The effects of low environmental cadmium exposure on bone density.

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9; 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta(2)M-U RBP, NAG), glomerular dysfunction (Alb-U and beta(2)M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone density.

Twenty years of Polish experience with three consecutive protocols for treatment of childhood acute myelogenous leukemia.

Until 1983, results of treatment of acute myelogenous leukemia (AML) in Poland with different regimens were very poor. In 1983, the Polish Pediatric Leukemia/Lymphoma Study Group introduced a unified treatment protocol--a modified version of BFM-83 protocol. This led to an increase in the curability of AML from 15% to approximately 32%. In 1994, a modification was made: the high-risk patients (>5% blasts in bone marrow on day 15 of therapy and all M5 cases) received two additional cycles with intermediate-dose cytarabine (ID-ARAC). This led to a nonsignificant improvement in the 5-year event-free survival (EFS) rate from 32 to 36%. A new treatment protocol employing idarubicin in place of daunorubicin was introduced in 1998 and produced better initial responses, increase in the number of patients attaining remission after induction therapy and proportional increase of standard-risk patients. The probability of 5-year EFS (pEFS) for the whole group of patients increased from 36 to 47%. In standard- and high-risk groups, the 5-year pEFS was 62 and 33%, respectively. The probability of 5-year disease-free survival was 58% in the whole group, and there were no differences between risk groups. Unsatisfactory treatment results in children classified into the high-risk group are principally due to the low remission rate.

Is P-glycoprotein a sufficient marker for multidrug resistance in vivo? Immunohistochemical staining for P-glycoprotein in children and adult leukemia: correlation with clinical outcome.

Seventy-eight patients: 45 children, 33 adults and 27 normal healthy donors were enrolled in the study. Expression of P-glycoprotein (P-gp) was evaluated with three monoclonal antibodies (MAb's) directed to intra-(C219, JSB-1) and extra-cellular (MRK-16) epitopes of P-gp and immunocytochemical (IC) APAAP staining method. Twenty-seven healthy donors peripheral blood mononuclear cells (PBMC) were investigated by means of IC and FACScan analysis. Positive staining for P-gp was detected in 31% children's and 33% adults' leukemia samples. No reactivity of three MAb's was observed with peripheral blood mononuclear cells (PBMC) by means of IC. Flow cytometry analysis with C219 MAb revealed staining for P-gp present on sub-population of lymphocytes and monocytes. P-gp (+) as well as P-gp (-) cases were compared in respect to clinical outcome, FAB classification and blood group. Complete remission (CR) was achieved in 12/14 (85%) children's and 9/11 (81%) adults' P-gp (+) leukemia cases. Within the P-gp (-) leukemia cases CR was observed in 24/29 (82%) and 18/22 (81%), respectively. Partial remission, relapse, resistance and death were noticed in 14% children's and 18% adults' P-gp (+) samples. In P-gp (-) cases these parameters were observed in 17% and 18%, respectively. These results raise the question whether the expression of P-gp can be used as single prognostic marker to detect multidrug resistance (MDR phenomenon) in vivo?

Effects of Na2CaEDTA on lead deposits in rabbit osseous tissue.

Radiochemical and autoradiographic methods were used for 210Pb determination after Na2CaEDTA administration to rabbits. 210Pb was determined in soft tissues, compact and trabecular bones and growing microareas on the endosteum of the long bone. After Na2CaEDTA injection lead was depleted from 'new' deposits mainly on the growing surface of both trabecular and compact bones.

Effect of cadmium on arterial blood pressure and lipid metabolism in rats.

A total dose of 8 mg cadmium acetate/kg body weight was administered by repeated i.p. injection to female Wistar rats for 12 weeks. Slight, but significant, increases in blood pressure were recorded. The lipid concentration in serum and other tissues examined was not significantly affected, apart from a decrease in hepatic triglyceride. The blood cadmium (Cd) concentration was increased 10 times and Cd in the aortic wall was 4 times higher in treated rats. Cd affects hepatic lipid metabolism and it is considered that the increase in blood pressure is associated with accumulation of Cd in the arterial walls.

Urinary excretion of chromium as an indicator of exposure to various chromium forms in MMA/SS welders.

