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B J Allen

Publications and source records attributed to B J Allen.

At least 37 records · Page 2Linked to original sources
PubMed2000

The predictive value of body protein for chemotherapy-induced toxicity.

BACKGROUND: The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy-induced neutropenia was examined in the current study. METHODS: TBN measurements were performed in 31 female outpatients with breast carcinoma who were undergoing standard cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy (median age, 48 years; range, 26- 77 years). TBN was measured using the in vivo neutron capture analysis technique on Day 1 of Cycles 2-6. The chemotherapy toxicity index used was the absolute neutrophil count nadir (ANCN). Neutropenia was defined as an ANCN < 1.0 x 10(9)/L. The nitrogen index (NI) (TBN expressed as a percentage of age-, gender-. and height-matched healthy patients) then was compared with the corresponding ANCN values. RESULTS: Using receiver operating characteristics analysis, a "cut-off" value of NI = 0.89 was found. In this group of patients, when the NI was < 0.89, 11 of 13 courses in 7 patients (85%) led to an ANCN of < 1.0 x 10(9)/L, and when the NI was > 0.89, 29 of 109 courses (27%) led to an ANCN of < 1.0 x 10(9)/L (P < 0.0001). CONCLUSIONS: In this small group of breast carcinoma patients, the NI was found to be the most powerful predictor of neutropenia after CMF-based chemotherapy. The authors conclude that NI may be a useful clinical tool in identifying patients at a higher risk of chemotherapy-induced toxicity when widely distributed drug combinations such as CMF are used, and warrants further study with other commonly used drugs or drug regimens.

Adenocarcinoma↗
PubMed2000

Comparing different methods of assessing body composition in end-stage renal failure.

BACKGROUND: Accurate measurement of nutritional status in patients with end-stage renal disease is important because of its clear association with prognosis. Total body water (TBW) has additionally been recently recognized as an independent prognostic value because of its relationship with hypertension and cardiac morbidity. The current study was designed to assess the utility of surrogate markers of nutritional state and TBW in patients with end-stage renal disease. METHODS: Fifty-four patients with renal disease were studied. TBW obtained using the deuterium dilution technique was compared with estimates derived from anthropometric measures of TBW, including 58% body weight, Watson equations, and bioelectrical impedance analysis (BIA). Anthropometrically derived fat-free mass (FFM) was compared with BIA-derived estimates. Total body nitrogen (TBN) measurements were correlated with TBW estimates and BIA-derived resistance. RESULTS: TBW was significantly underestimated by the Watson equation (mean difference, -1.751 L, P = 0.01) and the 58% body weight approximation significantly overestimated it (mean difference, 1.792 L, P = 0.04). The Kushner BIA estimation of TBW did not significantly differ from that of the gold standard determined from D2O dilution (mean difference, -1.221 L, P = 0.12) and was also the method that showed the best agreement with the D2O estimate. However, the limits of agreement were large. Accurate prediction equations for FFM (FFM = -21.768 + 0.001 x ht2 + 6630.669 x 1/R + 0.312 x wt, R2 = 0.95) and TBN (TBN = -668.324 - 3.963 x age + 10.133 x wt + 0. 045 x ht2 + 32141.457 x 1/R, R2 = 0.91) were derived from BIA obtained resistance. CONCLUSIONS: The estimation of TBW varies significantly depending on the method of calculation. BIA is the most accurate surrogate marker for the measurement of both TBW and other parameters of body composition.

Adipose Tissue↗
PubMed2000

Study of moderator thickness for an accelerator-based neutron irradiation facility for boron neutron capture therapy using the 7Li(p,n) reaction near threshold.

Accelerator neutron sources for epithermal neutron capture therapy utilizing the 7Li(p,n) nuclear reaction will require a moderator even in the threshold range of 1.89 to 1.95 MeV. The corresponding neutron energies allow for a thinner reflector and moderator, with less reduction of the epithermal flux. To estimate the useful neutron flux within the epithermal range (4 eV-40 keV), the optimal thickness of a heavy water moderator was determined using the two-dimensional neutron transport S(N) code DORT. Optimized results are compared with the epithermal fluxes reported for the higher proton energy range, and are found to be inferior. Thus, this study supports the 2.5-3.0 MeV proton energy range for accelerator boron neutron capture therapy.

