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Biomedical subjects

G Roberts

Publications and source records attributed to G Roberts.

At least 19 recordsLinked to original sources

Sexual selection and the evolution of evolvability.

Here we show that sexual selection can have an effect on the rate of mutation. We simulated the fate of a genetic modifier of the mutation rate in a sexual population with and without sexual selection (modelled using a female choice mechanism). Female choice for 'good genes' should reduce variability among male subjects, leaving insufficient differences to maintain female preferences. However, female choice can actually increase genetic variability by supporting a higher mutation rate in sexually selected traits. Increasing the mutation rate will be selected against because of the resulting decline in mean fitness. However, it also increases the probability of rare beneficial mutations arising, and mating skew caused by female preferences for male subjects carrying those beneficials with few deleterious mutations ('good genes') can lead to a mutation rate above that expected under natural selection. A choice of two male subjects was sufficient for there to be a twofold increase in the mutation rate as opposed to a decrease found under random mating.

Animals↗

A cumulative risk factor model for early identification of academic difficulties in premature and low birth weight infants.

OBJECTIVES: Premature and low birth weight children have a high prevalence of academic difficulties. This study examines a model comprised of cumulative risk factors that allows early identification of these difficulties. METHODS: This is a secondary analysis of data from a large cohort of premature (<37 weeks gestation) and LBW (<2500 g) children. The study subjects were 8 years of age and 494 had data available for reading achievement and 469 for mathematics. Potential predictor variables were categorized into 4 domains: sociodemographic, neonatal, maternal mental health and early childhood (ages 3 and 5). Regression analysis was used to create a model to predict reading and mathematics scores. RESULTS: Variables from all domains were significant in the model, predicting low achievement scores in reading (R (2) of 0.49, model p-value < .0001) and mathematics (R (2) of 0.44, model p-value < .0001). Significant risk factors for lower reading scores, were: lower maternal education and income, and Black or Hispanic race (sociodemographic); lower birth weight and male gender (neonatal); lower maternal responsivity (maternal mental health); lower intelligence, visual-motor skill and higher behavioral disturbance scores (early childhood). Lower mathematics scores were predicted by lower maternal education, income and age and Black or Hispanic race (sociodemographic); lower birth weight and higher head circumference (neonatal); lower maternal responsivity (maternal mental health); lower intelligence, visual-motor skill and higher behavioral disturbance scores (early childhood). CONCLUSIONS: Sequential early childhood risk factors in premature and LBW children lead to a cumulative risk for academic difficulties and can be used for early identification.

Child↗

Glioma: what is the role of c-Myc, hsp90 and telomerase?

The continuous advancements in cancer research have contributed to the overwhelming evidence of the presence of telomerase in primary and secondary tumours together with hsp90 and c-Myc. This review will discuss the important role of telomerase together with hsp90 and c-Myc within the initiation and progression of gliomas. Also it will review the differential expression of these genes in the different grades of gliomas and the possibility of new treatments targeting these specific genes.

Animals↗

Prevalence of latex allergy in the community at age 7 years.

BACKGROUND: Latex allergy has been highlighted as a problem in children during the last decade based on a number of case series of children with particular problems such as spina bifida. The actual prevalence of latex allergy in the general United Kingdom population is unclear. OBJECTIVE: To estimate the prevalence of childhood latex allergy in the general population. METHODS: The Avon Longitudinal Study of Parents and Children is a geographically based cohort that has been prospectively followed since birth. The children were invited for skin prick testing at 7 years of age. RESULTS: Four subjects out of 1877 tested were sensitized to latex. None had a history of clinical reactions to latex. CONCLUSION: This study suggests that the prevalence of latex sensitization and clinical latex allergy in the general childhood population are very low, 0.2% (95% confidence interval 0.1-0.6%) and 0.0% (0-0.2%), respectively.

Child↗

Relationship between aeroallergen and food allergen sensitization in childhood.

