Direct haemodynamic effects of pulmonary arteriovenous malformation embolisation

Background

Transcatheter embolisation is widely used to close pulmonary arteriovenous malformations (PAVMs) in patients with hereditary haemorrhagic telangiectasia (HHT). Data on the direct cardiovascular haemodynamic changes induced by this treatment are scarce.

Objectives

We investigated the direct haemodynamic effects of transcatheter embolisation of PAVMs, using non-invasive finger pressure measurements.

Methods

During the procedure, blood pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and delta pressure/delta time (dP/dt) were continuously monitored using a Finometer®. Potential changes in these haemodynamic parameters were calculated from the pressure registrations using Modelflow® methodology. Absolute and relative changes were calculated and compared using the paired sample t-test.

Results

The present study includes 29 HHT patients (mean age 39?±?15 years, 11 men) who underwent transcatheter embolotherapy of PAVMs. The total number of embolisations was 72 (mean per patient 2.5). Directly after PAVM closure, SV and CO decreased significantly by ?11.9 % (p?=?0.01) and ?9.5 % (p?=?0.01) respectively, without a significant change in HR (1.8 %). Mean arterial blood pressure increased by 4.1 % (p?=?0.02), while the TPR and dP/dt did not increase significantly (5.8 % and 0.2 %, respectively).

Conclusions

Significant haemodynamic changes occur directly after transcatheter embolisation of PAVMs, amongst which a decrease in stroke volume and cardiac output are most important.     

Epidemiology of pediatric primary malignant central nervous system tumors in Iran: A 10 year report of National Cancer Registry

BackgroundCNS tumors are the leading cause of cancer related deaths among children and adolescents. Nonetheless, the incidence of pediatric CNS tumors in developing countries is poorly understood. We aimed to provide epidemiologic features of primary malignant CNS tumors in Iranian children 0–19 years of age using National Cancer Registry (NCR) data bank.MethodsThe data recorded by NCR over a 10 year period (2000–2010) were reviewed.ResultsOf 1948 tumor cases, 93.3% were located in brain, 5.1% were found in the spinal cord & cauda equina, and 1.6% affected cranial nerves and other parts of the nervous system. The overall average annual age specific incidence rate was 1.43 per 100,000. Males were more likely to develop CNS tumors (1.65 per 100,000) compared to females (1.21 per 100,000, p < 0.01). Children under 5 years of age had the highest age specific incidence rate (1.86 per 100,000). Astrocytic tumors with the incidence rate of 0.61 per 100,000 were the most frequent specific histology followed by embryonal (0.38 per 100,000), and ependymal tumors (0.10 per 100,000). With regard to the histological distribution of tumors, some unique features including the high proportion of unspecified malignant neoplasms (7.6%) were noted.ConclusionThe overall incidence rate was markedly lower than western findings. Major differences were also observed in incidence rates of specific histologies. Although the discrepancies may be attributable to diversity in classification schemes and registration practices, a real ethnic and geographical variation in predisposition to development of pediatric CNS cancers is strongly suggested.     

Population-based survival analyses of central nervous system tumors from 1994 to 2008. An up-dated study in the temozolomide-era

The present population-based study describes the survival of malignant central nervous system (CNS) tumors diagnosed during 15 years. Also, we obtained individual data regarding the use of temozolomide to analyze the impact of this drug on the survival of patients diagnosed with glioblastoma. From 1994 to 2008, a total of 679 incident cases of primary CNS tumors were reported by the Girona Cancer Registry after excluding 39 cases diagnosed by death certificate only. Number of cases and the corresponding proportion for each CNS histological subtype in the study population were: 25 oligodendroglial and oligoastrocytics (3.7%), 22 ependymal tumors (3.2%), 24 embryonal (3.5%), 372 astrocytic (54.8%), 1 choroid plexus (0.1%) and 235 without histological confirmation (34.6%). Observed survival after 5 years since diagnosis for the histological subtype were: 58.8%; 47.5%; 37.0%; 14.5% and 6.5%, respectively (p < 0.001). Survival of patients diagnosed with glioblastoma according to temozolomide treatment (yes/no) was 60.8% vs. 13.6% and 5.9% vs. 2.5% after 1 and 5 years since diagnosis, respectively. Short-term survival was higher for patients diagnosed with glioblastoma and treated with temozolomide than patients not treated with temozolomide.     

