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Amoebic trophozoites were identified in the cervicovaginal smear of a U.S. patient without travel history at the time of intrauterine device (IUD) removal. Subsequent morphologic analysis and DNA sequencing identified a mixed cervicovaginal colonization of the female genital tract with both Entamoeba gingivalis and Entamoeba polecki in association with Actinomyces species bacteria. This highlights to the potential for colonization of the genital tract with E. gingivalis, particularly in association with IUD placement, and represents the first report of E. polecki in this context.

Background The United States is experiencing mumps outbreaks in settings with high 2-dose measles-mumps-rubella (MMR) vaccine coverage, mainly universities. The economic impact of mumps outbreaks on public health systems is largely unknown. During a 2015–2016 mumps outbreak at the University of Iowa, we estimated the cost of public health response that included a third dose of MMR vaccine. Methods Data on activities performed, personnel hours spent, MMR vaccine doses administered, miles traveled, hourly earnings, and unitary costs were collected using a customized data tool. These data were then used to calculate associated costs. Results Approximately 6300 hours of personnel time were required from state and local public health institutions and the university, including for vaccination and laboratory work. Among activities demanding time were case/contact investigation (36%), response planning/coordination (20%), and specimen testing and report preparation (13% each). A total of 4736 MMR doses were administered and 1920 miles traveled. The total cost was >$649 000, roughly equally distributed between standard outbreak control activities and third-dose MMR vaccination (55% and 45%, respectively). Conclusions Public health response to the mumps outbreak at the University of Iowa required important amounts of personnel time and other resources. Associated costs were sizable enough to affect other public health activities.

Objectives Clinical trials for progressive neurodegenerative disorders such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis have been hindered due to the absence of effective pharmacodynamics markers to assay target engagement. We tested whether measurements of new protein production would be a viable pharmacodynamics tool for RNA‐targeted therapies. Methods Transgenic animal models expressing human proteins implicated in neurodegenerative disorders – microtubule‐associated protein tau (hTau) or superoxide dismutase‐1 (hSOD1) – were treated with antisense oligonucleotides (ASOs) delivered to the central nervous system to target these human mRNA transcripts. Simultaneously, animals were administered 13C6‐leucine via drinking water to measure new protein synthesis after ASO treatment. Measures of new protein synthesis and protein concentration were assayed at designated time points after ASO treatment using targeted proteomics. Results ASO treatment lowered hTau mRNA and protein production (measured by 13C6‐leucine‐labeled hTau protein) earlier than total hTau protein concentration in transgenic mouse cortex. In the CSF of hSOD1 transgenic rats, ASO treatment lowered newly generated hSOD1 protein driven by decreases in newly synthesized hSOD1 protein, not overall protein concentration, 30 days after treatment. At later time points, decreases in newly generated protein were still observed after mRNA lowering reached a steady state after ASO treatment. Interpretation Measures of newly generated protein show earlier pharmacodynamics changes for RNA‐lowering therapeutics compared with total protein concentration. Early in ASO treatment, decreases in newly generated protein are driven by changes in newly synthesized protein. Measuring new protein production in CSF may be a promising early pharmacodynamics marker for RNA‐targeted therapeutics.

Importance The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources Genomewide association studies (GWAS) published up to January 15, 2015. Study Selection GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Data Extraction and Synthesis Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Main Outcomes and Measures Odds ratios (ORs) and 95%confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Results Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95%CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95%CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95%CI, 0.49-0.81]), celiac disease (OR, 0.42 [95%CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95%CI, 0.05-0.15]). Conclusions and Relevance It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

ImportanceUnderstanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population.ObjectiveTo establish an updated natural history of ALSSOD1.Design, setting and participantsRetrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000.Main outcomes and measuresAge of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis.ResultsMean age of disease onset was 49.7±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p

Antisense oligonucleotides (ASO) are short DNA-like chemicals that bind to RNA by Watson–Crick base pairing and modulate function of the RNA. These chemicals do not cross the blood brain barrier, but may be delivered directly to the cerebral spinal fluid (CSF) to achieve widespread distribution throughout the brain and spinal cord. ASO have been used to target genes associated with familial amyotrophic lateral sclerosis (ALS), such as SOD1 and C9orf72 as well as miRNAs. A Phase I trial for SOD1-targeting ASO showed excellent safety and important pharmacodynamics. ASO are a promising therapeutic approach for ALS.