BACKGROUND: Previous studies measuring the prevalence of allergen sensitization have been relatively small and used small numbers of allergens. To effectively evaluate children with atopic disease, we need an accurate knowledge of which allergens are important. OBJECTIVE: To measure the prevalence of sensitization within a large unselected birth cohort, to examine the associations between sensitization to different allergens and determine whether atopy can be defined by a small panel of allergens. METHODS: The Avon Longitudinal Study of Parents and Children is a population-based birth cohort of 13,638 singletons surviving to 4 weeks of age. The cohort was skin tested at 7 years of age to house dust mite (Dermatophagoides pteronyssinus), grass pollens, cat, peanuts, mixed tree nuts and egg and one of three other panels: animal danders, foods or aeroallergens. Sensitization was defined as a weal diameter of > or =3 mm. The strength of associations between sensitization to different allergens was tested by calculating the odds ratio adjusted for sensitization to D. pteronyssinus and grass pollen and gender. RESULTS: Valid data were obtained from 6412 singletons. Sensitization was most common to aeroallergens: grass pollens (8.5%), D. pteronyssinus (7.8%), cat (4.9%), D. farinae (3.6%), dog (2.7%), horse (1.4%), rabbit (1.4%). Of the foods tested, the most common sensitization was to peanut (1.4%) and mixed tree nuts (1.0%). More than 95% of subjects with sensitization to any of the 29 allergens tested were sensitized to one of grass, D. pteronyssinus or cat allergen. There were strong associations of multiple sensitizations both within and between different allergen classes (pollens, animals, foods, peanut and tree nuts). CONCLUSIONS: Seven-year-old children in the UK are primarily sensitized to aeroallergens, but also to peanuts and tree nuts. There are strong associations between sensitization within allergen groups as well as between allergen groups. Further studies are required to observe whether similar associations are seen with clinical allergy to these allergens.

Air Pollution↗

Impairment in quality of life is directly related to the level of allergen exposure and allergic airway inflammation.

BACKGROUND: Allergic disease has been shown to impair health-related quality of life (HRQL). The relationship between HRQL and either allergen exposure or allergic inflammation has not been previously assessed. OBJECTIVE: To assess the relationship between HRQL and both grass pollen exposure and airway inflammation using the Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ). This is a novel questionnaire previously developed to assess the multi-system aspects of allergic disease. METHODS: Eighty-four subjects, aged 6-17 years, with seasonal allergic rhinoconjunctivitis, asthma and/or cutaneous manifestations were assessed before and during the grass pollen season. They were assessed with the PADQLQ, a visual analogue scale (VAS) to assess quality of life, symptom diary and exhaled nitric oxide (FENO). RESULTS: HRQL, as measured by the PADQLQ, significantly correlated with the average pollen count in the previous week (regression coefficient 0.038, 95% confidence interval (CI) 0.027-0.049, P<0.001). The PADQLQ score was also found to be significantly associated with airway inflammation as measured by FENO (regression coefficient 0.410, 95% CI 0.175-0.646, P=0.001). Additionally, PADQLQ showed a high degree of correlation with symptom scores and quality of life as measured by a VAS, good within-subject reliability and a small minimal important difference (0.20, 95% CI -0.09 to 0.49 on a seven-point scale). CONCLUSION: HRQL is related to both allergen load and allergic inflammation and the PADQLQ has excellent cross-sectional and longitudinal validity with respect to quality of life and symptoms.

Adolescent↗

Inflammatory, hemostatic, and clinical changes in a baboon experimental model for heatstroke.

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory and hemostatic responses to heat stress, suggesting that immunomodulation may improve outcome. We postulated that an experimental baboon model of heatstroke will reproduce human responses and clinical outcome to allow testing of new therapeutic strategies. Eight anesthetized juvenile baboons (Papio hamadryas) were subjected to heat stress in an incubator maintained at 44-47 degrees C until rectal temperature attained 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. Rectal temperature at the end of heat stress was 42.5 +/- 0.0 and 43.3 +/- 0.1 degrees C, respectively. All heat-stressed animals had systemic inflammation and activated coagulation, indicated by increased plasma IL-6, prothrombin time, activated partial thromboplastin time, and D-dimer levels, and decreased platelet count. Biochemical markers and/or histology evidenced cellular injury/dysfunction: plasma levels of thrombomodulin, creatinine, creatine kinase, lactic dehydrogenase, and alanine aminotransferase were increased, and varying degrees of tissue damage were present in liver, brain, and gut. No baboon with severe heatstroke survived. Neurological morbidity but no mortality was observed in baboons with moderate heatstroke. Nonsurvivors displayed significantly greater coagulopathy, inflammatory activity, and tissue injury than survivors. Sham-heated animals had an uneventful course. Heat stress elicited distinct patterns of inflammatory and hemostatic responses associated with outcome. The baboon model of heatstroke appears suitable for testing whether immunomodulation of the host's responses can improve outcome.

