Critical care in the emergency department: patient transfer.
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Critical Care↗
Biomedical subjects
A J Gray
Publications and source records attributed to A J Gray.
In vivo protein transduction to the CNS.
Proteins and peptides are useful research and therapeutic tools, however applications are limited because delivery to the desired location is not easily achievable. There are two hurdles in protein/peptide delivery to the brain: the blood-brain barrier and intracellular penetration. Penetration to both brain and the intracellular space can be achieved by adjusting hydrophilicity, and small molecule pharmacological agents have been successfully developed using this approach. But with proteins and peptides, it is difficult to modify the hydrophilicity without influencing biological functions. Trans-acting factor protein from the human immunodeficiency virus contains a highly conserved cationic peptide sequence necessary for transduction across the cell membrane. While trans-acting factor peptide has been used for in vitro protein transduction, its in vivo application is very limited because it is rapidly degraded by proteolysis. Polyethylenimine is a chemically synthesized small molecule cationization agent; the charge density is greater than a peptide-based cationic cluster such as trans-acting factor, and it is resistant to proteolysis in vivo. We first tested intracellular protein transduction following direct brain injection in mice using polyethylenimine-conjugated green fluorescence protein and beta-galactosidase (molecular weights 29 and 540 kDa, respectively). Polyethylenimine-conjugates penetrated to the intracellular space immediately surrounding the injection site within one hour. We further tested polyethylenimine-mediated protein transduction following intranasal administration, which bypasses the blood-brain barrier. Polyethylenimine-conjugates in pH 7.5 solution did not reach the brain, probably because the polyethylenimine-conjugates penetrated into the intracellular space where first exposed to the tissue, i.e. at the nasal mucosae. We temporarily reduced the electrostatic interaction between cationized polyethylenimine-conjugates and cellular surfaces by adjusting the pH to 4.5; solution rapidly reached the brain and penetrated to the intracellular space. This study suggests that polyethylenimine is a useful protein transduction agent in the brain in vivo, and adjusting cationic charge interaction can determine the extent of brain penetration.
Administration, Intranasal↗
Monitoring the development of intertidal habitats on former agricultural land after the managed realignment of coastal defences at Tollesbury, Essex, UK.
The managed realignment of coastal defences and subsequent creation of intertidal habitats is one of several 'soft' engineering options that could reduce the costs of maintaining embankments and at the same time deliver environmental benefits. The managed realignment at Tollesbury was one of the first in the UK, undertaken as an experimental test case to improve understanding of the practical techniques and processes involved. Independent studies were undertaken on the development of soils, benthic invertebrates and vegetation within the site in addition to methods of enhancing the process of natural colonisation of saltmarsh plants. Bathymetric and vegetation monitoring were undertaken on the adjacent estuary to determine any breach effect that may be attributed to the realignment. This paper summarises the results from the vegetation, sedimentation and invertebrate monitoring and discusses the implications for other managed realignment schemes in the UK.
Agriculture↗
Early management of adults with an uncomplicated first generalised seizure.
A literature review of first seizures in adults was performed and a management algorithm was constructed. This review highlights the importance of a thorough history and examination, routine biochemistry and haematology, an electrocardiogram, selected neuroimaging, discharge planning with driving and lifestyle advice, and follow-up in a specialist clinic.
Adult↗
Prehospital trauma management: a national study of paramedic activities.
OBJECTIVES: The benefits of prehospital trauma management remain controversial. This study aimed to compare the processes of care and outcomes of trauma patients treated by paramedics, who are trained in advanced prehospital trauma care, with those treated by ambulance technicians. METHODS: A six year prospective study was conducted of adult trauma patients attended to by the Scottish Ambulance Service and subsequently admitted to hospital. Prehospital times, interventions, triage, and outcomes were compared between patients treated by paramedics and those treated by technicians. RESULTS: Paramedics attended more severely injured patients (16.5% versus 13.9%, p<0.001); they attended a higher proportion of patients with penetrating trauma (6.6% versus 5.7%, p = 0.014) and had longer prehospital times. Patients managed by paramedics were more likely to be taken to the intensive care unit, operating theatre or mortuary, (11.2% versus 7.8%, p<0.001) and had higher crude mortality rates (5.3% versus 4.5%, p = 0.07). However, no difference in mortality between the two groups was noted when corrected for age, Glasgow coma score and injury severity score. CONCLUSIONS: This large scale national study shows that paramedics show good triage skills and clinical judgement when managing trauma patients. However, the value of the individual interventions they perform could not be ascertained. Further controlled trials are necessary to determine the true benefits of advanced prehospital trauma life support.
