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A cohort study of cancer mortality among Biology Research Laboratory workers in The Netherlands.

OBJECTIVE: To examine cancer mortality among persons employed in biology research institutes. METHOD: A historical cohort study was undertaken in the Netherlands. The cohort, comprising 7307 laboratory workers employed by the four participating institutes between 1960 and 1992, was followed for mortality from 1960 to 1995 (median follow-up time 16.5 years). Causes of death were obtained for 98% of all deaths. Cancer mortality in the cohort was compared with that in the general population by computation of the standardized mortality ratio (SMR). The Cox proportional hazards model was used to compare cancer mortality among laboratory workers with that in an internal reference population consisting of unexposed research personnel (n = 2,404). RESULTS: All-cause mortality among laboratory workers was significantly lower than that in the general population. Total cancer mortality and lung cancer mortality were also significantly decreased (SMR = 0.8; 95% confidence interval CI = 0.7-0.9 and SMR = 0.7; 95% CI = 0.6-0.9), respectively. However, when compared to the internal reference population, laboratory workers had a slightly increased cancer mortality (relative risk (RR) = 1.3 95% CI = 0.9-1.9). Among men, a 2.5-fold (95% CI = 1.0-6.3) increase of lung cancer mortality was observed which could not be explained by differences in smoking habits. Lung cancer mortality increased with longer follow-up. Results with regard to a priori defined fields of research showed significantly increased cancer mortality (in particular from lung cancer) for men working in genetics (RR = 3.8), virology (RR = 4.1) and plant physiology (RR = 2.1). CONCLUSION: Laboratory workers have a favorable cancer mortality pattern as compared to the general population. However, this favorable pattern disappears when a comparison is made with a control group of unexposed research personnel. The excess lung cancer mortality among male laboratory workers was concentrated in certain fields of research, which warrants further research to identify specific exposures related to the increased risk.

Adult↗

Mortality pattern among biological research laboratory workers.

A cohort study was conducted to investigate the mortality of individuals employed by biological research institutes in the UK. The inclusion criteria were met by 12,703 individuals, of whom 95% were traced (11,502 alive, 395 deaths, 246 embarkations). All-cause mortality was significantly reduced in men (standardised) mortality ratio (SMR) 55 and women (SMR 52). Mortality was also significantly reduced for circulatory and respiratory diseases, and overall there was low mortality from malignant neoplasms. SMRs exceeded 100, but were not statistically significant, for infective and parasitic diseases. There were no statistically significant raised SMRs for any cancer site. Workers were categorised as ever worked in a laboratory (laboratory workers) and never worked in a laboratory (non-laboratory workers). The all-cause SMR was significantly reduced in both groups, as was mortality from circulatory and respiratory diseases. The SMR for malignant neoplams was also significantly reduced in laboratory workers. On the basis of follow-up to 31 December 1994, there is no evidence of any overall increased risk of mortality in biological research laboratory workers. However, the power of the analysis is limited by the young age of many cohort members and short duration of follow-up. Follow-up is continuing and the data will be reanalysed once more deaths have accumulated.

Agriculture↗

Consensus and accuracy in haematology laboratories of developing countries: the Jordanian experience.

A study lasting for 18 months using interlaboratory surveys was carried out to assess the analytical quality of Jordanian haematology laboratories that represent one of the developing countries. The study surveyed 50 laboratories constituting the majority of clinical laboratories in the central region of Jordan using 15 control specimens of whole fresh blood and eight freshly prepared blood smears. The study covered the routine haematological parameters of PCV, Hb, RBC, WBC and differential white blood cell count. More than 97% of Jordanian laboratories using cell counters achieved the medically useful criteria for analytical performance, this figure was reduced to 84% in laboratories using manual methods. Jordanian laboratories, however, were far from achieving the analytical goals that have been proposed based on intraindividual biological variation. This study stressed the need for a national EQA scheme in haematology, to reach a common level of standardization.

Bias↗

Office and laboratory blood pressures as predictors of daily blood pressure level in normotensive subjects and borderline and mild hypertensive subjects.

