Biomedical subjects
Publications and source records attributed to G Lafond.
Extracranial head and neck schwannomas are usually benign and rarely malignant tumors of peripheral nerve sheath origin. The clinical presentation of these tumors is reviewed in our series of 21 patients, emphasizing the diagnosis with dynamic infused CT scans. Management is suggested and outcome analysis is provided.
We have determined the structures and thermodynamic stabilities of the wild type Asn-52 and unusually thermostable mutant Ile-52 yeast iso-1-cytochromes c (Das, G., Hickey, D. R. McLendon, D., McLendon, G., and Sherman, F. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 496-499). Although both structures were similar, Water-166, buried within the wild type protein, is excluded from the Ile-52 mutant, which substantially reorganizes the local hydrogen bonding. Wild type Cys-102 was replaced with alanine or serine to eliminate dimerization in vitro. The Cys-102 (wild type), Ala-102, and Ser-102 proteins were equally stable, whereas the chemically modified Cys-102-SCH3 was less stable. The order of stability observed with replacements at positions 52 and 102 was as follows: Ile-52 Ala-102 greater than Ala-52 Ala-102 greater than Asn-52 Ala-102 ("normal") greater than Gly-52 Ala-102. No significant stabilization was attributed to potential energy interactions expressed as helix-forming propensities of replacements at position 52. A high correlation between differences in free energy changes and transfer free energies suggests hydrophobic interactions are the main factor for enhancing stability in the Ile-52 mutant. Additional possible contributions to the thermostability of the Ile-52 variant are energetic effects due to packing and hydrogen bonding changes surrounding position 52.
This study evaluated the effects of intravitreal injections of 300 micrograms of 6-hydroxydopamine (6-OHDA) on electroretinogram (ERG) amplitudes and implicit response times of adult pigmented rabbits. One eye was injected intravitreally with 300 micrograms 6-OHDA and 600 micrograms ascorbic acid in a 0.3 ml 0.9% NaCl solution; the fellow eye received a similar solution containing only 600 micrograms ascorbic acid. Following this treatment ERG recordings were performed at 1, 4, and 7 days. After the last recordings, animals were sacrificed and retinas were isolated for biochemical analyses. Significant and progressive reductions in retinal concentrations of dopamine (DA) and its main metabolites homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC) were found in treated retinas. Concentrations of norepinephrine (NE), serotonin (5HT), and 5 hydroxyindoleacetic acid (5-HIAA) were not affected, thus demonstrating the specific neurotoxic action of 6-OHDA on retinal dopaminergic neurons. Concurrently, significant increases in ERG a- and b-wave amplitudes as well as in implicit response times were observed. These electrophysiological changes were progressive reaching a maximum 7 days after intravitreal injections. Changes in b-wave amplitudes and response times were more pronounced at low intensities of stimulation. These results clearly show that, in rabbits, selective decreases in retinal DA concentrations result in pronounced ERG changes, which offer additional evidence supporting a role for this transmitter in lateral inhibition in the retina.
We studied the effect of optic nerve section on the pattern electroretinogram (PERG) of 10 pigeons. Base line PERG and flash ERG were measured prior to surgery and then one optic nerve was cut. We measured PERG at various time intervals up to 24 weeks after the section. There was a sharp drop in PERG amplitude immediately following the section. It gradually returned to normal levels in the following 24 weeks. Significant decreases in time to peak were noted at 1 and 16 weeks for 0.5 cycle per degree checks and at 1, 2 and 9 weeks for 0.25 cycle per degree checks. The ERG generated by a TV stimulus did not change in amplitude but had a shorter time to peak at 24 weeks for a high intensity stimulus and at 16, 18, 24 weeks for a low intensity stimulus. Light and electron microscopic sections (at 24 weeks) revealed an almost complete loss of nerve fibers in the optic nerve. Retinal sections revealed only a few surviving ganglion cells and a few nerve fibers. This suggests that in pigeons, PERG is not generated by ganglion cells.
Between January 1982 and December 1983 stereo colour photography covering 10 standard fields of 30 degrees and fluorescein angiography were performed in 64 consecutive patients with diabetes mellitus who had no clinical evidence of diabetic retinopathy. Fifty-two patients were excluded on the basis of the slightest photographic or angiographic evidence of retinopathy or any other ocular disease. Electroretinogram oscillatory potentials were recorded in the remaining 12 patients. Four of the 12 had normal oscillatory potentials, colour photographs and angiograms, while 8 had angiographic evidence of lobular delayed choroidal perfusion and abnormal oscillatory potentials. Although only a small number of patients in the preclinical stages of diabetic retinopathy were studied, the results warrant that further attention be given to lobular delayed choroidal perfusion, which may represent early evidence of choroidal involvement in diabetic retinopathy.
Two series of experiments are reported on incremental increases of ischemia and monitoring of recovery from total ischemia of varying duration. In the first, rods show hyper-responses and cones do not; changes in amplitude and delays appear at higher levels of ischemia in cones than they do in rods. In the second series, cones do not recover up to control values with total ischemias of 30 min or more, while rods do recover and even show hyper-responses. Cones appear more resistant than rods to ischemia, but once affected do not recover as well as rods. Discussion proposes that these differences are specific to receptor systems of each rather than secondary to vascularization patterns.
