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Biomedical subjects

G A Fishman

Publications and source records attributed to G A Fishman.

At least 109 records · Page 6Linked to original sources
PubMed1990

Multipoint linkage analysis and heterogeneity testing in 20 X-linked retinitis pigmentosa families.

Using multipoint linkage analysis in 20 families segregating for X-linked retinitis pigmentosa (XLRP), the lod scores on a map of eight RFLP loci were obtained. Our results indicate that under the hypothesis of homogeneity the maximal multipoint lod score supports one disease locus located slightly distal to OTC at Xp21.1. Heterogeneity testing for two XLRP loci suggested that a second XLRP locus may be located 8.5 cM proximal to DXS28 at Xp21.3. Further heterogeneity testing for three disease loci failed to detect a third XLRP locus proximal to DXS7 in any of our 20 XLRP families.

Alleles↗
PubMed1990

Localizing multiple X chromosome-linked retinitis pigmentosa loci using multilocus homogeneity tests.

Multilocus linkage analysis of 62 family pedigrees with X chromosome-linked retinitis pigmentosa (XLRP) was undertaken to determine the presence of possible multiple disease loci and to reliably estimate their map location. Multilocus homogeneity tests furnished convincing evidence for the presence of two XLRP loci, the likelihood ratio being 6.4 x 10(9):1 in favor of two versus a single XLRP locus and gave accurate estimates for their map location. In 60-75% of the families, location of an XLRP gene was estimated at 1 centimorgan distal to OTC, and in 25-40% of the families, an XLRP locus was located halfway between DXS14 (p58-1) and DXZ1 (Xcen), with an estimated recombination fraction of 25% between the two XLRP loci. There is also good evidence for a third XLRP locus, midway between DXS28 (C7) and DXS164 (pERT87), supported by a likelihood ratio of 293:1 for three versus two XLRP loci.

Chromosome Mapping↗
PubMed1990

Vitreous fluorophotometry in patients with Best's macular dystrophy.

Ten patients with Best's macular dystrophy were examined with vitreous fluorophotometry and results were compared with a normal population. Seventeen of the 20 affected eyes demonstrated an intact blood-retinal barrier with normal inward permeability of fluorescein dye. Despite diffuse functional impairment of the retinal pigment epithelium (RPE), determined by electro-oculography, as well as accumulation of a lipofuscin or lipofuscin-like substance within virtually all RPE cells, the blood-retinal barrier function of these cells remained intact as determined by clinical fluorophotometry. Similar findings have previously been noted in another hereditary retinal disorder (fundus flavimaculatus) in which a lipofuscin-like substance also accumulates diffusely within RPE cells.

Adolescent↗
PubMed1990

A form of congenital stationary night blindness with apparent defect of rod phototransduction.

We report findings obtained from an individual with an unusual form of congenital stationary night blindness (CSNB). Although the rhodopsin density difference of this subject was normal, there was no evidence of rod-mediated visual function. Dark-adapted thresholds were cone-mediated, and dark-adapted electroretinograms (ERGs) represented activity of the cone system exclusively. ERG a- and b-waves obtained under light-adapted conditions were normal. The absence of a rod a-wave but the presence of normal rhodopsin density, in combination with normal cone function, indicates that this form of CSNB likely involves a defect of phototransduction that is limited to the rods. In addition, light-adapted b-wave responses to high luminance flashes were larger than dark-adapted responses, whereas a-wave amplitudes were reduced by light adaptation. These ERG results address proposed mechanisms by which light adaptation might enhance cone system responses.

Adolescent↗
PubMed1989

Vitreous fluorophotometry in carriers of choroideremia and X-linked retinitis pigmentosa.

The status of the blood-retinal barrier (BRB) in carriers of choroideremia and X-linked retinitis pigmentosa (XLRP) was determined by vitreous fluorophotometry (VF) and compared with that in female control subjects. Electroretinographic (ERG) amplitudes were measured to determine the overall functional integrity of retinal rods and cones. Comparison of the VF results showed an abnormal BRB in at least some carriers of XLRP, particularly those with peripheral fundus pigmentary changes, but not in carriers of choroideremia with even moderately extensive pigmentary changes. The abnormal BRB in XLRP carriers, with or without peripheral fundus pigmentary changes, was associated with at least moderate to moderately extensive reduction in scotopic ERG amplitudes, while the normal VF results in choroideremia carriers were associated with normal scotopic ERG amplitudes. However, in XLRP carriers, mild to modest reductions in ERG scotopic responses were seen in the presence of normal VF findings.

Adolescent↗
PubMed1989

Acetazolamide for treatment of chronic macular edema in retinitis pigmentosa.

