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Biomedical subjects

R Andrews

Publications and source records attributed to R Andrews.

At least 37 records · Page 2Linked to original sources

A case of Brown-Sequard syndrome with associated Horner's syndrome after blunt injury to the cervical spine.

A 26 year old motorcyclist was received by the trauma team in our accident and emergency department after a head on collision with a motor vehicle. He had been correctly immobilised and his primary survey was essentially normal. He was alert and orientated with a Glasgow Coma score of 15 and had no symptoms or signs of spinal injury. His cervical spine radiography was also normal. Neurological examination however, revealed anisocoria, his left pupil being smaller than his right, and a Brown-Sequard syndrome, with a sensory level at C6. Immobilisation was maintained and he was transferred to the regional neurosurgical centre where magnetic resonance imaging revealed a contusion of the left half of the spinal cord adjacent to the 6th cervical vertebrae. Computed tomography revealed no bony injury but spinal column instability was demonstrated after flexion-extension spinal views and he underwent surgery to fuse his spine at the C5-C6 level. This report highlights the necessity to observe strict ATLS guidelines. This must include a thorough examination of the central and peripheral nervous system where spinal injury is suspected, even in the absence of radiographic abnormality and neck pain. This article also presents the unusual phenomena of Brown-Sequard syndrome and unilateral Horner's syndrome after blunt traumatic injury to the cervical spine.

Accidents, Traffic↗

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a nicotine derivative, induces apoptosis of endothelial cells.

Smoking causes endothelial cell (EC) injury; however, neither the components of cigarette smoke nor the mechanisms responsible for this injury are understood. The nitrosated derivative of nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), has been implicated in the carcinogenic effects of tobacco; however, the effects of NNK on the cardiovascular system are largely unknown. NNK binds to beta1- and beta2-adrenergic receptors. Because beta-adrenergic receptor activation causes arachidonic acid (AA) release and cellular injury, we postulated that NNK causes EC injury by a mechanism that involves beta-adrenergic-mediated release of AA. NNK stimulated [3H]AA release from ECs, and this effect was mediated by both beta1- and beta2-adrenergic receptors because pretreatment with atenolol or ICI 118,551 inhibited the response. NNK also induced EC apoptosis, as measured by terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling and annexin V staining. NNK-mediated apoptosis was attenuated by pretreatment with atenolol or ICI 118,551. Furthermore, depletion of cellular AA by incubation with eicosapentaenoic acid abolished the apoptotic effect of NNK. These data suggest that NNK causes EC apoptosis by a mechanism that involves beta1- and beta2-adrenergic receptor-mediated release of AA.

Animals↗

Unexpected difficult intubation in a patient with normal airway on assessment.

Routine preoperative assessment of the patient's airway includes an assessment of mouth opening and a grading of the view according to the Mallampati scale. This is carried out with the patient sitting and actively opening the mouth without phonation. This case report illustrates that the temporomandibular joint is a complex joint and that certain pathologies may prevent passive depression of the mandible after induction of anaesthesia.

Female↗

Measles: how many hospitalised cases are we missing?

We aimed to determine whether the Victorian measles surveillance system had missed hospitalised cases of measles during an inter-epidemic period. We searched the Victorian Inpatient Minimum Dataset (VIMD) for the period 1 January 1997 to 30 June 1998 to identify patients with ICD-9 discharge codes for measles (055). The data were compared with that held in the Victorian measles surveillance dataset. The hospital case notes of patients identified in the VIMD but not in the measles surveillance dataset were reviewed systematically to determine whether the patients met case definitions for laboratory-confirmed or clinically compatible measles. Sixteen admissions (15 patients) were identified with a measles ICD-9 code. Eight patients were not identified in the measles surveillance dataset. Of these, one was a laboratory confirmed case of measles and two met a clinical case definition but all should have been notified to the Department of Human Services as suspected cases. While the small number of missed notifications is encouraging in terms of overall measles surveillance, it highlights important deficiencies in the awareness of hospital staff of their role in the control of measles, particularly as Australia moves towards the elimination of measles.

Adult↗

Measles outbreak among young adults in Victoria.

