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Biomedical subjects

B Whitehead

Publications and source records attributed to B Whitehead.

At least 19 recordsLinked to original sources

Criteria for elective admission to the paediatric intensive care unit following adenotonsillectomy for severe obstructive sleep apnoea.

During the period 1997 to 2002, 42 children were electively admitted to the Paediatric Intensive Care Unit at the John Hunter Children's Hospital following adenotonsillectomy for severe obstructive sleep apnoea. Forty children had a preoperative sleep study, of which 33 were complete polysomnograms. Of the 42 children admitted, 35 required no intervention while seven (17%) required an additional intervention beyond supplemental oxygen. Our criteria for elective admission to Paediatric Intensive Care following adenotonsillectomy for severe obstructive sleep apnoea are presented.

Adenoidectomy↗

Exercise tolerance in children with cystic fibrosis undergoing lung transplantation assessment.

The aim of this study was to compare the 6-min walk test against the recently developed 3-min step test, as measures of exercise tolerance in children with moderate to severe cystic fibrosis (CF) lung disease referred for lung transplantation assessment. Twenty-eight children with CF (16 girls, 12 boys), with a mean age of 13.7 yrs (range 7.2-17.8 yrs) and mean forced expiratory volume in one second of 34% predicted (range 17%-67%) were recruited. All subjects performed both the 6-min walk and 3-min step-tests. Outcome measures were maximum rise in heart rate (HR), and maximum fall in arterial oxygen saturation (Sa,O2). There was no significant difference in resting HR or Sa,O2 prior to starting the two tests. Both step and walk tests produced significant rises in median HR (from 114-149 min(-1), p<0.0005, and 119-138 min(-1), p<0.0005, respectively) and significant falls in Sa,O2 (both from 94-92%, p<0.0005). The step test produced a significantly greater percentage rise in HR (30% versus 18%, p<0.0005) and a significantly greater percentage fall in Sa,O2 (4% versus 2%, p=0.002). Bland-Altman analysis gave wide 95% limits of agreement (10.7-29.3% for rise in HR, -2.14.6% for fall in Sa,O2). The step test was well tolerated. The 3-min step test produced a greater fall in Sa,O2 and a greater rise in HR than the 6-min walk test in children with moderate to severe CF lung disease. It may be of value when assessing a child's suitability for lung transplantation.

Adolescent↗

A model for predicting life expectancy of children with cystic fibrosis.

In this study the authors aimed to produce a model for predicting the life expectancy of children with severe cystic fibrosis (CF) lung disease. The survival of 181 children with severe CF lung disease referred for transplantation assessment 1988-1998 (mean age 11.5 yrs, median survival without transplant 1.9 yrs from date of assessment) were studied. Proportional hazards modelling was used to identify assessment measurements that are of value in predicting longevity. The resultant model included low height predicted forced expiratory volume in one second (FEV1), low minimum oxygen saturation (Sa,O2min) during a 12-min walk, high age adjusted resting heart rate, young age, female sex, low plasma albumin, and low blood haemoglobin as predictors for poor prognosis. Extrapolation from the model suggests that a 12-yr old male child with an FEV1 of 30% pred and a Sa,O2min of 85% has a 44% risk of death within 2 yrs (95% confidence interval (CI) 35-54%), whilst a female child with the same measurements has a 63% risk of death (95% CI 52-73%) within the same period. The model produced may be of value in predicting the life expectancy of children with severe cystic fibrosis lung disease and in optimizing the timing of lung transplantation.

Cause of Death↗

The effect of prelung transplant clinical status on post-transplant survival of children with cystic fibrosis.

The aim of this study was to determine whether transplanting paediatric cystic fibrosis (CF) patients later in the course of their disease was detrimental to their post-transplant survival. Data was collected from 51 children with CF undergoing lung or heart-lung transplantation May 1988-March 1999. The following risk factors were tested by Cox proportional hazards modelling: age at transplant; sex; donor/recipient sex mismatch; donor/recipient cytomegalovirus (CMV) mismatch; cold and warm graft ischaemic times; and donor age. Pretransplant forced expiratory volume in one second (FEV1), minimum oxygen saturation obtained during 12 min walk (Sa,O2min), and a survival probability score (SP) calculated from FEV1, age adjusted resting heart rate, age, sex, blood haemoglobin (Hb), and serum albumin were then added to the model. None of the risk factors were significantly correlated with death during the study period. No evidence that clinical status prior to transplant has any effect upon the post-transplant survival of children with cystic fibrosis was found.

Adolescent↗

An investigation of the oral status and reported oral care of children with heart and heart-lung transplants.

