Count Loss Research Articles

Consequences of and potential reasons for inadequate dead time measurements in isotope ratio mass spectrometry

Precise and accurate determination of the dead time of a pulse counting system is critical for correct isotope ratio determinations. In this paper, potential problems in the determination of dead time are investigated as well as the consequences of using an erroneous value when correcting for dead time. It is shown how the voltage setting of a SEM can affect the dead time of the system. This can be due to an increased pulse height distribution giving after-pulsing effects, which are not corrected for by a detector dead time model. This hypothesis is supported by pulse height measurements of the output signal of the SEM. Output signals of the amplifier and SEM of an Element2 are also studied and the different nature of these signals (extending vs non-extending) and the consequences of this in the correction of dead time count losses are discussed. It is also found that the dead time values determined via isotope ratio measurements can differ with up to 2.7 ns under optimised instrumental settings, and it is also shown that a relatively small difference (2 ns) in the actual dead time of the system and the value used to correct for dead time results in apparent non-linearity of the system which has been reported by other authors.

Generation of Leptin Receptor Bone Marrow Chimeras: Recovery From Irradiation, Immune Cellularity, Cytokine Expression, and Metabolic Parameters

Leptin regulates appetite and metabolism but also immunity and inflammation. Although functional leptin receptors (LepR) are expressed on hematopoietic cells, the role of these receptors in regulating immune function in vivo remains controversial. To clarify this issue, we performed bone marrow (BM) transplantation between obese db/db mice, lacking LepR, and wild-type (WT) mice. Results indicate that expression of LepR on BM-derived cells directly, though partially, regulates spleen and thymus cellularity, although the environment of db mice contributes to maintaining reduced cellularity of these organs. Selective expression of LepR on BM-derived cells also modulates leptin and adiponectin levels, with induction of a more favorable adipokine environment in the WT→db/db group. However, LepR signaling in BM-derived cells is not involved in regulation of body weight (BW) and composition, glycemia, hepatosteatosis or adipose tissue inflammation, although it modulates expression of interleukin (IL)-1β in the brain. Finally, data indicate that db mice have an increased susceptibility to irradiation compared to WT mice in terms of BW loss and recovery of leukocyte counts in peripheral blood. Therefore, interpretation of results obtained using BM chimeras between WT and db mice should take into account the difference in radiation sensitivity between the two types of animals.

Effect of bevel position on the corneal endothelium after phacoemulsification

To compare the extent of corneal endothelial (CE) cell loss changes in two groups of eyes submitted to phacoemulsification, with the conventional bevel-up tip position in one eye and with the bevel-down tip position in the fellow eye. This prospective clinical trial comprised 25 patients with bilateral cataracts subjected to lens removal by phacoemulsification with the conventional bevel-up tip position (GI) in one eye and with the bevel-down tip position (GII) in the fellow eye. The nuclei were graded clinically on the basis of hardness. The endothelial cell count (ECC) was evaluated preoperatively and 1, 3 and 6 months postoperatively. Total surgical time, effective ultrasound time and complications were also compared between the groups. Statistical analysis was performed by the Tukey Studentized Range test, with repeated measures for the selected periods. For the other parameters a paired t test was used. Data are presented as mean ± SD, with the level of significance set at p≤0.05. The mean effective ultrasound time was 8.08 ± 6.75 seconds in group I and 7.00 ± 5.75 seconds in GII (P=0.1792) and total surgical time was 10.01 ± 2.46 minutes in GI and 9.86 ± 2.17 minutes in GII (p=0.6267), respectively. The paired t test revealed no statistical differences between the groups. Complications were also similar between the groups. Mean endothelial cell count loss was 6.9% in GI and 2.8% in GII at one month; 6.9% in GI and 3.6% in GII at three months and 11.9% in GI and 7.6% in GII at six months postoperatively. Comparison of endothelial cell count (ECC) showed a statistically significant difference between the groups during the postoperative period. The conventional bevel-up tip position has a negative effect on corneal endothelial cells compared with the bevel-down position. Since the results of other surgical parameters were similar, the bevel-down tip position should be considered as an option in non-complicated phacoemulsification.

