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Biomedical subjects

H Simpson

Publications and source records attributed to H Simpson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch.

To ascertain if IGF-1 is a regulator of local muscle growth, total RNA was extracted from rabbit muscle induced to undergo rapid hypertrophy using active stretch and from control muscles. This was analysed by Northern hybridization with a 280 base pair probe containing sequences derived from exons 3 and 4 of the insulin-like growth factor 1 gene. Two types of insulin-like growth factor 1 mRNA were shown to be strong expressed in the stretched muscles. In situ hybridization using the same probe (280 base pair) showed that IGF-1 is strongly expressed in muscle that is induced to grow rapidly and is expressed in the muscle fibres themselves. Using RT-PCR a single insulin-like growth factor 1 isoform cDNA (IGF-1Ea) could be cloned from the normal resting muscles. However, an additional isoform of insulin-like growth factor 1 (insulin-like growth factor 1Eb) was found to be expressed in stretched muscle undergoing hypertrophy. The E domain sequence of the additional isoform differs from the liver insulin-like growth factor 1Ea by the presence a 52 base pair insert. This changes the reading frame of the derived carboxyl-terminal resulting in a different precursor insulin-like growth factor 1 isoform. This insulin-like growth factor 1 mRNA probably encodes the precursor insulin-like growth factor 1 isoform that is responsible for local muscle growth regulation in response to mechanical stimulation. To confirm that alternative splicing of the insulin-like growth factor 1 gene occurs in muscle in response to physical activity, oligonucleotide primers were made which specifically amplify the cDNAs of two isoforms (insulin-like growth factors 1Ea and Eb) in the human as well as the rabbit. Following altered physical activity for 2 h to 6 days, appreciable levels of insulin-like growth factor 1Eb (in human the Ec) isoform were detected in skeletal muscle by using RT-PCR. In contrast very little if any of this splice variant could be detected in control muscle not subjected to stretch or extra physical activity.

Animals↗
PubMed1996

Evaluation of Roche Amplicor PCR assay for Mycobacterium tuberculosis.

The Roche Amplicor Mycobacterium tuberculosis PCR test (RMtb-PCR) was compared with mycobacterial culture, with the BACTEC 460 system and inoculation on Lowenstein-Jensen media. Results were interpreted with an adjusted "gold standard" incorporating clinical diagnosis. A total of 1,480 clinical specimens from 1,155 patients, including tissues and fluids, as well as 141 specimens which demonstrated a positive growth index on the BACTEC 460 system were assessed. The sensitivity, specificity, and positive and negative predictive values of RMtb-PCR compared with the adjusted gold standard for clinical specimens were 79, 99, 93, and 98%, respectively. In smear-positive specimens, the sensitivity of RMtb-PCR was 98% versus 53% for smear-negative specimens. When RMtb-PCR was performed two times per week, PCR results were available an average of 21 days before the culture results. For specimens demonstrating a positive growth index on the BACTEC 460 system, RMtb-PCR had a sensitivity and specificity of 98 and 100%, respectively. This study demonstrates the value of a commercial nucleic acid amplification kit for rapid diagnosis of M. tuberculosis, particularly in smear-positive specimens or BACTEC culture-positive specimens.

Bacteriological Techniques↗
PubMed1996

Night cough in a population-based sample of children: characteristics, relation to symptoms and associations with measures of asthma severity.

Nocturnal cough in asthma is a common but poorly understood phenomenon. The aims of this study were to determine the relationship between recorded night cough, reported night cough and current wheeze in a population-based sample of children previously identified as wheezy, and to examine the relationship of nocturnal cough to current symptoms, markers of asthma severity and environmental exposure. Children were reassessed in the early school years by measuring current symptoms, ventilatory function, bronchial reactivity, peak flow variability, respiratory symptom diaries and home monitoring of overnight cough, transcutaneous arterial oxygen saturation, room temperature and humidity. Night studies were performed on 59 asymptomatic children and 41 children with current wheeze. Cough occurred more frequently in current wheezers compared to asymptomatic children (16 out of 41 (39%) vs 11 out of 59 (19%)), and more cough episodes were recorded (median 3.5 vs 2.0). Night cough was not associated with bronchial reactivity, peak flow variability, degree of morning dip, mean overnight arterial oxygen saturation, ventilatory function, maternal smoking or treatment of asthma. However, it was associated with lower overnight air temperature. Although night cough is more common in current wheezers, there is poor agreement between recorded and reported night cough. Objective tests of asthma severity are of little use in predicting its presence in this age group. The sleeping environment deserves further study.

