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Biomedical subjects

P Davies

Publications and source records attributed to P Davies.

At least 19 recordsLinked to original sources
PubMed2007

Anaesthetic outcome and predictive risk factors in children with mediastinal tumours.

PURPOSE: The aims were to identify and test the significance of specific factors associated with risks for anaesthesia in children with mediastinal tumours. PATIENTS AND METHOD: Clinical information was retrospectively collected from the records of 63 children presented with mediastinal tumour (1964-2002) in a regional Paediatric Oncology centre and correlated with the type and outcome of anaesthesia, using non-parametric analyses. RESULTS: Thirteen patients had local anaesthesia or sedation for diagnostic procedures and none developed any complication. Fifty children received general anaesthesia (GA) for diagnostic investigations or tumour resection. Two patients were excluded from the analysis because of treatment prior to GA. Problems with intubation, ventilation and cardiovascular collapse were encountered in 7 of 48 (15%) patients and this resulted in tracheostomy in one patient and death in 2 other cases. When compared with the 41 uncomplicated cases, the presence of at least 3 respiratory symptoms/signs, tracheal and vascular compression, and infection significantly increased the risk of GA. Of these, tracheal compression remained the strongest predictive factor. CONCLUSIONS: Decision to postpone GA should be considered if all these risk factors (tracheal compression, vascular compression, the presence of at least three respiratory symptoms/signs) are present in the same patient.

Adolescent↗
PubMed2006

A randomised trial comparing 5 mL/kg and 10 mL/kg of pentastarch as a volume preload before spinal anaesthesia for elective caesarean section.

BACKGROUND: Colloid solutions are more effective at preventing hypotension than crystalloids when used as a volume preload before caesarean delivery under spinal anaesthesia. The ideal volume to infuse has not been established. METHOD: In a randomised double-blind trial 70 women presenting for elective caesarean section received either 5 mL/kg of pentastarch (group A) or 10 mL/kg of pentastarch (group B) as a volume preload before spinal anaesthesia. Hypotension was defined as a systolic pressure below 90 mmHg or a decrease of 30% from a baseline value. Treatment was with 6-mg increments of ephedrine until resolution. RESULTS: In group B, 7/35 patients (20%) developed hypotension, significantly fewer than the 15/35 (42.8%) in group A (P<0.05). The patients in group B also required less ephedrine (total in group, 114 mg) than those in group A (total in group, 198 mg) CONCLUSIONS: Pentastarch, 10 mL/kg is more effective than 5 mL/kg at preventing hypotension following spinal anaesthesia for caesarean delivery.

Adult↗
PubMed2006

'Ready to drink' protein substitute is easier is for people with phenylketonuria.

UNLABELLED: In phenylketonuria (PKU), compliance with taking protein substitute is an issue in teenage and older patients. A 'ready to drink' protein substitute may overcome many of the practical issues associated with its administration. OBJECTIVE: To investigate the efficacy of a liquid protein substitute in a 6-week, three-part, randomized, crossover, controlled study. METHODS: 27 subjects (15 female; 12 male) with PKU with a median age of 30 years (range 8-49 years) were recruited. One subject withdrew from the study. Their median daily dose of protein equivalent was 60 g (range 45-75 g). In parts 1 and 2, subjects were randomized to either a liquid or a powder protein substitute with the same nutritional composition per unit (each 130 ml liquid pouch or 25 g powder sachet contained 15 g protein equivalent). In part 3, subjects chose liquid, powder or a combination of both. Weekly blood phenylalanine (Phe) concentrations were estimated, and during weeks 2, 4 and 6 subjects completed a daily questionnaire on administration issues. RESULTS: All but one of 26 subjects chose the liquid in part 3 as either their sole (69%, n = 18) or partial source (28%, n = 7) of protein substitute. Blood Phe concentrations were significantly better on the liquid (p = 0.03). With the liquid protein substitute, subjects were less self-consciousness (p = 0.003) and found it easier to take away from home (p = 0.001). Overall, the liquid was easier (p < 0.0001), more convenient (p = 0.002) and resulted in less wastage of protein substitute (p = 0.001). CONCLUSION: Liquid protein substitute was popular and efficacious, reduced self-consciousness and overall improved compliance of teenagers and adults with PKU.

