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Biomedical subjects

J Boyd

Publications and source records attributed to J Boyd.

At least 19 recordsLinked to original sources

Short-term and long-term outcomes in 133,429 emergency patients admitted with angina or myocardial infarction in Scotland, 1990-2000: population-based cohort study.

OBJECTIVE: To analyse short- and long-term outcomes and prognostic factors in a large population-based cohort of unselected patients with a first emergency admission for suspected acute coronary syndrome between 1990 and 2000 in Scotland. METHODS: All first emergency admissions for acute myocardial infarction (AMI) and all first emergency admissions for angina (the proxy for unstable angina) between 1990 and 2000 in Scotland (population 5.1 million) were identified. Survival to five years was examined by Cox multivariate modelling to examine the independent prognostic effects of diagnosis, age, sex, year of admission, socioeconomic deprivation and co-morbidity. RESULTS: In Scotland between 1990 and 2000, 133,429 individual patients had a first emergency admission for suspected acute coronary syndrome: 96 026 with AMI and 37,403 with angina. After exclusion of deaths within 30 days, crude five-year case fatality was similarly poor for patients with angina and those with AMI (23.9% v 21.6% in men and 23.5% v 26.0% in women). The longer-term risk of a subsequent fatal or non-fatal event in the five years after first hospital admission was high: 54% in men after AMI (53% in women) and 56% after angina (49% in women). Event rates increased threefold with increasing age and 20-60% with different co-morbidities, but were 11-34% lower in women. CONCLUSIONS: Longer-term case fatality was similarly high in patients with angina and in survivors of AMI, about 5% a year. Furthermore, half the patients experienced a fatal or non-fatal event within five years. These data may strengthen the case for aggressive secondary prevention in all patients presenting with acute coronary syndrome.

Adult↗

Accuracy of BRCA1 and BRCA2 founder mutation analysis in formalin-fixed and paraffin-embedded (FFPE) tissue.

BACKGROUND: A major limitation in counseling unaffected women from families with inherited breast and ovarian cancer is that a "true-negative" interpretation of wild type BRCA analysis of the proband cannot be inferred in the absence of demonstration of a BRCA mutation segregating in the kindred. Documentation of familial BRCA mutations from paraffin-derived DNA of deceased patients has been limited due to reports of technical complications leading to lack of reproducibility of BRCA testing of archival material. METHODS: DNA was extracted from formalin-fixed paraffin-embedded (FFPE) morphologically normal tissue of 161 blinded, coded samples from women previously genotyped for the three Ashkenazi Jewish BRCA founder mutations from lymphocyte-derived DNA. Multiplex PCR followed by denaturing polyacrylamide gel electrophoresis was performed for the three founder mutations to determine if analysis on FFPE tissue could produce results concordant with those of the lymphocyte-derived DNA. RESULTS: After disclosure of the sample codes, the results were compared with the original lymphocyte-derived DNA genotypes. Excluding one sample unevaluable due to PCR failure, there was 100% concordance of 160 genotypes (120 mutation samples) derived from DNA from archival FFPE tissue compared to peripheral lymphocytes. CONCLUSIONS: The method described reliably detected BRCA founder mutations in archival DNA derived from FFPE tissue. These results suggests that this technique may be useful in clinical settings to inform wild type BRCA results of unaffected probands, leading to avoidance of unnecessary intensified surveillance or risk-reducing surgery. With further validation this approach can also be applied to other populations where founder mutations are observed.

DNA↗

Comparison of 30 and the 100% inspired oxygen concentrations during early post-resuscitation period: a randomised controlled pilot study.

