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Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 19 recordsLinked to original sources
PubMed2007

Back pain as the presenting symptom of generalised tetanus.

Back pain is a common presenting symptom in emergency departments and primary care across the UK. The extensive differential diagnosis includes mechanical, infective, thoracic, abdominal and vascular causes. This case report describes a patient who presented with lower back pain with a rare diagnosis, which is becoming more common in certain population groups, and emphasises the importance of clinical skills and insuring adequate tetanus prophylaxis.

Abscess↗
PubMed2006

Childhood acute lymphoblastic leukemia and infections in the first year of life: a report from the United Kingdom Childhood Cancer Study.

The United Kingdom Childhood Cancer Study was designed to examine the relation between childhood cancer and preceding exposure to infectious diseases. The authors analyzed the relation between diagnosis (1991-1996) of acute lymphoblastic leukemia (ALL) at ages 2-5 years and clinically diagnosed infections in infancy. Almost all study children (96% of both cases and controls) were taken to a general practitioner for a non-immunization-associated visit at least once before their first birthday. Children diagnosed with ALL had significantly more clinically diagnosed infectious episodes in infancy than did controls; the average number of episodes was 3.6 (95% confidence interval (CI): 3.3, 3.9) versus 3.1 (95% CI: 2.9, 3.2). This case-control difference was most apparent in the neonatal period (< or =1 month); 18% of controls and 24% of ALL cases were diagnosed with at least one infection (odds ratio = 1.4, 95% CI: 1.1, 1.9; p < 0.05). Cases who had more than one neonatal infectious episode tended to be diagnosed with ALL at a comparatively young age; the mean age at ALL diagnosis was 37.7 months for cases with two or more episodes versus 45.3 months for cases with only one episode or none (p < 0.01). These findings support the hypothesis that a dysregulated immune response to infection in the first few months of life promotes transition to overt ALL later in childhood.

Age of Onset↗
PubMed2006

Identification of an excitatory amino acid-mediated component of the ventral tegmental area local field potential response to medial prefrontal cortex stimulation: effect of acute d-amphetamine.

The induction of sensitisation to the behavioural effects of d-amphetamine - a model of drug addiction - involves the potentiation of exctiatory amino acid (EAA)-ergic synapses on dopaminergic neurons in the ventral tegmental area (VTA). Such potentiation has been reported as early as 2 hr post-injection, however earlier time points have not been assessed. Consequently, we examined the effects of systemic d-amphetamine on an EAA-mediated component of the VTA local field potential response to stimulation of the medial prefrontal cortex, an EAAergic afferent critical for sensitisation, over the immediate 2 hr post-injection period. D-amphetamine and saline both depressed the amplitude of this component to a similar extent throughout the recording session. It is concluded that overt aspects of EAA-mediated potentiation appear to be delayed with respect to drug administration, which may have implications for sensitisation's putative role in linking drug-related environmental stimuli and the central effects of the drug.

Animals↗
PubMed2006

Prenatally diagnosed pulmonary atresia with ventricular septal defect: echocardiography, genetics, associated anomalies and outcome.

OBJECTIVE: To assess the accuracy of prenatal diagnosis, the association with genetic and extracardiac anomalies, and outcome in fetuses with isolated pulmonary atresia with ventricular septal defect (PA-VSD). DESIGN AND SETTING: Retrospective study in a tertiary centre for fetal cardiology. PATIENTS AND OUTCOME MEASURES: Echocardiographic video recordings of 27 consecutive fetuses with PA-VSD were reviewed for: (1) intracardiac anatomy; (2) presence of confluence and size of the branch pulmonary arteries; (3) source of pulmonary blood supply; and (4) side of the aortic arch. Postmortem and postnatal data were added. Karyotyping was performed in 25 patients and, in 23 of these, fluorescent in situ hybridisation to identify 22q11.2 deletion. RESULTS: PA-VSD was correctly diagnosed in 19 of 21 patients (90%) with postnatal or autopsy confirmation of diagnosis. Central pulmonary arteries were correctly identified in 79% (15/19), the source of pulmonary blood supply in 62% (13/21) and major aortopulmonary collateral arteries in 44% (4/9). Aneuploidy was detected in 4 of 25 patients (16%) and 22q11.2 deletion in 6 of 23 patients (26%). Five of 27 patients (19%) had extracardiac anomalies. Eleven pregnancies were interrupted. Eleven of 16 liveborn babies survived. Neonatal survival was 15 of 16 (94%, 95% confidence interval (CI) 70 to 100), one-year survival was 9 of 12 (75%, 95% CI 43 to 95) and two-year survival was 5 of 9 (56%, 95% CI 21 to 86). CONCLUSION: PA-VSD can be diagnosed by fetal echocardiography with a high degree of accuracy. However, it can be difficult to determine the morphology of the central pulmonary arteries and to locate the source of pulmonary blood supply. In most liveborn infants, complete surgical repair can be achieved.

