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Biomedical subjects

A J Adams

Publications and source records attributed to A J Adams.

At least 19 recordsLinked to original sources

Towards optimal filtering of "standard" multifocal electroretinogram (mfERG) recordings: findings in normal and diabetic subjects.

AIMS: To study the effects of two commonly used pre-amplifier filtering bandwidths on normal multifocal electroretinogram (mfERG) responses and their comparative abilities to detect retinal disease. METHODS: 103 standard mfERGs were recorded simultaneously in two channels with different pre-amplifier settings (10-100 Hz and 10-300 Hz) from one eye of each of 20 normal subjects, 17 diabetics with non-proliferative diabetic retinopathy (NPDR), and 12 diabetics without retinopathy. Signal to noise ratios (SNR) of the normal subjects' first order mfERGs were compared between channels. All subjects' amplitudes and implicit times were derived using a "template stretching" method. For comparison, implicit time was also measured using a "template sliding" method. mfERG amplitudes and implicit times were compared between the channels and among subject groups. RESULTS: Normal mean amplitudes and implicit times were similar for the two channels. However, normal 10-100 Hz recordings had significantly higher SNR and lower intersubject variability than 10-300 Hz recordings. In NPDR, the 10-100 Hz channel identified significantly more implicit time and amplitude abnormalities. In the diabetics without retinopathy, 10-100 Hz filtering identified significantly more implicit time abnormalities than 10-300 Hz filtering. For both filter settings, diabetic implicit times were more often abnormal than amplitudes. The 10-100 Hz channel was superior for both implicit time measurements. CONCLUSION: Standard mfERGs recorded from normal eyes and filtered 10-100 Hz contain less noise, higher SNR, and less intersubject variability than those filtered at 10-300 Hz. This underlies the finding that the 10-100 Hz filter setting identifies more retinal dysfunction than the 10-300 Hz setting.

Adult↗

The fast oscillation of the electrooculogram reveals sensitivity of the human outer retina/retinal pigment epithelium to glucose level.

The effect of acute blood glucose elevations on human outer retinal function was examined. Electrooculograms were recorded as the background light cycled on/off with a 2-min period, eliciting rapid changes in the corneo-retinal standing potential known as the fast-oscillation of the electrooculogram. Recordings were made while subjects fasted and after they consumed 100 g of D-glucose. In all subjects, blood glucose levels strongly affected fast oscillation amplitude, which reflects photoreceptor-driven changes in RPE cell chloride concentration. The sensitivity of RPE metabolism to glucose fluctuations may relate to changes in the blood-retinal barrier that are known to occur in diabetes (e.g. macular edema).

Adult↗

President's report.

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Academies and Institutes↗

Positive selection as a developmental progression initiated by alpha beta TCR signals that fix TCR specificity prior to lineage commitment.

During positive selection, immature thymocytes commit to either the CD4+ or CD8+ T cell lineage ("commitment") and convert from short-lived thymocytes into long-lived T cells ("rescue"). By formal precursor-progeny analysis, we now identify what is likely to be the initial positive selection step signaled by alpha beta TCR, which we have termed "induction". During induction, RAG mRNA expression is downregulated, but lineage commitment does not occur. Rather, lineage commitment (which depends upon the MHC class specificity of the alpha beta TCR) only occurs after downregulation of RAG expression and the consequent fixation of alpha beta TCR specificity. We propose that positive selection can be viewed as a sequence of increasingly selective developmental steps (induction-->commitment-->rescue) that are signaled by alpha beta TCR engagements of intrathymic ligands.

Animals↗

Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy.

