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PubMed2001

Anatomic review and topographic diagnosis.

Neuro-ophthalmologic disorders, affecting the afferent and efferent visual systems, are frequently encountered by ophthalmologists in clinical practice. This article focuses on aspects of ocular, orbital, and neuroanatomy that are most important to the diagnosis of afferent and efferent visual pathway lesions. The use of optic disc and fundus appearance, visual fields, and ocular motility and pupillary findings are emphasized in the discussions of topographical diagnosis.

Humans↗
PubMed1995

Motion perception deficits in glaucomatous optic neuropathy.

The mechanisms mediating impaired motion perception in glaucoma were investigated. Direction discrimination thresholds for low (4.2 deg/sec) and high (12.5 deg/sec) velocity random-dot kinematograms were measured in controls and patients with glaucoma or ocular hypertension. Thresholds were elevated significantly in glaucoma patients and individual ocular hypertensives. Threshold elevations were not due to blur or pupil size. After compensating for motion reversals, high but not low velocity thresholds remained elevated. Only high velocity thresholds correlated with differential luminance sensitivity. A hypothesis that different mechanisms mediate glaucoma-induced deficits at high and low velocities is presented.

Adult↗
PubMed2002

Selective loss of cholinergic sudomotor fibers causes anhidrosis in Ross syndrome.

Ross syndrome consists of segmental hyperhidrosis with widespread anhidrosis, Adie syndrome, and areflexia. The cause of this disorder is unknown. Selective degeneration of cholinergic fibers or of neural crest-derived structures has been suggested. We present clinical and skin biopsy data of 4 patients, providing evidence of reduced cholinergic sweat gland innervation in hypohidrotic skin by morphometric analysis. These findings indicate a selective degenerative process of the cholinergic sudomotor neurons.

Adult↗
PubMed1988

Buprenorphine: dose-related blockade of opioid challenge effects in opioid dependent humans.

This study assessed the blockade of hydromorphone challenge effects (cumulative s.c. doses of 0, 6 and 18 mg) during chronic buprenorphine treatment of opioid dependent subjects. Buprenorphine was administered daily via the sublingual route in ascending doses of 2, 4, 8 and 16 mg. Hydromorphone challenges were conducted after 10 to 14 days of chronic administration of each buprenorphine dose and 24 h after the last buprenorphrine dose. Buprenorphrine itself only produced dose-related effects in respiration rate. While subjects were maintained on 2 mg of buprenorphine, the hydromorphone challenge produced dose-related changes in physiological and self-report measures. As the dose of buprenorphine was increased, hydromorphone effects on self-report measures were attenuated to a greater extent than was noted for pupil diameter. The results of this study confirm previous reports of buprenorphine blockade of opioid agonist effects in humans and extent those findings by demonstrating both a buprenorphine dose-effect function and a dissociation between the potency of buprenorphine's opioid blockade for self-report vs. physiological measures.

Adult↗
PubMed2006

Cardiac malformations and midline skeletal defects in mice lacking filamin A.

The X-linked gene filamin A (Flna) encodes a widely expressed actin-binding protein that crosslinks actin into orthogonal networks and interacts with a variety of other proteins including membrane proteins, integrins, transmembrane receptor complexes and second messengers, thus forming an important intracellular signalling scaffold. Heterozygous loss of function of human FLNA causes periventricular nodular heterotopia in females and is generally lethal (cause unknown) in hemizygous males. Missense FLNA mutations underlie a spectrum of disorders affecting both sexes that feature skeletal dysplasia accompanied by a variety of other abnormalities. Dilp2 is an X-linked male-lethal mouse mutation that was induced by N-ethyl-N-nitrosourea. We report here that Dilp2 is caused by a T-to-A transversion that converts a tyrosine codon to a stop codon in the Flna gene (Y2388X), leading to absence of the Flna protein and male lethality because of incomplete septation of the outflow tract of the heart, which produces common arterial trunk. A proportion of both male and female mutant mice have other cardiac defects including ventricular septal defect. In addition, mutant males have midline fusion defects manifesting as sternum and palate abnormalities. Carrier females exhibit milder sternum and palate defects and misshapen pupils. These results define crucial roles for Flna in development, demonstrate that X-linked male lethal mutations can be recovered from ENU mutagenesis screens and suggest possible explanations for lethality of human males hemizygous for null alleles of FLNA.

Animals↗
PubMed1991

Acute glaucomas: diagnosis and treatment.

