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Biomedical subjects

R J Burns

Publications and source records attributed to R J Burns.

At least 19 recordsLinked to original sources

Synthesis and characterization of thiobutyltriphenylphosphonium bromide, a novel thiol reagent targeted to the mitochondrial matrix.

Mitochondria are continually exposed to oxidative stress due to superoxide formation by the respiratory chain which increases in pathological situations such as ischemia reperfusion and neurodegeneration. During oxidative stress there are a number of changes in mitochondrial low-molecular-weight and protein thiols. In particular, the mitochondrial glutathione pool becomes oxidized and forms mixed disulfides with protein thiols. To investigate changes in the redox state and conjugation of mitochondrial glutathione, and other mitochondrial thiols, we designed and characterized a thiol probe specifically targeted to the mitochondrial matrix. This molecule, thiobutyltriphenylphosphonium bromide, contains a thiol group linked to a lipophilic triphenylphosphonium cation which causes it to accumulate in the negatively charged mitochondrial matrix. Using [14C]thiobutyltriphenylphosphonium bromide we confirmed that it was selectively accumulated by isolated mitochondria. In the mitochondrial matrix the thiol group equilibrated with endogenous thiols and during oxidative stress became disulfide-bonded to protein and nonprotein thiols. Therefore, this novel thiol probe can be used to label protein thiol groups and to investigate changes in conjugation and redox state of mitochondrial thiols during oxidative stress.

Animals

Toxicity of Compound 1080 livestock protection collars to sheep.

The toxicity of Compound 1080 (sodium fluoroacetate) livestock protection collars (LPCs) to sheep was investigated. Lambs wearing punctured LPCs were observed to determine dermal toxicity, sheep were fed hay treated with LPC solution to find a lethal concentration, hay treated with a lethal concentration was subjected to sun and simulated rain to assess weathering influences, and sheep were held on pasture treated with LPC solution to evaluate grazing effects. Five lambs that wore punctured LPCs for up to seven days showed no dermal erythema or edema, but three died after ingesting 1080 from LPCs. All sheep died after eating 1.0 kg of hay treated with 3.75 ml, or more, of 1.0% LPC solution. Weathering 1.0 kg of hay treated with 3.75 ml of LPC solution in the sun for up to 12 weeks, reduced, but did not eliminate, toxicity; one inch or more of simulated rain eliminated toxicity. Survival of sheep in 250 m2 pens containing 1.1 m2 of forage treated with different amounts of LPC solution depended on the treatment and amount of treated forage consumed. LPC solution poses no dermal toxicity or irritation to sheep, and toxic effects on sheep from LPC solution on hay and forage was variable and situation dependent. Under conditions of exaggerated hazard, sheep can be poisoned by ingesting LPC solution, but adverse effects from normal LPC use are rare.

Animals

Prognostic significance of increased thallium-201 lung uptake during dipyridamole myocardial scintigraphy: comparison with exercise scintigraphy.

OBJECTIVE: To compare the incidence of cardiac events among patients with increased lung uptake of thallium after dipyridamole stress, matched subjects without such uptake and matched subjects with increased lung uptake during exercise stress. DESIGN: Retrospective case control study based on quantitative and semiquantitative visual consensus analysis of thallium scintigraphy. SETTING: Nuclear cardiology laboratory of a university teaching hospital. PATIENTS: Thirty-six patients with increased lung activity after dipyridamole stress and two groups of matched control subjects identified from 3150 consecutive thallium single photon emission computed tomography studies. INTERVENTIONS: Telephone follow-up and chart reviews to determine the incidence of cardiac events. MAIN RESULTS: Cardiac events were significantly less frequent in the study group with increased lung uptake after dipyridamole stress (two of 36,5%) than in the control group with increased thallium lung uptake at exercise scintigraphy (nine of 36,25%; P = 0.046). CONCLUSIONS: Increased lung uptake of thallium has less ominous short term prognostic significance when observed in association with dipyridamole stress rather than with exercise.

Aged

Identification of viable myocardium with technetium-99m-MIBI infusion.

A 50-yr-old man was evaluated using standard stress/rest 99mTc-methoxyisobutylisonitrile (MIBI) perfusion imaging, rest thallium infusion imaging and rest 99mTc-MIBI infusion imaging prior to revascularization. Resting 99mTc-MIBI infusion imaging demonstrated hibernating myocardium which was not detected with standard stress/rest 99mTc-MIBI imaging. The implication from this observation is that resting 99mTc-MIBI infusion scintigraphy can provide useful information when evaluating patients for the presence of hibernating myocardium. A prospective comparison of resting 99mTc-MIBI infusion scintigraphy with other noninvasive techniques used to identify viable myocardium may be warranted.

Coronary Artery Bypass

Benign familial disease with muscle mounding and rippling.

