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How to make sense of pertussis immunogenicity data.

Studies on serologic correlates to protection in pertussis were reviewed. Trials in the 1950s showed that agglutinogen titers correlated to protection of whole-cell vaccines, but postvaccination antibodies against pertussis toxin (PT) and against filamentous hemagglutinin did not in a later trial of acellular vaccines. However, in household studies nested in 2 recent trials, preexposure antibody levels against pertactin and against fimbriae correlated with protection against typical and mild pertussis, and anti-PT correlated only with protection against typical pertussis. These findings could be used by regulatory agencies to license pertussis vaccines. A reference laboratory for pertussis should distribute panels to control interlaboratory variation in recommended assays, and a minimal response should be set for each pertussis antigen. We conclude that 2 studies have shown correlates between measurable anti-pertactin, anti-fimbriae, and anti-PT antibody levels at exposure and individual protection against pertussis. We suggest that postvaccination response rates may be used as surrogate markers of protection.

Antibodies, Bacterial↗

A reference system for cortisol.

OBJECTIVES: The International Federation of Clinical Chemistry (IFCC) initiated a pilot study, with cortisol as an example, that aims to implement the concept of standardization of hapten immunoprocedures on the basis of metrological traceability. In fact, this standardization concept comes down to correct calibration of measurement procedures, so that measurement results for patient samples can be traced back to the metrologically highest reference of a result, i.e., an SI unit as embodied in the primary reference material. In consequence, demonstration of standardization of a test system on the basis of traceability requires evaluation of measurement results pertaining to patient samples for accuracy. Such an evaluation shall be done by a correlation study of the routine test system with an accuracy-based reference measurement procedure. DESIGN AND METHODS: The IFCC project will select a panel of single donation human serum samples, and assign them with values for cortisol by measurement with at least two isotope dilution-gas chromatography/mass spectrometry reference methods. Limited amounts of the panel will be distributed to manufacturers, with the object to measure the samples with their calibrated immunoprocedures. The patient correlation studies between the routine and the reference methods will then be interpreted in terms of specificity and accuracy. It will also be investigated whether the performed comparison can be used as a basis for re-calibration. From the experience gained through this pilot study for cortisol, IFCC will formulate recommendations and guidance to manufacturers on how to perform and reliably interpret patient correlation studies. In this way, it is to be expected that the project might form a basis for general implementation of the concept of standardization of hapten immunoassays on the basis of metrological traceability.

Clinical Laboratory Techniques↗

The Centers for Disease Control-National Heart, Lung and Blood Institute Lipid Standardization Program. An approach to accurate and precise lipid measurements.

In collaboration with the National Heart, Lung, and Blood Institute, the CDC has supported programs for standardizing lipid measurements for more than 30 years. These programs were begun because comparable and accurate quantitative measurements were needed for epidemiologic studies of coronary heart disease. Since the first program was initiated, over 500 national and international laboratories have participated in the various CDC lipid standardization programs. The cornerstone of these standardization programs has been an accuracy base of lipid reference materials and methods developed by CDC. Specifically, CDC has developed human, serum-based reference materials for cholesterol, HDL, triglyceride, and apolipoproteins A-I and B and reference methods for total cholesterol, HDL, and triglyceride. The CDC reference method for cholesterol has been adopted as the national reference method for cholesterol by the National Reference System for the Clinical Laboratory Council of the National Committee for Clinical Laboratory Standards. The approved CDC reference method along with an approved NBS definitive method, an approved NBS certified Reference Material, and the CDC certified serum-based secondary reference materials make up the accuracy base for serum cholesterol measurements in the United States, and together they are recognized as the National Reference System for Cholesterol. The NCEP Laboratory Standardization Panel recommends that cholesterol measurements made by all clinical laboratories should be standardized so that cholesterol values are traceable to the National Reference System for Cholesterol. In support of the NCEP's efforts, CDC will establish a standardization program permitting the laboratory and manufacturing community to trace cholesterol measurements and the development of cholesterol diagnostic products back to the national reference system. The major emphasis of this standardization effort is to establish a network of reference method laboratories (1) to assign cholesterol values to all commercially prepared lots of calibrators and control materials and (2) to provide reference measurements on individual "fresh" human serum specimens to manufacturers and clinical laboratories. CDC is also working to (1) provide reference materials to manufacturers, (2) collaborate with NBS to maintain documentation of the national reference system accuracy base, (3) cooperate with proficiency testing organizations to assist in the accurate labeling of reference materials, and (4) provide training and education pertinent to cholesterol standardization.(ABSTRACT TRUNCATED AT 400 WORDS)