A series of standardized laboratory tests [10 min sitting and supine, 9 min standing, dynamic; cycle ergometer (ERG) and isometric exercise; handgrip (HG)] were performed during intra-arterial blood pressure (BP) recording in 97 healthy unmedicated men, initially classified as normotensive (NT, n = 34), borderline hypertensive (BHT, n = 29) or mildly hypertensive (HT, n = 34) by repeated office blood pressure (OBP) measurements. After testing, a 24-h intra-arterial ambulatory BP (IABP) recording was obtained while subjects performed their normal activities. Day and night periods were analysed as well as 24-h averages for systolic BP (SBP) and diastolic BP (DBP) using Pearson correlations and multiple linear regressions. In normotensive subjects, the supine SBP predicted IABP measurements best (r range 0.39-0.69, P < 0.05-0.001). In multiple regression, supine SBP explained 49% of 24-h SBP variance (F = 12.4, P = 0.001). For BHT, supine SBP was also the best predictor (r range 0.09-0.64, P NS to P < 0.001), and it explained 37% of 24-h SBP variance (F = 15.6, P = 0.0005). In HT, ERG DBP correlated best with IABP (r range 0.52-0.75, P < 0.01-0.001). ERG SBP explained 49% of 24-h SBP (F = 31.0, P = 0.0000) and ERG DBP explained 56% of 24-h DBP (F = 35.4, P = 0.0000) variance. Laboratory BP correlations were generally better with day than with night measurements. OSBP correlated moderately well with IABP in NT, and weakly in BHT and HT; ODBP instead correlated with IABP in NT and HT but not significantly in BHT. In conclusion, OBP is less closely related to IABP than laboratory BP, but even laboratory BP generally explains less than 50% of IABP variance. Stressors such as exercise are useful only in HT. For BHT, the prediction of IABP with laboratory measures was even weaker than in other groups, and thus ambulatory measurements cannot be replaced by short-duration laboratory measurements and stress tests.

Adult↗

Clinical quality of removable dentures provided by dentists, denturists and laboratory technicians.

The aim of this study was to evaluate the clinical quality of removable dentures of elderly Finnish men, which had been prepared either by dentists, denturists or dental laboratory technicians. The participants comprised 242 denture-wearing subjects, with 231 maxillary and 177 mandibular removable dentures which had been prepared either by dentists, denturists or dental laboratory technicians. Clinical examinations were carried out without the examining dentist knowing who had provided the dentures. Complete dentures which had been illegally provided by laboratory technicians had significantly poorer retention and fitted less well in tuber and alveolar areas than those provided by either dentists or denturists. Complete maxillary dentures which had been provided illegally by laboratory technicians had significantly (P < 0.01) higher occurrence (90%) of some unacceptable characteristics than those (43%) provided by dentists or denturists. The difference between complete mandibular dentures was also obvious, 86% versus 59%, although statistically non-significant. Of those partial maxillary dentures provided by dentists 53% had some unacceptable characteristics, compared with 80% of those illegally provided by denturists or laboratory technicians (NS). In the case of partial mandibular dentures, 36% of those provided by dentists and 32% of those by denturists or laboratory technicians had some unacceptable characteristic (NS). Illegal provision of removable dentures seemed to be related to decreased clinical quality.

Aged↗

Laboratory cross-contamination of Mycobacterium tuberculosis: an investigation and analysis of causes and consequences.

BACKGROUND: The misdiagnosis of Mycobacterium tuberculosis infection has many ramifications. These include medical and psychological implications for patients and their families and financial and public health implications for health-care institutions. Microbiology laboratory procedures should minimize the possibility of laboratory cross-contamination of specimens and maximize the ability to recognize a cluster of false-positive cultures. Newer molecular typing methods provide rapid, accurate and effective means of identifying false-positive M. tuberculosis cultures. AIMS: To investigate a cluster of patients with positive M. tuberculosis cultures that were processed in the mycobacteriology laboratory on the same day. METHODS: Five patients' medical records and radiology results were reviewed to determine whether the cases were epidemiologically linked and whether there was clinical suspicion of tuberculosis. Restriction fragment length polymorphism (DNA fingerprinting) was performed using repetitive elements IS6110 and pTBN12. Laboratory processing procedures were analysed. RESULTS: On the basis of DNA fingerprinting using IS6110, the isolates from all five patients were identical. Molecular typing using pTBN12 was performed on four of the five isolates. All four had identical patterns. There was no epidemiological link between the patients. At least three (and probably four) of the five patients were misdiagnosed with tuberculosis. CONCLUSION: Microbiology laboratories should ensure that appropriate methodologies are in place to avoid cross-contamination of specimens. Clinicians need to critically interpret any positive laboratory result, especially in an unlikely clinical setting.

