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Biomedical subjects

J Arnold

Publications and source records attributed to J Arnold.

At least 19 recordsLinked to original sources
PubMed2006

Succinylcholine or rocuronium? A meta-analysis of the effects on intubation conditions.

This meta-analysis was undertaken to compare the effects of succinylcholine (SCH) and rocuronium (RCR) on endotracheal intubation (ETI) conditions. Eligible randomised controlled trials (RCTs) were identified via medline and a manual search of references. The frequencies of excellent and unacceptable ETI conditions in subjects receiving SCH 1.0-1.5 mg/kg and RCR 0.6-1.2 mg/kg were determined using standard statistical methods. Inclusion criteria were met by 16 RCTs, representing 1362 subjects. SCH was associated with a 17.7% increase (95% CI = 13-22) in the frequency of excellent ETI conditions and a 5.1% decrease (95% CI = -7.3 to -2.9) in the frequency of unacceptable ETI conditions, when compared with RCR. In the subgroup undergoing true rapid sequence intubation, SCH was associated with a 19.1% increase (95% CI = 13.7-24.5) in the frequency of excellent ETI conditions. SCH appears to be superior to RCR in creating excellent ETI conditions and avoiding unacceptable ETI conditions.

Androstanols↗
PubMed2006

Metabolic model of autoregulation in the Circle of Willis.

The Circle of Willis (CoW) is a ringlike structure of blood vessels found at the base of the brain. Its main function is to distribute oxygen-rich arterial blood to the cerebral mass. In a previous study, a one-dimensional (1D) model of the CoW was created to simulate a series of possible clinical scenarios such as occlusions in afferent arteries, absent or stringlike circulus vessels, or arterial infarctions (Moorhead et al., 2004, Comput. Methods Biomech. Biomed. Eng., 7(3), pp. 121-130). The model captured cerebral haemodynamic autoregulation by using a proportional-integral-derivative (PID) controller to modify efferent artery resistances. Although some good results and correlations were achieved, the model was too simple to capture all the transient dynamics of autoregulation. Hence a more physiologically accurate model has been created that additionally includes the oxygen dynamics that drive the autoregulatory response. Results very closely match accepted physiological response and limited clinical data. In addition, a set of boundary conditions and geometry is presented for which the autoregulated system cannot provide sufficient perfusion, representing a condition with increased risk of stroke and highlighting the importance of modeling the haemodynamics of the CoW. The system model created is computationally simple so it can be used to identify at-risk cerebral arterial geometries and conditions prior to surgery or other clinical procedures.

Animals↗
PubMed2006

Development of atrophy of the retinal pigment epithelium around disciform scars.

BACKGROUND/AIMS: Eyes with burnt out disciform scars secondary to age related macular degeneration (AMD) are regarded as visually stable. The aim of this study is to report the subsequent development of atrophy of the retinal pigment epithelium (RPE) around the scars and discuss the possible basis. METHODS: 20 eyes from 18 patients were observed to develop atrophy around choroidal neovascularisation (CNV). A method of measuring expansion of the atrophy over time is described using the Topcon Imagenet 2000 system. An additional 10 clinicopathological examples were reviewed. RESULTS: Clinically CNV became surrounded initially by a ring of pallor that progressed to an expanding band of atrophy of the RPE. It developed most rapidly in the first 3 years after CNV became quiescent but then continued to expand slowly to more than three times the size of the scar. Histopathological specimens showed large choroidal vessels entering the scars directly and a reduced number of small choroidal vessels beneath and around the scar CONCLUSIONS: Disciform scars may become surrounded by an expanding band of atrophy of the RPE, postulated to result from remodelling of the choroidal circulation. The ongoing enlargement of the resulting scotoma may need to be considered when planning management and assessing treatment outcomes.

Aged↗
PubMed2005

3D models of blood flow in the cerebral vasculature.

The circle of Willis (CoW) is a ring-like arterial structure located in the base of the brain and is responsible for the distribution of oxygenated blood throughout the cerebral mass. To investigate the effects of the complex 3D geometry and anatomical variability of the CoW on the cerebral hemodynamics, a technique for generating physiologically accurate models of the CoW has been created using a combination of magnetic resonance data and computer-aided design software. A mathematical model of the body's cerebral autoregulation mechanism has been developed and numerous computational fluid dynamics simulations performed to model the hemodynamics in response to changes in afferent blood pressure. Three pathological conditions were explored, namely a complete CoW, a fetal P1 and a missing A1. The methodology of the cerebral hemodynamic modelling is proposed with the potential for future clinical application in mind, as a diagnostic tool.

Blood Flow Velocity↗
PubMed2005

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families: functional analysis in heterozygous individuals.

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Adult↗
PubMed2005

Rationing in the emergency department: the good, the bad, and the unacceptable.