OBJECTIVES: High oxygen concentration in blood may be harmful in the reperfusion phase after cardiopulmonary resuscitation. We compared the effect of 30 and 100% inspired oxygen concentrations on blood oxygenation and the level of serum markers (NSE, S-100) of neuronal injury during the early post-resuscitation period in humans. METHODS: Patients resuscitated from witnessed out-of-hospital ventricular fibrillation were randomised after the return of spontaneous circulation (ROSC) to be ventilated either with 30% (group A) or 100% (group B) oxygen for 60 min. Main outcome measures were NSE and S-100 levels at 24 and 48 h after ROSC, the adequacy of oxygenation at 10 and 60 min after ROSC and, in group A, the need to raise FiO(2) to avoid hypoxaemia. Blood oxygen saturation <95% was the threshold for this intervention. RESULTS: Thirty-two patients were randomised and 28 (14 in group A and 14 in group B) remained eligible for the final analysis. The mean PaO(2) at 10 min was 21.1 kPa in group A and 49.7 kPa in group B. The corresponding values at 60 min were 14.6 and 46.5 kPa. PaO(2) values did not fall to the hypoxaemic level in group A. In another group FiO(2) had to be raised in five cases (36%) but in two cases it was returned to 0.30 rapidly. The mean NSE at 24 and 48 h was 10.9 and 14.2 microg/l in group A and 13.0 and 18.6 microg/l in group B (ns). S-100 at corresponding time points was 0.21 and 0.23 microg/l in group A and 0.73 and 0.49 microg/l in group B (ns). In the subgroup not treated with therapeutic hypothermia in hospital NSE at 24h was higher in group B (mean 7.6 versus 13.5 microg/l, p=0.0487). CONCLUSIONS: Most patients had acceptable arterial oxygenation when ventilated with 30% oxygen during the immediate post-resuscitation period. There was no indication that 30% oxygen with SpO(2) monitoring and oxygen backup to avoid SpO(2)<95% did worse that the group receiving 100% oxygen. The use of 100% oxygen was associated with increased level of NSE at 24h in patients not treated with therapeutic hypothermia. The clinical significance of this finding is unknown and an outcome-powered study is feasible.

Blood Pressure↗

Application of the lattice Boltzmann model to simulated stenosis growth in a two-dimensional carotid artery.

The lattice Boltzmann model is used to observe changes in the velocity flow and shear stress in a carotid artery model during a simulated stenosis growth. Near wall shear stress in the unstenosed artery is found to agree with literature values. The model also shows regions of low velocity, rotational flow and low near wall shear stress along parts of the walls of the carotid artery that have been identified as being prone to atherosclerosis. These regions persist during the simulated stenosis growth, suggesting that atherosclerotic plaque build-up creates regions of flow with properties that favour atherosclerotic progression.

Animals↗

Analysis of multiple casualty incidents - a prospective cohort study.

BACKGROUND: Our aim was to report the rate and causes for multiple casualty incidents (MCI) to analyse the prehospital part of responding to MCIs, report mortality and find areas for improvement. METHODS: A prospective cohort study conducted in an urban emergency medical service (EMS) between 1.3.1998 and 28.2.2004. RESULTS: Fifty-nine MCIs involving 263 patients (167 walking, 96 non-walking) occurred. The incidence of MCIs was 1.8/100,000 inhabitants year(-1). Traffic accidents were the most common cause followed by residential fires, intoxications and stabbings or shootings. Early MCI alarm by the dispatching centre was performed in 18 MCIs. Deviations from standard emergency medical care occurred in 12% of patients. Lack of immobilization of the neck or back in trauma patients and lack of administration of 100% oxygen in suspected carbon monoxide intoxication were the most common deviations. Deviations were related to the lack of presence of on-scene medical command (P = 0.0013) and inadequate resources (P = 0.0342). One hundred and ninety-two patients were transported to emergency departments. Mortality during the prehospital phase was 4.9% (13/263) and during the next 28 days 2.3% (6/263). Adequate resources for safe and effective management of a MCI were related to an early MCI alarm by the dispatching centre (P = 0,022) and to the presence of on-scene medical command (P < 0,001). CONCLUSIONS: Traffic accidents, residential fires and intoxications were the leading causes for MCIs. Emergency medical service could respond to most MCIs efficiently and safely. Majority of deviations from standard medical care seemed potentially preventable. Several areas for improvement were identified. From prehospital links, the dispatching centre and on-scene medical command had a vital role in the successful management of MCIs.

Accidents↗

The lagged effect of cold temperature and wind chill on cardiorespiratory mortality in Scotland.

AIMS: To investigate the lagged effects of cold temperature on cardiorespiratory mortality and to determine whether "wind chill" is a better predictor of these effects than "dry bulb" temperature. METHODS: Generalised linear Poisson regression models were used to investigate the relation between mortality and "dry bulb" and "wind chill" temperatures in the three largest Scottish cities (Glasgow, Edinburgh, and Aberdeen) between January 1981 and December 2001. Effects of temperature on mortality (lags up to one month) were quantified. Analyses were conducted for the whole year and by season (cool and warm seasons). MAIN RESULTS: Temperature was a significant predictor of mortality with the strongest association observed between temperature and respiratory mortality. There was a non-linear association between mortality and temperature. Mortality increased as temperatures fell throughout the range, but the rate of increase was steeper at temperatures below 11 degrees C. The association between temperature and mortality persisted at lag periods beyond two weeks but the effect size generally decreased with increasing lag. For temperatures below 11 degrees C, a 1 degrees C drop in the daytime mean temperature on any one day was associated with an increase in mortality of 2.9% (95% CI 2.5 to 3.4), 3.4% (95% CI 2.6 to 4.1), 4.8% (95% CI 3.5 to 6.2) and 1.7% (95% CI 1.0 to 2.4) over the following month for all cause, cardiovascular, respiratory, and "other" cause mortality respectively. The effect of temperature on mortality was not observed to be significantly modified by season. There was little indication that "wind chill" temperature was a better predictor of mortality than "dry bulb" temperature. CONCLUSIONS: Exposure to cold temperature is an important public health problem in Scotland, particularly for those dying from respiratory disease.