Increased levels of Cr discharged with urine after working shift, Cr-U (arithmetic mean 15.8 mu g/g creatinine), and Cr buildup during working shift, DeltaCr-U (arithmetic mean 3.8 mu g/g creatinine), were observed in 15 MMA/SS welders exposed during the working week to welding fumes containing Cr VI (33-56%) - mainly soluble (87%) and Cr III (44-67%) - mainly insoluble (72%). The highest correlation coefficients were obtained for DeltaCr-U vs. Cr total (r = 0.58), Cr VI (r = 0.56) and soluble Cr III in the air. Increased DeltaCr-U value for exposures at MAC Cr VI (16.8 mu g/g creatinine) was demonstrated in welders employed longer than 7 years and exposed to Cr VI below MAC level, which might suggest that the duration of employment affects that value within the low range of concentration of Cr VI in the air (< 0.03 mg/m3). Nevertheless, linear relationship between DeltaCr-U for exposures to Cr VI at MAC levels and duration of employment was not confirmed for wide range of air Cr VI (0.005-0.4 mg/m3). Similar DeltaCr-U values at MAC for Cr VI (6.4 and 6.6 mu g/g creatinine) were obtained for all welders, and those employed over 7 years, respectively, which may suggest that this parameter can be misleading.

Blood lead levels in industrial workers in Poland.

Occupational exposure to lead occurs in about 1,300 enterprises in Poland. According to the 1994 data, based on the reports of the State Sanitary Inspectorate, 1,970 persons were employed at that time under conditions of exposure exceeding the Polish MAC level of 0.050 mg/m3. The measurements of workers' blood lead concentrations (Pb-B) were carried out only in 90 factories. In 1996, the Minister of Health and Social Welfare issued a directive stating that the Pb-B determinations in employees occupationally exposed to lead are compulsory. The aim of the present study was to assess lead exposure of workers employed in different branches of the Polish economy, based on Pb-B determinations. The measurements were performed on 2,324 male and 165 female workers of 13 different types of industry, including manufacture of crystal glass, battery industry, copper and zinc smelters, welding in a repair shipyard and some other workposts under conditions of lead exposure. The results of the determinations indicate that exposure to lead continues to be a serious problem in Polish industry. Pb-B concentrations exceeded the newly introduced Polish biological exposure index (BEI) value of 500 micrograms/l for men workers in about 30% of workers examined in 1996. In about 65% of females under 45 years of age the Pb-B concentrations were higher than 300 micrograms/l recommended as BEI for this age group. Considering the WHO-recommended health-based maximum individual biological action level of 400 micrograms/l, the percentage of the employees for whom higher values were found amounted to about 45% for men workers. The results point to the necessity of enforcing the implementation of Pb-B determinations according to the ministerial ordinance as well as of removing from exposure the workers with Pb-B levels exceeding the present BEI values. The improvement of working conditions and the implementation of health education for workers are also the actions to be promptly undertaken. In order to achieve these goals a close cooperation is required between the State Sanitary Inspectorate, the institutes of occupational health as well as the employers and trade unions.

[Anemia in AIDS: the problem to avoid. Human recombinant erythropoietin in the treatment of HIV positive patients]. / Niedokrwistosc w AIDS--problem którego mozna uniknac. Ludzka rekombinowana erytropoetyna w leczeniu chorych HIV-dodatnich.

The most common hematological abnormality associated with HIV infection is anaemia. The aetiology is multifactorial and may include the HIV virus itself; the anaemia of chronic diseases (ACD); infection with other viruses, mycobacteria and fungi; medications, especially zidovudine; and even B12 deficiency. Erythropoietin insufficiency is present in all anaemic AIDS patients, probably as a result of the mechanism of ACD. The studies, performed in patients with PGL, ARC and AIDS stages of disease demonstrate that rHuEPO is safe, and in dose of 100-200 U/kg b.w. three times a week can alleviate the anemia in AIDS patients taking AZT whose baseline EPO levels are less than 500 mU/ml.

[Methods for determining lead and cadmium in blood; cadmium, copper, nickel and chromium in urine using flameless atomic absorption spectrometry]. / Metody oznaczania kadmu i olowiu we krwi, kadmu, miedzi, niklu i chromu w moczu technika bezplomieniowej absorpcyjnej spektrometrii atomowej.

