Increased risk for tooth extraction in primary hyperparathyroidism and hypercalcemia: a population study.

The aim of this study was to analyze dental comorbidities in untreated primary hyperparathyroidism (pHPT). Patients with pHPT subjected to parathyroidectomy (PTX) at Karolinska University Hospital, Stockholm, during 2011-2016 (n = 982) were selected from the Scandinavian Quality Register of Thyroid, Parathyroid and Adrenal surgery and compared to a general population cohort (n = 2944), matched for age and gender. Dental data was obtained from the Swedish Dental Health Registry for the 3 years prior to PTX. The incidence rate ratios (IRRs) of tooth loss by extraction, periodontal interventions, and dental visit rate were analyzed by Poisson regression models. In order to analyze the impact of disease severity, the PHPT cohort was sub-grouped based on preoperative serum levels of ionized calcium (S-Ca2+). The total number of tooth extractions, periodontal interventions, and number of visits were similar in the cohorts. PHPT patients belonging to the quartile with the highest S-Ca2+ (≥ 1.51 mmol/L) had increased risk for tooth extraction (IRR 1.85; 95% CI 1.39-2.46). Female gender independently amplified the risk (IRR 1.341, P < 0.027). This study indicates an association between pHPT and oral disorders reflected by increased tooth loss by extraction related to high S-Ca2. Increased awareness of dental comorbidity in primary hyperparathyroidism may benefit a large group of patients with a common disease through earlier detection and prevention.

Long-term variation of link strength in a simple benthic food web.

1. The predatory isopod Saduria entomon (L.) and its amphipod prey Monoporeia affinis (Lindström) are key components of the food web in the northern Baltic Sea, together representing 80-90% of the macrobenthic biomass. We use 20 years of stomach content data for Saduria to investigate how diet dynamics affect the stability of the interaction between Saduria and Monoporeia. 2. Consumption of the main prey, Monoporeia, fitted a type III functional response. Consumption rates of the most important alternative prey, mysids, were found to be unrelated to mysid densities but negatively related to the density of Monoporeia. The fit of consumption data to a model that assumes passive prey selection was poor. Thus we conclude that some form of active choice is involved. 3. The effect of consumption of mysids, the alternative prey, on the stability of this system was investigated using a 'one predator-two prey' model with stochastic environmental variation. Analysis of the model suggests that feeding on mysids leads to a decreased extinction risk for the predator, Saduria, and reduced density oscillations for both Saduria and its main prey, Monoporeia.

A long-term follow-up study on the natural course of oral leukoplakia in a Swedish population-based sample.

AIM: To assess the natural course of screening-detected oral leukoplakia (OL) among non-consulting individuals. METHODS: A cohort of 555 individuals with OL, confirmed in 1973-1974 during a population-based survey, were followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 104 drawn from the 297 surviving cohort members who still were living in the area in 1993-1995 was invited to a re-examination. Sixty-seven of them attended. RESULTS: At the time of re-examination OL had disappeared in 29 (43%) individuals. There was a statistically significant association between cessation of/no smoking habits in 1993-1995 and the disappearance of OL. Never/previous daily smokers were thus over-represented among individuals whose OL had disappeared compared to those with persisting OL [n = 23 (82%) vs. n = 18 (47%), P < 0.01]. Eighteen (78%) of the twenty three non-smokers with disappearing OL had quit after the initial examination. One man and two women developed oral cancer during follow-up while 0.7 and 0.07, respectively, were expected. CONCLUSION: Smoking cessation was associated with an increased disappearance of OL. Hence, at least one-fourth had lesions that could be classified as tobacco-related. Small observed and expected numbers prohibited firm conclusions about a possible excess risk of developing oral cancer.

On the natural course of oral lichen lesions in a Swedish population-based sample.

OBJECTIVES: The aim was to assess the natural course of oral lichen lesions (OLL) among unselected, non-consulting individuals. SUBJECTS AND METHODS: A cohort of 327 subjects with OLL, confirmed in 1973-1974 during a population-based survey in two Swedish municipalities, was followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 80 drawn from the 194 surviving subjects who still resided in the area in 1993-1995 was invited for interview and oral re-examination. RESULTS: At the end of follow-up, one case of oral cancer was detected, while 0.4 were expected. The overall mortality among subjects with OLL was not significantly different from that in the 15,817 OLL-free subjects who participated in the initial population based survey in 1973-1974. The lesion had disappeared in 14 (39%) of 36 re-examined subjects with white OLLs in 1973-1974, and four (11%) had transformed into red types. In the corresponding group of 19 with red forms initially, five (26%) had become lesion free and four (21%) had switched to white types. Although the cohort size does not permit firm conclusions regarding oral cancer risk, the natural course over up to 30 years appears to be benign in the great majority.

