A phase I, open-label, single-arm, dose-escalation study of E7107, a precursor messenger ribonucleic acid (pre-mRNA) splicesome inhibitor administered intravenously on days 1 and 8 every 21 days to patients with solid tumors.

The aim of this study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of E7107 in patients with advanced solid tumors. Patients in this phase I, open-label, single-arm, dose-escalation study had metastatic or locally advanced solid tumors and received E7107 as a 30-minute intravenous infusion at doses of 0.6, 1.2, 1.8, 2.4, 3.2, 4.3, and 5.7 mg/m(2). Twenty-six patients were enrolled in the study. At 5.7 mg/m(2), two patients experienced dose-limiting toxicities including diarrhea, vomiting, dehydration, and myocardial infarction on Days 1-3 following E7107 administration. Three additional patients were recruited at the lower dose and all six patients tolerated E7107 4.3 mg/m(2) with no dose-limiting toxicities. The maximum tolerated dose of E7107 was therefore 4.3 mg/m(2). The most common drug-related adverse events were nausea, vomiting, and diarrhea. Vision loss was experienced by two patients at Cycles 2 and 7, each patient receiving 3.2 mg/m(2) and 4.3 mg/m(2), respectively. This resulted in the study being put on clinical hold. Pharmacokinetic analysis showed that E7107 was rapidly distributed with a moderate elimination half-life (6-13 h) and high clearance. Exposure to E7107 was dose-related. The best tumor response was stable disease in eight patients. E7107 is a unique first-in-class molecule. The incidence of two cases of vision loss probably related to E7107 led to study discontinuation.

Progressive outer retinal necrosis presenting with isolated optic neuropathy.

Progressive outer retinal necrosis is a necrotizing herpetic retinopathy usually seen in immunocompromised patients. The authors describe two patients with this disease who initially had findings suggestive of an optic neuropathy. Vision declined after treatment with methylprednisolone, after which fundus examination became consistent with progressive outer retinal necrosis. These cases underscore the importance of careful examination of the retinal periphery before management of any presumed optic neuropathy with steroids.

Orbital presentations of giant cell arteritis.

BACKGROUND: giant cell arteritis (GCA) is a systemic vasculitis that may affect the optic nerve and cause blindness (e.g. ischemic optic neuropathy). Orbital inflammatory disease, however, is an uncommon presentation of GCA. PURPOSE: to alert clinicians to the orbital presentations of GCA. PATIENTS AND METHODS: a retrospective case series from tertiary care academic ophthalmic referral centers of four patients with orbital manifestations of giant cell arteritis. RESULTS: presentation of cases and review of the literature. In three cases, a temporal artery biopsy was diagnostic of GCA, but in one case, an orbital biopsy was needed to confirm the diagnosis. CONCLUSION: GCA can have orbital manifestations and clinicians should be aware of this unusual presentation of GCA in cases of presumed orbital inflammatory pseudotumor in the elderly.

Primary central nervous system lymphoma involving the optic chiasm in AIDS.

OBJECTIVE: To report visual loss resulting from chiasmal involvement by primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: Case report. RESULTS: A patient with the acquired immune deficiency syndrome (AIDS) presented with visual loss resulting from PCNSL involving the optic chiasm. The clinical findings, neuroimaging, pathology, and treatment of this patient are described. CONCLUSIONS: Although rare, clinicians should consider PCNSL in the differential of a hypothalamic/chiasmal mass, especially in a patient with AIDS.

A practice pathway for the initial diagnostic evaluation of isolated sixth cranial nerve palsies.

PURPOSE: To define a practice pathway for the evaluation of sixth-nerve palsies (SNPs) and to determine its cost-effectiveness and validity in a retrospective chart review. METHODS: A Medline search of the English-language literature from 1966 to 1995 was performed to define the available clinical evidence and develop the practice pathway. The authors retrospectively reviewed 407 charts with the diagnosis of SNP seen at three centers. Information obtained included: etiologic diagnosis if known; development of new neurologic or ophthalmologic findings; and results and costs of neuroimaging studies, if performed. RESULTS: Of the 407 patients, 98 underwent computed tomography scans and 212 underwent magnetic resonance imaging of the head. Eighty cases were non-isolated, 317 were isolated SNP, and ten could not be classified from chart information. Of the 317 cases of isolated SNP, 49 were classified as traumatic; 5, congenital; 158, vasculopathic; 63, nonvasculopathic; and 42, progressive or unresolved. Following the recommendations of the practice pathway, the 158 patients classified as having vasculopathic SNP would not have undergone neuroimaging studies, realizing a savings of $100,000 in this study population of 407 patients. CONCLUSION: The recommendations of the practice pathway are supported by review of the literature and the retrospective review of these cases. However, a prospective study with a matched control group is needed to demonstrate regional and specialty-specific variations in care and to strengthen the clinical certainty of the pathway recommendations.

