Nikolaos I. Stilianakis

Cadmium and children: exposure and health effects.

Cadmium exposure and accumulation in the body start at young age. Exposure routes in children are mainly via food, environmental tobacco smoke and house dust. Excretion from the body is limited. Cadmium accumulation in the kidney is responsible for effects such as nephrotoxicity and osteoporosis which are observed at adult age. Cadmium exposure through inhalation is also associated with lung cancer in adulthood. Although transfer to the neonate through the placenta and through breast milk is limited, teratogenic and developmental effects were observed in experimental animals. The database on human studies involving children is limited, yet effects on motoric and perceptual behaviour in children have been associated with elevated in utero cadmium exposure. In school age children urinary cadmium levels were associated with immune suppressive effects. More studies are needed to confirm these results. Experimental data in vitro and in animals refer to effects of cadmium on the hypothalamus‐pituitary axis at different levels. This may lead to disorders of the endocrine and/or immune system. Cadmium exposure at early age should be limited as much as possible to prevent direct effects on children and to prevent accumulation of cadmium which may have serious health effects only becoming manifest at older age.

Urinary di(2-ethylhexyl)phthalate (DEHP)--metabolites and male human markers of reproductive function.

INTRODUCTION Phthalates are suspected to act as endocrine modulators in humans and exert reproductive toxicity. The general population is exposed to phthalates through nutrition, consumer products, medications and medical devices. The aim of the present study is to explore whether internal phthalate exposure represented by metabolites of di(2-ethylhexyl) phthalate (DEHP) can be related to human markers of reproductive function (i.e. semen concentration, motility and morphology). METHODS We recruited 349 men who were part of subfertile couples and were referred for fertility work-up between April 2004 and November 2005. Semen analysis was performed according to recommendations of the World Health Organization (WHO). Parameters were dichotomized based on 1999 WHO reference values for sperm concentration (<20million/ml) and motility (<50% sperm with progressive motility), as well as Tygerberg strict criteria for morphology (<4% normal forms). We analyzed internal DEHP exposure in single spot urine samples by determining its secondary metabolites mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP), mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP) and 5carboxy-mono(2-ethylhexyl)phthalate (5cx-MEPP) next to the monoester metabolite mono(2-ethylhexyl)phthalate (MEHP). Logistic regression was performed for the three semen parameters (concentration, motility, and normal morphology) to estimate their dependence on the sum of the four DEHP metabolites (DEHP-4) under consideration. Adjustment was performed for age, duration of abstinence, and smoking status. RESULTS DEHP metabolites of n=349 men (age: median=34ys) were analysed. Median concentrations [microg/l] were MEHP (n=337) 4.35, 5OH-MEHP (n=341) 12.66, 5oxo-MEHP (n=341) 9.02, and 5cx- MEPP (n=292) 14.53. Semen parameters of n=349 men were analysed by logistic regression. Semen concentration (<20mio/ml: 35%) or sperm motility (WHO A+B <50%=20%) were not found to be associated statistically significantly with the sum the DEHP metabolites (DEHP-4). DISCUSSION Metabolites of DEHP and other phthalates analyzed in urine are very specific for determining recent internal phthalate exposure. According to our evaluation human reproductive parameters from semen analyses do not show significant associations with concentrations of DEHP metabolites determined in spot urine sampled at the day of andrological examination.

A direct comparison of noninvasive coronary angiography by electron beam tomography and navigator-echo-based magnetic resonance imaging for the detection of restenosis following coronary angioplasty.

Ropers D, Regenfus M, Stilianakis N, et al. A direct comparison of noninvasive coronary angiography by electron beam tomography and navigator-echo-based magnetic resonance imaging for the detection of restenosis following coronary angioplasty. Invest Radiol 2002;37:386–392. rationale and objectives. To compare electron beam tomography (EBT) with MR imaging (MRI) for detection of restenosis after coronary angioplasty (PTCA). methods. One hundred eighteen patients after PTCA were investigated. By EBT, 50 axial images were acquired (3-mm slice thickness, 120–160 mL radiographic contrast agent). MRI was performed using respiratory-gated sequences (24–48 cross-sections, 2-mm slice thickness, 20 mL Gd-DTPA). EBT and MRI images were evaluated concerning high-grade post-PTCA restenosis (≥70%) and validated against coronary angiography. results. In EBT, 28 patients and in MRI, 31 patients were not evaluable. In the remaining patients, sensitivity for restenosis detection was 90% in EBT (17/19) and 73% in MRI (11/15;P = 0.370). In EBT, specificity was significantly higher (66% vs. 49%, P = 0.043). Overall accuracy was 71% for EBT and 53% for MRI (P = 0.014). conclusions. For the detection of high-grade restenosis after PTCA, EBT demonstrated significantly higher accuracy than MRI.