Objective.To determine whether multidrug-resistant (MDR) gram-negative organisms are present in Afghanistan or Iraq soil samples, contaminate standard deployed hospital or modular operating rooms (ORs), or aerosolize during surgical procedures.Design.Active surveillance.Setting.US military hospitals in the United States, Afghanistan, and Iraq.Methods.Soil samples were collected from sites throughout Afghanistan and Iraq and analyzed for presence of MDR bacteria. Environmental sampling of selected newly established modular and deployed OR high-touch surfaces and equipment was performed to determine the presence of bacterial contamination. Gram-negative bacteria aerosolization during OR surgical procedures was determined by microbiological analysis of settle plate growth.Results.Subsurface soil sample isolates recovered in Afghanistan and Iraq included various pansusceptible members of Enterobacteriaceae,Vibriospecies,Pseudomonasspecies,Acinetobacter Iwojfii, and coagulase-negativeStaphylococcus(CNS). OR contamination studies in Afghanistan revealed 1 surface with aMicrococcus luteus. Newly established US-based modular ORs and the colocated fixed-facility ORs revealed no gram-negative bacterial contamination prior to the opening of the modular OR and 5 weeks later. Bacterial aerosolization during surgery in a deployed fixed hospital revealed a mean gram-negative bacteria colony count of 12.8 colony-forming units (CFU)/dm2/h (standard deviation [SD], 17.0) during surgeries and 6.5 CFU/dm2/h (SD, 7.5;P= .14) when the OR was not in use.Conclusion.This study demonstrates no significant gram-negative bacilli colonization of modular and fixed-facility ORs or dirt and no significant aerosolization of these bacilli during surgical procedures. These results lend additional support to the role of nosocomial transmission of MDR pathogens or the colonization of the patient themselves prior to injury.

The increased incidence of sexually transmitted infections has historically been associated with military personnel at war. The incidence of gonorrhea and Chlamydia in personnel deployed in the current wars in Iraq and Afghanistan has not been reported. An electronic records' review of testing done from January 2004 to September 2009 revealed higher rates of Chlamydia than gonorrhea, especially among females who deploy to Iraq. Additionally, increasing Chlamydia rates were noted over the study. Overall, the rates of gonorrhea and Chlamydia were the same or lower than age- and year-matched U.S. rates reported by the Center for Disease Control and Prevention. Ongoing education with emphasis on prevention and treatment are needed, as are development of specific projects to define the risk factors and timing of acquisition of sexually transmitted infections in combat zones.

Methicillin-resistant Staphylococcus aureus (MRSA) in health-care settings results in life-threatening infections. We examined the incidence of MRSA at the combat support hospital located at the Ibn Sina Hospital in Baghdad, Iraq. We compiled isolate data from 2005 to 2009 characterizing antibiotic susceptibilities, annual trends, patient populations, infection sites, and hospital locations. Approximately 46.1% of S. aureus were MRSA, with increase in numbers of yearly isolates. MRSA was isolated in higher numbers from U.S. military personnel. Non-U.S. patient isolates displayed higher antibiotic susceptibility compared to U.S. military personnel isolates. Outpatient clinic, forward operating bases, and intermediate care ward 1 isolated the most MRSA. Common isolation sites were wound and skin cultures. Community-acquired MRSA was likely present in 291 out of 303 isolates based on antibiotic susceptibility. Our data suggests that most MRSA were community-acquired with limited nosocomial spread. We recommend increases in combat support hospital molecular lab capability to rapidly identify both MRSA categories.

Staphylococcus aureus infections complicate care of combat-related injuries and can independently result in skin and soft-tissue infections during deployments or training. Community-associated methicillin-resistant S. aureus (CA-MRSA) strains seem to produce severe disease but retain susceptibility to many oral antimicrobials. This study characterizes 84 MRSA isolates recovered from wound cultures at a combat support hospital in Iraq.MRSA strains recovered from December 2007 through March 2009 were analyzed. Antimicrobial resistance testing was determined by broth microdilution and the BD Phoenix Automated Microbiology System. The genotypic pattern was analyzed by pulsed-field gel electrophoresis and polymerase chain reaction identification of resistance and virulence genes.No MRSA isolates from wound cultures were resistant to vancomycin. The most active oral antistaphylococcal agents were tetracycline (95% susceptibility), trimethoprim-sulfamethoxazole (94%), and clindamycin (94%). Of agents not typically recommended as monotherapy, 98% of isolates were susceptible to rifampin, 91% to moxifloxacin, and 60% to levofloxacin. The most common pulsed-field type (PFT) was USA300 (79%). The typical staphylococcal cassette chromosome mec IV elements carrying the CA-MRSA resistance genes were present in 88% of the isolates. Panton-Valentine leukocidin virulence genes were identified in 88% of isolates, including 100% of PFT USA300. The virulence gene associated with an arginine catabolic mobile element was present in 75% of isolates, including 94% of PFT USA300.This study is the first genotypic and phenotypic characterization of CA-MRSA recovered from wound cultures in a deployed combat hospital. The pattern noted was similar to that seen in soldiers stationed in the United States.

