Determination of benzo[a]pyrene diol epoxide-DNA adducts in white blood cell DNA from coke-oven workers: the impact of smoking

We have undertaken a study among coke-oven workers to test the feasibility of an enzyme-linked immunosorbent assay with anti-trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene- DNA antibodies for monitoring occupational exposure to polycyclic aromatic hydrocarbons (PAH). Coke-oven workers are occupationally exposed to relatively high levels of PAH and are at increased risk for lung cancer. Three blood samples were collected from each of the 56 coke-oven workers exposed to PAH and 44 unexposed workers employed in a steel-rolling factory of the same plant. In addition, PAH levels were measured in ambient air by personal sampling, and the excretion of 1-hydroxypyrene in urine was also measured on 3 consecutive working days. All participants were interviewed regarding working conditions, personal hygiene, and smoking habits. The results showed that the coke-oven workers were exposed to substantial concentrations of atmospheric PAH (1-186 micrograms/m3), including benzo[a]pyrene (0.1-7.8 micrograms/m3) and pyrene (0.6-23.6 micrograms/m3). Both benzo[a]pyrene and pyrene were shown to be representative for the whole group of PAH. Forty-seven percent of the coke-oven workers had detectable levels of PAH-DNA adducts in their white blood cells, compared with 30% of the controls. In both groups, smokers had significantly higher levels of PAH-DNA adducts than did nonsmokers. At one site, we found the correlation positive between DNA adducts and the duration of exposure (r = .47, P = .005). Generally, the correlation was not significant between PAH-DNA adducts in blood and the concentration of PAH in the air and 1-hydroxypyrene in urine.     

In vitro and in vivo antileukemic activity of B43-pokeweed antiviral protein against radiation-resistant human B-cell precursor leukemia cells

B-cell precursor (BCP) leukemia is the most common form of childhood cancer and represents one of the most radiation-resistant forms of human malignancy. In this study, we examined the antileukemic efficacy of the B43 (anti-CD19)-pokeweed antiviral protein (B43-PAP) immunotoxin against radiation-resistant BCP leukemia cells. B43-PAP caused apoptosis of radiation-resistant primary BCP leukemia cells, killed greater than 99% of radiation-resistant primary leukemic progenitor cells from BCP leukemia patients, and conferred extended survival to severe combined immunodeficiency (SCID) mice xenografted with radiation- resistant human BCP leukemia. Furthermore, the combination of B43-PAP and total body irradiation (TBI) was more effective than TBI alone in two SCID mouse bone marrow transplantation models of radiation- resistant human BCP leukemia. Thus, B43-PAP may prove useful in the treatment of radiation-resistant BCP leukemia.     

Effect of air space and depth dose in electron beam therapy

In electron beam therapy, alterations in dosimetry occur as a result of air space between the end-of-treatment cone and the skin surface. A large air gap may be introduced in order to obtain a field size larger than that available at the cone end. Needed dosimetry corrections related to these air space problems are discussed, along with a proposed method of measuring effective source-to-cone end distance. Data presented show the modifications of a dosimetric field which occur with an increase in the air space below the treatment cone.     

Measuring mental health of the Dutch population: a comparison of the GHQ-12 and the MHI-5

Backgroud

The objective is to compare the performance of the MHI-5 and GHQ-12, both measures of general mental health. Therefore, we studied the relationship of the GHQ-12 and MHI-5 with sociodemographic characteristics, self-reported visits to general practice and mental health care, and with diagnoses made by the general practitioner.

Methods

Data were used from the Second Dutch National Survey of General Practice, which was carried out in 104 practices. This study combines data from a representative sample of the Dutch population with data from general practice.

Results

The agreement between the GHQ-12 and MHI-5 is only moderate. Both instruments are however similarly associated with demographic characteristics (except age), self-reported health care use, and psychological and social diagnoses in general practice.

Conclusions

The performance of the MHI-5 and GHQ-12 in terms of predicting mental health problems and related help seeking behaviour is similar. An advantage of the MHI-5 is that it has been widely used, not only in surveys of mental health, but also in surveys of general health and quality of life, and it is shorter. A disadvantage of the MHI-5 is that there is no cut-off point. We recommend a study to establish a valid, internationally comparable cut-off point.

     

The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome

Abstract A numeric scoring system for the assessment of hypoxic ischaemic encephalopathy during the neonatal period was tested. The value of the score in predicting neurodevelopmental outcome at 1 y of age was assessed. Forty-five infants who developed hypoxic ischaemic encephalopathy after birth were studied prospectively. In addition to the hypoxic ischaemic encephalopathy score all but two infants had at least one cranial ultrasound examination. Thirty-five infants were evaluated at 12 months of age by full neurological examination and the Griffiths Scales of Mental Development. Five infants were assessed at an earlier stage, four who died before 6 months of age and one infant who was hospitalized at the time of the 12 month assessment. Twenty-three (58%) of the infants were normal and 17 (42%) were abnormal, 16 with cerebral palsy and one with developmental delay. The hypoxic ischaemic encephalopathy score was highly predictive for outcome. The best correlation with outcome was the peak score; a peak score of 15 or higher had a positive predictive value of 92% and a negative predictive value of 82% for abnormal outcome, with a sensitivity and specificity of 71% and 96%, respectively. For the clinician working in areas where sophisticated technology is unavailable this scoring system will be useful for assessment of infants with hypoxic ischaemic encephalopathy and for prognosis of neurodevelopmental outcome.     

A mitochondrial ATPase 6 mutation is associated with Leigh syndrome in a family and affects proton flow and adenosine triphosphate output when modeled in Escherichia coli

A multidisciplinary strategy was used to identify the molecular defect in a family with Leigh syndrome (LS). The propositus presented severe developmental delay, an ataxic-spastic gait and seizures. She died at 3.5 y of age from cardiorespiratory arrest. Postmortem examination disclosed pathological features typical of LS. A 12-y-old sister is affected with the same disease. Respiratory chain enzyme complex activities in skeletal muscle biopsy were normal. Adenosine triphosphate (ATP) synthesis during oxidative phosphorylation in skin fibroblasts mitochondria showed a severely hampered ATP production. Mitochondrial DNA sequencing revealed a new mutation in the ATPase 6 gene (T9176G). Site-directed mutagenesis in Escherichia coli strains was used to measure H⁺ pumping and ATP synthesis. Results were comparable to findings obtained in human cells. These data corroborate the use of E. coli strains as a feasible "animal" model for functional studies in pathogenic mutations of the ATPase 6 gene.