The estimation of environmental and occupational exposure to metals is based on the determination of metal concentrations in biological material. This paper describes methods for determining lead and cadmium in blood, and cadmium, copper, nickel and chromium in urine. The methods are evaluated in view of their linearity, precision, repeatability, reproducibility and detectability. The reliability of the methods was verified by determining lyphilized standards of known metal concentrations (Behring). The reproducibility expressed by the value of relative standard deviation ranged from 1.2% to 7.8%. In the case of lead and cadmium determinations, the reliability of results was confirmed due to the participation of our laboratory in the UK NEQAS external control project, the Queen Elizabeth Hospital, Birmingham. The results of external quality control (MR VIS = 19 for lead, as compared with the mean = 41 for all the project participants and MR VIS = 29 for cadmium, mean = 62) prove undoubtedly correctness of the methods applied. A small volume of sample to be analyzed is their major advantage, and due to adopted analytical parameters the methods can be used to determine metals in biological material in order to assess occupational or environmental exposure.

[Biological monitoring of lead: system and quality control]. / Monitoring biologiczny olowiu: system i kontrola jakosci.

The assessment of health effects of lead exposure is based on the determination of lead blood concentrations. The correctness of predicting these effects depends on the reliability of determination results. The latter can be confirmed only if the laboratory participates in the quality assurance programme for chemical analyses. The aim of the present study was to investigate the systems in use for quality control, methods of determining lead blood concentration and the results of a project on quality control for lead determination in Poland (project coordinated by the Nofer Institute of Occupational Medicine, Lodz, Poland). The paper discusses the principles of the quality assurance programme implemented in Poland, elements of good laboratory practice with respect to blood sampling, analytical equipment and the use of flameless AAS for determining lead blood concentration. The quality assurance programme for lead determinations covers nine laboratories. The initial stage of its implementation revealed that only 50% of the determinations were correct. Consequently, a series of audits was made at the laboratories and some training provided for the staff. The last round indicated an increase in the percentage of correct results of up to 80%. Proper performance of lead determinations carried out routinely for the assessment of industrial exposure to lead is of extreme importance in view of the fact that lead determinations in blood are planned to be made compulsory and to replace urinary determinations of the metal.

Effect of inhalation exposure to cadmium oxide on arterial blood pressure, lipid metabolism and tissue cadmium concentration in rats.

The arterial blood pressure, lipid content in serum and some organs, cadmium level in blood, aorta wall, lung and liver have been examined in rats repeatedly exposed to cadmium oxide fume 5 hours daily, 5 days a week, during 6 months. The blood pressure in rats exposed to cadmium oxide at concentration 0.02 mg Cd/m3 and 0.16 mg Cd/m3 was not changed, but it was slightly lowered at concentration 1.0 mg Cd/m3, which has been found lethal for rats. The concentration of total cholesterol, phospholipids and cholesterol esters in serum of female rats exposed at concentration of 0.16 mg Cd/m3 for 3 months was decreased, but was not affected after 6 months of exposure. The content of cholesterol and triglycerides in aorta wall, heart and liver was unchanged, although the content of cholesterol was decreased in adrenals of rats exposed for 3 months at concentration of 0.16 mg Cd/m3. Inhalation of cadmium oxide brought about the marked increase of Cd content in lung and kidney of rats exposed at all concentrations an increase of Cd blood level in rats exposed at concentrations of 0.16 mg Cd/m3 and 1.0 mg Cd/m3 and no increase of Cd content in aorta wall.

[Does residual mediastinal mass in children with completed treatment of Hodgkin's disease affect the incidence of relapses?]. / Czy resztkowy guz sródpiersia przetrwaly po zakonczeniu leczenia choroby Hodgkina u dzieci ma wplyw na czestosc wystepowania wznów?

Four hundred and four children with Hodgkin's disease (stage I-IV) were treated in seven cooperating centers of Polish Paediatric Leukaemia/Lymphoma Study Group between 1988 and 1996. Mediastinal masses and/or hilar involvement were found in 261 (65%) patients. Remission was obtained in 256 (98%) of this group. In 31 (12%) children residual mediastinal/hilar masses were found after completing the treatment. For this reason in 13 cases the number of chemotherapy courses and/or the dose of radiation therapy were increased. In two cases thoracotomy or thoracoscopy were performed, and in one case gallium scan was performed. In none of these patients active disease was found. Relapses occurred in 4 (12.9%) from the group of 31 children with residual mediastinal/hilar involvement 8-15 months after cessation of the therapy. Twenty seven children have been in first remission for 5-113 months (median, 34). In 225 patients with a complete resolution of their mediastinal/hilar masses, relapses occurred in 13 (5.7%) cases. Patients with residual mediastinal mass should be carefully evaluated before making a decision to complete their treatment, including CT scan, MRI, and gallium scan. In doubtful cases histopathological verification should be done.

