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Biomedical subjects

J M Bamford

Publications and source records attributed to J M Bamford.

At least 19 recordsLinked to original sources

Platelet GP IIIa PlA and GP Ib variable number tandem repeat polymorphisms and markers of platelet activation in acute stroke.

A number of polymorphisms of the platelet glycoprotein (GP) Ib-V-IX and IIb/IIIa complexes have been described, and the PlA polymorphism of GP IIIa has been associated with coronary thrombosis. We determined the levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) and the genotype distributions of PlA and a variable number tandem repeat (VNTR) polymorphism of GP 1b in subjects with acute stroke (n=609) and healthy control subjects (n=435). Levels of beta-TG were higher in patients both initially (47.4 [44.7 to 50.2] ng/mL, P<0.0001) and after 3 months (42.9 [40.3 to 45.7] ng/mL, P=0.03) compared with control subjects (39.4 [37.7 to 41.2] ng/mL). Initial levels of beta-TG were significantly higher in those who subsequently died (58.7 [52.3 to 65.8] ng/mL) compared with those still alive (42.7 [40.1 to 45.5] ng/mL, P<0.0001). In a logistic regression model, beta-TG remained an independent predictor of poststroke mortality, with an odds ratio for an increase in 10 ng/mL of 1.12 (1.03 to 1.21, P=0.006). In subjects who had never smoked, there was a significant difference in the genotype distributions of patients with atherothrombotic stroke (A1/A1=147, A1/A2=70, and A2/A2=2) compared with controls (A1/A1=165, A1/A2=47, and A2/A2=5, P=0.03). The PlA distribution of subjects with atherothrombotic stroke before the age of 50 years (A1/A1=19 and A1/A2+A2/A2=18) was also significantly different from age- and sex-matched controls (A1/A1=54 and A1/A2+A2/A2=20, P=0.02). We found no association of VNTR with stroke or poststroke mortality. These data indicate that there is a persistent state of enhanced platelet activation in subjects with acute stroke, which is associated with poststroke mortality. The increased frequency of the PlA2 allele in young subjects with atherothrombotic stroke lends further support for a role of the PlA polymorphism in acute thrombosis.

Aged

Gender-specific associations of the fibrinogen B beta 448 polymorphism, fibrinogen levels, and acute cerebrovascular disease.

Fibrinogen is an independent risk factor for the development of stroke. Factors influencing circulating levels of fibrinogen include age, smoking, gender, and genetic factors. The aim of this study was to determine the relationship between a polymorphism at position 448 of the B beta fibrinogen gene, fibrinogen levels, gender, and the risk of stroke. Fibrinogen levels were determined in 305 patients with stroke, taken within 10 days of the acute event and 3 months later, and in 197 control subjects. Initial fibrinogen levels in patients (4.49 g/L) were significantly higher than at 3 months (3.85 g/L, P < .0001), consistent with resolution of the acute-phase response. At 3 months, levels were only significantly higher than for control subjects in the male patients (3.86 g/L versus 3.31 g/L, P < .0001). Fibrinogen levels were associated with B beta 448 genotype in male patients at 3 months (1/1 = 3.62 g/L, 1/2 + 2/2 = 4.27 g/L, P = .01). There was a significant difference in the genotype distribution in female patients and control subjects (patients: 1/1 = 95, 1/2 = 34, 2/2 = 6; control subjects: 1/1 = 61, 1/2 = 50, 2/2 = 3, P = .008). These data suggest that the mechanisms linking fibrinogen and the development of cerebrovascular disease are different in males and females. In male patients, the increase in fibrinogen levels may be influenced by environmental factors, while in females there may be a functional difference in the fibrinogen molecule unrelated to fibrinogen levels.

Acute Disease

Polymorphisms of the factor VII gene and circulating FVII:C levels in relation to acute cerebrovascular disease and poststroke mortality.