An outbreak of laboratory confirmed measles involving 30 young adults and an infant is reported. Of the young adult cases, 17 (57%) were hospitalised. After a trip to India, the primary case returned to Sydney early in January 2001 and then visited Melbourne infecting several individuals. Secondary spread appears to have occurred at a nightclub. On the basis of RNA typing the measles strain involved is of genotype 'D'.

Adolescent↗

Range expansion of the tick Amblyomma triguttatum triguttatum, an australian vector of Q fever.

The tick Amblyomma triguttatum triguttatum has previously been reported from Western Australia, Queensland and New South Wales. A viable population of this species, including all developmental stages, has now been discovered on the southern end of Yorke Peninsula, South Australia. Species determination was carried out morphologically and using 18S and 16S rRNA. The data for 16S rRNA are the first published for this species. Amblyomma t. triguttatum is significant through its involvement in the natural, Australian cycle of Coxiella burnetti, the pathogen causing Q fever. The environment of Yorke Peninsula contains all of the components required for a natural Q fever cycle and three cases of this disease have been reported from this area since 1995. These findings reinforce the need to put in place effective mechanisms to monitor parasite distributions at a time of large scale global change.

Animals↗

Surveillance of pneumococcal disease in Australian states and territories.

Information on pneumococcal disease, including immunisation programs, and optimum future surveillance in each Australian State and Territory were discussed at the Pneumococcal Disease in Australia Workshop on 26-27 March 1999. Workshop participants further expanded on the surveillance aspects of the Workshop in this report. Most participants favoured notification by laboratories of pneumococcal isolates from sterile sites, to provide baseline surveillance data before immunisation programs are fully implemented. It was also thought that trends in antimicrobial resistance should be notified.

Australia↗

Laboratory-supported influenza surveillance in Victorian sentinel general practices.

Laboratory-supported influenza surveillance is important as part of pandemic preparedness, for identifying and isolating candidate vaccine strains, for supporting trials of anti-influenza drugs and for refining the influenza surveillance case definition in practice. This study describes the implementation of laboratory-supported influenza surveillance in Victorian sentinel general practices and provides an estimate of the proportion of patients with an influenza-like illness proven to have influenza. During 1998 and 1999, 25 sentinel general practices contributed clinical surveillance data and 16 metropolitan practices participated in laboratory surveillance. Serological, virus-antigen detection, virus culture and multiplex polymerase chain reaction procedures were used to establish the diagnosis of influenza. Two laboratories at major teaching hospitals in Melbourne provided additional data on influenza virus identification. General practice sentinel surveillance and laboratory identification of influenza provided similar data on the pattern of influenza in the community between May and September. The clinical suspicion of influenza was confirmed in 49 to 54 per cent of cases seen in general practice.

Adolescent↗

Hematopoietic differentiation activity of a recombinant human interleukin-6 (IL-6) isoform resulting from alternatively spliced deletion of the second exon.

We have previously identified and cloned an alternatively spliced form of human interleukin-6 mRNA lacking exon II, which encodes amino acid residues known to be important in gp130-mediated signal transduction pathways. We expressed and purified the recombinant protein (rIL6-alt) resulting from this alternatively spliced mRNA and now report the initial characterization of its biologic activities with comparison to full length IL6 (rIL6-full). rIL6-alt was found to have 10(4) to 10(5) fold less activity in proliferation assays with 7TD1 murine plasmacytoma cells and did not competitively inhibit the stimulatory activity of rIL6-full. In addition, like rIL6-full, rIL6-alt had antiproliferative activity toward M1 murine myeloblast cells and was 10-200-fold less active than rIL6-full. In contrast, in assays with human HL60 promyelocytic leukemia cells, rIL6-alt had greater antiproliferative activity than rIL6-full and more strongly upregulated phagocytosis as well as surface expression of the differentiation antigen CD11b. rIL6-full and rIL6-alt upregulated the level of lysozyme mRNA in HL60 cells approximately equally. These findings suggest that IL6-alt, which lacks amino acid residues encoded by the second exon of the gene, is not a natural inhibitor of IL6-full but may be relatively tissue specific and may play a role in modulation of hematopoietic cell growth and differentiation.

Alternative Splicing↗

Platelet alpha2-adrenergic receptor coupling efficiency to Gi protein in subjects with post-traumatic stress disorder and normal controls.

