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.

The effects of environmental cadmium exposure on kidney function: the possible influence of age.

The study aimed to assess the possible influence of long-term environmental exposure to cadmium and age at the time of exposure on renal function. The study was a follow-up of the 1991-1994 project concerning 2000 inhabitants of a cadmium-contaminated area in the vicinity of a zinc smelter. Since the smelter was built in the late 1950s but was not operated until 1968, some of the inhabitants were not exposed to cadmium during childhood. For the follow-up, 308 persons who in 1993 presented with Cd-U levels > or = 0.5 microg/L adjusted for specific gravity (1.020) were selected in 2000. The study population included 136 people who were exposed to cadmium in childhood (former children) and 172 adults (unexposed adults) with no such exposure. These two groups were divided into subgroups according to Cd-U levels: < or =1 (group 1), 1-2 (group 2), and > or =2 microg/g creatinine (group 3). Urinary and blood cadmium and the markers of renal tubular dysfunction (beta2 M-U, RBP-U, NAG, NAG-A, NAG-B) and glomerular dysfunction (Alb-U and beta2 M-S) were measured. Persons with a history of occupational exposure to cadmium were excluded from this project. In group 3 of the unexposed adults, concentrations of RPB-U, NAG, NAG-B, and Alb-U were significantly higher than those in group 1. In former children, this could be observed only for RPB-U and Alb-U. Urine concentrations of these markers were higher in all of the subgroups of former children than in the groups of unexposed adults (except for NAG and its two forms). However, these differences were significant only for RBP-U in group 3. The findings indicate that early renal effects in the general population may occur at Cd-U concentrations above 2 microg/g creatinine and at lower levels for NAG-B. Moreover, cadmium exposure in childhood may have a stronger impact the renal function, particularly tubular reabsorption, than the exposure of a mature organism.

Reversibility of microproteinuria in nickel-cadmium battery workers after removal from exposure.

OBJECTIVES: The study was aimed at assessing the reversibility of renal tubule dysfunction in workers exposed to cadmium according to the severity of microproteinuria, concentrations of cadmium in urine (Cd-U), and the time since removal from exposure. METHODS: The study was carried out in a nickel-cadmium battery factory. Exposure to cadmium was formerly very high. In 1983 and in 1986-1988, geometric mean concentrations of cadmium in blood (Cd-B) of workers amounted to 23.3 micro g/l and 55.7 microg/l, respectively. Workers with determinations of Cd-B, Cd-U and retinol binding protein in urine (RBP-U) in the past were eligible for the study. Fifty-eight workers who had met this profile and had been removed from exposure to cadmium before 1998 were investigated in 1998-1999. They were divided into three groups according to their RBP-U concentrations in 1986-1988: <300 ( n=26); 301-1,501 ( n=25) and >1501 microg/g creatinine ( n=7). RESULTS: In 1999, the RPB-U levels were below 300 microg/g creatinine in 85%, 64% and 42% of persons from groups 1, 2 and 3, respectively. Statistical analysis of the results by means of multi-parametric logistic regression analysis revealed that, from the viewpoint of reversibility of tubular proteinuria, its severity in 1986-1988 was most important. Also, the time since the removal from exposure to cadmium and Cd-U levels seemed to play some role, but the influence of these parameters was not statistically significant. Significant correlation between beta(2)-microglobulin in serum (beta(2)M-S) and RBP-U concentrations measured in 1998-1999 with apparent lack of correlation between beta(2)M-S and RBP-U concentrations in 1986-1988 supports the hypothesis that the glomerular impairment induced by cadmium may be secondary to the tubular lesion rather than independent from tubular effect. CONCLUSIONS: The results show that the tubular proteinuria, and maybe also the decline in glomerular filtration rate, may be reversible, even in the case of relatively high past exposure. The results confirm the necessity for monitoring urinary levels of low-molecular-weight proteins during periodic examination of workers exposed to cadmium.

Biological monitoring of occupational exposure to arsenic by determining urinary content of inorganic arsenic and its methylated metabolites.

A study was undertaken to assess the relationship between inhalation exposure to arsenic in copper smeltery workers and urinary excretion of total inorganic arsenic metabolites (Asitm), including inorganic arsenic (Asi), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). The methods applied made it possible, in principle, to determine all forms of airborne arsenic and to eliminate the influence of seafood-derived organoarsenicals on the level of urinary Asitm. Air samples were collected on the second day of work after the weekend break. Urine samples were collected just after shift-end on the same workday. The time-weighted average (TWA) concentrations of arsenic in the workers' breathing zone varied between 1 and 746 microg/m3 and Asitm concentrations in urine between 2 and 850 microg/l (s.g. 1.024). The urine samples with a specific gravity of lower than 1.010 and higher than 1.030 were not considered; neither were those subjects with an Asitm excretion efficiency of higher than 100% of the dose absorbed during the day of measurement. In total, 53 air samples and corresponding urine samples were obtained. The correlation coefficient between the airborne arsenic concentration in microg/m3 (X) and the concentration of urinary Asitm in microg/l, s.g. 1.024 (Y), was 0.723. The relation between the two variables can be presented using the following formula: Y = 6.29 x X0.616. According to the findings of this study, as well as the results of three other studies based on similar principles, the daily exposure to arsenic concentrations of 10 microg/m3 and 50 microg/m3 led to concentrations of Asitm in urine of about 30 microg/l and 70 microg/l (s.g. 1.024), respectively.

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.

