Pre-eclampsia during pregnancy and cardiovascular disease later in life: the case for a risk group.

INTRODUCTION: Women with pre-eclampsia (PE) have an increased risk of cardiovascular disease (CVD) later in life. This association might reflect an effect of pre-eclampsia on mechanisms inducing a higher risk of CVD or the presence of a group at risk. MATERIALS AND METHODS: The possibility that women with a magnesium deficiency might constitute a risk group was examined using published evidence form investigations on PE and CVD. RESULTS: Available data strongly suggest that a magnesium deficiency is a major risk factor for both PE and for CVD disease later in life. CONCLUSIONS: Magnesium homeostasis studies in women with PE should be undertaken for validation purposes. The results suggest that women with PE should be given dietary counselling to decrease future risks of CVD.

Diastolic blood pressure increase is a risk indicator for pre-eclampsia.

OBJECTIVES: A previous study demonstrated that the increase in diastolic blood pressure during pregnancy was reduced by supplementation with magnesium. The present study was undertaken to explore if increases in diastolic blood pressure could be useful for early identification of pre-eclampsia. STUDY DESIGN: Hospital records of nulliparous, singleton normal pregnancies (n = 100) and those diagnosed with pre-eclampsia (n = 109) were obtained from a register at an antenatal health care unit. Data on blood pressure at the regular visits to the unit were collected and analysed. RESULTS: The systolic and diastolic blood pressures were significantly higher at pregnancy week 12 among those who developed pre-eclampsia (p = 0.046 and 0.001, resp). An increase in diastolic blood pressure ≥15 mmHg occurred more frequently among women with pre-eclampsia. In 93 % of the cases, this increase was present before and at the same time as the clinical diagnosis of pre-eclampsia was established. CONCLUSION: The results suggest that a base-line diastolic blood pressure of ≥80 mmHg and an increase in diastolic blood pressure of ≥15 mmHg could be used to identify women at risk of pre-eclampsia (sensitivity 92 %, specificity 44 %) and as a selection criterion in treatment or prevention assays.

Inflammatory markers and pulmonary granuloma infiltration in sarcoidosis.

BACKGROUND AND OBJECTIVE: Previous studies have demonstrated increases of inflammatory mediators in sarcoidosis while epidemiological studies have also demonstrated an association with increased fungi exposure. This study measured the level of ß-glucan in the lungs and of inflammatory mediators in serum, and correlated both with the extent of pulmonary granuloma infiltration. METHODS: This is a cross-sectional study of 98 patients with sarcoidosis and 26 controls. ß-glucan, a cell wall constituent of fungi, was measured in bronchoalveolar lavage. Inflammatory mediator levels were determined in serum. The extent of granuloma infiltration was estimated on the chest X-ray. Exposure to fungi at home was determined by taking air samples in bedrooms and analysing for the presence of ß-N-acetylhexosaminidase. RESULTS: Significantly, higher levels of ß-glucan were found in broncho-alveolar lavage in subjects with sarcoidosis as compared with controls. There were significant positive relationships between the extent of granuloma infiltration and the levels of the different inflammatory mediators, except for interleukin-10. Domestic fungal exposure was higher among subjects with sarcoidosis. CONCLUSIONS: This is the first time that a specific agent, previously suspected to be related to the risk of sarcoidosis, has been detected in the lung of subjects with sarcoidosis and related to the levels of inflammatory mediators and the degree of home exposure to fungi. The results suggest that exposure to fungi should be explored when investigating patients with sarcoidosis.

Magnesium in drinking water - a case for prevention?

Studies in many countries have demonstrated a relationship between drinking water mineral content and the risk of death in cardiovascular disease (CVD). Particularly strong relationships have been found for magnesium and it has been suggested that magnesium be added to drinking water. The aim of this article is to evaluate the validity of this suggestion by reviewing information on possible causative agents. Major epidemiological studies on the drinking water content of calcium, magnesium, and hardness were analysed regarding exposure specificity, confounding factors, dose-response relationships and biological plausibility. Intervention experiments were analysed. The risk of death in CVD was related to the content of Ca, Mg and HCO(3-). The data demonstrate that Ca and Mg need to be considered together, and that HCO(3-) could play a role by intervening with the body acid load. There is no evidence to justify the addition of magnesium only to drinking water for preventive purposes. The data suggest that Ca and Mg could be administered together but no data are available regarding the relative proportions for an optimal effect.

Magnesium supplementation to prevent high blood pressure in pregnancy: a randomised placebo control trial.

