A Review on the Health Impact of Self-medication for Malaria on Port Harcourt Residents.

Self-medication is a widespread public health issue that has continued to grow without ever reaching a level, both in wealthy and underdeveloped countries. Residents of Port Harcourt, Nigeria, have faced danger to their health from malaria, and because they have limited access to healthcare, the majority of them turn to self-medication to treat the disease. The study's goal was to ascertain how well-informed Port Harcourt citizens were of the negative effects of self-medication for malaria on their health. Self-medication was a common practice among the research population. However, their understanding of how self-medication for malaria affects health is not particularly strong. The findings and explanations show that this is reflected in their attitude and behavior regarding self-medicating behaviors. The vast majority of people think they can treat their cases of malaria by using symptoms, prior experiences, and a suitable diagnostic laboratory test to confirm the disease. The two biggest causes of self-medication were low income and a lack of health insurance, while other minor factors included a lack of healthcare facilities, high medicine prices, an inability to pay for medical bills, being near a hospital, and having a negative attitude towards physicians. The findings show that self-medication is continuing to rise and that it will continue to have an influence on malaria prevention and treatment in the study region unless the government and other people in positions of authority do something about it.

L'automédication est un problème de santé publique répandu qui n'a cessé de croître, tant dans les pays riches que dans les pays en développement. Les habitants de Port Harcourt, au Nigeria, sont confrontés à un danger pour leur santé en raison du paludisme et, en raison de leur accès limité aux soins de santé, la majorité d'entre eux ont recours à l'automédication pour traiter la maladie. L'objectif de l'étude était de déterminer dans quelle mesure les habitants de Port Harcourt étaient informés des effets négatifs de l'automédication pour le paludisme sur leur santé. L'automédication était une pratique courante parmi la population étudiée. Cependant, leur compréhension de la manière dont l'automédication pour le paludisme affecte la santé n'est pas particulièrement solide. Les résultats et les explications montrent que cela se reflète dans leur attitude et leur comportement en ce qui concerne les comportements d'automédication. La grande majorité des personnes pensent qu'elles peuvent traiter leurs cas de paludisme en utilisant les symptômes, les expériences antérieures et un test de laboratoire de diagnostic approprié pour confirmer la maladie. Les deux principales causes de l'automédication étaient le faible revenu et le manque d'assurance maladie, tandis que d'autres facteurs mineurs comprenaient le manque d'infrastructures de santé, le coût élevé des médicaments, l'incapacité à payer les factures médicales, la proximité d'un hôpital et une attitude négative envers les médecins. Les résultats montrent que l'automédication continue de progresser et qu'elle continuera d'avoir une influence sur la prévention et le traitement du paludisme dans la région étudiée, à moins que le gouvernement et d'autres personnes en position d'autorité ne fassent quelque chose à ce sujet. Mots-clés: Attitude et comportement, absence d'assurance maladie, faible revenu, santé publique.

Effectiveness of etoposide chemomobilization in lymphoma patients undergoing auto-SCT.

The effectiveness of stem cell mobilization with G-CSF in lymphoma patients is suboptimal. We reviewed our institutional experience using chemomobilization with etoposide (VP-16; 375 mg/m(2) on days +1 and +2) and G-CSF (5 µg/kg twice daily from day +3 through the final day of collection) in 159 patients with lymphoma. This approach resulted in successful mobilization (>2 × 10(6) CD34+ cells collected) in 94% of patients (83% within 4 apheresis sessions). Fifty-seven percent of patients yielded at least 5 × 10(6) cells in 2 days and were defined as good mobilizers. The regimen was safe with a low rate of rehospitalization. Average costs were $14 923 for good mobilizers and $27 044 for poor mobilizers (P<0.05). Using our data, we performed a 'break-even' analysis that demonstrated that adding two doses of Plerixafor to predicted poor mobilizers at the time of first CD34+ cell count would achieve cost neutrality if the frequency of good mobilizers were to increase by 21%, while the frequency of good mobilizers would need to increase by 25% if three doses of Plerixafor were used. We conclude that chemomobilization with etoposide and G-CSF in patients with lymphoma is effective, with future opportunities for cost-neutral improvement using novel agents.

Analysis of hydroquinone and catechol in peripheral blood of benzene-exposed workers.

