Probabilistic approach to polychlorinated biphenyl (PCB) exposure through eel consumption in recreational fishermen vs. the general population.

Concentrations of the sum of the seven indicator PCBs (Sigma7 iPCBs) measured in non-commercial European eel (Anguilla anguilla L.) in Flanders are high: in 80% of all sampled localities, the Belgian PCB standard for fish was exceeded. The objective of this study was to assess the intake of the Sigma7 iPCBs through consumption of eel by recreational fishermen and to compare it to the intake of a background population. The median estimated intake for recreational fishermen varied between 18.4 and 237.6 ng iPCBs kg(-1) bw day(-1), depending on the consumption scenario, while the estimated intake of the background population (consumers only) was 4.3 ng iPCBs kg(-1) bw day(-1). Since the levels of intake via eel for two intake scenarios were, respectively, 50 and 25 times higher than the intake of the background population, the body burden (BB) might be proportionally higher and reach levels of toxicological relevance. The intake of the seven iPCBs via consumption of self-caught eel in Flanders is at a level to cause serious concern. The Flemish catch-and-release obligation for eel, established in 2002, should be maintained and supervised (more) carefully.

Simulated impact of a fish based shift in the population n--3 fatty acids intake on exposure to dioxins and dioxin-like compounds.

Due to the favourable health effects of LC n-3 PUFAs, marine products have been recognised as a food group of special importance in the human diet. However, seafood is susceptible to contamination by lipophilic organic pollutants. The objective of this study was to evaluate intake levels of PCDDs, PCDFs and dioxin-like PCBs, by a probabilistic Monte Carlo procedure, in relation to the recommendation on LC n-3 PUFAs given by Belgian Federal Health Council. Regarding the recommendation, two scenarios were developed differing in LC n-3 PUFAs intake: a 0.3 E% and a 0.46 E% scenario. Total exposure to dioxins and dioxin-like substances in the 0.3 E% LC n-3 PUFAs scenario ranges from 2.31 pg TEQ/kg bw/day at the 5th percentile, over 4.37 pg TEQ/kgbw/day at the 50th percentile to 8.41 pg TEQ/kgbw/day at the 95th percentile. In the 0.46 E% LC n-3 PUFAs scenario, 5, 50 and 95th percentile are exposed to 2.74, 5.52 and 9.98 pg TEQ/kgbw/day, respectively. Therefore, if the recommended LC n-3 PUFAs intake would be based on fish consumption as the only extra source, the majority of the study population would exceed the proposed health based guidance values for dioxins and dioxin-like substances.

Risk assessment of dietary acrylamide intake in Flemish adolescents.

Acrylamide has recently been found in a range of heat treated food items. As it is a neurotoxic agent and a probable, human carcinogen (IARC 2A), human exposure to this chemical might constitute an important public health issue. The purpose of the study was to estimate the acrylamide intake in Flemish adolescents (based on 7-day food record) and to evaluate the possible health risks due to the exposure. The Belgian Federal Agency for the Safety of the Food Chain collected 150 food items from different supermarkets and restaurants to analyse the acrylamide level. The limit of quantitation was 30 microg acrylamide/kg foodstuffs. Exposure modelling was based on Monte Carlo simulations. The estimated dietary intake of acrylamide per person given as the 5th, 50th and 95th percentile were 0.19, 0.51 and 1.09 mircog/kg bw/d. Bread, despite its low acrylamide content, is relevant as a source of acrylamide exposure at the lower percentiles. At higher percentiles the contribution of French fries and crisps is more important. It must be emphasised that the exposure assessment has several limitations. Risk of neurotoxicity seems negligible. The relevance of current intake levels in terms of cancer risk remains a subject of debate.

Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model.

BACKGROUND: Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice. METHODS: Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated. RESULTS: Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss. CONCLUSION: Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

Prostate cancer among pesticide applicators: a meta-analysis.