PURPOSE: To assess if hypertension during the last part of pregnancy could be prevented by magnesium supplementation. METHODS: Pregnant primagravida women from a local antenatal care unit were given an oral supply of 300 mg magnesium as citrate or placebo from pregnancy week 25 in a randomised double-blind setup. Blood pressure was recorded during pregnancy as well as pregnancy outcome. RESULTS: In the magnesium-supplemented group, the average diastolic blood pressure at week 37 was significantly lower than in the placebo group (72/1.4 mean/SEM vs 77/1.4, p = 0.031). The number of women with an increase in diastolic blood pressure of ≥15 mmHg was significantly lower in the magnesium group compared with the women who received placebo (p = 0.011). There was an inverse relation between the urinary excretion of magnesium during pregnancy and the diastolic blood pressure (p = 0.005). CONCLUSIONS: Magnesium supplementation prevented an increase in diastolic blood pressure during the last weeks of pregnancy. The relation between diastolic blood pressure and urinary excretion of magnesium suggests that magnesium is involved in the regulation of blood pressure and that the increase in diastolic blood pressure in pregnancy could be due to a lack of magnesium.

Fungal exposure in homes of patients with sarcoidosis - an environmental exposure study.

BACKGROUND: There is increasing evidence that exposure to moulds (fungi) may influence the development of sarcoidosis. To assess the influence of the environmental exposure, a study was undertaken to determine the exposure to fungi in homes of subjects with sarcoidosis. METHODS: Subjects were patients with clinically established sarcoidosis recruited during the period September 2007 till June 2010. Of these 55 were newly diagnosed and currently under treatment for less than one year, 25 had been treated and had no recurrence and 27 had been treated but had recurrence of the disease. Controls were healthy subjects without any respiratory symptoms (n = 30). Samples of air (about 2.5 m3) were taken in the bedroom of the subjects using a portable pump and cellulose ester filters. The filters were analysed for the content of the enzyme N-acetylhexosaminidase (NAHA) as a marker of fungal cell biomass, using a specific substrate and a fluorescent technique and expressed as NAHA units (U)/m3. RESULTS: Compared to controls, subjects undergoing treatment of the disease (newly diagnosed or with recurrence) had significantly higher activities of NAHA in their homes than controls (33.6 and 39.9 vs 10.0 U/m3, p < 0.001 and <0.001). Among controls only 5 out of 30 subjects had levels of NAHA above the second quartile value (14 U/m3). In homes of subjects with newly diagnosed disease with treatment less than one year, values above 14 NAHA U/m3 were found among 35 out of 55 and among those with recurrent disease among 18 out of 27. CONCLUSIONS: The higher activities of NAHA enzyme found in homes of subjects with active and recurrent sarcoidosis suggest that exposure to fungi is related to the risk of sarcoidosis. Further environmental studies to assess the importance of this exposure for subjects with sarcoidosis are warranted. The results suggest that remedial actions in homes with high levels of fungi may be justified.

Maternal exposures and risk of spontaneous abortion before and after a community oriented health education campaign.

BACKGROUND: In a district of Veneto (North-east Italy) where numerous females of childbearing age were occupationally exposed to organic solvents in nearly 400 shoe factories, a case-control study found significant associations between maternal exposures (from occupation and risky behavior) and spontaneous abortion (SAB). Thereafter, a health education campaign was undertaken to increase awareness of risk factors for pregnancy in the population. To evaluate the effects of this campaign maternal exposures and SAB risks were compared before and after the campaign. METHODS: Hospital records were collected from a local hospital for SAB cases and age- residence-matched controls with normal deliveries. Information on solvent exposure, coffee and alcohol consumption, smoking and the use of medication was collected using a questionnaire. Before and after differences were tested through a modified Chi-square test and linear and logistic regressions for survey data. Odds ratios (ORs) with 95% confidence interval (CI) were estimated using logistic regression models. RESULTS: The consumption of coffee (P = 0.003) and alcohol (P < 0.001) was lower after than before the campaign, controlling for age at pregnancy and level of education. There were no differences in reported solvent exposure or smoking (smokers were few). The previously detected increased risks of SAB in relation to solvent exposure and coffee consumption were no longer present. CONCLUSION: The results suggest that health education campaigns might reduce harmful maternal exposures and the risk of SAB.

Urinary calcium and magnesium excretion relates to increase in blood pressure during pregnancy.

