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S L Graham

Publications and source records attributed to S L Graham.

At least 37 records · Page 2Linked to original sources
PubMed2000

Objective perimetry in glaucoma.

PURPOSE: Objective perimetry in glaucoma is described using the multifocal pattern visually evoked potential (VEP). A multichannel recording technique was used to improve signal detection in healthy volunteers and assess its ability to detect glaucoma and early changes in patients with suspected glaucoma. DESIGN: Prospective, case-control study. PARTICIPANTS: Thirty healthy volunteers, 30 patients with suspected glaucoma, and 30 patients with glaucomatous visual field defects were tested. METHOD: The VEP was recorded using cortically scaled, multifocal, pseudorandomly alternated pattern stimuli with the VERIS system (Electro-Diagnostic Imaging, Inc., San Francisco, CA). An array of four bipolar occipital electrodes provided four differently oriented channels for simultaneous recording. Signals were compared for different locations within the field up to 26 degrees of eccentricity. Healthy volunteers, patients with suspected glaucoma, and glaucoma patients with established visual field defects were tested, and results were compared with Humphrey visual fields (Humphrey Systems, Dublin, CA) performed on the same day. For reproducibility, five healthy volunteers were each tested on four separate days. The patients with suspected glaucoma and the established glaucoma patients were analyzed for intereye asymmetry of signals, and these data were compared with the asymmetry values of the healthy volunteers. RESULTS: Multiple recording channels significantly enhanced the recording of signals from parts of the visual field not reliably sampled with a single channel technique in all healthy volunteers, particularly along the horizontal meridian (P: < 0.001). Signal amplitude did not decline with age in healthy volunteers. Recordings showed good reproducibility within individuals. In all 30 glaucoma patients, the Humphrey visual field defects were well demonstrated by the VEP, and topographic location was strongly correlated (r(s) = 0.79). Despite large interindividual variations in amplitude, scotomas were well demonstrated when compared with normal values. In the patients with suspected glaucoma, smaller changes in signal amplitude could be identified in parts of the field still normal on perimetry using intereye asymmetry analysis. CONCLUSIONS: The multifocal, multichannel VEP can objectively detect glaucomatous visual field defects. The nasal step region can be more reliably tested using multiple channels. Asymmetry analysis has the potential to detect early defects. This technique represents a significant step toward the clinical application of objective perimetry in glaucoma.

Adult↗
PubMed2000

Multifocal pattern electroretinogram does not demonstrate localised field defects in glaucoma.

PURPOSE: To determine if a multifocal PERG could be recorded in normals, and to examine changes in the multifocal PERG in glaucoma patients. To compare the ability of multifocal PERG and multifocal VEP responses in the same individuals to identify localised field defects in glaucoma. METHODS: Using the VERIS Scientific system multifocal PERGs were recorded from 19 sites of the visual field according to pseudo-random binary m-sequence. Twenty normals and 15 glaucoma subjects were tested. Multifocal pattern VEPs were also recorded in the glaucoma cases using a cortically scaled stimulus. RESULTS: The second order kernel of the PERG shows a consistent signal. The overall PERG amplitude decreases with age in normals. In glaucoma the PERG amplitude was reduced across the field, but reductions did not correspond to the area of the scotoma. The VEP showed localised signal reductions in all 15 cases of glaucoma. CONCLUSION: A multifocal PERG can be recorded in normals. However it did not reflect localised ganglion cell losses, whereas the multifocal pattern VEP recorded to a very similar stimulus in the same individual did show losses in the scotoma area.

Adult↗
PubMed2000

Objective VEP perimetry in glaucoma: asymmetry analysis to identify early deficits.