Mercury exposure in utero and during infancy.

Mercury in blood samples was speicated from mothers and their infants up to 2 mo after delivery. There were significant correlations between umbilical cord blood and maternal blood for methylmercury (MeHg) and inorganic mercury (I-Hg) levels. The MeHg levels in cord blood were significantly higher than in maternal blood, while I-Hg levels were significantly higher than in maternal blood, while I-Hg levels were about the same. The maternal MeHg and I-Hg levels remained stable during the sampling period, whereas the MeHg concentration in infant blood decreased more than 45% between the 72-h and 2 mo sampling times. The I-Hg levels in infant blood were low at birth, and remained low during the sampling period. The results of the present study do not support I-Hg absorption through milk as a significant source of exposure. However, the number of observations is small, and a larger study is warranted in order to verify the data.

Regulation of von Willebrand factor binding to the platelet glycoprotein Ib-IX by a membrane skeleton-dependent inside-out signal.

The platelet receptor for von Willebrand factor (vWF), glycoprotein Ib-IX (GPIb-IX), mediates initial platelet adhesion and activation. We show here that the receptor function of GPIb-IX is regulated intracellularly via its link to the filamin-associated membrane skeleton. Deletion of the filamin binding site in GPIb(alpha) markedly enhances ristocetin- (or botrocetin)-induced vWF binding and allows GPIb-IX-expressing cells to adhere to immobilized vWF under both static and flow conditions. Cytochalasin D (CD) that depolymerizes actin also enhances vWF binding to wild type GPIb-IX. Thus, vWF binding to GPIb-IX is negatively regulated by the filamin-associated membrane skeleton. In contrast to native vWF, binding of the isolated recombinant vWF A1 domain to wild type and filamin binding-deficient mutants of GPIb-IX is comparable, suggesting that the membrane skeleton-associated GPIb-IX is in a state that prevents access to the A1 domain in macromolecular vWF. In platelets, there is a balance of membrane skeleton-associated and free forms of GPIb-IX. Treatment of platelets with CD increases the free form and enhances vWF binding. CD also reverses the inhibitory effects of prostaglandin E1 on vWF binding to GPIb-IX. Thus, GPIb-IX-dependent platelet adhesion is doubly controlled by vWF conformation and a membrane skeleton-dependent inside-out signal.

Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study.

The frequency of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CdAD) was prospectively determined in a population of 2462 patients recruited from five Swedish hospitals, including divisions for infectious diseases, orthopaedics, surgery, geriatrics, nephrology and internal medicine. AAD developed in 4.9% of the treated patients. Faecal samples were obtained from 69% of patients with AAD and 55.4% were positive for C. difficile cytotoxin B. The frequency of AAD varied from 1.8 to 6.9% at the participating centres (P < 0.001). The frequency of AAD also varied considerably between medical disciplines and wards within different hospitals and was highest in the nephrology and geriatric units (6.7 and 7.1%, respectively). There was no difference in frequency of AAD when analysed with respect to gender or age. Medical interventions (laxative treatment, endoscopy and abdominal surgery) or presence of one concomitant disease (diabetes, malignancy, chronic renal disease and inflammatory bowel disease) did not significantly affect the frequency of AAD, whereas patients suffering from two or more of these illnesses had significantly (P = 0.001) higher frequencies of AAD. Patients treated with antibiotics for 3 days had a significantly (P = 0.009) lower frequency of AAD than those treated for longer periods. Treatment with cephalosporins, clindamycin or broad-spectrum penicillins was associated with an increased risk of AAD. With specimens from one centre, 62.5% of tested patients with AAD and 33.8% of asymptomatic patients were positive for cytotoxin B. Although C. difficile cytotoxin B in stool samples was significantly associated with AAD (P = 0.003), the causal relationship with diarrhoea is not always evident.

Mercury uptake and kinetics after ingestion of dental amalgam.

The aim of the present study was to investigate the G-1 uptake of mercury (Hg) after intake of a single dose of amalgam-Hg, followed by pharmacokinetic analysis of the data. Eleven volunteers without amalgam fillings ingested 1.00 g amalgam powder. Hg in plasma vs. time was analyzed with a two-compartment model by means of mixed-effects modeling. A fraction of the absorption rate of Hg to the central compartment was inversely proportional to the plasma ferritin levels. The population mean half-life of the terminal phase of Hg in plasma was 37 days, with a considerable standard deviation in the population. The absorbed fraction of the administered dose was estimated to be about 0.04%. It is concluded that the G-1 uptake of Hg is of quantitative importance during dental treatment.

