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R Vetter

Publications and source records attributed to R Vetter.

At least 37 records · Page 2Linked to original sources
PubMed1998

Exponential-type distribution of human muscle sympathetic nerve activity results in an automatic quantification method.

A new burst counting method based on a subject invariant characteristic demonstrates the limits of the actual automatic based methods. The exponential behaviour of the counted bursts in function of a variable threshold highlights a scaling property of the muscle sympathetic nerve activity. From experimental single unit recording results, we deduce the exponential-type (gamma) distribution of instantaneous spiking frequency within multi-unit recordings. We show that integrated muscle sympathetic nerve discharges must be gamma distributed with parameters proportional to the number of neurons in the recording pool and to the integration window width.

Adult↗
PubMed1998

Thyroid control of sarcolemmal Na+/Ca2+ exchanger and SR Ca2+-ATPase in developing rat heart.

Thyroid hormone (TH) levels increase in the postnatal life and are essential for maturation of myocardial Ca2+ handling. During this time, the sarcolemmal (SL) Na+/Ca2+ exchanger (NCX) function decreases and the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA2) function increases. We examined the effects of postnatal hypo- or hyperthyroidism on NCX and SERCA2 in rat hearts. Animals were rendered hypothyroid by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from days 2 to 21 postpartum. Hyperthyroidism was induced by daily injections of 10 microg/100 g body weight of 3,3',5-triiodo-L-thyronine during this period. Ventricular steady-state mRNA and protein levels of NCX and SERCA2 were analyzed by Northern and Western blotting. These were compared with SL Na+ gradient-induced and SR oxalate-supported Ca2+ transports in isolated membranes. In hypothyroidism, NCX mRNA and protein were elevated by 66 and 80%, respectively, and SERCA2 mRNA and protein were reduced to 55 and 70%, respectively (P < 0.05 vs. euthyroid). Corresponding differences were observed in the respective Ca2+ transports. Conversely, reduced NCX (by 50%) and elevated SERCA2 (by 150%) activities were found in hyperthyroidism (P < 0.05). The levels of NCX and SERCA2 mRNA and protein were, however, unchanged in hyperthyroidism, indicating that functional changes are not due to altered NCX and SERCA2 expression. In this case, a decline in noninhibitory phosphorylated phospholamban is a likely explanation for the elevated SR Ca2+ transport. In conclusion, physiological TH levels appear to be essential for normal reciprocal changes in the expression and function of myocardial NCX and SERCA2 during postnatal development.

Animals↗
PubMed1998

Mechanisms of thyroid hormone control over sensitivity and maximal contractile responsiveness to beta-adrenergic agonists in atria.

This paper discusses the mechanisms of two basic effects of thyroid hormones on atrial responses to beta-adrenergic agonists, i.e. increased inotropic sensitivity and decreased maximal contractile responsiveness. The increased sensitivity of atria to beta-adrenergic agonists under thyroid hormones appears to be related to increases in beta-adrenoceptor density and Gs/Gi protein ratio, leading to activation of Gs-mediated pathway, but suppression of Gi-mediated pathway of adenylate cyclase regulation. Therefore, the i/c concentrations of cAMP and corresponding inotropic responses achieve their maximums at lower doses of beta-adrenergic agonist. Thyroid hormones also decrease the expression of phospholamban, but increase the expression of sarcoplasmic reticulum Ca2+-pump. As a result, the basal activity of sarcoplasmic reticulum Ca2+-pump increases, but its beta-adrenergic activation through phosphorylation of phospholamban decreases. It is suggested that these changes are causal for decreased maximal inotropic and lusitropic responses of atria to beta-adrenergic agonists.

Adrenergic beta-Agonists↗
PubMed1998

Influence of different culture conditions on sarcoplasmic reticular calcium transport in isolated neonatal rat cardiomyocytes.

