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A model system consisting of Eu(3+) as the activator ion and BaZrO(3) as the host lattice is employed to demonstrate the potential of the vapor diffusion sol-gel method as a hydrolytic approach to the synthesis of fluorescent alkaline-earth perovskite oxide nanocrystals under ultrabenign conditions. The resulting nanocrystals are suitable precursors for nanostructured red-emitting phosphors.

In response to a hemorrhagic fever with renal syndrome case in November 2000, a seasonal rodent-borne disease surveillance program was initiated at Dagmar North Training Area (DNTA), Gyeonggi Province, Republic of Korea. From April 2001-December 2005, 1,848 small mammals were captured. Apodemus agrarius accounted for 92.5%, followed by Mus musculus (3.6%), Crocidura lasiura (2.1%), and Microtus fortis (1.1%). Three species of rodents were found to be antibody-positive (Ab+) for Hantaan virus (HTNV): A. agrarius (22.3%), M. musculus (9.1%), and M. fortis (5.0%). Ab+ rates for A. agrarius increased with increasing weight (age), except for those weighing10 g. The peak HTNV transmission period in Korea coincided with the peak reproductive potential of A. agrarius during the fall (August/September) surveys. HTNV strains from DNTA were distinct from HTNV strains from the People's Republic of China. From these studies, more accurate risk assessments can be developed to better protect personnel from rodent-borne diseases.

Rift Valley fever (RVF) virus is a mosquito-borne virus associated with epidemics in livestock and humans [1]. Since the 1970s, periodic epidemics of RVF associated with heavy rainfall and flooding have been reported in an increasing number of countries of eastern and southern Africa where the virus became endemic, including Kenya, Somalia, Sudan, Tanzania, Zimbabwe, South Africa, and Madagascar [2–8]. The RVF epidemics have also occurred in countries where virus activity was not previously detected, such as Egypt in 1977, Mauritania in 1983, and Saudi Arabia and Yemen in 2000 [2, 4, 7]. In these naive ecologies, propagation of the epidemic appears to be the result of spread of the newly introduced virus across nonimmune livestock and human populations through animal movement and mosquito vectors. This conclusion is supported by molecular epidemiological data showing that RVF virus strains recovered during epidemics in naive ecologies belonged to a single lineage with minimal genetic diversity [9, 10]. For example, comparison of 6 RVF virus isolates from the Egyptian epidemic of 1977 identified a single lineage of virus with 1100 suspected cases in humans resulting in 350 deaths were reported across the 3 countries, as well as thousands of livestock abortions and deaths [14, 17]. The early detection of the epidemics in each country enabled us to perform spatial mapping of the sequential outbreaks across 3 countries and to isolate and genetically characterize RVF virus strains from most of the outbreak foci.

The relative binding affinities of Mnt protein are determined for each possible base-pair at position 15 of the operator sequence, and for all combinations of G.C base-pairs at positions 15 and 17. The partitioning of each operator sequence is determined quantitatively with restriction enzymes. At position 15, the wild-type G.C base-pair provides the highest binding affinity but, unlike position 17, the primary distinction is between purine and pyrimidine bases on the top strand. The information content at position 15 is only about 0.16 bit. In comparison with previous measurements at position 17, it is determined that the interactions of the Mnt protein with positions 15 and 17 are independent, i.e. the specific binding energies for the two positions are additive. The relative binding affinities at position 17 are also determined in the background of a G to T mutation at position 5, the position equivalent to 17 on the other half of the symmetric operator. The relative affinities at position 17 are independent of whether position 5 is wild-type or mutant.

Vector-borne diseases such as malaria, dengue, and leishmaniasis are a threat to military forces deployed outside of the United States. The availability of specific information on the vector-borne disease threat (e.g., presence or absence of a specific disease agent, temporal and geographic distribution of competent vectors, and vector infection rates) allows for effective implementation of appropriate measures to protect our deployed military forces. Vector diagnostics can provide critical, real-time information crucial to establishing effective vector prevention/control programs. In this article we provide an overview of current vector diagnostic capabilities, evaluate the use of vector diagnostics in Operation Enduring Freedom and Operation Iraqi Freedom, and discuss the concept of operations under which vector diagnostics are employed.