AIM: To investigate the oral health status and oral microflora of children who have received heart and heart-lung transplants. Parental knowledge and current practice of oral health procedures by the child were also investigated. SAMPLE AND METHOD: Thirty-five children attending the Cardio-Thoracic Transplant Unit, Great Ormond Street Hospital for Children were included. Measurements were compared with children matched by age and gender attending the trauma clinic at the Department of Paediatric Dentistry, Eastman Dental Hospital. Teeth were examined for the presence or absence of caries or enamel defects. Plaque deposition, gingivitis, gingival bleeding and gingival enlargement were measured and a swab was taken to look at the oral microbial flora. A questionnaire was used to assess parental knowledge of dental health procedures and the current practice of these. RESULTS: There were no significant differences between transplant and control children in caries experience, plaque or gingivitis. Children with heart or heart-lung transplants had significantly greater numbers of enamel defects and more gingival enlargement than control children, children in the heart transplant group had significantly more gingival bleeding. There was little difference in the dental knowledge and reported behaviour of the transplant group compared to the control group. CONCLUSION: The dental needs of heart and heart-lung transplant patients treated at the Great Ormond Street Hospital for Children were similar to those of the control group in this study, however further improvement could be made in educating parents and children on the importance of caries prevention and good oral hygiene.

Adolescent↗

Lung transplantation and life extension in children with cystic fibrosis.

BACKGROUND: Lung transplantation has been available as therapy for end-stage lung disease since the early 1980s, but survival after transplantation remains poor, with continued controversy as to the survival benefit from the procedure. We examined the effect of lung or heart-lung transplantation on the survival of a cohort of children with cystic fibrosis and severe lung disease. METHODS: Between May, 1988, and May, 1998, 124 children with cystic fibrosis were accepted for lung transplantation. 47 received transplants, 68 died while they awaited organs, and nine remained on the active waiting list. We constructed a proportional-hazards model that used variables of prognostic significance in this population. By including transplant status as a time-dependent covariate, we were able to calculate a hazard ratio for transplantation. Date of entry into the study was the date when children were added to the list for transplantation, and measurements were taken at this time. Children were accepted for transplantation if they had a life expectancy of 2 years or less, a poor quality of life, and no contraindications to transplantation. FINDINGS: After 1 year, 35 (74%) children were still alive; after 5 years 12 (33%) children were alive. The univariate hazard ratio for transplantation was 0.41 (95% CI 0.23-0.74; p=0.003). Transplantation remained significantly associated with survival after correction for differences in age, sex, height-corrected forced expiratory volume in 1 s, minimum oxygen saturation during a 12 min walk, haemoglobin concentration, albumin concentration, and age-corrected resting heart rate (hazard ratio 0.31 [0.13-0.72]; p=0.007). INTERPRETATION: If centres follow our criteria for accepting patients for transplantation, and achieve similar survival after transplantation, they could expect a survival benefit for their patients in line with our results.

Adolescent↗

The EH1 domain of Eps15 is structurally classified as a member of the S100 subclass of EF-hand-containing proteins.

The Eps15 homology (EH) domain is a protein-protein interaction module that binds to proteins containing the asparagine-proline-phenylalanine (NPF) or tryptophan/phenylalanine-tryptophan (W/FW) motif. EH domain-containing proteins serve important roles in signaling and processes connected to transport, protein sorting, and organization of subcellular structure. Here, we report the solution structure of the apo form of the EH1 domain of mouse Eps15, as determined by high-resolution multidimensional heteronuclear NMR spectroscopy. The polypeptide folds into six alpha-helices and a short antiparallel beta-sheet. Additionally, it contains a long, structured, topologically unique C-terminal loop. Helices 2-5 form two EF-hand motifs. Structural similarity and Ca(2+) binding properties lead to classification of the EH1 domain as a member of the S100 subclass of EF-hand-containing proteins, albeit with a unique set of interhelical angles. Binding studies using an eight-residue NPF-containing peptide derived from RAB, the cellular cofactor of the HIV Rev protein, show a hydrophobic peptide-binding pocket formed by conserved tryptophan and leucine residues.

Adaptor Proteins, Signal Transducing↗

Heart or heart-lung transplantation: psychosocial outcome.

The psychosocial outcome of 23 heart and 21 heart-lung transplant recipients, aged 5-17 yrs, was determined and compared with the psychosocial outcome of a group of 46 children and adolescents who underwent conventional cardiac surgery. Preoperatively, and 12 months post-operatively, the patients' physical health status, mental state (ICD-9) and level of psychosocial functioning (GAF scale, DSM-IIIR) were assessed. There was an improvement in physical health in all groups. Preoperatively, psychiatric disorder, including anxiety and phobic states, depression and adjustment reaction, was noted in 6/23 (26%) children assessed for heart transplantation, 6/21 (28.5%) children assessed for heart-lung transplantation, and 12/46 (26%) children undergoing conventional cardiac surgery. The prevalence of psychiatric disorder remained in the transplant group but decreased in the non-transplant comparison group (6.5%). Improvement in overall levels of psychosocial functioning were found in all groups, but over 40% of all the participants were still functioning below normal levels. In summary, children with end-stage cardio-respiratory disease benefit physically and psychologically from heart or heart-lung transplantation treatment but there is a need for systematic psychosocial support both before and after transplantation.

