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Biomedical subjects

M Mackay

Publications and source records attributed to M Mackay.

At least 19 recordsLinked to original sources

Arterial ischaemic stroke in children.

OBJECTIVE: Arterial ischaemic stroke (AIS) in childhood is a serious disorder about which little is published. The aim of this study is to determine the epidemiology and outcome of AIS in Australian children. METHODS: Cases of childhood AIS occurring at the Royal Children's Hospital, Melbourne 1993-2001, were identified by medical record search using International Classification of Disease Codes. Information was collected on demographics, risk factors, arterial distribution, results of thrombophilic testing, management and outcome. RESULTS: During the 8 years of review 95 patients presented with 98 cases of AIS calculating an incidence of 1.8 per 100000 children per year. Children less than 12 months of age represented greater than one third of all cases. Identifiable risk factors were present in 64% of cases with congenital heart disease the major risk factor. Thrombophilic testing was incomplete with initial abnormalities present in 18% of cases tested. The estimated stroke-related mortality was 8.4%. Of the patients who survived and who had follow-up details available, 78% had a neurological deficit. Twenty-six patients (26%) received anticoagulation. There was no statistically significant association between treatment with anticoagulation and normal neurological outcome. CONCLUSION: AIS is over-represented in children under 12 months of age and results in death or residual neurological impairment in the majority of cases. Further prospective studies are needed to identify risk factors for poor outcome. The recently established Australian and New Zealand Stroke and Thrombophilia Registry should provide important information on clinical and laboratory based risk factors and create a basis for international clinical trials to improve the outcome of childhood AIS.

Adolescent↗

Reliability of cancer registration data in Scotland, 1997.

The aim of this study was to assess the reliability of cancer registration data in Scotland following a major re-organisation of the Scottish Cancer Registry. From a random sample of 3500 primary cancers (excluding non-melanoma skin cancers and death certificate only (DCO) registrations) diagnosed between April and September 1997, 3175 (90.7%) had medical records available for scrutiny. Data were re-abstracted by a team of trained medical coders and compared with information registered originally. Reliability was generally high for demographic, diagnostic, and fact of treatment details, but less reliable for grade of differentiation, staging variables and dates of treatment. Some discrepancies probably arose because of differing availability of information at the time of registration compared with the time of re-abstraction. Although data quality is high overall, further improvements might be achieved through continued training, structured recording of information by clinicians in medical records, and continued exploitation of the data.

Data Collection↗

Molybdopterin synthase mutations in a mild case of molybdenum cofactor deficiency.

Molybdenum cofactor deficiency is a rare inborn error of metabolism with generally severe symptoms, most often including neonatal seizures and severe developmental delay. We describe a patient with an unusually mild form of the disease. Two mutations in MOCS2A (molybdenum cofactor synthesis enzyme 2A) were identified: a single base change, 16C > T, that predicts a Q6X substitution on one allele and a 19G > T transversion that predicts a valine to phenylalanine substitution, V7F, on the second. It is postulated that the milder clinical symptoms result from a low level of residual molybdopterin synthase activity derived from the 19G > T allele.

Alleles↗

Pharmacokinetics of oral cyclosporin A when co-administered to enhance the absorption of orally administered docetaxel.

OBJECTIVE: To evaluate the pharmacokinetics of oral cyclosporin A (CsA) when co-administered to enhance the absorption of orally administered docetaxel. METHODS: Patients (n = 9) with histological proof of solid cancer received oral docetaxel 75 mg/m2 in combination with oral CsA 15 mg/kg. RESULTS: The area under the blood concentration-time curve (AUC) of CsA when combined with docetaxel 75 mg/m2 was 31.0+/-9.3 mg/l h (mean +/- SD). Compared with literature data of the same dose of CsA, AUC values in our study appear to be substantially higher. In addition, compared with the AUC values of CsA in combination with oral paclitaxel (previously published data), AUC values in this study are approximately 1.5-fold higher. CONCLUSIONS: The higher AUC values of CsA obtained in this study compared with literature data may be explained by competitive inhibition of cytochrome P450 (CYP) 3A4-mediated metabolism of CsA by docetaxel. In addition, the higher levels of CsA with docetaxel than with paclitaxel co-administration may be explained by the fact that docetaxel is almost exclusively metabolised by CYP 3A4, whereas paclitaxel is predominantly metabolised by CYP 2C8 and to a lesser extent by CYP 3A4.

Administration, Oral↗

Effect of creatine supplementation on metabolism and performance in humans during intermittent sprint cycling.