Boron Neutron Capture Therapy↗
PubMed2000

Total body protein in chronic diseases and in aging.

Substantial losses of total body protein (TBP) can occur in chronic diseases and in aging. Such losses impact negatively on immunity and quality of life, and on growth rates in children. Direct measurements of total body nitrogen (TBN) monitor the integrated changes in TBP over time and allow comparison with normal subjects. TBN assessment via neutron capture analysis is therefore the gold-standard method of TBP estimation, so that risk factors for protein deficit can be identified and patient management optimized. The nitrogen index (NI) can be used to predict prognostic outcome: an NI < 0.9 is associated with substantial wasting in HIV disease, an NI < 0.8 predicts significant pathophysiology in chronic renal failure, and a low NI is predictive of neutropenia in breast-cancer patients. These findings emphasize the central importance of adequate protein stores in recovery from disease or in maintaining quality of life. Aging appears to involve a gradual loss of TBP throughout adulthood. Cross-sectional data suggest that TBP declines curvilinearly with age, such that there is an accelerated decline after 65 years of age. However, longitudinal data are scarce, and little is known about the relative loss of visceral protein, as opposed to skeletal muscle protein. More clearly-defined data are essential if the effects of aging per se are to be separated from the effects of chronic disease. A further complication is the knowledge that physical activity also declines with age. Thus sarcopenia, the loss of skeletal muscle mass, could primarily result from disuse rather than aging. The economic impact of unsuccessful aging places a pressing need for multicompartment data in longitudinal study designs.

Adult↗
PubMed2000

Improved spatial resolution by MOSFET dosimetry of an x-ray microbeam.

Measurement of the lateral profile of the dose distribution across a narrow x-ray microbeam requires a dosimeter with a micron resolution. We investigated the use of a MOSFET dosimeter in an "edge-on" orientation with the gate insulating oxide layer parallel to the direction of the beam. We compared results using this technique to Gafchromic film measurements of a 200 micrometer wide planar x-ray microbeam. The microbeam was obtained by using a vernier micrometer-driven miniature collimator attached to a Therapax DXT300 x-ray machine operated at 100 kVp. The "edge-on" application allows utilization of the ultra thin sensitive volume of the MOSFET detector. Spatial resolution of both the MOSFET and Gafchromic film dosimeters appeared to be of about 1 micrometer. The MOSFET dosimeter appeared to provide more uniform dose profiles with the advantage of on-line measurements.

Biophysical Phenomena↗
PubMed2000

Radioimmunoconjugates for targeted alpha therapy of malignant melanoma.

Effective targeted cancer therapy requires high selectivity and cytotoxicity. To this end we have prepared and tested a new alpha-emitting radioimmunoconjugate (RIC) against malignant melanoma. The melanoma antibody 9.2.27 is specific for most melanoma cell lines. This antibody was labelled with an a emitter, bismuth-213 (213Bi), and a positron emitter, terbium-152 (152Tb), which is an analogue of the alpha-emitting radioisotope terbium-149. The chelators cDTPAa (a cyclic anhydride of diethylenetriamine pentacetic acid) and CHX-A" (a 2-(p-SCN-Bz)-cyclohexyl-DTPA ligand) were used in order to obtain high labelling yields for both isotopes with either chelator. The labelling efficiency with 213Bi was found to be 96% and 92% with cDTPAa and CHX-A", respectively. With 152Tb it was 93% and 89%, respectively. Serum stability studies showed 20% leaching with 213Bi over a period of 2.5 half-lives. For 152Tb the leaching was 13%. There was no difference in the melanoma cell binding of the labelled and unlabelled antibodies. DNA synthesis data were compared for both isotopes with either chelator. Based on these results, the therapeutic activity ratio for 213Bi a particles and 152Tb positrons for the same endpoint was calculated to be 120. The stability of the bismuth and terbium RICs, together with the outstanding cytotoxicity of the alpha emitter, provides the basis for a new approach to the potential control of micrometastatic melanoma.

