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Biomedical subjects

C S Murray

Publications and source records attributed to C S Murray.

13 recordsLinked to original sources

Effect of childhood eczema and asthma on parental sleep and well-being: a prospective comparative study.

BACKGROUND: The psychological impact of childhood atopic eczema on parents and carers is poorly quantified. Objectives To compare the impact of caring for a child with atopic eczema vs. asthma on parents' sleep and well-being. METHODS: Ninety-two parents of 55 children who had moderate to severe atopic eczema or asthma took part in this prospective, questionnaire-based study. It was conducted at regional eczema and asthma outpatient clinics within a U.K. tertiary paediatric hospital. The main outcome measures were the number and duration of parents' sleep disturbances, as well as their anxiety and depression scores. RESULTS: Mothers caring for children with atopic eczema lost a median of 39 min of sleep per night and fathers lost 45 min sleep per night. This compared with a median of 0 min sleep lost by parents who had children with asthma (P < 0.001). These differences were independent of the age of the children, and whether the child came from a single-parent or two-parent family. There was a direct correlation between the severity of sleep disturbance and the level of maternal anxiety (rho = 0.58; P = 0.002) and depression (rho = 0.73; P < 0.001), as well as the level of paternal anxiety (rho = 0.59; P = 0.01). CONCLUSIONS: Compared with looking after a child with chronic asthma, caring for a child with chronic atopic eczema was associated with greater parental sleep disturbances. Disruption to parental sleep correlated with anxiety levels and, in the case of mothers, depression scores.

Anxiety↗

Dietary intake in sensitized children with recurrent wheeze and healthy controls: a nested case-control study.

BACKGROUND: The rising prevalence of asthma and allergic disease remains unexplained. Several risk factors have been implicated including diet, in particular poly-unsaturated fats and antioxidant intake. METHODS: A nested case-control study comparing the dietary intake of sensitized children with recurrent wheeze (age 3-5 years) and nonsensitized children who had never wheezed was carried out within an unselected population-based cohort. Cases and controls were matched for age, sex, parental atopy, indoor allergen exposure and pet ownership. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire and nutrient analysis program. RESULTS: Thirty-seven case-control pairs (23 male, mean age 4.4 years) participated. Daily total polyunsaturated fat intake was significantly higher in sensitized wheezers (g/day, geometric mean, 95% confidence intervals: 7.1, 6.4-7.9) compared with nonsensitized nonwheezy children (5.6, 5.0-6.3, P = 0.003). Daily omega-3 and omega-6 fat intakes were not significantly different between the two groups. No significant differences were found in intake of any antioxidant or antioxidant cofactors between the groups. CONCLUSIONS: Young sensitized wheezy children had a significantly higher total polyunsaturated fat intake compared with nonsensitized nonwheezy children. However, we were unable to distinguish a significant difference in specific poly-unsaturated fat intakes. Otherwise the children in both groups had a very similar nutritional intake.

Antioxidants↗

Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children.

BACKGROUND: Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. METHODS: Eighty four children aged 3-17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. RESULTS: Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected (44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p<0.001). In a multiple conditional logistic regression (AA v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital (OR 19.4, 95% CI 3.7 to 101.5, p<0.001). CONCLUSIONS: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.

Adolescent↗

Thick melanoma: the challenge persists.

