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Biomedical subjects

D M Jacobson

Publications and source records attributed to D M Jacobson.

At least 55 records · Page 3Linked to original sources

Intracranial hypertension and the syndrome of acquired hyperopia with choroidal folds.

An idiopathic syndrome of acquired hyperopia with choroidal folds has been characterized. Orbital imaging correlates of this syndrome include flattening of the posterior globe and distention of the perioptic subarachnoid space. The mechanism responsible for the clinical and radiographic findings of this syndrome is undefined. Two patients with unusual presentations of papilledema are reported whose clinical and radiographic findings were otherwise identical to those described in the idiopathic syndrome of acquired hyperopia with choroidal folds. One patient had unilateral disc edema and bilateral choroidal folds. The other patient had bilateral choroidal folds observed 2 years before he developed papilledema in both eyes. Both patients had intracranial hypertension, idiopathic in the first, and related to severe chronic obstructive pulmonary disease and cor pulmonale in the second. A third patient is also described who had typical clinical and orbital imaging findings of idiopathic unilateral acquired hyperopia with choroidal folds. He was also found to have mild intracranial hypertension. Intracranial hypertension can cause acquired hyperopia and choroidal folds and may be the underlying mechanism in some patients with what appears to be idiopathic acquired hyperopia with choroidal folds.

Adult↗

A prospective evaluation of cholinergic supersensitivity of the iris sphincter in patients with oculomotor nerve palsies.

To evaluate the frequency and clinical correlates of preganglionic cholinergic supersensitivity of the iris sphincter, I prospectively tested 31 consecutive outpatients with oculomotor nerve palsies by comparing their pupil diameters in darkness before and 30 minutes after topical application of pilocarpine 0.1%. Supersensitive pupil responses were observed in the involved eye in five of 11 patients with compressive palsies, four of five patients with traumatic palsies, in the two patients with congenital palsies, and in none of the patients with ischemic palsies. Supersensitivity was statistically significantly associated with pupil involvement but not with aberrant regeneration of the extraocular muscles or pupil. The degree of supersensitivity was directly correlated with the amount of baseline anisocoria. These results establish that cholinergic supersensitivity of the pupil occurs frequently with nonischemic oculomotor nerve palsies and may be related to the degree of preganglionic injury to the pupillomotor fibers.

Adult↗

Effects of sonicated eosinophils on the in vitro sensitivity of human lymphoma cells to glucose oxidase.

We report here that cultured human lymphoma cells in the absence of sonicated eosinophils are sensitive to killing by glucose oxidase (beta-D-glucose:oxygen-oxido reductase; EC 1.1.3.4) at concentrations as low as 0.025 microgram/ml, a level that can be rapidly attained in s.c. tumor implants in mice that receive a single nonlethal injection of enzyme. Multiple clonogenic assays were used to measure the survival of human lymphoma cell lines (H9 and ARH-77) cultured for 14 days in complete RPMI 1640 supplemented with exogenous glucose oxidase (0.025-2.5 micrograms/ml) or an immunoconjugate containing glucose oxidase (0.25-25 micrograms/ml) in the presence or absence of catalase (10 micrograms/ml) or an equal number of sonicated human eosinophils with or without supplemental 100 microM Br-, I-, or SCN-. In addition, we used an immunoassay to measure the concentration of glucose oxidase in s.c. implants of the Sp 2/0 myeloma tumor at 0-30 min after an i.v. injection of 50 micrograms of enzyme into 21 BALB/c mice. Doses of glucose oxidase as small as 0.025 microgram/ml killed more than 3 logs of tumor cells. Catalase completely inhibited, and sonicated human eosinophils partially inhibited, the killing by glucose oxidase or immunoconjugate, whereas supplemental halides had no effect. Glucose oxidase i.v. produced levels > 0.04 microgram/g of tumor for 30 min after injection with a peak concentration of 0.079 microgram/g of tumor within 5 min of injection. These results are important because certain human lymphomas contain extensive extracellular deposits of eosinophil peroxidase, thereby making these tumors potentially less susceptible to killing by otherwise therapeutic doses of glucose oxidase.

Drug Screening Assays, Antitumor↗

Risk factors for ischemic ocular motor nerve palsies.