Low platelet membrane alpha2-adrenergic receptor (alpha2AR) density and low basal and forskolin-stimulated cyclic adenosine monophosphate responses, which have been reported in post-traumatic stress disorder (PTSD), suggest either abnormal alpha2AR coupling to G(i) protein or dysregulation in post-receptor signal transduction mechanisms. alpha2AR density in the high- and low-conformational states, agonist affinity in both states and coupling to G(i) protein were investigated in 23 drug-free combat PTSD patients and 25 normal controls. alpha2AR coupling measures were not different between PTSD patients and controls. Total alpha2AR density was higher in PTSD patients than controls, due to a higher density of the receptor in the high-conformational state. There were no differences in agonist affinity to the receptor in either conformational state. Results rule out dysregulation in alpha2AR coupling to G(i) protein. Studies of post-receptor signal transduction mechanisms are warranted.

Adult↗

Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls.

The symptomatology of post-traumatic stress disorder (PTSD) involves sympathetic hyperarousal. Several of these sympathetic symptoms are mediated through end-organ beta2-adrenergic receptors (beta2AR). Increased sympathetic activity in PTSD could therefore be due to increased betaAR function. This study investigated betaAR function in 30 healthy controls and 20 drug-free PTSD patients. BetaAR binding studies were conducted using antagonist-saturation and agonist-displacement experiments. Measures of beta2AR coupling to Gs protein were derived from agonist-displacement experiments. PTSD patients had significantly higher beta2AR density particularly in the high-conformational state and higher beta2AR coupling than controls, as reflected in a higher percentage of receptors in the high conformational state and a higher ratio of the agonist dissociaton constant from the receptor in the low/high-conformational state. Increased betaAR function in PTSD is consistent with the symptomatology of this disorder. Increased betaAR density and coupling may be consistent with downregulation of betaAR density and uncoupling by antidepressants and may underlie their partial efficacy in PTSD. Dysregulation in Gs protein function is postulated and, agonist-mediated regulation of betaAR expression and/or betaAR kinase activity in PTSD should be investigated in future studies.

Adult↗

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

AIMS: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. METHODS AND RESULTS: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). CONCLUSION: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

Death, Sudden, Cardiac↗

Multimodality stereotactic brain tissue identification: the NASA smart probe project.

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures.

Brain↗

Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders.

BACKGROUND: One-third of children diagnosed with autism spectrum disorders (ASDs) are reported to have had normal early development followed by an autistic regression between the ages of 2 and 3 years. This clinical profile partly parallels that seen in Landau-Kleffner syndrome (LKS), an acquired language disorder (aphasia) believed to be caused by epileptiform activity. Given the additional observation that one-third of autistic children experience one or more seizures by adolescence, epileptiform activity may play a causal role in some cases of autism. OBJECTIVE: To compare and contrast patterns of epileptiform activity in children with autistic regressions versus classic LKS to determine if there is neurobiological overlap between these conditions. It was hypothesized that many children with regressive ASDs would show epileptiform activity in a multifocal pattern that includes the same brain regions implicated in LKS. DESIGN: Magnetoencephalography (MEG), a noninvasive method for identifying zones of abnormal brain electrophysiology, was used to evaluate patterns of epileptiform activity during stage III sleep in 6 children with classic LKS and 50 children with regressive ASDs with onset between 20 and 36 months of age (16 with autism and 34 with pervasive developmental disorder-not otherwise specified). Whereas 5 of the 6 children with LKS had been previously diagnosed with complex-partial seizures, a clinical seizure disorder had been diagnosed for only 15 of the 50 ASD children. However, all the children in this study had been reported to occasionally demonstrate unusual behaviors (eg, rapid blinking, holding of the hands to the ears, unprovoked crying episodes, and/or brief staring spells) which, if exhibited by a normal child, might be interpreted as indicative of a subclinical epileptiform condition. MEG data were compared with simultaneously recorded electroencephalography (EEG) data, and with data from previous 1-hour and/or 24-hour clinical EEG, when available. Multiple-dipole, spatiotemporal modeling was used to identify sites of origin and propagation for epileptiform transients. RESULTS: The MEG of all children with LKS showed primary or secondary epileptiform involvement of the left intra/perisylvian region, with all but 1 child showing additional involvement of the right sylvian region. In all cases of LKS, independent epileptiform activity beyond the sylvian region was absent, although propagation of activity to frontal or parietal regions was seen occasionally. MEG identified epileptiform activity in 41 of the 50 (82%) children with ASDs. In contrast, simultaneous EEG revealed epileptiform activity in only 68%. When epileptiform activity was present in the ASDs, the same intra/perisylvian regions seen to be epileptiform in LKS were active in 85% of the cases. Whereas primary activity outside of the sylvian regions was not seen for any of the children with LKS, 75% of the ASD children with epileptiform activity demonstrated additional nonsylvian zones of independent epileptiform activity. Despite the multifocal nature of the epileptiform activity in the ASDs, neurosurgical intervention aimed at control has lead to a reduction of autistic features and improvement in language skills in 12 of 18 cases. CONCLUSIONS: This study demonstrates that there is a subset of children with ASDs who demonstrate clinically relevant epileptiform activity during slow-wave sleep, and that this activity may be present even in the absence of a clinical seizure disorder. MEG showed significantly greater sensitivity to this epileptiform activity than simultaneous EEG, 1-hour clinical EEG, and 24-hour clinical EEG. The multifocal epileptiform pattern identified by MEG in the ASDs typically includes the same perisylvian brain regions identified as abnormal in LKS. When epileptiform activity is present in the ASDs, therapeutic strategies (antiepileptic drugs, steroids, and even neurosurgery) aimed at its control can lead to a significa