Sand flies collected between April 2003 and November 2004 at Tallil Air Base, Iraq, were evaluated for the presence of Leishmania parasites using a combination of a real-time Leishmania-generic polymerase chain reaction (PCR) assay and sequencing of a 360-bp fragment of the glucose-6-phosphate-isomerase (GPI) gene. A total of 2,505 pools containing 26,574 sand flies were tested using the real-time PCR assay. Leishmania DNA was initially detected in 536 pools; however, after extensive retesting with the real-time PCR assay, a total of 456 pools were considered positive and 80 were considered indeterminate. A total of 532 samples were evaluated for Leishmania GPI by sequencing, to include 439 PCR-positive samples, 80 PCR-indeterminate samples, and 13 PCR-negative samples. Leishmania GPI was detected in 284 samples that were sequenced, to include 281 (64%) of the PCR-positive samples and 3 (4%) of the PCR-indeterminate samples. Of the 284 sequences identified as Leishmania, 261 (91.9%) were L. tarentolae, 18 (6.3%) were L. donovani-complex parasites, 3 (1.1%) were L. tropica, and 2 were similar to both L. major and L. tropica. Minimum field infection rates were 0.09% for L. donovani-complex parasites, 0.02% for L. tropica, and 0.01% for the L. major/tropica-like parasite. Subsequent sequencing of a 600-bp region of the "Hyper" gene of 12 of the L. donovani-complex parasites showed that all 12 parasites were L. infantum. These data suggest that L. infantum was the primary leishmanial threat to U.S. military personnel deployed to Tallil Air Base. The implications of these findings are discussed.

Hematogenous hip infections are rare in adults and the extent of infection into the bone or adjacent soft tissues may be underestimated, leading to inadequate surgical debridement. Using MRI, we sought to determine the extent of bone involvement and the presence of adjacent soft tissue abscesses in adults with hip osteomyelitis. We reviewed the records and MRIs in 11 adult patients (12 hips) with hematogenous osteomyelitis of the femoral head in 12 hips. Ten of 11 patients had one or more comorbidities. All patients underwent surgical debridement and received antibiotic therapy for 6 weeks. MRI revealed osteomyelitis distal to the femoral head in seven of 12 hips with extension into the medullary canal in three of these seven. Femoral head erosions were present in 10 hips, acetabulum osteomyelitis in 11, and acetabular erosions in six hips. Infection extended into adjacent soft tissues in eight of 12 hips. MRI demonstrated that the infection may extend distal to the femoral head or into the adjacent soft tissues. MRI may be useful for preoperative planning so that all regions affected by the infection can be treated. Level of Evidence: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

The migration patterns of naive and activated T cells are associated with the expression of distinct sets of chemokine receptors, but the molecular basis for this regulation is unknown. Here we identify Krupple-like factor 2 (KLF2) as a key transcriptional factor needed to prevent naive T cells from expressing inflammatory chemokine receptors and acquiring the migration patterns of activated T cells. Lineage-specific deletion of KLF2 resulted in fewer naive T cells in the blood and secondary lymphoid organs, whereas it expanded naive T cell numbers in nonlymphoid tissues; these effects were associated with altered expression of inflammatory chemokine receptors on naive T cells. KLF2 repressed the expression of several chemokine receptors, including CCR3 and CCR5. We thus conclude that KLF2 maintains proper T cell migration patterns by linking T cell movement and transcriptional regulation of chemokine receptor expression patterns.

