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FERMI@elettra is a fourth-generation light source user facility under construction at the Elettra Laboratory in Trieste, Italy. The high-quality 1.2 GeV electron beam drives two-seeded Free Electron Lasers (FELs) in the wavelength range 100−10 nm. Wavelength tunability, variable polarization and higher electron beam energies to reach even shorter output wavelengths are also in the machine delivery plan. This paper describes the physics processes that have been modelled to simulate FERMI@elettra and the computer codes used to optimize the machine design. The paper focuses on several design challenges and how these translate into modelling and simulation challenges.

We describe 3 cases of apparent odontogenic carcinomas that share histologic features not previously reported in the literature. The tumors involved one 72-year-old man and 2 women, 46-year old and 73-year old, respectively. Two cases occurred in the mandible and 1 in the maxilla. The tumors presented as expansile radiolucencies. Histopathologically, they were characterized by small nests and thin cords of small cuboidal or polygonal epithelial cells, featuring, only focally, cytoplasmic clearing. Pleomorphism was not remarkable and mitoses were extremely rare. The most striking feature of malignancy was skeletal muscle and perineural infiltration. Sclerosis of the stroma was remarkable. Immunohistochemically, all tumors stained for cytokeratins (CK) 5/6, CK19, and epsilon-cadherin, the latter exhibiting a fragmented cytoplasmic membranous staining. Positive nuclear staining was obtained with p63. Focal staining for CK7 was seen in 1 case. All tumors were negative for CK20, carcinoembryonic antigen, and CAM5.2. The patients were surgically treated and one of them received adjuvant radiation. Microscopic tumor nests and cords were found far beyond of what surgically seemed to be tumor-free margins. All patients are free of disease 5, 12, and 4 years after treatment, respectively. We propose the name sclerosing odontogenic carcinoma. As current classifications of odontogenic tumors do not include such examples, it is important that pathologists become aware of this entity. Finally, this report supports recent literature on positive nuclear p63 in odontogenic cysts and tumors.

Objective: This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months. Methods: The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non–enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained. Results: The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided χ 2 test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed ( p = 0.045 by one-sided, mid- p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) ( p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a ≥50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a ≥25% reduction) but not those randomly assigned to placebo (5% with a ≥25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients. Conclusion: Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.

Objective: To evaluate the efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for partial seizures in epilepsy. Methods: Patients more than 12 years old diagnosed with epilepsy with partial seizures and taking one to two baseline antiepileptic drugs were randomized to adjunctive once-daily lamotrigine XR or placebo in a double-blind, parallel-group trial. The study comprised a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase during which doses of study medication and concomitant antiepileptic drugs were maintained. Results: Of the 243 randomized patients, 239 (118 lamotrigine XR, 121 placebo) entered the escalation phase and received study medication. Lamotrigine XR was more effective than placebo with respect to median percent reduction from baseline in weekly partial seizure frequency (primary endpoint—entire 19-week treatment phase: 46.1% vs 24.2%, p = 0.0004 via Wilcoxon test; escalation phase: 28.0% vs 16.3%, p = 0.028; maintenance phase: 58.0% vs 26.7%, p p = 0.0037) and time to ≥50% reduction in partial seizure frequency ( p = 0.0007) also favored lamotrigine XR over placebo. A similar pattern of results was observed for secondarily generalized seizures. The most common adverse events were headache (lamotrigine XR 17%, placebo 15%) and dizziness (lamotrigine XR 18%, placebo 5%). Differences between lamotrigine XR and placebo on health outcomes measures were not significant. Conclusions: Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation. GLOSSARY: AED = antiepileptic drug; AEP = Adverse Experience Profile; CES-D = Center for Epidemiologic Studies-Depression Scale; ESS = Epworth Sleepiness Scale; IR = immediate-release; NDDI-E = Neurological Disorders Depression Inventory-Epilepsy; POMS = Profile of Mood States; QOLIE-31-P = Quality of Life in Epilepsy-31-P; SSQ = Seizure Severity Questionnaire; VNS = vagus nerve stimulators; XR = extended-release.

