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Biomedical subjects

Gunilla Lindström

Publications and source records attributed to Gunilla Lindström.

16 recordsLinked to original sources

Chemical and toxicological characterisation of PBDFs from photolytic decomposition of decaBDE in toluene.

A substantial formation of PBDF congeners was observed during photolytic decomposition of decaBDE in toluene. The decaBDE degradation was monitored by chemical and toxicological analysis and in all, twenty-seven mono- to hexasubstituted polybrominated dibenzofurans (PBDFs) were detected in toluene solutions of decabromodiphenyl ether (decaBDE) after irradiation with UV-A, UV-AB and UV-ABC. The concentration levels of PBDFs formed after 16 h of UV exposure increased with wider spectra and were determined to be 3.5, 4.2 and 14 microg/ml after UV-A, UV-AB and UV-ABC irradiation, respectively. In accordance, bioassay derived TEQs (bio-TEQs), determined with the DR-CALUX assay, increased with a similar pattern. The PBDFs formed after the three UV exposures accounted for 0.31%, 0.35% and 1.2% of the initial amount of decaBDE (molar basis). The PBDF congener patterns were consistent in all three UV experiments which imply that no alterations were induced in the PBDF formation or degradation processes due to differences in UV irradiation. However, these processes tended to increase with wider spectra and increasing radiation energy most likely due to the strong absorbance of for example decaBDE at shorter wavelengths. After total decaBDE decomposition the PBDF formation increased significantly in the UV-ABC experiment. The tetra to hexasubstituted BDFs constituted the majority of detected compounds in all experiments. In all samples, the estimated chemical TEQ indicate that the bio-TEQs observed are largely explained by the presence of non-2,3,7,8-substituted PBDFs with relatively low toxicological potencies.

Benzofurans↗

Levels of 12 perfluorinated chemicals in pooled australian serum, collected 2002-2003, in relation to age, gender, and region.

Pooled serum samples from 3802 Australian residents were analyzed for four perfluoroalkylsulfonates, seven perfluoroalkylcarboxylates, and perfluorooctanesulfonamide (PFOSA). Serum was collected from men and women of five different age groups and from rural and urban regions in Australia. The highest mean concentration was obtained for perfluorooctane sulfonate (PFOS, 20.8 ng/mL) followed by perfluorooctanoic acid (PFOA, 7.6 ng/mL), perfluorohexane sulfonate (PFHxS, 6.2 ng/mL), perfluorononanoic acid (PFNA, 1.1 ng/mL), and PFOSA (0.71 ng/mL). Additional four PFCs were detected in 5-18% of the samples at concentrations near the detection limits (0.1-0.5 ng/mL). An increase in PFOS concentration with increasing age in both regions and genders was observed. The male pool levels of some of the age groups compared to females were higherfor PFOS, PFOA, and PFHxS. In contrast, PFNA concentrations were higher in the female pools. No substantial difference was found in levels of PFCs between the urban and rural regions. The levels are equal or higher than previously reported serum levels in Europe and Asia but lower compared to the U.S.A. These results suggest that emissions from production in the Northern Hemisphere are of less importance for human exposure.

Adolescent↗

Perfluorinated chemicals in relation to other persistent organic pollutants in human blood.

In order to evaluate blood levels of some perfluorinated chemicals (PFCs) and compare them to current levels of classical persistent organic pollutants (POPs) whole blood samples from Sweden were analyzed with respect to 12 PFCs, 37 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (DDE), hexachlorobenzene (HCB), six chlordanes and three polybrominated diphenyl ethers (PBDEs). The median concentration, on whole blood basis, of the sum of PFCs was 20-50 times higher compared to the sum of PCBs and p,p'-DDE, 300-450 times higher than HCB, sum of chlordanes and sum of PBDEs. Estimations of the total body amount of PFCs and lipophilic POPs point at similar body burdens. While levels of for example PCBs and PBDEs are normalized to the lipid content of blood, there is no such general procedure for PFCs in blood. The distributions of a number of perfluorinated compounds between whole blood and plasma were therefore studied. Plasma concentrations were higher than whole blood concentrations for four perfluoroalkylated acids with plasma/whole blood ratios between 1.1 and 1.4, whereas the ratio for perflurooctanesulfonamide (PFOSA) was considerably lower (0.2). This suggests that the comparison of levels of PFCs determined in plasma with levels determined in whole blood should be made with caution. We also conclude that Swedish residents are exposed to a large number of PFCs to the same extent as in USA, Japan, Colombia and the few other countries from which data is available today.

