Search

Describes a person with confirmed human immunodeficiency virus (HIV) infection in whom enzyme immunoassay (EIA) for HIV antibody (HIV-EIAs) were persistently negative beyond the expected `window period.' Three reasons HIV-infected blood may test EIA negative for HIV antibody.

A vesicular, peeling rash characteristic of a phytophototoxic dermatitis developed on the hands and arms of 30 of 127 grocery workers. The rash subsequently healed with residual hyperpigmentation. Produce workers had the highest attack rate, 100% (8 of 8, p less than 0.0001). Although contact with celery had the highest relative risk for disease (relative risk, 6.3; 95% confidence interval, 2.6, 19.2) and the strongest dose-response effect, an association with celery alone could not be shown because workers were also exposed to other produce. However, anecdotal evidence also suggested that celery might be involved. The disease-resistant, high-quality brand of celery carried by these stores had higher levels of furanocoumarins, potent photosensitizers and a known cause of phytophotodermatitis, than other brands (p = 0.01). A randomly selected nationwide sample of stores in this chain showed dermatitis in 13 of 17 states and 26% of produce workers surveyed. Plant breeding to produce a more disease-resistant celery stock may lead to increased levels of endogenous furanocoumarins, resulting in phytophotodermatitis in grocery workers. [ABSTRACT FROM AUTHOR]

Describes an outbreak of coccidioidomycosis in workers at an archaeological site at Dinosaur National Monument in Utah during June-July 2001, and represents the first identification of coccidioidomycosis in northern Utah. Investigation of the work site, which revealed a desert environment; Recommendation to minimize soil disturbance and dust inhalation; Editorial note from the United States Centers for Disease Control & Prevention.

West Nile virus (WNV) is the most important and widespread mosquito-borne virus in the United States (U.S.). WNV has the ability to spread rapidly and effectively, infecting more than 320 bird and mammalian species. An examination of environmental conditions and the health of keystone species may help predict the susceptibility of various habitats to WNV and reveal key risk factors, annual trends, and vulnerable regions. Since 2002, WNV outbreaks in Wisconsin varied by species, place, and time, significantly affected by unique climatic, environmental, and geographical factors. During a 15 year period, WNV was detected in 71 of 72 counties, resulting in 239 human and 1397 wildlife cases. Controlling for population and sampling efforts in Wisconsin, rates of WNV are highest in the western and northwestern rural regions of the state. WNV incidence rates were highest in counties with low human population densities, predominantly wetland, and at elevations greater than 1000 feet. Resources for surveillance, prevention, and detection of WNV were lowest in rural counties, likely resulting in underestimation of cases. Overall, increasing mean temperature and decreasing precipitation showed positive influence on WNV transmission in Wisconsin. This study incorporates the first statewide assessment of WNV in Wisconsin.

Aims: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification., Methods and Results: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome., Conclusion: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Importance: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births., Objectives: To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments., Design: Epidemiological and retrospective observational study., Setting: Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test., Main Outcomes and Measures: Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked., Results: Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia., Conclusions and Relevance: Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

Beginning in early 2011, the Centers for Disease Control and Prevention and the Association of Public Health Laboratories launched the Laboratory Efficiencies Initiative (LEI) to help public health laboratories (PHLs) and the nation's entire PHL system achieve and maintain sustainability to continue to conduct vital services in the face of unprecedented financial and other pressures. The LEI focuses on stimulating substantial gains in laboratories' operating efficiency and cost efficiency through the adoption of proven and promising management practices. In its first year, the LEI generated a strategic plan and a number of resources that PHL directors can use toward achieving LEI goals. Additionally, the first year saw the formation of a dynamic community of practitioners committed to implementing the LEI strategic plan in coordination with state and local public health executives, program officials, foundations, and other key partners.

Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to assess the technical feasibility of a fetal trans-apical stent delivery into the pulmonary artery using a novel hybrid-intervention technique as a possible route for prenatal minimally invasive heart-valve-implantation approaches., Methods: Pregnant Pre-Alp sheep between 122 and 128 days' gestation (n = 3) underwent a midline laparotomy. The fetus was left in utero or partially externalized and its chest was opened via a left-sided minithoracotomy. The fetal heart was cannulated and a guide wire was introduced through the ductus arteriosus into the aorta. A 14-French delivery system was then mounted onto the guide wire and advanced to the landing zone in the pulmonary artery, where the stent was deployed. The position of the stent was confirmed using echocardiography, angiography as well as computed tomography., Results: The trans-apical implantation was successful in all animals. However, at necropsy in one animal, the stent was found to partly occlude one of the pulmonary valvular leaflets. Bleeding at the antero-apical incision occurred in all animals but could be managed without fetal demise. No fetal cardiopulmonary bypass was performed. In all animals, contrast angiography displayed normal perfusion of the pulmonary vasculature as well as the ductus arteriosus., Conclusions: Our study demonstrates the principal technical feasibility of a prenatal stent delivery into the pulmonary artery using a novel trans-apical hybrid-intervention technique. This approach demonstrates the first step towards possible future minimally invasive prenatal heart-valve-implantation procedures.