Emission rates of alpha particles from supports with different surface conditions in direct deposition sources

Direct deposition is the only method that can be utilised for the standardisation of radioactive solutions because there is no deposition loss on a support. The present study investigated how much the roughness of the support influences the emission rate of alpha particles for direct deposition sources from the practical viewpoint of use of the method. A number of samples were prepared by evaporating a 0.1-ml aliquot of a dilute nitric acid aqueous solution that contained (241)Am on stainless steel supports with four different surface conditions; untreated supports were either polished (using metal abrasives available commercially) or not polished, and buffed supports (grid size of #400) were either polished or not polished. Alpha spectrometry of the samples revealed that the detection efficiency was significantly different between the non-polished and polished supports; the former was lower by 3 % than the latter for both the untreated and buffed supports. Microscopic observations clarified that the counting loss was attributed to irregular flaws or polishing lines on the non-polished supports, most of which were found to be in the order of submicron in depth and were diminished on the polished supports. One may usually assume that a direct deposition source offers no counting loss if its entire energy spectrum is seen above a low-energy discrimination limit of the spectrometer. However, this should be experimentally confirmed using a solution with known activity. It was difficult to identify the counting loss for the buffed supports without polishing because their energy spectra showed little degradation.

Imaging Studies for Evaluating Impact of Position Sampling Techniques in PET Scanners

Previously we have evaluated two crystal calibration techniques that can be applied to pixelated detector designs to improve system spatial resolution without detector motion. The inter-crystal positioning technique utilizes sub-sampling in the crystal flood map to better sample the Compton scatter events in the detector. The Compton scatter rejection technique, on the other hand, rejects those events that are located further from individual crystal centers in the flood map. Here we performed imaging studies with a Mini Deluxe hot rod phantom and a hot sphere phantom (sphere diameters of 4.95 and 7.86-mm with 6:1 uptake relative to background) using the standard crystal calibration technique, as well as the inter-crystal and Compton rejection calibration techniques. Our results show improved separation of 1.6-mm diameter hot rods with the two new crystal calibration techniques that is consistent with improved spatial resolution. For the hot sphere phantom the contrast recovery is improved with both the inter-crystal and Compton rejection calibration techniques over the standard calibration technique. The only drawback of the inter-crystal calibration technique is the increase in the number of possible lines-of-response (LORs) (factor of 16) that may slow image reconstruction. With the Compton rejection calibration technique, loss of counts leads to increased noise in the images.

Age-related normogram for antral follicle count: McGill reference guide

To produce age-related normograms for antral follicle count in an infertile population without polycystic ovaries. Retrospective cohort analysis. University teaching center. Eighteen hundred sixty-six infertile patients. Baseline transvaginal ultrasound examination between days 2 and 4 of the menstrual cycle. Correlation between age and different percentiles of antral follicle count. The age-related normogram for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentile of antral follicle count showed a biphasic mode of antral follicle count decline with two different rates of antral follicle count loss: a steep-slope phase (high rate of antral follicle count loss) and a moderate-slope phase (restrained rate of antral follicle count losses). In the low antral follicle count percentiles (3rd, 10th, 25th), the phase of high loss rate of follicles preceded the phase of slow loss rate, whereas in the high antral follicle count percentiles (75th, 90th, 97th) the opposite was found. Age-related normograms in infertile women without polycystic ovaries demonstrate a biphasic pattern of decreased antral follicles. These normograms could provide a reference guide for the clinician in consulting with women with infertility. However, future validation with longitudinal data is still needed.