Adult↗

Improved adherence to Swedish national guidelines for acute myocardial infarction: the Quality Improvement in Coronary Care (QUICC) study.

BACKGROUND: The adherence to evidence-based treatment guidelines for acute myocardial infarction (AMI) is still suboptimal. Therefore, we designed a study to evaluate the effects of a collaborative quality improvement (QI) intervention on the adherence to AMI guidelines. The intervention used a national web-based quality registry to generate local and regular real-time performance feedback. METHODS: A 12-month baseline measurement of the adherence rates was retrospectively collected, comprising the period July 1, 2001, through June 30, 2002. During the intervention period of November 1, 2002, through April 30, 2003, multidisciplinary teams from 19 nonrandomized intervention hospitals were subjected to a multifaceted QI-oriented intervention. Another 19 hospitals, unaware of their status as controls, were matched to the intervention hospitals. During the postintervention measurement period of May 1, 2003, through April 30, 2004, a total of 6726 consecutive patients were included at the intervention (n = 3786) and control (n = 2940) hospitals. The outcome measures comprised 5 Swedish national guideline-derived quality indicators, compared between baseline and postintervention levels in the control and QUICC intervention hospitals. RESULTS: In the control and QI intervention hospitals, the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4% vs 12.6% (P = .002), lipid-lowering therapy 2.3% vs 7.2% (P = .065), clopidogrel 26.3% vs 41.2% (P = .010), heparin/low-molecular weight heparin 5.3% vs 16.3% (P = .010), and coronary angiography 6.2% vs 16.8% (P = .027), respectively. The number of QI intervention hospitals reaching a treatment level of at least 70% in 4 or 5 of the 5 indicators was 15 and 5, respectively. In the control group, no hospital reached 70% or more in just 4 of the 5 indicators. CONCLUSIONS: By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback, major improvements in the adherence to national AMI guidelines can be achieved.

Aged↗

Adipose tissue concentrations of persistent organic pollutants and the risk of prostate cancer.

OBJECTIVE: We sought to study the concentrations of certain persistent organic pollutants with endocrine-disrupting properties in cases with prostate cancer and controls with benign prostate hyperplasia. METHODS: Adipose tissue was obtained from 58 cases and 20 controls. RESULTS: The median concentration among controls was used as cut-off in the statistical analysis. In the total material, a greater-than median concentration of PCB congener 153 yielded an odds ratio (OR) of 3.15 and 95% confidence interval (CI) of 1.04-9.54 and one chlordane type, trans-chlordane, yielded OR 3.49 (95% CI = 1.08-11.2). In the group of case subjects with PSA levels greater than the median level of 16.5 ng/mL, PCB 153 was OR 30.3 (95% CI = 3.24-284), hexachlorobenzene OR = 9.84 (95% CI = 1.99-48.5), trans-chlordane OR = 11.0 (95% CI = 1.87-64.9), and the chlordane-type MC6 OR = 7.58 (95% CI = 1.65-34.9). The grouping of PCBs according to structural and biological activity was found to produce significantly increased risks for enzyme and phenobarbital-inducing PCBs and lower chlorinated PCBs in the case group with PSA levels greater than 16.5 ng/mL. CONCLUSIONS: These chemicals might be of etiologic significance but need to be further investigated. The biological relevance of the arbitrary cut-off point of PSA is unclear.

Adipose Tissue↗

High concentrations of organochlorines in a patient with kidney cancer and anorexia-cachexia syndrome.