Echocardiography↗
PubMed2006

Rapid sequence intubation in the emergency department: 5 year trends.

AIM: Airway management is a core aspect of emergency medicine. The technique of rapid sequence intubation (RSI) creates continuing debate between anaesthetists and emergency physicians in the UK, although similar complication rates for emergency department (ED) RSI have been shown for both specialties. This study examined prospectively collected data on every ED RSI performed in a university hospital in Glasgow over 5 years. METHODS: Data were prospectively recorded for every attempted RSI in the ED on a dedicated form (as used in previous studies) between January 1999 and December 2003. Immediate complications were specifically sought in the questionnaire, as was the immediate destination on leaving the ED. The chi2 test was used for categorical data. RESULTS: On average, 51 ED RSI were performed annually (range 42-60). Emergency physician RSI for trauma increased from 32% (7/22) in 1999 to 75% (21/28) in 2003 (chi2 = 9.32, df = 1, p = 0.002) and for non-trauma from 62% (18/29) in 1999 to 79% (23/29) in 2003 (chi2 = 2.08, df = 1, p = 0.15). Complication rates for emergency physician RSI decreased from 43% (3/7) to 14% (3/21) for trauma (chi2 = 2.55, df = 1, p = 0.11) and from 28% (5/18) to 4% (1/23) for non-trauma (chi2 = 4.44, df = 1, p = 0.035). This compares with mean complication rates for anaesthetists for trauma of 17% and for non-trauma of 22%. Incidence of hypotension decreased in all groups; however, oxygen desaturation is now the most common complication. The rate of ED RSI prior to computed tomography (CT) scans increased in both the trauma (79% v 42%; chi2 = 7.42, df = 1, p = 0.0065) and non-trauma (48% v 17%; chi2 = 5.85, df = 1, p = 0.016) groups. CONCLUSION: Emergency physician performed ED RSI is increasingly common but is not associated with overall higher numbers of RSIs being performed in the ED. Effective pre-oxygenation should be emphasised during training.

Emergency Service, Hospital↗
PubMed2006

Variations in consenting practice for laparoscopic cholecystectomy.

INTRODUCTION: To compare the variations in consenting practice amongst trainees and consultant surgeons for laparoscopic cholecystectomy with specific reference to the documentation of significant risks of surgery. PATIENTS AND METHODS: A proforma was devised which included significant and/or commonly recognised complications of laparoscopic cholecystectomy. This was then cross-referenced with the consent forms for the 80 patients included in the study and the documented risks explained in each case were noted. RESULTS: The results showed that there is considerable variation between the three grades of clinicians involved in obtaining a patient's consent for laparoscopic cholecystectomy. There was a clear difference in emphasis of the significant complications depending on the seniority of the consenter. Over 80% of the consents in this study were still being obtained by junior staff. CONCLUSIONS: More often than not, patients are not provided with consistent information to make an informed choice. We suggest that a preprinted consent form will provide a more uniform approach to consenting practice for laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗
PubMed2005

Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case-control study.

OBJECTIVE: To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK. PARTICIPANTS: 6305 children (aged 2-14 years) without cancer; 3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute lymphoblastic leukaemia (ALL). MAIN OUTCOME MEASURE: Day care and social activity during the first year of life were used as proxies for potential exposure to infection in infancy. RESULTS: Increasing levels of social activity were associated with consistent reductions in risk of ALL; a dose-response trend was seen. When children whose mothers reported no regular activity outside the family were used as the reference group, odds ratios for increasing levels of activity were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62 (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for formal day care (attendance at facility with at least four children at least twice a week) (P value for trend < 0.001). Although not as striking, results for non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When children with non-ALL malignancies were taken as the reference group, a significant protective effect for ALL was seen only for formal day care (odds ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell precursor common ALL and other subgroups, as well as for cases diagnosed above and below age 5 years. CONCLUSION: These results support the hypothesis that reduced exposure to infection in the first few months of life increases the risk of developing acute lymphoblastic leukaemia.

Adolescent↗
PubMed2005

Atrioventricular and ventriculoarterial discordance (congenitally corrected transposition of the great arteries): echocardiographic features, associations, and outcome in 34 fetuses.