Centers for Disease Control and Prevention, U.S.↗

Functional genes mapped on the chicken genome.

Microsatellite polymorphisms are finding increasing use in genetics. In addition to the random isolation of microsatellite markers, such markers can also be developed from sequences already present in public domain databases. An advantage of public domain databases is that these microsatellites are known to be located within or close to identified functional genes. In this study the GenBank and EMBL databases were screened for microsatellite markers and primers were defined for amplification. Subsequently, these markers were tested on a panel of five different birds from layer and broiler stocks and on the international reference families: the East Lansing reference family and the Compton reference family. Of the 33 loci tested, 25 were polymorphic on the test panel and from these 25, 14 were polymorphic in one or both reference families. Twelve of the 14 loci that could be mapped fell into previously defined linkage groups. The other two markers were not linked. Because three of the loci had previously been mapped to specific chromosomes by in situ hybridization, linkage groups E6 and C3 could be assigned to chromosome 6, E5 and C17 to chromosome 4 and E21 to one of the microchromosomes.

Animals↗

Acute low back problems in adults: assessment and treatment. Agency for Health Care Policy and Research.

This Quick Reference Guide for Clinicians contains highlights from the Clinical Practice Guideline version of Acute Low Back Problems in Adults, which was developed by a private-sector panel of health care providers and consumers. The Quick Reference Guide is an example of how a clinician might implement the panel's findings and recommendations on the management of acute low back problems in working-age adults. Topics covered include the initial assessment of patients presenting with acute low back problems, identification of red flags that may indicate the presence of a serious underlying medical condition, initial management, special studies and diagnostic considerations, and further management considerations. Instructions for clinical testing for sciatic tension, recommendations for sitting and unassisted lifting, tests for identification of clinical pathology, and algorithms for patient management are included.

Acute Disease↗

Meiotic linkage mapping of 52 genes onto the canine map does not identify significant levels of microrearrangement.

In an effort to extend our understanding of the evolutionary relationship between the canine and human genomes, we have developed and positioned 52 new gene-associated polymorphic markers on the canine meiotic linkage map. Canine-specific PCR primers were developed from the consensus of published sequences of several mammalian genomes and were designed to span intronic regions, thus optimizing the probability that a polymorphic site was included. The resulting markers were analyzed on a panel of three-generation canine reference families and the data were incorporated into the current meiotic linkage map. The data were compared with those generated by three chromosome paint studies in an effort to understand the distribution and frequency of microrearrangements within the canine genome. Forty-eight of 52 genes map to a chromosomal region predicted to contain genes from the corresponding region of the human genome according to all published reciprocal chromosome paint studies. Meiotic linkage mapping data for three genes can be used to resolve discrepancies between the published reciprocal chromosome paint studies, and for an additional two genes, meiotic mapping data allow evolutionary breakpoints to be more precisely defined. We conclude that microrearrangements of evolutionarily conserved segments between the canine and human genomes are rare, occurring for less than 0.5% of gene data reported to date. In addition, we have found that the placement of genes on the meiotic linkage map is a useful mechanism for resolving discrepancies between existing data sets.

Animals↗

Cost-effectiveness of inhaled steroids in asthma: impact of effect on bone mineral density.