OBJECTIVES: Waiting times in emergency departments (EDs) are an important government priority. Although substantial efforts are currently being made to reduce waiting times, little attention has been paid to the patients' view. We used qualitative methods to explore patients' perspectives on waiting times and other approaches to rationing and prioritisation. METHODS: Face to face, in depth, qualitative interviews (n = 11) explored how patients valued waiting times for non-urgent ED care. The framework approach (identifying a thematic framework through repeated re-reading) was used to analyse transcripts. RESULTS: Interviewees found some forms of rationing and prioritisation acceptable. They expected rationing by delay, but required explanations or information on the reason for their wait. They valued prioritisation by triage (rationing by selection) and thought that this role could be expanded for the re-direction of non-urgent patients elsewhere (rationing by deflection). Interviewees were mainly unwilling or unable to engage in prioritisation of different types of patients, openly prioritising only those with obvious clinical need, and children. However, some interviewees were willing to ration implicitly, labelling some attenders as inappropriate, such as those causing a nuisance. Others felt it was unacceptable to blame "inappropriate" attenders, as their attendance may relate to lack of information or awareness of service use. Explicit rationing between services was not acceptable, although some believed there were more important priorities for NHS resources than ED waiting times. Interviewees disagreed with the hypothetical notion of paying to be seen more quickly in the ED (rationing by charging). CONCLUSIONS: Interviewees expected to wait and accepted the need for prioritisation, although they were reluctant to engage in judgements regarding prioritisation. They supported the re-direction of patients with certain non-urgent complaints. However, they perceived a need for more explanation and information about their wait, the system, and alternative services.

Adult↗
PubMed2003

Analysis of the candidate 8p21 tumour suppressor, BNIP3L, in breast and ovarian cancer.

Loss of heterozygosity (LOH) on the short arm of chromosome 8, at 8p12-p23, is one of the most frequent genetic events in both breast and ovarian cancer, suggesting the location of a shared tumour suppressor gene. Microcell-mediated chromosome transfer of chromosome 8 suppresses tumorigenicity and growth of colorectal and prostate cancer cell lines, further supporting the presence of a tumour suppressor gene on 8p. We have taken a candidate gene approach to try to identify this tumour suppressor gene at 8p12-p23. BNIP3L, which has sequence homology to pro-apoptotic proteins and the ability to suppress colony formation in soft agar, is located at 8p21, within a region of ovarian cancer LOH, breast cancer LOH and prostate cancer metastasis suppression. BNIP3L expression was assessed by both RT-PCR and Northern blot analysis in breast and ovarian cancer cell lines and found to be expressed at similar levels relative to expression in their respective normal epithelial cell lines. Genetic analysis of BNIP3L in 40 primary ovarian and 25 primary breast tumours identified one somatic, intronic mutation in one ovarian tumour, as well as several polymorphisms, including one resulting in an amino-acid substitution. These data suggest that BNIP3L is unlikely to be the target of 8p LOH in ovarian or breast cancer.

Apoptosis↗
PubMed2003

[Experiences after 150 cartilage-bone-transplantations of the knee: a prospective analysis of the results].

INTRODUCTION: To evaluate the clinical outcome of cartilage-bone-transplantations of the knee in patients with different indications, we studied the clinical results of 45 patients with a follow-up of 24 months after operation. PATIENTS AND METHODS: 29 male and 16 female patients with a mean age of 37.7 yrs (16-58 yrs) were included. Indications for operation were osteochondritis dissecans (OD) (n=13), limited arthritis (n=20), traumatic lesions (n=5) and retropatellar lesions (n=7). The results were evaluated by clinical score (McDermott Score; preoperatively, and 3, 6, 12, 24 months postoperatively), magnetic resonance imaging, and re-arthroscopy for most patients. RESULTS: 42 of 45 patients judged the operation as successful. The mean score value of all patients raised from 66.3 pts (out of 100 pts) preoperatively to 92.7 pts 24 months postoperatively. The results of the patients with circumscript arthritic lesions (62.9 pts. preoperatively vs. 91.5 pts. postoperatively) were comparable to those of the other patients. CONCLUSION: We conclude that cartilage-bone-transplantation of the knee is a valuable procedure to improve joint function not only after OD or trauma, but also in joints with local arthritic lesions on condition that there is an adequate quality of the donor site.

Adolescent↗
PubMed2003

Clinical predictors of acute coronary syndromes in patients with undifferentiated chest pain.

BACKGROUND: Patients with acute, undifferentiated chest pain present a frequent diagnostic challenge to clinicians. Clinical features are often used to determine which patients may have acute coronary syndrome (ACS). AIM: To identify clinical features that independently predict ACS in patients with acute, undifferentiated chest pain. DESIGN: Prospective study of patients enrolled in a randomized controlled trial. METHODS: The presenting characteristics of participants in the ESCAPE randomized trial of chest pain unit vs. routine care were recorded in a standardized manner. Follow-up consisted of troponin T measurement at 2 days, postal questionnaire at 1 month, and telephone contact at 6 months. ACS was defined as elevated troponin T at 2 days or major adverse cardiac event within 30 days of presentation. Multivariate analysis identified independent clinical predictors of ACS. RESULTS: ACS was diagnosed in 77 (7.9%) of the 972 patients recruited. The following characteristics were independent predictors of ACS (odds ratio, p): age (1.09, p < 0.001), male gender (8.6, p < 0.001), indigestion or burning-type pain (3.0, p = 0.034), pain radiating to the left (2.4, p = 0.013) or right (5.7, p < 0.001) arm, vomiting (3.5, p = 0.007), and previous (5.1, p < 0.001) or current (3.7, p < 0.001) smoking. DISCUSSION: In addition to previously recognized predictors of ACS, it appears that indigestion or burning type pain predicts ACS in patients attending the emergency department with acute, undifferentiated chest pain. Diagnosis of acute 'gastro-oesophageal' chest pain should be avoided in this setting.