Performance Evaluation of the FLEX Triumph X-PET Scanner Using the National Electrical Manufacturers Association NU-4 Standards

The purpose of this work was to evaluate the performance characteristics of the preclinical X-PET subsystem of the FLEX Triumph PET/CT scanner based on the NU 4-2008 standards of the National Electrical Manufacturers Association (NEMA). The performance parameters evaluated include the spatial resolution, scatter fraction, count losses and random coincidences, sensitivity, and image-quality characteristics. The PET detector array consisted of 11,520 individual bismuth germanate crystals arranged in 48 rings and 180 blocks, with an axial field of view (FOV) of 11.6 cm and a inner ring diameter of 16.5 cm. The spatial resolution was measured with a small (22)Na point source (diameter, 0.25 mm) at different radial offsets from the center. Sensitivity was calculated using the same source by stepping the source axially through the axial FOV of the scanner. Scatter fraction and counting-rate performances were determined using a mouse- and rat-sized phantom with an (18)F line source insert. The NEMA image-quality phantom and rodent imaging were also performed to access the overall imaging capabilities of the scanner. Tangential spatial resolution in terms of full width at half maximum varied between 2.2 mm at the center of the FOV and 2.3 mm at a radial offset of 2.5 cm. The radial spatial resolution varied between 2.0 at the center and 4.4 mm at a radial offset of 2.3 cm. The peak system absolute sensitivity was 5.9% at the center of the FOV. The absolute system sensitivity was 0.67 counts/s/Bq, and the relative total system sensitivity was 73.9%. The scatter fraction for the mouse-sized phantom was 7.9%, with a peak true counting rate of 168 kilocounts per second (kcps) at 0.3 MBq/mL and a peak noise-equivalent counting rate of 106 kcps at 0.17 MBq/mL. The rat-sized phantom had a scatter fraction of 21%, with a peak true counting rate of 93 kcps at 0.034 MBq/mL and a peak noise-equivalent counting rate of 49 kcps at 0.02 MBq/mL. Recovery coefficients for the image-quality phantom ranged from 0.13 to 0.88. The performance of the X-PET scanner based on the NEMA NU 4-2008 standards was fully characterized. The overall performance demonstrates that the X-PET system is suitable for preclinical research.

Epileptic tolerance is associated with enduring neuroprotection and uncoupling of the relationship between CA3 damage, neuropeptide Y rearrangement and spontaneous seizures following intra-amygdala kainic acid-induced status epilepticus in mice

Brief, non-harmful seizures can activate endogenous protective programmes which render the brain resistant to damage caused by prolonged seizure episodes. Whether protection in epileptic tolerance is long-lasting or influences the subsequent development of epilepsy is uncertain. Presently, we investigated the relationship between hippocampal pathology, neuropeptide Y rearrangement and spontaneous seizures in sham- and seizure-preconditioned mice after status epilepticus induced by intra-amygdala kainate. Seizure-induced neuronal death at 24 h was significantly reduced in the ipsilateral hippocampal CA3 and hilus of tolerance mice compared to sham-preconditioned animals subject to status epilepticus. Damage to the CA3-hilus remained reduced in tolerance mice 21 days post-status. In sham-preconditioned mice subject to status epilepticus correlative statistics showed there was a strong inverse relationship between CA3, but not hilar, neuron counts and the number of spontaneous seizures. A strong positive association was also found between neuropeptide Y score and spontaneous seizure count in these mice. In contrast, there was no significant association between spontaneous seizure count and CA3 neuron loss or neuropeptide Y rearrangement in the tolerance mice. These data show that tolerance-conferred neuroprotection is long-lasting and that tolerance disrupts the normal association between CA3 damage, synaptic rearrangement and occurrence of spontaneous seizures in this model

Evaluation of the attenuation properties of MR equipment for its use in a whole-body PET/MR scanner

