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Biomedical subjects

N R Miller

Publications and source records attributed to N R Miller.

At least 145 records · Page 8Linked to original sources
PubMed1990

Bilateral ischemic optic neuropathy and retinal vascular occlusions associated with lymphoma and sepsis. Clinicopathologic correlation.

The authors report the clinicopathologic correlation of a patient with non-Hodgkin's mixed-cell lymphoma who had impairment of the circulation of the optic nerve and retina in both eyes. The results of histopathologic examination showed that the pial septa of the optic nerves were infiltrated by lymphoma and that there was extensive infarction of the orbital portions of both optic nerves and occlusion of both central retinal arteries and the right central retinal vein by thrombi with bacteria. The infiltration of the optic nerves seemed to be resistant to therapy.

Bacterial Infections↗
PubMed1990

Heteroplasmy in chronic external ophthalmoplegia: clinical and molecular observations.

Chronic progressive external ophthalmoplegia (CPEO) describes a recognizable clinical syndrome frequently associated with variable dysfunction in other organ systems. Histochemical and biochemical studies suggested primary dysfunction of oxidative phosphorylation. This has recently been confirmed by demonstration of partially deleted as well as normal mitochondrial DNA--heteroplasmy--in some of these patients, most of them sporadic. In the six heteroplasmic CPEO patients that we have examined to date, the partially deleted species has been detected in all tissues tested, albeit in vastly different proportions. We report here detection of physiologically significant proportions of partially deleted mitochondrial DNA in several organs taken at autopsy from a CPEO patient with severe multisystem disease. We discuss the relationship of CPEO to several other clinical phenotypes associated with mitochondrial dysfunction, and discuss the possible implications of heteroplasmy for the development of variable phenotypes.

Child↗
PubMed1990

Visual illusions associated with previous drug abuse.

We describe the visual illusions experienced by five patients with a history of previous use of hallucinogens, marijuana, or both. Symptoms included shimmering of images, illusory movement of images, visual perseveration of stationary objects, streaking of moving objects, and moving objects appearing as a consecutive series of stationary images. In all cases, the symptoms had persisted or recurred after periods of drug abstinence ranging from several months to several years. Despite thorough and repeated examinations and investigations, there was no evidence of neurologic ophthalmologic disease in these patients. When patients present with these and other visual illusions, a thorough drug history may afford the answer, provided that other recognized causes of these visual symptoms, such as migraine, epilepsy, and intracranial lesions have been excluded.

Adult↗
PubMed1989

Trigeminal schwannoma as a cause of chronic, isolated sixth nerve palsy.

We treated two patients with trigeminal schwannomas, each of whom had an isolated, ipsilateral, abducens nerve palsy. Both patients initially had normal computed tomographic scan results and no neurologic signs of trigeminal nerve dysfunction. Trigeminal dysfunction did not develop until several years after the initial sixth nerve palsy, at which time a repeat examination disclosed the schwannoma. Accurate detection of a trigeminal schwannoma requires a careful clinical examination and appropriate neuroimaging studies. When such studies give normal results, they should be repeated if symptoms worsen or if new symptoms develop.

Abducens Nerve↗
PubMed1989

The optic nerve as the site of initial relapse in childhood acute lymphoblastic leukemia.

Three children with acute lymphoblastic leukemia (ALL) developed isolated optic nerve relapse as the initial site of disease recurrence. They were part of an early cohort of 39 children with non-B-cell, non-T-cell ALL without central nervous system (CNS) involvement, treated regardless of initial leukocyte count with intrathecal chemotherapy for CNS prophylaxis. Although the optic nerve is a known site of relapse in patients with systemic and meningeal ALL, it has not been reported to occur in otherwise relapse-free patients. Early diagnosis and treatment prevented blindness and allowed for long-term survival (57+, 49+, and 97+ months, respectively) and possibly cure. Since these patients were treated in a new manner and exhibited a new pattern of relapse, their clinical courses were reviewed. Features considered worrisome, but not diagnostic of CNS leukemia may be of greater import when intrathecal medications are utilized as primary CNS prophylaxis. An expanded definition of CNS leukemia may be necessary.

Child↗
PubMed1989

Differential modulation of gene induction by glucocorticoids and antiglucocorticoids in rat hepatoma tissue culture cells.