BACKGROUND: Considerable resources have been channelled into primary and secondary prevention of cutaneous melanoma over the past 20 years. These efforts have been associated with a significant increase in the proportion of thin, good prognosis lesions and this is felt to be the principal reason for the current overall improvement in melanoma survival. OBJECTIVES: Analysis of Scottish Melanoma Group (SMG) data was carried out to identify the proportion of thick melanomas presenting over time. SMG data were used to characterize the patients presenting with thick melanoma. METHODS: Using data from the SMG database 915 patients (392 male and 523 female) first diagnosed with invasive melanoma > or = 3.5 mm thick in the two decades between 1979 and 1998, inclusive, were identified. The patients were from regions designated South-east Scotland, Tayside, Grampian and Highland, which together form half of all Scottish cases. RESULTS: The analysis shows that, although the proportion of thick, poor prognosis melanomas has decreased over time, the number presenting per year has not significantly altered. In the first decade, 50.5% of registrations were thick lesions and these fell to 31.0% in the second decade. In the first decade there were 419 cases (173 male), median age 66 years (range 5-99). Fifty-five patients were under the age of 40 years. Two hundred and twelve melanomas were nodular, 116 superficial spreading (SSM), 34 acral and 26 lentigo maligna melanoma. Sixty-nine patients had either lymph node involvement or distant spread at presentation. Despite a 93.3% increase in the total number of melanoma registrations by the end of the second decade, there was relatively little change in the absolute numbers of thick lesions. The total number of thick lesions was 496 (220 male), an increase of 18.4%. Median age was greater, at 70 years (range 1-98), and 31 patients were under the age of 40 years. Nodular was still the commonest type but its proportion had dropped significantly compared with the first decade, with a corresponding increase in SSM and acral types. CONCLUSIONS: Over a 20-year period there was little change in the absolute number of patients presenting with thick melanoma each year, though these form a diminishing proportion of the rising number of total melanomas. This thick melanoma group is characterized by an increasingly older age group and a changing type profile, nodular and SSM being the most common types. This work suggests that the resources currently directed at public and professional education on melanoma are having no effect on this group of patients and that alternative strategies may need to be considered.

Adolescent↗

Fecal microbiota in sensitized wheezy and non-sensitized non-wheezy children: a nested case-control study.

BACKGROUND: It has been suggested that intestinal microbiota of allergic and non-allergic children differs in composition, and that microbiota-immune system interactions may predispose children to develop sensitization. Previous studies have examined fecal microbiota of allergic children with atopic dermatitis, but little is known about that of atopic wheezy children. OBJECTIVE: To investigate the composition of the fecal microbiota of young sensitized wheezy and non-sensitized non-wheezy children, using molecular methods. METHODS: Within the context of a prospective birth cohort, we carried out a nested case-control study of sensitized wheezy children (cases) and non-sensitized non-wheezy controls. Cases and controls were matched for age, sex, parental atopy, allergen exposure, and pet ownership. We evaluated the composition of fecal microbiota by nucleic acid-based methods (PCR combined with denaturing gradient gel electrophoresis and quantification of bifidobacteria by fluorescent in situ hybridization). RESULTS: Thirty-three case-control pairs (mean age 4.4 years) provided stool samples. Comparison of total bacterial community profiles showed that each child had a unique fecal microbiota (mean Dice's similarity coefficient 22%, range 3.3-60.8%). There was no difference between the groups in prevalence of Lactic Acid bacteria (12/33 vs. 11/33, P=0.8) or bifidobacteria (30/33 vs. 31/33, P=1.00, cases vs. controls). The bifidobacterial species detected were similar in both groups. The percentage of bifidobacteria in total fecal microflora was no different between cases (median 1.7%, range 0-20.8%) and controls (1.9%, 0-18.2%, P=0.7). However, cases with eczema had significantly fewer bifidobacteria (median 1.6%, range 0-4.8%) than their controls (4.0%, 1.9-18.2%, P=0.05). CONCLUSION: We found no differences in fecal microbiota composition between sensitized wheezy and non-sensitized, non-wheezy children aged 3-5 years using nucleic acid-based methods. Differences appear to be isolated to those allergic children with eczema.

Bifidobacterium↗

Itching for progress.

The study of itch remains a neglected field, with a number of barriers limiting satisfactory therapy in the majority of instances. We review recent advances, focusing on the identification of the neural pathways, distinct from pain, that signal itch; methods to measure itch as scratch in humans; and the identification of a role for H4 receptors in mediating itch (in the mouse).

Animals↗

Reported versus confirmed wheeze and lung function in early life.

AIMS: To investigate the relation between parentally reported wheeze (unconfirmed), physician confirmed wheeze, and subsequent lung function. METHODS: Children at risk of allergic disease (one parent atopic) were recruited antenatally and followed prospectively from birth. During the first three years of life parents were asked to contact the study team if their child was wheezy. The presence of wheeze was confirmed or not by the primary care or study physician. Respiratory questionnaire and specific airway resistance measurement (sR(aw), body plethysmograph) were completed at age 3 years. RESULTS: A total of 454 children were followed from birth to 3 years of age. One hundred and eighty six (40.9%) of the parents reported their child wheezing in the first three years of life, and in 130 (28.6%) the wheeze was confirmed. A total of 428 children attended the three year clinic review, of whom 274 (64%) successfully carried out lung function tests. There was no significant difference in sR(aw) (kPa.s; geometric mean, 95% CI) between children who had never wheezed (n = 152; 1.03, 1.00 to 1.06) and those with a parentally reported but unconfirmed wheeze (n = 36; 1.02, 0.96 to 1.07, p = 1.00). sR(aw) was significantly higher in children with a physician confirmed wheeze (n = 86; 1.17, 1.11 to 1.22, p < 0.001) compared to those with no history of wheeze or with unconfirmed wheeze. CONCLUSIONS: Children with physician confirmed wheeze have significantly poorer lung function compared to those with parentally reported but unconfirmed and those who have never wheezed. A proportion of parents may have little understanding of what medical professionals mean by the term "wheeze".