Antibodies, Monoclonal↗
PubMed2000

Monte Carlo calculation for microplanar beam radiography.

In radiography the scattered radiation from the off-target region decreases the contrast of the target image. We propose that a bundle of collimated, closely spaced, microplanar beams can reduce the scattered radiation and eliminate the effect of secondary electron dose, thus increasing the image dose contrast in the detector. The lateral and depth dose distributions of 20-200 keV microplanar beams are investigated using the EGS4 Monte Carlo code to calculate the depth doses and dose profiles in a 6 cm x 6 cm x 6 cm tissue phantom. The maximum dose on the primary beam axis (peak) and the minimum inter-beam scattered dose (valley) are compared at different photon energies and the optimum energy range for microbeam radiography is found. Results show that a bundle of closely spaced microplanar beams can give superior contrast imaging to a single macrobeam of the same overall area.

Humans↗
PubMed1999

Transmission of chronic nociception by spinal neurons expressing the substance P receptor.

Substance P receptor (SPR)-expressing spinal neurons were ablated with the selective cytotoxin substance P-saporin. Loss of these neurons resulted in a reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states. This loss appeared to be permanent. Responses to mildly painful stimuli and morphine analgesia were unaffected by this treatment. These results identify a target for treating persistent pain and suggest that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain.

Animals↗
PubMed1999

Changes in body composition during breast cancer chemotherapy with the CMF-regimen.

Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1-3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4]. The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF-based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out-patients (median age 47, range 26-70 years) receiving adjuvant CMF-based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2-6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal. There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p < 0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p = 0.003) and mean fat mass of 1.49 kg (p = 0.008). We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.

Adult↗
PubMed1999

Targeted alpha therapy: evidence for potential efficacy of alpha-immunoconjugates in the management of micrometastatic cancer.

There can be little doubt that one of the most important problems in the management of cancer is control of metastatic disease. This objective must be achieved ideally with a systemic therapeutic modality that targets cancer cells and gives minimal collateral damage to critical normal cells. The efficacy of targeted cancer therapy relies on the ability of a toxin to be located in the target cancer cell. The ideal toxin is one that is active only in the cancer cell, and not in critical normal cells. Failing this, the next best approach is a toxin with a short effective lifetime to target early stage micrometastatic disease. This rules out chemical toxins, given that they remain effective until excreted from the body, and localization of dose to the cancer cell rules out beta-emitting radio-isotopes (RI). Alpha-emitting RI, however, are much more appropriate toxins because they are short-lived and because their cytotoxicity is the result of their high rate of energy loss and short range of the alpha particles. These radionuclides have properties that are particularly suited for the elimination of single cells in transit or small nests of cancer cells. In vitro and in vivo experiments with alpha RI show dramatic superiority over beta RI. Only a few nuclear hits are needed to kill cells, and the formation of metastatic lung lesions and subcutaneous lesions in mice can be inhibited by systemic administration of alpha emitters. But alpha RI have not been able to control solid tumours, for which beta RI are better suited. A small number of alpha-emitting radionuclides are currently under investigation. These are terbium (Tb)-149, astatine (At)-211, bismuth (Bi)-212 and Bi-213. Terbium-149 and At-211 both require accelerators in close proximity to the place of application. The Bi isotopes are produced by long-lived parents and, as such, can be obtained from generators. The first phase-1 dose escalation trial with Bi-213 radioimmunoconjugate (RIC) commenced in New York in 1997, and other trials are planned with At-211 RIC and At-211 methylene blue for melanoma. Actinium (Ac)-225 is obtained from the decay of thorium (Th)-229, which is a waste product in the enrichment of fissile Th-233. Alternative accelerator production routes are being investigated, beginning with the European Centre for Nuclear Research (CERN) GeV proton spallation source. The ready and low-cost availability of the Ac:Bi generator is an important element in the implementation of clinical trials for patients with poor prognoses but without evidence of metastatic disease.