Adult↗

Laboratory assessment as a critical component of the appropriate diagnosis and sub-classification of von Willebrand's disease.

von Willebrand's disease (VWD) is now recognized to be most common inherited bleeding disorder. It arises from defects or deficiencies in a protein called von Willebrand factor (VWF). VWD is a heterogeneous disorder, and patients are typed according to pathophysiology. The correct diagnosis and sub-classification of a patient's VWD is crucial because the presenting biological activity of VWF determines the haemorrhagic risk, and since subsequent clinical management will differ accordingly. Although clinical assessment of the propositus will provide the initial clue to, or an index of clinical suspicion for, a diagnosis of VWD, it is the laboratory process that will confirm or discount the diagnosis. A variety of assays may be employed by the laboratory undertaking the investigation, and these will not necessarily be restricted to an assessment of VWF. Due to the limitations of each potential laboratory assay, and because of VWD heterogeneity, no single test procedure is sufficiently 'robust' to permit detection of all VWD variants. This situation often leads to some clinical confusion in the process of laboratory interpretation regarding the likelihood of VWD, and the subtype of VWD. Classically, the test panel might include any combination of the following: (i) determination of (skin) bleeding times, (ii) VWF antigen (VWF:Ag) levels, (iii) 'functional' activity of Factor VIII (i.e. FVIII:coagulant or FVIII:C), (iv) 'functional' activity of VWF (e.g. Ristocetin Cofactor [VWF:RCof] assay), and/or Ristocetin induced platelet aggregation [RIPA] analysis), and (v) assessment of the VWF molecular weight or structural profile (i.e. VWF multimeric analysis or VWF:Multimers). There have also been a number of new diagnostic developments, and these are beginning to significantly influence the overall clinical VWD-diagnostic process. These include automation of existing assay procedures, a relatively new functional VWF assay called the Collagen Binding Assay (VWF:CBA), new automated platelet function analysers such as the PFA-100 and the Xylum Clot Signature Analyser, and specific VWF:FVIII binding assays. The current report focuses on the recommended laboratory process for investigation of VWD. An analysis of this process shows that selection of an appropriate test panel is a critical component for the proper diagnosis and classification. This review also outlines those new and emerging technologies that will help streamline the diagnostic process. Because VWD is just one manifestation of a 'bleeding' disorder (albeit the most common), the review also briefly mentions other related diagnostic processes and general approaches to the investigation of 'bleeding disorders'. The review also provides two algorithms to assist clinicians in making appropriate diagnostic choices in response to the clinical findings. A number of summary tables describing each laboratory assay in detail, and summarising the likely diagnostic findings for each Type of VWD, are also provided. This review should be of value to both haemostasis scientists and clinical specialists involved in VWD diagnosis.

Clinical Laboratory Techniques↗

Factor VIII inhibitors. Laboratory diagnosis of inhibitors.

The diagnosis of inhibitors of blood coagulation is often the most challenging problem in the clinical laboratory. Immediate attention must be given to the following patient groups whose principal laboratory abnormality is the prolonged activated partial thromboplastin time (aPTT): the patient with (1) hemophilia who previously responded to an adequate dose of clotting factor product and now fails to show effective clinical response to the same replacement concentrate; (2) previously benign clinical history who now presents with soft tissue bleeding or emergent internal hemorrhaging; (3) sudden onset of generalized ecchymoses who was previously well; (4) postpartum state; (5) malignancy, lymphoma, rheumatoid arthritis, or other autoimmune disorders; and (6) drug reactions. Immediate attention must be given to the prolonged prothrombin time (PT), aPTT, and thrombin time (TT) in order to respond to urgent queries from a perplexed internist, hematologist, intensivist, or surgeon caring for a patient with unexpected bleeding. Sometimes the problem of a prolonged "clotting time" arises preoperatively, causing unanticipated delay in operative procedures. For this reason, the laboratory support, usually in the coagulation section of a clinical laboratory or reference laboratory, must be quick, unequivocal and precise. The most common finding is an isolated mild, moderate, or severe prolongation of the aPTT with a normal PT, TT, and platelet count. The aPTT mixing study (The Mix), usually modified for time and temperature, along with appropriate controls, is the seminal test. This is the basis for all further testing. It may be supported by direct factor assays, and, therefore, the laboratory must know the reagent responsiveness and sensitivity for each clotting factor. By definition, complete correction of the aPTT in a 1:1 mix of patient and reference plasma is a factor deficiency. In this article, incomplete or minimal correction of The Mix will be characterized with particular attention to the various inhibitor assays, in other words, Oxford, Bethesda, and Nijmegen assays and the enzyme-linked immunosorbent assay (ELISA). An investigative approach to final characterization of the intensity (quantification) of the inhibitor and the exclusion of a lupus anticoagulant (LA) will be discussed.

