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Biomedical subjects

M D Simpson

Publications and source records attributed to M D Simpson.

At least 19 recordsLinked to original sources

Personal and professional use of complementary therapies by nurses in NSW, Australia.

In this study, we investigate the personal and professional use of complementary therapies by nurses in NSW, Australia. We found that the therapies and products used by respondents were similar to those used by the general population. Seventy-four percent of respondents had used a complementary therapy in the last year and 38% had used them with a patient. In addition, 67% indicated that they would refer to a complementary practitioner. Respondents were also found to have favourable views of complementary therapies with 85% believing they improve quality of life and only 0.8% indicating they serve no purpose. No major differences were seen between respondents residing in the city vs those in regional areas. The data from this study support the view that nurses are high users of complementary therapies and that they may be the health profession most open to the use of complementary therapies as an integral part of normal health care.

Adult↗

High use of complementary therapies in a New South Wales rural community.

In this study a postal questionnaire was used to investigate the use of complementary therapies (CT) in a rural region of New South Wales (NSW). A total of 70.3% of respondents reported using one or more therapies with 62.7% having visited a complementary practitioner. Vitamin/mineral therapy (68.7%), chiropractic (26.1%) and massage therapy (25.1%) were the most frequently used therapies, with the most commonly visited practitioners being chiropractors (55.3%) and those trained in vitamin/mineral therapy (47.9%). Of the vitamins, vitamin C and multivitamins were used most often, with garlic and Echinacea being the most used herbal products. The main source of information were friends (64.5%) with most people indicating that CT could improve quality of life and provide relief of symptoms. Results suggest that CT use in rural communities is high and that, in light of these findings, there is a need for training in CT to be included in the undergraduate and continuing education of health professionals. Furthermore, these professionals should be alert to the potential for increased numbers of herb-drug interactions in rural communities.

Adolescent↗

Complementary therapy use by nursing, pharmacy and biomedical science students.

Attitudes towards the use of complementary therapies by students of undergraduate Bachelor of Nursing, Pharmacy and Biomedical Sciences were determined using a self-administered questionnaire. Overall, 78% of students had used a complementary therapy in the past year and 56% had visited a complementary therapy practitioner. The therapies most used were those involving vitamins, mineral and other supplements. Practitioners specializing in this area were the most visited, followed by chiropractors. Commonly used products included vitamin C, multivitamins, B group vitamins, garlic, iron and echinacea. Most students thought complementary therapies improved quality of life, with friends and family providing the main sources of information. There were few differences attributable to course or gender. The results suggest that these students have favorable attitudes towards complementary therapies and that many choose to use them as part of normal health care.

Adult↗

Comparison of glutamate and gamma-aminobutyric acid uptake binding sites in frontal and temporal lobes in schizophrenia.

BACKGROUND: Theories of schizophrenia proposing deficiencies of amino acid [glutamate, gamma-aminobutyric acid (GABA)] neurons are in accord with the observed temporal lobe pathology of the disease rather than with the newer theory of glutamate hyperinnervation and hyperfunction in areas of prefrontal cortex. This study addresses the issue by measuring specific uptake sites as indices of glutamatergic and GABAergic neuron densities in frontal and temporal lobes. METHODS: Frontal cortex (six areas) and temporal lobe (six areas of cortex, amygdala, and hippocampus) were dissected from 19 control autopsy brains and 12 brains from neuroleptic drug-treated schizophrenic patients. Groups had similar ages, postmortem intervals, and storage times. Membranes, prepared from tissue homogenates, were incubated with D-[3H]aspartate to measure neuronal and glial glutamate uptake site binding in 14 areas and with [3H]nipecotic acid to measure neuronal GABA uptake site binding in 11 areas. RESULTS: Glutamate and GABA uptake sites were not reduced in prefrontal and temporal areas. Instead, we found small increases in glutamate uptake sites in prefrontal areas. Some tendency toward increased GABA uptake sites were not disease-related. CONCLUSIONS: Our findings concur with other studies that propose locally overabundant glutamate systems in prefrontal cortex in schizophrenia. Losses of amino acid neurons do not accompany the temporal lobe pathology.

Aged↗

Absence of basal ganglia amino acid neuron deficits in schizophrenia in three collections of brains.

