Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations.

The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004-2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.

Accuracy of transvaginal ultrasound versus MRI in the PreOperative Diagnostics of low-grade Endometrial Cancer (PODEC) study: a prospective multicentre study.

AIM: To investigate if the diagnostic accuracy of transvaginal ultrasound (TVUS) performed by gynaecologists is sufficient for preoperative assessment of low-grade endometrial cancer (EC) compared to magnetic resonance imaging (MRI). MATERIALS AND METHODS: MRI and TVUS performed by gynaecologists were assessed at the participating centres. The MRI examinations were interpreted by two radiologists at the tertiary centre. Deep myometrial and cervical stroma invasion were visually assessed and compared to postoperative histopathology. RESULTS: Two hundred and fifty-nine patients were included. There was a statistically significant difference in specificity assessing deep myometrial invasion between MRI and TVUS (MRI 0.88, TVUS 0.68). There was no difference in sensitivity (MRI 0.73, TVUS 0.68). When assessing cervical stroma infiltration, MRI had a higher specificity (MRI 0.96, TVUS 0.90), but there was no difference in sensitivity (MRI 0.41, TVUS 0.32). CONCLUSION: MRI has higher specificity than TVUS performed by gynaecologists for assessing deep MI and CSI in low-grade EC, but similar sensitivities. The use of TVUS as a first-line test, rather than MRI, may be supported by this study in centres where access to MRI may be limited.

The alarmins high mobility group box protein 1 and S100A8/A9 display different inflammatory profiles after acute knee injury.

OBJECTIVE: To compare the concentrations of high mobility group box 1 protein (HMGB1) and S100A8/A9 in synovial fluid between patients with knee injuries and osteoarthritis (OA), and knee healthy subjects. To investigate associations of alarmin levels with different joint injuries and with biomarkers of inflammation, Wnt signaling, complement system, bone and cartilage degradation. METHODS: HMGB1 and S100A8/A9 were measured in synovial fluid by immunoassays in patients with knee injuries, with OA and from knee healthy subjects, and were related to time from injury and with biomarkers obtained from previous studies. Hierarchical cluster and enrichment analyses of biomarkers associated to HMGB1 and S100A8/A9 were performed. RESULTS: The synovial fluid HMGB1 and S100A8/A9 concentrations were increased early after knee injury; S100A8/A9 levels were negatively associated to time after injury and was lower in the old compared to recent injury group, while HMGB1 was not associated to time after injury. The S100A8/A9 levels were also increased in OA. The initial inflammatory response was similar between the alarmins, and HMGB1 and S100A8/A9 shared 9 out of 20 enriched pathways. The alarmins displayed distinct response profiles, HMGB1 being associated to cartilage biomarkers while S100A8/A9 was associated to proinflammatory cytokines. CONCLUSIONS: HMGB1 and S100A8/A9 are increased as an immediate response to knee trauma. While they share many features in inflammatory and immunoregulatory mechanisms, S100A8/A9 and HMGB1 are associated to different downstream responses, which may have impact on the OA progression after acute knee injuries.

Impact of lymphadenectomy and lymphoedema on health-related quality of life 1 year after surgery for endometrial cancer. A prospective longitudinal multicentre study.

OBJECTIVE: To assess the impact of lymphadenectomy and lymphoedema of the lower limbs (LLL) on health-related quality of life (HRQoL) 1 year after surgery for endometrial cancer (EC). DESIGN: Prospective longitudinal cohort multicentre study. SETTING: Departments of obstetrics and gynaecology at four university hospitals, six central hospitals and four county hospitals in Sweden. POPULATION: Two-hundred-and-thirty-five women with early stage EC were included; 116 with high-risk EC underwent surgery including lymphadenectomy (+LA), and 119 with low-risk EC had surgery without lymphadenectomy (-LA). METHODS: The generic SF-36 and EQ-5D-3L and the lymphoedema-specific LYMQOL questionnaire were used to assess HRQoL. LLL was assessed by systematic circumferential measurements of the legs enabling volume estimation, clinical evaluation and patient-reported perception of leg swelling. All assessments were carried out on four occasions; preoperatively, and 4-6 weeks, 6 months and 1 year postoperatively. MAIN OUTCOME MEASURE: HRQoL scores. RESULTS: No significant differences were seen in HRQoL between the +LA and -LA groups 1 year postoperatively. Irrespective of method of determining LLL, women with LLL were significantly more affected in the LYMQOL domains Function, Appearance/body image and Physical symptoms, but not in the domain Emotion/mood, than women without LLL. No such differences were seen in the generic HRQoL or in the LYMQOL global score between the groups with and without LLL. CONCLUSIONS: Lymphadenectomy did not seem to affect generic HRQoL adversely. Irrespective of the method of measuring, LLL affected the lymphoedema-specific HRQoL negatively, mainly in physical domains, but had no impact on the generic HRQoL. TWEETABLE ABSTRACT: Lymphoedema has impact on lymphoedema-specific, but not on generic, HRQoL, 1 year after surgery for EC.

