A novel surgical treatment of type 3 congenital elbow luxation in a dog.

Congenital luxation of the ulnar and radius is a rare orthopaedic condition in the dog. This case report describes a novel surgical treatment for congenital elbow luxation in a medium-breed dog. A 6-week-old Kelpie presented for left forelimb lameness and deformity. Radiographs and computed tomography (CT) confirmed the diagnosis of unilateral ulnar and radius luxation. The surgical repair involved open reduction followed by fixation with an extraarticular pin and a transarticular external fixator. The outcome of surgery was improved leg function and weight-bearing, however, reluxation of the radial head was diagnosed 7 weeks following surgery. This technique may offer an alternative surgical option to improve clinical signs, as well as insight into improving the management of this condition.

Intra-articular methylprednisolone and bupivacaine for treatment of sesamoid disease in dogs.

INTRODUCTION: The sesamoid disease is a cause of lameness in dogs, and there is limited literature relating to diagnosis, treatment and outcome of treatment in dogs with the sesamoid disease. Our aim was to compare the efficacy of intra-articular metacarpophalangeal/metatarsophalangeal joint injection with methylprednisolone and bupivacaine (IMPB) or conservative management with nonsteroidal anti-inflammatories and rest (CMNR) for treatment of this disease. MATERIALS AND METHODS: We conducted a retrospective survey of dogs treated for the sesamoid disease with IMPB or CMNR. The medical records of all dogs that received IMPB or were recommended CMNR for treatment of sesamoid pain were reviewed, and a client questionnaire was delivered to owners. Response to treatment, rapidity of response, length of resolution and recurrence of clinical signs associated with the sesamoid disease were assessed. RESULTS: A total of 78 dogs were included in the study. One week after IMPB, 52/58 (89.7%) dogs demonstrated resolution of lameness compared with 1 week of CMNR, 0/18 (P < 0.001). There was limited statistical evidence in client satisfaction between treatment groups, IMPB 36/53 (67.9%) and CMNR 16/17 (94%) (P = 0.052). Dogs presenting with the sesamoid disease had comorbidities in 51/78 (65.4%) of cases. Elbow disease was the most common comorbidity 29/78 (37.2%). CONCLUSION: Our results support the use of IMPB for short-term (1 week) resolution of lameness associated with sesamoid disease in dogs. Dogs treated with CMNR had slower improvement; however, there was no difference in lameness or client satisfaction between treatment groups at long-term follow-up (12 months).

Local heroes or villains: tissue-resident memory T cells in human health and disease.

Tissue-resident memory T (TRM) cells are increasingly associated with the outcomes of health and disease. TRM cells can mediate local immune protection against infections and cancer, which has led to interest in TRM cells as targets for vaccination and immunotherapies. However, these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis, alopecia areata, and vitiligo. Here, we summarize the biology of TRM cells established in animal models and in translational human studies. We review the beneficial effects of TRM cells in mediating protective responses against infection and cancer and the adverse role of TRM cells in driving pathology in autoimmunity. A further understanding of the breadth and mechanisms of TRM cell activity is essential for the safe design of strategies that manipulate TRM cells, such that protective responses can be enhanced without unwanted tissue damage, and pathogenic TRM cells can be eliminated without losing local immunity.

Human immunology studies using organ donors: Impact of clinical variations on immune parameters in tissues and circulation.

Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here a coordinate analysis of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (2 months-93 years; n = 291) across eight clinical parameters. Overall, the blood of donors exhibited similar monocyte and lymphocyte content and low serum levels of pro-inflammatory cytokines as healthy controls; however, donor blood had increased neutrophils and serum levels of IL-8, IL-6, and MCP-1 which varied with cause of death. In tissues, the frequency and composition of monocytes, neutrophils, B lymphocytes and T cell subsets in lymphoid or mucosal sites did not vary with clinical state, and was similar in donors independent of the extent of clinical complications. Our results reveal that organ donors maintain tissue homeostasis, and are a valuable resource for fundamental studies in human immunology.