PURPOSE: The multifocal visual evoked potential (VEP) shows markedly symmetrical responses between the two eyes of control subjects. Patients with glaucoma and patients considered at high risk for glaucoma were examined to determine if VEP asymmetry could be identified and used for diagnosis and detection of early damage. METHODS: Multifocal pattern VEP recordings were performed using a single channel bipolar occipital electrode position and the Visual Evoked Response Imaging System (VERIS). There were 125 subjects: 24 control subjects, 70 patients with glaucoma, and 31 patients considered at high risk for glaucoma. A between-eye relative asymmetry coefficient (RAC) was determined for each of the 60 test points in the VEP field. The RAC for patients with glaucoma and patients considered at risk for glaucoma were compared with values from control subjects. Correlation between Humphrey thresholds and RAC scores was performed. RESULTS: Patients with glaucoma and patients considered at risk for glaucoma both showed significantly larger mean quadrant RAC values. When point by point analysis was performed, 69 out of 70 scotomas were identified with a cluster of at least 3 points of P < 0.05. For those considered at high risk for glaucoma, 10 out of 31 patients had abnormal areas in the VEP field. There was a strong correlation (r = 0.82) between quadrantic RAC mean values and Humphrey quadrant threshold scores in an asymmetric glaucoma subgroup. Abnormal VEP responses were identified in parts of the visual field that were still normal on perimetry. CONCLUSIONS: Asymmetry analysis correctly identifies patients with glaucomatous field loss and shows abnormalities in many patients considered at high risk for glaucoma who still have normal fields. Asymmetry analysis is able to identify objectively the extent of glaucomatous damage and may be able to detect changes before subjective field loss occurs.

Adolescent↗
PubMed2000

Comparison of the Humphrey swedish interactive thresholding algorithm (SITA) and full threshold strategies.

PURPOSE: To compare the Swedish interactive thresholding algorithm (SITA) strategy with the full threshold strategy in routine clinical practice. METHODS: Using the Humphrey visual field analyzer model 750 (Allergan Humphrey, San Leandro, CA), 108 subjects were tested with 24-2 SITA (version A9) and 24-2 full threshold strategies. Test results were compared for time taken and reliability and on the basis of seven criteria of abnormality. RESULTS: The SITA required on average 48.8% less time than the full threshold strategy. Patient reliability parameters were somewhat better with SITA. There was a strong correlation between mean deviation and pattern standard deviation. Average threshold sensitivity at each point was increased by 1.31 dB with SITA, but greater differences were seen at points with lower sensitivity. Using the full threshold strategy as our standard for comparison, the sensitivity of SITA varied from 83.0% to 93.2% in detecting the variously defined abnormalities. Fields shown as normal with full threshold strategy corresponded with those found to be normal with SITA in 79.0 to 96.3% cases depending on criteria for abnormality. There were a few cases in which SITA suggested an early abnormality but results of full threshold testing remained normal. On average, the size and depth of scotomas decreased slightly with SITA, but this difference was not statistically significant. Of the 70 patients surveyed about their preference, 65 (92.9%) preferred SITA. CONCLUSION: Full threshold and SITA strategies are comparable in detecting glaucomatous defects. The SITA strategy requires significantly less time to perform and is a satisfactory alternative to full threshold algorithms in clinical practice for diagnosis and management of glaucoma.

Adult↗
PubMed1999

Design and in vivo analysis of potent non-thiol inhibitors of farnesyl protein transferase.

Inhibitors of farnesyl protein transferase (FPTase) based upon a pseudotripeptide template are described that comprise an imidazole group substituted with a hydrophobic substituent. (1, 5)-Disubstitution of the imidazole group is shown to be the optimal array that leads to potent and selective inhibitors of FPTase. A variety of aryl and isoprenyl substituents are shown to afford effective inhibitors, and the mechanism by which these compounds inhibit FPTase has been investigated. The biochemical behavior of these compounds suggests that they bind to FPTase at the site usually occupied by the protein substrate. In experiments in cell culture, the methyl ester prodrugs of these inhibitors are cell permeant and potently inhibit the posttranslational modification of H-Ras protein. Additionally, these molecules revert the phenotype of ras transformed cells as evidenced by their ability to slow the growth of ras transformed cell lines in soft agar. One of the inhibitors, as its methyl prodrug, was evaluated in two in vivo models of tumor growth. The compound selectively inhibited the growth of tumors derived from H-ras transformed cells, in nude mice, and caused the regression of preexisting tumors in an H-ras transgenic animal model.

3T3 Cells↗
PubMed1999

Performance evaluation of a permeable reactive barrier for remediation of dissolved chlorinated solvents in groundwater.

