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Biomedical subjects

P Gaffney

Publications and source records attributed to P Gaffney.

At least 19 recordsLinked to original sources

Validation of a food-frequency questionnaire assessment of carotenoid and vitamin E intake using weighed food records and plasma biomarkers: the method of triads model.

BACKGROUND: Reliability or validity studies are important for the evaluation of measurement error in dietary assessment methods. An approach to validation known as the method of triads uses triangulation techniques to calculate the validity coefficient of a food-frequency questionnaire (FFQ). OBJECTIVE: To assess the validity of an FFQ estimates of carotenoid and vitamin E intake against serum biomarker measurements and weighed food records (WFRs), by applying the method of triads. DESIGN: The study population was a sub-sample of adult participants in a randomised controlled trial of beta-carotene and sunscreen in the prevention of skin cancer. Dietary intake was assessed by a self-administered FFQ and a WFR. Nonfasting blood samples were collected and plasma analysed for five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene) and vitamin E. Correlation coefficients were calculated between each of the dietary methods and the validity coefficient was calculated using the method of triads. The 95% confidence intervals for the validity coefficients were estimated using bootstrap sampling. RESULTS: The validity coefficients of the FFQ were highest for alpha-carotene (0.85) and lycopene (0.62), followed by beta-carotene (0.55) and total carotenoids (0.55), while the lowest validity coefficient was for lutein (0.19). The method of triads could not be used for beta-cryptoxanthin and vitamin E, as one of the three underlying correlations was negative. CONCLUSIONS: Results were similar to other studies of validity using biomarkers and the method of triads. For many dietary factors, the upper limit of the validity coefficients was less than 0.5 and therefore only strong relationships between dietary exposure and disease will be detected.

Adult↗

A neoantigenic determinant in the D-dimer fragment of fibrin.

Monoclonal antibody (mAb) III-3b binds D-dimer with K(d)=1.4 x 10(-10) M without cross-reaction with fibrin(ogen). The epitope for this mAb is in Bbeta134-190, presumably in Bbeta155-160. The latter site is buried in the coiled coil structure of fibrin(ogen) but it is exposed as a neoantigenic determinant in D-dimer upon plasmic lysis of fibrin. mAb III-3b may be used as a tool for immunodiagnostic quantification of D-dimer in blood plasma.

Antibodies, Monoclonal↗

A laboratory test request protocol system.

This paper describes the design, implementation and assessment of a computer-based protocol application to support requests by clinicians for laboratory investigations. As part of the motivation for the work a rigorous engineering software approach was adopted not just for purely technical reasons but also as a means of maximising the role of the user.

Clinical Laboratory Techniques↗

Association analysis of somatostatin receptor (SSTR1 and SSTR2) polymorphisms in breast cancer and solar keratosis.

The presence of somatostatin receptors (SSTR1-5) in tumour cells indicates a potential for somatostatin to bind and suppress growth, as well as allowing for therapeutic treatment with somatostatin analogues. The genes for SSTR1 and SSTR2 have been shown to contain dinucleotide repeat polymorphisms. We have performed association studies on breast cancer and solar keratosis populations to determine whether these genes play a role in the development of these conditions. Results showed that there was no significant difference between SSTR1 and SSTR2 polymorphism frequencies in the tested breast cancer population (P = 0.59 and P = 0.54, respectively) nor the solar keratosis population (P = 0.10 and P = 0.883, respectively) as compared to unaffected populations. Hence, these studies do not support a role for these receptor genes in either breast cancer or solar keratosis lesions.

Alleles↗

Vitamin deficiency in a toddler reluctant to use her arm.

Children frequently present to accident and emergency departments with limb pain, usually following trauma. An unusual cause of atraumatic limb pain in a toddler is described in this report. Rickets should be added to the differential diagnosis of atraumatic limb pain in this age group. The possibility of acute bony injury (following unwitnessed trauma) not apparent on X-ray needs to be considered in this case. Suspicion of rickets, based on clinical features and radiographic findings, can be confirmed by biochemical assays.

Arm Injuries↗

Paediatric prehospital care: postal survey of paramedic training managers.

