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Biomedical subjects

P Thompson

Publications and source records attributed to P Thompson.

At least 145 records · Page 8Linked to original sources

Anti-GM1/GD1b M-proteins damage human spinal cord neurons co-cultured with muscle.

IgM M-proteins in some motor neuron disease (MND) patients bind immunologically to shared determinants on gangliosides GM1 and GD1b. Since patients with these M-proteins have improved with immunotherapy the antibodies may be important in the pathogenesis of MND. To study how the M-proteins might damage motor neurons, we established co-cultures of human neurons from spinal cord explants and human myotubes. Antibodies from patient but not control serum bound to the cultured neurons. Neurons in co-cultures degenerated after incubation with patient but not control serum. These results demonstrate that anti-GM1 antibodies can bind to and destroy spinal cord neurons that are cultured with muscle. Nerve-muscle co-cultures can serve as a system to examine effects of anti-GM1/GD1b M-proteins on motor neurons.

Binding Sites↗

Extinction of the tumor necrosis factor locus, and of genes encoding the lipopolysaccharide signaling pathway.

The tumor necrosis factor (TNF-alpha or TNF) gene is activated by both lipopolysaccharide (LPS) and cycloheximide in RAW 264.7 macrophages, whereas neither stimulus activates the gene in 3T3 fibroblasts. Moreover, the pattern of CG methylation within the TNF gene is readily distinguishable in DNA derived from cells of these two types. These findings would suggest that the TNF gene has been rendered inaccessible to transcription in the 3T3 cell environment. When RAW 264.7 cells are fused with 3T3 cells, an immortal pentaploid hybrid results. In the hybrid cell, all three TNF genes contributed by the RAW 264.7 cell parent become highly methylated according to the pattern observed in the 3T3 cell parent. Permanently transfected chloramphenicol acetyl transferase (CAT) reporter constructs, bearing 2.2 kb of upstream sequence (including the entire TNF promoter and 5'-untranslated region [UTR]) as well as 1.0 kb of downstream sequence (including the entire TNF 3'-UTR and termination sequence), are accessible in both RAW 264.7 cells and 3T3 cells, but are silenced in transition from the RAW 264.7 cell to the hybrid cell environment. Moreover, the endotoxin signaling pathway is abrogated, as assessed by transient transfection of hybrid cells with LPS-responsive CAT reporter constructs. It would therefore appear that the fusion of 3T3 cells and RAW 264.7 cells activates a system that silences the TNF gene, as well as the LPS signaling pathway. This system may operate to determine TNF gene accessibility and LPS responsiveness in the course of cell differentiation. The DNA sequences targeted within the TNF gene are included in the CAT reporter construct; therefore, the silencing element has been circumscribed to a region of DNA 3.2 kb in length.

3T3 Cells↗

Olfactory information processing and temporal lobe epilepsy.

It has been suggested that olfactory information processing is impaired in patients with temporal lobe epilepsy. However, the existing evidence is not wholly in accordance with this notion. Patients with epileptogenic foci in the left temporal lobe, the right temporal lobe, or other brain regions were compared with normal control subjects in the identification and retention of common odors. All three patient groups were substantially and equally impaired in verbally labelling the odors in question. The patients with epilepsy associated with the left temporal lobe or with nontemporal regions showed no sign of any impairment on a test of immediate recognition memory for common odors. However, the patients with epilepsy associated with the right temporal lobe showed a specific disturbance in their retention of nameable odors. It is suggested that the latter patients were selectively impaired in their retrieval of the episodic memories which provide the context for the encoding of distinctive odors.

Adult↗

Patient assessment of a combined medical and nursing preparation to cytotoxic chemotherapy.

