Cumulative blood-cadmium and tubular proteinuria: a dose-response relationship

Summary Biological monitoring, i.e. using individual measures of exposure such as cadmium in blood, is supposed to reflect the real dose better than the more commonly used external measures such as air-cadmium. In order to investigate this, cumulative cadmium doses were estimated individually for 440 workers in a battery factory. Cumulative air-cadmium dose as well as two different cumulative blood-cadmium doses were computed for each study individual. Forty workers had evidence of tubular proteinuria and a clear dose-response relationship was found for each of the dose estimates. Our results suggest that cumulative blood-cadmium is a more sensitive indicator of cadmium-induced renal dysfunction than cumulative air-cadmium.This work was carried out at the Department of Environmental Hygiene, the Karolinska Institute in Stockholm     

A suggestion on how to use measurements of cadmium in blood as a cumulative dose estimate

Summary The individual cumulative cadmium dose was estimated for 44 smelter workers in a cadmium-copper alloy plant. Two different principles were used: cumulative respiratory dose and cumulative average annual blood-cadmium dose. Out of eight workers with a cumulative respiratory dose exceeding 500 mg Cd · h/m³, two of them (25%) had signs of a cadmium-induced renal dysfunction. These two men were the only workers that had a cumulative average annual blood cadmium dose exceeding 200 g Cd · year/1. Our results suggest that measurements of cadmium in the blood can be used as an indicator of the cadmium exposure of each individual and that, in order to prevent renal dysfunction, the average blood-cadmium concentration should not exceed 10 Cd/1 over periods of many years (decades).     

Mitogenic activity of chloroform and carbon tetrachloride in serum-deficient or calcium-deficient cultures of human embryonic lung fibroblasts

It was demonstrated that chloroform - studied in the non-toxicconcentration interval 0.025–0.1%p w/v - as well as carbontetrachloride at 0.0125–0.05%, can support proliferationof cell cycling human embryonic lung fibroblasts in Dulbecco'smodified Eagle's medium (DMEM) complemented with 0.5% foetalcalf serum. This serum concentration restricts the growth ofthe non-solvent treated fibroblast (control) cultures. Evenafter a pretreatment of the fibroblasts with the low serum-mediumfor up to 4 days, the cells responded to the mitogenic impulseof the solvents. This indicates that quiescent fibroblasts arealso sensitive to the mitosis-stimulating effect of the solvents.The effect of the solvents in serum-free DMEM was followed ina short-term study in order to determine if cofactor(s) fromserum are needed for expression of the mitosis-stimulating activityof the solvents. Carbon tetrachloride was shown to be mitogemcfor the fibroblasts. At solvent concentrations 0.00078% w/vthe cells were observed to proliferate about as rapidly as controlcells incubated in 10% serum-containing DMEM. After change fromsolvent-containing to solvent-free medium cell proliferationwas soon inhibited. Chloroform was not mitogenic in the serum-freemedium. The mitogenic activity of CHCl₃ or CCl₄ in solvent containing10% serum and reduced content of calcium ions (0.05 mM) wasthen determined. It was shown that the solvents under the non-physiologicalconditions support proliferation of the fibroblasts for 2–3days depending on the solvent concentration.     

Chronic conditions in children increase the risk for physical abuse – but vary with socio‐economic circumstances

Aim: To explore whether children (age 10, 12 and 15 years) with self‐reported chronic conditions are at higher risk of physical abuse and/or exposure to intimate‐partner violence than other children, while considering the importance of demographic factors. Methods: A national cross‐sectional study of 2771 pupils in grades 4, 6 and 9 from 44 schools in Sweden (91% response rate). Conflict Tactic Scales were used to measure physical abuse and separate questions measured exposure to intimate‐partner violence. A list of 13 diagnoses was used to estimate chronic conditions. Results: Children with chronic conditions had an increased risk for physical abuse (CPA) only (OR 1.67) as well as in combination with exposure to intimate‐partner violence (IPV) (OR 2.54), but not to IPV only, compared to children without chronic conditions. Furthermore, when chronic conditions were combined with country of birth other than Sweden and living in low‐income areas, the risk for CPA increased even more, indicating interactive effects. Conclusions: A wide range of chronic health conditions in children increased the risk for physical abuse. This indicates that certain factors unite this group of children, irrespective of the type of disability or degree of severity, but where a combination with socio‐economic circumstances is of importance.     

Amplification of ERBB2 (HER2) in embryonal rhabdomyosarcoma: A potential treatment target in rare cases?

The ERBB2 gene encodes a receptor tyrosine kinase also known as HER2. The gene is amplified and overexpressed in one-fifth of breast carcinomas; patients with such tumors benefit from targeted treatment with trastuzumab or other drugs blocking the receptor. In addition, ERBB2 has been shown to be amplified and/or overexpressed in a variety of other malignancies. Notably, both alveolar and embryonal rhabdomyosarcoma (RMS), especially in children, often show increased expression of ERBB2. Although high-level amplification of the gene has not been described in RMS, its frequent expression at the cell surface of RMS cells has been exploited for chimeric antigen receptor T-cell (CAR T)-based treatment strategies. We here describe two cases of pediatric, fusion-negative embryonal RMS with high-level amplification of the ERBB2 gene. One patient is currently treated with conventional chemotherapy for a recently detected standard risk RMS, whereas the other patient died from metastatic disease. Both tumors displayed focal amplicons (210 and 274 Kb, respectively) in chromosome band 17q12, with proximal and distal borders corresponding to those typically seen in breast cancer. In both tumors, the ERBB2 amplicon correlated with high expression at the RNA and protein levels. Thus, breast cancer-like ERBB2 amplification is a very rare, but recurrent feature of pediatric RMS, and should be exploited as an alternative treatment target.