Amino acid (glutamatergic, GABAergic) neuron deficiency theories of schizophrenia offer plausible explanations of pathogenesis. However, reports of disease-related reductions in amino acid synthesizing enzymes in post-mortem brains are contradictory. We measured neuronal uptake sites for gamma-aminobutyric acid (GABA; [3H]nipecotic acid binding) and nerve terminal/glial uptake sites for L-glutamate (D-[3H aspartate binding) in three independent groups of post-mortem brains from patients with schizophrenia and control subjects. Measurements were also made of the phencyclidine site of the glutamate N-methyl-D-aspartate (NMDA) receptor. Samples from patients showed no reductions in the binding of [3H]nipecotic acid or D-[3H]aspartate in caudate, putamen or globus pallidus. On the contrary, some increased binding of both ligands was observed in patients in many comparisons with controls. There were no clear-cut changes in NMDA receptor binding. The most consistent change in the brain sets was increased [3H]nipecotic acid binding in caudate-putamen. This could be due to neuroleptic treatment. The findings produce no evidence that schizophrenia involves major loss of GABA neuron terminals in the basal ganglia or losses of corticostriatal glutamatergic projections.

ATP-Binding Cassette Transporters↗

Familial and developmental abnormalities of front lobe function and neurochemistry in schizophrenia.

structural abnormalities of the cerebral cortex in schizophrenia have been revealed by magnetic resonance imaging, although it is not clear whether these abnormalities are diffuse or local. We predicted that changes in cortical structure would result in abnormalities in biochemical markers for the glutamate system in post-mortem brain, and that the pattern of neurochemical abnormalities would be a clue to the distribution and extent of pathology. A number of studies have now reported increases in biochemical and other markers of glutamatergic cell bodies and terminals in the frontal cortex in schizophrenia. These findings are consistent with the presence of an abnormally abundant glutamatergic innervation, which may be due to an arrest in the normal developmental process of synaptic elimination. In the anterior temporal cortex and hippocampus there is evidence of an asymmetric loss of glutamate terminals, and of reduced GABA function, which may be secondary to the glutamatergic deficit. Glutamate cell body markers are spared in the temporal lobe; we argue that the loss of glutamate uptake sites may reflect the loss of an extrinsic glutamatergic innervation of the polar temporal cortex which arises from the frontal cortex. These fronto-temporal projections may be vulnerable because they arise from a cytoarchitecture which has not been stabilized by remodelling during early post-natal life. There have been several therapeutic studies of drugs with actions on brain glutamate systems. Based on the glutamate deficiency theories, one approach has been to enhance glutamatergic function using agonists of the N-methyl-D-aspartate-linked glycine site. However, there are no clear therapeutic effects, and some studies report aggravation of positive symptoms. This might be expected if, as part of our post-mortem studies suggested, there is excess glutamatergic innervation in some brain regions in schizophrenia. There is neuropsychological evidence that frontal abnormalities in schizophrenia may be genetically determined. We found that first degree relatives of schizophrenic patients were selectively impaired in tests of frontal lobe function, whereas both frontal and temporal function is impaired in patients We conclude that the genetic predisposition to schizophrenia involves impaired frontal lobe function. Psychotic symptoms develop only when a second process results in a loss of fronto-temporal projections and leads to temporal lobe dysfunction.

Antipsychotic Agents↗

Autoradiography with [3H]8-OH-DPAT reveals increases in 5-HT(1A) receptors in ventral prefrontal cortex in schizophrenia.

We previously reported increased glutamatergic innervation in orbital frontal cortex in schizophrenia. In view of the evidence that one serotonin (5-HT) receptor, the 5-HT(1A) subtype, is associated with cortical glutamatergic neurons, we have used quantitative receptor autoradiography to measure the specific binding of the 5-HT(1A) receptor ligand [3H]8-OH-DPAT (2 nM) in sections of orbital frontal cortex taken from 18 control and 12 schizophrenic postmortem brains. Schizophrenic patients, as compared with controls, had increased 5-HT(1A) receptor binding in the three orbital frontal regions examined. These effects were pronounced in the male subgroup, and were most apparent in the outer cortical laminae. These data are consistent with the hypothesis that schizophrenia is associated with an abnormal glutamatergic afferent innervation of orbital frontal cortex.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Use of MRI for measuring structures in frozen postmortem brain.