Adult↗

Application of the lattice Boltzmann method to arterial flow simulation: investigation of boundary conditions for complex arterial geometries.

The application of the lattice Boltzmann method (LBM) to carotid artery blood flow is investigated, in particular, the importance of the boundary conditions is considered. Simulations are presented using two different boundary conditions: the traditional half-way bounce-back and an extrapolation scheme. The two methods are described and compared with respect to arterial flow simulation. The results indicate that the extrapolation scheme is preferable in narrow arteries, or when a stenosis is present in a larger artery.

Algorithms↗

The use of undiluted amiodarone in the management of out-of-hospital cardiac arrest.

INTRODUCTION: The Resuscitation 2000 Guidelines recommends amiodarone as the antiarrhythmic drug of choice in treatment of resistant ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). Amiodarone has been associated with side-effects and difficulty of administration, due to recommended dilution, rendering it suboptimal for out-of-hospital cardiac arrest (CA) management. In the present study we report experiences and side-effects of the use of undiluted amiodarone in CA management in Helsinki Emergency Medical Service (EMS) during a 2-year period. METHODS: On October 1, the Resuscitation 2000 Guidelines were put into practice in Helsinki EMS. Thus, in the cardiac arrest treatment protocol, after three ineffective shocks and 1 mg of adrenaline (epinephrine), a bolus of 300 mg of undiluted amiodarone (Cordarone 50 mg ml(-1), Sanofi-Synthelabo, Helsinki, Finland) was administered into a vein located as centrally as possible. The Helsinki EMS performs systematic data collection according to the Utstein Guidelines. The blood pressure levels, heart rates and the need for vasopressors, of the patients with sustained return of spontaneous circulation (ROSC), were collected from the ambulance charts. RESULTS: During October 1, 2000 and September 30, 2002, 712 patients were considered for resuscitation and 566 were resuscitated. The initial rhythms were as follows: 32% had VF/VT, 36% had asystole and 32% had pulseless electrical activity (PEA). Of the 180 patients with VF/VT, 75 (42%) received undiluted amiodarone in addition to other resuscitative measures. Of the patients with asystole or PEA, 12 (6%) and 18 (10%), respectively, received amiodarone. The blood pressure levels and the need vasopressors after ROSC and during transportation to the hospital were similar among the patients who received and those who did not receive amiodarone. CONCLUSIONS: The present study suggests that amiodarone can be administered undiluted without unmanageable haemodynamical side-effects in the treatment of out-of-hospital cardiac arrest. This is likely to save time and simplifies the treatment protocol in the prehospital setting.

Aged↗

Transinhibition and voltage-gating in a fungal nitrate transporter.

We have applied enzyme kinetic analysis to electrophysiological steady-state data of Zhou et al. (Zhou, J.J., Trueman, L.J., Boorer, K.J., Theodoulou, F.L., Forde, B.G., Miller, A.J. 2000. A high-affinity fungal nitrate carrier with two transport mechanisms. J. Biol. Chem. 275:39894-9) and to new current-voltage-time records from Xenopus oocytes with functionally expressed NrtA (crnA) 2H+-NO3- symporter from Emericella (Aspergillus) nidulans. Zhou et al. stressed two Michaelis-Menten (MM) mechanisms to mediate the observed nitrate-induced currents, I(NO3-). We show that a single straightforward reaction cycle describes the data well, pointing out that during exposure to external substrate, S = (2H+ + NO3-)o, the product concentration inside, [P] = [H+]i(2) x [NO3-]i, may rise substantially near the plasma membrane, violating the condition [P] << [S] for MM kinetics. Here, [P] and its changes during experimentation are treated explicitly. K(1/2) approximately 20 microM for I(NO3-) at pHo from Zhou et al. is confirmed. According to our analysis, NrtA operates between about 0.2 and 0.6 of the electrical distance in the membrane (outside 0, inside 1). In absence of thermodynamic gradients, the predominant orientation of the binding site(s) is probably inwards. The activity of the enzyme is sensitive to the transmembrane voltage, V, with an apparent gating charge of +1.0 +/- 0.5 for inactivation, and transition probabilities of 0.3-1.3 s(-1) at V = 0. This gating mode impedes loss of cellular NO3- during depolarization.