Bone-muscle indices as risk factors for fractures in men: the Osteoporotic Fractures in Men (MrOS) Study.

OBJECTIVE: To assess bone-muscle (B-M) indices as risk factors for incident fractures in men. METHODS: Participants of the Osteoporotic Fractures in Men (MrOS) Study completed a peripheral quantitative computed tomography scan at 66% of their tibial length. Bone macrostructure, estimates of bone strength, and muscle area were computed. Areal bone mineral density (aBMD) and body composition were assessed with dual-energy X-ray absorptiometry. Four year incident non-spine and clinical vertebral fractures were ascertained. B-M indices were expressed as bone-to-muscle ratios for: strength, mass and area. Discriminative power and hazards ratios (HR) for fractures were reported. RESULTS: In 1163 men (age: 77.2±5.2 years, body mass index (BMI): 28.0±4.0 kg/m(2), 4.1±0.9 follow-up years, 7.7% of men ⋝1 fracture), B-M indices were smaller in fractured men except for bending and areal indices. Smaller B-M indices were associated with increased fracture risk (HR: 1.30 to 1.74) independent of age and BMI. Strength and mass indices remained significant after accounting for lumbar spine but not total hip aBMD. However, aBMD correlated significantly with B-M indices. CONCLUSION: Mass and bending B-M indices are risk factors for fractures in men, but may not improve fracture risk prediction beyond that provided by total hip aBMD.

Volume measurement of bone erosions in magnetic resonance images of patients with rheumatoid arthritis.

The volume of bone erosions in the metacarpophalangeal joints is a radiological feature that can be used to track the progression of rheumatoid arthritis. We introduce a hybrid segmentation algorithm that combines region growing and level-set segmentation algorithms to semiautomatically measure the volume of bone erosions in magnetic resonance images. A total of 40 rheumatoid arthritis patients were included in the study. The scans of eight patients were used for training, whereas the remaining 32 scans were used to determine the accuracy, precision, and speed of the technique. The reproducibility of the semiautomated technique and that of manual segmentation was defined in terms of intraclass correlation coefficients. Both techniques were equally precise with intraclass correlation coefficient values greater than 0.9. The hybrid algorithm was highly accurate: the least squares fit between the semiautomated segmentations to those manually traced by a musculoskeletal radiologist resulted in a slope of 1.030 with an x-intercept of 1.385 mm(3) and an R(2) value of 0.923. The semiautomated technique was significantly faster than manual segmentation, which took two to four times longer to complete. Our hybrid algorithm shows promise in the quantitative assessment of radiological features of rheumatoid arthritis in a clinical setting.

The association of serum 25-hydroxyvitamin D with indicators of bone quality in men of Caucasian and African ancestry.

UNLABELLED: We examined the association of serum 25-hydroxyvitamin D [25(OH)D] with indices of bone quality in older men. Positive associations for 25(OH)D and bone mineral density, content, cortical thickness, and axial and polar strength strain indices were observed among Caucasians; however, among men of African descent findings were either null or negative. INTRODUCTION: There are limited data on serum 25(OH)D and bone measures in men of African ancestry. To better understand racial differences in vitamin D status and bone health, a cross-sectional study among 446 Caucasian men in the US and 496 men of African ancestry in Tobago (age ≥ 65 years) was conducted. METHODS: Serum 25(OH)D (liquid chromatography and tandem mass spectrometry) was measured, and peripheral quantitative computed tomography scans were administered. Bone measures estimated included trabecular and cortical volumetric bone mineral density (vBMD), bone mineral content (BMC), bone geometry (cross-sectional area and cortical thickness), and polar and axial strength strain indices (SSIp and SSIx). RESULTS: Men of African ancestry had higher 25(OH)D than Caucasians (34.7 vs. 27.6 ng/ml, p < 0.01). Among Caucasians, 25(OH)D was positively (p trend < 0.05) associated with cortical vBMD, total BMC, cortical thickness, SSIp, and SSIx at the distal radius after adjustment for potential confounders. Similar patterns were observed at the distal tibia. In contrast, in men of African ancestry, there was an inverse association (p trend < 0.05) between 25(OH)D and the cross-sectional area, and SSIx. Race modified (p for interaction < 0.05) the association between 25(OH)D and total BMC, cross-sectional area, SSIp, SSIx, and trabecular vBMD of the radius. In men of African ancestry, there was evidence of a threshold effect (at approximately 18 ng/ml) for 25(OH)D on tibial total BMC and cortical thickness. CONCLUSIONS: More studies are needed to better comprehend these race differences for 25(OH)D and bone density, geometry, and indices of bone strength.

