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G Devereux

Publications and source records attributed to G Devereux.

At least 19 recordsLinked to original sources
PubMed2004

Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers' syndrome? An analysis of a national surveillance study.

BACKGROUND: There has been concern that children with variant Creutzfeldt-Jakob disease (vCJD) might be misdiagnosed as cases of Alpers' syndrome, as a spongiform degeneration of the brain is seen in both conditions. OBJECTIVE: To report a national prospective surveillance study of children with progressive intellectual and neurological deterioration, designed to detect any children in the United Kingdom with vCJD, to see whether this misdiagnosis is occurring. METHODS: A monthly surveillance card is sent by the British Paediatric Surveillance Unit to all consultant paediatricians in the UK. The card lists the disorders currently under surveillance. Paediatricians are asked to return the card, reporting cases seen in the previous month. The BPSU office informs the surveillance groups about reported cases, and they obtain clinical information from the notifying paediatrician. RESULTS: After 5 years and 8 months of surveillance, 1244 children had been reported to the study. Alpers' syndrome was confirmed in two, although this was the suggested diagnosis in 11 children at the time of initial notification. CONCLUSIONS: The results show that Alpers' syndrome is rare and it is unlikely that vCJD cases are being misdiagnosed as Alpers' syndrome.

Adolescent↗
PubMed2004

Variations in neurodegenerative disease across the UK: findings from the national study of Progressive Intellectual and Neurological Deterioration (PIND).

AIMS: To identify any UK children with variant Creutzfeldt-Jakob disease (vCJD) and obtain information about the causes of progressive intellectual and neurological deterioration (PIND) and the geographical distribution of cases. METHODS: The PIND Study uses the monthly surveillance card that is sent to all UK paediatricians by the British Paediatric Surveillance Unit. Case details are obtained from the reporting paediatricians by telephone interview, site visit, or self completion of a questionnaire. A paediatric neurology expert group then classifies the anonymised cases. The Communicable Disease Surveillance Centre (CDSC) provides mapping support. RESULTS: After five years and five months of surveillance, 1400 children had been reported. In the UK the majority of PIND cases had a confirmed diagnosis (comprising 99 different conditions); 505 "no cases" and 97 "outstanding" cases were excluded. A total of 798 PIND cases were included as follows: 577 with a confirmed underlying diagnosis; six with definite or probable vCJD, 51 who had undiagnosed PIND but were not thought to have vCJD, and 164 cases who were still under investigation. In some districts there were unexpectedly high numbers of PIND cases with a heterogeneous mixture of underlying diagnoses. In the five districts with the largest numbers of resident cases the majority not only came from a particular ethnic group but also had high reported rates of consanguinity. CONCLUSIONS: In districts with large numbers of PIND cases there are major resource implications. These children and their families have complex problems and they need access to diagnostic facilities and appropriate service provision.

Adolescent↗
PubMed2002

Antenatal determinants of neonatal immune responses to allergens.

BACKGROUND: The environmental factors responsible for recent increases in the prevalence of asthma and atopic disease have been assumed to act after birth. Their possible effects on fetal immune development in utero have not been investigated systematically, although sensitization to allergens may occur before birth. OBJECTIVE: This prospective study determined whether the risk factors for asthma and atopic disease, namely family history of atopic disease, maternal smoking, birth order, or maternal dietary intake of antioxidant vitamins, exert antenatal effects on the fetal immune system that may predispose to childhood atopy. METHODS: The T helper (Th) cell proliferative responses of cord blood mononuclear cells (CBMC) from a sample of 223 neonates, representative of children born to a cohort of 2000 pregnant women, were measured and related to family, maternal and environmental factors associated with the pregnancy. RESULTS: The magnitude of CBMC-proliferative responses to allergens increased significantly in association with a family history of atopic disease or maternal smoking, and decreased significantly with increasing birth order and high maternal dietary intake of vitamin E. The epidemiological association between birth order and atopy may therefore be a consequence of antenatal influences rather than of protective effects of childhood infections. The association between maternal intake of vitamin E and CBMC responsiveness suggests that diet during pregnancy may influence the fetal immune system in such a way as to modulate the risk of childhood atopy. CONCLUSION: These results provide a new insight into the aetiology of atopic disease by demonstrating that the maternal environmental risk factors for atopy, diet, birth order and smoking, influence the development of the fetal immune system. This raises the prospect of preventative public health interventions during pregnancy.

Allergens↗
PubMed2002

Apparent but not real increase in asthma prevalence during the 1990s.

