Formaldehyde and cancer morbidity among male employees in Denmark

Formaldehyde, a genotoxic and potent animal carcinogen, is widespread in the working environment as well as in private homes. The risk for cancer morbidity in Denmark during 1970–84 was estimated from standardized proportionate incidence ratios (SPIR) among men whose longest employment had been held since 1964, at least 10 years before diagnosis, in 265 companies in which exposure to formaldehyde was identified. The results do not support the hypothesis that formaldehyde is associated with lung cancer (SPIR=1.0,410 cases). Significantly elevated risks were found for cancers of the colon (SPIR=1.2,166 cases), kidney (SPIR=1.3,60 cases), and sino-nasal cavities (SPIR=2.3,13 cases). For sino-nasal cancer, a relative risk of 3.0 (95 percent confidence interval=1.4–5.7) was found among blue-collar workers with no probable exposure to wood dust, the major confounder. This study provides further evidence that occupational exposure to formaldehyde increases the risk for sino-nasal cancer.     

In vitro effect of r-verapamil on acute myelogenous leukemia blast cells: studies of cytokine secretion and cytokine-dependent blast proliferation

The in vitro effect of the dextroisomer r-verapamil on blast cells derived from patients with acute myelogenous leukemia (AML) was studied. R-verapamil caused a dose-dependent inhibition of AML blast proliferation in the presence of stem-cell factor, leukemia inhibitory factor, interleukin 4, interleukin 6, and interleukin 10 when these cytokines were tested both alone and in different combinations. R-verapamil also inhibited the growth of clonogenic AML blast cells. The antiproliferative effect was not specific for AML blast cells, because r-verapamil also inhibited cytokine-dependent proliferation of blast cells derived from patients with acute lymphoblastic leukemia. The inhibitory effects of r-verapamil and anti-IL1 serum were additive, suggesting that the antiproliferative effect of r-verapamil does not depend solely on inhibition of IL1-mediated effects. Although r-verapamil inhibited spontaneous AML blast proliferation, for a majority of patients it caused only minimal, if any, inhibition of spontaneous cytokine secretion (IL1, IL1, TNF, IL6) by AML blast cells. Thus, although inhibition of IL1 effects may contribute in certain patients to the antiproliferative effect of r-verapamil, mechanisms other than IL1 inhibition seem to be more important in mediating the effects of r-verapamil.Abbreviations ALL Acute lymphocytic leukemia - AML acute myelogenous leukemia - cpm counts per minute - ELISA enzyme-linked immunosorbent assay - G-CSF granulocyte colony-stimulating factor - GM-CSF granulocyte-macrophage colony-stimulating factor - IL interleukin - IF leukemia inhibitory factor - PBMC peripheral blood mononuclear cells - RR relative response - SCF stem cell factor - TNF tumor necrosis factor      

Detection of polycyclic aromatic hydrocarbon metabolites by high-pressure liquid chromatography after purification on immunoaffinity columns in urine from occupationally exposed workers

Objective: The objective in our study was to quantitate benzo[a]pyrene (B[a]P) metabolites by a combination of immunoaffinity chromatography and high-pressure liquid chromatography (HPLC) with fluorescence detection in urine from workers exposed to high levels of polycyclic aromatic hydrocarbons (PAH). Furthermore, by the simultaneous quantitation of 1-hydroxypyrene, the correlation between the B[a]P-tetrol and 1-hydroxypyrene would provide a means of evaluating the validity of 1-hydroxypyrene as a surrogate biomarker for occupational exposure to the potent carcinogen B[a]P in an electrode paste plant. Methods: The study was carried out at an electrode paste plant that produces electrode paste for Söderberg electrodes. A total of 34 pre- and post-shift urine samples and 17 personal air samples were collected from 17 workers during a normal work week. The concentration of 1-hydroxypyrene was measured in all urine samples. A recent method of quantitating B[a]P-r-7, t-8, t-9, c-10-tetrol in urine of humans exposed to low levels of PAH has been described. A modified version of this method involving purification of urine samples on immunoaffinity columns and HPLC analysis with fluorescence detection was used on urine samples from workers exposed to high levels of PAH. A monoclonal antibody (8E11) with binding affinity to B[a]P-tetrols was used. This antibody also binds several PAH-DNA adducts and metabolites, including 1-hydroxypyrene. Gas chromatography/mass spectroscopy (GC/MS) was also used for identification of metabolites isolated by HPLC fractionation. Results: From personal air sampling the mean exposure to particulate PAHs was 38?μg/m³. The mean concentration of urinary 1-hydroxypyrene was 3.9?μmol/mol creatinine in preshift samples and 10.2?μmol/mol creatinine in postshift samples. We could not identify detectable amounts of urinary B[a]P-tetrol by HPLC or fluorescence spectroscopy after purification on immunoaffinity columns. However, in the HPLC analysis we identified several hydroxyphenantrene metabolites that were detected at relatively high concentrations in all of the workers' urine samples. We could not separate 2- and 3-hydroxyphenanthrene (2?+?3-OH-Phe) in peak 1, and peak 2 contained both 1- and 9-hydroxyphenanthrene (1?+?9-OH-Phe). The phenanthrene metabolites were mainly conjugated to glucuronic acid and sulfate. There was a significant correlation between the 1-hydroxypyrene concentration and 2?+?3-OH-Phe (r?=?0.73) and 1?+?9-OH-Phe (r?=?0.64) in the urine samples. 1-Hydroxypyrene was measured in all post-shift urine samples but was not significantly correlated with workplace pyrene exposure, indicating that skin exposure is an important route of pyrene exposure in this factory. As with 1-hydroxypyrene, dermal PAH uptake may also account for the poor correlation between 2?+?3- and 1?+?9-OH-Phe and ambient phenanthrene. Discussion: Since dermal uptake is likely to be important in occupational PAH exposure in addition to inhalation, estimation of total PAH exposure is best achieved by quantitation of PAHs excreted into body fluids. However, it remains unclear whether there might be a difference in uptake and urinary excretion of 3-ring, 4-ring, or 5-ring PAHs and in the correlation between these metabolites and ambient-air PAH measurements. In summary, using immunaffinity chromatography, we did not find detectable amounts of B[a]P-tetrol in urine from workers occupationally exposed to PAH. However, by an HPLC/immunoaffinity method, relatively high amounts of 1-hydroxypyrene as well as 2?+?3- and 1?+?9-OH-Phe were quantitated in the urine samples, both of which are relevant as biomarkers of PAH exposure.     