BACKGROUND: The process of prehospital care continues to develop in the UK. AIMS: To evaluate the availability of important paediatric resuscitation equipment in emergency ambulances and the extent of paramedic training in paediatric emergency medicine. METHODS: Postal survey of paramedic training managers. RESULTS: Completed questionnaires were returned by 41 (93%) training managers. No trust provided all of the equipment listed. Facemasks and self inflating bags (of appropriate sizes for all children) are provided by 32% and 42% of trusts respectively. Less than one third carry paediatric oximeter probes. Of the respondents, 16 (39%) trusts provide less than eight hours training in paediatric emergency medicine and five (12%) offer no training at all. Ongoing education varies from none to regular yearly updates. CONCLUSIONS: Paramedics seem ill prepared to deal with paediatric emergencies. Important deficiencies in the provision of equipment and training are noted. The results of this survey provide information against which improvements can be measured.

Allied Health Personnel↗

An analysis of calls referred to the emergency 999 service by NHS Direct.

INTRODUCTION: NHS Direct was launched in West Yorkshire in April 1999. A 999 ambulance can be dispatched to the patient as a result of a call to NHS Direct. The aim of this study is to compare cases that had been referred by NHS Direct via the 999 service, with those who had dialled 999 themselves. METHODS: The study was carried out in three accident and emergency (A&E) departments in West Yorkshire, between 1 April 1999 and 21 August 1999. NHS Direct generated 999 calls were identified. The comparison group was selected at random from a list of all other 999 cases attending the three departments. The study involved retrieving basic demographic data, as well as duration of symptoms before dialling 999, triage category on arrival in A&E and disposal of patient. Ethical approval and statistical advice were obtained. RESULTS: 91 NHS Direct generated 999 calls were identified. Of the comparison group (260 cases), 28 were excluded from the study. There were no differences in the triage categories assigned to the two groups on arrival in A&E. There were notable differences in presenting complaint between the two groups and in particular, trauma was less common among the NHS Direct patients (6.6%) compared with those who had self dialled (37.5%). Patients who had first called NHS Direct were younger (p=0.033) and had endured their symptoms for longer (p<0.001); they were less likely to be admitted, and if discharged, were less likely to have follow up arranged (p=0.014). CONCLUSIONS: Both groups received similar triage categories suggesting that severity of illness is equally well assessed by self as by NHS Direct. There are large differences in case mix between the two groups studied and these almost certainly explain the differences in outcome.

Diagnosis-Related Groups↗

Adult outcomes of pediatric recurrent abdominal pain: do they just grow out of it?

OBJECTIVE: To determine whether medically unexplained recurrent abdominal pain (RAP) in childhood predicts abdominal pain, irritable bowel syndrome (IBS), other somatic complaints, and psychiatric symptoms and disorders in young adulthood. METHODS: A sample of 28 young adults evaluated for RAP between the ages of 6 and 17 years were compared with 28 individually matched former childhood participants in a study of tonsillectomy and adenoidectomy. RAP caseness was established by structured retrospective chart review requiring agreement by 2 independent reviewers. Standardized assessments of abdominal pain, IBS, other somatic symptoms, psychopathology, perceived health, and history of maltreatment were performed an average of 11.1 years after the index visit. RESULTS: Former RAP patients were significantly more likely than controls to endorse anxiety symptoms and disorders, hypochondriacal beliefs, greater perceived susceptibility to physical impairment, poorer social functioning, current treatment with psychoactive medication, and generalized anxiety in first degree relatives. There were trends suggesting associations between childhood RAP and lifetime psychiatric disorder, depression, migraine, and family history of depression, but group differences on abdominal pain, IBS, other somatic symptoms, and history of maltreatment were not statistically significant. CONCLUSIONS: There is a strong and relatively specific association between childhood RAP and anxiety in young adulthood. Affected children may be at special risk to perceive physical symptoms as threatening, and should be evaluated for psychiatric disorder on initial presentation.

Abdominal Pain↗

Deterministic modeling of negative cross-resistance strategies for use in transgenic host-plant resistance.

