Evaluation of seasonal influences on adrenocorticotropic hormone response to the thyrotropin-releasing hormone stimulation test and its accuracy for diagnosis of pituitary pars intermedia dysfunction.

Pituitary pars intermedia dysfunction (PPID) is an age-related neurodegenerative disorder, affecting >20 % of older horses. There is a need for improved endocrine tests for early disease detection, and the thyrotropin-releasing hormone (TRH) stimulation test has been recommended for diagnosis of early or mild cases. However, it is currently not recommended for year-round use due to marked seasonal variability. The aims of this cohort study were to evaluate effects of month and season on adrenocorticotropic hormone (ACTH) responses to TRH stimulation and to derive monthly cut-offs for PPID diagnosis. Sixty-three horses were assigned to control (n = 17), subclinical PPID (n = 21) and clinical PPID (n = 25) groups, based on a composite reference standard that combined clinical history and examination findings with endocrine test results. TRH stimulation tests were performed monthly for a 12-month period. Circannual changes were evaluated with one- and two-way repeated-measures analysis of variance and receiver operating characteristic curve analysis was used to derive cut-off values for basal and TRH-stimulated ACTH. TRH-stimulated ACTH concentrations were lowest in February-May and highest in August-October. Specificity of both basal and 30 min post-TRH ACTH was generally higher than sensitivity, and TRH stimulation had improved diagnostic accuracy compared to basal ACTH, although its sensitivity was not significantly greater year-round. TRH stimulation tests yielded considerably more positive results than basal ACTH in the subclinical group, but few additional positive results in clinical PPID cases. There were large differences between cut-offs that maximised sensitivity or specificity for TRH-stimulated ACTH, highlighting the importance of considering clinical presentation alongside test results in diagnostic decision-making.

Effects of the bovine SLICK1 mutation in PRLR on sweat gland area, FOXA1 abundance, and global gene expression in skin.

The SLICK1 mutation in the prolactin receptor (PRLR) results in a short-hair coat and increased ability to regulate body temperature during heat stress. It is unclear whether the mutation affects capacity for sweating. The objective of this observational study was to evaluate whether the SLICK1 mutation in PRLR alters characteristics of skin related to sweat gland abundance or function. Skin biopsies from 31 Holstein heifers, including 14 wild-type (SL-/-) and 17 heterozygous slick (SL+/-), were subjected to histological analysis to determine the percent of the surface area of skin sections that are occupied by sweat glands. We detected no effect of genotype on this variable. Immunohistochemical analysis of the forkhead transcription factor A1 (FOXA1), a protein essential for sweating in mice, from 6 SL-/- and 6 SL+/- heifers indicated twice as much FOXA1 in sweat glandular epithelia of SL+/- heifers as in SL-/- heifers. Results from RNA sequencing of skin biopsies from 5 SL-/- and 7 SL+/- heifers revealed few genes that were differentially expressed and none that have been associated with sweat gland development or function. In conclusion, results do not support the idea that the SLICK1 mutation changes the abundance of sweat glands in skin, but do show that functional properties of sweat glands, as indicated by increased abundance of immunoreactive FOXA1, are modified by inheritance of the mutation in PRLR.

Clinical and echocardiographic characteristics of cardioembolic stroke.

BACKGROUND AND PURPOSE: Ischaemic stroke frequently has a cardioembolic (CE) source. Clinical and echocardiographic parameters associated with CE stroke were evaluated. METHODS: In all, 93 consecutive ischaemic stroke patients who underwent a transthoracic echocardiogram were retrospectively analysed; strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Echocardiographic parameters related to CE stroke, including left atrial volumes and function, were compared to 73 healthy controls. RESULTS: Of 93 patients (mean age 66.1 years, 56% male), nine (10%) had large artery atherosclerosis, 38 (41%) CE stroke, two (2%) small vessel disease, two (2%) other and 42 (45%) undetermined aetiology. Left atrial (LA) maximum volumes (LAVImax ) and minimum volumes (LAVImin ) were larger in the CE group than the non-CE group (45 vs. 32 ml/m2 , 32 vs. 13 ml/m2 , respectively, P < 0.001), whilst LA function indices including LA emptying fraction and LA function index (LAFI) were lower in the CE group (34% vs. 55%, and 0.12 vs. 0.35, respectively, P < 0.001). Adjusting for clinical characteristics, LAFI ≤0.3 was an independent predictor of CE stroke (adjusted odds ratio 5.3, P = 0.001). Additionally, LAVImax and LAVImin were larger (61 vs. 44 and 32 vs. 24 ml/m2 respectively, P < 0.01) and LAFI significantly lower (0.34 vs. 0.52, P < 0.001) in the undetermined aetiology group versus healthy controls. CONCLUSIONS: Left atrial enlargement with reduced LA function was associated with CE stroke and LAFI was the best independent predictor. LA parameters were also altered in the undetermined aetiology group, suggesting an underlying LA myopathy in this subset.

