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Biomedical subjects

J Grace

Publications and source records attributed to J Grace.

At least 19 recordsLinked to original sources
PubMed2001

Long-Term use of rivastigmine in patients with dementia with Lewy bodies: an open-label trial.

Patients with dementia with Lewy bodies (DLB) have progressive deficits in cognition, parkinsonism, and neuropsychiatric symptoms. Cholinesterase inhibitors have been used to ameliorate cognitive decline and neuropsychiatric symptoms in short-term trials. In this study, patients with DLB were treated with rivastigmine up to 96 weeks. Improvement from baseline was seen in cognitive function as measured by the Mini-Mental State Examination (MMSE), and neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) over the first 24 weeks of treatment. By 96 weeks, neither the MMSE scores nor the NPI scores were significantly worse than at baseline.

Aged↗
PubMed2000

Tropical forests and atmospheric carbon dioxide.

Tropical forests play a major role in determining the current atmospheric concentration of CO2, as both sources of CO2 following deforestation and sinks of CO2 probably resulting from CO2 stimulation of forest photosynthesis. Recently, researchers have tried to quantify this role. The results suggest that both the carbon sources and sinks in tropical forests are significantly greater than previously thought.

Journal Article↗
PubMed2000

Interaction of nutrient limitation and elevated CO2 concentration on carbon assimilation of a tropical tree seedling (Cedrela odorata).

Carbon assimilation by Cedrela odorata L. (Meliaceae) seedlings was investigated in ambient and elevated CO2 concentrations ([CO2]) for 119 days, using small fumigation chambers. A solution containing macro- and micronutrients was supplied at two rates. The 5% rate (high rate) was designed to avoid nutrient limitation and allow a maximum rate of growth. The 1% rate (low rate) allowed examination of the effect of the nutrient limitation-elevated CO2 interaction on carbon assimilation. Root growth was stimulated by 23% in elevated [CO2] at a high rate of nutrient supply, but this did not lead to a change in the root:shoot ratio. Total biomass did not change at either rate of nutrient supply, despite an increase in relative growth rate at the low nutrient supply rate. Net assimilation rates and relative growth rates were stimulated by the high rate of nutrient addition, irrespective of [CO2]. We used a biochemical model of photosynthesis to investigate assimilation at the leaf level. Maximum rate of electron transport (Jmax) and maximum velocity of carboxylation (Vcmax) did not differ significantly with CO2 treatment, but showed a substantial reduction at the low rate of nutrient supply. Across both CO2 treatments, mean Jmax for seedlings grown at a high rate of nutrient supply was 75 micromol m(-2) s(-1) and mean Vcmax was 27 micromol m(-2) s(-1). The corresponding mean values for seedlings grown at a low rate of nutrient supply were 36 micromol m(-2) s(-1) and 15 micromol m(-2) s(-1), respectively. Concentrations of leaf nitrogen, on a mass basis, were significantly decreased by the low nutrient supply rate, in proportion to the observed decrease in photosynthetic parameters. Chlorophyll and carbohydrate concentrations of leaves were unaffected by growth [CO2]. Because there was no net increase in growth in response to elevated [CO2], despite increased assimilation of carbon at the leaf level, we hypothesize that the rate of respiration of non-photosynthetic organs was increased.

Carbon↗
PubMed2000

Visualizing the function computed by a feedforward neural network.

A method for visualizing the function computed by a feedforward neural network is presented. It is most suitable for models with continuous inputs and a small number of outputs, where the output function is reasonably smooth, as in regression and probabilistic classification tasks. The visualization makes readily apparent the effects of each input and the way in which the functions deviate from a linear function. The visualization can also assist in identifying interactions in the fitted model. The method uses only the input-output relationship and thus can be applied to any predictive statistical model, including bagged and committee models, which are otherwise difficult to interpret. The visualization method is demonstrated on a neural network model of how the risk of lung cancer is affected by smoking and drinking.

Alcohol Drinking↗
PubMed2000

Pharmacokinetics of artemisinin-type compounds.

Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid. Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the 'depot' effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.

Animals↗
PubMed1999

Brief cognitive screening of right hemisphere stroke: relation to functional outcome.

OBJECTIVES: Traditional mental status screens have limited sensitivity in detection of focal brain damage and are particularly insensitive to right hemisphere stroke (RHS). Addition of a simple measure of constructional ability, clock drawing, should enhance the sensitivity of the Modified Mini-Mental State Exam (3MS) in RHS. The relation between the 3MS-clock drawing screen and functional outcome in RHS was also examined. DESIGN: Logistic regression analysis (Study 1) with cross validation on an independent sample (Study 2). SETTING: Inpatient medical rehabilitation. PATIENTS: Study 1: 32 acute RHS patients (mean age 75.2yrs) and 35 age- and education-matched healthy controls. Study 2 (cross-validation): 32 acute RHS patients (mean age 72.8yrs) and 36 matched healthy controls. OUTCOME MEASURES: 3MS, clock drawing, and Functional Independence Measure scores. RESULTS: The 3MS-clock screen accurately distinguished RHS patients from controls. The clock drawing was a valuable and unique addition to the 3MS. RHS patients who were impaired on the 3MS-clock drawing screen had significantly worse FIM scores at discharge than RHS patients who were not impaired on the cognitive screen. CONCLUSION: Clinicians can enhance the sensitivity of their brief mental status examination of RHS patients, in addition to obtaining useful prognostic information, by including a clock drawing task in their screen.

