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Biomedical subjects

S W Turner

Publications and source records attributed to S W Turner.

At least 19 recordsLinked to original sources
PubMed2006

Is the "instant flow" option on the NIOX analyser needed?

Asthmatics have increased gaseous nitric oxide in their exhaled breath. Measurements of the fraction of nitric oxide in exhaled breath (FE(NO)) are used for the diagnosis and management of asthma. One analyser (the NIOX chemiluminescence analyser) has a feature (restriction of instant flow, IF) which we suspected was responsible for reducing the success rate for obtaining FE(NO) measurements whilst not affecting the measurement itself. In a study involving 38 children, median age 10 years, we observed that FE(NO) values taken in the same individual with and without IF restriction did not differ. We also observed that the success in obtaining a FE(NO) measurement was higher (57%) when IF was not restricted and was lower (41%) when IF was restricted, p=0.002. Our findings do not support the use of restriction of IF on the NIOX analyser.

Adolescent↗
PubMed2005

The effect of age on the relationship between birth order and immunoglobulin E sensitization.

BACKGROUND: An association between birth order and IgE sensitization or allergic diseases has been reported in many studies. OBJECTIVE: To assess the effect of age on the relationship between reduced IgE sensitization and increased birth order and to test the hypothesis that this would decline with increasing age. METHODS: As part of a birth cohort study, IgE sensitization to common allergens was determined by skin prick testing at ages 6 and 12 months, 6 and 11 years. RESULTS: The original cohort numbered 253 individuals of whom 96 (38%) were first born. Compared with individuals with older siblings, first-born individuals had increased IgE sensitization at 6 (odds ratio (OR) 2.4 [95% confidence interval (CI) 1.0, 6.3], P=0.05, n=197) and 12 months of age (OR 6.7 [1.7, 25.0] P=0.002, n=172) and at 6 years of age (OR 2.3 [1.0, 5.6] P=0.05, n=113) but not at 11 years of age (OR 1.2, P>0.4, n=182). When age at onset of IgE sensitization was considered (n=61), 16 had infant onset IgE sensitization (nine were first born), 24 had early childhood onset IgE sensitization (nine first born) and 21 had late childhood onset IgE sensitization (two first born), P=0.0016. Further analysis revealed a similar pattern for children with older brothers (P=0.0097) but not older sisters (P=0.5). CONCLUSIONS: These findings indicated that having an older brother delays the onset of IgE sensitization but may not prevent IgE sensitization per se. The apparent protective effect of older siblings on allergic diseases reported elsewhere might involve delaying the onset of IgE sensitization.

Age of Onset↗
PubMed2005

Determinants of airway responsiveness to histamine in children.

Increased airway responsiveness (AR) is associated with asthma, but not all individuals with increased AR have asthma. The aim of this study was to identify factors, other than physician-diagnosed asthma (PDA), which are associated with increased AR. In a longitudinal study, data were collected on atopy and lower respiratory tract illness (LRTI) in infancy, and AR (expressed as dose-response slope (DRS)), atopy, tobacco-smoke exposure and PDA in childhood. At age 6 yrs, DRS was assessed in 102 children, of whom 22 (22%) had PDA; the corresponding figures at 11 yrs of age were 176 and 29 (15%). At age 6 yrs, DRS was significantly associated with PDA, current atopy and parental smoking (n = 83). At age 11 yrs, DRS was significantly associated with PDA, current atopy and LRTI in the first six months (n = 75). There was a significant positive interaction between atopy at age 12 months and PDA age 11 yrs. In conclusion, these data suggest that factors other than asthma or atopy may determine the level of airway responsiveness in children. In children with asthma, airway responsiveness may be influenced by the early onset of atopy. The current findings may explain the inconsistent relationship between airway responsiveness and asthma.

Age Distribution↗
PubMed2004

beta2 adrenoceptor Arg16Gly polymorphism, airway responsiveness, lung function and asthma in infants and children.

