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Biomedical subjects

John G L Morris

Publications and source records attributed to John G L Morris.

10 recordsLinked to original sources
PubMed2006

Evidence for L-dopa incorporation into cell proteins in patients treated with levodopa.

Levodopa (L-dopa) is the most widely used agent for the symptomatic relief of Parkinson's disease. There is concern that chronic L-dopa treatment may be detrimental, with some studies suggesting that L-dopa may be neurotoxic. A potentially important mechanism whereby L-dopa may exert neurotoxic effects has been overlooked: that of the incorporation of L-dopa into proteins by protein synthesis. L-Dopa competes with tyrosine as a substrate in protein synthesis in vitro. We provide evidence that L-dopa can also be incorporated into proteins in vivo. Blood from L-dopa-treated and -non-treated patients was separated into protein, erythrocyte and lymphocyte fractions and levels of protein-incorporated dopa quantified by HPLC. Levels of protein-incorporated dopa were significantly increased in lymphocyte cell proteins from L-dopa-treated patients. This has not arisen from oxidative pathways as there was no evidence of oxidative damage to proteins. In addition, there was no increase in protein-incorporated dopa in erythrocytes, which are not actively synthesizing proteins. We suggest that protein-incorporated dopa could also be generated in the CNS. The accumulation of protein-incorporated dopa in cells is associated with oxidative stress and impaired function and could contribute to some of the problems associated with long-term L-dopa treatment.

Aged↗
PubMed2006

Comparison of motor, cognitive, and behavioral features in progressive supranuclear palsy and Parkinson's disease.

Major clinical features and global measures were systematically evaluated and compared in progressive supranuclear palsy (PSP) and Parkinson's disease (PD). In addition to gaze palsy and early postural instability in PSP, absence of levodopa-induced dyskinesia, frontalis muscle overactivity, primitive reflexes, visuospatial impairment, and substantial frontal behavioral disturbances differentiated almost all patients with this disorder from PD. For PSP, behavioral changes related to severity of general disability, thereby challenging previous models of relationships between behavior, motor, and cognitive disturbance for this disorder.

Aged↗
PubMed2005

Sydney Multicenter Study of Parkinson's disease: non-L-dopa-responsive problems dominate at 15 years.

One-third of the 149 people recruited 15 to 18 years ago in the Sydney Multicenter Study of Parkinson's disease have survived. The original study compared low-dose levodopa with low-dose bromocriptine. We now report the problems experienced by people who survive 15 years from diagnosis. The standardized mortality ratio is significantly elevated at 1.86 and is not significantly different between treatment arms. Falls occur in 81% of patients, and 23% sustained fractures. Cognitive decline is present in 84%, and 48% fulfill the criteria for dementia. Hallucinations and depression are experienced by 50%. Choking has occurred in 50%, symptomatic postural hypotension in 35%, and urinary incontinence in 41%. No patient is still employed, and 40% of patients live in aged care facilities. Although approximately 95% have experienced L-dopa-induced dyskinesia/dystonia and end of dose failure of medication, in the majority, these symptoms are not disabling. Dyskinesia and dystonia were delayed by early use of bromocriptine, but end-of-dose failure appeared at a similar time once L-dopa was added. The rate of disease progression is similar in both arms of the study. We conclude that the most disabling long-term problems of Parkinson's disease relate to the emergence of symptoms that are not improved by L-dopa. Neuroprotective interventions in Parkinson's disease should be judged by their ability to improve non-L-dopa-responsive aspects of the disease, rather than just by their capacity to delay the introduction of L-dopa or reduce its associated side effects.

Aged↗
PubMed2005

Movement disorder emergencies.

Movement disorders may present acutely, and failure to recognize and exclude important differential diagnoses can result in significant morbidity or mortality. Unfortunately, much of the literature pertaining to this topic is scattered and not easily accessible. This review aims to address this deficit. Movement disorder emergencies are discussed according to their most likely mode of presentation. Diagnostic considerations and early management principles are reviewed, along with appropriate pathophysiology where relevant.