Asthma↗
PubMed1996

The effect of sleep deprivation on sleep states, breathing events, peripheral chemoresponsiveness and arousal propensity in healthy 3 month old infants.

We wished to investigate the effects of sleep deprivation on sleep, arousal propensity, respiratory events and peripheral chemoresponses in healthy infants, since these effects might be relevant to mechanisms concerned with some cases of sudden infant death syndrome. Paired observations were made overnight during natural sleep and following sleep deprivation, in a randomized fashion, in 15 healthy infants aged 78 (7) days (mean (SD)). Polysomnograms were recorded and sleep was scored using Anders' criteria. Respiratory events were categorized into central, mixed and obstructive apnoeas. Peripheral chemoresponses were measured during quiet sleep from the respiratory response to two-breath alternations in fractional inspiratory oxygen (F1, O2) (0.42 and 0.00). Arousal propensity was determined from awakening and arousal thresholds to graded photic and auditory stimuli during quiet sleep, and from spontaneous awakenings and limb movements. Compared with natural sleep, following sleep deprivation infants maintained a greater proportion of quiet sleep (39 vs 44%). There was no measurable change in arousal propensity. During quiet sleep, obstructed breathing events tended to be more common after sleep deprivation (0.1 vs 0 events.h-1) and the expiratory time during baseline breathing increased significantly (1.27 vs 1.58 s) although the decrease in respiratory rate was not significant (32 vs 30 breaths.min-1). Peripheral chemoresponses altered significantly, alternations in tidal volume/inspiratory time (VT/tI) as a measure of inspiratory drive increased after sleep deprivation (9 vs 21%). In conclusion, following short-term sleep deprivation in infancy, respiratory control alters, peripheral chemoresponsiveness increases in magnitude and the timing of baseline breathing alters, without any detectable alteration in arousal propensity. This state may be associated with an increased vulnerability to obstructive respiratory events.

Arousal↗
PubMed1996

Peripheral chemoresponses of infants measured by a minimally invasive method utilizing two-breath alternations in Fl,02.

The aim of this study was to develop a minimally invasive and reliable method for measuring peripheral chemoresponsiveness to oxygen in infants, and to establish baseline data from normal infants at 12 weeks of age. Two-breath alternations in fractional inspired oxygen (FI,O2), switching between 0.42 to 0.00 were given for 2 min periods via a face mask (held close to the face but without contact) to 18 healthy infants during quiet sleep. End-tidal oxygen concentrations alternated between 21 and 11%. Instantaneous minute ventilation (V'E) and its components tidal volume (VT), respiratory frequency (fR) inspiratory and expiratory times (tI and tE), inspiratory flow (VT/tT), and inspiratory duty cycle (tI/ttot) were measured by respiratory inductance plethysmography. Two-breath alternations in each of the ventilatory components were matched with the corresponding alternating end-tidal oxygen record and compared with contiguous pre- and post-test data obtained in control periods of air breathing. Alternations in all ventilatory components except fR changed significantly during FI,O2 alternations; VT 26%, tE-8%, VT/tI 18%, tI/ttot 11% and V'E 28% of baseline values. Within and between infant variances are reported for the individual components of ventilation. Differences among infants were best detected by alternations in V'E; within infant variance 76, between infant variance 171. We conclude that the test described is a safe, reliable and relatively easily applied method of measuring peripheral chemoresponsiveness, which is suitable for clinical application in infancy.

Analysis of Variance↗
PubMed1995

Chronic night cough and asthma severity in children with stable asthma.