Chronic treatment with epidermal growth factor stimulates growth of the urinary tract in the rat

Twenty-four male Wistar rats, 8 weeks old, were allocated into three groups and treated with human recombinant epidermal growth factor (EGF) administered subcutancously in doses of 0, 30, and 150 g/kg per day for 4 weeks. Blood sampling was done every 2nd week and urine sampling was done for 2 consecutive days every week. The most striking finding was that the ureters were dose dependently enlarged, due to growth of all layers of the ureteric wall. The urothelium of the bladder showed considerable hyperplasticity with a widening of the basal proliferative compartment and a normal differentiation pattern as observed by the expression of carbohydrate epitopes, characterized with lectinohistochemistry. Blood examination revealed a decrease in blood haemoglobin concentration and a slight increase in serum creatinine concentration in the high-dose group. There were no effects of EGF on the urinary excretion of electrolytes, proteins, and endogenous EGF.     

Schwangerschaft bei Konnektivitiden

Zusammenfassung Schwangerschaften bei Frauen mit Konnektivitiden sind häufig mit Risiken für Mutter und Kind verbunden. Ausschlaggebend sind der Umfang der Organbeteiligung, das Vorhandensein von Autoantikörpern und die Art der medikamentösen Behandlung. In dieser Übersicht werden die Besonderheiten einer Schwangerschaft bei rheumatoider Arthritis, systemischem Lupus erythematodes und ankylosierender Spondylitis vorgestellt. Risiken für die Mutter sind aktive Krankheit oder ein Schub während der Schwangerschaft. Risiken für den Schwangerschaftsverlauf und das Kind sind spontaner Abort, Präeklampsie, intrauterine Wachstumsstörung, Prämaturität und Krankheit des Neugeborenen. Das Vorliegen von Antiphospholipidantikörpern und Antikörpern gegen SS-A und SS-B erfordert eine sorgfältige Überwachung der Schwangerschaft. Eine medikamentöse Therapie erfolgt bei aktiver Krankheit während der Schwangerschaft oder prophylaktisch, um einen Schub zu vermeiden. Bei Konnektivitiden sollten die Schwangerschaften geplant sein und in einem Zustand der Remission und bei stabiler medikamentöser Therapie erfolgen. Regelmäßige Kontrolle und Überwachung des Fetus sind Bedingung für einen unkomplizierten Schwangerschaftsverlauf.     

Patients’ experience of partial tooth loss and expectations to treatment: a qualitative study in Danish and Swedish patients

Knowledge of impairments, wishes and expectations is essential to make correct decisions regarding oral rehabilitation. The purpose of this study was to investigate discomforts, wishes and expectations in patients’ with partial edentulism before entering oral rehabilitation. In Copenhagen, Denmark, and Malmö, Sweden, respectively, 20 patients with partial edentulism seeking rehabilitation were interviewed in a semistructured qualitative manner. The interviews were transcribed and analysed yielding overall domains. Six themes appeared as overall domains: (i) experienced impairments, (ii) experienced social awareness, (iii) expectation to treatment, (iv) expectation to durability/survival, (v) coping strategies dealing with the tooth loss including explanations of the tooth loss and (vi) modifications to experienced impairment. The impairments were mostly experienced as problems in social settings. Most participants expressed a simple wish to function normally; a fixed solution was preferred. Many Danish participants accepted a removable solution whereas only few Swedish participants did so. The domains ‘coping strategies’ and ‘modifications’ were not part of the chosen topics of interest, indicating a high wish of the participants to explain their tooth loss and how they coped with it. In conclusion, a large degree of social impairment was found in the patient group along with several coping strategies. The impairments were modified by a number of factors indicating that highly individualised care and treatment is needed. A state of normality was described as the primary treatment wish with a higher acceptance of removable solutions in Denmark than in Sweden. For final decision‐making, surrounding factors seemed to influence the patients’ choices.     

Skin Sensitization in School Children in Northern and Southern Norway

It has been suggested that environmental exposures and living conditions can explain some of the worldwide variation in atopic disorders. Norway has large environmental contrasts within the country. We compared skin prick sensitization rates among school children living in the southern subarctic and in the northern artic part of Norway. Approximately one quarter of the children were sensitized, mostly against pollen and animal dander, while mite and mould sensitization seemed to be a minor problem. Sensitization rates and profiles were similar in the north and south despite differences in living conditions and environmental exposures.