Background.Multidrug-resistant (MDR)Acinetobacter baumanniiandPseudomonas aeruginosahave emerged as the causes of nosocomial infections in critically ill patients.Objective.To characterize the incidence of these MDR bacteria over time in the military healthcare system, comparing isolates recovered from overseas combat casualties with isolates recovered from local military and civilian patients.Methods.Retrospective electronic records review of culture and/or susceptibility testing results of patients admitted to a military level I trauma center in San Antonio, Texas, during the period from January 2001 through December 2008. Multidrug resistance was defined as the first isolated organism resistant to 3 or more classes of antimicrobial agents.Results.Over time, the percentage of MDRA. baumanniiisolates increased from 4% to 55%, whereas the percentage of MDRP. aeruginosaisolates increased from 2% to 8%. Respiratory tract specimens had a higher percentage of MDRA. baumanniiisolates (49%), compared with specimens obtained from blood (30%), wound sites (24%), or urine (19%). No difference in the percentages of MDRP. aeruginosaisolates was observed with regard to source of specimen. The percentage of MDRA. baumanniiisolates recovered was higher among patients who had been deployed overseas (52%) than among local patients (20%). When isolates recovered from patients in the burn intensive care unit (53% of MDRA. baumanniiisolates) were removed from analysis, the percentage of MDRA. baumanniiisolates decreased from 38% to 30% while the percentage of MDRP. aeruginosaisolates remained unaffected.Conclusion.The percentage of MDRA. baumanniiisolates increased in this facility among combat casualties and among local patients, which indicates nosocomial transmission; however, there was no significant increase in the percentage of MDRP. aeruginosaisolates. Isolated changes in the MDR pathogens within a facility can occur. Possible interventions to limit the spread of these organisms could include implementing aggressive infection control practices, controlling antibiotic use, and using active culture surveillance.

OBJECTIVES/SPECIFIC AIMS: We aimed to develop an assay to measure new protein synthesis after Antisense Oligonucleotide treatment, which we hypothesized to be the earliest biochemical identification of RNA-targeting therapy efficacy. METHODS/STUDY POPULATION: We treated 2 transgenic animal models expressing proteins implicated in neurodegenerative disease: human tau protein (hTau) and human superoxide dismutase 1 (hSOD1), with ASO against these mRNA transcripts. Animals received isotope-labeled 13C6-Leucine via drinking water to label newly synthesized proteins. We assayed target protein synthesis and concentration after ASO treatment to determine the earliest identification of ASO target engagement. RESULTS/ANTICIPATED RESULTS: hTau ASO treatment in transgenic mice lowered hTau protein concentration 23 days post-treatment in cortex (95% CI: 0.05%–64.0% reduction). In the same tissue, we observed lowering of hTau protein synthesis as early as 13 days (95% CI: 29.4%–123%). In hSOD1 transgenic rats, we observed lowering of 13C6-leucine-labeled hSOD1 in the cerebrospinal fluid 30 days after ASO treatment compared with inactive ASO control (95% CI: 12.0%–48.4%). DISCUSSION/SIGNIFICANCE OF IMPACT: In progressive neurodegenerative diseases, it is crucial to develop measurements that identify treatment efficacy early to improve patient outcomes. These data support the use of stable isotope labeling of amino acids to measure new protein synthesis as an early pharmacodynamics measurement for therapies that target RNA and inhibit the translation of proteins.

Study design Retrospective cohort. Objective The purpose of this study is to determine the fusion rates of a consecutive series of anterior cervical decompressions and fusions with allograft patella using both static and dynamic plates. Summary of background data Anterior cervical diskectomy and fusion (ACDF) has been shown to improve symptoms of radiculopathy and myelopathy. The gold standard for obtaining fusion is using autogenous iliac crest bone graft (ICBG). The complication rate of using ICBG can be as high as 20%. To minimize this morbidity, various forms of allograft are presently used. We have used patellar allograft that we hypothesize exhibits a good combination of strength and sufficient porosity to facilitate fusion. Methods A consecutive series of 179 levels in 136 patients who underwent single and multilevel ACDF with allograft patella were retrospectively investigated. Final follow-up lateral cervical spine radiographs were evaluated for evidence of bony fusion. Fusions were graded independently by 2 of the investigators according to an interbody fusion classification proposed by Bridwell and colleagues, Spine, 1995. Fusion rates were compared with historical controls for single-level ACDF with autogenous ICBG and plating. Multivariate analysis was used to evaluate plate type, smoking, revision rate, and Odom's criteria compared with fusion. Results Ninety-one consecutive single and 81 multilevel anterior cervical decompression and fusions with allograft patella were reviewed. Demographics were similar (average age 47.75 y). Average follow-up was 19.3 months. Fusion rates were 86% (159/179). Our revision rate was 8%. Eighty-one percent (85/98) union rate was noted in the single-level group, and 85% (69/81 levels) or 74% (28/38 patients) in the multilevel group. Conclusions Fusion rates were 86%. Plate design (static vs. dynamic) did not seem to affect fusion rates or clinical outcomes. There was a higher nonunion rate at the most inferior level of the multilevel fusions. Nonunions in the dynamic group were more commonly revised and had more kyphosis at final follow-up.

