Ochratoxin A and citrinin nephrotoxicity in New Zealand White rabbits: an ultrastructural assessment.

In the present investigation, ochratoxin A (OTA) (0.75 mg/kg feed) and citrinin (CIT) (15 mg/kg feed) were fed alone and in combination to young growing New Zealand White rabbits for 60 days to evaluate renal ultrastructural alterations. The severity and intensity of renal ultrastructural changes varied with the type of the treatment, and predominant and consistent lesions were recorded in the proximal convoluted tubule (PCT) lining cells. The significant changes in mitochondria, the most affected cell organelle in all the treatment groups, included mitochondrial disintegration and distortion, pleomorphism, cluster formation and misshapen appearance such as signet ring, dumbbell, cup and U shapes. Intra-cisternal sequestrations of involuting mitochondria, and thickening of basal layer of PCT epithelial cells with partial detachment, were the characteristic features observed in OTA and combination treatments. CIT treatment revealed crenated nucleus, loss of nucleolus, depletion of cytoplasmic organelles, mitochondrial pleomorphism, nuclear fragmentation, uniform folding of cell membrane and cytoplasmic vacuolations in the PCTs. Focal thickening of the glomerular basement membrane and degeneration of endothelial cells were the prominent alterations in the glomeruli in OTA and combination treatments. Distal convoluted tubules were unaffected in CIT treatment, however, mild to moderate lesions were observed in OTA and combination treated rabbits. It may be concluded that on simultaneous exposure, CIT potentiated the toxic effects of OTA on renal ultrastructure.

A multicentre observational study of presentation and early assessment of acute stroke.

OBJECTIVE: To investigate delays in the presentation to hospital and evaluation of patients with suspected stroke. DESIGN: Multicentre prospective observational study. SETTING: 22 hospitals in the United Kingdom and Dublin. PARTICIPANTS: 739 patients with suspected stroke presenting to hospital. MAIN OUTCOME MEASURES: Time from onset of stroke symptoms to arrival at hospital, and time from arrival to evaluation by a senior doctor. RESULTS: The median age of patients was 75 years, and 400 were women. The median delay between onset of symptoms and arrival at hospital was 6 hours (interquartile range 1 hour 48 minutes to 19 hours 12 minutes). 37% of patients arrived within 3 hours, 50% within 6 hours. The median delay for patients using the emergency service was 2 hours 3 minutes (47 minutes to 7 hours 12 minutes) compared with 7 hours 12 minutes (2 hours 5 minutes to 20 hours 37 minutes) for referrals from general practitioners (P<0.0001). Use of emergency services reduced delays to hospital (odds ratio 0.45, 95% confidence interval 0.23 to 0.61). The median time to evaluation by a senior doctor was 1 hour 9 minutes (interquartile range 33 minutes to 1 hour 50 minutes) but was undertaken in only 477 (65%) patients within 3 hours of arrival. This was not influenced by age, sex, time of presentation, mode of referral, hospital type, or the presence of a stroke unit. Computed tomography was requested within 3 hours of arrival in 166 (22%) patients but undertaken in only 60 (8%). CONCLUSION: Delays in patients arriving at hospital with suspected stroke can be reduced by the increased use of emergency services. Over a third of patients arrive at hospital within three hours of stroke; their management can be improved by expediting medical evaluation and performing computed tomography early.