This study investigates sarcoplasmic reticulum (SR) calcium-(Ca2+) transport ATPase (SERCA2a) and phospholamban (PLB) in cultured spontaneously contracting neonatal rat cardiomyocytes (CM) to ascertain the function of both SR proteins under various culture conditions. The two major SR proteins were readily detectable in cultured CM by immunofluorescent microscopy using specific anti-SERCA2 and anti-PLB antibodies. Double labeling technique revealed that PLB-positive CM also labeled with anti-SERCA2. Coexpression of SERCA2 and PLB in CM was supported by measurement of cell homogenate oxalate-supported Ca2+ uptake which was completely inhibited by thapsigargin and stimulated by protein kinase A-catalyzed phosphorylation. Under serum-free conditions, incubation of CM with the SERCA2a expression modulator 3,3', 5-triiodo-L-thyronine (100 nM, 72 h) resulted in elevated Ca2+ uptake of +33%. Specific Ca2+ uptake activity was not altered if insulin was omitted from the serum-free culture medium but total SR Ca2+ transport activity was reduced under this culture condition. The results indicate that primary culture of spontaneously contracting neonatal rat CM can be employed as a useful model system for investigating both short- and long-term mechanisms determining the Ca2+ re-uptake function of the SR under defined culture conditions.

Animals↗
PubMed1997

Abundance and location of the small heat shock proteins HSP25 and alphaB-crystallin in rat and human heart.

BACKGROUND: In the heart, there are high constitutive levels of the two related small heat shock proteins, HSP25 and alphaB-crystallin. To gain insight into their functional role, we have analyzed abundance and location of both proteins in rat and human hearts at different stages of development and in diseased state. METHODS AND RESULTS: Immunoblotting analysis of rat ventricular tissue at fetal, neonatal, and adult stages reveals the level of HSP25 to decline strongly during development, whereas the level of alphaB-crystallin remains nearly constant. In parallel, the portion of phosphorylated isoforms of HSP25 decreases as shown by two-dimensional polyacrylamide gel electrophoresis. HSP25 is detected in cardiomyocytes and endothelial and vascular smooth muscle cells, whereas alphaB-crystallin is detected in cardiomyocytes only by immunofluorescence and immunoelectron microscopy. Both proteins colocalize in the I-band and M-line region of myofibrils in cardiomyocytes. In diseased and transplanted adult human hearts, HSP25 and alphaB-crystallin levels are considerably elevated compared with fetal hearts. In failing adult human hearts, phosphorylated isoforms of HSP25 predominate, and cardiomyocytes with a partial dislocation of HSP25 and alphaB-crystallin are observed. CONCLUSIONS: Differential accumulation and location of HSP25 and alphaB-crystallin in heart tissue during development imply distinct functions of both proteins, which seem to be involved in organization of cytoskeletal structures. As judged by level, phosphorylation state, and location of both small heat shock proteins, diseased adult human hearts share features with fetal hearts.

Aging↗
PubMed1997

Expression and function of the cardiac Na+/Ca2+ exchanger in postnatal development of the rat, in experimental-induced cardiac hypertrophy and in the failing human heart.

The diastolic and systolic dysfunction in the failing heart appear to be related to the altered Ca2+ handling of the cardiac myocyte. Disturbed Ca2+ handling might also affect influx and efflux of other ions, including Na+. In this context, the cardiac sarcolemmal Na+/Ca2+ exchanger represents an important exchange mechanism of Ca2+ versus Na+ transport across the sarcolemma. Expression and function of cardiac Na+/Ca2+ exchanger is highest in newborn rats and declines gradually in postnatal development. In pressure overload-induced hypertrophy, expression of cardiac Na+/Ca2+ exchanger is increased and translated into increased Na+/Ca2+ exchanger activity similar to the early phase of postnatal development in the rat. This suggests a common underlying mechanism in the control of Na+/ Ca2+ exchanger expression in the immature and the hypertrophied myocardium. Similar to experimental-induced hypertrophy, mRNA, protein and activity of Na+/ Ca2+ exchanger is increased in the failing human heart suggesting an increase in the number of functional exchanger molecules rather than an enhanced exchange rate by preexisting exchanger molecules. The potential functional implications of an increased cardiac Na+/Ca2+ exchanger activity in human heart failure may be limitation of diastolic intracellular Ca2+ overload. However, this may increase the arrhythmogenic potential of the failing heart, since additional Na+ influx via Na+/Ca2+ exchanger may affect the membrane potential.

Aging↗
PubMed1997

Thyroid hormones increase the contractility but suppress the effects of beta-adrenergic agonist by decreasing phospholamban expression in rat atria.

