Origins of afferents to visual suprageniculate nucleus of the cat.

Small iontophoretic ejections of horseradish peroxidase (HRP) were made from recording-multibarrel micropipette assemblies in areas of the cat's suprageniculate nucleus (SGn) that contained visually responsive neurones. The sources of afferents of the SGn were determined by locating the labeled cell bodies of neurones that were presumed to send their axons to the area of the SGn containing the light-sensitive cells. The greatest concentration of labeled cell bodies was found in the granular insular cortex and the adjacent area of agranular insula. Most cells projecting to SGn from these areas were distributed in the middle and lower laminae. A second intensely labeled region was found in stratum opticum and stratum griseum intermediate of the superior colliculus. Other areas containing labeled cells that were distributed with intermediate density included the ventral thalamic nuclear complex (basal, medial, and lateral divisions), periaqueductal gray (PAG), zona incerta, and pretectal nuclei (posterior, medial, and anterior divisions). Sparsely labeled sites included the fields of Forel, substantia nigra (pars reticulata), peri-insular cortex, superior colliculus (profundum), lateral suprasylvian cortex (posterolateral lateral suprasylvian, PLLS and posteromedial lateral suprasylvian, PMLS), anterior ectosylvian cortex, thalamic reticular complex, nucleus of the optic tract, basal part of the ventromedial hypothalamic nucleus, and the pontine reticular nucleus (oralis) and adjacent reticular formation. Together with previous electrophysiological and neuroanatomical studies, the findings suggest that the SGn provides an integrating link between limbic structures and certain modalities of sensory information.

Smooth pursuit dysfunction in Alzheimer's disease.

Smooth ocular pursuit was measured by magnetic search coil oculography in 13 patients with Alzheimer's disease and compared with control subjects. Smooth eye movement gain was uniformly reduced in Alzheimer's disease at all target velocities for several frequencies of sinusoidal target motion, signifying impairment of steady-state gain. Normal phase relationships between the target and eyes indicated an intact predictor mechanism for smooth pursuit. When peak target velocity was held constant, pursuit gain decreased markedly in response to small increments of target acceleration, indicating involvement of an acceleration saturating nonlinear element that limits smooth pursuit. Large-amplitude saccadic intrusions, in the direction of target motion, often disrupted pursuit; smooth eye movements continued in response to target velocity despite large position errors of the fovea from its target. These disorders of smooth eye movement control can quantify motor dysfunction in Alzheimer's disease.

Tonic pupils in neurosyphilis.

Of 60 patients with tonic pupils, 29 had serologic tests for syphilis. Five patients had positive blood serology and confirmatory tests; four had other manifestations of neurosyphilis and positive CSF serology. All seropositive patients had bilateral tonic pupils with light-near dissociation and denervation hypersensitivity. Of the 10 tonic pupils, only 1 was miotic and 1 dilated. Although tonic pupils tend to become small and bilateral, they should be distinguished readily from Argyll Robertson pupils, which react briskly, not tonically, to near stimuli. Patients with bilateral tonic pupils should have serologic tests for syphilis.

Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations.

Upward and downward gaze palsy was measured by a magnetic search coil technique and correlated with neuropathologic findings in a patient with a unilateral midbrain infarct. Oculography demonstrated (1) saccadic palsy above primary position and slow, limited vertical saccades below; (2) low-gain, restricted vertical pursuit; and (3) low-gain, abnormal phase lead, and restricted range of the vertical vestibulo-ocular reflex (VOR). Bidirectional palsy of vertical saccades is attributed to unilateral loss of burst cells in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and interruption of burst cell fibers from the opposite riMLF. Pathways mediating vertical pursuit and integration of the vertical VOR also traversed the infarct, which included the interstitial nucleus of Cajal.

On the cause of hyporeflexia in the Holmes-Adie syndrome.

Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) in the patients with depressed reflexes. The amplitude of the composite Ia EPSP in single soleus motoneurons was estimated from changes in firing probability of voluntarily activated soleus motor units in response to stimulation of low threshold afferents in the tibial nerve. These amplitudes were used to test the afferent side of the reflex pathway. Composite group Ia EPSPs in Holmes-Aide patients with hyporeflexia were smaller than normal or absent, indicating that the areflexia in the Holmes-Aide syndrome is due to loss of large spindle afferents or reduced effectiveness of their monosynaptic connections to motoneurons.

Congenital quadrantanopia with occipital lobe ganglioglioma.

A 24-year-old man with recent-onset seizures was found to have an occipital lobe ganglioglioma with homonymous quadrantanopia and trans-synaptic atrophy of retinal nerve fibers. This association indicates that gangliogliomas may arise during neural development and exist for many years before onset of symptoms.

Smooth pursuit during dose-related on-off fluctuations in Parkinson's disease.

Smooth pursuit was studied during predictable L-dopa dose-related "off" periods of morning akinesia and wearing off and during "on" periods in eight patients with idiopathic Parkinson's disease. Smooth pursuit gain was significantly reduced in patients during both on and off phases. Despite marked fluctuations between parkinsonism and periods of near normal skeletal motion, there were no changes in smooth pursuit gain. We conclude that unvarying paresis of smooth pursuit in Parkinson's disease signifies involvement of neural circuits that are distinct from the dopaminergic mechanisms that mediate the on-off phenomenon of somatic motor control.

Is the stepping test a specific indicator of vestibulospinal function?

We studied the effect of walking on a horizontally rotating disk (circular treadmill) on the stepping test in seven normal subjects. Subjects walked for 2 hours on the perimeter of the treadmill with eyes open while remaining stationary in space. Then, off the treadmill, they attempted to step in place with eyes closed for 50 paces without turning. All subjects exhibited post-treadmill turning in the same direction as that of the previous walking relative to the treadmill. Post-treadmill average angular velocities were 207 to 880 deg/min greater than pretreadmill values. No subject experienced any sensation of motion relative to ground or space. The stepping test may no longer be considered a specific indicator of vestibulospinal function.

Pulmonary epithelial-mesenchymal interactions: beyond organogenesis.

Epithelial-mesenchymal interactions are important regulators of lung growth and organogenesis, but later functional maturation of the fetal lung is though to be primarily under hormonal control. Recent evidence, however, suggests that hormonal effects on pulmonary cellular and biochemical maturation continue to involve intercellular interactions. Communication between cells may have wider importance than has hitherto been appreciated. It should be noted that in addition to organogenesis and biochemical development, mature lung requires an extensive capillary network in close proximity to areas of gas exchange. Recent attempts to isolate and culture pumonary endothelium may be expected to provide new insights into this neglected aspect of lung maturation. The possibility of hormonal or intercellular mediation of the differentiation of airway epithelium might also merit investigation.

Poly(2-hydroxyethyl methacrylate) sponges as implant materials: in vivo and in vitro evaluation of cellular invasion.

The pore size and the in vivo behaviour of four poly(2-hydroxyethyl methacrylate) sponges were investigated. The sponges were synthesized by polymerization of monomer in 70, 80 and 90 wt% water, respectively. In one of the formulations, a high amount of initiator was added. The average pore diameter was calculated with Ferry's equation and the results compared to those obtained by examination of samples using environmental scanning electron microscopy. The use of the equation greatly underestimated the size of pores. We also showed that the pores in polymers obtained in 70 wt% water were not interconnected, whilst the pores in polymers obtained in 80 and 90 wt% water, respectively, were larger and interconnected throughout the polymer. When implanted subcutaneously in rabbits, only the latter polymers allowed invasion and proliferation of cells. Penetration and proliferation of cells in these sponges were also assessed by an in vitro method using cultured human fibroblasts. The procedure included the overlaying of a glass plate covered by confluent cultured cells on to the surface of polymer impregnated with collagen. The depth of migration and number of sections needed to be cut to count a fixed number of invading cells were measured after incubation for 2 wk and used as indicators in comparing the ability of various sponges to allow cellular invasion. The assay showed that more cells invaded a hydrogel sponge produced in 80 wt% water than one produced in 90 wt% water. It also showed that the cut polymer surfaces allowed a greater cellular invasion than the moulded ones.