Studies of glucocorticoid and antiglucocorticoid induction of tyrosine aminotransferase (TAT) in two rat hepatoma cell lines (Fu5-5 and HTC) are described. These studies revealed several phenomena that are not consistent with the current models of steroid hormone action: (a) TAT induction occurred at glucocorticoid levels below those required for comparable receptor occupancy in Fu5-5, but not in HTC, cells; (b) the ability of antiglucocorticoids to induce TAT is higher in Fu5-5 than in HTC cells; (c) the values of the amount of TAT agonist activity with the antiglucocorticoid dexamethasone 21-mesylate and of log10 of the dexamethasone concentration required for half-maximal induction of TAT were not constant over time but varied in a linear, reciprocal manner. This modulation was seen for several glucocorticoids and antiglucocorticoids at the level of both TAT enzyme and mRNA but not for two other glucocorticoid inducible genes in the same cells. These results, plus the fact that a similar difference in the concentration required for half-maximal TAT induction in Fu5-5 cells was seen for both glucocorticoids and cyclic AMP, argue that the modulation occurs at some point distal to receptor-steroid complex binding to the biologically active nuclear sites but proximal to translation of TAT mRNA. In order to explain these results, it is pointed out that models involving second messengers are entirely appropriate for steroid hormone action. The participation of a modulated trans-acting factor in such a model may explain the above results.

Animals↗
PubMed1989

Treatment of carotid-cavernous sinus fistulas using a detachable balloon catheter through the superior ophthalmic vein.

Four consecutive patients with carotid-cavernous sinus fistulas that could not be treated by the standard techniques of endoarterial balloon occlusion or embolization were successfully treated by advancement of a detachable balloon catheter through the ipsilateral superior ophthalmic vein. Under angiographic monitoring, the balloon was passed into the cavernous sinus, inflated to close the fistula, and detached. Three of the patients had a spontaneous fistula, and one had a traumatic fistula that had previously been trapped unsuccessfully. All patients had complete resolution of symptoms and signs after occlusion of the fistula. There were no intraoperative or postoperative complications. The transvenous approach to the cavernous sinus through the superior ophthalmic vein is a safe, effective treatment of carotid-cavernous sinus fistulas, whether they are direct or dural in nature.

Adult↗
PubMed1989

Divisional oculomotor nerve paresis caused by intrinsic brainstem disease.

Two patients with findings ascribable to superior branch oculomotor nerve paresis and one patient with findings ascribable to an inferior branch paresis are described. In each patient the paresis was caused by an intra-axial midbrain lesion. These patients represent the first described cases of divisional oculomotor nerve paresis caused by intrinsic brainstem disease.

Adult↗
PubMed1989

Combining the detachable balloon technique and surgery in imaging carotid cavernous fistulae.

Among 143 carotid cavernous fistulae, 10 cases could not be successfully treated by standard endovascular techniques alone; some form of surgical assistance was required. The circumstances included incomplete closure of the fistula while the internal carotid artery was occluded, failure to occlude the fistula after both arterial and venous endovascular approaches, hairpin loop of the cervical portion of the internal carotid artery, failure of previous trapping procedures, and failure to cure spontaneous carotid cavernous fistulae of the dural type after embolization of the external carotid feeders. These ten patients were cured by combining a surgical procedure and an interventional technique.

Adult↗
PubMed1989

Visual outcome after surgical removal of craniopharyngiomas.

Thirty patients with craniopharyngiomas were examined preoperatively and immediately postoperatively to determine their level of visual impairment and the extent of visual recovery. Twenty-two patients also were examined during extended follow-up. Twelve of these patients were younger than 18 years of age and 18 were older than 18 years of age at the time of diagnosis. Visual acuity was reduced in 42% of eyes preoperatively. One week postoperatively, visual acuity was reduced in only 23% of eyes. Color vision was a more sensitive indicator of afferent system damage, being abnormal at presentation in 71% of patients. Visual field defects were typically bitemporal hemianopsias, but 20% of patients with evidence of optic neuropathy had no definite visual field deficit preoperatively. Postoperatively, 48% of patients had normal visual fields. There was no long-term improvement in visual acuity or field performance for patients with deficits present after the first postoperative month during an average 2.8 years of follow-up.

Adolescent↗
PubMed1989

Ocular pseudomyasthenia or ocular myasthenia 'plus': a warning to clinicians.

