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Biomedical subjects

S Fraser

Publications and source records attributed to S Fraser.

At least 55 records · Page 3Linked to original sources
PubMed1999

Thymic shared antigen-2: a novel cell surface marker associated with T cell differentiation and activation.

Thymic shared Ag-2 (TSA-2) is a 28-kDa, glycophosphatidylinitosol-linked cell surface molecule expressed on various T cell and thymic stromal cell subsets. It is expressed on most CD3-CD4-CD8-, CD4+CD8+, and CD3highCD4-CD8+ thymocytes but is down-regulated on approximately 40% of CD3highCD4+CD8- thymocytes. Expression on peripheral TCR-alphabeta+ T cells is similar to that of CD3+ thymocytes, although a transient down-regulation occurs with cell activation. Consistent with the recent hypothesis that emigration from the thymus is an active process, recent thymic emigrants are primarily TSA-2-/low. TSA-2 expression reveals heterogeneity among subpopulations of CD3highCD4+CD8- thymocytes and TCR-gamma delta+ T cell previously regarded as homogenous. The functional importance of TSA-2 was illustrated by the severe block in T cell differentiation caused by adding purified anti-TSA-2 mAb to reconstituted fetal thymic organ culture. While each CD25/CD44-defined triple-negative subset was present, differentiation beyond the TN stage was essentially absent, and cell numbers of all subsets were significantly below those of control cultures. Cross-linking TSA-2 on thymocytes caused a significant Ca2+ influx but no increase in apoptosis, unless anti-TSA-2 was used in conjunction with suboptimal anti-CD3 mAb. Similar treatment of mature TSA-2+ T cells had no effect on cell survival or proliferation. This study reveals TSA-2 to be a functionally important molecule in T cell development and a novel indicator of heterogeneity among a variety of developing and mature T cell populations.

Aging↗
PubMed1999

Detection of distal emboli in patients with peripheral arterial stenosis before and after iliac angioplasty: a prospective study.

PURPOSE: Embolism is believed to be the major cause of end-organ damage after angioplasty and endoluminal procedures. Recently, Doppler ultrasound scanning has been used to detect asymptomatic cerebral emboli. We determined whether asymptomatic embolic signals (ES) could be detected distal to a significant iliac artery stenosis of >60% both before and soon after iliac percutaneous transluminal angioplasty (PTA). METHODS: A 2-MHz Doppler scan probe was used to monitor for ES in the common femoral artery before and after 10 successful iliac artery PTAs and at various standardized times in the following 24 hours. The same protocol was used to study 10 patients in the control group after renal PTA. In addition, a single recording was performed in a second nonoperative control group of 10 patients who had no evidence of peripheral vascular disease. The Doppler scan signals were recorded on tape for a later blinded analysis. RESULTS: In the 24 hours before iliac PTA, asymptomatic ES were detected in four of 10 patients during a 1-hour recording but in no controls (P =.025). After iliac PTA, ES were detected at 30 minutes in nine of 10 iliac subjects but in only one of 10 renal subjects (P =.0003) and at 2 hours in eight of 10 iliac subjects but in only one of 10 renal subjects (P =.001). The occurrence of ES became less frequent, and ES were present at a lower frequency in eight of 10 iliac PTA subjects at 4 hours and in five of 10 at 24 hours but in no renal PTA subjects at these time points. CONCLUSIONS: ES can be detected in the common femoral artery with Doppler ultrasound scanning in patients with iliac artery stenosis both before and soon after iliac PTA despite preangioplasty aspirin and intra-angioplasty heparin therapies. The occurrences of ES were particularly frequent in the 2 hours after PTA. This technique can be used further to study factors that control plaque stability and to evaluate the effect of therapeutic interventions.

Aged↗
PubMed1999

Heparin-binding epidermal growth factor-like growth factor is expressed in the adhesive lesions of experimental focal glomerular sclerosis.