BACKGROUND: The effects of inhaled corticosteroid (ICS) preparations on bone health have been debated. Multiple analyses have been published examining the question, with mixed results. OBJECTIVES: We examined how assumptions about the effect of ICS on bone mineral density (BMD) influence the cost-effectiveness of ICS in asthma. METHODS: We developed a mathematical simulation model to estimate clinical outcomes and costs for a cohort with mild/moderate asthma. The analysis conformed to reference case recommendations of the US Panel on Cost-Effectiveness in Health and Medicine. Sensitivity analysis evaluated the stability of our results to uncertainty in treatment duration, age at treatment, and ICS dose. RESULTS: Assuming a dose of 200 microg twice per day of ICS, a literature-based average effect of ICS on BMD and a 10-year time horizon, we observed a minimal increase in the costs attributed to hip fracture and incremental cost effectiveness ratio of $26,000 per quality-adjusted life-year and $14.00 per symptom-free day gained. Over an extended the time horizon (lifetime), the incremental cost effectiveness ratio increased to $42,000/quality-adjusted life-year. Only under a scenario of high-dose ICS, a lifetime horizon, and a large effect of ICS on BMD did the potential impact of ICS on BMD dramatically affect the economic attractiveness of therapy. CONCLUSION: To minimize any potential impact, use of the lowest effective dose of ICS and measures to target and intervene in high-risk individuals are warranted. However, ICS therapy in mild/moderate asthma compares favorably with commonly accepted interventions over a wide range of assumptions regarding this treatment and its effects on BMD.

Administration, Inhalation↗

Detection of Colorado Tick Fever viral RNA in acute human serum samples by a quantitative real-time RT-PCR assay.

A quantitative real-time RT-PCR assay for the detection of Colorado Tick Fever (CTF) viral RNA in human clinical samples is presented. The sensitivity of this assay has been shown to be greater than that of the isolation of virus in Vero cells by standard plaque assay in a direct comparison. The specificity of the CTF quantitative real-time RT-PCR assay was determined by the exclusive detection of CTF viral RNAs when applied to a diverse panel of CTF viral isolates and reference strain agents known to circulate in areas of CTF virus transmission. Lastly, the quantitative real-time RT-PCR assay demonstrated exceptional sensitivity for the detection of CTF viral RNA in acute human serum. The quantitative real-time RT-PCR assay is efficient, sensitive and specific and as such is useful for the detection of CTF viral RNA in the diagnostic or research laboratory.

Colorado Tick Fever↗

Isolation and characterization of Mycoplasma arginini from camels (Camelus dromedarius) with pneumonia.

Post-mortem examinations of 100 camels with pneumonic lesions were made at a local abattoir for Mycoplasma species. Sixteen isolates with indistinguishable biochemical and immunological characters were identified. The biochemical profile of these isolates showed that they were sensitive to digitonin, negative for urease production, glucose fermentation, and phosphatase activity but were positive for arginine hydrolysis. The identity of these isolates was further confirmed by disk growth inhibition test using a panel of specific antisera against selected reference Mycoplasma spp. Based on the biochemical profile and growth inhibition results, the camel isolates were identified as M. arginini. The pathological findings associated with M. arginini isolation consisted mostly of chronic interstitial pneumonia. The isolation rate of M. arginini from these specimens was 8.8%. These results suggest that the role of M. arginini in pneumonia in camels should be explored in greater detail.

Animals↗

A radiation hybrid map of mouse genes.

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.

Animals↗

How should we diagnose suspected deep-vein thrombosis?