OBJECTIVE: Pregnancy-induced hypertension and preeclampsia are serious clinical manifestations during late pregnancy and the cause for increased maternal and foetal morbidity and mortality. The pathogenesis is unknown but experience from treatment schemes suggests that minerals may be of importance. Mineral homeostasis is influenced by acid-base conditions. The aim of the study was to elucidate the relation between acid-base balance, urinary mineral excretion and blood pressure during pregnancy. DESIGN: A prospective observational study of a general population. MATERIALS AND METHODS: The study was performed at the Midwife Health Center in Borås, Sweden, where practically all pregnant subjects in the catchment area are registered. First time pregnant subjects (n = 123) were voluntarily recruited without exclusion criteria. A 24 h urine sample was collected at pregnancy week 12 and analyzed for creatinine, calcium, magnesium, and urea as a proxy for acid conditions. Blood pressure was recorded every 2-3 weeks until delivery. RESULTS: There was a relation between the excretion of urea and calcium and magnesium at week 12. A blood pressure increase was found after pregnancy week 30 but only among subjects who had a high excretion of calcium and magnesium at week 12. CONCLUSIONS: If an increase in blood pressure during the later part of pregnancy a risk indicator for preeclampsia, the results suggest that an excessive secretion of calcium leading to a functional deficit might be a risk indicator for gestational hypertension and preeclampsia. Intervention experiments are required to assess this hypothesis.

Airborne enzyme measurements to detect indoor mould exposure.

Mould in buildings constitutes a threat to health. Present methods to determine the moulds comprise counting of spores or determination of viable moulds which give imprecise measures of total mould cell biomass. Analysis of ergosterol and ß-glucan as markers of mould cell biomass is expensive and cumbersome. To evaluate if airborne enzyme activity was related to mould in buildings air samples were taken using an impinger technique or cellulose filters in 386 rooms in 141 buildings. The samples were analysed for the activity of N-acetylhexosaminidase (NAHA) and expressed as enzyme units per m(3) (EU per m(3)). The highest value found in a building was used for the classification of the building and was related to the results from the subsequent technical inspection. In buildings without mould damage, the NAHA activity was generally below 20 EU per m(3). In buildings with mould damage, almost all the buildings had activities above 20 EU per m(3) (specificity 85%). At 30 EU per m(3) the specificity was 100%. Measurements of airborne enzyme activity have a high sensitivity and specificity to identify buildings with mould problems. The method can be used in the investigations of building related symptoms or for home exposure characteristics when investigating diseases such as asthma that can be related to mould exposure.

Otitis, rhinitis, and atopy in relation to domestic endotoxin and ß-glucan exposure among children in Singapore.

BACKGROUND: Exposure to microbial cell wall agents (MCWAs) has been related to the risk for atopy, otitis, and rhinitis. OBJECTIVES: To relate domestic exposure to two important MCWAs-ß-glucan and endotoxin-to the risk for otitis, rhinitis, atopy, and allergy in a sample of children from Singapore. METHODS: Subjects (n = 98) were recruited from July 2006 to December 2008. Blood samples were taken to determine nonspecific IgE and skin prick tests were performed. Dust samples were collected from the bedrooms of the subjects and analyzed for the content of ß-glucan and endotoxin, using the Limulus method. RESULTS: Levels of IgE were significantly higher among children with rhinitis, and these children also had a larger proportion of atopics. There were no differences in ß-glucan values between children with otitis, children with rhinitis, and controls. Endotoxin levels were lower in the homes of children with otitis, with a tendency for the levels to be lower in those with rhinitis. Among children with a high level of ß-glucan, there was a higher proportion of those with high IgE values and atopy. CONCLUSIONS: The results suggest that a low level of endotoxin is a risk factor for otitis and that a high level of ß-glucan is a risk factor for atopic sensitisation. Reactions to domestic indoor exposure are determined by several indoor agents and their relative exposure levels.

Chitotriosidase activity in sarcoidosis and some other pulmonary diseases.

BACKGROUND: Patients with sarcoidosis have elevated levels of several markers of inflammation. Particularly high levels have been reported for chitotriosidase. In this study, we evaluate whether determining chitotriosidase in serum would be useful in the diagnosis and clinical management of patients with sarcoidosis. METHODS: Patients with newly diagnosed sarcoidosis and patients with asthma, fibrosis, asbestosis, lung cancer or chronic obstructive pulmonary disease (n=190) were recruited from an outpatient department. Individuals with no disease (n=26) served as controls. An X-ray was taken, diffusion capacity was measured and blood samples were taken for analysis of chitotriosidase, soluble receptor for interleukin-2, tumour necrosis factor alpha and angiotensin converting enzyme. In most patients with sarcoidosis, the analyses were done before and after regular treatment with corticosteroids over 6 months. RESULTS: Some patients with sarcoidosis had markedly high activities of chitotriosidase, but activities above controls were also found among patients with asbestos, fibrosis and lung cancer. There were significant relationships between chitotriosidase and interleukin-2 receptor and angiotensin-converting enzyme. After treatment, chitotriosidase activity decreased in 52 of 69 patients. CONCLUSIONS: The results confirm that chitotriosidase activity is markedly increased in some cases of sarcoidosis. As increased activities are also found in other diseases, chitotriosidase cannot be considered a specific marker of sarcoidosis. In cases of sarcoidosis where high CTO activities are found, this enzyme could serve as a useful marker supporting the diagnosis of sarcoidosis when following the effects of treatment and in surveillance for recurrence of the disease.

