Diagnostic Yield and Therapeutic Impact of Face and Neck Imaging in Patients Referred with Otalgia without Clinically Overt Disease.

BACKGROUND AND PURPOSE: Otalgia may be secondary to serious pathology, such as upper aerodigestive tract malignancies, and CT or MR imaging of the skull base, face, and neck is often performed to detect clinically occult lesions. The diagnostic yield, management impact, and therapeutic impact of imaging in this clinical scenario, however, have yet to be elucidated. MATERIALS AND METHODS: CT and MR imaging in patients who presented with otalgia without clinically overt disease was retrospectively analyzed from a single center over a 9-year period. The cohort was subdivided into groups, depending on the presence of additional symptoms and a history of head and neck cancer. Relevant diagnostic outcome findings were categorized, and the diagnostic yield and impact of imaging on management and therapy were calculated for each group. RESULTS: In our study cohort of 235 patients, the diagnostic yield of imaging for otalgia, with or without other symptoms, in patients who lacked a history of head and neck cancer was negligible for upper aerodigestive tract malignancy (1%), abnormalities related to otalgia (2%), and other moderate or major findings (2%). Although equivocal or unimportant findings occasionally resulted in additional investigations, the therapeutic impact was also very low (2%). The diagnostic yield for upper aerodigestive tract malignancy (34%) and therapeutic impact increased (34%) when there was a history of head and neck cancer. CONCLUSIONS: The diagnostic yield and therapeutic impact of imaging for otalgia without clinically overt disease are very low, unless there is a history of head and neck cancer.

The influence of rising tropospheric carbon dioxide and ozone on plant productivity.

Human activities result in a wide array of pollutants being released to the atmosphere. A number of these pollutants have direct effects on plants, including carbon dioxide (CO2 ), which is the substrate for photosynthesis, and ozone (O3 ), a damaging oxidant. How plants respond to changes in these atmospheric air pollutants, both directly and indirectly, feeds back on atmospheric composition and climate, global net primary productivity and ecosystem service provisioning. Here we discuss the past, current and future trends in emissions of CO2 and O3 and synthesise the current atmospheric CO2 and O3 budgets, describing the important role of vegetation in determining the atmospheric burden of those pollutants. While increased atmospheric CO2 concentration over the past 150 years has been accompanied by greater CO2 assimilation and storage in terrestrial ecosystems, there is evidence that rising temperatures and increased drought stress may limit the ability of future terrestrial ecosystems to buffer against atmospheric emissions. Long-term Free Air CO2 or O3 Enrichment (FACE) experiments provide critical experimentation about the effects of future CO2 and O3 on ecosystems, and highlight the important interactive effects of temperature, nutrients and water supply in determining ecosystem responses to air pollution. Long-term experimentation in both natural and cropping systems is needed to provide critical empirical data for modelling the effects of air pollutants on plant productivity in the decades to come.

Automated approach for quantifying the repeated sit-to-stand using one body fixed sensor in young and older adults.

Much is known about the sit-to-stand (STS) and its biomechanics. Currently, however, there is little opportunity for instrumented quantification of the STS as part of screening or diagnosis in clinical practice. The objectives of the present study were to describe the feasibility of using an automated approach for quantifying the STS using one sensor location and to start testing the discriminative validity of this approach by comparing older and younger adults. 15 older subjects recruited from a residential care home and 16 young adults performed 5 repeated sit-to-stand and stand-to-sit movements. They were instrumented with a small and lightweight measurement system (DynaPort(®)) containing 1 triaxial seismic accelerometer and 3 uniaxial gyroscopes fixed in a belt around the waist. Durations of the (sub-)phases of the STS were analyzed and maximum angular velocities were determined. All successful STS cycles were automatically detected without any errors. The STS duration in the older adults was significantly longer and more variable in all phases (i.e., sit-to-stand, standing, stand-to-sit and sitting) compared to the young adults. Older adults also exhibited lower trunk flexion angular velocity. The results of this first fully automated analysis of instrumented repeated STS movements demonstrate that several STS parameters can be identified that provide a basis for a more precise, quantitative study of STS performance in clinical practice.