We have developed a gas chromatography-mass spectrometry method for analysis of benzene (BZ) metabolites in human urine and blood. Here we describe peripheral blood concentrations of hydroquinone (HQ(1)) and catechol (CAT(2)) in total, protein-bound, and unbound (free) forms obtained from BZ-exposed factory workers and controls. Total and unbound metabolites were directly measured in independent experiments, while bound forms were calculated as [total]-[unbound]. In this subset of a larger study, breathing zone benzene, toluene, and xylene were measured for the duration of a workshift, and end-shift blood samples taken from 143 subjects and controls. Potential lifestyle and environmental influences were assessed by questionnaire and bioassay, and single nucleotide polymorphisms in xenobiotic metabolizing enzymes NQO1, MPO, CYP2E1, and GSTT1 were also analyzed for potential contribution to differences in blood metabolite concentration. Total CAT, bound CAT, total HQ, and bound HQ correlated well with benzene exposure, while unbound CAT and HQ displayed no correlation. Nearly all of the metabolites found in blood were bound to protein (CAT 96-99+%, HQ 78-92+%), and when the ratio of bound to unbound metabolites were compared in subsets of exposed workers, the increase in blood metabolite concentration was nearly all due to an increase in the protein-bound molecule. These findings suggest that a threshold for conjugation does not exist within the exposure spectrum studied (0.01-78.8 mg/m(3)). This method demonstrates the feasibility of analyzing benzene metabolites in human blood, and should allow for further investigation of the health effects of benzene and its metabolites.

PU.1 phosphorylation correlates with hydroquinone-induced alterations in myeloid differentiation and cytokine-dependent clonogenic response in human CD34(+) hematopoietic progenitor cells.

The transcriptional regulatory factor PU.1 is important for the regulation of a diverse group of hematopoietic and myeloid genes. Posttranslational phosphorylation of PU.1 has been demonstrated in the regulation of a variety of promoters in normal cells. In leukemia cells, differing patterns of PU.1 phosphorylation have been described among acute myelogenous leukemia (AML) subtypes. Therefore, we hypothesized that modulation of PU.1-dependent gene expression might be a molecular mediator of alterations in myeloid cell growth and differentiation that have been demonstrated to be early events in benzene-induced leukemogenesis. We found that freshly isolated human CD34(+) hematopoietic progenitor cells (HPC) exhibit multiple PU.1-DNA binding species that represent PU.1 proteins in varying degrees of phosphorylation states as determined by phosphatase treatment in combination with electrophoretic mobility shift assay (EMSA). Maturation of granulocyte and monocyte lineages is also accompanied by distinct changes in PU.1-DNA binding patterns. Experiments reveal that increasing doses of the benzene metabolite, hydroquinone (HQ) induce a time-and dose-dependent alteration in the pattern of PU.1-DNA binding in cultured human CD34(+) cells, corresponding to hyperphosphorylation of the PU.1 protein. HQ-induced alterations in PU.1-DNA binding are concomitant with a sustained immature CD34(+) phenotype and cytokine-dependent enhanced clonogenic activity in cultured human HPC. These results suggest that HQ induces a dysregulation in the external signals modulating PU.1 protein phosphorylation and this dysregulation may be an early event in the generation of benzene-induced AML.

Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells.

Human leukemogens, including alkylating chemotherapeutic agents and benzene, enhance granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent proliferation of human CD34+ bone marrow (BM) cells. The extracellular signal-regulated kinase (ERK) pathway plays an important role in GM-CSF-dependent proliferation and also has been implicated in the pathogenesis of acute myelogenous leukemia. Therefore, we investigated the effects of the benzene metabolite, hydroquinone (HQ), on alterations in the GM-CSF signaling pathway in TF-1 erythroleukemia cells and human CD34+ BM cells. HQ treatment in TF-1 cells results in a strong proliferative response that is dependent on ERK activation and GM-CSF production. HQ also induces ERK-dependent AP-1 activation with concomitant increased transcriptional activity of AP-1 reporter gene. However, the kinetics of ERK activation are different between rhGM-CSF and HQ in TF-1 cells: rhGM-CSF results in immediate activation of ERK, whereas HQ activation of ERK is delayed. Further, HQ and rhGM-CSF together produce an immediate increase in ERK phosphorylation, which is sustained for over 48 h. HQ also stimulates colony formation, AP-1 DNA binding and GM-CSF production in human CD34+ BM cells. These results suggest that HQ stimulates proliferation via activation of ERK/AP-1 and is at least partially mediated via the production of GM-CSF.

Will alternative immediate care services reduce demands for non-urgent treatment at accident and emergency?