OBJECTIVE: The aim of the present study was to characterize the relationships between the thyroid-hormone-dependent changes in sarcoplasmic reticulum (SR) Ca2+ handling and contractile performance in atria. METHODS: Hypothyroidism in rats was induced by adding 0.05% 6-n-propyl-2-thiouracil to their drinking water for 6 weeks. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (1 microgram/g body weight) to euthyroid rats for 1 week. Left atria from the hearts with different thyroid states were examined by means of contractile measurements, SR oxalate-supported Ca(2+)-uptake, and Western blot of SR proteins. RESULTS: The tissue level of SR Ca(2+)-pump protein decreased in hypothyroid (46 +/- 6%) atria, but remained unchanged in hyperthyroid (110 +/- 8%) atria as compared with euthyroid atria. Hypothyroidism was associated with increased phospholamban expression (141 +/- 25%), whereas it was drastically downregulated under hyperthyroidism (21 +/- 4%). The rate of SR Ca(2+)-uptake, measured in the presence of the protein kinase A inhibitor, H-89, was higher in hyperthyroid atria and lower in hypothyroid atria than in euthyroid atria (397 +/- 40, 55 +/- 6 and 194 +/- 17 nmol Ca2+/g protein/min, respectively). However, the stimulation of SR Ca(2+)-uptake by the catalytic subunit of protein kinase A was relatively weaker in hyperthyroid (130 +/- 20% over control level without catalytic subunit) and stronger in hypothyroid (640 +/- 60%) than in euthyroid atria (280 +/- 40%). The rates of inotropic contraction (+dT/dt) were higher in the hyperthyroid atria (133 +/- 10 mN/s), but lower in hypothyroid atria (15 +/- 3 mN/s) than in their euthyroid counterparts (95 +/- 13 mN/s). Inversely, hypothyroid atria responded to isoproterenol with much larger increases in contractility (883 +/- 164% over the control values for the same muscle before addition of isoproterenol) and hyperthyroid with smaller increases (25 +/- 9%) than euthyroid preparations (207 +/- 17%) CONCLUSIONS: Thyroid hormones increase the contractility, but decrease the inotropic response to isoproterenol through decreasing the phospholamban/SR Ca(2+)-pump ratio in rat atria.

Adenosine Triphosphate↗
PubMed1997

Effects of alpha-adrenergic stimulation on the sarcolemmal Na+/Ca(2+)-exchanger in adult rat ventricular cardiocytes.

OBJECTIVE: The cardiac sarcolemmal Na+/Ca(2+)-exchanger (NCX) plays an important role in the maintenance of the myocardial Ca2+ homeostasis which is altered in cardiac hypertrophy and failure. The aim of the present study was to investigate whether alpha-adrenergic stimulation known to induce cardiac hypertrophy might be involved in the regulation of the sarcolemmal NCX. METHODS: Adult rat ventricular cardiocytes (ARC) were isolated from male Sprague-Dawley rats. Phenylephrine, an alpha-adrenergic agonist, was used as hypertrophic agent. NCX expression was measured by competitive RT-PCR and Western blot analysis. RESULTS: alpha-Adrenergic stimulation of ARC with 10 microM phenylephrine for 24 h resulted in a significant increase of the NCX mRNA (2.5-fold) and the NCX protein level (1.8-fold). The changes on the expression level were blocked by the alpha 1-adrenoceptor antagonist prazosin. CONCLUSIONS: The data demonstrate that the NCX expression level is up-regulated by the activation of the alpha-adrenergic signal transduction pathway. The increased NCX mRNA level induced by alpha-adrenergic stimulation appeared to be translated into increased NCX protein level.

Adrenergic alpha-Agonists↗
PubMed1997

Experimental and clinical experience with new pyeloureteral stents in pediatric urology.

In light of the many problems with the use of conventional external stents in supravesical reconstructive urinary tract surgery in children; e.g. the risk of infection, urodynamic malfunction, and lack of flexibility insertion methods, the return to internal pyeloureteral stenting is a much discussed topic in pediatric urology. In order to improve the generally unsatisfactory situation, we developed, together with the Rüsch Co., a new type of directable and deconnectable ureteral stent. This polyurethane catheter features a membrane valve made of soft Wiruthan at the bladder end, which closes automatically with increasing bladder pressure. Thus, urinary backflow from the urinary bladder into the renal pelvis is prevented. Experimental data from antireflux stenting justify the clinical use of such a stent in children, as the urodynamic in vivo criteria and requirements were fulfilled completely. We now have clinical experience with the application of 340 pyeloureteral DD stents in 241 children from 1993 through 1996; 259 stents were inserted intraoperatively, and 81 stents were applied by endoscope. It was impressive that secondarily, renal function that had been considerably reduced could be regained and stabilized by long-term stenting, even in some older children with chronic supravesical ureteral obstruction. Although small technical details have to be clarified, such as simplification of stent retrieval and an antireflux valve that can be applied using an anterograde approach, the DD valve stent used in this patient population after reconstruction of a malformed supravesical urinary tract can be recommended without any reservations.