Adolescent↗
PubMed2006

Viruses: agents of coral disease?

The potential role of viruses in coral disease has only recently begun to receive attention. Here we describe our attempts to determine whether viruses are present in thermally stressed corals Pavona danai, Acropora formosa and Stylophora pistillata and zoanthids Zoanthus sp., and their zooxanthellae. Heat-shocked P. danai, A. formosa and Zoanthus sp. all produced numerous virus-like particles (VLPs) that were evident in the animal tissue, zooxanthellae and the surrounding seawater; VLPs were also seen around heat-shocked freshly isolated zooxanthellae (FIZ) from P. danai and S. pistillata. The most commonly seen VLPs were tail-less, hexagonal and about 40 to 50 nm in diameter, though a diverse range of other VLP morphotypes (e.g. rounded, rod-shaped, droplet-shaped, filamentous) were also present around corals. When VLPs around heat-shocked FIZ from S. pistillata were added to non-stressed FIZ from this coral, they resulted in cell lysis, suggesting that an infectious agent was present; however, analysis with transmission electron microscopy provided no clear evidence of viral infection. The release of diverse VLPs was again apparent when flow cytometry was used to enumerate release by heat-stressed A. formosa nubbins. Our data support the infection of reef corals by viruses, though we cannot yet determine the precise origin (i.e. coral, zooxanthellae and/or surface microbes) of the VLPs seen. Furthermore, genome sequence data are required to establish the presence of viruses unequivocally.

Animals↗
PubMed2006

Paracetamol induced hepatotoxicity.

AIM: To identify the clinical and biochemical risk factors associated with outcome of paracetamol induced significant hepatotoxicity in children. METHODS: Retrospective case notes review of those with paracetamol overdose admitted from 1992 to 2002. Patients were analysed in two groups: group I recovered after conservative treatment and group II developed progressive liver dysfunction and were listed for liver transplantation. RESULTS: Of 51 patients (6 males, 45 females, aged 0.8-16.1 years), 6 (aged <7 years) received cumulative multiple doses, and 45 a single large overdose (median 345 mg/kg, range 91-645). The median (range) interval to hospital at presentation post-ingestion was 24 hours (4-65) and 44 hours (24-96) respectively in groups I and II. Patients received standard supportive treatment including N-acetylcysteine. All children in group I survived. In group II, 6/11 underwent orthotopic liver transplantation (OLT) and 2/6 survived; 5/11 died awaiting OLT. Cerebral oedema was the main cause of death. Children who presented late to hospital for treatment and those with progressive hepatotoxicity with prothrombin time >100 seconds, hypoglycaemia, serum creatinine >200 micromol/l, acidosis (pH <7.3), and who developed encephalopathy grade III, had a poor prognosis or died. Although hepatic transaminase levels were markedly raised in both groups, there was no correlation with necessity for liver transplantation or death. CONCLUSION: Accidental or incidental paracetamol overdose in children may be associated with toxic liver damage leading to fulminant liver failure. Delayed presentation and/or delay in treatment, and hepatic encephalopathy > or =grade III were significant risk factors, implying poor prognosis and need for OLT. Prompt identification of high risk patients, referral to a specialised unit for management, and consideration for liver transplantation is essential.

Acetaminophen↗
PubMed2006

Protein substitute dosage in PKU: how much do young patients need?

BACKGROUND: The optimal dose of protein substitute has not been determined in children with phenylketonuria (PKU). AIM: To determine if a lower dose of protein substitute could achieve the same or better degree of blood phenylalanine control when compared to the dosage recommended by the UK MRC.(1) METHODS: In a six week randomised, crossover study, two doses of protein substitute (Protocol A: 2 g/kg/day of protein equivalent; Protocol B: 1.2 g/kg/day protein equivalent) were compared in 25 children with well controlled PKU aged 2-10 years (median 6 years). Each dose of protein substitute was taken for 14 days, with a 14 day washout period in between. Twice daily blood samples (fasting pre-breakfast and evening, at standard times) for plasma phenylalanine were taken on day 8-14 of each protocol. The median usual dose of protein substitute was 2.2 g/kg/day (range 1.5-3.1 g/kg/day). RESULTS: When compared with control values, median plasma phenylalanine on the low dose of protein substitute increased at pre-breakfast by 301 mumol/l (95% CI 215 to 386) and in the evening by 337 micromol/l (95% CI 248 to 431). On the high dose of protein substitute, plasma phenylalanine concentrations remained unchanged when compared to control values. However, wide variability was seen between subjects. CONCLUSIONS: A higher dosage of protein substitute appeared to contribute to lower blood phenylalanine concentrations in PKU, but it did have a variable and individual impact and may have been influenced by the carbohydrate (+/- fat) content of the protein substitute.