Animals↗

Intense-field modulation of NO2 multiphoton dissociation dynamics.

We report on the dynamics of multiphoton excitation and dissociation of NO(2) at wavelengths between 395 and 420 nm and intensities between 4 and 10 TW cm(-2). The breakup of the molecule is monitored by NO A (2)Sigma(+)n(')=1,0-->X (2)Pi(r)n(")=0 fluorescence as a function of time delay between the driving field and a probe field which depletes the emission. It is found that generation of n(')=0 and 1 NO A (2)Sigma(+) results in different fluorescence modulation patterns due to the intense probe field. The dissociation dynamics are interpreted in terms of nuclear motions over light-induced potentials formed by coupling of NO(2) valence and Rydberg states to the applied field. Based on this model, it is argued that the time and intensity dependences of A (2)Sigma(+)n(')=0-->X (2)Pi(r)n(")=0 fluorescence are consistent with delayed generation of NO A (2)Sigma(+)n(')=0 via a light-induced bond-hardening brought about by the transient coupling of the dressed A (2)B(2) and Rydberg 3ssigma (2)Sigma(g) (+) states of the parent molecule. The increasingly prompt decay of A (2)Sigma(+)n(')=1-->X (2)Pi(r)n(")=0 fluorescence with increasing intensity, on the other hand, is consistent with a direct surface crossing between the X (2)A(1) and 3ssigma (2)Sigma(g) (+) dressed states to generate vibrationally excited products.

Journal Article↗

Analysis of paediatric dental care provided under general anaesthesia and levels of dental disease in two hospitals.

OBJECTIVE: To compare the level of dental disease and the pattern of dental treatment under controlled airway general anaesthesia for ASA I and II children and ASA III and IV children in two hospitals. DESIGN: Prospective analysis. SETTING: Hospital and postgraduate dental teaching institution, UK 1996 - 2000. SUBJECTS AND METHODS: During a four-year period (1996-2000), data were collected on children aged 1 to 16 years who were admitted for treatment of dental caries under general anaesthesia. Outcome measures Levels of dental disease (dmft/DMFT), treatment provided. RESULTS: A total of 515 ASA I and II and 430 ASA III and IV children were treated. The dmft and DMFT values of the ASA I and II children were significantly higher than those of the ASA III and IV children (p = 0.03). A significantly greater number of restorations and fissure sealants were carried out for permanent teeth in ASA III and IV children (p < 0.001). The number of extractions for both primary and permanent teeth was significantly greater in the ASA I and II group (p < 0.05). CONCLUSIONS: The ASA III and IV children had significantly lower levels of dental caries than the ASA I and II children and received a higher level of preventive and restorative care.

Adolescent↗

Allogeneic stem cell transplantation in patients with Fanconi's anemia and myelodysplasia or leukemia utilizing low-dose cyclophosphamide and total body irradiation.

Five patients with confirmed Fanconi's anemia (FA) and myelodysplasia and/or leukemia underwent stem cell transplantation (SCT) from related donors at KFSHRC. The median age at SCT was 12.6 year (range, 6.2-15 years). Conditioning regimen consisted of cyclophosphamide (CY) 5 mg/kg/day i.v. for 4 days, total body irradiation (TBI) 450 cGy in a single dose. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine and antithymocyte globulins (ATG). The median time to engraftment (defined as ANC>/=0.5 x 10(9)/l) was 16 days (range, 12-26 days). The median time to a self-sustaining platelet count of >/=20 x 10(9)/l was 27 days (range, 12-40 days). All patients engrafted. Two patients developed acute GVHD; one of the gut (grade 3) and the other of the skin (grade 1), and one patient developed chronic GVHD of the liver. Four are alive and well with no evidence of the disease; one patient died of bacterial sepsis after controlling her GVHD and clearing her pulmonary aspergillosis and CMV infection. We conclude that the use of low-dose CY plus TBI in patients with FA and MDS/AML undergoing SCT is adequate; the regimen is well tolerated and may be curative for such patients.

Adolescent↗

Influence of a multidisciplinary paediatric allergy clinic on parental knowledge and rate of subsequent allergic reactions.