Twelve patients with retinitis pigmentosa and chronic macular edema were prospectively treated for 2-week periods with acetazolamide or a placebo in a masked, crossover study. Ten of the 12 patients had both subjective and objective improvement in visual acuity when treated with acetazolamide. Improvement was seen even in patients with an acuity as good as 20/25 at baseline as well as in patients with macular edema present for more than a decade. A dosage of 500 mg/d was found to be more effective than 250 mg/d. Six patients (50%) showed lessening of their macular edema on fluorescein angiography. This angiographically demonstrated improvement was predominantly due to less detectable leakage from retinal capillaries rather than from choroidal capillaries through the retinal pigment epithelium. Improvement in visual acuity was seen in some patients without a detectable change in the amount of angiographic fluorescein leakage.

Acetazolamide↗
PubMed1989

Human macular pigment assessed by imaging fundus reflectometry.

A computerized, television-based, imaging fundus reflectometer was used to obtain estimates of the spatial distribution of macular pigment (xanthophylls) from seven normal subjects. Digitized images of the bleached macula of each subject were acquired at illuminating wavelengths from 462 to 697 nm. An analysis of spectral reflectances indicated that differences in short-wavelength reflectance between the foveal center and parafovea were influenced by spatial variations in melanin and oxyhemoglobin absorption as well as by the distribution of macular pigment. To provide an estimate of the spatial distribution of macular pigment alone, we have corrected fundus images obtained at 462 nm for the effect of melanin and oxyhemoglobin absorption. The spatial variation in macular pigment double density across the horizontal and vertical meridians of the retina was well described by Gaussian functions. The peak double densities for the individual subjects ranged from 0.22 to 0.45 and the standard deviations of the Gaussian functions averaged approx. 1 degree.

Adult↗
PubMed1989

The luminance-response function of the dark-adapted human electroretinogram.

A hyperbolic equation of the form (R/Rmax) = Ln/(Ln + Kn) has been used to describe the b-wave luminance-response function of the dark-adapted human electroretinogram (ERG). However, this equation accurately describes the function only at low to moderate flash luminances. At high flash luminances, a second amplitude increase or "limb" appears in the function. The results of the present study demonstrate that this limb does not represent a cone system response. First, the spectral sensitivity of the entire luminance-response function is rod-determined in normal subjects. Second, the limb was present in a rod monochromat, in whom cone system ERGs were indistinguishable from noise. Instead, the nonmonotonic nature of the luminance-response function may result from a luminance-dependent algebraic summation of the components that underlie the ERG waveform of the rod system.

Color Vision Defects↗
PubMed1989

Electroretinographic findings in human oculocutaneous albinism.

Electroretinograms (ERGs) were obtained under dark- and light-adapted conditions from 15 human oculocutaneous albinos and compared with the results from a group of 30 normally pigmented subjects. Amplitude and implicit time measures of the ERG recordings obtained from six autosomal recessive and three autosomal dominant tyrosinase-positive albinos fell within the normal range. The six tyrosinase-negative albinos examined also had normal ERGs at low-to-moderate flash luminances. However, at the highest flash luminances, the dark-adapted ERGs of five such subjects were at or just above the normal range in amplitude, and were shorter than normal in implicit time. The dark-adapted luminance-response functions of these subjects were positioned normally on the luminance axis; light-adapted functions were shifted slightly to the left of normal. The possibility that anterior parts of the retina responding to light passing through the anterior eyewall may contribute to the ERGs obtained from tyrosinase-negative albinos was examined by recording dark-adapted ERGs with the sclera occluded. Amplitudes were reduced compared with those obtained with the sclera unoccluded, suggesting that responses to transscleral illumination contributed to the ERG in this type of albinism.

Adolescent↗
PubMed1989

Histopathologic study of autosomal dominant vitreoretinochoroidopathy. Peripheral annular pigmentary dystrophy of the retina.

Autosomal dominant vitreoretinochoroidopathy (ADVIRC), a recently described disease, is clinically characterized by a slowly progressive or stationary circumferential peripheral pigmentary retinopathy with fibrillar condensation of the vitreous. Histopathologic study of an 88-year-old patient with this disease showed disorganization of the peripheral retina with focally atrophic retinal pigment epithelium (RPE). Altered pigment epithelial cells surrounded retinal blood vessels and lined the internal limiting membrane. At the equator, a remarkable and possibly unique multifocal loss of photoreceptor cells was seen. An extensive preretinal membrane, consisting of condensed vitreous with cellular debris and layers of Müller cells, was demonstrated by electron microscopic examination and immunohistochemistry. Histologically, this entity has some similarities to and some differences from retinitis pigmentosa. The clinical features are distinctive.

Aged↗
PubMed1989

Rod-cone dystrophy associated with a rod system electroretinogram obtained under photopic conditions.