Acid-base conditions regulate calcium and magnesium homeostasis.

BACKGROUND: Previous experimental studies demonstrate that the acid-base balance influences mineral homeostasis by regulating the absorption of calcium and magnesium in the kidneys. No intervention studies are available on population samples. AIMS: To study the urinary excretion of calcium and magnesium before and after an intervention with the aim of decreasing the acid load. METHODS: Healthy subjects aged 50-75 years were recruited by advertising. Urinary calcium, magnesium and urea as well as blood pressure were measured before and after the intervention. This comprised taking tablets containing potassium hydrogen carbonate or potassium chloride (placebo) during 7-10 days. RESULTS: There were significant relationships between the urinary excretion of urea and magnesium and calcium before the intervention. Comparing before and after intervention, the change in urinary excretion of urea was related to a change in urinary excretion of calcium and magnesium. There was a significant decrease in systolic as well as diastolic blood pressure both after administration of potassium hydrogen carbonate and citrate. CONCLUSION: The results confirm previous studies showing a relation between acid conditions in the body and the excretion of calcium and add new data on magnesium. A blood pressure decrease after potassium has been found in previous studies. This suggests an alternative for the treatment of moderately increased levels of blood pressure that should be further explored.

Drinking water constituents and disease.

Several epidemiological investigations over the last 50 y have demonstrated a relation between risk for cardiovascular disease and drinking water hardness or its content of magnesium and calcium. An additional parameter, first suggested in a study from Japan 50 y ago, is the acidity of the water. It is known that acid load influences the reabsorption of calcium and magnesium in the renal tubuli. Intervention studies have shown that acid-base conditions influence the homeostasis of minerals. Data from intervention studies using magnesium, calcium, and hydrogen carbonate are reviewed. It is suggested that the health effects related to drinking water found in some studies may be caused by an increased urinary excretion of minerals induced by acid conditions in the body and that drinking water should contain sufficient amounts of hydrogen carbonate to prevent this effect.

Microbial antigen treatment in sarcoidosis--a new paradigm?

Increasing evidence suggests that the risk for sarcoidosis is related to exposure to microbes, particularly molds. Microbial cell wall agents, even in the absence of clinical infection, could cause a late hypersensitivity reaction leading to the formation of granulomas. A few interventions studies using antimicrobial treatment demonstrate improvement in sarcoidosis. It is suggested that diagnostic tools for the presence of microbes are used in patients with sarcoidosis and that antimicrobial treatment is considered in cases resistant to corticosteroids.

DNA-based sputum cell image analysis for lung cancer in a clinical setting.

OBJECTIVE: To measure cell nuclei characteristics, previously reported to express probability for lung cancer, in subjects with different forms ofpulmonary disease and those without disease. STUDY DESIGN: Sputum and buccal cell samples were obtained from 846 patients without pulmonary disease, with nonmalignant disease, chronic obstructive pulmonary disease, asbestosis and lung cancer, stained for DNA, scanned by cytometer and scored. This was related to specificity and sensitivity for lung cancer. At score 4.5 sensitivity was 53.8% and specificity 70.9%. This score and higher were defined as high scores (HS) and used to compare groups with lung cancer and other pulmonary disease. RESULTS: Among subjects without disease, 21.1% had HS in sputum cells. Among those with nonmalignant pulmonary disease, 31.7% had HS, and among subjects with lung cancer, 53.8% had it. Repeated evaluations showed that about one third of those with HS on the first occasion were normal on repeat sampling. Among subjects without lung cancer, 33.8% of never-smokers had sputum cell HS compared to 22.7.2% among smokers. CONCLUSION: Results demonstrate that the DNA cellular characteristics on cytometry were more frequent among subjects with lung cancer but also among subjects with other pulmonary disease compared to subjects witbout pulmonary disease.

Antifungal treatment in sarcoidosis--a pilot intervention trial.