The combination of magnetic resonance imaging (MR) and positron emission tomography (PET) scanners can provide a powerful tool for clinical diagnosis and investigation. Among the challenges of developing a combined scanner, obtaining attenuation maps for PET reconstruction is of critical importance. This requires accounting for the presence of MR hardware in the field of view. The attenuation introduced by this hardware cannot be obtained from MR data. We propose the creation of attenuation models of MR hardware, to be registered into the MR-based attenuation map prior to PET reconstruction. Two steps were followed to assess the viability of this method. First, transmission and emission measurements were performed on MR components (RF coils and medical probes). The severity of the artifacts in the reconstructed PET images was evaluated. Secondly, a high-exposure computed tomography (CT) scan was used to obtain a model of a head coil. This model was registered into the attenuation map of PET/CT scans of a uniform phantom fitted with the coil. The resulting PET images were compared to the PET/CT reconstruction in the absence of coils. The artifacts introduced by misregistration of the model were studied. The transmission scans revealed 17% count loss due to the presence of head and neck coils in the field of view. Important sources of attenuation were found in the lock, signal cables and connectors. However, the worst source of attenuation was the casing between both coils. None of the measured medical probes introduced a significant amount of attenuation. Concerning the attenuation model of the head coil, reconstructed PET images with model-based correction were comparable to the reference PET/CT reconstruction. However, inaccuracies greater than 1–2 mm in the axial positioning of the model led to important artifacts. In conclusion, the results show that model-based attenuation correction is possible. Using a high-exposure scan to create an attenuation model of the coils has been proved feasible. However, adequate registration of the model is mandatory.

Beyond single photon counting X-ray detectors

Synchrotron radiation applications require detectors with a high sensitivity and a large dynamic range in order to study both the strong and weak features of the samples. Moreover, a high spatial resolution is necessary for imaging and diffraction studies. The photon counting technique is currently the best solution to these requirements but it presents some limitations which can only be partially overcome by technological improvements i.e. the count loss at high impinging intensities, due to the readout electronics shaping time, and the restrictions on the minimum pixel size, due to the charge diffusion in the sensor. In order to overcome both these limitations a new generation of charge integrating hybrid detectors with single photon sensitivity is being developed. These preserve the advantages of counting detectors and at the same time allow a processing of the analog information in order to enhance the spatial resolution and perform some spectral analysis. A comparison between purely counting and analog readout for 50 and 25 μ m pitch microstrip detectors is presented in terms of spectral reconstruction capability and spatial resolution.

Wall effect in ionization chambers for tritium measurements

Wall effect in ionization chambers for tritium measurements has been studied in this paper. Theoretical analysis with a model based on the continuous slowing-down approximation (CSDA) is employed to obtain the relationship between wall effect and pressure in the chamber, which follows cubic polynomial. Two ionization chambers of different volumes are used in the experiment. Results show that the counting losses due to wall effect are as much as 17.62% for ionization chamber of volume 1.1L at pressure 71mmHg, and 28.54% for 0.3L. Both linear polynomial with logarithm scale and cubic polynomial are used to fit the results, which agrees very well with the theoretical analysis. Monte Carlo simulations are also introduced to calculate the loss part of electrons due to wall effect, which show accordance with the experimental results.

SU‐GG‐I‐161: Multi‐Resolution Cumulative Summation (CUSUM) Images for Monitoring Gamma Camera Detector Uniformity

Purpose: Detect trends in gamma camera uniformity in order to predict service events. Materials and Methods: Cumulative summation statistical control (CUSUM) effectively detects subtle shifts in the expected mean of normally distributed data. This technique was applied to each pixel in a time series of gamma camera quality control floods to detect nonuniformities that might otherwise have gone undetected in any single flood image using NEMA uniformity calculations. One hundred statistically independent 10 M count uniformity floods were sequentially acquired in a 1024×1024 matrix. A progressively worsening nonuniformity was simulated beginning in the thirtieth flood image, where an attenuation disk 8 cm in diameter (∼1% count loss) was positioned in the central field‐of‐view (FOV). Additional disks were added to the stack every ten subsequent acquisitions in order to mimic progressive count loss, up to the point that normal NEMA analysis was expected to yield differential uniformity values that exceeded our institution's action limit of 3%. Mean and error images were calculated with respect to time using the first thirty floods in the series, and the time series was normalized to these values. The CUSUM images were calculated by summing the deviations between a reference value of one‐half of the standard deviation and each normalized pixel, adding to that the previous value of the CUSUM at each pixel location. Thus, the CUSUM images represent the accumulation of deviations between each normalized and expected pixel value. The process was repeated for larger pixel sizes and composite images were formed. Results and Conclusion: The results show a distinct signal at the location of the non‐uniformity by time point 60, well in advance of reaching the level of degradation expected to cause a single flood to fail clinical criteria, given the rate of degradation. Thus, this technique sensitively detects non‐uniformity trends.