OBJECTIVE: To identify risk factors associated with neurologically isolated ischemic ocular motor nerve palsies. DESIGN: Case-control study. SETTING: Multispecialty clinic providing primary, secondary, and tertiary care in central and northern Wisconsin. STUDY PARTICIPANTS: After applying strict, predetermined, inclusion and exclusion criteria to the medical records of patients with ocular motor nerve palsies, 65 case patients 50 years of age or older were identified with ischemic ophthalmoplegia. A control subject, matched for sex and exact year of age, was randomly selected for each case patient from individuals undergoing a comprehensive medical evaluation. MAIN OUTCOME MEASURES: Prevalence of potential risk factors in case patients and controls, including diabetes, hypertension, hypercholesterolemia, coronary artery disease, left ventricular hypertrophy, adiposity, tobacco use, prior ocular motor nerve palsy, and hematocrit. Risk factors were assessed using standardized definitions. RESULTS: After adjustment for potential confounding factors, significant risk factors and their associated odds ratios (ORs) and 95% confidence intervals (CIs) were as follows: previously diagnosed diabetes, OR = 5.75 (CI = 1.68 to 19.7); left ventricular hypertrophy, OR = 5.20 (CI = 1.30 to 20.82); and, hematocrit (per percentage increase), OR = 1.35 (CI = 1.13 to 1.61). CONCLUSION: In addition to the generally accepted risk factor of diabetes, left ventricular hypertrophy and elevated hematocrit appeared to be important determinants of ischemic ocular motor nerve palsy. Additional studies should be undertaken to confirm these findings.

Aged↗

Influence of pupil size, anisocoria, and ambient light on pilocarpine miosis. Implications for supersensitivity testing.

BACKGROUND: This study determines how pupil size, anisocoria, and ambient light influence miotic responses to dilute pilocarpine. The aim is to establish whether mechanical properties of the iris affect miotic behavior using a cholinergic agonist and, if so, to define a more specific clinical definition of supersensitivity testing for suspected tonic pupil disorders. METHODS: The right pupil of 42 normal subjects was first dilated with phenylephrine to create an experimental anisocoria. Then, pilocarpine 0.1% was placed in both eyes. Net constriction of the larger right pupil was determined by subtracting the amount of pilocarpine-induced constriction of the control left pupil from the amount of pilocarpine-induced constriction of the experimental right pupil. Pupil diameters were measured in room light and darkness. RESULTS: In only a few subjects, the larger right pupil became smaller than the left pupil after pilocarpine administration. Net constriction of the right pupil was greater when determined in room light than in darkness. The amount of net constriction of the right pupil showed good correlation with the degree of baseline anisocoria when evaluated in room light, but not so in darkness. CONCLUSION: Pupil size, degree of anisocoria, and light conditions influence the amount of pilocarpine-induced change in anisocoria. If a patient's larger pupil becomes the smaller pupil in darkness after dilute pilocarpine is applied to both eyes, then it is likely that such a response occurred independent of mechanical properties of the iris, and likely represents a supersensitive response. Ophthalmology.

Adolescent↗

Delayed visual loss due to trauma of the internal carotid artery.

The group of six patients in this study experienced delayed visual loss following head trauma. Visual loss occurred from 1 day to 13 years after the initial injury. All patients suffered indirect trauma to the internal carotid artery resulting in formation of either an aneurysm or pseudoaneurysm or a carotid-cavernous fistula. Review of the radiologic and clinical findings was performed in six patients. The diagnosis was established by computed tomography, magnetic resonance imaging, and angiography. All patients had follow-up clinical evaluation and imaging studies. Treatment by neurosurgical or interventional neuroradiologic procedures resulted in significant visual improvement in five patients. Different pathophysiologic mechanisms could be correlated with the delayed visual loss produced by the two types of lesions. The pathologic changes associated with the aneurysms/pseudoaneurysms included direct compression of optic nerves and/or chiasm and intracranial hematoma. A carotid-cavernous fistula caused delayed visual loss by either hematoma at the orbital apex or compression of the chiasm and/or optic nerves by saccular dilatation of the cavernous sinus. The delayed onset of decreased vision following head trauma should alert the physician to the possibility of a traumatic aneurysm/pseudoaneurysm or a carotid-cavernous fistula. Different neuro-ophthalmologic symptoms can usually be correlated with the pathologic changes demonstrated by neuroimaging procedures.

Adolescent↗

Impaired critical flicker frequency in recovered optic neuritis.

Thirteen patients with optic neuritis who recovered normal visual acuity and kinetic perimetry all showed impairment of foveal critical flicker frequency, a psychophysical test of visual temporal resolution. Because the magnocellular visual system demonstrates higher temporal resolution than the parvocellular system, this finding implicates involvement of axonal projections of magnocellular retinal ganglion cells in recovered optic neuritis.

Adolescent↗

Superior oblique palsy manifested during pregnancy.

The author describes his experience with diplopia during uncomplicated pregnancy in 3 of 25 (12%) women with neurologically isolated unilateral superior oblique palsy. These three patients had visual sensory and ocular motor findings that suggested they had longstanding latent vertical deviations that decompensated during pregnancy. Two of these three women experienced resolution of symptoms shortly after delivery. Increased recognition of the benign association between decompensation of a latent superior oblique palsy and pregnancy may obviate the need to further evaluate such patients with neuroimaging studies or other procedures.

Adult↗

Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans.