The purpose of this study was to examine the dose related effects of 6-hydroxydopamine (6-OHDA) on the electroretinographic (ERG) B-wave amplitude and on retinal concentrations of dopamine (DA) and its main metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Doses of 6-OHDA (60, 300 or 1200 micrograms) were dissolved in a 0.9 percent NaCl and ascorbic acid solution and administered intravitreally in 300 microliter volume in one eye of adult pigmented rabbits. The fellow eye received a similar volume of the drug vehicle. With the smallest dose of 6-OHDA (60 micrograms) no changes in ERG B-wave amplitude or retinal concentrations of DA, DOPAC or HVA were found. With the largest dose of 6-OHDA (1200 micrograms) complete extinction of the ERG and almost total disappearance of DA, DOPAC and HVA were observed. With the intermediate dose of 300 micrograms 6-OHDA significant increases in B-wave amplitudes and decreases in retinal DA, DOPAC and HVA concentrations were obtained. This latter dose did not affect retinal concentrations of serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and norepinephrine (NE). These results demonstrate that selective reductions of retinal dopamine and its metabolites can be obtained with a single intravitreal injection of 300 micrograms 6-OHDA in rabbits. The observed concomitant increase in B-wave amplitudes lends support to the hypothesis that DA acts as a mediator of lateral inhibition in the retina.
We have observed an increase in time to peak and a decrease in amplitude for both the pattern electroretinogram (PERG) and the electroretinogram (ERG) in pigeons following an elevation in intraocular pressure (IOP). The changes in PERG were highly correlated to the changes in ERG. However, they differed in that significant changes from baseline values occurred at lower levels of IOP for PERG than ERG for the amplitude, and in some cases for the time to peak.
Three groups of animals were studied during the four-hour period following their recovery from total occlusion of retinal circulation for periods of 30, 60 and 90 minutes. During incremental increases of ischemia, recovery followed a pattern that is the reverse of that previously reported, inasmuch as wave amplitude is concerned. From total extinction, ERGs recovered and showed hyperresponses. Delays, however, behaved differently: they increased with recovery time--the opposite of what was expected. All signs were inversely proportional to the duration of ischemia. Sixty minutes of occlusion appears to be a threshold beyond which ERGs do not recover as well.
The midline degloving approach to midfacial and nasosinal tumors is a procedure consisting of elevation of the midfacial soft tissue from a sublabial approach. A modification consisting of a composite flap laterally based on periosteum and soft tissue prevents flattening of the side of the nose. The method has distinct advantages over the transnasal, transpalatal, or lateral rhinotomy approach, giving wide exposure without external scars or disfigurement, and thus is suitable for benign as well as malignant lesions.
The time response of the Electroretinogram (ERG) is an essential part of the examination. Peak time of response increases with dark adaptation and decreases with the intensity of stimulation. When working with constant amplitude during dark adaptation sensitivity increases but the intensity of stimulation decreases. It is essential to clarify the relationship of these two factors for valid interpretation of results. The present work suggests that the state of adaptation or retinal sensitivity affects amplitude, while peak time of the response is modified by the absolute value of the stimulating source whatever the state of adaptation. This observation has been done on rod responses and is valid as long as pigments remain unbleached and able to respond.
We demonstrate the main electrophysiological events during dark adaptation. We correlate simultaneously the separate rod and cone responses, the ERC sensitivity curves, their timing and the biphasic dark adaptation curve.
We exposed adult Rhesus monkeys who were fully dark adapted to paired flashes of white light which increased in intensity by increments of 0.1 log. units. As intensity increased, the amplitudes of both the cone and rod systems increased while the implicit times decreased so that the responses overlapped. High intensities produce a complex waveform which prevents separation of the rod and cone components or timing of the peaks. On the other hand, low intensities separate the early and late receptor potentials (L.R.P.) of cones and rods well and make it easy to time normal and pathological variations.
When Royal College of Surgeons (RCS) rats are bred with Wistar albinos the offspring are deeply pigmented and have normally functioning retinas. From this second generation, various breeding possibilities exist. In the course of successive cross-breedings one can obtain albinos, tan striped (RCS type) or pigmented animals, any one of which may be normal, carrier or affected. The skin pigmentation trait and that of retinal degeneration are independently inherited and follow autosomal recessive Mendelian laws. However normals for ERG studies vary with skin pigmentation. It is suggested that only one group should be chosen and preferably the pigmented variety.
We studied tapeto-retinal degeneration in the offspring of Royal College of Surgeons (RCS) and Wistar albino rats. Normal ERG values vary according to skin pigmentation: thresholds and implicit times are different. We believe the best experimental material is to be found in the affected pigmented offspring. Evolution of the degeneration over more than 9 months has been observed before extinction and the expressivity of the disease varies from one individual to another. This animal model closely resembles the ERG findings observed clinically in certain pigmentary degenerations of the retina.
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