Cardiovascular and cancer mortality in relation to dietary polychlorinated biphenyls and marine polyunsaturated fatty acids: a nutritional-toxicological aspect of fish consumption.

BACKGROUND: Co-exposure to environmental contaminants present in fish could mitigate the beneficial effects of fish consumption and possibly explain the lack of association observed for mortality in some geographical regions. OBJECTIVE: To assess the independent associations of dietary exposure to polychlorinated biphenyls (PCBs) and long-chain omega-3 fish fatty acids intake with cardiovascular and cancer mortality. METHODS: We used the prospective population-based Swedish Mammography Cohort and the Cohort of Swedish Men comprising 32 952 women and 36 545 men, free from cancer, cardiovascular disease and diabetes at baseline in 1998. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] intake were obtained via a food frequency questionnaire at baseline. Information on death was ascertained through register linkage. RESULTS: During a mean follow-up of 15.5 years, we ascertained 16 776 deaths. We observed for cardiovascular mortality, comparing extreme quintiles in multivariable models mutually adjusted for PCBs and EPA-DHA, dose-dependent associations for dietary PCB exposure, hazard ratio (HR) 1.31 (CI 95%: 1.08 to 1.57; P-trend 0.005) and for dietary EPA-DHA intake, HR 0.79 (CI 95%: 0.66 to 0.95; P-trend 0.041). For cancer mortality, no clear associations were discerned. CONCLUSION: The beneficial effect of fish consumption on the cardiovascular system seems compromised by co-exposure to PCBs - one likely explanation for the inconsistent associations observed between fish consumption and mortality.

Incidence of distal radius fracture in a general population in southern Sweden in 2016 compared with 2001.

In this population-based study, we compared the incidence of distal radius fracture in 2016 with that in the same region's adult general population in 2001 using radiographs to identify fracture cases. We showed that the incidence decreased by 24% in 2016 compared with 2001 indicating an important development. INTRODUCTION: We conducted an epidemiological study on residents of northeastern Skåne in southern Sweden (population 182,000) to determine the overall incidence of distal radius fracture and the incidence according to age, sex, and fracture characteristics in the region's adult population during 2016, and to study the change in incidence in the same general population between 2001 and 2016 using wrist radiographs to identify fracture cases. METHODS: Two orthopedic surgeons examined all wrist radiographs performed at the only two emergency hospitals in the study region to identify individuals, above 18 years of age, who sustained fracture of the distal radius during 2016. We used Poisson regression analysis adjusting for age, sex, and at-risk population to compare the incidence in 2016 with the incidence in 2001, previously estimated using similar methodology. RESULTS: The overall incidence in 2016 was 22 (95% CI 20-25) per 10,000; the incidence in women was 34 (95% CI 30-39) and in men was 10 (95% CI 8-12) per 10,000. The overall incidence in 2016 was 0.76 (95% CI 0.70-0.82) of the incidence in 2001 (p < 0.0001). The incidence in the 3 age groups 19-49, 50-79, and ≥ 80 years was 0.91 (95% CI, 0.69-1.20), 0.67 (95% CI, 0.55-0.82), and 0.49 (95% CI, 0.25-0.97) of the incidence in 2001, respectively. CONCLUSION: In a general population in Sweden, a statistically significant and clinically important decrease in the incidence of distal radius fracture occurred between 2001 and 2016, driven by lower incidence in individuals 50 years or older.