Cerebrospinal Fluid and Plasma Oxidative Stress Biomarkers in Different Clinical Phenotypes of Neuroinflammatory Acute Attacks. Conceptual Accession: From Fundamental to Clinic

Oxidative stress is revealed as the main contributor in the pathophysiology of neuroinflammation. Analyzing plasma and cerebrospinal fluid (CSF) of patients with different clinical phenotypes of neuroinflammation, defined as clinically isolated syndrome (CIS), and those defined as relapsing remitting multiples sclerosis (RRMS), we tested peripheral and CNS oxidative stress intensity in these neuroinflammatory acute attacks. All obtained values changes were assessed regarding clinical and radiological features of CNS inflammation. The obtained results revealed an increase in malondialdehyde levels in plasma and CSF in CIS and RRMS patients compared to control values (p < 0.05). The obtained values were most prevailed in both study group, CIS and RRMS, in patients with severe clinical presentation (p < 0.05). Measured activities of catalase and total superoxide dismutase were higher in CIS and RRMS patients in plasma compared to control values (p < 0.05), parallel with an increased catalase activity and decrease in superoxide dismutase activity in CSF regarding values obtained in control group (p < 0.05). The positive correlations regarding clinical score were obtained for all tested biomarkers (p < 0.01). Although the positive correlations were observed in MDA levels in plasma and CSF, for both study patients, and their radiological findings (p < 0.01), and a negative correlation in plasma SOD activity and CIS patients’ radiological findings (p < 0.01), no other similar correlations were obtained. These findings might be useful in providing the earliest antioxidative treatment in neuroinflammation aimed to preserve total and CNS antioxidative capacity parallel with delaying irreversible, later neurological disabilities.     

Influence of heart failure on nucleolar organization and protein expression in human hearts

We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n=38) and DCM (n=27) patients, undergoing heart transplantation and control donors (n=6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p<0.05) and DCM (141%, p<0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p<0.05) and DCM (1.70-fold, p<0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p<0.0001), and it was increased in pathological hearts (p<0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p<0.05 and 131%, p<0.001) and DCM (56%, p<0.01 and 69%, p<0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p<0.001), perinucleolar chromatin (p<0.01) and dense fibrillar components (p<0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p<0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.     

Comparison of Ketosis,Clinical Mastitis,Somatic Cell Count,and Reproductive Performance between Free Stall and Tie Stall Barns in Norwegian Dairy Herds with Automatic Feeding

Differences in ketosis and clinical mastitis rates, mean somatic cell counts (SCC) and reproductive performance scores (fertility status index = FS-index) between herds housed in free stall (n = 533) and tie stall (n = 59) barns were measured in relation to management and environmental factors in a retrospective cohort study of Norwegian dairy farms with automatic grain feeding systems. Herds with tie stalls were found to have a higher clinical mastitis rate, (61.6 cases per 100 cow-years versus 46.4 cases per 100 cow-years (p<0.01)); a significantly higher proportion of herds with ketosis, (relative risk = 1.59, (p<0.01)); and a lower mean fertility status index, (67.3 versus 82.8 (p<0.01)). No significant difference in mean SCC was found between the 2 groups of dairies (p = 0.32). Large herds had higher Loge geometric mean SCC than small herds (p<0.01) and herds with high SCC had lower milk production than herds with low SCC (p<0.01). Herds that scored “very good” on cow cleanliness had significantly lower adjusted mean SCC than herds with scores of “average” or “good” (p<0.05). Herds in barns with a concrete floor had an adjusted mean number of cases of clinical mastitis of 51.4 per 100 cow-years, 14 per cent higher than herds in barns with rubber mats, litter bed or wood (45.2 cases per 100 cow-years) (p<0.05). Herds with high milk production level had higher FS-index than herds with low milk production (p<0.01). Lower disease rates and the higher fertility status measured in the present study favor free stall herds over tie stall herds.     

Pulmonary tuberculosis mortality risks in a cohort of HIV/AIDS patients in Puerto Rico.

