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Biomedical subjects

B J Allen

Publications and source records attributed to B J Allen.

At least 73 records · Page 4Linked to original sources
PubMed1995

Hydrogen background in total body nitrogen estimations.

Total body nitrogen (TBN) is measured by in vivo prompt gamma neutron capture analysis. Usually the background under the nitrogen peak is subtracted before calculating TBN from the ratio of nitrogen counts (at 10.8 MeV) to hydrogen counts (at 2.2 MeV). The hydrogen acts as an internal standard. The background under the hydrogen peak is usually ignored. The current study was undertaken to measure the variation of the hydrogen background (HB) in patients of different sizes and to determine whether the accuracy of TBN measurements is improved when an HB correction is incorporated. Heavy-water (D2O) phantoms were used to quantify patient HB. D2O simulates patient neutron scattering without contributing to the hydrogen peak. Equations were developed to predict HB in patient measurements. HB was found to vary from 9% of total counts for a 99 kg subject to 19% for a 7 kg infant. It was demonstrated that the accuracy of TBN measurements is improved for child-sized anthropometric phantoms of known composition when an HB correction is incorporated.

Adult↗
PubMed1995

Monte Carlo calculations of epithermal boron neutron capture therapy with heavy water.

Much work over the past decade has centred upon the development of epithermal neutron beams for boron neutron capture therapy (BNCT) in an effort to increase thermal-neutron flux penetration and dose homogeneity throughout the brain. While heavy water has been used extensively to improve neutron penetration associated with thermal neutron beams, the effects of heavy water with epithermal neutron beams remain largely unexplored. Applying the Monte Carlo code MCNP to a heterogenous ellipsoidal skull/brain model, the effects of heavy-water replacement are studied for the JRC/ECN Petten HFR epithermal neutron beam. Thermal neutron flux and induced gamma depth dose distributions are calculated for 20% D2O replacement in comparison to standard brain and skull materials. Results are presented for both unilateral and bilateral irradiation. With bilateral irradiation, thermal-neutron flux homogeneity is substantially increased with 20% D2O replacement, thus improving the potential to give lethal doses to boron-10-loaded, disseminated cancer cells whilst avoiding local 'hot spots' to healthy tissue. Additionally, the induced gamma dose is reduced by up to 30%, substantially lowering the background dose to healthy tissue. With bilateral irradiation, 20% D2O replacement increases the therapeutic ratio from 2.25 to 2.75 for over 4 cm depth centred at the midline of the brain. These calculations use documented tumour and blood 10B concentrations for boronophenylalanine (BPA) in humans and recently documented neutron relative biological effectiveness (RBE) values.

Boron Neutron Capture Therapy↗
PubMed1995

The influence of heavy water on boron requirements for neutron capture therapy.

Neutron penetration in tissue is a major limitation of thermal NCT, as such much work has centered upon the epithermal neutron beam in an effort to improve this situation. Further gains in neutron flux penetration, and thus therapeutic ratios, are possible if natural water is replaced with heavy water prior to therapy. Applying MCNP to a heterogeneous ellipsoidal skull/brain model, advantage depth and therapeutic depth parameters are studied as a function of heavy water replacement for a range of tumor to blood boron ratios. Both thermal (0.025 eV) and epithermal (2-7 keV) ideal neutron beams are analyzed. Using 10B ratios in the range of documented human uptake, the thermal advantage depth improved by approximately 0.7 cm for 20% D2O replacement, however, the therapeutic depth increased by less than half this value. For the epithermal beam, both the advantage depth and the therapeutic depth increased by over 1 cm. Effects of heavy water replacement on 10B requirements to therapeutically treat the midline of the brain are also evaluated.

Boron↗
PubMed1995

Total body nitrogen as a prognostic marker in maintenance dialysis.

