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Biomedical subjects

Joseph M Harrison

Publications and source records attributed to Joseph M Harrison.

7 recordsLinked to original sources
PubMed2006

A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence.

Prior studies have demonstrated inefficacy among dopamine receptor antagonists for treating cocaine dependence. An alternative approach would be to investigate the ability of indirect inhibitors of cortico-mesolimbic dopamine release, such as the 5-HT(3) receptor antagonist ondansetron, to reduce cocaine's reinforcing effects. We hypothesized that ondansetron might be more efficacious than placebo at reducing cocaine intake and promoting abstinence in cocaine-dependent individuals. In a pilot randomized, double-blind, 10-week controlled trial, 63 treatment-seeking, cocaine-dependent men and women received ondansetron (0.25 mg, 1.0 mg, or 4.0 mg twice daily) or placebo. Up to three times per week, participants were assessed on several measures of cocaine use, including urine benzoylecgonine. Cognitive behavioral therapy was administered weekly. Ondansetron was well tolerated, causing no serious adverse events. The ondansetron 4.0 mg group had the lowest dropout rate among all treatment groups and a greater rate of improvement in percentage of participants with a cocaine-free week compared with the placebo group (p = 0.02), whereas the ondansetron 1.0 mg group had a lower rate of improvement in percentage of weekly mean non-use days than did placebo recipients (p = 0.04). These results suggest the possibility of a non-linear dose-response function, with evidence supporting efficacy for the 4.0 mg group.

Adult↗
PubMed2005

Retinal function assessed by ERG before and after induction of ocular aspergillosis and treatment by the anti-fungal, micafungin, in rabbits.

This study was conducted to evaluate the effectiveness of a new antifungal drug, micafungin, and standard antifungal drugs against endophthalmitis induced in a rabbit by intravitreal injection of Aspergillus fumigatus, an important fungal pathogen. Effectiveness was evaluated by the preservation of b-wave amplitude at 72 h after injection of the fungus relative to the b-wave amplitude at baseline before any intravitreal injections. A 0.06 ml inoculum of 10(6) conidia of A. fumigatus was injected into the vitreous of the right eye of all rabbits; and, 12 h later, a 0.06 ml solution containing one of 3 antifungal drugs or saline was injected into the vitreous of both eyes. All three antifungal drugs produced significant b-wave preservation at 72 h in infected eyes compared to that in infected eyes receiving saline injections. There was no statistically significant difference between the effects of micafungin and amphotericin B in the right eyes with fungal endophthalmitis, and both produced significantly more preservation of b-wave amplitude than voriconazole. Amphotericin B, but neither micafungin nor voriconazole produced significant reduction of the b-wave amplitude in the left eyes.

Amphotericin B↗
PubMed2004

Tonopen measurement of intraocular pressure in mice.

PURPOSE: To standardize a method of non-invasive measurement of intraocular pressure (IOP) in mice. METHODS: Cannulated-eye study: IOP was measured simultaneously with a Tonopen and by direct cannulation of the vitreous compartment while pressure was manipulated in steps between 10 and 45 mmHg by a saline reservoir via a second vitreal cannula (five mice, one rat). Non-cannulated-eye study: Tonopen and servo-null measurements were performed in independent groups (48 mice) to verify Tonopen measurements in non-cannulated-eyes. Topical brimonidine (0.15%) was used to decrease IOP. RESULTS: In the rat, there was a similar relationship between Tonopen readings and direct measurements via cannulation of the eye as previously reported. Although readings from mice eyes were higher in variability than those obtained from the rat, the measurements were reproducible and the correlation between the invasive and the non-invasive methods was good (r = 0.97). The IOP lowering effect of brimonidine was detected with Tonopen as well as servo-null measurements (p < 0.001) and the results with both techniques were similar. CONCLUSION: The Tonopen can be used for rapid and reproducible measurements of IOP in mice. The method is easy to apply and can provide a useful means for IOP measurement in mouse models of induced ocular hypertension, in knock-out and transgenic mice, or in pharmacological studies.

Animals↗
PubMed2003

Modification of the Heidelberg retinal flowmeter to record pattern and flicker induced blood flow changes.

