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Biomedical subjects

G M Mackay

Publications and source records attributed to G M Mackay.

At least 19 recordsLinked to original sources
PubMed2006

Blood 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and melatonin levels in patients with either Huntington's disease or chronic brain injury.

Following a study of oxidative tryptophan metabolism to kynurenines, we have now analysed the blood of patients with either Huntington's disease or traumatic brain injury for levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and melatonin. There were no differences in the baseline levels of these compounds between patients and healthy controls. Tryptophan depletion did not reduce 5-HT levels in either the controls or in the patients with Huntington's disease, but it increased 5-HT levels in patients with brain injury and lowered 5-HIAA in the control and Huntington's disease groups. An oral tryptophan load did not modify 5-HT levels in the patients but increased 5-HT in control subjects. The tryptophan load restored 5-HIAA to baseline levels in controls and patients with brain injury, but not in those with Huntington's disease, in whom 5-HIAA remained significantly depressed. Melatonin levels increased on tryptophan loading in all subjects, with levels in patients with brain injury increasing significantly more than in controls. Baseline levels of neopterin and lipid peroxidation products were higher in patients than in controls. It is concluded that both groups of patients exhibit abnormalities in tryptophan metabolism, which may be related to increased inflammatory status and oxidative stress. Interactions between the kynurenine, 5-HT and melatonin pathways should be considered when interpreting changes of tryptophan metabolism.

Administration, Oral↗
PubMed2006

Purine metabolism and clinical status of patients with rheumatoid arthritis treated with dipyridamole.

The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.

Adenosine↗
PubMed2006

Tryptophan metabolism and oxidative stress in patients with chronic brain injury.

The kynurenine pathway generates the excitotoxic N-methyl-d-aspartate receptor agonist, quinolinic acid and the glutamate antagonist, kynurenic acid, as well as free-radical generators. We investigated the status of the pathway following severe brain injury sustained at least 1 year previously in 15 patients compared with controls. At baseline, patients with brain injury showed increased levels of neopterin, erythrocyte sedimentation rate, C-reactive protein and peroxidation products in the blood compared with controls, indicating persistent inflammation and oxidative stress. At baseline and following tryptophan depletion, more tryptophan was converted to kynurenine in patients than controls, but less kynurenine was converted into the neuroprotectant, kynurenic acid. This suggests that neuroprotection by kynurenic acid may be inadequate in brain-damaged patients even many years after injury. On tryptophan loading, patients metabolized more kynurenine into kynurenic acid than controls, a process which may be neuroprotective. In addition, lower levels of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in patients after tryptophan loading should be protective since these compounds generate free radicals. The results suggest that for brain-damaged patients, increased activation of the kynurenine pathway, oxidative stress and raised levels of inflammation continue many years after the original insult, possibly contributing to the continuing cerebral dysfunction in these patients.

Adult↗
PubMed2005

Tryptophan metabolism and oxidative stress in patients with Huntington's disease.

Abnormalities in the kynurenine pathway may play a role in Huntington's disease (HD). In this study, tryptophan depletion and loading were used to investigate changes in blood kynurenine pathway metabolites, as well as markers of inflammation and oxidative stress in HD patients and healthy controls. Results showed that the kynurenine : tryptophan ratio was greater in HD than controls in the baseline state and after tryptophan depletion, indicating increased indoleamine dioxygenase activity in HD. Evidence for persistent inflammation in HD was provided by elevated baseline levels of C-reactive protein, neopterin and lipid peroxidation products compared with controls. The kynurenate : kynurenine ratio suggested lower kynurenine aminotransferase activity in patients and the higher levels of kynurenine in patients at baseline, after depletion and loading, do not result in any differences in kynurenic acid levels, providing no supportive evidence for a compensatory neuroprotective role for kynurenic acid. Quinolinic acid showed wide variations in blood levels. The lipid peroxidation data indicate a high level of oxidative stress in HD patients many years after disease onset. Levels of the free radical generators 3-hydroxykynurenine and 3-hydroxyanthranilic acid were decreased in HD patients, and hence did not appear to contribute to the oxidative stress. It is concluded that patients with HD exhibit abnormal handling of tryptophan metabolism and increased oxidative stress, and that these factors could contribute to ongoing brain dysfunction.

Adolescent↗
PubMed2004

Tryptophan loading induces oxidative stress.

In previous studies tryptophan loads have been administered to human subjects in order to raise central levels of 5-hydroxytryptamine (5HT) and assess the effects of 5HT on behaviour and mood. However, tryptophan is metabolised primarily along the oxidative kynurenine pathway. In this study a 6 g oral tryptophan load was administered to 15 healthy volunteers and the levels of kynurenines and lipid peroxidation products (indicative of oxidative stress) were measured. The results demonstrate that tryptophan loading produces a highly significant increase in lipid peroxidation products in parallel with increased kynurenines. The oxidative stress may result from the generation of quinolinic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid, all of which are known to have the ability to generate free radicals. The results may have implications for the use of tryptophan loading in psychiatric practice, and for the chronic use of diets high in tryptophan.