Child↗
PubMed2006

The regulation of tau phosphorylation by PCTAIRE 3: implications for the pathogenesis of Alzheimer's disease.

In the course of Alzheimer's disease, phosphorylated tau aggregates to form paired helical filaments, highly ordered filamentous structures that accumulate within neurons and contribute to the formation of neurofibrillary tangles. This study examines the role of PCTAIRE 3, a cdc2 family protein kinase, within this disease process. We report an elevation in the protein levels of PCTAIRE 3 in the temporal cortex of AD relative to control brains. Analysis of paired helical filaments prepared from AD brain tissue indicates that PCTAIRE 3 is concentrated within this pathological material. Overexpression of PCTAIRE 3 in cell culture suggests that the protein acts indirectly to stimulate phosphorylation at the pT231 and pS235 sites on tau, residues that are modified early in the process of AD pathogenesis. The resurgence of cell cycle proteins is an important mechanism in Alzheimer's disease (AD), and we propose that PCTAIRE 3 is a PHF-associated kinase that modulates tau phosphorylation.

Actins↗
PubMed2006

Structural dynamics of the human androgen receptor: implications for prostate cancer and neurodegenerative disease.

The AR (androgen receptor) is a ligand-activated transcription factor that mediates the action of the steroids testosterone and dihydrotestosterone. Alterations in the AR gene result in a number of clinical disorders, including: androgen-insensitivity, which leads to disruption of male development; prostate cancer; and a neuromuscular degenerative condition termed spinal bulbar muscular atrophy or Kennedy's disease. The AR gene is X-linked and the protein is coded for by eight exons, giving rise to a C-terminal LBD (ligand-binding domain; exons 4-8), linked by a hinge region (exon 4) to a Zn-finger DBD (DNA-binding domain; exons 2 and 3) and a large structurally distinct NTD (N-terminal domain; exon 1). Identification and characterization of mutations found in prostate cancer and Kennedy's disease patients have revealed the importance of structural dynamics in the mechanisms of action of receptors. Recent results from our laboratory studying genetic changes in the LBD and the structurally flexible NTD will be discussed.

Amino Acid Sequence↗
PubMed2006

Should high-energy infant formula be given at full strength from its first day of usage?

OBJECTIVE: To evaluate the feeding tolerance of a high-energy (1 kcal mL(-1)) infant formula (HEIF) for infants with faltering growth, weighing 2.5-8 kg, when administered at full strength from day 1 compared with stepwise introduction. METHODS: Thirty infants (aged 2-43 weeks) from a supraregional children's hospital requiring a high-energy formula for faltering growth were randomly allocated to receive either a 1 kcal mL(-1) ready to feed infant formula at full strength from day 1 or the same formula in diluted form, graded to full strength over 3 days. Bowel actions, vomits and volume of feed taken were recorded daily for 2 weeks. Weight, length, head circumference and mid-upper arm circumference were recorded at recruitment and after 2 weeks. RESULTS: The number of bowel actions in the first 2 days was significantly higher for the full strength group than for the stepwise group (P = 0.02); younger infants (<12 weeks) had more bowel actions over the first 2 days on the HEIF at full strength (Spearman's correlation = -0.5; P = 0.04); and infants with a total higher energy intake (kJ kg(-1)) had more frequent bowel actions over the first 4 days (Spearman's correlation = 0.48; P = 0.01). There was no significant difference between groups for growth or vomiting. CONCLUSIONS: High-energy infant formula was generally well tolerated in infants under the age of 12 months with faltering growth when administered at full strength from day 1. However, younger infants (<12 weeks of age) may benefit from a graded introduction in order to avoid increased bowel frequency.

Double-Blind Method↗
PubMed2006

Home delivery of dietary products in inherited metabolic disorders reduces prescription and dispensing errors.

