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Biomedical subjects

N R Miller

Publications and source records attributed to N R Miller.

At least 19 recordsLinked to original sources
PubMed2006

Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional?

CSF is thought to flow continuously from the site of production in the ventricles into interconnected spaces; i.e. cisterns and subarachnoid spaces (SASs). Since the SAS of the optic nerve is defined by a cul-de-sac anatomy, it is not evident how local CSF might recycle from that region to the general SAS. The concept of free communication of CSF has recently been challenged by the description of a concentration gradient of beta-trace protein, a lipocalin-like prostaglandin d-synthase (L-PGDS), between the spinal CSF and that in the SAS of the optic nerve, indicating diminished local clearance or local overproduction of L-PGDS here. In fact, computed cisternography with a contrast agent in three patients with idiopathic intracranial hypertension and asymmetric papilloedema demonstrate a lack of contrast-loaded CSF in the SAS of the optic nerve despite it being present in the intracranial SAS, thus suggesting compartmentation of the SAS of the optic nerve. The concept of an optic nerve compartment syndrome is further supported by a concentration gradient of brain-derived L-PGDS between the spinal CSF and the CSF from the optic nerve SAS in the same patients.

Adult↗
PubMed2006

The optic nerve: a new window into cerebrospinal fluid composition?

Cerebrospinal fluid (CSF) pressure and composition are generally thought to be homogeneous within small limits throughout all CSF compartments. CSF sampled during lumbar puncture therefore should be representative for all CSF compartments. On the basis of clinical findings, histology and biochemical markers, we present for the first time strong evidence that the subarachnoid spaces (SAS) of the optic nerve (ON) can become separated from other CSF compartments in certain ON disorders, thus leading to an ON sheath compartment syndrome. This may result in an abnormal concentration gradient of CSF molecular markers determined in locally sampled CSF compared with CSF taken during lumbar puncture.

Adult↗
PubMed2005

Cook detachable coil embolization of a symptomatic, isolated orbital arteriovenous fistula via a superior ophthalmic vein approach.

Isolated arteriovenous fistulas of the posterior orbit occur with exceptional rarity, and their evaluation and management are not well characterized. We describe the clinical presentation and treatment of a spontaneous arteriovenous fistula of the right posterior orbit via a superior ophthalmic vein approach for embolization using platinum detachable coils.

Adult↗
PubMed2005

Feasibility of using ultrasound for real-time tracking during radiotherapy.

This study was designed to examine the feasibility of utilizing transabdominal ultrasound for real-time monitoring of target motion during a radiotherapy fraction. A clinical Acuson 128/XP ultrasound scanner was used to image various stationary and moving phantoms while an Elekta SL25 linear accelerator radiotherapy treatment machine was operating. The ultrasound transducer was positioned to image from the outer edge of the treatment field at all times. Images were acquired to videotape and analyzed using in-house motion tracking algorithms to determine the effect of the SL25 on the quality of the displacement measurements. To determine the effect on the dosimetry of the presence of the transducer, dose distributions were examined using thermoluminescent dosimeters loaded into an Alderson Rando phantom and exposed to a 10 x 10 cm2 treatment field with and without the ultrasound transducer mounted 2.5 cm outside the field edge. The ultrasound images acquired a periodic noise that was shown to occur at the pulsing frequency of the treatment machine. Images of moving tissue were analyzed and the standard deviation on the displacement estimates within the tissue was identical with the SL25 on and off. This implies that the periodic noise did not significantly degrade the precision of the tracking algorithm (which was better than 0.01 mm). The presence of the transducer at the surface of the phantom presented only a 2.6% change to the dose distribution to the volume of the phantom. The feasibility of ultrasonic motion tracking during radiotherapy treatment is demonstrated. This presents the possibility of developing a noninvasive, real-time and low-cost method of tracking target motion during a treatment fraction.

Algorithms↗
PubMed2004

Primary tumours of the optic nerve and its sheath.

PURPOSE: To describe the clinical, neuroimaging, and pathologic features of primary tumours of the optic nerve and its sheath. METHODS: Review of published cases and personal series. RESULTS: The most common primary tumour of the optic nerve is the benign glioma. This low-grade astrocytoma usually can be followed without intervention. Progression of visual symptoms and signs may necessitate either surgery to remove the tumour or radiation therapy. The most common tumour of the optic nerve sheath is the meningioma. The optimum treatment for this lesion is stereotactic or three-dimensional conformal fractionated radiation therapy, which generally results in stabilization or improvement in vision. A variety of other primary tumours may mimic, in both manifestations and imaging appearance, the more common glioma or meningioma. In such cases, the correct diagnosis may not be made until a biopsy is performed or the nerve is removed. CONCLUSION: Primary tumours of the optic nerve and its sheath are not uncommon. Diagnosis can often but not always be made by the results of a complete examination combined with imaging studies, particularly CT scanning and MR imaging. Management depends on the presumed or histologically verified nature of the tumour.