Animals↗
PubMed1996

Cardiac Na+/Ca2+ exchange activity in patients with end-stage heart failure.

OBJECTIVE: The aim of the present study was to investigate the functional activity and expression of the sarcolemmal Na+/Ca2+-exchanger in the failing human heart. METHODS: Left ventricular samples were taken from eleven patients with end-stage heart failure and six organ donors (normal controls). The Na+/Ca2+-exchanger activity was assessed by measuring Na+ gradient-induced 45Ca2+ transport into sarcolemmal vesicles of quantitatively collected crude membrane preparations. The abundance of the Na+/Ca2+-exchanger protein was determined by Western blot analysis using a specific antiserum and the results were normalized to myocyte specific beta-myosin heavy chain protein content. RESULTS: In membrane preparations of failing human hearts, both the Na+ gradient-induced 45Ca2+ transport activity and the level of immunoreactive Na+/Ca2+-exchanger protein were increased (P < 0.01) by 87% and 160% compared to controls, respectively. CONCLUSIONS: In human end-stage heart failure the increased sarcolemmal Na+/Ca2+-exchanger activity appears to be due to an elevated expression of this protein. An increase in the expression and activity of the Na+/Ca2+-exchanger in the failing human heart may be of important functional significance: while a resulting increase in Ca2+ extrusion across the sarcolemma may limit diastolic Ca2+ overload, a corresponding influx of Na+ may be associated with membrane depolarization and enhanced arrhythmogenesis if the Na+/Ca2+-exchanger operates primarily in the forward mode.

Adult↗
PubMed1995

Reciprocal changes in the postnatal expression of the sarcolemmal Na+-Ca(2+)-exchanger and SERCA2 in rat heart.

The aim of this study was to examine the relationship between sarcolemmal Na(+)-Ca2+ exchangers and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2) expression and the developmental differences in cardiac Ca2+ handling. Postnatal steady-state mRNA and protein levels were analysed in rat ventricular myocardium by Northern and immunoblot analysis, respectively. This was compared to Na+ gradient-induced and SR oxalate-supported Ca2 transport in isolated membranes. Na(+)-Ca2+ exchanger mRNA declined by 75% between day 1 and 30, whereas SR Ca2+ ATPase mRNA levels increased by 97% during this period. The Na(+)-Ca2+ exchanger mRNA/Ca(2+)-ATPase mRNA ratio was found to be inversely related to post-natal age. The changes in mRNA levels were associated with corresponding developmental differences in the Ca2+ transport activities of the respective membrane proteins. In crude membranes, the Na(+)-dependent Ca2+ transport activity (at 75 microM Ca2+) declined gradually (P < 0.01; mean +/- S.E.) from 17.7 +/- 2.4 nmoles Ca2+/g wet tissue/2s at day 1-3 (n = 5) to a value of 4.2 +/- 1.1 at day 40 (n =4). Conversely, SR Ca2+ uptake increased (P < 0.01) 2.6-fold during this period. The inversely related changes in the post-natal expression and function of the Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase suggest a coordinated control at the pretranslational level of the cellular Ca2+ transport processes mediated by the two membrane proteins.

Aging↗
PubMed1995

Differential influences of carnitine palmitoyltransferase-1 inhibition and hyperthyroidism on cardiac growth and sarcoplasmic reticulum phosphorylation.

