Sri Lanka: an amphibian hot spot.
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Animals↗
Biomedical subjects
C J Schneider
Publications and source records attributed to C J Schneider.
Acoustic divergence in two cryptic Hipposideros species: a role for social selection?
We present evidence that a relatively widespread and common bat from South East Asia comprises two morphologically cryptic but acoustically divergent species. A population of the bicoloured leaf-nosed bat (Hipposideros bicolor) from Peninsular Malaysia exhibits a bimodal distribution of echolocation call frequencies, with peaks in the frequency of maximum energy at ca. 131 and 142 kHz. The two phonic types are genetically distinct, with a cytochrome b sequence divergence of just under 7%. We consider the mechanisms by which acoustic divergence in these species might arise. Differences in call frequency are not likely to effect resource partitioning by detectable prey size or functional range. However, ecological segregation may be achieved by differences in microhabitat use; the 131kHz H. bicolor is characterized by significantly longer forearms, lower wing loading, a lower aspect ratio and a more rounded wingtip, features that are associated with greater manoeuvrability in flight that may enable it to forage in more cluttered environments relative to the 142 kHz phonic type. We suggest that acoustic divergence in these species is a consequence of social selection for a clear communication channel, which is mediated by the close link between the acoustic signal and receptor systems imposed by the highly specialized nature of the hipposiderid and rhinolophid echolocation system.
Animals↗
Office hours pulsed brachytherapy boost in breast cancer.
BACKGROUND AND PURPOSE: Radiobiological studies suggest equivalent biological effects between continuous low dose rate brachytherapy (CLDR) and pulsed brachytherapy (PB) when pulses are applied without interruption every hour. However, radiation protection and institute-specific demands requested the design of a practical PB protocol substituting the CLDR boost in breast cancer patients. An office hours scheme was designed, considering the CLDR dose rate, the overall treatment time, pulse frequency and tissue repair characteristics. Radiobiological details are presented as well as the logistics and technical feasibility of the scheme after treatment of the first 100 patients. MATERIALS AND METHODS: Biologically effective doses (BEDs) were calculated according to the linear quadratic model for incomplete repair. Radiobiological parameters included an alpha/beta value of 3 Gy for normal tissue late effects and 10 Gy for early normal tissue or tumour effects. Tissue repair half-time ranged from 0.1 to 6 h. The reference CLDR dose rate of 0.80 Gy/h was obtained retrospectively from analysis of patients' data. The treatment procedure was evaluated with regard to variations in implant characteristics after treatment of 100 patients. RESULTS: A PB protocol was designed consisting of two treatment blocks separated by a night break. Dose delivery in PB was 20 Gy in two 10 Gy blocks and, for application of the 15 Gy boost, one 10 Gy block plus one 5 Gy block. The dose per pulse was 1.67 Gy, applied with a period time of approximately 1.5 h. An inter-patient variation of 30% (1 SD) was observed in the instantaneous source strength. Taking also the spread in implant size into account, the net variation in pulse duration amounted to 38%. CONCLUSION: An office hours PB boost regimen was designed for substitution of the CLDR boost in breast-conserving therapy on the basis of the BED. First treatment experience shows the office hour regimen to be convenient to the patients and no technical perturbations were encountered.
Brachytherapy↗
Refugial isolation versus ecological gradients. Testing alternative mechanisms of evolutionary divergence in four rainforest vertebrates.
Hypotheses for divergence and speciation in rainforests generally fall into two categories: those emphasizing the role of geographic isolation and those emphasizing the role of divergent selection along gradients. While a majority of studies have attempted to infer mechanisms based on the pattern of species richness and congruence of geographic boundaries, relatively few have tried to simultaneously test alternative hypotheses for diversification. Here we discuss four examples, taken from our work on diversification of tropical rainforest vertebrates, in which we examine patterns of genetic and morphological variation within and between biogeographic regions to address two alternative hypotheses. By estimating morphological divergence between geographically contiguous and isolated populations under similar and different ecological conditions, we attempt to evaluate the relative roles of geographic isolation and natural selection in population divergence. Results suggest that natural selection, even in the presence of appreciable gene flow, can result in morphological divergence that is greater than that found between populations isolated for millions of years and, in some cases, even greater than that found between congeneric, but distinct, species. The relatively small phenotypic divergence that occurs among long-term geographic isolates in similar habitats suggests that morphological divergence via drift may be negligible and/or that selection is acting to produce similar phenotypes in populations occupying similar habitats. Our results demonstrate that significant phenotypic divergence: (1) is not necessarily coupled with divergence in neutral molecular markers; and (2) can occur without geographic isolation in the presence of gene flow.