Pulmonary tuberculosis (TB) has re-emerged in relation to the HIV epidemic. To gain knowledge of TB infection in HIV-infected patients, we studied 106 HIV-TB cases in a cohort of 2,646 patients in Puerto Rico between January 1992 and September 1999. The TB prevalence was 4%; 82% were males and 73.6% were injecting drug users (IDU). At the time of TB diagnosis, the mean CD4+ T-cell count was 174/mm3, 35% were in antiretroviral treatment and 42.5% had another AIDS related condition. Only 9% received two or more antiretroviral medications. The death rate in the first year after the TB diagnosis was 55%. A Cox proportional hazard analysis showed that CD4+ T-cells <200/mm3 (p<0.01), history of toxoplasmosis (p<0.01), wasting syndrome (p<0.01) and lack of antiretroviral treatment (p=0.12) increased their mortality risk. The studied patients had a highly compromised immune system at the time of TB diagnosis. Low CD4+ T-cells (essential to control the TB infection) significantly increased the hazard and mortality risk of the cases studied. Early antiretroviral therapy in combination is recommended in HIV-infected patients, particularly in those with IDU, TB history and low CD4+ T-cell levels, to ensure an optimal immune system function that limits the pulmonary TB morbidity and mortality.     

Recurrent pneumonia mortality risk in a HIV/AIDS Puerto Rican cohort.

Recurrent pneumonia (RP) within 12 months is one of the AIDS diagnosis criteria. To gain knowledge of RP infection in HIV-infected patients, we studied 145 RP cases detected in a cohort of 2,996 HIV patients in Puerto Rico between Jan. 1992-Dec. 2001. The RP prevalence was 4.8%; 77.2% were males and 62.1% were injecting drug users (IDU). At the time of RP diagnosis, the mean CD4+ T cell count was 93.8 cells/mm3, 59.3% were in antiretroviral treatment, 13% had received the pneumococcal vaccine and 84.8% had another AIDS related condition. Over 37% received two or more antiretroviral medications. The death rate in the first year after the RP diagnosis was 63.4%. A Cox proportional hazard analysis showed that CD4+ T cells <200/mm3 (p<0.05), history of toxoplasmosis (p<0.01), wasting syndrome (p<0.01), esophageal candidiasis (p<0.05) and lower number of antiretroviral medications (p<0.05) increased their mortality risk. The studied patients had a highly compromised immune system and a very low pneumococcal vaccination percent at the time of RP diagnosis. Low CD4+ T cells significantly increased the hazard and mortality risk of the cases studied. Antecedents of antiretroviral therapy in these patients ensure a better outcome with lower mortality. Efforts to increase the vaccination rate should reduce the RP incidence in our HIV-infected population.     

Protection of the ischaemic dog heart by oxfenicine

Myocardial ischaemia was produced in closed-chest anaesthetised dogs by coronary embolisation with Sephadex microspheres. Myocardial enzyme release and lactate production were used to quantitate the severity of ischaemia. In dogs pretreated with oxfenicine (S-4-hydroxyphenylglycine; 0.1mmol.kg^?1) 1h prior to embolisation, peak lactate production (extraction ratio ?25±13%) was significantly less than in control dogs (?72±5%; p < 0.01), and the time post-embolisation at which nett lactate uptake became re-established was reduced from 1.4h to 0.4h. Myocardial release of lactate dehydrogenase isoenzyme 1 (HBDH) up to 5h post-embolisation was reduced by 40% in oxfenicine pretreated dogs and there was a similar reduction in the HBDH arterio-coronary sinus difference. Since oxfenicine pretreatment did not modify the major haemodynamic determinants of myocardial oxygen consumption, we conclude that these beneficial effects result from the ability of oxfenicine to divert myocardial metabolism from fatty acid to carbohydrate oxidation, with a consequent reduction in oxygen demand.     

内蒙古地区乙型肝炎病毒的基因分型及临床意义

为了探讨乙型肝炎病毒在内蒙古地区的基因分型,为本地区乙型肝炎的临床治疗、病情进展和发病机制等方面研究提供有益的实验依据。2013年7月至2014年7月本研究在内蒙古自治区人民医院、内蒙古医科大学第一附属医院、通辽市医院的门诊及住院病例中随机选取已感染乙型肝炎病毒的253例。以荧光定量PCR法检测HBV基因分型和HBV病毒基因载量,Elisa法检测血清标志物HBeAg,全自动生化分析仪检测ALT、AST、TBA、TBIL和ALB。实验发现,内蒙古地区253例患者HBV基因分型结果以B型(49例,19.37%)、C型(188例,74.31%)为主,且C基因型显著多于B基因型(p<0.05);HBeAg阳性率为67.59%,且C基因型HBeAg阳性率高于B基因型;高载量病例中B型占31例(63.27%),而C型占162例(86.17%),C基因型组中HBV DNA载量显著高于B基因型组(p<0.01);B基因型与C基因型TBA、TBIL和ALB结果比较差异无统计学意义(p>0.05),但C基因型的ALT和AST这两项生化指标均显著高于B基因型组(p<0.05)。本研究结果初步说明,内蒙古地区HBV感染以B型和C型为主,尤以C型居多;且C型病毒的复制较活跃,致病力较强,HBV感染者更易转成严重肝病。     