We report on high resolution measurements of resonances in the spectrum of coherent synchrotron radiation (CSR) at the Canadian Light Source (CLS). The resonances permeate the spectrum at wavenumber intervals of $0.074 ~\textrm{cm}^{-1}$, and are highly stable under changes in the machine setup (energy, bucket filling pattern, CSR in bursting or continuous mode). Analogous resonances were predicted long ago in an idealized theory as eigenmodes of a smooth toroidal vacuum chamber driven by a bunched beam moving on a circular orbit. A corollary of peaks in the spectrum is the presence of pulses in the wakefield of the bunch at well defined spatial intervals. Through experiments and further calculations we elucidate the resonance and wakefield mechanisms in the CLS vacuum chamber, which has a fluted form much different from a smooth torus. The wakefield is observed directly in the 30-110 GHz range by RF diodes, and indirectly by an interferometer in the THz range. The wake pulse sequence found by diodes is less regular than in the toroidal model, and depends on the point of observation, but is accounted for in a simulation of fields in the fluted chamber. Attention is paid to polarization of the observed fields, and possible coherence of fields produced in adjacent bending magnets. Low frequency wakefield production appears to be mainly local in a single bend, but multi-bend effects cannot be excluded entirely, and could play a role in high frequency resonances. New simulation techniques have been developed, which should be invaluable in further work., 5 figures. Differs from first posting by correction of typo and inclusion of responses to referee's questions

Sialoblastoma is a rare congenital or perinatal salivary tumor that varies in histologic features and biologic potential. Seven cases from the files of the Armed Forces Institute of Pathology are presented. These tumors occurred in 4 males and 3 females with ages ranging from prenatal to 6 months at the time of discovery. Five lesions originated from the parotid gland; 2 lesions were from the submandibular gland. All lesions presented as nodular to multinodular swellings and ranged in size from 2.0 to 7.0 cm. The principal sign or symptom was rapid growth. Two histologic patterns with differing behavior predominated: (1) a favorable pattern had semiencapsulation of cytologically benign basaloid tumor cells with intervening stroma; and (2) an unfavorable histology of anaplastic basaloid tumor cells, minimal stroma, and broad pushing to infiltrative periphery. Four and three tumors had favorable and unfavorable growth patterns, respectively. One unfavorable lesion had vascular invasion, and another demonstrated perineural invasion. All 3 tumors with unfavorable histology recurred. Tumor cells in 3 cases were immunohistochemically reactive for keratin, S-100, smooth muscle actin, and calponin to varying degrees. All 3 tumors were reactive for p63. alpha-Fetoprotein was expressed in 2 unfavorable tumors. Ki67 was expressed at 3% in a favorable tumor and 40% and 80% in the 2 unfavorable lesions. Treatment involved surgical excision. One patient received adjuvant chemotherapy. Two sialoblastomas resulted in recurrences within a year and another developed a recurrence after 4 years. One sialoblastoma developed lung metastasis within 1 month of the original biopsy. Although a clinical correlation is suggested by a favorable/unfavorable histologic grading system the biologic behavior is nonetheless considered unpredictable.

Glandular odontogenic cyst (GOC) is a cyst of the gnathic bones that is characterized by squamous and glandular differentiation. The histopathologic features of GOC overlap considerably with central mucoepidermoid carcinoma (MEC), suggesting that GOC could be a precursor lesion to, or even a low-grade form of, central MEC. Differentiating the two lesions may be difficult or impossible on a limited biopsy. MAML2 rearrangements have been recently found to be specific for MEC, even those arising in the jaws. An analysis of MAML2 in GOCs could help clarify its relationship with central MEC. Tissue blocks from 21 GOCs and 5 central MECs were retrieved from the surgical pathology archives of The Johns Hopkins Hospital. Each MEC exhibited solid areas and clear-cut stromal invasion. In addition, 4 of the MECs demonstrated cystic areas that were histologically similar to GOC. Break-apart fluorescence in situ hybridization for MAML2 was performed. For the MECs, analysis was performed on both the solid components and the cystic areas that resembled GOC. MAML2 rearrangements were identified in all 5 of the MECs, but in none of the 21 GOCs (100 vs. 0 %; p

In self-consistent modeling of many-particle systems it is convenient to solve the Maxwell equations for self-fields in coordinates based in the laboratory with time as the evolution variable, but conventional and also convenient to follow particle motion in Frenet-Serret coordinates referred to a reference orbit, with arclength along that orbit as the evolution variable. We refer to these two pictures as the laboratory system and beam system descriptions, while emphasizing that a Lorentz transformation is not involved; it is only a matter of two alternative descriptions of motion in one inertial frame. The problem then arises of how to express the laboratory system charge/current density for the Maxwell equations in terms of the phase space density described in the beam system. We find the exact expression, then make justified approximations to put the formula in a simple and practical form. Incidentally, we derive exact and approximate equations of motion in the different coordinates, without the use of the canonical formalism. The results have been applied in a study of coherent synchrotron radiation in bunch compressors.