Adaptation, Biological↗
Radiosensitizing effect of carbogen breathing during pulsed irradiation of the rat R1H tumor.
The objective of the present study was to investigate the radiosensitizing effect of carbogen breathing during pulsed x-ray irradiation in an experimental tumor model. Rat R1H rhabdomyosarcoma tumors were irradiated with 36 Gy total dose in 1 Gy high dose rate pulses, either hourly repeated, or in an 'office hours' protocol with irradiation-free overnight intervals. With the hourly, pulsed irradiation scheme, tumor growth delay (TGD) was significantly increased from 24.4+/-0.7 days in air-breathing animals to 29.0+/-0.9 days in animals breathing carbogen during irradiation. With irradiation during office hours, the TGD was shortened, and carbogen was less effective. The data show that carbogen acts as a radiosensitizer when applied during pulsed irradiation. Translation of the experimental data to clinical practice indicates that hyperoxygenation of the tumor during pulsed dose rate (PDR) or high dose rate (HDR) brachytherapy might enhance the tumor response of patients.
Administration, Inhalation↗
Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma.
BACKGROUND: The feasibility and efficacy of high dose conformal radiotherapy were examined in the treatment of patients with locally advanced, unresectable pancreatic carcinoma. METHODS: Forty-four patients with pathologically confirmed, unresectable pancreatic adenocarcinoma without distant metastases were treated in a Phase II study. The patients received three-dimensional, planned, high dose conformal radiotherapy (70-72 grays). Toxicity was scored according to the World Health Organization criteria. Follow-up time ranged from 7 months to 25 months (median, 9 months). RESULTS: The treatment was feasible. Forty-one patients received the intended total dose. Treatment was never stopped because of toxicity. Acute toxicity was mainly Grade 1 and Grade 2 (in 70% and 57% of patients, respectively), whereas Grade 3 toxicity was seen in 9% of patients. One fatal event occurred that was not treatment related. Late Grade 3 and Grade 4 gastrointestinal toxicity was seen in 3 patients and 2 patients, respectively. Late (Grade 5) gastrointestinal bleeding was observed in 3 patients, 2 of whom had local tumor progression. At 3 months, reduction in tumor size was seen in 27% of patients, stable disease was seen in 20% of patients, and local disease progression was seen in 40% of patients. Ultimately, local disease progression was observed in 44% of patients. No true partial or complete responses were documented. The median survival from the time of diagnosis was 11 months (10 months from the start of radiotherapy). Seventeen of 25 patients (68%) experienced pain relief. CONCLUSIONS: High dose conformal radiotherapy for the treatment of patients with locally advanced pancreatic carcinoma is feasible with acceptable toxicity. In case of pain, it can offer palliation. The efficacy of the treatment in terms of prolongation of life is not proven. Distant metastases remain the major problem.
Adenocarcinoma↗
Natural selection and speciation.
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Adaptation, Physiological↗
A test of alternative models of diversification in tropical rainforests: ecological gradients vs. rainforest refugia.
Comparison of mitochondrial and morphological divergence in eight populations of a widespread leaf-litter skink is used to determine the relative importance of geographic isolation and natural selection in generating phenotypic diversity in the Wet Tropics Rainforest region of Australia. The populations occur in two geographically isolated regions, and within each region, in two different habitats (closed rainforest and tall open forest) that span a well characterized ecological gradient. Morphological differences among ancient geographic isolates (separated for several million years, judging by their mitochondrial DNA sequence divergence) were slight, but morphological and life history differences among habitats were large and occurred despite moderate to high levels of mitochondrial gene flow. A field experiment identified avian predation as one potential agent of natural selection. These results indicate that natural selection operating across ecological gradients can be more important than geographic isolation in similar habitats in generating phenotypic diversity. In addition, our results indicate that selection is sufficiently strong to overcome the homogenizing effects of gene flow, a necessary first step toward speciation in continuously distributed populations. Because ecological gradients may be a source of evolutionary novelty, and perhaps new species, their conservation warrants greater attention. This is particularly true in tropical regions, where most reserves do not include ecological gradients and transitional habitats.
Animals↗
Pulse frequency in pulsed brachytherapy based on tissue repair kinetics.
PURPOSE: Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics. METHOD: Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an alpha/beta ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h. RESULTS: The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any alpha/beta value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high alpha/beta ratio and fast or intermediate repair half-time, and the RE for tissue with low alpha/beta ratio and long repair half-time remains almost constant. CONCLUSION: Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics.