The relationship between night cough and other indices of asthma severity was studied in 21 children with clinically stable asthma and persistent night cough. Overnight cough was quantified and related to symptom scores, oxygen saturation (SaO2) during sleep, evening and morning peak flow recordings and daytime tests of lung function. In the index group the median number of coughing episodes was 23 (range 1-158). Only 4 children had counts of < 10 overnight, similar to the comparison group of 12 children all of whom had counts of < 10. There was a trend towards the association of overnight cough with reduced evening peak flow (r = -0.407, P = 0.07) and reduced SaO2 (r = -0.36, P = 0.10). Abnormalities in daytime tests of lung function were observed in 13 children. There was no relationship between night cough and daytime indices of lung function abnormality although children with more severe daytime abnormalities also had significant night cough. Conversely, five children with chronic night cough had normal daytime function. Conclusion. Night-time cough in children with asthma is not simply a reflection of daytime lung function status, whereas, overnight SaO2 correlates well. Other factors need to be explored to explain the variability of night-time cough in these children.

Adolescent↗
PubMed1995

The natural history of respiratory symptoms in preschool children.

We studied the natural history of preschool respiratory symptoms in a population-based sample of children followed during the early school years. Current symptoms, ventilatory function, bronchial responsiveness to methacholine (BR), atopic status, and peak expiratory flow variability (PEFV) were assessed. Among those initially asymptomatic (210 subjects), 83.3% remained symptom-free, 6.7% started to wheeze, and 10% developed recurrent cough. Nearly half (46.9%) of the initial wheezing group (145 subjects) became symptom-free, 37.9% continued to wheeze, and 15.2% reported recurrent cough. Over half (56.0%) of the cough group (127 subjects) became symptom-free, 7.2% developed wheeze, and 36.8% reported continuing cough. Preschool wheezers showed the greatest BR (geometric mean 1.91 mg/ml) and the highest atopic prevalence (AP) (43.6%) when compared with the preschool asymptomatic group (BR: 3.39 mg/ml; AP: 23.8%) and the cough group (BR: 2.62 mg/ml; AP: 26.7%) (p = 0.0001 and p = 0.006 respectively). Children whose wheeze had persisted from the preschool period exhibited the poorest ventilatory function, the highest BR, a high AP, and high PEFV. The study shows that fewer than half of preschool wheezy children continued to wheeze in the early school years but those with persistent wheeze display many of the clinical characteristics consistent with a diagnosis of asthma.

Age Factors↗
PubMed1995

Wheeze in preschool children: who is followed-up, who is treated and who is hospitalized?

This study determined the proportions of children < or = 5 yrs of age with reported wheeze who were undergoing medical follow-up, receiving anti-asthma medication, or admitted to hospital; and investigated factors important in determining which children would receive these treatments. The symptomatic children represented a wheeze prevalence of 16% of the study sample of 1,422 children. The cumulative incidence of treatment and hospitalization and point prevalence of current medical follow-up were determined using a parent-answered postal questionnaire study of a population-based random sample of 222 children. Odds ratios (OR) were calculated for wheeze severity, environmental, social, familial and demographic factors found to affect the likelihood of these treatment end-points. Among 222 children with wheeze, 99 (35%) were under current medical review, 165 (75%) had received medication, and 48 (22%) reported being hospitalized. Current follow-up was more likely in girls (OR 2.22; 95% confidence interval (95% CI) 1.12-4.38), with more than three attacks of wheeze in the last year (OR 17.44; 95% CI 5.22-58.3), or with a household pet (cat or dog) where inhalants were wheeze precipitants (OR 13.65; 95% CI 3.16-58.94). Treatment became more likely in older children (OR 3.91; 95% CI 1.10-12.71), with inhalants as wheeze precipitants (OR 4.66; 95% CI 1.08-20.14) or with a household pet (OR 2.28; 95% CI 1.04-5.03). Hospitalization was less likely with frequent wheeze (OR 0.30; 95% CI 0.12-0.77), but more likely if shortness of breath occurred with wheeze. Medical follow-up and treatment are related to wheeze severity and exposure to inhaled precipitants, whereas hospital admission occurred in children with attacks causing shortness of breath, and with decreasing frequency of attacks per year.

Analysis of Variance↗
PubMed1994

Evaluation of nested polymerase chain methods for the detection of human coronaviruses 229E and OC43.