We study the microbunching instability in a bunch compressor by a parallel code with some improved numerical algorithms. The two-dimensional charge/current distribution is represented by a Fourier series, with coefficients determined through Monte Carlo sampling over an ensemble of tracked points. This gives a globally smooth distribution with low noise. The field equations are solved accurately in the lab frame using retarded potentials and a novel choice of integration variables that eliminates singularities. We apply the scheme with parameters for the first bunch compressor system of FERMI@Elettra, with emphasis on the amplification of a perturbation at a particular wavelength and the associated longitudinal bunch spectrum. Gain curves are in rough agreement with those of the linearized Vlasov system at intermediate wavelengths, but show some deviation at the smallest wavelengths treated and show the breakdown of a coasting beam assumption at long wavelengths. The linearized Vlasov system is discussed in some detail. A new 2D integral equation is derived which reduces to a well-known 1D integral equation in the coasting beam case.

Objective To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy. Methods Female individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) therapy. Serum androgen levels were measured every 3 months. Urinary pregnanediol glucuronide levels were measured weekly for two 3-month periods. The primary end point was development of PCOS components (ie, hyperandrogenism or ovulatory dysfunction). A post hoc analysis was conducted in women more than 2 years after menarche (177 lamotrigine, (HA) 186 valproate) to exclude OD the confounding effect of puberty. Results More women in the valproate group than the lamotrigine group developed (OD) in the prospective (54% valproate, 38% lamotrigine; p = 0.010) and the post hoc (HA) analyses (36% valproate, 23% lamotrigine; p = 0.007). More women in the valproate group than the lamotrigine group developed PCOS (9 vs 2%; p = 0.007). Development of HA was more frequent with OD valproate than lamotrigine among those initiating treatment at age younger than 26 years (44% valproate, 23% lamotrigine; p = 0.002) but was similar if treatment was started at age 26 years or older (24% valproate, 22% lamotrigine). Interpretation Development of HA occurred more frequently with valproate than lamotrigine, especially if medication was started at age younger than 26 years. Ann Neurol 2008;64:200–211

This open-label study was designed to evaluate the long-term tolerability and efficacy of lamotrigine in 1- to 24-month-old infants with partial seizures. The study enrolled both lamotrigine-naïve patients and patients who had been previously exposed to lamotrigine in a randomized, double-blind, placebo-controlled study. Patients (n = 204) received lamotrigine according to a dosing schedule that depended on prior experience with lamotrigine and concurrent antiepileptic drug therapy for up to 48 weeks or their second birthday, whichever occurred last. Total duration of lamotrigine exposure (which included exposure during the placebo-controlled study in lamotrigine-experienced patients) was ≥24 weeks in 92% of patients, ≥48 weeks in 70% of patients, and ≥72 weeks in 20% of patients. A total of 20 (10%) patients (8 lamotrigine-naïve patients and 12 lamotrigine-experienced patients) transitioned to lamotrigine monotherapy. The most common adverse events were pyrexia (45% of patients), upper-respiratory tract infection (28%), and ear infection (22%). The only adverse event considered reasonably attributable to study medication in >2% of patients was irritability (n = 10; 5% of patients). No cases of serious rash were reported. The median percent reduction from baseline in partial seizure frequency in the sample as a whole was 74%. Seizure frequency was reduced by ≥50% from pre-lamotrigine baseline in 62% of patients in the sample as a whole, 60% of the lamotrigine-naïve subgroup, and 63% of the lamotrigine-experienced subgroup. In the sample as a whole, 13% of patients were seizure free during the Treatment Phase. Investigators considered clinical status at the last clinic visit to be improved (mildly, moderately, or markedly) relative to prelamotrigine clinical status in 76% of patients (150/197) and to be unchanged in 19% (37/197). In this study—the first large prospective investigation of the long-term tolerability and efficacy of an antiepileptic drug in a patient population 2 years and younger—lamotrigine administered for up to approximately 72 weeks was well tolerated and associated with good seizure control.