Dietary exposure to polychlorinated biphenyls is associated with increased risk of stroke in women.

OBJECTIVE: The potentially beneficial effects of fish consumption on stroke may be modified by major food contaminants in fish. Polychlorinated biphenyls (PCBs) in particular are proposed to play a role in the aetiology of stroke. The aim of this study was to assess the association between dietary PCB exposure and stroke risk with the intake of long-chain omega-3 fish fatty acids and fish consumption. DESIGN: The prospective population-based Swedish Mammography Cohort was examined. It was comprised of 34,591 women free of cardiovascular diseases and cancer at baseline in 1997 and followed up for 12 years. Validated estimates of dietary PCB exposure were obtained via a food frequency questionnaire at baseline. Incident cases of stroke were ascertained through register linkage. RESULTS: During 12 years of follow-up (397,309 person-years), there were 2015 incident cases of total stroke (1532 ischaemic strokes, 216 intracerebral haemorrhages, 94 subarachnoid haemorrhages and 173 unspecified strokes). Multivariable-adjusted relative risks (RR), controlled for known stroke risk factors and fish consumption, were 1.67 [95% confidence interval (CI), 1.29-2.17] for total stroke, 1.61 (95% CI, 1.19-2.17) for ischaemic stroke and 2.80 (95% CI, 1.42-5.55) for haemorrhagic stroke for women in the highest quartile of dietary PCB exposure (median 288 ng day(-1) ) compared with women in the lowest quartile (median 101 ng day(-1) ). CONCLUSION: Dietary exposure to PCBs was associated with an increased stroke risk in women, especially haemorrhagic stroke. The results provide important information regarding the risk-benefit analysis of fish consumption, particularly for cerebrovascular disease prevention.

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study.

BACKGROUND: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated. METHODS: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases). RESULTS: Mean dietary cadmium exposure was 19 µg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers. CONCLUSION: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

HIV care need not hamper maternity care: a descriptive analysis of integration of services in rural Malawi.

OBJECTIVE: To evaluate the use of reproductive health care and incidence of paediatric HIV infection during the expansion of antiretroviral therapy and services for the prevention of mother-to-child transmission in rural Malawi, and the influence of integration of these HIV-related services into general health services. DESIGN: Descriptive analysis. SETTING: Thyolo District, with a population of 600,000, an HIV prevalence of 21% and a total fertility rate of 5.7 in 2004. POPULATION: Women attending reproductive health services care in 2005 and 2010. METHODS: Review of facility records and databases for routine monitoring. MAIN OUTCOME MEASURES: Use of antenatal, intrapartum, postpartum, family planning and sexually transmitted infection services; incidence of HIV infection in infants born to mothers who received prevention of mother-to-child transmission care. RESULTS: There was a marked increase in the uptake of perinatal care: pregnant women in 2010 were 50% more likely to attend at least one antenatal visit (RR 1.50, 95% CI 1.48-1.51); were twice as likely to deliver at a healthcare facility (RR 2.05, 95% CI 2.01-2.08); and were more than four times as likely to present for postpartum care (RR 4.40, 95% CI 4.25-4.55). Family planning consultations increased by 40% and the number of women receiving treatment for sexually transmitted infections doubled. Between 2007 and 2010, the number of HIV-exposed infants who underwent testing for HIV went up from 421 to 1599/year, and the proportion testing positive decreased from 13.3 to 5.0%; infants were 62% less likely to test HIV positive (RR 0.38, 95% CI 0.27-0.52). CONCLUSIONS: During the expansion and integration of HIV care, the use of reproductive health services increased and the outcomes of infants born to HIV-infected mothers improved. HIV care may be successfully integrated into broader reproductive health services.

Dietary cadmium exposure and risk of epithelial ovarian cancer in a prospective cohort of Swedish women.