At Auckland hospital there is a combined medical and nursing preparation for patients receiving cytotoxic chemotherapy. The aim of the current study was to assess whether patients felt that this combined approach had prepared them adequately for chemotherapy. Patients were asked to complete three questionnaires anonymously at different times in their treatment programme: immediately prior to chemotherapy, after three cycles of chemotherapy and 2 months after completion of chemotherapy. A high level of satisfaction with the programme was demonstrated: 68% of patients thought the orientation programme had prepared them "very well", 32% "adequately" and none "poorly" for their chemotherapy. Separate interviews with medical and nursing staff were thought a "good idea" by 86% of patients and only 1 of 100 medical and 100 nursing interviews was assessed as "not worthwhile". This study suggests that a combined medical and nursing preparation is a worthwhile practice in preparing patients for cytotoxic chemotherapy.

Adult↗

Monoaminergic activities in Lewy body dementia: relation to hallucinosis and extrapyramidal features.

Serotonergic (5-HT) and dopaminergic activities have been examined in Lewy Body Dementia (LBD) and compared with Parkinson's disease (PD) and Alzheimer's disease (AD). In the neocortex the LBD subgroup experiencing hallucinations was distinguished from the other categories by an increase in the 5HIAA:5HT ratio measured in frontal cortex and by the serotonergic (5-HIAA or 5-HIAA:5-HT): cholinergic (choline acetyltransferase) ratio in frontal and temporal cortex. In the neostriatum (caudate nucleus), loss of dopamine and increased HVA:dopamine ratio correlated with the reduction in substantia nigra neurons in LBD but not PD, despite the greater loss of neurones and dopamine and the higher dopamine turnover ratio in PD. LBD patients experiencing severe Parkinsonism as a result of neuroleptic treatment tended to have lower neuron counts, in combination with higher turnover ratios, than the remainder. Qualitative differences between LBD and PD included decreased cortical 5-HT turnover in PD compared with the increase in LBD. There were no significant changes in any parameter in AD, with the exception of a reduction in temporal cortex 5HIAA. The results suggest that although the neurochemical pathology of LBD and PD involves similar systems, the nature of the derangements differs sufficiently between the diseases to account for differences in symptomatology.

Aged↗

Wiskott-Aldrich syndrome: no evidence of chromosome instability.

Patients with the immune deficiency disorder Wiskott-Aldrich syndrome (WAS) have an increased risk of malignancy, most notably non-Hodgkins lymphoma. To determine whether this susceptibility is due to chromosome instability, cytogenetic analysis was performed on phytohemagglutinin-stimulated lymphocytes from five patients with this disorder. Compared to matched controls, no excess of chromosome aberrations or structural rearrangements was identified. This study does not, therefore, support the view that WAS is a chromosome instability syndrome.

Adolescent↗

The Pulfrich pendulum phenomenon in stereoblind subjects.

The Pulfrich pendulum phenomenon, in which a pendulum swinging in the frontoparallel plane appears to swing in an ellipse when a neutral density filter is placed over one eye of the observer, was investigated in stereoblind subjects. It was found that such subjects can report the presence of the Pulfrich effect although they fail to fuse random-dot stereograms and fail to exhibit interocular transfer of the movement aftereffect. These findings suggest that 'stereoblind' subjects must retain some residual binocular mechanism for depth perception. Three possibilities are considered: (i) the stereoblind may be able to utilise contiguous temporal disparities as a cue for depth in the Pulfrich effect; (ii) they may retain some residual binocularity, sufficient to reveal the Pulfrich effect but not for other more demanding tasks for the binocular mechanisms; and (iii) they may retain some coarse magnocellular pathway disparity mechanism having lost their high-acuity parvocellular disparity system. There is little evidence to support any of these hypotheses, but the third shows promise.

Depth Perception↗

Streptococcus pneumoniae colonization, bacteremia, and immune response among persons with human immunodeficiency virus infection.

