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Biomedical subjects

R Mackenzie

Publications and source records attributed to R Mackenzie.

At least 19 recordsLinked to original sources
PubMed2007

Cuffed endotracheal tube use in paediatric prehospital intubation: challenging the doctrine?

Questioning traditional doctrines is essential if patient care is to improve and progress. Historically accepted teaching is to use uncuffed tubes in all children up to puberty. This has been the practice in anaesthesia, intensive care and paediatric resuscitation both in and out of hospital. The use of cuffed endotracheal tubes (ETTs) in pre-pubertal children is evolving in general anaesthesia and intensive care in hospital practice. In contrast, uncuffed tubes are still widely recommended for use in the prehospital environment in this age group. There are a number of good reasons why a cuffed tube should be considered in preference to an uncuffed tube in children intubated out of hospital, regardless of their age or size. There are also some counterarguments which are worthy of consideration. This article presents the arguments for and against the use of cuffed tubes in children in prehospital care with a view to stimulating open discussion and debate.

Age Factors↗
PubMed2006

Hyperimmune goat serum for amyotrophic lateral sclerosis.

The authors report a patient with amyotrophic lateral sclerosis (ALS) who showed a lessening of deterioration in respiratory muscle strength during treatment with hyperimmune goat serum (HGS) (Aimspro). Respiratory function tests (RFTs) were measured by established protocols, and all measurements were expressed as a percentage of normal predicted values. The rate of decline was calculated by linear regression analysis. Respiratory muscle strength decline was less during 13 months of treatment with HGS (mean 1.3% per month, range 0.8-1.7%) compared to the preceding 13 months (mean 2.3% per month, range 1.2-3.1%), while a greater decline would be expected with disease progression. Comparison with similarly affected patients in the literature suggest that a decline of 4-5% per month of predicted values may be expected during the treatment phase.

Amyotrophic Lateral Sclerosis↗
PubMed2005

London bombings July 2005: the immediate pre-hospital medical response.

On July 7th 2005 a series of terrorist bombs exploded in London. The transport system was targeted and at least 54 passengers were killed and around 700 injured. This paper describes the immediate pre-hospital medical response to the four scenes. From the perspective of the London Helicopter Emergency Medical Service the deployment, difficulties on scene and the initial lessons learned are discussed.

Blast Injuries↗
PubMed2005

Competence in prehospital care: evolving concepts.

Competence based training and assessment has become central to education and training for healthcare professionals. There continues to be uncertainty about the meaning of competence and how the principles underpinning competence based training and assessment can be applied to evolving subspecialty and multidisciplinary areas such as prehospital care. Considerable development work has been undertaken on a national level with the creation of a Competence Framework for Emergency Care. This article explores the concepts of competence, defines the terminology, and describes the role of a competence framework in education and training.

Clinical Competence↗
PubMed2004

Idiopathic recurrent stupor: a warning.

A proposal that an endogenous benzodiazepine-like agent named endozepine-4 might be responsible for presentations of recurrent stupor has gained wide acceptance. A case of recurrent stupor over two decades is presented with many similarities to previous cases of "endozepine stupor". This case, however, was caused by exogenous benzodiazepine administration and serves as a warning to clinicians to beware of this diagnosis.

Aged↗
PubMed2003

Acute coronary syndrome.

Acute coronary syndromes encompass a heterogenous group of patients with different clinical presentations, who have differences in both the extent and severity of underlying coronary atherosclerosis and who have different degrees of risk of progression to myocardial infarction. For each patient, the pre-hospital practitioner should make individual treatment decisions based on the history and examination, the ECG findings, the facilities and diagnostic equipment available and the transfer time to the nearest appropriate hospital. Patients with acute ischaemic chest pain should have oxygen, aspirin, nitrates and opioid analgesia. A 12 lead ECG should be performed within 5 minutes of initial assessment. If the ECG reveals ST-segment elevation or presumed new LBBB, this signifies acute myocardial infarction and in most cases immediate reperfusion therapy should be considered. The evidence of benefit in terms of mortality and morbidity following prompt anti-platelet and fibrinolytic therapy in such cases is unequivable. Pre-hospital fibrinolysis is now well established and should be undertaken in patients with acute infarction on clinical and ECG grounds if the transfer to hospital is likely to exceed 30 minutes and it is less than 12 hours since the onset of pain. Patients with no ECG evidence of infarction may still be at considerable risk and should still be conveyed to the nearest appropriate medical facility. Whilst en-route, they should receive aspirin, nitrates, low molecular weight heparin (LMWH) and beta blockers provided there are no contra-indications.