In order to assess long-term nutritional adequacy, 154 patients on maintenance dialysis (78 on hemodialysis (HD), 76 on continuous ambulatory peritoneal dialysis (CAPD)) underwent measurement of total body nitrogen (TBN) with concurrent recording of dietary history, anthropometrics, and serum albumin. Seventy-one patients were reassessed 23.3 +/- 2.2 (5 to 76) months later. In cross-sectional analyses, anthropometric measurements and dietary intake remained stable over time in all patients. However, a significant fall in TBN occurred in the HD population with increasing time on dialysis (P < 0.05). In the prospective analyses, CAPD patients (N = 26) had a significant increase in TBN (P < 0.02). In contrast, longitudinal measurements of TBN in HD patients (N = 36) tended to fall but did not reach significance (P = 0.18). TBN correlated with total caloric intake estimated from the dietary history (P < 0.05), but not with estimated protein intake. During follow-up, 38 patients died. These patients were older (P < 0.05), and in the CAPD population, they had been on dialysis for a longer time (P < 0.05). Those who died had a lower TBN expressed both as grams per kilogram lean body mass (P < 0.005) and as the nitrogen index (P < 0.05). The probability of death within 12 months in the patients with a nitrogen index (ratio of the measured nitrogen to the predicted nitrogen for a sex-, age-, and height-matched control) less than 80% of the predicted normal value was 48%. The relative risk of death in this population was 4.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗
PubMed1994

Brain cancer incidence, mortality and case survival: observations from two Australian cancer registries.

Data from 2 Australian cancer registries covering a population of 1.7 million people were combined for the purposes of analysing brain cancer incidence, mortality and survival patterns for the time period 1978 through 1992. A total of 1,752 cases of primary brain cancer were registered, representing age-standardised incidence rates of 6.7 per 100,000 in men and 4.6 in women. Histological confirmation was available for 94% of cases. The incidence rate among persons aged 75 or over was higher during 1986-1992 than during 1978-1985, the rate for men increasing from 16.3 to 26.2 and that for women increasing from 9.7 to 18.0. The largest increases in this age group occurred for cases of glioblastoma multiforme. During the study period, 1,411 brain cancer deaths were notified to the 2 registries at age-standardised rates of 5.3 in men and 3.4 in women. Mortality rates among persons aged 75 years or older were higher during 1986-1992 than 1978-1985, increasing from 15.7 to 28.4 in men and from 10.1 to 15.3 in women. Only among men aged 15-49 years was a decline in mortality rates observed, from 3.3 to 2.4. Survival analyses indicated that age and histological type were the most powerful prognostic indicators. There was no improvement in 5-year survival for any of the age groups or histological types. An improvement in 36-month survival was noted for the 15-49 year age group diagnosed with gliomas other than glioblastoma multiforme.

Adolescent↗
PubMed1994

The pharmacokinetics of p-Boronophenylalanine.fructose in human patients with glioma and metastatic melanoma.

PURPOSE: To study the biodistribution of p-Boronophenylalanine in patients undergoing surgery for intracranial tumors or metastatic melanoma. METHODS AND MATERIALS: D,L-p-Boronophenylalanine was administered as boronophenylalanine.fructose in an intravenous bolus 1-4 h before the operation. Blood samples were collected for 24 h from the time of administration of the compound, and the blood boron elimination parameters were determined. For the glioma patients tumor samples were obtained and skin, dura, periosteum, and surrounding brain samples were collected whenever possible. For the metastatic melanoma patients tumor, fat, skin, and muscle were collected. Determination of the boron content was performed using inductively coupled plasma-atomic emission spectrometry. Twelve melanoma patients and six glioma patients participated in the study. The melanoma patients included four cases of cutaneous metastatic melanoma, six cases of metastatic melanoma to the lymph nodes and two cases of cerebral metastasis. RESULTS: The results for the metastatic melanoma patients are encouraging with an average tumor:blood boron concentration ratio and standard deviation of about 4.4 +/- 3.2 and a maximum value of 10 for the cerebral metastasis. The glioma patients involved high grade glioma for which the tumor:blood ratio was 2.2 +/- 1.2. CONCLUSION: The tumor:blood ratios for melanoma fulfil requirements for epithermal boron neutron capture therapy for cerebral melanoma metastases, whereas those for high grade glioma do not.

