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Biomedical subjects

B J Allen

Publications and source records attributed to B J Allen.

At least 55 records · Page 3Linked to original sources

Evaluation of useful neutron flux for accelerator boron neutron capture therapy using the 7Li(p,n) reaction.

Accelerator neutron sources for epithermal neutron capture therapy utilising the 7Li(p,n) nuclear reaction are proposed to operate in the range of 1.88 to 2.5 MeV proton energy. Operation with proton energies closer to the reaction threshold decreases neutron yield but allows for smaller reflector and moderator, with less reduction of the epithermal flux, whereas high energies allow thicker targets to be used. The neutron yields for thick lithium targets are estimated in the energy range of 1.881 MeV to 2.5 MeV and useful neutron flux determined. The optimal range of proton energy is found to be 1.89-1.95 MeV, and this is recommended for more detailed studies of neutron transport properties for accelerator BNCT.

Biophysical Phenomena↗

Murine in vivo total body nitrogen by photoactivation.

A facility to measure total body nitrogen (TBN) by photoactivation analysis in rats, using the 14N(gamma, n)13N reaction, was designed, calibrated and evaluated. TBN provides a quantitative estimate of nutritional status. TBN in humans can be measured by neutron activation, however the small absolute amount of nitrogen in rats causes difficulties with this technique. Photoactivation analysis involved irradiating the specimen with high energy photons from an 18 MV Medical Linear Accelerator to a dose of approximately 2 Gy. The technique was calibrated using urea solution rat phantoms with 2.0-3.0% nitrogen content. By analysing the measured decay curve, the initial nitrogen count rate of 0.51 MeV photons was determined and the initial oxygen count rate, being an interfering source of 0.51 MeV photons, was shown to be constant. Within the range of nitrogen concentrations studied, the response is linear (r2 = 0.9) with a CV of 3.5%. Thus, photoactivation provides a relatively simple, in vivo technique for determining total body nitrogen in rats.

Animals↗

Internal calibration for a total body counter.

Whole body counting is used to monitor the ingestion of radioactivity by radiation workers when unsealed sources are used in biomedical or industrial applications. The whole body counter at Lucas Heights Research Laboratories has been running for four decades, and radiation workers are frequently monitored for radioactive contamination. In a retrospective study of total body potassium (TBK) values in radiation workers, it was found that the results varied markedly with time. In that TBK is a slowly varying quantity in healthy individuals, variation in TBK is therefore indicative of instability in the counting system. We conclude that TBK can be used as an internal calibration for the whole body counter. The activity of radioisotope contaminants can therefore be expressed relative to the value of the potassium activity in a given subject.

Humans↗

CT based 3D Monte Carlo radiation therapy treatment planning.

This paper outlines the "voxel reconstruction" technique used to model the macroscopic human anatomy of the cranial, abdominal and cervical regions directly from CT scans. Tissue composition, density, and radiation transport characteristics were assigned to each individual volume element (voxel) automatically depending on its greyscale number and physical location. Both external beam and brachytherapy treatment techniques were simulated using the Monte Carlo radiation transport code MCNP (Monte Carlo N-Particle) version 3A. To obtain a high resolution dose calculation, yet not overly extend computational times, variable voxel sizes have been introduced. In regions of interest where high attention to anatomical detail and dose calculation was required, the voxel dimensions were reduced to a few millimetres. In less important regions that only influence the region of interest via scattered radiation, the voxel dimensions were increased to the scale of centimetres. With the use of relatively old (1991) supercomputing hardware, dose calculations were performed in under 10 hours to a standard deviation of 5% in each voxel with a resolution of a few millimetres--current hardware should substantially improve these figures. It is envisaged that with coupled photon/electron transport incorporated into MCNP version 4A and 4B, conventional photon and electron treatment planning will be undertaken using this technique, in addition to neutron and associated photon dosimetry presented here.

Abdomen↗

Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor.

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.