Ganglioglioma↗
PubMed2004

Long term visual and neurological prognosis in patients with treated and untreated cavernous sinus aneurysms.

OBJECTIVE: To determine the long term visual and neurological outcome of patients diagnosed with cavernous sinus aneurysms (CCAs). METHODS: Prospective follow up for at least five years or until death of 31 retrospectively recruited patients (27 women, 4 men) with treated and untreated CCAs. RESULTS: There were 40 aneurysms in all. Mean age at diagnosis was 60.4 years (range 25 to 86; median 64). The most common symptoms were diplopia (61%), headache (53%), and facial or orbital pain (32%). Fifteen patients (48%) were diagnosed after they developed cranial nerve pareses, four (13%) after they developed carotid-cavernous sinus fistulas (CCFs), and 12 (39%) by neuroimaging studies done for unrelated symptoms. Twenty one patients (68%) had treatment to exclude the aneurysm from circulation, 10 shortly after diagnosis and 11 after worsening symptoms. Immediate complications of treatment occurred in six patients and included neurological impairment, acute ophthalmoparesis, and visual loss. Ten patients (32%) were observed without intervention. Over a mean (SD) follow up period of 11.8 (7.7) years, eight had improvement in symptoms, five remained stable, and eight deteriorated. Among the 10 patients followed without intervention, none improved spontaneously, three remained stable, and seven worsened. CONCLUSIONS: Most treated patients in this series improved or remained stable after treatment, but none improved without treatment. The long term prognosis for treated cases is relatively good, with most complications occurring immediately after the procedure. Endovascular surgery has decreased the morbidity and mortality of treatment so should be considered for any patient with a CCA.

Adult↗
PubMed2004

Reversible bilateral internuclear ophthalmoplegia associated with FK506.

A 50 year old man developed tonic-clonic seizures while receiving cyclosporin A after orthotopic cardiac transplant. The seizures resolved after cessation of cyclosporin A. Thirteen months later, he developed diplopia from bilateral internuclear ophthalmoplegia while receiving intravenous FK506. A temporal association was found between his symptoms and the serum FK506 concentrations. Withdrawal of the intravenous FK506 led to prompt resolution of the bilateral internuclear ophthalmoplegia.

Graft Rejection↗
PubMed2003

Polarity establishment requires dynamic actin in fucoid zygotes.

Previous work has demonstrated that actin plays important roles in axis establishment and polar growth in fucoid zygotes. Distinct actin arrays are associated with fertilization, polarization, growth, and division, and agents that depolymerize actin filaments (cytochalasins, latrunculin B) perturb these stages of the first cell cycle. Rearrangements of actin arrays could be accomplished by transport of intact filaments and/or by actin dynamics involving depolymerization of the old array and polymerization of a new array. To investigate the requirement for dynamic actin during early development, we utilized the actin-stabilizing agent jasplakinolide. Immunofluorescence of actin arrays showed that treatment with 1-10 microM jasplakinolide stabilized existing arrays and induced polymerization of new filaments. In young zygotes, a cortical actin patch at the rhizoid pole was stabilized, and in some cells supernumerary patches were formed. In older zygotes that had initiated tip growth, massive filament assembly occurred in the rhizoid apex, and to a lesser degree in the perinuclear region. Treatment disrupted polarity establishment, polar secretion, tip growth, spindle alignment, and cytokinesis but did not affect the maintenance of an established axis, mitosis, or cell cycle progression. This study suggests that dynamic actin is required for polarization, growth, and division. Rearrangements in actin structures during the first cell cycle are likely mediated by actin depolymerization within old arrays and polymerization of new arrays.

Actins↗
PubMed2003

Spontaneous retinal venous pulsation: aetiology and significance.

Spontaneous retinal venous pulsation is seen as a subtle variation in the calibre of the retinal vein(s) as they cross the optic disc. The physical principles behind the venous pulsations has been the point of much debate. Initial theories suggested that the pulsation occurred because of the rise in intraocular pressure in the eye with the pulse pressure. This article presents an argument that this is not the case. The pulsations are in fact caused by variation in the pressure gradient along the retinal vein as it traverses the lamina cribrosa. The pressure gradient varies because of the difference in the pulse pressure between the intraocular space and the cerebrospinal fluid. The importance of this is that as the intracranial pressure rises the intracranial pulse pressure rises to equal the intraocular pulse pressure and the spontaneous venous pulsations cease. Thus it is shown that cessation of the spontaneous venous pulsation is a sensitive marker of raised intracranial pressure. The article discusses the specificity of the absence of spontaneous venous pulsation and describes how the patient should be examined to best elicit this important sign.

Blood Pressure↗
PubMed2003

A controlled study comparing visual function in patients treated with vigabatrin and tiagabine.

