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Biomedical subjects

G Mackenzie

Publications and source records attributed to G Mackenzie.

At least 19 recordsLinked to original sources

An overview of acute otitis media in Australian Aboriginal children living in remote communities.

Australian Aboriginal children experience early, persistent and severe middle ear infections. We conducted a review of the medical literature that addressed acute otitis media (AOM) in Australian Aboriginal children. Comparisons were made with the recent guidelines on the diagnosis and management of AOM prepared by the American Academies of Pediatrics and Family Physicians (AAP & AAFP 2004). Otitis media in Aboriginal children living in remote communities begins in the first 3 months of life following early bacterial colonisation. Young children with persistent signs of suppurative disease (bulging of the tympanic membrane or middle ear discharge) are probably most at risk of developing chronic suppurative otitis media.

Australia↗

Molecular characterisation of pneumococcal serotype 16F: Established predominant carriage and otitis media serotype in the 7vPCV era.

Young Australian Aboriginal children in remote communities experience very high rates of pneumococcal carriage and otitis media. Prior to introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV, Prevenar), serotype 16F was an important type found in nasal and ear discharge swabs. Since commencement of pneumococcal immunisation for Aboriginal infants in 2001, 16F has become the predominant established serotype in carriage and otitis media in young Aboriginal children. BOX typing and multi-locus sequence typing revealed a diverse population of serotype 16F strains, and evidence of potential capsule switching from a vaccine serotype 4 to a serotype 16F.

Australia↗

Assessment of CAOS as a training model in spinal surgery: a randomised study.

The objectives of this study were (1) to quantify the benefit of computer assisted orthopaedic surgery (CAOS) pedicle screw insertion in a porcine cadaver model evaluated by dissection and computed tomography (CT); (2) to compare the effect on performance of four surgeons with no experience of CAOS, and varying experience of pedicle screw insertion; (3) to see if CT with extended windows was an acceptable method to evaluate the position of the pedicle screws in the porcine cadaver model, compared to dissection. This was a prospective, randomised, controlled and blinded porcine cadaver study. Twelve 6-month-old porcine (white skinned Landrace) lumbar spines were scanned pre-operatively by spiral CT, as required for the CAOS computer data set. Computer randomisation allocated the specimens to one of four surgeons, all new to CAOS but with different levels of experience in spinal surgery. The usual anatomical landmarks for the freehand technique were known to all four surgeons. Two pedicles at each vertebral level were randomly allocated between conventional free hand insertion and an electromagnetic image guided surgery (NAVITRAK) and 6.5 mm cancellous AO screws inserted. Post-operatively, spiral CT was blindly evaluated by an independent radiologist and the spine fellow to assess the accuracy of pedicle screw placement, by each method. The inter- and intra-observer reliability of CT was evaluated compared to dissection. The pedicle screw placement was assessed as perfect if within the pedicle along its central axis, or acceptable (within < 2 mm from perfect), and measured in millimetres from perfect thereafter. One hundred and sixty-six of 168 pedicles in 12 porcine spines were operated on. Complete data were present for 163 pedicles (81 CAOS, 82 freehand). In the CAOS group 84% of screws were deemed acceptable or perfect, compared to 75.6% with the freehand technique. Screw misplacement was significantly reduced using CAOS (P = 0.049). Seventy-nine percent of CAOS screws were ideally placed compared with 64% with a conventional freehand technique (P = 0.05). A logistic linear regression model showed that the miss placed pedicle screw rate was significantly reduced using CAOS (P = 0.047). CAOS benefited the least experienced surgeons most (the research registrars acceptable rate increased from 70 to 90% and the spine fellow from 76 to 86%). CAOS did not have a statistically significant effect on the experienced consultant spine surgeon increasing from 70 to 79% (P = 0.39). The experienced general orthopaedic surgeon did not benefit from CAOS (P = 0.5). CT compared to dissection showed an intra-observer reliability of 99.4% and inter-observer reliability of 92.6%. The conclusions of this study were as follows: (1) an increased number of pedicle screws were ideally placed using the CAOS electromagnetic guidance system compared to the conventional freehand technique; (2) junior surgeons benefited most from CAOS; (3) we believe CAOS (Navitrak) with porcine lumbar spines evaluated by post operative CT, represents a useful model for training junior surgeons in pedicle screw placement; (4) experienced spine surgeons, who have never used CAOS, may find CAOS less helpful than previously reported.

Animals↗

Naturally occurring spore particles at planar fluid interfaces and in emulsions.