Validation of seat-off and seat-on in repeated sit-to-stand movements using a single-body-fixed sensor.

The identification of chair rise phases is a prerequisite for quantifying sit-to-stand movements. The aim of this study is to validate seat-off and seat-on detection using a single-body-fixed sensor against detection based on chair switches. A single sensor system with three accelerometers and three gyroscopes was fixed around the waist. Synchronized on-off switches were placed under the chair. Thirteen older adults were recruited from a residential care home and fifteen young adults were recruited among college students. Subjects were asked to complete two sets of five trials each. Six features of the trunk movement during seat-off and seat-on were calculated automatically, and a model was developed to predict the moment of seat-off and seat-on transitions. The predictions were validated with leave-one-out cross-validation. Feature extraction failed in two trials (0.7%). For the optimal combination of seat-off predictors, cross-validation yielded a mean error of 0 ms and a mean absolute error of 51 ms. For the best seat-on predictor, cross-validation yielded a mean error of -3 ms and a mean absolute error of 127 ms. The results of this study demonstrate that seat-off and seat-on in repeated sit-to-stand movements can be detected semi-automatically in young and older adults using a one-body-fixed sensor system with an accuracy of 51 and 127 ms, respectively. The use of the ambulatory instrumentation is feasible for non-technically trained personnel. This is an important step in the development of an automated method for the quantification of sit-to-stand movements in clinical practice.

The clonal structure of Quercus geminata revealed by conserved microsatellite loci.

The scrub oak communities of the southeastern USA may have existed at their present locations for thousands of years. These oaks form suckers, and excavations of root systems suggest that clones may occupy very large areas. Resolution of the clonal nature of scrub oaks is important both to manage the tracts of this ecosystem that remain, and in conducting long-term ecological studies, where the study area must substantially exceed the area occupied by any single clone. Microsatellites were used to determine the genetic diversity of a dominant oak species within a 2-ha long-term experimental site on Merritt Island at the Kennedy Space Center. This area contains a long-term study of the effects of elevated CO2 on the ecosystem. Conservation of seven microsatellite loci, previously identified in the sessile oak, Quercus petraea, was tested in two Florida scrub oak species, Q. geminata and Q. myrtifolia. Sequence analysis revealed that all seven microsatellite loci were conserved in Q. geminata and five loci were conserved in Q. myrtifolia. Six microsatellite loci were polymorphic in Q. geminata and these were subsequently used to investigate the clonal structure of the Q. geminata population. Twenty-one unique combinations of microsatellites, or haplotypes, occurred only once, whereas the remaining 26 individuals belonged to a total of seven different haplotypes. Trees with identical haplotypes were in close proximity, supporting the interpretation that they were clones. The results showed that there is significant genetic diversity within the 2-ha experimental site. Microsatellites provided a powerful and noninvasive tool for distinguishing individual genotypes and determining an adequate area for long-term ecosystem studies.

Development of chemopreventive strategies for radiation-induced cancer: targeting radiation-induced genetic alterations.

Carcinogenesis is a multistage process involving dysregulation of signal transduction and cell cycle pathways. This dysregulation results in specific molecular and genetic alterations, including gene amplification, mutations, and chromosomal rearrangements. These aberrations can be measured to provide a novel means to assess carcinogenic risk or as targets for chemointervention. Recent human and in vivo studies have demonstrated that genetic alterations, such as oncogenes and oncoproteins, were observed in preneoplastic tissues or serum following exposure to chemical carcinogens or low-level radiation (LLR). Identification of preneoplastic changes following radiation exposure may provide information that will allow development of LLR chemopreventive strategies. Radiation carcinogenesis studies in vivo with a lung tumor model showed that a low-dose cobalt-60 radiation exposure induced persistent time-dependent genetic alterations, such as elevated ras expression. This radiation exposure also resulted in lung tumor formation in 26% of the irradiated animals at 232 days after irradiation. A significant and progressive increase in ras oncogene expression was measured using Northern blot analysis in 80% of the irradiated animals over the duration of the experiment. Pharmacological intervention strategies are being tested using buthionine-[S,R]-sulfoximine (BSO). BSO has been previously shown to down-regulate ras expression. Administration of BSO prevented radiation-induced changes in ras mRNA levels in this lung tumor model. Further studies are being conducted with an LLR-induced leukemia model in which detection of circulating levels of oncoproteins will be more feasible. Based on these preliminary results and on its clinical efficacy and low clinical toxicity, BSO warrants further study as an LLR chemopreventive agent. Furthermore, this strategy to target LLR-induced preneoplastic alterations may be an effective means of developing modulators of LLR-induced cancers.