We discuss our progress on the self-consistent calculation of the 4D phase space density (PSD) and electromagnetic fields in a Vlasov-Maxwell formulation. We emphasize coherent synchrotron radiation (CSR) from arbitrary curved planar orbits, with shielding from the vacuum chamber, but space charge forces are naturally included. Our focus on the Vlasov equation will provide simulations with lower numerical/statistical noise than standard PIC methods, and will allow the study of issues such as emittance degradation and microbunching due to space charge and CSR in bunch compressors. The fields excited by the bunch are computed in the lab frame from a new double integral formula. The field formula is derived from retarded potentials by changes of variables. It is singularity-free and requires no computation of retarded times. Ultimately, the Vlasov equation will be integrated in beam frame coordinates using our method of local characteristics. As an important intermediate step, we have developed a "self-consistent Monte Carlo algorithm", and a corresponding parallel code. This gives an accurate representation of the source and will help in understanding the PSD support. In addition we have (1) studied carefully a 2D phase space Vlasov analogue and (2) derived an improved expression of the field of a 1D charge/current distribution which accounts for the interference of different bends and other effects usually neglected. Bunch compressors will be emphasized.

This report describes the accelerator physics aspects, the engineering considerations and the choice of parameters that led to the accelerator design of the FERMI Free-Electron-Laser. The accelerator (also called the electron beam delivery system ) covers the region from the exit of the injector to the entrance of the first FEL undulator. The considerations that led to the proposed configuration were made on the basis of a study that explored various options and performance limits. This work follows previous studies of x-ray FEL facilities (SLAC LCLS [1], DESY XFEL [2], PAL XFEL [3], MIT [4], BESSY FEL[5], LBNL LUX [6], Daresbury 4GLS [7]) and integrates many of the ideas that were developed there. Several issues specific to harmonic cascade FELs, and that had not yet been comprehensively studied, were also encountered and tackled. A particularly difficult issue was the need to meet the requirement for high peak current and small slice energy spread, as the specification for the ratio of these two parameters (that defines the peak brightness of the electron beam) is almost a factor of two higher than that of the LCLS's SASE FEL. Another challenging aspect was the demand to produce an electron beam with as uniform as possible peak current and energy distributions along the bunch, a condition that was met by introducing novel beam dynamics techniques. Part of the challenge was due to the fact that there were no readily available computational tools to carry out reliable calculations, and these had to be developed. Most of the information reported in this study is available in the form of scientific publications, and is partly reproduced here for the convenience of the reader.

An important action item for the damping rings of the International Linear Collider (ILC) is to compute the broadband impedance and, from it, the threshold to the microwave instability. We report on the status of our study and provide a preliminary estimate of the instability threshold based on impedance models developed so far.

Direct numerical methods for solving the Vlasov equation offer some advantages over macroparticle simulations, as they do not suffer from the numerical noise inherent in using a number of macroparticles smaller than the bunch population. Unfortunately these methods are more time-consuming and generally considered impractical in a full 6D phase space. However, in a lower-dimension phase space they may become attractive if the beam dynamics is sensitive to the presence of small charge-density fluctuations and a high resolution is needed. In this paper we present a 2D Vlasov solver for studying the longitudinal beam dynamics in single-pass systems of interest for X-FEL's, where characterization of the microbunching instability is of particular relevance. The solver includes a model to account for the smearing effect of a finite horizontal emittance on microbunching. We explore the effect of space charge and coherent synchrotron radiation (CSR). The numerical solutions are compared with results from linear theory and good agreement is found in the regime where linear theory applies.

We take a detour from the main theme of this volume and present a discussion of coherent synchrotron radiation (CSR) in the context of storage rings rather than single-pass systems. Interest in this topic has been revived by a series of measurements carried out at several light source facilities. There is strong evidence that the observed coherent signal is accompanied by a beam instability, possibly driven by CSR itself. In this paper we review a “self-consistent” model of longitudinal beam dynamics in which CSR is the only agent of collective forces. The model yields numerical solutions that appear to reproduce the main features of the observations.