PURPOSE: We tested a prototype stimulator interfaced with a commercially available scanning laser ophthalmoscope designed to measure retinal capillary perfusion (Heidelberg Retina Flowmeter (HRF)). The add-on stimulator optically superimposed the image of a monitor display on to the subject's retina coaxially with the imaging optics of the HRF. The purpose of the study was to determine if flicker and pattern stimulation presented in this manner could evoke changes in retinal perfusion that could be measured by the HRF. METHODS: The prototype stimulator projected 55 degrees visual angle circular fields of homogeneous flicker, alternating checkerboard, and multi-focal m-sequence hexagonal patterns on the retina of 10 human subjects during acquisition of images by the HRF. RESULTS: Images were successfully acquired and processed. HRF perfusion values during flicker and pattern stimulation were not significantly different from control values. CONCLUSIONS: Results of the present study and a previously published study showing a flicker-induced increase in the HRF perfusion values are contradictory. Retinal perfusion measured by the HRF were not affected by flicker and pattern stimulation delivered through the prototype device. These data are not consistent with a large flicker or pattern induced increase in retinal perfusion. The instrumental modification appears promising. However, the raster scan stimulation technique or some other aspect of stimulation or image acquisition may account for the different results in the present study and previous studies in our laboratory and in the laboratories of other investigators.

Adult↗
PubMed2002

Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors.

Dopamine is a retinal neuromodulator that has been implicated in many aspects of retinal physiology. Photoreceptor cells express dopamine D4 receptors that regulate cAMP metabolism. To assess the effects of dopamine on photoreceptor physiology, we examined the morphology, electrophysiology, and regulation of cAMP metabolism in mice with targeted disruption of the dopamine D4 receptor gene. Photoreceptor morphology and outer segment disc shedding after light onset were normal in D4 knock-out (D4KO) mice. Quinpirole, a dopamine D2/D3/D4 receptor agonist, decreased cAMP synthesis in retinas of wild-type (WT) mice but not in retinas of D4KO mice. In WT retinas, the photoreceptors of which were functionally isolated by incubation in the presence of exogenous glutamate, light also suppressed cAMP synthesis. Despite the similar inhibition of cAMP synthesis, the effect of light is directly on the photoreceptors and independent of dopamine modulation, because it was unaffected by application of the D4 receptor antagonist l-745,870. Nevertheless, compared with WT retinas, basal cAMP formation was reduced in the photoreceptors of D4KO retinas, and light had no additional inhibitory effect. The results suggest that dopamine, via D4 receptors, normally modulates the cascade that couples light responses to adenylyl cyclase activity in photoreceptor cells, and the absence of this modulation results in dysfunction of the cascade. Dark-adapted electroretinogram (ERG) responses were normal in D4KO mice. However, ERG b-wave responses were greatly suppressed during both light adaptation and early stages of dark adaptation. Thus, the absence of D4 receptors affects adaptation, altering transmission of light responses from photoreceptors to inner retinal neurons. These findings indicate that dopamine D4 receptors normally play a major role in regulating photoreceptor cAMP metabolism and adaptive retinal responses to changing environmental illumination.

Adaptation, Ocular↗
PubMed2002

Flash visual evoked potentials in the hypomyelinated mutant mouse shiverer.

Myelin basic protein (MBP) is an essential component of central nervous system (CNS) myelin, as demonstrated by shiverer mutant mice that have deletions of most of the Mbp structural gene. These mutants do not produce detectable MBP protein, and their CNS is hypomyelinated. Although the function of the visual pathway is presumed to be adversely affected by hypomyelination of the optic nerve, it has never been studied. We compared flash visual evoked potentials (FVEPs) of shiverer homozygotes with those of their wild-type littermates in order to characterize any dysfunction. There was a statistically significant delay in the implicit times of a negative component peaking at 85 ms and a large positive component peaking at 170 ms in the FVEPs of the shiverer mice. The amplitudes of the two components did not differ significantly in the shiverers and wild-type controls. Barring a retinal pathology, which cannot be excluded by these data, the delayed FVEP of the shiverer can likely be attributed to effects of hypomyelination of the optic nerve, optic tract and visual radiations on conduction time in the visual pathway and subsequent further post-synaptic delays.

Animals↗