BACKGROUND: The proposed cadmium-induced oestrogen mimicking effects in reproductive tissues, suggest a role of this widespread food contaminant in the development of hormone-dependent malignancies. METHODS: We prospectively evaluated the association between tertiles of dietary cadmium exposure and epithelial ovarian cancer in 60,889 women from the population-based Swedish Mammography Cohort. Dietary cadmium was estimated using a food-frequency questionnaire at baseline (1987-1990) and in 1997. Multivariable-adjusted rate ratios (RR) were evaluated using Cox proportional hazards models. RESULTS: During a mean follow-up of 18.9 years (1,149,470 person-years), we identified 409 incident cases of epithelial ovarian cancer, including 215 serous, 27 mucinous, 62 endometrioid and 12 clear cell tumours. We found no association between dietary cadmium exposure and the risk of ovarian cancer. Compared with the lowest tertile of cadmium exposure, the multivariable-adjusted RR for the highest tertile was 0.90 (95% confidence interval (CI): 0.71-1.15) for total epithelial ovarian cancer. Likewise, no association was observed in subtypes modelled with continuous dietary cadmium exposure; multivariable RR for each 1 µg per day increment of cadmium: 0.97 (95% CI: 0.93-1.02) for serous tumours, 0.94 (95% CI: 0.82-1.07) for mucinous tumours and 1.00 (95% CI: 0.92-1.08) for endometrioid and clear cell tumours. CONCLUSION: Our study suggests that dietary cadmium exposure is not likely to have a substantial role in ovarian cancer development.

25-hydroxyvitamin D accumulation during summer in elderly women at latitude 60 degrees N.

OBJECTIVES: During half of the year, cutaneous synthesis of 25-hydroxyvitamin D (25(OH)D) is not detectable at northern latitudes, leaving the population dependent on other sources for optimal vitamin D status. During April to September, 25(OH)D status may be improved by solar exposure. In this study, we measured seasonal differences in serum 25(OH)D concentrations and identified the major predictors of summer 25(OH)D concentrations. DESIGN: We assessed serum 25(OH)D concentrations during both winter and summer amongst 100 women, aged 61-83 years, randomly sampled from the Swedish Mammography Cohort. Participants completed two detailed questionnaires covering diet, use of dietary supplements and sun-related behaviour, the first in January through March and a second time in August through September. RESULTS: The mean seasonal increase in serum 25(OH)D concentrations was 38% from mean 72 +/- 23 nmol L(-1) during winter to 99 +/- 29 nmol L(-1) in summer. High summer 25(OH)D concentrations were associated with higher winter concentrations, preference of staying in sun instead of shade, having a nonsensitive skin type and normal body mass index. Based on multiple linear regression modelling, preferring sun, having nonsensitive skin type and normal weight as compared with preferring shade, having sensitive skin type and being obese, was associated with a 64 nmol L(-1) higher 25(OH)D concentrations during summer. CONCLUSIONS: Women with high winter 25(OH)D serum concentrations, with preference of staying in the sun instead of shade during summer, a skin type allowing for longer sun exposure and a normal weight had the highest summer 25(OH)D concentrations.

Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women.

Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed in serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p,p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other.

High-frequency ultrasound of skin involvement in systemic sclerosis reflects oedema, extension and severity in early disease.

OBJECTIVE: The aim was to compare skin assessment by palpation and by high-frequency ultrasound in patients with SSc with disease duration <2 yrs. METHODS: Skin thickness and skin echogenicity were measured by 20 MHz ultrasound at five different anatomical sites in 106 individuals within 2 yrs from the first non-Raynaud's symptom and compared with the modified Rodnan skin score (mRss). RESULTS: The patients with short disease duration were characterized by high skin thickness and low skin echogenicity, which correlated inversely, reflecting oedema. Patients with diffuse skin involvement displayed higher skin thickness and lower skin echogenicity than did patients with limited skin involvement. The ultrasound measurements correlated to the local mRss from the corresponding anatomical region and also to the total mRss. However, there was a considerable overlap in both skin thickness and skin echogenicity between different local mRss at all five anatomical sites. Skin involvement of the chest could be detected earlier by ultrasound than by palpation. CONCLUSION: In SSc patients with short disease duration, high-frequency ultrasound can identify the oedematous phase that may precede palpable skin involvement and may thus be useful to identify patients with diffuse skin involvement very early in the disease process. Ultrasound measurements also reflect the severity of the overall skin involvement.