Recurrence in the pelvis after resection of a rectal or rectosigmoid cancer presents a dilemma. Resection offers the only reasonable probability for cure, but at the cost of marked perioperative morbidity and potential mortality. Clinical decision making remains difficult. Patients who underwent resection with curative intent for isolated pelvic recurrences after curative colorectal surgery from 1988 through 2003 were reviewed retrospectively. Clinical and pathological factors, salvage operations, and complications were recorded. The primary measured outcome was overall survival. Univariate and multivariate analyses were conducted to identify prognostic factors of improved outcome. Ninety patients underwent an attempt at curative resection of a pelvic recurrence; median follow-up was 31 months. Complications occurred in 53% of patients. Operative mortality occurred in 4 (4.4%) of 90 patients. Median overall survival was 38 months, and estimated 5-year survival was 40%. A total of 51 of 86 patients had known recurrences (15 local, 16 distant, 20 both). Multivariate analysis revealed that preoperative carcinoembryonic antigen level and final margin status were statistically significant predictors of outcome. The resection of pelvic recurrences after colorectal surgery for cancer can be performed with low mortality and good long-term outcome; however, morbidity from such procedures is high. Low preoperative carcinoembryonic antigen and negative margin of resection predict improved survival.

Identifying viral isolates from field-collected mosquitoes can be difficult and time-consuming, particularly in regions of the world where numerous closely related viruses are co-circulating (e.g., the Amazon Basin region of Peru). The use of molecular techniques may provide rapid and efficient methods for identifying these viruses in the laboratory. Therefore, we determined the complete nucleotide sequence of two South American eastern equine encephalomyelitis viruses (EEEVs): one member from the Peru-Brazil (Lineage II) clade and one member from the Argentina-Panama (Lineage III) clade. In addition, we determined the nucleotide sequence for the nonstructural P3 protein (nsP3) and envelope 2 (E2) protein genes of 36 additional isolates of EEEV from mosquitoes captured in Peru between 1996 and 2001. The 38 isolates were evenly distributed between lineages II and III virus groupings. However, analysis of the nsP3 gene for lineage III strongly suggested that the 19 isolates from this lineage could be divided into two sub-clades, designated as lineages III and IIIA. Compared with North American EEEV (lineage I, GA97 strain), we found that the length of the nsP3 gene was shorter in the strains isolated from South America. A total of 60 nucleotides was deleted in lineage II, 69 in lineage III, and 72 in lineage IIIA. On the basis of the sequences we determined for South American EEEVs and those for other viruses detected in the same area, we developed a series of primers for characterizing these viruses.

Circadian blood pressure monitoring in human and normotensive/ spontaneously hypertensive rats after embryo transfer into different wombs and cross-suckling Mary S. Lee, John S. Lee, Jong Y. Lee, Silvia H. Azar, Franz Halberg. Northwestern University Feinberg School of Medicine U Princeton University & UMN School of Medicine, Princeton /Minneapolis, MN, United States; UMN School of Medicine, Minneapolis, MN, United States

In order to investigate the prevalence of tick-borne infectious agents among ticks, ticks comprising five species from two genera ( Hemaphysalis spp. and Ixodes spp.) were screened using molecular techniques. Ticks (3,135) were collected from small wild-caught mammals or by dragging/flagging in the Republic of Korea (ROK) and were pooled into a total of 1,638 samples (1 to 27 ticks per pool). From the 1,638 tick samples, species-specific fragments of Anaplasma phagocytophilum (1 sample), Anaplasma platys (52 samples), Ehrlichia chaffeensis (29 samples), Ehrlichia ewingii (2 samples), Ehrlichia canis (18 samples), and Rickettsia rickettsii (28 samples) were amplified by PCR assay. Twenty-one pooled and individual tick samples had mixed infections of two (15 samples) or three (6 samples) pathogens. In addition, 424 spleen samples from small captured mammals (389 rodents, 33 insectivores, and 2 weasels) were screened for selected zoonotic pathogens. Species-specific DNA fragments of A. phagocytophilum (110 samples), A. platys (68 samples), E. chaffeensis (8 samples), E. ewingii (26 samples), E. canis (51 samples), and Rickettsia sp. (22 samples) were amplified by PCR assay. One hundred thirty small mammals had single infections, while 4, 14, and 21 striped field mice ( Apodemus agrarius ) had mixed infections of four, three, and two pathogens, respectively. Phylogenetic analysis based on nucleotide sequence comparison also revealed that Korean strains of E. chaffeensis clustered closely with those from China and the United States, while the Rickettsia (rOmpA) sequences clustered within a clade together with a Chinese strain. These results suggest that these agents should be considered in differential diagnosis while examining cases of acute febrile illnesses in humans as well as animals in the ROK.

