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Biomedical subjects

Kelly J Henrickson

Publications and source records attributed to Kelly J Henrickson.

7 recordsLinked to original sources

Current methods for the rapid diagnosis of bioterrorism-related infectious agents.

Bioterrorism is the calculated use of violence against civilians to attain political, religious, or ideologic goals using weapons of biological warfare. Bioterrorism is of particular concern because these weapons can be manufactured with ease and do not require highly sophisticated technology. Moreover, biologic agents can be delivered and spread easily and can effect a large population and geographic area. The terrorist attacks occurring around the world necessitate society's continued investment in adequate defense against these unpredictable and irrational events.

Bioterrorism↗

A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial.

OBJECTIVE: Critically ill neonates are at high risk for vascular catheter-related bloodstream infection (CRBSI), most often caused by coagulase-negative staphylococci. Most CRBSIs with long-term devices derive from intraluminal contaminants. The objective of this study was to ascertain the safety and the efficacy of a vancomycin-heparin lock solution for prevention of CRBSI. METHODS: A prospective, randomized double-blind trial was conducted during 2000-2001 at a community hospital level III NICU. Very low birth weight and other critically ill neonates with a newly placed peripherally inserted central venous catheter were randomized to have the catheter locked 2 or 3 times daily for 20 or 60 minutes with heparinized normal saline (n = 43) or heparinized saline that contained vancomycin 25 microg/mL (n = 42). The origin of each nosocomial bloodstream infection (BSI) was studied by culturing skin, catheter hubs, and implanted catheter segments and blood cultures, demonstrating concordance by restriction-fragment DNA subtyping. Surveillance axillary and rectal cultures were performed to detect colonization by vancomycin-resistant organisms. The main outcome measures were (1) CRBSIs and (2) colonization or infection by vancomycin-resistant Gram-positive bacteria. RESULTS: Two (5%) of 42 infants in the vancomycin-lock group developed a CRBSI as compared with 13 (30%) of 43 in the control group (2.3 vs 17.8 per 1000 catheter days; relative risk: 0.13; 95% confidence interval: 0.01-0.57). No vancomycin-resistant enterococci or staphylococci were recovered from any cultures. Vancomycin could not be detected in the blood of infants who did not receive systemic vancomycin therapy. Twenty-six neonates (8 vancomycin-lock group, 18 control group) had at the end of a catheter-lock period asymptomatic hypoglycemia that resolved promptly when glucose-containing intravenous fluids were restarted. CONCLUSIONS: Prophylactic use of a vancomycin-heparin lock solution markedly reduced the incidence of CRBSI in high-risk neonates with long-term central catheters and did not promote vancomycin resistance but was associated with asymptomatic hypoglycemia. The use of an anti-infective lock solution for prevention of CRBSI with long-term intravascular devices has achieved proof of principle and warrants selective application in clinical practice.

Anti-Bacterial Agents↗

Cost-effective use of rapid diagnostic techniques in the treatment and prevention of viral respiratory infections.

The most cost-effective current use of rapid respiratory virus diagnostics is through highly sensitive and specific molecular assays (mostly PCR-based) in the hospital setting or for chronically ill or immunocompromised outpatients. Specifically, this cost savings is the result of preventing hospitalization or decreasing length of hospitalization, decreasing unnecessary testing and procedures, directing specific therapy, and reducing unnecessary antibiotic use. Equally important is community surveillance by informing physicians rapidly what agents are in the community. Important ongoing issues regarding the cost-effective use of these assays include the cost of reagents or machinery, reimbursement for testing, the need for reliable commercial reagents, the need for open platforms that can respond to new "emerging" or "reemerging" agents, and the need for proficiency panels to share between laboratories. Rapid molecular diagnostic assays for the detection of respiratory viruses have moved into the mainstream of clinical testing. These assays already play important roles in select populations and clinical situations for critical patient management. In addition, there are numerous clinical scenarios where the use of these assays should have a positive cost/benefit ratio. Further work needs to be done to demonstrate this benefit to society. Further development of multiplex assays and decreasing the cost of testing will help improve the benefit of these assays to clinical care. Work is underway on large multiplex molecular assays with high sensitivity and specificity that will be able to be used in an outpatient setting both because of speed and low cost. The future holds great potential for physicians. who soon may be able to answer the age-old question, "Doc, what do I have?" with more than, "You probably have a virus."

Adolescent↗

Advances in the laboratory diagnosis of viral respiratory disease.