BACKGROUND AND PURPOSE: FVII:C has been shown to be an independent risk factor for myocardial infarction and is related to environmental and genetic factors. This study sought to investigate FVII:C levels and factor VII (FVII) gene polymorphisms in relation to stroke and disease outcome. METHODS: To examine the association of FVII:C and the Msp I and promoter insertion polymorphisms of the FVII gene in acute stroke, 317 patients and 198 age-matched control subjects were studied. RESULTS: FVII:C levels were significantly lower in patients at onset than 3 months later (119% versus 135%, respectively; P < .0005). Levels were significantly lower in patients at onset than in control subjects (124% [95% confidence interval, 120% to 129%] versus 141% [95% confidence interval, 135% to 148%], respectively; P < .0005) but were not significantly different at 3 months (135% [95% confidence interval, 128% to 141%] versus 141% [95% confidence interval, 135% to 148%], respectively). We found no difference in genotype distribution for either polymorphism between patients and control subjects, no difference in FVII:C level or genotype distribution between pathological types of stroke, and no relationship with poststroke mortality. Both polymorphisms were significantly associated with FVII:C levels in patients and control subjects. In a multiple regression model for patients, Msp I genotype, cholesterol, and smoking remained as independent predictors of FVII:C levels, accounting for 32% of interindividual variation. CONCLUSIONS: These results suggest that neither FVII:C levels nor FVII gene polymorphisms are associated with cerebrovascular disease. There were no genotype-specific correlations of environmental factors with FVII:C, but there was evidence of an acute-phase or consumptive fall in FVII:C levels at the time of stroke, whereas levels increased to those similar for healthy age-matched control subjects by 3 months, when the acute phase had presumably subsided.

Acute Disease

Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism and levels in subjects with cerebrovascular disease.

The exact role of the fibrinolytic system in the pathogenesis of stroke remains to be established. Elevated circulating levels of plasminogen activator inhibitor-1, the principle inactivator of the fibrinolytic system, have been related to the development of myocardial infarction. There is evidence that a polymorphism in the promoter region of the PAI-1 gene is associated with circulating PAI-1 levels. We studied a common single nucleotide insertion/deletion (4G/5G) polymorphism by PCR in 558 patients with stroke, the pathological type of which was established by cranial computed tomography, and in 172 controls. 4G/5G genotype and PAI-1 activity were investigated in relation to 1) stroke type and 2) mortality occurring within four weeks, three months and six months of the stroke. No difference in genotype frequency was observed when all cases of stroke were compared with controls nor between the clinically determined subtypes of cerebral infarction. PAI-1 activity was significantly higher in patients with stroke (n = 245) both at presentation (11.6 U/ml) and after three months (11.8 U/ml), in paired samples, than in control subjects (8.8 U/ml, p < 0.0001). Thirty-seven (6.2%), 86 (14.5%) and 122 (20.5%) patients had died within one, three and six months of admission, respectively. PAI-1 activity was independently associated with all-cause mortality at one and three months after stroke (p = 0.02 and p = 0.03 respectively), but not after six months. In this population the 4G/5G promoter polymorphism is not associated with an increased risk of stroke. PAI-1 levels were elevated at the time of acute stroke which persisted after three months. PAI-1 level but not genotype was associated with early mortality following stroke.

Aged

Use of botulinum toxin in stroke patients with severe upper limb spasticity.

OBJECTIVES: Spasticity can contribute to poor recovery of upper limb function after stroke. This is a preliminary evaluation of the impact of botulinum toxin treatment on disability caused by upper limb spasticity after stroke. METHODS: Seventeen patients with severe spasticity and a non-functioning arm were treated with intramuscular botulinum A neurotoxin (median age at treatment 54.5 years; median time between onset of stroke and treatment 1.5 years). Baseline and assessments two weeks after treatment were compared to assess efficacy. The duration of improvement in disability was documented. Outcome measures used were; passive range of movement at the shoulder, elbow, wrist, and fingers; modified Ashworth scale to assess spasticity of biceps and forearm finger flexors; an eight point scale to assess the degree of difficulty experienced by the patient or carer for each functional problem defined before treatment; the presence of upper limb pain. The biceps, forearm finger flexors, and flexor carpiulnaris were treated with intramuscular botulinum toxin. Up to a total dose of 400-1000 mouse units (MU) of Dysport (Speywood) or 100-200 MU of BOTOX (Allergan) was used in each patient. RESULTS: Functional problems reported by the patients before treatment were difficulty with cleaning the palm, cutting fingernails, putting the arm through a sleeve, standing and walking balance, putting on gloves, and rolling over in bed. Hand hygiene improved in 14 of 17 patients; difficulty with sleeves improved in four of 16; standing and walking balance improved in one of four; shoulder pain improved in six of nine; wrist pain improved in five of six. Passive range of movement at shoulder, elbow, and wrist improved after treatment. Benefit was noted within two weeks and lasted one to 11 months. No adverse effects occurred. CONCLUSION: This preliminary study suggests that intramuscular botulinum toxin is a safe and effective treatment for reducing disability in patients with severe upper limb spasticity.

