Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Stated and actual management of acute myocardial infarction among different specialties

OBJECTIVES: To examine the variation in stated management of acute myocardial infarction (AMI) among clinicians of different specialties, and to compare stated with actual practice. DESIGN: Mail survey using a hypothetical case history, and review of medical records. SETTING: 47 public hospitals in New South Wales. SUBJECTS: 224 cardiologists, general/other physicians and general practitioners (GPs) who manage patients with AMI; 390 patients admitted for AMI between February and June 1996. OUTCOME MEASURES: Stated and actual use of treatments and investigations for AMI. RESULTS: Stated use of aspirin, thrombolysis and beta-blockers (95%-100%, 95%-100% and 80%-86%, respectively) was high in all three specialties. Cardiologists were significantly more likely than GPs to state use of heparin (87% v 57%; P < 0.001), ACE inhibitors (84% v 49%; P < 0.001) and echocardiography or gated pool heart scan (79% v 26%; P < 0.001). Stated use of nitrates by cardiologists was significantly lower compared with the other specialties (29% v 50% and 44%; P = 0.027). Actual use of aspirin was high (> 80%) in all specialties. Actual use of thrombolysis was similar to stated use after adjusting for factors such as time to hospital arrival and ST-segment elevation. There were substantial differences between stated and actual use. CONCLUSIONS: There were differences in practice patterns between and among clinicians of different specialties in NSW, consistent with findings from other countries. The high stated and actual use of aspirin and thrombolysis is encouraging.     

Preferential resistance of dopaminergic neurons to glutathione depletion in a reconstituted nigrostriatal system

Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD), and could initiate dopaminergic neuronal degeneration. Nevertheless, we have previously demonstrated that mesencephalic dopaminergic neurons in primary monolayer cultures are more resistant to the toxicity of glutathione depletion than nondopaminergic neurons. To extend this finding to a system that more closely resembles the in vivo situation, we characterized the effects of glutathione depletion on reaggregate cultures derived from ventral mesencephalic and their striatal target neurons, as well as supporting elements including glia. Dopaminergic neurons were found to be more resistant to the toxicity of buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis, than other nigrostriatal neurons, while striatal target cells exhibited an intermediate susceptibility when examined after 48 h. Glutathione depletion, however, decreased the intracellular content of catecholamines after 48 h and eventually led to the loss of dopaminergic neurons after 7 days. Our data indicate that the intrinsic resistance of dopaminergic neurons to the toxicity of glutathione depletion occurs in a variety of experimental paradigms, and suggest that global glutathione depletion alone is unlikely to account for the selective loss of dopaminergic neurons in PD. Rather, it is more likely that either the selective loss of glutathione from dopaminergic neurons, or the combination of glutathione loss with other insults contributes to the preferential death of dopaminergic neurons in PD.     

Use of Block Copolymers of Poly(Ortho Esters) and Poly (Ethylene Glycol) Micellar Carriers as Potential Tumour Targeting Systems

Amphiphilic AB and ABA block copolymers have been prepared from poly (ortho esters) and poly (ethylene glycol). Such block copolymers readily form micellar dispersions in water, or buffers. The CMC is in the range of 3 × 10_-4–5 × 10_-4 g/l which is a value low enough to assure retention of micelle integrity upon intravenous injection. The size, as determined by dynamic light scattering was in the 40–70 nm range. The micelles can be stored in lyophilized form for at lest 8 months and easily reconstituted to the original properties. The micelles are stable in PBS at pH 7.4 and 37°C for 3 days and in a citrate buffer at pH 5.5 and 37°C for 2 h. Stability in the presence of bovine serum albumin depends on the structure of the block copolymer and especially the length of the POE block.     

Mediastinal teratoma as a rare cause of hydrops fetalis and death: report of 3 cases

BACKGROUND: Congenital mediastinal teratomas are rare and may present with nonimmune hydrops. The lesion may be misinterpreted on ultrasound. CASES: A 21-year-old woman, gravida 2, para 0111, was evaluated at 19 4/7 weeks of gestation for suspected fetal death. An ultrasonogram confirmed the death and revealed a posterior encephalocele and possible herniated liver in the chest. At autopsy a 5.2 x 7.5 x 1.0-cm mediastinal teratoma completely compressed the chest organs. No encephalocele was present. A 15-year-old woman, gravida 1, para 0, underwent an ultrasonogram at 27 weeks when fetal heart rate decelerations were detected. The ultrasound revealed hydrops and suggested a calcified left cardiac ventricular wall and diaphragmatic hernia. Autopsy of the stillborn female showed an 8.0 x 6.0 x 4.0-cm teratoma in the mediastinum, with small heart and lungs. A 23 2/7 weeks stillborn female was delivered to a 32-year-old woman, gravida 5, para 2, and noted to be hydropic. Ultrasound had suggested multiple anomalies and hydrops. Autopsy revealed a 23 g, 4.5 x 3.0 x 3.0-cm teratoma that filled the anterior mediastinum. CONCLUSION: Congenital mediastinal teratoma may be associated with fetal death. It is within the differential diagnosis of nonimmune hydrops, particularly if a thoracic mass is detected on ultrasonography.     

Correction to: Assessment of Psychosocial Functioning in a Large Cohort of Patients with Schizophrenia

Psychiatric Quarterly -