This double blind study investigated the effect of oral creatine supplementation (CrS) on 4 x 20 s of maximal sprinting on an air-braked cycle ergometer. Each sprint was separated by 20 s of recovery. A group of 16 triathletes [mean age 26.6 (SD 5.1) years. mean body mass 77.0 (SD 5.8) kg, mean body fat 12.9 (SD 4.6)%, maximal oxygen uptake 4.86 (SD 0.7) l.min-1] performed an initial 4 x 20 s trial after a muscle biopsy sample had been taken at rest. The subjects were then matched on their total intramuscular creatine content (TCr) before being randomly assigned to groups to take by mouth either a creatine supplement (CRE) or a placebo (CON) before a second 4 x 20 s trial. A muscle biopsy sample was also taken immediately before this second trial. The CrS of 100 g comprised 4 x 5 g for 5 days. The initial mean TCr were 112.5 (SD 8.7) and 112.5 (SD 10.7) mmol.kg-1 dry mass for CRE and CON, respectively. After creatine loading and placebo ingestion respectively, CRE [128.7 (SD 11.8) mmol.kg-1 dry mass] had a greater (P = 0.01) TCr than CON [112.0 (SD 10.0) mmol.kg-1 dry mass]. While the increase in free creatine for CRE was statistically significant (P = 0.034), this was not so for the changes in phosphocreatine content [trial 1: 75.7 (SD 6.9), trial 2: 84.7 (SD 11.0) mmol.kg-1 dry mass, P = 0.091]. There were no significant differences between CRE and CON for citrate synthase activity (P = 0.163). There was a tendency towards improved performance in terms of 1 s peak power (in watts P = 0.07; in watts per kilogram P = 0.05), 5 s peak power (in watts P = 0.08) and fatigue index (P = 0.08) after CrS for sprint 1 of the second trial. However, there was no improvement for mean power (in watts P = 0.15; in watts per kilogram P = 0.1) in sprint 1 or for any performance values in subsequent sprints. Our results suggest that, while CrS elevates the intramuscular stores of free creatine, this does not have an ergogenic effect on 4 x 20 s all-out cycle sprints with intervening 20-s rest periods.

Adult↗

Practical experience with bed occupancy management and planning systems: an Australian view.

Pressure is increasing on hospitals to do more with fewer resources. The appropriate management of hospital beds is crucial. The author's practical experience of applying the Harrison and Millard Flow Model (BOMPS) and Sorensen's multi-phased bed model to aspects of the public hospital system in South Australia are detailed. These techniques can provide decision makers with improved bed management information. Modelling enables the effects of decisions to be analyzed before implementation. Further development of these tools, together with other modelling approaches, cannot be ignored as a means of improving the strategic management of hospital beds.

Bed Occupancy↗

Docetaxel in 253 previously treated patients with progressive locally advanced or metastatic breast cancer: results of a compassionate use program in The Netherlands.

The aims of this study were to evaluate the efficacy and safety of docetaxel (Taxotere) in patients with progressive locally advanced or metastatic breast cancer, previously treated with at least one chemotherapy regimen, and the effect of the number of previous chemotherapy lines on response rate, progression-free survival and overall survival. Two-hundred and fifty-three patients from 10 hospitals in The Netherlands received docetaxel as part of a compassionate use program. The majority had received prior anthracycline-containing chemotherapy (84.2%). The recommended starting dose was 100 mg/m2 i.v. every 3 weeks. All patients received corticosteroid premedication. Two-hundred and thirty patients were evaluable for response. The overall response rates (ORR) to docetaxel when used as second-, third- or fourth-line treatment were, respectively, 40.2, 26.0 and 34.6% (p value 0.30). The median progression-free survival for this population was 4.9 months and the median overall survival of the whole group was 8.5 months, and both were not related to the number of previous chemotherapy regimens (p value, respectively, 0.71 and 0.16). The toxicity of docetaxel was manageable and neutropenia was the most frequently noted toxicity. This study confirms that docetaxel is an active cytotoxic agent in pretreated patients with progressive locally advanced or metastatic breast cancer and is still active when used as third- or fourth-line treatment.

Adult↗

Peripheral nerve repair and grafting techniques: a review.

In this review, various conventional nerve repair techniques including direct epineurial repair, grouped fascicular repair, fascicular repair, and nerve grafting are described. The indications for use, as well as the relative advantage and disadvantage, of each technique are discussed. The experimental and clinical evidence from a review of the pertinent literature does not demonstrate a significant difference in outcome of one method over the others. Surgical decisions should be made by a thorough evaluation of all aspects of the nerve injury and surgical methods. All nerve injuries cannot be repaired using only one type of nerve repair method. The surgeon should be familiar with all the techniques described and be prepared to use them under appropriate circumstances.

Humans↗

Measuring and modelling surgical bed usage.