Animals↗
Enhancement of radiosensitivity of rat rhabdomyosarcoma R1H with normobaric carbogen and hyperbaric oxygen (HBO) using conventionally fractionated irradiation.
Hypoxic clonogenic cells are an important contributory factor in tumour radioresistance. The objective of the present study was to evaluate whether hyperbaric oxygen enhances tumour radiosensitivity, using a conventionally fractionated irradiation schedule, and whether the radiosensitizing potential is different from carbogen. Experiments were performed using the rhabdomyosarcoma R1H model transplanted subcutaneously in the flank of WAG/Rij rats. A total of 30 X-ray fractions of 2 Gy were given either in air, normobaric carbogen or high pressure oxygen (HPO) (240 kPa, 2.37 atm) without anaesthesia. The time taken to achieve complete remission was 38.7 +/- 3.6 days, 36.7 +/- 2.7 days and 32.4 +/- 4.1 days for air, normobaric carbogen and HBO, respectively. The differences between air and HBO (p = 0.002) and carbogen and HBO (p = 0.015) were significant. Use of carbogen and HBO produced the same local control probability at 150 days and this was significantly higher than local control under ambient conditions (p < 0.0001). It was concluded that the time to achieve complete remission of the rat rhabdomyosarcoma R1H can be shortened by HBO. Furthermore, both HBO and carbogen give higher local control probabilities than treatment under ambient conditions when used with a conventionally fractionated radiation schedule.
Animals↗
Is hyperbaric oxygen more effective than carbogen/nicotinamide in tumor radiation response?
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Animals↗
Distinguishing between primary and secondary intergradation among morphologically differentiated populations of Anolis marmoratus.
Distinguishing between primary and secondary intergradation among differentiated populations, and the relative importance of drift and selection, are persistent problems in evolutionary biology. An historical perspective on population interactions can provide insight into the nature of contacts, and thus help resolve these questions. Continuously distributed populations of Anolis marmoratus from the island of Basse Terre in the Guadeloupean archipelago of the Lesser Antilles show a striking degree of geographic variation in morphology. Initial surveys of mtDNA variation from throughout the Guadeloupean Archipelago revealed one case where levels of sequence difference and phylogenetic relationships of alleles from morphologically differentiated populations from the east coast of Basse Terre were consistent with primary intergradation. In this paper, I examine the genetic population structure of a series of populations spanning this north-south cline in morphological variation to test the hypothesis of primary intergradation. Sequences of the mitochondrial cytochrome-b gene from 50 individuals representing five populations spanning the cline were obtained and fourteen unique haplotypes (differing by 2% or less) were detected. Patterns of nucleotide substitution among haplotypes do not deviate from neutral expectation indicating no effect of selection at the level of mtDNA sequences. Estimates of population structure and gene flow were made using both summary statistics for nucleotide diversity (Nst) and cladistic methods. The results are sensitive to the choice of gene flow model, and this is discussed in detail. Mitochondrial variation in the northern populations may not be at equilibrium, and the phylogeny of alleles is consistent with a recent increase in effective population size. Estimates of nucleotide diversity, gene flow, and the phylogenetic relationships of haplotypes indicate that the southern-most population (representing the extreme of morphological variation along this cline) has been relatively isolated from populations to the north and has experienced a reduced effective population size. The apparent clinal variation between the southern population and the others may therefore reflect secondary contact and introgression rather than primary intergradation.
Animals↗
The use of a current sheet applicator array for superficial hyperthermia: incoherent versus coherent operation.
There are a number of potential advantages to be gained by using an array of applicators in hyperthermia treatments compared with single applicator systems. These advantages include the possibility of greater spatial control of power deposition and conformability to nonplanar sites. Arrays of applicators can be driven either coherently or incoherently. In the case of coherent operation, an added advantage is the ability to steer power deposition by varying the phases of the antennas. In this study, we investigated the relative merits of the two modes of operation when a 2 x 2 planar array of current sheet applicators is used. The effective field size (EFS) of the array was calculated using a Gaussian beam representation of the applicators on a layered model in which the fat layer had its thickness varied. Good agreement was obtained between the square of the electric field distribution (E2) and quantitative experimental results. It is shown that when the planar array is used with a fat layer greater than about 2 mm present, it should be driven incoherently as this results in a significantly larger EFS than that obtained when the array is driven coherently.
Humans↗
Performance evaluation of annular arrays in practice: the measurement of phase and amplitude patterns of radio-frequency deep body applicators.
