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Biomedical subjects

C Fraser

Publications and source records attributed to C Fraser.

At least 19 recordsLinked to original sources
PubMed1997

Delineation of the human hematolymphoid system: potential applications of defined cell populations in cellular therapy.

Hematopoietic stem cells (HSC) have the capacity to reconstitute all the blood cells in the body. HSC are rare, representing on average 0.05% of the mononuclear cells present in healthy human bone marrow. Due to their capacity for self-renewal and their pluripotent, long-term reconstituting potential, HSC are considered ideal for transplantation to reconstitute the hematopoietic system after treatment for various hematologic disorders or as a target for the delivery of therapeutic genes. Human HSC also have potential applications in restoring the immune system in autoimmune diseases and in the induction of tolerance for allogeneic solid organ transplantation. With the increased interest in human HSC for clinical applications, technology for the isolation of candidate HSC and knowledge of human hematopoiesis have been growing rapidly. In this article, we discuss the functional characterization of a human CD34+Thy-1+ HSC population which is essentially free of residual disease, our efforts to generate alternate monoclonal antibodies for the isolation of clinically useful stem or progenitor cell populations, and the identification of a novel lymphoid progenitor as part of an exploration towards defining progenitors with potential application as adjuncts to HSC-based cellular therapy.

Adoptive Transfer↗
PubMed1996

TB testing.

Explore the source record for details and available documents.

Animals↗
PubMed1996

Effects of purine analogues on spontaneous alternation in mice.

The Y-maze was used to examine the effects of purines acting at A1 and A2 adenosine receptors upon spontaneous alternation, a model of working memory, in mice. In support of previous work, scopolamine produced a loss of spontaneous alternation behaviour to the 0.5 chance level. The A1 receptor selective agonist N6- cyclopentyladenosine (CPA) did not change spontaneous alternation behaviour alone, but it prevented the decrease of spontaneous alternation scores produced by scopolamine. The A1 receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX) blocked the effect of CPA in combination with scopolamine but had no effect alone. The A2 receptor selective agonist (N6-[2-(3,5-dimethoxyphenyl)-2-(2- methylphenyl)ethyl] adenosine (DPMA), and the A2 receptor selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect of alternation behaviour alone and did not modify the effect of scopolamine. The results indicate the ability of A1 but not A2 receptor activation to modify working memory deficits induced by scopolamine, but suggest that endogenous adenosine does not normally participate in working memory processes.

Adenosine↗
PubMed1996

Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation during recovery of arm and hand function after stroke.

We examined the relationship between the recovery of hand and arm function in a group of hemiplegic stroke patients and the presence of short-latency EMG responses to transcranial magnetic stimulation (TMS) in 4 different upper limb muscles (deltoid, biceps, extensor digitorum communis and the first dorsal interosseous). Twenty-one patients were examined within 5 weeks of stroke (median 2 weeks), and then at regular intervals over the next 12 months. Some patients recovered rapidly (Group A); in others, recovery was slow and incomplete (Group B). Even at the first test, Group A patients had responses to TMS in all muscles. Most Group B patients initially lacked responses in all tested upper limb muscles; in those that later were able to activate hand muscles, responses returned at or just before this stage of recovery. No such clear correlation between the presence of responses to TMS and ability to activate more proximal arm muscles was evident. Response latency was initially long and declined in a manner that was highly correlated with muscle strength and hand function test scores. Ipsilateral responses were elicited from both the affected and unaffected hemispheres. Ipsilateral responses from the latter were most common in the proximal muscles of the affected limb, and had latencies that were longer than those elicited in the contralateral (unaffected) arm. Nine cases of ipsilateral responses in hand muscles were found; such responses are not found in healthy subjects. Ipsilateral responses from the undamaged hemisphere were more prevalent in the poorly recovered patients; the underlying mechanisms may not be beneficial for recovery.

Adult↗
PubMed1996

False negative cytogenetic results following amniocentesis.