We have investigated the potential of utilizing naturally occurring spore particles of Lycopodium clavatum as sole emulsifiers of oil and water mixtures. The preferred emulsions, prepared from either oil-borne or aqueous-borne dispersions of the monodispersed particles of diameter 30 microm, are oil-in-water. The particles act as efficient stabilizers for oils of different polarity. Droplets as large as several millimeters are stable to coalescence indefinitely, despite the low coverage of interfaces by particles observed microscopically. Consistent with the emulsion findings, we discover that particles spontaneously adsorb to bare oil-water interfaces of single drops from oil dispersions, whereas adsorption is less spontaneous and extensive from aqueous dispersions. Monolayers of the spore particles at both air-water and oil-water planar interfaces contain particles in an aggregated state forming clusters and chains. The influence of particle concentration, oil/water ratio, and additives in the aqueous phase is studied.

Journal Article↗

Visual functioning and quality of life in the SubFoveal Radiotherapy Study (SFRADS): SFRADS report 2.

AIMS: To determine whether or not self reported visual functioning and quality of life in patients with choroidal neovascularisation caused by age related macular degeneration (AMD) is better in those treated with 12 Gy external beam radiotherapy in comparison with untreated subjects. METHODS: A multicentre single masked randomised controlled trial of 12 Gy of external beam radiation therapy (EBRT) delivered as 6 x 2 Gy fractions to the macula of an affected eye versus observation. Patients with AMD, aged 60 years or over, in three UK hospital units, who had subfoveal CNV and a visual acuity equal to or better than 6/60 (logMAR 1.0). METHODS: Data from 199 eligible participants who were randomly assigned to 12 Gy teletherapy or observation were available for analysis. Visual function assessment, ophthalmic examination, and fundus fluorescein angiography were undertaken at baseline and at 3, 6, 12, and 24 months after study entry. To assess patient centred outcomes, subjects were asked to complete the Daily Living Tasks Dependent on Vision (DLTV) and the SF-36 questionnaires at baseline, 6, 12, and 24 months after enrolment to the study. Cross sectional and longitudinal analyses were conducted using arm of study as grouping variable. Regression analysis was employed to adjust for the effect of baseline co-variates on outcome at 12 months and 24 months. RESULTS: Both control and treated subjects had significant losses in visual functioning as seen by a progressive decline in mean scores in the four dimensions of the DLTV. There were no statistically significant differences between treatment and control subjects in any of dimensions of the DLTV at 12 months or 24 months after study entry. Regression analysis confirmed that treatment status had no effect on the change in DLTV dimensional scores. CONCLUSIONS: The small benefits noted in clinical measures of vision in treated eyes did not translate into better self reported visual functioning in patients who received treatment when compared with the control arm. These findings have implications for the design of future clinical trials and studies.

Activities of Daily Living↗

Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration.

OBJECTIVE: To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration. DESIGN: A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only. SETTING: Three United Kingdom-based hospital units. PARTICIPANTS: Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better. METHODS: Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed. MAIN OUTCOME MEASURES: The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed. RESULTS: At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P =.08) or 6 or more (severe) (P =.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P =.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P =.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients. CONCLUSION: The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration.

Aged↗

Optimal time of arrival for performance at moderate altitude (1700 m).

PURPOSE: The time course of physiological exercise responses after acute ascent to moderate altitude was investigated. METHODS: Fifteen young male subjects (16.5 +/- 0.8 yr) completed one familiarization and then two further sea level sessions to determine sea level values (SL). Subjects were then tested 6 h (ALT1), 18 h (ALT2), and 47 h (ALT3) after arrival at 1700 m. Subjects completed a 5-min submaximal cycle test, shuttle run test, and 45-s repeated push-up test. Hemoglobin (Hb) and hematocrit (Hct) were measured. RESULTS: Cycle test heart rate (HR) was higher at ALT1 than SL (182 +/- 15 vs 177 +/- 16 b.min(-1), P < 0.01) but had returned to 177 +/- 13 and 176 +/- 12 b.min(-1) at ALT2 and ALT3, respectively. At ALT1, only five subjects completed the full 5 min. Postexercise plasma lactate was not different. Shuttle test HR was higher at ALT1 than SL (191 +/- 8 vs 185 +/- 14 b.min(-1), P = 0.01) but had returned to 185 +/- 10 and 183 +/- 16 b.min(-1) at ALT2 and ALT3. Shuttle run time (SRT) was 37% shorter at ALT1 than SL (251 +/- 134 vs 401 +/- 115 s, P < 0.001) and remained impaired at ALT2 and ALT3 (330 +/- 124 and 344 +/- 115 s, both P < 0.001 vs SL). There was a significant relationship between magnitude of increased HR and reduction in SRT between SL and ALT1 (r = 0.52, P < 0.05). Push-up HR, Hb, and Hct were not affected by altitude. CONCLUSIONS: These findings indicate that detrimental effects of acute ascent to 1700 m on exercise performance are greater after 6 h than after 18 or 47 h. Performance was not entirely restored to SL values even after 47 h, despite restoration of easily measured physiological parameters. The results suggest travel to moderate altitude should occur as early as is practical before competition.