BACKGROUND: We have previously reported a relationship between increased airway responsiveness (AR) in infancy and reduced childhood lung function. OBJECTIVE: The current study aimed to determine whether the Arg16Gly polymorphism of the beta2 adrenoceptor (beta2AR) gene was important to this relationship. METHODS: A cohort that initially numbered 253 individuals underwent assessments of AR and lung function aged 1 month, 6 and 11 years; genotyping for polymorphisms of the beta(2)AR was performed. RESULTS: At 1 month of age, the genotype homozygous Arg16 (n=24) was associated with a mean increase in log dose-response slope (AR) of 0.27 [95% confidence interval (CI) 0.07, 0.49] compared with the genotype homozygous Gly16 (n=58), P=0.01. At 11 years of age, the genotype homozygous Arg16 (n=35) was associated with a mean reduction in the percentage of forced expiratory volume in 1 s of 5.3% [95% CI 0.3, 10.2] compared with the genotype homozygous Gly16 (n=65), P=0.03. There was no association between the Arg16Gly polymorphism and atopy or diagnosed asthma. However, nine of 69 individuals with the genotype homozygous Gly16 were admitted to hospital with asthma compared with five out of 111 individuals with the remaining genotypes (P<0.05). CONCLUSION: The Arg16Gly polymorphism may be important to the association between increased AR in infancy and reduced lung function in childhood and may also be a determinant of asthma severity in children but not asthma per se.

Asthma↗
PubMed2004

Comparison of single-breath and tidal breathing exhaled nitric oxide levels in infants.

The aim of this study was to compare two different methods, tidal breathing (TB) and single-breath (SB), for measuring fractional exhaled nitric oxide (FENO) in infants. FENO was measured in 71 infants with either recurrent wheeze (n=32), recurrent cough (n=16) or no symptoms (healthy, n=23) using both methods. For TB measurements five breaths were collected into a gas sampling bag (off-line reservoir sampling). The SB method was modified from the raised volume rapid thoraco-abdominal technique. Agreement between the two methods was investigated and both methods were used to compare FENO in infants with and without symptoms. Flow dependence of SB FENO was demonstrated using two expiratory flows (11 and 40 mL x s(-1)). There was a moderate correlation (r=0.60) but poor agreement between levels using the TB and SB methods. A significant difference in FENO between healthy children and children with wheeze was found using the SB but not the TB method. Due to lower expiratory flow and reduced nasal nitric oxide contamination the single-breath technique may be more sensitive than the tidal breathing method for detecting differences in exhaled nitric oxide between infants with and without respiratory symptoms.

Breath Tests↗
PubMed2003

Zero-mode waveguides for single-molecule analysis at high concentrations.

Optical approaches for observing the dynamics of single molecules have required pico- to nanomolar concentrations of fluorophore in order to isolate individual molecules. However, many biologically relevant processes occur at micromolar ligand concentrations, necessitating a reduction in the conventional observation volume by three orders of magnitude. We show that arrays of zero-mode waveguides consisting of subwavelength holes in a metal film provide a simple and highly parallel means for studying single-molecule dynamics at micromolar concentrations with microsecond temporal resolution. We present observations of DNA polymerase activity as an example of the effectiveness of zero-mode waveguides for performing single-molecule experiments at high concentrations.

Biochemistry↗
PubMed2003

Exhaled nitric oxide and asthma: complex interactions between atopy, airway responsiveness, and symptoms in a community population of children.

BACKGROUND: Exhaled nitric oxide (FE(NO)) is raised in asthmatic children, but there are inconsistencies in the relationship between FE(NO) and characteristics of asthma, including atopy, increased airway responsiveness (AR), and airway inflammation. The aim of this study was to investigate the relationship between FE(NO) and asthma, atopy, and increased AR in children. METHODS: One hundred and fifty five children (79 boys) of mean age 11.5 years underwent an assessment that included FE(NO) measurements, spirometric tests, inhaled histamine challenge, and a skin prick test. Blood was collected for eosinophil count. Current and past asthma like symptoms were determined by questionnaire. RESULTS: In multiple linear regression analyses FE(NO) was associated with atopy (p<0.001), level of AR (p = 0.005), blood eosinophil count (p = 0.007), and height (p = 0.002) but not with physician diagnosed asthma (p = 0.1) or reported wheeze in the last 12 months (p = 0.5). Separate regression models were conducted for atopic and non-atopic children and associations between FE(NO) and AR, blood eosinophils and height were only evident in atopic children. Exhaled NO was raised in children with a combination of atopy and increased AR independent of symptoms. CONCLUSION: Raised FE(NO) seems to be associated with an underlying mechanism linking atopy and AR but not necessarily respiratory symptoms.