We report 2 cases where prenatal cytogenetic studies following amniocentesis yielded false negative results. Both mothers requested termination of pregnancy but were reassured by the normal chromosome analysis and therefore continued their pregnancies. When cytogenetic studies were repeated in the neonatal period, they demonstrated chromosomal abnormalities, which were confirmed when the initial specimens from amniocentesis were reviewed. Because of our findings, we suggest that if prenatal chromosome analysis is reported as normal, where there is a high index of suspicion of a chromosome abnormality, the result should be questioned and neonatal chromosome analysis undertaken.

Adult↗
PubMed1996

Graduate professional development programme dentistry.

This paper describes the development and structure of a pilot programme of professional development for new graduates initiated by the New Zealand Dental Association, the Dental Council of New Zealand, and the Faculty of Dentistry of the University of Otago. The programme consisted of a series of monthly evening seminars, co-ordinated by a facilitator, and led by experienced practitioners. Initially provided in Auckland, the programme subsequently extended to Wellington, Christchurch, and Waikato-Bay of Plenty. The award of a New Zealand Dental Association Travelling Fellowship enabled the author to observe the United Kingdom Vocational Training Scheme, and attendance at the 1994 meeting of the Fédération Dentaire Internationale provided opportunity to study systems used in other countries. The pilot programme has now been replaced by the ongoing Graduate Professional Development Programme Dentistry, a programme which extends beyond the recent graduate, but remaining based on the concepts developed in the pilot programme.

Education, Dental↗
PubMed1996

Proposed guidelines for the internal quality control of analytical results in the medical laboratory.

The factors involved in analytical quality relate to definition of quality, creation of quality, and control of quality, and errors arise from external and internal sources as well as from permanent and variable factors. Further, the two main types of error are classified as systematic and random errors. Internal quality control (IQC) systems can only operate on the variable factors which are related to batch-to-batch variations (external factors) and to the performance in the laboratory (internal factors). In creating an adequate internal control system, several problems are faced: (i) quality of control materials, (ii) types and frequency of possible errors, (iii) number and types of control materials, (iv) number of replicates of the control, (v) probability of error detection, (vi) probability of false rejection, (vii) consequences of reject signals, (viii) trouble-shooting systems, and (ix) prevention of errors among many other conditions. Gaussian distributions of control results are assumed and the statistical control rules are evaluated in relation to probability of false rejections, Pfr, and probability of error detection, Ped, for the different rules. Combinations of low Pfr and high Ped are obtained by combining results from e.g. four measurements of the same control sample by use of mean and range rules. Further, it is not possible to establish a common control system which can be used for all quantities and analytical procedures; on the contrary, each procedure should have its particular efficient IQC system. These aspects are discussed and a number of guidelines for statistical control rules and problem related internal quality control are presented.

Guidelines as Topic↗
PubMed1995

Psychological response to cervical screening.

BACKGROUND: Few studies have examined the psychological costs of cervical screening, despite expressed concern over possible negative sequelae. METHODS: Seventy-five women with mild or moderately dyskaryotic smears, under cytological surveillance, 75 women referred for colposcopy after a first-ever abnormal smear showing severe dyskaryosis, and 75 controls with recent negative cytology were interviewed at home, and their psychological adjustment was assessed. RESULTS: Levels of distress were higher among women with an abnormal smear than among controls with a recent negative smear. Anxiety (Hospital Anxiety and Depression Scale range 0-21, "normal" range 0-7) was highest among those referred for colposcopy (mean 8.12, controls 5.88, P < 0.001); afterward, distress fell (mean 6.61, P < 0.001) but more problems of social adjustment were evident (surveillance vs controls, P < 0.01). High anxiety was associated with social maladjustment (colposcopy, P < 0.001; surveillance, P < 0.01) and negative feelings about the self (P < 0.05). Current anxiety was unrelated to knowledge about abnormal smears, but in the surveillance group was related to satisfaction with the explanation provided (P < 0.05). CONCLUSION: A positive cervical smear may by psychologically traumatic for a significant minority of women, irrespective of management strategy.