We study a nonlinear integral equation that is a necessary condition on the equilibrium phase-space distribution function of stored, colliding electron beams. It is analogous to the Haïssinski equation, being derived from Vlasov-Fokker-Planck theory, but is quite different in form. The equation is analyzed for the case of the Chao-Ruth model of the beam-beam interaction in 1 degree of freedom, a so-called strong-strong model with nonlinear beam-beam force. We prove the existence of a unique solution, for sufficiently small beam current, by an application of the implicit function theorem. We have not yet proved that this solution is positive, as would be required to establish existence of an equilibrium. There is, however, numerical evidence of a positive solution. We expect that our analysis can be extended to more realistic models.

The authors evaluate the longitudinal coupling impedance of a toroidal chamber with rectangular cross section in the frequency domain below the synchronous resonant modes. With infinite wall conductivity the impedance is purely reactive and consists of a space charge term, proportional to gamma /sup -2/, and a curvature term which survives at large gamma . The curvature term is well represented as a quadratic function of frequency. Consequences for beam stability, if any, arise from high-frequency resonances, which can produce values of several ohms for Z/n. >

Dermoid cysts are rare developmental teratomatous lesions composed of ectodermally derived stratified squamous epithelium and mesodermally derived skin adnexal structures. As part of the teratomatous lesion group, dermoid cysts are related to teratoid cysts, true teratomas, and epignathi. Although several theories have been postulated, the pathogenesis of dermoid cysts, and teratomatous lesions in general, is unclear. Most commonly affecting sites within the head and neck, dermoid cysts may be found in the frontotemporal/lateral brow area, central nasal area, oral cavity, lateral neck, and other sites. We present what is believed to be the first reported case arising within the maxillary sinus and briefly discuss the possible pathogenesis.

The effect of hyperbaric oxygen on epiphyseal ischemia was evaluated using a pediatric rabbit model. Forty-five animals were compared in this study: 23 from a control pilot study and 22 hyperbaric exposed animals. In each animal the right distal femoral and proximal tibial epiphyses were isolated on a popliteal vascular pedicle. The left leg acted as the control. The growth difference between the rabbit's hindlimbs was the means of comparison throughout the groups established. Warm ischemia was induced by applying a vascular clamp to the right popliteal artery for 12 hours (20 animals) and 7 hours (17 animals). The remaining 8 animals underwent a sham operation without interruption of epiphyseal perfusion. On completion of the ischemic period hyperbaric oxygen therapy (HBOT) was performed on 12 12-hour (12h-HBOT) and 10 7-hour (7h-HBOT) animals at 2 atmospheres for 90 minutes twice per day for 4 postoperative days. The animals were killed on either postoperative day 14 or 90. Measurement of longitudinal bone growth was performed on the 90-day animals from serial radiographs at the time of surgery and then at 1 month, 2 months, and 3 months after surgery. There was no significant difference in longitudinal bone growth between the sham-operated and the 7h-HBOT animals at 1, 2, and 3 months. There was a statistically significant difference, however, between the normal growth of the 7h-HBOT group compared with the abnormal growth of the 7-hour, 12-hour, and 12h-HBOT animals. Histology was consistent, with the bone growth data demonstrating relative normalcy of the 7h-HBOT group epiphyseal plates versus severe architectural aberrance and necrosis of the 12h-HBOT group epiphyses. Our experimental data indicate that a clinical trial should be instituted using HBO for pediatric replantation patients when warm ischemia exceeds 7 hours. (J Hand Surg 2000;25A:159–165. Copyright © 2000 by the American Society for Surgery of the Hand.)