Although invasive pneumococcal infections are common among men infected with human immunodeficiency virus (HIV), the prevalence of pharyngeal colonization with Streptococcus pneumoniae was not significantly different among HIV-infected patients (8 [14%] of 56) and HIV-seronegative men (9 [9%] of 99) attending a sexually transmitted disease clinic. Sixteen HIV-infected men (mean CD4+ T cell count, 132 +/- 37/microL) developed pneumococcal bacteremia, accounting for 13.6% of 117 total cases and 42% of 38 cases in men 16-55 years old. Serum killing activity, a measure of functional humoral response to S. pneumoniae, was lower in 4 (67%) of 6 acute sera and 6 (54%) of 11 convalescent sera from bacteremic HIV-infected patients when compared with baseline sera of 7 HIV-seronegative healthy subjects. These findings suggest that the high rates of pneumococcal bacteremia among HIV-infected patients may be associated with low numbers of CD4+ T cells and impaired humoral responses to S. pneumoniae rather than to increased exposure to the organism.

Adolescent↗

The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years.

A 3-year placebo-controlled trial of sulphasalazine (SASP) in 89 patients with established AS (including radiological sacroiliitis) showed a reduced frequency of peripheral arthritis in the treated group but did not show any definite benefit in the maintenance of spinal mobility. Adverse effects causing treatment withdrawal occurred in five placebo-treated patients and eight SASP-treated patients, but 22 patients preferred to stop taking daily medication of unproven benefit for the full 3 years. The natural history of established AS suggested two groups of patients: the majority with principally spinal symptoms and infrequent peripheral arthritis or iritis, and a minority who tend to have recurrent extra-spinal problems.

Adult↗

Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson's and distinction from Alzheimer disease.

Senile dementia of Lewy body type or Lewy body dementia (LBD), characterized neuropathologically by the presence of Lewy bodies in the brainstem and cortex, and in most cases neocortical senile plaques (but few or no tangles), bears a closer resemblance to Parkinson's (PD) than to Alzheimer disease (AD) in its cholinergic neurochemical pathology. Thus, reductions in the biochemical activity of choline acetyltransferase were generally more extensive in neo- as opposed to archicortical regions in LBD (especially hallucinating cases) and in PD, whereas muscarinic receptor binding was significantly increased in LBD and PD but not in AD. Nerve growth factor receptor (P75) assessed immunocytochemically in the archicortex were decreased in PD and, to a lesser extent, in LBD in conjunction with reductions of neuronal numbers in the nucleus of Meynert (Ch4), but were relatively spared in AD. These observations indicate that although AD is primarily associated with dysfunction of cholinergic axonal input to the cortex, LBD and PD are more likely to involve degeneration of the basal forebrain cholinergic system. Relevance of the findings in terms of aetiopathology and cholinergic treatment strategies is discussed.

Aged↗

Medical care and case fatality from myocardial infarction and coronary death in Newcastle and Perth.

Coronary mortality rates are significantly higher in Newcastle than Perth. In this paper we examine the extent to which this might be due to differences in medical treatment and case fatality. Population-based disease registers were used to identify all cases of non-fatal definite myocardial infarction (MI) and coronary death in people aged 25-64 years in the study populations between July 1988 and June 1990. Case fatality (at 28 days from onset of symptoms) was not significantly different between the centres. Thrombolytic therapy was used for one third of all hospitalised events in both centres. Other drugs of proven benefit were, however, used more often in Perth than in Newcastle. For example, during hospitalisation 74% of patients in Perth received beta-blockers compared with 41% in Newcastle (difference = 33%, 95% confidence interval (CI): 28%, 37%) and 85% of patients in Perth compared with 72% in Newcastle received aspirin (difference = 13%, 95% CI: 9%, 17%). Median lengths of stay in a coronary care unit (CCU) and total hospital stay were one day shorter in Perth. As case fatality was similar, the differences in mortality rates can be attributed mainly to differences in attack rates. Greater use of cardio-active drugs in Perth apparently did not result in improved short-term outcome although potential long-term benefits cannot be judged yet.

Adult↗

Impact of a national educational campaign to reduce patient delay in possible heart attack.