Acute idiopathic blind spot enlargement. A big blind spot syndrome without optic disc edema.

We examined seven patients who had a syndrome of symptomatic monocular blind spot enlargement without optic disc edema. Two patients had previous blind spot enlargement that resolved over several months. The scotoma in each patients was absolute, measured 15 degrees to 20 degrees in diameter, had steep geographic margins, and extended to within 5 degrees to 10 degrees of fixation. Typically, patients had normal visual acuity, color vision, pupillary responses, and ophthalmoscopic findings. Photostress recovery, tested in two patients, was prolonged in the affected eye. Fluorescein angiography showed no abnormalities corresponding to the scotoma. Orbital computed tomographic scans in three patients and visual evoked responses in one patient were normal. Multifocal electroretinography, performed in two patients, showed loss of retinal waveforms in a large region surrounding the optic disc. Our findings suggest that retinal dysfunction produces this big blind spot syndrome, but we do not know its cause.

Spontaneous regression of optic gliomas: thirteen cases documented by serial neuroimaging.

OBJECTIVE: To demonstrate spontaneous regression of large, clinically symptomatic optic pathway gliomas in patients with and without neurofibromatosis type 1 (NF-1). METHODS: Patient cases were collected through surveys at 2 consecutive annual meetings of the North American Neuro-Ophthalmology Society (NANOS) and through requests on the NANOSNET Internet listserv. Serial documentation of tumor signal and size, using magnetic resonance imaging in 11 patients and computed tomography in 2 patients, was used to evaluate clinically symptomatic optic pathway gliomas. All tumors met radiologic criteria for the diagnosis of glioma and 4 patients had biopsy confirmation of their tumors. In 3 patients, some attempt at therapy had been made many years before regression occurred. In one of these, radiation treatment had been given 19 years before tumor regression, while in another, chemotherapy had been administered 5 years before signal changes in the tumor. In the third patient, minimal surgical debulking was performed 1 year before the tumor began to shrink. RESULTS: Spontaneous tumor shrinkage was noted in 12 patients. Eight patients did not have NF-1. In an additional patient without NF-1, a signal change within the tumor without associated shrinkage was detected. Tumor regression was associated with improvement in visual function in 10 of 13 patients, stability of function in 1, and deterioration in 2. CONCLUSIONS: Large, clinically symptomatic optic gliomas may undergo spontaneous regression. Regression was seen in patients with and without NF-1. Regression may manifest either as an overall shrinkage in tumor size, or as a signal change on magnetic resonance imaging. A variable degree of improvement in visual function may accompany regression. The possibility of spontaneous regression of an optic glioma should be considered in the planning of treatment of patients with these tumors.

Bilateral cancer of the breast: a review of clinical, histologic, and immunohistologic characteristics.

The clinical, histologic, and immunohistologic characteristics of 19 synchronous and 47 metachronous bilateral breast cancers was compared. Patients with metachronous tumors were 5 years younger and more likely to have a family history of breast cancer than those patients with synchronous cancers. The nondominant synchronous cancer was usually discovered mammographically accounting for small, node-negative tumors, and high prevalence of in situ lesions. The same was true of the second metachronous tumor when discovered mammographically. Patients with metachronous cancers who were not in a follow-up program had second cancers with characteristics similar to incidentally diagnosed unilateral cancer. The mean interval between metachronous cancers was 101 months. Significantly more first metachronous tumors were invasive lobular cancers. Histologic type of the first and second tumor was the same in only 68% of synchronous and 61% of metachronous cancers. Combined histologic evidence and differentiation was concordant in only 13% and 22% of tumors, respectively. Immunoperoxidase studies were performed with two human milk fat globule antibodies. Each antibody reacted similarly in the first and second tumor in less than 50% of tumors and concordance was less than 25% when both antibody reactions were assessed. Differences in histologic evidence, differentiation, and immunohistologic reaction suggest that both synchronous and metachronous cancers are morphologically and functionally dissimilar.