Acute angle-closure glaucoma is an uncommon disorder that must be diagnosed and managed quickly and effectively to prevent visual loss. Several conditions may appear as an acute angle-closure glaucoma and must be recognized since, in certain cases, treatment may be different from that required for an acute angle-closure attack. Once an acute angle-closure attack has been successfully managed through medical treatment, a laser iridotomy is indicated to prevent an attack from recurring.

Acute Disease↗
PubMed1987

Human pharmacology and abuse potential of meptazinol.

Meptazinol was assessed in nine opioid abusers according to a double-blind, randomized, crossover design to determine if it produced typical morphine effects. A comparison of physiologic and subjective effects was made between morphine, 7.5, 15, and 30 mg, meptazinol, 70, 140, and 280 mg, and placebo. Both drugs constricted pupils. Meptazinol, 140 and 280 mg, decreased body temperature. Valid relative potency estimates of morphine to meptazinol were obtained for self-reported liking, opiate symptoms, and pupillary constriction. Meptazinol did not increase euphoria or sedation scale scores but did increase dysphoria scale scores. In the therapeutic dose range, meptazinol produced miosis, morphine-like identification and symptoms, limited liking, and some dysphoria. Dysphoria predominated at the 280 mg dose of meptazinol. From these data, it is concluded that meptazinol is not a typical morphine-like drug and has limited abuse potential.

Adult↗
PubMed2005

Within- and between- subject variability in methadone pharmacokinetics and pharmacodynamics in methadone maintenance subjects.

AIMS: To investigate within- and between-subject variability of the pharmacodynamics and pharmacokinetics of (R)- and (S)-methadone in methadone maintenance subjects at steady-state. METHODS: Six non-holder subjects were studied on three occasions at 7-16 day intervals; doses (20-170 mg/day) remained unchanged. Blood samples and pharmacodynamic data were collected 10-12 times over a 24-h inter-dosing interval. All pharmacodynamic data were expressed as the area under the end-point versus time curve. Using analyses of variance with mixed effects, best estimates were made of the ratio of between- to within-subject variation, with corresponding 95% confidence intervals (CI) for within-subject variation at the average value. RESULTS: Subjects were relatively consistent between occasions, whereas there was much greater between-subject variability (P < 0.02) for all measures. Estimates of the ratio of between- to within-subject variation ranged from 2.2-12.8 for pharmacodynamic measures, and 1.3-7.9 for pharmacokinetic parameters. For pain, total mood disturbance, withdrawal, pupil size and respiration rate, 95% CI for within-subject measures ranged < or = 2-fold, while this was greater for subjective direct opioid effects (4.2-fold). For CL/F of the active (R)-methadone, the variance ratio was 4.9 (P < 0.0003), with 95% CI for within-subject measures ranging < or = 2-fold. (S)-methadone CL/F demonstrated greater within-subject variability (3.4-fold), possibly contributing to a smaller (2.7; P < 0.0003) ratio of between- to within-subject variance. CONCLUSIONS: Non-holder methadone maintenance treatment participants appear to respond consistently with respect to pharmacokinetics and pharmacodynamics over a 1-2 month period. Such knowledge may help prescribers to determine whether alternative dosing regimens or treatments might be more appropriate in this population.

Adult↗
PubMedDate not supplied

[Marcus Gunn Phenomenon: differential diagnosis of palpebral ptoses in children].

OBJECTIVE: The aim of this paper is to review existing literature on the subject and to report on and discuss a case of Marcus Gunn Phenomenon. DESCRIPTION: A five year-old female, otherwise a healthy patient, while still a few months old, was seen by a pediatrician who detected a disorder of the right eye, initially believed to be strabismus, at a follow-up childcare consultation. Several ophthalmologists failed to establish a precise diagnosis. After a pediatric ophthalmologist had examined the child at four years of age, a diagnosis of Marcus Gunn Phenomenon, otherwise known as jaw-winking phenomenon, was confirmed. Apart from this anomaly, physical, ophthalmological, and neurological examinations were normal. Since ptosis was mild and no association with strabismus, amblyopia or other conditions was established, no surgical procedures were necessary. COMMENTS: This report is an alert to pediatricians regarding the presence of this largely unknown phenomenon, making it possible for pediatricians to identify the phenomenon, refer the patient to an ophthalmologist, and establish differential diagnosis from other, more severe forms of ptosis, requiring more aggressive treatment.

Amblyopia↗
PubMed1982

Short-term effects of oral methadone in methadone maintenance subjects.

