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Biomedical subjects

D Kennedy

Publications and source records attributed to D Kennedy.

At least 55 records · Page 3Linked to original sources

Cognitive and behavioural performance in children with sleep-related obstructive breathing disorders.

Sleep-related obstructive breathing disorders (SROBD) are common in children. While the sequelae of cor pulmonae, and growth and developmental impairment have been well documented, neurocognitive deficits have been less well studied. There is emerging evidence that children with SROBD show reduced neurocognitive functioning especially in the inter-related areas of attentional capacity, memory and cognitive function. In addition, these children show increased problematic behaviour and reduced school performance. Early reports suggest that some of these deficits may be reversible with treatment. The genesis of the defects is unclear but may include hypoxaemia and subtle changes in sleep architecture. The natural history of SROBD and long-term effects on neurocognitive functioning and behaviour remain to be fully examined.

Journal Article↗

The relationship between the quality of life of children with asthma and family functioning.

The quality of life of 84 children with asthma, aged 7-12 years, and their family functioning was assessed using standard questionnaires. A significant relationship was found between children's reports of their quality of life and several key dimensions of family functioning. The results suggest that independent of their frequency, the extent to which asthma symptoms upset and bother children varies depending on the level of the functioning of the children's families. Treatment approaches designed to improve family functioning may reduce the extent to which children are bothered by their asthma symptoms and thus improve their quality of life.

Adult↗

Provider adherence to a clinical practice guideline for acute asthma in a pediatric emergency department.

UNLABELLED: Critics of the use of clinical practice guidelines (CPGs) in an emergency department (ED) setting believe that they are too cumbersome and time-consuming, but to the best of the authors' knowledge, potential barriers to CPG adherence in the ED have not been prospectively evaluated. OBJECTIVES: To measure provider adherence to an ED CPG based on National Asthma Education and Prevention Program (NAEPP) recommendations, and to determine factors associated with provider nonadherence. METHODS: Prospective, cohort study of children aged 1-18 years with the diagnosis of an acute exacerbation of asthma who were seen in a pediatric ED and requiring admission, as well as a random selection of children discharged to home following pediatric ED care. The following adherence parameters were assessed: at least three nebulized albuterol treatments in the first hour; early steroid administration (after the first nebulizer treatment); clinical assessments using pulse oximetry and peak expiratory flow (PEF) (for children >6 years old); and use of a clinical score to assess acute illness severity (Asthma Severity Score). Nonadherence was defined as any deviation of the above parameters. RESULTS: Between July 1, 1998, and June 30, 1999, 369 patients were studied. Of these, 38% (139) were discharged to home, 38% (140) were admitted to the observation unit, and 24% (90) were admitted to the inpatient unit. Illness severities at initial presentation to the ED were: 24% (86) had mild exacerbations, 59% (212) had moderate exacerbations, and 17% (62) had severe exacerbations. Sixty-eight percent (95% CI = 63% to 73%) of the patients were managed with complete adherence to the CPG. Of the 32% with some form of nonadherence, most (63%) were children older than 6 years; in this group 64% (48/75) were nonadherent due to lack of PEF assessment. When PEF assessment was disregarded, an 83% (95% CI = 79% to 87%) adherence to the CPG was achieved. Other nonadherence factors included: lack of at least three nebulized albuterol treatments provided timely within the first hour (5%); delay in steroid administration (6%); lack of pulse oximeter use (0.5%); and failure to record clinical score to assess severity (1.1%). Patient age, illness severity (acute and chronic), first episode of wheezing, and high ED volume periods (evenings and weekends) did not worsen adherence. CONCLUSIONS: Clinical practice guidelines can be used successfully in the pediatric ED and provide a more efficient management and treatment approach to acute exacerbations of childhood asthma. With a systematic and concise CPG, barriers to adherence in a pediatric ED appear to be minimal, with the exception of using PEF in the routine ED assessment.

Adolescent↗

Absent hematuria and expensive computerized tomography: case characteristics of emergency urolithiasis.