Aims: A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates., Methods and Results: Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue., Conclusion: Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses.

Tissue engineering aims at the creation of living neo-tissues identical or close to their native human counterparts. As basis of this approach, temporary biodegradable supporter matrices are fabricated in the shape of a desired construct, which promote tissue strength and provide functionality until sufficient neo-tissue is formed. Besides fully synthetic polymer-based scaffolds, decellularized biological tissue of xenogenic or homogenic origin can be used. In a second step, these scaffolds are seeded with autologous cells attaching to the scaffold microstructure. In order to promote neo-tissue formation and maturation, the seeded scaffolds are exposed to different forms of stimulation. In cardiovascular tissue engineering, this "conditioning" can be achieved via culture media and biomimetic in vitro exposure, e.g., using flow bioreactors. This aims at adequate cellular differentiation, proliferation, and extracellular matrix production to form a living tissue called the construct. These living autologous constructs, such as heart valves or vascular grafts, are created in vitro, comprising a viable interstitium with repair and remodeling capabilities already prior to implantation. In situ further in vivo remodeling is intended to recapitulate physiological vascular architecture and function. The remodeling mechanisms were shown to be dominated by monocytic infiltration and chemotactic host-cell attraction leading into a multifaceted inflammatory process and neo-tissue formation. Key molecules of these processes can be integrated into the scaffold matrix to direct cell and tissue fate in vivo.

The M-band is the prominent cytoskeletal structure that cross-links the myosin and titin filaments in the middle of the sarcomere. To investigate M-band alterations in heart disease, we analyzed the expression of its main components, proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac function was assessed by echocardiography and compared to the expression pattern of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis. Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM) was accompanied by specific M-band alterations. The dominant splice isoform in the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart and correlated with a decrease in cardiac function (R = -0.86). In addition, we have analyzed the expressions of myomesins in human myocardial biopsies (N = 40) obtained from DCM patients, DCM patients supported by a left ventricular assist device (LVAD), hypertrophic cardiomyopathy (HCM) patients and controls. Quantitative RT-PCR revealed that the EH-myomesin isoform was up-regulated 41-fold (P < 0.001) in the DCM patients compared to control patients. In DCM hearts supported by a LVAD and HCM hearts, the EH-myomesin expression was comparable to controls. Immunofluorescent analyses indicate that EH-myomesin was enhanced in a cell-specific manner, leading to a higher heterogeneity of the myocytes' cytoskeleton through the myocardial wall. We suggest that the up-regulation of EH-myomesin denotes an adaptive remodeling of the sarcomere cytoskeleton in the dilated heart and might serve as a marker for DCM in mouse and human myocardium.

Object: Cerebral cavernous malformations (CCMs) are among the most prevalent cerebrovascular malformations, and endothelial cells seem to play a major role in the disease. However, the underlying mechanisms, including endothelial intercellular communication, have not yet been fully elucidated. In this article, the authors focus on the endothelial junction proteins CD31, VE-cadherin, and occludin as important factors for functional cell-cell contacts known as vascular adhesion molecules and adherence and tight junctions., Methods: Thirteen human CCM specimens and 6 control tissue specimens were cryopreserved and examined for the presence of VE-cadherin, occludin, and CD31 by immunofluorescence staining. Protein quantification was performed by triplicate measurements using western blot analysis., Results: Immunofluorescent analyses of the CCM sections revealed a discontinuous pattern of dilated microvessels and capillaries as well as increased expression of occludin, VE-cadherin, and CD31 in the intima and in the enclosed parenchymal tissue compared with controls. Protein quantification confirmed these findings by showing upregulation of the levels of these proteins up to 2-6 times., Conclusions: A protocol enabling the molecular and morphological examination of the intercellular contact proteins in human CCM was validated. The abnormal and discontinuous pattern in these endothelial cell-contact proteins compared with control tissue explains the loose intercellular junctions that are considered to be one of the causes of CCM-associated bleeding or transendothelial oozing of erythrocytes. Despite the small number of specimens, this study demonstrates for the first time a quantitative analysis of endothelial junction proteins in human CCM.

To study the affect of mechanical stimuli on human laryngeal fibroblasts, we developed bioreactors capable of vibrating cell seeded substrates at frequencies and displacements comparable to measured phonation values in human subjects. In addition, we developed a means of harvesting the secreted matrix as a bulk biomaterial by removing the polymer foam using an organic solvent. Using the system human derived laryngeal fibroblasts were subjected to vibrational stimuli (100 Hz) for 1-21 days. Following mechanical conditioning, extracellular matrix and matrix related gene expression, cytokine production, matrix protein accumulation, and construct material properties were assessed with DNA microarray, enzyme linked immunosorbent, indirect immunofluorescent, and uni-axial tensile assays respectively. The results show that vocal fold-like vibrational stimuli is sufficient to influence the expression of several key matrix and matrix related genes, enhance the secretion of the profibrotic cytokine TGFbeta1, increase the accumulation of the extracellular matrix proteins, fibronectin and collagen type 1, as well as enhance construct stiffness compared to non-stimulated controls. Our results demonstrate that high frequency substrate vibration, like cyclic strain, can accelerate matrix deposition from human derived laryngeal fibroblasts. The study supports the notion that preconditioning regimens using human cells may be useful for producing cell derived biomaterials for therapeutic application.