Fourier optics of image formation in aberration-corrected LEEM.

We present the extended Fourier Optics (FO) approach for modeling image formation in aberration-corrected low energy electron microscopy (ac-LEEM). The FO formalism is also generalized for image simulations of one or two-dimensional objects in ac and uncorrected (nac) LEEM. A comparison is made of the extended FO approach presented here and the extended contrast transfer function (CTF) approach for ac-LEEM that was developed earlier. The mathematically rigorous extended FO approach gains an advantage under conditions, particularly defocus, that partial coherence of the illumination may compromise the validity of the approximate CTF intensity calculation. The drawback of the FO approach compared to the CTF approach, which is its slow computational speed, is mitigated partly here by the implementation of a multi-core, multi-threading programming architecture. This work broadens our capabilities to understand the origins of LEEM image contrast and to perform quantitative evaluation of contrast observed in an image focal series.

High throughput scanning µLEED imaging of surface structural heterogeneity: Defective graphene on Cu(111).

Micro-low energy electron diffraction (µLEED) is frequently used in conjunction with low energy electron microscopy (LEEM) to learn about local surface structural features in small selected areas. Scanning µLEED measurements performed with a very small electron beam (250 nm) can provide precise quantitative information about structural variations with high spatial resolution. We have developed the Source Extraction and Photometry (SEP) - Spot Profile Analysis (SPA) tool for evaluating scanning µLEED data with high throughput. The capability to automate diffraction peak identification with SEP-SPA opens up the possibility to investigate systems with complex diffraction patterns in which diffraction peak positions vary rapidly for small lateral displacements on the surface. The application of this tool to evaluate scanning µLEED data obtained for defective graphene on Cu(111) demonstrates its capabilities. A rich rotational domain structure is observed in which a majority of the graphene is co-aligned with the Cu(111) substrate and the significant remainder comprises domains with large rotations and small sizes that are comparable to the small beam size.

Comparing Fourier optics and contrast transfer function modeling of image formation in low energy electron microscopy.

A theoretical understanding of image formation in cathode lens microscopy can facilitate image interpretation. We compare Fourier Optics (FO) and Contrast Transfer Function (CTF) approaches that were recently adapted from other realms of microscopy to model image formation in low energy electron microscopy (LEEM). Although these two approaches incorporate imaging errors from several sources similarly, they differ in the way that the image intensity is calculated. The simplification that is used in the CTF calculation advantageously leads to its computational efficiency. However, we find that lens aberrations, and spatial and temporal coherence may affect the validity of the CTF approach to model LEEM image formation under certain conditions. In particular, these effects depend strongly on the nature of the object being imaged and also become more pronounced with increasing defocus. While the use of the CTF approach appears to be justified for objects that are routinely imaged with LEEM, comparison of theory to experimental observations of a focal image series for rippled, suspended graphene reveals one example where FO works, but CTF does not. This work alerts us to potential pitfalls and guides the effective use of FO and CTF approaches. It also lays the foundation for quantitative image evaluation using these methods.

Defocus in cathode lens instruments.

Accurately measuring defocus in cathode lens instruments (Low Energy Electron Microscopy - LEEM, and Photo Electron Emission Microscopy - PEEM) is a pre-requisite for quantitative image analysis using Fourier Optics (FO) or Contrast Transfer Function (CTF) image simulations. In particular, one must establish a quantitative relation between lens excitation and image defocus. One way to accomplish this is the Real-Space Microspot LEED method, making use of the accurately known angles of diffracted electron beams, and the defocus-dependent shifts of their corresponding real-space images. However, this only works if a sufficiently large number of diffracted beams is available for the sample under investigation. An alternative is to shift the sample along the optical axis by a known distance, and measure the change in objective lens excitation required to re-focus the image. We analytically derive the relation between sample shift and defocus, and apply our results to the measurement and analysis of achromats in an aberration-corrected LEEM instrument.

Durations of second stage of labor and pushing, and adverse neonatal outcomes: a population-based cohort study.