The Working Group on single-particle nonlinear dynamics has developed a set of tools to study nonlinear dynamics in a particle accelerator. The design of rings with large dynamic apertures is still far from automatic. The Working Group has concluded that nonlinear single-particle dynamics limits the performance of acclerators. (AIP)

As investigations into the forensic aspects of DNA analysis continue, the human tooth will play a dual role in identification. Dentin and enamel provide a protective enclosure for genomic and mitochondrial DNA as well as providing the basis for radiographic, biochemical, and ultrastructural forensic studies. The purpose of this investigation is to establish technical guidelines, based on histology and experimental evidence, for the management and sampling of dental DNA. The anatomic location of dental DNA is discussed with emphasis on the conservation of tooth structure during sampling. Ten pairs of maxillary right and left third molars were sampled for DNA following storage for 18 weeks at ambient temperature and humidity. Right third molars were crushed, whereas the left third molars were sectioned conservatively prior to sampling the DNA. The quantity and quality of human DNA obtained from each tooth was compared, as well as the radiographic appearance of remaining hard tissue and the overall simplicity of each approach. DNA typing was performed, both sequence and length based analyses, comparing teeth from the same individual and teeth from different donors. The results of this study suggest that the odontologist will maximize the dental DNA yield by crushing the entire specimen but that substantial yields of human DNA can be obtained by using a conservative technique that preserves the tooth structure. In addition, the method of sampling does not affect the ability to perform DNA typing analyses.

The role of oral pathologists as members of the comprehensive health care team is reviewed. The importance of utilizing an Oral Pathology Service in the everyday practice of dentistry and medicine and the inherent medicolegal considerations are discussed. Standards of care for submission of surgically removed oral tissues is an issue that warrants further delineation.

Abstract 4162 Introduction The CLASSIC II trial previously reported an overall remission rate of 46% (38% complete remission [CR] and 8% CR with incomplete platelet recovery [CRp]), median duration of remission 56 weeks, median disease-free survival 37 weeks, median overall survival 41 weeks, and 30- and 60-day mortality rates 10% and 16%, respectively (JCO 2009; 27:371s, A.7062). Among the patients achieving remission, 75% achieved a CR or CRp after the first induction cycle and 25% after the re-induction cycle. This trial allowed physicians the discretion to treat patients with inpatient (IP) or outpatient (OP) clofarabine (CLO). This report describes the experience with OP CLO treatment. Methods CLASSIC II was a single arm, Phase II study of patients ≥ 60 years of age with untreated AML with at least one unfavorable baseline prognostic factor (PF): age ≥70 years, ECOG performance status 2, antecedent hematological disorder (AHD), and/or intermediate/unfavorable risk karyotype. CLO was administered days 1-5 at 30 mg/m2 IV over 1hour during induction and at 20 mg/m2 during re-induction/consolidation for a maximum of 6 cycles. Patients with confirmed AML who received one dose of CLO were eligible for analysis. Results 112 patients (median age 71 years) received a median of 2 cycles of CLO. Thirty-five (31%) patients received OP CLO for a total of 72 outpatient cycles (Table). This report will focus only on OP CLO in cycles 2-6, since only 2 patients received OP CLO in cycle 1. 66 patients initiated a second cycle of clofarabine (38 as re-induction; 28 as consolidation). 33/66 (50%) patients received at least 1 OP cycle of CLO for a total of 70 OP cycles (57% of all cycles 2-6). 12/33 received at least 2 OP cycles of CLO. Patients received a median of 1 OP cycle (range 1-5). All 70 OP cycles were administered for 5 OP days except for 2 cycles given for 2 OP days followed by 3 IP days (associated with OP toxicities: Grade 3 rash in 1 patient and increasing transaminase levels in 1 patient). For the 70 OP cycles, 42 (60%) cycles did not require any subsequent hospitalization, while 28 (40%) cycles required hospitalization. Baseline patient and disease characteristics and treatment toxicities for patients receiving OP versus IP CLO and the reasons for hospitalization after OP CLO will be presented at the meeting. Conclusions Outpatient clofarabine can be safely administered to older patients with previously untreated AML and at least one unfavorable prognostic factor. OP CLO was primarily used for cycles 2-6, including both cycle 2 re-induction and consolidation. 60% of OP CLO cycles never required hospitalization. Proper patient selection, education, and monitoring for adverse events after OP CLO are necessary. OP CLO offers patients a more convenient option for treatment of their AML. TABLE . Induction Re-Induction Consolidation Cycle 1 Cycle 2 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Number of patients and CLO cycles 112 38 28 23 16 10 8 OP study drug administration * (n=70 for cycles 2-6) 2 (2%) 12 (32%) 18 (64%) 14 (61%) 11 (69%) 8 (80%) 7 (88%) OP cycles not requiring subsequent hospitalization (% OP cycles) (n=42 for cycles 2-6) 0 (0%) 4 (33%) 8 (44%) 10 (71%) 8 (73%) 6 (75%) 6 (86%) OP cycles requiring subsequent hospitalization (% OP cycles) (n=28 for cycles 2-6) 2 (100%) 8 (67%) 10 (56%) 4 (29%) 3 (27%) 2 (25%) 1 (14%) Days in hospital for OP cycles requiring hospitalization, median (range) 22 (19-25) 6 (2-17) 11 (6-52) 9 (1-11) 8 (2-39) 5 (5-5) 7 (NA) * All OP cycles = 5 days except 2 patients with 2 days OP followed by 3 days IP Disclosures: Claxton: Genzyme: Research Funding. Myers: Genzyme: Employment. Erba: Lilly: Research Funding; Antisoma: Research Funding; Wyeth: Research Funding; Cephalon: Honoraria, Research Funding; MGI Pharma: Honoraria; Pharmion: Honoraria; Celgene: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; Gemin-X: Research Funding; Kanisa: Research Funding. Faderl: Genzyme: Research Funding. Arellano: Genzyme: Research Funding. Lyons: Celgene: Consultancy; JohnsonJ GlaxoSmithKline: Consultancy, Speakers Bureau; Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genzyme: Research Funding. Kovacsovics: Genzyme: Research Funding. Gabrilove: Genzyme: Research Funding. Warnock: Genzyme: Employment. Kantarjian: Genzyme: Research Funding.