Adolescent↗
PubMed2002

Reduced lung function both before bronchiolitis and at 11 years.

BACKGROUND AND AIMS: We have previously shown an association between reduced premorbid lung function (V'maxFRC) and bronchiolitis. We hypothesised that individuals with bronchiolitis will go on to have reduced lung function and increased respiratory symptoms in childhood. METHODS: V'maxFRC was measured at 1 month of age; individuals with bronchiolitis were prospectively identified. Annual symptom questionnaires were completed from 3 to 6 years. At 11 years of age, children underwent an assessment including questionnaire, lung function, airway response to histamine (AR), and skin prick testing. RESULTS: Eighteen individuals with bronchiolitis were ascertained from 253 cohort members. Children with bronchiolitis had increased viral induced wheeze at 3 (OR 5.8, 95% CI 1.4 to 25.2; n = 103) and 5 years (OR 5.3, 95% CI 1.1 to 25.5; n = 101). At 11 years of age, 194 children were assessed including 16 with past bronchiolitis. These 16 individuals had reduced mean z scores for % V'maxFRC compared with other children (-0.56 and 0.06 respectively) and mean z scores for % FEF(25-75) at 11 years (-0.53 and 0.06 respectively). At 11 years, FEV(1), FVC PEF, AR, atopy, wheeze, and diagnosed asthma were not different between groups. CONCLUSIONS: Reduced lung function is present before and after bronchiolitis; the level of reduction is comparable. The mechanism for wheeze and reduced lung function after bronchiolitis appears to be related to premorbid lung function and not bronchiolitis per se.

Bronchiolitis↗
PubMed2001

Comparison of telemetric and tail-cuff blood pressure monitoring in adrenocorticotrophic hormone-treated rats.

1. The aim of the present study was to validate a telemetric blood pressure (BP) monitoring system against tail-cuff blood pressure in both adrenocorticotrophic hormone (ACTH)- and sham-treated rats. In the statistical analyses, we first tested whether there was a detectable effect on systolic blood pressure (SBP) of 10 days treatment with ACTH compared with saline. Second, we compared results of telemetered and tail-cuff measurements and, third, we developed a novel method for estimating the relative power of the two techniques. 2. Twenty-three male Sprague-Dawley rats were randomly divided into two groups: (i) ACTH (100 microg/kg per day, s.c; n = 12) treated; or (ii) sham treated (0.9% saline, s.c; n = 11). Systolic BP was measured by the telemetric system (sampled for 10 s every 2 min) continuously for 4 h (n = 16) or for 30 min (n = 23) and also by the indirect tail-cuff method daily (n = 23). Data were compared within and between groups; ordinary least products (OLP) regression analysis was then performed to test for bias between the two methods. Sample size/power estimations were also performed. 3. Adrenocorticotrophic hormone treatment raised telemetered SBP by 11 mmHg (P < 0.001) compared with 14 mmHg (P < 0.001) using the tail-cuff method. There was no fixed or proportional bias between the two methods of measurement, as shown by regression analysis. Power calculations indicate that a minimum sample size of six gives a power of telemetered to tail-cuff of 0.84/0.86 = 0.98. The power of 4 h versus 30 min BP measurements was 0.99/0.82 = 1.2. 4. Telemetry gave very similar results to the tail-cuff method. Telemetry allows for a longer period of measurement, giving greater power to the study so that fewer animals are needed.

Adrenocorticotropic Hormone↗
PubMed2001

Nitric oxide synthase activity in adrenocorticotrophin-induced hypertension in the rat.

1. The nitric oxide (NO) system has been implicated in the pathogenesis of various forms of experimental hypertension. We studied nitric oxide synthase (NOS) activity as a possible indicator of NO production in adrenocorticotrophin (ACTH)-induced hypertension in the rat. 2. Haemodynamic, metabolic and biochemical parameters were examined in sham (saline)- and ACTH (100 microg/kg per day)-treated male Sprague-Dawley rats (n = 20). 3. Adrenocorticotrophin treatment increased systolic blood pressure, serum corticosterone, adrenal NOS activity and adrenal nitrate and nitrite concentrations and decreased bodyweight and plasma nitrate/nitrite. 4. Previous observations of diminished NO production in ACTH- and corticosterone-induced hypertension in the rat were confirmed, but could not be explained by reduced NOS activity in the present study.