U.S. combat casualties from Iraq and Afghanistan continue to develop infections with multidrug-resistant (MDR) bacteria. This study assesses the infection control database and clinical microbiology antibiograms at a single site from 2005 to 2007, a period when all Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) casualties admitted to the facility underwent initial isolation and screening for MDR pathogens. During this 3-year period, there were 2,242 OIF/OEF admissions: 560 in 2005, 724 in 2006, and 958 in 2007. The most commonly recovered pathogens from OIF/OEF admission screening cultures were methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae and Acinetobacter. The yearly nosocomial infection rate of these three pathogens among OIF/OEF admissions ranged between 2 and 4%. There were remarkable changes in resistance profiles for Acinetobacter, K. pneumoniae, and S. aureus over time. Despite aggressive infection control procedures, there is continued nosocomial transmission within the facility and increasing antimicrobial resistance in some pathogens. Novel techniques are needed to control the impact of MDR bacteria in medical facilities.

Study Design. Explant analysis for bone ingrowth of retrieved cervical disc prosthesis in chimpanzees and humans. Objectives. To assess the bone ingrowth into retrieved Bryan Cervical Discs. Summary of Background Data. Bone ingrowth in cervical disc prothesis has not been documented in the literature. Methods. Chimpanzee: Two chimpanzees underwent placement of the Bryan disc at C3–C4 and 3 months later had explantation and interbody fusion. Human: Two patients had removal of their Bryan disc and interbody fusion for failure to resolve symptoms at 8 and 10 months. The explants were analyzed for bone ingrowth. Results. Chimpanzee: Histologic analysis showed bony ingrowth through the interstices of the porous coating and apposition ranging from 10% to 50% of toluidine blue-stained sections. New ingrowth, rather than bony impaction, was confirmed with fluorochrome-labeled sections Human: Bone ingrowth was a mean of 30.1% (12% SD). No difference was observed between peripheral, intermediate, or central locations. Conclusions. Adequate bony apposition was found in all primate device-to-vertebral body interfaces. Human retrievals also demonstrated significant ingrowth in all four surfaces. This compares with hip and knee arthroplasty percent ingrowth rates of 10% to 30%. All implants had stable fixation judged by radiographs and at the time of implant removal.

An optimal system for determining whether simulcast coding (400) or spatial scalability coding (100) should be used to encode video for clients with a specific communication link. Operating points (A', B', C') for both simulcast coding and spatial scalability are also determined. Adaptive switching (3130, 3140) is provided, with the operating points and decision boundaries being used to guide the switching to optimize the quality of the higher-resolution data based on a bit allocation to the associated lower-resolution data. A system for determining the point (A', C') of equal quality in both layers of simulcast and spatial scalability coding is also disclosed. The proportion of bits allocated to the base layer to achieve equal quality is essentially independent of the total bit rate for both simulcast and spatial scalability.

Topical anesthetics are commonly used in the evaluation of nasal pathology. The anesthetics routinely used, 4% lidocaine with phenylephrine, or 4% cocaine, have been demonstrated to have varying inhibitory effects on bacterial cultures. The present study examined the antimicrobial activity of these topical anesthetics used in nasal procedures. The pathogens used were Branhamella catarrhalis, Enterobacter sp., Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae. Organisms were against two-fold serial dilutions of stock preparations of 4% lidocaine with 0.25% phenylephrine, 0.25% phenylephrine, 0.1% methylparaben, 250 mg/ml ampicillin, and 4% cocaine. The minimum inhibitory concentration and minimum bactericidal concentration for each of the solutions were obtained. The bacteria studied varied gently in their susceptibility to lidocaine with phenylephrine versus cocaine: Cocaine consistently exhibited greater antimicrobial activity than lidocaine. Phenylephrine and methylparaben showed slight antimicrobial activity. These topical anesthetics have slight bactericidal activity against nasal pathogens, which can sometimes lead to false-negative results. Otolaryngologists should recognize the possible antimicrobial effects of topical anesthetics when culturing specimens. This is especially important when the specimen will be used for guidance of antimicrobial therapy, as in the case of the critically ill patient who requires aspiration for organism-specific therapy. Further studies, specifically in vivo experiments, are needed to determine if use of the drugs produces a significant change in the ability to culture organisms from these sites. This type of study would, however, be difficult to perform, since most patients requiring aspiration are already on high-dose antibiotics that would inhibit the growth of most microorganisms. A modified aspiration technique using a less concentrated topical anesthetic will likely be required to increase the chances of obtaining positive cultures.