Optimizing the therapeutic approach of transurethral alprostadil.

OBJECTIVE: To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 microg and 500 microg, MUSE, Vivus Inc., Menlo Park, CA, USA, and Astra Läkemedel AB, Södertälje, Sweden) and the need for dose titration in a general population with erectile dysfunction. PATIENTS AND METHODS: In a 12-week randomized and open multicentre study with parallel groups, 166 patients were randomised to a starting dose of either 250 or 500 microg of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 microg) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attained. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. RESULTS: The lowest dose of MUSE with which the patients achieved at least one EAS score of 4 or 5 was 125 microg for 1% of participants, 250 ++microg for 27%, 500 microg for 32%, 1000 microg for 6%, and finally 1000 microg plus a pubic band for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients (> 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 microg). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least once in course of the study. More patients reported penile pain while treated with 500 microg than with 250 microg (P < 0.05) during the first 4 weeks. However, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the clinic or at home. CONCLUSION: Recommending 500 microg as a starting dose increased the percentage of patients reporting at least one EAS of 4-5, with or without sexual intercourse, from 28% to 60%. No serious dose-related systemic effects were seen. When starting on 500 microg, patients were more likely to find directly the dose that gave sufficient response and treatment satisfaction. We suggest that the appropriate starting dose of MUSE should be 500 microg.

Analysis of the roles of 14-3-3 in the platelet glycoprotein Ib-IX-mediated activation of integrin alpha(IIb)beta(3) using a reconstituted mammalian cell expression model.

We have reconstituted the platelet glycoprotein (GP) Ib-IX-mediated activation of the integrin alpha(IIb)beta(3) in a recombinant DNA expression model, and show that 14-3-3 is important in GPIb-IX signaling. CHO cells expressing alpha(IIb)beta(3) adhere poorly to vWF. Cells expressing GPIb-IX adhere to vWF in the presence of botrocetin but spread poorly. Cells coexpressing integrin alpha(IIb)beta(3) and GPIb-IX adhere and spread on vWF, which is inhibited by RGDS peptides and antibodies against alpha(IIb)beta(3). vWF binding to GPIb-IX also activates soluble fibrinogen binding to alpha(IIb)beta(3) indicating that GPIb-IX mediates a cellular signal leading to alpha(IIb)beta(3) activation. Deletion of the 14-3-3-binding site in GPIbalpha inhibited GPIb-IX-mediated fibrinogen binding to alpha(IIb)beta(3) and cell spreading on vWF. Thus, 14-3-3 binding to GPIb-IX is important in GPIb-IX signaling. Expression of a dominant negative 14-3-3 mutant inhibited cell spreading on vWF, suggesting an important role for 14-3-3. Deleting both the 14-3-3 and filamin-binding sites of GPIbalpha induced an endogenous integrin-dependent cell spreading on vWF without requiring alpha(IIb)beta(3), but inhibited vWF-induced fibrinogen binding to alpha(IIb)beta(3). Thus, while different activation mechanisms may be responsible for vWF interaction with different integrins, GPIb-IX-mediated activation of alpha(IIb)beta(3) requires 14-3-3 interaction with GPIbalpha.

Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus.

Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in SHIV(DH12)-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previously reported that the administration of anti-human CD8 mAb to rhesus macaques at the time of primary SHIV(DH12) infection resulted in marked elevations of virus loads. One of the treated animals experienced rapid and profound depletions of circulating CD4(+) T lymphocytes. Although the CD4(+) T cell number partially recovered, this monkey subsequently suffered significant weight loss and was euthanized. A tissue culture virus stock derived from this animal, designated SHIV(DH12R), induced marked and rapid CD4(+) cell loss after i.v. inoculation of rhesus monkeys. Retrospective analyses of clinical specimens, collected during the emergence of SHIV(DH12R) indicated: (i) the input cloned SHIV remained the predominant virus during the first 5-7 months of infection; (ii) variants bearing only a few of the SHIV(DH12R) consensus changes first appeared 7 months after the administration of anti-CD8 mAb; (iii) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (iv) no neutralizing antibody against SHIV(DH12R) ever developed.

The cytoplasmic domain of the platelet glycoprotein Ibalpha is phosphorylated at serine 609.