OBJECTIVES: To estimate the potential of general practice, minor injury units, walk in centres and NHS Direct to reduce non-urgent demands on accident and emergency (A&E) departments taking into account the patient's reasons for attending A&E. METHODS: A questionnaire survey and notes review of 267 adults presenting to the A&E department of a large teaching hospital in Sheffield, England, triaged to the two lowest priority treatment streams, was conducted over seven weeks. Using defined criteria, patients were classified by the suitability of the presenting health problem to be managed by alternative immediate care services or only by A&E, and also by the likelihood, in similar circumstances, of patients presenting to other services given their reasons for seeking A&E care. RESULTS: Full data were obtained for 96% of participants (255 of 267). Using objective criteria, it is estimated that 55% (95% CI 50%, 62%) of the health problems presented by a non-urgent population attending A&E are suitable for treatment in either general practice, or a minor injury unit, or a walk in centre or by self care after advice from NHS Direct. However, in almost one quarter (24%) of low priority patients who self referred, A&E was not the first contact with the health services for the presenting health problem. The reason for attending A&E cited most frequently by the patients was a belief that radiography was necessary. The reason given least often was seeking advice from a nurse practitioner. Taking into account the objective suitability of the health problem to be treated elsewhere, and the reasons for attending A&E given by the patients, it is estimated that, with similar health problems, as few as 7% (95% CI 3%, 10%) of the non-urgent A&E population may be expected to present to providers other than A&E in the future. CONCLUSIONS: The increasing availability of alternative services offering first contact care for non-urgent health problems, is likely to have little impact on the demand for A&E services.

Benzene metabolites antagonize etoposide-stabilized cleavable complexes of DNA topoisomerase IIalpha.

Chronic exposure to benzene is associated with hematotoxicity and acute myelogenous leukemia. Inhibition of topoisomerase IIalpha (topo II) has been implicated in the development of benzene-induced cytogenetic aberrations. The purpose of this study was to determine the mechanism of topo II inhibition by benzene metabolites. In a DNA cleavage/relaxation assay, topo II was inhibited by p-benzoquinone and hydroquinone at 10 microM and 10 mM, respectively. On peroxidase activation, inhibition was seen with 4,4'-biphenol, hydroquinone, and catechol at 10 microM, 10 microM, and 30 microM, respectively. But, in no case was cleavable complex stabilization observed and the metabolites appeared to act at an earlier step of the enzyme cycle. In support of this conclusion, several metabolites antagonized etoposide-stabilized cleavable complex formation and inhibited topo II-DNA binding. It is therefore unlikely that benzene-induced acute myelogenous leukemia stems from events invoked for leukemogenic topo II cleavable complex-stabilizing antitumor agents. (Blood. 2001;98:830-833)

Comparative toxicity of dithiocarbamates and butadiene metabolites in human lymphoid and bone marrow cells.

Apparent differences in the pattern of leukemia risk have been observed between workers employed in 1,3-butadiene (BD) monomer production and those working in styrene-butadiene rubber production (SBR). There are a number of possible explanations for these discrepancies, including differences in disease classification and diagnosis as well as possible quantitative and qualitative differences in occupational exposure between these two industries. This led us to evaluate the possibility that the pattern of disease observed in SBR might be influenced by the presence of an important class of biologically reactive chemicals, dithiocarbamates (DTC), that were present in SBR but not BD monomer production. Therefore, we compared the immunotoxic and hematotoxic activities of DTC and BD metabolites in human immune and hematopoietic cells. Relative to the mouse, human CD34+ bone marrow cells are relatively resistant to the direct effects of BD metabolites, with only the bis-oxide producing any evidence of suppression of clonogenic response at concentrations between 1 and 10 microM. Similarly, treatment of human CD4+ lymphocytes with known (2,3-epoxybutene) and putative BD metabolites (D,L-butane-bis-oxide, (2S,3R)-3-epoxybutane-1,2-diol) does not result in appreciable T-cell toxicity at concentrations likely to be encountered in vivo. In contrast, treatment of human cells with DTC at concentrations as low as 100 nM results in significant suppression of hematopoietic clonogenic response and T-lymphocyte function. Additional studies in our laboratory and others suggest a role for copper in DTC toxicity in both human lymphocytes and bone marrow cells, although the pattern of altered transcriptional regulation observed is markedly different in these two cell populations. These results are consistent with the pattern of DTC toxicity previously observed in clinical and molecular studies.