Adrenocorticotropic Hormone↗
PubMed2001

Circadian blood pressure variability in adrenocorticotrophin-induced hypertension in the rat.

OBJECTIVES: Secondary hypertension is often characterized by loss of diurnal blood pressure variability. This study examined circadian (24 h) blood pressure variability in adrenocorticotrophin (ACTH)-induced hypertension in the Sprague-Dawley rat. METHODS: Male Sprague-Dawley rats were randomly allocated to sham (0.9% saline, s.c.), n = (9), ACTH (0.5 microg/kg per day, s.c., n = 8) or ACTH (100 microg/kg per day, s.c., n = 7) in a room with a 12 h light/dark cycle (0600 h to 1800 h). A radio telemetry transducer was used to measure blood pressure in unrestrained animals over 3 control days (C1-C3) and 10 treatment days (T1-T10). Heart rate, systolic (SBP), mean arterial (MAP) and diastolic (DBP) blood pressure were continuously recorded. Body weight was measured daily and serum corticosterone concentration ([B]) prior to death. RESULTS: Sham treatment had no effect on any parameters. ACTH 100 microg/kg per day increased SBP from 124+/-2 pooled control (PC) to 134+/-2 mmHg (T10), MAP from 105+/-2 to 115+/-2 mmHg and DBP from 87+/-1 to 99+/-2 mmHg and decreased heart rate from 305+/-6 to 249+/-5 beats/min and body weight from 299+/-6 (C3) to 280+/-8 g (T10) (all P' < 0.0036). Serum [B] was higher in ACTH- (881+/-44 ng/ml) than sham-treated rats (384+/-17 ng/ml, P < 0.001). There were no differences between sham treatment and ACTH 0.5 microg/kg per day. SBP, MAP, DBP and heart rate were consistently higher for ACTH 100 microg/kg per day and sham-treated animals during the dark cycle (1800 h to 0600 h) than the light cycle (0600 h to 1800 h). CONCLUSIONS: ACTH 100 microg/kg per day raises blood pressure in conscious unrestrained Sprague-Dawley rats without any change in normal diurnal rhythm.

Adrenocorticotropic Hormone↗
PubMed2000

Attachment of astroglial cells to microfabricated pillar arrays of different geometries.

We studied the attachment of astroglial cells on smooth silicon and arrays of silicon pillars and wells with various widths and separations. Standard semiconductor industry photolithographic techniques were used to fabricate pillar arrays and wells in single-crystal silicon. The resulting pillars varied in width from 0. 5 to 2.0 micrometer, had interpillar gaps of 1.0-5.0 micrometer, and were 1.0 micrometer in height. Arrays also contained 1.0-micromter-deep wells that were 0.5 micrometer in diameter and separated by 0.5-2.0 micrometer. Fluorescence, reflectance, and confocal light microscopies as well as scanning electron microscopy were used to quantify cell attachment, describe cell morphologies, and study the distribution of cytoskeletal proteins actin and vinculin on surfaces with pillars, wells, and smooth silicon. Seventy percent of LRM55 astroglial cells displayed a preference for pillars over smooth silicon, whereas only 40% preferred the wells to the smooth surfaces. Analysis of variance statistics performed on the data sets yielded values of p > approximately.5 for the comparison between pillar data sets and < approximately.0003 in the comparison between pillar and well data sets. Actin and vinculin distributions were highly polarized in cells found on pillar arrays. Scanning electron microscopy clearly demonstrated that cells made contact with the tops of the pillars and did not reach down into the spaces between pillars even when the interpillar gap was 5.0 microm. These experiments support the use of surface topography to direct the attachment, growth, and morphology of cells. These surfaces can be used to study fundamental cell properties such as cell attachment, proliferation, and gene expression. Such topography might also be used to modify implantable medical devices such as neural implants and lead to future developments in tissue engineering.

Actins↗
PubMed2000

Vasopressin V1a receptor antagonism does not reverse adrenocorticotrophin-induced hypertension in the rat.

