A Plasmodium chabaudi protein contains a repetitive region with a predicted spectrin-like structure.

cDNA and genomic DNA clones covering the entire open reading frame (ORF) for a Plasmodium chabaudi 96V protein were isolated. From the first ATG codon the intronless gene codes for a 229-kDa protein. Antisera raised against recombinant polypeptides coded by two different regions of the gene reacted with a 240/225-kDa doublet on Western blots of parasite extracts. In immunofluorescence studies the same sera detected the antigen at the apical end of the merozoite, possibly in rhoptry organelles. In Western blotting experiments the recombinant polypeptides were recognised by antibodies induced by natural infection. A 364-amino acid residue repetitive region, based on 32 11-mer repeats divided by two 6-mer repeats into three blocks, is located in the centre of the protein. Analysis of this repetitive region led us to propose a model in which each of the three units forms an alpha-helical coiled-coil triple-helix containing a possible leucine-histidine zipper. Each unit resembles in structure the units present in spectrin. The repeat region is flanked by predicted heptad based alpha-helical coiled-coil regions, and we propose that the protein forms a dimer. The 229-kDa protein has the overall character of a cytoskeletal protein. We have named the 229-kDa protein repetitive organellar protein (ROPE) and suggest that ROPE may be involved in the process of invasion, possibly by interacting with the erythrocyte cytoskeleton, and that the leucine histidine-zipper may be involved in molecular mimicry of spectrin.

Current status of the Plasmodium falciparum genome project.

The Plasmodium falciparum Genome Project is a collaborative effort by many laboratories that will provide detailed molecular information about the parasite, which may be used for developing practical control measures. Initial goals are to prepare an electronically indexed clone bank containing partially sequenced clones representing up to 80% of the parasite's genes and to prepare an ordered set of overlapping clones spanning each of the parasite's 14 chromosomes. Currently, clones of genomic DNA, prepared as yeast artificial chromosomes, are arranged into contigs covering approximately 70% of the genome of parasite clone 3D7, gene sequence tags are available from more than contigs covering approximately 70% of the genome of parasite clone 3D7, gene sequence tags are available from more than 20% of the parasite's genes, and approximately 5% of the parasite's genes are tentatively identified from similarity searches of entries in the international sequence databases. A total of > 0.5 Mb of P. falciparum sequence tag data is available. The gene sequence tags are presently being used to complete YAC contig assembly and localize the cloned genes to positions on the physical map in preparation for sequencing the genome. Routes of access to project information and services are described.

Technique for determining glaucomatous visual field progression by using animation graphics.

The first two visual field examinations of each of 16 glaucoma suspects and 16 glaucoma patients, who were followed up for a median of 7.46 years with seven examinations, were averaged. Three-dimensional color-coded images of the visual field were then generated. After correcting for test-retest variability, the images, as well as additional interpolated images, were aligned and presented in rapid succession to create an animation sequence. Five glaucoma specialists trained themselves to classify the visual fields as either progressing or not progressing. The interobserver and intraobserver agreement rates were then calculated. Perfect agreement (100% concordance) between the observers was obtained for 18 (56.3%) subjects, and at least 80% concordance was obtained for 27 (84.4%) subjects. Of the eight sequences that were repeated to test intraobserver agreement, four of the five observers had a value of at least 87.5%.

Optic disc topography in patients with low-tension and primary open angle glaucoma.

Computerized optic disc topographic measurements (cup-disc ratio, neuroretinal rim area, disc volume) and automated visual field parameters (total field loss, mean sensitivity) were similar in 48 eyes with primary open angle glaucoma and 27 eyes with low-tension glaucoma. In open angle glaucoma, the neuroretinal rim area was negatively correlated with the cup-disc ratio and the disc volume. Total field loss was positively correlated with the cup-disc ratio and the disc volume and negatively correlated with the neuroretinal rim area. Eyes with low-tension glaucoma showed a negative correlation between neuroretinal rim area and cup-disc ratio, and between total field loss and rim area. However, low-tension glaucomatous eyes did not have significant correlations between disc volume and rim area and between total field loss and cup-disc ratio or disc volume. Cupping in low-tension glaucoma was broadly sloping, resulting in less disc volume alteration.

Effect of patient experience on the results of automated perimetry in glaucoma suspect patients.