Syndecan-1 and Syndecan-4 Are Independent Indicators in Breast Carcinoma

Syndecan proteoglycans may be key regulators of tumor invasion and metastasis because this four-member family of transmembrane receptors regulates cell adhesion, proliferation, and differentiation. Their expression can also serve as prognostic markers. In breast carcinomas, syndecan-1 overexpression correlates with poor prognosis and aggressive phenotype. Syndecan-4 is expressed in most breast carcinoma cell lines, but its role in malignancy is unclear. A possible relationship between syndecan-1 and syndecan-4 expression and established prognostic factors in breast carcinomas was examined. Duplicate samples of 114 benign and malignant breast disease cases were stained for the two syndecans. Clinicopathological information was available for all cases. Syndecan-1 was detected in 72.8% of cases, with significant association between its expression and histological tumor type (p<0.05) and high grade tumors (p<0.05). Syndecan-4 was expressed in 66.7% of cases; expression correlated significantly with positive estrogen (p<0.01) and progesterone (p<0.01) receptor status. Independent expression of the two syndecans was noted from an analysis of single and double positive cases. There was a statistical relationship between syndecan-1 presence in high-grade tumors and absence of syndecan-4, whereas syndecan-4 presence in cases positive for estrogen and progesterone receptor associated with syndecan-1 absence. These syndecans may, therefore, have distinct roles in regulating breast carcinoma cell behavior.     

Cryptococcemia. An analysis of 28 cases with emphasis on the clinical outcome and its etiologic agent

Clinical protocols of 28 cases of cryptococcemia studied between April 1995 and November 2002 were reviewed. The varieties of Cryptococcus neorformans, the underlying disease, and the severity and outcome of the disease were emphasized. Most patients were immunossupressed (89.3% with AIDS) and Cryptococcus neoformans var. grubii was the main recovered variety (92.8%). Regardless of antifungal treatment, in-hospital mortality was 41% strongly associated with APACHE II score, >14 (p<0.01).     

Sleep Parameters among Offshore Workers: An Initial Assessment in the Campos Basin,Rio De Janeiro,Brazil

Shift work has potentially adverse effects on health, particularly on sleep. The purpose of the present study was to assess sleep parameters among personnel working in oil and gas offshore installations in the Campos Basin, Rio de Janeiro, Brazil. One hundred and seventy-nine subjects were asked to complete a sleep questionnaire with multiple-choice answers. Offshore workers were divided into two groups according to their work schedule: (1) fixed daytime workers (n = 86; age: 35.8 ± 9.6 yrs) and (2) shift (n = 87) or night (n = 6) workers (total n = 93; age: 37.7 ± 9.7 yrs). Shift/night workers reported poor sleep more frequently than the daytime workers (20.4% vs. 1.2%, p < 0.01), as well as habitual difficulty in falling asleep (15.1% vs. 4.7%, p < 0.01), long latency of sleep onset (28% vs. 7%, p < 0.01), fragmented sleep (45.2% vs. 16.3%, p < 0.01), short sleep episodes (44.1% vs. 16.3%, p < 0.01), irregular bedtimes (29.0% vs. 12.8%, p < 0.01), and feeling tired upon awakening (15.1% vs. 3.5%, p < 0.01). Habitual napping and loud snoring were reported twice as often in shift/night than in day workers (p < 0.01). Nightmares, somnambulism, and unpleasant feeling in the legs were equality reported by both groups (p > 0.05). Few offshore workers had sought medical help for their sleep problems. A higher number of shift/night workers reported feelings of sadness compared with day workers (26.9% vs. 9.3%, p < 0.01). The findings of this study show that subjective reports of sleep-related problems are quite common among Brazilian offshore shift workers. Reliance on self-reported sleep problems and a cross-sectional design are the main limitations of our study.     