Currently, the diagnosis of human respiratory coronavirus infection is either slow or insensitive. This paper describes nested polymerase chain reaction assays for the detection of human coronaviruses OC43 and 229E. The specificity and sensitivity of the assays have been determined and they have been applied to the detection of the viruses in nasal aspirates. These assays are more rapid and sensitive than cell culture and may replace the latter as the diagnostic method of choice.

Animals↗
PubMed1994

Relationship between respiratory symptoms and cough receptor sensitivity.

The relationship was studied between preschool and current respiratory symptoms and cough receptor sensitivity in children. Forty six white children aged 7 years were investigated. They were divided into three groups: (i) healthy children; (ii) children with a history of idiopathic cough; and (iii) children with a history of wheezing. Cough receptor sensitivity was assessed by the inhalation of serially increasing concentrations of nebulised citric acid. The concentration which first induced a cough was the cough threshold and was taken as a measure of cough receptor sensitivity. The cough threshold was unrelated to respiratory symptoms, bronchial responsiveness, parental smoking, and atopic status. A wide variation in cough threshold was seen. Although these results suggest that idiopathic cough is unrelated to cough receptor sensitivity as assessed by the citric acid cough threshold, it is unclear whether threshold measurements are an accurate reflection of receptor sensitivity.

Bronchi↗
PubMed1994

Wheeze in preschool children and its relation with doctor diagnosed asthma.

OBJECTIVE: To describe the characteristics of wheeze and its relation with doctor diagnosed asthma in children aged 5 years and under. DESIGN: Questionnaire survey of population based random sample of children registered on Leicestershire Health Authority's child health index for immunisation; questionnaire completed by parents. SUBJECTS: 1650 white children born in 1985 to 1989 who were surveyed in 1990. MAIN OUTCOME MEASURES: Age distribution, severity, precipitants, seasonal characteristics, and diurnal variation of wheeze, family history of asthma/atopy, and their association(s) with doctor diagnosed asthma. RESULTS: There were 1422 replies (86.2%). Two hundred and twenty two (15.6%) were reported to have wheezed and of these 121 (8.6%) had formally been diagnosed as having asthma. More than 80% of the former had recurrences of wheeze and 40% (72) had three or more episodes in the preceding 12 months. Age, number of episodes per year, the severity of shortness of breath with attacks, and precipitants other than colds were the major factors determining the probability that a wheezy child will be diagnosed as having asthma. The data also suggest that despite the strong association of symptom based criteria with the label asthma, asthma was not diagnosed by these same severity criteria in one quarter of cases. CONCLUSIONS: Clinical and physiological follow up studies of children identified as asthmatic by the above criteria during the preschool years should validate or refute the predictive value of these measures of wheeze severity.

Age Distribution↗
PubMed1994

Pulmonary function in infants with cystic fibrosis: the effect of antibiotic treatment.

Since 1982 all infants born within the East Anglian Regional Health Authority have been screened for cystic fibrosis. Between April 1985 and April 1992 infants identified in this way have been entered into a randomised prospective controlled trial of antibiotic prophylaxis. Approximately half the infants received continuous oral flucloxacillin and the remainder received antibiotics when clinically indicated. Infants underwent tests of respiratory function at 3-4 months and at 1 year of age. Measurements of thoracic gas volume and airway conductance were made with an infant whole body plethysmograph, and maximum expiratory flow by the 'squeeze' technique. A total of 73 tests was performed of 42 infants. To facilitate comparisons, measurements were expressed as scores. The mean values of the scores for the two groups of infants fell within normal limits. There was no difference between the treatment groups at either age. A reduction in airways conductance was observed between the two tests.

Administration, Oral↗
PubMed1994

Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination.