Adaptation, Psychological↗
PubMed1995

Prospective study of patients aged 55 years or less with acute myocardial infarction between 1981 and 1985: outcome 7 years and beyond.

OBJECTIVE: To determine the long-term prognosis of patients after a myocardial infarction (MI) at a young age. DESIGN: Prospective cohort study of patients aged 55 years or less suffering a myocardial infarction. SETTING: A single coronary care unit admitting patients from the community. PATIENTS: 255 consecutive patients (210 men) aged 55 years or less admitted between 1981 and 1985 after acute MI. Twenty four patients died in hospital or within 3 months of infarction and 11 were lost to further follow up after discharge. Of the remaining patients, 150 (mean (SD) age 48 (5.7) years) able to exercise 3 weeks after infarction and who agreed to undergo coronary angiography were recruited to a study group and seen 18 months, and 3, 5, and 7 years after MI. In addition, a cross sectional analysis of survival was made to a median of 120 months. Seventy 3 month survivors (mean (SD) age 48 (5.8) years) were not recruited to the study group but were traced for late survival through their general practitioners and family health service associations to a median of 130 months. MAIN OUTCOME MEASURES: Survival in young patients after MI and the survival of 3 month survivors stratified by their ability to exercise and agreement to undergo angiography. The rate of coronary artery surgery (CAGB) and reinfarction during the first 7 years after index MI in patients recruited to the study group. RESULTS: Sixteen patients (6%) died in hospital and eight (3%) within 3 months of the index infarction. The 7 and 11 year survival rates in the whole cohort of 255 patients were 80% and 66% respectively using life table methods. Survival 7 years after MI, in patients recruited to the study group was better than in those not recruited (93% v 79%, P = 0.001), but thereafter mortality in the study group accelerated and there was no significant difference in survival 11 years after infarction (76% v 67%, P = 0.05). There was a trend towards higher mortality in patients with multivessel disease and severely impaired left ventricular function. During the first 7 years after MI, 38 of 150 patients in the study group underwent CABG and 19 suffered reinfarction, which was fatal in three. CONCLUSION: The medium-term prognosis of young survivors of MI is good, particularly in patients recruited to the study group. After 7 years there is an increase in mortality and the long-term prognosis is less favourable. This should be taken into account when planning future management and follow up of young patients after MI.

Adult↗
PubMed1995

Cytokine-mobilized peripheral blood CD34+Thy-1+Lin- human hematopoietic stem cells as target cells for transplantation-based gene therapy.

Gene-therapy of blood-borne disorders may be best achieved using hematopoietic stem cells (HSC) which have extensive self renewal potential as well as multilineage repopulating potential as a cellular target. The human HSC, which is CD34+Thy-1+Lin- has been isolated from fetal, adult bone marrow and cytokine-mobilized peripheral blood (MPB) (1-3). Results presented in this study show that the degree of mobilization of HSC into peripheral blood of cancer patients is highly variable and that the combined use of high dose chemotherapy and GM-CSF as a mobilization strategy is superior to the use of G-CSF with regard to the mobilization of true HSC. A multistep cell isolation procedure has been developed which utilizes high speed flow-cytometric cell sorting and allows the isolation of sufficient numbers of HSC from MPB to permit their use as an hematopoietic graft for clinical transplantation. Hematopoietic stem cells isolated from MPB are capable of self-renewal and differentiation into multiple hematopoietic lineages as shown by their behavior in both in vitro and in vivo assays. Mobilized PB mononuclear cells isolated from cancer patients are frequently contaminated with tumor cells. Using this cell isolation procedure, HSC preparations from patients with multiple myeloma have been created with greatly reduced tumor cell burdens. These CD34+Thy-1+Lin- cells are capable of being stably transduced at high efficiency (32-75%) by co-culture on a cell line producing recombinant retroviruses containing the neomycin-resistant gene. These HSC cell populations are likely ideal targets for hematopoietic cell-based gene therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