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Biomedical subjects

G MacKenzie

Publications and source records attributed to G MacKenzie.

At least 19 recordsLinked to original sources
PubMed2005

The use of atypical antipsychotics in the treatment of schizophrenia in North Staffordshire.

AIMS: To examine the long-term effectiveness of atypical antipsychotics in a naturalistic setting for patients with schizophrenia. METHOD: A retrospective analysis of atypical antipsychotic prescribing in one Health District between 1994 and 2001. Time to discontinuation of the first atypical antipsychotic prescribed was calculated using survival analysis. RESULTS: 253 patients were identified. Clozapine had a significantly lower discontinuation rate compared with olanzapine and risperidone (p = 0.018). Patients taking risperidone were 1.3 times more likely to discontinue than those taking olanzapine (p = 0.23). Older age (p = 0.0001), male sex (p = 0.016) and exposure to antidepressants (p = 0.014) significantly predicted compliance. CONCLUSIONS: Clozapine is an effective long-term schizophrenia treatment. The trend to superior effectiveness of olanzapine over risperidone in the long-term has not been reported before and warrants further investigation.

Adult↗
PubMed2000

Pheasant ataxia: a new condition in pheasant poults.

Between 1995 and 1997 a neurological condition in pheasant poults from 24 sites in England and Scotland was investigated. Affected birds showed varying degrees of ataxia and incoordinated movements and, in severe cases, recumbency, but generally remained alert with their heads held upright. The condition characteristically affected poults from seven weeks of age and the incidence on any one site was low. No significant bacteria were isolated consistently from brain tissue. The condition was characterised histologically by a non-suppurative meningoencephalitis, in which lesions were found predominantly in the cerebellum in 61 of 81 samples examined (75.3 per cent). A non-suppurative myelitis was recorded in 16 of 20 spinal cords examined. No lesions were recorded in peripheral neural tissue and lesions were rare in other tissues. The condition appeared not to have been recorded previously in pheasants. A viral aetiology was suspected but Newcastle disease virus was not involved.

Animals↗
PubMed2000

A comparison of patient characteristics and survival in two trauma centres located in different countries.

INTRODUCTION: The aim of the study was to compare patient characteristics and mortality in severely injured patients in two trauma centres located in different countries, allowing for differences in case-mix. It represents a direct bench-marking exercise between the trauma centres at the North Staffordshire Hospital (NSH), Stoke-on-Trent, UK and the Oregon Health Sciences University (OHSU) Hospital, Portland, Oregon, USA. METHODS: Patients of all ages admitted to the two hospitals during 1995 and 1996 with an Injury Severity Score >15 were included, except for those who died in the emergency departments. Twenty-three factors were studied, including the Injury Severity Score, Glasgow Coma Score, mechanism of injury and anatomical site of injury. Outcome analysis was based on mortality at discharge. RESULTS: The pattern of trauma differed significantly between Stoke and Portland. Patients from Stoke tended to be older, presented with a lower conscious level and a lower systolic blood pressure and were intubated less frequently before arriving at hospital. Mortality depended on similar factors in both centres, especially age, highest AIS score, systolic blood pressure and Glasgow Coma Score.The crude analysis of mortality showed a highly significant odds-ratio of 1.64 in Stoke compared with Portland. Single-factor adjustments were made for the above four factors, which had a similar influence on mortality in both centres. Adjusting for the first three factors individually did not alter the odds-ratio, which stayed in the range 1.53-1.59 and remained highly significant. Adjusting for the Glasgow Coma Score reduced the odds-ratio to 0.82 and rendered it non-significant. In a multi-factor logistic regression model incorporating all of the factors shown to influence mortality in either centre, the odds-ratio was 1.7 but was not significant. CONCLUSION: The analysis illustrates the limitations and pitfalls of making crude outcome comparisons between centres. Highly significant differences in crude mortality were rendered non-significant by case-mix adjustments, supporting the null hypothesis that the two centres were equally effective in terms of this short-term indicator of outcome. To achieve a meaningful comparison between centres, adjustments must be made for the factors which affect mortality.

Adult↗
PubMed2000

Chronic systemic pesticide exposure reproduces features of Parkinson's disease.