Potential loss of methionine following extended storage of newborn screening samples prepared for tandem mass spectrometry analysis

Background Methionine (Met) is a key metabolite used in the newborn screening of homocystinuria by tandem mass spectrometry (MS/MS). Recently, a loss of ion counts in both Met and its deuterium-labeled internal standard ( 2H 3-Met) was observed by the CDC's Newborn Screening Quality Assurance Program laboratory. We report on the stability of labeled and unlabeled Met solutions and their storage in two types of 96 well microtiter plates to illustrate the potential loss of Met following storage of samples prior to MS/MS analysis. Methods Neat labeled and unlabeled Met standards were prepared and added (25, 50 and 100 μl) to two different types of microtiter plates, dried under nitrogen and stored for up to 168 h. All samples were reconstituted in mobile phase and analyzed as free acids for simplification of the study. Results and conclusions Met appears to interact significantly with polystyrene microtiter plates and to a much lesser extent with polypropylene microtiter plates. Furthermore, the loss is greatest for lower concentrations of methionine. While this loss of Met signal may be unimportant due to a presumption of equal loss of 2H 3-Met, a significant decline in ion signals will cause greater error in the calculation of concentration. These results suggest that polypropylene may be a better choice for Met analysis. Furthermore, storing prepared samples prior to analysis may impact the quality of the MS/MS analysis for Met and potentially other metabolites. Plates used by newborn screening laboratories should be evaluated periodically if the signal intensity for Met is reduced.

Metabolic Vulnerability Disposes Retinal Ganglion Cell Axons to Dysfunction in a Model of Glaucomatous Degeneration

We tested the hypothesis that glaucoma disrupts electrophysiological conduction properties and axon function in optic nerve as a function of intraocular pressure (IOP) levels and age in the DBA/2J mouse model of glaucoma. The amplitude and the integral of electrical signals evoked along the axons decreased considerably by 6 months of age as a function of increasing IOP levels. At young ages, raised IOP was directly associated with increased vulnerability to metabolic challenge. Changes in the physiological function of the optic nerves were accentuated with aging, leading to loss of compound action potential in an entire population of fibers: small, slow conducting axons. This loss was accompanied with loss of small fiber axon counts and declining metabolic reserve by demonstrating IOP-dependent ATP decrease in mouse optic nerves. These data shed light on a novel potential mechanism of glaucoma pathology whereby increased IOP and declining metabolic capacity lead to axon liability and eventually dysfunction and loss.

Mortality after failure of antiretroviral therapy in sub‐Saharan Africa

To assess the outcome of patients who experienced treatment failure with antiretrovirals in sub-Saharan Africa. Analysis of 11 antiretroviral therapy (ART) programmes in sub-Saharan Africa. World Health Organization (WHO) criteria were used to define treatment failure. All ART-naive patients aged >or=16 who started with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen and had at least 6 months of follow-up were eligible. For each patient who switched to a second-line regimen, 10 matched patients who remained on a non-failing first-line regimen were selected. Time was measured from the time of switching, from the corresponding time in matched patients, or from the time of treatment failure in patients who remained on a failing regimen. Mortality was analysed using Kaplan-Meier curves and random-effects Cox models. Of 16 591 adult patients starting ART, 382 patients (2.3%) switched to a second-line regimen. Another 323 patients (1.9%) did not switch despite developing immunological or virological failure. Cumulative mortality at 1 year was 4.2% (95% CI 2.2-7.8%) in patients who switched to a second-line regimen and 11.7% (7.3%-18.5%) in patients who remained on a failing first-line regimen, compared to 2.2% (1.6-3.0%) in patients on a non-failing first-line regimen (P < 0.0001). Differences in mortality were not explained by nadir CD4 cell count, age or differential loss to follow up. Many patients who meet criteria for treatment failure do not switch to a second-line regimen and die. There is an urgent need to clarify the reasons why in sub-Saharan Africa many patients remain on failing first-line ART.

