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Changes in the DC electroretinogram in Briard dogs with hereditary congenital night blindness and partial day blindness.

Five Briard dogs, 7-12 months old, with congenital night blindness and severely reduced day vision (offspring of a sister and brother with congenital and supposedly stationary night blindness but with normal or nearly normal day vision) and three normal control dogs were studied by means of direct current (DC) electroretinography in order to analyse fast and slow retinal and pigment epithelial (RPE) potentials. No definite a- and b-waves were seen in the affected dogs in the dark-adapted state, which indicates severely impaired rod function. All affected dogs responded to 30 Hz flickering light in the light-adapted state, although with an amplitude reduced by 50-70%. Thus, cone function was better preserved than rod function. The control dogs showed a small c-wave and a deep negative trough between the b- and c-waves, indicating that slow PIII from the Müller cells, as well as the photoreceptor potential, are very prominent. In the affected dogs, there was no c-wave, but from a stimulus intensity of 3 log U above the normal b-wave threshold, a slow negative potential appeared, the latency and peak time of which were very long, 5-7 and 11-15 sec, respectively. With increasing stimulus intensities, both parameters decreased substantially, whereas the amplitude increased to a maximum of 2400 microV. In the light-adapted state, the dog with the best day vision showed a negative potential of short duration (peak time about 0.2 sec), followed by a positive potential (peak time about 1.2 sec).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ultrastructural changes of the retina and the retinal pigment epithelium in Briard dogs with hereditary congenital night blindness and partial day blindness.

The offspring of two Briard dogs (brother and sister) with congenital, clinically stationary night blindness showed an aggravation of the disease with severe impairment of day vision in addition to night blindness. This ultrastructural study was performed on four such second generation puppies at the age of 4 months. The neuroretina and retinal pigment epithelium (RPE) from four locations were studied: the central area (immediately temporal to the optic disc); the centre of the tapetal area; the upper periphery (border of tapetal area); and the lower periphery (non-tapetal area). The RPE showed large inclusions, seemingly lipid in nature, mainly in the central and tapetal areas of the retina. Small, membrane bound, electron-dense inclusions were scattered in the RPE cytoplasm in all areas examined. The small inclusions were found to be less numerous in normal than in affected dogs and may be lysosomal in nature. Forty to fifty percent of the rod outer segments in the tapetal area showed disorientation of the disc membranes, whereas the corresponding figures were 20-40% in the central and lower peripheral areas and 6-25% in the upper peripheral area. No structural abnormalities were found in the rod inner segments or synaptic bodies. The cones were better preserved. The inner retina appeared normal. These electron microscopic findings seem to correspond to a previously published electrophysiologic evaluation, indicating a defective and delayed rod function (virtually no scotopic a- and b-waves), a better preserved cone function (photopic flicker responses present, although reduced) and impaired RPE activity (a prominent, slow negative potential of long latency at the site of the c-wave). It appears that these Briard dogs, showing structural changes of the rod outer segments in addition to pigment epithelial inclusions, mainly located in the posterior pole, comprise a pigment epitheliopathy and retinopathy morphologically different from other hereditary canine retinopathies that have been described earlier in the literature and different from animal models of congenital night blindness.

Animals↗

Genetic heterogeneity of day blindness in Alaskan Malamutes.

Day blindness is a progressive and specific degeneration of cone photoreceptors in the retina of young dogs. This disorder has been associated with a breed-specific non-synonymous substitution in exon 6 of the cyclic nucleotide gated channel beta3 (CNGB3) gene in German Shorthaired Pointer dogs and a genomic deletion removing the entire gene in Alaskan Malamute dogs from the USA. To further investigate this disorder, we characterized CNGB3 in a three-generation pedigree of Alaskan Malamute dogs from Australia segregating for day blindness. Fifteen of the dogs showed clinical signs of day blindness. Four of these were definitively diagnosed by standardized electroretinography. Polymerase chain reaction amplification of exon 6 of CNGB3 was attempted, and as expected, amplification was successful in the 18 unaffected or carrier dogs. However, a non-mutated exon 6 was also amplified and sequenced in six of the 15 affected dogs. On sequencing each exon and exon/intron boundary in two such affected individuals and two unaffected individuals, three exonic substitutions and 12 intronic changes were noted. These sequence variations in affected individuals were also present in one or both unaffected dogs and so appear to have no obvious effect on the protein's function. Hence, day blindness shows genetic heterogeneity within the Alaskan Malamute population of Australia, a result that is somewhat unexpected given the relatively small effective population size of this breed.

Animals↗

Day-blindness in three dogs: clinical and electroretinographic findings.