Adolescent

Otoacoustic emission versus ABR screening: the effect of external and middle ear abnormalities in a group of SCBU neonates.

Twenty neonates in a special care baby unit (SCBU) were tested using automated procedures for obtaining auditory brainstem responses (ABR) and transient evoked otoacoustic emissions (TEOAE). All 40 ears passed the initial ABR screen, while the pass rate for the TEOAE screen was only 52.5%. Ears with no external or middle ear abnormalities (group A) had a significantly higher TEOAE pass rate (94.7%) than those with at least one abnormality (group B) as detected by otoscopic examination and tympanometry (14.3%). Other variables, such as age at test, gestational age at birth and birth weight, did not differ significantly between groups A and B. We conclude that external/middle ear abnormalities in this group of neonates had no effect on the ABR screening results, but had a significant effect on the TEOAE screening results.

Acoustic Impedance Tests

Real ear to coupler differences in children having otitis media with effusion.

The aim of this study was to investigate the effects of otitis media with effusion (OME) on the 'real ear to coupler difference' (RECD) in children. RECDs are important in the procedures used for selection of appropriate amplification characteristics for children with permanent (usually sensorineural) hearing impairment. Subjects were 28 children aged between 4.6 and 7.6 years, 14 of whom had OME. There was no evidence of middle ear pathology in the remaining 14 who comprised the control group. All real-ear and coupler measures showed good test-retest repeatability at 4.0 kHz and below. The mean RECDs in frequency range 0.2-3.0 kHz were found to be up to 3.5 dB greater for the children having OME than for those without OME, although when statistically analysed only the differences in RECD at 1.0 kHz and 1.5 kHz were significant. Due to low correlation between the root mean square (RMS) sound pressure level (SPL) in the ear canal and ear canal volume, and low correlation between the subject's maximum RECD and ear canal volume, neither of these other variables could be used to predict an individual's RECD in this study. Large inter-subject variability was found, with a maximum standard deviation of 5.6 dB at 0.2 kHz, so this study greatly supports the need for individual RECD measurements to be made whenever possible, rather than using averaged transformation figures, particularly if the individual has OME.

Child

Probe-tube microphone measures with very young infants: real ear to coupler differences and longitudinal changes in real ear unaided response.

OBJECTIVE: The feasibility and practicalities of performing probe-tube microphone measures with infants is addressed, as well as two aspects of acoustic functioning of infant ears: the real ear unaided response (REUR) and the real ear to coupler difference (RECD). DESIGN: Part 1 is a longitudinal study involving 12 infants. Serial measures of REUR were obtained over an 18-mo period. Infants were < or = 3 mo for the first test and < or = 21 mo at the last test visit. Practicalities of probe-tube microphone testing of unsedated infants and changes in the position (i.e., frequency) of the primary REUR peak were addressed. For part 2 of the project, 33 infants under 12 mo of age took part. A comparison of real ear hearing aid gain versus coupler gain was made. Test-retest differences for real ear aided response were estimated. RESULTS: Part 1 results indicate that probe-tube microphone measures in unsedated infants are feasible and show good within-subject repeatability. REUR measures for the more alert and mobile older subjects, as for the younger infants, showed an acceptably small degree of intersubject variability. The frequency of the primary REUR peak decreased during the first year of life, with a group mean of 2932 Hz reached at the end of the first year. However, thereafter, instead of stabilizing at around this value there was considerable fluctuation in the frequency of REUR peak. For Part 2, results a) confirmed the large RECD value for infants in the first year of life and b) showed a high degree of intersubject variability. Test retest measures of real ear aided response (REAR) gave values small enough to indicate the clear potential of probe-microphone use with infants during the hearing aid selection and fitting process. CONCLUSION: These findings should encourage attempts to carry out individual probe-tube microphone measurements with very young infants. They point to the need for infant hearing aid fitting procedures which involve such measurements to secure appropriate amplification.