OBJECTIVE: The associations between duration of second stage of labor, pushing time and risk of adverse neonatal outcomes are not fully established. Therefore, we aimed to examine such relationships. STUDY DESIGN: A population-based cohort study including 42 539 nulliparous women with singleton infants born in cephalic presentation at ⩾37 gestational weeks, using the Stockholm-Gotland Obstetric Cohort, Sweden, and the Swedish Neonatal Quality Register, 2008 to 2013. Poisson regression was used to analyze estimated adjusted relative risks (RRs), with 95% confidence intervals (CIs). Outcome measures were umbilical artery acidosis (pH <7.05 and base excess <-12), birth asphyxia-related complications (including any of the following conditions: hypoxic ischemic encephalopathy, hypothermia treatment, neonatal seizures, meconium aspiration syndrome or advanced resuscitation after birth) and admission to neonatal intensive care unit (NICU). RESULTS: Overall rates of umbilical artery acidosis, birth asphyxia-related complications and admission to NICU were 1.08, 0.63 and 6.42%, respectively. Rate of birth asphyxia-related complications gradually increased with duration of second stage: from 0.42% at <1 h to 1.29% at ≥4 h (adjusted RR 2.46 (95% CI 1.66 to 3.66)). For admission to NICU, corresponding rates were 4.97 and 9.45%, and adjusted RR (95% CI) was 1.80 (95% CI 1.58 to 2.04). Compared with duration of pushing <15 min, a duration of pushing ⩾60 min increased rates of acidosis from 0.57 to 1.69% (adjusted RR 2.55 (95% CI 1.51 to 4.30)). CONCLUSION: Prolonged durations of second stage of labor and pushing are associated with increased RRs of adverse neonatal outcomes. Clinical assessment of fetal well-being is essential when durations of second stage and pushing increases.

A framework for automated contour quality assurance in radiation therapy including adaptive techniques.

Contouring of targets and normal tissues is one of the largest sources of variability in radiation therapy treatment plans. Contours thus require a time intensive and error-prone quality assurance (QA) evaluation, limitations which also impair the facilitation of adaptive radiotherapy (ART). Here, an automated system for contour QA is developed using historical data (the 'knowledge base'). A pilot study was performed with a knowledge base derived from 9 contours each from 29 head-and-neck treatment plans. Size, shape, relative position, and other clinically-relevant metrics and heuristically derived rules are determined. Metrics are extracted from input patient data and compared against rules determined from the knowledge base; a computer-learning component allows metrics to evolve with more input data, including patient specific data for ART. Nine additional plans containing 42 unique contouring errors were analyzed. 40/42 errors were detected as were 9 false positives. The results of this study imply knowledge-based contour QA could potentially enhance the safety and effectiveness of RT treatment plans as well as increase the efficiency of the treatment planning process, reducing labor and the cost of therapy for patients.

Probing buried magnetic interface structure with the quantum size effect in spin-dependent electron reflectivity.

The quantum size effect (QSE) in electron reflectivity from Fe thin films grown on a W(110) surface precovered with a two monolayer Cu film has been investigated using spin polarized low energy electron microscopy. Spin-dependent QSE-induced oscillations in the reflected intensity occur with energy and film thickness. The series of intensity peaks that is observed identifies spin-dependent quantum well resonances in the Fe film that are sensitive to electronic band structure and details of the buried interface. Information about the spin-dependent unoccupied bands of the Fe film in the ΓΝ direction normal to the film plane is obtained by analyzing the observed quantum well resonance conditions. The spin-split bands that are determined are uniformly shifted downward by 1.7 eV compared to bulk-like bands determined previously in Fe films on a bare W(110) substrate by the same method. Evidence is also obtained that the buried interface that defines the thin film quantum well boundary is located one layer above the W(110) surface. These results suggest that the Cu layer in direct contact with the substrate remains largely intact, but the weakly-bound second Cu layer mixes or segregates freely.

Spin polarized low energy electron microscopy of quantum well resonances in Fe films on the Cu-covered W(110) surface.

Spin polarized low energy electron microscopy has been used to investigate the quantum size effect (QSE) in electron reflectivity from Fe films grown on a pseudomorphic Cu layer on a W(110) surface. Intensity oscillations caused by the QSE as functions of Fe film thickness and incident electron energy identify quantum well resonance conditions in the film. Evaluation of these intensity oscillations using the phase accumulation model provides information on the unoccupied spin polarized band structure in the Fe film above the vacuum level. We also find evidence that the presence of the non-magnetic Cu layer shifts spin polarized quantum well resonances in the Fe layer uniformly downward in energy by 1.1eV compared to Fe/W(110) films without an interface Cu layer, suggesting that the Cu layer gives a small degree of control over the quantum well resonances.

