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Standardizing lung function laboratories for multicenter trials.

Multi-center studies provide advantages in clinical research but differences between centers can introduce bias. Three specialist pediatric respiratory laboratories standardized their methodology and examined differences between centers. The specific aims were to (i) assess the variability of measurements on adults within and between centers and (ii) to exchange and cross-analyze data from children to assess the extent of agreement between centers. Each laboratory used identical equipment and software. Inter-laboratory visits were used to (i) standardize protocols for data collection and analysis and (ii) make spirometric and plethysmographic measurements on participating staff at each location. Staff also had repeat measurements in their home laboratories. Measurements from children in each laboratory were exchanged on disk, cross-analyzed, and data compared by ANOVA. There were no significant within-subject, between-center differences in FVC, FEV1, FEF50, FRCpleth, or VC. There was a slight trend for TLC and RV (P=0.07) to be higher at one center. The 95% limits of agreement within and between centers were similar for all parameters. There were no differences between centers in cross-analyzed data from 10 children. By standardizing hardware, software, and protocol, potential inter-laboratory differences can be minimized. We recommend that this approach be adopted prior to multi-center studies.

Adult↗

Quantification of acetochlor degradation in the unsaturated zone using two novel in situ field techniques: comparisons with laboratory-generated data and implications for groundwater risk assessments.

Degradation of the herbicide acetochlor in the unsaturated zone was quantified using two unique in situ field techniques. The DT50 values generated at two different sites on surface soil and two subsoil depths using these techniques were compared with values generated under aerobic laboratory-incubation conditions (typically 20 degrees C, 40% maximum water holding capacity). Additionally, laboratory-degradation data were generated on surface and subsoils from four other sites. All subsoils were treated with acetochlor at 5% of the surface soil application rate. Acetochlor degradation in both field- and laboratory-incubated subsoils was rapid and often exceeded surface soil rates. Field and laboratory DT50 values from all sites ranged from 2 to 88 days in subsoil, compared with a range of 1 to 18 days in surface soils. The DT50 results from in situ field techniques were comparable with those generated from laboratory incubations in the same soils, confirming the validity of performing laboratory-based degradation studies to determine pesticide DT50 values in subsoils. Microbiological characterisation of selected soils revealed that subsoils had a viable and active population, although direct counts of bacteria were consistently lower in subsoil (10(8)-10(9) g-1 dry soil) compared with surface soils (10(10) g-1 dry soil). The leaching models used to perform groundwater risk assessments (e.g. PELMO, PESTLA, MACRO-DB, PRZM and the FOCUS EU leaching scenarios) have provision for inclusion of subsoil degradation rates. However, conservative default estimates are typically used, as no other alternative is available. Results presented here show that these default values may significantly underestimate true subsoil degradation contributions, and therefore not accurately predict pesticide concentrations in groundwater. The degradation data generated for acetochlor were applied to the mathematical model PELMO to demonstrate the importance of the inclusion of subsoil degradation data in groundwater risk assessment models and thereby in the registration of pesticides in Europe.

Biodegradation, Environmental↗

Field and laboratory selection of Frankliniella occidentalis (Pergande) for resistance to insecticides.

Response of western flower thrips, Frankliniella occidentalis (Pergande), to selection for resistance to insecticides commonly used to control this pest in Murcia (south-east Spain) was studied under field and laboratory conditions. In the field, plots within sweet pepper crops in commercial and experimental greenhouses were treated under different selection strategies: insecticide rotation versus formetanate reiteration, formetanate reiteration versus acrinathrin reiteration, and formetanate reiteration versus methiocarb reiteration. Thrips populations were sampled monthly and bioassayed against methiocarb, methamidophos, acrinathrin, endosulfan, deltamethrin and formetanate. In the laboratory, F occidentalis strains were selected against each insecticide for several generations. To evaluate cross-resistance, each selected strain was bioassayed with the other insecticides. Frankliniella occidentalis populations showed a rapid development of acrinathrin resistance, reaching high levels in field and laboratory conditions. Formetanate and methiocarb resistance were also observed, although development was slower and at moderate levels. Cross-resistances between acrinathrin/deltamethrin and acrinathrin/formetanate were detected under field and laboratory conditions. Formetanate/methiocarb cross-resistance was suspected in laboratory selections, but not in field assays. Simultaneous moderate resistance levels to the three specific insecticides against thrips (formetanate, methiocarb and acrinathrin) were shown in laboratory selection strains, indicating a general mechanism of resistance, probably metabolic.