Animals↗

Noxious cutaneous thermal stimuli induce a graded release of endogenous substance P in the spinal cord: imaging peptide action in vivo.

Dorsal root ganglia (DRG) neurons synthesize and transport substance P (SP) to the spinal cord where it is released in response to intense noxious somatosensory stimuli. We have shown previously that SP release in vivo causes a rapid and reversible internalization of SP receptors (SPRs) in dorsal horn neurons, which may provide a pharmacologically specific image of neurons activated by SP. Here, we report that noxious heat (43 degrees, 48 degrees, and 55 degrees C) and cold (10 degrees, 0 degrees, -10 degrees, and -20 degrees C) stimuli, but not innocuous warm (38 degrees C) and cold (20 degrees C) stimuli, applied to the hindpaw of anesthetized rats induce SPR internalization in spinal cord neurons that is graded with respect to the intensity of the thermal stimulus. Thus, with increasing stimulus intensities, both the total number of SPR+ lamina I neurons showing SPR internalization and the number of internalized SPR+ endosomes within each SPR immunoreactive neuron showed a significant increase. These data suggest that thermal stimuli induce a graded release of SP from primary afferent terminals and that agonist dependent receptor endocytosis provides evidence of a spatially and pharmacologically unique "neurochemical signature" after specific somatosensory stimuli.

Animals↗

Clinical assessment of adrenergic tone and responsiveness to beta-blocker therapy in patients with symptomatic ventricular tachycardia and no apparent structural heart disease.

To further define the relation between changing adrenergic tone, beta-blocker therapy, and clinical ventricular tachycardia (VT), we evaluated these factors in 35 patients with VT unrelated to coronary artery disease or ventricular dysfunction. Testing included Holter monitoring (91% had VT), exercise test (69% had VT), Adrenergic responsiveness of VT was graded according to diurnal variation, response to exercise, isoproterenol infusion, and response to beta-blockers. beta-Blockers were effective and well tolerated in this population. There was also a predictable relation between changing adrenergic tone and the arrhythmia response to beta-blocker therapy.

Adolescent↗

Selective uptake of boronated low-density lipoprotein in melanoma xenografts achieved by diet supplementation.

The lipid core of human plasma low-density lipoprotein (LDL) was extracted using hexane and the LDL reconstituted with the addition of n-octyl-carborane. Biodistribution studies of the boronated LDL were performed in BALB/c mice bearing subcutaneous Harding-Passey melanoma xenografts. When diet supplementation with coconut oil and cholesterol for 21 days and regular dosing with hydrocortisone for 7 days before the studies was used to down-regulate the liver LDL receptors and the adrenal receptors, respectively, the tumour-blood boron concentration ratio of 5:1 was achieved.

Adrenal Glands↗

Calibration of a total body potassium monitor with an anthropomorphic phantom.

An anthropomorphic phantom was used to calibrate a supine geometry sodium iodide total body potassium monitor. Correction factors accommodating variability in subject size were empirically determined. Measurements on 12 males of weight 45-96 kg, height 161-184 cm and 18 females of weight 48-89 kg, height 153-175 cm, showed that the 40K calibration factor (F, counts s-1 (g of potassium)-1) was significantly correlated (r = 0.88, p < 0.0001) to subject (weight/height)0.5, indicating comparable accuracy to 42K-based calibration procedures. Fat-free mass determined from the potassium measurements of 16 subjects correlated significantly with fat-free mass estimated from skinfold thickness (r = 0.98, p < 0.0001), dual-energy x-ray absorptiometry (r = 0.99, p < 0.0001) and bioimpedance analysis (r = 0.98, p < 0.0001). These data, together with the precision (coefficient of variation, CV = 1.5%) and accuracy (CV = 4.5%) of the system, indicate that this calibration procedure represents a relatively low-cost, non-invasive alternative to 42K-based methods of calibrating total body potassium monitors.