Adult↗
PubMed1996

Venepuncture: the medicolegal hazards.

Venepuncture is commonly regarded as a trivial procedure allocated to the most junior medical staff. The result of this policy is that junior doctors are required to perform a minimally invasive procedure on consenting patients without any structured venepuncture training or assessment. Consequently, inexperienced doctors may perform multiple and sometimes unnecessary, venepunctures, which could damage essential venous access, eg, in the diabetic or renal patient. We review the medicolegal position and suggest that structured venepuncture training is essential and argue that unskilled treatment may be regarded by the Courts as demonstrating the mens rea of assault in the form of recklessness.

Clinical Competence↗
PubMed1995

How drivers sit in cars.

This paper presents results from a study to measure the separation of the driver's head and shoulder to various internal features of the car. Drivers were filmed whilst driving in general traffic flow, hence were unaware that they were involved in a study. The results show that certain sub-groups of the driver population are likely to be more at risk for certain impact types. Small females are considerably closer to the steering wheel than the rest of the population, and therefore prone to head strikes in frontal impacts. Large males are likely to interact with the cant rail and B-pillar in side impacts.

Accidents, Traffic↗
PubMed1995

The limitations of current seatbelts in Europe--some population considerations.

Seatbelts are most likely to function as they were designed if the car occupants' survival space remains uncompromised during an impact. Crashed cars with negligible passenger compartment intrusion were used to study seatbelt effectiveness in that situation. Belted front seat occupants were investigated together with their front impacted vehicles. Current model seatbelts were seen to prevent many more forward contacts than those seen in a similar study 15 years ago. In the earlier study, head contacts occurred to 65% of drivers whereas the current sample contained 24%. The present study also found that thigh or knee contacts were common occurrences for drivers and front seat passengers, as were thoracic injuries caused by loads from the belt itself and neck injuries caused by deceleration. The results emphasize how real people, unlike crash test dummies, have varied characteristics that influence seatbelt performance.

Accidents, Traffic↗
PubMed1995

Vertebral column injuries and lap-shoulder belts.

OBJECTIVE: To present cases of vertebral column fractures or fracture dislocations that occur to restrained front seat occupants where there is no evidence of body contact with interior car components based on both medical records and car inspection. MATERIALS AND METHODS: Reviewed were car crash injury cases investigated at the University of Michigan Transportation Research Institute and at the University of Birmingham (England) as well as the National Accident Severity Study files of the National Highway Traffic Safety Administration. Medical records and car inspections in the cases presented did not indicate any evidence of body contact with interior car structures. MAIN RESULTS: Vertebral fractures or fracture dislocations sustained by front seat occupants who were wearing lap-shoulder belts are rare, as evidenced by the relatively few cases identified in the literature and in the crash injury files reviewed. CONCLUSIONS: Infrequently, in frontal crashes, vertebral fractures or fracture dislocations can occur to lap-shoulder belted front seat car occupants without head or torso impacts with interior car structures. Cervical spine injuries are due to neck flexion over the shoulder portion of the restraint. Thoracolumbar fractures can occur in the frontal crash even at low crash velocity.

Accidents, Traffic↗
PubMed1995

Benefits realised from a blood transfusion policy for elective joint arthroplasty.

Transfusion practice and blood ordering policy for major joint replacement was studied during 1989-93. Existing practice requiring automatic preoperative cross-match was prospectively audited. A blood ordering policy rationalising transfusion practice, using the group and screen technique, was then introduced. This resulted in a decrease in the total number of units cross-matched and increased the transfusion fraction significantly. The percentage of blood returned to the blood bank decreased by 46% for knees and 41% for hip arthroplasty. After the introduction of low molecular weight heparin (LMWH) as routine deep vein thrombosis (DVT) prophylaxis for all major total joint arthroplasties, the total transfusion requirement did not increase. In fact, the average number of units transfused per case after its introduction was marginally less at 1.3 units per hip, and 0.9 units per knee.

Arthroplasty↗
PubMed1995

Consent in medicine and sport.

Last year's football World Cup serves to highlight the confusion now surrounding the classical aim of both sport and sports medicine, namely a healthy mind in a healthy body. The recent focus on violent injuries and the exponential increase in medical litigation suggests that this relationship is not so clearly defined. One cornerstone of this traditional relationship is the concept of informed consent. We review the legal position of consent in sport, especially soccer, which still awaits clarification and draw clear parallels with surgical consent.

Female↗
PubMed1994

Chest and abdominal injuries caused by seat belt loading.