In 1989 the National Heart Foundation (NHF) of Australia's Heart Week campaign was directed towards encouraging those with symptoms of possible myocardial infarction (MI) to seek help as promptly as possible. To evaluate its effect, three surveys were conducted of patients admitted to 22 coronary care units (CCUs). Two (335 and 221 patients) preceded and one (253 patients) followed the public education campaign. During the third survey a subset of patients were asked why they delayed, how long they thought one should wait before seeking help, whether they were aware of the media campaign and whether this had influenced their behaviour. Overall, only 42% of 809 patients sought help within one hour (median delay 1.2 hours). The median time of arrival and the proportion of patients arriving within one, two and four hours was not altered after this campaign. Those who admitted to having been aware of the campaign sought help no more promptly. The Heart Week campaign could not be shown to have produced any clinically important change in patient delay. Future campaigns will need to be modified in the light of this experience.

Female↗

Epilepsy and poor memory: who complains and what do they mean?

The aim of this study was to increase the understanding of the major causes of memory complaints made by people with epilepsy. Neuropsychological test performance, patients' self-reports of memory failures and the use of memory support strategies were compared in two groups of 30 patients with epilepsy differing in level of memory complaints. Those reporting significant memory difficulties performed more poorly on two of the six measures of memory administered. Age of onset of seizures was significantly later in the 'complaining' group but none of the other treatment and epilepsy variables considered differentiated the groups. Patients who complained of memory problems, however, were significantly more depressed and anxious than non-complainers. These findings may have implications for memory rehabilitation interventions in the population.

Adult↗

Today's ethics committees face varied issues. A CHA survey reveals committees' functions, authority, and structure.

In a survey of Catholic Health Association member hospitals, 92 percent indicated they have formal ethics committees at their institutions. Sixty-two percent said their ethics committees were formed between 1983 and 1989. The survey found that current ethics committees are still committed to their traditional roles--education, policy development, and case review--but the education is directed to more diverse audiences than in the past. Support for medical and nursing staffs may be emerging as another possible function of ethics committees. The issues that precipitated the formation of institutional ethics committees have become more complex. In particular, questions involving the appropriate use of technology, the renewed awareness of patients' rights, changing relationships among healthcare providers, and conflicting social values have continued to require the intervention of ethics committees. However, the frequency with which respondents said their committees provide case consultations seems lower than it should be if committees were used to their full advantage. The institutional ethics committee can play a part in enlarging the current healthcare reform debate and promoting moral values. It can address such important questions as, Should the well-being of individuals take precedence over the well-being of communities?

Bioethical Issues↗

Characterization of typical and atypical antipsychotic drugs based on in vivo occupancy of serotonin2 and dopamine2 receptors.

Atypical antipsychotic drugs related to clozapine may be distinguishable from typical antipsychotic drugs by having a greater potency in vitro at serotonin2 (5-HT2) receptors relative to dopamine2 (D2) receptors. The in vivo potencies of 10 typical and 10 putative atypical antipsychotic drugs in occupying D2 and 5-HT2 receptors in rat brain are reported here. There is no significant difference in the average potency of the two groups of antipsychotic drugs in preventing the in vivo binding of N-[3H] methylspiperone to 5-HT2 receptors in the cortex. However, the average potency of the atypical antipsychotic drugs is about 8-fold less than typical antipsychotic drugs in preventing N-[3H] methylspiperone binding to D2 receptors in the striatum. Thus, all of the atypical antipsychotic drugs that are clozapine-like have a greater relative affinity in vivo for the 5-HT2 than the D2 receptor. As a group, the typical antipsychotic drugs tend to be equipotent at both receptors. The average relative potency of the group of typical antipsychotic drugs at 5-HT2 vs. D2 receptors is essentially equal when examined in vivo vs. in vitro. Atypical antipsychotic drugs are slightly but significantly more potent in vivo at D2 receptors in the olfactory tubercle than the striatum. For only the typical antipsychotic drugs, the in vivo and in vitro potencies in occupying D2 receptors are correlated with their average clinical dosage. Thus, the relative in vivo potency of clozapine-related drugs at 5-HT2 vs. D2 receptors may help identify these compounds as atypical antipsychotic drugs.

Animals↗