Strengthening the Reporting of Observational Studies in Epidemiology - nutritional epidemiology (STROBE-nut): An extension of the STROBE statement.

Concerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by extending the STROBE statement into Strengthening the Reporting of Observational Studies in Epidemiology - Nutritional Epidemiology (STROBE-nut). Recommendations for the reporting of nutritional epidemiology and dietary assessment research were developed following a systematic and consultative process, co-ordinated by a multidisciplinary group of 21 experts. Consensus on reporting guidelines was reached through a three-round Delphi consultation process with 53 external experts. In total, 24 recommendations for nutritional epidemiology were added to the STROBE checklist. When used appropriately, reporting guidelines for nutritional epidemiology can contribute to improve reporting of observational studies with a focus on diet and health.

Serum transferrin receptor: a specific marker of iron deficiency in pregnancy.

BACKGROUND: Current markers of iron deficiency tend to be less reliable in pregnancy. OBJECTIVE: Our aim was to study the usefulness of soluble serum transferrin receptor (sTfR) as a marker for iron deficiency during early and late gestation and to define iron status in 254 pregnant Swedish women. DESIGN: We performed a cross-sectional and longitudinal evaluation of sTfR in comparison with concentrations of serum ferritin and hemoglobin in blood collected around gestational weeks 11 and 36. RESULTS: The specificity of sTfR was 100%. The sensitivity in relation to both anemia and depleted iron stores was approximately 70%, but this figure is less reliable because of few samples. sTfR in early pregnancy was low: 11% of women had a value below the reference interval. sTfR increased significantly from early to late pregnancy even in the group of women with persisting iron stores. In late pregnancy, 14% of women developed tissue iron deficiency and 5% had iron deficiency according to a combination of all 3 markers. CONCLUSIONS: sTfR seems to be a specific and sensitive marker of iron deficiency in pregnancy and may have advantages over serum ferritin and hemoglobin. The low sTfR concentration in early gestation seems to be caused by reduced erythropoiesis, whereas the increase from early to late pregnancy reflects increased erythropoiesis, and in case of iron deficiency, also tissue iron deficiency. Further studies are needed to verify whether decreased erythropoiesis reduces the possibility of detecting iron deficiency during early gestation by sTfR.

Esophageal scintigraphy of systemic sclerosis.

UNLABELLED: Esophageal involvement is common in systemic sclerosis, and esophageal scintigraphy can be used to detect and follow esophageal dysfunction. This study assesses the value of visual and quantitative analysis of esophageal scintigraphy performed as a multiple swallow test in normals and patients with systemic sclerosis. METHODS: Forty patients with systemic sclerosis and 40 sex- and age-matched healthy subjects (controls) were studied. A multiple swallow technique was used and both quantitative and qualitative analyses were performed. Visual analysis of condensed images was performed independently by two physicians. Each swallow was assigned a score on a scale from 1 to 4. In the quantitative analysis, time-activity curves based on the mean condensed images were used to calculate the following 3 parameters: residual activity 12 or 25 sec after the beginning of the swallow, measured with or without baseline correction, respectively, and time from onset of swallow to 50% of peak activity. RESULTS: Both visual and quantitative analysis showed a highly significant (p < 0.001) difference between the patient group and the control group. Visual analysis was best reflected by the residual activity 25 sec after the beginning of the swallow without correction for background. Receiver operating characteristic curves were used to study the ability to separate the two groups using visual or quantitative analysis. A high rate of positive tests in the patient group was achieved only at the cost of a relatively high rate of positive tests in the control group. CONCLUSION: Our results indicate high variability in esophageal motility in controls. This variability impairs the possibilities of developing a screening test to identify asymptomatic patients early in the disease course.

Phlebotomy increases cadmium uptake in hemochromatosis.