Blood Coagulation Tests↗

External quality assessment and the laboratory diagnosis of thrombophilia.

External quality assessment is a tool to compare the result of a particular laboratory test in relation to those of other laboratories as well as to assess the performance of a laboratory test over a prolonged period of time. We evaluated the relationship between the between-laboratory variation and the sample category (normal, borderline, and abnormal) for antithrombin, protein C, protein S, and the activated protein C resistance test. Only for antithrombin and protein S was a significant relationship (0.004 < p < 0.012) observed. The effect of the between-laboratory variation of the different sample categories on the clinical interpretation was investigated. With the exception of free protein S antigen, all variables showed a significant relationship (0.004 < p < 0.045) between the sample category and the percentage of misclassification. Because in clinical practice a stable test performance over a prolonged period of time is important, we evaluated the quality of test performance using the long-term analytical coefficient of variation (LCVa). A wide range in the LCVa was observed for antithrombin, protein C, and protein S. Less than half of the participants could fulfill the quality specification for diagnostic testing (LCVa < or = 0.58 x total biological variation). This study shows that a more stable performance of laboratory tests involved in the screening of thrombophilia over a prolonged period of time is necessary.

Antithrombins↗

Characterizing formaldehyde emission rates in a gross anatomy laboratory.

The evaporation of formaldehyde from cadavers in gross anatomy laboratories can produce high exposures among students and instructors. To understand the system that produces exposures and to plan for implementing control options, the generation of formaldehyde vapors must be characterized. A gross anatomy laboratory with 47 dissecting tables was studied during 15 lab sessions over a period of 16 weeks. Area concentrations were measured using National Institute of Occupational Safety and Health (NIOSH) method 3500. Average daily area concentrations in the laboratory ranged from 0.635 to 1.82 mg/m3. The ventilation was characterized on three separate days. The laboratory had a general ventilation rate of 9.8 air changes per hour. There was no local exhaust ventilation. The concentration measurements were used in a mass balance model along with ventilation rates to determine formaldehyde emission rates. The daily average formaldehyde emission rate from all sources in the laboratory ranged from 95.2-274 mg/min, with an average of 148 mg/min over the course of the study. This total emission rate was used along with the number of dissecting tables to develop an emission factor of 3.15 mg/min per table. The emission factor is a generalizable tool that can be used in laboratories of various sizes to predict emission rates and develop control strategies. This emission factor is applicable where the cadavers are prepared with similar embalming fluid consisting of approximately 10 percent formaldehyde.

Air Pollutants, Occupational↗

Thermal loading as a causal factor in exceeding the 0.1 PPM laboratory fume hood control level.

Tracer gas testing per ANSI/ASHRAE 110-1995 Method of Testing Performance of Laboratory Fume Hoods was used to investigate the role of thermal loading in exceeding laboratory fume hood control levels. Three types of typical laboratory burners (blast, Meeker, and economy) were used to provide a thermal challenge. Heat outputs of between 0 and 61,610 Btu/hr were based on fuel heat capacity (for liquid propane gas) and fuel gas flow rates. Breathing zone concentrations were measured with a MIRAN 1B2 infrared gas analyzer. Also, for each test, the difference between the room and duct temperatures (delta temperature) was measured. Results indicated a linear relationship between heat loads and tracer gas breathing zone concentrations for both Btu/hr and delta temperature. Control levels of 0.1 ppm were exceeded at less than 12,000 Btu/hr. Also, control levels were exceeded at a lower heat load when the tracer gas generation rate was increased. These results indicate that thermal loads in laboratory fume hoods increase the risk of exceeding laboratory fume hood control levels. Some compensatory measures relative to hood configuration and flow rates are recommended for laboratory operations involving heat sources.