BACKGROUND: Many different approaches are used to diagnose suspected deep-vein thrombosis (DVT), but there has been little formal comparison of strategies. AIM: To identify the most cost-effective strategy for the UK National Health Service (NHS). DESIGN: Systematic review, meta-analysis and cost-effectiveness analysis. METHODS: We identified 18 strategies and estimated the diagnostic performance of constituent tests by systematic review and meta-analysis. Outcomes of testing and treatment were estimated from published data or by an expert panel. Costs were estimated from NHS reference costs and published data. We built a decision-analysis model to estimate, for each strategy, the overall accuracy, costs, and outcomes (valued as quality-adjusted life-years, QALYs), compared to a 'no testing, no treatment' alternative. Probabilistic analysis estimated the net benefit of each strategy at varying thresholds for willingness to pay for health gain. RESULTS: At the thresholds for willingness to pay recommended by the National Institute for Clinical Excellence (20,000 pounds sterling-30,000 pounds sterling per QALY), the optimal strategy was to discharge patients with a low or intermediate Wells score and negative D-dimer, limiting ultrasound to those with a high score or positive D-dimer. Strategies using radiological testing for all patients were only cost-effective at 40,000 pound sterling per QALY or more. DISCUSSION: The optimal strategy for DVT diagnosis is to use ultrasound selectively in patients with a high clinical risk or positive D-dimer. Radiological testing for all patients does not appear to be a cost-effective use of health service resources.

Cost-Benefit Analysis↗

Self help for platelet serologists: the Australian Platelet Antibody Workshops.

The first three Australian Platelet Antibody Workshops (APAW) were held under the auspices of the Australasian Society of Blood Transfusion (ASBT) in 1989, 1990 and 1991. Participants submitted serum samples to the convenor who coded and distributed samples to laboratories routinely performing platelet serology. Results were summarized and discussed at the annual ASBT meetings. This report documents the evolution of platelet antibody tests in Australia and demonstrates the marked improvements in the participants' ability to differentiate platelet-specific antibodies from HLA antibodies and to identify the alloantigenic specificity of platelet antibodies. Five reference laboratories in Australia now hold panels typed for at least three platelet alloantigens.

Antigens, Human Platelet↗

EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias.

Cluster headache and the other trigeminal-autonomic cephalalgias [paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome] are rare but very disabling conditions with a major impact on the patient's quality of life. The objective of this study was to give evidence-based recommendations for the treatment of these headache disorders based on a literature search and consensus amongst a panel of experts. All available medical reference systems were screened for any kind of studies on cluster headache, paroxysmal hemicrania and SUNCT syndrome. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies resulting in level A, B or C recommendations and good practice points. For the acute treatment of cluster headache attacks, oxygen (100%) with a flow of at least 7 l/min over 15 min and 6 mg subcutaneous sumatriptan are drugs of first choice. Prophylaxis of cluster headache should be performed with verapamil at a daily dose of at least 240 mg (maximum dose depends on efficacy or tolerability). Although no class I or II trials are available, steroids are clearly effective in cluster headache. Therefore, the use of at least 100 mg methylprednisone (or equivalent corticosteroid) given orally or at up to 500 mg i.v. per day over 5 days (then tapering down) is recommended. Methysergide, lithium and topiramate are recommended as alternative treatments. Surgical procedures, although in part promising, require further scientific evaluation. For paroxysmal hemicranias, indomethacin at a daily dose of up to 225 mg is the drug of choice. For treatment of SUNCT syndrome, large series suggest that lamotrigine is the most effective preventive agent, with topiramate and gabapentin also being useful. Intravenous lidocaine may also be helpful as an acute therapy when patients are extremely distressed and disabled by frequent attacks.

Advisory Committees↗

Rapid identification of ascomycetous yeasts from clinical specimens by a molecular method based on flow cytometry and comparison with identifications from phenotypic assays.