Acute Disease↗
PubMed2002

The discovery of PD 89211 and related compounds: selective dopamine D4 receptor antagonists.

The dopamine (DA) D2 family of receptors consists of the D2, D3, and D4 receptors. The DA D4 receptor is of interest as a target for drugs to treat schizophrenia based upon its high affinity for the atypical antipsychotic clozapine and its localization to the limbic and cortical regions of the brain. As part of a program to identify novel DA D4 receptor antagonists, a high-volume screen using the Parke-Davis compound library was initiated. This led to the discovery of PD 89211 (benzenemethanol, 2-chloro-4-[4-[(1H-benzimidazol-2-yl)methyl]-1-piperzinyl]) that displaced [3H]spiperone binding to hD4.2 with an affinity (Ki) of 3.7 nM. PD 89211 exhibited high selectivity for the DA D4.2 receptor (> 800-fold) as compared to other hDA receptor subtypes, rat brain serotonin, and adrenergic receptors. In vitro, PD 89211 had D4 receptor antagonist activity reversing quinpirole-induced [3H]thymidine uptake in CHOpro5 cells (IC50 = 2.1 nM). Limited structure-activity relationship (SAR) studies indicated that compounds with a 4-chloro-, 4-methyl-, and 3-chloro- substituents on the phenyl ring retained high affinity for D4 receptors, while those with a 4-methoxy- and no substituent had less affinity. While all clinically effective antipsychotics increase DA synthesis (DOPA accumulation) in rodents, PD 89211 did not increase DA synthesis in the DA-enriched striatum, indicating no effect on DA turnover and low propensity for exhibiting motor side effects. However, it did increase catecholamine synthesis in rat hippocampus, as did clozapine. Moreover, PD 89211 selectivity increased catecholamine synthesis in the hippocampus of wild type but not in mice lacking D4 receptors, suggesting that one function of D4 receptors may be to modulate DA/norepinephrine (NE) turnover in this brain area known to possess D4 receptors. The discovery of compounds like PD 89211 provides a tool to help in understanding the function of DA D4 receptors in the CNS.

Animals↗
PubMed2002

(E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), a selective and orally active inhibitor of tumor necrosis factor-alpha convertase.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by inflammatory cells, has been implicated in several inflammatory disease states. (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), is a potent, orally active inhibitor of the TNF-alpha convertase (TACE), an enzyme responsible for proteolytic cleavage of the membrane bound precursor, pro-TNF-alpha. Ro 32-7315 inhibited a recombinant form of TACE (IC(50) = 5.2 nM) with selectivity over related matrix metalloproteinases. In a cellular assay system, THP-1 cell line, and in human and rat whole blood, Ro 32-7315 significantly reduced lipopolysaccharide (LPS)-induced TNF-alpha release with IC(50) values of 350 +/- 14 nM (n = 5), 2.4 +/- 0.5 microM (n = 5), and 110 +/- 18 nM (n = 5), respectively. Oral administration of Ro 32-7315 to Wistar rats caused a dose-dependent inhibition of LPS-induced release of systemic TNF-alpha with an ED(50) of 25 mg/kg. Treatment (days 0-14) of Allen and Hamburys hooded rats with Ro 32-7315 (2.5, 5, 10, and 20 mg/kg, i.p., twice daily) significantly reduced adjuvant-induced secondary paw swelling (42, 71, 83, and 93%, respectively) as compared with the vehicle group. In the Ro 32-7315-treated group, the reduced paw swelling was associated with improved lesion score and joint mobility. Furthermore, in a placebo-controlled, single-dose study, Ro 32-7315 given orally (450 mg) significantly suppressed ex vivo, LPS-induced TNF-alpha release in the whole-blood samples taken from healthy male and female volunteers (mean inhibition of 42% over a 4-h duration, n = 6). These data collectively support the potential use of such a compound for the oral treatment of inflammatory disorders.

ADAM Proteins↗
PubMed2002

The injured child.

Pre-hospital immediate care for seriously injured children is rarely required, but when it is, the response must be prompt and effective. The key to an effective and confident approach to injured children lies in understanding the age related anatomical and physiological differences between adults and children. These differences are most exaggerated in the first few years of life and excellent training courses and materials are available to help practitioners develop their confidence and skills in this age group. An easy to use length based aide memoire and a set of equipment packed according to size are essential to ensure safe management in the pre-hospital environment. Care of the seriously ill child, emergency childbirth and neonatal resuscitation are beyond the scope of this article. Nonetheless, pre-hospital practitioners should develop an understanding of assessment of ill children and normal delivery and be prepared to assist with emergency childbirth and neonatal resuscitation. Excellent educational material, courses and web based resources are available to achieve this (54). This is the sixth article in the add on series in pre-hospital care. The series is edited by Maj R Mackenzie. Maj RC Sutcliffe is a general practitioner and regimental medical officer. Maj R Mackenzie is a Specialist Registrar in Accident and Emergency Medicine and an immediate care doctor. While every effort has been made to ensure correct drug dosages are quoted, readers should always check these before use.