LEEM image phase contrast of MnAs stripes.

Low energy electron microscopy (LEEM) imaging of strained MnAs layers epitaxially grown on GaAs(001) reveals striped contrast features that become more pronounced and vary systematically in width with increasing defocus, but that are completely absent in focus. Weaker subsidiary fringe-like features are observed along the stripe lengths, while asymmetric contrast reversal occurs between under-focus and over-focus conditions. A Fourier optics calculation is performed that demonstrates that these unusual observations can be attributed to a phase contrast mechanism between the hexagonal α phase and orthorhombic ß phase regions of the MnAs film, which self-organize into a periodic stripe array with ridge-groove morphology. The unequal widths of the α and ß phase regions are determined accurately from the through focus series, while the height variation in this system can also be determined in principle from the energy dependence of contrast.

Commissioning of the Varian TrueBeam linear accelerator: a multi-institutional study.

PURPOSE: Latest generation linear accelerators (linacs), i.e., TrueBeam (Varian Medical Systems, Palo Alto, CA) and its stereotactic counterpart, TrueBeam STx, have several unique features, including high-dose-rate flattening-filter-free (FFF) photon modes, reengineered electron modes with new scattering foil geometries, updated imaging hardware/software, and a novel control system. An evaluation of five TrueBeam linacs at three different institutions has been performed and this work reports on the commissioning experience. METHODS: Acceptance and commissioning data were analyzed for five TrueBeam linacs equipped with 120 leaf (5 mm width) MLCs at three different institutions. Dosimetric data and mechanical parameters were compared. These included measurements of photon beam profiles (6X, 6XFFF, 10X, 10XFFF, 15X), photon and electron percent depth dose (PDD) curves (6, 9, 12 MeV), relative photon output factors (Scp), electron cone factors, mechanical isocenter accuracy, MLC transmission, and dosimetric leaf gap (DLG). End-to-end testing and IMRT commissioning were also conducted. RESULTS: Gantry/collimator isocentricity measurements were similar (0.27-0.28 mm), with overall couch/gantry/collimator values of 0.46-0.68 mm across the three institutions. Dosimetric data showed good agreement between machines. The average MLC DLGs for 6, 10, and 15 MV photons were 1.33 ± 0.23, 1.57 ± 0.24, and 1.61 ± 0.26 mm, respectively. 6XFFF and 10XFFF modes had average DLGs of 1.16 ± 0.22 and 1.44 ± 0.30 mm, respectively. MLC transmission showed minimal variation across the three institutions, with the standard deviation <0.2% for all linacs. Photon and electron PDDs were comparable for all energies. 6, 10, and 15 MV photon beam quality, %dd(10)x varied less than 0.3% for all linacs. Output factors (Scp) and electron cone factors agreed within 0.27%, on average; largest variations were observed for small field sizes (1.2% coefficient of variation, 10 MV, 2 × 2 cm(2)) and small cone sizes (<1% coefficient of variation, 6 × 6 cm(2) cone), respectively. CONCLUSIONS: Overall, excellent agreement was observed in TrueBeam commissioning data. This set of multi-institutional data can provide comparison data to others embarking on TrueBeam commissioning, ultimately improving the safety and quality of beam commissioning.

Superdiffusive motion of the Pb wetting layer on the Si(111) surface.

Mass transport in the Pb wetting layer on the Si(111) surface is investigated by observing nonequilibrium coverage profile evolution with low energy electron microscopy and microlow energy electron diffraction. Equilibration of an initial coverage step profile occurs by the exchange of mass between oppositely directed steep coverage gradients that each move with unperturbed shape. The bifurcation of the initial profile, the shape of the profile between the two moving edges, and the time dependence of equilibration are all at odds with expectations for classical diffusion behavior. These observations signal a very unusual coverage dependence of diffusion or may even reveal an exceptional collective superdiffusive mechanism.

Part I. Molecular and cellular characterization of high nitric oxide-adapted human breast adenocarcinoma cell lines.