Adolescent↗
Epidemiology, clinical characteristics, and management of adults referred to a teaching hospital first seizure clinic.
BACKGROUND: There are scarce data describing the epidemiology, clinical characteristics, and management of adults who suffer a suspected first seizure. AIM: To describe the epidemiology, clinical characteristics, and management of adults with a suspected first seizure who are referred to a teaching hospital first seizure clinic over a one year period. DESIGN: Prospective descriptive study. METHODS: Data were collected on consecutive adults referred to the Royal Infirmary of Edinburgh between 4 February 2003 and 10 February 2004. RESULTS: 232 patients were referred to the first seizure clinic. Median age was 32 years; 53% of patients were male. Lower socioeconomic groups were more likely to present with a suspected first seizure. Nineteen per cent of patients were admitted to hospital after their suspected seizure episode. Appropriate driving advice was reported in 64% of cases. Seventy two per cent of patients were offered a first seizure clinic appointment within six weeks of referral. Nine per cent of patients had a subsequent seizure while awaiting review. Fifty two per cent of patients were confirmed as having a first seizure at the clinic, of which 56% were provoked by alcohol, recreational drugs, or sleep deprivation. Electroencephalography and computed tomography of the brain were the most common investigations ordered at the first seizure clinic (22% and 22% of patients respectively). CONCLUSION: Adults who suffer a suspected first seizure, and who make a full neurological recovery, can be safely managed as an outpatient. Around half of these patients will have a specialist diagnosis of first seizure and alcohol will be a common precipitating factor.
Adolescent↗
A1 and A2 transitions in superfluid 3He in 98% porosity aerogel.
Superfluid 3He in high porosity aerogel is the system in which the effects of static impurities on a p-wave superfluid can be investigated in a systematic manner. We performed shear acoustic impedance measurements on this system (98% porosity aerogel) in the presence of magnetic fields up to 15 T at the sample pressures of 28.4 and 33.5 bars. We observed the splitting of the superfluid transition into two transitions in high fields in both bulk and liquid in aerogel. The field dependence of the splitting in aerogel resembles that of the bulk superfluid 3He caused by the presence and growth of the A1 phase. Our results provide the first evidence of the A1 phase in superfluid (3)He/aerogel.
Journal Article↗
Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema.
BACKGROUND: Continuous positive airways pressure (CPAP) and bilevel non-invasive ventilation may have beneficial effects in the treatment of patients with acute cardiogenic pulmonary oedema. The efficacy of both treatments was assessed in the UK emergency department setting, in a randomised comparison with standard oxygen therapy. METHODS: Sixty patients presenting with acidotic (pH<7.35) acute, cardiogenic pulmonary oedema, were randomly assigned conventional oxygen therapy, CPAP (10 cm H(2)O), or bilevel ventilation (IPAP 15 cm H(2)O, EPAP 5 cm H(2)O) provided by a standard ventilator through a face mask. The main end points were treatment success at two hours and in-hospital mortality. Analyses were by intention to treat. RESULTS: Treatment success (defined as all of respiratory rate<23 bpm, oxygen saturation of>90%, and arterial blood pH>7.35 (that is, reversal of acidosis), at the end of the two hour study period) occurred in three (15%) patients in the control group, seven (35%) in the CPAP group, and nine (45%) in the bilevel group (p = 0.116). Fourteen (70%) of the control group patients survived to hospital discharge, compared with 20 (100%) in the CPAP group and 15 (75%) in the bilevel group (p = 0.029; Fisher's test). CONCLUSIONS: In this study, patients presenting with acute cardiogenic pulmonary oedema and acidosis, were more likely to survive to hospital discharge if treated with CPAP, rather than with bilevel ventilation or with conventional oxygen therapy. There was no relation between in hospital survival and early physiological changes. Survival rates were similar to other studies despite a low rate of endotracheal intubation.