The intestinal absorption of the nephrotoxic environmental pollutant cadmium increases markedly when iron stores are depleted. This may be mediated by an up regulation of the recently identified mucosal transporter DMT1 (Nramp2 or DCT1) for divalent cations. We tested whether the highly increased iron absorption in hereditary hemochromatosis (HH) was accompanied by an enhanced absorption of cadmium and lead. Cadmium and lead in blood and iron status markers were determined in 21 nonsmoking subjects with HH genetically tested for the HFE mutations and in 21 nonsmoking controls matched for age and sex. In subjects with HH on maintenance phlebotomy treatment, blood concentrations of cadmium, but not lead, were significantly higher than in paired controls. There was a strong age-independent positive association between blood cadmium and the number of years of phlebotomy treatment. Blood lead showed a similar but less pronounced consequence of treatment. All HH subjects with lower blood cadmium than the corresponding controls had either no mutation in the HFE gene, were not phlebotomized, or were phlebotomized for only a limited time. Our findings indicate that the treatment rather than the disease increased the cadmium uptake in homozygous HH. Further studies are needed to confirm whether the disease decreased cadmium absorption and whether the absorption was dependent on the genotype.

Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake.

Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS)

A qualitative and quantitative method for in situ characterization of the inflammatory response in experimental myocarditis.

Coxsackie virus B3 causes myocarditis in Balb/c inbred mice. In this model mortality is about 60% on day 7 and 95% on day 12 after inoculation. Significant inflammatory infiltrates appear on day 7. Recent research has focused on the immune response to explain the ensuing tissue damage. Thus we were interested in mapping cellular interaction and time course to understand the development of a possible autoimmune attack. By a newly developed immunohistochemical staining technique single lymphocytes could be visualized and different lymphocyte subpopulations enumerated. Stained cells were easily detectable and readily distinguishable from non-stained cells. Before day 7 Th cells could only occassionally be seen. The number of pan T lymphocytes increased almost 10-fold from day 7 to 12. The T helper/T killer ratio did not change significantly but indicated a predominant increase in Tk-cells. The B cell population also increased, roughly about ten times. The number of class II positive cells was constant. No expression of Il-2 receptor was found. In preliminary studies, exercise and methylprednisolone treatment tended to influence the expression of class II antigens. Cyclophosphamide and cyclosporine A reduced the number of inflammatory cells more than 10-fold. No clear concurrent reduction in mortality was observed.

Toxic and essential elements in placentas of Swedish women.

OBJECTIVES: To evaluate interactions between toxic and essential elements in the mother-fetus relationship and possible predictors of trace element concentrations in placenta and cord blood. DESIGN AND METHODS: A group of 106 Swedish women was investigated for concentrations of cadmium, lead, and several essential elements in placenta as well as cadmium, lead, zinc, and selenium in venous blood collected at gestational week (gw) 36 and umbilical cord blood. Relations between these elements and maternal and child's characteristics were examined. RESULTS: The concentrations of cadmium in placenta ranged from 10 to 170 nmol/kg, with the median value (Md) being 46 nmol/kg. Cord blood cadmium (Md of 0.19 nmol/L) was only about 10% of that in maternal blood. Smokers had significantly higher cadmium concentrations in blood (p < 0.001) and placenta (p = 0.001) than non-smokers. The median placental concentration of lead was 26 nmol/kg (range 0-630 nmol/kg). The lead levels in cord blood (Md of 54 nmol/L) were almost the same as in maternal blood. Statistically significant negative associations were found between cord blood lead, on one hand, and child's weight, length, and head circumference, on the other. The placental levels (medians and ranges) of the essential elements (micromol/kg) were 160 (120-280) for zinc, 2.4 (2.0-3.3) for selenium, 15 (10-20) for copper, 0.084 (0.02-0.32) for cobalt, 0.055 (0.03-0.12) for molybdenum, and 1.2 (0. 65-5.1) for manganese, respectively. Several of the essential elements in placenta correlated significantly with each other. Multiparous mothers had significantly lower concentrations of zinc (p = 0.002) and selenium (p = 0.049) in serum as well as zinc (p = 0. 001) and calcium (p = 0.004) in placenta than nulliparous ones. Also, cord blood zinc decreased with parity. CONCLUSIONS: The results showed that lead, but not cadmium crossed easily the placental barrier. There were no negative effects of cadmium on the zinc status. Cord blood lead, on the other hand, was a negative predictor of child's birth weight, length and head circumference, indicating that lead might have negative influence on growth in children even at very low exposure levels. There was a depletion of maternal stores of essential elements with increasing parity.