Telomerase activity has been detected in a wide variety of human malignancies. It appears to be one of the fundamental ingredients necessary for cellular immortality. We sought to determine the incidence of telomerase activity in solid transitional cell carcinoma (TCC) specimens, benign urothelium, bladder washings, and voided urine from patients with TCC identified cystoscopically compared with controls. Telomerase activity was measured in 26 solid bladder cancers and 13 benign urothelial specimens using the telomere repeat amplification protocol (TRAP), a polymerase chain reaction (PCR) based assay. Telomerase activity was further measured in the centrifuged cellular material obtained from the bladder washings of 26 patients with TCC and 40 with benign urologic disease found to have a normal cystoscopy. All patients with hematuria were additionally evaluated with an upper tract radiographic examination and found to be free of malignancy. Voided urine was likewise evaluated in 11 patients with TCC, 12 with benign urologic diseases, and 56 asymptomatic control subjects. Telomerase activity was detected in 25 of 26 (96%) solid specimens, 21 of 26 (81%) bladder washings, and 6 of 11 (54%) voided urine specimens from patients with histologically confirmed TCC. In the control group, 2 of 13 (15%) benign urothelial specimens and 2 of 56 (4%) voided urine specimens from the asymptomatic volunteer group demonstrated telomerase activity. Of those with benign urologic disease, 16 of 40 (40%) bladder barbotage specimens and 6 of 12 (50%) voided urine specimens demonstrated telomerase activity. Sensitivity and specificity of telomerase as a marker for TCC were 81% and 60%, respectively, in the bladder washings group and 54% and 50%, respectively, in voided urine. These data indicate that activation of telomerase is frequent in solid TCC and appears to be a sensitive marker in bladder washings of patients with TCC. We noted an unexpectedly high false positive detection rate in patients with benign urologic diseases, especially those with symptomatic benign prostatic hyperplasia. An additional study of a larger number of both bladder cancer patients and those at risk is necessary to determine if telomerase activity could play a role as a diagnostic and/or surveillance marker of TCC. Published by Elsevier Science Inc.

A culling rate> 30% in dairy cattle is common in United States and Canada, despite general recommendations to lower cull rates in order to save on replacement costs. Also, higher cull rates are sometimes viewed as a sign of management failure, but the association between culling and disease at the cow level may not hold true at the herd level. Therefore, the objective of this study was to explore the relationship between disease events and individual-cow survival, and the relationship between herd-level disease incidence and culling rate., American Association of Bovine Practitioners Proceedings of the Annual Conference, 2013

An animal model was developed in which the anti-inflammatory effects of dexamethasone could be examined histologically in periapical tissues following endodontic overinstrumentation. Mandibular first molars containing vital or partially necrotic pulp tissue were instrumented beyond the apical foramen in rats. Fifty microliters of sterile saline or dexamethasone sodium phosphate (0.4 mg/ml) were administered in a blind manner by supraperiosteal infiltration into the buccal vestibule. The rats were killed after 6, 24, and 48 h. Block sections of the mandibular molars were processed for histological examination and stained with hematoxylin and eosin. The number of polymorphonuclear neutrophils present in the periapical tissues was counted in a blind manner and statistical analysis of the results was performed by two-way analysis of variance. Following endodontic overinstrumentation, local infiltration of dexamethasone produced a significant anti-inflammatory effect on the periapical tissues of teeth with vital or partially necrotic pulp tissue.

Biopsy reports from 150 periradicular tissue specimens obtained from teeth refractory to nonsurgical endodontic therapy were reviewed. The specimens were submitted by postdoctoral dental students in the Department of Endodontics, and the biopsy reports were prepared by oral pathologists at the University of Texas Health Science Center at San Antonio. The study found that 59.3% of the periradicular lesions were granulomas, 22% cysts, 12% scars, and 6.7% other pathoses. The majority (56%) of endodontically treated cases which failed to heal were recognized within 2 yr after the completion of therapy. The most common location for surgical retreatment was the anterior maxilla, followed by the posterior maxilla, the posterior mandible, and the anterior mandible. The periapical granuloma was the predominant pathosis at each location.

Quality assurance (QA) in the clinical laboratory is a process that ensures accurate and high-quality results. Successful QA programs avoid mistakes, provide consistent test results and data integrity, and are cost effective. In traditional hospitals, QA is an integral part of the laboratory with dedicated staff and published guidelines and regulations. The Department of Defense provides little direction for a QA program in the deployed environment. AR 40-3 and ARTEP 8-705-MTP implement the Tri-Service Clinical Laboratory Improvement Program (CLIP) regulations/standards for the clinical laboratory in medical treatment facilities (MTFs) and combat support hospitals. 1,2 Deployed units are not regulated by CLIP, but must meet minimal requirements. These include training verifi cation and competency, updating test standard operating procedures (SOPs), maintaining document quality control, quality assurance, and equipment maintenance programs, validation of all procedures, and participating in continuing education. 3 The Army Medical Department Center and School (AMEDDC&S) publishes and updates a fi eld laboratory information program (FLIP) disk, providing the latest SOPs and forms. However, the FLIP disk does not publish guidelines on QA. This editorial discusses the need to establish a set of guidelines to be used during deployment. Current Status in Theater In the Iraq theater of operations (ITO), military hospitals have varying capabilities, instrumentation, and laboratory test menus. Several universal issues affect the fl ow of operations of each MTF. These problems include: laboratory information system (LIS) interoperability, instrument maintenance, specimen shipping, personnel availability, reagent acquisition, and kit duplication.