Child↗
PubMed2002

Spinal injuries.

The pre-hospital care of patients with suspected spinal injuries involves early immobilisation of the whole spine and the institution of measures to prevent secondary injury from hypoxia, hypoperfusion or further mechanical disruption. Early ventilation and differentiation of haemorrhagic from neurogenic shock are the key elements of pre-hospital resuscitation specific to spinal injuries. Falls from a significant height, high-impact speed road accidents, blast injuries, direct blunt or penetrating injuries near the spine and other high energy injuries should all be regarded as high risk for spinal injury but clinical examination should determine whether the patient requires full, limited or no spinal immobilisation. Although there is little conclusive evidence in the literature that supports pre-hospital clinical clearance of the spine, the similarities between pre-hospital immobilisation decisions and in-hospital radiography decisions are such that it is likely that clinical clearance will be effective for selected patients. This decision can be made at the scene provided the patient has no evidence of: Altered level of consciousness or mental status Intoxication Neurological symptoms or signs A distracting painful injury (e.g. chest injuries, long bone fracture) Midline spinal pain or tenderness. Where there is evidence to support spinal immobilisation, then the full range of devices and techniques should be considered. In the remote or operational environment where pre-hospital times are prolonged, full immobilisation, analgesia and re-assessment may allow localisation of the injury and a reduction in the degree of immobilisation. Common reasons for missing significant spinal injuries include failing to consider the possibility of spinal injuries in patients who are either unconscious, intoxicated or uncooperative (54,55). The application of the decision rule discussed here will ensure that no clinically significant spinal injuries are missed in pre-hospital care.

Emergency Medical Services↗
PubMed2002

Immediate assessment and management of acute medical emergencies.

The pre-hospital management of acute medical emergencies can be difficult. Critically ill patients must be evaluated quickly and accurately to ensure that immediately life-threatening problems are identified and treated. Figure 1 and Box 2 provide a structured method for rapid assessment in the pre-hospital phase. Although the majority of medically unwell patients will not require an aggressive resuscitation phase during the primary survey, the use of the structured approach in all patients will ensure that 'time critical' pre-hospital medical emergencies are identified. This approach also emphasizes that once immediately correctable problems have been treated, the priority is transfer the patient to the nearest resuscitation facility.

Abdominal Pain↗
PubMed2001

Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels.

BACKGROUND: In a randomized, controlled trial comparing a pH neutral, bicarbonate/lactate (B/L)-buffered PD solution to conventional acidic, lactate-buffered solution (C), the overnight dialysate levels of markers of inflammation/wound healing [hyaluronic acid (HA)], mesothelial cell mass/membrane integrity [cancer antigen 125 (CA125)], and fibrosis [transforming growth factor-beta1 (TGF-beta1) and procollagen I peptides (PICP)] were assessed over a six-month treatment period. METHODS: One hundred six patients were randomized (2:1) to either the B/L group or C group. Overnight effluents were collected at entry into the study (time = 0 all patients on control solution) and then at three and six months after randomization. Aliquots were filtered, stored frozen, and assayed for HA, CA125, TGF-beta1, and PICP. Differences between groups were assessed by repeated-measures analysis of variance for unbalanced data using the SAS procedure MIXED. RESULTS: In patients treated with B/L, there was a significant (P = 0.03) increase in CA125 after six months compared with time = 0 (19.76 +/- 11.8 vs. 24.4 +/- 13.8 U/mL; mean +/- SD; N = 51). In the same group of patients, HA levels were significantly decreased at both three and six months in the B/L-treated group (time = 0, 336.0 +/- 195.2; time = 3 months, 250.6 +/- 167.6; and time = 6 months, 290.5 +/- 224.6 ng/mL; mean +/- SD; P = 0.006, N = 47 and P = 0.003, N = 48, respectively). No significant changes in CA125 or HA levels were observed in the control group. There were no significant changes observed in the levels of PICP or TGF-beta1 in the B/L or C group over the six-month treatment period. CONCLUSIONS: These results suggest that continuous therapy with the B/L solutions modulates the levels of putative markers of peritoneal membrane integrity and inflammation. In the long term, this may positively impact the peritoneal membrane, increasing its life as a dialyzing organ.

Adult↗