Adaptation, Physiological↗

Asymmetric synthesis of novel isoindolines: azasaccharide mimics as potential enzyme inhibitors.

2',3'-Dideoxy-2',3'-didehydronucleosides and azasaccharides are known to possess antiviral activity. The synthesized 1-methoxyisoindoline system (10), which is related to the above nucleosides, is potentially stable in-vivo. The 1-methoxyisoindoline was synthesized from the achiral phthalaldehyde in 10 steps via an enantiomerically pure diol obtained by Sharpless asymmetric dihydroxylation. The new heterocyclic compound is an azosaccharide mimic which provides an access to a new series of nucleoside analogues with potential as antiretroviral agents (anti-HIV) and as glycosidase inhibitors.

Dideoxynucleosides↗

Optimizing the initial 12-lead electrocardiographic diagnosis of acute myocardial infarction.

AIMS: The optimum definition of ST elevation for diagnosis of acute myocardial infarction, with respect to both the minimum height and the minimum numbers of leads, is unknown. Furthermore, only 50% of patients with acute myocardial infarction present with ST elevation. We thus quantified the sensitivity and specificity of different ST elevation criteria for diagnosis of acute myocardial infarction, and determined whether models incorporating multiple QRST features in addition to ST elevation, could improve detection of acute myocardial infarction. METHODS AND RESULTS: The study population comprised 1190 subjects: 1041 consecutive patients presenting with chest pain (335 with acute myocardial infarction) and 149 controls without chest pain. Subjects were randomly divided into a training set (587) and a validation set (603). ECG prediction models for acute myocardial infarction incorporating different ST elevation criteria and/or additional QRST features (Q waves, ST depression, T wave inversion, bundle branch block, axes deviations, and left ventricular hypertrophy) were developed in training set patients using forward stepwise multiple logistic regression. Models were then prospectively tested in the validation set patients. The optimum ST elevation model (based on > or =1 mm ST elevation in > or = 1 inferior/lateral leads, or > or =2 mm ST elevation in > or =1 anteroseptal leads) correctly classified 83.1% of subjects (55.8% sensitivity, 94. 0% specificity). The choice of ST elevation definition had marked influence on the sensitivity (45.4-68.6%) and specificity (81.2-98. 1%) for diagnosis of acute myocardial infarction. The addition of multiple QRST variables only marginally improved overall classification but did result in high specificity (92.6-96.1%). CONCLUSION: Different definitions of 'significant' ST elevation led to marked variations in sensitivity and specificity for diagnosis of acute myocardial infarction. Multiple QRST features in addition to ST elevation only marginally improved overall classification.

Aged↗

Issues that influence patient/physician discussion of complementary therapies.

This article explores what patients expect from physicians when discussing complementary therapies. Counsellors at four cancer centres, under the auspices of the British Columbia Cancer Agency, discuss their clinical observations in working with oncology patients. They present perspectives of factors that influence the patient/physician discussion of complementary therapies. Some of the common themes include desire for collaboration and control, need for understanding treatment information, maintenance of hope, and trust of the physician.

Attitude of Health Personnel↗

Communication between hospitals and isolated aboriginal community health clinics.

OBJECTIVE: This study described the communication dynamics, identified problems and recommended changes to improve patient follow-up and communication between Royal Darwin Hospital (RDH) and isolated Aboriginal community health clinics (CHC) in the Northern Territory (NT). METHOD: In 1995, staff interviews were conducted and an audit of isolated Aboriginal patients' RDH discharge summaries (DS). RESULTS: Eighteen per cent of RDH DSs never arrived in CHCs. DSs were often prepared late and more likely to be in CHC records if written on time and if the referral source was specified. Interviews revealed discontent between CHCs and RDH regarding: communication, DS documentation, the supply of discharge medication, as well as different hospital and community perceptions of Aboriginies' reliability to carry a DS and CHC desire for patients to be given DSs at discharge. CONCLUSION: Aboriginal patients should be given a DS at discharge and resident medical officers should be educated as to the function and importance of the DS. In 18 months following this study, RDH appointed unit-based Aboriginal health workers and a policy was produced for written communication between hospital and CHCs, as well as a discharge planning manual for Aboriginal communities. IMPLICATIONS: Projects investigating communication between hospitals and isolated Aboriginal clinics and patient follow-up may result in significant policy changes concerning these processes.