BACKGROUND: BCG vaccination alters the response to tuberculin testing and influences the potential validity of the Heaf test in the diagnosis of tuberculosis. This study used a purified protein derivative 1 tuberculin unit (TU) Mantoux test with a cut off of 5 mm induration as an indicator of tuberculous infection in high risk children to determine whether this would distinguish infection from previous neonatal BCG vaccination. METHODS: Children at high risk of tuberculosis on chest radiography, Heaf test, or contact history who had been screened in the contact tracing clinic and referred for further assessment were included in the study. After clinical examination, chest radiography, and Mantoux testing they were assigned to three groups (tuberculous disease, chemoprophylaxis, or no treatment) and followed up for 6-24 months in the outpatient clinic and subsequently by postal questionnaire. RESULTS: Comparison of the Heaf and Mantoux tests showed a difference in the results with 82% of cases positive by the Heaf test and 59% positive by the Mantoux test. Using the Mantoux test result in combination with clinical and radiographic findings 194 children were allocated to the three groups as follows: primary tuberculosis (5), chemoprophylaxis (101), no treatment (88). During follow up for a mean (range) time of 46 (11-102) months four additional cases received treatment for primary tuberculosis, two in the chemoprophylaxis group and two in the untreated group. CONCLUSIONS: The use of the 1 TU Mantoux test after neonatal BCG vaccination reduced the number of children receiving treatment from 129 to 93-that is, by 36%. Although the numbers are small, there was no increase in the later development of tuberculosis.

Adolescent↗
PubMed1994

Clinical findings and respiratory function in infants following repair of oesophageal atresia and tracheo-oesophageal fistula.

Survival rates for infants undergoing surgical repair of oesophageal atresia with tracheo-oesophageal fistula (OA-TOF) have improved dramatically, but this condition remains associated with substantial morbidity. Most studies of patients following OA-TOF repair have concentrated on school-age and older people; whereas, the most hazardous period is infancy. We aimed to assess respiratory function in a group of infants following primary operative repair, and to relate the results to clinical findings during the first year of life. We studied 16 infants within 3 months of primary repair of OA-TOF. Measurements were made of maximum expiratory flow at functional residual capacity (VmaxFRC), thoracic gas volume (TGV) and airways resistance (Raw). Ten infants had tests repeated, usually to assess progress alongside continuing symptoms, or to ascertain improvement following additional surgery. Seven infants had essentially normal initial respiratory function tests, and six remained either symptom-free or developed only minor clinical problems. One infant subsequently developed stridor, with spontaneous improvement towards the end of the first year. The remaining nine infants had abnormal initial respiratory function tests: one was symptom-free at that time. The remainder developed respiratory and/or gastro-oesophageal symptoms. The functional abnormalities appeared to reflect the severity of the clinical problems encountered. We conclude that respiratory function testing in infants following OA-TOF repair may augment the value of clinical appraisal, help define postoperative respiratory status, and provide a general guide to likely clinical progress.

Airway Resistance↗
PubMed1993

Serum sialic acid and acute phase proteins in type 1 and type 2 diabetes mellitus.

Serum sialic acid is a risk factor for cardiovascular disease in the general population. Serum total sialic acid concentrations were therefore measured in 20 type 1 diabetic patients and in 20 age- and sex-matched non-diabetic subjects. Serum sialic acid were not significantly different in the type 1 diabetic patients and the normal subjects (2.00 +/- 0.37 vs. 1.98 +/- 0.67 mmol/l), but was significantly correlated with serum total cholesterol (r = 0.55, P < 0.02) and serum triglyceride concentration (r = 0.63, P < 0.01) in the type 1 diabetic patients. There was no relationship of sialic acid levels to age, duration of diabetes, smoking, body mass index, systolic or diastolic blood pressure, plasma glucose, serum fructosamine, or daily insulin dosage. Six of the type 1 diabetic patients with retinopathy had higher total serum sialic acid concentrations than those patients without retinopathy (2.38 +/- 0.33 vs. 1.85 +/- 0.26 mmol/l, P < 0.01). A further study of 16 type 1 and 16 type 2 diabetic patients matched for serum fructosamine and blood glucose concentrations and without tissue complications showed that the serum total sialic acid concentration was significantly higher in the type 2 diabetic patients compared with the type 1 patients (2.32 +/- 0.41 vs. 1.84 +/- 0.24 mmol/l, P < 0.001). Although the serum concentrations of the non-sialylated acute phase protein, C-reactive protein, was higher in type 2 than type 1 diabetes, sialylated acute phase protein levels did not explain differences in serum total sialic acid in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