Adaptation, Physiological↗

Role of the clinical microbiology laboratory in the diagnosis of infections.

The proper use and interpretation of clinical microbiology test results may be complicated but critical to the care of cancer patients. The microbiology laboratory director is often available to offer advice concerning the differential diagnosis, choice of specimens, as well as the optimal stains and cultures to facilitate diagnosis. Additionally, the rapid interpretation of Gram-stained smears provides useful, occasionally lifesaving, information relative to the etiologic diagnosis and empiric antimicrobial therapy. The microbiology laboratory director should also provide further interpretation of culture and antimicrobial testing results that allow the clinical service to focus on the most critical data. Person-to-person or telephone conversations discussing important laboratory information should be followed up by a written summary report placed in the patient's chart so all services involved share the same interpretation (Figure 2). The clinical service has an important responsibility to communicate with the laboratory to optimize care of the patient with cancer. The laboratory compiles data collected from groups of patients that is available and useful to physicians. Review and discussion of test utilization is essential for cost-effective, quality health care. This may include analysis of blood cultures documenting an acceptable level of contamination, appropriate number collected per day, and sufficient blood volume per culture. In addition, information about changing resistance patterns or nosocomial transmission can be provided to the clinician. As patients with malignancies become more complex and their infections increasingly difficult to treat, regular interaction between the laboratory and clinician is likely to improve patient care.

Diagnosis, Differential↗

Laboratory workshop on the characterization of anti-platelet antibodies in immune thrombocytopenic purpura.

The aim of this laboratory workshop was to evaluate the state of knowledge concerning the demonstration of membrane glycoprotein specific anti-platelet antibodies. The main interest lay in investigating whether specific antibody detection offers possibilities to distinguish the chronic from the acute form of ITP. In five laboratories four different methods were applied to demonstrate such antibodies. These methods are briefly described and compared. In all, except two, of the 45 ITP samples anti-platelet antibodies could be detected by at least one participating laboratory, in 85% of the samples antibodies were found by two or more laboratories. For seven out of eight control samples no positive results were reported. The comparison of glycoprotein specific anti-platelet antibodies shows partly considerable differences which may be due to the different methods as well as the different antibodies used (monoclonal antibody against membrane glycoprotein and antihuman globulin sera). This laboratory workshop leads to the conclusion that by exchange of reagents and patient samples the different methods may be compared and evaluated. The results obtained allowed no further characterization of ITP. All participants agreed on the usefulness of further similar laboratory workshops.

Acute Disease↗

Thermoregulation during prolonged actual and laboratory-simulated bicycling.

Thermoregulatory and cardiorespiratory responses to bicycling 55 km (mean speed 9.7 m X s-1) outdoors (15 degrees C DB) were compared to equivalent cycle ergometry (90 min at 65% VO2max) in the laboratory (20-23 degrees C DB, 50% RH) in 7 trained cyclists. Outdoor environmental conditions were simulated with fans and lamps, and were contrasted with standard no-wind, no-sun laboratory conditions. Sweating rate was similar during outdoor and laboratory simulated outdoor cycling (0.90 and 0.87 to 0.94 1 X h-1 respectively). During outdoor bicycling, mean heart rate (161 bt X min-1) was 7-13% higher (p less than .05) than under laboratory conditions, suggesting a greater strain for a similar external work rate. The increase in rectal temperature (0.8 degrees C) was 33-50% less (p less than 0.05) at the cooler outdoor ambient temperature than in the laboratory. Thermoregulatory stress was greater under the no-fan, no-lamp laboratory condition than during simulated outdoor conditions (36-38% greater (p less than 0.05) sweating rate, 15-18% greater (p less than 0.01) mean skin temperature, 6.4 to 7.8 fold greater (p less than 0.01) amount of clothing-retrained sweat). The cooling wind encountered in actual road bicycling apparently reduces thermoregulatory and circulatory demands compared with stationary cycle ergometry indoors. Failure to account for this enhanced cooling may result in overestimation of the physiological stress of actual road cycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neurological evaluation of chronic headache patients: is laboratory testing always necessary?