Injuries will inevitably occur when restraining loads are exerted on a car occupant by a seat belt during a crash. This study investigated the nature, frequency, and severity of such injuries to the chest and abdomen. Vehicle, occupant, and injury details were obtained from accidents occurring in the Midlands of England. The sample was chosen with emphasis on fatal and serious injuries while also representing slight injuries as rated by the British government scheme. All causes of injuries to 3,276 front-seat restrained occupants were considered. 29.6% had a minor (Abbreviated Injury Scale [AIS] 1) injury caused by seat belt loading, more than from any other cause. The study went on to focus on 1,025 occupants sustaining injuries caused solely by seat belt loading. Of those, 19.4% sustained chest/abdominal injuries rated at Maximum AIS > or = 2 with sternum fractures predominating, and 4.5% were rated at Maximum AIS > or = 3. Occupants were not excluded if they had injuries at other body regions enabling the frequency and severity of head injuries to be considered also. The role played by impact type, speed change at impact, seat belt usage problems, and some aspects of occupant characteristics were investigated. While females were at much greater risk of serious injury (AIS > or = 3) when aged > or = 70 years, the effects of aging were more obvious in the cases with chest injuries rated at AIS 2. Serious chest injuries were predominantly a function of higher speed changes at impact. Occupant height and weight were shown to influence injury outcome, and the study concluded that work is required to further define occupants most at risk. Comparisons were made with two studies into other types of injury at other body regions, and injuries rated AIS > or = 2 caused by seat belt loading were seen to be relatively unlikely. It must also be stressed that casualties sustained seat belt injuries would most likely have received more severe injuries had a seat belt not been worn.

Abbreviated Injury Scale↗
PubMed1993

A review of cervical fractures and fracture-dislocations without head impacts sustained by restrained occupants.

Crash injury reduction via lap-shoulder belt use has been well documented. Like any other interior car component, lap-shoulder belts may be related to injury in certain crashes. Relatively unknown is the fact that cervical fractures or fracture-dislocations to restrained front seat occupants occur where no head contact was evidenced by both medical records and car inspection. A review of the available literature on car crash injuries revealed more than 100 such cases. A review of the National Accident Severity Study (NASS) 80-88 file was also conducted, revealing more examples. Case capsule descriptions from the authors' files are also detailed along with examples of such injuries in infants and children in child restraints. However, cervical fractures or fracture dislocations are rare, as evidenced by the relatively few cases identified in the literature, in the author's files, and by an analysis of NASS 80-90 data that revealed a cervical spine injury frequency of only .4% at the AIS-3 level (Huelke, Morris, and Mackay 1992).

Accidents, Traffic↗
PubMed1993

Restrained occupants on the nonstruck side in lateral collisions.

Of injury-producing collisions with high seat belt use, some 25% to 30% are lateral collisions. This paper describes some of the characteristics of those collisions as they relate to the front-seat occupant sitting on the side opposite to the impact. The data came from a stratified sample of in-depth crash investigations conducted in the Birmingham region in the period 1983 to 1989 involving current model cars. Crash severity was assessed using the Vehicle Deformation Index (VDI) of the Collision Deformation Classification (CDC) ratings and velocity change. Injury severity was assessed using AIS 85 for each body region. 193 cases of restrained occupants in nonstruck side collisions were examined. Of those occupants with head injuries of AIS < or = 2, 35% came out of the shoulder section of the seat belt. Of abdominal injuries of AIS < or = 2, 72% came from the seat belt itself. Interaction between front seat occupants was not a frequent cause of injury to the nonstruck side occupant. Some aspects of seat belt geometry might be changed so that the trajectory and loading of the nonstruck side occupant are improved.

Accidents, Traffic↗
PubMed1992

Restrained front seat car occupant fatalities--the nature and circumstances of their injuries.

The circumstances of a rural and urban sample of fatalities in vehicles less than six years old is described. The data originate from an in-depth, multidisciplinary study of accidents conducted in England since 1983. The sample is biased towards collisions that result in occupant injury, and this paper will concentrate on those accidents in which an occupant has been fatally injured. The initial police reporting of the fatalities included 11% of the deaths occurring from natural causes. Of the crash-related deaths with complete data, some 43% were frontal and lateral impacts, and they are analysed in greater detail. Thirty-six percent of restrained occupants died in lateral collisions. In both frontal and lateral crashes, large amounts of intrusion result in direct loading of the head and chest, particularly. Under-run crashes with large trucks constitute 30% of frontal death cases, and only 12% of fatalities received fatal injuries from belt loads. Of those cases, additional loading by unrestrained rear passengers could have been an important feature. Multiplicity of severe injuries is the rule for restrained fatalities, with head injuries as the most common cause of death. Eighty-two percent died within an hour of their crashes. Some consequences for vehicle compatibility in crashes are discussed.

Accidents, Traffic↗
PubMed1992

Maxillofacial injuries following steering wheel contact by drivers using seat belts.

Maxillofacial injuries are common sequelae in road traffic accidents. For the restrained driver, impact against the steering wheel is the most prevalent cause of injury. A sample of drivers restrained by seat belts with facial injury caused by the steering wheel was taken from data at the Accident Research Unit, University of Birmingham, UK. Two hundred and forty facial injuries occurred in 135 drivers, and these are described. Superficial contusion, laceration and nasal fractures predominated. There were 504 injuries at other body regions, and these were often caused by other vehicle components. These were, for 57% of drivers, no more serious than the facial injury caused by steering wheel contact. The role of steering wheel design in maxillofacial trauma is discussed and new solutions briefly reviewed.

Abbreviated Injury Scale↗