Intravascular large B cell lymphoma: an elusive cause of pyrexia of unknown origin diagnosed postmortem.

Intravascular large B cell lymphoma (IVLBCL) is a rare cause of pyrexia of unknown origin. Because of its protean clinical manifestations, diagnosis is elusive and is often made postmortem. We report here a case of IVLBCL that evaded diagnosis despite multiple investigations in vivo for pyrexia of unknown origin over a 5‐month period.

Association between severe pandemic 2009 influenza A (H1N1) virus infection and immunoglobulin G(2) subclass deficiency.

BACKGROUND: . Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G(2) (IgG(2)) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection. METHODS: Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women. RESULTS: Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P < .001), anemia (P < .001), and low levels of total IgG (P= .01), IgG(1) (P= .022), and IgG(2) (15 of 19 vs 5 of 20; P= .001; mean value +/- standard deviation [SD], 1.8 +/- 1.7 g/L vs 3.4 +/- 1.4 g/L; P= .003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P= .02) and low mean IgG(2) levels (P= .043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG(2)-deficient patients at a mean (+/- SD) of 90 +/- 23 days (R, 38-126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG(2) deficient. Among 17 healthy pregnant control subjects, mildly low IgG(1) and/or IgG(2) levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG(2) (P= .001). CONCLUSIONS: Severe H1N1 infection is associated with IgG(2) deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG(2) level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG(2) deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.

The relationships between bone mineral density in the spine, hip, distal femur and proximal tibia and medial minimum joint space width in the knees of healthy females.

OBJECTIVE: To investigate the relationships between bone mineral density (BMD) in the hip, spine, distal femur and proximal tibia and minimum joint space width (mJSW) in the knees of healthy women. METHODS: Women 22-68 years old without a history of knee pain, bone or joint disease or injury underwent a single, fixed-flexion knee X-ray. Radiographs were graded according to the Kellgren-Lawrence scale and analyzed for mJSW using a computer algorithm. Dual X-ray absorptiometry scans of the spine, hip, distal femur and proximal tibia were also acquired for each participant. Femur and tibia scans were acquired and analyzed using a modified version of the lumbar spine software. RESULTS: Forty-five females, mean [standard deviation (SD)] age and body mass index (BMI) of 40.1 (13.9) years and 24.6 (4.5)kg/m(2), respectively, participated. The mean (SD) mJSW was 4.64 (0.68)mm. Linear regression analyses controlling for age and BMI revealed that BMD in the femoral trochanter and the central two regions of the tibia (T2 and T3) was significantly related to mJSW in the knee. A backwards regression analysis performed to determine which region of interest is most significantly related to mJSW revealed that femoral trochanter BMD (beta-value=0.416) is the most significant. CONCLUSIONS: In contrast to the suggestion that BMD is negatively correlated with mJSW in the knees of osteoarthritic individuals, these results suggest that increasing BMD in the femoral trochanter and tibia is significantly associated with increasing mJSW in healthy females. Further investigation of this relationship is warranted.

Automated measurement of radiographic hip joint-space width.