We evaluated the molestus form of Culex pipiens pipiens (L.) (hereafter referred to as "molestus") captured near Tashkent, Uzbekistan, for their ability to transmit Japanese encephalitis (family Flaviviridae, genus Flavivirus, JEV) and West Nile (family Flaviviridae, genus Flavivirus, WNV) viruses under laboratory conditions. These molestus were highly competent laboratory vectors of WNV, with infection and dissemination rates of 96 and 81%, respectively. Approximately 75% of female molestus that fed after development of a disseminated infection transmitted virus by bite. Therefore, approximately 60% of those molestus taking a second bloodmeal between 16 and 25 d after an infectious bloodmeal would be expected to transmit WNV by bite. In contrast, these molestus were less efficient vectors of JEV, with infection and dissemination rates of 51 and 25%, respectively. In addition, only 33% of individuals with a disseminated infection transmitted JEV by bite, indicating a significant salivary gland barrier. Therefore, only approximately 8% of orally exposed individuals would be expected to transmit JEV by bite if they took a second bloodmeal 16-25 d later. These data indicate that the molestus form of Cx. p. pipiens should be considered a potentially important vector of WNV in Uzbekistan and may become involved in the transmission of JEV, should this virus be introduced into Uzbekistan.

The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

We investigated the prevalence of Bartonella infections in ticks, mites and small mammals (rodents, insectivores and weasels) collected during 2001 through 2004, from various military installations and training sites in Korea, using PCR and sequence analysis of 16S rRNA, 23S rRNA and groEL heat shock protein genes. The prevalence of Bartonella spp. was 5.2% (n = 1,305 sample pools) in ticks, 19.1% (n = 21) in mesostigmatid mites and 13.7% (n = 424 individuals) in small mammals. The prevalence within the family Ixodidae was, 4.4% (n = 1,173) in Haemaphysalis longicornis (scrub tick), 2.7% (n = 74) in H. flava, 5.0% (n = 20) in Ixodes nipponensis, 11.1% (n = 9) in I. turdus, 33.3% (n = 3) in I. persulcatus and 42.3% (n = 26) in Ixodes spp. ticks. In rodents, the prevalence rate was, 6.7% (n = 373) in Apodemus agrarius (striped field mouse) and 11.1% (n = 9) in Eothenomys regulus (Korean red-backed vole) and in an insectivore,Crocidura lasiura, 12.1% (n = 33). Neither of the two weasels were positive for Bartonella spp. Phylogenetic analysis based on amino acid sequence of a portion of the groEL gene amplified from one A. agrarius spleen was identical to B. elizabethae species. We demonstrated the presence of Bartonella DNA in H. longicornis, H. flava and I. nipponensis ticks, indicating that these ticks should be added to the growing list of potential tick vectors and warrants further detailed investigations to disclose their possible roles in Bartonella infection cycles.

We report here a previously unrecognized mosquito species from the Republic of South Korea that is closely related to Anopheles (Anopheles) sinensis. We also present an rDNA ITS2-based method for identification of this and the other morphologically similar Anopheles from the country. The PCR assay is a multiplex of seven primers in a single reaction that unambiguously identifies all included species. The other species include An. sinensis, An. lesteri, An. pullus, and a previously reported unknown Anopheles. Based on the ITS2 sequence, the two unnamed species have genetic distances from An. sinensis of 9.1% (unknown 1) and 10.7% (unknown 2), and are 10.6% different from each other. Adult females of An. sinensis and unknown 2 are morphologically indistinguishable, while unknown 1, An. lesteri and An. pullus can usually be separated from each other and from An. sinensis using available keys and descriptions. This PCR identification tool offers vector biologists and malaria epidemiologists a means to identify the potential vectors of malaria parasites in South Korea.