A 14-year-old girl with a history of night blindness and poor visual acuity was examined. Cystic-appearing lesions were apparent in the fovea, and pigmentary changes were observed in the midperipheral retina. Electroretinograms (ERGs) recorded from the dark- and light-adapted eye were similar in waveform, implicit time, and approximate amplitude. Results of examination of the spectral characteristics of the light-adapted ERG demonstrated that the recordings represented activity of the rod system, despite the presence of a background field, which eliminates the response of the rod system in normal subjects.

Adaptation, Ocular↗
PubMed1989

Letter contrast sensitivity in retinitis pigmentosa patients assessed by Regan charts.

Regan Contrast Sensitivity Letter Charts were used to assess the effects of reduced contrast and luminance on visual acuity in retinitis pigmentosa (RP) patients. Letter acuity was measured monocularly in 17 RP patients and in 14 age-similar normals using charts of three different contrast levels presented at each of four levels of illumination. Despite visual acuities of 20/40 or better under standard clinical test conditions, an appreciable number of RP patients were unable to identify any letters on the intermediate- and/or low-contrast Regan charts. For example, even at the recommended test luminance, 5 patients could not read any letters on the intermediate (11%) contrast chart, and 9 could not be scored on the low (4%) contrast chart. Consequently, the Regan charts were found to have limited usefulness in quantifying the exact extent of visual impairment in this group of RP patients. Nevertheless, our results document the degree of visual acuity loss that can be experienced by RP patients under conditions of low contrast and luminance.

Adolescent↗
PubMed1989

Evaluation of pure tone and speech discrimination changes in Usher's syndrome.

Twenty-three adult patients with type 2 Usher's syndrome were evaluated for changes in pure tone average (PTA), discrete frequency thresholds, and speech discrimination scores. These patients were evaluated over a period of 5 years on the average (range, 2 to 9 years). Analyses of ear data showed a less than 10-dB change on PTA and discrete frequency thresholds for most ears. Of the ears that showed a threshold change greater than or equal to 10 dB, statistical significance was reached only at 4,000 Hz (p less than .01), where 11 ears representing ten patients dropped 10 to 15 dB. Speech discrimination data showed a greater than or equal to 16% change in score for 18 ears (12 patients). Sixteen of those ears (ten patients) had a 16% to 52% decrease in score (p less than .01), and the remaining two ears (two patients) showed a 20% and 30% improvement in score. These findings document little or no change in pure tone sensitivity for type 2 Usher's syndrome patients, but demonstrate the importance of monitoring their speech discrimination performance.

Adult↗
PubMed1988

Abnormal axonemes in X-linked retinitis pigmentosa.

Sperm of patients with X-linked retinitis pigmentosa (RP) was studied to assess the state of the axoneme in this genetic subtype. Semen samples were collected from eight patients with X-linked RP and compared with a database of 31 controls. Semen was also collected from two patients with other retinal degenerations (choroideremia and fundus flavimaculatus) and patients with simplex RP. All controls and patients were studied under a masked protocol. There was a significant increase in the percentage of abnormal sperm tails at both the light and electron microscopic levels in patients with X-linked RP only. Thus, X-linked RP is associated with an alteration in sperm axoneme structure. Sperm cell analysis may serve as a useful model system for additional investigations into the pathogenesis of this disease.

Adult↗
PubMed1988

X-linked retinitis pigmentosa. Profile of clinical findings.

An evaluation of 56 patients with X-linked retinitis pigmentosa revealed a profile of findings that include the following: night blindness within the first two decades of life; spherical refractive errors of -2.00 diopters or greater in addition to an increased prevalence of a cylindrical correction of +1.50 diopters or greater; appreciable impairment of central visual acuity to 20/200 or less by the fifth decade of life; characteristic patterns of field loss; presence of a foveal lesion in up to 75% of the study group; posterior subcapsular lens opacities; and nondetectable electroretinographic amplitudes in more than two thirds of the patients (using conventional full-field recording procedures). These observations are of general value in diagnosis of this disease and for counseling of patients afflicted with this severe form of hereditary night blindness.

Actuarial Analysis↗
PubMed1988

Histopathologic findings in Best's vitelliform macular dystrophy.

Postmortem donor eyes from a 69-year-old man with Best's vitelliform macular dystrophy showed retinal pigment epithelial cells across the entire fundus that had accumulated an excessive amount of lipofuscin as defined by ultrastructural appearance, autofluorescence studies, and staining properties. Lipofuscin accumulation was particularly notable in some pigment epithelial cells in the fovea. An accumulation of heterogeneous material located between Bruch's membrane and the pigment epithelium in the fovea was believed to represent the location of a previtelliform lesion. This material appeared to be derived from degenerating pigment epithelial cells and contained few intact lipofuscin granules. Foveal photoreceptor loss occurred above the lesion and in midperipheral sites where the subretinal space contained collections of outer segment debris and phagocytic cells. Best's vitelliform macular dystrophy appears to be a generalized disorder of the pigment epithelium that secondarily affects focal areas of the retina.

Adult↗