The authors investigated changes in asthma prevalence and perception of bronchoconstriction over 6 yrs in adults of Newcastle-upon-Tyne. Postal questionnaires were sent to 6,000 subjects aged 20-44 yrs in 1992-1993 and 1998-1999. Random samples of 600 responders had assessments of atopy, airway responsiveness, and their ability to perceive methacholine-induced bronchoconstriction. The prevalences of asthmatic symptoms, physician-diagnosis, and medication use increased by an average of 4.4%, particularly in subjects aged <30 yrs (8.7 versus 2.7). Atopy prevalence increased from 25% to 31% but atopics and nonatopics had similar mean changes in questionnaire data (5.2 versus 3.4). The probability of a positive methacholine test decreased as did the mean methacholine dose/response slope (0.00527 to 0.00379), indicating lower levels of airway responsiveness. This can be largely explained by an increase in use of inhaled corticosteroids (5.0-9.3%). The proportion of subjects perceiving bronchoconstriction during methacholine tests increased from 63 to 77%. The authors conclude that current changes in asthma epidemiology in adults may result from increased awareness of symptoms (and/or an increased willingness to report them), and from an increased willingness of physicians to make the diagnosis and prescribe treatment, not from increased disease prevalence.

Adolescent↗
PubMed2001

An application of the United Kingdom Working Party diagnostic criteria for atopic dermatitis in Scottish infants.

The United Kingdom Working Party diagnostic criteria for atopic dermatitis have been characterized in infants and children; however, the need for visual confirmation of flexural dermatitis by a trained investigator limits their use in large epidemiologic studies. We have administered the complete United Kingdom Working Party criteria in a postal questionnaire format to the mothers of year old infants and determined the concordance between mothers' and trained investigator's reports of visual flexural dermatitis. Based on mothers' responses to the questionnaire, 59 infants with atopic dermatitis and 59 controls were identified. In subsequent home interviews conducted by a trained investigator, the United Kingdom criteria questions were repeated and sites of current visible dermatitis were identified by mothers and the investigator as per United Kingdom Working Party protocol. Agreement between the mothers' postal and home interview responses was high: kappa= 0.75-0.94 for individual criteria; kappa= 0.93 for diagnosed atopic dermatitis. Agreement between the mothers' and investigator's observations of visible flexural dermatitis was high for all sites: kappa= 0.88-1.0. The results demonstrate that mothers are able to apply the United Kingdom criteria and accurately report visible flexural dermatitis in their year old infants. The postal application of the United Kingdom Working Party's diagnostic criteria for atopic dermatitis in year old infants appears to be a practical, reliable, epidemiologic tool in the investigation of atopic dermatitis with results comparable with formal application of the criteria by a trained investigator.

Adult↗
PubMed2001

In utero priming of allergen-specific helper T cells.

BACKGROUND: Allergic diseases are major health problems in developed countries. Cord blood mononuclear cells (CBMC) at birth can proliferate after stimulation with allergen and this has led to the widespread view that the sensitization of the fetal immune system by allergens is a key determinant in establishing immunological bias towards allergy. However, the notion that the immune system can be primed by allergen in utero remains unproven. Determination of the CD45 isoform of responding T helper cells is an established method of determining the activation status of responding T helper cells because unsensitized cells express CD45RAhigh and previously sensitized cells CD45ROhigh. OBJECTIVE: To determine if sensitization of allergen-specific T helper cells can occur in utero by determining the CD45 isoform of CBMC proliferating in response to allergen. METHODS: CBMC proliferative responses were measured after stimulation in culture with a panel of allergens, mitogen and control antigen. To ascertain whether any responding T helper cells had been primed in utero, depletion experiments established whether they carried the CD45ROhigh marker of previous activation or the CD45RAhigh marker of unstimulated T cells. RESULTS: CBMC from a high proportion of 223 randomly selected neonates were stimulated to proliferate in vitro by allergens, with 76% responding to timothy grass pollen. In 50% of such responses to timothy grass, the CD45 isoform of the T cells that proliferate indicated that they had been previously activated. However, the remaining 50% of responses to timothy grass were mediated by previously unstimulated T cells. Proliferative responses mediated by CBMC sensitized in utero tended to be greater in magnitude than those mediated by unsensitized cells (P = 0.08). Seventy-five per cent of CBMC samples proliferated after stimulation with mycobacterial PPD and, as in BCG-vaccinated adults, all such CBMC proliferative responses at birth were predominately mediated by sensitized cells. CONCLUSION: Allergen- and antigen-specific Th cells can be primed in utero.