UNLABELLED: In the UK, for patients with inherited metabolic disorders (IMD) the traditional system for acquiring essential dietary products [patient prompted prescriptions generated by a medical general practitioner (GP) and dispensed by a chemist] is problematic. OBJECTIVE: To investigate the efficacy of a home delivery service (HDS) for essential dietary products (EDP) (i.e. protein substitutes, milk replacements, energy and vitamin and mineral supplements) for subjects with IMD, particularly examining any prescription and dispensing errors, metabolic control and consumer satisfaction. METHODS: A prospective, controlled, home delivery trial for EDP was conducted in patients with IMD for 12 months. Sixty-two patients with IMD [50 with phenylketonuria (PKU); 12 with other IMD: aged 6 months-30 years] were recruited. Thirty subjects used a monthly HDS (Homeward: Nutricia) to receive EDP, 32 remained on the traditional system. Each month, the HDS checked home stock levels of EDP, obtained their prescriptions directly from GP's, and then delivered them to the subjects' homes. An independent researcher completed monthly telephone interviews with patients/parents about any EDP prescription errors or delay in receipt. RESULTS: Incorrect protein substitute was dispensed once by the HDS compared with nine subjects who had 12 errors in the control group (P = 0.01); incorrect flavours of protein substitute were dispensed to the home delivery group once compared with eight subjects getting 11 errors via the chemist (P = 0.03). The HDS delayed delivery of protein substitute for one subject on three occasions compared with 39 occasions in 16 subjects via the chemist (P = 0.001). In patients with PKU, plasma phenylalanine control deteriorated in the control group (P < 0.05) but not in the HDS group. CONCLUSIONS: The long-term use of a HDS for EDP in IMD is safer, effective and more reliable than conventional systems.

Adolescent↗
PubMed2006

Deep brain stimulation for neuropathic cephalalgia.

The aim of this study was to determine the efficacy of deep brain stimulation (DBS) in the treatment of various types of intractable head and facial pains. Seven patients underwent the insertion of DBS electrodes into the periventricular/periaqueductal grey region and/or the ventroposteromedial nucleus of the thalamus. We have shown statistically significant improvement in pain scores (visual analogue and McGill's) as well as health-related quality of life (SF-36v2) following surgery. There is wide variability in patient outcomes but, overall, DBS can be an effective treatment. Our results are compared with the published literature and electrode position for effective analgesia is discussed.

Adult↗
PubMed2005

Tau protein abnormalities associated with the progression of alzheimer disease type dementia.

The degree to which neurofibrillary tangles (NFT), the hallmark lesions of Alzheimer disease (AD), contribute to the development of the cognitive symptoms of AD has been debated. NFTs are comprised of abnormally phosphorylated and conformationally altered tau proteins. Conformational changes in tau have been proposed to be among the earliest neurobiological changes in AD. This study examined whether conformational changes detected by antibodies MC1 and TG3 represent early abnormalities in the disease process by assessing their presence at different stages of dementia in multiple brain regions. Postmortem specimens from several neocortical regions were examined for conformational changes in tau by ELISA in subjects [n=81] who died at different stages of cognitive impairment. Concentrations of conformationally altered tau increased with increasing dementia severity and the levels of MC1 immunoreactivity increased in the frontal cortex of mildly demented subjects before the appearance of NFT bearing neurons, suggesting that conformational alterations in tau occur early in the course of AD and its cognitive symptoms and may precede histologically identified NFTs.

Aged↗
PubMed2005

Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment.

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.

Aged↗
PubMed2005

A serial cross-sectional study of the prevalence of rabbit haemorrhagic disease on three farms in the lower North Island of New Zealand.