This study was designed to compare the identification of ascomycetous yeasts recovered from clinical specimens by using phenotypic assays (PA) and a molecular flow cytometric (FC) method. Large-subunit rRNA domains 1 and 2 (D1/D2) gene sequence analysis was also performed and served as the reference for correct strain identification. A panel of 88 clinical isolates was tested that included representatives of nine commonly encountered species and six infrequently encountered species. The PA included germ tube production, fermentation of seven carbohydrates, morphology on corn meal agar, urease and phenoloxidase activities, and carbohydrate assimilation tests when needed. The FC method (Luminex) employed species-specific oligonucleotides attached to polystyrene beads, which were hybridized with D1/D2 amplicons from the unidentified isolates. The PA identified 81 of 88 strains correctly but misidentified 4 of Candida dubliniensis, 1 of C. bovina, 1 of C. palmioleophila, and 1 of C. bracarensis. The FC method correctly identified 79 of 88 strains and did not misidentify any isolate but did not identify nine isolates because oligonucleotide probes were not available in the current library. The FC assay takes approximately 5 h, whereas the PA takes from 2 h to 5 days for identification. In conclusion, PA did well with the commonly encountered species, was not accurate for uncommon species, and takes significantly longer than the FC method. These data strongly support the potential of FC technology for rapid and accurate identification of medically important yeasts. With the introduction of new antifungals, rapid, accurate identification of pathogenic yeasts is more important than ever for guiding antifungal chemotherapy.

Ascomycota↗

Circulating rheumatoid and antinuclear factors in asbestos workers.

In an unselected series of 80 patients with asbestos exposure referred to the London Pneumoconiosis Medical Panel, antinuclear and rheumatoid factors were found in 28 and 27% respectively. This probably represents at least a fourfold increase over their incidence in random populations. The presence of these autoantibodies was not related to the duration of exposure, but was related to the extent of radiographic abnormality.

Adult↗

Shape of small opacities and lung function in coalworkers.

Lung function and chest radiographs were reviewed in 357 coalworkers who had been referred from the Cardiff Pneumoconiosis Medical Panel. The chest films were read according to the 1980 ILO classification of radiographs by three experienced readers. An irregularity score, reflecting the shape of the small opacities, was derived from the readings and compared with the lung function variables. Men with higher irregularity scores had significant reductions in ventilatory capacity and gas transfer factor, with no change in total lung capacity, after age, height, profusion of small opacities, and smoking habit had been taken into account. The effects were present both in those with and in those without large opacities. The agreement between readers over the shape of opacities was almost as good as for their profusion. Men with rounded opacities had a lower gas transfer factor if they were predominantly of the "p" type. The results are consistent with those for a combination of emphysema and interstitial fibrosis, which has been found in coalworkers with irregular opacities.

Adult↗

Relationships among rheological and sensorial properties of young cheeses.

This study investigated the sensory and rheological properties of young cheeses in order to better understand perceived cheese texture. Mozzarella and Monterey Jacks were tested at 4, 10, 17, and 38 d of age; process cheese was tested at 4 d. Rheological methods were used to determine the linear and nonlinear viscoelastic and fracture properties. A trained sensory panel developed a descriptive language and reference scales to evaluate cheese texture. All methods differentiated the cheeses by variety. Principal component analysis of sensory texture revealed that three principal components explained 96.1% of the total variation in the cheeses. The perception of firmness decreased as the cheeses aged, whereas the perception of springiness increased. Principal component analysis of the rheological parameters (three principal components: 87.9% of the variance) showed that the cheeses' solid-like response (storage modulus and fracture modulus) decreased during aging, while phase angle, maximum compliance, and retardation time increased. Analysis of the instrumental and sensory parameters (three principal components: 82.1% of the variance) revealed groupings of parameters according to cheese rigidity, resiliency, and chewdown texture. Rheological properties were highly associated with rigidity and resiliency, but less so with chewdown texture.

Cheese↗

The HIV-positive dentist: balancing the rights of the health care worker and the patient.

We describe a hypothetical case of an HIV-positive dentist without cognitive impairment who uses proper infection control procedures. The dentist's physician notifies the medical officer of health without the dentist's consent. Although HIV-positive health care workers, including dentists, have been identified in the past, proven HIV transmission to patients is very rare. Most authorities recommend that an HIV-positive health care worker be monitored by an expert panel, which could then, if necessary, refer to the regulatory body to revoke or restrict the person's license to practice. Mandatory HIV testing is not required for health care workers because they generally do not pose a risk for infecting their patients; they are, however, ethically and legally obligated to report their HIV status to their profession's regulatory body.

Dentists↗