Aorto-left atrial fistula secondary to aortic infective endocarditis in a dog with a bicuspid aortic valve.

An 11-year-old male neutered American bulldog was presented for evaluation of thrombocytopenia, acute onset of ataxia, and vomiting. A new murmur was auscultated on physical examination. Transthoracic echocardiographic examination revealed a bicuspid aortic valve, vegetative lesions on the aortic valve, and continuous shunting from the aortic root to the left atrium through an aorta to left atrial fistula. The dog was euthanized due to its guarded prognosis and critical condition. Pathological examination confirmed presence of a bicuspid aortic valve, aorto-left atrial fistula, and aortic infective endocarditis. Antemortem blood culture revealed two unusual organisms: Achromobacter xylosoxidans and Fusobacterium mortiferum.

Dynamics of active subglacial lakes in Recovery Ice Stream.

Recovery Ice Stream has a substantial number of active subglacial lakes that are observed, with satellite altimetry, to grow and drain over multiple years. These lakes store and release water that could be important for controlling the velocity of the ice stream. We apply a subglacial hydrology model to analyze lake growth and drainage characteristics together with the simultaneous development of the ice stream hydrological network. Our outputs produce a good match between modeled lake location and those identified using satellite altimetry for many of the lakes. The modeled subglacial system demonstrates development of pressure waves that initiate at the ice stream neck and transit to within 100 km of the terminus. These waves alter the hydraulic potential of the ice stream and encourage growth and drainage of the subglacial lakes. Lake drainage can cause large R-channels to develop between basal overdeepenings that persist for multiple years. The pressure waves, along with lake growth and drainage rates, do not identically repeat over multiple years, due to basal network development. This suggests that the subglacial hydrology of Recovery Ice Stream is influenced by regional drainage development on the scale of hundreds of kilometers rather than local conditions over tens of kilometers.

Amputations: no longer the end of the road.

BACKGROUND: The aim of this prospective study was to assess the effect of an intensive in-patient rehabilitation programme upon the mobility of amputees. METHODS: All major lower limb amputations between 1997 and 1999 received a pre-operative mobility assessment and, where appropriate, were referred for a vigorous rehabilitation programme. RESULTS: 92 lower limb amputations were performed in 87 patients (57 below knee, 33 above knee, two hip disarticulations). Overall, 63% of patients were able to ambulate independently following rehabilitation. Univariate analysis revealed that the only predictor of mobility was the level of amputation, below knee gaining better mobility than above knee (p=0.002). CONCLUSION: Lower limb amputees should participate in an aggressive in-patient physiotherapy regimen since reasonable mobility can be achieved in the majority of patients.

5-Methyl-2'-deoxy-4'-thio-alpha-uridine (R)-S-oxide.

The pyrimidine ring of the title compound, C(10)H(14)N(2)O(5)S, is planar to within 0.024 (1) A and makes an angle of 75.46 (10) degrees with the mean plane of the thiosugar ring. In terms of standard nucleoside nomenclature, this ring has the C3'-endo conformation. The O5'-C5'-C4'-C3' torsion angle is 166.5 (3) degrees and the glycosidic torsion angle S4'-C1'-N1-C2 is -52.1 (2) degrees (syn).

Anti-(herpes simplex virus) activity of 4'-thio-2'-deoxyuridines: a biochemical investigation for viral and cellular target enzymes.

The antiviral activity of several nucleoside analogues is often limited by their rapid degradation by pyrimidine nucleoside phosphorylases. In an attempt to avoid this degradation, several modified nucleosides have been synthesized. A series of 4'-thio-2'-deoxyuridines exhibits an anti-[herpes simplex virus (HSV)] activity significantly higher (20-600 times) than that shown by the corresponding 4'-oxy counterpart. We investigated the mode of action of these compounds and we found that: (i) several 4'-thio-2'-deoxyuridines are phosphorylated to the mono- and di-phosphates by HSV-1 thymidine kinase (TK) more efficiently than their corresponding 4'-oxy counterpart; (ii) both are inhibitors of cellular thymidylate synthase; (iii) 4'-thio-2'-deoxyuridines are resistant to phosphorolysis by human thymidine phosphorylase; (iv) both 4'-oxy- and 4'-thio-2'-deoxyuridines are phosphorylated to deoxyribonucleotide triphosphate in HSV-1-infected cells and are incorporated into viral DNA; (v) 4'-thio-2'-deoxyuridines are better inhibitors than their 4'-oxy counterparts of [(3)H]thymidine incorporation in HSV-1-infected cells; (vi) 4'-thio-2'-deoxyuridines are not recognized by HSV-1 and human uracil-DNA glycosylases. Our data suggest that 4'-thio-2'-deoxyuridines, resistant to pyrimidine phosphorylase, can be preferentially or selectively phosphorylated by viral TK in HSV-infected cells, where they are further converted into triphosphate by cellular nucleotide kinases. Once incorporated into viral DNA, they are better inhibitors of viral DNA synthesis than their corresponding 4'-oxy counterpart, either because they are not recognized, and thus not removed, by viral uracil-DNA glycosylase, or because they preferentially interfere with viral DNA polymerase.