OBJECTIVE: To identify fetal echocardiographic features, associations, and outcome of atrioventricular and ventriculoarterial discordance. DESIGN: Retrospective analysis of videotape recordings of fetal echocardiograms and examination of departmental database and patient records to establish outcome. SETTING: Tertiary centre for fetal cardiology. PATIENTS: 34 consecutive fetuses with a prenatal diagnosis of double discordance seen between January 1993 and December 2003. MAIN OUTCOME MEASURES: Echocardiographic features including reversed differential insertion, identification of the right ventricle through the moderator band, and the origin and orientation of the great arteries. All associated cardiac abnormalities and outcome. RESULTS: Reversed differential insertion was identified in 26 fetuses. The right ventricle could be identified by the moderator band in 30 fetuses and was left sided in all but one. A parallel or abnormal orientation of the great arteries was seen in all fetuses. Only five of 34 cases were isolated from a cardiac viewpoint. There was a ventricular septal defect in 21, Ebstein's anomaly in 8, pulmonary stenosis in 12, coarctation of the aorta in 6, tricuspid atresia in 2, congenital heart block in 2 fetuses prenatally, and dextrocardia in 6. Nineteen babies survived; one baby died in the neonatal period and three in infancy. Eleven pregnancies were interrupted. CONCLUSIONS: A left sided or posterior right ventricle, identified by reversed differential insertion or the moderator band, in association with abnormal orientation of the great arteries should alert a sonographer to the diagnosis of double discordance. Isolated cases are rare prenatally (14%) but the short term survival in our fetal series is good. Where pregnancy was continued, 19 of 23 babies (82%) remained alive.

Abortion, Induced↗
PubMed2005

Perinatal and reproductive factors: a report on haematological malignancies from the UKCCS.

The United Kingdom Childhood Cancer Study was designed to examine the potential aetiological role of a range of perinatal and reproductive factors. Our use of clinical records permitted a more exact characterisation of reproductive events than is possible in investigations that rely on self-reporting; and the increased specificity with which antecedent events were measured produced more precise risk estimates, albeit ones based on progressively smaller numbers. Information on the conduct of this component of the study and results for 1485 children with haematological malignancies and 4864 controls are presented. The 'find' rate for obstetric records was high at 86% for cases, with 81% having information on both matched controls. Associations were seen for severe hyperemesis (Odds Ratio=3.6, 95%Confidence Interval=1.3-10.1, for all leukaemias), polyhydramnios (OR=4.0, 95%CI=1.5-10.3, for acute myeloid leukaemia (AML)), anaemia (haemoglobin <10 g, OR=2.6, 95%CI=1.7-4.1, for AML), and pre-eclampsia (OR=1.7, 95%CI=1.1-2.7, for non-Hodgkin's lymphoma). Babies who developed leukaemia were heavier at birth (>4000 g, OR=1.2, 95%CI=1.0-1.4), as were their older siblings (>4000 g, OR=1.4, 95%1.0-1.9). Mothers' whose children developed common B-cell precursor acute lymphoblastic leukaemia (ALL) were more likely to have had a previous molar pregnancy (OR=5.2, 95%CI=1.9-14.7). Gender-specific analysis revealed that findings often differed markedly for boys and girls; and, in common with other reports, strong associations with Down's syndrome were seen for both ALL and AML.

Acute Disease↗
PubMed2005

Relationships between perinatal and maternal characteristics and hepatoblastoma: a report from the UKCCS.

Within the context of a national population-based case-control study--the United Kingdom Childhood Cancer Study (UKCCS)--we aimed to explore relationships between perinatal and maternal factors and childhood hepatic tumours, for participants with data available from medical records. 26/28 children with hepatic tumours (22/24 hepatoblastomas, 4/4 hepatocellular carcinomas (HCC)) and 4753 age- and sex-matched controls were included. Polyhydramnios was associated with 0.9% of control pregnancies and 13.6% of case pregnancies (Odds Ratio (OR)=28.64, 95% Confidence Interval (CI)=6.94-118.21, P<0.0001); eclampsia or severe pre-eclampsia complicated the pregnancies of 16.7% of mothers whose children developed hepatoblastoma compared with 0.5% of control pregnancies (OR=52.50, 95% CI=10.75-257.05, P<0.0001). Three children with hepatoblastoma weighed <1500 g at birth, two of whom weighed <1000 g (OR for birthweight <1500 g=69.00, 95% CI=11.98-397.17, P<0.0001). Of children with hepatoblastoma, 50% (11/22) had records of congenital anomalies, as did two of their mothers. Three mothers of children with hepatoblastoma had diagnoses of cancer--two of papillary carcinoma of the thyroid and one of acute lymphoblastic leukaemia (ALL). Paediatricians and others should be alert to the possibility of familial or genetic syndromes in children with hepatoblastomas. Potential links between maternal pre-eclampsia, low birthweight and subsequent malignancy merit further investigation. Hepatoblastoma is an extremely rare childhood tumour, but understanding the mechanism(s) underlying severe pre-eclampsia and eclampsia may also shed light on factors that contribute to the development of hepatoblastoma.