[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.

Blood lead in the general population in Poland.

Lead concentration in venous blood (Pb-B) was investigated in 1122 inhabitants (including 555 children under 10 years of age) of five Polish towns with no large industrial lead emitters (group I) and in 1246 persons (707 children under 10 years of age) living in the vicinity of zinc and copper mills (group II). The samples were analysed using electrothermal atomic absorption spectrometry (ETAAS) and the performing laboratory participated in the external quality control scheme during the study period (1992-1994). In group I the mean geometric Pb-B concentrations ranged from 23.8 to 48.3 micrograms/l in females, from 42.5 to 76.8 micrograms/l in males and from 29.9 to 62.5 micrograms/l in children. In group II, the mean geometric Pb-B concentrations were significantly higher and ranged from 49.4 to 105 micrograms/l in females, from 98.5 to 149 micrograms/l in males and from 73.7 to 114 micrograms/l in children, the values decreasing as the distance from the source of emission increased. Cigarette smoking was found to bring about a significant increase in Pb-B levels for both males and females. A significant correlation was noted between Pb-B concentrations in mothers and children. The ratio between child and maternal Pb-B concentrations amounted to approximately 1.0 for group I and to about 0.5 for group II. These findings indicate the necessity of undertaking preventive activities over the lead-contaminated areas. However, the lead hazard in Poland seems to be associated with point sources of emission and hence does not concern the whole population.

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?

[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.

Standard and intermediate risk acute lymphoblastic leukemia in Poland: a report of the Polish Children's Leukemia/Lymphoma Study Group.

A total of 527 children with acute lymphoblastic leukaemia (ALL) from the most frequent risk groups: standard risk group (SRG) and intermediate risk group (IRG) were treated between 1987 and 1991 according to an intensified treatment program (based on the BFM protocol) including the use of an intermediate dose of methotrexate in the IRG. A comparison of the treatment results in this group from 513 children treated between 1981 and 1987 indicates that the chance for a 6 year event-free survival has increased to 73% (previously 55%).

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.

[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.

[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.

Relapses after termination of therapy of acute lymphoblastic leukemia in children.

In the past 16 years, 2004 children with acute lymphoblastic leukemia (ALL) have been treated in the Polish Pediatric Group centers. Eight hundred and eighty-seven (44.3%) of these patients discontinued treatment after the first remission. Acute lymphoblastic leukemia relapse occurred in 180 patients (20.3%). This group was analyzed for the method of treatment and its influence on long-term survival, the time between cessation of treatment and relapse, the character and localization of relapse and later follow-up. It was shown that the patients with the best chance of a second remission are those with late testicular relapse. The most frequent and prognostically poor are bone marrow (BM) relapses which warrant intensive chemotherapy with BM transplantation. Patients with ALL relapse still have the possibility of a second remission and long-term survival.

[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.

[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.

[Compression fractures of the vertebrae in children with acute lymphoblastic leukemia]. / Zlamania kompresyjne kregów w ostrej bialaczce limfoblastycznej u dzieci.

Compression fractures of vertebrae were noted in 20 out of 1,700 children with the acute lymphoblastic leukemia. Usually prognosis in these cases has been favourable (70% of patients are alive from 5 months to 19 years). Percentage of recovery from compression fractures has been relatively high. Lymphoblastic leukemia with infiltrations localized in the spine is relatively non-aggressive, develops slowly, and despite extensive lesions to the bones its outcome results are favourable. Main symptom of spinal involvement include severe and persisting back aches which make walking impossible. Such symptoms should indicate the diagnosis of leukemia and advocate proper hematological examinations.

[Recurrences after completion of the treatment of acute lymphoblastic leukemia in children]. / Wznowy po zakonczeniu leczenia ostrej bialaczki limfoblastycznej u dzieci.

Within the past 16 years, 2004 children with the acute lymphoblastic leukemia were treated at the Centres of the Polish Pediatric Study Group. The treatment was completed in 887 patients (44.3%) with the first remission. Recurrence was noted in 180 children (20.3%). This group was analysed in view of the type of therapy and its effect on the survival rate, significance of recurrence following therapy, character and localization of recurrent disease, and further fate of patients. It was found, that patients with isolated late nuclear recurrence have greatest chances to achieve subsequent remission. Most frequent and severe is recurrent bone marrow involvement which requires intensive chemotherapy combined with bone marrow transplantation due to unfavourable prognosis. Patients with the first recurrence of the acute lymphoblastic leukemia have a chance to achieve subsequent remission and long-term survival.

Integrated index of occupational exposure to cadmium as a predictor of kidney dysfunction.

In a study carried out in an alkaline battery factory, the study group consisted of 141 factory workers exposed to cadmium, while 206 workers in the textile industry constituted the control group. Cadmium in blood (Cd-B), cadmium in urine (Cd-U) as well as beta 2-microglobulin and retinol-binding protein (RBP) in urine were determined. Exposure to cadmium in the factory was high. In 1988, Cd-B concentrations in different departments averaged 11.2-29.9 micrograms/l. To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index [Cd-B (micrograms/l) x years of exposure] is proposed. According to the dose-response relationship, an increase in low molecular weight protein excretion in urine can be expected in 10% of subjects at an integrated exposure index of about 300 micrograms/l x years of exposure. The data obtained confirmed the validity of the recommended health-based limits for occupational exposure of 10 micrograms/l and 10 micrograms/g creatinine for Cd-B and Cd-U respectively.