Negative cross-resistance refers to a situation in which an insect population that is tolerant (resistant, virulent) to one insecticide is hyper-sensitive (avirulent) to a second insecticide and insects hyper-sensitive to the first compound are tolerant to the second. Most research dealing with negative cross-resistance has focused on the molecular biology and chemical aspects of this phenomenon. We explored, from a population genetics perspective, whether negative cross-resistance is feasible in the control of an insect population. As a first step towards this goal, we used a deterministic approach to evaluate different control scenarios and to identify some of the potential limitations of negative cross-resistance strategies. Specifically, we investigated how such approaches could be used in a host-plant resistance program. Homo- and heterozygous insect fitness influenced the effectiveness of the toxins in controlling the insect population. The negative cross-resistance strategy was most useful when the insects' virulence to both host-plant toxins was recessive. When virulence was dominant, there were many periods when intervention with an outside (or third) class of compounds, which had a different mode of action than that of the negative cross-resistance compounds, was needed to control the insect population. The greater the number of insect generations per plant generation, in the absence of immigration or emigration in the insect population, the greater the requirement for intervention with a third class of compound to maintain effective control of the insect population. When the toxins were rotated every insect generation, and virulence in the insect was recessive to both toxins, effective control of the insect population was maintained without intervention of a third class of compounds.

Animals↗

Toxicological screening in trauma.

OBJECTIVES: To determine the prevalence and patterns of alcohol and drug use in patients with major trauma. METHODS: Consecutive trauma patient enrollment, 24 hours a day, was envisaged with anonymised patient data on gender, age band, and mechanism of injury collected. The study group had surplus plasma quantitatively analysed for ethanol concentration, and urine samples were initially screened, via immunoassay, for opiates, cannabinoids, amphetamines, benzodiazepines, cocaine, and methadone. Confirmation and specification of individual positive results was then performed using thin layer or gas-liquid chromatography. Drugs of treatment given in the resuscitation room, if subsequently detected in the urine samples, were excluded from the final results. RESULTS: There were 116 eligible trauma patients assessed and treated in the resuscitation room over a six month period, of which 93 (80%) were enrolled. Altogether 27% of this trauma population had plasma ethanol concentrations greater than 80 mg/dl. There was a significantly higher prevalence of alcohol intoxication in the group not involved in a road traffic accident (RTA) compared with the group who were involved in a RTA. Initial screening of urine for drugs revealed a prevalence of 51%. After 12 exclusions due to iatrogenic administration of opiates, the final confirmed prevalence was 35% in this trauma population. The individual drug prevalence was 13% for cannabinoids, 11% for codeine, 8% for morphine, 6% for amphetamine, 6% for benzodiazepines, 3% for cocaine, 1% for dihydrocodeine, and 1% for methadone. CONCLUSIONS: There is a notable prevalence of drug and alcohol use in this British accident and emergency trauma population. A significantly higher prevalence for alcohol intoxication was found in the non-RTA group compared with the RTA group. The patterns of drug usage detected reflect local influences and less cocaine use is seen compared with American studies. The association between alcohol, drugs, and trauma, together with ethically acceptable methods of screening, are discussed.

Accidental Falls↗

The domestic iron. A danger to young children.

OBJECTIVES: To study the epidemiology of thermal injury caused by the domestic iron in children 5 years old or less. METHODS: Retrospective review of case notes held in the accident and emergency (A&E) department of a large teaching hospital over a 36 month period. Data regarding demographics, site and extent of injury, mechanism of injury and outcome were retrieved. RESULTS: 62 thermal injuries were identified in 59 patients. Of these, 60 were contact burns and two were scalds. The male to female ratio was 2:1. The mean age was 24 months. Fifty five per cent were aged between 1 and 2 years old. The hand was the commonest site of injury (63%) and, of these, two thirds were on the palm. Interestingly 10% occurred on the face. Iron contact burns accounted for 23.5% of all contact burns in this age group over this period. The majority of contact burns were partial thickness and most were less than 1% body surface area. Inadequate supervision is a recurring theme in many of these cases. A suspicion of non-accidental injury was raised in 10 cases and confirmed in nine of these. CONCLUSIONS: Iron burns are common in young children, particularly boys aged between 1 and 2 years old. Most can be treated in the A&E clinic. The potential for serious injury does exist. Non-accidental injury always needs to be considered. Efforts at prevention and increasing public awareness are needed.

Accidents, Home↗

Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial.