OBJECTIVE: Vigabatrin treatment is frequently associated with irreversible retinal injury and produces retinal electrophysiological changes in nearly all patients. Concern has been raised that tiagabine and other antiepilepsy drugs (AEDs) that increase brain gamma-aminobutyric acid (GABA) might produce similar electrophysiological and clinical changes in visual function. The study compared visual function between groups of patients with epilepsy treated long term with tiagabine, vigabatrin, and patients treated with other AEDs. METHODS: A cross sectional study comparing visual acuity, colour vision, static and kinetic perimetry, and electroretinograms between groups of patients treated with tiagabine, vigabatrin, and other AEDs (control patients). Patients were adults receiving stable AED treatment for >6 months. RESULTS: Vigabatrin treated patients had marked visual field constrictions in kinetic perimetry (mean radius 39.6 degrees OD, 40.5 degrees OS), while tiagabine patients had normal findings (mean 61 degrees OD, 62 degrees OS) (differences OD and OS, p=0.001), which were similar to epilepsy control patients (mean 60 degrees OD, 61 degrees OS). Vigabatrin patients had abnormal electroretinographic photopic B wave, oscillatory, and flicker responses, which correlated with visual field constrictions. These electroretinographic responses were normal for tiagabine patients and control patients. Patients were treated with vigabatrin for a median of 46 months compared with 29 months for tiagabine. Patients taking other AEDs that may change brain GABA had normal visual function. CONCLUSION: Unlike vigabatrin, tiagabine treatment is associated with normal electroretinography and visual fields and ophthalmological function similar to epilepsy control patients. Differences between vigabatrin and other GABA modulating AEDs in retinal drug concentrations and other effects might explain why tiagabine increases in GABA reuptake do not cause retinal injury.

Adult↗
PubMed2002

ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency.

T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent on the host major histocompatibility complex classes I and II (MHC-I and MHC-II) antigens. Here we report that both inherent, host-dependent immune responses to SIVmac251 infection and vaccination-induced immune responses to viral antigens were able to reduce virus replication and/or CD4+ T-cell loss. Both the presence of the MHC-I Mamu-A*01 genotype and vaccination of rhesus macaques with ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) contributed to the restriction of SIVmac251 replication during primary infection, preservation of CD4+ T cells, and delayed disease progression following intrarectal challenge exposure of the animals to SIV(mac251 (561)). ALVAC-SIV-gpe immunization induced cytotoxic T-lymphocyte (CTL) responses cumulatively in 67% of the immunized animals. Following viral challenge, a significant secondary virus-specific CD8+ T-cell response was observed in the vaccinated macaques. In the same immunized macaques, a decrease in virus load during primary infection (P = 0.0078) and protection from CD4 loss during both acute and chronic phases of infection (P = 0.0099 and P = 0.03, respectively) were observed. A trend for enhanced survival of the vaccinated macaques was also observed. Neither boosting the ALVAC-SIV-gpe with gp120 immunizations nor administering the vaccine by the combination of mucosal and systemic immunization routes increased significantly the protective effect of the ALVAC-SIV-gpe vaccine. While assessing the role of MHC-I Mamu-A*01 alone in the restriction of viremia following challenge of nonvaccinated animals with other SIV isolates, we observed that the virus load was not significantly lower in Mamu-A*01-positive macaques following intravenous challenge with either SIV(mac251 (561)) or SIV(SME660). However, a significant delay in CD4+ T-cell loss was observed in Mamu-A*01-positive macaques in each group. Of interest, in the case of intravenous or intrarectal challenge with the chimeric SIV/HIV strains SHIV(89.6P) or SHIV(KU2), respectively, MHC-I Mamu-A*01-positive macaques did not significantly restrict primary viremia. The finding of the protective effect of the Mamu-A*01 molecule parallels the protective effect of the B*5701 HLA allele in HIV-1-infected humans and needs to be accounted for in the evaluation of vaccine efficacy against SIV challenge models.

Animals↗
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↗
PubMed2001

Peripheral homonymous scotomas from a cavernous angioma affecting fibers subserving the intermediate region of the striate cortex.

PURPOSE: To report the case of a pure peripheral homonymous visual field defect and to delineate the representation of the visual field on the striate cortex. METHODS: Observational case report. Neuro-ophthalmologic and neuroimaging assessment of a patient with a cavernous angioma of the right parieto-occipital lobe. RESULTS: The patient had left homonymous scotomas located 40 degrees to 60 degrees from the vertical meridian. Neuroimaging indicated that the lesion was affecting the optic radiations at their termination in the intermediate portion of the striate cortex or the striate cortex itself. CONCLUSION: Homonymous field defects are typically located within 10 degrees of fixation. This patient had a peripheral homonymous field defect from damage to the intermediate striate cortex. Correlation of the neuroimaging findings in this case with the most commonly used maps of the representation of the visual field on the striate cortex suggests that none of the maps correctly predicts the location or extent of lesions that affect the intermediate portion of the cortex.

Adult↗