PURPOSE: To determine persistent organic pollutants in adipose tissue in a patient with kidney cancer. METHODS: Adipose tissue was sampled from the abdominal wall during autopsy of a 75-year old man who had died from a kidney cancer. The concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyltrichloroethane (DDE), hexachlorobenzene (HCB), chlordanes and tetrabromodiphenyl ether (TeBDE) were determined on lipid basis. For comparison results from 29 male population based subjects aged 70-80 years were used. RESULTS: All concentrations except for TeBDE were very high in the patient; sum of PCBs 18 808 ng/g fat (median for controls 997), DDE 14 183 (median for controls 751), HCB 424 (median for controls 46), and sum of chlordanes 2 389 (median for controls 62). The patient lost weight from 80 kg to 48 kg when he died, which may have contributed wholly or partly to the very high concentrations of organochlorines. CONCLUSION: Changes in weight must be recorded in cancer patients and the concentrations of persistent organic pollutants should be normalized to weight. The concentrations in this patient were 10- to almost 40-times higher than in the controls. Such very high concentrations may give clinical symptoms in the final stage of a wasting cancer patient.

Adipose Tissue↗

In utero exposure to persistent organic pollutants in relation to testicular cancer risk.

Testicular cancer is the most common tumour type in young men. In Sweden the annual age-adjusted incidence increased significantly by 2.4% during the time period 1984-1993 and during 1994-2003 by 1.4%. Exposure to endocrine disrupting chemicals during the foetal period has been postulated to be a risk factor. In this investigation we studied the concentrations of chlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB), chlordanes and polybrominated diphenylethers (PBDEs) in 58 cases with testicular cancer and 61 age-matched controls. Furthermore, case and control mothers were also asked to participate and 44 case mothers and 45 control mothers agreed. No significant differences were found between cases and controls. Case mothers had in general higher concentrations of these chemicals. For the sum of PCBs an odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.4-10 was calculated using the median concentration for the controls as cut-off value. For HCB OR = 4.4, CI = 1.7-12 and for PBDE OR = 2.5, 95% CI = 1.02-6.0 were obtained, whereas OR was not significantly increased for pp'-DDE and sum of chlordanes. The cases were born during a period with high concentrations of persistent organic pollutants (POPs) in humans. The decline of the increasing incidence of testicular cancer during recent years may reflect decreasing body burden of certain POPs since the 1980s.

Case-Control Studies↗

Development of a solid-phase extraction-HPLC/single quadrupole MS method for quantification of perfluorochemicals in whole blood.

A method for the determination of perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) simultaneously with 10 closely related perfluorochemicals (PFCs) in human whole blood was developed and validated. PFOS and PFOA are used in various applications, for example, as surfactants and plastic additives, and are subject to environmental and health research due to their persistence. The main part of the data on PFCs in human blood is from serum samples, analyzed mainly by ion pair extraction followed by high-performance liquid chromatography (HPLC) and negative electrospray (ESI) tandem mass spectrometry (MS/MS). The analytical method developed here is suitable for human whole blood and involves solid-phase extraction (SPE) and HPLC negative electrospray single quadrupole mass spectrometry (HPLC/ES-MS). A whole blood aliquot was treated with formic acid and extracted on a octadecyl (C18) SPE column. The PFCs were isolated with methanol, and quantification was performed using single quadrupole mass spectrometry and perfluoroheptanoic acid as internal standard. Validation was performed in the range 0.3-194 ng/mL with recovery between 64 and 112% and limit of detection in the 0.1-0.5 ng/mL range for 11 of the 12 PFCs studied. We applied this method to 20 whole blood samples collected in 1997-2000 from the Swedish population in the ages 24-72. Eleven of the 12 PFCs were detected, and they were quantitatively and qualitatively confirmed using triple quadrupole LC/MS/MS analysis. PFOS, perfluorooctanesulfonamide, perfluorohexanesulfonate, PFOA and perfluorononanoic acid were quantified in all samples. In addition, perfluorohexanoic acid, perfluorodecanoic acid, perfluorodecanesulfonate, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotetradecanoic acid were detected in some samples. This study shows that SPE and single quadrupole MS can be applied for extraction and quantification of PFCs in human whole blood, resulting in selectivity and low detection limits.