To characterize interventions resulting in 'physiological' growth of the heart, Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) had hyperthyroidism induced (0.05 mg.kg-1.day-1 triiodothyronine for 6 days) or were treated with a high dose of the carnitine palmitoyltransferase-1 inhibitor, etomoxir (15 mg.kg-1.day-1 for 5 weeks). Etomoxir increased cardiac growth evenly, but hyperthyroidism resulted in an over-proportional higher right ventricular weight. Both interventions increased the proportion of the myosin isozyme V1. The rate of sarcoplasmic reticulum (SR) Ca2+ uptake was increased to a greater extent in hyperthyroid rats than in etomoxir-treated rats (P < 0.05). Left ventricular levels of immunoreactive phospholamban (semiquantitative ELISA) were moderately decreased (P < 0.05) in hyperthyroid rats but not in etomoxir-treated rats. The protein kinase A-catalyzed in vitro 32P-incorporation into the SR Ca2+ pump modulator phospholamban was greatly reduced (P < 0.05) in hyperthyroid rats, indicating an increased in vivo phosphorylation. Etomoxir did not affect phospholamban phosphorylation in WKY rats. Thus, both a higher in vivo phospholamban phosphorylation state and a greater number of active Ca2+ pumps contributed to an increased rate of SR Ca2+ uptake in hyperthyroidism. The etomoxir treatment primarily increased the number of active Ca2+ pumps. A scheme is proposed focusing on long-term vs short-term regulation of the SR Ca2+ pump/phospholamban system in diseased states.

Animals↗
PubMed1995

Alterations of cardiac contractile function are related to changes in membrane calcium transport in spontaneously hypertensive rats.

OBJECTIVE: Transport activities of cardiac sodium-calcium exchange and sarcoplasmic reticulum calcium ATPase were measured biochemically in spontaneously hypertensive rats (SHR) with hypertrophied myocardium and in normotensive Wistar-Kyoto (WKY) rats and it was tested whether possible differences have consequences for the contractile properties of papillary muscle. METHODS: Sarcolemmal sodium-dependent calcium transport via sodium-calcium exchange and oxalate-supported sarcoplasmic reticulum calcium uptake were measured in left ventricular membranes of 22-week-old rats. Postextrastimulatory potentiated contractions, postrest potentiated contractions, the twitch-to-twitch decay of those potentiations and the response to increasing stimulation frequency of left ventricular papillary muscles were analysed. RESULTS: Compared with WKY rats we found in SHR: a significant increase in sodium-calcium exchange (65%) and in sarcoplasmic reticulum calcium uptake (24%); a steeper twitch-to-twitch decay in postextrastimulatory potentiated contractions and postrest potentiated contractions, suggesting a lower calcium fraction recirculating between myofilaments and sarcoplasmic reticulum and, consequently, a relatively higher calcium efflux via sodium-calcium exchange; a stronger rest-dependent decrease in recirculating calcium fraction in postrest potentiated contractions accompanied by accelerated relaxation, suggesting an increasing driving force for calcium extrusion via sodium-calcium exchange, probably caused by decreasing intracellular sodium during rest; a greater transient decrease in peak force of subsequent twitches after postrest potentiated contractions below pre-interventional level, indicating higher cellular calcium loss; and a smaller negative inotropic effect in response to doubling of stimulation rate as a manoeuvre to increase the intracellular sodium level. CONCLUSION: In SHR, the contractile properties suggest an increased contribution of sodium-calcium exchange to cellular calcium removal, which is strongly supported by the enhanced sodium-calcium exchange activity in cardiac membrane vesicles.

Animals↗
PubMed1995

Dietary medium-chain triglycerides can prevent changes in myosin and SR due to CPT-1 inhibition by etomoxir.

To define determinants of subcellular structures of heart, Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated for 5 wk with 15 mg.kg-1.day-1 etomoxir [reduces mitochondrial carnitine palmitoyltransferase-1 (CPT-1) activity and fatty acid synthesis]. To bypass CPT-1 inhibition, etomoxir-treated rats were fed a medium-chain fatty acid (MCFA) diet. Etomoxir induced a proportionate growth of heart, which could partially (WKY, P < 0.05) or completely (SHR, P < 0.05) be prevented by the MCFA diet. Also the etomoxir-induced increase in myosin V1 was partially prevented (P < 0.05). Etomoxir increased (P < 0.05) rate of sarcoplasmic reticulum (SR) Ca2+ uptake of WKY and SHR ventricular homogenates in the presence or absence of the SR Ca2+ release inhibitor ruthenium red. The MCFA diet resulted in SR Ca2+ uptake rates that were in between those of etomoxir-treated and untreated rats. The in vitro 32P incorporation into phospholamban and troponin I did not differ significantly in WKY. Etomoxir induced, however, an increase (P < 0.05) in the phosphorylated intermediate of the Ca2+ adenosinetriphosphatase in WKY that was prevented by the MCFA diet. In SHR, etomoxir increased the in vitro phospholamban phosphorylation, which was reduced compared with WKY. The data show that myosin and SR are affected by a chronically altered substrate utilization of heart.