Acute Disease↗
PubMed2005

A matter of motion or an emotional matter? Management of depression in Parkinson's disease.

Depression is one of the most frequent comorbidities occurring in Parkinson's disease, affecting up to 50% of patients. Depression is associated with severe negative symptoms and has been shown to contribute to an increased rate of decline of both cognitive and motor function, profoundly impacting on the patient's quality of life. The symptoms of depression overlap with the motor features of Parkinson's disease, making detection difficult. Moreover, the lack of specialized screening tools means that depression remains undiagnosed and untreated in a high percentage of patients. However, depression in Parkinson's disease, when identified early, can be effectively treated with a variety of antidepressant medications, improving quality of life and preserving daily function. The focus of this review is to provide an overview of current knowledge regarding depression in Parkinson's disease, followed by a practical discussion addressing the issues of the detection, diagnosis and treatment.

Antidepressive Agents↗
PubMed2002

Dopa-responsive parkinsonism secondary to right temporal lobe haemorrahage.

A 46-year-old man developed a symmetrical parkinsonian syndrome 7 weeks after large right temporal intracerebral haemorrhage resulting from a ruptured arteriovenous malformation. His signs included bradykinesia, rigidity, start hesitation, and poor postural reflexes, without a resting tremor. He also had signs of a Parinaud's syndrome. Computed tomography and magnetic resonance imaging of the brain demonstrated changes in the right temporal lobe associated with the haemorrhage but no abnormality of the basal ganglia or midbrain. Levodopa therapy produced a dramatic improvement within a few days of commencement. We postulate that the parkinsonism resulted from midbrain compression secondary to transtentorial herniation. Although parkinsonism is a rare complication of lobar intracerebral haemorrhage, it is important to recognise as it may be potentially treatable.

Antiparkinson Agents↗
PubMed2002

Athetosis II: the syndrome of mild athetoid cerebral palsy.

We describe 8 patients who presented with continuous, irregular movements occurring independently in individual fingers and, in some cases, toes, in the setting of mild dystonia present since early childhood and not associated with major disability. The finger movements varied from low-amplitude quivering or wriggling to larger amplitude movements in the plane of abduction-adduction as well as flexion-extension; they were asymmetrical but not unilateral. Quivering or working of the facial muscles was seen in 5 patients. Most patients reported worsening of the movements over the years, but there was no other evidence of a progressive neurological disease. We classify the movement disorder as athetosis as described by Hammond and Shaw and the syndrome as mild athetoid cerebral palsy.

Adolescent↗
PubMed2002

Loss of reflex inhibition following muscle tendon stimulation in essential tremor.

Electrical stimulation of human upper limb muscle tendons produces a reflex inhibition (I(1)) in the same muscles. This inhibition is reduced in Parkinson's disease (PD), prompting a similar study of essential tremor (ET). In essential tremor, two of eight subjects had no discernible inhibition, even following supramaximal stimulation (< 80 mA) of the tendons from extensor digitorum communis and extensor pollicis brevis. In the remaining six subjects, the mean thresholds for I(1) in these muscles were increased by 270 and 320%, respectively, relative to controls. The maximal amplitude of the inhibition was significantly reduced in the ET group, as was the following excitation (E(1)). The latency and duration of I(1) were not different in ET subjects and controls. The maximal duration of I(1) was correlated with tremor frequency in individuals, and tendon stimulation was effective in initiating ongoing tremor cycles. These results disclose a peripheral reflex abnormality in ET that is mediated by tendon afferents and can be linked to the coexistent tremor. The response in ET was distinguished from that in PD by its different time-course and by failure of the response to appear in the antagonist muscle. The abnormality may prove a useful marker for ET, which currently lacks a definitive pathological or neurophysiological marker to support objective clinical diagnosis.

Electric Stimulation↗