AIM: To estimate over a 3-year period following the first release of rabbit haemorrhagic disease virus (RHDV) the prevalence of rabbit haemorrhagic disease (RHD) and the abundance of rabbits (Oryctolagus cuniculus) in an area that historically had low rabbit densities. METHODS: Three farms grazing predominantly sheep and beef cattle, located close together and with low initial rabbit densities, were selected for study. RHDV had been deliberately released on all farms in December 1997. Farms were visited 2-3 times per year between June 1998 and April 2001. At each visit, rabbits were shot with the aid of spotlights at night and blood samples were collected for detection of RHDV antibodies. Rabbit carcasses were necropsied and the age of the animals was determined. Rabbit abundance on each property was measured throughout the study using spotlight night counts. Logistic regression was used to identify factors associated with the risk of carcasses being seropositive for RHDV. RESULTS: Rabbit density differed initially between farms (8.2, 9.9, 2.3 rabbits per spotlight km in June 1998), and declined on all three properties over time (1.2, 2.4, 1.1 rabbits per spotlight km in November 2000). Highest antibody titres to RHDV were initially evident on the farm on which rabbits were most abundant. The average prevalence of seropositive rabbits overall was 21% (95% CI=15-28%). Female rabbits tended to be less likely to be seropositive for RHDV than males (OR=0.47; 95% CI=0.21-1.02). The odds of becoming seropositive were reduced for rabbits born in the breeding season of 1999-2000 (OR=0.17; 95% CI=0.05-0.64). CONCLUSIONS: The temporal pattern of outbreaks measured by peaks of seroprevalence differed between closely-spaced farms when they had different rabbit densities, but were similar when rabbit densities were similar. Microclimate and vegetation influencing abundance of insect vectors for RHDV and intrinsic population-related factors like rabbit breeding behaviour are also likely to be involved in local patterns of spread.

Animals↗
PubMed2005

Generation and characterization of monoclonal antibodies to human PCTAIRE 3.

Monoclonal antibodies specific for the unique N-terminal domain of the PCTAIRE 3 protein kinase have been produced and characterized. The specificity of these antibodies has been assessed by ELISA, Western blot, and immunoflorescence techniques. These reagents are specific for recombinant PCTAIRE 3 of human origin and do not cross-react with PCTAIRE 1 or PCTAIRE 2, despite the high homology between members of the PCTAIRE subfamily of cdc2-like kinases. Immunoblotting of transfected cells reveals that all of the antibodies recognize both isoforms of the PCTAIRE 3 kinase. Epitope mapping reveals three distinct classes of PCTAIRE 3 antibodies that recognize different sites within an immunodominant region of the N-terminal domain of the protein. The creation of highly specific PCTAIRE 3 monoclonal reagents will be useful for assessing the native distribution and function of this protein.

Amino Acid Sequence↗
PubMed2005

Seasonal occurrence of impetigo: a retrospective 8-year review (1996-2003).

Impetigo, a common skin infection, has shown seasonal variation in African, Australian and Indian studies. We investigated seasonal variation of impetigo in a UK paediatric population. A total of 1552 children with impetigo were seen in the Accident and Emergency (A&E) department between 1996 and 2003. The number of impetigo cases was always higher in late summer than in winter, and furthermore, increased year on year. These changes could not be accounted for by variation in total patient numbers seen in A&E, and suggest a correlation between impetigo frequency and climatic temperature. Possible reasons for these findings include exposed skin due to loose clothing in the summer leading to more skin-to-skin contact and minor trauma.

Child↗
PubMed2005

Influence of weather conditions on fly abundance and its implications for transmission of rabbit haemorrhagic disease virus in the North Island of New Zealand.

Blowflies (Diptera: Calliphoridae) and flesh flies (Diptera: Sarcophagidae) are potential vectors of rabbit haemorrhagic disease virus (RHDV) in New Zealand. The associations between habitat and weather factors on the abundance of these flies were investigated. Between October 1999 and June 2001, flies were trapped on open pasture and in dense vegetation patches on farmland in the Himatangi area of the North Island. Five calliphorid species were trapped commonly at scrub edges and the most abundant sarcophagid, Oxysarcodexia varia Walker, was trapped mainly on open pasture. An abundance peak of O. varia was probably associated with the occurrence of a rabbit haemorrhagic disease (RHD) outbreak in the study area. Overall abundance of flies varied according to habitat and species, and species numbers differed between seasons and years. The all-day minimum temperature 3 weeks before trapping was a significant variable in all models of fly abundance, whereas average rainfall did not affect fly abundance. The all-day temperature range was significant only for O. varia. The influence of other climatic factors varied between fly species. Climate dependent variations in fly abundance may contribute to the risk of transmission of RHD, which occurred intermittently on the site during the study period.

Animals↗