, lifetime smokeless tobacco use, buying cigarettes, receiving cigarette offers, and expected friends' reaction if the respondent smoked. For several other variables (lifetime cigarette smoking prevalence, susceptibility to smoking, and number of friends who smoked), Hispanic adolescents were at higher risk than all other ethnic groups including multi-ethnic adolescents. Although susceptibility to smoking was highest among Hispanics, multi-ethnic adolescents scored significantly higher on susceptibility than the three other single-ethnic groups. CONCLUSIONS: Multi-ethnic adolescents may be at increased risk for smoking and may have easier access to cigarettes. Culturally targeted smoking prevention interventions for adolescents should address the unique social challenges faced by multi-ethnic adolescents that may increase their risk for smoking.

Adolescent↗

Blood pressure, LDL cholesterol, and intima-media thickness: a test of the "response to injury" hypothesis of atherosclerosis.

The "response to injury" hypothesis is a plausible model of the development of atherosclerosis supported by observations from animal models. The present study uses epidemiological data to investigate the hypothesis that wall damage due to hypertension is a precursor of low density lipoprotein cholesterol (LDL-C)-mediated atherosclerosis. The Los Angeles Atherosclerosis Study is following a cohort of 576 participants who were aged 40 to 60 years and were free of symptomatic cardiovascular disease at recruitment. Common carotid artery intima-media thickness (IMT) was assessed by B-mode ultrasonography. After exclusion for nonfasting blood draw and other missing data, 511 subjects were available for analysis. IMT was regressed on LDL-C within tertiles of systolic blood pressure (SBP): low (93 to 122 mm Hg), middle (123 to 132 mm Hg), and high (133 to 175 mm Hg). Covariates were age, sex, body height, body mass index, ethnicity, smoking status, diabetes, and pharmacological treatment for hypertension or hypercholesterolemia. IMT was significantly related to LDL-C in the high SBP group (beta=0.025+/-0.008, where beta values are IMT [mm]/LDL-C [mmol/L]; P=0.002) but not in the middle (beta=-0.006+/-0.008, P=0.39) or low (beta=-0.004+/-0.009, P=0.64) SBP group. The slope in the high SBP group was significantly greater than in the middle (P=0.004) or low (P=0.014) SBP group. Results were similar for women and men, and after the exclusion of diabetics and persons using antihypertensive or lipid-lowering medications. Elevated LDL-C was associated with increased IMT in the upper tertile of SBP but not in the lower tertiles. These findings are consistent with the hypothesis that wall injury due to elevated SBP increases the susceptibility of the artery wall to LDL-C-mediated atherogenesis.

Adult↗

Aliasing for rapidly counterphasing stimuli: a failure to demonstrate an M-cell sampling limit to resolution.

We investigated whether resolution is sampling limited for stimuli optimized for detection by magnocellular mechanisms. We measured peripheral (15 degrees and 30 degrees) spatial detection and resolution thresholds using 50% and 90% contrast flicker-defined gratings (25 Hz) and 90% contrast counterphasing sinusoidal gratings (25 Hz). Direction-discrimination performance for 90% contrast counterphasing sinusoidal gratings (25 Hz) was measured foveally. Our results indicate that resolution of rapidly counterphasing stimuli is sampling limited in peripheral vision but is consistent with limiting of performance by parvocellular mechanisms. Also, undersampling may not be necessary to account for motion reversals observed with gratings that both drift and flicker.

Adult↗