BACKGROUND: In this study, we attempted to determine whether heparin-binding epidermal growth factor-like growth factor (HB-EGF) was up-regulated in two chronic models of proteinuria. METHODS: Chronic passive Heymann nephritis (PHN) and puromycin aminonucleoside (PAN) models were induced in Sprague-Dawley rats. HB-EGF expression was studied by Northern blotting, in situ hybridization, and immunohistochemistry. RESULTS: The chronic PAN model was associated with the development of glomerular lesions of focal glomerular sclerosis (FGS), severe interstitial fibrosis, and renal failure. Lesions of FGS were seen in approximately 80% of glomeruli at all time points, with a slight increase in the number of glomeruli showing extensive adhesion between 40 and 90 days. Northern blots of whole kidney tissue showed a 3- to 5.8-fold increased expression of HB-EGF mRNA in the chronic PAN group. Increased mRNA and protein were localized by in situ hybridization and immunohistochemistry to tubules, glomerular epithelial cells (GECs), and cells of Bowman's capsule. HB-EGF mRNA and protein were strongly expressed by epithelial cells involved in the formation of the lesions of FGS. By contrast, in chronic PHN, there was a small increase in HB-EGF, and the extensive lesions of FGS did not develop despite continued, heavy proteinuria. CONCLUSIONS: These data suggest that HB-EGF may contribute to formation of the lesions of FGS, perhaps through stimulation of abortive mitogenesis in GECs or an adhesive interaction between transmembrane HB-EGF and the exposed glomerular basement membrane.

Actins↗
PubMed1999

Retrospective analysis of risk factors for late presentation of chronic glaucoma.

BACKGROUND: Why some individuals present to the ophthalmologist in the early stages of chronic glaucoma but others present with very advanced visual field loss is a question which has received little attention. This study is an attempt to identify some basic characteristics of people who present with late glaucoma. METHODS: A retrospective case-control study by medical record review was employed. 100 cases and 100 controls were identified from the notes of patients presenting to Moorfields Eye Hospital glaucoma service between July 1993 and July 1995. Cases were defined as new patients presenting with absolute field loss within five degrees of fixation and a cup to disc ratio of greater than 0.8 in one or both eyes. Controls were new patients with no absolute field loss within 20 degrees in either eye, but otherwise typical glaucomatous field loss and a cup to disc ratio of greater than 0.5 or a difference of 0.2 or more between the discs. RESULTS: The ethnic origin, sex, referral source, presenting IOP, and age of the subjects studied were independently associated with late presentation. An African Caribbean patient is estimated to be four and a half times more likely to attend with advanced field loss than a white patient of similar age, sex, IOP, and referral source (adj OR: 4.55, 95% CI [1.57, 13.18]). A female patient is estimated to be one third (0.34, [0.15, 0.74]) as likely to attend late than a male patient of the similar age, IOP, ethnic origin, and referral source. A patient referred via any source other than an optometrist with the correct diagnosis is estimated to be greater than four times (4.32 [1.89, 9.88]) more likely to be a late attender than a patient of the same sex, ethnicity, and similar age but referred with a diagnosis of glaucoma. There was a trend of increasing odds of late presentation with increasing age (adj OR per 10 years, baseline 40-49 years 1.68 [1.22, 2.20]). A patient whose presenting IOP is 21-25 mm Hg is estimated to be a quarter (0.24, [0.09, 0.64]) as likely to attend with advanced field loss than a patient of the same ethnic origin, sex, age, referral source, but with presenting IOP of greater than 31 mm Hg. CONCLUSIONS: These data strongly suggest that certain subgroups of patients with glaucoma are likely to be at greater risk of presenting with advanced and irremediable field loss.

Adult↗
PubMed1999

Risk factors for late presentation in chronic glaucoma.

