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Biomedical subjects

J Wickens

Publications and source records attributed to J Wickens.

10 recordsLinked to original sources
PubMed2003

Ocular photodynamic therapy with verteporfin for choroidal neovascularization secondary to ocular histoplasmosis syndrome.

PURPOSE: To evaluate the use of ocular photodynamic therapy (OPT) with verteporfin in patients with choroidal neovascularization (CNV) from ocular histoplasmosis syndrome (OHS) and to compare these results with those for a natural history group. METHODS: A retrospective chart review was performed to identify cases of CNV secondary to OHS treated with OPT. Complete data were available for 38 of 41 eligible eyes. Data regarding the following variables were abstracted from the patient charts: demographic characteristics, previous surgery, angiographic features, number and timing of treatments with OPT, follow-up time, and visual acuity. The visual acuity results of eyes receiving photodynamic therapy were compared with those for a natural history cohort. RESULTS: On average, OHS patients who received treatment developed 0.88 line of visual improvement. Visual acuity improved or stayed the same in 69% (22 of 32) of eyes, improved by > or = 2 lines in 44% (14 of 32), and improved by > or = 4 lines in 22% (7 of 32). Patients who received OPT were 2.07 times more likely to have improved or constant vision than were those in the natural history group as described in one retrospective series (odds ratio = 2.07; 95% confidence interval, 0.78-5.56; P = 0.162). Thirty-eight percent (12 of 32) of eyes had undergone submacular surgery for CNV before any OPT. CONCLUSIONS: Ocular photodynamic therapy with verteporfin may be beneficial in patients with CNV secondary to OHS, even in the setting of previous submacular surgery.

Adolescent↗
PubMed1999

Long-term survival characteristics of 832 resin-retained bridges and splints provided in a post-graduate teaching hospital between 1978 and 1993.

The clinical performance of 832 resin-retained bridges and splints provided in the adult fixed prosthodontic clinic of a post-graduate teaching hospital was reviewed. Recall data was available for 58.4% of cases and the median survival was 7 years and 10 months. Analysis of clinical variables influencing survival revealed that the design and retainer coverage were significant factors. The experience of the operator carrying out treatment also had a pronounced effect which was not readily explained in terms of the distribution of other significant factors. Resin-retained restorations made with minimal tooth preparation are shown to be capable of extended clinical service and their failure rarely resulted in adverse consequences for the patient. Patient satisfaction with their treatment was reportedly high.

Adolescent↗
PubMed1998

Striatal mechanisms in Parkinson's disease: new insights from computer modeling.

We review data and hypotheses concerning the functional anatomy of the striatum and the role of its corticostriatal and nigrostriatal afferents in Parkinson's disease (PD). Starting from molecular mechanisms of glutamatergic and dopaminergic actions in the striatum we have developed a compartmental model of striatal principal neurons that displays a significant degree of biological realism. Simulations of a network of striatal projection neurons under conditions likely to be found in healthy subjects as well as untreated and therapeutic situations of advanced PD provide clues concerning the dynamics of neuronal interactions and their possible effects on downstream motor structures in the generation of positive and negative motor symptoms. We present tentative biological explanations of the symptoms of rigidity and akinesia in PD leading to predictions concerning the origin of abnormal movements and the beneficial effects of dopaminergic treatment. Although these attempts are not yet sufficient to account for the complexity of clinical symptoms found in PD they can guide further empirical research and foster fruitful interactions between experimentalists, theoreticians, and clinicians in unraveling the functional anatomy of the basal ganglia.

Computer Simulation↗
PubMed1998

Does having to remember the position of a target improve reaction time?

In the monkey, reaction time in a precued delayed response task was found to be faster when the animals had to remember the precue than when it was continually available (Smyrnis, Taira, Ashe, & Georgopoulos, 1992). We investigated whether this reflects a general principle that applies to all types of precued tasks. However, we found the opposite result in a simpler task in humans. Our findings suggest that the beneficial effect of a memory requirement on reaction time in the monkey may reflect an effect of task difficulty, rather than a fundamental process involved in all precued movement tasks.

Adult↗
PubMed1996

Surface treatment of gold alloys for resin adhesion.

This in vitro study compared three methods of surface treating gold alloys to improve resin adhesion. The tensile bond strengths and modes of failure between specimen pairs cemented with a chemically adhesive resin were recorded. Heat-treated gold alloy specimens were significantly more resistant to bond failure under tensile loading than were either alumina-blasted or tin-plated gold specimens. There was no statistically significant difference in bond failure between alumina-blasted and tin-plated gold specimens. The surface treatment altered the mode of failure from adhesive and/or adhesive-cohesive for alumina-blasted and tinplated gold specimens to cohesive (within the resin) for heat-treated gold specimens. Three case reports are presented to illustrate clinical applications of heat-treated gold alloys.

Adult↗
PubMed1995

Interactions of glutamate and dopamine in a computational model of the striatum.