PURPOSE: To identify local retinal abnormalities in diabetic patients with and without retinopathy, by using the multifocal electroretinogram (M-ERG). METHODS: Electroretinograms were recorded at 103 discrete retinal locations in each eye of eight persons with nonproliferative diabetic retinopathy (NPDR) and eight diabetic persons without retinopathy, using VERIS (EDI, San Mateo, CA). The amplitude and implicit time of each local (first-order) retinal response were derived and compared with normal values obtained from 16 age-matched, nondiabetic subjects. Maps of local response amplitude and implicit time were compared with fundus photographs taken at the time of testing. RESULTS: In eyes with NPDR, the implicit times of responses from retinal sites manifesting clinical pathologic fundus lesions (e.g., microaneurysms and focal edema), were markedly delayed (e.g., up to 7 msec from normal). Responses from adjacent retinal sites that were more normal in clinical appearance were also delayed, but to a lesser extent (e.g., 2-5 msec). Smaller, yet significant local response delays were also found in eyes without retinopathy. By contrast, local response amplitudes bore no consistent relationship to fundus abnormalities in eyes with retinopathy, and amplitudes were typically normal in eyes without retinopathy. CONCLUSIONS: The M-ERG reveals local retinal dysfunction in diabetic eyes even before retinopathy. The magnitude of delay of local ERG implicit time reflects the degree of local clinical abnormality in eyes with retinopathy. Local response delays found in some eyes without retinopathy suggest that the M-ERG detects subclinical local retinal dysfunction in diabetes. Analysis of M-ERG implicit time, independent of amplitude, improves the sensitivity of detection of local retinal dysfunction in diabetes.

Adult↗

Flow cytometric analysis of lymphocyte subsets in migraine patients during and outside of an acute headache attack.

We have conducted flow cytometric studies of two subsets of lymphocyte markers in groups of migraineurs during (n = 12; group B) and outside (n = 10; group C) of a migraine without aura attack (total n = 22; group A), including a group of patients tested in both of these phases (n = 5; group D), and compared these results with those obtained from a population of age-comparable, sex- and race-matched healthy volunteers (n = 12; group E). Comparison of the first set of lymphocytes (CD3+CD16 + 56+, CD3-CD16 + 56+, CD3-CD19+, CD3+CD19+, and CD3+HLA - DR+) between the patients in group A and the controls (group E) showed differences, reflecting greater group A percentages of CD3+CD16 + CD56+ and CD3-CD19+ lymphocytes. Furthermore, these differences reached statistical significance only for the CD3+CD16 + CD56+ lymphocytes, and then solely for the patients in group C (Scheffe's test, p < 0.05). Paired analysis of the above lymphocyte markers for subjects in group D failed to show significant differences between patients when they were having and not having a migraine attack, raising the possibility that results from a larger study could show meaningful increases in percentages of CD3+CD16 + CD56+ lymphocytes as one of the immune parameters useful for differentiating migraineurs from controls. Comparison of a second set of lymphocyte markers (CD19+CD5+, CD20+CD72-, CD20-CD72+, CD20+CD72+) among either the different groups of patients or between the patients and controls failed, however, to show statistically significant differences, emphasizing the apparent specificity of the findings described above for CD3+CD16 + CD56+ lymphocytes. Our results, albeit of a preliminary nature, suggest the occurrence of significant, differential changes in lymphocyte subset immunophenotyping between groups of pain-free migraineurs and patients during an acute migraine episode or controls. Corroboration of these findings may prove useful in clinical laboratory practice to identify changes in immunological parameters specifically associated with migraineurs, and help towards a better understanding of the etiology and pathophysiology of this condition.

Acute Disease↗

Optical and structural development of the crystalline lens in childhood.

PURPOSE: To document the development of key optical and structural parameters of the crystalline lens throughout childhood and examine possible mechanisms by which lens power remains coordinated with the growth of the eye to maintain emmetropia. METHODS: Using cycloplegic autorefraction, video-based phakometry, and ultrasonography, the authors measured refractive error and crystalline lens parameters in 994 children in the first through eighth grades, who participated in the Orinda Longitudinal Study of Myopia, between one and five times from 1989 through 1993. Polynomial growth curves were fit to the data by maximum likelihood estimation. The average annual rates of change in each parameter from each subject's longitudinal data were also estimated. RESULTS: The lens radii of curvature flattened throughout childhood, yet decreases in lens equivalent power stopped after 10 years of age. This indicates that the refractive index of the lens increased during later childhood. Lens thinning in early childhood also ceased after 10 years of age. The spherical volume of the lens showed no appreciable net increase, but the axial length of the eye continued to grow throughout childhood. The prevalence of myopia in our data increased sharply at age 10 years, reaching 21.3% by the age of 14 years. CONCLUSIONS: Concurrent thinning and flattening of the crystalline lens imply that the lens is mechanically stretched by the equatorial growth of the eye during childhood. Changes in the patterns of lens development near the age of 10 years, concurrent with the onset of myopia, suggest that forces arise which interfere with equatorial growth. Such forces might diminish the decreases in lens power and amplify axial elongation to promote myopia.