The first four Octopus-automated visual field examinations of 29 patients with elevated intraocular pressure but apparently normal optic discs and Goldmann visual fields were studied for the presence of a learning effect on the visual field parameters of mean sensitivity, number of disturbed test locations, total field loss, and short-term fluctuation. A learning effect, if present, would manifest itself as an improvement in the visual field as patients become more experienced with the test. There was no apparent effect of patient experience on the mean sensitivity of the whole visual fields or the mean sensitivity of the test locations within 20 degrees of fixation. There was a significant (P = 0.012) increase in mean sensitivity for the test locations outside 20 degrees of fixation. There were significant (P less than 0.01) improvements in short-term fluctuation, total loss, and number of disturbed points between the first and second visual field examinations. The results indicated that there was a learning effect between the first and second automated visual field in glaucoma suspect patients who had previous experience with manual perimetry. It was not, however, very large in most patients and seems to be present in the peripheral portions of the visual field only. In most cases, it was not necessary to obtain more than two "baseline" examinations unless a patient demonstrated unusually high short-term fluctuation or had visual field defects inconsistent with the remainder of their clinical examination.

Variability of automated visual fields in clinically stable glaucoma patients.

The total variability of the visual field was measured in 20 patients with open-angle glaucoma who appeared to be clinically stable and well controlled on medical therapy. All patients had at least four visual fields performed on the Octopus 201 perimeter with at least 12 months follow-up since their first visual field. The four most recently performed visual fields were analyzed. Two different methods for calculating total variability were used. One was based on the variance of the threshold determinations and the other was based on the range. The average total variability per subject was 2.8 decibels (db) using the variance-based calculation and 5.1 db using the range-based calculation. Ninety-five percent of the test locations had a variability of less than 6 db by the variance-based calculation method and 13 db by the range-based calculation method. We discuss the possibility of using this type of data to develop criteria for detection of progressive visual field loss in glaucoma.

Bilateral argon laser trabeculoplasty in primary open-angle glaucoma.

We performed bilateral argon laser trabeculoplasty on 34 patients with medically uncontrolled open-angle glaucoma. Preoperative intraocular pressure was greater than 21 mm Hg, with a less than 3-mm Hg difference between the two eyes. Laser treatment (360 degrees) was performed on both eyes within a three-month interval. Mean (+/- S. D.) baseline intraocular pressure was similar in the first- (26.9 +/- 3.7 mm Hg) and second- (26.5 +/- 3.3 mm Hg) treated eyes. One hour after treatment, four first- and four second-treated eyes had a greater than 30% increase in intraocular pressure. The one-hour change in pressure was highly correlated between the two eyes (r = .794, P less than .0001). Intraocular pressure was reduced (P less than .0001) one, two, and three years after treatment in both the first and second-treated eyes. The percentages of first- and second-treated eyes with a pressure of less than or equal to 21 mm Hg were similar at one, two, and three years. Pressure response between the two eyes was correlated (P less than .0001) at year 1 (r = .815), 2 (r = .757), and 3 (r = .886) after laser therapy.

Variability and reproducibility of optic disk topographic measurements with the Rodenstock Optic Nerve Head Analyzer.

Variability of optic disk topographic measurements obtained with the Rodenstock Optic Nerve Head Analyzer was determined by obtaining three separate images on one eye of ten normal subjects and nine subjects without glaucoma. Marking of the disk margin was performed in a random and masked fashion on each image three times by three independent observers. The overall variabilities of the measurements of the subjects with glaucoma were not statistically different from those of the normal subjects. Overall variability was about 0.2 mm2 for total disk area, 0.08 for cup/disk ratio, 0.2 mm2 for disk rim area, and 0.07 mm3 for cup volume. The largest component of the variability was the result of acquisition of separate images of the optic disk at different times. Observer inconsistency in marking the disk edge was relatively small. Based on the expected amount of random variability of the measurements, we proposed criteria for detecting significant change in the optic disk over time.

Effect of patient experience on the results of automated perimetry in clinically stable glaucoma patients.

The first four automated visual field examinations of 20 patients with clinically stable chronic open-angle glaucoma who had previously undergone manual perimetry were studied for the presence of a learning effect on mean sensitivity, number of disturbed test locations, total loss, and short-term fluctuation. A learning effect, if present, would manifest itself as an improvement in the visual field as patients become more experienced with the test. There was no apparent effect of patient experience on the mean sensitivity, total loss, or the number of disturbed test locations. There was a significant (P less than 0.0001) decrease in short-term fluctuation as measured by the root mean square between the first and second visual field examinations. These results indicate that a learning effect did not play an important role in the clinical interpretation of automated perimetry in patients with glaucoma who have previous experience with manual perimetry. In most cases, it was not necessary to obtain more than one "baseline" examination unless a patient demonstrated unusually high short-term fluctuation or had visual field defects inconsistent with the rest of the clinical examination.