Serum and tissue levels of six trace elements and copper/zinc ratio in patients with cervical cancer and uterine myoma

The aim of this study is to investigate the relationship between trace elements and the incidence of cervical cancer. Tissue and serum levels of six elements (Cu, Zn, Fe, Mn, Ca, and Se) and the Cu/Zn ratio in 40 cases of patients with cervical cancer, 30 cases of uterine myoma, and 50 healthy subjects were measured by atomic absorption spectrophotometry; the selenium content was determined by atomic fluorescence spectrometry. The results showed that the tissue contents of Zn, Se, and Ca were significantly lower and the Cu and Fe concentrations and Cu/Zn ratio were significantly higher in cervical cancer tissue than that for paired nonlesion tissue (p<0.02 and p<0.001, respectively). The serum levels of Zn, Se, Ca, and Fe were lower and Cu and Mn levels and Cu/Zn ratio were higher in patients with cervical cancer than in healthy subjects (p<0.01 and p<0.001, respectively) and in the uterine myoma group compared with healthy subjects (p< 0.05–0.001). There are no significant differences in the contents of six elements and the Cu/Zn ratio between uterine myoma tissue and paired nonlesion tissue. The results showed also that the Fe level and Cu/Zn ratio were significantly higher and the Zn and Se levels were significantly lower in cervical cancer tissue than in uterine myoma tissue (p<0.01 and p<0.001, respectively). The serum Cu level and Cu/Zn ratio were significantly higher in the cervical cancer group than the uterine myoma group (p<0.01). Data were also analyzed using multivarate logistic regression. After adjustment for age, occupation, life habit, and other covariates for the development of cervical cancer, the odds ratios were 22.64 (95% confidence interval [CI]: 5.64–90.88, p=0.001) for Cu, 0.11 (95% CI: 0.034–0.373; p=0.005) for Zn, and 0.60 (95% CI: 0.36–0.99, p=0.01) for Se. Thus, the serum and tissue levels of Cu increase and the deficiency of Zn and Se may be risk factors for the development of cervical cancer.     

Kinematic and EMG characteristics of simple shoulder movements with proprioception and visual feedback.

The objective of this study was to determine if simple, shoulder movements use the dual control hypothesis strategy, previously demonstrated with elbow movements, and to see if this strategy also applies in the absence of visual feedback. Twenty subjects were seated with their right arm abducted to 90 degrees and externally rotated in the scapular plane. Subjects internally rotated to a target position using a custom shoulder wheel at three different speeds with and without visual feedback. Kinematics were collected with a motion analysis system and electromyographic (EMG) recordings of the pectoralis major (PECT), infraspinatus (INFRA), anterior and posterior (ADELT, PDELT) deltoid muscles were used to evaluate muscle activity patterns during movements. Kinematics changed as movement speed increased with less accuracy (p<0.01). Greater EMG activity was observed in the PECT, PDELT, and INFRA with shorter durations for the ADELT, PDELT and INFRA. Movements with only kinesthetic feedback were less accurate (p<0.01) and performed faster (p<0.01) than movements with visual feedback. EMG activity suggests no major difference in CNS control strategies in movements with and without visual feedback. Greater resolution with visual feedback enables the implementation of a dual control strategy, allowing greater movement velocity while maintaining accuracy.     

The neuronal EGF-related gene Nell2 interacts with Macf1 and supports survival of retinal ganglion cells after optic nerve injury