Carcinoma, Hepatocellular↗
PubMed2005

Differential regulation of osteoblasts by substrate microstructural features.

Microtextured titanium implant surfaces enhance bone formation in vivo and osteoblast phenotypic expression in vitro, but the mechanisms are not understood. To determine the roles of specific microarchitectural features in modulating osteoblast behavior, we used Ti surfaces prepared by electrochemical micromachining as substrates for MG63 osteoblast-like cell culture. Cell response was compared to tissue culture plastic, a sand-blasted with large grit and acid-etched surface with defined mixed microtopography (SLA), polished Ti surfaces, and polished surfaces electrochemically machined through a photoresist pattern to produce cavities with 100, 30 and 10 microm diameters arranged so that the ratio of the microscopic-scale area of the cavities versus the microscopic-scale area of the flat region between the cavities was equal to 1 or 6. Microstructured disks were acid-etched, producing overall sub-micron-scale roughness (Ra=0.7 microm). Cell number, differentiation (alkaline phosphatase; osteocalcin) and local factor levels (TGF-beta1; PGE(2)) varied with microarchitecture. 100 microm cavities favored osteoblast attachment and growth, the sub-micron-scale etch enhanced differentiation and TGF-beta1 production, whereas PGE(2) depended on cavity dimensions but not the sub-micron-scale roughness.

Biocompatible Materials↗
PubMed2005

Aniridia and optic nerve hypoplasia.

BACKGROUND: This study evaluates, in patients with aniridia, the prevalence of optic nerve hypoplasia and its association with foveal hypoplasia. METHODS: The medical records of 56 patients with aniridia (31 female, 25 male, mean age 33 years, range 2-74 years) were retrospectively evaluated for optic nerve and foveal hypoplasia. The difference in prevalence of foveal hypoplasia in patients with and without optic nerve hypoplasia was compared using Fisher's exact test. RESULTS: Six of 56 patients, 10.7% (95% CI: 4.8-21.5%), had optic nerve hypoplasia; hypoplasia was found in both eyes of five binocular patients and in one monocular patient. The prevalence of foveal hypoplasia was higher in aniridia patients with optic nerve hypoplasia than in those without (50.0 vs 6.0%); this difference did not achieve statistical significance (P=0.10). CONCLUSIONS: Clinically apparent optic nerve hypoplasia is found in roughly 10% of patients with aniridia and may occur independently or in association with foveal hypoplasia.

Abnormalities, Multiple↗
PubMed2005

Serotonin transporter function and expression are reduced in mice with TNBS-induced colitis.

Regulated release of serotonin (5-HT) from enterochromaffin (EC) cells activates neural reflexes that are involved in gut motility, secretion, vascular perfusion and sensation. The 5-HT-selective reuptake transporter (SERT) terminates serotonergic signalling in the intestinal mucosa. The aim of this investigation was to determine whether mucosal 5-HT content, release, and/or reuptake are altered in a murine model of immune cell-mediated colitis. Experiments were conducted 6 days after colitis was induced by 2,4,6-trinitrobenzene sulfonic acid, a time point when macroscopic and histological damage scores indicated significant inflammation. During inflammation, SERT transcript levels and immunoreactivity were reduced, and the uptake of [3H] 5-HT was impaired. Increases in mucosal 5-HT content and the number of 5-HT-immunoreactive mast cells in the lamina propria were also detected in the inflamed region, whereas EC cell numbers did not change. Mucosal 5-HT released under basal and stimulated conditions was unchanged in animals with colitis. These data suggest that murine colitis alters 5-HT signalling by increasing 5-HT availability through decreased 5-HT uptake by mucosal epithelial cells. These findings support the concept that altered 5-HT signalling could be a contributing factor in altered gut function and sensitivity in inflammatory bowel disease.