Myasthenia gravis (MG) commonly presents with weakness and fatigability of the lids and extraocular muscles, which respond to treatment with anticholinesterase medication. However, certain intracranial mass lesions may mimic these features of MG; alternatively, MG may mask the signs of a coexistent intracranial mass. We describe 8 patients originally diagnosed as having MG by knowledgeable clinicians, in whom an intracranial lesion instead of, or in addition to, MG was later identified. The lesions included parasellar tumors and aneurysms. In patients presenting with clinical features of ocular MG, it is therefore essential to establish a definite diagnosis of MG, to exclude other possible causes of "pseudomyasthenia," and to exclude other diseases that might be masked by coexisting myasthenic weakness. We recommend that patients with clinical features of MG limited to the ocular or cranial musculature be thoroughly evaluated for intracranial mass lesions, using CT or MRI if warranted.

Adolescent↗
PubMed1988

Steroid binding to hepatoma tissue culture cell glucocorticoid receptors involves at least two sulfhydryl groups.

The presence of a thiol in the steroid binding cavity of glucocorticoid receptors has recently been proved by our affinity labeling of Cys-656 in the steroid binding domain of rat receptors (Simons, S. S., Jr., Pumphrey, J. G., Rudikoff, S., and Eisen, H. J. (1987) J. Biol. Chem. 262, 9676-9680). Studies with the sterically small, thiol-specific reagent methyl methanethiolsulfonate (MMTS) now reveal the involvement of at least two sulfhydryl groups in steroid binding. While the dose-response curves for [3H]dexamethasone binding versus thiol reagent are normally sigmoidal, an unusual bimodal curve is obtained with MMTS in which dexamethasone binding is eliminated at low, but maintained at intermediate, MMTS concentrations. This bimodal dose-response curve demands the involvement of two (or more) thiol groups. Those receptors pretreated with intermediate concentrations of MMTS retain approximately 70% of the initial binding capacity and one-fifth the affinity for dexamethasone. Solutions of this low affinity form of receptor contain essentially no accessible -SH groups, and all of the usual covalent labeling by dexamethasone 21-mesylate of various proteins, including the receptor, is blocked. The facts, that this low affinity form of the receptor is not affected by added iodoacetamide, cannot be produced from the nonsteroid binding form of receptor simply by adding more MMTS, and displays different kinetics of formation than does the nonsteroid binding form of receptor all argue that reaction of the receptor with intermediate and low MMTS, concentrations occurs via different pathways. Nevertheless, the effects of both concentrations of MMTS on the receptor are fully reversible with added dithiothreitol. The kinetics of inhibition of [3H]dexamethasone binding at low MMTS concentrations are independent of receptor concentration, indicating an intramolecular reaction. Collectively these data suggest a model of steroid binding involving two thiols, one of which appears to be Cys-656. Low concentrations of MMTS induce the formation of an intramolecular disulfide, which prevents steroid binding, while the intermediate MMTS concentrations convert both thiols directly to mixed disulfides, and steroid binding persists. Thus, reduced thiols do not appear to be required for steroid binding if the steric bulk of the oxidized thiols is small.

Animals↗
PubMed1988

Optic atrophy in children.

We reviewed the records of 218 children in whom a diagnosis of optic atrophy had been made between 1978 and 1987. A cause for the atrophy was determined for 195 patients (89%). Tumor, the most frequent cause, was found in 63 patients (29%). The most common tumor was a glioma of the anterior visual pathway; it was found in 27 patients (43% of tumors; 12% overall). The second most frequently encountered tumor, a craniopharyngioma, was found in 14 patients. Inflammation, the second most common cause of optic atrophy, occurred in 38 children (17%). Trauma caused optic atrophy in 24 patients (11%). No cause could be found for 23 patients (11%). Thirteen patients were less than 1 year of age at the time of diagnosis. Three of these patients had tumors. One was a cerebral glioblastoma, and the other two were optic gliomas. The diagnosis of optic atrophy in infancy does not imply a benign cause.

Adolescent↗
PubMed1988

Uremic optic neuropathy.

Vision loss progressing over several days, reduced pupil reactions to light, and swollen optic nerves were the clinical features in six patients with severe renal disease manifested by uremia, anemia, and (in four patients) moderately or severely elevated blood pressure. In two patients pale edema of the optic nerve head extended into the macula. One patient with renal transplant rejection was in the early phases of cryptococcal meningitis that went undiagnosed for two weeks. Medical management with hemodialysis was followed by improvement of vision in four patients. In one patient, resumption of oral corticosteroid therapy was followed by improvement in vision. The patient whose vision improved the most rapidly was managed by prompt use of both dialysis and oral corticosteroid therapy. The patient with cryptococcal meningitis did not recover vision.

Adolescent↗