A Comparison of Posterior Lamellar Keratoplasty Modalities: DLEK vs. DSEK

PurposeTo compare clinical outcomes after deep lamellar endothelial keratoplasty (DLEK) with Descemet stripping endothelial keratoplasty (DSEK) performed as initial cases by a single surgeon.MethodsSixteen patients with corneal endothelial were enrolled. Eight patients (8 eyes) underwent DLEK and 8 patients (8 eyes) DSEK. We measured uncorrected visual acuity, best corrected visual acuity (BCVA), manifest refraction, corneal endothelial count, interface opacity via Schiempflug imaging, and contrast sensitivity, as well as tracked postoperative complications over the first postoperative year.ResultsPrimary graft failure occurred in two DLEK cases and one DSEK case, all of which were excluded for further analysis. The average 12-month postoperative BCVA was 20/70 in the DLEK group and 20/50 in the DSEK group, with the difference not statistically significant. No significant differences were identified between the 2 groups in terms of mean spherical equivalent and refractive astigmatism, although individuals in the DSEK group tended toward hyperopia. The average endothelial cell count at postoperative month 12 was 1849±494 in the DLEK group and 1643±417 cells/mm2 in the DSEK group, representing cell losses of 26.2% and 31.9%, respectively. No significant differences in endothelial cell count or endothelial cell loss were observed between groups. Early postoperative donor disc dislocation occurred in two eyes after DLEK and one eye after DSEK. Interface opacities and contrast sensitivities were similarly not significantly different between groups.ConclusionsNo significant differences in any assessed clinical outcome were observed between individuals undergoing DLEK and DSEK, when performed as initial cases by a single surgeon.

Random coincidence summing of gamma rays and dead time count loss corrections in HPGe-detector based gamma ray spectrometry

Random coincidence summing of gamma rays and dead time count losses are a potential source of errors in gamma ray spectrometry. In this work, the magnitudes of count rate losses due to the random coincidence summing and dead time effect, alongwith corresponding corrections, have been studied. Experiments were performed in two independent gamma ray spectroscopic laboratories (referred as LAB-A & LAB-B), utilizing low activity reference nuclides 65 Zn and 60 Co. The low activity reference radionuclide 65 Zn was produced by using 10 MW nuclear reactor (PARR-1) at PINSTECH for use in one Lab. The gamma ray spectra were acquired using HPGe-detector based gamma ray spectrometers at fixed shaping times of the amplifier and positions of the reference nuclides. The MCA dead times of the spectrometers were varied to incur the count rate losses to the peaks of interest. Three procedures were adopted to determine the dead time and random summing correction factors. The corrections to count rate data measured at LAB-A, which represented a maximum of 46% losses, were obtained within standard deviation figures of 2.9%, 1.3% and 0.4% and in LAB-B case the losses of 41%, were corrected to within 1.8%, 1.1% and 0.6%, respectively with the described three procedures. The best-achieved precision (difference between the measured count rate with negligible dead time and the average of corrected count rates) in the case of LAB-A and LAB-B were within 1 x 10 ―3 and 2 x 10 ―2 %. The new procedure on the basis of fitting function is also evolved as a result of this study, which has produced the highly consistent results. The experimental data from the literature are also incorporated in this study for comparison purposes.

Standardization of radium-223 by liquid scintillation counting

Liquid scintillation (LS) counting was undertaken as part of the primary standardization of (223)Ra. Radium-223 decays with a half life of 11.43 d through a chain of shorter-lived daughter radionuclides, resulting in five alpha decays and three beta decays. The CIEMAT/NIST method of tritium efficiency tracing was employed, with the beta efficiencies being calculated using the program CN2004, developed by the Physikalisch-Technische Bundesanstalt (PTB). The total calculated LS efficiency, considering all daughter radionuclides, was approximately 598%. Separate experiments were performed to rule out loss of the 3.96 s (219)Ra daughter from the cocktail and possible counting loss of the 1.78 ms (215)Po daughter due to LS counter dead-time. No loss was observed in either experiment. In the final experiment an expanded uncertainty (k=2) of 0.55% was achieved. Results were in excellent agreement with confirmatory measurements performed by 2pialpha proportional counting. However, results are not in agreement with methods based on gamma ray measurements.