The alpha chain of the platelet von Willebrand factor receptor, glycoprotein (GP) Ib, is not known to be phosphorylated. Here, we report that the cytoplasmic domain of GPIbalpha is phosphorylated at Ser(609); this was detected by immunoblotting with an anti-phosphopeptide antibody, anti-pS609, that specifically recognizes the GPIbalpha C-terminal sequence S(606)GHSL(610) only when Ser(609) is phosphorylated. Immunoabsorption with anti-pS609 removed almost all of the GPIbalpha from platelet lysates, indicating a high proportion of GPIbalpha phosphorylation. Anti-pS609 inhibited GPIb-IX binding to the intracellular signaling molecule, 14-3-3zeta. Dephosphorylation of GPIb-IX with potato acid phosphatase inhibited anti-pS609 binding and also 14-3-3zeta binding. A synthetic phosphopeptide corresponding to the GPIbalpha C-terminal sequence (SIRYSGHpSL), but not a nonphosphorylated identical peptide, abolished GPIb-IX binding to 14-3-3zeta. Thus, phosphorylation at Ser(609) of GPIbalpha is important for 14-3-3zeta binding to GPIb-IX. In certain regions of spreading platelets, particularly at the periphery, there was a reduction in GPIbalpha staining by anti-pS609 as observed under a confocal microscope, indicating that a subpopulation of GPIbalpha molecules in these regions is dephosphorylated. These data suggest that phosphorylation and dephosphorylation at Ser(609) of GPIbalpha regulates GPIb-IX interaction with 14-3-3 and may play important roles in the process of platelet adhesion and spreading.

Infection of HIV-1 transgenic mice with Mycobacterium avium induces the expression of infectious virus selectively from a Mac-1-positive host cell population.

Infection of HIV-1-transgenic mice with Mycobacterium avium, a common opportunistic pathogen in AIDS patients, was shown to result in increased tissue expression of viral specific transcripts. Moreover, by coculturing splenocytes from the transgenic animals with human T cells it was possible to demonstrate that the elevation in HIV-1 mRNA triggered by M. avium infection reflects increased production of infectious virions. Viral immune activation was also shown to correlate with a marked elevation of p24 in supernatants of ex vivo-cultured tissues and, more importantly, in systemic increases in the HIV-1 protein in plasma. Interestingly, these tissue and systemic p24 responses were found to be differentially regulated. Thus, while in vitro p24 production by cultured splenocytes increased concurrently with bacterial loads during the first 6 wk of infection, levels of the Ag in plasma actually decreased. In situ localization experiments together with FACS analysis of HIV-1-expressing splenocytes indicated that virus production is restricted largely to cells of the monocyte/macrophage lineage. Indeed, in vitro p24 expression by cells from noninfected transgenic mice was up-regulated by polyclonal stimulation of macrophages but not T cells. Together these results underscore the importance of the macrophage reservoir in persistent virus expression and establish a convenient and relevant animal model for studying the factors responsible for immune activation of HIV-1 induced by mycobacterial as well as other common coinfections encountered by AIDS patients.

Potent and stable attenuation of live-HIV-1 by gain of a proteolysis-resistant inhibitor of NF-kappaB (IkappaB-alphaS32/36A) and the implications for vaccine development.

Live-attenuated human immunodeficiency viruses (HIVs) are candidates for Acquired Immunodeficiency Syndrome (AIDS) vaccine. Based on the simian immunodeficiency virus (SIV) model for AIDS, loss-of-function (e.g. deletion of accessory genes such as nef) has been forwarded as a primary approach for creating enfeebled, but replication-competent, HIV-1/SIV. Regrettably, recent evidence suggests that loss-of-function alone is not always sufficient to prevent the emergence of virulent mutants. New strategies that attenuate via mechanisms distinct from loss-of-function are needed for enhancing the safety phenotype of viral genome. Here, we propose gain-of-function to be used simultaneously with loss-of-function as a novel approach for attenuating HIV-1. We have constructed an HIV-1 genome carrying the cDNA of a proteolysis-resistant nuclear factor-kappaB inhibitor (IkappaB-alphaS32/36A) in the nef region. HIV-1 expressing IkappaB-alphaS32/36A down-regulates viral expression and is highly attenuated in both Jurkat and peripheral blood mononuclear cells. We provide formal proof that the phenotypic and attenuating characteristics of IkappaB-alphaS32/36A permit its stable maintenance in a live, replicating HIV-1 despite 180 days of forced ex vivo passaging in tissue culture. As compared with other open-reading frames embedded into HIV/SIV genome, this degree of stability is unprecedented. Thus, IkappaB-alphaS32/36A offers proof-of-principle that artifactually gained functions, when used to attenuate the replication of live HIV-1, can be stable. These findings illustrate gain-of-function as a feasible strategy for developing safer live-attenuated HIVs to be tested as candidates for AIDS vaccine.

A compartmental model for the kinetics of mercury vapor in humans.