OBJECTIVES: To analyse data from peer-reviewed, case-referent and cohort studies, studying the occurrence of prostate cancer in pesticide applicators and in some other, related, occupational categories, in order to determine a possible relationship of cancer of the prostate with pesticide exposure; to calculate a meta-rate ratio and to compare it with the meta-rate ratios obtained in a previous meta-analysis performed over a shorter time (1995-2001) in a broader exposure category, including many pesticide-related agricultural and non-agricultural occupations. METHODS: Medline was searched for the years between 1966 and 2003, and relevant studies were identified from 1986 on. We conducted a meta-analysis of 22 studies complying with the inclusion criteria in order to pool their relative risk (RR) estimates. Studies were summarised and assessed for homogeneity and publication bias. RESULTS: The meta-rate ratio, based on 22 estimates of RR, is 1.24 [95% confidence interval (95% CI) 1.06-1.45]. This pooled risk estimate for the occupational categories selected is higher than the one previously calculated for farmers in general over a shorter period of publication. Substantial heterogeneity of rate ratios exists between the different studies. The major source of heterogeneity identified is geographic location. Increased meta-rate ratios are observed for studies derived from North America as well as from Europe, the meta-rate ratios from Europe being lower than those from North America. There is no obvious indication of publication bias. CONCLUSION: The increased meta-rate ratio for prostate cancer in agricultural pesticide applications provides additional evidence for a possible relationship between pesticide exposure and prostate cancer. The homogeneity observed between the individual rate ratios, after we had regrouped the data according to geographic location, tends to increase the consistency of the association. However, the data available from the individual studies do not provide sufficient exposure information for firm conclusions to be drawn about pesticide exposure as the cause of prostate cancer, independently from other factors.

Survivin mRNA expression is elevated in malignant urothelial cell carcinomas and predicts time to recurrence.

BACKGROUND: Expression of the inhibitor of apoptosis protein survivin is up-regulated in many tumors of epithelial origin and frequently shows a relationship with disease prognosis. MATERIALS AND METHODS: We investigated survivin mRNA expression in 32 urothelial cell carcinomas by use of real-time quantitative PCR. Expression values were normalized to transcript levels of the housekeeping gene cyclophilin. RESULTS: All bladder tumor tissues expressed survivin mRNA. The median normalized survivin mRNA expression values were 0.26 for superficial tumors (n = 17) and 0.78 for invasive tumors (n = 15). A significant relationship with increasing pathological stage (p < 0.001) and grade (p < 0.001) was observed. Although survivin mRNA expression did not relate to disease progression or the patient survival period, patients with superficial bladder tumors and normalized survivin values over 0.26 had an increased risk of recurrence (log-rank test: p = 0.018). CONCLUSION: Our results suggest that quantitative measurement of survivin mRNA 1) can identify invasive and high-grade urothelial cell carcinomas and 2) may be used as an indicator for early recurrence of superficial tumors.

Occupation related pesticide exposure and cancer of the prostate: a meta-analysis.

AIMS: To summarise recent literature on the risk of prostate cancer in pesticide related occupations, to calculate the meta-rate ratio, and to compare it to data from meta-analyses previously published. METHODS: A meta-analysis of 22 epidemiological studies, published between 1995 and 2001, was conducted in order to pool their rate ratio estimates. Studies were summarised and evaluated for homogeneity and publication bias. RESULTS: The meta-rate ratio estimate, based on 25 estimators of relative risk from 22 studies, was 1.13 (95% CI 1.04 to 1.22). Significant heterogeneity of rate ratios existed among the different studies. Therefore, a stratified analysis was carried out. Major sources of heterogeneity identified were geographic location, study design, and healthy worker effect. Overall, pooled risk estimates for studies derived from Europe were lower than those derived from the USA/Canada. A significant increase in rate ratio was observed for the occupation category of pesticide applicators, whereas no significant increase was observed for farmers. There was no evidence of publication bias. CONCLUSION: This increased meta-rate ratio for prostate cancer in different pesticide related occupations, including farmers, is very similar to three, previously published, meta-rate ratios for prostate cancer in farmers calculated from studies published before 1995. Although the underlying data do not identify pesticide exposure as an independent cause for prostate cancer, the fact that an increased meta-rate ratio is again obtained points to occupational exposure to pesticides as a possible factor. Future epidemiological studies should focus, as far as possible, on reliable methods to estimate actual exposure.