A review of records was conducted to examine the utility of doing routine laboratory testing (EEG and skull X rays) versus testing at the discretion of the attending neurologist on patients presenting for the nonpharmacological treatment of chronic headache. A total of 278 patients underwent neurological evaluation as part of a routine assessment prior to beginning self-regulatory treatment for headache. The first 112 subjects received routine laboratory tests of EEG and skull X-ray films. The second set of 166 subjects received laboratory tests only when deemed necessary by the neurologist. The rate of abnormal EEG in chronic headache sufferers was no greater than that found in the normal population, and only one or two potentially serious abnormalities were found on any laboratory test. A higher rate of abnormality was found when the CT scan was used in conjunction with clinical judgment. The majority of clients with abnormal laboratory tests (most of which were mildly abnormal) still saw substantial headache reduction with self-regulatory treatment for chronic headache. The authors suggest that routine laboratory testing may not be necessary and should be left to the discretion of a qualified neurologist.

Adult↗

How relevant are house dust mite-fungal interactions in laboratory culture to the natural dust system?

Both house dust and house dust mites Dermatophagoides pteronyssinus contained a wider range of fungi than laboratory mite cultures. In total, nine species of fungi were isolated from D. pteronyssinus in house dust, and these included three xerophilic species (Eurotium amstelodami, Aspergillus penicillioides and Wallemia sebi) commonly found in laboratory cultures of D. pteronyssinus. It is concluded that mites do interact with a similar range of fungi in natural dust and in laboratory culture, but that the diversity of fungal species in the laboratory is reduced and the density of individual fungal species in culture exceeds that of house dust. In a second experiment, dust samples were incubated at room temperature with 75% relative humidity. The diversity of fungi invariably declined from up to 13 genera to the few species recorded in laboratory culture. This suggests that the dominance of xerophilic fungi in laboratory mite rearings is mediated primarily by low relative humidity, and the exclusion of air-borne spores.

Air Microbiology↗

Quality control for estrogen receptor quantification by dextran-coated charcoal assay: a single laboratory's experience.

Wide fluctuations in results obtained by different laboratories for the content of estrogen receptors from a single source of tissue powder were reported by several investigators at the 1979 NCI Consensus Committee Meeting for Steroid Receptors in Breast Cancer and were further supported by data collected by our laboratory for the Eastern Cooperative Oncology Group. In a multilab study the inconsistency in the receptor content is a product of the variations associated with the assay procedures used by different laboratories and those due to unavoidable daily changes in the experimental conditions within each laboratory. In this report we present data on the variation of estrogen receptor measurements obtained by a single laboratory for any single source of tissue powder repeatedly analyzed. A retrospective analysis of the data collected on the receptor content of several different batches of calf uteri analyzed on different days (inter-assay variation) under uniform conditions revealed a coefficient of variation averaging +/- 35% (standard deviation divided by mean X 100). Experiments showed that the fluctuations in the receptor yield from aliquots of the same tissue powder are primarily an effect of the homogenization step that precedes cytosol preparation. Therefore, for establishing quality control, distribution of lyophilized cytosols should precede lyophilized powders to test the efficiency of performance of laboratories. A homogenizer designed to minimize thermal denaturation is also essential.

Animals↗

Multi-laboratory comparison of eight commercially available Helicobacter pylori serology kits. Helicobacter pylori Serology Study Group.