An immunoassay for human D dimer using monoclonal antibodies.

Monoclonal antibodies (MAb) were raised against human D dimer. The hybridomas were screened with a solid phase enzyme immunoassay against D dimer and fibrinogen degradation products. Among the panel of MAb identified, two distinct patterns emerged; the majority belonging to a panspecific class reacting against epitopes present on both D dimer and fibrinogen degradation product Dcate and a monospecific class reacting with determinants apparently present only on D dimer. A number of MAb were further characterised for their ability to specifically capture antigen in a solid phase enzyme immunoassay and assays were developed which have a sensitivity of 10 ng/ml for D dimer or crosslinked fibrin derivatives and may be suitable for detection of crosslinked derivatives in serum and plasma samples in a clinical situation.

Relative afferent pupillary defects in patients with Leber hereditary optic neuropathy and unilateral visual loss.

PURPOSE: It has been suggested that the pupillary light reaction is relatively preserved in the affected eyes of patients with Leber hereditary optic neuropathy (LHON). To test the hypothesis that visual-pupillomotor dissociation exists in LHON, we performed a retrospective study to evaluate the magnitude of the relative afferent pupillary defect (RAPD) in patients who had experienced monocular visual loss. We also compared the size of the measured RAPD with the size of the RAPD that would be expected on the basis of documented visual field loss. METHODS: We identified a cohort of patients with LHON and monocular visual loss, whose pupillary reactions had been quantified using neutral density filters. From a review of the case records, we determined whether an RAPD was present, as well as the magnitude of the documented RAPDs. We also calculated the expected size of the RAPD for each patient, using previously established templates that correlated the size of the RAPD with the degree of visual field loss. RESULTS: An RAPD was identified in all 10 patients in this study. There was no significant difference between the size of the measured and predicted RAPD, nor did the size of the RAPD correlate with visual acuity or the time interval between the onset of visual loss and evaluation. CONCLUSION: The results of this study do not support the hypothesis that visual-pupillomotor dissociation is a common feature of LHON.

Photodynamic endometrial ablation in the nonhuman primate.

OBJECTIVE: To test the effectiveness of 5-aminolevulinic acid (ALA)-induced photodynamic endometrial ablation in the rhesus monkey under varying conditions of light delivery (fractionated versus continuous) and steroid priming. METHODS: Photodynamic endometrial ablation was carried out in 17 rhesus monkeys that were either postmenopausal or in the early proliferative phase. Four hours after intralumenal injection of ALA (250 mg in 1 mL hyskon), a quartz fiber with a diffusing tip was inserted. A KTP tunable dye laser delivered 300 mW of light (635 nm) for 60 minutes in either continuous or fractionated fashion (20 minutes on, 5 minutes off, and 40 minutes on). In some experiments, thermistors were used to monitor temperature in the lumen and myometrium during light treatment. Hysterectomy was performed 3 or 4 days after treatment, and endometrial damage was assessed histologically. Two additional monkeys (one rhesus and one cynomolgus monkey) were exposed to the same protocol, except hyskon was substituted for ALA to control for potential ablative effects due to light treatment alone. RESULTS: Endometrial ablation was evident in all ALA-photosensitized specimens. The degree of ablation around the light fiber ranged from moderate to complete. The depth of ablation ranged from 1.14 +/- 0.54 to 2.15 +/- 1.62 mm (mean +/- standard deviation). Ablation was most complete in uteri of menopausal monkeys. Light treatment after ALA increased lumenal temperature from 36 C to 50 C, whereas temperature was not significantly increased by light treatment in the controls. CONCLUSION: This is the first report of endometrial destruction in the primate using a photodynamic approach. Whereas clinical application of photodynamic therapy (PDT) requires complete endometrial ablation to produce long-lasting amenorrhea, our results suggest that PDT may offer a simple office-based approach to endometrial ablation.