Psychological procedures, such as self-hypnosis in the form of autogenic training, have been proposed for correcting a deviant, e.g., high blood pressure (BP). In view of the overwhelming evidence for the circadian (CD) stage dependence of any treatment effects, the CD stage dependence of the effects of diaphragmatic breathing (DB) on BP and heart rate (HR) was explored in data from a clinically healthy normotensive subject who, following 3 weeks of ambulatory monitoring as a reference standard, measured BP and HR with a manual monitor at 1-min intervals for 5 min before and after DB (three deep diaphragmatic breaths) and who performed DB for about 2 weeks at about 2-h intervals while awake. The 3-week data series were analyzed by cosinor, involving the least-squares fit of cosine curves with periods of 24, 12 and 168 h. A CD rhythm was detected for BP and HR (P < 0.001 in each case), peaking in the afternoon. Some about-weekly (circaseptan; CS) BP rhythms and 12-h (circasemidian) components were also statistically significant. DB was found to reduce systolic (S) BP. Overall, SBP decreased by 5.9 +/- 0.8 mmHg (P < 0.001) and diastolic (D) BP by 1.4 +/- 0.8 mmHg (P < 0.005), while HR remained at about the same average. The effect of DB on BP was CD-dependent, the largest response occurring in the afternoon, 2-3 h before the peaks in SBP and DBP found in the reference data of the same subject. There was also a 5-10% decrease in SBP around the weekend (Friday, Saturday and Sunday). The results on a single subject suggest the need to collect similar data on others for optimizing by clock-hour, day of the week, and eventually by the marker rhythms BP and/or HR the best times for DB and other procedures. The personalized best time for people on different work/rest schedules for relaxation may be several hours before their BP has reached its highest point in the 24-h span. HR may serve as a marker for DB timing, but the effect on HR of DB was only of borderline statistical significance in the subject investigated.

We assess circadian (CD) and circaseptan (CS) changes in the blood pressure (BP) response to a 1-min immersion of the hand into ice water, the cold pressor test (CPT). An about 8 mmHg BP increase in the CPT reported by others for health and an elevation25 mmHg for patients with "hypertension" have been viewed as predisease, but variables related to the vascular system exhibit prominent CD, CS and circannuals, among other components of their genetically anchored time structure or chronome, and may also have to be considered. Hence, a 16-year-old adolescent (ML) immersed her hand into ice water every 2-4 h for 2 days and once daily in the morning thereafter for 1 week (N = 25), as did, only for2 days (or =24 h), four adults 20-66 years of age. BP and heart rate (HR) were monitored automatically around the clock at 15-min intervals and at 1-min intervals before and immediately after the CPT. Data were analyzed by cosinor. The difference between the first post-CPT BP value and the mean of the last seven values prior to the CPT was a measure of CPT response (at 1-min). Overall, ML's systolic (S) BP increased by 8.2 +/- 1.4 mmHg and her diastolic (D) BP by 6.2 +/- 0.9 mmHg (P0.001). Increases were found in 96% of the tests for SBP, 92% for DBP and 20% for HR. There was only one tie for HR (4%), resulting in a HR decrease in 76% of CPTs. The BP response to CPT at 1 min was CS-dependent. The CS double amplitudes are 12.5 +/- 4.1 for SBP (P = 0.019) and 7.8 +/- 2.8 mmHg for DBP (P = 0.030), with acrophases occurring on late Sunday, early Monday (at -50 degrees and -67 degrees from 00:00 h from Saturday to Sunday for SBP and DBP, respectively, with 360 degrees identical with 1 week). The response of HR did not allow the detection of a CS rhythm (P = 0.969). The CD response peaked in the early morning hours; with 24 h identical with 360 degrees and 0 degrees = local midnight, the acrophase (phi) for SBP is at -80 degrees and for DBP at -113 degrees, in keeping with earlier results from four adult subjects (SBP: -37 degrees; DBP: -42 degrees ), individual differences notwithstanding. The average timing of the largest overall response of BP to CPT coincides with the timing of the response to other stimuli. The CS acrophases coincide with the times of increased morbidity/mortality from vascular diseases. Chronomes, time structures broader than circadian, notably their about-weekly components, should be considered, not only at the extremes of life when the CS and about-half-weekly rhythms are particularly prominent in BP and HR but also in interpreting BP responses as a gauge of vascular disease status in adolescents.