Boron↗
PubMed1994

Monte Carlo modelling of neutron depth dose distributions in optimizing prompt gamma in vivo neutron activation analysis systems.

Optimization of prompt gamma in vivo neutron activation analysis systems is best achieved using Monte Carlo simulation. In this study the modelling of the dimensions and materials for source holders and collimators is described and compared with experimentally derived results where feasible. Results show that valid depth doses are obtained by modelling only the central part of an IVNAA system and that the use of borated paraffin as a reflector provides acceptable thermal fluence and depth dose.

Americium↗
PubMed1994

Teatment planning figures of merit in thermal and epithermal boron neutron capture therapy of brain tumours.

The boron neutron capture therapy (BNCT) figures of merit of advantage depth, therapeutic depth, modified advantage depth and maximum therapeutic depth have been studied as functions of 10B tumour to blood ratios and absolute levels. These relationships were examined using the Monte Carlo neutron photon transport code, MCNP, with an ideal 18.4 cm diameter neutron beam incident laterally upon all ellipsoidal neutron photon brain-equivalent model. Mono-energetic beams of 0.025 eV (thermal) and 35 eV (epithermal) were simulated. Increasing the tumour to blood 10B ratio predictably increases all figures of merit. concentration was also shown to have a strong bearing on the figures of merit when low levels were present in the system. This is the result of a non-10B dependent background dose. At higher levels however, the concentration of 10B has a diminishing influence. For boron sulphydryl (BSH), little advantage is gained by extending the blood 10B level beyond 30 ppm, whilst for D,L,-p-boronophenylalanine (BPA) this limit is 10 ppm. To achieve a therapeutic depth of 6 cm (brain mid-line from brain surface) using the thermal beam, a tumour to blood ratio of 25 with 10 ppm 10B in the blood is required for BPA. Similarly, a tumour to blood ratio of 8.5 with 30 ppm blood 10B is required for the maximum therapeutic depth of BSH to reach the brain mid-line. These requirements are five times above current values for these compounds in humans. Applying the epithermal beam under identical conditions, the therapeutic depth reaches the brain mid-line with a tumour to blood 10B ratio of only 5.7 for BPA. For BSH, the maximum therapeutic depth reaches the brain mid-line with a tumour to blood ratio of only 1.9 with 30 ppm in the blood. Human data for these compounds are very close to these requirements.

Benchmarking↗
PubMed1994

Protein repletion and treatment in anorexia nervosa.

Body fat and total body nitrogen (TBN) were quantified before and after refeeding in 32 female anorexia nervosa patients and in 29 matched control subjects by using the techniques of anthropometry and in vivo neutron-capture analysis (IVNCA). Mean body weight of patients (mean body mass index; BMI, in kg/m2), 15.4 +/- 1.3, was 72.7% of that of control subjects, increasing to 89.8% of mean weight of control subjects after refeeding (mean BMI 19.0 +/- 1.2). Mean BMI of control subjects was 21.6 +/- 2.7. Compared with the control group, patients' nitrogen was initially depleted by 24.5%, increased by 18.4%, but remained 10.6% below control values (P < 0.001). Body fat was depleted by 58.4%, increased by 89.7%, but remained 21.8% below control values (P < 0.001). Thus, despite a greater initial depletion and subsequently a greater net gain, body fat remained relatively more depleted after treatment than did nitrogen and protein. Anorexia nervosa patients were shown to readily replenish protein during nutritional rehabilitation.

Adolescent↗
PubMed1994

Total body nitrogen in children with chronic renal failure and short stature.