PURPOSE: To identify the risk factors for having advanced glaucomatous visual field loss on the first visit at three hospital eye services. METHODS: This was a hospital-based, case-control study involving patients newly diagnosed with glaucoma at first visit to one of three ophthalmic departments in the United Kingdom. Patients with a previous history of ocular hypertension or any documented suspicion of glaucoma (within the hospital eye service) were excluded. RESULTS: Occupational group, initial intraocular pressure (IOP), family history of glaucoma, method of referral to hospital, and the number of years since the last visit to an optometrist were found to be independently associated with late presentation. A linear trend of increasing odds of late attendance was associated with increasing Standard Occupational Classification. Those in managerial (category II) and skilled (category III) groups estimated (95% confidence intervals) to be, respectively. 0.2 (0.00, 0.16) and 0.27 (0.1, 0.8) as likely to attend with advanced glaucomatous field loss as unskilled (category V) people with similar initial IOP, family history, referral route, and time since last optometrist visit. The data strongly suggest an association between IOP and advanced field loss at initial hospital examination. There was a 1.2 (1.12, 1.28) increase in the OR of late presentation per unit increase in millimeters of mercury after adjustment for the other mentioned factors. People with a family history of glaucoma were estimated to be almost one third (adjusted OR, 0.29 [0.12, 0.74]) as likely to have advanced field loss as those with no family history. People referred by any source other than an optometrist who has made the correct diagnosis of glaucoma were 4.5 times (adjusted OR, 4.53 [1.52, 13.48]) more likely to be late attenders than patients so referred but similar in other mentioned factors. These data also provide strong evidence that the more years since the last visit to an optometrist, the greater the likelihood of having advanced glaucomatous visual field loss on the first visit to the eye service (adjusted OR per year, 1.25 [1.10, 1.42]). CONCLUSIONS: These data strongly suggest that certain subgroups of people with glaucoma were at greater risk of having advanced and irremediable field loss on first visiting the eye services studied.

Adult↗
PubMed1998

Age-specific patterns of factors related to fatal motor vehicle traffic crashes: focus on young and elderly drivers.

This population-based study examines patterns of fatal motor vehicle traffic crashes (MVTCs) by age group (16-24, 25-64, 65+) among Canadian drivers. The Canadian Traffic Accident Information Databank (TRAID) provided information about fata MVTCs between 1984 and 1993. Distribution of risk factors was compared by age group. Crude odds ratios and 95% CIs were calculated for both young and elderly drivers compared with middle-aged drivers. The middle-age group was selected as reference population since it demonstrates the lowest risk of fatality. Compared to the middle-aged group, young drivers demonstrated excess risk for (1) risk-taking behaviours and conditions, specifically alcohol and illicit drug use, speeding, non use of seat belts, fatigue and falling asleep, and inexperience; (2) crashes during the summer, during weekends and at night; and (3) single-vehicle collisions and on performing overtaking manoeuvres. Excess risk among elderly drivers was noted for (1) medical and physical conditions, inattention and inexperience; (2) driver actions, for example, improper turning, failure to yield right-to-way; (3) occurrence on weekdays and during the day; and (4) collisions at intersection and vehicle--vehicle sideswipes. The results show notable differences in risk factors by age group and confirm the need for preventive efforts that incorporate age-specific strategies.

Accidents, Traffic↗
PubMed1998

BD8 certification of visually impaired people.

BACKGROUND: There is debate as to the completeness of the blind and partial sight registers in England and Wales. The purpose of this study was to estimate the proportion of eligible visually impaired people attending the hospital eye service who have a BD8 certificate and to identify factors associated with not being certified. METHODS: Cross sectional survey of patients attending outpatients by medical record review analysed by multiple logistic regression. RESULTS: 51% (43%, 58%) of patients identified as eligible for registration did not have a BD8 certificate. The severity of visual impairment and the main diagnosis in terms of requirements for treatment, permanence of visual loss, and visual field loss were independently associated with non-certification. A partially sighted patient is estimated to be three times more likely to not have a BD8 certificate as a blind patient of similar diagnosis (adj OR: 3.4 (95% CI: 1.7, 6.8)). A patient whose impairment is due to abnormal visual fields is estimated to be greater than three times more likely to be non-certified than one with low visual acuity of similar severity and cause (adj OR: 3.6 (95% CI: 1.0, 12.7)). People whose impairment is potentially reversible are estimated to be eight times (8.3 (2.2, 31.4)) more likely not to have a certificate compared with people who had permanent non-treatable visual loss; and in those with permanent visual loss, a requirement for ongoing treatment was found to be associated with a lower odds of certification. CONCLUSIONS: These data strongly suggest that epidemiological data collected during registration are biased towards permanent, non-treatable causes of visual loss and those which affect central rather than peripheral vision. Certain subgroups of the visually impaired are likely to be at greater risk of non-certification. BD8 guidelines need to be simplified.