Surgical departments treat two groups of inpatients--the simple and the complex--consequently a single average fails to describe the use being made of the occupied beds. Using decision support techniques, we show why indicators such as the average length, the average occupancy and the average admissions mislead. Furthermore, by analysing the fluctuating pattern of weekly admissions we show how weekends and the Christmas holiday periods impact on bed usage. Next, we demonstrate that flow process models can be used to describe how the in-patient workload concerns two groups of patients. On an average day, 71.4% of the beds contained patients who will have an average (exponential) stay of 4.8 days, and the other beds, 28.6%, contain patients who will have an average (exponential) stay of 22.8 days. The article concludes by demonstrating the short and long-term impact on daily admissions of a 10% change in four different parameters of the model. The data used come from a surgical department in Adelaide, as UK data sets report finished consultant episodes rather than completed in-patient spells.

Bed Occupancy↗

Age and gender effects on injury outcome for restrained occupants in frontal crashes: a comparison of UK and US data bases.

Field accident data from NASS/CDS in the US and CCIS in the UK are compared. The UK sample is deliberately weighted to conform to the same AIS proportions (within AIS 2-6) as the weighted NASS data so that crash severity distributions can be compared for various selected outcomes. Age and gender have a significant effect on the delta V distributions and median delta V values. These differences are documented both for overall AIS 2-6, 3-6, and 4-6, and also for body regions of the head, neck, chest, abdomen and upper and lower extremities. Anomalies between the two samples are profound which raises doubts about the recording of belt use in NASS and the calculation of delta V at lower crash severities.

Abbreviated Injury Scale↗

Protamine-like sperm nuclear basic proteins in the primitive frog Ascaphus truei and histone reversions among more advanced frogs.

Sperm nuclear basic proteins (SNBPs) that condense chromatin are very diverse. In animals, evolution of SNBPs has proceeded from lysine-rich histone H type in sponges to more arginine-rich protamine-like PL and protamine P types. Yet sporadic PL/P to H reversions are known to occur in both protostomes and deuterostomes. To determine why this is the case, we have examined SNBPs in eleven anuran species. We find that sperm of the primitive, internally fertilizing archeobatrachian frog A. truei (family Ascaphidae) has PL/P type (42 mol % arginine), with an electrophoretic profile similar to SNBPs in another archeobatrachian, externally fertilizing Leiopelma hochstetteri (family Leiopelmatidae). Cytochemistry of sperm nuclei in the advanced, externally fertilizing neobatrachian frogs Crinia signifera and C. deserticola (family Myobatrachidae) indicates that they have reverted to H type SNBPs. This is also known to be the case in externally fertilizing Rana (family Ranidae) and Silurana, a subgenus of Xenopus (family Pipidae). Such a trend, from PL/P type SNBPs in two archeobatrachians to sporadic reversions to H type in more advanced frogs, parallels the ultrastructural simplification from complex A. truei introsperm to neobatrachian aquasperm that Jamieson et al. (1993. Herpetologica 49:52-65) attribute as a secondary reversion to external fertilization.

Animals↗

Structure of the human VIPR2 gene for vasoactive intestinal peptide receptor type 2.

The VPAC(2) (vasoactive intestinal peptide (VIP)(2)) receptor is a seven-transmembrane spanning G protein-coupled receptor which responds similarly to VIP and pituitary adenylate cyclase activating polypeptide (PACAP) in stimulating cAMP production. Recently, we reported the localisation of the human VPAC(2) receptor gene (VIPR2) to chromosome 7q36.3 (Mackay, M. et al. (1996) Genomics 37, 345-353). Here, we describe the characterisation of the VIPR2 gene structure and promoter region. The VIPR2 gene is encoded by 13 exons, the initiator codon of the 438 amino acid open reading frame is located in exon 1 and the termination signal and a poly-adenylation signal sequence are located in exon 13. The 5' untranslated region extends 187 bp upstream of the initiator codon and is extremely GC-rich (80%). The poly-adenylation signal is located 2416 bp downstream of the stop codon. Intron sizes range from 68 bp (intron 11) to 45 kb (intron 4) and the human gene spans 117 kb.

5' Untranslated Regions↗

Application and comparison of two modelling techniques for hospital bed management.

The use of the bed occupancy management and planning system (BOMPS) and the Sorensen multi-phased bed model were used to assess the implications of a hospital expanding its emergency facility. BOMPS flow modelling generates resource utilisation data dependent on the best visual and statistical fit between mixed exponential equations and time of bed occupancy; the Sorensen model creates models based on probabilities and length of stay distributions. Both models identified the presence of two streams of flow. However, there were differences in the number of beds identified as being short and longer stay. The advantage of flow modelling is that it enables decision-makers to pre-test their decisions.