Heavy ion induced changes in small intestinal parameters.

The effects on 17 different structural parameters of mouse small intestine three days after treatment with three types of heavy ion (neon, iron and niobium) are compared, the first two being of particular relevance to space flight. The data for niobium are given in full, showing that changes after niobium ion treatment are not standard and are concentrated in the epithelial compartment, with few of the parameters having a response which is dose dependent. When comparisons are made for the three types of heavy ion, the damage is greatest after neon ion irradiation, implying that the additional non-epithelial damage produced as LET rises from X rays through neutrons to neon ions is not necessarily maintained as LET continues to rise. Further understanding is therefore needed of the balance between changes affecting the vascular and absorptive components of the organ. Variation from group to group is also important, as is variation of strain or gastrointestinal status. All such factors are important in the understanding of changes in multicellular organs after exposure to heavy ion radiation.

The influence of dose, dose-rate and particle fragmentation on cataract induction by energetic iron ions.

Because activities in space necessarily involve chronic exposure to a heterogeneous charged particle radiation field it is important to assess the influence of dose-rate and the possible modulating role of heavy particle fragmentation on biological systems. Using the well-studied cataract model, mice were exposed to plateau 600 MeV/amu 56Fe ions either as acute or fractionated exposures at total doses of 5 - 504 cGy. Additional groups of mice received 20, 360 and 504 cGy behind 50 mm of polyethylene, which simulates body shielding. The reference radiation consisted of 60Co gamma radiation. The animals were examined by slit lamp biomicroscopy over their three year life spans. In accordance with our previous observations with heavy particles, the cataractogenic potential of the 600 MeV/amu 56Fe ions was greater than for low-LET radiation and increased with decreasing dose relative to gamma-rays. Fractionation of a given dose of 56Fe ions did not reduce the cataractogenicity of the radiation compared to the acute regimen. Fragmentation of the beam in the polyethylene did not alter the cataractotoxicity of the ions, either when administered singly or in fractions.

Relative cataractogenic effects of X rays, fission-spectrum neutrons, and 56Fe particles: a comparison with mitotic effects.

The eyes of Sprague-Dawley rats were irradiated with doses of 2.5-10 Gy 250-kVp X rays, 1.25-2.25 Gy fission-spectrum neutrons (approximately 0.85 MeV), or 0.1-2.0 Gy 600-MeV/A 56Fe particles. Lens opacifications were evaluated for 51-61 weeks following X and neutron irradiations and for 87 weeks following X and 56Fe-particle irradiations. Average stage of opacification was determined relative to time after irradiation, and the time required for 50% of the irradiated lenses to achieve various stages (T50) was determined as a function of radiation dose. Data from two experiments were combined in dose-effect curves as T50 experimental values taken as percentages of the respective T50 control values (T50-% control). Simple exponential curves best describe dose responsiveness for both high-LET radiations. For X rays, a shallow dose-effect relationship (shoulder) up to 4.5 Gy was followed at higher doses by a steeper exponential dose-effect relationship. As a consequence, RBE values for the high-LET radiations are dose dependent. Dose-effect curves for cataracts were compared to those for mitotic abnormalities observed when quiescent lens epithelial cells were stimulated mechanically to proliferate at various intervals after irradiation. Neutrons were about 1.6-1.8 times more effective than 56Fe particles for inducing both cataracts and mitotic abnormalities. For stage 1 and 2 cataracts, the X-ray Dq was 10-fold greater and the D0 was similar to those for mitotic abnormalities initially expressed after irradiation.

Collared crypts in irradiated small intestine.