BACKGROUND: Studies have demonstrated that families of children with food allergy have significant deficiencies in their knowledge of how to avoid allergen exposure and how to manage allergic reactions. This study aims to assess the impact of a multidisciplinary paediatric allergy clinic consultation on parental knowledge of food allergy and to determine the rate of subsequent allergic reactions. METHODS: Sixty-two subjects (<17 years) referred with food allergy were prospectively enrolled. Parental knowledge was assessed by questionnaire and EpiPen trainer. Families saw a paediatric allergist, clinical nurse specialist and dietician. Knowledge was reassessed after 3 months and rate of allergic reactions after 1 year. RESULTS: After one visit to the paediatric allergy clinic, there was a significant improvement in parental knowledge of allergen avoidance (26.9%, P < 0.001), managing allergic reactions (185.4%, P < 0.0001) and EpiPen usage (83.3%, P < 0.001). Additionally, there was a significant reduction in allergic reactions (P < 0.001). Children with egg, milk or multiple food allergies were more likely to suffer subsequent reactions. CONCLUSIONS: A single visit to a multidisciplinary allergy clinic considerably improves families' abilities to manage allergic reactions to foods with an accompanying reduction in allergic reactions. Young children with egg, milk or multiple food allergies were at greatest risk of further reactions.

Adolescent↗

Morbidity following dental treatment of children under intubation general anaesthesia in a day-stay unit.

OBJECTIVES: To determine which variables were best related to the overall morbidity of a child undergoing dental general anaesthetic (GA) and then to use these variables to determine those factors that might influence the extent and severity of morbidity experienced by healthy children following dental GA. SAMPLE AND METHODS: Data were collected on anxiety, pain and morbidity, GA procedure and dental procedure from 121 children attending a day stay GA unit for dental treatment. Patients were interviewed preoperatively, postoperatively before discharge then four further times over the next 148 h. Data were analysed using multivariate regression. RESULTS: Thirty-one per cent of subjects had restorative work, 60% had at least one tooth extracted, 54% had a surgical procedure. Use of local analgesia reduced postoperative pain whilst an increase in the number of surgical procedures increased it. Increase in anaesthetic time was related to increased odds of feeling sleepy and nauseous, females were more likely to complain of sleepiness or weakness. Feelings of dizziness were increased if the patient was given local analgesia during the procedure. CONCLUSIONS: Pain following dental GA was the most prevalent and long lasting symptom of postoperative morbidity in this study. Reductions in operating time and improvement in pain control have the potential to reduce reported morbidity following dental GA.

Adolescent↗

Longitudinal study of grass pollen exposure, symptoms, and exhaled nitric oxide in childhood seasonal allergic asthma.

BACKGROUND: Exhaled nitric oxide (NO) has been proposed as a marker of airway eosinophilic inflammation in asthma. There is currently a paucity of longitudinal data relating it to allergen exposure and asthma symptoms. METHODS: Forty four children (6-16 years) with seasonal allergic asthma were sequentially followed before and during the grass pollen season. Asthma symptoms, lung function, NO levels, and pollen counts were recorded. The relationship between exhaled NO and both the pollen levels and asthma control were assessed longitudinally, comparing a subject's measurements with their previous ones. RESULTS: The median exhaled NO concentration was significantly increased during the pollen season (6.2 v 9.2 parts per billion (ppb), p<0.002; median change 2.9 ppb, 95% confidence interval 1.5 to 5.4). Exhaled NO was best associated with the mean pollen count in the week before measurement. It was also significantly associated with asthma control. CONCLUSIONS: The results suggest that, within a longitudinal model, the exhaled NO concentration is related to preceding allergen exposure and asthma control. It may be clinically more useful to compare exhaled NO values with a subject's previous values than to compare them with a population based normal range.

Adolescent↗

UK laboratory intercomparison on internal dosimetry.

A laboratory intercomparison for internal dose assessment from a variety of intake scenarios is described. This is the first UK intercomparison using the revised ICRP Human Respiratory Tract and biokinetic models. Four United Kingdom laboratories participated and six cases were assessed. Overall, the agreement in internal dose assessments between laboratories was considered satisfactory with 79% of the assessed committed effective doses, e(50), for cases within a band of +/- 40% of the median value. The range (highest/lowest) in e(50) estimated by the laboratories was smallest (1.2) for a case involving inhalation of 137Cs. The range was greatest (6.0) for a case involving a wound with, and possible inhalation of, 238Pu, 239Pu and 241Am; the variation between laboratories in assessment of intakes could not be considered to be satisfactory in this case. Judgements on the most appropriate data to use in estimating intakes, choice of parameter values for use with the ICRP models and allowing for the effects of treatment with DTPA were important sources of variability between laboratories.