Probabilistic intake assessment and body burden estimation of dioxin-like substances in background conditions and during a short food contamination episode.

The objective was to perform a dioxin body burden estimate based on a probabilistic intake assessment of PCDDs, PCDFs and dioxin-like PCBs because of the so-called 1999 'Belgian dioxin incident'. Monte Carlo simulation techniques were used to combine detailed 7-day food intake data on the individual level from a sample of 14-18-year-old adolescents with 'background' and 'incident-related' food contamination data. In background conditions, 3% of the adolescents had an intake <1 pg TEQ kg(-1) bw day(-1), while 85% had <4 pg TEQ kg(-1) bw day(-1). Milk and other dairy products were the basic source of dioxin-like contaminants, while fish constituted the main source at the higher percentiles of intake. During the dioxin incident, the estimated median dioxin intake showed a moderate increase. At the 99th percentile, the highest intake level, and the 95% upper bound uncertainty level, peak body burden-23.73 ng TEQ kg(-1) bw-remained below body burdens that in the experimental animal or in man are accompanied by a population-based observable increase in the incidence of adverse effects. The 1999 Belgian dioxin incident most likely did not affect public health in Belgium in a measurable way, although exceptions remain possible on the individual level.

Microalbuminuria in patients with Type 2 diabetes mellitus from general practice: course and predictive value.

AIMS: To assess the course of microalbuminuria in patients with Type 2 diabetes mellitus in general practice and the predictive value of urinary albumin concentration on all-cause mortality, cardiovascular mortality and cardiovascular morbidity. METHODS: Cohort study in Type 2 diabetic patients tested for microalbuminuria in 1992, and re-tested in 1998. During follow-up all cardiovascular morbidity and mortality were recorded. RESULTS: Of the original sample of 317 patients, 163 patients were re-tested. The mean change in urinary albumin concentration was +16.2 mg/l (range -122.0 to +602 mg/l). Seventy-five per cent of the patients without microalbuminuria in 1992 still had no microalbuminuria in 1998 and 40% of those with microalbuminuria in 1992 reverted to normoalbuminuria in 1998. Cox survival analysis, stratified for age, showed that microalbuminuria at baseline resulted in a risk ratio of all-cause mortality of 1.4 (95% confidence interval 0.8-2.7), of cardiovascular mortality of 1.2 (0.5-2.8) and of new cardiovascular events (including cardiovascular mortality) of 1.4 (0.8-2.3). CONCLUSIONS: In the majority of patients the change of urinary albumin excretion was small, but the range was wide. A weak non-significant relationship between microalbuminuria and all-cause mortality and cardiovascular morbidity was observed.

Clinical experience with icodextrin in children: ultrafiltration profiles and metabolism.

Icodextrin use in adults provides sustained ultrafiltration (UF) in long-term dwells. No information is available on UF and metabolism in children. In 11 children, a volume of 1,049+/-138 ml/m2 of the study fluid (1.36% glucose, 7.5% icodextrin, 3.86% glucose) was administered for 12 h. Net UF with icodextrin (339+/-147 ml/1.73 m2) did not differ from UF with 3.86% glucose (450+/-306 ml/1.73 m2, P=0.53) and was higher than UF with 1.36% glucose (-87+/-239 ml/1.73 m2, P=0.003). Icodextrin added 0.52+/-0.07 to the weekly Kt/V. Over 6 weeks, icodextrin was used for 12-h daytime dwell. Total icodextrin reached a steady-state level of 2.91+/-1.22 g/l at 2 weeks. The main icodextrin metabolites were maltose, maltotriose, and maltotetraose. After 2 weeks, steady state levels were 2.02+/-0.66 mmol/l, 1.46+/-0.35 mmol/l, and 0.45+/-0.12 mmol/l. No icodextrin or metabolites were detectable 4 weeks after the study. We conclude that 7.5% icodextrin is capable of maintaining UF during 12-h dwell in children and is comparable to UF obtained with 3.86% glucose. Steady-state levels of icodextrin and metabolites were reached at 2 weeks and disappeared after the study.