Analysis of Variance↗

Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population.

BACKGROUND: Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association. METHODS: Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V'maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age. RESULTS: Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V'maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). CONCLUSION: Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.

Cough↗

The role of indoor allergen exposure in the development of sensitization and asthma.

The role of indoor allergen exposure in the development of sensitization and asthma remains a subject of controversy. From a number of cross-sectional and longitudinal studies we can conclude that there is a very close association between allergen exposure and the sensitization of an individual. The dose-response relationships seem to differ between allergens; house dust mite and cockroach allergens appear to have a positive linear relationship, whereas cat allergens appear to act quite differently, with maximum sensitization developing at moderate exposure levels. Very low levels of cat allergen exposure are likely to induce no response and very high levels are likely to develop a form of tolerance, with a modified T helper cell type 2 response and the production of IgG4 antibodies and but not IgE. The relationship between indoor allergen exposure and asthma is, however, less clear. The proposed mechanism for the development of disease is that allergen exposure causes sensitization, and continued exposure leads to airway responsiveness and inflammation. As yet, the evidence for allergen exposure being a primary cause of asthma remains weak, and the results of ongoing prospective, randomized allergen avoidance trials are awaited to clarify this issue.

Air Pollution, Indoor↗

Morbidity in reflex sympathetic dystrophy.

Reflex sympathetic dystrophy (RSD), an unusual diagnosis in general paediatrics, is well recognised by paediatric rheumatologists. This study reports the presentation and the clinical course of 46 patients (35 female, age range 8-15.2) with RSD. The patients saw professionals from an average of 2.3 specialties (range 1-5). Twenty five (54%) had a history of trauma. Median time to diagnosis was 12 weeks (range 1-130). Many children had multiple investigations and treatments. Once diagnosis was made, treatment followed with physiotherapy and analgesics. Median time to recovery was seven weeks (range 1-140), with 27.5% relapsing. Nine children required assessment by the child and adolescent psychiatry team. This disease, though rare, has significant morbidity and it is therefore important to raise clinicians' awareness of RSD in childhood. Children with the condition may then be recognised and referred for appropriate management earlier, and spared unnecessary investigations and treatments which may exacerbate the condition.

Adolescent↗

Nucleotide sequence of a Porphyromonas gingivalis gene encoding a surface-associated glutamate dehydrogenase and construction of a glutamate dehydrogenase-deficient isogenic mutant.

The nucleotide sequence for a surface-associated protein (A. Joe, A. Yamamoto, and B. C. McBride, Infect. Immun. 61:3294-3303, 1993) of Porphyromonas gingivalis was determined. The structural gene comprises 1,338 bp and codes for a protein of 445 amino acids. The deduced molecular weight of the protein is 49,243. A data base search for homologous proteins revealed significant sequence similarity to the subunit protein of glutamate dehydrogenases (GDHs) isolated from various sources. This protein, which was previously labelled PgAg1, will now be called GDH. Recombinant GDH was purified to homogeneity, and native GDH was partially purified from P. gingivalis. Both preparations exhibited NAD-dependent GDH activity. Intact P. gingivalis and an extract of cell surface components also demonstrated NAD-dependent GDH activity. To help elucidate the role of this protein, an isogenic mutant of P. gingivalis lacking the GDH protein was generated by deletion disruption. Biological characterization of the mutant strain, P. gingivalis E51, demonstrated complete loss of GDH activity. Immunogold bead labelling of intact cells showed that GDH was no longer present on the surface of the bacterial cell. The GDH-negative mutant displayed impaired cell growth, as demonstrated by an increased generation time and an inability to grow to the same cell density as the parent.

Amino Acid Sequence↗