Collaborative telemedicine between optometry and ophthalmology: an initiative from the University of Houston.

The University of Houston College of Optometry (UHCO) has developed a strong Telemedicine Optometry/Ophthalmology program. Patient care, clinical teaching and research benefit from utilizing Telemedicine technology. This initiative between Optometry and Ophthalmology is at the forefront of eyecare! Presented here: clinical teaching opportunities via tele-education including retinal, uveitic, neuro-ophthalmic disorders and glaucoma. Seminars introduce students to this technology and enhance their clinical experience through exposure to eye pathologies often related to systemic diseases. UHCO's affiliated clinics include multidisciplinary centers staffed by optometrists: the Frost Eye Clinic (HIV multidisciplinary care), Good Neighbor Health Clinic and Rusk School Health Promotion Project (indigent multidisciplinary care). These centers can converse on line with eyecare professionals. Large sites interested in low vision/visual rehabilitation include: The Institute for Rehabilitation and Research (TIRR), the Social Security Hospital (Lima, Peru), the Matagorda General Hospital and the Quentin Mease Hospital. These sites, do offer quality care but require visual rehabilitation programs provided by UHCO. These sites also provide exposure to pathology for the students. A residency program trains optometrists in Telemedicine. The research program focuses on optics and imaging necessary to diagnose glaucoma, diabetic retinopathy, and neuro-ophthalmic disorders through Telemedicine. UHCO supports the advancement of standards in tele-eyecare.

Telemedicine enters eye care: practical experience.

1. A combination of store-and-forward technology and videoconferencing technology can be used in eye care and other medical specialties. 2. Bandwidth is a rate-limiting factor for obtaining a high-resolution, real-time image. 3. Protocols, clinical and technical, must be used to implement telemedicine in an efficient and high-quality manner.

Neuro-ophthalmologic manifestations of adenoid cystic carcinoma.

Intracranial adenoid cystic carcinoma is uncommon. We report two unusual cases of intracranial adenoid cystic carcinoma. The first patient presented with a steroid-responsive optic neuropathy from an orbital mass that simulated orbital pseudotumor, and subsequently developed intracranial involvement, presumably by contiguous perineural spread. The second patient presented with proptosis of the left eye, right facial weakness and numbness, and an intracranial mass, presumably from hematogenous metastatic spread.

A sellar misadventure--imaging considerations.

This report describes a patient with a headache and a bitemporal hemianopsia immediately following endoscopic ethmoid and sphenoid sinus surgery. Computed tomographic imaging revealed tension pneumocephalus caused by surgical interruption of the boundaries between the sinus(es) and the anterior cranial cavity. The delineation of the central chiasmal injury required follow-up magnetic resonance imaging.

Incidental asymptomatic orbital calcifications.

OBJECTIVE: To use modern computed tomography (CT) imaging to quantify the incidence of asymptomatic incidental orbital calcifications and describe their histological features. MATERIALS AND METHODS: One hundred orbital CT scans were reviewed. In addition, patients who had orbital calcification(s) detected on a brain CT scan were examined by the ophthalmology service. RESULTS: Of the orbital CT scans, 2% had bilateral drusen of the optic nerve head, 3% had calcified scleral plaques anterior to the medial or lateral rectus muscles, and 3% had bilateral ossification of the trochlear apparatus. Routine brain CT scans detected asymptomatic calcifications of the sclera and dura surrounding the proximal optic nerves. CONCLUSION: Incidental asymptomatic orbital calcifications are commonly encountered on modern high-resolution CT images of the brain and orbit. This article should help the clinician to confidently distinguish these densities from foreign bodies or pathological calcifications.

Effect of MR imaging on the normal human pineal body: measurement of plasma melatonin levels.

Production of melatonin, a hormone synthesized and secreted by the pineal body, has been suppressed by electromagnetic fields in some but not all animal studies. Magnetic resonance (MR) imaging at 1.5 T was evaluated for its ability to modulate the level of melatonin in eight male volunteers. Subjects were exposed to three conditions, respectively, between 1:00 and 2:00 AM on different nights: (a) a series of routine MR pulse sequences for brain imaging in dark conditions, (b) dark control conditions, and (c) bright-light control conditions. Plasma was analyzed for melatonin and cortisol levels. Hormonal changes were analyzed by one-factor repeated measures within-subject analysis of variance. These conditions were associated with significant differences in melatonin levels: F(2, 6) = 7.95, and P = .021. Subjects exposed to darkness showed a typical increase in melatonin concentration. Subjects exposed to bright light showed a characteristic suppression of melatonin concentration. Those exposed to the MR imaging fields showed an increase in melatonin level similar to that seen in the dark control condition. Light and MR imaging had no significant effects on cortisol levels. Thus, MR imaging at field strengths known to modulate melatonin levels in rats did not suppress melatonin production in human subjects.