The cause of Parkinson's disease (PD) is unknown, but epidemiological studies suggest an association with pesticides and other environmental toxins, and biochemical studies implicate a systemic defect in mitochondrial complex I. We report that chronic, systemic inhibition of complex I by the lipophilic pesticide, rotenone, causes highly selective nigrostriatal dopaminergic degeneration that is associated behaviorally with hypokinesia and rigidity. Nigral neurons in rotenone-treated rats accumulate fibrillar cytoplasmic inclusions that contain ubiquitin and alpha-synuclein. These results indicate that chronic exposure to a common pesticide can reproduce the anatomical, neurochemical, behavioral and neuropathological features of PD.

Animals↗
PubMed2000

External beam radiotherapy in exudative age-related macular degeneration: a pooled analysis of phase I data.

In recent years external beam radiotherapy (EBRT) has been proposed as a treatment for the wet form of age-related macular degeneration (AMD) where choroidal neovascularization (CNV) is the hallmark. While the majority of pilot (Phase I) studies have reported encouraging results, a few have found no benefit, i.e. EBRT was not found to result in either improvement or stabilization of visual acuity of the treated eye. The natural history of visual loss in untreated CNV of AMD is highly variable. Loss of vision is influenced mainly by the presenting acuity, and size and composition of the lesion, and to a lesser extent by a variety of other factors. Thus the variable outcome reported by the small Phase I studies of EBRT published to date may simply reflect the variation in baseline factors. We therefore obtained information on 409 patients treated with EBRT from eight independent centres, which included details of visual acuity at baseline and at subsequent follow-up visits. Analysis of the data showed that 22.5% and 14.9% of EBRT-treated eyes developed moderate and severe loss of vision, respectively, during an average follow-up of 13 months. Initial visual acuity, which explained 20.5% of the variation in visual loss, was the most important baseline factor studied. Statistically significant differences in loss of vision were observed between centres, after considering the effects of case mix factors. Comparisons with historical data suggested that while moderate visual loss was similar to that of the natural history of the disease, the likelihood of suffering severe visual loss was halved. However, the benefit in terms of maintained/improved vision in the treated eye was modest.

Aged↗
PubMed1999

Mitochondrial dysfunction in Parkinson's disease.

The cause of Parkinson's disease (PD) is unknown, but reduced activity of complex I of the electron-transport chain has been implicated in the pathogenesis of both mitochondrial permeability transition pore-induced Parkinsonism and idiopathic PD. We developed a novel model of PD in which chronic, systemic infusion of rotenone, a complex-I inhibitor, selectively kills dopaminergic nerve terminals and causes retrograde degeneration of substantia nigra neurons over a period of months. The distribution of dopaminergic pathology replicates that seen in PD, and the slow time course of neurodegeneration mimics PD more accurately than current models. Our model should enhance our understanding of neurodegeneration in PD. Metabolic impairment depletes ATP, depresses Na+/K(+)-ATPase activity, and causes graded neuronal depolarization. This relieves the voltage-dependent Mg2+ block of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, which is highly permeable to Ca2+. Consequently, innocuous levels of glutamate become lethal via secondary excitotoxicity. Mitochondrial impairment also disrupts cellular Ca2+ homoeostasis. Moreover, the facilitation of NMDA-receptor function leads to further mitochondrial dysfunction. To a large part, this occurs because Ca2+ entering neurons through NMDA receptors has 'privileged' access to mitochondria, where it causes free-radical production and mitochondrial depolarization. Thus there may be a feed-forward cycle wherein mitochondrial dysfunction causes NMDA-receptor activation, which leads to further mitochondrial impairment. In this scenario, NMDA-receptor antagonists may be neuroprotective.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Body-surface map models for early diagnosis of acute myocardial infarction.