Assessment and treatment of addictive sexual disorders: relevance for chemical dependency relapse.

Despite some skepticism about the existence of sexual addiction, the addiction model has proven very useful for treating compulsive sexual behaviors. Addictive sexual disorders often coexist with chemical dependency and are a frequently unrecognized cause of chemical dependency relapse. Sex addiction also contributes significantly to the spread of HIV disease. This paper reviews the differential diagnosis of addictive sexual disorders, their assessment. their treatment, and their interaction with chemical dependency, and provides information about 12-step (mutual-help) resources.

Comparative toxicity of known and putative metabolites of 1, 3-butadiene in human CD34(+) bone marrow cells.

Species-specific susceptibility to the hematotoxic effects of 1, 3-butadiene (BD) is well known. Previous studies have revealed that murine bone marrow is uniquely susceptible to toxicity following exposure to the parent compound in vivo or exposure of bone marrow cells to the monoepoxide metabolite, 3,4-epoxybutane, in vitro. Studies described herein compare the relative ability of putative and known BD metabolites to produce concentration dependent suppression of colony formation and cytotoxicity in human CD34(+) bone marrow cells. Compounds evaluated included 3,4-epoxybutane, D, L-butane-bis-oxide, meso-butane-bis-oxide and (2S, 3R)-3-epoxybutane-1,2-diol. In contrast to results previously observed in mice, only the bis-oxides produced significant suppression of colony formation at potentially relevant concentrations (10(-8) to 10(-3) M). No enantiospecific differences were observed between the meso- and D,L-bis-oxides and no significant lineage-specific differences in susceptibility to inhibition of clonogenic response were observed among early multi-potential myeloid and erythroid hematopoietic progenitor cells. The relative potencies of the bis-oxides were found to be comparable to that of the prototype hematotoxic compound, hydroquinone. These results confirm previous studies that reveal marked species-specific differences in the susceptibility of bone marrow cells to 3,4-epoxybutane. Moreover, these results suggest that the bis-oxides of BD are capable of suppressing the clonogenic function of human hematopoietic progenitor cells, if, in fact, they are produced in human bone marrow in significant concentration. Further interpretation of these findings requires a better understanding of the metabolism of BD in humans.

Hydroquinone inhibits PMA-induced activation of NFkappaB in primary human CD19+ B lymphocytes.

Hydroquinone (HQ), a reactive metabolite of benzene, is known to inhibit mitogen-stimulated activation of both T and B lymphocytes. Despite extensive study, the underlying mechanism for the immunotoxicity of the HQ is not clear. We have previously demonstrated that 1 micromol/L HQ inhibits TNF-induced activation of NFkappaB in CD4+ T cells, resulting in decreased IL-2 production. NFkappaB, known to be important in T lymphocytes, also plays a critical role in normal B cell development and activation. We therefore hypothesized that alterations in NFkappaB might be involved in HQ-induced B cell immunosuppression as well. In this study, we demonstrate that 1-10 micromol/L HQ inhibits PMA/ionomycin-induced activation of NFkappaB in primary human CD19+ B cells. Inhibition of NFkappaB is accompanied by a dose-dependent decrease in PMA-stimulated production of TNF with no corresponding loss in viability or increased apoptosis. HQ also does not appear to alter NFkappaB directly, as preincubation of B cell nuclear extracts with HQ does not diminish DNA binding activity of this protein. In contrast to T cells, inhibition of NFkappaB by HQ in B cells is not reversible after 72 h in culture, suggesting a long-term functional suppression. These data support our original findings in T cells and indicate that NFkappaB is particularly susceptible to inhibition by HQ. We further hypothesize that inhibition of NFkappaB in lymphocytes, and perhaps other cell types as well, may play a significant role in the observed toxicity of HQ.

Dithiocarbamates inhibit hematopoiesis via a copper-dependent mechanism.

