Induction of chromosomal aberrations and spindle disturbances in Chinese hamster epithelial liver cells in culture by pyrene and benzo[a]pyrene quinones

Regioisomers of pyrene and benzo[a]pyrene quinones were testedfor their ability to induce structural and numerical aberrationsand spindle disturbance in Chinese hamster epithelial liver(CHEL) cells in culture. All quinones tested were clastogenicPyrene-1,8-quinone (P-1,8-Q) and benzo[a]pyrene–3,6–quinone(BP-3,6-Q) induced strikingly high levels of triradials. Inaddition, dicentrics and ring chromosomes were very common inBP-3,6-Q-treated cultures. Isomers of these compounds, pyrene-1,6-quinone(P-1,6-Q) and benzo[a]pyrene-1,6-quinone (BP-1,6-Q), inducedunobtrusive patterns of chromosomal aberrations. We suspectthat the P-1,8-Q and BP-3,6-Q moieties bound to the DNA werestill reactive, and formed crosslinks and/or underwent redoxcycling leading to high local concentrations of reactive oxygenspecies. In addition, P-1,8-Q and BP-3,6-Q induced c-mitoses,hyperdiploidies and polyploidies, in particular endoreduplications.These effects were not seen with the other two test compounds,or they were only detected at the highest concentrations used,which were strongly cytotoxic (c-mitoses with P-1,6-Q, polyploidieswith BP-1,6-Q). ⁶To whom correspondence should be addressed at: European Centre for the Validation of Alternative Methods (ECVAM), Joint Research Centre (JRC), TP58O, 1–21020 Ispra, Italy     

Akathisia as a side effect of antipsychotic treatment with quetiapine in a patient with Parkinson's disease.

Due to its low profile for extrapyramidal side-effects, quetiapine has become an alternative to clozapine in the treatment of dopamimetic psychosis in patients with Parkinson's disease (PD). We describe the case of a patient with PD who developed severe akathisia, a common complication with classical antipsychotics, with quetiapine.     

Comparison of three immunoassays for diagnosing sensitization to latex in children with spina bifida

As natural rubber latex (latex) has become more widespread in our environment, physicians have become increasingly aware of the problem of possible allergic reactions. Many fatal and near-fatal incidents have been reported (mainly during surgery) (1—3) and data has been published on groups frequently exposed to latex, such as patients with spina bifida (4—9), healthcare professionals (10—12) and occupationally exposed persons (13). The incidence of latex allergy in children seems to be increasing (14). Tests are therefore needed which can reliably detect sensitization to latex. Our aim was to compare the diagnostic accuracy of three commercial immunoassays for measuring specific IgE in serum to latex.     

An anti-CD44 antibody does not enhance engraftment of DLA-identical marrow after low-dose total body irradiation

920 cGy total body irradiation (TBI) is adequate for consistently successful engraftment of marrow from dog leukocyte antigen (DLA)-identical littermates; however, the dose is inadequate to ensure a marrow graft from DLA-nonidentical unrelated donors. Such mismatched grafts are successful only after 1800 cGy, given in three fractions. While anti-T-cell reagents enhance engraftment of DLA-identical littermate marrow after 920 cGy, they fail to be effective in the DLA-nonidentical setting. However, a monoclonal antibody (mAb) to CD44, S5, was found to be very effective in enhancing engraftment of DLA-nonidentical marrow. The current study asked whether mAb S5 was also effective in the setting of DLA-identical littermate transplants. To this purpose, the TBI dose was lowered to 450 cGy, a dose after which 70% of such grafts failed. Four dogs were treated with antibody S5, 0.2 mg/kg on days −7 though −2 (per previously published protocol), given 450 cGy TBI followed by marrow grafts from their DLA-identical littermates. All four dogs rejected their grafts; two of these died from marrow aplasia, and two survived with endogenous marrow recovery. This result was not statistically significantly different from that in 17, historical (n = 5) and concurrent (n = 12), control dogs where 11 of 17 animals rejected. Even if ten experimental animals were transplanted and all six remaining dogs engrafted, the results still would not have been significantly different from control. This result is in contrast to the successful engraftment promoted by pretreatment with antibody S5 of DLA-nonidentical unrelated dogs, consistent with the notion that different host cells are involved in graft rejection in the two disparate histocompatibility settings.     

Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.     

Emergency Treatment of Multiply Injured Patients with Unstable Disruption of the Posterior Pelvic Ring by Using the “C–Clamp”

Abstract Purpose: Evaluation of the therapeutic usefulness of the “pelvic C–clamp” (PCC) during emergency treatment of multiply injured patients with unstable disruption of the posterior pelvic ring. Patients and Methods: The data of 28 patients with polytrauma in combination with an unstable fracture of the posterior pelvic ring (average Injury Severity Score [ISS]: 49 points; average Polytrauma Score [PTS]: 41 points) were retrospectively analyzed from the moment they were admitted to the emergency room until 48 h after admittance. The PCC was used immediately for primary stabilization of the pelvis after clinical diagnosis of the unstable pelvic fracture. Main outcome measurements: development of mean blood pressure, development of oxygenation level, period of time until the PCC was placed, number of blood units needed, period of time until circulatory stabilization occurred. Results: The PCC was applied in all cases within an average of 64.7 min after trauma. Seven patients (25%) died within the first 45 min after admission. The surviving patients showed:• an increase in mean blood pressure of 25% 20 min after application of the PCC,• a hemodynamic stabilization 6 h after application of the PCC,• a stabilization of the oxygenation level 6 h after application of the PCC,• a decrease in the number of required blood units 6 h after application of the PCC. Conclusion: The present study shows, that the application of the PCC to critically injured patients with unstable pelvic fractures leads to stabilization of the vital parameters within a short period of time.     

Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients.

BACKGROUND: Dyslipidaemia, inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients. Dialysis modalities affect uraemic dyslipidaemia, possibly by modifying oxidative stress, but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins (LDL) are unknown. METHODS: We performed a randomized crossover study in 36 patients on haemodialysis to analyse the effect of dialyser flux and membrane material on plasma lipids, apolipoproteins and markers of inflammation and oxidative stress. Stable patients on low-flux dialysis with polysulphone for >/=6 weeks were assigned to high-flux polysulphone or high-flux modified cellulose with similar dialyser surface area and permeability characteristics and crossed over twice every 6 weeks. RESULTS: Thirty patients completed the study per protocol. Treatments with high-flux polysulphone and modified cellulose lowered serum triglyceride (by 20% and 10%, respectively; P<0.05) and remnant-like particle cholesterol by 32% (P<0.001) and 11% (NS) after the first 6 weeks of treatment. Oxidized LDL decreased significantly with high-flux polysulphone, but not with modified cellulose. Apolipoproteins CII and CIII were reduced, whereas the ratio CII/CIII was increased (all P<0.05). Acute-phase proteins and LDL and high-density lipoprotein cholesterol remained unaffected. CONCLUSIONS: This randomized crossover study demonstrates a potent effect of high-flux haemodialysis on uraemic dyslipidaemia. Polysulphone membrane material showed superiority on oxidatively modified LDL, an indicator of oxidative stress in haemodialysis patients.