Radiographic joint-space narrowing (JSN) is the principle indicator of cartilage loss in osteoarthritis (OA). JSN is usually assessed qualitatively by visual inspection or in clinical research, is measured manually with a graduated handheld lens directly applied to the x-ray film, or from digitized radiographs by hand tracing the joint margins with a mouse. The minimum joint-space width (mJSW) and joint-space area (JSA) are recorded as the indices of OA progression in epidemiological studies and clinical drug trials. We present a computerized method that automatically finds the articular margins of the hip to improve determination of mJSW and JSA. The algorithm requires that three seed points are manually identified on the femoral head and uses three steps to process each digitized hip x-ray. First, a Hough transform finds the center and radius (R) of a circle that approximates the femoral head. Finding R indicates whether magnification differences must be corrected on repeat exams. Second, a gradient algorithm finds the edge of the femoral head and acetabulum. Third, the mid-line of the femoral neck is automatically found and used to define the joint portion (theta) that is assessed for narrowing. theta is fixed for follow-up exams of the same subject. The algorithm was evaluated in three ways to determine its performance characteristics. First, the inter-reader and intra-reader variability for mJSW and JSA associated with the selection of the seed points was found to be negligible (< 1%) compared to the variability associated with manual scoring with a lens or by tracing the joint margins with a mouse. Second, from duplicate hip x-rays of 19 subjects with OA, the Root Mean Square Standard Deviation and coefficient of variation for mJSW and JSA defined by the algorithm was determined to be better than manual techniques by at least a factor of 2. Third, the algorithm correctly identified the joint margin in more than 85% of the 105 cases tested. Automated measures of radiographic hip joint-space narrowing is less subjective than manual methods and may be applicable for monitoring OA progression in clinical research.

A glucoamylase::GFP gene fusion to study protein secretion by individual hyphae of Aspergillus niger.

Although Aspergillus niger is used as a host for heterologous protein production, yields are generally lower than those obtained for homologous proteins. Mechanisms of protein secretion and the secretory pathway in filamentous fungi are poorly characterised, although there is evidence to suggest that secretion occurs by a mechanism similar to that in other eukaryotes, but with proteins destined for secretion being directed to the hyphal tip. We report on a method using a glucoamylase: GFP gene fusion which allows us for the first time to monitor, in vivo, protein secretion in A. niger at the single hyphal level. A synthetic green fluorescent protein (sGFP(S65T)) was fused to truncated A. niger glucoamylase (GLA:499). Southern blot analysis of transformants confirmed that the gene fusion had successfully integrated into the A. niger genome. Confocal and fluorescence microscopy revealed that the GLA::GFP fusion protein is fluorescent in A. niger and appears to be directed to the hyphal tip. In young mycelia, hyphal cell wall fluorescence is apparent and immunogold labelling of GFP confirmed that GFP was partially localised within the hyphal cell wall. Using Western blotting, extracellular GLA::GFP was detected only in culture filtrates of young mycelia grown in a soya milk medium. The actin inhibitor latrunculin B was used to disrupt the secretion process, and its effects on the distribution of GLA::GFP were monitored.

Is there any association between the presence of bone disease and cumulative exposure to lead?

There is evidence from cell culture experiments, animal studies, and from measurements in humans that lead may exert detrimental effects on bone mineral metabolism. In order to explore a possible association between lead and bone disease, both cortical and trabecular bone lead content as well as serum lead concentration was measured in 117 patients who attended a metabolic bone disease clinic (n = 92) or were undergoing dialysis for renal failure (n = 25). Cortical bone lead content was higher in patients suffering from Paget's disease than it was in controls, patients with osteoporosis, and patients on dialysis. Trabecular bone lead content was lowest in patients with Paget's disease or osteitis fibrosa. There was no association between bone lead content and serum alkaline phosphatase concentration in patients suffering from osteoporosis. No statistically significant differences in serum lead concentrations were found between groups. Our results do not distinguish between the two possibilities that increased bone turnover due to Paget's disease releases lead from trabecular bone which is then available for deposition into cortical bone or the alternative possibility that an increased lead content in cortical bone may cause increased turnover with release of lead from trabecular bone.

Accuracy of cortical and trabecular bone measurements with peripheral quantitative computed tomography (pQCT).