Infections caused by multidrug-resistant (MDR) pathogens are associated with significant morbidity and mortality in patients with burn injuries. We performed a 6-year antibiotic susceptibility records review from January 2003 to December 2008 to assess the prevalence of MDR isolates by pathogen at the US Army Institute of Surgical Research Burn Center. During the study period Acinetobacter baumannii (780 isolates [22%]) was the most prevalent organism recovered, followed by Pseudomonas aeruginosa (703 isolates [20%]), Klebsiella pneumoniae (695 isolates [20%]), and Staphylococcus aureus (469 isolates [13%]). MDR prevalence rates among these isolates were A. baumannii 53%, methicillin-resistant S. aureus (MRSA) 34%, K. pneumoniae 17% and P. aeruginosa 15%. Two isolates, 1 A. baumannii and 1 P. aeruginosa, were identified as resistant to all 4 classes of antibiotics tested plus colistin. A. baumannii isolates recovered from patients with burns greater than 30% of total body surface area (TBSA) were more likely to be MDR (61%) with no significant difference for P. aeruginosa and K. pneumoniae. A higher proportion of MDR P. aeruginosa isolates were recovered from respiratory specimens compared to blood specimens (24% vs. 9%) while the opposite was true for MRSA (35% vs. 54%). A comparison of A. baumannii recovered during hospitalization days 1-5 and 15-30 revealed higher MDR levels as length of stay increased (48% vs. 75%) while no significant trends were observed for P. aeruginosa and K. pneumoniae. A similar pattern was observed for MDR A. baumannii levels for the facility between 2003 and 2005 and 2006-2008 (39% vs. 70%), with no significant increase in MDR P. aeruginosa and MDR K. pneumoniae. Increasing antibiotic resistance patterns of the most prevalent isolates recovered during extended hospitalization, impact of % TBSA and other clinical parameters may affect empirical antimicrobial therapy and patient management decisions during treatment.

Considerable advancements in shock resuscitation and wound management have extended the survival of burned patients, increasing the risk of serious infection. We performed a 6-year review of bacteria identification and antibiotic susceptibility records at the US Army Institute of Surgical Research Burn Center between January 2003 and December 2008. The primary goal was to identify the bacteria recovered from patients with severe burns and determine how the bacteriology changes during extended hospitalization as influenced by population and burn severity. A total of 460 patients were admitted to the burn ICU with 3507 bacteria recovered from 13,727 bacteriology cultures performed. The most prevalent organisms recovered were Acinetobacter baumannii (780), Pseudomonas aeruginosa (703), Klebsiella pneumoniae (695) and Staphylococcus aureus (469). A. baumannii was most often recovered from combat-injured (58%) and S. aureus the most frequent isolate from local (46%) burn patients. Culture recovery rate of A. baumannii and S. aureus was highest during the first 15 hospital days (73% and 71%); while a majority of P. aeruginosa and K. pneumoniae were recovered after day 15 (63% and 53%). All 4 pathogens were recovered throughout the course of hospitalization. A. baumannii was the most prevalent pathogen recovered from patients with total body surface area (TBSA) burns less than 30% (203) and 30-60% (338) while P. aeruginosa was most prevalent in patients with burns greater than 60% TBSA (292). Shifting epidemiology of bacteria recovered during extended hospitalization, bacteriology differences between combat-injured and local burn patients, and impact of % TBSA may affect patient management decisions during the course of therapy.

Diagonal wear on tires is a significant problem that can cause noise and vibration, and reduce the useful life of the tire. A wear model is used to show how diagonal wear can develop across the tread under certain conditions of toe and camber on a nondrive axle. In a simple wear model, tread wear is taken to be proportional to abrasion and sliding length. Triaxial stress measurements made in the laboratory on the tread blocks of rolling tires provide data for the wear prediction model. Under nonzero toe and camber the magnitude of the predicted wear is increased and its pattern becomes diagonal; a higher wear rate is predicted near the leading edge of contact on one side of the tire and near the trailing edge on the opposite side. This prediction agrees with the diagonal wear pattern seen on tires run on the road at similar toe and camber settings.