Activities of Daily Living↗
PubMed1999

Acetylcholine in mind: a neurotransmitter correlate of consciousness?

The cholinergic system is one of the most important modulatory neurotransmitter systems in the brain and controls activities that depend on selective attention, which are an essential component of conscious awareness. Psychopharmacological and pathological evidence supports the concept of a 'cholinergic component' of conscious awareness. Drugs that antagonize muscarinic receptors induce hallucinations and reduce the level of consciousness, while the nicotinic receptor is implicated as being involved in the mechanism of action of general (inhalational) anaesthetics. In degenerative diseases of the brain, alterations in consciousness are associated with regional deficits in the cholinergic system. In Alzheimer's disease (AD), there is a loss of explicit (more than implicit) memory and hypoactivity of cholinergic projections to the hippocampus and cortex, while the visual hallucinations experienced by subjects with Dementia with Lewy bodies (DLB) are associated with reductions in neocortical ACh-related activity. In Parkinson's disease, the additional loss of pedunculopontine cholinergic neurones, which control REM (rapid eye movement) sleep or dreaming, is likely to contribute to REM abnormalities, which also occur in DLB. Widespread basal-forebrain and rostral brainstem cholinergic pathways, which include converging projections to the thalamus, appear to be located strategically for generating and integrating conscious awareness. Alleviation of a range of cognitive and non-cognitive symptoms by drugs that modulate the cholinergic system, which are being developed for the treatment of AD and related disorders, could be caused by changes in consciousness.

Acetylcholine↗
PubMed1999

Assessing frontal lobe behavioral syndromes with the frontal lobe personality scale.

Reliability and construct validity are reported for the Frontal Lobe Personality Scale (FLOPS), a brief neurobehavior rating scale. The FLOPS Family form was completed by family members of 24 frontal lobe brain-damaged patients, 15 non-frontal lobe brain- damaged patients, and 48 healthy controls. Intrascale reliability was demonstrated (internal consistency.96; split half.93). Validity studies of frontal lobe patients post-lesion compared to their pre-lesion status, to healthy controls, and of frontal lobe patients pre- and post-lesion compared to non-frontal lobe patients pre- and post-lesion, indicated that frontal lobe patients post-lesion showed significantly more frontal behavior than (a) pre-lesion frontal lobe patients, (b) healthy controls, and (c) post-lesion non-frontal lobe patients. The FLOPS appears to be useful for quantifying frontal lobe behavior in clinical and research settings.

Adult↗
PubMed1999

Olanzapine in dementia with Lewy bodies: a clinical study.

OBJECTIVES: Dementia with Lewy bodies (DLB) is now a well-recognized form of dementia in which psychosis and behavioural disturbance are common. Treatment with conventional neuroleptics is often very poorly tolerated. Olanzapine, a newly introduced atypical neuroleptic which binds to multiple receptor types with relatively low affinity for D2 receptors, may be a useful treatment option in DLB. MAIN OUTCOME MEASURES: The Behavioural Pathology in Alzheimer's Disease Rating Scale, The Neuropsychiatric Inventory, Unified Parkinson's Disease Rating Scale and The Webster Disability Scale. DESIGN: We present the results of eight DLB patients with associated psychotic and behavioural difficulties. All patients were given olanzapine 2.5-7.5 mg. Their psychotic phenomena and behavioural and extrapyramidal symptoms were monitored at 2-weekly intervals. RESULTS: Three out of the eight patients could not tolerate olanzapine even at the lowest available dose. Two patients had clear improvement in psychotic and behavioural symptoms. Three patients were able to tolerate olanzapine but gained only minimal benefit. CONCLUSIONS: Olanzapine at the doses used conferred little advantage over conventional neuroleptics and should only be given with great caution to patients with DLB. The utility of smaller doses deserves further evaluation.

Aged↗
PubMed1998

Changes in the carbon balance of tropical forests: evidence from long-term plots

The role of the world's forests as a "sink" for atmospheric carbon dioxide is the subject of active debate. Long-term monitoring of plots in mature humid tropical forests concentrated in South America revealed that biomass gain by tree growth exceeded losses from tree death in 38 of 50 Neotropical sites. These forest plots have accumulated 0.71 ton, plus or minus 0.34 ton, of carbon per hectare per year in recent decades. The data suggest that Neotropical forests may be a significant carbon sink, reducing the rate of increase in atmospheric carbon dioxide.

Journal Article↗
PubMed1998

What are the relations between Lewy body disease and AD?

Several hospital based autopsy series indicate dementia with Lewy bodies (DLB) to be the second most common pathological subtype of degenerative dementia in elderly subjects. The majority of DLB cases have high densities of beta amyloid senile plaques, whereas neocortical neurofibrillary tangle density is only slightly increased above age-matched normal control values and over tenfold lower than the average in Alzheimer's disease. The interpretation of this Alzheimer type pathology is problematic, reflecting in part changing views about the neuropathological diagnosis of AD itself. AD is characterised by hyperphosphorylation of the microtubular associated protein tau, and DLB by neurofilament abnormalities including phosphorylation, ubiquitination, proteolysis, and cross-linking of constituent proteins. The two diseases appear therefore to be distinct at an ultrastructural and molecular level, a conclusion which is consistent with the fact that the clinical syndromes associated with DLB and AD are sufficiently differentiated to allow for accurate antemortem diagnosis.

Alzheimer Disease↗