Adolescent↗

Effect of fingerspelling task on temporal characteristics and perceived naturalness of speech in simultaneous communication.

This study investigated the effect of fingerspelling task length on temporal characteristics and perceived naturalness of speech produced during simultaneous communication. Stimulus words at four levels of fingerspelling task length were embedded in a sentence that was spoken and produced with simultaneous communication. Five temporal measures were calculated from acoustic recordings, and perceived speech naturalness was rated by a panel of listeners using a 9-point scale. Results indicated significant differences in temporal measures and naturalness ratings between the speech and simultaneous communication conditions and among levels of fingerspelling task length. Speech produced during simultaneous communication was rated as less natural and demonstrated increased interword interval, diphthong, word, and sentence durations. Regression analysis indicated significant correlations between temporal measures and perceived speech naturalness, and analysis of variance showed significant increases in segmental and interword interval durations and perceived speech unnaturalness as fingerspelling task length increased. These results are discussed in relation to previous findings regarding production and perception characteristics of speech that is altered in temporal parameters by a variety of conditions.

Communication↗

Incomplete adherence after pediatric heart and heart-lung transplantation.

BACKGROUND: Poor adherence to treatment after organ transplantation is life threatening. Clinical experience indicates that failure to adhere to the medical regimen after pediatric heart or heart-lung transplantation is more common than might be anticipated. This is the first empirical study of adherence in this population. METHODS: The subjects were 53 children and adolescents (mean age 10.3 years) who underwent transplantation and were followed up for 12 months after transplantation. At each attendance blood levels of cyclosporine were measured and medical diaries checked. For children who had undergone heart-lung transplantation, serial measures of respiratory function were obtained, both at home and in the laboratory. Levels of adherence to the immunosuppressive therapy and completion of the medical diary were determined on the basis of prior operational definitions. RESULTS: Satisfactory adherence to medication and satisfactory completion of the diaries were found in 37 children (70%). Satisfactory adherence to medication but unsatisfactory completion of the diaries were found in 11 children (21%). There was poor adherence to medication in 5 other children (9%) regardless of whether the diary was satisfactorily completed. Independent variables associated with poor adherence to medication were heart-lung as opposed to heart transplantation, one-parent or blended families, and family adjustment. CONCLUSION: Nearly one third of the sample showed unsatisfactory adherence to the treatment regimen. This relatively high prevalence indicates the importance of close monitoring of adherence. The identification of family characteristics as risk factors indicates a need for more intensive psychoeducational family counseling in the 12 months after transplantation.

Adaptation, Psychological↗

Psychosocial morbidity in children, and their families, awaiting heart or heart-lung transplantation.

Awaiting heart or heart lung transplantation is a time of extreme stress for child and family, but there has been little evaluation of the psychosocial morbidity in this population. This preliminary study monitored changes in the mental health status of these children and their families. Fifty-one children considered suitable for transplantation and their families were assessed at the time of acceptance onto the waiting list and 6 months later. Twenty-five percent of the children had a psychiatric disorder, and 60% had a degree of impairment in psychosocial functioning. These high levels of morbidity indicate the need for a more comprehensive approach to treatment for this population.

Adolescent↗

Complexes formed between calmodulin and the antagonists J-8 and TFP in solution.

The binding of the antagonists N-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide (J-8) and trifluoperazine (TFP) to intact calcium-saturated bovine calmodulin (CaM) and also of J-8 to the C-terminal domain (tr2c) has been investigated. Using a combination of NMR methods, including NOESY data, mobility measurements, and chemical shift and line-shape analysis, we show that the primary interaction between J-8 and tr2c is between the naphthalene ring of the antagonist and the hydrophobic pocket of the protein, similar to the binding of the hydrophobic side-chain residues of calmodulin target peptides. Comparison of the mobility of the drug, the intensity and pattern of intermolecular NOESY cross-peaks, and chemical shift changes shows that there is no significant change in the binding mode in J-8. CaM compared to J-8.tr2c, with one molecule binding to each domain. In particular, we find that the mobility of the aliphatic amino "tail" of J-8 remains highly mobile in both systems. This contrasts with the notion that the tail may bridge between the two domains to give a "globular" form of CaM. We also show that TFP induces very similar shift changes to J-8 and that the stoichiometry of the major binding event in all three cases is one drug molecule per domain. It also appears that secondary binding sites for the drug molecules are present in all three systems.

Animals↗

Pulmonary alveolar microlithiasis in childhood: diagnosis by transbronchial biopsy.

A 7-year-old girl of Arabic origin by consanguineous parents presented with a miliary pattern on chest x-ray. Transbronchial lung biopsy revealed a histological diagnosis of pulmonary alveolar microlithiasis, a condition rarely described in childhood. This report highlights the clinical and radiological features, documents the transbronchial lung biopsy as a useful diagnostic procedure, and suggests a possible genetic etiology with autosomal recessive inheritance.

Bronchoalveolar Lavage Fluid↗