Adolescent↗
PubMed2000

Variant Creutzfeldt-Jakob disease in UK children: a national surveillance study.

BACKGROUND: Variant Creutzfeldt-Jakob Disease (vCJD) was first reported in 1996; the youngest patient developed symptoms at 16 years of age. We have done 3 years of prospective active surveillance for progressive intellectual and neurological deterioration (PIND) in UK children, and have searched for vCJD among the children who were reported. METHODS: Since May, 1997, there has been active surveillance for patients younger than 16 years old with PIND by means of a monthly card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical'details of cases of PIND are obtained from reporting paediatricians by telephone interview or site visit, and an expert group of paediatric neurologists then classifies the cases. FINDINGS: After 3 years, 885 patients with suspected PIND have been reported. Among them were two fatal cases of definite vCJD and one case of probable vCJD; all were reported in 1999. One girl was age 12 years at onset--the youngest ever case of vCJD. No other children with the clinical features of vCJD were identified. The expert group has discussed 655 cases, of which 360 have a confirmed underlying cause, being categorised into 88 known neurodegenerative diseases. INTERPRETATION: That this prospective active surveillance in the UK has found few children with suspected vCJD is relatively reassuring. However, 3 years is a short time to survey a disease with an unknown incubation period. Since one probable and two definite cases of vCJD were reported to the study in 1999, there is concern that more childhood cases may appear.

Adolescent↗
PubMed2000

Measurement of T-helper cytokines secreted by cord blood mononuclear cells in response to allergens.

It has been proposed that in utero factors may predispose towards the development of childhood atopy. To test this hypothesis, it will be necessary to measure T-helper cell (Th) cytokines secreted by human cord blood mononuclear cells (CBMC) stimulated by allergens. However, to date, it has proven impossible to measure allergen-specific CBMC secretion of the key Th cytokine interleukin-4 (IL-4) using conventional sandwich ELISA techniques. We report for the first time the successful measurement of IL-4 secreted by CBMC stimulated by the allergens timothy grass pollen and house dust mite extract. The method is an adaptation of a novel cell-based ELISA (celELISA), which demonstrated an increased (up to 20-fold) sensitivity to detect IL-4. The method is simple, precise, is no more costly than a conventional ELISA, and can identify individuals in a general population whose CBMC exhibit different cytokine biases in response to allergens. The frequency distribution of IL-4 and interferon-gamma (IFN-gamma) CBMC responses to allergens in the general population approximates to a log-normal distribution, which will permit the application of linear regression techniques in the identification of in utero factors which influence Th bias.

Allergens↗
PubMed2000

Split-night versus full-night studies for sleep apnoea/hypopnoea syndrome.

Investigation and treatment of sleep apnoea/hypopnoea syndrome (SAHS) is placing increasing demands on healthcare resources. This workload may be reduced by using split-night studies instead of the standard full-nights of diagnostic polysomnography and continuous positive airway pressure (CPAP) titration. Split-night studies involve polysomnography in the first half of the night followed, if there is an abnormal frequency of apnoeas and hypopneas, by CPAP titration for the remainder of the night. The authors' database of all patients prescribed a CPAP trial 1991-1997 was used to compare long-term outcomes in all 49 (46 accepting CPAP) patients prescribed split-night studies with those in full-night patients, matched 1:2 using an apnoea/ hypopnoea index (AHI) of +/-15% and Epworth score of +/-3 units. Classical symptoms of SAHS were the main reason for the split-night studies (n=27). There were no differences between the groups in long-term CPAP use, median nightly CPAP use (split-night 6.0 h x night-1, interquartile range (IQR) 3.8-7.4, full-night; 6.2 h x night-1, IQR 3.7-7.0, p=0.9), post-treatment Epworth scores and frequency of nursing interventions/clinic visits required. The median time from referral to treatment was less for the split-night patients (13 months, IQR 11-20 months) than for full-night patients (22 months, IQR 12-34 months; p=0.003). Split-night studies, in selected patients, result in equivalent long-term continuous positive airway pressure use to full-night studies with shorter treatment times and less healthcare utilization.

Adult↗
PubMed2000

Diet, infection and wheezy illness: lessons from adults.