The case of an anterior mandibular radiolucent area, which unexpectedly yielded salivary gland tissue, is described. Salivary gland depressions in the posterior mandible are readily recognized because of their almost pathognomonic radiographic appearance. A salivary gland inclusion in the anterior mandible in the proximity of teeth may create a diagnostic dilemma where superimposed periapical pathosis is present. The clinical importance lies in the recognition and appropriate treatment of the lesion. For the anterior salivary gland inclusion, a biopsy and a microscopic examination provide the most reliable diagnosis.

The role of oral pathologists as members of the comprehensive health care team is reviewed. The importance of utilizing an Oral Pathology Service in the everyday practice of dentistry and medicine and the inherent medicolegal considerations are discussed. Standards of care for submission of surgically removed oral tissues is an issue that warrants further delineation.

As investigations into the forensic aspects of DNA analysis continue, the human tooth will play a dual role in identification. Dentin and enamel provide a protective enclosure for genomic and mitochondrial DNA as well as providing the basis for radiographic, biochemical, and ultrastructural forensic studies. The purpose of this investigation is to establish technical guidelines, based on histology and experimental evidence, for the management and sampling of dental DNA. The anatomic location of dental DNA is discussed with emphasis on the conservation of tooth structure during sampling. Ten pairs of maxillary right and left third molars were sampled for DNA following storage for 18 weeks at ambient temperature and humidity. Right third molars were crushed, whereas the left third molars were sectioned conservatively prior to sampling the DNA. The quantity and quality of human DNA obtained from each tooth was compared, as well as the radiographic appearance of remaining hard tissue and the overall simplicity of each approach. DNA typing was performed, both sequence and length based analyses, comparing teeth from the same individual and teeth from different donors. The results of this study suggest that the odontologist will maximize the dental DNA yield by crushing the entire specimen but that substantial yields of human DNA can be obtained by using a conservative technique that preserves the tooth structure. In addition, the method of sampling does not affect the ability to perform DNA typing analyses.

Topically applied 5-fluorouracil has recently gained acceptance in the treatment of actinic keratosis of the lip; however, histologic evidence confirming the effectiveness of the therapy has not yet been established. Pretreatment biopsies were performed on six patients to confirm actinic damage and grade the degree of dysplasia. After 5-fluorouracil therapy, biopsies of tissue adjacent to the previous biopsy sites were performed to determine the success of treatment. Histologic evaluation showed residual dysplasia in all posttreatment biopsy material, even though the clinical stigmata of the actinic lesions had been improved or eliminated.

A 62-year-old male patient with a varied medical history and oral lesions consistent with stomatitis areata migrans is discussed. The stomatitis areata migrans affected essentially all oral soft tissues, including rarely involved gingival tissues. Clinical and histologic documentation of the gingival involvement is presented.