BACKGROUND: In recent years significant advances in the laboratory diagnostics available to detect respiratory viral infections have been achieved. METHODS: This article presents the types of diagnostic methods currently available to the practitioner, as well as those on the horizon. The article covers tissue culture, serology and direct examination as well as some rapid diagnostic techniques and molecular assays, previewing developing new technology. CONCLUSIONS: Laboratory diagnosis will likely be clinically useful in some but not all cases of viral infection. As new diagnostic methods become widely available, it is increasingly important to develop guidelines for laboratory testing when viral illness is suspected.

Clinical Laboratory Techniques↗

National disease burden of respiratory viruses detected in children by polymerase chain reaction.

BACKGROUND: The epidemiology of community-acquired respiratory viruses at the Children's Hospital of Wisconsin between 1996 and 1998 was examined with molecular [multiplex (M) PCR] and standard virologic methods. METHODS AND RESULTS: A total of 3325 patients with lower respiratory infection (LRI) [bronchiolitis (42%), pneumonia (38%) and croup (12%)] were identified. It is estimated that 545,000 LRI hospitalizations occur each year in the United States in children younger than 18 years old (viral, 428,000; pneumonia, 221,000; bronchiolitis, 222,000; croup, 65,000), including a continued increase in bronchiolitis hospitalizations (47.8/1000; <1 year). The most common viruses detected each year in hospitalized children included respiratory syncytial virus (A and B; 117,000), parainfluenza virus (PIV-1 and -2, 48 000; PIV-3, 18,000) and influenza (A and B, 39,000). With multiplex reverse transcription polymerase chain reaction (MPCR), different patient populations demonstrated different LRI epidemiology in relation to specific syndromes and viral causes. At least 21% of LRI hospitalizations were in children with significant medical problems.PIVs were detected much more frequently in immunocompromised children than in previously healthy children (33% vs. 16%). Similarly 15% of respiratory syncytial virus was detected between May and October, mostly in immunocompromised children. Influenza caused 19% of bronchiolitis in previously healthy children, and no virus could be reliably predicted based on clinical presentation, including wheezing. Of children hospitalized for LRI, 40% tested positive for the seven most common respiratory viruses by MPCR. CONCLUSIONS: Work is under way to expand the number of viruses detected by MPCR and to determine whether newly discovered viruses, such as human metapneumovirus, contribute to the burden of pediatric LRI hospitalizations.

Adolescent↗

Rapid detection and identification of human adenovirus species by adenoplex, a multiplex PCR-enzyme hybridization assay.

Human adenoviruses (AdV) have been implicated in a wide variety of diseases and are ubiquitous in populations worldwide. These agents are of concern particularly in immunocompromised patients, children, and military recruits, resulting in severe disease or death. Clinical diagnosis of AdV is usually achieved through routine viral cell culture, which can take weeks for results. Immunofluorescence and enzyme-linked immunosorbent assay-based techniques are more timely but lack sensitivity. The ability to distinguish between the six different AdV species (A to F) is diagnostically relevant, as infections with specific AdV species are often associated with unique clinical outcomes and epidemiological features. Therefore, we developed a multiplex PCR-enzyme hybridization assay, the Adenoplex, using primers to the fiber gene that can simultaneously detect all six AdV species A through F in a single test. The limit of detection (LOD) based on the viral 50% tissue culture infective dose/ml for AdV A, B, C, D, E, and F was 10(-2), 10(-1), 10(-1), 10(-2), 10(-1), and 10(-2), respectively. Similarly, the LOD for the six DNA controls ranged from 10(2) to 10(3) copies/ml. Twelve common respiratory pathogens were tested with the Adenoplex, and no cross-reactivity was observed. We also validated our assay using clinical specimens spiked with different concentrations of AdV strains of each species type and tested by multiplex PCR and culture. The results demonstrated an overall sensitivity and specificity of Adenoplex of 100%. This assay can be completed in as few as 5 h and provides a rapid, specific, and sensitive method to detect and subtype AdV species A through F.

Adenoviridae Infections↗

Parainfluenza viruses.

Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has been accumulated. This has led to significant changes in both the nomenclature and taxonomic relationships of these viruses. HPIV is genetically and antigenically divided into types 1 to 4. Further major subtypes of HPIV-4 (A and B) and subgroups/genotypes of HPIV-1 and HPIV-3 have been described. HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each subtype can cause somewhat unique clinical diseases in different hosts. HPIV are enveloped and of medium size (150 to 250 nm), and their RNA genome is in the negative sense. These viruses belong to the Paramyxoviridae family, one of the largest and most rapidly growing groups of viruses causing significant human and veterinary disease. HPIV are closely related to recently discovered megamyxoviruses (Hendra and Nipah viruses) and metapneumovirus.

Animals↗