A pilot-scale permeable reactive barrier (PRB) consisting of granular iron was installed in May 1995 at an industrial facility in New York to evaluate the use of this technology for remediation of chlorinated volatile organic compounds (VOCs) in groundwater. The performance of the barrier was monitored over a 2-year period. Groundwater velocity through the barrier was determined using water level measurements, tracer tests, and in situ velocity measurements. While uncertainty in the measured groundwater velocity hampered interpretation of results, the VOC concentration data from wells in the PRB indicated that VOC degradation rates were similar to those anticipated from laboratory results. Groundwater and core analyses indicated that formation of carbonate precipitates occurred in the upgradient section of the iron zone, however, these precipitates did not appear to adversely affect system performance. There was no indication of microbial fouling of the system over the monitoring period. Based on the observed performance of the pilot, a full-scale iron PRB was installed at the site in December 1997.

Carbonates↗
PubMed1999

Objective perimetry in glaucoma: recent advances with multifocal stimuli.

The introduction of multifocal stimulus recording has enhanced our ability to examine the human visual field with electrophysiologic techniques. We have adapted the multifocal pattern visual evoked potential (PVEP) to detect visual field loss. In glaucoma patients we sought to determine the extent to which the PVEP amplitudes correlate with perimetric thresholds. Multifocal pseudorandomly alternated pattern stimuli, which were cortically scaled in size, were presented with use of the VERIS-Scientific system. Bipolar occipital straddle electrode positions were used. The visual field up to 25 degrees of eccentricity was investigated. Forty-three glaucoma patients with reproducible visual field defects were tested. The bipolar PVEP corresponded well with Humphrey visual field defects, showing loss of signal in the scotoma area. For Humphrey quadrant threshold totals and PVEP quadrant amplitudes, the correlation coefficient was strong (r = 0.49, P < 0.0001). The multifocal PVEP demonstrates good correspondence with the topography of the visual field. This technique represents the first practical application of the multifocal PVEP to objective detection of visual field defects in glaucoma.

Chronic Disease↗
PubMed1999

Nocturnal hypotension: role in glaucoma progression.

The role of systemic blood pressure in glaucomatous damage remains undefined, with systemic hypertension and hypotension being implicated in different studies. We have previously reported that the physiologic nocturnal blood pressure "dip" may be exaggerated in some glaucoma patients with progressive field loss. A 24-hour ambulatory blood pressure recording was originally performed on 84 patients with glaucoma. The mean result across all our glaucoma patients were within the ranges reported in the literature for normal subjects. The normal-tension glaucoma and primary open-angle glaucoma groups did not differ significantly in blood pressure variables. Nocturnal blood pressure variables were lower in the patients with progressive field defects compared to those with stable visual fields. To determine long-term outcomes in these patients, we reevaluated the visual fields of the original 84 patients studied. In 70 patients with long-term visual field data (mean, 5.1 years), those who had shown greater nocturnal blood pressure dips were more likely to have shown field progression at some stage, despite good intraocular pressure control. Patients who had field progression showed significantly lower nocturnal blood pressure variables, with the dips of the systolic, diastolic, and mean arterial pressure significantly larger (systolic dip, P = 0.01). They also had a greater history of disk hemorrhages. A review of other 24-hour blood pressure studies in the literature shows that most are in agreement with these findings. The nocturnal reduction in blood pressure may, therefore, be an additional risk factor in glaucoma patients.

Blood Pressure↗
PubMed1999

Multifocal pattern VEP perimetry: analysis of sectoral waveforms.