Autistic Disorder↗

Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).

BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.

Aged↗

Spontaneous cervical hemorrhage with near-complete airway obstruction.

BACKGROUND: Retropharyngeal hematoma is a rare entity which may progress rapidly to airway obstruction. Previously documented causes have included coagulopathic states, trauma, infection, parathyroid adenoma rupture, and foreign-object ingestion. Four cases of spontaneous retropharyngeal hematomas without any known predisposing risk factors have been previously reported. Two of these cases had fatal outcomes. METHODS: A case report is presented and the literature reviewed. RESULTS: Spontaneous cervical hematoma with parapharyngeal and retropharyngeal involvement which caused near-complete respiratory obstruction occurred in an otherwise healthy young man following straining. Initial management involved fiberoptic nasotracheal intubation. Subsequent right neck exploration revealed hemorrhage from a branch of the external carotid artery, which was ligated. An arteriogram revealed minimal flow through the right external carotid artery and its branches. The patient was extubated and discharged uneventfully on the fourth postoperative day. CONCLUSION: The possible etiology for this case is discussed, and a review of the literature and the role of surgery in the management of this entity is outlined.

Adult↗

The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure.

AIMS: To assess the effects of dietary creatine supplementation on skeletal muscle metabolism and endurance in patients with chronic heart failure. METHODS: A forearm model of muscle metabolism was used, with a cannula inserted retrogradely into an antecubital vein of the dominant forearm. Maximum voluntary contraction was measured using handgrip dynanometry. Subjects performed handgrip exercise, 5 s contraction followed by 5 s rest for 5 min at 25%, 50%, and 75% of maximum voluntary contraction or until exhaustion. Blood was taken at rest and 0 and 2 min after exercise for measurement of lactate and ammonia. After 30 min the procedure was repeated with fixed workloads of 7 kg, 14 kg and 21 kg. Patients were assigned to creatine 20 g daily or matching placebo for 5 days and returned after 6 days for repeat study. RESULTS: Contractions (median (25th, 75th interquartiles)) until exhaustion at 75% of maximum voluntary contraction increased after creatine treatment (8 (6, 14) vs 14 (8, 17), P = 0.025) with no significant placebo effect. Ammonia per contraction at 75% maximum voluntary contraction (11.6 mumol/l/contraction (8.3, 15.7) vs 8.9 mumol/l/contraction (5.9, 10.8), P = 0.037) and lactate per contraction at 75% maximum voluntary contraction (0.32 mmol/l/contraction (0.28, 0.61) vs 0.27 mmol/l/contraction (0.19, 0.49), P = 0.07) fell after creatine but not after placebo. CONCLUSIONS: Creatine supplementation in chronic heart failure augments skeletal muscle endurance and attenuates the abnormal skeletal muscle metabolic response to exercise.

Aged↗