Anthrax, a disease usually associated with herbivores, is caused by the bacterium Bacillus anthracis . The current vaccine licensed for human use requires a six-dose primary series and yearly boosters and causes reactogenicity in up to 30% of vaccine recipients. A minimally reactogenic vaccine requiring fewer inoculations is warranted. Venezuelan equine encephalitis (VEE) virus has been configured for use as a vaccine vector for a wide variety of immunogens. The VEE vaccine vector is composed of a self-replicating RNA (replicon) containing all of the VEE virus nonstructural genes and a multiple-cloning site in place of the VEE structural genes. Four different anthrax vaccines were constructed by cloning the protective antigen (PA) gene from B. anthracis into the VEE vaccine vector. The anthrax vaccines were produced by assembling the vectors into propagation-deficient VEE replicon particles in vitro. A/J mice inoculated subcutaneously with three doses of the mature 83-kDa PA vaccine were completely protected from challenge with the Sterne strain of B. anthracis . Similar results were obtained with vaccines composed of the PA gene fused to either the B. anthracis secretory sequence or to a tissue plasminogen activator secretory sequence in three additional mouse strains. Mice were unprotected from challenge after inoculation with the carboxy-terminal 63-kDa PA vaccine. These results suggest that these VEE-vectored vaccines may be suitable as candidate vaccines against anthrax.

A candidate vaccine against staphylococcal enterotoxin B (SEB) was developed using a Venezuelan equine encephalitis (VEE) virus vector. This vaccine is composed of a self-replicating RNA, termed "replicon," containing the VEE nonstructural genes and cis-acting elements and a gene encoding mutagenized SEB (mSEB). Cotransfection of baby hamster kidney cells with the mSEB replicon and 2 helper RNA molecules resulted in the release of propagation-deficient mSEB-VEE replicon particles (mSEB-VRPs). Mice inoculated subcutaneously with mSEB-VRPs were protected (15 of 20 mice) from a challenge with 5 median lethal dose units of wild-type (wt) SEB. T cells from mice vaccinated with mSEB-VRP responded normally both in vitro to wt SEB and in recall response to the inactivated mSEB polypeptide. The profile of cytokines measured after challenge with wt SEB suggested that the mode of protection was predominantly Th1 dependent. Our results suggest that the VEE replicon is a practical and convenient model system for evaluating efficacy of vaccines for the control of bacterial diseases.

A candidate vaccine against botulinum neurotoxin serotype A (BoNT/A) was developed by using a Venezuelan equine encephalitis (VEE) virus replicon vector. This vaccine vector is composed of a self-replicating RNA containing all of the VEE nonstructural genes and cis -acting elements and also a heterologous immunogen gene placed downstream of the subgenomic 26S promoter in place of the viral structural genes. In this study, the nontoxic 50-kDa carboxy-terminal fragment (H C ) of the BoNT/A heavy chain was cloned into the replicon vector (H C -replicon). Cotransfection of BHK cells in vitro with the H C -replicon and two helper RNA molecules, the latter encoding all of the VEE structural proteins, resulted in the assembly and release of propagation-deficient, H C VEE replicon particles (H C -VRP). Cells infected with H C -VRP efficiently expressed this protein when analyzed by either immunofluorescence or by Western blot. To evaluate the immunogenicity of H C -VRP, mice were vaccinated with various doses of H C -VRP at different intervals. Mice inoculated subcutaneously with H C -VRP were protected from an intraperitoneal challenge of up to 100,000 50% lethal dose units of BoNT/A. Protection correlated directly with serum enzyme-linked immunosorbent assay titers to BoNT/A. The duration of the immunity achieved was tested at 6 months and at 1 year postvaccination, and mice challenged at these times remained refractory to challenge with BoNT/A.