The standard 12-lead ECG is only 50% sensitive for the detection of acute myocardial infarction (AMI). The majority of leads for optimal classification of AMI probably lie outside the area covered by the 6 precordial leads. Thus, body-surface mapping (BSM) may be more helpful, as a larger thoracic area is sampled. We recorded 64-lead anterior BSMs in 635 patients with chest pain suggestive of AMI and abnormal electrocardiograms (ECGs), and 125 controls without chest pain. Of the 635 patients, 325 had AMI according to World Health Organization (WHO) criteria (203 presenting with ST segment elevation, and 122 with nondiagnostic ECG), and 310 had an "abnormal ECG but not AMI." QRS and ST-T isointegrals and variables describing map shape were derived. Subjects were randomly allocated to a training set (63 controls, 321 patients) and a validation set (62 controls, 314 patients). Multiple logistic regression was used in the training set to identify which variables gave best discrimination between groups. A model with these variables was then tested prospectively in the validation set. In stage 1 (all subjects), controls were compared with patients. In the training set, a model containing 21 variables classified 58/63 controls (specificity 92%) and 316/321 patients (sensitivity 98%). In the validation set, the model classified 48/62 controls (specificity 77.4%) and 302/314 patients (sensitivity 96%). In stage 2 (studying patients only), patients with AMI were compared with patients who had an abnormal ECG-not AMI. In the training set, a model containing 28 variables classified 132/165 patients (sensitivity 80%) with AMI and 134/156 patients (specificity 86%) with an abnormal ECG-not AMI. In the validation set, the model classified 123/160 patients (sensitivity 77%) with AMI and 131/154 patients (specificity 85%) with an abnormal ECG-not AMI. Combining results of both stages in a two-step algorithm gave an overall classification in the training set of controls 92%, abnormal ECG-not AMI 84%, AMI 80%, and in the validation set of controls 77%, abnormal ECG-not AMI 82%, AMI 74%. Thus, in conclusion, when compared with the 12-lead ECG, BSM models results in higher sensitivity and specificity for detection of AMI, particularly in patients presenting with chest pain and nondiagnostic ECG changes. The use of BSM models in such patients, may lead to the earlier detection of AMI and appropriate administration of fibrinolytic therapy and/or anti-platelet agents.

Body Surface Potential Mapping↗
PubMed1996

Teletherapy for subfoveal choroidal neovascularisation of age-related macular degeneration: results of follow up in a non-randomised study.

AIM: A preliminary report indicated stable or improved vision in 12 of 19 patients with subfoveal choroidal neovascularisation treated with 12 or 15 Gy of 6 MV photons to the affected macula after an average follow up of 18 months. Here the prolonged follow up findings in this group of treated patients is reported which was further increased to 41. METHODS: Forty one patients with subfoveal choroidal neovascularisation were treated with 10, 12, or 15 Gy of 6 MV photons to the macula of the affected eye. Thirteen eyes of 12 patients were also observed as a non-randomised comparison group. RESULTS: At 12, 18, and 24 months of follow up the mean change in visual acuity in eyes treated with radiotherapy was less than 1 Bailey-Lovie line from that measured at presentation. By contrast, the eyes in the comparison group lost 3.7 lines of acuity at 12 months which increased to 4.5 at 24 months. These differences were highly significant at each of the time points. When initial visual acuity was taken into account, treated eyes lost on average 12% of baseline acuity throughout follow up, whereas eyes belonging to the untreated group lost 50% of baseline acuity at 1 year, and 75% at 2 years. There was no significant difference in visual outcome between the three dose regimens used, which may simply be a reflection of the small sample size in each group. There was no evidence of radiation induced retinopathy or optic neuropathy in any treated patients. CONCLUSIONS: Teletherapy appeared to have a treatment effect in eyes with subfoveal choroidal neovascularisation resulting in maintained visual function without significant radiation induced morbidity.

Aged↗
PubMed1995

Body surface ECG potential maps in acute myocardial infarction.

An algorithm for the early detection of acute myocardial infarction (MI) using body surface electrocardiographic potential mapping has been developed. The mapping system consists of a 64-hydrogel electrode harness applied rapidly to the anterior chest, from which electrocardiographic signals are stored on a memory card and processed by computer. At each of the 64 points, QRS and ST-T isointegrals and 10 other features of the QRST segment are measured. Using these measurements, new variables are derived that express the shape of the three-dimensional geometric surface of the map. The isointegrals, features, and shape variables are used in a variety of techniques to discriminate between MI and control subjects. Maps were recorded from 69 patients at initial presentation of chest pain suggestive of acute MI and from 80 healthy control subjects. Using a multiple logistic regression technique, 14 variables were identified that correctly classified 79 of the 80 control subjects (specificity, 98.8%) and 65 of the 69 MI patients (sensitivity, 94.2%). The algorithm based on these 14 variables was applied prospectively to maps recorded on a further 48 control subjects and 59 patients with acute MI. Of the MI patients, 31 had inferior, 13 inferoposterior, 10 anterior, 2 posterior, 1 lateral, 1 inferior with right bundle branch block, and 1 anterior non Q wave MI. The algorithm correctly classified all 48 control subjects (specificity, 100%) and 57 of the 59 MI patients (sensitivity, 96.6%). Marked differences in the three-dimensional geometric map surfaces between the control subjects and MI patients were demonstrated. Variables derived from these surfaces form the basis of an algorithm with a high sensitivity and specificity for the automated detection of acute MI. The design of adaptive algorithms and their application to patients with chest pain and atypical electrocardiographic changes, particularly ST depression, may lead to the earlier detection of MI and greater numbers of patients receiving thrombolytic therapy.