A comparison of experienced clinical observers and statistical tests in detection of progressive visual field loss in glaucoma using automated perimetry.

The visual fields of 30 patients (subjects) with glaucoma were sent to six experienced clinicians (observers). Each subject had at least four visual field examinations on the OCTOPUS 201 automated perimeter spanning at least one year. Each observer was asked to review the visual field data of each subject and determine whether the visual fields were stable, improved, or worse over time. The visual field data were then analyzed using six different statistical models. In only 15 of the 30 subjects did at least five of the six human observers agree on the behavior of the visual field. Agreement among the statistical models was better, with at least five of the six models agreeing on 22 of the 30 subjects. It was concluded that there is, at present, no validated technique for detecting progressive visual field loss in glaucoma using automated perimetry when relatively few visual fields are available for analysis.

Effect of a topical carbonic anhydrase inhibitor, 6-hydroxybenzo[b]thiophene-2-sulfonamide, on intraocular pressure in normotensive subjects.

A prospective randomized clinical trial was carried out to determine the efficacy of 6-hydroxybenzo[b]thiophene-2-sulfonamide, a potent new carbonic anhydrase inhibitor, in lowering intraocular pressure (IOP) in normotensive volunteers. The drug was administered as a 2% suspension twice daily for 1 week to one eye in 10 subjects. Ten other subjects, serving as controls, received a placebo drop to one eye on the same schedule. Subjects and examiners were unaware of whether the drug or placebo was being used. IOP was measured before the study began and twice daily on days 1, 2, 4 and 8 of the study. The drug had no significant effect on IOP. The most likely explanation is failure of an adequate concentration of the drug to reach the ciliary body.

Intraocular pressure and visual field defects after argon laser trabeculoplasty in chronic open-angle glaucoma.

Nineteen patients undergoing argon laser trabeculoplasty for open-angle glaucoma were studied prospectively. All patients had glaucomatous visual field defects with inadequate medical control of intraocular pressure (IOP) before laser treatment. All patients had two automated visual fields immediately before laser treatment. They also had follow-up automated perimetry at 1, 4, 8, and 12 months posttreatment. The serial visual fields were compared using a one-way analysis of variance and trend analysis. After the laser trabeculoplasty, six patients showed visual field improvement, eight showed no change, and five showed progressive visual field deterioration. Patients with little fluctuation of IOP measurements after laser treatment had a better prognosis for visual field retention. The mean IOP level, however, was a poor predictor of visual field progression. Patients with more extensive visual field damage before laser treatment did not do worse than patients with less extensive visual field loss.

Argon laser trabeculoplasty in black and white patients with primary open-angle glaucoma.

The effect of argon laser trabeculoplasty (ALT) on lowering intraocular pressure (IOP) was studied retrospectively in 68 black patients and 42 white patients with uncontrolled primary open-angle glaucoma on maximally tolerated medical therapy. Patients with the diagnosis of pigmentary or pseudoexfoliation glaucoma and those having previous intraocular or laser surgery were excluded. While the mean age of the black patients (66.9 years) was lower than the white patients (72.2 years), the prelaser IOP was similar between the two groups: 26.2 mmHg for the black patients and 25.5 mmHg for the white patients. The mean IOP one year (18.4 mmHg for black patients and 18.4 mmHg for white patients) and two years (19.5 mmHg and 20.3 mmHg, respectively) after ALT was the same between the two groups of patients. A similar percentage of black (85%) and white (83%) patients showed more than a 15% decrease in IOP from their prelaser values one year after treatment. The IOP lowering effect of ALT decreased during the second post-operative year; but the diminished response was identical in patients of both races, with 71% of patients of both groups still showing greater than 15% reduction from their pre-laser IOP. We conclude that ALT is equally effective in lowering IOP for black and white patients with medically uncontrolled primary open-angle glaucoma.

Relationship between baring of circumlinear vessels of the optic disc and glaucomatous visual field loss.

Stereo disc photographs of the eyes of 232 patients with normal or elevated intraocular pressure were reviewed to assess the value of baring of circumlinear vessels of the optic nerve head as a sign of glaucomatous damage. Baring and the presence of glaucomatous visual field defects were significantly correlated, as were this sign and consistent elevation of the intraocular pressure in patients without a visual field defect. Baring was absent in 35% of the eyes with circumlinear vessels and known glaucomatous visual field defects. However, it was present in only 6% of the eyes with normal pressure, a normal visual field and circumlinear vessels. Therefore, this sign should lead to further evaluation.