Acidosis↗
Most psychiatrists oppose plans for new mental health act.
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Attitude of Health Personnel↗
Olfactory identification is impaired in clinic-based patients with vascular dementia and senile dementia of Alzheimer type.
AIMS: It is now well established that there are abnormalities in the sense of smell in patients suffering from Alzheimer's disease (AD). They have both raised olfactory thresholds and impaired odour identification. The situation in vascular dementia is unclear. We used the University of Pennsylvania Smell Identification Test (UPSIT), a 40-item, forced choice, cued, 'scratch-and- sniff' test, to examine olfactory identification in vascular dementia and to determine whether it would differentiate the disorder from AD and normal elderly. METHODS: We investigated three matched subject groups: 13 people having a Cambridge Examination for Mental Disorders in the Elderly (CAMDEX) diagnosis of definite senile dementia of Alzheimer type, 13 having a CAMDEX diagnosis of definite vascular dementia and 13 non-cognitively impaired controls. The subjects were then tested with the UPSIT in their own home by an independent blind researcher to see if the test could distinguish the different diagnostic groups in this setting. RESULTS: The median UPSIT score was 30 (out of a maximum of 40) for controls, 12 for the vascular group and 15 for the AD group. The difference was significant (p = 0.05) between both demented groups and the normal controls. Similarly there was a significant difference in the UPSIT score between the AD group and controls (p = 0.001) and between the vascular dementia group and controls (p = 0.001), but there was no significant difference between the AD group and the vascular dementia group. The UPSIT score correlated strongly with the degree of cognitive impairment as measured by the CAMCOG (r(s) = 0.683, p = 0.01) CONCLUSIONS: Patients with vascular dementia had a similar degree of olfactory impairment to those with AD. The UPSIT successfully differentiated between dementia patients and normal elderly British subjects tested in their own homes. The UPSIT did not differentiate between those with AD and vascular dementia.
Aged↗
An evaluation of semiautomatic approaches to contour segmentation applied to fungal hyphae.
Semiautomatic image analysis techniques are particularly useful in biological applications, which commonly generate very complex images, and offer considerable flexibility. However, systematic study of such methods is lacking; most research develops fully automatic algorithms. This paper describes a study to evaluate several different semiautomatic or computer-assisted approaches to contour segmentation within the context of segmenting degraded images of fungal hyphae. Four different types of contour segmentation method, with varying degrees and types of user input, are outlined and applied to hyphal images. The methods are evaluated both quantitatively and qualitatively by comparing results obtained by several test subjects segmenting simulated images qualitatively similar to the hyphal images of interest. An active contour model approach, using control points, emerges as the method to be preferred to three more traditional approaches. Feedback from the image provider indicates that any of the methods described have something useful to offer for segmentation of hyphae.
Algorithms↗
The role of non-invasive ventilation in the emergency department.
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Acute Disease↗
Use of light handles in the laminar flow operating theatre--is it a cause of bacterial concern?
Airborne bacteria introduced during routine joint replacement surgery are known to be an important source of joint sepsis with disastrous results. Recently, Robinson et al. [Robinson AHN, Bentley G, Drew S, Anderson J, Ridgway GL. Suction tip contamination in the ultraclean air operating theatre. Ann R Coll Surg Engl 1993; 75: 254-6] have demonstrated that the conventional surgical sucker forms a focus for airborne pathogens which results in septic loosening of hip prostheses. Similarly, the potential contamination of theatre light handles, commonly used during total hip and knee replacements, gives cause for concern. To assess if there was any evidence of contamination, we cultured bacterial swabs taken from the light handles before and after 15 such procedures, all of which were held in a conventional orthopaedic operating theatre. Fortunately, our study found no reason to stop the use of light handles in joint replacement operations.