Alpha Particles↗
PubMed1999

Determination of skeletal muscle and fat-free mass by nuclear and dual-energy x-ray absorptiometry methods in men and women aged 51-84 y (1-3).

BACKGROUND: Skeletal muscle mass (SMM) and fat-free mass (FFM) are important variables in nutritional studies. Accurate techniques for measuring these variables have not been thoroughly validated in elderly subjects. OBJECTIVES: The objectives of this study were to 1) compare SMM values derived from dual-energy X-ray absorptiometry (DXA) with those calculated by a nuclear method from total body potassium (TBK) and total body nitrogen (TBN) measurement (both: KN) in older subjects, and 2) assess the accuracy of FFM measurement by DXA in these subjects. DESIGN: TBK, TBN, DXA (model XR36; Norland, Fort Atkinson, WI), bioimpedance, and anthropometric measurements were performed on healthy women (n = 50) and men (n = 25) aged 51-84 y. RESULTS: Mean SMM by KN was not significantly different from SMM by DXA in either sex. SMM by KN predicted SMM by DXA with an SEE of 2.1 kg (r = 0.95, P < 0.0001 for women and men together). In the men, FFM by DXA agreed well with FFM estimated by TBK, skinfold thicknesses, bioimpedance analysis, and a multicompartment model. In women, FFM by DXA was 4-5 kg less than that by the other methods (P < 0.01). Truncal fat was related to intermethod FFM differences (r = 0.58, P < 0.0001). CONCLUSIONS: These data indicate that 1) either the nuclear or the DXA method can be applied to estimate SMM in healthy older subjects, and 2) the Norland DXA instrument significantly underestimates FFM in older women, in part, because of the influence of truncal adiposity.

Absorptiometry, Photon↗
PubMed1999

Fission converter and metal-oxide-semiconductor field effect transistor study of thermal neutron flux distribution in an epithermal neutron therapy beam.

The depth distribution of the thermal neutron flux is a major factor in boron neutron capture therapy (BNCT) in determining the efficiency of cell sterilization. In this paper the fission detector method is developed and applied to measure the in-phantom thermal neutron flux depth distribution. Advantages of the fission detector include small size, direct measurement of thermal neutron flux in a mixed radiation field of BNCT beam, self-calibration, and the possibility of on-line measurement. The measurements were performed at epithermal a BNCT facility. The experimental results were compared with the thermal neutron flux calculated by the Monte Carlo method and found to be in good agreement.

Biophysical Phenomena↗
PubMed1999

Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury.

Upon noxious stimulation, substance P (SP) is released from primary afferent fibers into the spinal cord where it interacts with the SP receptor (SPR). The SPR is located throughout the dorsal horn and undergoes endocytosis after agonist binding, which provides a spatial image of SPR-containing neurons that undergo agonist interaction. Under normal conditions, SPR internalization occurs only in SPR+ cell bodies and dendrites in the superficial dorsal horn after noxious stimulation. After nerve transection and inflammation, SPR immunoreactivity increases, and both noxious as well as nonnoxious stimulation produces SPR internalization in the superficial and deep dorsal horn. We investigated the primary afferent fibers that contribute to enhanced SPR internalization in the spinal cord after nerve transection and inflammation. Internalization evoked by electrical stimulation of the sciatic nerve was examined in untreated animals, at 14 days after sciatic nerve transection or sham surgery and at 3 days after hindpaw inflammation. Electrical stimulation was delivered at intensities to excite Abeta fibers only, Abeta and Adelta fibers or A and C fibers as determined by the compound action potential recorded from the tibial nerve. Electrical stimuli were delivered at a constant rate of 10 Hz for a duration of 5 min. Transection of the sciatic nerve and inflammation produced a 33.7 and 32.5% increase in SPR and immunoreactivity in lamina I, respectively. Under normal conditions, stimulation of Adelta or C fibers evoked internalization that was confined to the superficial dorsal horn. After transection or inflammation, there was a 20-24% increase in the proportion of SPR+ lamina I neurons that exhibited internalization evoked by stimulation of Adelta fibers. The proportion of lamina I SPR+ neurons that exhibited internalization after stimulation of C-fibers was not altered by transection or inflammation because this was nearly maximal under normal conditions. Moreover, electrical stimulation sufficient to excite C fibers evoked SPR internalization in 22% of SPR+ lamina III neurons after nerve transection and in 32-36% of SPR+ neurons in lamina III and IV after inflammation. Stimulation of Abeta fibers alone never evoked internalization in the superficial or deep dorsal horn. These results indicate that activation of small-caliber afferent fibers contributes to the enhanced SPR internalization in the spinal cord after nerve transection and inflammation and suggest that recruitment of neurons that possess the SPR contributes to hyperalgesia.