In two experiments the physiologic and subjective status of methadone maintenance patients was assessed during the presumed peak (0 to 6 hr postmethadone) and during the presumed nadir of the daily methadone effect (18 to 30 hr postmethadone). In the first experiment physiologic and subjective responses were measured in seven ambulatory subjects at 2, 4, and 6 hr after a regular daily dose of methadone or placebo. In the second, physiologic measures were continuously monitored for 4 hr in six inactive seated subjects. In both studies, pupil diameter decreased after moderate to high methadone doses (35 to 80 mg). In the second experiment, heart rate fell and skin temperature rose significantly after methadone. Responses to the morphine-benzedrine group scale of the Addiction Research Center Inventory were elevated after methadone for most subjects in both studies, although there were individual differences in the magnitude and time course of this effect. Finally, low methadone maintenance doses of 10 and 20 mg/day had little or no effect on physiologic or subjective responses in two subjects. These studies showed that short-term effects of oral methadone can be readily detected during a 24-hr dosing regimen. The changes in function after the regular maintenance dose may result both from short-term opiate effects and relief of mild withdrawal.

Adult↗
PubMed2000

[Ultrasound biomicroscopic examination of secondary pupillary block glaucoma].

OBJECTIVE: To study the imaging characteristics of ultrasound biomicroscopy of secondary pupillary block glaucoma. METHODS: 11 cases with pupillary block glaucoma diagnosed by ultrasound biomicroscopy were studied which had been suspected as malignant glaucoma at the beginning. RESULTS: There were no obviously typical characteristics of pupillary block glaucoma shown in the images of ultrasound biomicroscopy in these cases. However, the existence of posterior chamber in each case strongly supported the diagnosis of pupillary block glaucoma. The imaging characteristics of ultrasound biomicroscopy were different in terms of the different primary disorders which resulted in the pupillary block glaucoma including iridocyclitis, lens subluxation resulted from trauma and glaucoma filtration surgery. In the cases of lens subluxation, the main characteristic was the increase of the distance between the lens and the ciliary process at the site of subluxation and the lens forward movement. In the cases of iridocyclitis, anterior and posterior synechiae were the main characteristics. And in the cases of glaucoma filtration surgery there were two main characteristics. One was that the distance between the ciliary process and the equator of lens existed obviously, and the other was the occlusion of the inner ostium of glaucoma filtration surgery or peripheral iridectomy. CONCLUSION: Ultrasound biomicroscopy (UBM) has important value in the diagnosis of secondary pupillary block glaucoma and the differentiation between it and malignant glaucoma. Whether the posterior chamber exists or not is the differential point between the pupillary block glaucoma and the malignant glaucoma.

Adult↗
PubMed1996

The relative afferent pupillary defect and a novel method of fusion recovery with the Worth 4-dot test.

OBJECTIVE: To examine the relation of the relative afferent pupillary defect and commonly used clinical tests of visual cortex binocular cell activity, namely, fusion and stereopsis. METHODS: Sixty-seven subjects with neuro-ophthalmologic disorders underwent measurement of relative afferent pupillary defect and assessment of binocular sensory status by fusion on the Worth 4-dot test and stereopsis on the Titmus stereo test. Recovery of fusion on the Worth 4-dot test and improvement of stereopsis were tested by placing increasing neutral density filters in front of the eye that did not have the afferent pupillary defect. RESULTS: Recovery of fusion on the Worth 4-dot test occurred with use of neutral density filters (Worth 4-dot neutralization test). No improvement of stereopsis was observed. A significant positive association was identified between the measured afferent pupillary defect and the measured log filter required for fusion (r = .83, P < .001 by the Spearman rank correlation coefficient). In no case was a relative afferent pupillary defect observed when fusion without use of neutral density filters was present at baseline. For subjects with relative afferent pupillary defects, the measurements of the Worth 4-dot neutralization test were equal before and after pupillary dilation. CONCLUSIONS: The relative afferent pupillary defect is a dynamic process that results from an imbalance of brightness sensitivity between the two eyes. Altering the latency ("timing") and amplitude of the light stimuli by use of neutral density filters can restore fusion on the Worth 4-dot neutralization test but does not alter stereopsis. The Worth 4-dot neutralization test may be a useful adjunct in the assessment of visual dysfunction.

Adolescent↗
PubMed2004

Subjective and physiological responses among racemic-methadone maintenance patients in relation to relative (S)- vs. (R)-methadone exposure.