Animals↗

Incidence of malignant neoplasms among HIV-infected persons in Scotland.

Among 2574 persons diagnosed with HIV throughout Scotland and observed over the period 1981-1996, cancer incidence compared to the general population was 11 times higher overall; among homosexual/bisexual males, it was 21 times higher and among injecting drug users, haemophiliacs and heterosexuals it was five times higher, mostly due to AIDS-defining neoplasms. However, liver, lung and skin cancers (all non-AIDS-defining) were also significantly increased.

Adolescent↗

Serious overdoses involving buprenorphine in Helsinki.

BACKGROUND: Buprenorphine is used as maintenance therapy for opioid-dependent patients. In comparison with other opioids it is thought to be safer because it is less likely to cause serious respiratory depression. However, concomitant use of psychotropics, especially benzodiazepines, and intravenous injection of dissolved buprenorphine tablets increase the risk of a serious overdose. METHODS: As part of a larger retrospective study of opioid overdoses in Helsinki, the emergency medical services (EMS) records from January 1995 to April 2002 were reviewed for overdoses involving buprenorphine. Hospital records were reviewed when available. RESULTS: We report 11 overdoses in which buprenorphine was involved. The classic symptoms and signs of an opioid overdose (respiratory depression, miosis and central nervous system depression) were present in most of the cases. At least eight of the patients had an overdose that was potentially fatal. One of the patients had a heroin overdose and was reportedly 'treated' by his friends with intravenously administered buprenorphine. CONCLUSION: The high-dosage formulation of buprenorphine used for opioid-dependent patients might have caused several dangerous and potentially fatal overdoses in Helsinki. However, it does cause considerably less serious overdoses than heroin. Drug abusers might be intravenously administering buprenorphine themselves to treat heroin overdoses.

Adult↗

The role of ultrasound in monitoring reconstruction of mandibular continuity defects using osteogenic protein-1 (rhOP-1).

Introducing bone bioengineering concepts in craniofacial surgery demands development of novel imaging strategies, which overcome the shortcomings of radiography such as exposure to ionizing radiation. This study is aimed to investigate the usefulness of ultrasonography (US) in monitoring reconstruction of continuity osteoperiosteal mandibular defects in sheep using rhOP-1. The study was conducted on six adult sheep in which a critical size defect was created at the body of the mandible and was reconstructed using rhOP-1 with type-I collagen as a carrier. Ultrasound images were used to assess onset of bone formation, contour, and surface topography. The results were then compared to corresponding plain radiographs and to post-mortem observations. US showed bone union in all the subjects that concurred with radiographic and post-mortem examinations. US was superior to plain radiography in monitoring early events of ossification. However, it was relatively less efficient in describing the contour of the newly formed bone. It was possible to describe the pattern of bone formation and the dynamic changes in contour and surface topography via US during the follow-up period. In experienced hands, ultrasonography can offer valuable information about bone healing comparable with those obtained by plain radiography. US may replace plain radiography in becoming a routinely used tool for monitoring bone healing in selected sites of the craniofacial skeleton.

Animals↗

The founder mutation MSH2*1906G-->C is an important cause of hereditary nonpolyposis colorectal cancer in the Ashkenazi Jewish population.

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in the mismatch-repair genes. We report here the identification and characterization of a founder mutation in MSH2 in the Ashkenazi Jewish population. We identified a nucleotide substitution, MSH2*1906G-->C, which results in a substitution of proline for alanine at codon 636 in the MSH2 protein. This allele was identified in 15 unrelated Ashkenazi Jewish families with HNPCC, most of which meet the Amsterdam criteria. Genotype analysis of 18 polymorphic loci within and flanking MSH2 suggested a single origin for the mutation. All colorectal cancers tested showed microsatellite instability and absence of MSH2 protein, by immunohistochemical analysis. In an analysis of a population-based incident series of 686 Ashkenazi Jews from Israel who have colorectal cancer, we identified 3 (0.44%) mutation carriers. Persons with a family history of colorectal or endometrial cancer were more likely to carry the mutation than were those without such a family history (P=.042), and those with colorectal cancer who carried the mutation were, on average, younger than affected individuals who did not carry it (P=.033). The mutation was not detected in either 566 unaffected Ashkenazi Jews from Israel or 1,022 control individuals from New York. In hospital-based series, the 1906C allele was identified in 5/463 Ashkenazi Jews with colorectal cancer, in 2/197 with endometrial cancer, and in 0/83 with ovarian cancer. When families identified by family history and in case series are included, 25 apparently unrelated Ashkenazi Jewish families have been found to harbor this mutation. Although this pathogenic mutation is not frequent in the Ashkenazi Jewish population (accounting for 2%-3% of colorectal cancer in those whose age at diagnosis is <60 years), it is highly penetrant and accounts for approximately one-third of HNPCC in Ashkenazi Jewish families that fulfill the Amsterdam criteria.