Validation of histologic changes induced by external irradiation in mandibular bone. An experimental animal model

The present experimental study sought to determine the effect of high-dose irradiation on the rat mandible in order to establish an experimental model of radiogenic bone damage. The left mandibles of 20 adult Wistar rats were irradiated (single fraction 1500cGy, total dose 60Gy) by means of a hypofractionated stereotactic radiotherapy (hfSRT) over a period of 6 weeks. Follow-up was 6 weeks (group 1, n=10) and 12 weeks (group 2, n=10). The contralateral mandibles as well as 5 non-irradiated animals served as controls. Primary endpoints were fibrosis, loss of cell count, decreased immunohistochemical labelling for bone morphogenetic protein-2 (BMP-2) and osteocalcin as well as increased expression of transforming growth factor (TGF-beta). Cell loss, progressive fibrosis, and focal necrosis were detected in all irradiated sites. Quantitative measurement revealed 32.0+/-8.7% and 37.3+/-9.5% empty osteocyte lacunae for groups 1 and 2 resp., compared to 16.3+/-4.7% and 18.9+/-4.9% on the contralateral side and 7.9+/-1.7% for unirradiated controls (Mann-Whitney U test; p<.01). BMP-2 and osteocalcin labelling showed a marked decrease in irradiated and contralateral sides while TGF-beta was expressed strongly in irradiated sites only (for all p<.05). External hypofractionated irradiation with a total dose of 60Gy is feasible in rats and yields all histologic changes attributed to osteoradionecrosis (ORN) after a follow-up of 6 weeks. The irradiation protocol is suitable for an assessment of regenerative options in severe radiogenic bone damage. As a split mouth design entails major inaccuracies healthy animals have to be used as controls.

Renal Tubulocystic Carcinoma Is Closely Related to Papillary Renal Cell Carcinoma: Implications for Pathologic Classification

Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor with unique gross and microscopic features unlike other types of renal cell carcinoma (RCC). Several recent studies recommend that it should be classified as a distinct RCC subtype. In this study, we provide pathologic and cytogenetic evidence supporting that TC-RCC is closely related to papillary RCC (PRCC). This study included 20 cases of renal tumors that partially or exclusively comprised a TC-RCC component. Pathologic examination documented the gross and microscopic features of TC-RCC, including multicentricity and the presence of concomitant PRCC and papillary adenoma. Formalin-fixed, paraffin-embedded sections from 12 TC-RCC and 20 PRCC were subjected to a multicolor fluorescence in situ hybridization assay containing probes for chromosomes 7, 17, and Y. One hundred nuclei were examined to enumerate the copy numbers of chromosomes in each tumor and its corresponding normal kidney tissue. A tumor with a percentage of cells harboring a chromosomal change > or = mean+3 SD of normal tissue was considered to harbor that chromosomal change, and a tumor with a percentage of cells with null Y chromosome count (loss of Y chromosome) > or = mean+3 SD of normal tissue was considered to harbor Y chromosome loss. Four of the 20 TC-RCCs were multicentric. Ten had associated PRCC or papillary adenoma within the same kidney as the TC-RCC. In 4 cases, the tubulocystic and papillary components were admixed together within the same lesion. The tumor cells lining both the tubulocystic and papillary components had similar cytologic features. Ten of 12 TC-RCCs had a chromosome 7 gain, 8 of 12 cases had a chromosome 17 gain, and 8 of 9 cases had a loss of Y chromosome. Six of 9 cases with all 3 chromosomes studied had a gain of chromosomes 7 and 17 and a loss of Y chromosome. Our study shows that TC-RCCs and PRCCs are closely related entities. With its distinctive gross and microscopic features, TC-RCC may be considered a unique "morphologic entity." However, before it is accepted as a distinct renal cell carcinoma subtype, further studies are needed to document a characteristic molecular signature associated with this tumor.