Afferent Pathways↗
PubMed1999

Contrast enhancement in microplanar beam radiography.

In x-ray radiography, the target produces a useful shadow from absorption of the primary beam, while the scattered radiation into the off-target region decreases the contrast of the target image. A bundle of closely spaced microplanar beams can reduce the scattered radiation and give superior image contrast compared with a single macrobeam of the same dimensions. To further reduce the scattered radiation and increase the image contrast, we place an air gap between the tissue phantom and the detector. The primary and scattered photon flux of a single microplanar beam is measured as a function of thickness inside the phantom and in the air gap. Results show that a bundle of closely spaced, microplanar beams increase the image contrast by 22% and a 2 cm air gap decreases the scattered photon flux by about half, improving the contrast by an additional 16%. Thus an overall improvement of 41% in contrast can be achieved with microplanar beam radiography.

Cadmium Radioisotopes↗
PubMed1998

Theoretical treatment of human haemopoietic stem cell survival following irradiation by alpha particles.

PURPOSE: To calculate survival of human haemopoietic stem cells irradiated by alpha particles from 149Tb (initial energy 3.97 MeV) and 211At (average initial energy 6.87 MeV). METHODS: Following as closely as possible radiobiological data, Monte Carlo methods were used to calculate passages of alpha particles (originating in three geometries) through the nuclei of haemopoietic stem cells. Survival of stem cell populations was calculated from the probability of surviving each passage (a function of LET). RESULTS: For decays targeted to the surface of individual cells 37% survival was found at 1.3 passages per nucleus for 149Tb and 6.5 for 211At/Po decays. For decays distributed in a large volume the D0 doses were 0.81 and 0.87 for 149Tb and 211At respectively. When 36% of the marrow is occupied by fat cells alphas from 149Tb are more effective with a D0 of 0.68Gy compared to 0.82Gy for the 211At/Po combination. CONCLUSIONS: When the isotopes are targeted to the cell, in terms of passages, 149Tb is five times more effective at cell killing than 211At, which when expressed in terms of dose, increases to a factor of 9. When the isotopes are broadly distributed (such as in marrow or in vitro) the differences are considerably reduced.

Alpha Particles↗
PubMed1998

Calculation of microplanar beam dose profiles in a tissue/lung/tissue phantom.

Recent advances in synchrotron generated x-ray beams with a high fluence rate permit investigation of the application of an array of closely spaced, parallel or converging microplanar beams in radiotherapy. The proposed technique takes advantage of the hypothesized repair mechanism of capillary cells between alternate microbeam zones, which regenerates the lethally irradiated endothelial cells. The lateral and depth doses of 100 keV microplanar beams are investigated for different beam dimensions and spacings in a tissue, lung and tissue/lung/tissue phantom. The EGS4 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams (up to 20 x 20 cm square cross section). The maximum dose on the beam axis (peak) and the minimum interbeam dose (valley) are compared at different depths, bundles, heights, widths and beam spacings.

Animals↗