AIMS: To investigate the possibility that (S)-methadone influences therapeutic and adverse responses to rac-methadone maintenance treatment, by examining how subjective and physiological responses among rac-methadone maintenance patients vary in relation to relative exposure to (S)- vs. (R)-methadone. METHODS: Mood states (Profile of Mood States), opioid withdrawal (Methadone Symptoms Checklist), physiological responses (pupil diameter, heart rate, respiration rate, blood pressure), and plasma concentrations (CP) of (R)- and (S)-methadone were measured concurrently 11-12 times over a 24-h interdosing interval in 55 methadone maintenance patients. Average steady-state plasma concentrations (C(av)) and pharmacodynamic responses were calculated using area under the curve (AUC). Linear regression was used to determine whether variability in pharmacodynamic responses was accounted for by (S)-methadone C(av) controlling for (R)-methadone C(av) and rac-methadone dose. Ratios of (S)-:(R)-methadone using AUC(CP) and trough values were correlated with pharmacodynamic responses for all subjects and separately for those with daily rac-methadone doses > or = 100 mg. RESULTS: (S)-methadone C(av) accounted for significant variability in pharmacodynamic responses beyond that accounted for by (R)-methadone C(av) and rac-methadone dose, showing positive associations (partial r) with the intensity of negative mood states such as Tension (0.28), Fatigue (0.31), Confusion (0.32), and opioid withdrawal scores (0.30); an opposite pattern of relationships was evident for (R)-methadone. The plasma (S)-:(R)-methadone AUC(CP) ratio (mean +/- SD 1.05 +/- 0.21, range 0.65-1.51) was not significantly related to pharmacodynamic responses for the subjects as a whole but showed significant positive associations (r) with the intensity of negative mood states such as Total Mood Disturbance (0.61), Tension (0.69), Fatigue (0.65), Confusion (0.64), Depression (0.49) and heart rate (0.59) for the > or = 100-mg dose range. CONCLUSIONS: These findings agree with previous evidence that (S)-methadone is associated with a significant and potentially adverse profile of responses distinct from that of (R)-methadone. Individual variability in relative (S)- vs. (R)-methadone exposure may be associated with variability in response to rac-methadone maintenance treatment.

Adult↗
PubMed2004

Isolated relative afferent pupillary defect secondary to contralateral midbrain compression.

BACKGROUND: Relative afferent pupillary defects are typically related to ipsilateral lesions within the anterior visual pathways. OBJECTIVE: To describe a patient who had a workup for headache and was found to have an isolated left relative afferent pupillary defect without any other neurological findings. DESIGN: We review the neuroanatomy of the pupillary light reflex pathway and emphasize the nasotemporal bias of decussating fiber projections, which accounts for the relative afferent pupillary defect contralateral to the described lesion. Result Magnetic resonance imaging of the brain revealed a pineal tumor compressing the right rostral midbrain. CONCLUSION: While rare, a relative afferent pupillary defect can occasionally occur secondary to lesions in the postchiasmal pathways. In these circumstances, the pupillary defect will be observed to be contralateral to the side of the lesion.

Adult↗
PubMed2001

Quantification of optic nerve axon loss associated with a relative afferent pupillary defect in the monkey.

OBJECTIVE: To quantify the amount of optic nerve axonal loss associated with the presence of a mild relative afferent pupillary defect (RAPD) in an experimental monkey model. METHODS: The right macula of 5 rhesus monkeys (Macaca mulatta) was treated with concentrically enlarging diode laser burns until an RAPD was detected using a transilluminator light and measured with neutral density filters. Intervals between treatments were 3 to 7 days over a period of 2 months. Pupillary responses to light stimulation were recorded with a monocular infrared television pupillometer. Two months after detection of an RAPD, 5 treated and 4 control monkeys underwent euthanasia and enucleation. Histopathologic analysis and quantification of optic nerve axon counts using an image analysis system were performed. RESULTS: No RAPD was observed despite an estimated ganglion cell loss of up to 26%. A 0.6 log unit RAPD was present in 5 monkeys when the laser scar incorporated the entire macula within the temporal vascular arcades. One eye had progressive vitreomacular traction with worsening of the RAPD to 1.8 log units without further laser treatment. Histopathologic evaluation disclosed complete loss of the normal retinal architecture within the macula. The average fiber loss for the 4 treated eyes with 0.6 log unit RAPDs compared with fellow eyes was 53.3% (95% confidence interval [CI], 45.0%-61.6%). The average difference in axon counts between untreated pairs of optic nerves was 12.8% (95% CI, 10.0%-15.6%). Optic nerve axon loss between pairs of experimental and control eyes was statistically significant (P<.001). CONCLUSION: In rhesus monkeys, an RAPD develops after an approximate unilateral loss between 25% and 50% of retinal ganglion cells. CLINICAL RELEVANCE: Owing to redundancy in the anterior visual pathways, unilateral retinal ganglion cell loss may occur prior to the observation of an RAPD. The presence of an RAPD measuring 0.6 log units implies that significant retinal ganglion cell injury has occurred.

Animals↗