1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrophin (ACTH)-induced hypertension in Sprague-Dawley rats using the non-peptide AVP V1a receptor antagonist OPC 21268. 2. In an acute study, six rats were pretreated with ACTH for 11 days and direct arterial blood pressure (4 h), plasma osmolality and electrolyte concentrations were measured after OPC 21268 gavage. In a chronic study, 40 rats were randomly divided into four groups: (i) sham injection + sham gavage; (ii) ACTH + sham gavage; (iii) sham injection + OPC 21268; or (iv) ACTH + OPC-21268 for 16 days. Systolic blood pressure (SBP), water intake, urine volume (UV), urine osmolality and electrolytes, food intake, bodyweight and plasma osmolality and electrolyte concentrations were measured. 3. In the acute study, direct mean arterial blood pressure did not change with OPC 21268 (122+/-2 and 120+/-3 mmHg at 0 and 240 min, respectively). 4. In the chronic study, OPC 21268 did not affect ACTH-induced rises in blood pressure (from 125+/-2 (control) to 145+/-5 mmHg (group 4) compared with 122+/-3 (control) to 149+/-5 mmHg (group2)). Water intake and UV increased (from 29+/-2 to 83+/-6 mL/day; and from 5+/-1 to 36+/-5 mL/day, respectively) and the change in bodyweight decreased from 0+/-2 to -107+/-7 g. 5. These results suggest that AVP (at the V1a receptor) does not play a significant role in the maintenance of ACTH-induced hypertension.

Adrenocorticotropic Hormone↗
PubMed2000

L-arginine partially reverses established adrenocorticotrophin-induced hypertension and nitric oxide deficiency in the rat.

BACKGROUND: L-arginine treatment prevents adrenocorticotrophin (ACTH) induced hypertension in the rat. This study examined whether L-arginine treatment could reverse established ACTH hypertension and its effects on markers of decreased NO activity. METHODS: Sixty-four male Sprague-Dawley rats were randomly divided into 6 groups given 12 days of treatment: (1) sham (0.9% NaCl, 0.5 ml/kg, subcutaneously, sc, n = 16); (2) ACTH (0.5 mg/kg/day, sc, n = 16); (3) sham + L-arginine (0.6% in food, from treatment day 8 onwards, n = 10); (4) ACTH + L-arginine (n = 10); (5) sham + D-arginine (0.6% in food, from T 8 onwards) (n = 6); and (6) ACTH + D-arginine (n = 6). Systolic blood pressure, water intake, urine volume, and body weight were measured every second day. At the end of the experiments, plasma and urinary nitrate/nitrite (NOx), plasma amino acid concentrations (in groups 1-4), and urinary cyclic guanosine monophosphate (cGMP) concentrations were measured. RESULTS: Sham, sham + L-arginine, and sham + D-arginine treatments did not affect blood pressure. ACTH increased systolic blood pressure (from 121 +/- 1 to 147 +/- 2 mmHg, p < 0.001, pooled control vs treatment day 12, mean +/- sem), and this was partially reversed by L-arginine (group 4: from 141 +/- 2 on day 8 to 133 +/- 1 mmHg on day 12, n = 10, p < 0.001). In contrast, D-arginine did not affect blood pressure in ACTH-treated rats (group 6). ACTH increased water intake and urine volume and decreased body weight, and L-arginine administration did not alter these parameters. ACTH decreased plasma citrulline (group 1 vs 2: 115 +/- 7 vs 67 +/- 6 micro M/L, n = 16, p < 0.001) and NOx concentrations (group 1 vs 2: 8.3 +/- 0.8 vs 4.5 +/- 0.6 microM/L, n= 10, p < 0.001) and these decreases were reversed by L-arginine treatment (group 4: citrulline 98 +/- 9 micro M/L, NOx 9.1 +/- 1.6 micro M/L, group 2 vs 4, both p < 0.05). ACTH produced marked increases in urinary cGMP excretion (group 1 vs 2: 0.5 +/- 0.1 vs 1.9 +/- 0.4 nmol/24 h, p < 0.01). CONCLUSION: Supplementation with L-arginine partly reversed established ACTH-induced hypertension and restored plasma NOx and citrulline concentrations to levels seen in sham-treated rats. These data are consistent with previous studies suggesting that functional NO deficiency has a role in ACTH-induced hypertension in rats.

Adrenocorticotropic Hormone↗
PubMed2000

The role of corticosterone in corticotrophin (ACTH)-induced hypertension in the rat.

