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Evaluation of the rigor and appropriateness of CLIA '88 toxicology proficiency testing standards.

The proposed rule for the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) describes uniform standards for the design of proficiency testing (PT) challenges and for the evaluation of laboratory performance. Successful performance on PT is a condition for laboratory certification by the federal Department of Health and Human Services. We conducted a retrospective evaluation of PT data collected from laboratories participating in the New York State therapeutic substance monitoring/quantitative toxicology PT program to determine how well laboratories performed by proposed PT standards. We found that the unsuccessful performance rate is very low (less than 0.4%) and that laboratories providing limited services are more susceptible to program sanctions than are full-service laboratories. The performance criteria are empirically fixed limits that are not consistent with either the state of practice or the analytical goals based on clinical requirements for good patient care. We suggest that the performance standards, if adopted, would be a weak challenge to the capability of today's therapeutic drug monitoring service and will not provide the impetus to bring analytical performance characteristics into full compliance with analytical goals.

Laboratories↗

Differences in learning between hyperprolinemic mice and their congenic controls.

These experiments expanded earlier work on hyperprolinemic mice which showed learning deficits. The following behavioral tasks were used: step-through, passive avoidance; T-maze acquisition; shuttlebox acquisition, and radial-arm maze. Mouse species included PRO/Re-bb (genetically hyperprolinemic mice) and PRO/Re-aa (congenic nonhyperprolinemic controls) obtained from the Jackson Breeding Laboratories. Hyperprolinemic mice were impaired in acquiring T-maze and shuttlebox footshock avoidance behavior. One-trial passive avoidance behavior did not clearly differentiate between the groups. Radial maze performance was poor in both groups due possibly to observed acrophobia and lack of exploratory behavior. The results of this study combined with previously published work suggest that high-brain proline in conjunction with other amino acid changes account for the learning deficits.

Amino Acid Metabolism, Inborn Errors↗

[Cancer between infection and heredity: genes, viruses and mice at National Cancer Institute (1937-1977)].

After World War II, in the United States,viral explanation of cancer replaced a vision of the disease emphasizing genetic factors. From the mid 1950s onwards, experimental oncologists favored the notion that cancer was initiated by infectious agents passed from one generation to the next. In order to analyze this displacement, the present paper focuses on the part played by new experimental systems, i.e. mice showing tumors induced by viruses. Since animal models are agencies which "represent" human diseases, and mediate between different social worlds, their uses often result in opposing views. Mouse models thus provided tractable resources which favored the alternation between heredity and infection. The paper describes the emergence, in the late 1930s, at the Jackson Memorial Laboratory, of an agent enhancing the formation of mammary tumors in mice. This laboratory was then involved in the production of marketable inbred mice as well as in research concerned with genetic factors that may cause cancer. After World War II, loose theories and conflicting results helped turn the agent into a virus. At the National Cancer Institute, the virus was associated with a whole range of particles causing leukemia in mice. Owing to the Virus Cancer Program, the value of mouse tumor viruses increased in the late 1960s. This research effort then aimed at finding human tumor viruses, and at crafting cancer vaccines. It was modeled after the experience of the NCI chemotherapy program stemming from war research. In addition to the fact that biomedical research became a state enterprise, the study emphasizes three parameters. First, loose practices--both theoretical and experimental--helped manage the variability of animal models. Secondly, the standardization and mass production of animals and reagents encouraged the stabilization of research programs. Thirdly, private biotechnology companies working under NCI contracts implemented preclinical work, and mediated between virology laboratories and clinical settings.

Animals↗

Cresyl violet: a rapid, simple, easily interpretable stain for detecting Pneumocystis carinii in sputum.

Over a three-month period at the pathology laboratory of Jackson Memorial Hospital, 110 sputum samples from 62 hospitalized patients with suspected AIDS were examined for Pneumocystis carinii. Sputum specimens were either expectorated spontaneously (most patients) or expectorated after the inhalation of small amounts of nebulized normal saline. Each sputum sample was cytocentrifuged onto two slides. One slide was stained with Gomori methenamine-silver (GMS) and the other with cresyl violet (CV). Among the 62 study patients, 18 were proven to have no histologic evidence of P carinii pneumonia. Of the remaining 44 patients, P carinii organisms were found by GMS stain in 14 (32%) and by CV stain in 18 (41%). Among those with a positive CV stain, the diagnosis was made on the first sputum specimen in 14 patients and on the second specimen in the remaining four patients. CV stain is at least as sensitive as GMS in detecting P carinii cysts in the sputum of AIDS patients with P carinii pneumonia, and its diagnostic sensitivity may exceed 40% under field conditions. Further, CV stain is much simpler to prepare than GMS and much simpler to interpret than Giemsa. It could be easily adapted for general use to expedite the diagnosis and treatment of P carinii pneumonia.

Adult↗

Rapid detection of West Nile Virus in birds using the VecTest WNV Antigen Assay.

OBJECTIVE: To determine if the VecTest West Nile Virus Antigen Assay (for testing mosquitoes) could be adapted to detect West Nile virus (WNV) rapidly and accurately in birds for screening purposes. DESIGN: Cloacal swabs and tissue (kidney and spleen) were harvested from 40 fresh dead birds. The VecTest was used for each swab specimen for detection of WNV; PCR was used for each tissue specimen for confirmation of WNV. SETTING: Mississippi Veterinary Diagnostic Laboratory (MVDL) in Jackson Mississippi and College of Veterinary Medicine-Mississippi State University (CVM-MSU) in Starkville Mississippi. SPECIMENS/SUBJECTS: Forty birds of the Corvid family (31 blue jays and 9 American crows) were included in the study. Fresh dead birds that died from no obvious cause were submitted for testing. RESULTS: VecTest results were 35 positives and 5 negatives. PCR results were 35 positives and 5 negatives. CONCLUSION: The VecTest showed 100% accuracy.