The performance of eight commercially available EIA kits in detecting antibody to Helicobacter pylori was evaluated by a panel of 17 laboratories using serum from 59 patients selected from endoscopy clinics in Belgium, Ireland, Italy, the Netherlands and Switzerland. Each laboratory received a randomly numbered set of sera and was ignorant of the culture results of the patients. The performance of the kits was assessed in terms of diagnostic accuracy compared to culture (measured by sensitivity and specificity), the inter-laboratory variability in diagnostic accuracy and the number of laboratories that experienced problems in using the kits. Grey zone results, which are routinely used to highlight the uncertain interpretation of results that lie near the cut-off point between positive and negative diagnoses, were accounted for in the analysis. Laboratories experienced practical problems in using some kits, whilst other kits were found to have high inter-laboratory variation or low diagnostic accuracy. There was no single kit that performed better on every criterion than the others. The Orion kit was a good all-round performer, whilst the Roche kit was excellent at detecting positive results, although it had a slightly raised false-positive rate.

Evaluation Studies as Topic↗

Confirming the species-sensitivity distribution concept for endosulfan using laboratory, mesocosm, and field data.

In Australia, water-quality trigger values for toxicants are derived using protective concentration values based on species-sensitivity distribution (SSD) curves. SSD curves are generally derived from laboratory data with an emphasis on using local or site-specific data. In this study, Australian and non-Australian laboratory-species based SSD curves were compared and the concept of species protection confirmed by comparison of laboratory-based SSD curves with local mesocosm experiments and field monitoring data. Acute LC50 data for the organochlorine pesticide endosulfan were used for these comparisons; SSD curves were fitted using the Burr type III distribution. SSD curves indicated that the sensitivities of Australian fish and arthropods were not significantly different from those of corresponding non-Australian taxa. Arthropod taxa in the mesocosm were less sensitive than taxa in laboratory tests, which suggests that laboratory-generated single-species data may be used to predict concentrations protective of semifield (mesocosm) systems. SSDs based on laboratory data were also protective of field populations.

Animals↗

Effects of soil copper on black bindweed (Fallopia convolvulus) in the laboratory and in the field

The present study aims to identify factors of importance to the extrapolation from laboratory toxicity test to field effects using copper and black bindweed as a model. In the laboratory the influence of Cu on seed germination and seedling survival was studied in both soil spiked with Cu in the laboratory and soil collected at a Cu-polluted site. Maternal effects were also studied. We found that seeds from Cu-stressed plants germinated more readily after a short, cold storage than control seeds, but no differences were found after a longer storage. The low germination of control seeds compared to maternal treated seeds could not be attributed to differences in thickness of the seed coat. Germination was slightly stimulated at 232 mg Cu kg-1. At the highest Cu level (i.e. 1,330 mg Cu kg-1) only 5% of the seeds germinated. Mortality of the seedlings increased with increasing Cu concentration reaching 40% at 391 mg Cu kg-1. At higher concentrations mortality decreased. Germination was not affected in laboratory tests with soil from a Cu-polluted site, but the biomass of the plants decreased with increasing Cu concentration. The distribution of the plants on a Cu-polluted site was registered in relation to soil Cu concentration. Cu was analyzed using three different extractors, i.e. HNO3, CaCl2, and DTPA. The distribution of the plant in the field was predicted from calculated lifetime effect of a given Cu soil concentration based on the laboratory tests. The results revealed that growth is more sensitive in the field than should be expected from laboratory tests due to several stressors in the former situation. Bioavailability was lower in the field soil but this was counteracted by the increased effect. Incorporating bioavailability in the prediction of field effects thus reduced the fit of the model and bioavailability measures could not be further evaluated.

Journal Article↗

Results of common laboratory tests in solvent-exposed workers.

