Failure of iron chelators to reduce tumor growth in human neuroblastoma xenografts.

Neuroblastoma (NB) is a high risk tumor of childhood, and raised serum ferritin is an adverse prognostic factor. The hypothesis that iron chelation therapy impacts tumor status and patient prognosis through changes in iron metabolism has been systematically evaluated here in a xenograft model of human NB. One of two iron chelators was given in seven different regimens to nude mice xenografted s.c. with either IMR-32, an established cell line, or JBN-1, heterotransplanted directly from a patient. Nude mice (a total of 160 in 24 cohorts) were given: desferrioxamine (DFO) by s.c. bolus or reservoir; 1,2-dimethyl-3-hydroxypyridin-4-one (L1), i.p. or orally; or saline. Measurements of mean Hb and liver iron levels were compared with corresponding saline cohorts per regimen as well as for pooled cohorts per agent for both cell lines. For IMR-32 xenografts, significant differences in Hb were achieved with L1 (10.9 g/dl pooled versus 13.7 g/dl controls) and in liver iron with DFO and L1 (235 microg/g and 306 microg/g, respectively, versus 520 microg/g). For JBN-1, the pattern was similar. With L1, H6 was 10.2 g/dl and controls were 11.7 g/dl (individual DFO cohorts were also significant); liver iron with DFO was 303 microg/g, liver iron with L1 was 270 microg/g, and controls were 387 microg/g. Additional therapy prior to tumor injection (67 mice and 10 cohorts) did not increase the depletion. Despite documentation of iron depletion, no reductions in tumor engraftment, latency, or tumor size at end point were achieved in the chelator-treated mice, compared with controls populations. Accordingly, inclusion of these iron chelators in clinical trials for NB appears unwarranted.

Ferritin production and desferrioxamine cytotoxicity in human neuroblastoma cell lines.

In patients with neuroblastoma, elevated serum ferritin is correlated with adverse outcome. In this investigation, three human neuroblastoma cell lines have been characterised in terms of their levels of both intracellular and secreted ferritin and their response to the iron-chelating agent, desferrioxamine (deferoxamine). The cell lines differed markedly in respect of ferritin production as determined by radioimmunoassay. Intracellular and secreted ferritin concentrations for SH-SY5Y and BE(2)-C cells were several fold higher than that determined for IMR-32 cells. IMR-32 cells were most sensitive to desferrioxamine, BE(2)-C intermediate and SH-SY5Y the most resistant to the drug in terms of the respective ID50 values. Combining the differentiating agent retinoic acid with desferrioxamine did not enhance cytotoxicity in the neuroblastoma cells. The present data suggest that neuroblastoma cells secreting a relatively low levels of ferritin may be most responsive to iron chelating agents.

[Occupationally-induced diseases, a contribution to epidemiologic methodology with results from mining]. / Arbeitsbedingte Erkrankungen, ein Beitrag zur epidemiologischen Methodik mit Ergebnissen aus dem Bergbau.

For mining exposures the work-relatedness of morbidity measures and functional organ-related disorders was analysed on the base of data concerning medical screening, occupational exposure and disablement. Morbidity corresponds with intensity of occupational exposure. Using risiko measures results for disorders were interpreted in relation to a hypothesis, which allows to distinguish in our opinion diseases without work-relatedness from work-related and occupational diseases. The availability of a "normal exposed" control group and the choice of a well-defined exposed group, for which the definition of selected diseases as work-related is applicable alone, are decisive for the results. For mining exposures functional disorders of muscular and skeletal system require particular consideration.

[Observations on the course of borderline hypertension in workers in ore mining with variable occupational body burden]. / Beobachtungen zum Verlauf der Grenzwerthypertonie bei Werktätigen im Erzbergbau mit unterschiedlichen professionellen Belastungen.

The blood pressure response of 198 ore miners--working above ground as well as underground--suffering from borderline-hypertension was checked over a period of 5 years. After a period of 5 years 40.9% of the test persons developed a hypertension in 18.7% of the miners the blood pressure returned to normal and with 40.4% it remained within the limits. No statistically significant relationship could be established between the blood pressure response and the various work loads such as the complex work load on face workers, work above ground and underground, shift work, the total time away from home, physically heavy work as well as exposure of the body or part of it to vibrations. Since the individual risk of developing hypertension, particularly with regard to people affected by borderline-hypertension, cannot be predicted the factory doctor has to provide for the adequate health care the group in question.