Air Pollution, Indoor↗

Health, safety and environmental criteria for siting of laboratory facilities.

The development of applicable criteria for assessing the suitability of a site for construction of full and partial containment laboratories for the analysis of unknown and highly toxic chemicals is described. The criteria, based on considerations of health, safety and environmental factors, are used to define critical considerations in site selection to minimize the risk to non-laboratory personnel and the surrounding environment. Criteria are synthesized from several sources using the assumption of a worst-case chemical release. Mechanical failures, human failures, critical events and social/legal limitations are investigated, as are the characteristics of a site which may limit construction of such a facility. A detailed description is made of the various types of laboratories and the types of samples analyzed in them. The final recommendations are summarized for five typical laboratory settings; they are based primarily on the potential impacts on people, property and natural resources. A single occupancy building in a rural setting is recommended as the most suitable site for a full containment laboratory. A single occupancy building in an industrial park setting is acceptable, while multiple occupancy buildings and sites which are more highly developed are unacceptable. Similar recommendations are made for partial containment and conventional laboratories.

Containment of Biohazards↗

Performance of asbestos fiber counting laboratories in the NIOSH proficiency analytical testing (PAT) program.

Asbestos fiber counting data reported in the NIOSH Proficiency Analytical Testing (PAT) Program are used in this study to evaluate the analytical performance of participating laboratories and to determine if overall performance has improved during a ten-year period. PAT laboratories have achieved intralaboratory precision of 0.18 to 0.28 relative standard deviation (RSD), and interlaboratory precision of 0.33 to 0.44 RSD. In addition, there was higher variability between PAT laboratories from 1974 to 1978, when the program underwent considerable change and growth than the variability found during previous or subsequent time periods. The improvements in interlaboratory precision by approximately one-third since 1974 and the tendency of laboratories with little PAT experience to have poorer interlaboratory precision than more experienced laboratories raises a concern that interlaboratory precision may deteriorate as large numbers of new laboratories start to enroll in the PAT Program with the increased emphasis on asbestos removal in public buildings.

Asbestos↗

Monitoring the performance of occupational health laboratories.

To monitor the performance of occupational health laboratories analyzing workplace air, the American Industrial Hygiene Association (AIHA), with assistance from the National Institute for Occupational Safety and Health, has established four national quality assurance programs. They are the Proficiency Analytical Testing (PAT) Program, the AIHA Laboratory Accreditation Program, the Asbestos Analysts Registry, and the Bulk Quality Assurance Program. This paper focuses on the PAT program, a quality audit program that provides samples of asbestos, silica, metals, and solvents to laboratories quarterly. PAT data for asbestos, silica, and lead were examined for trends in precision. Simple graphs of coefficient of variation during the 18-yr history of the program provide evidence of improved agreement among laboratories performing these analyses. The improvement took place in spite of growth in the number of laboratories and decreases in the levels being analyzed. The improvement is attributed to several factors, including improved analytical methods and the very existence of the PAT and AIHA Laboratory Accreditation Programs.

Air Pollutants, Occupational↗

Performance of laboratories measuring silica in the Proficiency Analytical Testing program.

A statistical study was performed on the results reported by laboratories analyzing silica samples in the first 101 rounds of the Proficiency Analytical Testing (PAT) program. Five laboratories participated in the first round of the PAT program in 1972, and participation grew to 130 laboratories before falling to 105 in Round 101. The laboratories use all three of the major methods of analysis: colorimetry, x-ray diffractometry, and infrared spectroscopy. The objectives of the study were to determine bias between methods, the variability associated with the methods, and any changes in bias or variability caused by a number of factors. The colorimetric method has consistently given the lowest results, particularly at higher loadings. X-ray diffractometry results were biased higher than infrared spectroscopy results during one period but not in the following period. Between the two periods, the procedures and materials used to prepare PAT samples changed in a number of ways, but the switch to quartz dust with a smaller particle size is a likely explanation for the bias difference. Generally, silica analyses have improved in precision over time, and this improvement has taken place for all three of the methods. The colorimetric method has shown the poorest precision of the three methods, but, unlike the differences in bias, the differences in precision have diminished considerably over time. Precision estimates from other studies were compared to those from this study to learn more about sources of variability. The largest source of variability, the differences between laboratories, was large even when laboratories used the same method, as they did in a collaborative study of silica methods.