A 6-month-old Rhodesian ridgeback-cross, a 6-year-old Chihuahua and a 12-month-old Australian cattle dog were presented to the authors with a history of colliding with obstacles in daylight. Ophthalmic examination was normal and all three dogs successfully negotiated obstacle courses in dim light. In daylight the dogs became suddenly blind and repeatedly collided with obstacles. Elecroretinography (ERG) revealed no retinal activity to high frequency (30 Hz), bright intensity blue light retinal stimulation by any dog, confirming cone dysfunction. Achromatopsia has previously been recorded in Alaskan malamutes and miniature poodles. This clinical case series illustrates the characteristic behavioral presentation and the electroretinographic findings of severe day-blindness and demonstrates that this condition may exist in other breeds of dogs.

Animals↗

Day-blindness.

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Blindness↗

Canine inherited retinal degenerations: update on molecular genetic research and its clinical application.

Inherited retinal degenerations in the dog include generalised progressive retinal atrophy, retinal pigment epithelial dystrophy, congenital stationary night blindness and day blindness (hemeralopia). The clinical phenotype and pathology of these diseases closely resemble some types of human inherited retinal degeneration, in particular retinitis pigmentosa, one of the most common inherited causes of blindness in man. Molecular genetic investigations aim to identify the genetic mutations underlying the canine inherited retinal degenerations. Two major research strategies, candidate gene analysis and linkage analysis, have been used. To date, candidate gene analysis has definitively identified the genetic mutations underlying nine inherited retinal degenerations, each in a different breed of dog, and linkage studies have identified genetic markers for a further retinal degeneration which is found in at least six different breeds. This review outlines the research strategy behind candidate gene and linkage studies and summarises recent results in the search for genetic causes of canine inherited retinal degenerations. The aim is to increase awareness of this rapidly changing field and to show how the research can be used to develop genetic tests for these diseases and thereby reduce the incidence of inherited eye disease in dogs.

Animals↗

Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls.

BACKGROUND: Increased generation of reactive oxygen species (ROS) and oxidative stress may be of crucial importance in the pathogenesis of endothelial damage. Furthermore, there is understood to be a relationship between endothelial damage, glycemic control, disorders of lipid metabolism, and coagulative hemostatic disorders. OBJECTIVE: This study investigated within- and between-group changes in various circulating markers of oxidation-reduction balance and endothelial function after a balanced moderate-fat meal with and without antioxidant supplementation in patients with early-stage, untreated type 2 diabetes mellitus; subjects with impaired glucose tolerance (IGT); and healthy controls. METHODS: In this single-blind, controlled clinical study, groups of patients with type 2 diabetes and subjects with IGT were identified and compared with a group of healthy controls. All groups followed a controlled, well-balanced diet for 10 days before and throughout the study. Before and after consumption of a standardized moderate-fat meal, plasma levels of oxidants (malondialdehyde, 4-hydroxynonenal, oxidized low-density lipoprotein), the antioxidant glutathione peroxidase, and markers of endothelial function (NO, endothelin-1, von Willebrand factor [vWF], vascular cell adhesion molecule-1 [VCAM-1]) were determined. These measures were then reassessed after 15 days of standard antioxidant treatment consisting of a thiol-containing antioxidant (N-acetylcysteine 600 g/d), a bound antioxidant (vitamin E 300 g/d), and an aqueous phase antioxidant (vitamin C 250 mg/d). The efficacy of antioxidant treatment in reversing abnormalities in oxidation-reduction balance after a moderate-fat meal was assessed by evaluating changes in plasma levels of ROS on the morning of the 16th day following an overnight fast. Safety was monitored in terms of adverse events, vital signs, physical findings, and laboratory values. RESULTS: The study included 46 patients with type 2 diabetes (23 men, 23 women; mean [SD] age, 41 [3] years; mean body mass index [BMI], 24 [2] kg/m(2)), 46 with IGT (23 men, 23 women; mean age, 39 [3] years; mean BMI, 23 [3] kg/m(2)), and 46 control subjects (23 men, 23 women; mean age, 40 [1] years; mean BMI, 22 [1] kg/m(2)). Before supplementation, all 3 groups had significantly increased levels of oxidants, vWF, and VCAM-1 (all, P < 0.001) and significantly decreased levels of antioxidants and NO (both, P < 0.001) after consumption of a moderate-fat meal. After 15 days of antioxidant treatment, significant improvements in these measures were seen in all groups (P < 0.05). CONCLUSIONS: This study showed changes in oxidation-reduction balance, NO bioavailability, and nonthrombogenic endothelial factors after a moderate-fat meal in patients with type 2 diabetes and those with IGT, but these postprandial changes were reverse in all subjects after 15 days of standard antioxidant supplementation. These findings suggest that the use of anti-oxidants may have decreased oxidative stress in these subjects.

Acetylcysteine↗

Generalized progressive retinal atrophy in two Akita dogs.

Two distantly related, two- to three-year-old male Akita dogs developed partial or complete night blindness which progressed to day blindness. Clinical features were attenuated retinal blood vessels, diffuse exaggerated tapetal reflex, and hyperreflective horizontal lines in the tapetal fundus. The principal histologic change was regional photoreceptor cell degeneration. Areas of moderately atrophic sensory retina alternated, concentrically to the papilla, with areas of severely atrophic retina. Ultrastructurally, there was disorganization of photoreceptor outer segments, retinal gliosis, focal loss with reorganization of the outer limiting membrane, and retinal invasion by pigment epithelium-derived macrophages. Clinical observations on five additional Akitas with generalized retinal atrophy suggest that the condition is heritable.