Consequences of infections for three-month length increment in young children in rural Zambia.

It was the aim of this study to describe the relationship of infections with subsequent 3-mo length increment in children below 2 y of age in rural Zambia. Children aged 6-9 mo ('infants'; n = 84) and 14-20 mo ('toddlers'; n = 81) attending Mother-and-Child Health clinics, were included and followed up after 3.0 mo (min-max; 2.1-3.7 mo). Anthropometric measurements were taken at each visit. At baseline, C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), retinol and malaria parasitaemia were assessed. Length increment during the 3.0+/-0.5 mo was 1.0+/-0.5 cm/mo for infants and 0.6+/-0.4 cm/mo for toddlers; 50-71% of the children showed increased acute phase proteins, 79-83% had malaria parasitaemia and 55-64% had low serum retinol concentrations. In the total group of children, serum AGP concentrations (r = -0.18; p = 0.03) and serum CRP concentrations (r = -0.15; p = 0.05) showed a negative relation with length increment. After correcting for micronutrient status, dietary intake and maternal height, results of multiple regression analyses showed that the relation between serum AGP concentration and subsequent length increment remained significant. We conclude that, within the multifactorial model, presence of infections in these Zambian children contributes to the short-term retardation of linear growth.

Dichlorvos and carcinogenicity: a systematic approach to a regulatory decision.

On the request of the Belgian Health Council, the authors performed a systematic review of the available evidence in the literature and in expert panel reports, with regard to a possible carcinogenic effect of dichlorvos. Following the evaluation procedure developed by IARC, they first concluded that dichlorvos should be classified as a possible carcinogen for man. This preliminary conclusion, and its possible consequences of withdrawal of several product authorizations, was then communicated by the Health Council to all stakeholders. As a result, the interpretation of the animal experimental data was confronted with the conclusions of a U.S. "Blue Ribbon Panel" of independent experts, who reviewed all the data that were available to them. After an exchange of views, the Health Council downgraded its classification of dichlorvos toward nonclassifiable with regard to cancer in man. This paper describes the review and decision-making processes, focusing on the major arguments underlying the original interpretation of the animal data and its eventual modification.

Severe linear growth retardation in rural Zambian children: the influence of biological variables.

BACKGROUND: The prevalence of stunting in preschool children in Zambia is high; stunting has detrimental effects on concurrent psychomotor development and later working capacity. OBJECTIVE: Our objective was to investigate biological variables that may contribute to linear growth retardation in preschool children in Samfya District, Zambia. DESIGN: Children aged 6-9 mo (n = 108) and 14-20 mo (n = 102) attending mother-and-child health clinics were included. With a mixed-longitudinal design, they were followed up 9 and 21 mo later. Height and weight of children and their mothers were measured. Biochemical measures (eg, serum zinc, retinol, thyrotropin, iron, and acute phase protein concentrations), malaria parasitemia, and intestinal parasitosis were assessed. RESULTS: Height-for-age z scores (HAZ) were low, indicating a high prevalence of stunting (36-79%). Ninety percent of the children were anemic, 53-71% had elevated acute phase proteins, and 80% had malaria parasitemia. Regression analyses showed that maternal height predicted the children's height at 6-9 mo (regression coefficient = 0.05; 95% CI: 0.02, 0.08). The children's height at an early age (6-9 and 14-20 mo) showed a strong relation with their height at later ages (22-30 and 34-41 mo). Serum micronutrient status did not show a significant relation with later HAZ. CONCLUSION: Unlike other studies, we did not identify specific biological factors, such as health and micronutrient status, which contribute to the retardation of linear growth. The normal zinc and iodine statuses of the children suggest that at least these factors are not causal.