There is a lack of understanding of the casual mechanisms behind the observation that some breast adenocarcinomas have identical morphology and comparatively different cellular growth behavior. This is exemplified by a differential response to radiation, chemotherapy, and other biological intervention therapies. Elevated concentrations of the free radical nitric oxide (NO), coupled with the up-regulated enzyme nitric oxide synthase (NOS) which produces NO, are activities which impact tumor growth. Previously, we adapted four human breast cancer cell lines: BT-20, Hs578T, T-47D, and MCF-7 to elevated concentrations of nitric oxide (or high NO [HNO]). This was accomplished by exposing the cell lines to increasing levels of an NO donor over time. Significantly, the HNO cell lines grew faster than did each respective ("PARENT") cell line even in the absence of NO donor-supplemented media. This was evident despite each "parent" being morphologically equivalent to the HNO adapted cell line. Herein, we characterize the HNO cells and their biological attributes against those of the parent cells. Pairs of HNO/parent cell lines were then analyzed using a number of key cellular activity criteria including: cell cycle distribution, DNA ploidy, response to DNA damage, UV radiation response, X-ray radiation response, and the expression of significant cellular enzymes. Other key enzyme activities studied were NOS, p53, and glutathione S-transferase-pi (GST-pi) expression. HNO cells were typified by a far more aggressive pattern of growth and resistance to various treatments than the corresponding parent cells. This was evidenced by a higher S-phase percentage, variable radioresistance, and up-regulated GST-pi and p53. Taken collectively, this data provides evidence that cancer cells subjected to HNO concentrations become resistant to free radicals such as NO via up-regulated cellular defense mechanisms, including p53 and GST-pi. The adaptation to NO may explain how tumor cells acquire a more aggressive tumor phenotype.

Low energy electron microscopy and photoemission electron microscopy investigation of graphene.

Low energy electron microscopy (LEEM) and photoemission electron microscopy (PEEM) are two powerful techniques for the investigation of surfaces, thin films and surface supported nanostructures. In this review, we examine the contributions of these microscopy techniques to our understanding of graphene in recent years. These contributions have been made in studies of graphene on various metal and SiC surfaces and free-standing graphene. We discuss how the real-time imaging capability of LEEM facilitates a deeper understanding of the mechanisms of dynamic processes, such as growth and intercalation. Numerous examples also demonstrate how imaging and the various available complementary measurement capabilities, such as selected area or micro low energy electron diffraction (µLEED) and micro angle resolved photoelectron spectroscopy (µARPES), allow the investigation of local properties in spatially inhomogeneous graphene samples.

A Contrast Transfer Function approach for image calculations in standard and aberration-corrected LEEM and PEEM.

We introduce an extended Contrast Transfer Function (CTF) approach for the calculation of image formation in low energy electron microscopy (LEEM) and photo electron emission microscopy (PEEM). This approach considers aberrations up to fifth order, appropriate for image formation in state-of-the-art aberration-corrected LEEM and PEEM. We derive Scherzer defocus values for both weak and strong phase objects, as well as for pure amplitude objects, in non-aberration-corrected and aberration-corrected LEEM. Using the extended CTF formalism, we calculate contrast and resolution of one-dimensional and two-dimensional pure phase, pure amplitude, and mixed phase and amplitude objects. PEEM imaging is treated by adapting this approach to the case of incoherent imaging. Based on these calculations, we show that the ultimate resolution in aberration-corrected LEEM is about 0.5 nm, and in aberration-corrected PEEM about 3.5 nm. The aperture sizes required to achieve these ultimate resolutions are precisely determined with the CTF method. The formalism discussed here is also relevant to imaging with high resolution transmission electron microscopy.

SU-E-T-107: Uncertainty Estimate of a Practical EBT-2 Film Dosimetry Approach: Transpose-And-Scan Technique.