Absorptiometry, Photon↗

Safety and efficacy of nandrolone decanoate for treatment of wasting in patients with HIV infection.

OBJECTIVE: To evaluate the safety and efficacy of the anabolic steroid, nandrolone decanoate (Deca Durabolin) in patients with HIV wasting who are resistant to nutritional intervention. DESIGN: A 16-week open trial with subjects who had lost 5-15% of their usual body weight. SETTING: HIV/AIDS specialist ambulatory care services, both public and private, in sydney, Australia. PARTICIPANTS: Two hundred and twenty men entered the pre-therapy phase, and of these, 24 failed to gain weight and were enrolled. Seventeen subjects (81%) completed the 16-week trial. INTERVENTIONS: Pre-therapy nutritional assessment and education was conducted by the clinical dietitian. Those who failed to gain weight (10.9%) were treated with nandrolone decanoate (100 mg/ml) by deep intramuscular injection every 2 weeks for 16 weeks. MAIN OUTCOME MEASURES: Changes in weight and body composition (lean body mass, total body water and nitrogen index) were measured by anthropometry, bioelectrical impedance, and in vivo neutron activation. Changes in quality of life were assessed by the 30-item Medical Outcomes Study short form questionnaire. Changes in biochemistry, haematology and immunology were also measured. RESULTS: There were significant increases in weight (mean, 0.14 kg per week; P < 0.05) and lean body mass (mean, 3 kg by anthropometry; P < 0.005). The change in lean body mass was of similar magnitude across all measurement modalities. Quality of life parameters, especially functionality, increased significantly during the trial. No subject experienced toxicity. CONCLUSION: Nandrolone decanoate has beneficial effects on weight, lean body mass and quality of life in selected patients who have mild to moderate HIV wasting.

Acquired Immunodeficiency Syndrome↗

Alpha- and beta-emitting radiolanthanides in targeted cancer therapy: the potential role of terbium-149.

The efficacy of systemic cancer therapy rests on the ability of a toxin to be preferentially located in cancer cells, so that cancer cell kill is maximized and normal tissue spared. This requires that the lifetime of the toxin be less than the lifetime of the carrier in the body, effectively ruling out chemical toxins, as they remain effective until excreted from the body. The requirement of localization of dose to the cancer cell makes radioactive beta-emitting radionuclides unattractive. Alpha-emitting radionuclides are much more appropriate toxins, as their efficacy depends on the high energy and short range of the alpha particles, and terbium-149 is shown to be the most efficacious of these. However, the merit of various alpha- and beta-emitting radionuclides depends on the stage and type of cancer. Recommendations are made with respect to the matching of the target cancer with required properties of the radiolabel and carrier.

Alpha Particles↗

Body protein in prepubertal children with phenylketonuria.

OBJECTIVE: To assess body protein and protein deposition in prepubertal children with phenylketonuria (PKU). DESIGN: Cross-sectional study with nested longitudinal cohort. SETTING: A tertiary referral paediatric hospital. SUBJECTS: 37 PKU patients (3.9-11.0 years) and 27 unselected healthy controls (4.0-11.5 years) of whom 29 PKU patients and 17 controls were followed longitudinally. INTERVENTIONS: All had measurements of height, weight, body fat and total body nitrogen (TBN) by neutron capture analysis; PKU patients and their unaffected siblings (n = 16) also had measurements of four day weighed food record and plasma amino acids by HPLC. RESULTS: The children with PKU compared with the controls were significantly shorter (height SD score -0.42 +/- 0.89 vs 0.17 +/- 0.94, respectively, P < 0.02) and had a lower TBN (575 +/- 200 vs 710 +/- 215g, respectively, P < 0.02). TBN in the controls was significantly correlated with lean body mass (LBM), weight, height and age (r = 0.97, 0.95, 0.95, 0.88, respectively, P < 0.001). The children with PKU had significantly lower TBN when predicted from LBM, weight and age (93%, 92%, 92% of predicted, respectively), but normal TBN predicted from height (102% of expected). The annual accretion of nitrogen was similar for the PKU and controls (86 +/- 45 and 77 +/- 58 g/y, respectively). There was no difference between the two groups in protein intake or plasma amino acids except for phenylalanine. CONCLUSION: The children with PKU had a deficit in height and body protein despite a normal to higher accretion of protein. If the deficit occurs early in life, amino acid supplementation and other nutritional practices used at this time need to be reviewed.