OBJECTIVE: To directly assess the body protein content of children with chronic renal failure (CRF) and short stature. SETTING: A tertiary referral paediatric hospital. SUBJECTS: There were: (i) 17 patients (10 male, nine pre-pubertal; mean age 12.90 +/- 3.20 years) with CRF and height standard deviation (SD) score < -2.00, and (ii) 43 normal children (18 male, 27 pre-pubertal; mean age 10.34 +/- 3.34 years). INTERVENTIONS: CRF patients had the following measurements: anthropometry, total body nitrogen (TBN) by neutron capture analysis, 4 day weighed food record and serum albumin levels. Control subjects had TBN and anthropometric measurements only. RESULTS: Although older than the controls, the CRF patients had significantly lower TBN values (645 +/- 265 vs 930 +/- 365 g, P < 0.01). Mean values for TBN and TBN/height (percentages of expected) in the CRF patients were significantly reduced to 54% and 63% respectively, when predicted from age. However, their TBN predicted from height was 100% of expected. %TBN (predicted from age) correlated significantly with height SD score (r = 0.79), weight SD score (r = 0.87), upper arm muscle area percentile (r = 0.62) and serum albumin (r = 0.62). Mean oral energy and protein intakes were 65% and 172% of recommended dietary intake respectively. CONCLUSIONS: Children with CRF and short stature are significantly protein-depleted for age although not for height. Chronic energy deficiency may contribute to impaired protein deposition which, in turn, may be important in the pathogenesis of growth failure in CRF.

Adolescent↗
PubMed1993

Loss of differentiation control in transformed 3T3 T proadipocytes.

Nontransformed 3T3 T mesenchymal/proadipocyte stem cells can be readily induced to differentiate, yet previous work has shown that 3T3 T cells that are spontaneously or virally transformed not only lose their normal growth control mechanisms but also lose the ability to differentiate. Loss of growth control can be due to autocrine mechanisms in some transformed cells, but the mechanisms involved in disrupting differentiation control are poorly understood. Our goal is to further define the growth and differentiation defects that arise in neoplastically transformed cells and the mechanisms underlying those defects. For example, exogenous transforming growth factor beta and tumor necrosis factor, both of which are secreted aberrantly by some tumor cells, are known inhibitors of different steps of the normal 3T3 T adipocyte differentiation process, suggesting a potential role as autocrine factors in disrupting differentiation of transformed 3T3 T cells. In the current study we transformed 3T3 T cells in vitro with chemical or UV irradiation treatment in order to determine if the acquisition of the transformed phenotype after these treatments is also associated with loss of differentiation control as it is with spontaneously or virally transformed cells. Four chemically and two UV-treated 3T3 T cell lines were isolated from type III foci and all have been found to be tumorigenic in syngeneic animals and to have lost the ability to differentiate. Relative to the parental cell line the differentiation abilities of the transformed clones ranged from 0 to less than 5%. In this regard, we also analyzed the normal and aberrant expression of three growth factors and differentiation inhibitors in transformed cells. Both transforming growth factor alpha and beta were found to be expressed in non-transformed 3T3 T cells as determined by Northern blot analyses. In addition, both were found to be down-regulated during differentiation of 3T3 T cells. Transformed/differentiation-defective 3T3 T cells expressed varied levels of transforming growth factor alpha and beta. Three of the new transformed clones expressed particularly high levels of transforming growth factor alpha. Very low levels of tumor necrosis factor expression were found in the normal cells and the transformed cells appeared to express tumor necrosis factor at similar levels. In contrast, none of the transformed cells expressed any of the differentiation-specific genes tested (lipoprotein lipase, glycerol-3-phosphate dehydrogenase, etc.). Even a transformed clone which could undergo growth arrest but not morphological differentiation expressed no differentiation-specific genes. Together, these data suggest that neoplastic transformation in general disrupts differentiation control.(ABSTRACT TRUNCATED AT 400 WORDS)

3T3 Cells↗