Four members of a family in three generations exhibited unusual clinical features of localised transient swelling of muscle induced by percussion (muscle mounding or myoedema) and were able, voluntarily, to induce rhythmic waves of contraction in certain muscles (muscle rippling or rolling). All had raised serum creatine kinase activity. Muscle biopsy in two members showed no specific abnormality. Experimental studies performed on excised intercostal muscle showed that abnormal "after-contractions" and increased sarcolemmal excitability could be demonstrated in vitro.

Action Potentials

Late hemodynamic effects of the preserved papillary muscles during mitral valve replacement.

BACKGROUND: The late hemodynamic effects of preserving the papillary muscles during mitral valve replacement have not been evaluated. METHODS AND RESULTS: Sixteen patients who had chronic mitral regurgitation due to myxomatous degeneration were randomized to preservation (Pres group, n = 8) or no preservation (No Pres group, n = 8) of the chordae tendineae and papillary muscles during mitral valve replacement. Rest and exercise nuclear ventriculograms were performed early (3 months) and late (5 years) after surgery. Early after surgery, the No Pres group had lower ejection fractions and stroke work indexes (P < .05 by repeated-measures [rm] ANOVA) than the Pres group did at similar end-diastolic volume indexes. The No Pres group had similar cardiac indexes after exercise because heart rate increased (P < .005 by rm ANOVA). Late after surgery, ejection fraction was greater at similar end-diastolic volume indexes (P < .005 by rm ANCOVA), and preload recruitable stroke work indexes (P < .001 by rm ANCOVA) were better in the Pres group. CONCLUSIONS: Preserving chordal attachments enhanced the late hemodynamic recovery after mitral valve replacement for mitral regurgitation.

Chordae Tendineae

Protracted form of encephalitis with good outcome.

OBJECTIVE: To present four patients seen over a five-year period who developed severe protracted encephalitic illnesses but whose outcomes were favourable. CLINICAL FEATURES: Of the four patients, aged 18, 22, 34 and 19, three presented with acute psychosis, and all had a prolonged clinical course requiring intensive care management. One patient had residual generalised seizures and the other three recovered fully. No infective or toxic agent could be identified but viral encephalitis was considered most likely. OUTCOME: Despite the protracted courses, the outcomes were favourable. This is in contrast to the generally poor outcomes in encephalitis caused by established infective agents such as herpes simplex type 1. CONCLUSIONS: When the aetiology and hence the natural history of the encephalitis is unknown, long-term intensive support is appropriate.

Adolescent

Postoperative haemodynamic and pharmacological responses in patients with positive technetium pyrophosphate single-photon emission computed tomography following CABG.

The aim of this prospective study was to evaluate the postoperative haemodynamic variables and medication requirements in patients with perioperative myocardial infarction (PMI), following elective coronary artery bypass graft (CABG) surgery, as documented by technetium pyrophosphate scintigraphy using single-photon emission computed tomography (TcPPi-SPECT). A high-dose fentanyl anaesthetic technique was applied. Twelve of 58 patients (21%) developed PMI with an infarcted myocardial mass of 35.7 +/- 3.9 g. Over the 48 hr postoperative period, patients with positive TcPPi-SPECT (n = 12) did not differ from those with negative TcPPi-SPECT (n = 46) in mean heart rate (below 100 bpm), systolic blood pressure (100-120 mmHg) or central venous pressure (8-16 mmHg). However, patients with positive TcPPi-SPECT had higher pulmonary artery diastolic pressures at 5-8 hr after surgery. No differences were found in the incidence and dosage requirements for postoperative sedative or vasoactive drugs (morphine, diazepam, propranolol, lidocaine, nitroglycerin and nitroprusside) between the two groups. There was no difference in the incidence of dopamine requirement between the groups (positive-scan: 16.7%, negative-scan: 13.0%). However, the dopamine dosage for inotropic support was higher in the positive TcPPi-SPECT group over 24 hr (318.5 +/- 125.2 mg vs 71.2 +/- 24.7 mg, P less than 0.05) and 48 hr (869.1 +/- 19.0 mg vs 142.3 +/- 49.4 mg, P less than 0.001) periods after surgery. We postulate that careful control of postoperative haemodynamic variables did not prevent but may limit the extent of PMI in elective CABG patients.

Coronary Artery Bypass

Reverse redistribution on exercise thallium scintigraphy: relationship to coronary patency and ventricular function after myocardial infarction.