PURPOSE: The objective detection of local visual field defects using multi-focal pattern visual evoked potentials (VEP) has recently been described. The individual waveforms show variable polarity in different parts of the visual field due to underlying cortical convolutions. Normal trace arrays were examined to determine if certain areas of similar waveform could be grouped for analysis, while minimising cancellation of data. METHOD: The VEP was assessed using multi-focal pseudo-randomly alternated pattern stimuli which were cortically scaled in size. Bipolar occipital electrodes were used for recording. Waveforms were compared for different locations within the field up to 25 degrees of eccentricity. Analysis of sectors showing similarly shaped waveforms was performed. Twelve normal subjects were studied. RESULT: Grouping waveforms by sectors of similar waveform increased the total calculated upper hemifield amplitude by 60%, compared with simple summations of responses for the whole hemifield. The inferior hemifield showed more consistent waveforms throughout, with the amplitude only increasing by 11% with sectoral summation. Intra-subject variability (10.6%) is less for sectors than for individual points (17.3%). Inter-subject amplitude differences are high, calculated at 56% for individual points and 45% for sectors. CONCLUSIONS: Due to differences in waveform as a result of underlying cortical anatomy, individual VEP responses from multifocal recordings should be grouped as sectors along the vertical meridian and above and below the horizontal, rather than by hemifields or quadrants. This finding is significant if one is considering within-field grouping strategies similar to the glaucoma hemifield test used in conventional perimetry, or reporting derived overall VEP amplitudes and latencies from a multifocal recording. Large amplitude variations between individuals and small signals from horizontal and upper field seen in single channel recording, still limit the application of this technique as a form of objective perimetry.

Evoked Potentials, Visual↗
PubMed1999

The diagnostic significance of the multifocal pattern visual evoked potential in glaucoma.

The concept of objective perimetry is an exciting one because it strives to assess glaucoma damage without relying on psychophysical testing. The recent introduction of multifocal stimulus recording has enhanced our ability to examine the human visual field using electrophysiology. A multifocal pattern visual evoked potential can now be recorded, testing up to 60 sites within the central 25 degrees. The test requires only that the subject fixate on a target, while a cortically scaled dartboard pattern stimulus undergoes pseudorandom alternation within each of the test segments. In its present configuration the test requires at least 8 minutes recording time per eye. Modified bipolar electrode positions are required to ensure that adequate signals are detected from all parts of the visual field. In glaucoma patients, pattern visual evoked potential amplitudes have been shown to reflect visual field loss with reduction of signal amplitude in the affected areas. This technique represents the first major step toward objective detection of visual field defects in glaucoma.

Evoked Potentials, Visual↗
PubMed1999

Early magnocellular loss in glaucoma demonstrated using the pseudorandomly stimulated flash visual evoked potential.

PURPOSE: Components of the pseudorandomly stimulated flash visual evoked potential (VEP) have now been identified that appear to arise predominantly from each of the magnocellular (M-cell) and parvocellular (P-cell) systems. In this study, the relative damage to magnocellular and parvocellular systems at different stages of glaucoma using pseudorandomly stimulated flash VEP was investigated. METHODS: Pseudorandomly stimulated flash VEP was recorded in 15 normal eyes and 28 eyes with different stages of glaucoma using the VERIS-3 recording system (Electro-Diagnostic Imaging, San Francisco, CA). Two levels of luminance contrast of the stimulus (32% and 99%) were tested. The first slice of the second-order kernel from only the central (8 degrees) stimulated area was extracted for analysis. RESULTS: Data recorded from normal eyes demonstrated early saturation of the response/contrast function of the first slice of the second-order kernel. The ratio of the VEP amplitude recorded at 32% and 99% of the luminance contrast was close to unity. In eyes with early glaucoma, although the amplitude of the responses to both low- and high-contrast stimulation decreased, the relative reduction of the low-contrast VEP (M-cell) was more prominent. However, the amplitude of the high-contrast response (P-cell) declined more rapidly later in the disease. CONCLUSION: These results are consistent with relatively earlier damage of the magnocellular pathway in glaucoma.

Adult↗
PubMed1998

Potent, non-thiol inhibitors of farnesyltransferase.

The structure-activity relationship of a series of non-thiol CaaX analogs, which are inhibitors of farnesyltransferase, is described. These inhibitors contain a substituted phenyl group at the N terminus, which may occupy a novel binding domain on the Ras protein.

Alkyl and Aryl Transferases↗
PubMed1998

Clavaric acid and steroidal analogues as Ras- and FPP-directed inhibitors of human farnesyl-protein transferase.