OBJECTIVE: Corticotrophin (ACTH)-induced hypertension in the rat is prevented by L- but not D-arginine. We examined the effects of exogenous corticosterone in the male Sprague Dawley (SD) rat to determine whether ACTH-induced hypertension is mediated by corticosterone. METHODS: Exogenous corticosterone (10, 20 or 40 mg/kg per day) or sham (polyethylene glycol (PEG) 1 ml/kg per day) was injected subcutaneously in divided doses (s/c b.d.) over 15 treatment days to 40 SD rats (n = 10 each group). Subsequently, the effects of L-arginine, D-arginine or L-arginine + N-nitro-L-arginine (NOLA) on corticosterone-induced hypertension (corticosterone 20 mg/kg per day) were examined. Systolic blood pressure (SBP) and metabolic parameters were measured every two days. RESULTS: Twenty and 40 mg/kg per day of corticosterone increased SBP compared with sham (P< 0.01, P< 0.05 respectively, sham versus respective group). Forty mg/kg per day of corticosterone raised serum corticosterone concentration compared with sham (502 +/- 20 versus 364 +/- 25 ng/ml, P < 0.001). L-arginine prevented the rise in SBP produced by corticosterone (131 +/- 3 to 131 +/- 2 mmHg, control versus day 10) but D-arginine did not (129 +/- 3 to 142 +/- 4 mmHg on day 8, P < 0.01). NOLA blocked the effect of L-arginine and amplified the rise in blood pressure produced by corticosterone (130 +/- 3 to 171 +/- 6 mmHg on day 10, P < 0.001). CONCLUSIONS: The haemodynamic features of ACTH-induced hypertension were reproduced by corticosterone excess, at concentrations of corticosterone similar to those in studies of exogenous ACTH administration. It is likely that ACTH-stimulated adrenal production of corticosterone accounts for the features of ACTH-induced hypertension in the rat

Adrenocorticotropic Hormone↗
PubMed1999

Sorting by diffusion: an asymmetric obstacle course for continuous molecular separation.

A separation technique employing a microfabricated sieve has been demonstrated by observing the motion of DNA molecules of different size. The sieve consists of a two-dimensional lattice of obstacles whose asymmetric disposition rectifies the Brownian motion of molecules driven through the device, causing them to follow paths that depend on their diffusion coefficient. A nominal 6% resolution by length of DNA molecules in the size range 15-30 kbp may be achieved in a 4-inch (10-cm) silicon wafer. The advantage of this method is that samples can be loaded and sorted continuously, in contrast to the batch mode commonly used in gel electrophoresis.

Chemical Fractionation↗
PubMed1999

Adrenocorticotrophic hormone-induced hypertension in the rat: effects of the endothelin antagonist bosentan.

1. The effects of the endothelin antagonist bosentan on adrenocorticotrophic hormone (ACTH)-induced hypertension were examined in the conscious male Sprague-Dawley rat. 2. In order to confirm endothelin antagonism, 18 rats were randomly divided into two groups: receiving either (i) endothelin-1 (0.125, 0.25, 0.5 and 1 nmol/kg, i.v.); or (ii) endothelin-1 at these doses following bosentan (100 mg/kg gavage) and mean arterial pressure recorded (study A). Subsequently, 40 male rats (320 +/- 5 g) were randomly divided into four groups (n = 10): (i) Sham (0.9% saline, s.c.) + 5% acacia gum gavage; (ii) ACTH (500 micrograms/kg per day, s.c.) + 5% acacia gum gavage; (iii) Sham injection + bosentan (100 mg/kg per day) gavage; or (iv) ACTH + bosentan. Six control days (C1-C6) were followed by 11 treatment days (T0-T10). Systolic blood pressure, water intake, urine volume, food intake and bodyweight were measured every second day (study B). 3. Bosentan significantly attenuated the endothelin-1-induced blood pressure rise at 0.125 nmol/kg (P < 0.05), but not at higher doses. 4. Bosentan at a dose which attenuated endothelin-1-induced blood pressure increase had no effect on either blood pressure or metabolic parameters in ACTH-treated rats. 5. These results suggest that endothelin does not play a major role in ACTH-induced hypertension.

Adrenocorticotropic Hormone↗