A network model of simplified striatal principal neurons with mutual inhibition was used to investigate possible interactions between cortical glutamatergic and nigral dopaminergic afferents in the neostriatum. Glutamatergic and dopaminergic inputs were represented by an excitatory synaptic conductance and a slow membrane potassium conductance, respectively. Neuronal activity in the model was characterized by episodes of increased action potential firing rates of variable duration and frequency. Autocorrelation histograms constructed from the action potential activity of striatal model neurons showed that reducing peak excitatory conductance had the effect of increasing interspike intervals. On the other hand, the maximum value of the dopamine-sensitive potassium conductance was inversely related to the duration of firing episodes and the maximal firing rates. A smaller potassium conductance restored normal firing rates in the most active neurons at the expense of a larger proportion of neurons showing reduced activity. Thus, a homogeneous network with mutual inhibition can produce equally complex dynamics as have been proposed to occur in a striatal network with two neuron populations that are oppositely regulated by dopamine. Even without mutual inhibition it appears that increased dopamine concentrations could partially compensate for the effects of reduced glutamatergic input in individual neurons.

Action Potentials↗
PubMed1994

Cortical cell assemblies: a possible mechanism for motor programs.

The concept of a motor program has been used to interpret a diverse range of empirical findings related to preparation and initiation of voluntary movement. In the absence of an underlying mechanism, its exploratory power has been limited to that of an analogy with running a stored computer program. We argue that the theory of cortical cell assemblies suggests a possible neural mechanism for motor programming. According to this view, a motor program may be conceptualized as a cell assembly, which is stored in the form of strengthened synaptic connections between cortical pyramidal neurons. These connections determine which combinations of corticospinal neurons are activated when the cell assembly is ignited. The dynamics of cell assembly ignition are considered in relation to the problem of serial order. These considerations lead to a plausible neural mechanism for the programming of movements and movement sequences that is compatible with the effects of precue information and sequence length on reaction times. Anatomical and physiological guidelines for future quantitative models of cortical cell assemblies are suggested. By taking into account the parallel re-entrant loops between the cerebral cortex and basal ganglia, the theory of cortical cell assemblies suggests a mechanism for motor plans that involve longer sequences. The suggested model is compared with other existing neural network models for motor programming.

Journal Article↗
PubMed1990

Striatal dopamine in motor activation and reward-mediated learning: steps towards a unifying model.

On the basis of behavioural evidence, dopamine is found to be involved in two higher-level functions of the brain: reward-mediated learning and motor activation. In these functions dopamine appears to mediate synaptic enhancement in the corticostriatal pathway. However, in electrophysiological studies, dopamine is often reported to inhibit corticostriatal transmission. These two effects of dopamine seem incompatible. The existence of separate populations of dopamine receptors, differentially modulating cholinergic and glutamatergic synapses, suggests a possible resolution to this paradox. The synaptic enhancement which occurs in reward-mediated learning may also be involved in dopamine-mediated motor activation. The logical form of reward-mediated learning imposes constraints on which mechanisms can be considered possible. Dopamine D1 receptors may mediate enhancement of corticostriatal synapses. On the other hand, dopamine D2 receptors on cholinergic terminals may mediate indirect, inhibitory effects of dopamine on striatal neurons.

Animals↗
PubMed1988

Electrically coupled but chemically isolated synapses: dendritic spines and calcium in a rule for synaptic modification.

An influential model of learning assumes synaptic enhancement occurs when there is pre- and post-synaptic conjunction of neuronal activity, as proposed by Hebb (1949) and studied in the form of long-term potentiation (LTP). There is evidence that LTP has a post-synaptic locus of control and is triggered by an elevation of intracellular calcium ion concentration, [Ca2+]i. Since synapses which undergo LTP are usually situated on dendritic spines, three effects of spine morphology on this system should be considered: (i) synapses on spines are chemically isolated by the barrier to Ca2+ diffusion due to the spine neck dimensions; (ii) the resistance of the spine neck permits a given synaptic current to bring about greater depolarization (of the spine head membrane) than the same current into a dendrite; while (iii) the spine neck resistance does not significantly attenuate current flow (in the dendrite to spine direction) because of the relatively high impedance of the spine head, and this permits electrical coupling via the dendritic tree. The specificity of LTP to activated synapses on depolarized cells has recently been attributed to special properties of the receptor-linked channel specifically activated by N-methyl-D-aspartate (NMDA). This admits calcium and other ions only when there is both depolarization and receptor activation. However, consideration of point (ii) suggests that, for spines with high resistance necks, the current through a synapse on the spine head will cause sufficient depolarization to unblock the NMDA channel. Thus, the properties of the NMDA channel do not account for the requirement for conjunction of pre- and post-synaptic activity, if these channels are located on the spine head. This suggests that additional mechanisms are required to explain why it is necessary to depolarize the post-synaptic cell in order to induce LTP. As an alternative, it is postulated that there exist voltage-sensitive calcium channels (VSCCs) on the spine head membrane, of a type which require greater membrane depolarization for activation. To generate the greater depolarization required, both pre- and post-synaptic activation would be necessary. If so, the role of dendritic or somatically located NMDA channels may be to "prime" neurons for LTP by enchancing voltage-dependent responses. A corollary is that spine resistance may regulate the threshold number of synapses required to produce LTP. It is predicted that, on spines with very high neck resistance (say, greater than 600 M omega), synaptic current alone may produce sufficient depolarization to activate VSCCs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