Animals↗

Developing a lean culture in the laboratory.

The Director of Pathology at Jackson Memorial Hospital was interested in improving the operational efficiencies of the department in order to enhance the department's level of service in conjunction with the expansion of the overall health system. The decision was made to implement proven Lean practices in the laboratory under the direction of a major consulting firm. This article details the scope of the initial project as well as the operating principles of Lean manufacturing practices as applied to the clinical laboratory. The goals of the project were to improve turnaround times of laboratory results, reduce inventory and supply costs, improve staff productivity, maximize workflow, and eliminate waste. Extensive data gathering and analysis guided the work process by highlighting the areas of highest opportunity. This systematic approach resulted in recommendations for the workflow and physical layout of the laboratory. It also included the introduction of "standard workflow" and "visual controls" as critical items that streamlined operational efficiencies. The authors provide actual photographs and schematics of the reorganization and improvements to the physical layout of the laboratory. In conclusion, this project resulted in decreased turnaround times and increased productivity, as well as significant savings in the overall laboratory operations.

Clinical Laboratory Techniques↗

Laboratory, reading center, and coordinating center data management methods in the Jackson Heart Study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in the United States. In comparison to whites, African-Americans have a higher risk of dying from CVD and have a worse risk factor profile. The Jackson Heart Study (JHS) is designed to investigate the origin and natural history of CVD in African-Americans. METHODS: Reading centers for electrocardiograms, echocardiograms, carotid ultrasonograms, pulmonary function tests, and ambulatory blood pressure monitoring provide training for data accrual, quality assurance assessments, and specialized measurements for research objectives. Laboratories adhering to well-established quality assurance programs provide blood and urine analyses, as well as storage of specimens for future assays. A new Coordinating Center was created to perform functions analogous to those of coordinating centers for multisite studies, including protocol development, data management, statistical analyses, and operational support for the study. An established coordinating center serves as a resource to the JHS Coordinating Center, providing assistance in preparing procedure manuals and data collection forms. This group also designed and developed the JHS data management system. RESULTS: This network of specialized research organizations is implementing state- of-the-science methodologies to assess prevalence, progression, and incidence of CVD and subclinical atherosclerosis, and to evaluate a myriad of risk factors. From November 2000 through March 2004, JHS collected 4000 data fields on each of more than 5300 African-American participants. CONCLUSIONS: This article describes the roles of specialized research agencies contributing to JHS, and the methodologies being utilized to accumulate study data. A diverse collection of scientific disciplines is required to collect the information needed to meet the objectives of the JHS.

Arteriosclerosis↗

Surgical prosthetic splints as an adjunct in treating facial fractures.

Surgical splints are a valuable adjunct in managing certain mandible and maxillary fractures. Of the various splint materials, acrylic is the easiest, fastest, and least expensive. Acrylic splints are rigid, strong, easily adjusted and repaired, translucent, lightweight, and tolerated well by the oral mucosa. Splints are beneficial not only in the edentulous adult, but also in the child with deciduous dentition and in the patient with a partial dentition. Splints are helpful in managing fractures of the symphysis, parasymphyseal region, body, and alveolar ridges of the mandible, sagittal fractures of the hard palate, and severely comminuted mandible fractures. Construction of acrylic splints is simple and rapid if the surgeon uses the services of a dentist or a dental laboratory.

Acrylates↗

Relations among questionnaire and laboratory measures of rhinovirus infection.

Due to high incidence and quality-of-life impact, upper respiratory infection substantially impacts on population health. To test or compare treatment effectiveness, a well-designed and validated illness-specific quality-of-life instrument is needed. Data reported in the current study were obtained from a trial testing echinacea for induced rhinovirus infection. Laboratory-assessed biomarkers included interleukin (IL)-8, nasal neutrophil count (polymorphonuclear neutrophils (PMN)), mucus weight, viral titre and seroconversion. The questionnaires used included the general health short form (SF)-8 (24-h recall version), the eight-item Jackson cold scale, and the 44-item Wisconsin Upper Respiratory Symptom Survey (WURSS). In total, 399 participants were inoculated with rhinovirus and monitored over 2,088 person-days. Statistically significant associations were found among nearly all variables. Between-questionnaire correlations were: WURSS-Jackson = 0.81; WURSS-SF-8 = 0.62; and Jackson-SF-8 = 0.60. Correlations with laboratory values were as follows: WURSS-mucus weight = 0.53; Jackson-mucus weight = 0.55; WURSS-viral titre = 0.37; Jackson-viral titre = 0.46; WURSS-IL-8 = 0.31; Jackson-IL-8 = 0.36; WURSS-PMN = 0.31; and Jackson-PMN = 0.28. Neither WURSS nor Jackson yielded satisfactory cut-off scores for diagnosis of infection. Symptomatic and biological outcomes of upper respiratory infection are highly variable, with only modest associations. While Wisconsin Upper Respiratory Symptom Survey and Jackson questionnaires both correlate with biomarkers, neither is a good predictor of induced infection. The inclusion of functional and quality-of-life items in the Wisconsin Upper Respiratory Symptom Survey does not significantly decrease the strength of association with laboratory-assessed biomarkers.

Adult↗