Crypts of Lieberkuhn are radiosensitive: the technique of crypt counting is an established method of assessing radiation induced changes in the small intestine. However, there has been little work done on the surface contours of the crypts, as they open into the intervillous cleft. The current paper describes the structure of control mouse crypt mouths as unobtrusive openings approximately 5 microns in diameter. After radiation with heavy ion particles, the crypt mouths are substantially larger (up to 10 microns in diameter) with a marked collar which is similar to that sometimes seen in coeliac disease. The shape and incidence of the collared crypts is described for specimens irradiated with neon, silicon and iron ions, with treatment with iron producing the most marked collars: it is suggested that the size and incidence of the collared crypts may be related to the LET of the beam used. It is of interest that the abnormal crypts are not produced after single doses of X-irradiation. The consideration of the structure of the collared crypts may require a redefinition of the terms crypt and villus with priority being given to the position of subepithelial vessels rather than surface shape. Finally, although the collared crypts can not be directly equated with 'tunnel' or 'channel' lesions, it is pointed out that they do represent localised damage with a specific position and shape.

Comparison of recovery from potential mitotic abnormality in mitotically quiescent lens cells after X, neutron, and 56Fe irradiations.

After exposure to various doses of 250 kVp X radiation, 0.85 Me V fission spectrum neutrons, or 600 MeV/A iron (Fe) particles, mitotically quiescent rat lens cells showed no visible evidence of radiation injury. However, following the mitogenic stimulus of wounding, mitotic abnormalities became evident when responding cells entered mitosis. Latent damage and recovery therefrom were monitored at 3, 7, 14, and 28 days after irradiation. Following doses of 1 to 10 Gy of X radiation, the recovery rate, indicated by a decrease in abnormalities with time, was proportional to dose, and the dose-effect slope decreased exponentially with time. Virtually no recovery occurred during the 28 days after 1.25 to 2.25 Gy of fission neutron radiation. After doses of 0.5 to 3.0 Gy of Fe particles, an increased expression of mitotic damage or recovery than recovery occurred. As a consequence of the differing patterns in time for expression of damage or recovery following X rays and the high-LET radiations, the relative biological effectiveness (RBE) increased from 3.6 to 16 for neutrons and from 2 to 10 for Fe particles over the 28-day observation period.

Tissue responses to low protracted doses of high LET radiations or photons: early and late damage relevant to radio-protective countermeasures.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for gamma-radiation. When total doses of 96 or 247 cGy of neutrons or gamma rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and gamma-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or gamma rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for gamma rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

Comparison of intestine and bone marrow radiosensitivity of the BALB/c and the C57BL/6 mouse strains and their B6CF1 offspring.

The radiosensitivity as measured by LD50/6 or LD50/30 of the F1 hybrid B6CF1 (C57BL/6 X BALB/c) is similar to that of C57BL/6 mice but markedly different from BALB/c. The LD50/6 for BALB/c mice was about 8.8 Gy compared to 16.4 Gy for the B6CF1. The difference in LD50/6 between the parent strains or between BALB/c and the F1 hybrid could not be explained by any differences in crypt cell number, cell cycle time, or transit time. Likewise, the observed differences in the LD50/6 do not appear to result from marked differences in the radiosensitivity of marrow stem cells (CFU-S) since the D0's for the three genotypes of mice were similar. Also, there were no apparent differences in the red blood cell contents of several enzymes associated with antioxidant defenses. The microcolony assay was used to determine the D0 for the crypt clonogenic cells and the D0 values for 60Co gamma rays were about 0.8 Gy for BALB/c mice and 1.4 Gy for B6CF1 mice. However, the D0 values for JANUS fission neutrons were similar; 0.6 Gy for the BALB/c mice and 0.5 for the B6CF1 mice. A comparison of clonogenic cell kinetics, using prolonged colcemid block to distinguish between slowly and rapidly cycling cells suggest that, normally, the stem cells are slowly cycling in both the BALB/c and the B6CF1 hybrid. However, the stem cells of the B6CF1 appear to go into rapid cell cycle more rapidly than those of the BALB/c following irradiation or prolonged colcemid treatment. The more rapid recovery in intestinal epihelial cell production in the B6CF1 hybrid after irradiation may provide an increased mucosal barrier and may, in part, explain the difference in the response to radiation compared to that in the BALB/c.