e19580 Background: Ifos chemotherapy is known to cause central nervous system toxicity. Risk factors have not been well identified in the literature, with limited information on the onset, duration, and severity of this toxicity. No clinical tools are available to assess and document N. Methods: We developed a clinical nursing assessment tool based upon review of the literature. Patients initiating inpatient Ifos chemotherapy, after informed consent was obtained under an IRB approved protocol, were prospectively monitored for signs and symptoms of N during 1 cycle of therapy. A full neurologic nursing assessment of 24 signs and symptoms including a hand writing sample was done at baseline and a basic assessment evaluating alertness, orientation, sense of well being and a hand writing sample was repeated every 12 hours. In the event N was identified, a full assessment was repeated; observed N was graded using the NCI CTC, version 3. Other variables collected were demographic traits, dose per day, hydration, and potential risk factors for N: renal function, albumin, largest pelvic tumor dimension, prior Ifos or cisplatin, use of other medications with potential for N, and alcohol use history. Individual factors were analyzed using Fisher’s exact test or the Wilcoxon two-sample test. Results: Eighty patients were accrued from 5/09-1/12. Median age was 54.5 (range: 21-85), 51% were males, PS 0 in 26.3%, 1 in 65%, 2 in 6.3% and 3 or 4 in 1.3% each. Diagnosis was sarcoma in 73.75%, lymphoma 22.5%, or germ cell tumor 3.75%. N was observed in 47.5% of patients. Toxicities in >15% of patients were sleepiness (25%), lethargy and restlessness (16.25% for each), and dizziness (15%). The majority were grade 1-2 (89.6%). Factors associated with N included generic versus brand formulation of Ifos (p=0.041) and prior history of a drug related neurotoxicity (p=0.047). BSA, performance status, gender, age, dose per m2, total planned dose, pretreatment Cr, and pretreatment albumin were not associated. Conclusions: The incidence of Ifos N is common using this nursing assessment tool, although usually low grade. We identified the formulation of Ifos and a prior history of drug related N as statistically correlated with developing N.

10090 Background: Patients with advanced GIST progressing following IM and S often continue with good performance statuses and need additional therapy. This study tested the benefit of N, a second ...

Comprehensive quarterly serosurveillance on scrub typhus in small mammals collected from military training sites located near the Demilitarized Zone (DMZ), northern Gyeonggi-do (Province), ROK was conducted to determine the potential rodent-borne and associated ectoparasite disease risks to military personnel. A total of 1,196 rodents and insectivores representing 8 species, Apodemus agrarius (87.3%, n = 1,044), Mus musculus (5.4%, n = 65), Crocidura lasiura (3.3%, n = 40), Microtus fortis (2.6%, n = 31), Micromys minutus (0.3%, n = 4), Tscherskia triton (0.3%, n = 4), Rattus norvegicus (0.3%, n = 4), and Myodes regulus (0.3%, n = 4) were assayed for the presence of antibodies to Orientia tsutsugamushi. O. tsutsugamushi antibodies were detected in 6 of 8 species and seroprevalence determined; A. agrarius (45.6%), M. musculus (23.1%), M. fortis (48.4%), M. minutus (50.0%), T. triton (50.0%), and R. norvegicus (25.0%). A total of 31,184 chigger mites collected from 508 rodents and insectivores were slide-mounted and 10 species belonging to 4 genera were identified. Leptotrombidium pallidum (53.4%) was the most frequently collected, followed by L. palpale (15.7%), Neotrombicula tamiyai (14.3%), L. orientale (10.7%), L. zetum (3.1%), Walchia fragilis (2.1%), and L. gemiticulum (0.8%), while the remaining 3 species, L. subintermedium, N. gardellai, and Euschoengastia koreaensis were rarely observed (prevalence < 10%). In contrast to previous surveys, higher chigger indices of the primary scrub typhus vectors, L. pallidum (165.4), L. orientale (45.0), and L. palpale (21.4), were observed during the spring season.

Purpose: The Spetzler-Martin grade (SMG) accurately predicts outcome after surgical resection of arteriovenous malformations (AVM); however, its application to radiosurgery is limited because of ins

9668 Background: Human Fibroblast Activation Protein (FAP)/seprase is a 97-kd surface glycoprotein with dipeptidyl peptidase and gelatinolytic activity expressed on tumor associated fibroblasts in the majority of epithelial cancers including colon adenocarcinomas. FAP overexpression has been shown to promote tumor growth in animal models, and clinical trials targeting FAP enzymatic activity have been initiated. The primary objective of this study was to evaluate expression levels of FAP in human colon cancers by immunohistochemisty and relate its expression to clinical outcome. Methods: Sections of paraffin-embedded resected primary human colon cancer specimens from 1996 through 2001 within the Fox Chase Cancer Center tumor bank were stained with D8 antibody directed against FAP/seprase. Grading of staining was performed by assessment of FAP staining intensity (none, light, medium, dark) and overall percent of stromal staining (0, 1–10%, 11–50%, 51%+) as previously established. Survival time and time to r...