OBJECTIVES: The screening and identification of occupational liver or other organ-system injury related to long-term, low-level solvent exposure are difficult in clinical practice. We studied the feasibility of the use of common laboratory tests combined with a detailed exposure history. METHODS: The relationships between laboratory tests and exposure to organic solvents were studied in regression modelling adjusted to age, alcohol consumption, gender and body mass index (BMI). The subjects were 29 solvent-exposed workers and 19 referents. Laboratory tests included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), alkaline phosphatase (ALP), creatinine, cholesterol, HDL-cholesterol, triglycerides, blood glucose and total and conjugated bilirubin. Positive hepatitis serology, systemic diseases or medications with known hepatic effects and current pregnancy were exclusion criteria. The main exposures of each subject were identified. Current solvent exposure status, exposure during the past 3 months, exposure during the past 5 and 10 years, and total life-time exposure were recorded. RESULTS: AST (P=0.0031), ALT (P=0.0015) and cholesterol (P=0.0110) correlated positively with cumulative solvent exposure in the past 5 years, total bilirubin with current exposure (P=0.0380), and glucose with exposure in the past 5 (P<0.0001) and 10 (P=0.0003) years. Triglycerides correlated positively with exposure in the past 5 (P=0.0025) and 10 (P=0.0059) years and with life-time exposure (P=0.0005). Creatinine correlated negatively with exposure in the past 10 years (P=0.0300) and life-time exposure (P=0.0005). Most laboratory values were within the normal range. CONCLUSIONS: These results suggest a multi-system health effect of solvents. The laboratory data had some similarities with those in the metabolic syndrome. The screening and diagnostics of solvent-related conditions should be based on a thorough work history and a set of carefully selected laboratory tests. No single test seems sufficient for this purpose.

Adult↗

The impact of structured laboratory routines in computerized medical records in a primary care service setting.

Inappropriate laboratory ordering is a problem affecting medical systems worldwide. An intervention was called for as a result of increasing laboratory costs. Thus, we aimed to assess the impact of introducing computerized laboratory routines to a computerized primary care setting. The study included 380 primary care physician practices of Clalit Health Service (HMO) southern district (CHS-SD) in Israel, caring for 470,000 members. Consensus laboratory routines order sets were electronically introduced into all physicians' computerized medical record (CMR) software, after consensus and internal marketing process. The primary findings were that a previously observed annual increase in laboratory test utilization was stopped, a 2% reduction in total number of tests and a 4 % reduction in the total number of tests per age adjusted person was observed. In conclusion the wide use of CMRs and communication technology combined with an appropriate organizational process can be used to increase appropriate utilization of laboratory tests.

Diagnostic Techniques and Procedures↗

Comparison of implantation of nonthoracotomy defibrillators in the operating room versus the electrophysiology laboratory.

Implantable cardioverter-defibrillators (ICDs) with nonthoracotomy lead systems are widely available, and are implanted either in the electrophysiology laboratory or the operating room. The purpose of this study was to prospectively evaluate the safety and efficacy of nonthoracotomy ICD implantation in an electrophysiology laboratory versus an operating room. During a 7-month period, 62 consecutive ICDs with nonthoracotomy lead systems were implanted in patients in an electrophysiology laboratory. During the next 10 months, 110 consecutive ICDs were implanted in patients in a surgical operating room. All ICD implantations were performed under general anesthesia by electrophysiologists. There were no differences in age (58 +/- 14 vs 62 +/- 12 years, p = 0.06), gender distribution (p = 0.3), frequency of structural heart disease (97% vs 97%, p = 0.9), ejection fraction (0.31 +/- 0.15 vs 0.29 +/- 0.13, p = 0.3), or presentation with cardiac arrest (65% vs 53%, p = 0.2) between patients undergoing ICD implantation in the electrophysiology laboratory and operating room, respectively. The rate of successful implantation and of complications for systems implanted in the electrophysiology laboratory (95% and 13%, respectively) and in the operating room (98% and 14%, respectively) were similar (p = 0.4 and p = 0.8, respectively). Specifically, the rate of infection (0% vs 4%, p = 0.3) and hematoma formation (2% vs 4%, p = 0.8) were not statistically significantly different. Three patients who had undergone ICD implantation in an operating room died within 30 days. ICDs with nonthoracotomy lead systems can be implanted with a similarly high rate of success and acceptable complication rate in the electrophysiology laboratory and in the operating room.