Chest Pain↗
PubMed2002

An ensemble method for identifying regulatory circuits with special reference to the qa gene cluster of Neurospora crassa.

A chemical reaction network for the regulation of the quinic acid (qa) gene cluster of Neurospora crassa is proposed. An efficient Monte Carlo method for walking through the parameter space of possible chemical reaction networks is developed to identify an ensemble of deterministic kinetics models with rate constants consistent with RNA and protein profiling data. This method was successful in identifying a model ensemble fitting available RNA profiling data on the qa gene cluster.

Genes, Fungal↗
PubMed2002

Simulation code for the interaction of 14 MeV neutrons on cells.

The structure of the survival curve of melanoma cells irradiated by 14 MeV neutrons displays unusual features at very low dose rate where a marked increase in cell killings at 0.05 Gy is followed by a plateau for survival from 0.1 to 0.32 Gy. In parallel a simulation code was constructed for the interaction of 14 MeV neutrons with cellular cultures. The code describes the interaction of the neutrons with the atomic nuclei of the cellular medium and of the external medium (flask culture and culture medium), and is used to compute the deposited energy into the cell volume. It was found that the large energy transfer events associated with heavy charged recoils can occur and that a large part of the energy deposition events are due to recoil protons emitted from the external medium. It is suggested that such events could partially explain the experimental results.

Cell Survival↗
PubMed2002

A prospective, observational study of a chest pain observation unit in a British hospital.

OBJECTIVES: To establish a chest pain observation unit, monitor its performance in terms of appropriate discharge after assessment, and estimate the cost per patient. METHODS: Prospective, observational, cohort study of patients attending a large, city, teaching hospital accident and emergency department between 1 March 1999 and 29 February 2000 with acute undifferentiated chest pain. Patients were managed on a chest pain observation unit, entailing two to six hours of observation, serial electrocardiograph recording, cardiac enzyme measurement, and, where appropriate, exercise stress test. Patients were discharged home if all tests were negative and admitted to hospital if tests were positive or equivocal. The following outcomes were measured-proportion of participants discharged after assessment; clinical status three days after discharge; cardiac events and procedures during the following six months; and cost of assessment and admission. RESULTS: Twenty three participants (4.3%) had a final diagnosis of myocardial infarction. All were detected and admitted to hospital. A total of 461 patients (86.3%) were discharged after assessment, 357 (66.9%) avoided hospital admission entirely. At review three days later these patients had no new ECG changes and only one raised troponin T measurement. In the six months after assessment, three cardiac deaths, two myocardial infarctions, and two revascularisation procedures were recorded among those discharged. The mean cost of assessment and hospital admission was 221 pound per patient, or 323 pound if subsequent interventional cardiology costs were included. CONCLUSIONS: The chest pain observation unit is a practical alternative to routine care for acute chest pain in the United Kingdom. Negative assessment effectively rules out immediate, serious morbidity, but not longer term morbidity and mortality. Costs seem to be similar to routine care.

Angina Pectoris↗
PubMed2001

Reactivity of a titanium dinitrogen complex supported by guanidinate ligands: investigation of solution behavior and a novel rearrangement of guanidinate ligands.

The titanium dinitrogen complex, [[(Me(2)N)C(N(i)Pr)(2)]( 2)Ti](2)(N(2)) (2), was synthesized by reduction of the dichloride precursor, [(Me(2)N)C(N(i)Pr)(2)](2)TiCl(2) (1). The dinitrogen complex reacts with phenyl azide to yield the titanium imido complex, [(Me(2)N)C(N(i)Pr)(2)](2)TiNPh (3). The fluxional behavior of the guanidinate ligands in compounds 1-3 was investigated using variable temperature and two-dimensional NMR techniques; guanidinate ligand rotation and racemization reactions were observed. Rearrangement of the guanidinate ligand to an asymmetrical bonding mode utilizing the dimethylamino and amide-nitrogen atoms is observed in the bridging oxo and sulfido derivatives (4 and 5). These compounds are formed by the reactions of 2 with pyridine N-oxide and propylene sulfide, respectively. The ligand rearrangement was observed to be reversible for the bridging sulfido complex 5; the structure of this compound is sensitive to temperature and solvent. The solid-state and solution structures of compounds 1-5 are discussed.

Journal Article↗