Air Pollutants, Occupational↗

Comparative study of antiphospholipid antibody detection in eleven Belgian laboratories.

Twenty-six plasma samples have been sent to 11 different Belgian laboratories in order to detect the presence of antiphospholipid antibodies, either by immunological methods and/or by coagulation tests. A good concordance between laboratories was observed for coagulation tests. Laboratories using detection tests and performing mixing procedures and neutralisation procedures displayed the highest sensitivity as compared with laboratories which did not perform one of these two latter procedures. The concordance between laboratories for the immunological methods was much worse as compared with coagulation tests. This may be attributable either to an intrinsic problem of the immunological tests or to a selection bias due the fact that the plasmas used in this study were selected in coagulation laboratories only where the chance to find a lupus anticoagulant positive/ELISA antiphospholipid negative sample is high.

Adult↗

Activity rhythms of wild and laboratory golden hamsters (Mesocricetus auratus) under entrained and free-running conditions.

The golden hamster (Mesocricetus auratus) is one of the most frequently used laboratory animals, particularly in chronobiological studies. One reason is its very robust and predictable rhythms, although the question arises whether this is an inbreeding effect or rather is typical for the species. We compared the daily (circadian) activity rhythms of wild and laboratory golden hamsters. The laboratory hamsters were derived from our own outbred stock (Zoh:GOHA). The wild hamsters included animals captured in Syria and their descendants (F1). Experiments were performed under entrained (light: dark [LD] 14h:0h) and under free-running (constant darkness, DD) conditions. Locomotor activity was recorded using passive infrared detectors. Under entrained conditions, the animals had access to a running wheel for a certain time to induce additional activity. After 3 weeks in constant darkness, a light pulse (15 min, 100 lux) was applied at circadian time 14 (CT14). Both laboratory and wild hamsters showed well-pronounced and very similar activity rhythms. Under entrained conditions, all hamsters manifested about 80% of their total 24h activity during the dark portion of the LD cycle. The robustness of the daily rhythms was also similar. However, interindividual variability was higher in wild hamsters for both measures. All animals used the running wheels almost exclusively during the dark portion of the LD cycle, although the wild hamsters were three times more active. The period length, measured in constant darkness, was significantly shorter in wild (23.93h +/- 0.10h) than in laboratory hamsters (24.06 +/- 0.07h). The light-induced phase changes were not different (about 1.5h). In summary, these results indicate that the laboratory hamster is not much different from the wild type.

Activity Cycles↗

Glycated hemoglobin assessment in clinical practice: comparison of the A1cNow point-of-care device with central laboratory testing (GOAL A1C Study).

BACKGROUND: The Glycemic Optimization with Algorithms and Labs At Po1nt of Care (GOAL A1C) Study assessed the effect of titration monitoring strategies and methods of A1C testing on glycemic control in patients with type 2 diabetes failing oral therapy and beginning basal insulin glargine. The availability of both point-of-care (POC) and central laboratory A1C values provided an opportunity to evaluate correlation and statistical agreement between these methods of testing. This analysis forms the basis of the current report. METHODS: This is a 24-week, randomized, four-arm, open-label study conducted in 7,758 subjects enrolled at 2,130 sites. At baseline, patients had A1C measurements both by POC testing using the A1cNow device (Metrika, Inc., Sunnyvale, CA), which applies an immunoassay method, and by central laboratory analysis using ion exchange high-performance liquid chromatography. These measures were compared statistically. RESULTS: An r value of 0.72 was calculated for POC and laboratory A1C assessments. Although the mean POC A1C values were in agreement with the central laboratory values, there was a large range in individual POC A1C values. CONCLUSIONS: POC testing of A1C in predominantly primary care settings using the A1cNow device was correlated with central laboratory results. The correlation was less than expected based on each method's reproducibility data. Although there was agreement between the average POC A1C values and the corresponding central laboratory values, the dispersion of individual POC A1C values was large. Thus, we conclude that these two methods of A1C testing should not be used interchangeably.

Aged↗