Intraperitoneal hypercoagulation and hypofibrinolysis is present in childhood peritonitis.

An increased rate of obstruction of peritoneal dialysis catheters is observed during peritonitis. Hypercoagulation and hypofibrinolysis may explain this increased occurrence. We studied plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA), D-dimer (DD), plasmin-alpha2-antiplasmin complexes (PAP), and thrombin-antithrombin III complexes (TAT) in 7 children with peritonitis (group A) and 12 children during stable peritoneal dialysis (group B). Albumin, beta2-microglobulin, IgG, and alpha2-macroglobulin were measured for baseline transperitoneal protein transport. After a dwell of 6 h with 1.36% Dianeal, dialysate and serum samples were collected. Dialysate to plasma ratios of all proteins were calculated. During peritonitis (group A) TAT was higher: 34.7 versus 22.0 (P=0.01). PAI-1 was increased in group A: 76.5 versus 22.9 (P=0.004). PAP was decreased during peritonitis (group A): 24.9 versus 39.3 (P=0.01). In group A, DD were decreased. 10.8 versus 26.7 (P=0.002). t-PA was similar in both groups (23.7 in group A vs. 27.7 in group B; P=0.26). In both groups TAT, PAI-1, t-PA, PAP, and DD were significantly higher than in baseline transperitoneal transport, suggesting intraperitoneal production. Hypercoagulability and hypofibrinolysis were present during peritonitis compared with the control situation.

[The magnitude of the 'anion gap']. / De grootte van de 'anion gap'.

The anion gap is used to evaluate disturbances in the acid-base balance, in particular metabolic acidosis. Due to the introduction of new clinical chemical techniques and modern analysers the reference range of the anion gap has changed. Clinical chemical laboratories should establish or verify their own anion gap reference range. Better communication between the laboratory and the clinician with regard to the anion gap is desirable.

Detection of tumour DNA in serum of colorectal cancer patients.

Circulating tumour DNA has previously been detected in serum and plasma of patients with lung cancer and head and neck cancer. These observations could potentially lead to new, specific and non-invasive tools for diagnosis, prognosis and follow-up in neoplastic disease, if found to be a more general phenomenon. To test if tumour DNA is also present in serum of patients with colorectal cancer, we selected 14 colorectal cancer patients with advanced disease. In seven patients, K-ras mutations were detected in the primary tumour, using mutant-specific primers for point mutations in codon 12 or 13 of the K-ras gene. All patients were analysed for mutant DNA in serum. Tumour-specific point mutations, corresponding to the K-ras mutations found in the primary tumour were detected in the serum of all patients but one. No mutant K-ras could be detected in the serum of seven patients without K-ras mutations in the primary tumour. These results may be useful in assessing tumour burden in patients with neoplastic disease. Moreover, consecutive testing of serum tumour DNA after surgery or chemotherapy may be used as a tumour marker for recurrent disease.

Increase of the bioavailability of intraperitoneal erythropoietin in children on peritoneal dialysis by administration in small dialysis bags.