Amino Acids↗

Measurements and Monte Carlo simulations of the fluence and dose characteristics of microplanar photon beams.

The lateral absorbed dose, depth dose and photon fluence in a water phantom of a single microplanar beam is investigated using the Monte Carlo method. To validate the calculated axial and scattered photon fluence, an experiment is carried out using a NaI(TI) detector and 20 mCi Cd-109 source at energies of 22 keV and 88 keV. A 150 microns collimator is used to produce the microplanar beam, and the integrated scattered photon fluence is measured over 2.5 microns increments. The axial (depth) photon fluence is in good agreement with the calculated results. The scattered (lateral) photon fluence results agree to within two standard deviations.

Cadmium Radioisotopes↗

Effect of L-10B-p-boronophenylalanine-fructose and the boron neutron capture reaction on mouse brain dopaminergic neurons.

Radiation damage to the dopamine tracts caused by enriched L-10B-p-boronophenylalanine (L-10BPA)-fructose and the boron neutron capture reaction was investigated using the mouse model. Following various treatments with L-10BPA and neutron irradiation of the head, the brain was perfusion fixed and removed; 50-microns frozen sections were cut. Dopaminergic neurons were visualized using immunohistochemistry for tyrosine hydroxylase. The administration of L-10BPA had no permanent effect on dopaminergic tracts. Neutron capture therapy with L-10BPA caused a reduction in tyrosine hydroxylase immunohistochemical activity within 4 h of irradiation, but by 48 h, this reduction reversed. No damage was observed at 120 h postirradiation.

Animals↗

Is the time domain signal-averaged electrocardiogram helpful in patients with ventricular tachycardia without apparent structural heart disease?

The signal-average electrocardiogram (SAECG) has been a screening method for identifying patients at risk for ventricular tachycardia (VT) in the setting of coronary artery disease (CAD). Its significance in patients with VT unrelated to CAD or left ventricular dysfunction is undetermined. In order to define the value of SAECG in this patient population further, we compared the time domain SAECG at 25, 40, and 80 Hz filters in 35 patients with clinically symptomatic VT in the absence of structural heart disease was compared with 10 normal controls and 10 patients with CAD and inducible VT. SAECG data in patients without structural heart disease were intermediate between normal controls and patients with CAD. No single or combined SAECG criterion helped to differentiate between patients with inducible and noninducible VT. There was no concordance to other arrhythmia testing. It was concluded that signal-averaged electrocardiography may have little screening value in VT unrelated to CAD or left ventricular dysfunction.

Adult↗

Life-threatening alterations in heart rate after the use of adenosine in atrial flutter.

Adenosine has become the preferred treatment for common types of supraventricular tachycardia because it is extremely effective and rarely associated with with serious side effects. It has also been advocated as an intervention for diagnostic use to assess uncommon types of tachycardia. Evidence is shown in this report that adenosine was associated with dangerous worsening of arrhythmia in patients with atrial flutter. In two patients, adenosine precipitated acceleration of ventricular response, in one case necessitating emergent cardioversion. Both patients had atrial flutter with 2 to 1 atrioventricular block that evolved into 1 to 1 atrioventricular conduction. In three other patients, adenosine was associated with prolonged bradyasystole and hypotension. In each of the five patients, adenosine was given in a standard fashion (6 or 12 mg). In summary, adenosine should be recognized as a potentially dangerous intervention in patients with atrial flutter. If it is used for diagnostic purposes, resuscitative equipment should be readily available.

Adenosine↗