Adult↗

Postdoctoral training in clinical chemistry: laboratory training aspects.

OBJECTIVE: To provide a general outline for a 2-year postdoctoral training program in clinical chemistry, and a detailed outline of the first year laboratory training program. METHODS & RESULTS: Essential elements of the 2-year Postdoctoral Training Program in Clinical Chemistry at the University of Toronto are its didactic courses and a comprehensive, structured laboratory rotation in the first year. Residents rotate in hospital laboratories in both years of the Program. The hospital laboratory rotation in first year includes a 36-week laboratory rotation based on the Laboratory Training Program Manual. In the second year, they consolidate the basic knowledge acquired in first year and gain experience in pediatric testing and other specialty areas. In both years, residents attend teaching and ward rounds on a regular basis, investigate unusual test requests and patient results, and make regular presentations at case presentation and journal club sessions. They undertake research and development projects which lead to presentations at scientific meetings and to publication. Residents attend departmental management meetings, arrange discussions on management topics, and attend a short course on key management topics. Approaches for strengthening the knowledge and skills of residents in the areas of hematology, microbiology and pathology are being developed. CONCLUSION: The program outline described should provide a useful framework for other such programs both nationally and internationally.

Academic Medical Centers↗

Laboratory assessment of nutritional metabolic bone disease in infants.

OBJECTIVES: There are numerous laboratory investigations available for the assessment of an infant with suspected metabolic bone disease (MBD); thus, comprehensive laboratory investigations on every aspect of MBD would impose unnecessary stress to the infant and the costs involved would be prohibitive. An overview of the assessment of an infant with suspected MBD, in particular, nutrition-related bone disease, is presented. Our objectives include an understanding of: 1. the importance of appropriate information from history and physical examination to guide the laboratory investigations; 2. relevance and limitations of specific laboratory investigations: a. radiologic studies include diagnostic radiographs and quantitative bone mass determination by dual energy x-ray absorptiometry, b. biochemical measurements to determine mineral homeostasis and bone turnover, c. vitamin (vitamin D metabolites) and hormonal (parathyroid hormone and calcitonin) measurements; with respect to diagnosis and monitoring of the natural progress or response to therapy. CONCLUSION: Relevant information from clinical history and physical examination, and an understanding of the role and limitations of various laboratory investigations, would allow the optimal utilization of laboratory tests in the assessment of an infant with MBD.

Absorptiometry, Photon↗

Blood pressure in healthy men and women under laboratory and naturalistic conditions.

Thirty healthy nonsmoking men and 30 women underwent a laboratory reactivity assessment with systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) recorded at rest and during behavioral (mirror image tracing, mental arithmetic, color word conflict task and a semistructured Type A interview), and physical tasks (isometric exercise and the cold pressor test). Causal SBP and DBP were measured in a physician's clinic. Four months earlier SBP, DBP and HR had been monitored during a day at work and a day at home. Readings obtained in the clinic, at rest and during stress in the laboratory were related to real-life levels, reactivity (work-home difference) and variability. For men level of cardiovascular activation at rest and during all stressors in the laboratory correlated with levels at work and at home. The best laboratory/real-life relation was observed for SBP. Systolic blood pressure levels during stress correlated with the work-home difference. Systolic blood pressure reactivity (laboratory stress levels - rest levels) to most behavioral tasks correlated with SBP levels at work and home. Daily variability and reactivity correlated with SBP reactivity to mental arithmetic and the color word conflict task. For women, levels of SBP and HR at rest and during all stressors correlated with SBP and HR at work and at home. The best laboratory/real-life relation for women was observed for HR reactivity. Casual BP in the clinic correlated with work blood pressure but generally not with daily reactivity or variability. We conclude that BP and HR levels measured in the laboratory generalizes to real life BP and HR in both men and women and also to real life SBP reactivity in men. Laboratory induced SBP reactivity also shows a weak relation to real life SBP levels, variability and reactivity in men.

Adult↗