An approach to a solution of two major problems in operating Annular Phased Arrays in deep body hyperthermia is presented: an E-field sensor capable of measuring phase and amplitude at 70 MHz and the concept of a power transmission factor to determine the effective amplitude of each applicator. In the four-waveguide Phased Array operating at 70 MHz, which is in clinical use at the department of Radiotherapy of the Academic Medical Center (AMC), the incident fields of the waveguides were scanned in phase and amplitude over the complete aperture midplane, inside an elliptical and a square phantom filled with saline. As a check on the application of the superposition principle, superpositions of the incident fields were compared with the electric field in the measured interference set-ups. With all four applicators radiating at equal amplitude and in phase, the maximum difference over the complete midplane of the phantom between superimposed and measured interference scans was 20% and 10 degrees in the elliptical phantom, and 20% and 30 degrees in the square phantom. After having determined nominal amplitude and phase patterns by a vector probe, any interference set-up can be superimposed from measurement of the actual incident field of each applicator. Therefore, the availability of a vector sensor as described here will contribute to solve a problem of hyperthermia quality assurance: the performance evaluation of Phased Arrays.
Humans↗
Peripheral blood progenitor cell generation and harvesting.
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Antineoplastic Agents↗
Pharmacological heterogeneity among calcium channels that subserve acetylcholine release in vertebrate forebrain.
Inhibition of calcium-evoked [3H]ACh release by different classes of calcium channel blockers was compared among calcium-naive synaptosomes from chick, frog and rat forebrain tissues. In all three species, [3H]ACh release was insensitive to nifedipine (0.03-3 microM) but was completely inhibited by cadmium (IC50 range = 0.7-1.7 microM) or cobalt (190-350 microM). In contrast, the peptide omega-conotoxin revealed marked species heterogeneity in that [3H]ACh release was potently blocked in chick and rat synaptosomes (IC50 congruent to 1 nM), whereas frog tissue was notably resistant (IC50 greater than 100 nM). Together, these data provide functional evidence for pharmacological heterogeneity among presynaptic calcium channels that subserve [3H]ACh release.
Acetylcholine↗
Risk factors for childhood sledding injuries: a case-control study.
We report the results of a case-control study designed to identify modifiable risk factors for childhood sledding injuries. Cases included all children injured while sledding (n = 17) during a five-day winter storm who presented for care to a Seattle pediatric emergency department. Two controls were chosen randomly for each case from children who presented to the same emergency department during the ensuing two months for any illness that did not require hospitalization. To qualify as controls, children had to have sledded during the same five-day period but not sustained an injury requiring medical attention. Data were collected on cases and controls using a telephone questionnaire. Analysis of risk factors revealed a significant increase in risk of injury for children who sledded in streets versus those who sledded in a park (OR = 5.1; 95% CI = 1.1-24.1), those who sledded without adult supervision (OR = 5.6; 95% CI = 1.1-26.9), and those whose parents had an annual income > or = $50,000 (OR = 5.7; 95% CI = 1.5-20.8). No difference in risk of injury was found regarding the type of sled used, the number of children, or their position on the sled or for those children with a history of prior sledding experience. We conclude that safe alternatives to sledding in the streets and an increase in adult supervision may reduce the number of childhood sledding injuries.
Adolescent↗
Characterization of divalent cation-induced [3H]acetylcholine release from EGTA-treated rat hippocampal synaptosomes.
Calcium-naive synaptosomes were used to assess the effects of divalent cations on [3H]acetylcholine release from rat hippocampal homogenates. Following equilibration with calcium-free buffer (containing 10 microM EGTA), calcium reversibly increased [3H]acetylcholine efflux (up to five-fold) while causing no measurable efflux of lactate dehydrogenase. When substituted for calcium, strontium and barium behaved similarly although barium exhibited three-fold greater efficacy. In the presence of elevated potassium, 4-aminopyridine or tetraethylammonium, the secretagogue efficacy of calcium (but not barium) was markedly increased. The release-promoting effects of both cations were inhibited by lanthanum, magnesium, cadmium, and omega-conotoxin but were insensitive to nifedipine and cobalt (both 10 microM). In addition, stimulation of muscarinic cholinergic autoreceptors substantially inhibited both calcium and barium-evoked [3H]acetylcholine release. Taken together, these results indicate that cation-evoked transmitter release from calcium-naive synaptosomes is subject to normal neuroregulatory mechanisms and therefore should be useful for investigating presynaptic modulation of neuronal exocytosis.
Acetylcholine↗