Alanine↗

Trends in case-fatality in 22968 patients admitted for the first time with atrial fibrillation in Scotland, 1986-1995.

BACKGROUND: Although atrial fibrillation (AF) is an important cause of cardiovascular morbidity and mortality there is a paucity of data describing hospitalisation rates and case-fatality associated with this common arrhythmia. This study examines recent trends in first-ever hospitalisations for AF in Scotland. METHODS: Using the linked Scottish Morbidity Record Scheme, we identified all 22968 patients admitted to Scottish hospitals for the first time with a principal diagnosis of AF between 1986 and 1995. For each calendar year we calculated short (30-day) and medium (31 day to 2 years) case-fatality rates. Adjusting for each patient's age, sex, deprivation status, concurrent diagnoses and prior hospitalisation status, we examined whether case-fatality rates had significantly improved during this 10-year period. RESULTS: Between 1986 and 1995 the number of men hospitalised for the first time with AF increased by 926 (125%) to 1730 per annum and the number of women and by 875 (105%) to 1712 (both P<0.001). Hospitalisation rates increased from 0.31 to 0.70/1000 men and from 0.32 to 0.65/1000 women (both P<0.001). By the end of this period the proportion of men had increased from 48 to 50%. In both sexes, the median age of patients rose--in men from 66 to 68 years and in women from 74 to 75 years (both P<0.01). Despite the increasing age of patients and greater comorbidity, short-term (30-day) case-fatality declined from 4.0 to 3.1% in men (P<0.001) and 4.1 to 3.8% (P<0.01) in women. Similarly, medium-term (31-day to 2-year) case-fatality fell from 25 to 22% in men and 27 to 25% (both P<0.001) in women. Adjusting for the age, sex, extent of deprivation, secondary diagnoses and prior hospitalisation of hospitalised patients, we found that the risk of short-term case-fatality in the 1995 male and female cohort significantly declined by 21% (P<0.05) and 24% (P<0.05), respectively, in comparison to the 1986 cohort. The adjusted risk of case-fatality in the medium term also declined significantly in men by 30% (P<0.05) over this period and by 20% (P<0.05) in women relative to 1986. CONCLUSION: The number of first-ever hospitalisations for AF has increased twofold during the 10-year period 1986-1995. Although the age of patients has progressively increased during this period, short and medium case-fatality rates have declined, especially in men. This may partly reflect better treatment of AF. However, changing admission thresholds and other factors could also have led to an apparent improvement in prognosis. Nevertheless, medium-term case fatality remains substantial after a first ever admission to hospital with AF.

Aged↗

Mental health services and young people with intellectual disability: is it time to do better?

BACKGROUND: There is evidence that the mental health needs of children with disabilities are inadequate. The aim of the present study was to determine the extent of specialist health service use during adolescence by a group of individuals with intellectual disability (ID) and mental health problems. METHOD: The study population consisted of 80 young people with ID, who were examined in childhood and adolescence for psychiatric and behaviour disorder. These young people were interviewed again in early adult life for the presence of psychiatric and behaviour disorder. Evaluation questionnaires were used during the follow-up study to assess service use from adolescence. RESULTS: The key finding was that the great majority (64%) of subjects with persistent challenging behaviour from childhood into adult life and those with an established childhood psychiatric disorder received no specialist mental health care. CONCLUSIONS: The development of mental health services for this vulnerable group with complex psychiatric and behaviour disorders has been poor for a number of reasons, including lack of recognition at the primary care level and insufficient numbers of trained professionals within specialist services.

Adolescent↗

Cytotoxicity of paclitaxel or cisplatin on carcinoma cell lines is not inhibited by leukemia inhibitory factor (LIF).

We have established a reliable, reproducible and objective growth assay to measure whether leukemia inhibitory factor (LIF) was able to protect tumour-derived cell lines from toxic effects of the chemotherapy agents, cisplatin and paclitaxel. Using this assay, we demonstrated that LIF did not alter the cytotoxic action of these drugs, on a panel of seven cancer cell lines. This was not because of the inactivity of the LIF or because the cell lines did not express components of the LIF receptor. These findings suggest that the potential clinical use of LIF, as a neuroprotective agent, in conjunction with chemotherapy will not interfere with the anti-tumour treatment.

Antigens, CD↗