Aged↗
Air emboli with Haemaccel(R)
We report two cases of venous air embolism which occurred in association with infusion of Haemaccel(R) using a pressure bag. As a result of these incidents, we performed a study that showed that up to 45 ml of air can be infused into a patient from a pressurised Haemaccel(R) plastic bottle using a standard administration set. We also demonstrated that the volume of air infused was influenced by the type and size of the pressure bag and the warming of the Haemaccel(R) plastic container.
Aged↗
Stevens-Johnson syndrome in patients on phenytoin and cranial radiotherapy.
The use of phenytoin as a prophylactic anticonvulsant after brain surgery, particularly for brain tumors, is a common practice, regardless of whether the patient has a previous history of convulsions. This treatment policy assumes that the benefits exceed the risks. Four cases are described of adverse reactions to phenytoin during the concomitant use of cranial radiotherapy. In one patient this proved fatal. There is increasing anecdotal support in the literature for a synergistic effect between phenytoin therapy and cranial radiotherapy that can result in the life-threatening Stevens-Johnson syndrome. While the association is uncommon, four cases within 24 months in one department suggest that the routine use of postoperative phenytoin as a prophylactic anticonvulsant in the absence of a history of seizures may not be warranted, particularly if the patient is to receive cranial radiotherapy.
Adult↗
The aftermath of the Bristol case. Deaths are acceptable in some specialties but not all.
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Clinical Competence↗
Thrombin stimulates fibroblast procollagen production via proteolytic activation of protease-activated receptor 1.
Thrombin is a multifunctional serine protease that has a crucial role in blood coagulation. It is also a potent mesenchymal cell mitogen and chemoattractant and might therefore have an important role in the recruitment and local proliferation of mesenchymal cells at sites of tissue injury. We hypothesized that thrombin might also affect the deposition of connective tissue proteins at these sites by directly stimulating fibroblast procollagen production. To address this hypothesis, the effect of thrombin on procollagen production and gene expression by human foetal lung fibroblasts was assessed over 48 h. Thrombin stimulated procollagen production at concentrations of 1 nM and above, with maximal increases of between 60% and 117% at 10 nM thrombin. These effects of thrombin were, at least in part, due to increased steady-state levels of alpha1(I) procollagen mRNA. They could furthermore be reproduced with thrombin receptor-activating peptides for the protease-activated receptor 1 (PAR-1) and were completely abolished when thrombin was rendered proteolytically inactive with the specific inhibitors d-Phe-Pro-ArgCH2Cl and hirudin, indicating that thrombin is mediating these effects via the proteolytic activation of PAR-1. These results suggest that thrombin might influence the deposition of connective tissue proteins during normal wound healing and the development of tissue fibrosis by stimulating fibroblast procollagen production.
Connective Tissue↗
Long-term results of accelerated radiation treatment for advanced head and neck cancer.
BACKGROUND AND PURPOSE: This report presents long-term follow-up data from a prospective but unrandomized trial of a continuous 3.5-week course of accelerated radiation treatment (ART) used as primary treatment for patients with loco-regionally advanced head and neck cancer. MATERIALS AND METHODS: Ninety-three patients in three centres in New Zealand and Australia were treated with ART (59.40 Gy in 33 fractions over 24-25 days). Their disease originated from three anatomical regions (oral cavity, 35 patients; pharynx, 31 patients; larynx, 27 patients). Seventy-nine of these patients had stage III or IV cancers. RESULTS: Follow-up ranged from 68 to 203 months (median 139 months). Loco-regional (LR) failure occurred in 52 patients leading to a 10-year actuarial expectation of LR control of 38%. The actuarial expectation of LR control at 10 years was highly dependent on stage and for stage III, IVA and IVB patients it was 57+/-8.1%, 32+/-1.7% and 7+/-0.5%, respectively. Multivariate analysis could not confirm an independent impact of primary site or histological differentiation on LR failure. Two patients died of acute toxicity of treatment and six patients developed grade 3/4 late complications affecting soft tissues only, yielding an actuarial expectation of complications of this severity at 5 years of 9%. No cases of osteoradionecrosis or myelitis were observed. CONCLUSION: This ART, which has proved easy to use at a number of large and small centres, has produced encouraging long-term LR control at a cost of limited soft tissue morbidity.
Adolescent↗