BACKGROUND: The use of sunscreens on the skin can prevent sunburn but whether long-term use can prevent skin cancer is not known. Also, there is evidence that oral betacarotene supplementation lowers skin-cancer rates in animals, but there is limited evidence of its effect in human beings. METHODS: In a community-based randomised trial with a 2 by 2 factorial design, individuals were assigned to four treatment groups: daily application of a sun protection factor 15-plus sunscreen to the head, neck, arms, and hands, and betacarotene supplementation (30 mg per day); sunscreen plus placebo tablets; betacarotene only; or placebo only. Participants were 1621 residents of Nambour in southeast Queensland, Australia. The endpoints after 4.5 years of follow-up were the incidence of basal-cell and squamous-cell carcinomas both in terms of people treated for newly diagnosed disease and in terms of the numbers of tumours that occurred. Analysis of the effect of sunscreen was based only on skin cancers that developed on sites of daily application. All analyses were by intention to treat. FINDINGS: 1383 participants underwent full skin examination by a dermatologist in the follow-up period. 250 of them developed 758 new skin cancers during the follow-up period. There were no significant differences in the incidence of first new skin cancers between groups randomly assigned daily sunscreen and no daily sunscreen (basal-cell carcinoma 2588 vs 2509 per 100,000; rate ratio 1.03 [95% CI 0.73-1.46]; squamous-cell carcinoma 876 vs 996 per 100,000; rate ratio 0.88 [0.50-1.56]). Similarly, there was no significant difference between the betacarotene and placebo groups in incidence of either cancer (basal-cell carcinoma 3954 vs 3806 per 100,000; 1.04 [0.73-1.27]; squamous-cell carcinoma 1508 vs 1146 per 100,000; 1.35 [0.84-2.19]). In terms of the number of tumours, there was no effect on incidence of basal-cell carcinoma by sunscreen use or by betacarotene but the incidence of squamous-cell carcinoma was significantly lower in the sunscreen group than in the no daily sunscreen group (1115 vs 1832 per 100,000; 0.61 [0.46-0.81]). INTERPRETATION: There was no harmful effect of daily use of sunscreen in this medium-term study. Cutaneous squamous-cell carcinoma, but not basal-cell carcinoma seems to be amenable to prevention through the routine use of sunscreen by adults for 4.5 years. There was no beneficial or harmful effect on the rates of either type of skin cancer, as a result of betacarotene supplementation.

Adult↗

PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2.

BACKGROUND: Protein kinase B (PKB) is activated by phosphorylation of Thr308 and of Ser473. Thr308 is phosphorylated by the 3-phosphoinositide-dependent protein kinase-1 (PDK1) but the identity of the kinase that phosphorylates Ser473 (provisionally termed PDK2) is unknown. RESULTS: The kinase domain of PDK1 interacts with a region of protein kinase C-related kinase-2 (PRK2), termed the PDK1-interacting fragment (PIF). PIF is situated carboxy-terminal to the kinase domain of PRK2, and contains a consensus motif for phosphorylation by PDK2 similar to that found in PKBalpha, except that the residue equivalent to Ser473 is aspartic acid. Mutation of any of the conserved residues in the PDK2 motif of PIF prevented interaction of PIF with PDK1. Remarkably, interaction of PDK1 with PIF, or with a synthetic peptide encompassing the PDK2 consensus sequence of PIF, converted PDK1 from an enzyme that could phosphorylate only Thr308 of PKBalpha to one that phosphorylates both Thr308 and Ser473 of PKBalpha in a manner dependent on phosphatidylinositol (3,4,5) trisphosphate (PtdIns(3,4,5)P3). Furthermore, the interaction of PIF with PDK1 converted the PDK1 from a form that is not directly activated by PtdIns(3,4,5)P3 to a form that is activated threefold by PtdIns(3,4,5)P3. We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies. CONCLUSIONS: PDK1 and PDK2 might be the same enzyme, the substrate specificity and activity of PDK1 being regulated through its interaction with another protein(s). PRK2 is a probable substrate for PDK1.

3-Phosphoinositide-Dependent Protein Kinases↗

Healthcare users and computerised resources.

This paper concerns users' views on computerised resources. The focus concerns a software tool that could be used to allow safety conscious user manipulation of the combination of these computerised resources. It is of concern to the authors that computerised resources used in healthcare should reflect users' working practices rather than working practices being changed to reflect computerised resources.

Attitude to Computers↗