A method was developed for magnetic resonance imaging (MRI) of human autopsy brains stored long-term at -70 degrees C. Scanning brains at temperatures between -70 and -8 degrees C gave minimal MRI signals consistent with protons having limited freedom of movement at low temperature. Raising brain temperature improved the signal such that scanning at -1 degree C generated images with good in-plane resolution, grey/white matter contrast, and fine detail of cortical sulcal/gyral patterns. To validate the method, volume and area measurements were made using computerized image analysis on stored digital images of 14 brains from adult subjects of both genders and various ages. The data confirmed that brain volume was inversely correlated with age, and female subjects had smaller brains. This is a valuable new method for acquiring morphometric data from previously unscanned pathologic brains that are to be used for neurochemical and molecular investigations.

Analysis of Variance↗

Effect of smear layer removal on the diffusion permeability of human roots.

Ten human maxillary incisors, extracted because of periodontal disease or nonrestorable caries, were obtained and instrumented to a size #70 K-Flex file at the working length using a standard stepback technique. Tritiated water (3H2O) was placed in the root canals and allowed to diffuse to the external surface of the roots until it reached a constant rate. The smear layer in each of the experimental roots was then removed using 0.5 M EDTA followed by 5.25% sodium hypochlorite (NaOCI). The constant rate diffusion of 3H2O was remeasured. The roots were then stored in deionized H2O for 2 months and the constant rate diffusion of 3H2O was remeasured. A statistically significant difference was noted between all three groups. A decrease in the diffusion permeability of the root to 3H2O was noted immediately after smear layer removal and the highest permeability was recorded after storage in the deionized water for 2 months.

Dentin↗

Age-related changes in binding to excitatory amino acid uptake site in temporal cortex of human brain.

The binding of D-[3H]aspartate to the specific uptake site for the excitatory amino acids glutamate and aspartate was measured in homogenates of temporal lobe cortex taken at postmortem from 76 human infant and adult brains. Binding levels were very low in brains of preterm and term infants but increased rapidly during the first 20 postnatal weeks to reach levels which exceeded those in adult brains. Linear regression analysis which compared the amount of D-[3H]aspartate binding with the age of the infant, showed a positive correlation up to 25 postnatal weeks. Saturation analysis showed that the maximum number of D-[3H]aspartate binding sites (Bmax) in temporal cortex from infants aged 20 postnatal weeks was 3 times greater than the number of sites in adult brain. The findings show that the number of excitatory amino acid uptake sites, which may be associated in part with presynaptic terminals, increase in number rapidly after birth. Furthermore, the data may indicate that a slow regression of excitatory amino acid terminals occurs during the later stages of brain development.

Aging↗

Regionally selective deficits in uptake sites for glutamate and gamma-aminobutyric acid in the basal ganglia in schizophrenia.

In a post-mortem study of schizophrenic and control subjects, the sodium-dependent binding of D-[3H]aspartate and [3H]nipecotic acid were used to investigate uptake sites of glutamate and gamma-aminobutyric acid (GABA), respectively, in subcortical brain regions. Binding to the glutamate uptake site was substantially reduced in both the putamen and lateral pallidum of the schizophrenic subjects. Binding to the GABA uptake site was substantially reduced in the putamen; smaller reductions were apparent in the caudate nucleus and lateral pallidum. The results suggest that glutamatergic and GABAergic mechanisms in the basal ganglia are abnormal in schizophrenia. These abnormalities could be relevant to the development of psychosis but could also relate to the spectrum of mild motor disturbances often described in the disease.

Aspartic Acid↗

Effects of aluminum oxalate/glycine pretreatment solutions on dentin permeability.

Aluminum oxalate buffered with glycine to pH 0.5-2.5 has been proposed as a dentin pretreatment for the Gluma bonding system. In this experiment, the effects of 1-minute treatments of smear layers with these aluminum oxalates on the permeability of human dentin were determined in vitro. The aluminum oxalate solutions at pH 0.5-1.5 removed most of the original smear layer but occluded the tubules with crystalline deposits which decreased dentin permeability. Those solutions used at pH 2.0 and 2.5 increased dentin permeability. All dentin pretreatments increased dentin permeability when measured after a 24-hour storage period, especially the solutions at pH 2.0 and 2.5. The SEM correlates of these permeability changes indicated that these solutions remove the smear layer but reocclude the tubules with precipitates which are probably different forms of calcium oxalate, aluminum phosphate and calcium phosphates.