Efficient syntheses of (E)-5-(2-bromovinyl)-2'-deoxy-4'-thiouridine; a nucleoside analogue with potent biological activity.

(E)-5-(2-Bromovinyl)-2'-deoxy-4'-thiouridine (S-BVDU) is a potent antiherpesvirus agent and its use in gene therapy as an anticancer agent has recently been described. We here outline 2 efficient methods for the synthesis of S-BVDU. The decision as to which method is to be used depends upon the starting materials available but starting from BVU, an overall yield of beta-nucleoside of 35% can be expected. From 5-ethyl-2'-deoxy-4'-thiouridine, radical bromination using bromine will give a quantitative conversion to S-BVDU if unreacted starting material is recycled (50%) or using N-bromosuccinimide, a one step yield in excess of 80% can be obtained.

Some 6-aza-5-substituted-2'-deoxyuridines show potent and selective inhibition of herpes simplex virus type 1 thymidine kinase.

The synthesis and X-ray crystal structures of a series of 5-substituted-6-aza-2'-deoxyuridines is reported. These nucleoside analogues inhibit the phosphorylation of thymidine by HSV-1 TK but have no effect on the corresponding human enzyme. Detailed examination of one analogue proves it to be a competitive inhibitor of thymidine with a Ki of 0.34 microM and is a very poor substrate. The analogues are not substrates for the enzyme and also do not inhibit the degradation of thymidine by thymidine phosphorylase. Molecular modelling showed that the inhibitors fit well in the active site of HSV-1 TK, provided the conformation of the sugar moiety is the same for thymidine in the complex.

Trichomonas vaginalis thymidine kinase: purification, characterization and search for inhibitors.

We report that a thymidine kinase (TK) activity is present in Trichomonas vaginalis and can be separated from the deoxyribonucleoside phosphotransferase. T. vaginalis TK, purified 11200-fold to apparent homogeneity, has a molecular mass of 31500 Da. It phosphorylates not only thymidine (Km 0.18 microM) but also deoxycytidine (Km 0.88 microM) and deoxyuridine (Km 0.14 microM). In contrast with T. vaginalis deoxyribonucleoside phosphotransferase, the TK activity is strongly inhibited by novel deoxyuridine analogues such as 5-methyl-4'-thio-2'-deoxyuridine (MTdU) (Ki 20 nM) and 5-iodo-4'-thio-2'-deoxyuridine (ITdU) (Ki 24 nM). MTdU and ITdU are phosphorylated by T. vaginalis TK in vitro. In vivo they inhibit [3H]thymidine incorporation in T. vaginalis cultured cells and T. vaginalis growth (IC50 7.5 and 24 microM respectively; minimal lethal dose 100 microM). Thus the TK inhibitors described here demonstrate the key role of T. vaginalis TK for protozoal growth and viability and indicate TK as a new target for the design of antitrichomonal drugs.

Sealing capacity in vitro of thermoplasticized gutta-percha with a solid core endodontic filling technique.

This study assessed the sealing capacity of two endodontic gutta-percha filling techniques. Thirty-four single-rooted fully developed teeth were endodontically accessed, instrumented and randomly divided into two experimental groups (n = 12) and two control groups (n = 5). In Group A, root canals were obturated using a solid core thermoplastic technique (Densfil), in Group B and Group C (negative control) canals were obturated with laterally condensed gutta-percha, and in Group D (positive control) canals were left unobturated. AH-26 was used as the sealer. Two days later, the teeth were conventionally prepared for testing apical and coronal leakage, immersed in india ink for 5 days and subsequently cleared. The linear coronal and apical extent of dye penetration was measured under a light dissecting microscope. The mean apical leakage for Group A was 1.39 mm, and for Group B 2.76 mm, whereas the mean coronal leakage for Group A was 2.87 mm, and for Group B 4.03 mm. The differences between the groups were not statistically significant (P > 0.05).