Impaired visual motion perception in the contralateral hemifield following unilateral posterior cerebral lesions in humans.

Contrast thresholds for a number of tasks were measured in the contralateral and ipsilateral upper quadrants of the visual field (eccentricity = 10 degrees) before and after an occipito-parietal surgical resection, in one patient, carried out for intractable epilepsy. Postoperatively the contrast thresholds for discriminating the speed of movement of drifting sine-wave gratings were elevated by greater than a log unit in the contralateral field with little or no change in the detection thresholds for the same stimuli. Contrast thresholds for opposite direction-of-motion (DOM) discrimination of a contrast modulated (CMod) grating (a 'non-Fourier' motion stimulus) were also elevated by about a log unit in the contralateral hemifield but thresholds for DOM discrimination of a sine-wave (luminance modulated, LMod) grating were unaffected. Contrast thresholds for orientation discrimination of stationary gratings (a non-motion task) were unaffected. This general pattern of results was found in two other patients following lateral occipital surgical resections. Eight other patients with occipito-temporal (two cases), parietal (three cases) and medial occipital lobe lesions (three cases) showed no difference between the two hemifields on any of the tasks. Comparison of the location of the lesions leads to the conclusion that damage to the lateral occipital gyri is responsible for the pattern of visual deficit observed. Damage to an extra-striate visual area concerned with motion perception (the human homologue of primate V5-MT) may have occurred. There has been no previous description of impairment of motion perception localized to a hemifield in humans. The characteristics of the residual motion perception in these cases is described further in the accompanying article [Plant and Nakayama (1993), Brain, 116, 1337-1353].

Superior sagittal sinus thrombosis and pulmonary embolism: a syndrome rediscovered.

Pulmonary emboli as a fatal complication of superior sagittal sinus thrombosis was once well recognized in the literature but appears to have been forgotten. The sagittal sinus appeared to be the source of pulmonary emboli in previously reported cases. Even in patients with no evidence of systemic thrombosis, but who have sagittal sinus thrombosis, the possibility of dislodging pulmonary emboli should be strongly considered. We report a case of nontraumatic sagittal sinus thrombosis complicated by multiple pulmonary emboli and a fatal saddle embolism, likely originating from the thrombosed sinus. Our review of the literature between 1942 and 1990 yielded 203 cases of intracranial venous thrombosis. The overall mortality rate was 49.3%. In 23 cases (11.3%), the venous sinus thrombosis was associated with pulmonary emboli and in these the overall mortality rate was 95.6%. In the 203 cases in our review, those patients who received anticoagulation therapy also had a statistically significant better outcome. Therefore, the presence of pulmonary emboli in association with sagittal sinus thrombosis mandates a sober assessment of the need of anticoagulation therapy in the absence of obvious contraindication.

Post-irradiation neuromyotonia affecting trigeminal nerve distribution: an unusual presentation.

We describe two patients who developed neuromyotonia of the floor of the mouth after irradiation of a motor branch (V3) of the trigeminal nerve. The neuromyotonia manifested as sustained muscle contraction due to peripheral nerve dysfunction. The neuromyotonia in both patients was controlled with carbamazepine. Radiation-exposed nerves can become symptomatic months or years after completion of radiation therapy.

Differential cell adhesion and expression of N-cadherin among retinoblastoma cell lines.

Retinoblastoma (RB) is the most common intraocular childhood cancer, but little is known regarding its cellular biology and the factors that might regulate its progression and metastatic potential. Although alterations in cell-adhesion interactions could contribute to the metastatic behavior of RB, no specific cell-adhesion molecules have been identified in RB cells. The current study examined the adhesive properties of three RB cell lines (Weri-Rb1, Weri-Rb27, and Y79) and determined whether N-cadherin, a specific cell-adhesion protein expressed during normal retinal development, was expressed by these cell lines. This study revealed marked differences in the cell-adhesive properties of the three cell lines with respect to several parameters assayed, including cell morphology, calcium dependence of the cell adhesion, and the presence of N-cadherin. N-cadherin was expressed by human RB cells, but the level of expression, determined both functionally and biochemically, varied among different RB cell lines.