An increase in asthma and atopic disease has been recorded in many countries where society has become more prosperous. We have investigated two possible explanations: a reduction in childhood infections and a change in diet. In a cohort of people followed up since 1964, originally selected as a random sample of primary school children, we have investigated the relevance of family size and the common childhood infectious diseases to development of eczema, hay fever and asthma. Although membership of a large family reduced risks of hay fever and eczema (but not asthma), this was not explained by the infections the child had suffered. Indeed, the more infections the child had had, the greater the likelihood of asthma, although measles gave a modest measure of protection. We have investigated dietary factors in two separate studies. In the first, we have shown the risks of bronchial hyper-reactivity are increased seven-fold among those with the lowest intake of vitamin C, while the lowest intake of saturated fats gave a 10-fold protection. In the second, we have shown that the risk of adult-onset wheezy illness is increased five-fold by the lowest intake of vitamin E and doubled by the lowest intake of vitamin C. These results were supported by direct measurements of the vitamins and triglycerides in plasma. We have proposed that changes in the diet of pregnant women may have reflected those observed in the population as a whole and that these may have resulted in the birth of cohorts of children predisposed to atopy and asthma. The direct test of this is to study the diet and nutritional status of a large cohort of pregnant women and to follow their offspring forward. This is our current research.

Adult↗
PubMed1999

Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome.

Patients with the sleep apnea/hypopnea syndrome (SAHS) treated by nasal continuous positive airway pressure (CPAP) need to use CPAP long-term to prevent recurrence of symptoms. It is thus important to clarify the level of long-term CPAP use and the factors influencing long-term use. We examined determinants of objective CPAP use in 1, 211 consecutive patients with SAHS who were prescribed a CPAP trial between 1986 and 1997. Prospective CPAP use data were available in 1, 155 (95.4%), with a median follow-up of 22 mo (interquartile range [IQR], 12 to 36 mo). Fifty-two (4.5%) patients refused CPAP treatment (these were more often female and current smokers); 1,103 patients took CPAP home, and during follow-up 20% stopped treatment, primarily because of a lack of benefit. Methods of survival analysis showed that 68% of patients continued treatment at 5 yr. Independent predictors of long-term CPAP use were snoring history, apnea/hypopnea index (AHI), and Epworth score; 86% of patients with Epworth > 10 and an AHI >/= 30 were still using CPAP at 3 yr. Average nightly CPAP use within the first 3 mo was strongly predictive of long-term use. We conclude that long-term CPAP use is related to disease severity and subjective sleepiness and can be predicted within 3 mo.

Adult↗
PubMed1998

Adverse effects of a single dose of (+)-sotalol in patients with mild stable asthma.

AIMS: To investigate the effect of (+)-sotalol, which is not thought to possess clinically significant beta-adrenoceptor blocking activity, on airway responsiveness in subjects with mild asthma. METHODS: A placebo controlled, double-blind, single dose, cross over study, evaluating the effects of oral (+)-sotalol 300 mg and oral (+/-)-sotalol 240 mg, on airway responsiveness, FEV1, and heart rate in 18 asthmatic volunteers with quantifiable levels of airway responsiveness. RESULTS: Compared with placebo, (+)-sotalol induced a significant increase in airway responsiveness, and a significant decrease in FEV1, but there was no significant change in heart rate. Following (+/-)-sotalol there was no significant effect on airway responsiveness, but there were significant decreases in FEV1 and heart rate. In one subject both (+)-sotalol and (+/-)-sotalol provoked a 49% decrement in FEV1, and in another there were decrements of 20% and 18%, respectively. CONCLUSIONS: Despite theoretical considerations, it cannot be assumed that (+)-sotalol is safe in patients with asthma.

Adolescent↗
PubMed1998

Perception of respiratory symptoms after methacholine-induced bronchoconstriction in a general population.

In an epidemiological study, methacholine-induced bronchoconstriction was used as a physical illustration of the sensations associated with asthma. The objective of this study was to assess whether familiarity with these sensations could be used as a measure of asthma prevalence. Eight hundred and seventy six subjects aged 20-44 yrs completed a respiratory questionnaire and a measurement of airway responsiveness (the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20)). Subjects were asked about their perception of, familiarity with and description of the respiratory sensations experienced at the time of maximal bronchoconstriction. The questionnaire-derived lifetime prevalences of wheeze, chest tightness and undue breathlessness were 43, 35 and 22% respectively. Asthma medication was used by 8% and the lifetime prevalence of diagnosed asthma was 12%. Quantifiable levels of airway responsiveness were measured in 34%, and airway responsiveness in the range considered to be consistent with untreated active asthma was present in 21%. Bronchoconstriction was perceived by 59%. Perception of bronchoconstriction was associated with the magnitude of bronchoconstriction, younger age, female sex and questionnaire-reported symptoms. Of subjects able to perceive bronchoconstriction, 58% reported previous experience of (familiarity with) the associated respiratory sensations. Familiarity with the sensations of bronchoconstriction was associated with questionnaire-reported symptoms, diagnosed asthma and increasing levels of airway responsiveness. There was poor agreement between the respiratory symptoms reported by questionnaire before the methacholine test and the words used to describe respiratory sensations induced by the test. Familiarity with the sensations of methacholine-induced bronchoconstriction has all the appropriate associations of a measure of asthma prevalence and may be a useful adjunct to symptom questionnaires and airway responsiveness measurements in epidemiological studies. A sizeable number of subjects can be identified with intermediate levels of airway responsiveness, who are able to perceive bronchoconstriction and are familiar with the sensations associated with it, yet who are not recognized to suffer from asthma.