Adolescent↗

Temporal response characteristics of the spatiochromatic visual evoked potential: nonlinearities and departures from psychophysics.

Although the visual evoked potential (VEP) for isoluminant stimuli has been characterized in terms of spatiochromatic parameters, temporal tuning along various chromatic directions has received less systematic attention. Additionally, there has been little categorical comparison of psychophysical appearance with VEP responses obtained for temporal variation of these patterns. At appropriate contrasts the VEP's for color axes (LM, S) show a robust and contrast-sensitive temporal tuning peak at 4 Hz. Contrast response functions at 4 Hz for the LM color axis are markedly nonmonotonic. However, there is a clear monotonicity with contrast for VEP latencies along these color axes. The anomalous behavior does not appear to be due to interactions between chromatic signals, to luminance artifact, or to rod intrusion. These anomalies in the temporal characteristics of the chromatic VEP may reflect interactions between chromatic responses and inherent cortical responsivity not linked to psychophysical behavior.

Color Perception↗

Acute effects of blood glucose on chromatic visually evoked potentials in persons with diabetes and in normal persons.

PURPOSE: To determine whether specific chromatic pathways are selectively affected by short-term variations in blood glucose levels in observers with and without diabetes. METHODS: Ten subjects with diabetes, all with type 1 diabetes and no retinopathy, and eight age-similar normal subjects were tested. Cortical visually evoked potentials (VEPs) in response to stimuli designed to selectively activate the short-wavelength-sensitive (S) or long- and middle-wavelength-sensitive (LM) chromatic (isoluminant) pathways or the achromatic pathway were recorded over a period of several hours. Capillary blood glucose also was measured repeatedly over the same period. The relation between VEP latency and blood glucose was determined. RESULTS: The S-pathway VEP latency was correlated significantly with blood glucose in a slight majority (6/10) of persons with diabetes; S-pathway latency was longer at higher blood glucose levels. This association between S-pathway latency and blood glucose was not dependent on the pattern of blood glucose variation over time (i.e., significant correlations between blood glucose and latency were observed in persons for whom blood glucose increased, decreased, or rose and then fell over time). No dependence on blood glucose was observed for LM- or achromatic-pathway VEP latency in subjects with diabetes. CONCLUSIONS: Acute variations in blood glucose of subjects with diabetes over hours selectively affect the function of the short-wavelength-sensitive chromatic pathway. The findings are discussed within the context of known mechanisms by which elevated glucose affects cellular metabolism with a time course consistent with the transient nature of the effect observed.

Adult↗

Optimum parameters for short-wavelength automated perimetry.

PURPOSE: To determine the optimum parameters for short-wavelength automated perimetry (SWAP) and to recommend these for standardization of the procedure. METHODS: We used a variety of stimulus and background configurations to determine the optimum background spectral distribution and luminance, and the optimum target spectral distribution, maximum luminance, and duration. We measured threshold versus intensity curves to determine which combination provided (a) the greatest isolation of the short-wavelength sensitive mechanisms and (b) the largest dynamic range for perimetry. We also evaluated the effect of lens absorption and cataract on these two factors. RESULTS: A broad-band yellow background at 100 candela/m2 with a narrow-band 440-nm (27-nm half-bandwidth), 1.8 degrees diameter (Goldmann size V) stimulus presented for 200 ms was optimum at all retinal eccentricities. Specific recommendations for how to modify existing perimeters are given. CONCLUSION: Agreement regarding the optimum parameters for SWAP should lead to standardization of the test that will facilitate comparison of results from different centers. Normative data can be collected at several sites and incorporated into statistical analysis packages currently available with various perimeters. This will greatly improve the clinical utility of this test.

Aged↗

Short-wavelength automated perimetry in low-, medium-, and high-risk ocular hypertensive eyes. Initial baseline results.