Adult↗

Fluid and protein flux across the pulpodentine complex of the dog in vivo.

Dentinal fluid volume and protein concentrations were measured from cavities prepared in the dentine of dog molars. Fluid was collected under spontaneous conditions, during the application of negative pressures, and during a recovery period. The data allowed the calculation of dentine permeability as hydraulic conductances, fluid flux, protein flux, reflection coefficients and pulpal tissue pressures. In general, the protein concentration of dentinal fluid was about one-fifth that of plasma during spontaneous conditions and it fell when fluid flux was increased by the application of external negative pressures. The collection and analysis of dentinal fluid looks promising as a non-invasive method of assessing the state of the underlying pulp.

Animals↗

Analysis of laminar distribution of kappa opiate receptor in human cortex: comparison between schizophrenia and normal.

Quantitative receptor autoradiography using the ligand [3H]U 69593 and tritium sensitive film was used to visualize the kappa subtype of opiate receptor in sections from 4 normal human postmortem brains. Data obtained from cortical scans, which measured receptor densities across the left and right parahippocampal gyri, were subject to Fourier analysis. This revealed that the kappa receptor distribution was described by a curve having significant first and second component harmonics. This analysis method can be used to describe a binding pattern mathematically, thus enabling a comparison to be made between normal and diseased brains. The same analysis was applied to [3H]U 69593 autoradiograms prepared from sections of 4 schizophrenic postmortem brains. The kappa receptor distribution in the schizophrenic group not only failed to produce the same pattern as the controls, but also showed no consistent pattern within the group. The method described can be used to investigate alterations in receptor distribution which occur in neuropsychiatric diseases involving neuronal dysplasia or atrophy.

Adult↗

Alterations in phencyclidine and sigma binding sites in schizophrenic brains. Effects of disease process and neuroleptic medication.

The specific binding of [3H]TCP and [3H](+)3-PPP, radioligands which respectively label PCP-NMDA and sigma binding sites was measured in tissue homogenates prepared from dissected areas of control and schizophrenic postmortem brains. [3H]TCP binding was bilaterally increased in orbital frontal cortex (Brodmann area 11) of schizophrenic brains. This finding may be due to an increased glutamatergic innervation of orbital frontal cortex since it parallels our findings of increased [3H]kainate and [3H]D-aspartate binding in this area. In contrast, [3H](+)3-PPP binding was reduced in each of the four brain regions examined. The reductions were greatest in brains from the schizophrenic subjects receiving neuroleptics at the time of death. Neuroleptics remaining in the brains of these subjects may compete in vitro with [3H](+)3-PPP for binding to the sigma site.

Antipsychotic Agents↗

Identification and distribution of 5-HT3 recognition sites within the human brainstem.

The present studies demonstrate the presence of specific [3H]GR65630 binding sites within the human brainstem using the techniques of in vitro receptor autoradiography and ligand binding to homogenates. Autoradiography revealed the greatest accumulation of specific binding in the area postrema and subpostrema (AP/ASP). A lower level of specific binding was identified in the nucleus tractus solitarius (excluding area subpostrema). No specific binding was evident in the remainder of the hindbrain at this level. Discrete dissection followed by ligand binding to homogenates revealed that the specific binding of [3H]GR65630 (defined by the presence of 30 microM metoclopramide) was differentially distributed with highest levels in the AP/ASP (112.1 fmol/mg protein) and lower levels in the dorsal vagal complex (nucleus tractus solitarius--excluding the area subpostrema--dorsal motor nucleus of the vagus and hypoglossal nucleus) (DVC) and olivary nucleus (ON) (22.9 and 3.9 fmol/mg, respectively). No specific binding was detectable in the reticular formation (RF) located ventral to the dorsal vagal complex. The specific [3H]GR65630 binding site was pharmacologically similar to the 5-HT3 receptor since the potent and selective 5-HT3 receptor antagonists ICS 205-930 and zacopride (100 nM) and the agonist 5-HT (10 microM) inhibited binding to the same extent as metoclopramide in each of the individual areas (90, 60 and 20% in the AP/ASP, DVC and ON, respectively). The 5-HT1-like and 5-HT2 receptor antagonist methysergide (10 microM) failed to compete for the binding site. 5-HT3 receptor recognition sites within the AP/ASP and the DVC may be functionally involved in the ability of 5-HT3 receptor antagonists to control emesis.

Adult↗