Australia↗

On a non-proportional hazards regression model for repeated medical random counts.

A wholly parametric non-proportional hazards survival model is introduced. The model retains Cox's constant of proportionality as the leading term in the relative risk but permits additional flexibility by modelling the relative risk as a function of time. Covariate effects are modelled on the log odds scale, a choice which is more in keeping with the spirit of the multiple logistic function, rather than on the logarithmic scale, as in the proportional hazards model. Some basic properties of the model are described. A special feature of the model is that, when the proportional hazards model applies, Cox's regression coefficients are easily recovered and the computation of other time dependent quantities of interest is routine. A semi-Markov version of the model is derived to analyse recurrent sequential state processes and this is applied to a study of valvotomies conducted in the Regional Medical Cardiology Centre in Belfast, Northern Ireland. The results obtained are compared with those from the classical proportional hazards analysis.

Adult↗

Stability of the antiproliferative effect of mitomycin-C after reconstitution.

PURPOSE: The purpose of this study was to determine the long-term stability of the antiproliferative effect of mitomycin-C (MMC) following reconstitution. METHODS: Identical MMC preparations were reconstituted from the crystalline form and then stored at room temperature or 4 degrees C. Cultured human Tenon's fibroblasts were exposed to MMC (0.5 mg/ml) for 2.5 min at 0, 3, 7, 10, 14, 21, 28, 35, and 42 days following reconstitution. After removal of the drug, fibroblast proliferation was measured by tritiated thymidine uptake. RESULTS: The percentage of inhibition was maintained at > 85% for both the room temperature and the 4 degrees C groups, and this inhibition persisted for the duration of the experiment. There was no statistically significant difference in the results between the storage temperatures. CONCLUSIONS: These data suggest that MMC retains its antiproliferative effect for at least 6 weeks following reconstitution and that this effect is not changed by storage temperature. Cost savings may be realized by storing MMC in unit-dose reconstituted aliquots for these longer periods, providing sterility can be assured.

Analysis of Variance↗

Synthesis of 4- and 5-amino-1-(2-deoxy-D-erythro-pentofuranosyl)imidazole nucleosides by chemical and biotransformation methods.

(2-Deoxy-D-erythro-pentofuranosyl)imidazole nucleosides have been synthesised by glycosylation of the sodium salt of ethyl 5-aminoimidazole-4-carboxylate with 2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranosyl chloride. Glycosylation of ethyl 5-aminoimidazole-4-carboxylate with 2-deoxy-beta-D-erythro-pentofuranose was also achieved enzymically using E. coli, immobilised by ionotropic gelation in an alginate gel, with 2'-deoxyuridine as glycosyl donor. 5-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)imidazole-4-carboxylic acid 5'-phosphate and 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)imidazole-5-carboxylic acid 5'-phosphate were synthesised by phosphorylation of the respective nucleosides and examined as inhibitors of phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21) and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (EC 6.3.2.6), which are involved in the de novo biosynthesis of purine nucleotides.

Biotransformation↗

Which factors determine the development of late potentials after first myocardial infarction? A multifactorial analysis.

A multifactorial analysis was performed to study the factors that contributed to the occurrence of late potentials on the signal-averaged electrocardiogram in 106 consecutive patients with a first myocardial infarction. Ninety-three (88%) patients received intravenous thrombolytic therapy within 6 hours of symptom onset. Thirty-two (30%) patients had a late potential on the signal-averaged electrocardiogram on day 6, including 17 of 31 (55%) in whom the infarct-related artery was occluded and 15 of 75 (20%) in whom it was patent (P = 0.0004). Twenty-three variables were analyzed by a multifactorial stepwise regression analysis. Predictors of a late potential were (1) an occluded infarct-related coronary artery (t = -3.653, P = 0.0004) and (2) the extent of myocardial necrosis as indicated by the peak serum lactate dehydrogenase level (t = 3.094, P = 0.0025). The lower incidence of late potentials when the infarct-related coronary artery was patent was independent of left ventricular ejection fraction and peak enzyme levels after infarction.

Arrhythmias, Cardiac↗