PURPOSE: To estimate the uncertainty of a practical EBT2 film dosimetry approach that has been established at our institution and used for routine patient-specific plan verifications, particularly for SBRT and RapidArc, as well as planning system commissioning. Our technique is unique from other common dosimetry protocols with respect to calibration, irradiation and scanning. METHODS: Film dosimetry for patient-specific quality assurance of 29 patient plans were retrospectively reviewed. For each case, four films were irradiated; two for calibration and two for treatment plan. Each pair of two films were irradiated together in a phantom with one film transposed (rotated 180 degrees relative to the other) to compensate for asymmetric film response. After a minimum of 12 hrs post-irradiation, each film was scanned in four different orientations to mitigate non-uniform response of the scanner light and detector elements. The scanned 8 calibration and 8 plan images were averaged into one calibration and one plan film image, respectively. Each color channel of the calibration film was correlated to the reference dose matrix to produce a 3rd order polynomial calibration curve. Finally, each color channel of the plan film was converted to a dose map using the corresponding calibration curve. Average dose maps of the red and green channels were correlated to the treatment planning dose matrix, and the mean dose differences at the center of dose distributions (5×5mm̂2 area) as well as a gamma analysis were evaluated. RESULTS: The absolute dose differences were -0.8±1.7% (range=-4.5-3.0%). The gamma pass-rates (3%/3mm) were 94±7% (min.=74%). The pass rate increased to 99±3%(min.=87%) with the film scaled relatively to the plan doses. CONCLUSIONS: Based on a large number of cases, our approach appears to be robust to non-uniform film and scanner responses, and is shown to have an uncertainty (1SD) of less than 2% for absolute film dosimetry.

SU-E-T-487: Spatial Assessment of Dose Distributions for Patients with Lung Cancer Treated with Stereotactic Ablative Radiotherapy (SABR).

PURPOSE: We hypothesize that PTV margin dose is an important factor for local tumor control. We evaluated dose distributions for patients originally treated with pencil-beam (PB)-based plans and retrospectively calculated with Monte Carlo (MC) method, with emphasis on the spatial region between the ITV and PTV (PTV-margin), where the largest dose differences were expected. METHODS: Forty-six stage I-II lung cancer patients with 51 lesions treated with SABR were retrospectively analyzed (23 central and 28 peripheral tumors). All patients received 4DCT imaging, and an ITV was generated from the maximum intensity projection and subsequent review of four 4DCT phases. An isotropic 3mm ITV-to-PTV margin was used. The iPlan TPS was used to generate the original treatment plans using PB-based heterogeneity correction. MC doses were recalculated using the same MUs as in the PB plan. Dose distributions for the ITV, PTV-margin, and PTV were analyzed using generalized equivalent uniform dose (gEUD) with a = - 20. Student's paired t-test elucidated differences between PB and MC-based gEUD and the two different tumor locations. RESULTS: Mean ITV and PTV volumes were 24.2 cc (range: 2.2 to 99.3 cc) and 50.4 cc (range: 6.4 to 229.7 cc), respectively. The mean gEUDs of ITV, PTV-margin and PTV, normalized to PB-based 100% isodose were 1.02+/-0.04, 1.01+/-0.04 and 1.01+/-0.04 for PB-based plans, compared to 0.94+/-0.06, 0.88+/-0.08 and 0.90+/-0.08 (all p<0.05) for MC-based plans. The maximum overestimations with the PB algorithm in the PTV-margin average dose were 10.4% and 19.6% (p < 0.05) for peripheral tumor cases and central tumor cases, respectively. CONCLUSIONS: PB-based dose distributions showed the highest dose overestimation (relative to MC) in the PTV-margin spatial region. Analysis of spatial dose differences is an important precursor toward assessment of patterns-of-local failure, to be investigated in future work to explore possible association between dose and regions of failure. Acknowledgement: supported in part by grants from NIH R01 CA106770 and from Varian Medical Systems.

Effects of alendronate on bone healing after tooth extraction in rats.

OBJECTIVES: Tooth extraction has been identified as an important risk factor for bisphosphonate-induced osteonecrosis of the jaw. Therefore, the main goal of this study was to determine the effects of alendronate on healing of the extraction socket and on interdental alveolar bone after tooth extraction in rats. MATERIALS AND METHODS: Animals were injected subcutaneously with vehicle or alendronate for 3-4 weeks before the first mandibular molar was extracted and these treatments were continued during post-extraction periods of 10, 21, 35 and 70 days. Mandibles were processed to evaluate healing of the extraction socket and adjacent alveolar bone by assessing bone formation, bone resorption and vascularity by histomorphometric techniques. RESULTS: Alendronate decreased new woven bone formation, blood vessel area, perimeter and number in the extraction socket at 10 days postextraction, but not at later time points. Furthermore, alendronate-treated rats had increased interdental alveolar bone volume and height only at 10 days postextraction. In addition, a 2.5-fold increase in the percentage of empty osteocyte lacunae was found in alveolar bone of alendronate-treated rats only at 10 days postextraction. CONCLUSIONS: Alendronate transiently decreases bone formation and vascularity in the extraction socket and delays the removal of interdental alveolar bone after tooth extraction in rats.