OBJECTIVE: To establish the effectivity of administration of erythropoietin intraperitoneally in a small amount of fluid in children with renal anemia on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective study in which children with renal anemia on CAPD were treated with erythropoietin intraperitoneally, administered in a specially designed bag containing 50 mL NaCl 0.9%. SETTING: University hospital. PATIENTS: The patient population consisted of 9 children treated with CAPD and 1 treated with nightly intermittent peritoneal dialysis. The median age was 7.8 years (range 4.1-15.2). Four of these children had not been treated with erythropoietin before (group A), and 6 had been treated with erythropoietin administered intraperitoneally in 250 mL of dialysis fluid (group B). INTERVENTIONS: Patients in group A started on a dose of approximately 300 units/kg per week (group A). Patients in group B received their previous dose. Dosage was adjusted to achieve a target hemoglobin level of 6.5-7.0 mmol/L (104-112 g/L). Serum ferritin levels and transferrin saturation were monitored and iron supplementation was prescribed in the case of iron deficiency. MAIN OUTCOME MEASURES: Weekly erythropoietin dose in relation to hemoglobin level. RESULTS: In group A, median hemoglobin level rose from 5.3 mmol/L (85 g/L) to 6.6 mmol/L (106 g/L) after 6 months of therapy, whereas the median erythropoietin dose decreased from 266 to 234 U/kg/week. In group B, hemoglobin levels remained stable and median erythropoietin dose decreased from 262 to 194 U/kg/week. One patient in this group, for unknown reasons, never responded to erythropoietin treatment. He was excluded from further analysis. In the remaining 5 patients the median cumulative erythropoietin dose was 3250 U/kg in the 3-month period prior to the start of the study and 2713 in the 3-month period starting 6 months after the beginning of the study. This difference of 17% was statistically significant using a Wilcoxon test (p < 0.05). CONCLUSION: Intraperitoneal administration of erythropoietin in a small amount of dialysis fluid leads to a decrease in the required dose.

Role of bacteria in the pathogenesis of short bowel syndrome-associated D-lactic acidemia.

Previously, we have demonstrated that short bowel syndrome (SBS) patients suffer daily from D-lactic acidemia; in these patients rather high amounts of (bacterial) D-lactate emerge in blood and urine with a circadian rhythm. The aim of this study was to establish the microbial basis of D-lactic acidemia in SBS. Therefore, faecal flora of (young and adult) SBS-patients was analysed qualitatively and quantitatively, and compared to that of controls. The isolated bacterial species were screened for massive D- and/or L-lactate production after in vitro growth. After introduction of oral feeding in SBS-infants shortly after the resection, lactobacilli increased from < or = 1% up to 60 +/- 5% of the faecal flora within 2-3 weeks. In the faeces of patients with oral feeding the lactate producers Lactobacillus acidophilus and Lactobacillus fermentum were the major resident bacteria (each with 10(10)-10(12) cfu/g faeces). During active growth in vitro these lactobacilli produced massive amounts of D- and L-lactic acid from glucose. Use of oral antibiotics in two SBS-children did not reduce the total numbers of lactobacilli, but caused shifts within the intestinal populations of at least lactobacilli. It is concluded that the strongly reduced intestinal capacity for carbohydrate absorption and the oral consumption of easily fermentable carbohydrates form the physiological basis for D-lactic acidemia in SBS, and that the fermentative D-lactate production by intestinal bacteria, especially the abundant, resident lactobacilli, forms its microbial basis. In these patients the antimicrobial and therapeutic effects of antibiotics are unpredictable.

Coating in vitro of erythrocytes with Tamm Horsfall-protein.

A method is described to coat isolated peripheral blood erythrocytes in vitro with Tamm-Horsfall Protein (THP, uromodulin). Coating of erythrocytes with THP was accomplished by incubation of the cells in the presence of THP, made monomeric by incubation in a high urea concentration. THP-coating of erythrocytes was dependent on the THP-concentration, maximal coating being obtained at a protein concentration > or = 250 mg/ml. The best coating results were obtained if, during the co-incubation of erythrocytes with THP, urea was removed while the sodium chloride concentration was increased up to a physiologic concentration by means of dialysis. This alteration in chemical conditions promotes THP-polymerisation. Erythrocytes coated in this way could be preserved for at least 5 weeks in preserving solution, making them an interesting source of testing and control material. Coating of erythrocytes with THP could also be accomplished under conditions in which THP was preserved in a monomeric form, which suggests that peripheral blood erythrocytes having binding-sites for THP.