Alkanesulfonic Acids↗

Congener-specific accumulation and food chain transfer of polybrominated diphenyl ethers in two arctic food chains.

Congener-specific accumulation and prey to predator transfer of 22 polybrominated diphenyl ethers (PBDEs) were assessed in polar cod, ringed seal, polar bear, and beluga whale. Although the concentrations found were relatively low, these results show that PBDEs have reached the Arctic. PBDE congeners 47, 99, and 100 were dominant in all species studied. The pattern in ringed seal was somewhat simpler than in polar cod, with PBDE 47 accounting for more than 90% of the total PBDEs. In contrast, beluga whales, feeding on prey similar to that of ringed seals, showed higher PBDE levels and a more complex PBDE pattern than ringed seals. In contrast, polar bears contained only PBDE 47 in relatively small amounts. These differences in levels and patterns are likely due to species-specific differences in PBDE metabolism and accumulation. The metabolic index suggested that PBDEs 47 and 99 accumulate to the same magnitude as PCB 153 (PCB = polychlorinated biphenyl) in ringed seals and beluga whales. In contrast to beluga whales, ringed seals can metabolize PBDE 100 to some extent. Polar bears are seemingly capable of metabolizing virtually all PBDEs and are therefore unsuitable as indicators for PBDE contamination in the environment.

Animals↗

PCDD/F and non-ortho PCB concentrations in adipose tissue of individuals living in the vicinity of a hazardous waste incinerator.

To assess the influence of a new hazardous waste incinerator (HWI) on public health, a preoperational monitoring program was established during the period of construction. In this study, the levels of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) accumulated in adipose tissue of 15 autopsied subjects living in the area under potential impact of the HWI were determined after approximately 3 years of regular operations in the facility. The non-ortho PCBs 77, 126 and 169 were also determined. PCDD/F concentrations ranged between 1.5 and 41 pg WHO-TEQ/g fat (2.4 and 72 WHO-TEQ/g fat, respectively, including PCBs), with a mean value of 11 pg WHO-TEQ/g fat and a median value of 7.4 pg WHO-TEQ/g fat (22 and 13 WHO-TEQ/g fat, respectively, including PCBs). In the baseline study, the mean level of PCDD/Fs was 36 pg WHO-TEQ/g fat (61 pg WHO-TEQ/g fat, including non-ortho PCBs 77, 126 and 169), which means a reduction of 70% (64% including PCBs). This notable reduction is in accordance with the important decrease observed in recent years in PCDD/F intake through the diet. The current concentrations of PCDD/Fs in human adipose tissue, as well as recent data on PCDD/F levels in plasma and breast milk of subjects living in the vicinity of the same HWI, indicate that there is not any additional significant exposure to PCDD/Fs for this population.

Adipose Tissue↗

Adipose tissue concentrations of p,p'-DDE and the risk for endometrial cancer.

OBJECTIVE: To evaluate in a case-control study possible risk of endometrial cancer associated with environmental endocrine disruptors. METHODS: We analyzed the adipose tissue concentrations of polychlorinated biphenyls, hexachlorobenzene (HCB), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE), chlordanes, and polybrominated biphenyls in 76 cases with endometrial cancer and 39 controls with benign endometrial hyperplasia. RESULTS: For the different chemicals, odds ratios (ORs) and 95% confidence intervals (CI) were close to unity taking the median concentration among the controls as cutoff value. However, for p,p'-DDE OR = 1.9, 95% CI = 0.8-4.8 was obtained. Additional estrogen replacement therapy yielded in this category OR = 2.3, 95% CI = 0.6-8.6. CONCLUSION: The results suggest an interaction between p,p'-DDE and estrogen replacement drugs in the etiology of endometrial cancer, although no significant associations were found.

Adipose Tissue↗

Concentrations of polychlorinated biphenyls in blood and the risk for testicular cancer.