A 32-year-old male patient with severe factor VIII (FVIII) deficiency had developed a high-titer FVIII inhibitor at age 13. Recurrent hemarthroses caused bony destruction in both knees, significantly impairing his ability to walk. Knee examination revealed 20 degrees of varus, destruction of the medial joint line, and flexion contracture. Total knee arthroplasty was performed using recombinant factor VIIa (rFVIIa, NovoSeven) for hemostatic control. rFVIIa (85 microg/kg given intravenously over 3-5 minutes) was given just prior to surgery. The dose was repeated every 2 hours during and for the first 48 hours after surgery. When the tourniquet was removed, rFVIIa had not been infused for 1.5 hours, and significant hemorrhage was noted. The hemorrhage responded promptly to rFVIIa infusion. The infusion interval was extended to every 4 hours for an additional 48 hours, and subsequent doses were given every 6 hours until the patient returned to the clinic 2 days postdischarge. Hemoglobin levels dropped from 16.9 gm/dL on admission to 9.1 gm/dL at discharge. After 2 months, the patient returned to work. We recommend that tourniquet release be performed immediately after rFVIIa administration and that aggressive physical therapy be considered in the early postoperative period when rFVIIa infusions are frequent.

The enhancement layer in many scalable coding algorithms is composed of residual coding information. There is another type of information that can be transmitted instead of (or in addition to) residual coding. Since the encoder has access to the original sequence, it can utilize adaptive format conversion (AFC) to generate the enhancement layer and transmit the different format conversion methods as enhancement data. This paper investigates the use of adaptive format conversion information as enhancement data in scalable video coding. Experimental results are shown for a wide range of base layer qualities and enhancement bitrates to determine when AFC can improve video scalability. Since the parameters needed for AFC are small compared to residual coding, AFC can provide video scalability at low enhancement layer bitrates that are not possible with residual coding. In addition, AFC can also be used in addition to residual coding to improve video scalability at higher enhancement layer bitrates. Adaptive format conversion has not been studied in detail, but many scalable applications may benefit from it. An example of an application that AFC is well-suited for is the migration path for digital television where AFC can provide immediate video scalability as well as assist future migrations.

Quantitative tools to assess vascular macromolecular distributions have been limited by low signal‐to‐noise ratios, reduced spatial resolution, postexperimental motion artifact, and the inability to provide multidimensional drug distribution profiles. Fluorescence microscopy offers the potential of identifying exogenous compounds within intact tissue by reducing autofluorescence, the process by which endogenous compounds emit energy at the same wavelength as fluorescent labels. A new technique combining fluorescence microscopy with digital postprocessing has been developed to address these limitations and is now described in detail. As a demonstration, histologic cross‐sections of calf carotid arteries that had been loaded endovas‐cularly with FITC‐Dextran (20 kD) ex vivo were imaged at two different locations of the electromagnetic spectrum, one exciting only autofluorescent structures and the other exciting both autofluorescent elements and exogenous fluorescent labels. The former image was used to estimate the autofluorescence in the latter. Subtraction of the estimated autofluorescence resulted in an autofluorescence‐corrected image. A standard curve, constructed from arteries that were incubated until equilibrium in different bulk phase concentrations of FITC‐Dextran, was used to convert fluorescent intensities to tissue concentrations. This resulted in a concentration map with spatial resolution superior to many of the previous methods used to quantify macromolecular distributions. The transvascular concentration profiles measured by quantitative fluorescence microscopy compared favorably with those generated from the proven en face serial sectioning technique, validating the former. In addition, the fluorescence method demonstrated markedly increased spatial resolution. This new technique may well prove to be a valuable tool for elucidating the mechanisms of macromolecular transport, and for the rational design of drug delivery systems.

BACKGROUND: A proposed etiology of tumor activation involves p53 mutations while telomerase may serve as a key enzyme for maintenance of tumor cell proliferation. METHODS: Telomerase activity levels were measured in colorectal adenocarcinomas and corresponding normal tissue using a modified telomeric repeat amplification protocol, and p53 mutations were identified using immunohistochemical staining. Results were compared with staging data using regression analysis. RESULTS: Telomerase activity was present in 23 of 23 (100%) of the tumors and only 2 (9%) of. normal specimens (P

Human recombinant interferon (IFN)-alpha (alpha)-2b was given to a 57-year-old man with hypereosinophilia syndrome refractory to prednisone and hydroxyurea. One year later, he developed progressive renal failure and nephrotic-range proteinuria. Percutaneous kidney biopsy showed focal and segmental glomerular and mesangial sclerosis, chronic interstitial nephritis, and focal tubular necrosis. Discontinuation of cytokine therapy led to marked improvement in renal function and significant reduction in proteinuria. The potential role of IFN-alpha as the cause of renal failure and nephrotic-range proteinuria is discussed. The spectrum of renal disease attributed to IFN-alpha and the proposed pathogenic mechanisms are reviewed.