Amplifiers, Electronic

Selecting the gain for radio microphone (FM) systems: theoretical considerations and practical limitations.

This paper provides theoretical estimates of the signal-to-noise (S/N) ratio advantage that can be gained from a radio microphone (FM) system used with an environmental (EV) microphone, compared with the S/N ratio delivered by a conventional hearing aid alone. These estimates show that the S/N advantage gained is a function of the speaker/listener distance and the FM/EV gain difference, the greater the distance and the closer the FM gain is to the EV gain, the greater the S/N advantage. The implications for choice of FM and EV gain when fitting FM systems are discussed. The two goals of equating the FM and EV outputs and maximizing the S/N ratio are mutually incompatible. It is concluded that the FM gain should be set to be 10dB less than the EV gain unless the situation can be closely monitored, in which case the FM gain should be set as high as possible consistent with loudness tolerance and acceptable levels of distortion.

Acoustics

Long-term survival after first-ever stroke: the Oxfordshire Community Stroke Project.

BACKGROUND AND PURPOSE: There have been relatively few community-based studies of long-term prognosis after acute stroke. This study aimed to provide precise estimates of the absolute and relative risks of dying in an unselected cohort of patients with a first-ever stroke. METHODS: Six hundred seventy-five patients were registered by a community-based stroke register (the Oxfordshire Community Stroke Project) and prospectively followed up for up to 6.5 years. Their relative risk of death was calculated using age- and sex-specific mortality rates for Oxfordshire. RESULTS: During the first 30 days, 129 (19%) patients died. Patients who survived at least 30 days after a first-ever stroke thereafter had an average annual risk of death of 9.1%, 2.3-fold the risk in people from the general population. Although the absolute (about 15%) and relative (about threefold) risks of death were highest in these 30-day survivors over the first year after the stroke, they were at increased risk of dying over the next few years (range of relative risk for individual years, 1.1-2.9). Predictably, older patients had a worse absolute survival but, relative to the general population, stroke also increased the relative risk of dying in younger patients. During the first 30 days stroke accounts for most deaths; after this time nonstroke cardiovascular disease becomes increasingly important and is the most common cause of death after the first year. CONCLUSIONS: These data highlight the importance of long-term secondary prevention of vascular events in stroke patients, targeted as much at the cardiovascular as at the cerebrovascular circulation.

Age Factors

Probe-tube microphone measurements with very young infants.

The practicalities of performing probe-tube microphone measurements in a clinical environment with unsedated infants were examined. External ear resonance curves (unaided response) were obtained for both ears of a group of infants aged 0-6 months and an adult comparison group. A repeat measure (with probe-tube repositioning) was made to estimate the test-retest reliability of these measures. Results showed that the mean infant resonance frequency (4200 Hz) occurred at a significantly (P less than 0.005) higher frequency than the mean adult resonance frequency (2950 Hz). Infants test-retest differences for resonance frequency (mean = 286 Hz, s.d. = 404 Hz) and size of peak (mean = 2.2 dB, s.d. = 2.6 dB) showed acceptable stability for the measurements. Size of resonance peak was found to vary positively with ear canal volume; however, estimation of ear canal volume from tympanometry did not provide a useful indicator of the size of the peak. The probe-microphone measurements were found to be feasible, repeatable and practical with these infants.

Acoustic Impedance Tests