Adult↗
PubMed1996

Asthma, airways responsiveness and air pollution in two contrasting districts of northern England.

BACKGROUND: To assess the possible magnitude of differences between normal populations an epidemiological investigation of asthma was conducted in two strongly contrasting districts of northern England--rural West Cumbria on the west coast and urban Newcastle upon Tyne on the east coast. METHODS: A cross sectional survey of randomly identified men aged 20-44 years was conducted in two phases: phase 1, a postal survey of respiratory symptoms and asthma medication in 3000 men from each district; and phase 2, a clinical assessment of 300 men from each district comprising investigator administered questionnaires, skin prick tests, spirometry, and methacholine challenge tests. RESULTS: The phase 1 (but not phase 2) study showed a small excess of "ever wheezed" in Newcastle (44% versus 40%), but neither phase showed differences between the two districts for recent wheeze or for other symptoms characteristic of asthma. There were also no differences with regard to diagnosed asthma, current asthma medication, spirometric parameters, or airways responsiveness. The prevalence of quantifiable airways responsiveness (PD20 < or = 6400 micrograms) was 27.7% in West Cumbria and 28.2% in Newcastle. Regression analyses showed that PD20 was negatively associated with atopy and positively with forced expiratory volume in one second (FEV1); that an association between PD20 and current smoking could be explained by diminished FEV1; and that PD20 was not related to geographical site of residence. CONCLUSIONS: Neither airways responsiveness nor the other parameters of diagnostic relevance to asthma varied much between the two study populations, despite the apparent environmental differences. The most obvious of these were the levels of outdoor air pollution attributable to vehicle exhaust emissions, the ambient levels of which were 2-10 fold greater in Newcastle. Our findings consequently shed some doubt over the role of such pollution in perceived recent increases in asthma prevalence. It is possible, however, that an air pollution effect in Newcastle has been balanced by asthmagenic effects of other agents in West Cumbria.

Adult↗
PubMed1995

Effect of dietary sodium on airways responsiveness and its importance in the epidemiology of asthma: an evaluation in three areas of northern England.

BACKGROUND: Although several investigations have shown a relationship between asthma (or its surrogate, airways responsiveness) and dietary or urinary sodium, others have not, and the matter remains controversial. This "salt effect" has been investigated during two recent epidemiological surveys of men in northern England. The first assessed the possible effect on airways responsiveness of occupational exposure to welding fumes, and the second characterised airways responsiveness in two geographically distinct residential areas. Thus, three separate study areas/populations were involved. METHODS: Investigation 1 involved 1059 shipyard workers aged 16-27 years who were exposed variously to welding fumes, and Investigation 2 involved 587 men aged 20-44 years who lived in rural West Cumbria or in urban Newcastle upon Tyne. In Investigation 1, a 24 hour urine specimen was requested from each subject with quantifiable airways responsiveness (PD20 < or = 6400 micrograms methacholine) and from an equal number of subjects without measurable airways responsiveness from the same occupational subgroup. In Investigation 2, every subject was asked to provide a 24 hour urine specimen. RESULTS: Of the men undergoing methacholine tests, satisfactory 24 hour urine specimens were obtained from 234 (22.1%) in Investigation 1 and 232 (39.5%) in Investigation 2. Analysis using multiple linear regression, multiple linear logistic regression, and multiple regression for censored data produced consistent results within each study population but conflicting results between them, such that there was no hint of a relationship between airways responsiveness and 24 hour urinary sodium excretion in the shipyard workers of Investigation 1 nor in the rural West Cumbrian population of Investigation 2, but an association was found in the urban Newcastle population of Investigation 2. All study populations were sufficiently large to demonstrate anticipated relationships between airways responsiveness and atopy, baseline FEV1, and (Newcastle only) age. CONCLUSIONS: If airways responsiveness is related to dietary sodium the relationship is not likely to be strong.

Adolescent↗