Adolescent↗
PubMed1994

Discriminant function analysis of body surface potential maps in acute myocardial infarction.

Using a newly developed 64-electrode portable mapping device, QRS and ST-T isointegral maps were compared in 194 control subjects and 101 patients. One hundred ninety-four control subjects (mean age, 48 years; 120 men) with no history of cardiac disease were selected randomly and mapped. One hundred one patients (mean age, 62 years; 77 men) were mapped at presentation of chest pain suggestive of first myocardial infarction (MI); all patients had classic 12-lead electrocardiographic findings--46 with anterior and 55 with inferior MI. The diagnosis was confirmed in all cases by a significant rise in serial cardiac enzymes. The mean delay between onset of chest pain to map recording was 163 minutes. Of the 101 patients, 78 were first mapped outside the hospital. Applying discriminant function analysis to the isointegral measurements made on the control subjects and on the first map of MI patients achieved a correct classification of 97% of the control subjects (189 of 194) and 72% of the anterior (33 of 46) and 76% of the inferior (42 of 55) MI groups. This preliminary study suggests that discriminant function analysis, based on isointegral maps, not only provides a method of separating control subjects from MI patients but that it can also differentiate between types of infarct. Further studies are required to improve the predictive values of discriminant function and to extend the methodology to assess both the site and size of MI.

Adult↗
PubMed1994

Time delays to lytic therapy and outcome in 100 consecutive patients with a history suggestive of acute myocardial infarction in an area with access to a mobile coronary care unit.

Time delays to fibrinolytic treatment and outcome were assessed in 100 consecutive patients, with suggestive symptoms and electrocardiographic changes of acute myocardial infarction, admitted to the coronary care unit of this hospital. All patients admitted from out-of-hospital had access to a mobile coronary care unit. Initially, 40 patients called a general practitioner, 30 called the '999' operator, 12 called the mobile coronary care unit, 10 reported directly to the Accident and Emergency Department, seven were in-hospital and one spoke to the general practitioner's receptionist. Subsequently, 59 patients were attended by the mobile coronary care unit, 34 were admitted via the Accident and Emergency Department and seven had symptoms in-hospital. Thrombolytic therapy was initiated in 45/59 (76%) patients by the mobile coronary care unit staff and in 29/34 (85%) patients in the Accident and Emergency Department by cardiac staff. The remaining 26 patients received thrombolytic treatment in the hospital coronary care unit or cardiac department. The mean (+/- SEM) time from symptom onset to the initiation of thrombolytic therapy was 127 (+/- 11 min) for those patients treated by the mobile coronary care unit staff and for those treated in the Accident and Emergency Department was 187 (+/- 13 min) (P = 0.005). Multiple regression analysis showed significant reductions in total time delay if patients received thrombolytic therapy by the mobile coronary care unit staff out-of-hospital, when chest pain began in-hospital, or if patients had a previous myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulances↗
PubMed1994

Portable cardiac mapping assessment of acute ischaemic injury.

A portable cardiac mapping system is used to improve the accuracy of diagnosis of acute ischaemic injury outside hospital. Patients presenting chest pain suggestive of myocardial infarction (MI) were mapped by attendant medical personnel operating from a mobile coronary unit. These first MI maps were compared against average normal maps using QRS and ST-T isointegral values. Discriminant function analysis performed on the parameters achieved a sensitivity of 90% and a specificity of 96%.

Body Surface Area↗