An increasing incidence of testicular cancer has been reported from several western countries during the last decades. According to current hypothesis testicular cancer is initiated during the foetal period and exposure to endocrine disruptors such as some persistent organic pollutants has been of concern. We have previously reported the results for concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB) and chlordanes in 58 cases with testicular cancer, 61 age-matched controls and 44 case mothers and 45 control mothers. In that report, significant increase of odds ratio (OR) was found for sum of PCBs, HCB, trans- and cis-nonachlordane in case mothers. These data have now been further analysed for 37 congeners of PCBs. No significant differences were found among cases and controls. However, case mothers had significantly increased concentrations of a number of PCB congeners. A priori decided grouping of PCBs yielded for oestrogenic PCBs OR = 2.4, 95% confidence interval (CI) = 0.95-6.0, enzyme-inducing PCBsOR = 2.6, 95% CI = 1.03-6.5 and toxic equivalents (TEQ) yielded OR = 3.3, 95% CI = 1.3-8.4. These data further elucidate the role of foetal exposure to different PCB congeners in the aetiology of testicular cancer.

Humans↗

Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer.

An increasing incidence of testicular cancer has been reported from several countries in the Western world during the last decades. According to current hypothesis, testicular cancer is initiated during the fetal period, and exposure to endocrine disruptors, i.e., xenoestrogens, has been of concern. In this investigation we studied the concentrations of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched controls. Furthermore, case and control mothers were also asked to participate, and 44 case mothers and 45 control mothers agreed. They were of similar age. In cases only the concentration on lipid basis of cis-nonachlordane was significantly increased, whereas case mothers showed significantly increased concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio (OR) of 3.8; 95% confidence interval (CI), 1.4-10 was calculated using the median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 (95% CI, 1.7-12); for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11); for cis-nonachlordane, OR = 3.1 (95% CI, 1.2-7.8); and for sum of chlordanes, OR = 1.9 (95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma or nonseminoma testicular cancer.

Case-Control Studies↗

Is DDT exposure during fetal period and breast-feeding associated with neurological impairment?

The concentration of certain persistent organic pollutants was determined in a family including both parents and one son with neurological impairment suggested to be Attention Deficit-Hyperactivity Disorder (ADHD). For comparison control subjects from other ongoing studies were used. They were of the same sex and age group as the respective family member. For polychlorinated biphenyls, hexachlorobenzene, and chlordanes similar results were found in the study groups. The concentration of DDE, the main metabolite of DDT, was increased in the mother, 782 ng/g lipid, compared with mean 403, median 259 (range 51-1354) for the female controls. Also, the son had an increased concentration of 259 ng/g lipid, compared with mean 104, median 72 (range 46-349) for controls. A low concentration was found in the father, 127 ng/g lipid. As a child and as a teenager to the age of 17, the mother was exposed to DDT in her home environment. We discuss the potential of fetal and breast-feeding exposure of the son. Neurodevelopmental impairment has been reported for dioxins and PCBs, but DDT seems to have been less investigated in this respect.

Adult↗

Comparing electron ionization high-resolution and electron capture low-resolution mass spectrometric determination of polybrominated diphenyl ethers in plasma, serum and milk.

Gas chromatography coupled to low-resolution mass spectrometry with electron capture negative ionization as detection mode (GC-LRMS (ECNI)) has been compared to gas chromatography coupled to high-resolution mass spectrometry using electron ionization as detection mode (GC-HRMS (EI)) for determination of polybrominated diphenyl ethers (PBDEs) in biological samples. Extracts of 5.0 g plasma, serum and milk samples were analyzed using both methods. The GC-LRMS (ECNI) and GC-HRMS (EI) systems were found to be equally well suited for determination of PBDEs in the biological samples, as well as in standard solutions, with respect to response, detection limits and repeatability at the pg-level. The estimated limits of detection (LOD) in milk extracts ranged from 0.3-0.6 pg PBDE/g milk and 0.4-0.7 pg PBDE/g milk, for the GC-LRMS (ECNI) and GC-HRMS (EI) systems, respectively. The method repeatability including sample preparation was in the range 4.7-8.4% and 0.6-10% relative standard deviation (RSD) for the GC-LRMS (ECNI) and GC-HRMS (EI) systems, respectively.

Calibration↗