Today's epidemics in children: possible relations to environmental pollution and suggested preventive measures.

Background: Facts and hypotheses on the relationship between some childrens diseases or disorders and external stressors during the developmental stage of a child, both prenatally and postnatally are described in literature. In this paper the following changes in patterns and causes of the main childhood illnesses are summarized and recommendations for actions are made.

Dynamics of infectious disease transmission by inhalable respiratory droplets

Transmission of respiratory infectious diseases in humans, for instance influenza, occurs by several modes. Respiratory droplets provide a vector of transmission of an infectious pathogen that may contribute to different transmission modes. An epidemiological model incorporating the dynamics of inhalable respiratory droplets is developed to assess their relevance in the infectious process. Inhalable respiratory droplets are divided into respirable droplets, with droplet diameter less than 10 µm, and inspirable droplets, with diameter in the range 10–100 µm: both droplet classes may be inhaled or settle. Droplet dynamics is determined by their physical properties (size), whereas population dynamics is determined by, among other parameters, the pathogen infectivity and the host contact rates. Three model influenza epidemic scenarios, mediated by different airborne or settled droplet classes, are analysed. The scenarios are distinguished by the characteristic times associated with breathing at contact and with hand-to-face contact. The scenarios suggest that airborne transmission, mediated by respirable droplets, provides the dominant transmission mode in middle and long-term epidemics, whereas inspirable droplets, be they airborne or settled, characterize short-term epidemics with high attack rates. The model neglects close-contact transmission by droplet sprays (direct projection onto facial mucous membranes), retaining close-contact transmission by inspirable droplets.

The hypothesis of an impact of ozone on the occurrence of completed and attempted suicides

Air pollution and its impact on human health are of growing concern throughout the world. Recent studies have mainly focussed on respiratory and vascular mortality. The existence of seasonality of ozone distribution and also of the occurrence of suicides as well as suicide attempts is generally accepted, though an interconnection of both phenomena has not yet been established. This hypothesis of an influence of ozone on the occurrence of suicidality was tested on preliminary data (1008 suicides and 917 suicide attempts from a larger epidemiological sample in Middle-Franconia from 2004 to 2007). A higher suicide rate than expected could be observed from July to September, whereas the rates of the suicide attempts did not show a seasonality in relation to ozone levels. To further strengthen the hypothesis, ozone levels differed significantly (T = -2.5; p = 0.014) between days where one or no suicide were observed (mean ozone: 79.8 microg/m(3); SD: 36.3) and days with two or more suicides (mean ozone: 86.4 microg/m(3); SD: 39.4). This phenomenon might be explained including sociological, biological as well as psychological effects. Sociologically, behaviour precipitating suicide might be influenced by climatic variables such as the weather or air pollution causing fatigue or cardio-respiratory symptoms influencing individual well-being in general thereby possibly leading to the decision to end ones life. Biologically, ozone is able to influence the immune system, is a strong trigeminal irritant and might influence neurotransmitter systems such as serotonin, which are known to vary with season and play a major role in impulsivity, aggression, depression and thereby suicidality. Putative psychological explanations for the suicide peak in summer include the influence of a higher ambient temperature leading individuals to a more disinhibited, aggressive and violent behaviour possibly resulting in an increased proneness for suicidal acts that is influenced by ozone. This might lead one to speculate whether ozone is able to account - at least amongst others - for the seasonal distribution of suicides or might even be a causative agent in the multifactorial genesis of a suicide. If this hypothesis is found to be true, further research should focus on the underlying mechanisms. Furthermore, this might be a strong argument to further encourage environment protection.

Influences on human internal exposure to environmental platinum

Different influences on internal exposure to platinum are investigated and for the first time weighted in environmentally exposed subjects as far as individual internal platinum concentrations are concerned. Detailed medical and environmental histories as well as oral cavity status were assessed in 84 dermatological patients, and internal platinum exposure was determined by analyzing platinum in urine using adsorptive voltammetry (AV). Platinum concentrations ranged from <0.9 (detection limit) to 65.5 ng Pt/l urine. Influence of different types and age of alloy restorations and therefore relevance of the exposure pathway due to solubilization of platinum in saliva could be demonstrated. No platinum-related health effects (contact stomatitis, asthma or kidney conditions) were observed. Analysis of covariance showed the number of noble dental alloy restorations (P<0.0001) and to a lesser extent age (P=0.0017) to independently influence internal platinum exposure. Even though spread of environmental platinum has increased, internal platinum exposure is low in subjects without assessable medical or dental devices (usually <4.5 ng/l urine) and not related to adverse health effects. For the first time, detailed individual information on possible exposure pathways to platinum were considered in an analysis of relevant influential factors: Car traffic exposure and dermatological condition showed no association with internal platinum exposure. Uptake from platinum containing noble metal dental alloy restorations (NMDAR) is of greatest relevance, surmounting the influence of each year of lifetime on platinum body load by more than 10-fold.