PURPOSE: We validated the descriptive characteristics of emergency cases presenting with urolithiasis, determined the incidence of normal urinalysis in such cases and compared the expense of diagnostic computerized tomography (CT) and excretory urography (IVP). MATERIALS AND METHODS: We retrospectively reviewed the charts of all consecutive patient visits to a community emergency department for 48 months. Explicit protocols for case selection, data abstraction and monitoring were used to maximize accuracy. Entry criteria were urolithiasis diagnosed by IVP, CT or stone passage, and urinalysis. Data analysis included descriptive statistics and the calculation of confidence intervals. RESULTS: From 159,083 emergency visits during this period 397 met study entry criteria. Absent hematuria was noted in 9% (95% confidence interval 7% to 12%) of patients with proved urolithiasis. There was no correlation of the degree of obstruction with absent hematuria. Most patients presenting with painful urolithiasis were male (73%), in the fifth decade of life (mean age 47 years), had stones in the mid ureter (32%) or at the ureterovesicular junction (44%) and received opiates for pain control (91%). Of the patients 48% presented between 5 p.m. and 7 a.m. when the radiology department was available only for emergency imaging. The diagnosis was made by CT in half of the patients, who were charged $1,409. The maximal insurance reimbursement was $673. The diagnosis was made by IVP in half of the patients, who were charged $445. The maximal insurance reimbursement was $141. CONCLUSIONS: Hematuria is not universally present in patients with painful urolithiasis and does not correspond to the degree of obstruction. Despite previous reports to the contrary, CT is significantly more expensive for patients than IVP.

Adolescent↗

Triple play.

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Animals↗

UNCL, the mammalian homologue of UNC-50, is an inner nuclear membrane RNA-binding protein.

We isolated a mammalian homologue of the C. elegans gene unc-50 that we have named UNCL. The 777 kb rat UNCL cDNA encodes a 259 amino acid protein that is expressed in a wide variety of tissues with highest mRNA levels in brain, kidney and testis. Hydropathy plot analysis and in vitro translation experiments with microsomal membranes indicate that UNCL is a transmembrane protein. Hemagglutinin tagged UNCL was stably transfected into SaOS-2 osteosarcoma cells and exhibited a nuclear rim staining pattern which was retained following extraction with 1% Triton X-100, suggesting that UNCL localizes to the inner nuclear membrane. UNCL-HA was extractable in 350 mM NaCl, suggesting that UNCL is not associated with the nuclear matrix. Homopolymer RNA-binding assays performed on in vitro translated UNCL protein and 'structural modeling by homology' suggest that UNCL binds RNA via an amino-terminal RNA Recognition-like Motif. Since unc-50 is required for expression of assembled muscle-type nicotinic receptors in the nematode we investigated whether UNCL had a similar function for mammalian nicotinic receptors. When UNCL was co-expressed with neural nicotinic receptors in Xenopus oocytes or COS cells it increased expression of functional cell surface receptors up to 1. 6-fold. We conclude that UNCL is a novel inner nuclear membrane protein that associates with RNA and is involved in the cell-surface expression of neuronal nicotinic receptors. UNCL plays a broader role because UNCL homologues are present in two yeast and a plant species, none of which express nicotinic receptors and it is also found in tissues that lack nicotinic receptors.

Amino Acid Sequence↗

Coming aboard.

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Periodicals as Topic↗

Inverted duplication of the distal short arm of chromosome 3 associated with lobar holoprosencephaly and lumbosacral meningomyelocele.

A fetus with lobar holoprosencephaly and lumbosacral meningomyelocele associated with duplication of the short arm of chromosome 3 is reported. The anomalies were detected on fetal ultrasound at 20 weeks' gestation and the autopsy findings correlated well with the prenatal findings. The fetal karyotype was 46,XY,der(3)del(3)(p26) dup(3)(p26p21.3). The association of holoprosencephaly with duplication 3p is well known, but to the best of our knowledge this is the first reported association of meningomyelocele with 3p duplication. These findings suggest that a gene or genes with a crucial role in central nervous system development are located on the short arm of chromosome 3.

Abnormalities, Multiple↗

Interaction of Pex5p, the type 1 peroxisome targeting signal receptor, with the peroxisomal membrane proteins Pex14p and Pex13p.

Pex5p, a receptor for peroxisomal matrix proteins with a type 1 peroxisome targeting signal (PTS1), has been proposed to cycle from the cytoplasm to the peroxisomal membrane where it docks with Pex14p and Pex13p, the latter an SH3 domain-containing protein. Using in vitro binding assays we have demonstrated that binding of Pex5p to Pex14p is enhanced when Pex5p is loaded with a PTS1-containing peptide. In contrast, Pex5p binding to Pex13p, which involves only the SH3 domain, occurs at 20-40-fold lower levels and is reduced when Pex5p is preloaded with a PTS1 peptide. Pex14p was also shown to bind weakly to the Pex13p SH3 domain. Site-directed mutagenesis of the Pex13p SH3 domain attenuated binding to Pex5p and Pex14p, consistent with both of these proteins being binding partners for this domain. The SH3 binding site in Pex5p was determined to lie within a 114-residue peptide (Trp(100)-Glu(213)) in the amino-terminal region of the protein. The interaction between this peptide and the SH3 domain was competitively inhibited by Pex14p. We interpret these data as suggesting that docking of the Pex5p-PTS1 protein complex at the peroxisome membrane occurs at Pex14p and that the Pex13p SH3 domain functions as an associated component possibly involved in sequestering Pex5p after relinquishment of the PTS1 protein cargo to components of the translocation machinery.