Dithiocarbamates (DTC), an important class of therapeutic and industrial chemicals, have alternatively been reported to be either beneficial or toxic to the hematopoietic and immune systems. In the present study, we investigated the potential of dimethyl- and diethyl-dithiocarbamate to alter clonogenic response of primary human CD34(+) bone marrow cells in vitro. Our results demonstrate that both compounds are potent inhibitors of clonogenic response in human CD34(+) bone marrow cells, suppressing cytokine-induced colony formation at concentrations between 100 and 500 nM. Pretreatment of bone marrow cells for 1 h with very high doses of DTC (30 microM) had no effect on colony formation. DTCs are known inhibitors of nuclear factor-kappa B (NF-kappa B); however, data presented herein demonstrate that DTC do not inhibit cytokine activation of NF-kappa B in CD34(+) bone marrow cells. Additional experiments demonstrate that DTCs induce a dose-related increase in apoptosis, potentially acting via a cytotoxic mechanism. We further demonstrate that the addition of copper sulfate greatly potentiates the hematotoxicity of DTC and that the addition of a copper-specific chelator completely abrogates DTC clonogenic suppression. These data support a role for copper in DTC-induced hematotoxicity.

The benzene metabolite, hydroquinone, selectively induces 5q31- and -7 in human CD34+CD19- bone marrow cells.

OBJECTIVE: Chronic exposure to high concentrations of benzene is associated with an increased incidence of myelodysplastic syndrome and acute myelogenous leukemia. Acute myelogenous leukemia developing in patients treated with alkylating agents for other cancers or occupationally exposed to benzene exhibit a pattern of cytogenetic aberrations predominantly involving loss of all or part of chromosomes 5 and/or 7. In contrast, trisomy 8 is observed equally in both de novo and secondary acute myelogenous leukemia. Studies using peripheral lymphocytes or lymphoblastoid cell lines have observed dose-dependent loss of chromosomes 5, 7, and 8 following treatment with the benzene metabolite, hydroquinone. The purpose of this study was to determine the dose response and specificity of hydroquinone-induced aberrations on chromosomes 5, 7, and 8 using human CD34+CD19 bone marrow cells. MATERIALS AND METHODS: Fluorescence in situ hybridization analysis was performed on CD34+CD19- bone marrow cells using the locus-specific probes, 5q31, 5p15.2, and centromeric probes specific for human chromosomes 7 and 8 following hydroquinone exposure. RESULTS: Hydroquinone exposure results in -7, selective deletion of 5q31 but not chromosome 5 and no loss or gain of chromosome 8 in human CD34+CD19- cells. CONCLUSION: CD34+ bone marrow cells are more susceptible and show a different pattern of cytogenetic aberrations as a result of hydroquinone exposure compared to lymphocytes. CD34+ bone marrow cells exhibit unique susceptibility to the development of specific chromosome aberrations that have been identified as the earliest structural changes occurring in the development of secondary myelodysplastic syndrome and acute myelogenous leukemia.

Hematotoxicity of the chinese herbal medicine Tripterygium wilfordii hook f in CD34-positive human bone marrow cells.

T2, a chloroform/methanol extract of the herb Tripterygium wilfordii Hook f, has been used in China for the treatment of autoimmune and inflammatory diseases for many years. Recent experimental evidence has confirmed that T2 has potent anti-inflammatory and immunosuppressive activity, and a United States Food and Drug Administration-approved clinical trial is currently exploring the efficacy of T2 in the treatment of rheumatoid arthritis. Despite the potential therapeutic benefits of T2, there is ample documentation that T2 is toxic, targeting, among other things, the hematopoietic system, and its use has resulted in cases of leukopenia, thrombocytopenia, and aplastic anemia. This investigation was undertaken to characterize the in vitro effects of T2 on primary human CD34-positive (CD34+) bone marrow cells. Our results demonstrate that T2 has a potent inhibitory effect on the clonogenic response of human bone marrow cells to exogenously added hematopoietic growth factors. The inhibition of colony formation by T2 is not the result of direct cytotoxicity or increased apoptosis and indicates a functional suppression of hematopoiesis. Additional experiments demonstrate that T2 also alters transcriptional regulation in bone marrow cells by inhibiting nuclear factor-kappaB. This transcription factor is found in CD34+ bone marrow cells and has been recently shown to be a requirement for colony formation. These results demonstrate that therapeutic concentrations of T2 exert a significant hematotoxic effect by inhibiting growth factor response in CD34+ bone marrow cells and suggest that inhibition of nuclear factor-kappaB may play a role in the blood dyscrasias encountered with the use of this drug.

An essential role for NF-kappaB in human CD34(+) bone marrow cell survival.