Chiasmal gliomas: appearance and long-term changes demonstrated by computerized tomography.

A survey of 22 cases showed the broad spectrum of lesions collectively termed "chiasmal gliomas." Three computerized tomography (CT) patterns were diagnostic: a tubular thickening of the optic nerve and chiasm, a suprasellar tumor with contiguous optic nerve expansion, and a suprasellar tumor with optic tract involvement. Globular suprasellar tumors lacking these features required a histological examination for diagnosis. Tumor growth was documented by CT in only three chiasmal gliomas; all were the globular type. Failing visual function did not reflect chiasmal tumor growth, and stable vision did not exclude it. Both patients with tubular optic nerve thickening and two of three patients with unilateral optic nerve expansion had neurofibromatosis. Five tumors became smaller after irradiation. Complications of radiation therapy included calcification of lenticular nuclei and remote infarcts. In patients who underwent biopsy, the CT appearance did not differentiate juvenile pilocytic astrocytoma from anaplastic astrocytoma. Thus, CT guides the diagnosis and neurosurgical treatment of chiasmal gliomas, establishing the need for biopsy or ventricular shunting.

Rupture of cavernous carotid artery aneurysm causing subdural hematoma and death. Case report.

Aneurysms of the intracavernous portion of the internal carotid artery may become very large, but they very rarely rupture. A case is described in which rupture of such a lesion resulted in a lethal massive subdural hematoma with transtentorial herniation. This is the second reported case of substantiated intracranial rupture from a wholly intracavernous carotid artery aneurysm.

Further studies on ultraviolet-absorbing hydrogels for intraocular lenses: relationship between concentration of a polymerizable benzophenone, absorption, and extractability.

A tendency to reduce the use of benzophenone absorbers is currently evident in the manufacture of the UV-absorbing IOLs, mainly because the cutoff wavelengths are inferior to those provided by benzotriazoles. In principle, by incorporating large amounts of benzophenones it may be possible to achieve high cutoff wavelengths. A covalently bondable benzophenone UV absorber, Cyasorb UV-2098, was incorporated in poly(2-hydroxyethyl methacrylate) (PHEMA) in increasing concentrations, and certain associated phenomena were investigated. At 4% w/w absorber content, the nonhydrated polymers turned partially opaque. In water-swollen hydrogels, opacification occurred at a lower absorber content (2% w/w). By using extraction techniques and gas chromatography, we also found that up to 8% w/w of the absorber remained unpolymerized and could leach out from any material containing less than 5% w/w absorber. In samples with higher initial content of absorber, the amount of unreacted, leachable absorber was significantly higher (25% to 30%). Based on this study model (hydrogel/Cyasorb UV-2098), we concluded that benzophenone absorbers cannot provide cutoff wavelengths higher than those provided by benzotriazoles.

Monoclonal antibodies directed against Brucella abortus cell surface antigens.

A panel of monoclonal antibodies (MAb) has been raised against Brucella abortus cell surface antigens from mice immunized with either heat/phenol treated or UV killed bacterial suspensions of B. abortus. The hybridomas were screened by either a microagglutination procedure or by an indirect enzyme immunoassay (EIA) on sonicated bacterial preparations. From a large number of MAb generated by various procedures, two distinct types of MAb emerged. The most numerous type was capable of agglutinating B. abortus and reacting with a soluble preparation of lipopolysaccharide (LPS). A second type was not capable of agglutinating the bacterial suspensions or of binding to the soluble LPS preparation but reacted with an antigen present in bacterial sonicates. Two MAb of this type react differentially with sonicates prepared from virulent and avirulent strains of B. abortus. There appeared to be sufficient evidence from our analysis of the relative degree of cross reaction with antigens present on a range of B. abortus strains and Brucella and xenogenic bacterial species to conclude that each of the seven MAb was recognising a separate antigenic site on the B. abortus cell surface.