Body Burden↗

Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial.

BACKGROUND: The relative efficacies of aminophylline and salbutamol in severe acute childhood asthma are currently unclear. A single bolus of salbutamol was compared with a continuous aminophylline infusion in children with severe asthma in a randomised double blind study. METHODS: Children aged 1-16 years with acute severe asthma were enrolled if they showed little improvement with three nebulisers (combined salbutamol and ipratropium) administered over an hour and systemic steroids. Subjects were randomised to receive either a short intravenous bolus of salbutamol (15 micro g/kg over 20 minutes) followed by a saline infusion or an aminophylline infusion (5 mg/kg over 20 minutes) followed by 0.9 mg/kg/h. RESULTS: Forty four subjects were enrolled, with 18 randomly allocated to receive salbutamol and 26 to receive aminophylline. The groups were well matched at baseline. An intention to treat analysis showed that there was no statistically significant difference in the asthma severity score (ASS) at 2 hours between the two groups (median (IQR) 6 (6, 8) and 6.5 (5, 8) for salbutamol and aminophylline respectively, p=0.93). A similar improvement in ASS to 2 hours was seen in the two groups (mean difference -0.08, 95% CI -0.97 to 0.80), there was a trend (p=0.07) towards a longer duration of oxygen therapy in the salbutamol group (17.8 hours (95% CI 8.5 to 37.5) v 7.0 hours (95% CI 3.4 to 14.2)), and a significantly (p=0.02) longer length of hospital stay in the salbutamol group (85.4 (95% CI 66.1 to 110.2) hours v 57.3 hours (95% CI 45.6 to 72.0)). There was no significant difference in adverse events between the two groups. CONCLUSIONS: This study suggests that, in severe childhood asthma, there is no significant difference in the effectiveness of a bolus of salbutamol and an aminophylline infusion in the first 2 hours of treatment. Overall, the aminophylline infusion was superior as it significantly reduced the length of stay in hospital.

Abdominal Pain↗

Acute renal failure complicating HELLP syndrome, SLE and anti-phospholipid syndrome: successful outcome using plasma exchange therapy.

Renal disease is very common in patients with systemic lupus erythematosis (SLE) and it may emerge during pregnancy or the post-partum period. Patients with anti-phospholipid syndrome (APS)are also at risk of renal disease. We present a case of acute renal failure in the post-partum period in a patient with SLE and APS. This case illustrates the potential difficulties in reaching a diagnosis in such a patient. It also illustrates the complexities of management and the potential interactions between SLE, Haemolysis, elevated liver enzymes and low platelets syndrome, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome and APS. We also review the role of plasma exchange therapy in managing our patient.

Acute Kidney Injury↗

Intravenous antibiotic regimens and prophylaxis of odontogenic bacteraemia.

OBJECTIVES: This study retrospectively examines the efficacy of prophylactic intravenous antibiotic regimens in the prevention of odontogenic bacteraemia in children with severe congenital heart defects receiving comprehensive dental treatment under general anaesthesia. PATIENTS AND METHODS: Blood cultures were taken from children with congenital cardiac defects 30 seconds after completion of dental treatment under general anaesthesia. Antibiotic prophylaxis had been given intravenously immediately before dental treatment. The choice of antibiotics and the extent of dental treatment were recorded. The percentage prevalence of bacteraemia was compared with published data following multiple dental extractions using the same clinical and microbiological methodology. RESULTS: The overall percentage prevalence of positive cultures in children receiving intravenous prophylactic antibiotics was 16%. The percentage of positive blood cultures in cardiac children who received ampicillin alone was not significantly different from that in children having a combination of amikacin and teicoplanin (16.7% v 22.2%) respectively [Chi Square = 0.385, df = 1, P= 0.535]. When compared with multiple extractions, both ampicillin alone and amikacin with teicoplanin were effective in reducing the prevalence of odontogenic bacteraemia. CONCLUSIONS: In children with cardiac defects, bacteraemia after dental treatment is reduced by antibiotics but is still detected on 16% of occasions. In comparison with children receiving ampicillin alone, the combination of amikacin and teicoplanin is as effective in reducing bacteraemia in children who are either allergic to penicillins or who have received them within the previous month.

Adolescent↗