OBJECTIVE: To define prevalence, pathophysiology and relation to thrombolytic therapy of reverse redistribution (appearance of a new, or worsening of an existing, scintigraphic defect on 4 h delayed images compared with the stress thallium image). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral centre. PATIENTS: Sixty-three patients with acute myocardial infarction. INTERVENTIONS: Tomographic exercise thallium scintigraphy, radionuclide angiography, and quantitative coronary angiography. MAIN RESULTS: Tomographic exercise thallium scintigraphy performed at day 10 revealed fixed defects in 15 patients, reversible defects in 22 patients and reverse redistribution in 26 patients; no difference in treatment assignment (tissue plasminogen activator versus placebo) was found among the three groups. Left ventricular function was similar in patients with fixed or reversible defects and reverse redistribution; global ejection fraction was 48 +/- 14, 51 +/- 10 and 48 +/- 5%, respectively, and regional infarct ejection fraction was 36 +/- 15, 40 +/- 13 and 37 +/- 18%, respectively. However, nitroglycerin administration resulted in a significantly greater improvement in regional ejection fraction in reverse redistribution patients (5 +/- 4%) than that in patients with fixed defect (2 +/- 5%, P < 0.05) or reversible defects (3 +/- 5%, P < 0.05). The infarct-related artery had a greater cross-sectional area in reverse redistribution patients (1.5 +/- 1.42 mm2) compared with those with reversible defects (0.50 +/- 0.26 mm2, P < 0.05), but was similar to fixed defect patients (1.04 +/- 0.88). CONCLUSIONS: Reverse redistribution on tomographic thallium scintigraphy is a frequent phenomenon (occurring in 40% of patients following acute myocardial infarction) and is independent of thrombolytic therapy. Patients with reverse redistribution have a more widely patent infarct-related artery and similar ventricular function, but significantly greater functional improvement following nitroglycerin administration compared with those with reversible or fixed defects. These data suggest myocardial salvage within the infarct zone in some patients with reverse redistribution.

Animals

Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole.

Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB.

Aged

South Australian carotid endarterectomy study.

OBJECTIVE: To determine the operative morbidity and mortality of carotid endarterectomy in South Australia. DESIGN: This was a prospective study on consecutive patients already selected independently by their treating clinicians for carotid endarterectomy. Patients were assessed before and after the operation by independent neurologists. SETTING AND PARTICIPANTS: The study involved all patients undergoing carotid endarterectomy in South Australia in public and private hospitals over the 20-months period of the study. All vascular surgeons agreed to participate. INTERVENTION: Two hundred and thirty-nine carotid endarterectomies were performed on 223 patients, always as primary procedures. MAIN OUTCOME MEASURES: Patient characteristics, angiographic findings and indications for surgery were documented before the operation by neurologists who then carried out postoperative assessments and determined neurological status at discharge. Follow-up at six and twelve months was by letter and telephone enquiry to general practitioners or direct to patients. RESULTS: The perioperative death and stroke rate was 6.3% including one stroke after angiography and before endarterectomy. Fourteen patients (5.9%) had strokes after the operation and three died as a result (1.3%). Three patients had reversible ischaemic neurological deficits. In 58 asymptomatic patients, operative morbidity was 3.4%. However, in 42 patients who had had a stroke before the operation, there were seven who had operative complications (16.7%). Neurological complication rates for individual surgeons varied from 0 to 13.8%. In the subsequent 12 months, follow-up of 214 patients revealed nine additional deaths (three known to be caused by stroke, four not caused by stroke and two of unknown cause) and six more cerebral infarctions (involving both operated and unoperated sides), an annual mortality plus stroke morbidity rate of 4.2%-5.1%. CONCLUSIONS: The morbidity and mortality of carotid endarterectomy in South Australia is acceptable by world standards but is high in the subgroup with a preceding stroke. In this audit, carotid endarterectomy had an average risk at least equal to one year of untreated carotid artery disease and did not diminish the expected stroke and death incidence after one year.

Adult

Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety.

Twenty patients with moderately severe Parkinson's disease entered an open study of the efficacy and safety of a slow release preparation containing levodopa 200 mg and carbidopa 50 mg per tablet ('Sinemet CR4'). Following an initial four week baseline stabilisation period on conventional 'Sinemet' tablets, the patients were transferred to 'Sinemet CR4' and observed at intervals over the next 12 months. Fifteen patients completed the full year observation period. When compared with the baseline period, treatment with 'Sinemet CR4' was associated with longer periods of functional improvement and less fluctuation of response following each dose. The median (range) dose frequency was reduced from three (three-12) to two (two-seven) times daily (p less than 0.001) on 'Sinemet CR4' although median (range) total daily dose of levodopa was increased from 700 (375-2525) to 800 (400-2800) mg without any increase in adverse effects. Three patients developed peripheral neuropathy while receiving Sinemet CR4, but the association with this therapy is unclear. Overall 'Sinemet CR4' allowed a longer dosage interval and provided more stable control of disease manifestations than conventional 'Sinemet'.

Aged

A clinical and pathological study of progressive supranuclear palsy.

The clinical features of 26 patients diagnosed as progressive supranuclear palsy are reviewed. The atypical findings were the relatively low frequency of visual complaints (23%) and of significant dementia (20%). As well, the characteristic eye signs, supranuclear ophthalmoplegia of vertical gaze, occurred some years after the onset of the initial symptoms in a small but substantial number (31%), which significantly delayed the diagnosis, in one case by as long as 18 years. The pathological studies on 2 of the clinical cases and an additional 6 cases showed the characteristic pattern of involvement of particular subcortical and brainstem nuclei. In particular, significant degeneration of the pedunculopontine tegmental nucleus was confirmed. Degeneration of the pedunculopontine tegmental nucleus may well play an important role in the motor disability in progressive supranuclear palsy.

Adult