Rapid Progression of Native Renal Artery Fibromuscular Dysplasia Following Kidney Donation

Fibromuscular dysplasia is the second commonest anatomical abnormality apart from multiple renal arteries in the potential live donors. Pretransplant evaluation of the donors may include an angiography to evaluate the renal arteries, and failure to recognize renal arterial stenosis, particularly fibromuscular dysplasia, by noninvasive methods may eventually lead to hypertension and ischemic renal failure. We report a case of fibromuscular dysplasia that was undetected by computed tomographic angiography prior to donation. One year after kidney donation, it rapidly progressed to severe symptomatic stenosis with hypertension and acute renal failure. Following renal artery angioplasty, her blood pressure normalized over a period of 2 weeks without any need for antihypertensive medications and the serum creatinine returned to her baseline. The acceptability of renal donors with fibromuscular dysplasia depends on the age, race and the availability of the other suitable donors. Mild fibromuscular dysplasia in a normotensive potential renal donor cannot be considered a benign condition. Such donors need regular follow-up postdonation for timely detection and treatment.     

(iii) Minimal invasive techniques in the management of tibial plateau fractures

Intra-articular fractures of the proximal tibia present a wide spectrum of injury patterns with associated soft tissue injury. The last two decades have seen the techniques of management evolve from extensive open reduction and rigid internal fixation to arthroscopy-assisted minimal invasive surgery (MIS) and biologically benign internal fixation. The ultimate aim is to prevent the occurrence of late degenerative arthritis. This could be achieved in selected patients using minimal invasive surgery, which offers the advantages of better visualisation and management of intra-articular soft tissue injuries, confirmation of fracture reduction viewed from the joint surface, faster rehabilitation and fewer wound complications.     

Allergy to barium sulfate suspension with angioedema of the stomach and small bowel

Hypersensitivity reactions occurring during barium studies of the gastrointestinal tract are rare. A case is presented with radiographically demonstrated angioedema in the stomach and small bowel accompanied by allergic rhinitis, which was apparently an allergic response to the barium sulfate suspension. The reaction was documented twice during separate challenges to the barium suspension performed several months apart.     

Inhibition of rat mixed lymphocyte pancreatic islet cultures with anti-Ia immunotoxin

Studies reported here indicate that an anti-Ia immunotoxin can eliminate the allostimulatory subpopulation of cells present within the islets of Langerhans without damaging the hormone-secreting cells. Such studies made use of an in vitro correlate of transplantation rejection, the mixed lymphocyte islet cell (MLIC) reaction. Using the MLIC, it was demonstrated that an anti-Ia immunotoxin removed cells capable of stimulating the MLIC in a dose-dependent fashion without altering the hormone-secreting functions of the remaining cells when challenged with glucose and theophylline. These studies suggest the feasibility of using such anti-Ia immunotoxins in islet allograft transplantation models to circumvent problems inherent in complement-mediated cytotoxicity, a previously documented effective form of inducing islet allotransplantation tolerance.     

Comparative uptake and retention of adriamycin andN-benzyladriamycin-14-valerate in human CEM leukemic lymphocyte cell cultures

Summary N-Benzyladriamycin-14-valerate (AD 198) is a new lipophilic adriamycin (ADR) analogue that shows marked therapeutic superiority to ADR in murine tumor model systems yet differs mechanistically from ADR in a number of ways. Among its other properties, AD 198 produces a delayed but profound effect on cell-cycle progression and a pattern of continuing DNA damage in cultured cells briefly exposed to the drug. Using radiolabeled drug forms and radioassays combined with HPLC separation and fluorimetric detection techniques, aspects of drug accumulation, biotransformation, and retention in cultured human CEM leukemic lymphocytes were studied, in part to determine a possible pharmacologic basis for the latent effects seen with this drug. In addition, the cellular pharmacology of AD 198 and ADR were comparatively examined under identical experimental conditions. When CEM cells were incubated with drug at equi-growth inhibitory/minimally cytotoxic concentrations (AD 198, 1.0 M; ADR, 0.1 M), a number of differences were apparent. Under conditions of continuous 24-h drug exposure, a slow cellular accumulation and equilibration was observed with ADR (cell: medium equilibrium, 1:11 after 4–6 h), whereas the uptake of AD 198 was rapid and extensive (cell: medium equilibrium, 3:1 within 30 min). In drug-retention studies, when cells were pretreated at the same drug concentrations as before (AD 198 for 1 h; ADR for 4 h) and then transferred to drug-free media, both compounds re-equilibrated their intracellular drug content with the fresh media, losing about 50% of their respective anthracycline levels. Liquid chromatographic analysis of ADR-treated cultures under both sets of conditions showed the parent drug to be the only intracellular anthracycline species, whereas analysis of AD 198-treated cultures revealed two fluorescent signals corresponding to the parent drug and its 14-deesterified biotransformation product,N-benzyladriamycin (AD 288). Levels of AD 288 rose from 2% of the total intracellular anthracycline content immediately on drug admixture to 61% following 24 h continuous drug exposure and to 69% at 24 h in cells exposed to drug for 1 h and then continued in drug-free media for 24 h. At all times, the balance of the intracellular anthracycline fluorescence was attributable to the parent drug; no ADR was detectable in AD 198-treated cells by either fluorescence detection or radioassay. Thus, AD 198 is not a prodrug form of ADR, and the in vitro effects of this agent, including the latent effects on cell-cycle inhibition and DNA damage seen in cells following short-term drug exposure, can be explained on the basis of the high levels of active parent drug and biotransformation product that accumulate and persist in the cells.Abbreviations ADR adriamycin (doxorubicin) - AD 198 N-benzyladriamycin-14-valerate - AD 288 N-benzyladriamycin - AD 32 N-trifluoroacetyladriamycin-14-valerate - AD 143 N-trifluoroacetyladriamycin-14-0-hemiadipate - AD 41 N-trifluoroacetyladriamycin - [¹⁴C]-AD 198 [benzyl]--methylene-¹⁴C]-N-benzyladriamycin-14-valerate - [¹⁴C]-ADR [14-¹⁴C]-adriamycin - HPLC high-performance liquid chromatography - TLC thin-layer chromatography - DMSO dimethylsulfoxide - S-MEM Eagle's minimum essential medium for suspension culture - PBS phosphate-buffered saline (pH 7.0)