The transcription factor, NF-kappaB, is important for T-cell activation, B-cell maturation, and human immunodeficiency virus transcription and plays a role in alternatively mediating and protecting against apoptosis in a variety of cell types. However, a role for NF-kappaB in human CD34(+) bone marrow cells has not been described. We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappaB that can be activated by exposure to phorbol 12-myristate 13-acetate and a variety of cytokines, eg, tumor necrosis factor alpha, interleukin-3, and granulocyte-macrophage colony-stimulating factor. In addition, we demonstrate that NF-kappaB may be required for human CD34(+) bone marrow cell clonogenic function and survival. These results offer insight into a new role for NF-kappaB in maintaining survival and function in hematopoietic stem and progenitor cells and suggest that proposed strategies involving inhibition of NF-kappaB activation as an adjunct to cancer chemotherapy should be approached with caution.

The benzene metabolites hydroquinone and catechol act in synergy to induce dose-dependent hypoploidy and -5q31 in a human cell line.

Chronic exposure to high concentrations of benzene is associated with an increased incidence of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Studies of patients occupationally exposed to benzene show a pattern of cytogenetic aberrations involving loss of all or part of chromosomes 5 and/or 7 as well as trisomy 8 and we have previously reported that hydroquinone (HQ) induces deletions of 5, 7 and 8. Benzene metabolism is a requirement for bone marrow toxicity and the phenolic metabolites, HQ and catechol (CAT), have been implicated in benzene hematotoxicity. A research project was designed to determine whether CAT by itself and in conjunction with HQ could directly induce loss of chromosome 5 and/or 7 and gain of chromosome 8. Using fluorescence in situ hybridization with chromosome-specific 5, 7, and 8 probes we demonstrate that 5 to 150 uM CAT does not produce chromosomal aberrations, however CAT and 25 uM HQ can act in synergy to induce dose dependent loss of these chromosomes. In addition HQ/CAT selectively induces -5q which is not observed for HQ only. These results demonstrate for the first time that CAT/HQ act in synergy to induce specific chromosome loss found in secondary MDS/AML.

Dimethyldithiocarbamate inhibits in vitro activation of primary human CD4+ T lymphocytes.

Dithiocarbamates (DTC), a diverse group of industrial and therapeutic chemicals, have been reported to inhibit, enhance or have no effect on the immune system. These apparent inconsistencies reflect the complexity of the DTCs biological activities and are probably due in part to differences in dose, route of exposure, animal species used and/or specific compound tested. The studies described herein were undertaken to investigate the immunotoxicity of one member of this family, dimethyldithiocarbamate (DMDTC). We demonstrate that 0.1-0.5 microM DMDTC inhibits TNF-alpha-induced activation of NF-kappaB in primary human CD4+ T cells. This inhibition is not accompanied by a loss in viability, and DMDTC-treated T cells retain other active signaling pathways throughout the exposure duration. The inhibition of NF-kappaB is apparently permanent as DMDTC-treated T cells did not regain normal TNF-alpha activation, even after 72 h in culture. DMDTC does not appear to alter NF-kappaB directly as pre-incubation of nuclear extracts with DMDTC does not diminish binding activity of this protein. We further demonstrate that 0.1-0.5 microM DMDTC inhibits intracellular IL-2 production and decreases surface expression of CD25 (the alpha subunit of the IL-2 receptor) in T cells stimulated with phorbol ester. These data demonstrate that DMDTC is a potent immunosuppressive compound in vitro.

Dithiocarbamates as potential confounders in butadiene epidemiology.

Hematopoietic neoplasms associated with occupational exposure to 1,3-butadiene (BD) have been the subject of controversy. This has largely been due to the inconsistent results of epidemiology studies that have reported alternatively no or weak associations between exposure to BD and hematopoietic neoplasms. Moreover, the specificity of association of BD exposure with individual leukemia types remains unclear. In addition, a distinct difference in the pattern of leukemia risk has been observed between workers employed in BD monomer production and those involved in styrene-butadiene rubber (SBR) production: with no increase in leukemia risk observed for exposure to BD monomer alone. These observations are consistent with an increase in leukemia risk associated with the SBR process but not BD monomer and suggest the possibility that the increase may be the result of exposure to confounding factors previously not considered. In this regard, evidence is accumulating to suggest that SBR studies may be confounded by the presence of an important class of biologically active chemicals employed in the rubber industry, dithiocarbamates. The hematotoxicity and immunotoxicity of dithiocarbamates have been implicated in a wide range of clinical, animal and molecular studies, and an extremely high concordance exists between the risk of developing leukemia in SBR production and opportunity for exposure to this class of agents. Based on these findings additional studies on the epidemiology, carcinogenesis and molecular biology of dithiocarbamates are clearly warranted.