After programmed cell death, a cell corpse is engulfed and quickly degraded by a neighboring cell. For degradation to occur, engulfing cells must recognize, phagocytose and digest the corpses of dying cells. Previously, three genes were known to be involved in eliminating cell corpses in the nematode Caenorhabditis elegans: ced-1, ced-2 and nuc-1. We have identified five new genes that play a role in this process: ced-5, ced-6, ced-7, ced-8 and ced-10. Electron microscopic studies reveal that mutations in each of these genes prevent engulfment, indicating that these genes are needed either for the recognition of corpses by other cells or for the initiation of phagocytosis. Based upon our study of double mutants, these genes can be divided into two sets. Animals with mutations in only one of these sets of genes have relatively few unengulfed cell corpses. By contrast, animals with mutations in both sets of genes have many unengulfed corpses. These observations suggest that these two sets of genes are involved in distinct and partially redundant processes that act in the engulfment of cell corpses.

Animals↗

Frequency and clinical significance of Lyme seropositivity in patients with isolated optic neuritis.

We evaluated antibody reactivity against Borrelia burgdorferi in 20 consecutive patients with newly diagnosed isolated optic neuritis who resided in a region endemic for Lyme disease. Four (20%) patients had positive serology. All three patients who had follow-up serologies showed rising convalescent levels of Borrelia-specific IgM. One patient refused lumbar puncture, one had normal CSF constituents except for an elevated Lyme antibody index, and two had CSF lymphocytic pleocytosis that remained unexplained after extensive evaluations for causes other than Lyme disease. We treated both patients who had CSF pleocytosis with intravenous ceftriaxone; the pleocytosis and optic nerve function improved. The other two patients received oral antibiotics and showed excellent recovery of visual acuity. We believe that serologic testing for Lyme disease is warranted for individuals with optic neuritis who reside in an endemic region, and patients with rising convalescent antibody levels or unexplained CSF pleocytosis should receive antibiotic treatment for Lyme disease.

Adolescent↗

Difficulty differentiating Leber's from dominant optic neuropathy in a patient with remote visual loss.

A 31-year-old man who inexplicably lost vision as a child was referred for evaluation of bilateral optic atrophy. Other family members had also suffered unexplained visual loss. He had asymmetric impairment of visual acuity, central scotomas, and optic disc pallor. He also had a tritan color vision defect and excavation of the temporal portion of his optic discs, two features that were consistent with autosomal dominant optic atrophy. However, examination of the mitochondrial DNA of the proband and of two of his relatives revealed a mutation at nucleotide 11778, known to be associated with Leber's hereditary optic neuropathy. This case illustrates the difficulty physicians may encounter when trying to clinically differentiate Leber's from dominant optic atrophy in patients with remote visual loss, and it emphasizes the importance of obtaining a molecular assay for a mitochondrial mutation in cases of ambiguously classified hereditary optic neuropathy.

Adult↗

A clinical triad to diagnose paraneoplastic retinopathy.

Two elderly men developed photosensitivity and light-induced glare, transient visual symptoms, and progressive visual loss several months before small cell carcinoma of the lung was discovered. Both patients had impaired visual acuity and color vision, ring scotomas, and attenuated retinal arteriole caliber. Electroretinography demonstrated abnormal cone and rod-mediated responses. Antiretinal antibodies were identified in their serum. Their visual sensory function improved following therapy with immunosuppressive agents. The triad of photosensitivity, ring scotomatous visual field loss, and attenuated retinal arteriole caliber should alert one to a paraneoplastic disorder affecting the retina.

Adenocarcinoma↗

Pupillary responses to dilute pilocarpine in preganglionic 3rd nerve disorders.

Supersensitivity of the iris sphincter to dilute parasympathomimetic agents is considered a diagnostic hallmark of a postganglionic oculomotor nerve disorder. Nine of 13 patients with preganglionic 3rd nerve palsies showed supersensitive pupillary responses using pilocarpine 0.1%. The presence of supersensitivity was not related to the cause of 3rd nerve dysfunction or interval time from onset to testing, but was related to the extent of associated iris sphincter paresis. Some patients with long-standing preganglionic 3rd nerve palsies had features of postganglionic damage, including light-near dissociation and segmental paresis of the iris sphincter. These observations suggest that 1 mechanism of cholinergic supersensitivity in some chronic cases of preganglionic 3rd nerve disorders may be transsynaptic degeneration of postganglionic fibers. In another set of experiments, pharmacologically dilated pupils in normal subjects constricted more to dilute pilocarpine than their normal-sized fellow pupils. Cholinergic supersensitivity in pupil-involving 3rd nerve palsies might also occur simply because the affected pupil is larger than the unaffected pupil.

Adolescent↗

Computed tomography ventricular size has no predictive value in diagnosing pseudotumor cerebri.

We compared linear indices of computed tomography ventricular size in patients with pseudotumor cerebri and in age-matched controls, and found no difference between these populations. Two physicians showed poor agreement and sensitivity when blindly judging whether patients and controls had "slit-like" ventricles. We conclude that ventricular size on routine CT has no predictive value when evaluating patients with suspected pseudotumor cerebri.

Adult↗