Spatial dynamics of airborne infectious diseases

Abstract Disease outbreaks, such as those of Severe Acute Respiratory Syndrome in 2003 and the 2009 pandemic A(H1N1) influenza, have highlighted the potential for airborne transmission in indoor environments. Respirable pathogen-carrying droplets provide a vector for the spatial spread of infection with droplet transport determined by diffusive and convective processes. An epidemiological model describing the spatial dynamics of disease transmission is presented. The effects of an ambient airflow, as an infection control, are incorporated leading to a delay equation, with droplet density dependent on the infectious density at a previous time. It is found that small droplets ( ∼ 0.4 μ m ) generate a negligible infectious force due to the small viral load and the associated duration they require to transmit infection. In contrast, larger droplets ( ∼ 4 μ m ) can lead to an infectious wave propagating through a fully susceptible population or a secondary infection outbreak for a localized susceptible population. Droplet diffusion is found to be an inefficient mode of droplet transport leading to minimal spatial spread of infection. A threshold air velocity is derived, above which disease transmission is impaired even when the basic reproduction number R 0 exceeds unity.

A Note on the Comparison of Particle Number Counters

Comparison between two systems (methods) of measurement is predominantly performed by linear regression, which in some cases can be misleading. In this note, we employ the example of comparing two particle number counters to show how the limits of agreement statistical approach, used extensively in clinical research, can be an alternative and more reliable way to compare methods.

Assessment of somatic complaints in environmental health

In patients attributing their health complaints to environmental factors (EnvPat) evidence based medical diagnostics usually do not confirm environmental and somatic causes of symptoms. Many symptoms remain unexplained. Aim of the study was the systematic assessment of medically unexplained physical symptoms (MUPS) in EnvPat and comparison to symptom rates reported by subjects of an environmental study exposed to environmental odors (EnvExp). This specific exposure was chosen, as odors are associated by an unclear mechanism with physical symptoms. By this we aimed to enlighten the open question as to likeliness that MUPS of EnvPat are caused by hitherto unrevealed environmental exposures or result from somatization. MUPS were measured with SOMS-2 in EnvPat n=92, patients presenting in a university environmental outpatients clinic, and different study groups exposed to environmental odors (EnvExp). These were: (1) subjects exposed to annoying odors and medically relevant concentrations of bioaerosols, such as airborne microorganisms (EnvExp-1, n=74), and (2) subjects exposed to odors alone (EnvExp-2, n=282) as well as unexposed controls (Controls, n=235). Logistic regression and analysis of variance were applied to analyze rates of single complaints and the sum index of complaints (SOMS-CoIx). In EnvPat rates of MUPS were highest - significant (p<0.05) adjusted OR in 23 of 25 MUPS compared to controls - and highest SOMS-CoIx (mean 15.3 (S.D. +/-9.3). Rates of MUPS were lower in environmentally exposed subjects with difference in the two strata: while EnvExp-1 differed in several complaints, i.e., nausea and SOMS-CoIx (mean 7.2, S.D. +/-6.9) from controls (p<0.05), EnvExp-2 (SOMS-CoIx mean 4.8, S.D. +/-5.2) showed relevant differences only in two single complaints and not in the SOMS-CoIx from controls, SOMS-CoIx mean 3.9, S.D. +/-5.0. This remained when adjusting for age, gender, and school education. Rates of MUPS in environmental patients were clearly higher than in subjects with actual environmental exposure, making it unlikely that their symptoms are due to undetected environmental factors. MUPS of EnvPat show similarities to psychosomatic patients. In the environmental survey symptom assessment by SOMS-2 was sensitive to different environmental scenarios, i.e., higher rates of physical complaints were only found in subjects with hazardous residential bioaerosols pollution as well as an annoying odor exposure and interestingly not in subjects exposed to annoying odors alone. This underlines that questionnaire data of somatic complaints need to be interpreted on the basis of exposure assessment in order to unjustly attribute health complaints to annoyance.