Pyoderma gangrenosum (PG) is a rare pathergy associated with systemic diseases such as ulcerative colitis and polycythemia vera. Its recognition in the differential diagnosis of other ulcerative lesions is important in managing an affected patient. A patient who developed lower extremity, oral, and cervical manifestations of this disease on separate occasions is presented. It is imperative that every clinician be aware of this entity because of the potential untoward effects of delayed or improper treatment including unnecessary surgery. Systemic and intralesional steroids are the treatment of choice.

The squamous odontogenic tumor is a rare odontogenic neoplasm occurring primarily in the anterior maxilla and posterior mandible. The clinical presentation is that of tooth mobility with a semicircular or triangular, well-defined radiolucent area. Histologic features include dense fibrous connective stroma with scattered islands of bland epithelium exhibiting no ameloblastomatous features. Conservative surgical treatment in most cases is sufficient; however, lesions in the maxilla may require more extensive surgical procedures to ensure resolution.

The case reported is that of an ameloblastic fibro-odontoma in an 11-year-old male. The radiographic and clinical findings were typical, appearing as a well-defined radiolucent-radiopaque lesion coronal to an erupting permanent tooth. Treatment consisted of surgical removal (enucleation) of the hard and soft tissue mass. Recurrence of the lesion is not anticipated.

The effects of exposure of animals to 100% O2 and NO2 on the rate of prostaglandin metabolism by lung and kidney were studied in vitro. Exposure of guinea pigs to 100% O2 for 48 h inhibited the metabolism of prostaglandin F2 alpha by both NAD+- and NADP+-dependent prostaglandin dehydrogenase in lung, but had no effect on the metabolism in kidney. Succinate dehydrogenase, but not glucose 6-phosphate dehydrogenase, in guinea-pig lung was inhibited by exposure to 100% O2. Exposure to 46 p.p.m. but not 16 or 29 p.p.m. NO2 for 6 h inhibited guinea-pig lung prostaglandin dehydrogenase in vitro. The inhibition of pulmonary prostaglandin dehydrogenase by exposure to 100% O2 or to 49 p.p.m. NO2 was dependent on the duration of exposure, but returned to control values within 7 days after cessation of the exposure. The pulmonary transport system responsible for removing circulating prostaglandins from the blood was not affected by exposure to 100% O2 as measured by using the isolated perfused lung. Kinetic analysis of the inhibition of pulmonary prostaglandin dehydrogenase activity in guinea pig exposed to 100% O2 showed non-competitive inhibition with respect to both prostaglandin F2 alpha and NAD+, which suggests destruction or inactivation of the enzyme. Pulmonary prostaglandin dehydrogenase appears to be inhibited by exposure to oxidant gases, which may lead to elevated prostaglandin concentrations in the lungs or in the systemic circulation.

Vascular tumors (vascular malformations and hemangiomas) of the temporal bone are uncommon, and guidelines for their management have not been published. In an effort to develop an approach to their management, the present study examined the pathological, clinical, and surgical experience with ten of these lesions treated at the Otologic Medical Group, Inc., and St. Vincent Medical Center in Los Angeles from 1960 to 1980. Intratemporal vascular tumors occurred most frequently at two sites, the internal auditory canal and the geniculate ganglion. Histological features and clinical behavior did not correlate. Both vascular malformations and hemangiomata invaded the facial nerve. Surgical excision in these cases required severence and repair of the involved facial nerve. Complete surgical excision is the treatment of choice of vascular lesions of the temporal bone.

Gingival plane xanthomas are unusual oral presentations of hyperlipidemia and they may be of minimal clinical significance to the patient because they are asymptomatic. However, the presence of gingival xanthomas should be considered as a possible precursor of an underlying life-threatening disease process. Many of these systemic conditions may severely compromise dental therapy; they include atherosclerotic coronary disease, peripheral vascular disease, diabetes mellitus, biliary cirrhosis, multiple myelomas, leukemia, and hyperthyroidism. Clinicians should be aware of this association and its important implications.

A case involving a 22-year-old male patient with early aggressive cemento-ossifying fibroma in the mandible is discussed. The historical difficulty in categorizing fibro-osseous lesions is reviewed, and the importance of clinical, radiographic, and surgical findings to the ultimate diagnosis and correct treatment of these lesions is emphasized.