In order to assess the accuracy of peripheral QCT (Stratec XCT 960) we analysed scans of the European Forearm Phantom and another phantom consisting of K2HPO4 encased in aluminium tubes to simulate cortical walls. Additionally 14 cadaveric forearm specimen scans were compared to CT scans acquired on a GE9800Q. The accuracy for density assessment of the European Forearm Phantom was better than 3%. A small increase in density was observed with increasing thickness of the aluminium wall (10% for each mm). Density measurements within the wall were confounded by limited spatial resolution. For a thickness of less than 4 mm, the density within the wall was underestimated by up to 40%. The measurement of mineral content was not influenced by this effect and showed an accuracy error of less than 6%. The agreement of density measurements on the different CT systems was very strong (R2 > 0.96; RMSE < 6.2%). Our findings suggest that the Stratec pQCT scanner very accurately measures volumetric trabecular and total bone mineral densities at the distal radius while the assessment of cortical density is associated with considerable inaccuracies due to limited spatial resolution.

Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation of lead in bone and blood in lead smelter workers.

Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydratase (ALAD) is one of the most sensitive indicators of blood lead levels. ALAD is polymorphic, with about 20% of Caucasians expressing the rarer ALAD2 allele. Previous studies indicated that this polymorphism may be a genetic factor in lead transport, metabolism, and/or distribution. Whole blood lead, serum lead, and ALAD genotype were determined for 381 lead smelter workers, including 70 workers expressing the ALAD2 allele, whose blood lead elevations were observed for more than 20 years of employment. The same employees demonstrated higher serum lead levels. Using a cumulative blood lead index (CBLI) for each worker, based on individual blood lead histories, and in vivo X-ray fluorescence measurements of bone lead to estimate total lead body burden, the slopes of linear relations of bone lead to CBLI were greater for workers homoallelic for ALAD1, indicating more efficient uptake of lead from blood into bone. This effect was most significant in calcaneus bone and for workers hired since 1977 [ALAD1-1: 0.0528 +/- 0.0028 and ALAD1-2 or 2-2: 0.0355 +/- 0.0031 (P < 0.001)]. Decreased transfer of blood lead into bone in individuals expressing the ALAD2 allele contrasted with increased blood lead. Thus the ALAD genotype affected lead metabolism and potentially modified lead delivery to target organs including the brain; however, the ALAD genotype did not significantly affect the net accumulation of lead in bone.

Relation between image-based assessment of distal radius trabecular structure and compressive strength.

OBJECTIVE: To investigate the degree to which an image-based assessment of trabecular bone structure can predict bone strength. METHODS: Transaxial high-resolution magnetic resonance imaging (MRI) images and peripheral quantitative computed tomography (pQCT) images were obtained for a set of 9 isolated radii. Trabecular bone was segmented from fat, and indices relating to the connectivity of the bone network and the size of the marrow space were derived. Bone mineral density was also assessed in each radius by means of dual-energy x-ray absorptiometry and pQCT. Each bone was subjected to a mechanical load consistent with a fall from a standing height, and measures of density and trabecular structure were compared to the compressive load. RESULTS: In the 9 bones tested, measures of bone mineral density explained approximately 50% of the variability with load (0.52 < r2 < 0.57, p < 0.03), and indices relating to the size of the marrow spaces explained an additional 25% to 30% of the variance. This held true whether the indices quantifying the marrow space were derived from the MRI images (r2 = 0.70, p = 0.03) or the pQCT images (r2 = 0.82, p = 0.006). CONCLUSION: Our findings suggest that image-based assessments of trabecular bone structure relate to bone strength in vitro.

Image-based assessment of spinal trabecular bone structure from high-resolution CT images.