[Thiotepa in the treatment of central nervous system leukemia in children]. / Thiotepa w leczeniu bialaczki osrodkowego ukladu nerwowego u dzieci.

The authors report beneficial effects of thiotepa on leukaemic involvement of the central nervous system. The drug was given to 4 children with central nervous system leukaemia refractory to methotrexate and cytarabine. Intrathecal thiotepa caused regression of changes in the cerebrospinal fluid and in the neurological status of these children. No side effects were observed during this treatment.

[Cytogenetic examination of children with acute leukemia]. / Badania cytogenetyczne w ostrych bialaczkach u dzieci.

Cytogenetic examinations were carried out in 40 children with acute leukaemia. In 18 cases karyotype changes were demonstrated, in 8 cases the karyotype was normal, in 14 cases no cell division was obtained and these patients were excluded from further analysis. In the group with karyotype changes in most cases poor prognosis indices were found, including high number of blasts, extramedullary presence of leukaemic infiltrations and FAB L2 or L3. Chromosomal abnormalities included presence of aberrations in the form of translocation, mosaicism of karyotypes with nearly tetraploidy line, accessory marker chromosomes and other anomalies. In this group 8 children died (30% of all observed cases), while in the group without karyotype changes 2 children died (about 8%). In summary the authors stress the correlation between the presence of clinical prognostic factors (risk factors) and karyotype changes and worse prognosis in cases with chromosomal abnormalities. Attention is called to the great usefulness of cytogenetic examinations in the prognosis and treatment of leukaemias in children.

[Results of treating chronic myelogenous leukemia in children]. / Wyniki leczenia przewleklej bialaczki szpikowej u dzieci.

Retrospective analysis of the results of treatment chronic myeloid (CML) leukemia in 80 children was done. From among 72 children treated by conventional methods the probability of 10 years survival had 17%. Statistically significant better results was obtained in the group of children with adult than juvenile type of CML (23 and 8%). Allogenic bone marrow transplantation was performed in six children, two children were treated with interferon. New approaches of treatment may offer the better chance for constitution of normal bone marrow function.

[Results of treatment for severe acquired aplastic anemia in children]. / Wyniki leczenia ciezkiej, nabytej niedokrwistosci aplastycznej u dzieci.

The authors evaluated results of treatment of 106 children with acquired aplastic anemia. The patients were divided into 3 groups depending on the severity of their disease. Thirty-nine patients were classified as very severe, 30 as severe and 37 as non-severe according to the modified Camitta criteria. Among them, 47 children were treated with oxymetholone and prednisolone. In this group 32 died. Antilymphocyte globulin (ALG) was given to 48 patients and 20 received cyclosporin A (CsA). The results obtained by these two methods are nearly the same and 5 year survival was 61% and 59% respectively. Bone marrow was transplanted in only one child, who is still in complete remission. Statistical analysis showed a steady increase in incidence of aplastic anemia in the years 1987-1989, which might coincide with the Czarnobyl explosion. However, further research is required to prove this point.

Acute lymphoblastic leukemia in children below two years of age.

From among 1464 children with ALL 167 (11.4%) at diagnosis had two or less than two years, 53 of them were infants. Most of them had a great tumor bulk, 15 had initial CNS infiltration and 31 WBCc greater than or equal to 100000/ML. 66 were treated according to St. Jude or LSA2L2 programs (the I group), 101 according to BFM programs (the II group). Complete remission was obtained in 85% of patients. In 63 children relapses occurred in the course of treatment whereas in 5 after the therapy cessation. In majority of cases, there were isolated relapses, mostly, they involved bone marrow. CNS involvement was found, in both mixed and isolated relapses, in 28 children (20%). 64 children are alive, in 43 of them the therapy was stopped. Kapla-Meier estimates for event free survival (EFS) after 8 years were 19 +/- 4.7% in the first group vs 37.38 +/- 6.3% in the second group. Due to therapy intensification the treatment results have been improved (p = 0.05) but still they are not satisfactory, particularly in case of infants and children with WBC greater than or equal to 100000/ML. Analysis of the lot of children showed that apart from age at ALL diagnosis and the initial WBC the methods of treatment are also the prognostic factors.