Australia↗

Prescribed drugs: a major cause of ill health.

Harm caused by ill-effects of prescribed drugs is largely unrecognised, but when looked for has been found to be an important cause of ill health. Perhaps 6% of all hospital admissions and some 800 deaths a year are caused by prescribed medication in Australia. The elderly, especially those in institutions, are particularly prone to injury by drugs. Attempts to use visiting pharmacists to influence the prescribing habits of doctors have resulted in unspectacular success. It is suggested that prescribing habits may more effectively be changed by visiting from specially trained practising doctors.

Aged↗

1997 Volvo Award winner in clinical studies. Degenerative lumbar spondylolisthesis with spinal stenosis: a prospective, randomized study comparing decompressive laminectomy and arthrodesis with and without spinal instrumentation.

STUDY DESIGN: This prospective study analyzed the influence of transpedicular instrumented on the operative treatment of patients with degenerative spondylolisthesis and spinal stenosis. OBJECTIVES: To determine whether the addition of transpedicular instrumented improves the clinical outcome and fusion rate of patients undergoing posterolateral fusion after decompression for spinal stenosis with concomitant degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Decompression is often necessary in the treatment of symptomatic patients who have degenerative spondylolisthesis and spinal stenosis. Results of recent studies demonstrated that outcomes are significantly improved if posterolateral arthrodesis is performed at the listhesed level. A meta-analysis of the literature concluded that adjunctive spinal instrumentation for this procedure can enhance the fusion rate, although the effect on clinical outcome remains uncertain. METHODS: Seventy-six patients who had symptomatic spinal stenosis associated with degenerative lumbar spondylolisthesis were prospectively studied. All patients underwent posterior decompression with concomitant posterolateral intertransverse process arthrodesis. The patients were randomized to a segmental transpedicular instrumented or noninstrumented group. RESULTS: Sixty-seven patients were available for a 2-year follow-up. Clinical outcome was excellent or good in 76% of the patients in whom instrumentation was placed and in 85% of those in whom no instrumentation was placed (P = 0.45). Successful arthrodesis occurred in 82% of the instrumented cases versus 45% of the noninstrumented cases (P = 0.0015). Overall, successful fusion did not influence patient outcome (P = 0.435). CONCLUSIONS: In patients undergoing single-level posterolateral fusion for degenerative spondylolisthesis with spinal stenosis, the use of pedicle screws may lead to a higher fusion rate, but clinical outcome shows no improvement in pain in the back and lower limbs.

Aged↗

Effect of muscle glycogen availability on maximal exercise performance.

This investigation determined the influence of pre-exercise muscle glycogen availability on performance during high intensity exercise. Nine trained male cyclists were studied during 75 s of all-out exercise on an air-braked cycle ergometer following muscle glycogen-lowering exercise and consumption of diets (energy content approximately 14 MJ) that were either high (HCHO(80% CHO) or low (LCHO-25% CHO) in carbohydrate content. The exercise-diet regimen was successful in producing differences in pre-exercise muscle glycogen contents [HCHO: 578(SEM 55) mmol x kg(-1) dry mass; LCHO: 364 (SEM 58) P < 0.05 mmol x kg(-1) dry mass]. Despite this difference in muscle glycogen availability, there were no between trial differences for peak power [HCHO 1185 (SEM 50)W, LCHO 1179 (SEM 48)W], mean power [HCHO 547 (SEM 5)W, LCHO 554 (SEM 8)W] and maximal accumulated oxygen deficit [HCHO 54.4 (SEM 2.3) ml x kg(-1), LCHO 54.6 (SEM 2.0) ml x kg(-1)]. Postexercise muscle lactate contents (HCHO 95.9 (SEM 4.6) mmol x kg(-1) dry mass, LCHO 82.7 (SEM 12.3) mmol x kg(-1) dry mass, n = 8] were no different between the two trials, nor were venous blood lactate concentrations immediately after and during recovery from exercise. These results would indicate that increased muscle glycogen availability has no direct effect on performance during all-out high intensity exercise.

Adult↗

The challenges of clinical nursing research: strategies for successful conduct.

Although the literature is replete with stringent methodological guidelines for designing experimental and quasi-experimental studies, there is a paucity of literature addressing the challenges of conducting these studies in the "real world" of the clinical setting. This article describes the challenges experienced by a team of researchers conducting a study in the acute care setting, including those associated with navigating organizational restructuring and managing within a climate of uncertainty. The study focused on the evaluation of a nurse-delivered smoking cessation intervention for hospitalized cardiac patients. As each particular challenge emerged, strategies were developed. By explicating these challenges and strategies, we hope to help clinical researchers deal with challenges proactively rather than reactively.

Clinical Nursing Research↗