BACKGROUND: Sarcoidosis is generally treated with corticosteroids that are not always an effective therapy. OBJECTIVES: To assess if treatment with antifungal drugs would improve the clinical status of patients with sarcoidosis. METHODS: Patients (n=18) with sarcoidosis grades II and III according to established criteria and without clinical and immunological signs of fungal infection, were treated with antifungal medication together with corticosteroids for 3-6 months. Pulmonary X-ray infiltration, lung function, and severity of symptoms were registered before and after the treatment and at follow up 9-58 months later. RESULTS: The treatment resulted in statistically significant decreases in the degree of pulmonary infiltration with an average decrease in the group from 2.0 to 1.0. There were also significant increases in diffusion capacity and decreases in the severity of symptoms. CONCLUSION: It is suggested that treatment with antifungal drugs may be useful, at least in certain cases of sarcoidosis.

ß-glucan in the lymph nodes in sarcoidosis and in Kveim-Siltzbach test reagent.

Background: Previous studies have demonstrated a relationship between biomass of fungi exposure in the home and the risk of sarcoidosis. ß-glucan was present in the bronchial alveolar lavage fluid (BALF) of patients with sarcoidosis. The Kveim-Siltzbach test reagent (KSTR) induces a sarcoidosis specific, granulomatous, cutaneous response and was used to establish the diagnosis. To date, the granuloma-inducing component of KSTR is still unknown. The present study was undertaken to investigate the presence of ß-glucan in the lymph nodes of patients with sarcoidosis and to determine the relationship between the amounts of this agent with disease severity and to investigate the presence of ß-glucan in KSTR. Materials and methods: Lymph node aspirations were collected by transbronchial needle aspiration (TBNA) in region R4 or 7 from patients with newly diagnosed sarcoidosis. The samples were treated to isolate ß-glucan and analyzed using a Limulus-based assay. Cultures of Propionibacterium ac. and Mycobacterium gordonae as well as samples of Kveim-Siltzbach test reagent were analyzed to determine ß-glucan content. Results: A significant relationship was observed between the amount of the ß-glucan in the lymph nodes and the extent of granuloma formation in the lung parenchyma, and the size of the lymph nodes in the mediastinum (r=0.787, p=0.0001 and r=0.664, p<0.001 respectively, Spearman's test). The samples of Kveim-Siltzbach test reagent contained high levels of ß-glucan. Cultures of Propionibacterium ac. and Mycobacterium gordonae contained ß-glucan, the levels of which were lower in the Mycobacterium cultures. Comments: The results support the hypothesis that ß-glucan, and thus fungal exposure, are involved in the pathogenesis of sarcoidosis. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 130-135).

Endotoxin and occupational airway disease.

PURPOSE OF REVIEW: This review provides an update on the role of bacterial endotoxin in occupational airway disease, a problem of importance from diagnostic and preventive points of view. RECENT FINDINGS: Data from human inhalation studies have increased our understanding of the cell mechanisms underlying diseases related to endotoxin exposure. In addition, knowledge from molecular genetics may help us to identify individuals at risk. Several investigations have demonstrated that, apart from endotoxin, other microbial cell wall agents are also related to the risk for symptoms of occupational lung diseases, with pathogenic mechanisms different to those caused by endotoxin. Diagnostic methods have progressed from traditional lung function measurements to sampling of indicators of inflammation in the blood, nasal lavage and induced sputum. Investigations of a longitudinal design have provided important findings on the relationship between acute and chronic effects as well as exposures of risk and risk factors among individuals. SUMMARY: Endotoxin, as well as other agents derived from microbes, are important causative agents for occupational respiratory and other diseases, and exposure may occur in a large variety of occupational environments. Recent data from longitudinal studies provide important information on diagnostic and preventive measures.

Magnesium Status in Alzheimer's Disease: A Systematic Review.

The interest in poor magnesium (Mg) status as risk factor for Alzheimer's disease (AD) is increasing due to its antioxidant and neuroprotective properties. A systematic PubMed literature search of studies investigating Mg status was undertaken comparing AD to healthy controls (HCs) or patients with medical illness (medical controls [MCs]). Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) were calculated for all outcomes. Of 192 potentially eligible studies, 13 were included (559 patients with AD, 381 HCs, and 126 MCs). Compared to HCs, patients with AD had significantly lower Mg in cerebrospinal fluid (2 studies; SMD = -0.35;P= .02) and in hair (2 studies; SMD = -0.75;P= .0001). No differences between AD and controls were evident for serum Mg. In conclusion, AD seems to be associated with a lower Mg status when compared to HCs, while the scarcity of studies limited the findings about MCs.