We have identified a novel fungal metabolite that is an inhibitor of human farnesyl-protein transferase (FPTase) by randomly screening natural product extracts using a high-throughput biochemical assay. Clavaric acid [24, 25-dihydroxy-2-(3-hydroxy-3-methylglutaryl)lanostan-3-one] was isolated from Clavariadelphus truncatus; it specifically inhibits human FPTase (IC50 = 1.3 microM) and does not inhibit geranylgeranyl-protein transferase-I (GGPTase-I) or squalene synthase activity. It is competitive with respect to Ras and is a reversible inhibitor of FPTase. An alkaline hydrolysis product of clavaric acid, clavarinone [2,24,25-trihydroxylanostan-3-one], lacking the 3-hydroxy-3-methylglutaric acid side chain is less active as a FPTase inhibitor. Similarly, a methyl ester derivative of clavaric acid is also inactive. In Rat1 ras-transformed cells clavaric acid and lovastatin inhibited Ras processing without being overtly cytotoxic. Excess mevalonate reversed the effects of lovastatin but not of clavaric acid suggesting that the block on Ras processing by clavaric acid was due to inhibition of FPTase and not due to inhibition of HMG-CoA reductase. Despite these results, the possibility existed that clavaric acid inhibited Ras processing by directly inhibiting HMG-CoA reductase. To directly examine the effects of clavaric acid and clavarinone on HMG-CoA reductase, cholesterol synthesis was measured in HepG2 cells. No inhibition of HMG-CoA reductase was observed indicating that the inhibition of Ras processing by this class of compounds is due to inhibition of FPTase. To date, clavaric acid is the second reported nitrogen-free compound that competes with Ras to inhibit FPTase activity. A series of related compounds derived from computer-based similarity searches and subsequent rational chemical synthetic design provided compounds that exhibited a range of activity (0.04 --> 100 microM) against FPTase. Modest changes in the structures of these inhibitors dramatically change the inhibitory activity of these inhibitors.

Alkyl and Aryl Transferases↗
PubMed1998

N-Arylalkyl pseudopeptide inhibitors of farnesyltransferase.

Inhibitors of Ras protein farnesyltransferase are described which are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Reduction of the carbonyl groups linking the first three residues of the tetrapeptide leads to active inhibitors which are chemically unstable. Stability can be restored by alkylating the central amine of the tetrapeptide. Studies of the SAR of these alkylated pseudopeptides with concomitant modification of the side chain of the third residue led to 2(S)-(2(S)-¿[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)- methylpentyl]naphthalen-1-ylmethylamino¿acetylamino)-4 -methylsulfany lbutyric acid (11), a subnanomolar inhibitor. The methyl ester (10) of this compound exhibited submicromolar activity in the processing assay and selectively inhibited anchorage-independent growth of Rat1 cells transformed by v-ras at 2.5-5 microM.

3T3 Cells↗
PubMed1998

Electrophysiology: a review of signal origins and applications to investigating glaucoma.

Because different electrophysiological responses can be isolated to different retinal and cortical cell types and levels, the proportion in which the different signals are reduced can reflect the primary areas of damage. The knowledge of electrophysiology component sources can thus be applied when examining ophthalmic disorders. The present review covers the proposed origins and the usefulness of the conventional electrophysiological responses. Their application to glaucoma is discussed, with particular reference to the pattern electroretinogram. In the second part of the current review, we present some recent developments that relate to the use of multifocal pseudorandomly stimulated recording. This technique enables a new approach to the electrical assessment of visual responses. Analysis for temporal non-linearities and spatial distribution of the response throughout the visual field can be implemented. This type of recording has the potential to provide a method of objective visual field assessment in glaucoma and other disorders of the visual system.

Animals↗
PubMed1998

Electrode position and the multi-focal visual-evoked potential: role in objective visual field assessment.

PURPOSE/METHODS: To improve the performance of visual-evoked potentials (VEP) in the assessment of the human visual field, the multi-focal cortically scaled pattern VEP was recorded up to 250 of eccentricity in normal subjects. Monopolar and varying bipolar electrode positions were used. RESULTS: The monopolar response was strongly biased towards the lower hemifield. Bipolar leads straddling the inion (2 cm above and below) achieved approximately equal signals from the upper and lower visual field. Division into sectors of similar wave-form augments the analysis compared with summed full-field responses. CONCLUSION: With this technique, the multi-focal VEP can be used to objectively assess the visual field.

Cerebral Cortex↗