[The effect of occupational stress on blood pressure of miners in ore mines]. / Einfluss der Arbeitsbelastung auf das Blutdruckverhalten von Bergarbeitern im Erzbergbau.

It was tried to analyse the influence of occupational load on the blood pressure reaction of miners. 200 miners at the age of 25-45 years with a large number of simultaneously affecting loadings at the place of work were examined with regard to the incidence of hypertension within a period of 5 years. The incidence of hypertension was 0.90%. To investigate the blood pressure reactions during an eight-hour shift we chose 2 technologies of mining differing concerning the loading factors, especially the intensity of physical load. In each case 5 miners of the technologies propulsion and mining were examined before the descent, during the eight-hour shift and after having finished the shift and the blood pressure was taken paying attention to standard conditions. The systolic blood pressure taken during an underground mining shift was significantly lower than the systolic blood pressure before the descent and after the shift, while a slight ascent of the diastolic blood pressure was insignificant. In spite of the different physical load we found no signs for a relevant displacement of the blood pressure level. A influence of working on the blood pressure reaction was found neither in the incidence of hypertension nor in the measurements of the blood pressure during an eight-hour miner's shift.

[Diagnostic specific values of disability duration--a contribution to the epidemiologic analysis of empirical morbidity figures]. / Diagnosenspezifische Falldauerwerte--ein Beitrag zur epidemiologischen Analyse empirischer Krankenstandskennziffern.

In view of the great importance of the disablement period for the sickness figure, a method for interpreting empirical distributions of disablement periods is presented which yields practical information for optimizing diagnosis-specific disablement case periods. By approximating the disablement period distribution via a log-normal distribution, the location parameters mode, median and other quantiles can uniquely determined. The cumulatively determined frequencies of the disablement days with reference to chosen location parameters illustrate the possibilities of maintaining the capacity to work and the necessity of intensifying the medical care if diagnosisuntypical disablement periods are exceeded. To establish these requires further research of concrete long-dated disablement cases.

Asbestosis en trabajadores expuestos

Se estudia la prevalencia de asbestosis en ochenta y dos (82) trabajadores de la Fábrica Dominicana de Asbesto, encontrándose un alto porcentaje de la misma en forma que tal el 42.6% de los trabajadores padecían la enfermedad. La mayoría laboraba horas extras y enía más de diez años en contacto con el asbecto. Cabe destacar que el 49% del los trabajadores investigados desconocían los potenciales peligros del asbesto para la salud

[Drug-taking behavior of workers with hypertension in the health service of the Wismut public health district]. / Untersuchungen des Medikamenten-Einnahmeverhaltens bei Werktätigen mit Bluthochdruck im Betreuungsbereich des Gesundheitswesens Wismut.

In 353 workers with a medicamentously stabilized high blood pressure following an educational lecture on hypertension the compliance was determined by means of a patients' questionnaire. Circa 70% of the hypertensives reported to take regularly the medicaments prescribed, in which cases approximately 50% admitted to discontinue the taking of medicaments without having conferred with the attending physician when the well-being was disturbed. As essential factors influencing the compliance 4 features were determined: the opinion concerning the duration of the treatment of hypertension, the attitude to the prescription of medicaments, the frequency of taking the tablets and the observation of the terms of control of blood pressure, whereas, for instance, age, working place, professional activity and shift work had no remarkable influence. Before long an improvement of the compliance can be achieved by the decrease of the information deficit proved and by an improved motivation in form of the group therapy. A necessary prerequisite is the complete registration and comprehensive treatment in the dispensary of the works medical officer with established control terms, short times of waiting and sufficient time for a talk between physician and patient.

[Epidemiology of chronic bronchitis from the viewpoint of occupational medicine]. / Zur Epidemiologie der chronischen Bronchitis unter arbeitsmedizinischem Aspekt.

In a comprehensive epidemiological study the influence of age, smoking and exposure to dust upon the prevalence of chronic bronchitis could be confirmed and quantified. From the quantified contributing factors it is evident that chronic bronchitis after exposure to dust cannot generally be declared as occupational disease. The relative risk of heavy smokers of 1,9 is of the same order as the relative risk after 20 years' exposure to dust. Individual measures of health control and health care are necessary and should be intensified after 10 years of exposure.