Animals↗
PubMed1994

Quantitative investigations of acetylcholinesterase activities in colorectal malformations.

In cases of colorectal innervation disturbance the histological and histochemical findings are well placed to classify the morphological state and to indicate to the pediatric surgeon the therapeutic direction. Any limitation of their value results from technical errors, age dependent localization of morphological structures and the subjectivity of the assessment. For this reason a quantitative biochemical investigation of cholinesterase activity in homogenized investigation of cholinesterase activity in homogenized rectal mucosa specimens and resected bowel segments was performed. The biochemical standard value of the AChE-activity amounts up to 3-6 x 10(-7) mol ACh/min/g in healthy test patients and the ratio of specific/unspecific esterases 1.1 to 1.3. The percentage of AChE to the total enzyme activity was 47.5%. The standard distribution of the different globular and asymmetric cholinesterase structures is described by the proportion of the molecular types G1/G2/G4 and A12. These main types determine the biochemical nature of the human rectum. Hypertrophy of cholinergic nerve fibres in aganglionic bowel segments correlates pathobiochemically with the increase of the cholinesterases caused by the high molecular tetramer G4. However, the Hirschsprung's disease could not be differentiated by the percentage of the AChE-activity to the total ChE-activity because of the continuous increase in the BChE in the aganglionic tissue. Neuronal intestinal dysplasias with their main cholinergic nerve fibre hyperplasias are characterized by disturbances of the dualism and interrelation of different cholinesterases. By means of pathogiochemical investigations the subjective factor in the assessment of histochemical states is avoided and the diagnostic accuracy increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

CPT-1 inhibition by etomoxir has a chamber-related action on cardiac sarcoplasmic reticulum and isomyosins.

To characterize the effect of an altered substrate utilization for cardiac sarcoplasmic reticulum (SR) Ca2+ transport, normotensive rats were treated for 5 wk with 15 mg.kg-1.day-1 enantiomeric etomoxir, which inhibits mitochondrial carnitine palmitoyltransferase-1 (CPT-1) and fatty acid synthesis. Ca2+ uptake rates of left and right ventricular homogenates were differentially (P < 0.05, two-way analysis of variance) increased by 38 and 13%, respectively. Increased (P < 0.05) transport rates were also observed in the presence of ryanodine. The differences were considerably reduced in the protein kinase A-stimulated state. The levels of phosphorylated phospholamban (PLB) and troponin I as well as immunoreactive PLB were not affected. By contrast, phosphoenzyme levels (E-P) of the SR Ca2+ pump were increased in left ventricular (LV) homogenates. Values of LV E-P and Ca2+ uptake were linearly correlated (P < 0.05) with the myosin V1 proportions in control (31.7 +/- 1.8% V1) and treated (58.3 +/- 2.5% V1) rats. Thus in the left ventricle the metabolic influences have a coordinated action on two distinct proteins involved in relaxation or contraction. The chamber-specific differences in SR function suggest a more pronounced effect of etomoxir in functional states characterized by a reduced Ca2+ transport rate and myosin V1 proportion.

Animals↗
PubMed1993

Validity of exposure in one job as a surrogate for exposure in a cohort study.

Frequently, information pertaining to only one job is available or used to evaluate risk estimates of disease in occupational epidemiologic research. The amount of misclassification that such a practice could create has not, however, been examined. We used data from a mortality study of workers employed in 10 formaldehyde-producing or -using plants to address how closely several parameters of exposure based on the first, longest, or last job held in a company compared with those based on the worker's entire employment history at the plant. The best predictor for cumulative formaldehyde exposure at the plant was the longest job at that plant, with a correlation coefficient (r) of 0.70. The correlation with average exposure over the worker's employment was 0.77 for the first job and 0.74 for the longest and last jobs. Peak exposures and highest exposure levels experienced in the plant were more closely related to the first job (r = 0.72 and r = 0.74). The highest correlation with any of the measures was never with the last job. Variation between plants for each of these comparisons, however, was wide. These findings indicate that the use of a single job as a surrogate for exposure received at a particular worksite can result in different degrees of misclassification for different exposure measures. Even though the correlations were generally high, the associated misclassification of exposure could lead to a substantial underestimation of the relative risks in some situations. In this report two hypothetical examples show what effect the misclassification rates could have on estimates of disease risks.

Chemical Industry↗