To the Editor: Thalidomide is used to treat multiple myeloma because of its apoptotic1 and antiangiogenic2 properties. Common side effects of thalidomide in patients with multiple myeloma include s...

An estimated 25 million people in the US alone rely on implanted medical devices, ∼2.5 million implanted within the nervous system. Even though many devices perform adequately for years, the host response to medical devices often severely limits tissue integration and long-term performance. This host response is believed to be particularly limiting in the case of intracortical microelectrodes, where it has been shown that glial cell encapsulation and localized neuronal cell loss accompany intracortical microelectrode implantation. Since neuronal ensembles must be within ∼50 µm of the electrode to obtain neuronal spikes and local field potentials, developing a better understanding of the molecular and cellular environment at the device-tissue interface has been the subject of significant research. Unfortunately, immunohistochemical studies of scar maturation in correlation to device function have been inconclusive. Therefore, here we present a detailed quantitative study of the cellular events and the stability of the blood-brain barrier (BBB) following intracortical microelectrode implantation and cortical stab injury in a chronic survival model. We found two distinctly inverse multiphasic profiles for neuronal survival in device-implanted tissue compared to stab-injured animals. For chronically implanted animals, we observed a biphasic paradigm between blood-derived/trauma-induced and CNS-derived inflammatory markers driving neurodegeneration at the interface. In contrast, stab injured animals demonstrated a CNS-mediated neurodegenerative environment. Collectively these data provide valuable insight to the possibility of multiple roles of chronic neuroinflammatory events on BBB disruption and localized neurodegeneration, while also suggesting the importance to consider multiphasic neuroinflammatory kinetics in the design of therapeutic strategies for stabilizing neural interfaces.

We demonstrate that the absolute separation between an atomic force microscope (AFM) tip and a solid substrate can be measured in the presence of an irreversibly adsorbed polymer film. The separation is obtained from the analysis of a scattered evanescent wave that is generated at the surface of the solid. By comparing our scattering measurements to conventional AFM measurements, we also show an example where a conventional AFM measurement gives the incorrect force-distance profile. We validate the measurement of separation from scattering by examining the force-separation profile in the presence of surfactant solution. This validation is possible because the tip can be used to desorb the surfactant film that forms in surfactant solution, so we are able to measure both the scattering and the cantilever deflection when the tip is in contact with the solid substrate. The main limitation of our technique now is the lack of a rigorous method for predicting the intensity of scattering from the tip in contact w...

Serum leukoagglutinating activity against the leukocytes of four patients with neutropenia was demonstrated using a modified microcapillary agglutination test. Cells from a panel of donors proved useful in attempting to define the identity of the antigens involved. In one instance anti-HLA-A9 activity could be demonstrated in a patient possessing HLA-A9. In the other three individuals no definite antigen assessment to HLA Series A and B antigens or the Lalezari series of neutrophil antigens could be made. Two of the patients' sera showed cross-reactivity and may be reactive with the same antigen or antigenic group. The microcapillary agglutination test appears to be useful in the evaluation of possible cases of autoimmune neutropenia.

A general computer-based system has been developed and implemented for acquiring and viewing medical image data. Originally developed for neuroanatomic studies (1), including investigations of cell topography and connectivity in brainstem nuclei, the system has become a versatile and powerful tool for three-dimensional analysis and display of a variety of types of image data, including studies of cardiac morphometry and 2-d gel electrophoresis. The system includes components for data input via video frame digitizer or digitizing tablet; graphical output through a high-resolution color graphics display or hardcopy plotter. Keys to the system's flexibility and power are a tree-structured data file system, in which line segments and shaded strips may be combined to form complex three-dimensional structures, and a disk-based virtual memory system which permits greater numerical accuracy and use of larger structures than would be otherwise possible with a 16-bit minicomputer.

Computed tomography (CT) can generate a set of serial contiguous slices which form a volume of medical image data. We have developed new techniques for creating computer synthesized 3-D images directly from a volume encoded as a three-dimensional array. The operator can place the eye anywhere in object space to selectively view a portion of the volume from any angle. A set of volume processing tools have been recently developed to allow interactive manipulation of image data within the volume. These tools allow the system to be used for surgical planning, and craniofacial implant design.

There is a growing use of computer technology for neuroanatomical studies. First uses began nearly as soon as small laboratory computers became available in the late 1960’s and early ‘70’s. The benefits of being able to quantitate what could only be photographed and verbally described were obvious to many workers. It was also a hope that machine storage of two and three dimensional information would lead to new methods of imaging of what could only be represented numerically. However, it was not clear at the outset, perhaps due to the novelty of the concept, hew long these procedures would take to develop, and exactly what power and capacity the computing machines would be needed in order to bring the concepts into regular use in the neuroanatomical laboratory.