Aged↗
PubMed1998

Workshop report. National initiative to improve cancer survival information.

This workshop (held June 19 20, 1997, in Ottawa, Ontario) brought together major stakeholders to establish a Canadian initiative to develop systematic collection of population-based information on cancer survival. The broad goals of the workshop were to delineate the current needs regarding such data and to recommend practical mechanisms to systematically generate this information. Three key areas for discussion were identified: collection of staging data, collection of treatment data and standardized approaches to analysis. Presentations (summarized in report), designed to establish common ground for workshop discussions, provided background information on population-based collection mechanisms, data and methodology requirements for conducting meaningful cancer survival surveillance, and practical examples of using cancer survival information.

Canada↗
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↗
PubMed1995

Dorsal and ventral cell types can arise from common neural tube progenitors.

To challenge the developmental potential of dorsal neural tube cells and test whether single neuroepithelial cells can give rise to the full range of neural tube derivatives, we grated a notochord lateral to the closing neural folds. This results in juxtaposition of dorsal and ventral cell types, by inducing floor plate cells and motor neurons dorsally. Clonal analysis with the vital dye lysinated rhodamine dextran showed that both "dorsal" and "ventral" neural tube derivatives can arise from a single precursor. Cells as diverse as sensory ganglion cells, presumptive pigment cells, roof plate cells, motor neurons, and floor plate cells were observed in the same clone. The presence of such diversity within single clones indicates that the responses to dorsal and ventral signals are not mutually exclusive; even in the early neural tube, neuroepithelial cells are not restricted to form only dorsal or ventral neural tube derivatives.

Animals↗
PubMed1995

A prospective study of nosocomial infection in a neonatal intensive care unit.

OBJECTIVE: To determine the incidence of and organisms responsible for neonatal nosocomial infection (after 72 h of age). METHODOLOGY: A 1-year evaluation of 321 consecutive septic work-ups performed on 130 of 1008 babies admitted to a neonatal intensive care unit (NICU) for more than 72 h. Fifty-seven (89%) of 64 infants of birthweight 500-999 g, 36 (34%) of 105 infants 100-1499 g, 27 (6%) of 422 infants 1500-2499 g and 10 (28%) of 477 infants of birthweight > 2500 g had at least one septic work-up. RESULTS: In addition to blood culture, the evaluations included haematological score on full blood count in 94.7%, abdominal X-ray in 48%, endotracheal tube tip culture in 32.7% and lumbar puncture in only 13.1%. Blood culture was positive on 92 occasions in 75 infants (28.7% of work-ups and 7.4% of all babies admitted). Infection status was classified as definite on 40 occasions in 30 babies, and due to contamination 52 in 45 babies. Twenty of the 30 babies with definite infection were of birthweight 500-999 g. Of the 40 definite infections coagulase-negative staphylococci (CONS) were cultured from 23 babies, Gram negative bacilli in 14 and Candida spp. in three babies. Sepsis caused or contributed to the deaths of six babies. CONCLUSION: This study identifies infants of birthweight < 1000 g as the highest risk group for nosocomial infection especially CONS. New strategies in prevention, surveillance and treatment are required for extremely low birthweight infants.

Chi-Square Distribution↗