Microscopic haematuria as a relative contraindication for tranexamic acid

Tranexamic acid has been advocated for patients with severe bleeding tendency due to thrombocytopenia not responding to platelet transfusions. Macroscopic haematuria is a well-known contraindication for its use in such patients. We present three clinical cases with microscopic haematuria, in whom tranexamic acid caused problems of clot formation in the urinary tract, indicating that microscopic haematuria should also be considered as a contraindication for tranexamic acid.     

Cocaine tolerance: Interactions among random-ratio and random-interval reinforcement-schedule parameters and repeated exposure to cocaine

Food-deprived pigeons were trained to peck a key under either a three-component multiple random-ratio 5, random-ratio 25, random-ratio 125 schedule or a three-component multiple random-interval 10-sec, random-interval 30-sec, random-interval 125-sec schedule of food presentation. Following determination of acute effects of cocaine (1.0-13.0 mg/kg), are-sponse-rate-reducing dose was given before each daily session. Once performance under conditions of daily administration had become stable, other doses occasionally were substituted for the usual daily dose so that dose effects could be assessed. Tolerance, i.e., a rightward shift in the dose-effect curve was observed in all subjects. For subjects studied under the random-ratio schedules, however, the robustness of the tolerance usually was related to the schedule-parameter value; tolerance was great at lower random values. By contrast, subjects whose responding was maintained by random-interval schedules were less likely to show tolerance that was schedule-parameter dependent. The results also provide suggestive evidence that dose may be an important factor in determining effects of repeated cocaine exposure; repeated administration of larger doses may be less likely to result in tolerance than similar exposure to smaller doses.     

Long-term structural alterations to endothelial cells in vein-to-artery grafts: a quantitative electron microscopic study

The intracellular structure of endothelium lining vein-to-artery grafts in rats was analysed, using transmission electron microscopy and morphometry, to determine the ultrastructural adaptations of endothelial cells in this altered vascular environment. Autogenous 4-mm sections of iliolumbar veins were inserted microsurgically into the left common iliac arteries of 16 male Wistar rats. At 3, 6, 26 and 52 weeks the cytoplasmic-vesicular, mitochondrial and rough endoplasmic reticular contents of endothelial cells lining the grafts, the opposite iliac arteries and the remaining ilio-lumbar veins were analysed morphometrically. There was a significant increase in the amount of all these cytoplasmic structures in endothelial cells at 3, 6 and 26 weeks; at 52 weeks there was also a significant increase in the volumes of mitochondria and cytoplasmic vesicles, but not in rough endoplasmic reticulum. It was concluded that the ultrastructure of endothelial cells lining these grafts is changed chronically after graft insertion, and we propose that this may be attributable to altered haemodynamic stresses within the graft.     

A novel nucleotide-containing antigen for human blood γδ T lymphocytes

The stimulation of human γδ T cells by mycobacteria occurs through recognition of four distinct nonpeptide phosphorylated antigens termed TUBag1–4. Among these latter, TUBag4 has already been biochemically characterized as a γ-X derivative of 5′-deoxythymidine triphosphate (Constant, P., Davodeau, F., Peyrat, M. A., Poquet, Y., Puzo, G., Bonneville, M. and Fournié, J.-J., Science 1994. 264: 267). However, despite chemical synthesis of weakly stimulatory nucleotide-containing analogs, these mycobacterial compounds remained the sole nucleotide-containing antigens actually isolated from natural sources. Here, we present the complete isolation of the TUBag3 antigen from Mycobacterium fortuitum and demonstrate that this nonpeptide molecule contains a 5′-UTP nucleotide moiety. On selected Vγ9/Vδ2 clones, T cell responses can be triggered with nanomolar concentrations of TUBag3. Like crude mycobacterial extracts, this purified nucleotide conjugate elicits a strong polyclonal response of γδ PBL from healthy donors. Furthermore, we present evidence that this compound is distinct from the recently synthesized γ-isopentenyl 5′-UTP, a nucleotide conjugate of isopentenyl pyrophosphate that was found to be stimulatory for human γδ T cells (Tanaka, Y., Morita, C. T., Tanaka, Y., Nieves, E., Brenner, M. B. and Bloom, B. R., Nature 1995. 375: 155). Since it appears that both mycobacterial nucleotide antigens are molecules structurally related to peculiar precursors of nucleic acid synthesis, we propose that TUBag-reactive T cells might be specifically devoted to surveillance of proliferating cells.     

Peripheral avian yolk assemblage and its persistence in the blastoderm, studied by trypan blue-induced fluorescence

Summary Shortly after subcutaneous or intraperitoneal injection of nontoxic quantities of trypan blue into laying Japanese quails, red fluorescent yolk granules appear in the peripheral ooplasm of their oocytes at the end of the lampbrush stage or subsequently. Later a red fluorescence can be observed in the apical cytoplasm of the granulosa cells. The results obtained by this method confirm our previous results (Callebaut 1974) obtained by autoradiography after ³H-leucine administration and furnish interesting additional data. The trypan blue-induced fluorescence method gives a good indication of the permeability of the oocytal cortex and its derivative the germinal disc. The avian yolk which is, or has been peripherally assembled (primordial, true white and yellow yolk) can be characteristically labelled by the administration of trypan blue. The injection of higher, still nontoxic quantities of trypan blue has a prolonged retarding effect and permits the marking of a broader part of the germinal disc or eventually of the blastoderm which develops from it.