In an earlier study, we exposed nine healthy volunteers to known concentrations of mercury (Hg) vapor in air (median 399; range 365-430 micrograms/m3) for 15 min during light physical exercise (50 W) (Sandborgh-Englund, G., et al., Toxicol. Appl. Pharmacol. 150, 146-153, 1998). Exhaled air, urine, and plasma samples were collected. In the present study, the experimental observations from eight of these volunteers were subjected to an analysis with the aid of the software NONMEM. A four-compartment model, including two depot compartments to account for retention in lungs and kidneys, respectively, gave the best fit to the data. The fraction of dose excreted from the central compartment directly into urine was found to be positively correlated with the preexposure excretion rate of Hg via urine. The median half time in the respiratory depot compartment was estimated to 1.81 days (range 1.60-1.92). The median half time in the excretion depot was estimated to 63.2 days (range 12.8-98.9). The model was tested by simulating two experiments found in the literature and agreed well with these older data sets. Further simulations indicated that the excretion of Hg via urine would not reach a plateau until several months postexposure for most subjects.

Acute exposure to mercury from amalgam: no short-time effect on the peripheral blood lymphocytes in healthy individuals.

Mercury, released from dental amalgam, has been considered to adversely affect the human immune system. This study has been performed in order to evaluate if an acute low-dose mercury exposure, achieved by total amalgam removal in 10 healthy individuals, would affect the immunocompetent cells in human blood when the mercury level in blood and plasma was increasing. Induction of lymphocyte proliferation, measured as spontaneous de novo DNA synthesis, and total T cells, CD4+ T cells, CD8+ T cells, and B cells, was studied prior to and 7, 31, and 48 h after amalgam removal. In addition, the levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in serum/plasma were measured. Despite a significant increase of the plasma mercury levels within 24 h after intervention, no significant influence on the peripheral blood lymphocytes could be detected during the first 48 h. The serum IL-6 levels increased significantly within 48 h after intervention, but were still low and within normal range. No influence on the CRP levels up to 7 d after amalgam removal was detected.

Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain.

We compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P <0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.

The absorption, blood levels, and excretion of mercury after a single dose of mercury vapor in humans.

Nine healthy volunteers without amalgam fillings were exposed to 400 micrograms/m3 mercury vapor (Hg0) for 15 min, corresponding to 5.5 nmol Hg0/kg body wt (median range: 4.4-7.2). Frequent sampling of blood, urine, and exhaled air was performed for 30 days after exposure. The median retention of Hg0 was 69% of the inhaled dose. During the first 3 days after exposure 7.5-12% of the absorbed dose was lost by exhalation, with the median half time of Hg0 in expired breath being 2.0 days. In blood and plasma, a rapid absorption phase of Hg was seen, followed by a biexponential decline of the curves in both media. A substantial interindividual variation was observed in the area under the concentration-time curves of Hg in blood and plasma. In plasma the median half time of the second phase was 10 days. About 1.0% of the absorbed Hg was excreted via urine during the first 3 days after exposure, whereas the estimated amount excreted during 30 days ranged from 8 to 40%. In order to evaluate the chronic exposure to mercury from dental amalgam in the general population, the daily Hg dose from the fillings were estimated based on the plasma Hg levels found in subjects with amalgam fillings and on the plasma Hg clearance obtained in the present study. The daily Hg dose was estimated to 5-9 micrograms/day in subjects with an ordinary number of amalgam fillings.

Determination of low levels of total mercury in blood and plasma by cold vapour atomic fluorescence spectrometry.

A sensitive and semi-automated analytical method allowing determination of low and normal levels of total mercury in human blood and plasma using cold vapour atomic fluorescence is described. Samples are digested overnight, or at an elevated temperature for 4 h, followed by bromination at room temperature. After reduction with tin (II), analysis is performed using automated continuous flow vapour generation coupled to a fluorescence detector, allowing 20 samples to be analysed per hour. Detection limits for blood and plasma were found to be 0.9 and 0.5 nmol Hg l-1, respectively. The method precision at various concentrations of mercury was determined. For whole blood at 8.1 nmol Hg l-1 and 12.9 nmol Hg l-1, the within-day precision was 5% and 6% and the between-day precision 9% and 6%, respectively. For plasma at 1.3 nmol Hg l-1, the within-day precision was 13% while the between-day precision was 17%. Accuracy was evaluated by an inter-laboratory comparison study. At blood mercury concentrations below 60 nmol Hg l-1 the results from the current method were almost identical to those obtained with radiochemical neutron activation analysis, commonly regarded as a reference method. The present method should have merits in relation to previously used methods using atomic absorption spectrometry.