Infection with human immunodeficiency virus (HIV) is routinely and easily diagnosed with use of enzyme immunoassay (EIA) test kits. We describe an unusual patient who developed AIDS despite testing negative for antibodies to HIV 35 times over a 4-year period. HIV infection was confirmed by the results of p24-antigen assays and polymerase chain reaction amplification of proviral DNA. Sequence analysis of the virus demonstrated that it was closely related to a strain obtained from the patient's sexual partner. The explanation for this patient's persistently negative EIA results is unclear. However, this case does suggest that physicians who treat patients with AIDS-defining conditions but for whom standard HIV antibody testing is negative should consider the possibility that HIV infection is present and may be identified by additional testing procedures.

These guidelines provide scientific information for policy development by state health departments considering appropriate use of newborn screening specimens after screening tests are finished. Information was collected, debated, and formulated into a policy statement by the Newborn Screening Committee of the Council of Regional Networks for Genetic Services (CORN), a federally funded national consortium of representatives from 10 regional genetics networks. Newborn screening programs vary widely in approaches and policies concerning residual dried blood spot samples (DBS) collected for newborn screening. Recognition of the epidemiological utility of DBS samples for HIV seroprevalence surveys and a growing interest in DBSs for DNA analysis has intensified consideration of issues regarding retention, storage, and use of residual DBS samples. Potentially these samples provide a genetic material "bank" for all newborns nationwide. Their values as a resource for other uses has already been recognized by scientists, administrators, and judicial officials. Programs should promulgate rules for retention and use of residual newborn screening DBS samples based on scientifically valid information. Banking of newborn samples as sources of genetic material should be considered in light of potential benefit or harm to society.

Nosocomial Gram-negative bacillary meningitis and bacteremia occurred in a patient who was receiving intrathecal and intravenous amphotericin B. An epidemiologic investigation found the amphotericin B to be contaminated with Enterobacter agglomerans, Pseudomonas fluorescens, and P aeruginosa. These contaminants were traced to a lot ot sodium phosphate buffer that was added to all intrathecal and intravenous amphotericin B preparations. The phosphate buffer underwent prolonged storage at room temperature and was not subject to terminal sterilization nor sterility testing. This parenteral admixture prepared in the hospital is now steam autoclaved and sterility tested before use.

Between Feb 1 and Aug 31, 1984, an outbreak of 18 symptomatic cases of Q fever occurred in Idaho; these numbers represent an increase over the three cases reported in 1982 and the five reported in 1983. Four of the patients in the outbreak required hospitalization for two to five weeks; there were no fatalities. Eight of the cases had documented Q fever hepatitis, and one had pneumonia. All 18 of the 1984 cases for whom information was available were epidemiologically linked to visiting or working at a sheep research station and/or being exposed to animals from this research station. In this outbreak, patients typically had a hepatitislike illness associated with fever and severe headache. Severity of illness ranged from asymptomatic to life threatening. Cases of pneumonia and hepatitis due to Q fever continue to occur in the United States, especially among persons exposed to livestock.

A practical slide agglutination test, with commercial antisera (Difco) and live antigens (antigens of live bacteria) taken directly from 24-h antimicrobial susceptibility plates, has been established for serotyping Pseudomonas aeruginosa. Until recently, the lack of both a standard antigenic scheme and a source of commercial antisera has made serological typing of this organism impractical. A simplified procedure with 17 unabsorbed antisera and live antigens prepared from materials readily available in most clinical microbiology laboratories makes epidemiological typing of this organism possible in hospital laboratories. The distribution of each serotype examined in this study was determined by using 425 consecutive patient isolates from six different hospitals. The distribution of O antigen groups (live antigen) was as follows: O1, 11.5%; O2, 1.6%; O3, 3.8%; O4, 7.8%; O5, 4.2% O6, 27.1%; O7,8, 5.9%; O9, 6.8%; O10, 2.4%; O11, 8.2%; O12 through O17, each less than 1%. Ten and six-tenths percent of the above agglutinated in two antisera, 3.3% agglutinated in more than two antisera, and 5.2% did not agglutinate in any antisera. A comparison of live and heated antigens shows that 93.2% were typable with the live antigen, and 94.5% were typable with the heated antigen. When both antigens were used, we typed 96.3% of 725 isolates. The reproductibility and specificity of the serological procedure were examined. We recommend using the live antigen for routine serological typing in clinical microbiology laboratories for "in house" epidemiology and reserving the heated antigen for reference and research typing (and for those few cases where results cannot be obtained using the live antigen). The application of serotyping in the study of outbreaks of P. aeruginosa is also presented.