Animals↗
PubMed2005

Use of confocal immunofluorescence microscopy to localize viral nonstructural proteins and potential sites of replication in pigs experimentally infected with foot-and-mouth disease virus.

Replication of foot-and-mouth disease virus in infected pig epithelium has been studied by immunofluorescence labeling of the viral nonstructural protein 3ABC and confocal microscopy. The results were correlated with viral RNA copy numbers in tissue samples from adjacent sites determined by reverse transcription-PCR (RT-PCR). Lesion formation was seen in the tongues and coronary band epithelia of infected pigs 2 days after infection. Viral replication was observed in cells of the epithelium of the tongue and coronary band but not in the associated stromal cells. Infected epithelial cells were present in the stratum spinosum, away from the lesion, with small lesions formed above the basement membrane. Viral replication was markedly reduced in tongue epithelium by day 3 postinfection but remained apparent in the coronary band tissue up to 5 days postinfection. These results were confirmed by the RNA copy number determined by RT-PCR.

Animals↗
PubMed2004

High-spin structure beyond band termination in 157Er.

The angular-momentum induced transition from a deformed state of collective rotation to a noncollective configuration has been studied. In 157Er this transition manifests itself as favored band termination near I=45 Planck's. The feeding of these band terminating states has been investigated for the first time using the Gammasphere spectrometer. Many weakly populated states lying at high excitation energy that decay into these special states have been discovered. Cranked Nilsson-Strutinsky calculations suggest that these states arise from weakly collective "core-breaking" configurations.

Journal Article↗
PubMed2004

RGD-containing peptide GCRGYGRGDSPG reduces enhancement of osteoblast differentiation by poly(L-lysine)-graft-poly(ethylene glycol)-coated titanium surfaces.

Osteoblasts exhibit a more differentiated morphology on surfaces with rough microtopographies. Surface effects are often mediated through integrins that bind the RGD motif in cell attachment proteins. Here, we tested the hypothesis that modulating access to RGD binding sites can modify the response of osteoblasts to surface microtopography. MG63 immature osteoblast-like cells were cultured on smooth (Ti sputter-coated Si wafers) and rough (grit blasted/acid etched) Ti surfaces that were modified with adsorbed monomolecular layers of a comb-like graft copolymer, poly-(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), to limit nonspecific protein adsorption. PLL-g-PEG coatings were functionalized with varying amounts of an integrin-receptor-binding RGD peptide GCRGYGRGDSPG (PLL-g-PEG/PEG-RGD) or a nonbinding RDG control sequence GCRGYGRDGSPG (PLL-g-PEG/PEG-RDG). Response to PLL-g-PEG alone was compared with response to surfaces on which 2-18% of the polymer sidechains were functionalized with the RGD peptide or the RDG peptide. To examine RGD dose-response, peptide surface concentration was varied between 0 and 6.4 pmol/cm(2). In addition, cells were cultured on uncoated Ti or Ti coated with PLL-g-PEG or PLL-g-PEG/PEG-RGD at an RGD surface concentration of 0.7 pmol/cm(2), and free RGDS was added to the media to block integrin binding. Analyses were performed 24 h after cultures had achieved confluence on the tissue culture plastic surface. Cell number was reduced on smooth Ti compared to plastic or glass and further decreased on surfaces coated with PLL-g-PEG or PLL-g-PEG/PEG-RDG, but was restored to control levels when PLL-g-PEG/PEG-RGD was present. Alkaline phosphatase specific activity and osteocalcin levels were increased on PLL-g-PEG alone or PLL-g-PEG/PEG-RDG, but PLL-g-PEG/PEG-RGD reduced the parameters to control levels. On rough Ti surfaces, cell number was reduced to a greater extent than on smooth Ti. PLL-g-PEG coatings reduced alkaline phosphatase and increased osteocalcin in a manner that was synergistic with surface roughness. The RDG peptide did not alter the PLL-g-PEG effect but the RGD peptide restored these markers to their control levels. PLL-g-PEG coatings also increased TGF-beta1 and PGE(2) in conditioned media of cells cultured on smooth or rough Ti; there was a 20x increase on rough Ti coated with PLL-g-PEG. PLL-g-PEG effects were inhibited dose dependently by addition of the RGD peptide to the surface. Free RGDS did not decrease the effect elicited by PLL-g-PEG surfaces. These unexpected results suggest that PLL-g-PEG may have osteogenic properties, perhaps correlated with effects that alter cell attachment and spreading, and promote a more differentiated morphology.

Alkaline Phosphatase↗