The goal of this study was to assess whether a high-resolution CT measure of trabecular bone structure can enhance the discrimination between subjects with or without a vertebral fracture and having overall low hip or spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Sixty-one women with low BMD by DXA (T-score < -2.5 at hip or spine) were examined. Twenty women had sustained a vertebral fracture. Quantitative CT (QCT) BMD and high-resolution CT spinal scans were performed on a whole-body CT scanner. For the high-resolution images (0.31 mm pixel, 1.5 mm thick slice), trabecular bone was segmented from marrow using an adaptive threshold, region growth and skeletonization step. From the processed image we measured the apparent trabecular bone fraction (BV/TV), apparent trabecular thickness (I.Th) and apparent trabecular spacing (I.Sp). We also assessed the connectivity of the marrow space using region growing to derive a mean (HA) and maximum (HM) hole size. Despite the fact that the study population was preselected to have a low BMD by DXA, QCT BMD was highly associated with (p < 0.005) with fracture status. All structural parameters were correlated (r approximately 0.64 to 0.79) with BMD with p < 0.003 and showed significant differences between the fracture and non-fracture group. However, except for HA, this difference did not remain significant after adjustment for BMD. When BMD and then HA was entered into a paired linear regression model to predict fracture outcome, HA contributed with p = 0.03 and BMD with p = 0.86. ROC analysis was applied and showed that HA, BMD, I.Th and I.Sp discriminated the two groups with areas of 0.76, 0.75, 0.71 and 0.68, respectively. These findings suggest that an assessment of vertebral trabecular structure from high-resolution CT images is useful in discriminating subjects with vertebral fractures and potentially useful for predicting future fractures.

In vivo assessment of trabecular bone structure at the distal radius from high-resolution magnetic resonance images.

In this study a method of assessing trabecular bone structure at the distal end of the radius from high-resolution magnetic resonance images is described. Trabecular bone is segmented from the marrow and soft tissue background using an adaptive threshold, a region growth, and a skeletonization step. From the processed image we measured the connectivity and orientation of the trabecular bone network. Connectivity was assessed by a proposed connectivity index (CI) and marrow space was quantitated by a mean hole area (HA). Significant age-related changes in CI and HA were observed in a mixed group of normal volunteers. CI decreased at a rate of 0.18 yr-1 (r = 0.72, n = 14, p < 0.05) and HA increased at a rate of 0.018 mm2 yr-1 (r = 0.69, n = 14, p < 0.05). Gradient analysis was used to examine trabecular orientation, and revealed that the individual trabeculae at the distal end of the radius are organized anisotropically along the bone. These findings suggest that clinical magnetic resonance scanners can be used to assess trabecular bone structure in vivo.

Further experience with bone lead content measurements in residents of southern Ontario.

Bone lead content of the mid-tibia was measured by in vivo fluorescence excitation in 90 females and 59 males aged between 6 and 81. The cross-sectionally derived rate of increase of tibia lead content was 0.24 +/- 0.03 microgram [g mineral]-1 yr-1. In 93 adult women, the corresponding rate of increase for calcaneus lead content was 0.12 +/- 0.11 microgram [g mineral]-1 yr-1. Comparison with European values show that, in Canada, the rates of lead accumulation are greater than those found in N. Sweden and Finland, similar to those of S. Sweden and less than values measured in England.

Accumulated body burden and endogenous release of lead in employees of a lead smelter.

Bone lead levels for 367 active and 14 retired lead smelter workers were measured in vivo by X-ray fluorescence in May-June 1994. The bone sites of study were the tibia and calcaneus; magnitudes of concentration were used to gauge lead body burden. Whole blood lead readings from the workers generated a cumulative blood lead index (CBLI) that approximated the level of lead exposure over time. Blood lead values for 204 of the 381 workers were gathered from workers returning from a 10-month work interruption that ended in 1991; their blood level values were compared to their tibia and calcaneus lead levels. The resulting relations allowed constraints to be placed on the endogenous release of lead from bone in smelter works. Calcaneus lead levels were found to correlate strongly with those for tibia lead, and in a manner consistent with observations from other lead industry workers. Relations between bone lead concentration and CBLI demonstrated a distinctly nonlinear appearance. When the active population was divided by date of hire, a significant difference in the bone lead-CBLI slope emerged. After a correction to include the component of CBLI existing before the workers' employment at the smelter was made, this difference persisted. This implies that the transfer of lead from blood to bone in the workers has changed over time, possibly as a consequence of varying exposure conditions.