Animals↗

Ultrastructural study of the distribution of calcium in the pineal gland of the rat subjected to manipulation of the photoperiod.

Using the pyroantimoniate technique, a study was conducted at electron microscope level on the distribution of the calcium ion in the pineal glands of normal adult Sprague-Dawley rats with initial weights of 150-200 g subjected to a 12:12 light dark cycle and others under the same conditions were subjected to modifications in the noradrenergic signal, such as continuous illumination over 7 days, blinding by bilateral enucleation (7 or 90 days) before sacrifice and bilateral superior cervical gangliectomy at 21 days before sacrifice. All the animals were sacrificed by decapitation, half of them at midday and the other half at midnight. Abundant fine precipitations of calcium were found in the intercellular spaces of the pineal glands of the normal rats. By contrast, in the gangliectomized animals subjected to constant illumination and chronic binding these precipitations were few in number. Additionally, two types of pinealocytes were observed regarding the distribution and concentration of intracytoplasmic calcium in both the normal and experimentally manipulated animals. Type I correspond to the classic light pinealocytes, with an absence of intracytoplasmic precipitations, although in the normal and gangliectomized animals sacrificed at midnight it was possible to observe fine deposits inside the mitochondrial matrix. Type II correspond to the classic dark pinealocytes, with a dense cytoplasmic matrix and numerous deposits of intracytoplasmic and intranuclear calcium; these were never seen in the type I pinealocytes.

Adrenergic Fibers↗

Can a day 4 bone scan accurately determine the presence or absence of scaphoid fracture?

STUDY OBJECTIVE: To evaluate the accuracy of day 4 bone scans in predicting the presence or absence of fracture in patients with "clinical scaphoid fracture." DESIGN: Prospective sensitivity study of ED patients with clinical scaphoid fractures. Each patient was immobilized in a thumb spica cast and had day 4 bone scans of both wrists and hands. Blinded day 4 bone scan results were ultimately compared with the diagnosis on day 14 when patients returned for repeat clinical examination and radiographs. In cases of equivocal radiographic or clinical examination results, a day 14 bone scan was performed. SETTING: Two tertiary care teaching hospital emergency departments. PARTICIPANTS: All ED patients older than 16 years with the diagnosis of clinical scaphoid fracture were eligible. RESULTS: Ninety-nine patients were enrolled and successfully completed the study protocol from October 1990 through November 1992. One patient had bilateral injury, for a total of 100 completed studies. Day 4 bone scans were 100% sensitive and 92% specific, for a positive predictive value of 65%, a negative predictive value of 100%, and accuracy of 93% (95% confidence interval, 88%, to 98%). Many other types of fractures were identified on the day 4 scans, including those of the triquetra, distal radius, capitate, hamate, trapezoid, trapezium, and metacarpals. CONCLUSION: Day 4 bone scans are an accurate means of ruling out scaphoid fracture. However, because of a significant number of false-positive scans at day 4, they do not reliably confirm the diagnosis of scaphoid fracture. The bone scans also permitted identification of several other wrist fractures that had not been radiographically apparent.

Adolescent↗

Identifying responders to acid suppression in dyspepsia using a random starting day trial.

BACKGROUND: Functional dyspepsia is a heterogeneous condition and a uniform response to drug treatment is not likely. This may be the reason for the general failure of acid suppression in clinical trials in these patients. It may be more rewarding to identify true responders to drug treatment by a single subject trial. AIM: To develop and to test a novel single subject trial design (random starting day trial) in dyspeptic patients. PATIENTS AND METHODS: A total of 301 dyspeptic patients entered a 16-day trial. All patients received placebo for the first 4 days and switched to omeprazole at a randomized and blinded day between day 5 and day 14. Response was defined as a sustained >/= 50% decrease in symptom score occurring in relation to drug shifting. RESULTS: Spontaneous response varied between 0.3% and 10.6% per day, uniformly distributed over time. Overall, 53-61% of patients with organic dyspepsia had a symptom response in relation to shifting to active treatment, compared to only 23% of patients with functional dyspepsia. The only predictor of response was symptoms suggesting gastro-oesophageal reflux. CONCLUSIONS: A random starting day trial may be a valuable tool to identify response to acid suppression in dyspeptic patients.

Adult↗

Blindness and play fighting in juvenile rats.

Play behavior of blinded and sighted juvenile rats was measured using the brief paired-encounter procedure. Dyads of sighted-sighted, blind-blind, or sighted-blind rats were observed in a large or small chamber on alternate days for ages 28 through 43 days. Blinded rats played as frequently as sighted rats regardless of pair composition or chamber size. Vision is not essential for initiating or maintaining play fighting.

Aggression↗