Treatment of a bifurcation lesion at the anastomosis of a vein graft by true 'Y' stenting

We describe the treatment of a bifurcation lesion at the anastomosis of a vein graft by 'true Y' stenting which preserved both antegrade and retrograde flow away from the graft.     

Evolution of spore release mechanisms in the saprolegniaceae (Oomycetes): evidence from a phylogenetic analysis of internal transcribed spacer sequences

Classical studies on spore release within the Saprolegniaceae (Oomycetes) led to the proposition that different mechanisms of sporangial emptying represent steps in an evolutionary transition series. We have reevaluated this idea in a phylogenetic framework using internal transcribed spacer sequences of four genera. These data were compared with the response to osmotic stress exhibited by each taxon. Saprolegnia emerges as the most basal genus, sister to Achlya, Thraustotheca, and Dictyuchus. Achlya and Thraustotheca are most closely related, while Dictyuchus appears to have evolved along a separate evolutionary lineage. The resulting phylogenetic framework is consistent with the idea that the mechanism of sporangial emptying exhibited by Saprolegnia represents the plesiomorphic condition from which the other mechanisms were derived independently. These alternative mechanisms of spore release may have resulted from a small number of mutations that inhibited axonemal development and altered the temporal and spatial expression of lytic enzymes that degrade the sporangial wall. Copyright 1998 Academic Press.     

Enantioselective metabolism of primaquine by human CYP2D6

Given the threat of resistance of human malaria parasites, including to artemisinin derivatives, new agents are needed. Chloroquine (CQ) has been the most widely used anti-malarial, and new analogs (CQAns) presenting alkynes and side chain variations with high antiplasmodial activity were evaluated. Six diaminealkyne and diaminedialkyne CQAns were evaluated against CQ-resistant (CQ-R) (W2) and CQ-sensitive (CQ-S) (3D7) Plasmodium falciparum parasites in culture. Drug cytotoxicity to a human hepatoma cell line (HepG2) evaluated, allowed to calculate the drug selectivity index (SI), a ratio of drug toxicity to activity in vitro. The CQAns were re-evaluated against CQ-resistant and -sensitive P. berghei parasites in mice using the suppressive test. Docking studies with the CQAns and the human (Hss LDH) or plasmodial lactate dehydrogenase (Pf LDH) enzymes, and, a β-haematin formation assay were performed using a lipid as a catalyst to promote crystallization in vitro. All tested CQAns were highly active against CQ-R P. falciparum parasites, exhibiting half-maximal inhibitory concentration (IC50) values below 1 μΜ. CQAn33 and CQAn37 had the highest SIs. Docking studies revealed the best conformation of CQAn33 inside the binding pocket of Pf LDH; specificity between the residues involved in H-bonds of the Pf LDH with CQAn37. CQAn33 and CQAn37 were also shown to be weak inhibitors of Pf LDH. CQAn33 and CQAn37 inhibited β-haematin formation with either a similar or a 2-fold higher IC50 value, respectively, compared with CQ. CQAn37 was active in mice with P. berghei, reducing parasitaemia by 100%. CQAn33, -39 and -45 also inhibited CQ-resistant P. berghei parasites in mice, whereas high doses of CQ were inactive. The presence of an alkyne group and the size of the side chain affected anti-P. falciparum activity in vitro. Docking studies suggested a mechanism of action other than Pf LDH inhibition. The β-haematin assay suggested the presence of an additional mechanism of action of CQAn33 and CQAn37. Tests with CQAn34, CQAn37, CQAn39 and CQAn45 confirmed previous results against P. berghei malaria in mice, and CQAn33, 39 and 45 were active against CQ-resistant parasites, but CQAn28 and CQAn34 were not. The result likely reflects structure-activity relationships related to the resistant phenotype.     

Reliability of cardiotocography in predicting baby's condition at birth.

A prospective study of 6825 labours was undertaken to determine the relation between the Apgar scores of the babies at one minute and the cardiotocograph tracing in labour. The sensitivity of an abnormal tracing was 35.2% for babies who needed intermittent positive pressure ventilation and 20.0% for babies who did not but who had Apgar scores of less than 7. The sensitivity of an abnormal tracing for all babies with an Apgar score of less than 7 was 23.2%. The positive predictive value of an abnormal tracing was 8.7% for babies who needed intermittent positive pressure ventilation and 18.7% for babies who did not but who had an Apgar score of less than 7. The positive predictive value of an abnormal tracing was 27.4% for all babies with an Apgar score of less than 7. The specificity of the tracing was 93.4% for babies with an Apgar score of 7 or over. The relatively high incidence of false positive predictions might be explained on the grounds that abnormalities in the cardiotocograph tracing are a more sensitive indicator of hypoxia than the Apgar score. False negative predictions might have been due to adverse factors other than hypoxia--for example, fetal trauma, compression of the head, infection, and analgesia in labour. These findings suggest that the current overdependence on fetal monitoring by cardiotocography alone should be examined and that other reliable indicators for non-hypoxic fetal distress should be sought.     

Recurrent stent thrombosis associated with lupus anticoagulant due to renal cell carcinoma

A case is presented of recurrent stent thrombosis unexplained by angiographic appearance, which subsequently revealed a diagnosis of antiphospholipid syndrome secondary to renal cell carcinoma.