Nell2 is a neuron-specific protein containing six epidermal growth factor-like domains. We have identified Nell2 as a retinal ganglion cell (RGC)-expressed gene by comparing mRNA profiles of control and RGC-deficient rat retinas. The aim of this study was to analyze Nell2 expression in wild-type and optic nerve axotomized retinas and evaluate its potential role in RGCs. Nell2-positive in situ and immunohistochemical signals were localized to irregularly shaped cells in the ganglion cell layer (GCL) and colocalized with retrogradely-labeled RGCs. No Nell2-positive cells were detected in 2 weeks optic nerve transected (ONT) retinas characterized with approximately 90% RGC loss. RT-PCR analysis showed a dramatic decrease in the Nell2 mRNA level after ONT compared to the controls. Immunoblot analysis of the Nell2 expression in the retina revealed the presence of two proteins with approximate MW of 140 and 90 kDa representing glycosylated and non-glycosylated Nell2, respectively. Both products were almost undetectable in retinal protein extracts two weeks after ONT. Proteome analysis of Nell2-interacting proteins carried out with MALDI-TOF MS (MS) identified microtubule-actin crosslinking factor 1 (Macf1), known to be critical in CNS development. Strong Macf1 expression was observed in the inner plexiform layer and GCL where it was colocalizied with Thy-1 staining. Since Nell2 has been reported to increase neuronal survival of the hippocampus and cerebral cortex, we evaluated the effect of Nell2 overexpression on RGC survival. RGCs in the nasal retina were consistently more efficiently transfected than in other areas (49% vs. 13%; n = 5, p<0.05). In non-transfected or pEGFP-transfected ONT retinas, the loss of RGCs was approximately 90% compared to the untreated control. In the nasal region, Nell2 transfection led to the preservation of approximately 58% more cells damaged by axotomy compared to non-transfected (n = 5, p<0.01) or pEGFP-transfected controls (n = 5, p<0.01).     

Role of hepatic arterial embolisation in the carcinoid syndrome.

Eighteen patients with severe symptoms of the carcinoid syndrome were assessed for hepatic embolisation. Four were too ill, and one had mild symptoms; thus 13 received a periembolisation regimen of cyproheptadine, fenclonine, aprotinin, methylprednisolone, tobramycin, flucloxacillin, and metronidazole. Embolisation was not performed in one patient with an occluded portal vein and was unsatisfactory in two others, in one because she was moribund and in the other because the hepatic artery had been ligated. Dramatic improvement in symptoms occurred in the nine patients in whom embolisation was successfully carried out, with abolition of flushing, severe abdominal pain, and wheeze and reduction in diarrhoea from 10.5 (SD 7.6) to 1.6 (0.9) stools/day. Urinary excretion of 5-hydroxyindole acetic acid fell from 1048 (716) to 289 (184) mumol/24 h (200 (137) to 55 (35) mg/24 h). Complications included one death from septicaemia, a hepatic abscess requiring surgical drainage, abdominal pain in three patients, pleural effusion in two, and transient encephalopathy in one. Relief of symptoms lasted for one to 24 months, and second embolisation in two patients produced further remissions of four to six months. Five patients died, one to 40 months after embolisation, in four cases because of metastases or heart failure. Hepatic embolisation is the treatment of choice for symptoms of the carcinoid syndrome resistant to medical treatment.     

Determination of isocyanate biomarkers in construction site workers.

4,4'-Methylenediphenyl diisocyanate (MDI) is the most important isocyanate in the manufacture of polyurethanes, dyes, pigments and adhesives. High concentrations of isocyanates are a potent respiratory irritant. Therefore, it is important to develop methods to monitor exposure to such compounds. We monitored biological samples from 40 non-exposed and 45 exposed construction site workers. 4,4'-Methylenedianiline (MDA) and N-acetyl-4,4'-MDA (AcMDA) were determined from untreated urine (U-MDA, U-AcMDA) and MDA was analysed from acid-treated urine (U-MDA-tot). Haemoglobin (Hb) adducts of MDA (Hb-MDA) were determined in all workers. The levels of biomarkers decreased in the following order: U-MDA-tot>U-AcMDA>U-MDA>Hb-MDA. The same order was found for the percentage of samples, which were found positive in exposed workers: 100%, 91%, 91%, 27%. The urine levels U-MDA-tot correlate with U-MDA, U-AcMDA and Hb-MDA with r=0.79, 0.86 and 0.39, respectively (Spearman rank order, p<0.01). U-AcMDA correlates with U-MDA and Hb-MDA with r=0.77 and 0.47, respectively (p<0.01). U-MDA correlates with Hb-MDA (r=0.38, p<0.05). The levels in the controls were significantly lower than in the exposed workers for all compounds (Mann-Whitney test, p<0.01). The median isocyanate-specific IgE-level was higher in the exposed workers, but the difference was statistically not significant. The change of the biomarker levels was compared in a group of workers (n=20), which were analysed prior to isocyanate exposure and after the exposure for approximately 4-7 months. All urine MDA metabolites and the Hb-adduct levels increased significantly (Wilcoxon sign test, p<0.01). Total IgE increased significantly after the exposure with isocyanate activity (p<0.01). With the present work it could be shown that outdoor workers are exposed to a similar extent as workers from a MDI factory.