Morphological criteria for comparing effects of X-rays and neon ions on mouse small intestine.

Several techniques have been used to assess changes in different parts of mouse small intestine three days after a single dose of either 16.5 Gy X-rays or 11 Gy neon beam. The doses were chosen to be approximately equivalent in terms of their effect on the number of microcolonies present. In qualitative terms, villous damage was seen after both types of radiation exposure: collared crypts, similar to those seen in biopsies taken from patients suffering from coeliac disease, were conspicuous after neon irradiation. In semi quantitative terms the doses used, although estimated from previous work to give biologically equivalent damage, produced a greater drop in microcolony numbers after X-irradiation. This makes all the more important the fact that significantly greater changes were seen after neon irradiation-a greater drop was seen in the number of villous profiles and the number of goblet cells per villus. There was also greater breakdown in the integrity of the villous basement membrane. Different responses after the two types of irradiation are therefore seen in the cryptal and villous compartment. Progress is being made towards identifying and quantitating radiation induced changes in different populations of cells or tissues in the small intestine.

A histological study on the cataractogenic effects of heavy charged particles.

The morphology of the mouse lens was studied by light and electron microscopy between 4 and 30 months after graded single doses of photons or charged particle exposure. Four-month-old mice were given upper body or head only doses of 220 kVp x-rays or to 40Ar (570 MeV/amu), 40Ar(500 MeV/amu), 20Ne(470 MeV/amu) and 12C (400 MeV/amu) particles. The lenses examined in this pilot study were largely from mice dedicated to other designed experiments; nor all radiation conditions are represented at each sample time. At 4 months after 0.05, 0.3 or 0.9 Gy 20Ne radiation, the micronuclei appeared in the epithelial cells at the bow region. The anterior fibers showed swollen cytoplasm containing amphorous materials after 0.3 or 0.9 Gy 20Ne exposure. The posterior fibers were relatively normal. The results at 15 months after irradiation indicated heavy charged particles were more effective than x-rays for inducing morphological changes; however there were no qualitative differences in damage produced by heavy charged particles and x-rays. Characteristic changes after irradiation included abnormal bow patterns, posterior and anterior migration of nucleated cells in the cortex, swelling of fibers and the development of swirls of epithelium at the anterior pole. The results also indicated that the degree of degenerative changes in lens fibers increases with increasing radiation dose and sampling time. The radiation-induced injury to lens fibers also showed a relationship to linear energy transfer (LET). The qualitative observations at 24 months indicated that low energy 40Ar (600 KeV/micron) is less effective than high energy 40Ar particles (100 KeV/micron)1 and radiation-induced injury in the lens fibers shows an LET-dependence when the ionizing density is less than 100 KeV/micron. At 30 months after heavy charged particle irradiation, the changes in control lens were the swollen fibers, while in the 40Ar-irradiated animals, aberrant fibers with abnormal nuclei, amorphous materials and debris were observed.

Radioprotection of mouse colony forming units-spleen against heavy-charged particle damage by WR 2721.

The effectiveness of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR 2721) to protect against the heavy-charged particle beams with dose-averaged LET infinity's ranging from 26 to 260 keV/micron was studied using the marrow colony forming units-spleen as a model system. WR 2721 (400 mg/kg) was injected ip 30 min before whole-body irradiation in the plateau ionization region of the Bragg curve. Significant protection was observed at 26, 51, and 135 keV/micron LET values where the data were collected with 20Ne, 28Si, and 40Ar ions, respectively. The largest component of protection was the slope change, where at LET values of 26 and 51 keV/micron the DMFs (slope) were 2.1 and 2.3, respectively, which are very close to the gamma-ray value of 2.4 (gamma LET approximately equal to 0.2 keV/micron). Protection, however, decreased with increase in LET from 51 to 135 keV/micron to the DMF value of 1.2 and no significant protection was observed against 56Fe ions at 260 keV/micron. Significant increases in extrapolation number occurred with gamma rays and neon particles. The results are discussed in terms of charged particle track structure, radiation chemistry, and potential clinical applications.