Amino Acid Sequence↗

Association between parental perception of children's vulnerability to illness and management of children's asthma.

This study examined the relationship between asthma management strategies used by parents and parental perception of children's vulnerability to illness. Home interviews were conducted with 101 parents of children previously hospitalized with asthma. The child vulnerability scale (CVS) was employed to assess parents' perception of their children's vulnerability to illness. The asthma severity index (ASI) was used to measure the frequency and intensity of asthma symptoms experienced by children in the preceding 12 months. Five markers of parental asthma management were assessed: (i) school absences; (ii) visits to the general practitioner (GP); (iii) visits to the emergency room (ER); (iv) hospitalizations; and (v) whether children are using a regular preventer. After controlling for the frequency and intensity of children's asthma symptoms, parents who perceived that their children were more vulnerable to medical illness were significantly more likely to keep their children home from school (P = 0.01), were more likely to take their children to the GP for acute asthma care (P = 0.02), and were more likely to be giving their children regular preventer medication (P = 0.02). In contrast, the use of tertiary pediatric care services was not significantly associated with parental perceptions of their children's vulnerability. The results suggest that parental attitudes and beliefs about the vulnerability of their children to illness were associated with greater use of GP services by parents and more frequent school absences for children. The use of hospital services by parents appeared to be more strongly associated with the actual level of children's asthma symptoms than their vulnerability to illness.

Absenteeism↗

Comparison of serum and urine assays for biochemical markers of bone resorption in postmenopausal women with and without hormone replacement therapy and in men.

Biochemical markers of bone resorption have been used to characterize metabolic bone disease and assess therapeutic response. Most studies have used the urinary measurement of collagen crosslinks, but serum assays have recently been developed that may have less analytic and biologic variability. In the present study, we measured urine and serum N- and C-terminal crosslinked telopeptides of type I collagen (NTX and CTX) and serum bone sialoprotein (BSP) in postmenopausal women with or without hormone replacement therapy (HRT) and in men of similar age. In these populations, the variability of serum and urine markers was similar, except that serum NTX showed somewhat lower variability in postmenopausal women. Urine and serum assays correlated well with one another and were significantly lower in postmenopausal women on HRT compared with untreated women. The difference in women on HRT was similar for sNTX, uNTX and BSP (35-40%) and greater for sCTX and uCTX (52-53%). There was an inverse correlation between markers and bone mineral density, largely attributable to the high correlation in women not on HRT. Fractional excretion of NTX and CTX were estimated at 0.20+/-0.07 and 0.44+/-0.11, respectively. These values were independent of the concentration of the marker or of creatinine in the urine. We conclude that serum markers are useful measures of bone resorption in these populations, in whom the use of such markers is likely to be helpful in the management of osteoporosis.

Adult↗

Cerebral mucormycosis: proton MR spectroscopy and MR imaging.

Proton magnetic resonance spectroscopy (MRS) was integrated with magnetic resonance imaging (MRI) in the evaluation of a case of cerebral mucormycosis. MRS showed markedly elevated lactate, depleted N-acetyl aspartate and metabolite resonances attributable to succinate and acetate. The spectroscopy profile is essentially similar to that of bacterial abscess but without the commonly seen resonances of the amino acids valine, leucine and isoleucine. Our extensive literature review did not yield any reports of MRS findings on cerebral mucormycosis. MRS prospectively limited the differential diagnoses given the otherwise nonspecific and complex MR imaging findings in our immunosuppressed patient.

Adult↗

The relationship between asthma severity, family functioning and the health-related quality of life of children with asthma.

This study compared the health-related quality of life (HRQL) of 236 children with mild or moderate/severe asthma with that of a large representative sample of children in the general community. The study also examined the relationship between the HRQL of children with asthma and their demographic characteristics, asthma severity and family functioning. Children with asthma had a significantly poorer HRQL than other children in the community. Amongst the children with asthma, parents reported that children living in single-parent families had poorer physical health, mental health and social functioning than children in two-parent families. There was a significant relationship between the mental health of children with asthma and family functioning but no significant relationship between their physical health and family functioning. These findings suggest that the domains comprising the HRQL of children with asthma are related to both disease and non-disease factors. A better understanding of these relationships will facilitate the development of new interventions to help children with asthma.

Asthma↗