OBJECTIVE: To examine the relationship between the prevalence of short-wavelength sensitivity losses in the central 30 degrees visual field and risk factors for development of glaucomatous visual field loss in ocular hypertension. DESIGN: A modified Humphrey Field Analyzer was used to perform standard automated perimetry and short-wavelength automated perimetry (SWAP), which is a technique that isolates the activity of short-wavelength-sensitive ("blue") mechanisms. In addition, an assessment of the risk of developing glaucomatous visual field loss was determined, based on a validated model that utilized intraocular pressure, a family history of glaucoma, age, and the vertical cup-to-disc ratio. PATIENTS: Both eyes of 232 ocular hypertensive patients were examined and compared with results from an age-matched control group of normal subjects. Both ocular hypertensive patients and normal subjects had to have normal visual fields on standard automated perimetry, good visual acuity, and no evidence of other ocular or neurologic disease or surgery. Intraocular pressure in the ocular hypertensive patients was 21 mm Hg or greater OU (without medication), and it was less than 20 mm Hg OU in normal control subjects. RESULTS: Less than 10% of the low-risk ocular hypertensive eyes had a SWAP deficit, as compared with 20% of the moderate-risk and 33% of the high-risk ocular hypertensive eyes. Intraocular pressure and a family history of glaucoma showed no meaningful relationship with the prevalence of SWAP deficits, but both age and the vertical cup-to-disc ratio demonstrated a strong association with the SWAP abnormalities. CONCLUSIONS: The SWAP results that were found in the ocular hypertensive eyes were associated with other risk factors that have been reported to be predictive of the development of glaucomatous visual field loss, especially the vertical cup-to-disc ratio and age. These findings support the notion that the SWAP deficits represent early glaucomatous damage and may be related to early changes that occur at the optic nerve head.

Adult↗

The equivalent refractive index of the crystalline lens in childhood.

Despite the importance of crystalline lens power in ocular development, schematic refractive index values used to calculate lens power have been validated for children. We measured refractive error and ocular component dimensions in 519 schoolchildren, calculating lens power using phakometrically measured lens radii and three different refractive index profiles: (1) Gullstrand-Emsley schematic indices [Gullstrand-Emsley lens power (GELP)]; (2) a 10-shell gradient index model [gradient index lens power (GILP)]; and (3) the equivalent refractive index (IND) needed to bring calculated and measured refractive error into agreement [calculated lens power (CLP)]. GELP was significantly lower than either GILP or CLP, indicating the Gullstrand-Emsley refractive index of 1.416 is too low for use in children. Variation in IND cannot be explained by measurement error alone. GILP and CLP also differed as a function of lens shape, with GILP greater than CLP at steeper external curvatures and less than CLP at flatter external curvatures. Variation in equatorial gradient index profile as a function of lens shape is proposed as an explanation for this bias. Equivalent index appears to be a useful tool for encompassing individual variation in lens gradient profiles as well as for assessing the relative role of lens surface curvature and refractive index changes during lens power development in childhood.

Adolescent↗

Longitudinal evidence of crystalline lens thinning in children.

PURPOSE: Most earlier studies indicated that the eye's crystalline lens grows continually throughout life, but cross-sectional results of crystalline lens thinning during childhood have been reported. The authors investigated crystalline lens thickness in childhood using cross-sectional and longitudinal data. METHODS: The Orinda Longitudinal Study of Myopia is a community-based study of normal eye growth and myopia development in school-age children. During a 1-to 3-year period, A-scan ultrasonographic lens thickness measurements of 869 children 6 through 14 years of age were analyzed. RESULTS: On average, between the ages of 6 and 10 years, the crystalline lens thins in its axial dimension by almost 0.2 mm. This thinning can be depicted by a cubic model. In this sample, the children with myopia had thinner crystalline lenses than the children with emmetropia of the same age. CONCLUSIONS: This article provides the first longitudinal evidence that the crystalline lens thins during the period of coordinated ocular growth between the ages of 6 and 10 years. Further, it shows that lens thickness is associated with refractive error. Thinner crystalline lenses in children with myopia may result from one of two underlying mechanisms: Either the crystalline lens exhausts its ability to compensate for axial elongation after undergoing accelerated lens thinning before the onset of myopia, or the crystalline lens in the myopic eye may be thinner throughout childhood, during which it thins at a rate consistent with other refractive errors. If mechanical forces link eye growth to crystalline lens compensation, more complex, visually guided feedback loops may not be needed to explain the normal eye growth that results in emmetropization.

Adolescent↗