Radial keratotomy was performed on six stumptail monkey eyes (Macaca speciosa) and 22 owl monkey eyes (Aotus trivirgotus). Changes in keratometry, specular microscopy, and tonometry have been studied postoperatively for three to six months. Sixteen radial incisions in stumptail monkey eyes resulted in a significant mean corneal flattening of 2.75 diopters (P less than 0.005). This effect was stable with a mean 2.50 diopters flattening remaining six months after surgery. Sixteen radial incisions in ten owl monkey eyes resulted in a much greater short-term effect, with a mean 10.50 diopters of flattening present at two weeks postoperatively. This flattening deteriorated over the observation period, and no significant effect was noted three months after surgery. A comparison of 8 vs 16 incisions on owl monkey eyes demonstrated that these two procedures are equally effective in initially flattening the cornea. Complications and side effects encountered included perforations, irregular astigmatism, corneal neovascularization, transitory increase in pachometry, and decrease in central corneal endothelial cell density in isolated cases.

Purpose Patients with advanced GIST following standard imatinib and sunitinib often have good performance status and need additional therapy. This study tested nilotinib, a second-generation tyrosine kinase inhibitor, in patients with advanced GIST refractory to standard therapies. Methods This single-center open-label phase II study has a primary objective to determine progression-free survival at 6 months. Using a novel statistical design, 17 patients were to be enrolled; if ≥10 were progression free (PF) at 2 months, 19 additional patients would be enrolled. The therapy was considered of benefit if ≥13 of 36 patients were PF at 6 months. All patients signed informed consent and entry criteria included normal cardiac function. Exploratory analyses correlating genotype with response were also performed. Results Thirteen patients were treated; 2 had received agents after imatinib and sunitinib. Treatment was well tolerated with one grade 4 anemia attributed to nilotinib. No measurable responses were observed; median time to progression was 2 months. One patient remained on study with stable disease for 12 months. Mutation testing is available from 10 primary tumors with 7 exon 11 mutations, 1 exon 9 mutation, and 2 without KIT/PDGFR mutations. Two samples from recurrent disease had 2 mutations, both primary exon 11 mutations with an additional exon 17 mutation, including the patient with prolonged stable disease. Conclusions Nilotinib was well tolerated in these patients with advanced GIST. Accrual was halted due to insufficient clinical benefit. However, nilotinib may provide benefit to specific subsets of advanced GIST with exon 17 mutations.

We performed radial keratotomy using the Fyodorov techniques on 14 Eye Bank eyes. Using stepwise regression and best subset statistical analysis, we examined the effects of incision depth, corneal curvature, corneal thickness, corneal diameter, and incision length. We found that the most significant variables affecting postoperative corneal curvature were the incision depth and length. The histologic examination of serial sections of the Eye Bank eyes after this procedure revealed that the average achieved incision depth, using a standard blade depth setting, had variations of up to 30% between eyes. This inability to standardize incision depth may lead to the variable surgical results reported in radial keratotomy.

Radial keratotomy in fresh human cadaver eyes produced corneal flattening varying from 6 to 11 diopters (D). There was no significant difference in the effectiveness of the incisions to the incisions to the limbus compared to incisions through the limbus. Eighty to ninety percent of the flattening effect was obtained after the first eight incisions. The preoperative keratotomy reading was not helpful in predicting the final result. Histopathology of the incised corneas revealed considerable variation in incision depth and demonstrates the difficulty in achieving deep incisions safely.

An 81-year-old black woman with severe rheumatoid arthritis presented with an enlarging black lesion on the medial sclera of the left eye. Scleromalacia perforans was suspected. At surgical exploration, a deeply pigmented tumor was encountered, with extension into the orbit, along the medial rectus muscle. Biopsy revealed a benign melanocytoma.